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Fingernail Infection; Causes, Symptoms, Diagnosis, Treatment

Fingernail Infection is the most common nail infective disorder, and it is responsible for about 50% of all consultations for nail disorders. Fingernail infection or Onychomycosis has been reported as a gender- and age-related disease, being more prevalent in males and increases with age in both genders [rx]. In the elderly, onychomycosis may have an incidence of>40% [rx]. Predisposing factors are diabetes mellitus, peripheral arterial disease, immunosuppression due to HIV or immunosuppressive agents [rx].

Onychomycosis or fingernail infection, also known as tinea unguium, is a fungal infection of the nail.^[rx] Symptoms may include white or yellow nail discoloration, thickening of the nail, and separation of the nail from the nail bed.^[rx]^[rx] Toenails or fingernails may be affected, but it is more common for the toenails to be affected.^[rx] Complications may include cellulitis of the lower leg.^[rx] A number of different types of fungus can cause onychomycosis including dermatophytes and Fusarium.^[rx] Risk factors include athlete’s foot, other nail diseases, exposure to someone with the condition, peripheral vascular disease, and poor immune function.^[rx] The diagnosis is generally suspected based on the appearance and confirmed by laboratory testing.^[rx]

Types of Fingernail infection^[rx]

Distal subungual onychomycosis or fingernail infection – is the most common form of tinea unguium^[rx] and is usually caused by Trichophyton rubrum, which invades the nail bed and the underside of the nail plate.
White superficial onychomycosis or fingernail infection– (WSO) is caused by fungal invasion of the superficial layers of the nail plate to form white islands on the plate. It accounts for around 10 percent of onychomycosis cases. In some cases, WSO is a misdiagnosis of keratin granulations which are not a fungus, but a reaction to nail polish that can cause the nails to have a chalky white appearance. A laboratory test should be performed to confirm.^[rx]
Proximal subungual onychomycosis or fingernail infection – is fungal penetration of the newly formed nail plate through the proximal nail fold. It is the least common form of tinea unguium in healthy people but is found more commonly when the patient is immunocompromised.^[rx]
Candidal onychomycosis fingernail infection – is Candida species invasion of the fingernails, usually occurring in persons who frequently immerse their hands in water. This normally requires the prior damage of the nail by infection or trauma.

Causes of Fingernail Infection

Onychomycosis

Fungi thrive in moist, warm areas, such as locker rooms, tanning beds, swimming pools, and skin folds; accordingly, those that cause dermatophytosis may be spread by using exercise machines that have not been disinfected after use, or by sharing towels, clothing, or footwear, such as rental bowling shoes, ski boots, ice skates or roller skates.
Opportunistic infections (infections that are caused by a diminished immune system) are frequent. The fungus from an athlete’s foot infection can spread to the groin through clothing. Tight, restrictive clothing, such as jockstraps, traps heat and moisture, providing an ideal environment for the fungus.^[rx]

Innate Immune Response

Dermatophytes contain cell wall carbohydrate molecules (β-glucan) that are recognized by innate immune mechanisms, such as Dectin-1 and Dectin-2, which activate toll-like receptors 2 and 4 (TLR-2 and TLR-4). Dectin-1 amplifies the production of tumor necrosis factor-α and IL-17, IL-6, and IL-10, all of which stimulate adaptive immunity.[rx,rx]
Keratinocytes in the presence of dermatophyte antigens, such as trichophyton, release IL-8, a potent neutrophilic chemo-attractant. A recent study shows the involvement of TLR-2 and TLR-4 in localized and disseminated dermatophytosis due to T. rubrum. Reduced expression of TLR-4 in the lower and upper epidermis of both localized and disseminated dermatophytosis patients was found compared to controls; TLR-2 expression was preserved in the upper and lower epidermis of all three groups.[rx,rx]

