6 Factors That Contribute to Toenail Fungus

The term onychomycosis (toenail fungus) refers to a fungal infection of the nail caused by dermatophytes, non-dermatophyte molds or yeasts. There are four clinically distinct forms of onychomycosis. Diagnosis is based on CON examination, microscopy and histology. Most often, treatment includes systemic and local therapy, sometimes resorting to surgical removal.

Onychomycosis is a fungal infection of the toenails

Factors contributing to nail fungus

  1. Increased sweating (hyperhidrosis).
  2. Vascular insufficiency. Violation of the structure and tone of the veins, especially the veins of the lower extremities (typical of toenail onychomycosis).
  3. Age. The incidence of the disease in men increases with age. In 15 to 20% of the population, the pathology occurs between the ages of 40 and 60.
  4. Diseases of internal organs. Disruption of the nervous, endocrine (onychomycosis most often occurs in people with diabetes) or immune systems (immunosuppression, especially HIV infection).
  5. A large mass of nails, consisting of a thick nail plate and the contents underneath, can cause discomfort when wearing shoes.
  6. Traumatization. Constant nail trauma or injury and lack of proper treatment.

Disease prevalence

Onychomycosis– the most common nail disease, which causes 50% of all cases of onychodystrophy (destruction of the nail plate). It affects up to 14% of the population, and both the prevalence of the disease among older people and the overall incidence are increasing. The incidence of onychomycosis in children and adolescents is also increasing: onychomycosis represents 20% of dermatophyte infections in children.

The increased prevalence of the disease may be associated with the wearing of tight shoes, an increase in the number of people undergoing immunosuppressive treatment, and the increasing use of public changing rooms.

Nail disease usually begins with ringworm before spreading to the nail bed, where eradication is difficult. This area serves as a reservoir for local relapses or spread of infection to other areas. Up to 40% of patients with onychomycosis of the toes have combined skin infections, most commonly ringworm of the feet (approximately 30%).

The causative agent of onychomycosis

In most cases, onychomycosis is caused by dermatophytes, with T. rubrum and T. interdigitale being the causative agents of infection in 90% of cases. T. tonsurans and E. floccosum have also been documented as etiologic agents.

Non-dermatophyte yeasts and molds such as Acremonium, Aspergillus, Fusarium, Scopulariopsis brevicaulis and Scytalidium cause onychomycosis of the toes in approximately 10% of cases. Interestingly, Candida species are the causative agents of 30% of cases of finger onychomycosis, whereas non-dermatophytic molds are not found in affected nails.

Pathogenesis

Dermatophytes possess a wide range of enzymes which, acting as virulence factors, ensure the adhesion of the pathogen to the nails. The first stage of infection is adhesion to keratin. Due to the subsequent breakdown of keratin and the cascade release of mediators, an inflammatory reaction develops.

Appearance of a nail plate affected by fungus

The stages of the pathogenesis of fungal infection are as follows.

Membership

Fungi overcome several lines of host defense before hyphae begin to survive in keratinized tissues. The first is the successful adhesion of arthroconidia to the surface of keratinized tissues. The first lines of nonspecific host defense include fatty acids found in sebum, as well as competitive bacterial colonization.

Several recent studies have examined the molecular mechanisms involved in the adhesion of arthroconidia to keratinized surfaces. Dermatophytes have been shown to selectively use their proteolytic reserves during adhesion and invasion. Some time after adhesion, the spores germinate and move on to the next stage: invasion.

Invasion

Traumatization and maceration constitute a favorable environment for the penetration of fungi. The invasion of the germinal elements of the fungus ends with the release of various proteases and lipases, in general, various products that serve as nutrients for the fungi.

The owner's reaction

Fungi face multiple protective barriers in the host, such as inflammatory mediators, fatty acids and cellular immunity. The first and most important barrier are keratinocytes, which are encountered by invading fungal elements. The role of keratinocytes: proliferation (to promote desquamation of horny scales), secretion of antimicrobial peptides, anti-inflammatory cytokines. As soon as the fungus penetrates deeper, more and more new non-specific protective mechanisms are activated.

The severity of the host inflammatory response depends on the immune status as well as the natural habitat of the dermatophytes involved in the invasion. The next level of defense is a delayed-type hypersensitivity reaction, caused by cell-mediated immunity.

The inflammatory response associated with this hypersensitivity is associated with clinical destruction, while a defect in cell-mediated immunity can lead to chronic and recurrent fungal infection.

Despite epidemiological observations indicating a genetic predisposition to fungal infections, there are no proven molecular studies.

Clinical picture and symptoms of toenail and fingernail lesions

There are four characteristic clinical forms of infection. These forms can be isolated or include several clinical forms.

Distal-lateral subungual onychomycosis

This is the most common form of onychomycosis and can be caused by any of the pathogens listed above. It begins with pathogenic invasion into the stratum corneum of the hyponychium and the distal nail bed, resulting in a whitish or brownish-yellow opacification of the distal end of the nail. The infection then spreads proximally up the nail bed to the ventral aspect of the nail plate.

