Category Archive Arthritis Pain

Causes of Reiter Syndrome

Pathophysiology

Reactive arthritis is an immune-mediated syndrome triggered by a recent infection. It is hypothesized that when the invasive bacteria reach the systemic circulation, T lymphocytes are induced by bacterial fragments such as lipopolysaccharide and nucleic acids. These activated cytotoxic-T cells then attack the synovium and other self-antigens through molecular mimicry. This is supported by the evidence of Chlamydia trachomatis and C pneumoniae ribosomal RNA transcripts, enteric bacterial DNA, and bacterial degradation products in the synovial tissue and fluid. It is believed that anti-bacterial cytokine response is also impaired in reactive arthritis, resulting in the decreased elimination of the bacteria. It is, however, unclear why such localization of inflammation occurs.

The prevalence of HLA-B27 in reactive arthritis is estimated at 30% to 50% in patients with reactive arthritis, although values range widely. In hospital-based studies with more severely affected patients, frequencies as high as 60% to 80% have been reported. HLA-B27 should not be used as a diagnostic tool for a diagnosis of acute ReA. The presence of HLA-B27 is believed to potentiate reactive arthritis by presenting bacterial antigens to T cells, altering self-tolerance of the host immune system, increased TNF-alpha production, promoting the invasion of microbes in the gut, and delayed clearance of causative organisms.[rx]

Symptoms of Reiter Syndrome

Reactive arthritis may cause arthritis symptoms, such as joint pain and inflammation. It can also cause urinary tract symptoms and eye infection (conjunctivitis). Symptoms can last from 3 to 12 months. In a small number of people, the symptoms may turn into chronic disease. Symptoms can happen a bit differently in each person, and may include:

Arthritis symptoms	Joint pain and inflammation that often affect the knees, feet, and ankles Inflammation of a tendon that is attached to bone. This may cause heel pain or shortening and thickening of the fingers. Bony growths in the heel (heel spurs) that can cause chronic pain Inflammation of the spine (spondylitis) Inflammation of the lower back joints (sacroiliitis)
Urinary tract symptoms	Men: Increased urine Burning sensation during urination Discharge from penis Inflamed prostate gland (prostatitis) Women: Inflamed cervix Inflamed urethra. This causes a burning sensation during urination. Inflamed fallopian tubes (salpingitis) Inflamed vulva and vagina (vulvovaginitis)
Eye symptoms	Red eyes Painful and irritated eyes Blurry vision Inflamed mucous membrane that covers the eyeball and eyelid (conjunctivitis) Inflammation of the inner eye (uveitis)

Inflammation sitesOpen pop-up dialog box

The signs and symptoms of reactive arthritis generally start one to four weeks after exposure to a triggering infection. They might include:

• Because common systems involved include the eye, the urinary system, and the hands and feet, one clinical mnemonic in reactive arthritis is “Can’t see, can’t pee, can’t climb a tree.”^[rx]
• The classic triad consists of:
  • Conjunctivitis
  • Nongonococcal urethritis
  • Asymmetric oligoarthritis
• Symptoms generally appear within 1–3 weeks but can range from 4 to 35 days from the onset of the inciting episode of the disease.
• The classical presentation of the syndrome starts with urinary symptoms such as burning pain on urination (dysuria) or an increased frequency of urination. Other urogenital problems may arise such as prostatitis in men and cervicitis, salpingitis and/or vulvovaginitis in women.
• It presents with monoarthritis affecting the large joints such as the knees and sacroiliac spine causing pain and swelling. Asymmetrical inflammatory arthritis of interphalangeal joints may be present but with relative sparing of small joints such as the wrist and hand.
• The patient can have enthesitis presenting as heel pain, Achilles tendonitis or plantar fasciitis, along with balanitis circinata (circinate balanitis), which involves penile lesions present in roughly 20 to 40 percent of the men with the disease.
• A small percentage of men and women develop small hard nodules called keratoderma blennorrhagicum on the soles of the feet and, less commonly, on the palms of the hands or elsewhere. The presence of keratoderma blennorrhagica is diagnostic of reactive arthritis in the absence of the classical triad. Subcutaneous nodules are also a feature of this disease.
• Ocular involvement (mild bilateral conjunctivitis) occurs in about 50% of men with urogenital reactive arthritis syndrome and about 75% of men with enteric reactive arthritis syndrome. Conjunctivitis and uveitis can include redness of the eyes, eye pain and irritation, or blurred vision. Eye involvement typically occurs early in the course of reactive arthritis, and symptoms may come and go.
• Dactylitis, or “sausage digit”, diffuse swelling of a solitary finger or toe, is a distinctive feature of reactive arthritis and other peripheral spondylarthritides but can also be seen in polyarticular gout and sarcoidosis.
• Mucocutaneous lesions can be present. Common findings include oral ulcers that come and go. In some cases, these ulcers are painless and go unnoticed. In the oral cavity, the patients may suffer from recurrent aphthous stomatitis, geographic tongue, and migratory stomatitis in higher prevalence than the general population.^[rx]
• Some patients suffer serious gastrointestinal problems similar to those of Crohn’s disease.
• About 10 percent of people with reactive arthritis, especially those with a prolonged course of the disease, will develop cardiac manifestations, including aortic regurgitation and pericarditis. Reactive arthritis has been described as a precursor of other joint conditions, including ankylosing spondylitis.
• Pain and stiffness – The joint pain associated with reactive arthritis most commonly occur in your knees, ankles, and feet. You also might have pain in your heels, low back, or buttocks.
• Eye inflammation – Many people who have reactive arthritis also develop eye inflammation (conjunctivitis).
• Urinary problems – Increased frequency and discomfort during urination may occur, as can inflammation of the prostate gland or cervix.
• Inflammation of soft tissue where it enters bone (enthesitis) – This might include muscles, tendons and ligaments.
• Swollen toes or fingers – In some cases, your toes or fingers might become so swollen that they resemble sausages.
• Skin problems – Reactive arthritis can affect your skin a variety of ways, including a rash on your soles and palms and mouth sores.
• Low back pain – The pain tends to be worse at night or in the morning.

Symptoms By Specific Organ

The symptoms of reactive arthritis usually develop shortly after you get an infection, such as a sexually transmitted infection or bowel infection.The main, and sometimes only, symptom of reactive arthritis is pain, stiffness and swelling in the joints and tendons.It can also affect the:

• genital tract
• eyes

However, not everyone will get symptoms in these areas. You should see your GP as soon as possible if you have any of these symptoms, especially if you have recently had diarrhea or problems peeing.

Joint symptoms

Reactive arthritis can affect any joints, but it’s most common in the knees, feet, toes, hips and ankles.

Symptoms include:

• pain, tenderness and swelling in your joints
• pain and tenderness in some tendons, especially at the heels
• pain in your lower back and buttocks
• sausage-like swelling of your fingers and toes
• joint stiffness – particularly in the morning

Genital tract symptoms

Sometimes, you can also have symptoms of a urinary tract infection. These include:

• needing to pee suddenly, or more often than usual
• pain or a burning sensation when peeing
• smelly or cloudy pee
• blood in your pee
• pain in your lower tummy
• feeling tired and unwell

Eye symptoms

Occasionally, you may get inflammation of the eyes (conjunctivitis or, rarely, iritis).

Symptoms can include:

• red eyes
• watery eyes
• eye pain
• swollen eyelids
• sensitivity to light

See an eye specialist or go to A&E as soon as possible if one of your eyes becomes very painful and the vision becomes misty.

This could be a symptom of iritis – and the sooner you get treatment, the more successful it is likely to be.

Other symptoms

Reactive arthritis can also cause:

• flu-like symptoms
• a high temperature (fever)
• weight loss
• mouth ulcers
• a scaly rash on the hands or feet

References

Causes of Reactive Arthritis

Pathophysiology

Reactive arthritis is an immune-mediated syndrome triggered by a recent infection. It is hypothesized that when the invasive bacteria reach the systemic circulation, T lymphocytes are induced by bacterial fragments such as lipopolysaccharide and nucleic acids. These activated cytotoxic-T cells then attack the synovium and other self-antigens through molecular mimicry. This is supported by the evidence of Chlamydia trachomatis and C pneumoniae ribosomal RNA transcripts, enteric bacterial DNA, and bacterial degradation products in the synovial tissue and fluid. It is believed that anti-bacterial cytokine response is also impaired in reactive arthritis, resulting in the decreased elimination of the bacteria. It is, however, unclear why such localization of inflammation occurs.

The prevalence of HLA-B27 in reactive arthritis is estimated at 30% to 50% in patients with reactive arthritis, although values range widely. In hospital-based studies with more severely affected patients, frequencies as high as 60% to 80% have been reported. HLA-B27 should not be used as a diagnostic tool for a diagnosis of acute ReA. The presence of HLA-B27 is believed to potentiate reactive arthritis by presenting bacterial antigens to T cells, altering self-tolerance of the host immune system, increased TNF-alpha production, promoting the invasion of microbes in the gut, and delayed clearance of causative organisms.[rx]

Symptoms of Reactive Arthritis

Reactive arthritis may cause arthritis symptoms, such as joint pain and inflammation. It can also cause urinary tract symptoms and eye infection (conjunctivitis). Symptoms can last from 3 to 12 months. In a small number of people, the symptoms may turn into chronic disease. Symptoms can happen a bit differently in each person, and may include:

Arthritis symptoms	Joint pain and inflammation that often affect the knees, feet, and ankles Inflammation of a tendon that is attached to bone. This may cause heel pain or shortening and thickening of the fingers. Bony growths in the heel (heel spurs) that can cause chronic pain Inflammation of the spine (spondylitis) Inflammation of the lower back joints (sacroiliitis)
Urinary tract symptoms	Men: Increased urine Burning sensation during urination Discharge from penis Inflamed prostate gland (prostatitis) Women: Inflamed cervix Inflamed urethra. This causes a burning sensation during urination. Inflamed fallopian tubes (salpingitis) Inflamed vulva and vagina (vulvovaginitis)
Eye symptoms	Red eyes Painful and irritated eyes Blurry vision Inflamed mucous membrane that covers the eyeball and eyelid (conjunctivitis) Inflammation of the inner eye (uveitis)

Inflammation sitesOpen pop-up dialog box

The signs and symptoms of reactive arthritis generally start one to four weeks after exposure to a triggering infection. They might include:

• Because common systems involved include the eye, the urinary system, and the hands and feet, one clinical mnemonic in reactive arthritis is “Can’t see, can’t pee, can’t climb a tree.”^[rx]
• The classic triad consists of:
  • Conjunctivitis
  • Nongonococcal urethritis
  • Asymmetric oligoarthritis
• Symptoms generally appear within 1–3 weeks but can range from 4 to 35 days from the onset of the inciting episode of the disease.
• The classical presentation of the syndrome starts with urinary symptoms such as burning pain on urination (dysuria) or an increased frequency of urination. Other urogenital problems may arise such as prostatitis in men and cervicitis, salpingitis and/or vulvovaginitis in women.
• It presents with monoarthritis affecting the large joints such as the knees and sacroiliac spine causing pain and swelling. Asymmetrical inflammatory arthritis of interphalangeal joints may be present but with relative sparing of small joints such as the wrist and hand.
• The patient can have enthesitis presenting as heel pain, Achilles tendonitis or plantar fasciitis, along with balanitis circinata (circinate balanitis), which involves penile lesions present in roughly 20 to 40 percent of the men with the disease.
• A small percentage of men and women develop small hard nodules called keratoderma blennorrhagicum on the soles of the feet and, less commonly, on the palms of the hands or elsewhere. The presence of keratoderma blennorrhagica is diagnostic of reactive arthritis in the absence of the classical triad. Subcutaneous nodules are also a feature of this disease.
• Ocular involvement (mild bilateral conjunctivitis) occurs in about 50% of men with urogenital reactive arthritis syndrome and about 75% of men with enteric reactive arthritis syndrome. Conjunctivitis and uveitis can include redness of the eyes, eye pain and irritation, or blurred vision. Eye involvement typically occurs early in the course of reactive arthritis, and symptoms may come and go.
• Dactylitis, or “sausage digit”, diffuse swelling of a solitary finger or toe, is a distinctive feature of reactive arthritis and other peripheral spondylarthritides but can also be seen in polyarticular gout and sarcoidosis.
• Mucocutaneous lesions can be present. Common findings include oral ulcers that come and go. In some cases, these ulcers are painless and go unnoticed. In the oral cavity, the patients may suffer from recurrent aphthous stomatitis, geographic tongue, and migratory stomatitis in higher prevalence than the general population.^[rx]
• Some patients suffer serious gastrointestinal problems similar to those of Crohn’s disease.
• About 10 percent of people with reactive arthritis, especially those with a prolonged course of the disease, will develop cardiac manifestations, including aortic regurgitation and pericarditis. Reactive arthritis has been described as a precursor of other joint conditions, including ankylosing spondylitis.
• Pain and stiffness – The joint pain associated with reactive arthritis most commonly occur in your knees, ankles, and feet. You also might have pain in your heels, low back, or buttocks.
• Eye inflammation – Many people who have reactive arthritis also develop eye inflammation (conjunctivitis).
• Urinary problems – Increased frequency and discomfort during urination may occur, as can inflammation of the prostate gland or cervix.
• Inflammation of soft tissue where it enters bone (enthesitis) – This might include muscles, tendons and ligaments.
• Swollen toes or fingers – In some cases, your toes or fingers might become so swollen that they resemble sausages.
• Skin problems – Reactive arthritis can affect your skin a variety of ways, including a rash on your soles and palms and mouth sores.
• Low back pain – The pain tends to be worse at night or in the morning.

Symptoms By Specific Organ

The symptoms of reactive arthritis usually develop shortly after you get an infection, such as a sexually transmitted infection or bowel infection.The main, and sometimes only, symptom of reactive arthritis is pain, stiffness and swelling in the joints and tendons.

It can also affect the:

• genital tract
• eyes

However, not everyone will get symptoms in these areas. You should see your GP as soon as possible if you have any of these symptoms, especially if you have recently had diarrhea or problems peeing.

Joint symptoms

Reactive arthritis can affect any joints, but it’s most common in the knees, feet, toes, hips and ankles.

Symptoms include:

• pain, tenderness and swelling in your joints
• pain and tenderness in some tendons, especially at the heels
• pain in your lower back and buttocks
• sausage-like swelling of your fingers and toes
• joint stiffness – particularly in the morning

Genital tract symptoms

Sometimes, you can also have symptoms of a urinary tract infection. These include:

• needing to pee suddenly, or more often than usual
• pain or a burning sensation when peeing
• smelly or cloudy pee
• blood in your pee
• pain in your lower tummy
• feeling tired and unwell

Eye symptoms

Occasionally, you may get inflammation of the eyes (conjunctivitis or, rarely, iritis).

Symptoms can include:

• red eyes
• watery eyes
• eye pain
• swollen eyelids
• sensitivity to light

See an eye specialist or go to A&E as soon as possible if one of your eyes becomes very painful and the vision becomes misty.

This could be a symptom of iritis – and the sooner you get treatment, the more successful it is likely to be.

Other symptoms

Reactive arthritis can also cause:

• flu-like symptoms
• a high temperature (fever)
• weight loss
• mouth ulcers
• a scaly rash on the hands or feet

References

Causes of Reactive Arthritis

Pathophysiology

Reactive arthritis is an immune-mediated syndrome triggered by a recent infection. It is hypothesized that when the invasive bacteria reach the systemic circulation, T lymphocytes are induced by bacterial fragments such as lipopolysaccharide and nucleic acids. These activated cytotoxic-T cells then attack the synovium and other self-antigens through molecular mimicry. This is supported by the evidence of Chlamydia trachomatis and C pneumoniae ribosomal RNA transcripts, enteric bacterial DNA, and bacterial degradation products in the synovial tissue and fluid. It is believed that anti-bacterial cytokine response is also impaired in reactive arthritis, resulting in the decreased elimination of the bacteria. It is, however, unclear why such localization of inflammation occurs.

The prevalence of HLA-B27 in reactive arthritis is estimated at 30% to 50% in patients with reactive arthritis, although values range widely. In hospital-based studies with more severely affected patients, frequencies as high as 60% to 80% have been reported. HLA-B27 should not be used as a diagnostic tool for a diagnosis of acute ReA. The presence of HLA-B27 is believed to potentiate reactive arthritis by presenting bacterial antigens to T cells, altering self-tolerance of the host immune system, increased TNF-alpha production, promoting the invasion of microbes in the gut, and delayed clearance of causative organisms.[rx]

Symptoms of Reactive Arthritis

Reactive arthritis may cause arthritis symptoms, such as joint pain and inflammation. It can also cause urinary tract symptoms and eye infection (conjunctivitis). Symptoms can last from 3 to 12 months. In a small number of people, the symptoms may turn into chronic disease. Symptoms can happen a bit differently in each person, and may include:

Arthritis symptoms	Joint pain and inflammation that often affect the knees, feet, and ankles Inflammation of a tendon that is attached to bone. This may cause heel pain or shortening and thickening of the fingers. Bony growths in the heel (heel spurs) that can cause chronic pain Inflammation of the spine (spondylitis) Inflammation of the lower back joints (sacroiliitis)
Urinary tract symptoms	Men: Increased urine Burning sensation during urination Discharge from penis Inflamed prostate gland (prostatitis) Women: Inflamed cervix Inflamed urethra. This causes a burning sensation during urination. Inflamed fallopian tubes (salpingitis) Inflamed vulva and vagina (vulvovaginitis)
Eye symptoms	Red eyes Painful and irritated eyes Blurry vision Inflamed mucous membrane that covers the eyeball and eyelid (conjunctivitis) Inflammation of the inner eye (uveitis)

Inflammation sitesOpen pop-up dialog box

The signs and symptoms of reactive arthritis generally start one to four weeks after exposure to a triggering infection. They might include:

• Because common systems involved include the eye, the urinary system, and the hands and feet, one clinical mnemonic in reactive arthritis is “Can’t see, can’t pee, can’t climb a tree.”^[rx]
• The classic triad consists of:
  • Conjunctivitis
  • Nongonococcal urethritis
  • Asymmetric oligoarthritis
• Symptoms generally appear within 1–3 weeks but can range from 4 to 35 days from the onset of the inciting episode of the disease.
• The classical presentation of the syndrome starts with urinary symptoms such as burning pain on urination (dysuria) or an increased frequency of urination. Other urogenital problems may arise such as prostatitis in men and cervicitis, salpingitis and/or vulvovaginitis in women.
• It presents with monoarthritis affecting the large joints such as the knees and sacroiliac spine causing pain and swelling. Asymmetrical inflammatory arthritis of interphalangeal joints may be present but with relative sparing of small joints such as the wrist and hand.
• The patient can have enthesitis presenting as heel pain, Achilles tendonitis or plantar fasciitis, along with balanitis circinata (circinate balanitis), which involves penile lesions present in roughly 20 to 40 percent of the men with the disease.
• A small percentage of men and women develop small hard nodules called keratoderma blennorrhagicum on the soles of the feet and, less commonly, on the palms of the hands or elsewhere. The presence of keratoderma blennorrhagica is diagnostic of reactive arthritis in the absence of the classical triad. Subcutaneous nodules are also a feature of this disease.
• Ocular involvement (mild bilateral conjunctivitis) occurs in about 50% of men with urogenital reactive arthritis syndrome and about 75% of men with enteric reactive arthritis syndrome. Conjunctivitis and uveitis can include redness of the eyes, eye pain and irritation, or blurred vision. Eye involvement typically occurs early in the course of reactive arthritis, and symptoms may come and go.
• Dactylitis, or “sausage digit”, diffuse swelling of a solitary finger or toe, is a distinctive feature of reactive arthritis and other peripheral spondylarthritides but can also be seen in polyarticular gout and sarcoidosis.
• Mucocutaneous lesions can be present. Common findings include oral ulcers that come and go. In some cases, these ulcers are painless and go unnoticed. In the oral cavity, the patients may suffer from recurrent aphthous stomatitis, geographic tongue, and migratory stomatitis in higher prevalence than the general population.^[rx]
• Some patients suffer serious gastrointestinal problems similar to those of Crohn’s disease.
• About 10 percent of people with reactive arthritis, especially those with a prolonged course of the disease, will develop cardiac manifestations, including aortic regurgitation and pericarditis. Reactive arthritis has been described as a precursor of other joint conditions, including ankylosing spondylitis.
• Pain and stiffness – The joint pain associated with reactive arthritis most commonly occur in your knees, ankles, and feet. You also might have pain in your heels, low back, or buttocks.
• Eye inflammation – Many people who have reactive arthritis also develop eye inflammation (conjunctivitis).
• Urinary problems – Increased frequency and discomfort during urination may occur, as can inflammation of the prostate gland or cervix.
• Inflammation of soft tissue where it enters bone (enthesitis) – This might include muscles, tendons and ligaments.
• Swollen toes or fingers – In some cases, your toes or fingers might become so swollen that they resemble sausages.
• Skin problems – Reactive arthritis can affect your skin a variety of ways, including a rash on your soles and palms and mouth sores.
• Low back pain – The pain tends to be worse at night or in the morning.

