Dermatomyositis – Causes, Symptoms, Diagnosis, Treatment

Dermatomyositis is a rare acquired or autoimmune humoral-mediated muscle disease characterized by muscle weakness and a skin rash that causes muscle inflammation and disease condition in which antigen-specific antibodies are deposited in the microvasculature, either secondary to immune complex deposition or specific anti-endothelial cell binding [rx, rx]. It presents with symmetric proximal muscle weakness, skin rash, and extramacular manifestations, such as esophageal dysfunction and interstitial lung disease. Dermatomyositis is strongly associated with malignancy, especially in adults. This activity outlines the evaluation and management of dermatomyositis and highlights the role of the interprofessional team in improving care for patients with this condition. [rx][rx] Dermatomyositis presents with characteristic skin findings and symmetric proximal skeletal muscle weakness. Also, it can affect other organ systems such as the pulmonary, cardiovascular, and gastrointestinal systems.[rx]

Dermatomyositis is a rare autoimmune inflammatory myositis of unknown etiology affecting both children and adults. It involves striated muscles and skin. The juvenile form is associated with multisystemic vasculitis and a high frequency of calcinosis. However, unlike the adult form, it does not have an increased risk of malignancy. This activity explains when this condition should be considered, articulates how to properly evaluate for this condition, and highlights the interprofessional team’s role in caring for patients with this condition.

Types of Dermatomyositis

There are 6 different types of DM; they are

• Classic dermatomyositis (CDM),
• Amyopathic dermatomyositis (ADM),
• Homeopathic dermatomyositis (HDM),
• Amyopathic dermatomyositis (CADM), which evolves into classic DM (CADM → CDM) and juvenile dermatomyositis (JDM).^[rx]
• CDM is defined as the hallmark cutaneous manifestation with signs of proximal muscle weakness after the onset of skin disease within the first 6 months.^[rx]
• ADM is also associated with cutaneous involvement, it may occur within 6 months or greater of DM diagnosis, without any clinical or laboratory evidence of any skin or muscle disease.^[rx] In HDM, there is no subjective muscle weakness, especially after the first 6 months.

Causes of Dermatomyositis

The cause is unknown, but it may result from an initial viral infection or cancer, either of which could raise an autoimmune response.^[rx]

Between 7 and 30% of dermatomyositis arises from cancer, probably as an autoimmune response.^[rx] The most commonly associated cancers are ovarian cancer, breast cancer, and lung cancer.^[rx] 18 to 25% of people with amyopathic DM also have cancer.^[rx] Malignancy in association with dermatomyositis is more prevalent after age 60. Some cases are inherited, and HLA subtypes HLA-DR3, HLA-DR52, and HLA-DR6 seem to create a disposition to autoimmune dermatomyositis.^[rx]

Although the cause of dermatomyositis is unknown, several genetic, immunologic, and environmental factors are implicated in this condition.

• Genetic Factors – Multiple studies have indicated that patients with particular human leukocyte antigen (HLA) types are at higher risk of dermatomyositis. High-risk haplotypes include HLA-A68 in North American Whites[rx], HLA-DRB1*0301 in African Americans,[rx] HLA-DQA10104, and HLA-DRB107 in Han Chinese,[rx] DQA105 and DQB1*02 in people from the UK. Also, the DRB103-DQA105-DQB102 haplotype is strongly associated with the development of interstitial lung disease in dermatomyositis.[rx]
• Immunologic Factors – Although autoantibodies are detected in patients with dermatomyositis, it is unclear whether they play a role in pathogenesis.
• Infections – Viruses such as Coxsackie B virus, enterovirus, and parvovirus have been suspected of acting as triggers of dermatomyositis. There are multiple theories about the mechanisms of virus-induced autoimmunity. These include alteration of cellular proteins, breakdown of self-tolerance, an unmasking of previously hidden epitopes, autoantibody induced B cell activation, and molecular mimicry.[rx]
• Drugs – Several drugs can trigger dermatomyositis. These include antineoplastic drugs (hydroxyurea, cyclophosphamide), anti-infectious agents (penicillin, sulfonamides, isoniazid), non-steroidal anti-inflammatory drugs (diclofenac, phenylbutazone), D-penicillamine, statins, and certain vaccines.[rx]
• Radiation – Dermatomyositis has been observed to occur more frequently among women exposed to high-intensity ultraviolet radiation.[rx]

Genetic susceptibility is no longer in doubt since predisposing HLA systems have been identified. There is an activation of the complement leading to the deposition of the membrane attack complex in the wall of blood vessels, which causes microangiopathy and an inflammatory reaction.