Distal-lateral subungual onychomycosis on the leg

Hyperproliferation or impaired differentiation of the nail bed resulting from a response to infection causes subungual hyperkeratosis, while progressive invasion of the nail plate results in increased nail dystrophy. nail.

Proximal subungual onychomycosis

It occurs following infection of the proximal nail fold, primarily by the organisms T. rubrum and T. megninii. Clinical: opacification of the proximal part of the nail with a white or beige tint. This opacification gradually increases and affects the entire nail, ultimately leading to leukonychia, proximal onycholysis and/or destruction of the entire nail.

Patients with proximal subungual onychomycosis should be examined for HIV infection, since this form is considered a marker of this disease.

White superficial onychomycosis

This occurs due to direct invasion of the dorsal nail plate and appears as well-defined white or dull yellow spots on the nail surface. The pathogens are usually T. interdigitale and T. mentargophytes, although non-dermatophyte molds such as Aspergillus, Fusarium and Scopulariopsis are also known pathogens of this form. Candida species can invade the hyponychium of the epithelium and eventually infect the nail throughout the thickness of the nail plate.

Candidiasis onychomycosis

Damage to the nail plate caused by Candida albicans is observed exclusively in chronic mucocutaneous candidiasis (a rare disease). Usually all nails are affected. The nail plate thickens and acquires various shades of yellow-brown color.

Diagnosis of onychomycosis

Although onychomycosis accounts for 50% of nail dystrophy cases, it is advisable to obtain laboratory confirmation of the diagnosis before starting toxic systemic antifungal medications.

The study of subungual masses with KOH, cultural analysis of nail plate material and subungual masses on Sabouraud dextrose agar (with and without antimicrobial additives) and staining of nail clippings by the PAS methodare the most informative methods.

Study with CON

This is a standard test if onychomycosis is suspected. However, this often gives a negative result even with a high index of clinical suspicion, and cultural analysis of the nail material in which the hyphae were found during the study with CON is often negative.

The most reliable way to minimize false negative results due to sampling errors is to increase the sample size and repeat sampling.

Cultural analysis

This laboratory test determines the type of fungus and determines the presence of dermatophytes (organisms that respond to antifungal medications).

Perform a culture test to diagnose a fungal infection

To distinguish pathogens from contaminants, the following recommendations are proposed:

  • if the dermatophyte is isolated in culture, it is considered pathogenic;
  • Non-dermatophytic molds or yeasts isolated in culture are only relevant if hyphae, spores or yeast cells are observed microscopically and recurrent active growth of the non-dermatophytic mold pathogen is observed without isolation.

Cultural analysis, PAS - method of staining nail clippings is the most sensitive and does not require waiting for results for several weeks.

Pathohistological examination

During pathohistological examination, the hyphae are located between the layers of the nail plate, parallel to the surface. In the epidermis, spongiosis and focal parakeratosis can be observed, as well as an inflammatory reaction.

In superficial white onychomycosis, the microorganisms are found superficially at the back of the nail, displaying a pattern consisting of their unique "piercing organs" and modified hyphal elements called "bitten leaves. "With candidal onychomycosis, invasion of pseudohyphae is observed. Histological examination of onychomycosis is carried out using special dyes.

Differential diagnosis of onychomycosis

Most likely Sometimes probable Rarely found
  • Psoriasis
  • Leukonychia
  • Onycholysis
  • Congenital pachyonychia
  • Acquired leukonychiosis
  • Congenital leukonychiosis
  • Darier-White disease
  • Yellow nail syndrome
  • Lichen planus
Melanoma

Treatment methods for nail fungus

Treatment for toenail fungus depends on the severity of the toenail lesion, the presence of associated tinea pedis, and the effectiveness and potential side effects of the treatment regimen. If nail damage is minimal, localized treatment is a rational decision. In association with dermatophytosis of the feet, especially in the context of diabetes mellitus, it is imperative to prescribe treatment.

Topical antifungal medications

In patients with distal nail involvement or contraindications to systemic treatment, local treatment is recommended. However, it should be remembered that only local therapy with antifungal agents is not effective enough.

  1. A varnish from the oxypyridone group is gaining popularity, applied daily for 49 weeks, mycological cure is achieved in approximately 40% of patients and nail cleaning (clinical cure) in 5% of cases of mild or moderate onychomycosis caused bydermatophytes. .

    Despite its much lower effectiveness than systemic antifungal drugs, local use of the drug avoids the risk of drug interactions.

  2. Another drug, specially developed in the form of nail polish, is used 2 times a week. It is a representative of a new class of antifungal drugs, derived from morpholine, active against yeasts, dermatophytes and molds responsible for onychomycosis.

    This product may have higher mycological cure rates than the previous polish; however, controlled studies are needed to determine a statistically significant difference.