Symptoms By Specific Organ

The symptoms of reactive arthritis usually develop shortly after you get an infection, such as a sexually transmitted infection or bowel infection.

The main, and sometimes only, symptom of reactive arthritis is pain, stiffness and swelling in the joints and tendons.

It can also affect the:

• genital tract
• eyes

However, not everyone will get symptoms in these areas. You should see your GP as soon as possible if you have any of these symptoms, especially if you have recently had diarrhea or problems peeing.

Joint symptoms

Reactive arthritis can affect any joints, but it’s most common in the knees, feet, toes, hips and ankles.

Symptoms include:

• pain, tenderness and swelling in your joints
• pain and tenderness in some tendons, especially at the heels
• pain in your lower back and buttocks
• sausage-like swelling of your fingers and toes
• joint stiffness – particularly in the morning

Genital tract symptoms

Sometimes, you can also have symptoms of a urinary tract infection. These include:

• needing to pee suddenly, or more often than usual
• pain or a burning sensation when peeing
• smelly or cloudy pee
• blood in your pee
• pain in your lower tummy
• feeling tired and unwell

Eye symptoms

Occasionally, you may get inflammation of the eyes (conjunctivitis or, rarely, iritis).

Symptoms can include:

• red eyes
• watery eyes
• eye pain
• swollen eyelids
• sensitivity to light

See an eye specialist or go to A&E as soon as possible if one of your eyes becomes very painful and the vision becomes misty.

This could be a symptom of iritis – and the sooner you get treatment, the more successful it is likely to be.

Other symptoms

Reactive arthritis can also cause:

• flu-like symptoms
• a high temperature (fever)
• weight loss
• mouth ulcers
• a scaly rash on the hands or feet

References

Sacroiliac Joint Arthritis/Sacroiliac Joint Dysfunction or sacroiliitis are common terms used to describe the pain of the sacroiliac joint. It is usually caused by abnormal motion (i.e. hyper- or hypo-mobile) or malalignment of the sacroiliac joint. The joint can be hyper or hypo-mobile which can cause pain. Pain is usually localized over the buttock. Patients usually describe the pain as sharp, dull, achy, stabbing, or shooting pain directly over the affected joint.

Sacroiliac joint (SIJ) pain refers to the pain arising from the SIJ joint structures. SIJ dysfunction generally refers to an aberrant position or movement of SIJ structures that may or may not result in pain. This paper aims to clarify the difference between these clinical concepts and present currently available evidence regarding the diagnosis and treatment of SIJ disorders.

Sacroiliitis is inflammation within the sacroiliac joint. It is a feature of spondyloarthropathies, such as axial spondyloarthritis (including ankylosing spondylitis), psoriatic arthritis, reactive arthritis or arthritis related to inflammatory bowel diseases, including ulcerative colitis or Crohn’s disease. It is also the most common presentation of arthritis from brucellosis.

Anatomy of Sacroiliac Joint Arthritis

Six variants of the sacroiliac joints have been observed: accessory joints, iliosacral complex, bipartite iliac bony plate, crescent-like iliac bony plate, semicircular defects at the sacral or iliac side and ossification centers.

• Accessory sacroiliac joint – Accessory sacroiliac joint is found medial to the posterior superior iliac spine and lateral to the second sacral foramen amongst a rudimentary transverse tuberosity. On CT imaging, accessory joints have articular surfaces that resemble osseous projects from the ilium to the sacrum.  An accessory joint can be present at birth; however, they more commonly result from the stress of weight-bearing.  Accessory joints are more commonly present in the obese population and the older population, as well as a higher prevalence in women with 3 or more childbirths, compared to 2 or less.
• Iliosacral complex – Iliosacral complex forms from a projection from the ilium articulating with a complementary sacral recess. These complexes can be unilateral or bilateral, and like accessory joints, these complexes exist at the posterior sacroiliac joint from the level of first to the second sacral foramen. This variant has been seen more in older patients greater than 60 years, as well as obese women more so than normal-weight women.
• Bipartite iliac bony plate – Bipartite iliac bony plate is located at the posterior portion of the sacroiliac joint and appears as described, consisting of two parts and appears unilaterally.
• Semicircular defects on the iliac/sacral side – The fourth variant is semicircular defects on either the sacral or iliac aspects of the articular surface of the sacroiliac joint. These can be unilateral or bilateral and again are present at the posterior portion of the sacroiliac joint from the level of the first to the second sacral foramen. This defect has been observed more in women than men and in patients older than 60 years.
• Crescent-like iliac bony plate – The fifth variant is a crescent-like articular surface which may be present unilaterally or bilaterally. CT imaging demonstrates a crescent-like iliac plate with accompanying a bulged sacral surface. This defect is found usually at the posterior portion of the sacral iliac joint spanning the levels of the first and second sacral foramen. This defect was observed only in women and more commonly in patients greater than 60 years old.
• Ossification centers of the sacral wings – The sixth anatomical variant observed is ossification centers presenting as triangular osseous bodies located within the joint space at the anterior portion of the sacroiliac joint. This defect is found at the level of the first sacral foramen, typically unilaterally.[rx][rx]

Causes of Sacroiliac Joint Arthritis

Diagnosis of Sacroiliac Joint Arthritis

In most clinical evaluations, common laboratory findings in the aseptic setting include:

• WBC count – usually normal (elevated in infection/septic presentation)
• ESR – elevated
• CRP – elevated
• HLA-B27 – About 1-2% of patients with ankylosing spondylitis will be HLA-B27 positive
• Rheumatoid Factor (RF) – Negative in the setting of true ankylosing spondylitis

Treatment of Systemic Lupus Erythematosus/The Systemic Lupus Erythematosus (SLE) is a systemic autoimmune disease, with multisystemic involvement. The disease has several phenotypes, with varying clinical presentations in patients ranging from mild mucocutaneous manifestations to multiorgan and severe central nervous system involvement. Several immunopathogenic pathways play a role in the development of SLE. The lupus erythematosus (LE cell) was described by Hargraves in 1948. Several pathogenic autoantibodies have since been identified.

The systemic lupus erythematosus (SLE) is characterized by overt polyclonal B-cell activation and autoantibody (Ab) production. By contrast, cellular immune responses against all- or recall antigens are significantly impaired. Many pieces of evidence indicate that IL-10 overproduction plays a pivotal role in the disease and the contribution of the IL-10/IL-12 imbalance to the pathophysiology of SLE will be extensively discussed. The authors will further summarize the available data about the involvement of IFN-γ, TNF-α, TGF-β, and TALL-1. Other cytokines (IL-1, IL-2, IL-4, IL-6, IL-16, IL-17, and IL-18) will be briefly discussed.

Systemic Lupus Erythematosus

Types of Systemic Lupus Erythematosus

About 25% of patients with systemic lupus erythematosus (SLE) initially present with skin involvement. It is important to correctly classify cutaneous lupus erythematosus (CLE), as it helps determine the underlying type and severity of SLE. About 5–10% of patients with CLE develop SLE, and CLE is associated with less severe forms of SLE.

Skin manifestations of lupus erythematosus are commonly divided into lupus erythematosus–specific and non–specific disease. Note that four of the nine American College of Rheumatology criteria for SLE are skin signs (ie, malar/butterfly rash, discoid plaques, photosensitivity, and oral ulcers).

Lupus erythematosus–specific disease

Acute cutaneous lupus erythematosus

Forms of acute CLE include the following:

• Localised acute CLE — this presents with malar or ‘butterfly’ rash (symmetrical erythema and edema of the cheeks, forehead, chin, and V of the neck but sparing the nasolabial folds or ‘smile lines’)
• Generalised acute CLE — this presents with a widespread exanthematous eruption on the extensor surfaces, trunk, sun-exposed areas, and hands (but sparing the knuckles)
• Toxic epidermal necrolysis-like acute CLE — this is a life-threatening variant of acute CLE that presents with a massive epidermal injury; it occurs predominantly on sun-exposed skin and has a gradual, insidious onset, unlike toxic epidermal necrolysis.

Acute CLE is typically triggered or exacerbated by exposure to ultraviolet (UV) radiation. On recovery, there may be postinflammatory hyperpigmentation without scarring.

Subacute cutaneous lupus erythematosus

The subacute cutaneous lupus erythematosus (SCLE) starts as macules or papules that progress to hyperkeratotic plaques. SCLE is photosensitive so plaques usually occur on sun-exposed skin; these plaques do not lead to scarring but can result in postinflammatory hyperpigmentation or hypopigmentation. SCLE should be monitored to exclude any progression to SLE.

Forms of SCLE include:

• Annular SCLE — this subtype presents with slightly raised red lesions with central clearing
• Papulosquamous SCLE — this subtype presents with eczematous or psoriasis-like lesions on sun-exposed skin.

Chronic cutaneous lupus erythematosus

Chronic CLE is not as photosensitive as acute CLE or SCLE. Forms of chronic CLE include:

• The discoid lupus erythematosus (DLE) — this affects the face, outer ears, neck, sun-exposed areas and lips, and presents with discoid plaques (erythematous, well-demarcated plaques covered by scale) that become hyperkeratotic, leading to atrophy and scarring; there is follicular involvement, causing both reversible and irreversible (scarring) alopecia (hair loss); depigmentation of the peripheries is also common in certain ethnicities (Asian, Indian).
• Hypertrophic or verrucous lupus erythematosus — this is a rare form of CLE presenting with severe hyperkeratosis of the extensor surfaces of the arms, upper back and face; it has overlapping features with lichen planus.
• Mucosal lupus erythematosus — this affects 25% of patients with CLE; most commonly, painless erythematous patches on the oral mucosa develop into chronic plaques that can centrally ulcerate and also affect nasal, conjunctival and genital mucosa; oral lupus erythematosus rarely degrades to oral cancer (squamous cell carcinoma).

Drug-induced lupus erythematosus

Many drugs are thought to induce SLE and drug-induced lupus erythematosus often includes cutaneous signs. Drugs that induce lupus erythematosus include:

• Hydralazine
• Isoniazid
• Chlorpromazine
• Procainamide
• Phenytoin
• Minocycline
• Anti–tumour necrosis factor medications.

Rarer types of lupus erythematosus

The rarer types of lupus erythematosus include:

• Lupus profundus/lupus panniculitis — this is a rare form of chronic CLE with firm nodules in the lower dermis and subcutaneous tissue that causes lipodystrophy; some use the term lupus panniculitis to refer to subcutaneous involvement only, and lupus profundus when there is a combination of lupus panniculitis with DLE.
• Chilblain lupus erythematosus — this presents with purple-red patches, papules and plaques on toes, fingers and face, and is associated with nail fold telangiectasia; it is precipitated by exposure to the cold, so often presents in winter.
• Lupus erythematosus tumidus —this is a variant of chronic CLE with succulent or indurated erythematous plaques without surface change.

Lupus erythematosus — non–specific disease

Lupus erythematosus-nonspecific disease can relate to SLE or another autoimmune disease, but nonspecific cutaneous features are most often associated with SLE.

Common cutaneous features seen include:

• Photosensitivity — this is an abnormal response to UV radiation that is present in 50–93% of patients with SLE
• Mouth ulcers — these are present in 25–45% of patients with SLE
• Non–scarring hair loss in SLE — presenting as coarse, dry hair with increased fragility (also referred to as ‘lupus hair’).

Cutaneous vascular disease is also common. Forms of cutaneous vascular disease include

• Raynaud phenomenon — this presents with focal ulceration in the fingertips and periungual areas that can cause pitted scarring, hemorrhage and other nail fold complications
• Vasculitis — leukocytoclastic vasculitis: urticarial vasculitis presenting with tender papules and plaques over bony prominences; and medium or large vessel vasculitis can occur, presenting with purpuric plaques with stellate borders, often with necrosis and ulceration or subcutaneous nodules
• Thromboembolic vasculopathy — these may have a similar clinical presentation to vasculitis, but vessel occlusion is due to blood clots
• Livedo reticularis — characterized by net-like blanching red-purple rings that commonly arise on the lower limbs
• Erythromelalgia — characterized by burning pain in the feet and hands, and with macular erythema; it is associated with heat exposure.

Specific cutaneous SLE

Cutaneous lupus (CLE) has specific acute, subacute and chronic manifestations.

• Typically, SLE presents with acute CLE.
• About half of patients with subacute cutaneous LE develop mild SLE
• Only 5% of patients with chronic CLE have SLE, as CLE presents as a skin problem without the involvement of other organs.

Acute CLE

• Central face malar or “butterfly” violaceous erythema with a sharp cutoff at lateral margins, resolves without scarring (may result in persistent telangiectasia)
• Bullous systemic lupus erythematosus: a blistering rash, if severe, this may resemble toxic epidermal necrolysis
• A maculopapular rash resembling morbilliform drug eruption
• Mucosal erosions and ulcerations (lips, nose, mouth, genitals)
• Photosensitivity: lupus rashes are mainly on sun-exposed sites. Photosensitivity can be mild to very severe with the rash appearing after minimal light exposure.
• Diffuse hair loss (nonscarring alopecia) with brittle hair shafts

Subacute cutaneous LE

• Flat, scaly patches resembling psoriasis, often in a network pattern
• Annular (ring-shaped) polycyclic (overlapping circular) lesions
• Lesions resolve with minimal scarring
• Affects trunk and arms
• Flares on exposure to the sun, but usually spares face and hands

Chronic CLE

• Chronic CLE affects 25% of patients with SLE
• Classic discoid lupus is most common: indurated hyperpigmented plaques
• Localized (above the neck in 80%) or generalized (above and below the neck in 20%)
• Hypertrophic (warty) lupus
• Tumid lupus
• Lupus panniculitis/profundus
• Mucosal lupus (lips, nose, mouth, genitals)
• Chilblain lupus erythematosus
• Discoid lupus/lichen planus overlap
• Discoid lesions and panniculitis resolve with scarring

A more thorough categorization of lupus includes the following types

• acute cutaneous lupus erythematosus
• subacute cutaneous lupus erythematosus
• the discoid lupus erythematosus (chronic cutaneous
  • • childhood discoid lupus erythematosus
    • generalized discoid lupus erythematosus
    • localized discoid lupus erythematosus
  • the chilblain lupus erythematosus (Hutchinson)
  • lupus erythematosus-lichen planus overlap syndrome
  • lupus erythematosus panniculitis (lupus erythematosus profundus)
  • tumid lupus erythematosus
  • the verrucous lupus erythematosus (hypertrophic lupus erythematosus)
  • cutaneous lupus mucinosis
• complement deficiency syndromes
• drug-induced lupus erythematosus
• neonatal lupus erythematosus
• systemic lupus erythematosus

Causes of Systemic Lupus Erythematosus

Factors leading to SLE include:

• Genetic predisposition, including haplotype HLA-B8, -DR₃
• Exposure to sunlight
• Viral infection, particularly Epstein-Barr virus
• Hormones
• Toxins such as cigarette smoke
• Drugs in drug-induced LE
• Emotional upset.

The manifestations of SLE are due to loss of regulation of the patient’s immune system.

• Nuclear proteins are not processed properly.
• Nuclear debris accumulates within the cell.
• This leads to the production of autoantibodies against nuclear proteins.
• Immune complexes are not removed.
• The complement system is activated.
• Inflammation leads to cell and tissue injury.

Symptoms of Systemic Lupus Erythematosus

Common symptoms include:

• Chest pain during respiration
• Joint pain
• Oral ulcer
• Fatigue
• Weight loss
• Fever with no other cause
• General discomfort, uneasiness, or ill feeling (malaise)
• Hair loss
• Sensitivity to sunlight
• A “butterfly” facial rash, seen in about half people with SLE
• Swollen lymph nodes

Photosensitivity

Photosensitivity is a known symptom of lupus, but its relationship to and influence on other aspects of the disease remain to be defined.^[rx] Causes of photosensitivity may include:

• Change in autoantibody location
• Cytotoxicity
• Induction of apoptosis with autoantigens in apoptotic blebs
• Upregulation of adhesion molecules and cytokines
• Induction of nitric oxide synthase expression
• Ultraviolet-generated antigenic DNA.
• Tumor necrosis factor-alpha

Other symptoms include

• General – tiredness, malaise, chronic pain, fever with flares
• Joints – arthritis or synovitis causing swelling, pain and morning stiffness
• Lungs – pleurisy or pleural effusions
• Heart – pericarditis or pericardial effusions
• Kidneys – protein, casts in urine, glomerulonephritis
• Brain – seizures, psychosis, confusion
• Nervous system – mono neuritis multiplex, myelitis, peripheral neuropathy
• Blood – reduced numbers of red cells, white cells and platelets
• Cutaneous mucinosis  – characterized by indurated papules, nodules, or plaques on the trunk or arms
• Lupus nail dystrophy –  presenting as nail pitting, ridging, leukonychia, onycholysis, and red lunula
• Spontaneous chronic urticaria
• Lichen planus
• Acanthosis nigricans
• Sclerodactyly (spindle-shaped fingers)
• Erythema multiforme
• Cutis laxa
• Rheumatoid nodules.

• The acute cutaneous lupus erythematosus (including “butterfly rash“)
• The chronic cutaneous lupus erythematosus (e.g., localized or generalized discoid lupus erythematosus)
• Oral ulcers (on palate and/or nose)
• Non-scarring alopecia
• Synovitis (≥ 2 joints) or tenderness on palpation (≥ 2 joints) and morning stiffness (≥ 30 min)
• Serositis (pleurisy or pericardial pain for more than 1 day)
• Renal involvement (single urine: protein/creatinine ratio or 24-hour urine protein, >0.5 g)
• Neurological involvement (e.g., seizures, psychosis, myelitis)
• Hemolytic anemia
• Leukopenia (<4000/μL) or lymphopenia (<1000/μL)
• Thrombocytopenia (<100 000/μL)

Immunological criteria

• ANA level above the laboratory reference range
• Anti-dsDNA antibodies
• Anti-Sm antibodies
• Antiphospholipid antibodies (anticardiolipin and anti- β 2-glycoprotein I [IgA-, IgG- or IgM-] antibodies; false-positive VDRL [Venereal Disease Research Laboratory] test)
• Low complement (C3, C4, or CH50)
• Direct Coombs test (in the absence of hemolytic anemia)

Diagnosis of Systemic Lupus Erythematosus

Screening laboratory tests

• Erythrocyte sedimentation rate
• Blood count, differential blood count
• Creatinine
• Urinary status and sediment
• Antinuclear antibodies (ANA) (HEp-2 cell test with fluorescence pattern)

Further laboratory tests after positive screening^*1 (particularly in case of positive ANA)

• Further differentiation of ANA (particularly anti-Sm, -Ro/SSA, -La/SSB, -U1RNP antibodies, etc.)
• Anti-dsDNA antibodies (ELISA; confirmation by radioimmunoassay or immunofluorescence test with Crithidia luciliae)
• Complement C3, C4
• Antiphospholipid antibodies, lupus anticoagulant
• Glomerular filtration rate; 24-hour urine (if urine protein positive), alternatively: protein/creatinine ratio in single urine sample; investigation for dysmorphic erythrocytes in sediment
• Liver enzymes; lactate dehydrogenase; creatine kinase in presence of muscular symptoms
• Further laboratory tests depending on clinical symptoms
• Screening for comorbidities
• Assessment of vaccination status (vaccination recommendations [in German] at [rx)

Follow-up (SLE: every 3 to 6 months depending on disease course; lupus nephritis: initially every 2 to 4 weeks for the first 2 to 4 months)^*2

• Medical history (including new symptoms, comedication, infections), physical examination
• Evaluate disease activity with standardized score
• Evaluate damage according to standardized score (1 ×/year)
• Repeat screening for comorbidities (at least 1 ×/year)
• Ocular examination in patients taking hydroxychloroquine or chloroquine: baseline, then every 6 months (currently being revised by the German Society of Rheumatology in light of recommendations from the USA) (rx, rx)

Laboratory tests

• Erythrocyte sedimentation rate
• C-reactive protein (in suspected infection or pleurisy)
• Urine tests for hyaline casts, creatinine, protein and blood
• Blood pressure
• Chest X-ray, ultrasound, CT and MRI scans
• Electrocardiograph (ECG) and echocardiography
• Nerve and muscle testing
• Ophthalmological examination
• Endoscopy of the gastrointestinal tract
• Kidney biopsy.
• Blood count, differential blood count
• Creatinine
• Liver enzymes
• Urinary status (protein/creatinine ratio, 24-hour urine and microscopic examination of urinary sediment as needed)
• Complement C3, C4
• Anti-dsDNA antibodies
• Instrument-based diagnostics as needed

Modified after (2, 8), modified after (rx, rx, rx, rx, rx)

Using the SLICC criteria, SLE is diagnosed if the patient has either of the following over time:

• Four criteria including ≥ one clinical criterion and ≥ one immunological criterion
• Biopsy-proven lupus nephritis and antinuclear antibodies or anti-double-stranded DNA antibodies

These criteria depend on history, clinical examination, exclusion of other causes of the symptoms, and the results of investigations—including blood tests and biopsy of the affected tissue. Four of the 17 SLICC criteria relate to the skin.