Adaptive Immune response

Humoral immunity – Humoral immunity to dermatophytes is not protective. High levels of specific IgE and IgG4 are detected in patients with chronic dermatophytosis which is responsible for positive (IgE mediated) IH tests to Trichophyton. On the other hand, Ig levels are low in patients that present positive delayed type hypersensitivity (DTH) skin test. The IH skin test for Trichophyton is associated with the presence of serum IgE and IgG (mostly IgG4) against Trichophyton antigens, hallmarks of a Th2 response. Here, IL-4 produced by CD4 T-cells (Th2 cells) induces antibody isotype switching to IgG4 and IgE
Cell-mediated immunity – Several experiments have shown that the resolution of dermatophytosis is mediated by DTH. Immunity to pathogens could be regulated by Th1 or Th2 subsets which would ultimately determine the outcome of the infection. An acute inflammatory response correlates with a positive DTH skin test to trichophytin and clearing of the infection whereas chronic infection is associated with high IH and low DTH.[rx]

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Possible risk factors associated with foot mycosis based on the questionnaire.

Risk factors	Patients with foot mycosis		p-value
Risk factors	Number	%	p-value
*Chronic diseases*
Diabetes history
Present	41	11.8	0.815
Absent	305	88.1	0.815
Peripheral vascular disease
Present	76	21.9	0.293
Absent	270	78.03	0.293
Immunosuppressive drugs
Present	19	5.4	0.018
Absent	327	94.5	0.018
*Skin disorders*
Psoriasis
Present	6	1.7	0,368
Absent	340	98.2	0,368
Fungal infection of the skin
Present	7	2.02	0,330
Absent	339	97.9	0,330
Dermatological pathology
Present	11	3.1	0.220
Absent	335	96.8	0.220
Associated fingernails onychomycosis
Present	26	7.5	0.010
Absent	320	92.4	0.010
Lifestyle
Family history of foot mycosis
Present	99	28.6	0.244
Absent	247	71.3	0.244
Ritual washing
Present	196	56.6	0.410
Absent	150	43.3	0.410
Physical activities
Present	51	14.7	0.049
Absent	295	85.2	0.049
Wearing used shoes
Present	91	26.3	0.001
Absent	255	73.6	0.001
Occlusive shoes
Present	46	13.2	0,008
Absent	300	86.8	0,008
Nail trauma
Present	92	26.5	0.019
Absent	254	73.4	0.019
Swimming pools
Present	28	8.09	0,045
Absent	318	91.9	0,045
Communal shower
Present	175	50.5	0.631
Absent	171	49.4	0.631
Smoking
Present	13	3.7	0,181
Absent	333	96.2	0,181
Obesity
Present	8	2.3	0.297
Absent	338	97.6	0.297
Walking barefoot
Present	34	9.82	0,524
Absent	312	90.1	0,524
Thermal station
Present	29	8.3	0.021
Absent	317	91.6	0.021
Pedicure
Present	49	14.1	0,006
Absent	297	85.9	0,006
Application of henna
Present	6	1.73	0.832
Absent	340	98.2	0.832
Antifungal therapy
Present	89	25.7	0.013
Absent	257	74.2	0.013

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Symptoms of Fingernail Infection

Onychomycosis

Specific signs can be

Red, scaly, itchy or raised patches
Patches may be redder on outside edges or resemble a ring
Patches that begin to ooze or develop a blister
Bald patches may develop when the scalp is affected
Nails may thicken, discolor or begin to crack^[10]
Cracking and peeling skin on your feet, most commonly between your toes and on your soles
Dry skin on your soles or sides of your feet
Raw skin on your feet
Discolored, thick, and crumbly toenails
Toenails that pull away from the nail bed
Itchy erosions and/or scales between the toes, especially between 4^th and 5^th toes
Scale covering the sole and sides of the feet (hyperkeratotic/moccasin type, usually caused by T. rubrum)
mall to medium-sized blisters, usually affecting the inner aspect of the foot (vesiculobullous type).
It can also uncommonly cause oozing and ulceration between the toes (ulcerative type), or pustules (these are more common in tinea pedis due to T. interdigitale than that due to T. rubrum).

Diagnosis of Fingernail Infection

Laboratory investigations

The following are the various laboratory tests that can be used for confirming a diagnosis of dermatophytosis.

