Onychomycosis

Overview

The most prevalent nail infective condition is onychomycosis. It is mostly caused by anthropophilic dermatophytes, specifically Trichophyton rubrum. The second cause of onychomycosis is caused by yeasts such as Candida albicans and Candida parapsilosis, as well as molds such as Aspergillus spp.

Mycology should corroborate the clinical suspicion of onychomycosis. Onychoscopy is a novel technology that can assist the clinician since it displays a characteristic fringed proximal border in onychomycosis. Treatment is determined by the mode of nail invasion, the fungus type, and the quantity of infected nails.

Oral therapies are frequently hampered by medication interactions, and topical antifungal lacquers are less effective. A mix of oral and systemic medication is frequently the best option. 

Onychomycosis will be examined in terms of disease burden, clinical forms, staging, diagnosis, and therapy.

Onychomycosis definition

Onychomycosis is a fungus that infects the nail unit. Tinea unguium is the name given to onychomycosis produced by dermatophytes. Onychomycosis refers to infections caused by yeasts and saprophytic molds as well as dermatophytes.

Onychomycosis can infect both fingernails and toenails, however, toenail onychomycosis is far more common. Many different forms of fungus (yeasts or molds) that reside in the environment might cause fungal nail infections. Small breaks in your nail or the surrounding skin might allow these bacteria to penetrate and infect your nail.

Epidemiology

Trichophyton rubrum, Trichophyton mentagrophytes var. interdigitale, and Trichophyton mentagrophytes var. interdigitale are the most common anthropophilic dermatophytes that cause this illness. Non-dermatophyte molds, such as Scopulariopsis brevicaulis and Aspergillus spp., can be the main pathogens or contamination agents and secondary pathogens in onychomycosis.

Fusarium spp., Acremonium spp., Alternaria spp., and Neoscytalidium sp. have also been identified from afflicted nails. The global prevalence of non-dermatophyte mold onychomycosis is believed to be 10%–15%. Yeasts, such as Candida albicans and Candida parapsilosis, are the third cause of nail fungal infection, and they only arise when predisposing conditions, including immunosuppression and diabetes, are present.

Toenails are more usually afflicted than fingernails: onychomycosis frequently includes many nails in these cases, and dry-type plantar tinea pedis is widespread. Depending on the mode of nail invasion, there are many clinical forms of onychomycosis. Onychomycosis requires laboratory confirmation for clinical diagnosis, and therapy is dependent on a variety of criteria, including the fungus species and the number of infected nails.

Onychomycosis in childhood is uncommon, affecting only around 0.5 percent to 2.6 percent of all children. Distal subungual onychomycosis is the most prevalent presentation in children, and toenails are more typically afflicted than fingernails. Children get the fungus via a dystrophic or traumatic nail deformity, or indirectly from a parent through environmental contamination. A genetic propensity to fungal invasion of the soles and nails appears to be required from a young age.

Patients have been found to be genetically predisposed to dermatophyte infections in an autosomal dominant manner. Aging, diabetes, tinea pedis, psoriasis, immunodeficiency, and living with onychomycosis-infected family members are all risk factors.

Etiology 

Onychomycosis is a frequent illness that is becoming more common. Trichophyton rubrum is the most common cause of onychomycosis, however other dermatophytes, such as Trichophyton mentagrophytes and Epidermophyton floccosum, can also cause it. Dermatophytes are found in 90% of toenail onychomycosis cases and 50% of fingernail onychomycosis cases.

Candida albicans is responsible for 2% of onychomycosis, which is most common in fingernails. Toe nails are used to cultivate nondermatophytic mold onychomycosis. Fusarium, Aspergillus, Acremonium, Scytalidium, and Scopulariopsis brevicaulis are examples of saprophytic molds. They account for around 8% of all nail infections.

Pathophysiology

Hotel carpets, public baths, and pool decks may all be cultivated for causal microbes. Onychomycosis is usually preceded by asymptomatic, dry hyperkeratotic tinea pedis. The dark, warm, damp environment of shoes, as well as micro traumatic pressure on the nail unit, weaken and break the hyponychial barrier over time, allowing the dermatophyte to enter the nail bed.

Wet job exposes fingernails to water on a regular basis, which weakens them. Dermatophytes can only survive by feeding on the keratin of dead corneocytes in the skin, nails, and hair. Dermatophytes create keratinases in the foot, which start the infection between the lesser toes, travel to the hyperkeratotic sole, and progressively spread to the distal hyponychial space of micro-traumatized nail units.