Clinical criteria

• Acute or subacute cutaneous lupus
• Chronic cutaneous lupus
• Oral ulcers
• Nonscarring alopecia
• Synovitis involving 2 or more joints
• Serositis involving lungs or heart
• Renal involvement
• Neurological involvement
• Hemolytic anemia
• leukopenia or lymphopenia
• Thrombocytopenia

Immunological criteria

• Raised ANA level
• A raised anti-dsDNA antibody level
• Presence of anti-Sm
• Positive antiphospholipid antibody (lupus anticoagulant, false-positive rapid plasma reagin, high-titer anticardiolipin antibody, positive anti–2-glycoprotein I)
• Low complement levels
• Positive direct Coombs’ test

SLICC Systemic Lupus International Collaborating Clinics; ANA antinuclear antibody; anti-dsDNA anti-double-stranded DNA

Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI)

The Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) was developed in an attempt to classify the severity of CLE. [2] A score of activity and damage due to the disease is calculated in each of 12 anatomical locations (refer to the original published paper for details).

The total activity score is made up of:

• The degree of redness (0–3) and scale (0–2)
• Mucous membrane involvement (0–1)
• Recent hair loss (0–1), nonscarring alopecia (0–3)

Total damage score is made up of:

• The degree of dyspigmentation (0–2), and scarring (0–2)
• Persistence of dyspigmentation more than 12 months doubles the depigmentation score
• Scalp scarring (0,3,4,5,6)

Biopsy findings

Patients with SLE often undergo skin biopsy.

• Acute CLE: nonspecific dermatitis.
• Subacute CLE: features of lupus noted in the epidermis and superficial dermis
• Chronic discoid CLE: typical features of lupus with atrophy and scarring
• Direct immunofluorescence is positive in sun-protected healthy skin in SLE

Blood tests

Multiple autoantibodies are typically present in SLE, often in high titre (see immunological criteria above). Relating to skin disease in SLE:

• About 70% of patients with subacute CLE have positive extractable nuclear antibodies anti-Ro (also called anti-SSA) and anti-La (also called anti-SSB).
• Anti Ro/La is also associated with Sjogren syndrome and neonatal lupus.
• Low serum complement in SLE has been associated with urticarial vasculitis and renal disease.
• Antiphospholipid antibodies are associated with livedo reticularis, thrombosis, and pregnancy complications (antiphospholipid syndrome).
• Anti-annexin 1 antibodies may be a diagnostic marker for discoid CLE

Patients with SLE should also have renal, liver, and thyroid function and markers of inflammation performed, such as C-reactive protein (CRP), immunoglobulins, and rheumatoid factor.

Photoprovocation tests

• Photoprovocation tests  – are sometimes carried out to confirm that a skin eruption is precipitated by exposure to particular wavelengths of ultraviolet or visible radiation.
• Echocardiogram – Echocardiogram shows Pericardial effusion, mitral valve prolapse, left ventricular hypertrophy, and changes secondary to pulmonary hypertension.
• EKG – Abnormal EKG findings include hemiblock, bundle branch block, atrioventricular block, changes secondary to pericarditis, and pericardial effusion.
• Pulmonary function testing – Reduction in diffusion capacity for carbon monoxide, forced vital capacity, forced expiratory volume, and six-minute walk tests occur in ILD.
• Computed tomogram – High resolution computed tomogram is very sensitive in diagnosing ILD. Common findings include ground-glass opacities, linear opacities, subpleural micronodules, septal thickening, traction bronchiectasis usually with peripheral and lower lobe predominance. Honeycombing, airspace consolidation, emphysema, and centrilobular nodules are less common findings.[rx]
• Angiogram – Medium-sized arterial occlusions can occur in patients with Raynaud phenomenon.
• Right heart catheterization – Definitive diagnosis of pulmonary hypertension in MCTD requires right heart catheterization demonstrating mean pulmonary arterial pressure at rest greater than 25mmHg.

• Biopsy: histology, immunofluorescence if indicated

Joints

• Conventional X-ray
• Arthrosonography
• Magnetic resonance imaging (MRI)

Muscle

• Creatine kinase
• Electromyography
• MRI
• Muscle biopsy

Kidney

• Sonography
• Renal biopsy

Lung/heart

• Chest X-ray
• Thoracic high-resolution computed tomography (HR-CT)
• Lung function test including diffusion capacity
• Bronchoalveolar lavage
• (Transesophageal) echocardiography
• Cardiac catheterization
• Cardiac MRI
• Myocardial scintigraphy
• Coronary angiography

Eye

• Funduscopy/special investigations in patients on antimalarials

Central and peripheral nervous system

• Electroencephalography
• Primarily cranial MRI, special MRI techniques if indicated
• Computed tomography
• Cerebrospinal fluid analysis
• Transcranial Doppler/angiography
• Neuropsychiatric examination
• Measurement of nerve conduction velocity

Treatment of Systemic Lupus Erythematosus

• Nonsteroidal anti-inflammatory drugs (NSAIDs) – Over-the-counter NSAIDs, such as naproxen sodium (Aleve) and ibuprofen (Advil, Motrin IB, others), may be used to treat pain, swelling, and fever associated with lupus. Stronger NSAIDs are available by prescription. Side effects of NSAIDs include stomach bleeding, kidney problems, and an increased risk of heart problems.
• Antimalarial drugs – Medications commonly used to treat malaria, such as hydroxychloroquine (Plaquenil), affect the immune system and can help decrease the risk of lupus flares. Side effects can include stomach upset and, very rarely, damage to the retina of the eye. Regular eye exams are recommended when taking these medications.
• Corticosteroids – Prednisone and other types of corticosteroids can counter the inflammation of lupus. High doses of steroids such as methylprednisolone (A-Methapred, Medrol) are often used to control serious disease that involves the kidneys and brain. Side effects include weight gain, easy bruising, thinning bones (osteoporosis), high blood pressure, diabetes, and increased risk of infection. The risk of side effects increases with higher doses and longer-term therapy.
• Immunosuppressants – Drugs that suppress the immune system may be helpful in serious cases of lupus. Examples include azathioprine (Imuran, Azasan), mycophenolate mofetil (CellCept), and methotrexate (Trexall). Potential side effects may include an increased risk of infection, liver damage, decreased fertility and an increased risk of cancer.
• Biologics – A different type of medication, belimumab (Benlysta) administered intravenously, also reduces lupus symptoms in some people. Side effects include nausea, diarrhea and infections. Rarely, the worsening of depression can occur.
• Rituximab (Rituxan) –  can be beneficial in cases of resistant lupus. Side effects include allergic reaction to the intravenous infusion and infections.
• Hydroxychloroquine – Commonly used to help keep mild lupus-related problems, such as skin and joint disease, under control. This drug is also effective at preventing lupus flares.
• Cyclophosphamide –  A chemotherapy drug that has very powerful effects on reducing the activity of the immune system. It is used to treat severe forms of lupus, such as those affecting the kidneys or brain.
• Azathioprine – A medication originally used to prevent the rejection of transplanted organs. It is commonly used to treat the more serious features of lupus.
• Methotrexate – Another chemotherapy drug used to suppress the immune system. Its use is becoming increasingly popular for skin disease, arthritis, and other non-life-threatening forms of disease that have not responded to medications such as hydroxychloroquine or low doses of prednisone.
• Belimumab – This drug weakens the immune system by targeting a protein that may reduce the abnormal B cells thought to contribute to lupus. People with active, autoantibody-positive lupus may benefit from Benlysta when given in addition to standard drug therapy.
• Mycophenolate mofetil – A drug that suppresses the immune system and is also used to prevent the rejection of transplanted organs. It is being used increasingly to treat serious features of lupus, especially those previously treated by Cytoxan.

Preventative measures

The following measures are essential to reduce the chance of flares and organ damage.

• Careful protection from sun exposure using clothing, accessories and SPF 50+ broad-spectrum sunscreens. Sunscreens alone are not adequate.
• Smoking cessation
• Rest when needed.

Topical therapy

Intermittent courses of potent topical corticosteroids are important in the treatment of CLE. They should be applied accurately to the skin lesions.

The calcineurin inhibitors tacrolimus ointment and pimecrolimus cream can also be used.

Systemic therapy

Treatment of SLE depends on which are the predominant organs involved in the disease. Typically, any of the following drugs may be used alone or in combination.

• Systemic corticosteroids, such as prednisone or prednisolone. These are the mainstay of treatment in a seriously ill patient with acute LE.
• Hydroxychloroquine and other antimalarials—response rates are about 80% in CLE.
• Methotrexate—best response in subacute CLE and discoid CLE
• Immunosuppressives such as azathioprine, mycophenolate and cyclophosphamide
• Intravenous immunoglobulin
• Aspirin is recommended for antiphospholipid syndrome.
• Targeted biologic therapies under evaluation for SLE include belimumab (intravenous and subcutaneous formulations were registered by FDA for use in SLE in 2017) and off-label rituximab, abatacept, tocilizumab and eculizumab.

CLE is also sometimes treated with

• Retinoids (isotretinoin and acitretin)
• Dapsone.

Lifestyle and Home Remedies

Take steps to care for your body if you have lupus. Simple measures can help you prevent lupus flares and, should they occur, better cope with the signs and symptoms you experience. Try to:

• See your doctor regularly – Having regular checkups instead of only seeing your doctor when your symptoms worsen may help your doctor prevent flare-ups, and can be useful in addressing routine health concerns, such as stress, diet and exercise that can be helpful in preventing lupus complications.
• Be sun smart – Because ultraviolet light can trigger a flare, wear protective clothing — such as a hat, long-sleeved shirt and long pants — and use sunscreens with a sun protection factor (SPF) of at least 55 every time you go outside.
• Get regular exercise – Exercise can help keep your bones strong, reduce your risk of heart attack and promote general well-being.
• Don’t smoke – Smoking increases your risk of cardiovascular disease and can worsen the effects of lupus on your heart and blood vessels.
• Eat a healthy diet – A healthy diet emphasizes fruits, vegetables and whole grains. Sometimes you may have dietary restrictions, especially if you have high blood pressure, kidney damage or gastrointestinal problems.
• Ask your doctor if you need vitamin D and calcium supplements – There is some evidence to suggest that people with lupus may benefit from supplemental vitamin D. A 1,200- to 1,500-milligram calcium supplement taken daily may help keep your bones healthy.

Complications

Inflammation caused by lupus can affect many areas of your body, including your:

• Kidneys – Lupus can cause serious kidney damage, and kidney failure is one of the leading causes of death among people with lupus.
• Brain and central nervous system – If your brain is affected by lupus, you may experience headaches, dizziness, behavior changes, vision problems, and even strokes or seizures. Many people with lupus experience memory problems and may have difficulty expressing their thoughts.
• Blood and blood vessels – Lupus may lead to blood problems, including anemia and an increased risk of bleeding or blood clotting. It can also cause inflammation of the blood vessels (vasculitis).
• Lungs – Having lupus increases your chances of developing an inflammation of the chest cavity lining (pleurisy), which can make breathing painful. Bleeding into the lungs and pneumonia also are possible.
• Heart – Lupus can cause inflammation of your heart muscle, your arteries, or heart membrane (pericarditis). The risk of cardiovascular disease and heart attacks increases greatly as well.
• Infection – People with lupus are more vulnerable to infection because both the disease and its treatments can weaken the immune system.
• Cancer – Having lupus appears to increase your risk of cancer; however, the risk is small.
• Bone tissue death (avascular necrosis) – This occurs when the blood supply to a bone diminishes, often leading to tiny breaks in the bone and eventually to the bone’s collapse.
• Pregnancy complications – Women with lupus have an increased risk of miscarriage. Lupus increases the risk of high blood pressure during pregnancy (preeclampsia) and preterm birth. To reduce the risk of these complications, doctors often recommend delaying pregnancy until your disease has been under control for at least six months.

References

Test Diagnosis of Systemic Lupus Erythematosus/The Systemic Lupus Erythematosus (SLE) is a systemic autoimmune disease, with multisystemic involvement. The disease has several phenotypes, with varying clinical presentations in patients ranging from mild mucocutaneous manifestations to multiorgan and severe central nervous system involvement. Several immunopathogenic pathways play a role in the development of SLE. The lupus erythematosus (LE cell) was described by Hargraves in 1948. Several pathogenic autoantibodies have since been identified.

The systemic lupus erythematosus (SLE) is characterized by overt polyclonal B-cell activation and autoantibody (Ab) production. By contrast, cellular immune responses against all- or recall antigens are significantly impaired. Many pieces of evidence indicate that IL-10 overproduction plays a pivotal role in the disease and the contribution of the IL-10/IL-12 imbalance to the pathophysiology of SLE will be extensively discussed. The authors will further summarize the available data about the involvement of IFN-γ, TNF-α, TGF-β, and TALL-1. Other cytokines (IL-1, IL-2, IL-4, IL-6, IL-16, IL-17, and IL-18) will be briefly discussed.

Systemic Lupus Erythematosus

Types of Systemic Lupus Erythematosus

About 25% of patients with systemic lupus erythematosus (SLE) initially present with skin involvement. It is important to correctly classify cutaneous lupus erythematosus (CLE), as it helps determine the underlying type and severity of SLE. About 5–10% of patients with CLE develop SLE, and CLE is associated with less severe forms of SLE.

Skin manifestations of lupus erythematosus are commonly divided into lupus erythematosus–specific and non–specific disease. Note that four of the nine American College of Rheumatology criteria for SLE are skin signs (ie, malar/butterfly rash, discoid plaques, photosensitivity, and oral ulcers).

Lupus erythematosus–specific disease

Acute cutaneous lupus erythematosus

Forms of acute CLE include the following:

• Localised acute CLE — this presents with malar or ‘butterfly’ rash (symmetrical erythema and edema of the cheeks, forehead, chin, and V of the neck but sparing the nasolabial folds or ‘smile lines’)
• Generalised acute CLE — this presents with a widespread exanthematous eruption on the extensor surfaces, trunk, sun-exposed areas, and hands (but sparing the knuckles)
• Toxic epidermal necrolysis-like acute CLE — this is a life-threatening variant of acute CLE that presents with a massive epidermal injury; it occurs predominantly on sun-exposed skin and has a gradual, insidious onset, unlike toxic epidermal necrolysis.

Acute CLE is typically triggered or exacerbated by exposure to ultraviolet (UV) radiation. On recovery, there may be postinflammatory hyperpigmentation without scarring.

Subacute cutaneous lupus erythematosus

The subacute cutaneous lupus erythematosus (SCLE) starts as macules or papules that progress to hyperkeratotic plaques. SCLE is photosensitive so plaques usually occur on sun-exposed skin; these plaques do not lead to scarring but can result in postinflammatory hyperpigmentation or hypopigmentation. SCLE should be monitored to exclude any progression to SLE.

Forms of SCLE include:

• Annular SCLE — this subtype presents with slightly raised red lesions with central clearing
• Papulosquamous SCLE — this subtype presents with eczematous or psoriasis-like lesions on sun-exposed skin.

Chronic cutaneous lupus erythematosus

Chronic CLE is not as photosensitive as acute CLE or SCLE. Forms of chronic CLE include:

• The discoid lupus erythematosus (DLE) — this affects the face, outer ears, neck, sun-exposed areas and lips, and presents with discoid plaques (erythematous, well-demarcated plaques covered by scale) that become hyperkeratotic, leading to atrophy and scarring; there is follicular involvement, causing both reversible and irreversible (scarring) alopecia (hair loss); depigmentation of the peripheries is also common in certain ethnicities (Asian, Indian).
• Hypertrophic or verrucous lupus erythematosus — this is a rare form of CLE presenting with severe hyperkeratosis of the extensor surfaces of the arms, upper back and face; it has overlapping features with lichen planus.
• Mucosal lupus erythematosus — this affects 25% of patients with CLE; most commonly, painless erythematous patches on the oral mucosa develop into chronic plaques that can centrally ulcerate and also affect nasal, conjunctival and genital mucosa; oral lupus erythematosus rarely degrades to oral cancer (squamous cell carcinoma).

Drug-induced lupus erythematosus

Many drugs are thought to induce SLE and drug-induced lupus erythematosus often includes cutaneous signs. Drugs that induce lupus erythematosus include:

• Hydralazine
• Isoniazid
• Chlorpromazine
• Procainamide
• Phenytoin
• Minocycline
• Anti–tumour necrosis factor medications.

Rarer types of lupus erythematosus

The rarer types of lupus erythematosus include:

• Lupus profundus/lupus panniculitis — this is a rare form of chronic CLE with firm nodules in the lower dermis and subcutaneous tissue that causes lipodystrophy; some use the term lupus panniculitis to refer to subcutaneous involvement only, and lupus profundus when there is a combination of lupus panniculitis with DLE.
• Chilblain lupus erythematosus — this presents with purple-red patches, papules and plaques on toes, fingers and face, and is associated with nail fold telangiectasia; it is precipitated by exposure to the cold, so often presents in winter.
• Lupus erythematosus tumidus —this is a variant of chronic CLE with succulent or indurated erythematous plaques without surface change.

Lupus erythematosus — non–specific disease

Lupus erythematosus-nonspecific disease can relate to SLE or another autoimmune disease, but nonspecific cutaneous features are most often associated with SLE.

Common cutaneous features seen include:

• Photosensitivity — this is an abnormal response to UV radiation that is present in 50–93% of patients with SLE
• Mouth ulcers — these are present in 25–45% of patients with SLE
• Non–scarring hair loss in SLE — presenting as coarse, dry hair with increased fragility (also referred to as ‘lupus hair’).

Cutaneous vascular disease is also common. Forms of cutaneous vascular disease include

• Raynaud phenomenon — this presents with focal ulceration in the fingertips and periungual areas that can cause pitted scarring, hemorrhage and other nail fold complications
• Vasculitis — leukocytoclastic vasculitis: urticarial vasculitis presenting with tender papules and plaques over bony prominences; and medium or large vessel vasculitis can occur, presenting with purpuric plaques with stellate borders, often with necrosis and ulceration or subcutaneous nodules
• Thromboembolic vasculopathy — these may have a similar clinical presentation to vasculitis, but vessel occlusion is due to blood clots
• Livedo reticularis — characterized by net-like blanching red-purple rings that commonly arise on the lower limbs
• Erythromelalgia — characterized by burning pain in the feet and hands, and with macular erythema; it is associated with heat exposure.

Specific cutaneous SLE

Cutaneous lupus (CLE) has specific acute, subacute and chronic manifestations.

• Typically, SLE presents with acute CLE.
• About half of patients with subacute cutaneous LE develop mild SLE
• Only 5% of patients with chronic CLE have SLE, as CLE presents as a skin problem without the involvement of other organs.