Direct microscopic examination – [rx] Treatment of skin specimen with 10–20% potassium hydroxide (KOH) is a quick and inexpensive bedside tool to provide evidence of dermatophyte infection. Positive scrapings are characterized by the presence of refractile, long, smooth, undulating, branching, and septate hyphal filaments with or without arthroconidiospores. False-negative results are seen in 15% of cases. Fluorescent staining with optical brighteners (diamino stilbene) is the most sensitive method to microscopically detect fungi in skin scales as well as in specimens from nails and hair.[rx] These substances bind to chitin, the main cell wall component of fungi
Culture and antifungal sensitivity – [rx] Sabouraud dextrose agar (SDA, 4% peptone, 1% glucose, agar, water) is the most commonly used isolation media for dermatophytosis and serves as the medium on which most morphologic descriptions are based. The development of the colony takes 7–14 days. Modified SDA, with the addition of gentamicin, chloramphenicol, and cycloheximide is more selective for dermatophytes as chloramphenicol inhibits the growth of saprophytic fungus. The dermatophyte test medium is an alternative to isolation media that contain pH indicator phenol red. It is incubated at room temperature for 5–14 days.

Antifungal Susceptibility Testing

Microdilution method – The broth microdilution assay for antifungal susceptibility testing of dermatophytes has been previously developed as a modification of the Clinical and Laboratory Standards Institute M38-A2 standard method. The final concentrations of terbinafine and itraconazole used is 0.06–32.0 μg/ml and for fluconazole, 0.13–64.0 μg/ml.[rx] A standardized inoculum is prepared by counting the microconidia microscopically. Cultures are grown on SDA slants for 7 days at 35°C to produce conidia.
Sterile normal saline (85%) – is added to the agar slant, and the cultures are gently swabbed with a cotton-tipped applicator to dislodge the conidia from the hyphal mat. The suspension is transferred to a sterile centrifuge tube, and the volume is adjusted to 5 ml with sterile normal saline. The resulting suspension is counted on a hemacytometer and is diluted in RPMI 1640 medium to the desired concentration.
Minimum fungicidal concentration (MFC) determination – For determination of the MFC, 100-μl aliquots are removed from the assay wells showing no visible growth at the end of incubation and streaked onto SDA plates. The plates are incubated at 30°C for 7 days. The MFC is defined as the lowest drug concentration at which no visible fungal growth or colonies developed
Dermatophyte identification – This can be based on colony characteristics, microscopic morphology, and physiologic tests. Dermatophytes can be distinguished based upon their morphology of the macroconidia. Few physiological tests are available which help in confirmation of certain species.

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Histopathology

Histology may be used in the diagnosis of Majocchi’s granuloma in which KOH examination of scale on the surface may more often be negative.
When present, hyphae may be appreciated in stratum corneum on hematoxylin and eosin staining. Special stains most commonly used are periodic acid-Schiff and Gomori methenamine silver which helps to highlight hyphae.

Dermoscopy

The comma hairs, which are slightly curved, fractured hair shafts, and corkscrew hair shave been described as the dermoscopic marker of tinea capitis. Broken and dystrophic hairs are also seen. However, in tinea corporis, the involvement of vellus hair as seen on dermoscopy is an indicator of systemic therapy.[rx]

Polymerase chain reaction and nucleic acid sequence-based amplification

These tests not only help in the rapid and early diagnosis of infection but also help in determining drug resistance,[rx] and include:

Uniplex PCR for direct dermatophyte detection in clinical samples: A PCR for the direct detection of dermatophytes in skin scales is available as in-house PCR-ELISA assay which separately identifies numerous dermatophyte species. In a pilot study, the sensitivity and specificity of the test compared to cultures was 80.1% and 80.6%
Multiplex PCR for fungal detection in dermatophytes: Commercially available multiplex PCR tests enable simultaneous amplification of 21 dermatomycotic pathogens with subsequent DNA detection by means of agarose gel electrophoresis.

New molecular methods like matrix-assisted laser desorption ionization-time of flight mass spectrometry

It is based on the detection of biochemical characteristics, proteolytic degradation product which is a result of the activity of mycological infections or noninfectious diseases. These are represented by proteolytic degradation products of native proteins.
The peptide patterns of affected samples are identified by comparison with known peptide spectra from skin disorders stored in an already existing database. This procedure is immensely time-saving, as it enables simultaneous identification of up to 64 dermatophyte strains, with results coming back within 24 h.[rx]

Reflectance confocal microscopy

It provides in vivo imaging of the epidermis and superficial dermis at cellular level resolution and can be used to detect cutaneous fungi and parasitic infestations.[rx] Branching fungal hyphae can be detected over an erythematous annular scaly patch. The advantage of the test is noninvasive and in a retrospective analysis of the test by Friedman et al. sensitivity was found to be 100%.

