The term onychomycosis (toenail fungus) describes a fungal nail infection caused by dermatophytes, non-dermatophyte molds or fungi. There are four clinically distinct forms of onychomycosis. The diagnosis is made based on examination with CON, microscopy and histology. The most common treatment includes systemic and local therapy, sometimes resorting to surgical removal.
Factors that contribute to the development of nail fungus
- Increased sweating (hyperhidrosis).
- Vascular insufficiency. Damage to the structure and tone of the veins, especially the veins of the lower extremities (typical for toenail onychomycosis).
- Age. The incidence of the disease in humans increases with age. In 15-20% of the population, the pathology occurs at the age of 40-60.
- Diseases of internal organs. Disorder of the nervous, endocrine (onychomycosis most often occurs in people with diabetes) or immune (immunosuppression, especially HIV infection) system.
- A large nail mass, consisting of a thick nail plate and the contents below it, can cause discomfort when wearing shoes.
- Traumatization. Constant nail trauma or injury and lack of proper treatment.
Disease prevalence
Onychomycosis– the most common nail disease, which is the cause of 50% of all cases of onychodystrophy (destruction of the nail plate). It affects up to 14% of the population, and the prevalence of the disease in older people and the overall incidence are increasing. The frequency of onychomycosis in children and adolescents is also increasing; onychomycosis accounts for 20% of dermatophyte infections in children.
The increase in the prevalence of the disease may be related to the wearing of tight shoes, the increase in the number of people taking immunosuppressive therapy and the increasing use of public changing rooms.
Nail disease usually begins with tinea pedis before it spreads to the nail, where eradication is difficult. This area serves as a reservoir for local recurrences or spread of infection to other areas. Up to 40% of patients with onychomycosis on the toes have combined skin infections, most often tinea pedis (about 30%).
The causative agent of onychomycosis
In most cases, onychomycosis is caused by dermatophytes, with T. rubrum and T. interdigitale causing infection in 90% of all cases. T. tonsurans and E. floccosum have also been documented as etiological agents.
Yeasts and non-dermatophytic organisms such as Acremonium, Aspergillus, Fusarium, Scopulariopsis brevicaulis and Scytalidium are the source of onychomycosis of the fingers in approximately 10% of cases. It is interesting that Candida species are the causative agents in 30% of cases of toe onychomycosis, while non-dermatophytic molds are not found in the affected nails.
Pathogenesis
Dermatophytes have a wide range of enzymes that, acting as virulence factors, ensure adherence of the pathogen to the nails. The first stage of infection is adhesion to keratin. Due to the further breakdown of keratin and the cascade release of mediators, an inflammatory reaction develops.
The stages of the pathogenesis of a fungal infection are as follows.
Adhesion
Fungi overcome several lines of host defense before hyphae can survive in keratinized tissue. The first is the successful adherence of arthroconidia to the surface of keratinized tissue. Early nonspecific lines of host defense include fatty acids 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 to the next stage - invasion.
Invasion
Traumatization and maceration are a favorable environment for the penetration of fungi. The invasion of the germinating elements of the fungus ends with the release of various proteases and lipases, generally 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 is the keratinocytes, which are encountered by the invasion of fungal elements. The role of keratinocytes: proliferation (to enhance the desquamation of corneous scales), secretion of antimicrobial peptides, anti-inflammatory cytokines. As soon as the fungus penetrates deeper, more and more new non-specific protection mechanisms are activated.
The severity of the host's 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 the delayed-type hypersensitivity reaction, which is 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 molecularly proven studies.
Clinical picture and symptoms of damage to nails on feet and hands
There are four characteristic clinical forms of infection. These forms can be isolated or include several clinical forms.
Distal-lateral subungual onychomycosis
It is the most common form of onychomycosis and can be caused by any of the pathogens listed above. It begins with the invasion of the pathogen into the stratum corneum of the hyponychium and the distal nail bed, which results in a whitish or brownish-yellow clouding of the distal end of the nail. The infection then spreads proximally along the nail to the ventral aspect of the nail plate.
Hyperproliferation or impaired differentiation in the nail bed as a result of the response to infection causes subungual hyperkeratosis, while progressive invasion of the nail plate leads to increased nail dystrophy.