Acute CLE

• Central face malar or “butterfly” violaceous erythema with a sharp cutoff at lateral margins, resolves without scarring (may result in persistent telangiectasia)
• Bullous systemic lupus erythematosus: a blistering rash, if severe, this may resemble toxic epidermal necrolysis
• A maculopapular rash resembling morbilliform drug eruption
• Mucosal erosions and ulcerations (lips, nose, mouth, genitals)
• Photosensitivity: lupus rashes are mainly on sun-exposed sites. Photosensitivity can be mild to very severe with the rash appearing after minimal light exposure.
• Diffuse hair loss (nonscarring alopecia) with brittle hair shafts

Subacute cutaneous LE

• Flat, scaly patches resembling psoriasis, often in a network pattern
• Annular (ring-shaped) polycyclic (overlapping circular) lesions
• Lesions resolve with minimal scarring
• Affects trunk and arms
• Flares on exposure to the sun, but usually spares face and hands

Chronic CLE

• Chronic CLE affects 25% of patients with SLE
• Classic discoid lupus is most common: indurated hyperpigmented plaques
• Localized (above the neck in 80%) or generalized (above and below the neck in 20%)
• Hypertrophic (warty) lupus
• Tumid lupus
• Lupus panniculitis/profundus
• Mucosal lupus (lips, nose, mouth, genitals)
• Chilblain lupus erythematosus
• Discoid lupus/lichen planus overlap
• Discoid lesions and panniculitis resolve with scarring

A more thorough categorization of lupus includes the following types

• acute cutaneous lupus erythematosus
• subacute cutaneous lupus erythematosus
• the discoid lupus erythematosus (chronic cutaneous
  • • childhood discoid lupus erythematosus
    • generalized discoid lupus erythematosus
    • localized discoid lupus erythematosus
  • the chilblain lupus erythematosus (Hutchinson)
  • lupus erythematosus-lichen planus overlap syndrome
  • lupus erythematosus panniculitis (lupus erythematosus profundus)
  • tumid lupus erythematosus
  • the verrucous lupus erythematosus (hypertrophic lupus erythematosus)
  • cutaneous lupus mucinosis
• complement deficiency syndromes
• drug-induced lupus erythematosus
• neonatal lupus erythematosus
• systemic lupus erythematosus

Causes of Systemic Lupus Erythematosus

Factors leading to SLE include:

• Genetic predisposition, including haplotype HLA-B8, -DR₃
• Exposure to sunlight
• Viral infection, particularly Epstein-Barr virus
• Hormones
• Toxins such as cigarette smoke
• Drugs in drug-induced LE
• Emotional upset.

The manifestations of SLE are due to loss of regulation of the patient’s immune system.

• Nuclear proteins are not processed properly.
• Nuclear debris accumulates within the cell.
• This leads to the production of autoantibodies against nuclear proteins.
• Immune complexes are not removed.
• The complement system is activated.
• Inflammation leads to cell and tissue injury.

Symptoms of Systemic Lupus Erythematosus

Common symptoms include:

• Chest pain during respiration
• Joint pain
• Oral ulcer
• Fatigue
• Weight loss
• Fever with no other cause
• General discomfort, uneasiness, or ill feeling (malaise)
• Hair loss
• Sensitivity to sunlight
• A “butterfly” facial rash, seen in about half people with SLE
• Swollen lymph nodes

Photosensitivity

Photosensitivity is a known symptom of lupus, but its relationship to and influence on other aspects of the disease remain to be defined.^[rx] Causes of photosensitivity may include:

• Change in autoantibody location
• Cytotoxicity
• Induction of apoptosis with autoantigens in apoptotic blebs
• Upregulation of adhesion molecules and cytokines
• Induction of nitric oxide synthase expression
• Ultraviolet-generated antigenic DNA.
• Tumor necrosis factor-alpha

Other symptoms include

• General – tiredness, malaise, chronic pain, fever with flares
• Joints – arthritis or synovitis causing swelling, pain and morning stiffness
• Lungs – pleurisy or pleural effusions
• Heart – pericarditis or pericardial effusions
• Kidneys – protein, casts in urine, glomerulonephritis
• Brain – seizures, psychosis, confusion
• Nervous system – mono neuritis multiplex, myelitis, peripheral neuropathy
• Blood – reduced numbers of red cells, white cells and platelets
• Cutaneous mucinosis  – characterized by indurated papules, nodules, or plaques on the trunk or arms
• Lupus nail dystrophy –  presenting as nail pitting, ridging, leukonychia, onycholysis, and red lunula
• Spontaneous chronic urticaria
• Lichen planus
• Acanthosis nigricans
• Sclerodactyly (spindle-shaped fingers)
• Erythema multiforme
• Cutis laxa
• Rheumatoid nodules.

• The acute cutaneous lupus erythematosus (including “butterfly rash“)
• The chronic cutaneous lupus erythematosus (e.g., localized or generalized discoid lupus erythematosus)
• Oral ulcers (on palate and/or nose)
• Non-scarring alopecia
• Synovitis (≥ 2 joints) or tenderness on palpation (≥ 2 joints) and morning stiffness (≥ 30 min)
• Serositis (pleurisy or pericardial pain for more than 1 day)
• Renal involvement (single urine: protein/creatinine ratio or 24-hour urine protein, >0.5 g)
• Neurological involvement (e.g., seizures, psychosis, myelitis)
• Hemolytic anemia
• Leukopenia (<4000/μL) or lymphopenia (<1000/μL)
• Thrombocytopenia (<100 000/μL)

Immunological criteria

• ANA level above the laboratory reference range
• Anti-dsDNA antibodies
• Anti-Sm antibodies
• Antiphospholipid antibodies (anticardiolipin and anti- β 2-glycoprotein I [IgA-, IgG- or IgM-] antibodies; false-positive VDRL [Venereal Disease Research Laboratory] test)
• Low complement (C3, C4, or CH50)
• Direct Coombs test (in the absence of hemolytic anemia)

Diagnosis of Systemic Lupus Erythematosus

Screening laboratory tests

• Erythrocyte sedimentation rate
• Blood count, differential blood count
• Creatinine
• Urinary status and sediment
• Antinuclear antibodies (ANA) (HEp-2 cell test with fluorescence pattern)

Further laboratory tests after positive screening^*1 (particularly in case of positive ANA)

• Further differentiation of ANA (particularly anti-Sm, -Ro/SSA, -La/SSB, -U1RNP antibodies, etc.)
• Anti-dsDNA antibodies (ELISA; confirmation by radioimmunoassay or immunofluorescence test with Crithidia luciliae)
• Complement C3, C4
• Antiphospholipid antibodies, lupus anticoagulant
• Glomerular filtration rate; 24-hour urine (if urine protein positive), alternatively: protein/creatinine ratio in single urine sample; investigation for dysmorphic erythrocytes in sediment
• Liver enzymes; lactate dehydrogenase; creatine kinase in presence of muscular symptoms
• Further laboratory tests depending on clinical symptoms
• Screening for comorbidities
• Assessment of vaccination status (vaccination recommendations [in German] at [rx)

Follow-up (SLE: every 3 to 6 months depending on disease course; lupus nephritis: initially every 2 to 4 weeks for the first 2 to 4 months)^*2

• Medical history (including new symptoms, comedication, infections), physical examination
• Evaluate disease activity with standardized score
• Evaluate damage according to standardized score (1 ×/year)
• Repeat screening for comorbidities (at least 1 ×/year)
• Ocular examination in patients taking hydroxychloroquine or chloroquine: baseline, then every 6 months (currently being revised by the German Society of Rheumatology in light of recommendations from the USA) (rx, rx)

Laboratory tests

• Erythrocyte sedimentation rate
• C-reactive protein (in suspected infection or pleurisy)
• Urine tests for hyaline casts, creatinine, protein and blood
• Blood pressure
• Chest X-ray, ultrasound, CT and MRI scans
• Electrocardiograph (ECG) and echocardiography
• Nerve and muscle testing
• Ophthalmological examination
• Endoscopy of the gastrointestinal tract
• Kidney biopsy.
• Blood count, differential blood count
• Creatinine
• Liver enzymes
• Urinary status (protein/creatinine ratio, 24-hour urine and microscopic examination of urinary sediment as needed)
• Complement C3, C4
• Anti-dsDNA antibodies
• Instrument-based diagnostics as needed

Modified after (2, 8), modified after (rx, rx, rx, rx, rx)

Using the SLICC criteria, SLE is diagnosed if the patient has either of the following over time:

• Four criteria including ≥ one clinical criterion and ≥ one immunological criterion
• Biopsy-proven lupus nephritis and antinuclear antibodies or anti-double-stranded DNA antibodies

These criteria depend on history, clinical examination, exclusion of other causes of the symptoms, and the results of investigations—including blood tests and biopsy of the affected tissue. Four of the 17 SLICC criteria relate to the skin.

Clinical criteria

• Acute or subacute cutaneous lupus
• Chronic cutaneous lupus
• Oral ulcers
• Nonscarring alopecia
• Synovitis involving 2 or more joints
• Serositis involving lungs or heart
• Renal involvement
• Neurological involvement
• Hemolytic anemia
• leukopenia or lymphopenia
• Thrombocytopenia

Immunological criteria

• Raised ANA level
• A raised anti-dsDNA antibody level
• Presence of anti-Sm
• Positive antiphospholipid antibody (lupus anticoagulant, false-positive rapid plasma reagin, high-titer anticardiolipin antibody, positive anti–2-glycoprotein I)
• Low complement levels
• Positive direct Coombs’ test

SLICC Systemic Lupus International Collaborating Clinics; ANA antinuclear antibody; anti-dsDNA anti-double-stranded DNA

Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI)

The Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) was developed in an attempt to classify the severity of CLE. [2] A score of activity and damage due to the disease is calculated in each of 12 anatomical locations (refer to the original published paper for details).

The total activity score is made up of:

• The degree of redness (0–3) and scale (0–2)
• Mucous membrane involvement (0–1)
• Recent hair loss (0–1), nonscarring alopecia (0–3)

Total damage score is made up of:

• The degree of dyspigmentation (0–2), and scarring (0–2)
• Persistence of dyspigmentation more than 12 months doubles the depigmentation score
• Scalp scarring (0,3,4,5,6)

Biopsy findings

Patients with SLE often undergo skin biopsy.

• Acute CLE: nonspecific dermatitis.
• Subacute CLE: features of lupus noted in the epidermis and superficial dermis
• Chronic discoid CLE: typical features of lupus with atrophy and scarring
• Direct immunofluorescence is positive in sun-protected healthy skin in SLE

Blood tests

Multiple autoantibodies are typically present in SLE, often in high titre (see immunological criteria above). Relating to skin disease in SLE:

• About 70% of patients with subacute CLE have positive extractable nuclear antibodies anti-Ro (also called anti-SSA) and anti-La (also called anti-SSB).
• Anti Ro/La is also associated with Sjogren syndrome and neonatal lupus.
• Low serum complement in SLE has been associated with urticarial vasculitis and renal disease.
• Antiphospholipid antibodies are associated with livedo reticularis, thrombosis, and pregnancy complications (antiphospholipid syndrome).
• Anti-annexin 1 antibodies may be a diagnostic marker for discoid CLE

Patients with SLE should also have renal, liver, and thyroid function and markers of inflammation performed, such as C-reactive protein (CRP), immunoglobulins, and rheumatoid factor.

Photoprovocation tests

• Photoprovocation tests  – are sometimes carried out to confirm that a skin eruption is precipitated by exposure to particular wavelengths of ultraviolet or visible radiation.
• Echocardiogram – Echocardiogram shows Pericardial effusion, mitral valve prolapse, left ventricular hypertrophy, and changes secondary to pulmonary hypertension.
• EKG – Abnormal EKG findings include hemiblock, bundle branch block, atrioventricular block, changes secondary to pericarditis, and pericardial effusion.
• Pulmonary function testing – Reduction in diffusion capacity for carbon monoxide, forced vital capacity, forced expiratory volume, and six-minute walk tests occur in ILD.
• Computed tomogram – High resolution computed tomogram is very sensitive in diagnosing ILD. Common findings include ground-glass opacities, linear opacities, subpleural micronodules, septal thickening, traction bronchiectasis usually with peripheral and lower lobe predominance. Honeycombing, airspace consolidation, emphysema, and centrilobular nodules are less common findings.[rx]
• Angiogram – Medium-sized arterial occlusions can occur in patients with Raynaud phenomenon.
• Right heart catheterization – Definitive diagnosis of pulmonary hypertension in MCTD requires right heart catheterization demonstrating mean pulmonary arterial pressure at rest greater than 25mmHg.

• Biopsy: histology, immunofluorescence if indicated

Joints

• Conventional X-ray
• Arthrosonography
• Magnetic resonance imaging (MRI)

Muscle

• Creatine kinase
• Electromyography
• MRI
• Muscle biopsy

Kidney

• Sonography
• Renal biopsy

Lung/heart

• Chest X-ray
• Thoracic high-resolution computed tomography (HR-CT)
• Lung function test including diffusion capacity
• Bronchoalveolar lavage
• (Transesophageal) echocardiography
• Cardiac catheterization
• Cardiac MRI
• Myocardial scintigraphy
• Coronary angiography

Eye

• Funduscopy/special investigations in patients on antimalarials

Central and peripheral nervous system

• Electroencephalography
• Primarily cranial MRI, special MRI techniques if indicated
• Computed tomography
• Cerebrospinal fluid analysis
• Transcranial Doppler/angiography
• Neuropsychiatric examination
• Measurement of nerve conduction velocity

Treatment of Systemic Lupus Erythematosus

• Nonsteroidal anti-inflammatory drugs (NSAIDs) – Over-the-counter NSAIDs, such as naproxen sodium (Aleve) and ibuprofen (Advil, Motrin IB, others), may be used to treat pain, swelling, and fever associated with lupus. Stronger NSAIDs are available by prescription. Side effects of NSAIDs include stomach bleeding, kidney problems, and an increased risk of heart problems.
• Antimalarial drugs – Medications commonly used to treat malaria, such as hydroxychloroquine (Plaquenil), affect the immune system and can help decrease the risk of lupus flares. Side effects can include stomach upset and, very rarely, damage to the retina of the eye. Regular eye exams are recommended when taking these medications.
• Corticosteroids – Prednisone and other types of corticosteroids can counter the inflammation of lupus. High doses of steroids such as methylprednisolone (A-Methapred, Medrol) are often used to control serious disease that involves the kidneys and brain. Side effects include weight gain, easy bruising, thinning bones (osteoporosis), high blood pressure, diabetes, and increased risk of infection. The risk of side effects increases with higher doses and longer-term therapy.
• Immunosuppressants – Drugs that suppress the immune system may be helpful in serious cases of lupus. Examples include azathioprine (Imuran, Azasan), mycophenolate mofetil (CellCept), and methotrexate (Trexall). Potential side effects may include an increased risk of infection, liver damage, decreased fertility and an increased risk of cancer.
• Biologics – A different type of medication, belimumab (Benlysta) administered intravenously, also reduces lupus symptoms in some people. Side effects include nausea, diarrhea and infections. Rarely, the worsening of depression can occur.
• Rituximab (Rituxan) –  can be beneficial in cases of resistant lupus. Side effects include allergic reaction to the intravenous infusion and infections.
• Hydroxychloroquine – Commonly used to help keep mild lupus-related problems, such as skin and joint disease, under control. This drug is also effective at preventing lupus flares.
• Cyclophosphamide –  A chemotherapy drug that has very powerful effects on reducing the activity of the immune system. It is used to treat severe forms of lupus, such as those affecting the kidneys or brain.
• Azathioprine – A medication originally used to prevent the rejection of transplanted organs. It is commonly used to treat the more serious features of lupus.
• Methotrexate – Another chemotherapy drug used to suppress the immune system. Its use is becoming increasingly popular for skin disease, arthritis, and other non-life-threatening forms of disease that have not responded to medications such as hydroxychloroquine or low doses of prednisone.
• Belimumab – This drug weakens the immune system by targeting a protein that may reduce the abnormal B cells thought to contribute to lupus. People with active, autoantibody-positive lupus may benefit from Benlysta when given in addition to standard drug therapy.
• Mycophenolate mofetil – A drug that suppresses the immune system and is also used to prevent the rejection of transplanted organs. It is being used increasingly to treat serious features of lupus, especially those previously treated by Cytoxan.

Preventative measures

The following measures are essential to reduce the chance of flares and organ damage.

• Careful protection from sun exposure using clothing, accessories and SPF 50+ broad-spectrum sunscreens. Sunscreens alone are not adequate.
• Smoking cessation
• Rest when needed.

Topical therapy

Intermittent courses of potent topical corticosteroids are important in the treatment of CLE. They should be applied accurately to the skin lesions.

The calcineurin inhibitors tacrolimus ointment and pimecrolimus cream can also be used.

Systemic therapy

Treatment of SLE depends on which are the predominant organs involved in the disease. Typically, any of the following drugs may be used alone or in combination.

• Systemic corticosteroids, such as prednisone or prednisolone. These are the mainstay of treatment in a seriously ill patient with acute LE.
• Hydroxychloroquine and other antimalarials—response rates are about 80% in CLE.
• Methotrexate—best response in subacute CLE and discoid CLE
• Immunosuppressives such as azathioprine, mycophenolate and cyclophosphamide
• Intravenous immunoglobulin
• Aspirin is recommended for antiphospholipid syndrome.
• Targeted biologic therapies under evaluation for SLE include belimumab (intravenous and subcutaneous formulations were registered by FDA for use in SLE in 2017) and off-label rituximab, abatacept, tocilizumab and eculizumab.

CLE is also sometimes treated with

• Retinoids (isotretinoin and acitretin)
• Dapsone.

Lifestyle and Home Remedies

Take steps to care for your body if you have lupus. Simple measures can help you prevent lupus flares and, should they occur, better cope with the signs and symptoms you experience. Try to:

• See your doctor regularly – Having regular checkups instead of only seeing your doctor when your symptoms worsen may help your doctor prevent flare-ups, and can be useful in addressing routine health concerns, such as stress, diet and exercise that can be helpful in preventing lupus complications.
• Be sun smart – Because ultraviolet light can trigger a flare, wear protective clothing — such as a hat, long-sleeved shirt and long pants — and use sunscreens with a sun protection factor (SPF) of at least 55 every time you go outside.
• Get regular exercise – Exercise can help keep your bones strong, reduce your risk of heart attack and promote general well-being.
• Don’t smoke – Smoking increases your risk of cardiovascular disease and can worsen the effects of lupus on your heart and blood vessels.
• Eat a healthy diet – A healthy diet emphasizes fruits, vegetables and whole grains. Sometimes you may have dietary restrictions, especially if you have high blood pressure, kidney damage or gastrointestinal problems.
• Ask your doctor if you need vitamin D and calcium supplements – There is some evidence to suggest that people with lupus may benefit from supplemental vitamin D. A 1,200- to 1,500-milligram calcium supplement taken daily may help keep your bones healthy.

Complications

Inflammation caused by lupus can affect many areas of your body, including your:

• Kidneys – Lupus can cause serious kidney damage, and kidney failure is one of the leading causes of death among people with lupus.
• Brain and central nervous system – If your brain is affected by lupus, you may experience headaches, dizziness, behavior changes, vision problems, and even strokes or seizures. Many people with lupus experience memory problems and may have difficulty expressing their thoughts.
• Blood and blood vessels – Lupus may lead to blood problems, including anemia and an increased risk of bleeding or blood clotting. It can also cause inflammation of the blood vessels (vasculitis).
• Lungs – Having lupus increases your chances of developing an inflammation of the chest cavity lining (pleurisy), which can make breathing painful. Bleeding into the lungs and pneumonia also are possible.
• Heart – Lupus can cause inflammation of your heart muscle, your arteries, or heart membrane (pericarditis). The risk of cardiovascular disease and heart attacks increases greatly as well.
• Infection – People with lupus are more vulnerable to infection because both the disease and its treatments can weaken the immune system.
• Cancer – Having lupus appears to increase your risk of cancer; however, the risk is small.
• Bone tissue death (avascular necrosis) – This occurs when the blood supply to a bone diminishes, often leading to tiny breaks in the bone and eventually to the bone’s collapse.
• Pregnancy complications – Women with lupus have an increased risk of miscarriage. Lupus increases the risk of high blood pressure during pregnancy (preeclampsia) and preterm birth. To reduce the risk of these complications, doctors often recommend delaying pregnancy until your disease has been under control for at least six months.

References

Symptoms of Systemic Lupus Erythematosus/The Systemic Lupus Erythematosus (SLE) is a systemic autoimmune disease, with multisystemic involvement. The disease has several phenotypes, with varying clinical presentations in patients ranging from mild mucocutaneous manifestations to multiorgan and severe central nervous system involvement. Several immunopathogenic pathways play a role in the development of SLE. The lupus erythematosus (LE cell) was described by Hargraves in 1948. Several pathogenic autoantibodies have since been identified.