Antifungal drugs for oral administration

Systemic antifungal medication is necessary in cases of onychomycosis involving the matrix area, or if a shorter course of treatment or a higher chance of recovery and cure is desired. When choosing an antifungal medication, one should first consider the etiology of the pathogen, potential side effects, and the risk of drug interactions in each patient.

  1. A drug from the allylamine group, which has a fungistatic and fungicidal effect against dermatophytes, Aspergillus, is less effective against Scopulariopsis. The product is not recommended for Candida onychomycosis as it has variable effectiveness against Candida species.

    A standard dose of 6 weeks is effective for most toenail injections, while a minimum of 12 weeks is required for toenail injections. Most side effects are related to problems with the digestive system, including diarrhea, nausea, taste changes, and increased liver enzymes.

    Data indicate that a 3-month continuous dosing regimen is currently the most effective systemic treatment for toenail onychomycosis. The clinical cure rate in various studies is approximately 50%, although treatment rates are higher in patients over 65 years of age.

  2. A drug from the azole group that has a fungistatic effect against dermatophytes, as well as non-dermatophyte molds and yeasts. Safe and effective treatment regimens include daily pulse dosing for one week per month or continuous daily dosing, both of which require two months or two cycles of therapy for nails and at least three months or three pulse therapies for nails. toenail lesions.

    In children, the drug is administered individually based on weight. Although the drug has a broader spectrum of action than its predecessor, studies have shown a significantly lower cure rate and a higher relapse rate.

    Elevated liver enzyme levels occur in less than 0. 5% of patients during treatment and return to normal within 12 weeks after stopping treatment.

  3. Drug that acts fungistatically against dermatophytes, certain non-dermatophyte molds and Candida species. This medication is usually taken once a week for 3 to 12 months.

    There are no clear criteria for laboratory monitoring of patients receiving the above drugs. It makes sense to perform a complete blood count and liver function tests before treatment and 6 weeks after starting treatment.

  4. A grisan group drug is no longer considered a standard treatment for onychomycosis due to the long duration of treatment, potential side effects, drug interactions, and relatively low cure rates.

Combination regimens may produce higher clearance rates than systemic or topical treatment alone. Ingestion of an allylamine drug in combination with application of a morpholine varnish results in clinical cure and a negative mycological test in approximately 60% of patients, compared to 45% of patients receiving only a systemic antifungal drug allylamine. However, another study showed no additional benefit when combining a systemic allylamine agent with a solution of an oxypyridone medication.

Other medications

The fungicidal activity demonstrated in vitro for thymol, camphor, menthol, and Eucalyptus citriodora oil indicates the potential for additional therapeutic strategies in the treatment of onychomycosis. An alcohol solution of thymol can be used in the form of drops on the nail plate and hyponychia. The use of local preparations based on thymol for nails leads to healing in isolated cases.

Surgery

Final treatment options for treatment-resistant cases include surgical removal of the nail with urea. To remove more crumbled masses from the affected nail, special tweezers are used.

Many doctors believe that the main and first method of treating nail fungus is mechanical removal of the nail. Most often, surgical removal of the affected nail is recommended, and less often, removal using keratolytic patches.

Traditional methods of combating nail fungus

Despite the large number of different traditional recipes for eliminating nail fungus, dermatologists do not recommend choosing this treatment option and starting with "home diagnosis". It is wiser to start treatment with local drugs that have undergone clinical trials and proven to be effective.

Course and prediction

Signs of poor prognosis are pain that appears due to thickening of the nail plate, the addition of secondary bacterial infection and diabetes mellitus. The most effective way to reduce the risk of relapse is to combine treatment methods. Treatment of onychomycosis is a long path that does not always lead to complete cure. However, remember that the effect of systemic treatment can reach 80%.

Prevention

Prevention includesa number of events, thanks to which you can significantly reduce the percentage of onychomycosis infection and reduce the risk of relapse.

  1. Disinfection of personal and public objects.
  2. Systematic disinfection of shoes.
  3. Treatment of feet, hands, folds (in favorable conditions - preferred location) with local antifungals with the recommendations of a dermatologist.
  4. If the diagnosis of onychomycosis is confirmed, it is necessary to consult a doctor for monitoring every 6 weeks and at the end of systemic treatment.
  5. If possible, at each visit to the doctor, you should disinfect the nail plates.

Conclusion

Onychomycosis (fingernail and toenail fungus) is an infection caused by various fungi. This disease affects the nail plate of the fingers or toes. When making a diagnosis, examine all skin and nails and also exclude other diseases mimicking onychomycosis. If there is any doubt about the diagnosis, it should be confirmed either by culture (preferably) or by histological examination of nail clippings followed by staining.

Treatment includes surgical removal, local and general medications. Treatment of onychomycosis is a long process that can last several years, so cure "with just one pill" should not be expected. If you suspect nail fungus, consult a specialist to confirm the diagnosis and prescribe an individual treatment plan.