Onychomycosis is the most common nail disease.
Fungal infections have been linked to 50% of cases of nail plate changes.Epidemiological studies conducted in Russia and abroad have shown that the incidence of onychomycosis is high, ranging from 2% to 13% in the general population.Older patients are at the highest risk for onychomycosis.For example, the prevalence of onychomycosis in people over the age of 70 can reach 50% or higher.This is thought to be due to slower growth of the nail plate and impaired peripheral and primary circulation in older adults.A high incidence of onychomycosis is also found in immunocompromised patients (including those with AIDS) and patients with diabetes.
Often, patients and some doctors view onychomycosis as a purely aesthetic problem.However, this is a chronically occurring, serious disease that, in the setting of immunodeficiency or decompensation of endocrine disease, may lead to widespread mycoses of the skin and its appendages.Onychomycosis is often associated with serious complications, such as diabetic foot, chronic erysipelas of the limbs, lymphatic stasis, and elephantiasis.The disease can lead to the development of invasive mycosis in patients receiving cytosuppressive or immunosuppressive therapy.This is why treatment for onychomycosis is necessary and should be done promptly.
Just a few decades ago, treatment for onychomycosis was labor-intensive, time-consuming, and bleak.Drugs used to treat fungal diseases of the skin and appendages have the characteristics of low efficacy and high toxicity.To achieve positive results, long-term treatment or increased drug dosage is required, which is often accompanied by serious complications.Some treatments may be life-threatening.For example, the use of X-ray therapy, thallium, and mercury has caused patients to develop skin cancer, brain, and internal organ disease.
The emergence of highly effective and low-toxic antifungal drugs has greatly facilitated the treatment of fungal diseases of the skin and appendages.However, the results of using new antifungal drugs are unsatisfactory.Controlled clinical trials have shown that systemic antifungal agents are 40% to 80% effective after treatment and 14% to 50% after 5 years.At the same time, the effectiveness of onychomycosis treatment increases with the use of complex therapeutic methods, which involve the use of symptomatic drugs and agents that influence the pathogenesis.In addition, the results of clinical trials conducted in European countries found that the combined use of systemic antifungals and antifungal varnishes containing amorolfine can increase the efficacy of treating onychomycosis by an average of 15%.
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For the treatment of onychomycosis, the drugs used differ in their chemical composition, mechanism of action, pharmacokinetics and spectrum of antifungal activity.One of their common properties is a specific effect on pathogenic fungi.This group consists of azoles (itraconazole, fluconazole, ketoconazole), allylamines (terbinafine, naftifine), griseofulvin, amorolfine, ciclopirox.For the treatment of onychomycosis, systemic drugs belonging to the azoles group are used - itraconazole, fluconazole, as well as drugs belonging to the allylamine group - terbinafine.Griseofulvin and ketoconazole are not currently used to treat onychomycosis due to low efficacy and high risk of adverse events.Varnishes and solutions containing amorolfine and ciclopirox are used as topical agents for onychomycosis.
AllylamineIt is a synthetic antifungal drug.Allylamine mainly acts on skin fungi and also has a bactericidal effect.Their mechanism of action is the inhibition of squalene epoxidase, an enzyme involved in the synthesis of ergosterol, the main structural component of the dermatophyte cell membrane.Allylamines include terbinafine and naftifine.
Allylamine is active against most dermatophytes (Epidermophyton spp., Trichophyton spp., Microsporum spp., Malassezia spp.), chromomycosis and some other fungal pathogens.
Indications for oral terbinafine are onychomycoses, common forms of dermatomycoses, scalp mycoses, pigmented mycoses.Indications for topical use of terbinafine and naftifine include limited skin lesions caused by mycoses, tinea versicolor, and cutaneous candidiasis.Terbinafine is highly bioavailable and is well absorbed from the gastrointestinal tract regardless of the amount of food consumed.At high concentrations, the drug accumulates in the stratum corneum of the skin, nail plates, and hair, and is secreted with sweat and sebaceous gland secretions.The absorption rate of terbinafine from topical application is less than 5%, naftifine - 4-6%.The concentrations of terbinafine and naftifine in the skin and its appendages significantly exceed the MICs for the major pathogens of dermatomycoses.Modification of the terbinafine dosing regimen may be necessary when used concomitantly with an inducer (rifampicin) or a microsomal liver enzyme inhibitor (cimetidine), as the former increases its clearance and the latter decreases its clearance.
A large number of controlled multi-center controlled clinical trials have found that terbinafine is the most effective antifungal drug in the treatment of onychomycosis.
TerbinafineFor the treatment of widespread skin lesions, onychomycoses, pigmented mycoses, in this case, terbinafine is taken orally.Terbinafine is the drug of choice for the treatment of onychomycosis because it is most effective against the dermatophyte fungus, the main causative agent of onychomycosis.Contraindications to the use of allylamine are allergic reactions to allylamine drugs, pregnancy, breastfeeding, under 2 years of age, liver disease with impaired liver function (elevated transaminases).