The systemic lupus erythematosus (SLE) is characterized by overt polyclonal B-cell activation and autoantibody (Ab) production. By contrast, cellular immune responses against all- or recall antigens are significantly impaired. Many pieces of evidence indicate that IL-10 overproduction plays a pivotal role in the disease and the contribution of the IL-10/IL-12 imbalance to the pathophysiology of SLE will be extensively discussed. The authors will further summarize the available data about the involvement of IFN-γ, TNF-α, TGF-β, and TALL-1. Other cytokines (IL-1, IL-2, IL-4, IL-6, IL-16, IL-17, and IL-18) will be briefly discussed.

Systemic Lupus Erythematosus

Types of Systemic Lupus Erythematosus

About 25% of patients with systemic lupus erythematosus (SLE) initially present with skin involvement. It is important to correctly classify cutaneous lupus erythematosus (CLE), as it helps determine the underlying type and severity of SLE. About 5–10% of patients with CLE develop SLE, and CLE is associated with less severe forms of SLE.

Skin manifestations of lupus erythematosus are commonly divided into lupus erythematosus–specific and non–specific disease. Note that four of the nine American College of Rheumatology criteria for SLE are skin signs (ie, malar/butterfly rash, discoid plaques, photosensitivity, and oral ulcers).

Lupus erythematosus–specific disease

Acute cutaneous lupus erythematosus

Forms of acute CLE include the following:

• Localised acute CLE — this presents with malar or ‘butterfly’ rash (symmetrical erythema and edema of the cheeks, forehead, chin, and V of the neck but sparing the nasolabial folds or ‘smile lines’)
• Generalised acute CLE — this presents with a widespread exanthematous eruption on the extensor surfaces, trunk, sun-exposed areas, and hands (but sparing the knuckles)
• Toxic epidermal necrolysis-like acute CLE — this is a life-threatening variant of acute CLE that presents with a massive epidermal injury; it occurs predominantly on sun-exposed skin and has a gradual, insidious onset, unlike toxic epidermal necrolysis.

Acute CLE is typically triggered or exacerbated by exposure to ultraviolet (UV) radiation. On recovery, there may be postinflammatory hyperpigmentation without scarring.

Subacute cutaneous lupus erythematosus

The subacute cutaneous lupus erythematosus (SCLE) starts as macules or papules that progress to hyperkeratotic plaques. SCLE is photosensitive so plaques usually occur on sun-exposed skin; these plaques do not lead to scarring but can result in postinflammatory hyperpigmentation or hypopigmentation. SCLE should be monitored to exclude any progression to SLE.

Forms of SCLE include:

• Annular SCLE — this subtype presents with slightly raised red lesions with central clearing
• Papulosquamous SCLE — this subtype presents with eczematous or psoriasis-like lesions on sun-exposed skin.

Chronic cutaneous lupus erythematosus

Chronic CLE is not as photosensitive as acute CLE or SCLE. Forms of chronic CLE include:

• The discoid lupus erythematosus (DLE) — this affects the face, outer ears, neck, sun-exposed areas and lips, and presents with discoid plaques (erythematous, well-demarcated plaques covered by scale) that become hyperkeratotic, leading to atrophy and scarring; there is follicular involvement, causing both reversible and irreversible (scarring) alopecia (hair loss); depigmentation of the peripheries is also common in certain ethnicities (Asian, Indian).
• Hypertrophic or verrucous lupus erythematosus — this is a rare form of CLE presenting with severe hyperkeratosis of the extensor surfaces of the arms, upper back and face; it has overlapping features with lichen planus.
• Mucosal lupus erythematosus — this affects 25% of patients with CLE; most commonly, painless erythematous patches on the oral mucosa develop into chronic plaques that can centrally ulcerate and also affect nasal, conjunctival and genital mucosa; oral lupus erythematosus rarely degrades to oral cancer (squamous cell carcinoma).

Drug-induced lupus erythematosus

Many drugs are thought to induce SLE and drug-induced lupus erythematosus often includes cutaneous signs. Drugs that induce lupus erythematosus include:

• Hydralazine
• Isoniazid
• Chlorpromazine
• Procainamide
• Phenytoin
• Minocycline
• Anti–tumour necrosis factor medications.

Rarer types of lupus erythematosus

The rarer types of lupus erythematosus include:

• Lupus profundus/lupus panniculitis — this is a rare form of chronic CLE with firm nodules in the lower dermis and subcutaneous tissue that causes lipodystrophy; some use the term lupus panniculitis to refer to subcutaneous involvement only, and lupus profundus when there is a combination of lupus panniculitis with DLE.
• Chilblain lupus erythematosus — this presents with purple-red patches, papules and plaques on toes, fingers and face, and is associated with nail fold telangiectasia; it is precipitated by exposure to the cold, so often presents in winter.
• Lupus erythematosus tumidus —this is a variant of chronic CLE with succulent or indurated erythematous plaques without surface change.

Lupus erythematosus — non–specific disease

Lupus erythematosus-nonspecific disease can relate to SLE or another autoimmune disease, but nonspecific cutaneous features are most often associated with SLE.

Common cutaneous features seen include:

• Photosensitivity — this is an abnormal response to UV radiation that is present in 50–93% of patients with SLE
• Mouth ulcers — these are present in 25–45% of patients with SLE
• Non–scarring hair loss in SLE — presenting as coarse, dry hair with increased fragility (also referred to as ‘lupus hair’).

Cutaneous vascular disease is also common. Forms of cutaneous vascular disease include

• Raynaud phenomenon — this presents with focal ulceration in the fingertips and periungual areas that can cause pitted scarring, hemorrhage and other nail fold complications
• Vasculitis — leukocytoclastic vasculitis: urticarial vasculitis presenting with tender papules and plaques over bony prominences; and medium or large vessel vasculitis can occur, presenting with purpuric plaques with stellate borders, often with necrosis and ulceration or subcutaneous nodules
• Thromboembolic vasculopathy — these may have a similar clinical presentation to vasculitis, but vessel occlusion is due to blood clots
• Livedo reticularis — characterized by net-like blanching red-purple rings that commonly arise on the lower limbs
• Erythromelalgia — characterized by burning pain in the feet and hands, and with macular erythema; it is associated with heat exposure.

Specific cutaneous SLE

Cutaneous lupus (CLE) has specific acute, subacute and chronic manifestations.

• Typically, SLE presents with acute CLE.
• About half of patients with subacute cutaneous LE develop mild SLE
• Only 5% of patients with chronic CLE have SLE, as CLE presents as a skin problem without the involvement of other organs.

Acute CLE

• Central face malar or “butterfly” violaceous erythema with a sharp cutoff at lateral margins, resolves without scarring (may result in persistent telangiectasia)
• Bullous systemic lupus erythematosus: a blistering rash, if severe, this may resemble toxic epidermal necrolysis
• A maculopapular rash resembling morbilliform drug eruption
• Mucosal erosions and ulcerations (lips, nose, mouth, genitals)
• Photosensitivity: lupus rashes are mainly on sun-exposed sites. Photosensitivity can be mild to very severe with the rash appearing after minimal light exposure.
• Diffuse hair loss (nonscarring alopecia) with brittle hair shafts

Subacute cutaneous LE

• Flat, scaly patches resembling psoriasis, often in a network pattern
• Annular (ring-shaped) polycyclic (overlapping circular) lesions
• Lesions resolve with minimal scarring
• Affects trunk and arms
• Flares on exposure to the sun, but usually spares face and hands

Chronic CLE

• Chronic CLE affects 25% of patients with SLE
• Classic discoid lupus is most common: indurated hyperpigmented plaques
• Localized (above the neck in 80%) or generalized (above and below the neck in 20%)
• Hypertrophic (warty) lupus
• Tumid lupus
• Lupus panniculitis/profundus
• Mucosal lupus (lips, nose, mouth, genitals)
• Chilblain lupus erythematosus
• Discoid lupus/lichen planus overlap
• Discoid lesions and panniculitis resolve with scarring

A more thorough categorization of lupus includes the following types

• acute cutaneous lupus erythematosus
• subacute cutaneous lupus erythematosus
• the discoid lupus erythematosus (chronic cutaneous
  • • childhood discoid lupus erythematosus
    • generalized discoid lupus erythematosus
    • localized discoid lupus erythematosus
  • the chilblain lupus erythematosus (Hutchinson)
  • lupus erythematosus-lichen planus overlap syndrome
  • lupus erythematosus panniculitis (lupus erythematosus profundus)
  • tumid lupus erythematosus
  • the verrucous lupus erythematosus (hypertrophic lupus erythematosus)
  • cutaneous lupus mucinosis
• complement deficiency syndromes
• drug-induced lupus erythematosus
• neonatal lupus erythematosus
• systemic lupus erythematosus

Causes of Systemic Lupus Erythematosus

Factors leading to SLE include:

• Genetic predisposition, including haplotype HLA-B8, -DR₃
• Exposure to sunlight
• Viral infection, particularly Epstein-Barr virus
• Hormones
• Toxins such as cigarette smoke
• Drugs in drug-induced LE
• Emotional upset.

The manifestations of SLE are due to loss of regulation of the patient’s immune system.

• Nuclear proteins are not processed properly.
• Nuclear debris accumulates within the cell.
• This leads to the production of autoantibodies against nuclear proteins.
• Immune complexes are not removed.
• The complement system is activated.
• Inflammation leads to cell and tissue injury.

Symptoms of Systemic Lupus Erythematosus

Common symptoms include:

• Chest pain during respiration
• Joint pain
• Oral ulcer
• Fatigue
• Weight loss
• Fever with no other cause
• General discomfort, uneasiness, or ill feeling (malaise)
• Hair loss
• Sensitivity to sunlight
• A “butterfly” facial rash, seen in about half people with SLE
• Swollen lymph nodes

Photosensitivity

Photosensitivity is a known symptom of lupus, but its relationship to and influence on other aspects of the disease remain to be defined.^[rx] Causes of photosensitivity may include:

• Change in autoantibody location
• Cytotoxicity
• Induction of apoptosis with autoantigens in apoptotic blebs
• Upregulation of adhesion molecules and cytokines
• Induction of nitric oxide synthase expression
• Ultraviolet-generated antigenic DNA.
• Tumor necrosis factor-alpha

Other symptoms include

• General – tiredness, malaise, chronic pain, fever with flares
• Joints – arthritis or synovitis causing swelling, pain and morning stiffness
• Lungs – pleurisy or pleural effusions
• Heart – pericarditis or pericardial effusions
• Kidneys – protein, casts in urine, glomerulonephritis
• Brain – seizures, psychosis, confusion
• Nervous system – mono neuritis multiplex, myelitis, peripheral neuropathy
• Blood – reduced numbers of red cells, white cells and platelets
• Cutaneous mucinosis  – characterized by indurated papules, nodules, or plaques on the trunk or arms
• Lupus nail dystrophy –  presenting as nail pitting, ridging, leukonychia, onycholysis, and red lunula
• Spontaneous chronic urticaria
• Lichen planus
• Acanthosis nigricans
• Sclerodactyly (spindle-shaped fingers)
• Erythema multiforme
• Cutis laxa
• Rheumatoid nodules.

• The acute cutaneous lupus erythematosus (including “butterfly rash“)
• The chronic cutaneous lupus erythematosus (e.g., localized or generalized discoid lupus erythematosus)
• Oral ulcers (on palate and/or nose)
• Non-scarring alopecia
• Synovitis (≥ 2 joints) or tenderness on palpation (≥ 2 joints) and morning stiffness (≥ 30 min)
• Serositis (pleurisy or pericardial pain for more than 1 day)
• Renal involvement (single urine: protein/creatinine ratio or 24-hour urine protein, >0.5 g)
• Neurological involvement (e.g., seizures, psychosis, myelitis)
• Hemolytic anemia
• Leukopenia (<4000/μL) or lymphopenia (<1000/μL)
• Thrombocytopenia (<100 000/μL)

Immunological criteria

• ANA level above the laboratory reference range
• Anti-dsDNA antibodies
• Anti-Sm antibodies
• Antiphospholipid antibodies (anticardiolipin and anti- β 2-glycoprotein I [IgA-, IgG- or IgM-] antibodies; false-positive VDRL [Venereal Disease Research Laboratory] test)
• Low complement (C3, C4, or CH50)
• Direct Coombs test (in the absence of hemolytic anemia)

Diagnosis of Systemic Lupus Erythematosus

Screening laboratory tests

• Erythrocyte sedimentation rate
• Blood count, differential blood count
• Creatinine
• Urinary status and sediment
• Antinuclear antibodies (ANA) (HEp-2 cell test with fluorescence pattern)

Further laboratory tests after positive screening^*1 (particularly in case of positive ANA)

• Further differentiation of ANA (particularly anti-Sm, -Ro/SSA, -La/SSB, -U1RNP antibodies, etc.)
• Anti-dsDNA antibodies (ELISA; confirmation by radioimmunoassay or immunofluorescence test with Crithidia luciliae)
• Complement C3, C4
• Antiphospholipid antibodies, lupus anticoagulant
• Glomerular filtration rate; 24-hour urine (if urine protein positive), alternatively: protein/creatinine ratio in single urine sample; investigation for dysmorphic erythrocytes in sediment
• Liver enzymes; lactate dehydrogenase; creatine kinase in presence of muscular symptoms
• Further laboratory tests depending on clinical symptoms
• Screening for comorbidities
• Assessment of vaccination status (vaccination recommendations [in German] at [rx)

Follow-up (SLE: every 3 to 6 months depending on disease course; lupus nephritis: initially every 2 to 4 weeks for the first 2 to 4 months)^*2

• Medical history (including new symptoms, comedication, infections), physical examination
• Evaluate disease activity with standardized score
• Evaluate damage according to standardized score (1 ×/year)
• Repeat screening for comorbidities (at least 1 ×/year)
• Ocular examination in patients taking hydroxychloroquine or chloroquine: baseline, then every 6 months (currently being revised by the German Society of Rheumatology in light of recommendations from the USA) (rx, rx)

Laboratory tests

• Erythrocyte sedimentation rate
• C-reactive protein (in suspected infection or pleurisy)
• Urine tests for hyaline casts, creatinine, protein and blood
• Blood pressure
• Chest X-ray, ultrasound, CT and MRI scans
• Electrocardiograph (ECG) and echocardiography
• Nerve and muscle testing
• Ophthalmological examination
• Endoscopy of the gastrointestinal tract
• Kidney biopsy.
• Blood count, differential blood count
• Creatinine
• Liver enzymes
• Urinary status (protein/creatinine ratio, 24-hour urine and microscopic examination of urinary sediment as needed)
• Complement C3, C4
• Anti-dsDNA antibodies
• Instrument-based diagnostics as needed

Modified after (2, 8), modified after (rx, rx, rx, rx, rx)

Using the SLICC criteria, SLE is diagnosed if the patient has either of the following over time:

• Four criteria including ≥ one clinical criterion and ≥ one immunological criterion
• Biopsy-proven lupus nephritis and antinuclear antibodies or anti-double-stranded DNA antibodies

These criteria depend on history, clinical examination, exclusion of other causes of the symptoms, and the results of investigations—including blood tests and biopsy of the affected tissue. Four of the 17 SLICC criteria relate to the skin.

Clinical criteria

• Acute or subacute cutaneous lupus
• Chronic cutaneous lupus
• Oral ulcers
• Nonscarring alopecia
• Synovitis involving 2 or more joints
• Serositis involving lungs or heart
• Renal involvement
• Neurological involvement
• Hemolytic anemia
• leukopenia or lymphopenia
• Thrombocytopenia

Immunological criteria

• Raised ANA level
• A raised anti-dsDNA antibody level
• Presence of anti-Sm
• Positive antiphospholipid antibody (lupus anticoagulant, false-positive rapid plasma reagin, high-titer anticardiolipin antibody, positive anti–2-glycoprotein I)
• Low complement levels
• Positive direct Coombs’ test

SLICC Systemic Lupus International Collaborating Clinics; ANA antinuclear antibody; anti-dsDNA anti-double-stranded DNA

Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI)

The Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) was developed in an attempt to classify the severity of CLE. [2] A score of activity and damage due to the disease is calculated in each of 12 anatomical locations (refer to the original published paper for details).

The total activity score is made up of:

• The degree of redness (0–3) and scale (0–2)
• Mucous membrane involvement (0–1)
• Recent hair loss (0–1), nonscarring alopecia (0–3)

Total damage score is made up of:

• The degree of dyspigmentation (0–2), and scarring (0–2)
• Persistence of dyspigmentation more than 12 months doubles the depigmentation score
• Scalp scarring (0,3,4,5,6)

Biopsy findings

Patients with SLE often undergo skin biopsy.

• Acute CLE: nonspecific dermatitis.
• Subacute CLE: features of lupus noted in the epidermis and superficial dermis
• Chronic discoid CLE: typical features of lupus with atrophy and scarring
• Direct immunofluorescence is positive in sun-protected healthy skin in SLE

Blood tests

Multiple autoantibodies are typically present in SLE, often in high titre (see immunological criteria above). Relating to skin disease in SLE:

• About 70% of patients with subacute CLE have positive extractable nuclear antibodies anti-Ro (also called anti-SSA) and anti-La (also called anti-SSB).
• Anti Ro/La is also associated with Sjogren syndrome and neonatal lupus.
• Low serum complement in SLE has been associated with urticarial vasculitis and renal disease.
• Antiphospholipid antibodies are associated with livedo reticularis, thrombosis, and pregnancy complications (antiphospholipid syndrome).
• Anti-annexin 1 antibodies may be a diagnostic marker for discoid CLE

Patients with SLE should also have renal, liver, and thyroid function and markers of inflammation performed, such as C-reactive protein (CRP), immunoglobulins, and rheumatoid factor.

Photoprovocation tests

• Photoprovocation tests  – are sometimes carried out to confirm that a skin eruption is precipitated by exposure to particular wavelengths of ultraviolet or visible radiation.
• Echocardiogram – Echocardiogram shows Pericardial effusion, mitral valve prolapse, left ventricular hypertrophy, and changes secondary to pulmonary hypertension.
• EKG – Abnormal EKG findings include hemiblock, bundle branch block, atrioventricular block, changes secondary to pericarditis, and pericardial effusion.
• Pulmonary function testing – Reduction in diffusion capacity for carbon monoxide, forced vital capacity, forced expiratory volume, and six-minute walk tests occur in ILD.
• Computed tomogram – High resolution computed tomogram is very sensitive in diagnosing ILD. Common findings include ground-glass opacities, linear opacities, subpleural micronodules, septal thickening, traction bronchiectasis usually with peripheral and lower lobe predominance. Honeycombing, airspace consolidation, emphysema, and centrilobular nodules are less common findings.[rx]
• Angiogram – Medium-sized arterial occlusions can occur in patients with Raynaud phenomenon.
• Right heart catheterization – Definitive diagnosis of pulmonary hypertension in MCTD requires right heart catheterization demonstrating mean pulmonary arterial pressure at rest greater than 25mmHg.