When the distal nail hyponychium is breached, dermatophytes infect the nail bed and spread proximally as onycholysis and subungual hyperkeratosis. The predominant location of infection is the nail bed, where the acute infection begins with a low-grade inflammatory response and escalates to a chronic nail bed infection known as complete dystrophic onychomycosis. Onychomycosis appears histologically as spongiosis, acanthosis, papillomatosis with edema, and hyperkeratosis. These symptoms are similar to the pathophysiology of psoriasis.

A thick inflammatory infiltration develops, as it does in most infections. Onychomycosis infects the viable nail matrix. Secondarily, onychomycosis affects the nail matrix by causing the nail bed to become hyperkeratotic and thicker in an attempt to shed the fungal infection. The dermatophyte also infiltrates the underlying nail plate, gradually detaching and distorting it.

As the infection progresses to the chronic complete dystrophic clinical stage of onychomycosis, the nail plate becomes raised and misplaced (TDO). There is a substantial quantity of compact hyperkeratosis, hypergranulosis, acanthosis, and papillomatosis with scant perivascular infiltration during this chronic stage of the illness. Dermatophytosis and subungual seromas are possible complications.

Clinical Features

Distal and Lateral Subungual Onychomycosis

Fungi enter the nail through the hyponychium and spread proximally to the undersurface of the nail unit plate. Distal and lateral subungual onychomycosis (DLSO) typically affects one or both great toe nails and is often linked with tinea pedis. The nail plate is yellow-white, separated from the nail bed due to onycholysis, and has distal subungual hyperkeratosis.

A brown, black, or orange staining of the onycholytic nail is found less commonly. Dermatophytoma, a subungual deposition of hyphae and scales that antifungals cannot reach, necessitates excision of the region and systemic therapy, is one probable presentation of DLSO caused by dermatophytes. When the infection is the Melanoides variety of Trichophyton rubrum or other fungi that generate melanin, such as Neoscytalidium dimidiatum or Aspergillus niger, DLSO may be linked with black nail pigmentation ("fungal melanonychia"). Non-dermatophyte onychomycosis is usually accompanied by severe periungual irritation.

White Superficial Onychomycosis

Fungi infiltrate the dorsal nail plate, forming colonies that look as white opaque forms that may be scraped away. Trichophyton interdigitale causes the traditional type, in which dermatophytes populate the most superficial layers of the nail plate without piercing it, although Fusarium spp. and other molds can induce white superficial onychomycosis (WSO) with a deeper nail invasion.

Proximal Subungual Onychomycosis

Fungal elements are most commonly found in the ventral nail plate, resulting in proximal leukonychia. Proximal subungual onychomycosis (PSO) caused by dermatophytes is extremely uncommon, and the type caused by T. rubrum was once thought to be a symptom of HIV infection. It appears as a white spot under the proximal nail plate, near the lunula. PSO is a common symptom of non-dermatophyte mold infection, particularly Aspergillus sp. and Fusarium sp., and acute periungual inflammation is frequently observed. Acute bacterial paronychia and pustular psoriasis of the nail are possible differential diagnoses.

Diagnosis

Determining the severity and clinical stage of an infection aids in the direction of therapy and improves results. Distal lateral subungual onychomycosis is the most prevalent clinical subtype of onychomycosis (DSLO). Partial distal onycholysis with subungual hyperkeratosis or crumbling is the most common symptom. White superficial onychomycosis (WSO), which shows as white chalky deposits on the surface of the infected nail plate, is far less prevalent.

It is readily removed with a curette or rotary burr. Proximal subungual onychomycosis (PSO), which develops overlaying the nail matrix, is the most uncommon kind. It has been linked to acquired immunodeficiency syndrome (AIDS) and may be transferred hematogenously. The inside of the nail plate gets infected first in the endonyx subtype, and the important hallmark of subungual hyperkeratosis of the nail bed is absent.

Total dystrophic onychomycosis (TDO) is the most advanced form of the disease. TDO is a severe stage of chronic subungual dermatophyte infection that can develop over a period of 10 to 15 years. Subungual hyperkeratosis is present, as well as disintegration of the atypical nail plate and ridging of the nail bed.

It is not only the most difficult stage to treat, but it also carries the greatest risk of developing subungual ulcers, secondary bacterial infection, and triggering gangrene in individuals with poor peripheral circulation. Because almost half of all abnormally looking toenails are not mycotic, mycological testing is required to provide an accurate diagnosis.

This is especially critical if systemic therapy is being considered. The traditional potassium hydroxide (KOH) wet mount preparation of subungual debris is only 60% sensitive and does not allow for species identification. However, if the KOH is positive, it can distinguish between dermatophytes and saprophytes.