Because the disorder appears to have seasonal clustering, it is believed that some infectious organisms may be playing a role in self-tolerance and the generation of the autoimmune response. Infections implicated include:

• Parvovirus B19
• Coxsackievirus
• Streptococcus
• Enteroviruses

Non-infectious agents implicated include silica exposure, silicone implants, and medications that decrease lipids. There is a strong association of JDM with HLA-DR3.

Symptoms of Dermatomyositis

The signs and symptoms of dermatomyositis can appear suddenly or develop gradually over time. The most common signs and symptoms include

• Skin changes – A violet-colored or dusky red rash develops, most commonly on your face and eyelids and on your knuckles, elbows, knees, chest, and back. The rash, which can be itchy and painful, is often the first sign of dermatomyositis.
• Muscle weakness – Progressive muscle weakness involves the muscles closest to the trunk, such as those in your hips, thighs, shoulders, upper arms, and neck. The weakness affects both the left and right sides of your body and tends to gradually worsen.
• Common characteristics of DM include proximal muscle weakness, muscle inflammation, and skin rash
• Skin involvement in DM usually manifests with characteristic papules over digits, erythema over the elbows and knees, a heliotrope rash around the eyes, periungual telangiectasias, and dystrophic cuticles.[rx] Muscle involvement usually manifests as proximal muscle weakness initially, with or without myalgias or tenderness. An amyopathic variant with minimal to no muscle inflammation has been described.[rx] There is a well-established association of DM with an increased risk of internal malignancy.[rx]
• One form the rashes take is called “heliotrope” (a purplish color) or lilac, but may also be red. It can occur around the eyes along with swelling, but also occurs on the upper chest or back what is called the “shawl” (around the neck) or “V-sign” above the breasts and may also occur on the face, upper arms, thighs, or hands.^[rx] Another form the rash takes is called Gottron’s sign which are red or violet, sometimes scaly, slightly raised papules that erupt on any of the finger joints (the metacarpophalangeal joints or the interphalangeal joints).^[rx][rx] Gottron’s papules may also be found over other bony prominences including the elbows, knees, or feet. All these rashes are made worse by exposure to sunlight, and are often very itchy, painful, and may bleed.^[rx]

Diagnosis of Dermatomyositis

History

The typical histopathologic findings of DM in muscle include perifascicular atrophy, endothelial cell swelling, vessel wall membrane attack complex (MAC) deposition, papillary necrosis, infarcts, major histocompatibility complex (MHC) I upregulation, and the presence of an inflammatory infiltrate consisting of T and B lymphocytes, macrophages, and plasma cells.[rx]

A comprehensive history and physical exam should be conducted in suspected cases of dermatomyositis, keeping in mind the following objectives:

• Identify the typical muscular and cutaneous signs and symptoms of dermatomyositis
• Exclude other causes of muscle weakness e.g., inherited, infectious or endocrine myopathy
• Conduct a detailed review of systems to determine if other organ systems are involved (respiratory, cardiac, esophageal)
• Evaluate for signs and symptoms of a possible underlying malignancy and perform age-appropriate cancer screening when indicated

Muscle weakness and skin findings comprise the main presenting symptoms in dermatomyositis. The onset of the disease may be insidious or acute with a waxing and a waning course.

Physical Examination

The hallmark clinical feature of IIM is symmetric proximal muscle weakness. It is manifested as difficulty in getting up from sitting position, climbing stairs, lifting heavy objects, and overhead abduction of the arm. In addition to muscle weakness, patients with dermatomyositis (DM) often present with a characteristic skin rash. Gottron papule and heliotrope rash are the pathognomonic skin finding of DM.