• Biopsy: histology, immunofluorescence if indicated

Joints

• Conventional X-ray
• Arthrosonography
• Magnetic resonance imaging (MRI)

Muscle

• Creatine kinase
• Electromyography
• MRI
• Muscle biopsy

Kidney

• Sonography
• Renal biopsy

Lung/heart

• Chest X-ray
• Thoracic high-resolution computed tomography (HR-CT)
• Lung function test including diffusion capacity
• Bronchoalveolar lavage
• (Transesophageal) echocardiography
• Cardiac catheterization
• Cardiac MRI
• Myocardial scintigraphy
• Coronary angiography

Eye

• Funduscopy/special investigations in patients on antimalarials

Central and peripheral nervous system

• Electroencephalography
• Primarily cranial MRI, special MRI techniques if indicated
• Computed tomography
• Cerebrospinal fluid analysis
• Transcranial Doppler/angiography
• Neuropsychiatric examination
• Measurement of nerve conduction velocity

Treatment of Systemic Lupus Erythematosus

• Nonsteroidal anti-inflammatory drugs (NSAIDs) – Over-the-counter NSAIDs, such as naproxen sodium (Aleve) and ibuprofen (Advil, Motrin IB, others), may be used to treat pain, swelling, and fever associated with lupus. Stronger NSAIDs are available by prescription. Side effects of NSAIDs include stomach bleeding, kidney problems, and an increased risk of heart problems.
• Antimalarial drugs – Medications commonly used to treat malaria, such as hydroxychloroquine (Plaquenil), affect the immune system and can help decrease the risk of lupus flares. Side effects can include stomach upset and, very rarely, damage to the retina of the eye. Regular eye exams are recommended when taking these medications.
• Corticosteroids – Prednisone and other types of corticosteroids can counter the inflammation of lupus. High doses of steroids such as methylprednisolone (A-Methapred, Medrol) are often used to control serious disease that involves the kidneys and brain. Side effects include weight gain, easy bruising, thinning bones (osteoporosis), high blood pressure, diabetes, and increased risk of infection. The risk of side effects increases with higher doses and longer-term therapy.
• Immunosuppressants – Drugs that suppress the immune system may be helpful in serious cases of lupus. Examples include azathioprine (Imuran, Azasan), mycophenolate mofetil (CellCept), and methotrexate (Trexall). Potential side effects may include an increased risk of infection, liver damage, decreased fertility and an increased risk of cancer.
• Biologics – A different type of medication, belimumab (Benlysta) administered intravenously, also reduces lupus symptoms in some people. Side effects include nausea, diarrhea and infections. Rarely, the worsening of depression can occur.
• Rituximab (Rituxan) –  can be beneficial in cases of resistant lupus. Side effects include allergic reaction to the intravenous infusion and infections.
• Hydroxychloroquine – Commonly used to help keep mild lupus-related problems, such as skin and joint disease, under control. This drug is also effective at preventing lupus flares.
• Cyclophosphamide –  A chemotherapy drug that has very powerful effects on reducing the activity of the immune system. It is used to treat severe forms of lupus, such as those affecting the kidneys or brain.
• Azathioprine – A medication originally used to prevent the rejection of transplanted organs. It is commonly used to treat the more serious features of lupus.
• Methotrexate – Another chemotherapy drug used to suppress the immune system. Its use is becoming increasingly popular for skin disease, arthritis, and other non-life-threatening forms of disease that have not responded to medications such as hydroxychloroquine or low doses of prednisone.
• Belimumab – This drug weakens the immune system by targeting a protein that may reduce the abnormal B cells thought to contribute to lupus. People with active, autoantibody-positive lupus may benefit from Benlysta when given in addition to standard drug therapy.
• Mycophenolate mofetil – A drug that suppresses the immune system and is also used to prevent the rejection of transplanted organs. It is being used increasingly to treat serious features of lupus, especially those previously treated by Cytoxan.

Preventative measures

The following measures are essential to reduce the chance of flares and organ damage.

• Careful protection from sun exposure using clothing, accessories and SPF 50+ broad-spectrum sunscreens. Sunscreens alone are not adequate.
• Smoking cessation
• Rest when needed.

Topical therapy

Intermittent courses of potent topical corticosteroids are important in the treatment of CLE. They should be applied accurately to the skin lesions.

The calcineurin inhibitors tacrolimus ointment and pimecrolimus cream can also be used.

Systemic therapy

Treatment of SLE depends on which are the predominant organs involved in the disease. Typically, any of the following drugs may be used alone or in combination.

• Systemic corticosteroids, such as prednisone or prednisolone. These are the mainstay of treatment in a seriously ill patient with acute LE.
• Hydroxychloroquine and other antimalarials—response rates are about 80% in CLE.
• Methotrexate—best response in subacute CLE and discoid CLE
• Immunosuppressives such as azathioprine, mycophenolate and cyclophosphamide
• Intravenous immunoglobulin
• Aspirin is recommended for antiphospholipid syndrome.
• Targeted biologic therapies under evaluation for SLE include belimumab (intravenous and subcutaneous formulations were registered by FDA for use in SLE in 2017) and off-label rituximab, abatacept, tocilizumab and eculizumab.

CLE is also sometimes treated with

• Retinoids (isotretinoin and acitretin)
• Dapsone.

Lifestyle and Home Remedies

Take steps to care for your body if you have lupus. Simple measures can help you prevent lupus flares and, should they occur, better cope with the signs and symptoms you experience. Try to:

• See your doctor regularly – Having regular checkups instead of only seeing your doctor when your symptoms worsen may help your doctor prevent flare-ups, and can be useful in addressing routine health concerns, such as stress, diet and exercise that can be helpful in preventing lupus complications.
• Be sun smart – Because ultraviolet light can trigger a flare, wear protective clothing — such as a hat, long-sleeved shirt and long pants — and use sunscreens with a sun protection factor (SPF) of at least 55 every time you go outside.
• Get regular exercise – Exercise can help keep your bones strong, reduce your risk of heart attack and promote general well-being.
• Don’t smoke – Smoking increases your risk of cardiovascular disease and can worsen the effects of lupus on your heart and blood vessels.
• Eat a healthy diet – A healthy diet emphasizes fruits, vegetables and whole grains. Sometimes you may have dietary restrictions, especially if you have high blood pressure, kidney damage or gastrointestinal problems.
• Ask your doctor if you need vitamin D and calcium supplements – There is some evidence to suggest that people with lupus may benefit from supplemental vitamin D. A 1,200- to 1,500-milligram calcium supplement taken daily may help keep your bones healthy.

Complications

Inflammation caused by lupus can affect many areas of your body, including your:

• Kidneys – Lupus can cause serious kidney damage, and kidney failure is one of the leading causes of death among people with lupus.
• Brain and central nervous system – If your brain is affected by lupus, you may experience headaches, dizziness, behavior changes, vision problems, and even strokes or seizures. Many people with lupus experience memory problems and may have difficulty expressing their thoughts.
• Blood and blood vessels – Lupus may lead to blood problems, including anemia and an increased risk of bleeding or blood clotting. It can also cause inflammation of the blood vessels (vasculitis).
• Lungs – Having lupus increases your chances of developing an inflammation of the chest cavity lining (pleurisy), which can make breathing painful. Bleeding into the lungs and pneumonia also are possible.
• Heart – Lupus can cause inflammation of your heart muscle, your arteries, or heart membrane (pericarditis). The risk of cardiovascular disease and heart attacks increases greatly as well.
• Infection – People with lupus are more vulnerable to infection because both the disease and its treatments can weaken the immune system.
• Cancer – Having lupus appears to increase your risk of cancer; however, the risk is small.
• Bone tissue death (avascular necrosis) – This occurs when the blood supply to a bone diminishes, often leading to tiny breaks in the bone and eventually to the bone’s collapse.
• Pregnancy complications – Women with lupus have an increased risk of miscarriage. Lupus increases the risk of high blood pressure during pregnancy (preeclampsia) and preterm birth. To reduce the risk of these complications, doctors often recommend delaying pregnancy until your disease has been under control for at least six months.

References

Causes of Systemic Lupus Erythematosus/The Systemic Lupus Erythematosus (SLE) is a systemic autoimmune disease, with multisystemic involvement. The disease has several phenotypes, with varying clinical presentations in patients ranging from mild mucocutaneous manifestations to multiorgan and severe central nervous system involvement. Several immunopathogenic pathways play a role in the development of SLE. The lupus erythematosus (LE cell) was described by Hargraves in 1948. Several pathogenic autoantibodies have since been identified.

The systemic lupus erythematosus (SLE) is characterized by overt polyclonal B-cell activation and autoantibody (Ab) production. By contrast, cellular immune responses against all- or recall antigens are significantly impaired. Many pieces of evidence indicate that IL-10 overproduction plays a pivotal role in the disease and the contribution of the IL-10/IL-12 imbalance to the pathophysiology of SLE will be extensively discussed. The authors will further summarize the available data about the involvement of IFN-γ, TNF-α, TGF-β, and TALL-1. Other cytokines (IL-1, IL-2, IL-4, IL-6, IL-16, IL-17, and IL-18) will be briefly discussed.

Systemic Lupus Erythematosus

Types of Systemic Lupus Erythematosus

About 25% of patients with systemic lupus erythematosus (SLE) initially present with skin involvement. It is important to correctly classify cutaneous lupus erythematosus (CLE), as it helps determine the underlying type and severity of SLE. About 5–10% of patients with CLE develop SLE, and CLE is associated with less severe forms of SLE.

Skin manifestations of lupus erythematosus are commonly divided into lupus erythematosus–specific and non–specific disease. Note that four of the nine American College of Rheumatology criteria for SLE are skin signs (ie, malar/butterfly rash, discoid plaques, photosensitivity, and oral ulcers).

Lupus erythematosus–specific disease

Acute cutaneous lupus erythematosus

Forms of acute CLE include the following:

• Localised acute CLE — this presents with malar or ‘butterfly’ rash (symmetrical erythema and edema of the cheeks, forehead, chin, and V of the neck but sparing the nasolabial folds or ‘smile lines’)
• Generalised acute CLE — this presents with a widespread exanthematous eruption on the extensor surfaces, trunk, sun-exposed areas, and hands (but sparing the knuckles)
• Toxic epidermal necrolysis-like acute CLE — this is a life-threatening variant of acute CLE that presents with a massive epidermal injury; it occurs predominantly on sun-exposed skin and has a gradual, insidious onset, unlike toxic epidermal necrolysis.

Acute CLE is typically triggered or exacerbated by exposure to ultraviolet (UV) radiation. On recovery, there may be postinflammatory hyperpigmentation without scarring.

Subacute cutaneous lupus erythematosus

The subacute cutaneous lupus erythematosus (SCLE) starts as macules or papules that progress to hyperkeratotic plaques. SCLE is photosensitive so plaques usually occur on sun-exposed skin; these plaques do not lead to scarring but can result in postinflammatory hyperpigmentation or hypopigmentation. SCLE should be monitored to exclude any progression to SLE.

Forms of SCLE include:

• Annular SCLE — this subtype presents with slightly raised red lesions with central clearing
• Papulosquamous SCLE — this subtype presents with eczematous or psoriasis-like lesions on sun-exposed skin.

Chronic cutaneous lupus erythematosus

Chronic CLE is not as photosensitive as acute CLE or SCLE. Forms of chronic CLE include:

• The discoid lupus erythematosus (DLE) — this affects the face, outer ears, neck, sun-exposed areas and lips, and presents with discoid plaques (erythematous, well-demarcated plaques covered by scale) that become hyperkeratotic, leading to atrophy and scarring; there is follicular involvement, causing both reversible and irreversible (scarring) alopecia (hair loss); depigmentation of the peripheries is also common in certain ethnicities (Asian, Indian).
• Hypertrophic or verrucous lupus erythematosus — this is a rare form of CLE presenting with severe hyperkeratosis of the extensor surfaces of the arms, upper back and face; it has overlapping features with lichen planus.
• Mucosal lupus erythematosus — this affects 25% of patients with CLE; most commonly, painless erythematous patches on the oral mucosa develop into chronic plaques that can centrally ulcerate and also affect nasal, conjunctival and genital mucosa; oral lupus erythematosus rarely degrades to oral cancer (squamous cell carcinoma).

Drug-induced lupus erythematosus

Many drugs are thought to induce SLE and drug-induced lupus erythematosus often includes cutaneous signs. Drugs that induce lupus erythematosus include:

• Hydralazine
• Isoniazid
• Chlorpromazine
• Procainamide
• Phenytoin
• Minocycline
• Anti–tumour necrosis factor medications.

Rarer types of lupus erythematosus

The rarer types of lupus erythematosus include:

• Lupus profundus/lupus panniculitis — this is a rare form of chronic CLE with firm nodules in the lower dermis and subcutaneous tissue that causes lipodystrophy; some use the term lupus panniculitis to refer to subcutaneous involvement only, and lupus profundus when there is a combination of lupus panniculitis with DLE.
• Chilblain lupus erythematosus — this presents with purple-red patches, papules and plaques on toes, fingers and face, and is associated with nail fold telangiectasia; it is precipitated by exposure to the cold, so often presents in winter.
• Lupus erythematosus tumidus —this is a variant of chronic CLE with succulent or indurated erythematous plaques without surface change.

Lupus erythematosus — non–specific disease

Lupus erythematosus-nonspecific disease can relate to SLE or another autoimmune disease, but nonspecific cutaneous features are most often associated with SLE.

Common cutaneous features seen include:

• Photosensitivity — this is an abnormal response to UV radiation that is present in 50–93% of patients with SLE
• Mouth ulcers — these are present in 25–45% of patients with SLE
• Non–scarring hair loss in SLE — presenting as coarse, dry hair with increased fragility (also referred to as ‘lupus hair’).

Cutaneous vascular disease is also common. Forms of cutaneous vascular disease include

• Raynaud phenomenon — this presents with focal ulceration in the fingertips and periungual areas that can cause pitted scarring, hemorrhage and other nail fold complications
• Vasculitis — leukocytoclastic vasculitis: urticarial vasculitis presenting with tender papules and plaques over bony prominences; and medium or large vessel vasculitis can occur, presenting with purpuric plaques with stellate borders, often with necrosis and ulceration or subcutaneous nodules
• Thromboembolic vasculopathy — these may have a similar clinical presentation to vasculitis, but vessel occlusion is due to blood clots
• Livedo reticularis — characterized by net-like blanching red-purple rings that commonly arise on the lower limbs
• Erythromelalgia — characterized by burning pain in the feet and hands, and with macular erythema; it is associated with heat exposure.

Specific cutaneous SLE

Cutaneous lupus (CLE) has specific acute, subacute and chronic manifestations.

• Typically, SLE presents with acute CLE.
• About half of patients with subacute cutaneous LE develop mild SLE
• Only 5% of patients with chronic CLE have SLE, as CLE presents as a skin problem without the involvement of other organs.

Acute CLE

• Central face malar or “butterfly” violaceous erythema with a sharp cutoff at lateral margins, resolves without scarring (may result in persistent telangiectasia)
• Bullous systemic lupus erythematosus: a blistering rash, if severe, this may resemble toxic epidermal necrolysis
• A maculopapular rash resembling morbilliform drug eruption
• Mucosal erosions and ulcerations (lips, nose, mouth, genitals)
• Photosensitivity: lupus rashes are mainly on sun-exposed sites. Photosensitivity can be mild to very severe with the rash appearing after minimal light exposure.
• Diffuse hair loss (nonscarring alopecia) with brittle hair shafts

Subacute cutaneous LE

• Flat, scaly patches resembling psoriasis, often in a network pattern
• Annular (ring-shaped) polycyclic (overlapping circular) lesions
• Lesions resolve with minimal scarring
• Affects trunk and arms
• Flares on exposure to the sun, but usually spares face and hands

Chronic CLE

• Chronic CLE affects 25% of patients with SLE
• Classic discoid lupus is most common: indurated hyperpigmented plaques
• Localized (above the neck in 80%) or generalized (above and below the neck in 20%)
• Hypertrophic (warty) lupus
• Tumid lupus
• Lupus panniculitis/profundus
• Mucosal lupus (lips, nose, mouth, genitals)
• Chilblain lupus erythematosus
• Discoid lupus/lichen planus overlap
• Discoid lesions and panniculitis resolve with scarring

A more thorough categorization of lupus includes the following types

• acute cutaneous lupus erythematosus
• subacute cutaneous lupus erythematosus
• the discoid lupus erythematosus (chronic cutaneous
  • • childhood discoid lupus erythematosus
    • generalized discoid lupus erythematosus
    • localized discoid lupus erythematosus
  • the chilblain lupus erythematosus (Hutchinson)
  • lupus erythematosus-lichen planus overlap syndrome
  • lupus erythematosus panniculitis (lupus erythematosus profundus)
  • tumid lupus erythematosus
  • the verrucous lupus erythematosus (hypertrophic lupus erythematosus)
  • cutaneous lupus mucinosis
• complement deficiency syndromes
• drug-induced lupus erythematosus
• neonatal lupus erythematosus
• systemic lupus erythematosus

Causes of Systemic Lupus Erythematosus

Factors leading to SLE include:

• Genetic predisposition, including haplotype HLA-B8, -DR₃
• Exposure to sunlight
• Viral infection, particularly Epstein-Barr virus
• Hormones
• Toxins such as cigarette smoke
• Drugs in drug-induced LE
• Emotional upset.

The manifestations of SLE are due to loss of regulation of the patient’s immune system.

• Nuclear proteins are not processed properly.
• Nuclear debris accumulates within the cell.
• This leads to the production of autoantibodies against nuclear proteins.
• Immune complexes are not removed.
• The complement system is activated.
• Inflammation leads to cell and tissue injury.

Symptoms of Systemic Lupus Erythematosus

Common symptoms include:

• Chest pain during respiration
• Joint pain
• Oral ulcer
• Fatigue
• Weight loss
• Fever with no other cause
• General discomfort, uneasiness, or ill feeling (malaise)
• Hair loss
• Sensitivity to sunlight
• A “butterfly” facial rash, seen in about half people with SLE
• Swollen lymph nodes

Photosensitivity

Photosensitivity is a known symptom of lupus, but its relationship to and influence on other aspects of the disease remain to be defined.^[rx] Causes of photosensitivity may include:

• Change in autoantibody location
• Cytotoxicity
• Induction of apoptosis with autoantigens in apoptotic blebs
• Upregulation of adhesion molecules and cytokines
• Induction of nitric oxide synthase expression
• Ultraviolet-generated antigenic DNA.
• Tumor necrosis factor-alpha

Other symptoms include

• General – tiredness, malaise, chronic pain, fever with flares
• Joints – arthritis or synovitis causing swelling, pain and morning stiffness
• Lungs – pleurisy or pleural effusions
• Heart – pericarditis or pericardial effusions
• Kidneys – protein, casts in urine, glomerulonephritis
• Brain – seizures, psychosis, confusion
• Nervous system – mono neuritis multiplex, myelitis, peripheral neuropathy
• Blood – reduced numbers of red cells, white cells and platelets
• Cutaneous mucinosis  – characterized by indurated papules, nodules, or plaques on the trunk or arms
• Lupus nail dystrophy –  presenting as nail pitting, ridging, leukonychia, onycholysis, and red lunula
• Spontaneous chronic urticaria
• Lichen planus
• Acanthosis nigricans
• Sclerodactyly (spindle-shaped fingers)
• Erythema multiforme
• Cutis laxa
• Rheumatoid nodules.

• The acute cutaneous lupus erythematosus (including “butterfly rash“)
• The chronic cutaneous lupus erythematosus (e.g., localized or generalized discoid lupus erythematosus)
• Oral ulcers (on palate and/or nose)
• Non-scarring alopecia
• Synovitis (≥ 2 joints) or tenderness on palpation (≥ 2 joints) and morning stiffness (≥ 30 min)
• Serositis (pleurisy or pericardial pain for more than 1 day)
• Renal involvement (single urine: protein/creatinine ratio or 24-hour urine protein, >0.5 g)
• Neurological involvement (e.g., seizures, psychosis, myelitis)
• Hemolytic anemia
• Leukopenia (<4000/μL) or lymphopenia (<1000/μL)
• Thrombocytopenia (<100 000/μL)

Immunological criteria

• ANA level above the laboratory reference range
• Anti-dsDNA antibodies
• Anti-Sm antibodies
• Antiphospholipid antibodies (anticardiolipin and anti- β 2-glycoprotein I [IgA-, IgG- or IgM-] antibodies; false-positive VDRL [Venereal Disease Research Laboratory] test)
• Low complement (C3, C4, or CH50)
• Direct Coombs test (in the absence of hemolytic anemia)

Diagnosis of Systemic Lupus Erythematosus

Screening laboratory tests

• Erythrocyte sedimentation rate
• Blood count, differential blood count
• Creatinine
• Urinary status and sediment
• Antinuclear antibodies (ANA) (HEp-2 cell test with fluorescence pattern)

Further laboratory tests after positive screening^*1 (particularly in case of positive ANA)

• Further differentiation of ANA (particularly anti-Sm, -Ro/SSA, -La/SSB, -U1RNP antibodies, etc.)
• Anti-dsDNA antibodies (ELISA; confirmation by radioimmunoassay or immunofluorescence test with Crithidia luciliae)
• Complement C3, C4
• Antiphospholipid antibodies, lupus anticoagulant
• Glomerular filtration rate; 24-hour urine (if urine protein positive), alternatively: protein/creatinine ratio in single urine sample; investigation for dysmorphic erythrocytes in sediment
• Liver enzymes; lactate dehydrogenase; creatine kinase in presence of muscular symptoms
• Further laboratory tests depending on clinical symptoms
• Screening for comorbidities
• Assessment of vaccination status (vaccination recommendations [in German] at [rx)

Follow-up (SLE: every 3 to 6 months depending on disease course; lupus nephritis: initially every 2 to 4 weeks for the first 2 to 4 months)^*2

• Medical history (including new symptoms, comedication, infections), physical examination
• Evaluate disease activity with standardized score
• Evaluate damage according to standardized score (1 ×/year)
• Repeat screening for comorbidities (at least 1 ×/year)
• Ocular examination in patients taking hydroxychloroquine or chloroquine: baseline, then every 6 months (currently being revised by the German Society of Rheumatology in light of recommendations from the USA) (rx, rx)

Laboratory tests

• Erythrocyte sedimentation rate
• C-reactive protein (in suspected infection or pleurisy)
• Urine tests for hyaline casts, creatinine, protein and blood
• Blood pressure
• Chest X-ray, ultrasound, CT and MRI scans
• Electrocardiograph (ECG) and echocardiography
• Nerve and muscle testing
• Ophthalmological examination
• Endoscopy of the gastrointestinal tract
• Kidney biopsy.
• Blood count, differential blood count
• Creatinine
• Liver enzymes
• Urinary status (protein/creatinine ratio, 24-hour urine and microscopic examination of urinary sediment as needed)
• Complement C3, C4
• Anti-dsDNA antibodies
• Instrument-based diagnostics as needed

Modified after (2, 8), modified after (rx, rx, rx, rx, rx)

Using the SLICC criteria, SLE is diagnosed if the patient has either of the following over time:

• Four criteria including ≥ one clinical criterion and ≥ one immunological criterion
• Biopsy-proven lupus nephritis and antinuclear antibodies or anti-double-stranded DNA antibodies

These criteria depend on history, clinical examination, exclusion of other causes of the symptoms, and the results of investigations—including blood tests and biopsy of the affected tissue. Four of the 17 SLICC criteria relate to the skin.