Treatment of Fingernail Infection

Non-pharmacological

Non-pharmacological treatment focuses on educating patients about the predisposing factors, and the chronic nature of the disease. Also, measures that are aimed at eliminating the moisture that provides the environment for infection and its recurrence should be discussed fully with the patients. Instructions about wearing open-toed shoes and avoiding skin maceration are essential.

Some of the prescription medications your doctor may prescribe for athlete’s foot include:

Topical, prescription-strength clotrimazole or miconazole
Oral antifungal medications such as itraconazole, fluconazole, or prescription-strength terbinafine (Lamisil)
Topical steroid medications to reduce painful inflammation
Oral antibiotics if bacterial infections develop due to raw skin and blisters

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List of Oral Antifungal Therapies, Their Dosages, and Their Possible Side Effects

DRUG	DOSE	SIDE EFFECTS
1. Griseofulvin*	375–500 mg QD 3–6 months	Nausea, Hepatotoxic, Photosensitivity, Headache, Leukopenia⁺, Neutropenia⁺
2. Azoles
A. Ketoconazole**	200–400 mg QD 6–8 weeks	Hepatotoxic, Hepatitis Idiosyncratic rxn, Nausea, Vomiting, Diarrhea
B. Itraconazole	100 mg QD 2–4 weeks	Abdominal pain, Increased transaminases
	400 mg QD 1 week
C. Fluconazole	50 mg QD 6 weeks	Hepatotoxic⁺, Anaphylaxis
	100 mg QD 8 weeks
	150 mg q week 6 weeks
3. Allylamines
A. Terbinafine	125 mg QD 8 weeks	Headache, Rash, Cholestatic hepatitis, Blood dyscrasia Steven-Johnson Syndrome
	250 mg QD 2–6 weeks

*—Estimated retail price based on information obtained at http://www.goodrx.com. Accessed June 20, 2014. Generic price listed first; brand price listed in parentheses.

Antifungal Agents for the Treatment of Tinea Infections

AGENT	DOSAGE	COST (GENERIC)*
Tinea unguium
Terbinafine (Lamisil)	250 mg orally every day for 12 weeks†or	$1,171 ($1,047 to $1,080)
Terbinafine (Lamisil)	500 mg orally every day during the first week of each month for four months	$780 ($696 to $720)
Itraconazole (Sporanox)	200 mg orally every day for 12 weeks or	$1,838 ($1,241 to $1,713)
Itraconazole (Sporanox)	400 mg orally every day during the first week of each month for four months‡	$1,225 ($828 to $1,142)
Tinea capitis
Griseofulvin, micronized (Grifulvin)	20 mg per kg per day for eight weeks	$467 ($467 to $578) for a child weighing 30 kg
Terbinafine	62.5 mg per day for four weeks§	$105 (—) for a child older than two years weighing 20 kg
Tinea corporis, pedis, cruris
Butenafine (Mentax)	Applied to the lesion and a 2-cm area surrounding the lesion once daily for approximately 14 days	30 g: $84 (—)
Terbinafine	Applied to the lesion and a 2-cm area surrounding the lesion twice daily for approximately 14 days	15 g: — ($32 to $38)
Miconazole (Micatin)	Applied to the lesion and a 2-cm area surrounding the lesion twice daily for approximately 14 days	30 g, 2%: — ($3.20 to $3.30)
Clotrimazole (Lotrimin AF)	Applied to the lesion and a 2-cm area surrounding the lesion twice daily for approximately 14 days	24 g: $9.77 ($6.42 to $8.60)

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*— Estimated cost to the pharmacist based on average wholesale prices (rounded to the nearest dollar) in Red Book. Montvale, N.J.: Medical Economics Data; 2008. Cost to the patient will be higher, depending on prescription filling fee.

†— Higher cure rate among nail regimens.