Azoles- Largest group of synthetic antifungals.Ketoconazole, the first azole systemic antifungal drug, was put into practice in 1984, followed by fluconazole in 1990 and itraconazole in 1992.
Azoles used as systemic drugs have primarily fungicidal activity.An important advantage of azoles compared to other drugs is their broad antifungal activity.Itraconazole is active in vitro against most onychomycosis pathogens - dermatophytes (Epidermophyton spp., Trichophyton spp., Microsporum spp.), Candida spp.(Candida albicans, Candida parapsilosis, Candida tropicalis, Candida lusitania, etc.), Aspergillus, Fusarium, Salmonella schenckii, etc.Fluconazole is active against dermatophytes (Epidermophyton spp., Trichophyton spp., Microsporum spp.) and Candida spp.(Candida albicans, Candida parapsilosis, Candida tropicalis, Candida lusitania, etc.), but does not affect Aspergillus, Scopus, Scedosporium spp.
Different azoles have different pharmacokinetics.Fluconazole (90%) is well absorbed from the gastrointestinal tract.For good absorption of itraconazole, normal acidity is necessary.If a patient taking these drugs has lower acidity, their absorption will be reduced, resulting in less bioavailability.Itraconazole solutions are better absorbed than itraconazole capsules.Itraconazole capsules should be taken with food, and itraconazole solution should be taken on an empty stomach.
Itraconazole is metabolized in the liver and excreted through the gastrointestinal tract.It is also secreted in small amounts by sebaceous and sweat glands.Fluconazole is partially metabolized and excreted mainly unchanged via the kidneys (80%).
Itraconazole interacts with many drugs.The bioavailability of ketoconazole and itraconazole may be decreased when taking antacids, anticholinergics, H2 blockers, proton pump inhibitors, and didanosine.Itraconazole is an active inhibitor of cytochrome P450 isoenzymes and can alter the metabolism of many drugs.Fluconazole has a minor effect on drug metabolism.Azoles should not be taken with terfenadine, astemizole, cisapride, or quinidine because fatal ventricular arrhythmias may occur.Concomitant use of azoles and oral antidiabetic agents requires continuous monitoring of blood glucose levels as hypoglycemia may occur.Administration of coumarin and azole indirect anticoagulants may be associated with hypocoagulation and bleeding; therefore, hemostatic control is necessary.Itraconazole may increase blood concentrations and cause toxic effects of cyclosporine, digoxin, and fluconazole-theophylline.Dosage adjustments and continuous monitoring of drug concentrations in the blood are required.Itraconazole is contraindicated in combination with lovastatin, simvastatin, rifampicin, isoniazid, carbamazepine, cimetidine, clarithromycin, and erythromycin.Fluconazole should not be used with isoniazid and terfenadine.
itraconazoleUsed for dermatomycoses (athlete's foot, trichophyton, microsporomycosis), tinea versicolor, candidiasis of the skin, nails and mucous membranes, esophageal, vulvovaginal candidiasis, cryptococcosis, aspergillosis, dark mycosis, sporotrichosis, chromomycosis, endemic mycoses, and for the prevention of AIDS mycosis.
FluconazoleFor the treatment of systemic candidiasis, all forms of invasive candidiasis, including candidiasis in immunocompromised patients, genital candidiasis, cutaneous, adnexal and mucosal candidiasis.In recent years, due to its safety profile and good tolerability, fluconazole has been increasingly used to treat dermatomycoses in patients with damage to the skin and its appendages (nails and hair).
AmorolfineContained in varnish used to treat onychomycosis.Amorolfine's mechanism of action is to disrupt the synthesis of ergosterol, the main component of fungal cell membranes.It has fungistatic and fungicidal properties.Has a wide scope of action.Amorolfine concentrations in the nail plate significantly exceeded the MIC for the major pathogens of dermatomycosis for 7 consecutive days.Therefore, the drug should be used no more than 1-2 times a week, which makes its use economical.Contraindications: Hypersensitivity reaction to amorolfine, infants and young children.Use varnish as a single therapy when no more than 1-3 nail plates are affected and no more than 1/2 of the distal area is affected.Amorolfine may also be used in combination with systemic antifungals to treat more extensive nail lesions.
CiclopiroxHas antifungal effect.Active against dermatophytes, yeast-like and filamentous fungi, molds and some Gram-negative and Gram-positive bacteria.Use ciclopirox (varnish) as monotherapy when no more than 1-3 nail plates are affected and no more than 1/2 of the distal area is affected.Ciclopirox may also be used in combination with systemic antifungals to treat more extensive nail lesions.Contraindications: Hypersensitivity reaction to ciclopirox, infancy and early childhood, pregnancy and lactation.
Recommended laboratory testing checklist when prescribing systemic antifungal agents.