Clinical criteria

• Acute or subacute cutaneous lupus
• Chronic cutaneous lupus
• Oral ulcers
• Nonscarring alopecia
• Synovitis involving 2 or more joints
• Serositis involving lungs or heart
• Renal involvement
• Neurological involvement
• Hemolytic anemia
• leukopenia or lymphopenia
• Thrombocytopenia

Immunological criteria

• Raised ANA level
• A raised anti-dsDNA antibody level
• Presence of anti-Sm
• Positive antiphospholipid antibody (lupus anticoagulant, false-positive rapid plasma reagin, high-titer anticardiolipin antibody, positive anti–2-glycoprotein I)
• Low complement levels
• Positive direct Coombs’ test

SLICC Systemic Lupus International Collaborating Clinics; ANA antinuclear antibody; anti-dsDNA anti-double-stranded DNA

Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI)

The Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) was developed in an attempt to classify the severity of CLE. [2] A score of activity and damage due to the disease is calculated in each of 12 anatomical locations (refer to the original published paper for details).

The total activity score is made up of:

• The degree of redness (0–3) and scale (0–2)
• Mucous membrane involvement (0–1)
• Recent hair loss (0–1), nonscarring alopecia (0–3)

Total damage score is made up of:

• The degree of dyspigmentation (0–2), and scarring (0–2)
• Persistence of dyspigmentation more than 12 months doubles the depigmentation score
• Scalp scarring (0,3,4,5,6)

Biopsy findings

Patients with SLE often undergo skin biopsy.

• Acute CLE: nonspecific dermatitis.
• Subacute CLE: features of lupus noted in the epidermis and superficial dermis
• Chronic discoid CLE: typical features of lupus with atrophy and scarring
• Direct immunofluorescence is positive in sun-protected healthy skin in SLE

Blood tests

Multiple autoantibodies are typically present in SLE, often in high titre (see immunological criteria above). Relating to skin disease in SLE:

• About 70% of patients with subacute CLE have positive extractable nuclear antibodies anti-Ro (also called anti-SSA) and anti-La (also called anti-SSB).
• Anti Ro/La is also associated with Sjogren syndrome and neonatal lupus.
• Low serum complement in SLE has been associated with urticarial vasculitis and renal disease.
• Antiphospholipid antibodies are associated with livedo reticularis, thrombosis, and pregnancy complications (antiphospholipid syndrome).
• Anti-annexin 1 antibodies may be a diagnostic marker for discoid CLE

Patients with SLE should also have renal, liver, and thyroid function and markers of inflammation performed, such as C-reactive protein (CRP), immunoglobulins, and rheumatoid factor.

Photoprovocation tests

• Photoprovocation tests  – are sometimes carried out to confirm that a skin eruption is precipitated by exposure to particular wavelengths of ultraviolet or visible radiation.
• Echocardiogram – Echocardiogram shows Pericardial effusion, mitral valve prolapse, left ventricular hypertrophy, and changes secondary to pulmonary hypertension.
• EKG – Abnormal EKG findings include hemiblock, bundle branch block, atrioventricular block, changes secondary to pericarditis, and pericardial effusion.
• Pulmonary function testing – Reduction in diffusion capacity for carbon monoxide, forced vital capacity, forced expiratory volume, and six-minute walk tests occur in ILD.
• Computed tomogram – High resolution computed tomogram is very sensitive in diagnosing ILD. Common findings include ground-glass opacities, linear opacities, subpleural micronodules, septal thickening, traction bronchiectasis usually with peripheral and lower lobe predominance. Honeycombing, airspace consolidation, emphysema, and centrilobular nodules are less common findings.[rx]
• Angiogram – Medium-sized arterial occlusions can occur in patients with Raynaud phenomenon.
• Right heart catheterization – Definitive diagnosis of pulmonary hypertension in MCTD requires right heart catheterization demonstrating mean pulmonary arterial pressure at rest greater than 25mmHg.

• Biopsy: histology, immunofluorescence if indicated

Joints

• Conventional X-ray
• Arthrosonography
• Magnetic resonance imaging (MRI)

Muscle

• Creatine kinase
• Electromyography
• MRI
• Muscle biopsy

Kidney

• Sonography
• Renal biopsy

Lung/heart

• Chest X-ray
• Thoracic high-resolution computed tomography (HR-CT)
• Lung function test including diffusion capacity
• Bronchoalveolar lavage
• (Transesophageal) echocardiography
• Cardiac catheterization
• Cardiac MRI
• Myocardial scintigraphy
• Coronary angiography

Eye

• Funduscopy/special investigations in patients on antimalarials

Central and peripheral nervous system

• Electroencephalography
• Primarily cranial MRI, special MRI techniques if indicated
• Computed tomography
• Cerebrospinal fluid analysis
• Transcranial Doppler/angiography
• Neuropsychiatric examination
• Measurement of nerve conduction velocity

Treatment of Systemic Lupus Erythematosus

• Nonsteroidal anti-inflammatory drugs (NSAIDs) – Over-the-counter NSAIDs, such as naproxen sodium (Aleve) and ibuprofen (Advil, Motrin IB, others), may be used to treat pain, swelling, and fever associated with lupus. Stronger NSAIDs are available by prescription. Side effects of NSAIDs include stomach bleeding, kidney problems, and an increased risk of heart problems.
• Antimalarial drugs – Medications commonly used to treat malaria, such as hydroxychloroquine (Plaquenil), affect the immune system and can help decrease the risk of lupus flares. Side effects can include stomach upset and, very rarely, damage to the retina of the eye. Regular eye exams are recommended when taking these medications.
• Corticosteroids – Prednisone and other types of corticosteroids can counter the inflammation of lupus. High doses of steroids such as methylprednisolone (A-Methapred, Medrol) are often used to control serious disease that involves the kidneys and brain. Side effects include weight gain, easy bruising, thinning bones (osteoporosis), high blood pressure, diabetes, and increased risk of infection. The risk of side effects increases with higher doses and longer-term therapy.
• Immunosuppressants – Drugs that suppress the immune system may be helpful in serious cases of lupus. Examples include azathioprine (Imuran, Azasan), mycophenolate mofetil (CellCept), and methotrexate (Trexall). Potential side effects may include an increased risk of infection, liver damage, decreased fertility and an increased risk of cancer.
• Biologics – A different type of medication, belimumab (Benlysta) administered intravenously, also reduces lupus symptoms in some people. Side effects include nausea, diarrhea and infections. Rarely, the worsening of depression can occur.
• Rituximab (Rituxan) –  can be beneficial in cases of resistant lupus. Side effects include allergic reaction to the intravenous infusion and infections.
• Hydroxychloroquine – Commonly used to help keep mild lupus-related problems, such as skin and joint disease, under control. This drug is also effective at preventing lupus flares.
• Cyclophosphamide –  A chemotherapy drug that has very powerful effects on reducing the activity of the immune system. It is used to treat severe forms of lupus, such as those affecting the kidneys or brain.
• Azathioprine – A medication originally used to prevent the rejection of transplanted organs. It is commonly used to treat the more serious features of lupus.
• Methotrexate – Another chemotherapy drug used to suppress the immune system. Its use is becoming increasingly popular for skin disease, arthritis, and other non-life-threatening forms of disease that have not responded to medications such as hydroxychloroquine or low doses of prednisone.
• Belimumab – This drug weakens the immune system by targeting a protein that may reduce the abnormal B cells thought to contribute to lupus. People with active, autoantibody-positive lupus may benefit from Benlysta when given in addition to standard drug therapy.
• Mycophenolate mofetil – A drug that suppresses the immune system and is also used to prevent the rejection of transplanted organs. It is being used increasingly to treat serious features of lupus, especially those previously treated by Cytoxan.

Preventative measures

The following measures are essential to reduce the chance of flares and organ damage.

• Careful protection from sun exposure using clothing, accessories and SPF 50+ broad-spectrum sunscreens. Sunscreens alone are not adequate.
• Smoking cessation
• Rest when needed.

Topical therapy

Intermittent courses of potent topical corticosteroids are important in the treatment of CLE. They should be applied accurately to the skin lesions.

The calcineurin inhibitors tacrolimus ointment and pimecrolimus cream can also be used.

Systemic therapy

Treatment of SLE depends on which are the predominant organs involved in the disease. Typically, any of the following drugs may be used alone or in combination.

• Systemic corticosteroids, such as prednisone or prednisolone. These are the mainstay of treatment in a seriously ill patient with acute LE.
• Hydroxychloroquine and other antimalarials—response rates are about 80% in CLE.
• Methotrexate—best response in subacute CLE and discoid CLE
• Immunosuppressives such as azathioprine, mycophenolate and cyclophosphamide
• Intravenous immunoglobulin
• Aspirin is recommended for antiphospholipid syndrome.
• Targeted biologic therapies under evaluation for SLE include belimumab (intravenous and subcutaneous formulations were registered by FDA for use in SLE in 2017) and off-label rituximab, abatacept, tocilizumab and eculizumab.

CLE is also sometimes treated with

• Retinoids (isotretinoin and acitretin)
• Dapsone.

Lifestyle and Home Remedies

Take steps to care for your body if you have lupus. Simple measures can help you prevent lupus flares and, should they occur, better cope with the signs and symptoms you experience. Try to:

• See your doctor regularly – Having regular checkups instead of only seeing your doctor when your symptoms worsen may help your doctor prevent flare-ups, and can be useful in addressing routine health concerns, such as stress, diet and exercise that can be helpful in preventing lupus complications.
• Be sun smart – Because ultraviolet light can trigger a flare, wear protective clothing — such as a hat, long-sleeved shirt and long pants — and use sunscreens with a sun protection factor (SPF) of at least 55 every time you go outside.
• Get regular exercise – Exercise can help keep your bones strong, reduce your risk of heart attack and promote general well-being.
• Don’t smoke – Smoking increases your risk of cardiovascular disease and can worsen the effects of lupus on your heart and blood vessels.
• Eat a healthy diet – A healthy diet emphasizes fruits, vegetables and whole grains. Sometimes you may have dietary restrictions, especially if you have high blood pressure, kidney damage or gastrointestinal problems.
• Ask your doctor if you need vitamin D and calcium supplements – There is some evidence to suggest that people with lupus may benefit from supplemental vitamin D. A 1,200- to 1,500-milligram calcium supplement taken daily may help keep your bones healthy.

Complications

Inflammation caused by lupus can affect many areas of your body, including your:

• Kidneys – Lupus can cause serious kidney damage, and kidney failure is one of the leading causes of death among people with lupus.
• Brain and central nervous system – If your brain is affected by lupus, you may experience headaches, dizziness, behavior changes, vision problems, and even strokes or seizures. Many people with lupus experience memory problems and may have difficulty expressing their thoughts.
• Blood and blood vessels – Lupus may lead to blood problems, including anemia and an increased risk of bleeding or blood clotting. It can also cause inflammation of the blood vessels (vasculitis).
• Lungs – Having lupus increases your chances of developing an inflammation of the chest cavity lining (pleurisy), which can make breathing painful. Bleeding into the lungs and pneumonia also are possible.
• Heart – Lupus can cause inflammation of your heart muscle, your arteries, or heart membrane (pericarditis). The risk of cardiovascular disease and heart attacks increases greatly as well.
• Infection – People with lupus are more vulnerable to infection because both the disease and its treatments can weaken the immune system.
• Cancer – Having lupus appears to increase your risk of cancer; however, the risk is small.
• Bone tissue death (avascular necrosis) – This occurs when the blood supply to a bone diminishes, often leading to tiny breaks in the bone and eventually to the bone’s collapse.
• Pregnancy complications – Women with lupus have an increased risk of miscarriage. Lupus increases the risk of high blood pressure during pregnancy (preeclampsia) and preterm birth. To reduce the risk of these complications, doctors often recommend delaying pregnancy until your disease has been under control for at least six months.

References

Types of Systemic Lupus Erythematosus/The Systemic Lupus Erythematosus (SLE) is a systemic autoimmune disease, with multisystemic involvement. The disease has several phenotypes, with varying clinical presentations in patients ranging from mild mucocutaneous manifestations to multiorgan and severe central nervous system involvement. Several immunopathogenic pathways play a role in the development of SLE. The lupus erythematosus (LE cell) was described by Hargraves in 1948. Several pathogenic autoantibodies have since been identified.

The systemic lupus erythematosus (SLE) is characterized by overt polyclonal B-cell activation and autoantibody (Ab) production. By contrast, cellular immune responses against all- or recall antigens are significantly impaired. Many pieces of evidence indicate that IL-10 overproduction plays a pivotal role in the disease and the contribution of the IL-10/IL-12 imbalance to the pathophysiology of SLE will be extensively discussed. The authors will further summarize the available data about the involvement of IFN-γ, TNF-α, TGF-β, and TALL-1. Other cytokines (IL-1, IL-2, IL-4, IL-6, IL-16, IL-17, and IL-18) will be briefly discussed.

Systemic Lupus Erythematosus

Types of Systemic Lupus Erythematosus

About 25% of patients with systemic lupus erythematosus (SLE) initially present with skin involvement. It is important to correctly classify cutaneous lupus erythematosus (CLE), as it helps determine the underlying type and severity of SLE. About 5–10% of patients with CLE develop SLE, and CLE is associated with less severe forms of SLE.

Skin manifestations of lupus erythematosus are commonly divided into lupus erythematosus–specific and non–specific disease. Note that four of the nine American College of Rheumatology criteria for SLE are skin signs (ie, malar/butterfly rash, discoid plaques, photosensitivity, and oral ulcers).

Lupus erythematosus–specific disease

Acute cutaneous lupus erythematosus

Forms of acute CLE include the following:

• Localised acute CLE — this presents with malar or ‘butterfly’ rash (symmetrical erythema and edema of the cheeks, forehead, chin, and V of the neck but sparing the nasolabial folds or ‘smile lines’)
• Generalised acute CLE — this presents with a widespread exanthematous eruption on the extensor surfaces, trunk, sun-exposed areas, and hands (but sparing the knuckles)
• Toxic epidermal necrolysis-like acute CLE — this is a life-threatening variant of acute CLE that presents with a massive epidermal injury; it occurs predominantly on sun-exposed skin and has a gradual, insidious onset, unlike toxic epidermal necrolysis.

Acute CLE is typically triggered or exacerbated by exposure to ultraviolet (UV) radiation. On recovery, there may be postinflammatory hyperpigmentation without scarring.

Subacute cutaneous lupus erythematosus

The subacute cutaneous lupus erythematosus (SCLE) starts as macules or papules that progress to hyperkeratotic plaques. SCLE is photosensitive so plaques usually occur on sun-exposed skin; these plaques do not lead to scarring but can result in postinflammatory hyperpigmentation or hypopigmentation. SCLE should be monitored to exclude any progression to SLE.

Forms of SCLE include:

• Annular SCLE — this subtype presents with slightly raised red lesions with central clearing
• Papulosquamous SCLE — this subtype presents with eczematous or psoriasis-like lesions on sun-exposed skin.

Chronic cutaneous lupus erythematosus

Chronic CLE is not as photosensitive as acute CLE or SCLE. Forms of chronic CLE include:

• The discoid lupus erythematosus (DLE) — this affects the face, outer ears, neck, sun-exposed areas and lips, and presents with discoid plaques (erythematous, well-demarcated plaques covered by scale) that become hyperkeratotic, leading to atrophy and scarring; there is follicular involvement, causing both reversible and irreversible (scarring) alopecia (hair loss); depigmentation of the peripheries is also common in certain ethnicities (Asian, Indian).
• Hypertrophic or verrucous lupus erythematosus — this is a rare form of CLE presenting with severe hyperkeratosis of the extensor surfaces of the arms, upper back and face; it has overlapping features with lichen planus.
• Mucosal lupus erythematosus — this affects 25% of patients with CLE; most commonly, painless erythematous patches on the oral mucosa develop into chronic plaques that can centrally ulcerate and also affect nasal, conjunctival and genital mucosa; oral lupus erythematosus rarely degrades to oral cancer (squamous cell carcinoma).

Drug-induced lupus erythematosus

Many drugs are thought to induce SLE and drug-induced lupus erythematosus often includes cutaneous signs. Drugs that induce lupus erythematosus include:

• Hydralazine
• Isoniazid
• Chlorpromazine
• Procainamide
• Phenytoin
• Minocycline
• Anti–tumour necrosis factor medications.

Rarer types of lupus erythematosus

The rarer types of lupus erythematosus include:

• Lupus profundus/lupus panniculitis — this is a rare form of chronic CLE with firm nodules in the lower dermis and subcutaneous tissue that causes lipodystrophy; some use the term lupus panniculitis to refer to subcutaneous involvement only, and lupus profundus when there is a combination of lupus panniculitis with DLE.
• Chilblain lupus erythematosus — this presents with purple-red patches, papules and plaques on toes, fingers and face, and is associated with nail fold telangiectasia; it is precipitated by exposure to the cold, so often presents in winter.
• Lupus erythematosus tumidus —this is a variant of chronic CLE with succulent or indurated erythematous plaques without surface change.

Lupus erythematosus — non–specific disease

Lupus erythematosus-nonspecific disease can relate to SLE or another autoimmune disease, but nonspecific cutaneous features are most often associated with SLE.

Common cutaneous features seen include:

• Photosensitivity — this is an abnormal response to UV radiation that is present in 50–93% of patients with SLE
• Mouth ulcers — these are present in 25–45% of patients with SLE
• Non–scarring hair loss in SLE — presenting as coarse, dry hair with increased fragility (also referred to as ‘lupus hair’).

Cutaneous vascular disease is also common. Forms of cutaneous vascular disease include

• Raynaud phenomenon — this presents with focal ulceration in the fingertips and periungual areas that can cause pitted scarring, hemorrhage and other nail fold complications
• Vasculitis — leukocytoclastic vasculitis: urticarial vasculitis presenting with tender papules and plaques over bony prominences; and medium or large vessel vasculitis can occur, presenting with purpuric plaques with stellate borders, often with necrosis and ulceration or subcutaneous nodules
• Thromboembolic vasculopathy — these may have a similar clinical presentation to vasculitis, but vessel occlusion is due to blood clots
• Livedo reticularis — characterized by net-like blanching red-purple rings that commonly arise on the lower limbs
• Erythromelalgia — characterized by burning pain in the feet and hands, and with macular erythema; it is associated with heat exposure.

Specific cutaneous SLE

Cutaneous lupus (CLE) has specific acute, subacute and chronic manifestations.

• Typically, SLE presents with acute CLE.
• About half of patients with subacute cutaneous LE develop mild SLE
• Only 5% of patients with chronic CLE have SLE, as CLE presents as a skin problem without the involvement of other organs.