Proximal subungual onychomycosis
It occurs as a result of infection of the proximal nail fold, mainly by organisms T. rubrum and T. megninii. Clinic: clouding of the proximal part of the nail with a white or beige shade. This opacification gradually increases to involve the entire nail, eventually leading to leukonychia, proximal onycholysis, and/or destruction of the entire nail.
Patients with proximal subungual onychomycosis should be examined for HIV infection, because this form is considered a marker of this disease.
White superficial onychomycosis
It is caused by direct invasion of the dorsal nail plate and appears as white or dull yellow, well-defined 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 epithelium and eventually infect the nail along the entire thickness of the nail plate.
Candidal onychomycosis
Damage to the nail plate caused by Candida albicans is observed exclusively in chronic mucocutaneous candidiasis (a rare disease). All nails are usually affected. The nail plate thickens and takes on different shades of yellow-brown.
Diagnosis of onychomycosis
Although onychomycosis accounts for 50% of cases of nail dystrophy, it is advisable to obtain laboratory confirmation of the diagnosis before starting the use of toxic systemic antifungal drugs.
The study of subungual masses with KOH, cultural analysis of the material of the nail plate and subungual masses on Sabouraud dextrose agar (with and without antimicrobial additives) and staining of nail sections with the PAS method are the most informative methods.
Learn with CON
It is the standard test for suspected onychomycosis. However, it very often gives a negative result even with a high index of clinical suspicion, and cultural analysis of nail material in which hyphae were found during the study with CON is often negative.
The most reliable way to minimize false negatives due to sampling errors is to increase the sample size and repeat the sampling.
Cultural analysis
This laboratory test determines the type of fungus and determines the presence of dermatophytes (organisms that respond to antifungal drugs).
To distinguish pathogens from contaminants, the following recommendations are offered:
- if a dermatophyte is isolated in culture, it is considered a pathogen;
- Nondermatophytic mold or yeast organisms isolated in culture are relevant only if hyphae, spores, or yeast cells are observed under a microscope and repeated active growth of the nondermatophytic mold pathogen is observed without isolation.
Cultural analysis, PAS - the method of staining cut nails is the most sensitive and does not require waiting for results for several weeks.
Pathohistological examination
During pathohistological examination, hyphae are located between the layers of the nail plate, parallel to the surface. In the epidermis, spongiosis and focal parakeratosis, as well as an inflammatory reaction, can be observed.
In superficial white onychomycosis, the microorganisms are found superficially on the back of the nail, displaying a pattern of their unique "perforating organs" and modified hyphal elements called "bite sheets. "Pseudohyphae invasion is observed in candidal onychomycosis. Histological examination of onychomycosis is performed with special dyes.
Differential diagnosis of onychomycosis
| Most likely | Sometimes probably | Rarely found |
|---|---|---|
|
|
Melanoma |
Methods of treating nail fungus
Treatment of nail fungus depends on the severity of the nail lesion, the presence of associated tinea pedis, and the effectiveness and potential side effects of the treatment regimen. If nail involvement is minimal, local therapy is a rational decision. In combination with foot dermatophytosis, especially on the background of diabetes mellitus, it is necessary to prescribe therapy.
Topical antifungal drugs
In patients with involvement of the distal nail or contraindications for systemic therapy, local therapy is recommended. However, we must remember that only local therapy with antifungal agents is not effective enough.
Lacquer from the oxypyridone group is increasingly popular, which is applied daily for 49 weeks, mycological cure is achieved in about 40% of patients, and nail cleaning (clinical cure) in 5% of cases of mild or moderate onychomycosis caused by dermatophytes.
Despite much lower efficacy compared to systemic antifungal drugs, local use of the drug avoids the risk of drug-drug interactions.
Another drug, specially developed in the form of nail polish, is used twice a week. It is a representative of a new class of antifungal drugs, morpholine derivatives, active against yeasts, dermatophytes and molds that cause onychomycosis.
This product may have higher mycological curing rates than the previous varnish; 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 better chance of clearance and cure is desired. When choosing an antifungal drug, the etiology of the causative agent, potential side effects, and the risk of drug interactions in each individual patient should first be taken into account.
A drug from the group of allylamines, which has a fungistatic and fungicidal effect against dermatophytes, Aspergillus, is less effective against Scopulariopsis. The product is not recommended for candidal onychomycosis because it shows different effectiveness against Candida species.