- Clinical blood tests.
- General urinalysis.
- Biochemical blood tests (ALT, AST, bilirubin, creatinine).
- Ultrasound examination of abdominal organs and kidneys (preferred).
- Pregnancy test (preferred).
Treat underlying conditions.The effectiveness of the use of antifungal drugs increases with the correction of the pathological conditions that lead to the development of onychomycosis.Before starting antifungal therapy in patients with somatic, endocrine, neurological diseases and circulatory disorders of the extremities, it is necessary to perform an examination to identify the main symptoms leading to the development of dermatomycoses.Therefore, the main goals of pathogenesis treatment are to improve the microcirculation of the distal limbs, venous return of the limbs, normalize thyroid-stimulating hormone levels in patients with thyroid disease, carbohydrate metabolism in patients with diabetes, etc.After years of research, it has been established that one of the main causes of dermatomycosis is dermatomycosis disorders.Pituitary-hypothalamic-gonadal system.This results in distal circulatory, microcirculatory, and peripheral innervation disturbances in the extremities.A range of measures aimed at correcting these disorders include acupuncture, transcranial electrical stimulation of the subcortical centers of the brain, and the prescription of medications that correct sympathetic and parasympathetic autonomic nervous system function.All this enables faster clinical results in the treatment of dermatomycoses.For patients with dermatomycosis who have underlying medical conditions, it is recommended that pathogenic treatment be initiated before symptomatic treatment and continued throughout the course of taking antifungal drugs.
Symptomatic treatmentTreatment of dermatomycosis aims to reduce the patient's subjective complaints and objective manifestations of the disease and cannot replace symptomatic treatment.But when used in combination with antifungals, it can quickly improve a patient's condition, reduce discomfort and eliminate cosmetic imperfections.For onychomycosis, patients are most worried about nail curvature, which is caused by deformation and significant thickening (hypertrophy) of the nail plate.To correct this situation, a hardware pedicure can be used.Using a device similar to a dental turbine, altered areas of the nail, areas of hyperkeratosis, keratinous patches of skin, and calluses can be mechanically removed in a short time.In this case, the nail matrix is not damaged and the patient remains functional after the procedure.
For limited nail lesions (no more than 3 nail plates and no more than 1/2 of the area from the distal edge), topical preparations may be used.It is recommended to begin treatment by cleaning the affected area of the nail plate with a hardware pedicure or cuticle remover.Next, apply an antifungal medication to the affected nail plate.Apply amorolfine solution containing ciclopirox to the nail plate 1-2 times per week.You do not need to clean the first few layers of preparation on the nail plate before applying varnish.Apply varnish daily until a healthy nail plate has fully grown.On Day 7, clean your nail plate using any cosmetic nail polish remover.There are conflicting reports in the literature regarding the effectiveness of this treatment.Patient cure rates range from 5% to 9% to 50%.
If the nail plate on the finger is extensively damaged, a combination of treatments including systemic antifungals, nail cleaning, and external treatment with antifungals should be used.To prevent reinfection, it is necessary to dispose of the patient's gloves and disinfect personal hygiene items (towels, washcloths, nail files, graters and scrapers for handling skin and nails).
The drug of choice for treating onychomycosis on any site is terbinafine.Adults and children weighing more than 10 kg, 250 mg daily for 6 weeks.The terbinafine dose for children older than 2 years weighing less than 20 kg is 67.5 mg/kg per day, and 20 to 40 kg to 125 mg/kg per day for 6 weeks.Reserve medicines are products containing itraconazole and fluconazole.Itraconazole is available in two treatment regimens: 200 mg daily for 3 months during the first and fifth weeks of treatment, or 200 mg twice daily for 7 days.Itraconazole is not used to treat onychomycosis in children.It is recommended to take fluconazole 150 mg weekly for 3-6 months.
A combination of systemic antifungals, nail cleansing, topical antifungals, and anti-epidemiological measures can ensure efficient treatment of onychomycosis of the foot.Terbinafine is indicated for adults and children weighing more than 10 kg, 250 mg daily for 12 weeks or longer.For children over 2 years of age weighing less than 20 kg, the drug is prescribed at a dose of 67.5 mg/kg per day, 20 to 40 kg - 125 mg/kg per day for 12 weeks.Fluconazole is recommended at a dose of 150-300 mg once weekly for 6-12 months.Itraconazole is available in two treatment regimens: 200 mg daily for 3 months, or 200 mg twice daily for 7 days, in weeks one, five, and nine.If the big toe is affected, a fourth course of pulse therapy is recommended 13 weeks after the start of treatment.Itraconazole is not used to treat onychomycosis in children.
The criterion for mycological cure of onychomycosis is negative microscopic and cultural examination of the nail plate.After treatment with itraconazole and terbinafine, the healthy nail plate does not grow completely, so full clinical recovery is not observed until 2-4 months after the end of the antifungal medication.