Description of the major skin findings in DM is given below

• Heliotrope rash – Violaceous rash on the eyelids sometimes associated with periorbital edema
• Gottron papules – Erythematous rash with variable papules on the extensor aspect of digits (metacarpophalangeal, proximal interphalangeal, and distal interphalangeal joints)
• Gottron sign – Erythematous papules, macules, or patches on sites other than hands, particularly extensor surfaces of elbows, knees, and ankles.
• Shawl sign – Erythematous rash on the anterior chest (in a V-sign) and upper back
• Mechanic’s hands – Dilated capillary loops at the base of the fingernails, irregular and thickened cuticles, and cracked palmar fingertips
• Holster sign – Poikiloderma on the lateral aspects of the thigh (areas protected from sunlight)

These lesions (except holster sign) are photosensitive and may be aggravated by ultraviolet radiation. Other manifestations include dystrophic cuticles, peri-ungual erythema, abnormal nail bed capillary loops, diffuse flat erythema over the forehead, chin, and knees; photosensitivity; shawl sign; V-sign; panniculitis; and calcinosis cutis.

Dermatomyositis includes several clinically distinct phenotypes, and specific autoantibodies are associated with each unique phenotype.

Muscular

• Muscle weakness is the most common presenting symptom in dermatomyositis. The weakness usually has a subacute onset with the development of gradually progressive symmetric proximal muscle weakness. Patients may report difficulty in carrying out activities such as climbing stairs, getting up from a seated position, lifting objects, combing hair, and raising their head from a pillow.
• Distal muscle weakness, muscle pain, and stiffness are uncommon in dermatomyositis. In severe cases, dysphagia, or dysphonia may be present. The examination may reveal reduced muscle strength of proximal muscles, such as the deltoids, hip flexors, and neck flexors. Usually, muscle tenderness is mild, and distal muscle strength is preserved. Depressed deep tendon reflexes and muscle atrophy are not seen unless the disease is severe and long-standing.

Cutaneous

Skin changes may precede or may coincide with the onset of muscular symptoms. Patients can present with several types of skin rashes, photosensitivity, changes in pigmentation, and pruritis. Dermatomyositis can also cause nail changes and alopecia.

Pathognomonic findings of dermatomyositis include the following:

• Gottron papules – dorsal metacarpophalangeal and interphalangeal joints may show the presence of overlying erythematous or violaceous papules with or without scaling or ulceration.
• Heliotrope rash – This is a characteristic skin finding of dermatomyositis and presents with a violaceous, or an erythematous rash affecting the upper eyelids with or without periorbital edema. This finding may not be apparent in patients with dark skin patients.

Other skin findings that may help differentiate dermatomyositis from other conditions include the following

• Gottron sign – erythematous macules or patches over the elbows or knees
• Facial erythema – erythema over the cheeks and nasal bridge involving the nasolabial folds. The rash may extend up to the forehead and laterally up to the ears.
• Shawl sign – erythema over the posterior aspect of the neck, upper back, and shoulders at times, extending to the upper arms.
• V sign – ill-defined erythematous macules involving the anterior aspect of the neck and the upper chest.
• Poikiloderma – atrophic skin with changes in pigmentation and telangiectasia in photo-exposed or non-exposed areas.
• Holster sign – poikiloderma involving the lateral aspects of the thighs.
• Periungual involvement – telangiectasias and cuticular overgrowth
• Mechanic’s hands – hyperkeratotic, cracked horizontal lines on the palmar and lateral aspects of the fingers.
• Scalp involvement – diffuse poikiloderma, with scaling and pruritis.
• Calcinosis cutis – calcium deposits in the skin

Associate

• Joints – Dermatomyositis can cause non-erosive polyarthritis or arthralgia of the small joints of the hands. Patients may present with joint pain or swelling.
• Respiratory – Patients may present with exertional dyspnea, exercise intolerance, and non-productive cough due to underlying interstitial lung disease (ILD). Auscultation of the chest may reveal the presence of bilateral dry crackles. Reduced chest movement may be seen due to respiratory muscle weakness.
• Esophageal – Patients may report difficulty swallowing solids and liquids due to the weakness of the muscles of the oropharynx and upper esophagus. They may also have symptoms of gastroesophageal reflux.
• Other findings – Other findings that may present in dermatomyositis include Raynaud’s phenomenon, gastrointestinal ulcers, and cardiac symptoms. Systemic symptoms such as fever, malaise, and weight loss may be present, which may indicate an occult malignancy. The following factors may predict malignancy; male gender, older age at onset, the presence of dysphagia, and the absence of interstitial lung disease.[rx].