‡— Lowest cost among nail regimens.

§— Lower cost among scalp regimens.

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List of Possible Drug-Drug Interactions with Oral Antifungal Therapy

1. Griseofulvin:

Aspirin, Oral contraceptives, Phenobarbital, Porfimer, Theophylline, Warfarin

2. Ketoconazole:

Alcohol, Oral hypoglycemics, Phenytoin

3. Itraconazole:

Alfentanil, Alprazolam, Amphotericin B, Agenerase, Antacids, Atorvastatin, Bexarotene, Buspirone, Busulfan, Carbamazepine, Cilostazol, Cimetidine, Cisapride, Citalopram, Clarithromycin, Cyclosporine, Diazepam, Didanosine, Digitoxin, Docetaxel, Dofetilide, Erythromycin, Famotidine, Felodipine, Grapefruit juice, Haloperidol, Indinavir, Isoniazid, Lansoprazole, Lovastatin, Methylprednisone, Midazolam, Nevirapine, Nifedipine, Omeprazole, Oral hypoglycemics, Phenobarbital, Phenytoin, Pimozide, Quinidine, Ranitidine, Rifabutin, Rifampin, Ritonavir, Saquinavir, Sildenafil, Simvastatin, Sirolimus, Sodium bicarbonate, Sucralfate, Tacrolimus, Triazolam, Trimetrexate, Verapamil, Vincristine, Warfarin

4. Fluconazole:

Amphotericin B, Celecoxib, Cimetidine, Cisapride, Citalopram, Cyclosporine, Dofetilide, Felodipine, Glipizide, Glyburide, Hydrochlorothiazide, Lovastatin, Midazolam, Oral hypoglycemics, Phenytoin, Pimozide, Prednisone, Quinidine, Rifabutin, Rifampin, Sildenafil, Simvastatin, Sirolimus, Tacrolimus, Theophylline, Triazolam, Warfarin, Zidovudine

5. Terbinafine:

Cimetidine, Cyclosporine, Nortriptyline, Rifampin, Terfenadine, Theophylline, Warfarin

Home Care

Your doctor may recommend that you soak your feet in saltwater or diluted vinegar to help dry up blisters.

Alternative Therapy

Tea tree oil has been used as an alternative therapy for treating athlete’s foot with some success. A study from 2002 reported that a 50 percent solution of tea tree oil effectively treated an athlete’s foot in 64 percent of trial participants.

Prevention

Because fungi grow particularly well in a moist environment, it’s important to make sure you keep your feet dry. You might try the following, for example:

Wash your feet with soap and water every day and dry them thoroughly, especially between the toes.
Wash socks, bedding, and towels in water that’s 140°F (60°C) or higher. Combining washing socks and application of OTC antifungal recommendations should treat most cases of athlete’s foot. You can disinfect your shoes by using disinfectant wipes (like Clorox wipes) or sprays.
Put antifungal powder on your feet every day.
Don’t share socks, shoes, or towels with others.
Wear sandals in public showers, around public swimming pools, and in other public places.
Wear socks made out of breathable fibers, such as cotton or wool, or made out of synthetic fibers that wick moisture away from your skin.
Thoroughly dry your feet with a towel after having a shower or bath, or after swimming
Wearing shoes that aren’t too tight and let your feet breathe
Not wearing the same pair of shoes two days in a row
Taking your shoes off as often as possible
Dry feet and toes meticulously after bathing
Use desiccating foot powder once or twice daily
Avoid wearing occlusive footwear for long periods
Thoroughly dry shoes and boots
Clean the shower and bathroom floors using a product containing bleach
Great shoes with antifungal powder. If treatment of tinea pedis is unsuccessful, consider reinfection, coexistent untreated fungal nail infection, reinfection due to an untreated family member, or an alternative diagnosis.

The following things can help keep you from getting athlete’s foot from infected flakes of skin and stop it from coming back:

Wearing flip-flops when using swimming pools, communal showers and changing rooms
Not sharing towels, shoes, or socks
Washing socks, bedding, and towels at 60 degrees Celsius or more
Adding special anti-fungal laundry sanitizers if washing at lower temperatures

There haven’t been any good studies on how effective these preventive measures are.