A standard dose of 6 weeks is effective for most toenail injections, while toenail injections require at least 12 weeks. Most side effects are related to digestive problems, including diarrhea, nausea, taste changes, and increased liver enzymes.
Data indicate that a three-month continuous dosing regimen is currently the most effective systemic therapy for onychomycosis of the toenails. The clinical cure rate in various studies is approximately 50%, although cure rates are higher in patients over 65 years of age.
A drug from the azole group that has a fungistatic effect on dermatophytes, as well as non-dermatophyte molds and yeast organisms. Safe and effective regimens include daily pulse dosing for one week per month or continuous daily dosing, both of which require two months or two cycles of nail therapy and at least three months or three pulse therapies for toenail lesions.
In children, the drug is dosed individually depending on weight. Although the drug has a wider spectrum of action than its predecessor, studies have shown a significantly lower cure rate with it and a higher relapse rate.
Elevated liver enzyme levels occur in less than 0. 5% of patients during therapy and return to normal within 12 weeks after cessation of therapy.
A fungistatic drug against dermatophytes, some non-dermatophyte molds and Candida species. This medicine is usually taken once a week for 3 to 12 months.
There are no clear criteria for laboratory monitoring of patients receiving the above-mentioned drugs. It makes sense to have a complete blood count and liver function tests done before treatment and 6 weeks after starting treatment.
The drug from the grisan group is no longer considered standard therapy for onychomycosis due to the long course of treatment, potential side effects, drug-drug interactions, and relatively low cure rates.
Combination therapy regimens may result in higher clearance rates than systemic or topical therapy alone. Ingestion of an allylamine drug in combination with the use of a morpholine varnish resulted in clinical cure and a negative mycological test result in approximately 60% of patients, compared with 45% of patients who received only a systemic allylamine antifungal drug. However, another study showed no additional benefit when combining systemic allylamine with oxypyridone solution.
Other drugs
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. Alcoholic solution of thymol can be used in the form of drops on the nail plate and hyponychia. The use of topical preparations with thymol for the nails leads to healing in isolated cases.
Operation
Final treatment options for treatment-resistant cases include surgical removal of the nail with urea. Special pliers are used to remove a large amount of crushed mass from the affected nail.
Many doctors believe that the main and first method of treating nail fungus is mechanical removal of the nail. Surgical removal of the affected nail is most often recommended, and removal with keratolytic patches is less common.
Traditional methods in the fight against nail fungus
Despite the large number of different folk recipes for the removal of nail fungus, dermatologists do not recommend choosing this treatment option and starting "home diagnosis". It is wiser to start the therapy with local drugs that have undergone clinical trials and proven to be effective.
Flow and forecast
Bad prognostic signs are pain that occurs due to thickening of the nail plate, the addition of secondary bacterial infection and diabetes mellitus. The most useful way to reduce the likelihood of recurrence is to combine treatment methods. Onychomycosis therapy is a long road that does not always lead to complete recovery. However, do not forget that the effect of systemic therapy is up to 80%.
Prevention
Prevention includesa series of events, thanks to which you can significantly reduce the percentage of onychomycosis infection and reduce the likelihood of recurrence.
- Disinfection of personal and public things.
- Systematic disinfection of footwear.
- Treatment of feet, hands, folds (under favorable conditions - favorite localization) with local antifungal agents with the recommendation of a dermatologist.
- If the diagnosis of onychomycosis is confirmed, it is necessary to visit a doctor for control every 6 weeks and after the completion of systemic therapy.
- If possible, the nail plates should be disinfected at each visit to the doctor.
Conclusion
Onychomycosis (toenail fungus) is an infection caused by various fungi. This disease affects the nail plate on the hands or feet. When making a diagnosis, examine all the skin and nails, and also rule out other diseases that mimic onychomycosis. If there is any doubt about the diagnosis, it must be confirmed either by culture (preferably) or by histological examination of cut nails followed by staining.
Therapy includes surgical removal, local and general medications. Treatment of onychomycosis is a long-term process that can last several years, so you should not expect recovery "from one pill". If you suspect nail fungus, contact a specialist to confirm the diagnosis and prescribe an individual treatment plan.