Muscle Biopsy

Muscle biopsy often shows the following findings, which can be diagnostic

• Perivascular and perimysial inflammatory infiltrate – The infiltrate in dermatomyositis is concentrated around the perivascular and interfascicular regions and consists of B cells, CD4+ T helper cells, macrophages, and plasmacytoid dendritic cells. In contrast to polymyositis, CD8+ T cells and NK cells are rarely present.
• Perifascicular atrophy – Atrophy of muscle fibers, especially around the periphery of fascicles, is a hallmark histopathological feature of dermatomyositis. Degenerating and regenerating muscle fibers may be observed in the perifascicular region.
• Microangiopathy – Injury to intramuscular blood vessels takes the form of immunoglobulin and complement (C5b-C9 membrane attack complex) deposits on endomysial capillaries. A reduced capillary density and endothelial hyperplasia may be observed.[rx][rx]

Skin Biopsy

• Skin biopsy findings in dermatomyositis are similar to those found in systemic lupus erythematosus. Typical findings include vacuolar changes of the basal layer, increased lymphocytic infiltrate, and increased mucin deposition in the dermis.[rx]

Lab Investigations

• Muscle Enzymes – Initial testing in suspected cases of dermatomyositis should include muscle enzymes, such as creatine kinase (CK), aldolase, lactate dehydrogenase (LDH), aspartate aminotransferase (AST), and alanine aminotransferase (ALT). Testing for muscle enzymes helps to guide further diagnostic studies and to assess response to therapy. In some cases, the elevation of muscle enzymes occurs prior to the appearance of muscle weakness.
• Autoantibodies – Antinuclear antibodies (ANA) are present in a majority of patients with dermatomyositis but do not help to make a diagnosis. Instead, testing should focus on detecting myositis-specific autoantibodies (MSA), which are present in approximately 30% of dermatomyositis and polymyositis patients. Testing for myositis-specific antibodies offers valuable information for determining the prognosis and can help to predict the pattern of organ involvement. Aminoacyl-transfer (t) ribonucleic acid synthetase (also known as an antisynthetase antibody) is the most common myositis-specific autoantibody associated with dermatomyositis. Anti-Jo is the most common antisynthetase antibody found in dermatomyositis.
• An abnormal elevation of serum – activities of muscle enzymes is the most common biological finding in JDM.  Elevation of creatine kinase is expected in 75% to 85% of cases with average values around 2000 U/L plus or minus 1000. A normal rate can be observed at the beginning of the disease and in amyopathic forms. Regular creatine phosphokinase (CPK) monitoring is recommended during the evolution under treatment to evaluate its effectiveness.

The following autoantibodies are associated with specific complications and findings

• Anti-Jo – antisynthetase syndrome consisting of interstitial lung disease, mechanic’s hands, Raynaud phenomenon, sclerodactyly, and arthritis.
• Anti-Mi2 (directed against-helicase) – Acute onset disease, V-neck sign, and shawl rash
• Anti- SRP (directed against signal recognition particle) – severe myositis, resistant to treatment
• Anti- MDA5 (melanoma differentiation-associated gene 5) – severe cutaneous involvement, amyopathic dermatomyositis, and rapidly progressive ILD
• Anti- TIF-1 gamma (transcription intermediary factor) /Anti-p155/140 – malignancy
• Anti-SAE (ubiquitin-like modifier activating enzyme) – dysphagia, skin disease preceding myositis
• Anti-NXP2 (nuclear matrix protein 2) – calcinosis cutis[rx]

Electromyography (EMG)

Electromyography helps to identify which groups of muscles are most affected and provides guidance about which muscles to biopsy. It also helps to distinguish dermatomyositis from neuropathic conditions. However, the electromyographic findings are not specific and may be absent in 11% of patients.[rx] Findings suggestive of dermatomyositis include the following:

• Increased insertional activity
• Spontaneous fibrillations
• Positive sharp waves
• Complex repetitive discharges
• Early recruitment
• Low-amplitude, short polyphasic motor unit potentials