A pathologist-interpreted nail clip biopsy stained with periodic acid-Schiff (PAS) with Grocott methenamine silver is now the most sensitive test (95 percent). Fungal culture testing now requires the interpretation of a mycologist. Fungal cultures are extremely specific but not extremely sensitive (60 percent ). Fungal cultures develop slowly, which adds weeks and money to the process.

To determine the source of the infection, a fungal culture or PCR is necessary. They can be used to assist pinpoint the source of infection in unusual instances or when primary saprophytic infection is suspected. Before deciding that the saprophyte is the primary pathogen and not a contaminant, two consecutive cultures of the same saprophytic mold should be collected to validate this supposition. PCR enhances species-specific identification of dermatophytes by 20% when compared to fungal cultures alone.

Onychomycosis can be clinically diagnosed via dermoscopy. It can help tell the difference between onychomycosis and nail dystrophy. Onychomycosis is indicated by the presence of subungual small spikes and longitudinal striae, whereas transverse onycholysis is consistent with micro traumatic nail dystrophy.

Other novel diagnostic methods for onychomycosis include the dermatophyte test strip, fluorescence microscopy, and Raman spectroscopy. The dermatophyte test strip is an immunochromatography test that employs a monoclonal antibody that interacts with Trichophyton species and provides a positive signal after 15 minutes of contact with one of these dermatophytes.

It is a ready-to-use kit that is quick, simple, and inexpensive. Because the test has high sensitivity and negative predictive value, it may be used to rule out onychomycosis in all suspicious cases. The method has previously been tested in a limited series on onychomycosis.

Fluorescence microscopy is the examination of suspected onychomycosis nail clippings stained with PAS under a fluorescent microscope. This approach does not discriminate between various fungal species or between alive and dead hyphae, but it is less expensive than PAS stain. The downsides include the requirement for training and expertise, the difficulty in distinguishing false positives from actual fungal fluorescence, and the reduced specificity when compared to PAS and other special stains.

Raman spectroscopy is a vibrational spectroscopic method used to investigate the molecular composition of materials using the molecular specificity of spectral bands in a vibration spectrum. 

Management

Systemic antifungals are the most effective therapies for onychomycosis. Because of the increased risk of subungual ulceration, oral antifungal medication should be considered in moderate to severe illness, particularly in individuals with diabetes mellitus. The use of topical medicines, periodic debridement, or chemical nail avulsion in conjunction with systemic medication may give greater outcomes than systemic treatment alone.

The newest topical antifungal medications have increased cure rates in mild to moderate infections and in individuals who wish to forego systemic antifungals. According to meta-analyses, terbinafine has a 76 percent mycological cure rate, itraconazole pulse dosing has a 63 percent mycological cure rate, and fluconazole has a 48 percent mycological cure rate, while efinaconazole has a 55 percent mycological cure rate and tavaborole or ciclopirox has a 36 percent mycological cure rate.

The best criterion for measuring efficacies is the full cure rate, which is defined as both negative mycology and 100 percent clean nail. However, it is a highly strict criterion since residual nail dystrophy from persistent infection may scar the nail plate and prevent certain outcomes from being regarded entirely clean even if there is great clinical improvement. The nail unit, on the other hand, may be completely clean, but the post-treatment fungal culture may reveal fungal infection. Systemic terbinafine has a full cure rate of 38%.

Although oral medication is the most effective treatment for severe onychomycosis, it is medically unsuitable for some individuals. Furthermore, many patients have a strong preference for a non-systemic therapy. If the effectiveness rates were higher, topical medication would appear to be a good solution to the problem.

There are several over-the-counter and prescription medications available, implying that there is no obviously effective topical option. According to the data, full cure rates for FDA-approved topical medicines have lately improved, rising from 8.5 percent for ciclopirox lacquer to 18 percent for an efinaconazole solution. In mild to severe distal subungual onychomycosis, the tavaborole solution had a full cure rate of 9.1 percent.

It is critical to thoroughly examine the patient's history for alcohol use disorder and hepatitis. Before starting continuous treatment, alanine aminotransferase and aspartate aminotransferase liver function tests are ordered to establish a baseline. If there is a history of residing in a country where hepatitis is endemic, a hepatitis antigen screening panel might be included to the workup.

Five-week follow-up liver function tests are used to detect the fewer than 2% of idiosyncratic responses. If the follow-up tests are considerably high, the medicine can be stopped and retested.

Concurrent medicines may also prevent the use of oral antifungals. Terbinafine has the potential to modify the metabolism of a variety of medicines, therefore careful monitoring is required. Concerns about drug-to-drug interactions with statin medication and systemic antifungal therapy pertain to the azole class of antifungals rather than terbinafine. In individuals on psychotropic medicines, it may be advisable to avoid systemic treatment.