Acute CLE

• Central face malar or “butterfly” violaceous erythema with a sharp cutoff at lateral margins, resolves without scarring (may result in persistent telangiectasia)
• Bullous systemic lupus erythematosus: a blistering rash, if severe, this may resemble toxic epidermal necrolysis
• A maculopapular rash resembling morbilliform drug eruption
• Mucosal erosions and ulcerations (lips, nose, mouth, genitals)
• Photosensitivity: lupus rashes are mainly on sun-exposed sites. Photosensitivity can be mild to very severe with the rash appearing after minimal light exposure.
• Diffuse hair loss (nonscarring alopecia) with brittle hair shafts

Subacute cutaneous LE

• Flat, scaly patches resembling psoriasis, often in a network pattern
• Annular (ring-shaped) polycyclic (overlapping circular) lesions
• Lesions resolve with minimal scarring
• Affects trunk and arms
• Flares on exposure to the sun, but usually spares face and hands

Chronic CLE

• Chronic CLE affects 25% of patients with SLE
• Classic discoid lupus is most common: indurated hyperpigmented plaques
• Localized (above the neck in 80%) or generalized (above and below the neck in 20%)
• Hypertrophic (warty) lupus
• Tumid lupus
• Lupus panniculitis/profundus
• Mucosal lupus (lips, nose, mouth, genitals)
• Chilblain lupus erythematosus
• Discoid lupus/lichen planus overlap
• Discoid lesions and panniculitis resolve with scarring

A more thorough categorization of lupus includes the following types

• acute cutaneous lupus erythematosus
• subacute cutaneous lupus erythematosus
• the discoid lupus erythematosus (chronic cutaneous
  • • childhood discoid lupus erythematosus
    • generalized discoid lupus erythematosus
    • localized discoid lupus erythematosus
  • the chilblain lupus erythematosus (Hutchinson)
  • lupus erythematosus-lichen planus overlap syndrome
  • lupus erythematosus panniculitis (lupus erythematosus profundus)
  • tumid lupus erythematosus
  • the verrucous lupus erythematosus (hypertrophic lupus erythematosus)
  • cutaneous lupus mucinosis
• complement deficiency syndromes
• drug-induced lupus erythematosus
• neonatal lupus erythematosus
• systemic lupus erythematosus

Causes of Systemic Lupus Erythematosus

Factors leading to SLE include:

• Genetic predisposition, including haplotype HLA-B8, -DR₃
• Exposure to sunlight
• Viral infection, particularly Epstein-Barr virus
• Hormones
• Toxins such as cigarette smoke
• Drugs in drug-induced LE
• Emotional upset.

The manifestations of SLE are due to loss of regulation of the patient’s immune system.

• Nuclear proteins are not processed properly.
• Nuclear debris accumulates within the cell.
• This leads to the production of autoantibodies against nuclear proteins.
• Immune complexes are not removed.
• The complement system is activated.
• Inflammation leads to cell and tissue injury.

Symptoms of Systemic Lupus Erythematosus

Common symptoms include:

• Chest pain during respiration
• Joint pain
• Oral ulcer
• Fatigue
• Weight loss
• Fever with no other cause
• General discomfort, uneasiness, or ill feeling (malaise)
• Hair loss
• Sensitivity to sunlight
• A “butterfly” facial rash, seen in about half people with SLE
• Swollen lymph nodes

Photosensitivity

Photosensitivity is a known symptom of lupus, but its relationship to and influence on other aspects of the disease remain to be defined.^[rx] Causes of photosensitivity may include:

• Change in autoantibody location
• Cytotoxicity
• Induction of apoptosis with autoantigens in apoptotic blebs
• Upregulation of adhesion molecules and cytokines
• Induction of nitric oxide synthase expression
• Ultraviolet-generated antigenic DNA.
• Tumor necrosis factor-alpha

Other symptoms include

• General – tiredness, malaise, chronic pain, fever with flares
• Joints – arthritis or synovitis causing swelling, pain and morning stiffness
• Lungs – pleurisy or pleural effusions
• Heart – pericarditis or pericardial effusions
• Kidneys – protein, casts in urine, glomerulonephritis
• Brain – seizures, psychosis, confusion
• Nervous system – mono neuritis multiplex, myelitis, peripheral neuropathy
• Blood – reduced numbers of red cells, white cells and platelets
• Cutaneous mucinosis  – characterized by indurated papules, nodules, or plaques on the trunk or arms
• Lupus nail dystrophy –  presenting as nail pitting, ridging, leukonychia, onycholysis, and red lunula
• Spontaneous chronic urticaria
• Lichen planus
• Acanthosis nigricans
• Sclerodactyly (spindle-shaped fingers)
• Erythema multiforme
• Cutis laxa
• Rheumatoid nodules.

• The acute cutaneous lupus erythematosus (including “butterfly rash“)
• The chronic cutaneous lupus erythematosus (e.g., localized or generalized discoid lupus erythematosus)
• Oral ulcers (on palate and/or nose)
• Non-scarring alopecia
• Synovitis (≥ 2 joints) or tenderness on palpation (≥ 2 joints) and morning stiffness (≥ 30 min)
• Serositis (pleurisy or pericardial pain for more than 1 day)
• Renal involvement (single urine: protein/creatinine ratio or 24-hour urine protein, >0.5 g)
• Neurological involvement (e.g., seizures, psychosis, myelitis)
• Hemolytic anemia
• Leukopenia (<4000/μL) or lymphopenia (<1000/μL)
• Thrombocytopenia (<100 000/μL)

Immunological criteria

• ANA level above the laboratory reference range
• Anti-dsDNA antibodies
• Anti-Sm antibodies
• Antiphospholipid antibodies (anticardiolipin and anti- β 2-glycoprotein I [IgA-, IgG- or IgM-] antibodies; false-positive VDRL [Venereal Disease Research Laboratory] test)
• Low complement (C3, C4, or CH50)
• Direct Coombs test (in the absence of hemolytic anemia)

Diagnosis of Systemic Lupus Erythematosus

Screening laboratory tests

• Erythrocyte sedimentation rate
• Blood count, differential blood count
• Creatinine
• Urinary status and sediment
• Antinuclear antibodies (ANA) (HEp-2 cell test with fluorescence pattern)

Further laboratory tests after positive screening^*1 (particularly in case of positive ANA)

• Further differentiation of ANA (particularly anti-Sm, -Ro/SSA, -La/SSB, -U1RNP antibodies, etc.)
• Anti-dsDNA antibodies (ELISA; confirmation by radioimmunoassay or immunofluorescence test with Crithidia luciliae)
• Complement C3, C4
• Antiphospholipid antibodies, lupus anticoagulant
• Glomerular filtration rate; 24-hour urine (if urine protein positive), alternatively: protein/creatinine ratio in single urine sample; investigation for dysmorphic erythrocytes in sediment
• Liver enzymes; lactate dehydrogenase; creatine kinase in presence of muscular symptoms
• Further laboratory tests depending on clinical symptoms
• Screening for comorbidities
• Assessment of vaccination status (vaccination recommendations [in German] at [rx)

Follow-up (SLE: every 3 to 6 months depending on disease course; lupus nephritis: initially every 2 to 4 weeks for the first 2 to 4 months)^*2

• Medical history (including new symptoms, comedication, infections), physical examination
• Evaluate disease activity with standardized score
• Evaluate damage according to standardized score (1 ×/year)
• Repeat screening for comorbidities (at least 1 ×/year)
• Ocular examination in patients taking hydroxychloroquine or chloroquine: baseline, then every 6 months (currently being revised by the German Society of Rheumatology in light of recommendations from the USA) (rx, rx)

Laboratory tests

• Erythrocyte sedimentation rate
• C-reactive protein (in suspected infection or pleurisy)
• Urine tests for hyaline casts, creatinine, protein and blood
• Blood pressure
• Chest X-ray, ultrasound, CT and MRI scans
• Electrocardiograph (ECG) and echocardiography
• Nerve and muscle testing
• Ophthalmological examination
• Endoscopy of the gastrointestinal tract
• Kidney biopsy.
• Blood count, differential blood count
• Creatinine
• Liver enzymes
• Urinary status (protein/creatinine ratio, 24-hour urine and microscopic examination of urinary sediment as needed)
• Complement C3, C4
• Anti-dsDNA antibodies
• Instrument-based diagnostics as needed

Modified after (2, 8), modified after (rx, rx, rx, rx, rx)

Using the SLICC criteria, SLE is diagnosed if the patient has either of the following over time:

• Four criteria including ≥ one clinical criterion and ≥ one immunological criterion
• Biopsy-proven lupus nephritis and antinuclear antibodies or anti-double-stranded DNA antibodies

These criteria depend on history, clinical examination, exclusion of other causes of the symptoms, and the results of investigations—including blood tests and biopsy of the affected tissue. Four of the 17 SLICC criteria relate to the skin.

Clinical criteria

• Acute or subacute cutaneous lupus
• Chronic cutaneous lupus
• Oral ulcers
• Nonscarring alopecia
• Synovitis involving 2 or more joints
• Serositis involving lungs or heart
• Renal involvement
• Neurological involvement
• Hemolytic anemia
• leukopenia or lymphopenia
• Thrombocytopenia

Immunological criteria

• Raised ANA level
• A raised anti-dsDNA antibody level
• Presence of anti-Sm
• Positive antiphospholipid antibody (lupus anticoagulant, false-positive rapid plasma reagin, high-titer anticardiolipin antibody, positive anti–2-glycoprotein I)
• Low complement levels
• Positive direct Coombs’ test

SLICC Systemic Lupus International Collaborating Clinics; ANA antinuclear antibody; anti-dsDNA anti-double-stranded DNA

Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI)

The Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) was developed in an attempt to classify the severity of CLE. [2] A score of activity and damage due to the disease is calculated in each of 12 anatomical locations (refer to the original published paper for details).

The total activity score is made up of:

• The degree of redness (0–3) and scale (0–2)
• Mucous membrane involvement (0–1)
• Recent hair loss (0–1), nonscarring alopecia (0–3)

Total damage score is made up of:

• The degree of dyspigmentation (0–2), and scarring (0–2)
• Persistence of dyspigmentation more than 12 months doubles the depigmentation score
• Scalp scarring (0,3,4,5,6)

Biopsy findings

Patients with SLE often undergo skin biopsy.

• Acute CLE: nonspecific dermatitis.
• Subacute CLE: features of lupus noted in the epidermis and superficial dermis
• Chronic discoid CLE: typical features of lupus with atrophy and scarring
• Direct immunofluorescence is positive in sun-protected healthy skin in SLE

Blood tests

Multiple autoantibodies are typically present in SLE, often in high titre (see immunological criteria above). Relating to skin disease in SLE:

• About 70% of patients with subacute CLE have positive extractable nuclear antibodies anti-Ro (also called anti-SSA) and anti-La (also called anti-SSB).
• Anti Ro/La is also associated with Sjogren syndrome and neonatal lupus.
• Low serum complement in SLE has been associated with urticarial vasculitis and renal disease.
• Antiphospholipid antibodies are associated with livedo reticularis, thrombosis, and pregnancy complications (antiphospholipid syndrome).
• Anti-annexin 1 antibodies may be a diagnostic marker for discoid CLE

Patients with SLE should also have renal, liver, and thyroid function and markers of inflammation performed, such as C-reactive protein (CRP), immunoglobulins, and rheumatoid factor.

Photoprovocation tests

• Photoprovocation tests  – are sometimes carried out to confirm that a skin eruption is precipitated by exposure to particular wavelengths of ultraviolet or visible radiation.
• Echocardiogram – Echocardiogram shows Pericardial effusion, mitral valve prolapse, left ventricular hypertrophy, and changes secondary to pulmonary hypertension.
• EKG – Abnormal EKG findings include hemiblock, bundle branch block, atrioventricular block, changes secondary to pericarditis, and pericardial effusion.
• Pulmonary function testing – Reduction in diffusion capacity for carbon monoxide, forced vital capacity, forced expiratory volume, and six-minute walk tests occur in ILD.
• Computed tomogram – High resolution computed tomogram is very sensitive in diagnosing ILD. Common findings include ground-glass opacities, linear opacities, subpleural micronodules, septal thickening, traction bronchiectasis usually with peripheral and lower lobe predominance. Honeycombing, airspace consolidation, emphysema, and centrilobular nodules are less common findings.[rx]
• Angiogram – Medium-sized arterial occlusions can occur in patients with Raynaud phenomenon.
• Right heart catheterization – Definitive diagnosis of pulmonary hypertension in MCTD requires right heart catheterization demonstrating mean pulmonary arterial pressure at rest greater than 25mmHg.

• Biopsy: histology, immunofluorescence if indicated

Joints

• Conventional X-ray
• Arthrosonography
• Magnetic resonance imaging (MRI)

Muscle

• Creatine kinase
• Electromyography
• MRI
• Muscle biopsy

Kidney

• Sonography
• Renal biopsy

Lung/heart

• Chest X-ray
• Thoracic high-resolution computed tomography (HR-CT)
• Lung function test including diffusion capacity
• Bronchoalveolar lavage
• (Transesophageal) echocardiography
• Cardiac catheterization
• Cardiac MRI
• Myocardial scintigraphy
• Coronary angiography

Eye

• Funduscopy/special investigations in patients on antimalarials

Central and peripheral nervous system

• Electroencephalography
• Primarily cranial MRI, special MRI techniques if indicated
• Computed tomography
• Cerebrospinal fluid analysis
• Transcranial Doppler/angiography
• Neuropsychiatric examination
• Measurement of nerve conduction velocity

Treatment of Systemic Lupus Erythematosus

• Nonsteroidal anti-inflammatory drugs (NSAIDs) – Over-the-counter NSAIDs, such as naproxen sodium (Aleve) and ibuprofen (Advil, Motrin IB, others), may be used to treat pain, swelling, and fever associated with lupus. Stronger NSAIDs are available by prescription. Side effects of NSAIDs include stomach bleeding, kidney problems, and an increased risk of heart problems.
• Antimalarial drugs – Medications commonly used to treat malaria, such as hydroxychloroquine (Plaquenil), affect the immune system and can help decrease the risk of lupus flares. Side effects can include stomach upset and, very rarely, damage to the retina of the eye. Regular eye exams are recommended when taking these medications.
• Corticosteroids – Prednisone and other types of corticosteroids can counter the inflammation of lupus. High doses of steroids such as methylprednisolone (A-Methapred, Medrol) are often used to control serious disease that involves the kidneys and brain. Side effects include weight gain, easy bruising, thinning bones (osteoporosis), high blood pressure, diabetes, and increased risk of infection. The risk of side effects increases with higher doses and longer-term therapy.
• Immunosuppressants – Drugs that suppress the immune system may be helpful in serious cases of lupus. Examples include azathioprine (Imuran, Azasan), mycophenolate mofetil (CellCept), and methotrexate (Trexall). Potential side effects may include an increased risk of infection, liver damage, decreased fertility and an increased risk of cancer.
• Biologics – A different type of medication, belimumab (Benlysta) administered intravenously, also reduces lupus symptoms in some people. Side effects include nausea, diarrhea and infections. Rarely, the worsening of depression can occur.
• Rituximab (Rituxan) –  can be beneficial in cases of resistant lupus. Side effects include allergic reaction to the intravenous infusion and infections.
• Hydroxychloroquine – Commonly used to help keep mild lupus-related problems, such as skin and joint disease, under control. This drug is also effective at preventing lupus flares.
• Cyclophosphamide –  A chemotherapy drug that has very powerful effects on reducing the activity of the immune system. It is used to treat severe forms of lupus, such as those affecting the kidneys or brain.
• Azathioprine – A medication originally used to prevent the rejection of transplanted organs. It is commonly used to treat the more serious features of lupus.
• Methotrexate – Another chemotherapy drug used to suppress the immune system. Its use is becoming increasingly popular for skin disease, arthritis, and other non-life-threatening forms of disease that have not responded to medications such as hydroxychloroquine or low doses of prednisone.
• Belimumab – This drug weakens the immune system by targeting a protein that may reduce the abnormal B cells thought to contribute to lupus. People with active, autoantibody-positive lupus may benefit from Benlysta when given in addition to standard drug therapy.
• Mycophenolate mofetil – A drug that suppresses the immune system and is also used to prevent the rejection of transplanted organs. It is being used increasingly to treat serious features of lupus, especially those previously treated by Cytoxan.

Preventative measures

The following measures are essential to reduce the chance of flares and organ damage.

• Careful protection from sun exposure using clothing, accessories and SPF 50+ broad-spectrum sunscreens. Sunscreens alone are not adequate.
• Smoking cessation
• Rest when needed.

Topical therapy

Intermittent courses of potent topical corticosteroids are important in the treatment of CLE. They should be applied accurately to the skin lesions.

The calcineurin inhibitors tacrolimus ointment and pimecrolimus cream can also be used.

Systemic therapy

Treatment of SLE depends on which are the predominant organs involved in the disease. Typically, any of the following drugs may be used alone or in combination.

• Systemic corticosteroids, such as prednisone or prednisolone. These are the mainstay of treatment in a seriously ill patient with acute LE.
• Hydroxychloroquine and other antimalarials—response rates are about 80% in CLE.
• Methotrexate—best response in subacute CLE and discoid CLE
• Immunosuppressives such as azathioprine, mycophenolate and cyclophosphamide
• Intravenous immunoglobulin
• Aspirin is recommended for antiphospholipid syndrome.
• Targeted biologic therapies under evaluation for SLE include belimumab (intravenous and subcutaneous formulations were registered by FDA for use in SLE in 2017) and off-label rituximab, abatacept, tocilizumab and eculizumab.

CLE is also sometimes treated with

• Retinoids (isotretinoin and acitretin)
• Dapsone.

Lifestyle and Home Remedies

Take steps to care for your body if you have lupus. Simple measures can help you prevent lupus flares and, should they occur, better cope with the signs and symptoms you experience. Try to:

• See your doctor regularly – Having regular checkups instead of only seeing your doctor when your symptoms worsen may help your doctor prevent flare-ups, and can be useful in addressing routine health concerns, such as stress, diet and exercise that can be helpful in preventing lupus complications.
• Be sun smart – Because ultraviolet light can trigger a flare, wear protective clothing — such as a hat, long-sleeved shirt and long pants — and use sunscreens with a sun protection factor (SPF) of at least 55 every time you go outside.
• Get regular exercise – Exercise can help keep your bones strong, reduce your risk of heart attack and promote general well-being.
• Don’t smoke – Smoking increases your risk of cardiovascular disease and can worsen the effects of lupus on your heart and blood vessels.
• Eat a healthy diet – A healthy diet emphasizes fruits, vegetables and whole grains. Sometimes you may have dietary restrictions, especially if you have high blood pressure, kidney damage or gastrointestinal problems.
• Ask your doctor if you need vitamin D and calcium supplements – There is some evidence to suggest that people with lupus may benefit from supplemental vitamin D. A 1,200- to 1,500-milligram calcium supplement taken daily may help keep your bones healthy.

Complications

Inflammation caused by lupus can affect many areas of your body, including your:

• Kidneys – Lupus can cause serious kidney damage, and kidney failure is one of the leading causes of death among people with lupus.
• Brain and central nervous system – If your brain is affected by lupus, you may experience headaches, dizziness, behavior changes, vision problems, and even strokes or seizures. Many people with lupus experience memory problems and may have difficulty expressing their thoughts.
• Blood and blood vessels – Lupus may lead to blood problems, including anemia and an increased risk of bleeding or blood clotting. It can also cause inflammation of the blood vessels (vasculitis).
• Lungs – Having lupus increases your chances of developing an inflammation of the chest cavity lining (pleurisy), which can make breathing painful. Bleeding into the lungs and pneumonia also are possible.
• Heart – Lupus can cause inflammation of your heart muscle, your arteries, or heart membrane (pericarditis). The risk of cardiovascular disease and heart attacks increases greatly as well.
• Infection – People with lupus are more vulnerable to infection because both the disease and its treatments can weaken the immune system.
• Cancer – Having lupus appears to increase your risk of cancer; however, the risk is small.
• Bone tissue death (avascular necrosis) – This occurs when the blood supply to a bone diminishes, often leading to tiny breaks in the bone and eventually to the bone’s collapse.
• Pregnancy complications – Women with lupus have an increased risk of miscarriage. Lupus increases the risk of high blood pressure during pregnancy (preeclampsia) and preterm birth. To reduce the risk of these complications, doctors often recommend delaying pregnancy until your disease has been under control for at least six months.

References