Radiology

• Chest radiography – Every patient with dermatomyositis should undergo chest radiography to screen for interstitial lung disease. If the patient has respiratory symptoms or abnormal chest X-ray findings, further testing with high-resolution computer tomography (HRCT) of the chest. In addition, pulmonary function tests should be performed. Findings on HRCT suggestive of interstitial lung disease include nodules, fibrosis, linear opacities, honey-combing, or consolidation.
• Magnetic resonance imaging (MRI) – Magnetic resonance imaging of skeletal muscles is a non-invasive and sensitive test to evaluate myositis. Typical findings include muscle edema, areas of inflammation; that appear hyperintense on T2-weighted images; and fat suppression.[rx]
• Barium swallow – may be done if esophageal dysfunction is present.
• Using testing of electric signaling in muscles, finding all three of – erratic, repetitive, high-frequency signals; short, low-energy signals between skeletal muscles and motor neurons that have multiple phases; and sharp activity when a needle is inserted into the muscle

Histopathology

• Muscle biopsy is the most accurate test to confirm the diagnosis of dermatomyositis and to exclude other causes of muscle weakness or skin rash. However, choosing the right muscle for a biopsy is crucial to prevent a missing diagnosis.
• Muscle biopsy should be obtained on weak muscles as identified by physical exam or contralateral to the abnormal muscles, as identified by electromyography.
• A muscle biopsy should be obtained from patients with suspected dermatomyositis but who lack the characteristic skin findings. Similarly, patients who have the characteristic skin manifestations of dermatomyositis but lack muscle weakness should undergo a skin biopsy procedure.[rx]

Other Investigations

Other baseline lab investigations include

• Using a blood test, finding higher levels of enzymes found in skeletal muscle, including creatinine kinase, aldolase, and glutamate oxaloacetate, pyruvate transaminases and lactate dehydrogenase
• A complete blood count with differential,
• Creatinine,
• Liver function tests, and inflammatory markers
• Erythrocyte sedimentation rate (ESR) and
• C-reactive protein (CRP)
• Serum Thyroid-stimulating hormone (TSH) may be ordered to exclude hypothyroidism.
• Electrocardiography (ECG) may be ordered to look for conduction abnormalities that might be subclinical.
• Pulmonary function tests may be conducted to assess the severity of pulmonary involvement. Patients with interstitial lung disease show a restrictive defect on pulmonary function tests with reduced forced vital capacity (FVC), reduced total lung capacity (TLC), and diminished diffusing capacity.

Investigations for Malignancy

• Colonoscopy (or fecal occult blood test),
• Urine analysis, mammography, and pap smears. Women at high risk of ovarian cancer should be screened, with serial measurements of CA-125 and
• Transvaginal ultrasound. There is no consensus on the frequency and how extensively patients with dermatomyositis should undergo cancer screening. [rx]

Treatment of Dermatomyositis

The goals of managing dermatomyositis are focused on treating muscle weakness, skin disease, and addressing any other underlying complications.

Medications

Medications used to treat dermatomyositis include:

• Systemic glucocorticoids – The first-line treatment of muscle disease in dermatomyositis is systemic glucocorticoids with or without immunosuppressants. Although there is no standard systemic steroid regimen specified for dermatomyositis, the general principles of therapy are the same. Although systemic glucocorticoids can control muscle disease, they are not effective in controlling skin disease.
• Prednisolone – is given at high doses for the first few months until the muscle enzyme levels decline, and muscle strength improves. During this time, patients should be regularly evaluated for an adequate response, keeping in mind that it takes approximately six weeks for muscle enzymes to normalize. Also, it may require as long as three months for muscle weakness to improve. Once an adequate response occurs, the administration of systemic steroids is gradually tapered off over time. The total duration of therapy with systemic steroids usually spans between nine and twelve months. It is important to note that administering high-dose glucocorticoids for more than six weeks may lead to glucocorticoid myopathy.
• Immuno-suppressants – First-line agents include azathioprine and methotrexate. Administration of an immuno-suppressant such as azathioprine is preferred in patients with liver involvement, interstitial lung disease, and those who are unable to abstain from alcohol. On the other hand, methotrexate has the advantage of once-a-week dosing. The choice of immunosuppressant depends on many factors, including dosing frequency, systemic involvement, adverse effects, and alcohol use. Patients who do not respond satisfactorily to therapy with steroids and azathioprine or methotrexate are considered resistant. Treatment options for resistant cases include rituximab, mycophenolate mofetil, calcineurin inhibitors, intravenous immunoglobulin (IVIG), and cyclophosphamide. Rituximab is an anti-CD 20 agent and is the recommended first-line agent in resistant cases. If this fails, intravenous immunoglobulin or a combination of azathioprine and methotrexate can be used as second-line therapy. Mycophenolate mofetil and tacrolimus are useful in refractory cases, especially if there is a concomitant interstitial lung disease. Cyclophosphamide is preferred in cases of rapidly progressive interstitial lung disease.
• Cotreatment with folic acid or leucovorin  – can help to minimize these adverse effects. Azathioprine can cause a flu-like reaction, which may require discontinuation of therapy. It also causes myelosuppression and pancreatitis. Cyclophosphamide increases the risk of malignancy and should be avoided unless multiple drug therapies have failed.
• Corticosteroid-sparing agents – When used with a corticosteroid, these drugs can decrease the dose and side effects of the corticosteroid. The two most common medications for dermatomyositis are azathioprine (Azasan, Imuran) and methotrexate (Trexall). Mycophenolate mofetil (Cellcept) is another medication used to treat dermatomyositis, particularly if the lungs are involved.
• Antimalarial medications – For a persistent rash, your doctor might prescribe an antimalarial medication, such as hydroxychloroquine (Plaquenil).
• Sunscreens – Protecting your skin from sun exposure by applying sunscreen and wearing protective clothing and hats is important for managing the rash of dermatomyositis. These measures should include sun-protective measures, such as sunlight avoidance, the use of sun-protective clothing, and sunscreen with sun protective factor (SPF) of 30 or higher.
• Cream, patches, gel, ointment – due to skin disease can be disabling and can be managed by employing local agents (pramoxine, menthol, camphor) or oral drugs (e.g., sedating antihistamines, amitriptyline, gabapentin). Medical therapy for skin disease includes topical agents and systemic medications. Topical agents include corticosteroids and calcineurin inhibitors. The most commonly used systemic agents to treat skin disease are hydroxychloroquine and methotrexate.
• Calcinosis – which occurs more frequently in juvenile dermatomyositis, can be managed with calcium channel blockers such as diltiazem. In some cases, surgical removal of calcinotic nodules may be indicated. Adjunctive hygienic-dietary measures, as well as daily supplementation with calcium and vitamin D,  must be systematic.
• Vitamin E capsule – Vitamin E is a group of eight fat-soluble compounds that include four tocopherols and four tocotrienols. Vitamin E deficiency, which is rare and usually due to an underlying problem with digesting dietary fat rather than from a diet low in vitamin E, can cause nerve problems.
• Vitamin B Complex – is a class of water-soluble vitamins that play important roles in cell metabolism. Though these vitamins share similar names, they are chemically distinct compounds that often coexist in the same foods. In general, dietary supplements containing all eight are referred to as a vitamin B complex. Individual B vitamin supplements are referred to by the specific number or name of each vitamin.
• Anti-resorptive therapy – may be indicated in patients on long-term systemic corticosteroids in order to prevent osteoporosis. Patients on high-dose systemic glucocorticoids or immunosuppressants should be considered for prophylaxis against Pneumocystis jirovecii with trimethoprim and sulfamethoxazole. Lastly, all patients should receive the appropriate immunizations prior to receiving immunosuppressants.

Therapy

Physical therapy and rehabilitation play an essential role in management. Patients with mild disease should be encouraged to participate in active exercise programs. Range of motion exercises can help in preventing contractures. Patients with esophageal dysfunction may require consultation with speech therapy and may also require measures to prevent aspiration. Anti-aspiration measures include elevation of the head off the bed, thickening of feeds, and even feeding via gastric tubes when indicated.

Depending on the severity of your symptoms, your doctor might suggest

• Physical therapy – A physical therapist can show you exercises to help maintain and improve your strength and flexibility and advise you about an appropriate level of activity.
• Speech therapy – If your swallowing muscles are affected, speech therapy can help you learn how to compensate for those changes.
• Dietetic assessment – Later in the course of dermatomyositis, chewing and swallowing can become more difficult. A registered dietitian can teach you how to prepare easy-to-eat foods.

Surgical and other procedures

• Intravenous immunoglobulin (IVIg) – IVIg is a purified blood product that contains healthy antibodies from thousands of blood donors. These antibodies can block the damaging antibodies that attack muscle and skin in dermatomyositis. Given as an infusion through a vein, IVIg treatments are expensive and might need to be repeated regularly for the effects to continue.
• Surgery – Surgery might be an option to remove painful calcium deposits and prevent recurrent skin infections.

References