Terbinafine is contraindicated when used with phenothiazines and pimozide due to an increased risk of QT prolongation. According to Gupta, terbinafine may be used safely in both youngsters and the elderly. However, doctors should always be cautious when dealing with patients who have a high level of polypharmacy. Emerging treatment possibilities include photosensitizers for photodynamic therapy (PDT) and a novel laser system. PDT employs the use of a photosensitizer and a light source to produce reactive oxygen species, resulting in the chemical death of nail fungus. 

A recent analysis gathered a total of six publications on the use of PDT in onychomycosis in vivo, although all but two clinical studies are case reports with tiny numbers of patients. This study recommends that before to applying photosensitizer, a nail abrasion or maceration (for example, using 20% urea ointment in occlusion) is required.

The large number of sessions asked by PDT is a limitation. Typically, three to twelve sessions are requested. The number of sessions might be lowered by increasing the quantity of irradiation, but this would result in greater negative side effects such as temporary discomfort and burning. Because the best light source and number/frequency of treatments have yet to be determined, more clinical trials are required to assess a standardized procedure.

Differential Diagnosis

Differential diagnosis includes:

• nail changes in psoriasis, 
• lichen planus, 
• alopecia areata, 
• chronic dermatitis,
• onychogryphosis,
• chronic paronychia, 
• onychogryphosis,
• median nail dystrophy, 
• melanonychia striata, 
• subungual melanoma, 
• pemphigus vulgaris, 
• pemphigoid, 
• epidermolysis bullosa acquisita,
• subungual wart,
• subungual keratoacanthoma,
• rheumatoid arthritis,
• scleroderma, 
• lupus erythematosus, 
• scabies, 
• yellow nail syndrome,
• traumatic onychodystrophy,
• onychomatricoma, idiopathic onycholysis, 
• porphyria, amyloidosis, myxoid cyst, fibroma, glomus tumor, Bowen disease, and 
• squamous cell carcinoma.

Complications

Tinea pedis, tinea corporis, and tinea cruris can all be caused by onychomycosis. The fungus may potentially spread to adjacent nails. Bacterial infections, such as cellulitis and paronychia, are more common in immunocompromised people, including diabetics.

Severe onychomycosis can make standing, walking, nail function, and daily activities difficult. If left untreated, the disease can cause discomfort, soreness, paresthesia, nail abnormalities such transverse over-curvature, difficulty cutting thick nail plates, difficulty fitting shoes, and poor self-esteem. Furthermore, onychomycosis can be unattractive and socially uncomfortable (particularly for females), and it can have a negative impact on quality of life.

Prevention

Because fungi grow in damp, warm settings, patients should be urged to wear non-occlusive shoes, keep their feet dry and cool, wear absorbent socks, and keep their nails clipped short. Tinea pedis should be treated if it is present. In addition, family members with tinea pedis and onychomycosis should be treated accordingly.

Some authors recommend topical antifungal medication once weekly or twice monthly in high-risk individuals for up to two years following treatment completion to avoid recurrence. An UV C-based treatment device for footwear, as well as washing non-leather running shoes in hot water, can be explored.

Prognosis

With effective therapy, the prognosis is often favorable. A poor response to therapy is accompanied with yellow streaks along the lateral border of the nail, the presence of dermatophytoma, and onychomycosis caused by non-dermatophyte molds (particularly Fusarium species). Noncompliance, elderly age, severe illness, nail matrix involvement, subungual hyperkeratosis larger than 2 mm, two feet-one hand syndrome, and immunodeficiency are all linked with a poor response.

Poor therapeutic response may also be caused by poor diffusion of topical antifungal medications over the nail plate, as well as the deep-seated and resistant nature of fungal infection. Recurrences are common, with reported rates ranging from 10% to 53%. Recurrences often occur within three years of completing therapy. Relapse or reinfection can both induce recurrence.

Conclusion 

Onychomycosis is a fungus that infects the nail plate, nail bed, or both. Infections can be distal subungual, with nail thickening and yellowing with keratin and debris collection beneath the nail (top); proximal subungual (not depicted); or white superficial, with chalky white scale spreading beneath the nail surface (bottom).

Poor treatment response may also be caused by inadequate distribution of topical antifungal drugs throughout the nail plate, as well as the deep-seated and resistant nature of fungal infection. Recurrences are common, with reported rates ranging from 10% to 53%. Recurrences are common within three years of finishing therapy. Both relapse and reinfection can result in recurrence.