Onychomycosis is the most common nail disease.
It has been determined that 50% of cases of changes in the nail plate are associated with mycotic infections.Epidemiological studies conducted in Russia and foreign countries have revealed a high incidence of onychomycosis, which ranges from 2 to 13% in the general population.The risk of getting onychomycosis is highest in older patients.For example, in people over 70 years of age, the prevalence of foot onychomycosis can be 50% or higher.It is believed that this is facilitated by the slow growth of the nail plate, impaired peripheral and primary circulation in the elderly.A high incidence of onychomycosis is also detected in patients with immunodeficiency conditions (including AIDS patients) and in patients with diabetes mellitus.
Often patients and some doctors consider onychomycosis as a purely aesthetic problem.However, this is a serious disease that occurs chronically and in cases of immune deficiency or endocrine disease decompensation can lead to the development of widespread skin mycosis and its appendages.Onychomycosis is often accompanied by the development of severe complications, such as diabetic foot, chronic erysipelas on the feet, lymphostasis, and elephantiasis.In patients receiving cytostatic or immunosuppressive therapy, this disease can cause the development of invasive mycoses.That is why onychomycosis treatment is necessary and should be carried out on time.
Only a few decades ago, the treatment of onychomycosis was labor intensive, long and unpromising.Medicines used to treat fungal diseases of the skin and appendages are characterized by low efficacy and high toxicity.To achieve a positive result, long-term treatment or an increase in the dose of the drug is required, which is often accompanied by severe complications.Some treatments are potentially life-threatening.For example, X-ray therapy, the use of thallium and mercury lead to the development of skin cancer, diseases of the brain and internal organs in patients.
The emergence of highly effective and low-toxic antimycotic drugs has facilitated the treatment of fungal diseases of the skin and appendages.However, the results of using new antimycotics are not satisfactory.Controlled clinical trials have shown that the effectiveness of systemic antimycotics after treatment is from 40 to 80%, and after 5 years - from 14 to 50%.At the same time, the effectiveness of therapy for onychomycosis increases with the use of complex treatment methods, which involve the use of drugs and etiotropic agents that affect pathogenesis.In addition, as a result of clinical trials conducted in European countries, it was found that the effectiveness of the treatment of onychomycosis can be increased by an average of 15% with the use of a combination of systemic antimycotics and antifungal varnish containing amorolfine.
Treatment
For the treatment of onychomycosis, drugs are used that differ in chemical composition, mechanism of action, pharmacokinetics, and spectrum of antifungal activity.A common property for them is a specific effect on pathogenic fungi.This group consists of azoles (itraconazole, fluconazole, ketoconazole), allylamines (terbinafine, naftifine), griseofulvin, amorolfine, ciclopirox.To treat onychomycosis, systemic drugs are used that belong to the azole group - itraconazole, fluconazole, as well as the allylamine group - terbinafine.Griseofulvin and ketoconazole are not currently prescribed for the treatment of onychomycosis because of their low efficacy and high risk of adverse events.Varnishes and solutions containing amorolfine and ciclopirox are used as external agents for onychomycosis.
Allylaminesis a synthetic antifungal.Allylamines mainly act on dermatomycetes, while they have a fungicidal effect.Their mechanism of action is to inhibit the enzyme squalene epoxidase, which participates in the synthesis of ergosterol, the main structural component of the cell membrane of dermatomycetes.Allylamines include terbinafine and naftifine.
Allylamines are active against most dermatomycetes (Epidermophyton spp., Trichophyton spp., Microsporum spp., Malassezia spp.), causative agents of chromomycosis and some other fungi.
Indications for oral administration of terbinafine are onychomycosis, common forms of skin dermatomycosis, scalp mycosis, chromomycosis.Indications for external use of terbinafine and naftifine include limited skin lesions due to mycoses, pityriasis versicolor, and skin candidiasis.Terbinafine has high bioavailability and is well absorbed from the gastrointestinal tract regardless of food intake.In high concentrations, the drug accumulates in the stratum corneum of the skin, nail plates, hair, and is secreted by sweat secretions and sebaceous glands.Absorption of terbinafine when used topically is less than 5%, naftifine - 4-6%.Concentrations of terbinafine and naftifine in the skin and appendages significantly exceeded the MIC for the main pathogens of dermatomycosis.Correction of the dosage regimen of terbinafine may be necessary when combined with inducers (rifampicin) or inhibitors of microsomal liver enzymes (cimetidine), because the former increases its clearance, and the latter decreases it.
As a result of many controlled multicenter comparative clinical trials, it was found that terbinafine is the most effective antimycotic in the treatment of onychomycosis.
Terbinafineused for widespread skin lesions, onychomycosis, chromomycosis, in such cases terbinafine is prescribed orally.Terbinafine is the drug of choice in the treatment of onychomycosis, because it is most effective against the main causative agent of onychomycosis - dermatomycetes.Contraindications for the use of allylamine are allergic reactions to drugs of the allylamine group, pregnancy, breastfeeding, age under 2 years, liver disease accompanied by impaired liver function (increased transaminases).
Azoles- the largest group of synthetic antifungals.In 1984, the first systemic antifungal drug from the azole group, ketoconazole, was introduced into practice, in 1990, fluconazole, and in 1992, itraconazole.
Azoles used as systemic drugs have mostly fungistatic activity.An important advantage of azoles over other drugs is their broad spectrum of antifungal activity.Itraconazole is active in vitro against most pathogens of onychomycosis - dermatomycetes (Epidermophyton spp., Trichophyton spp., Microsporum spp.), Candida spp.(C. albicans, C. parapsilosis, C. tropicalis, C. lusitaniae, etc.), Aspergillus spp., Fusarium spp., S. Shenckii, etc.Fluconazole is active against dermatomycetes (Epidermophyton spp., Trichophyton spp., Microsporum spp.) and Candida spp.) (C. albicans, C. parapsilosis, C. tropicalis, C. lusitaniae, etc.), but does not affect Aspergillus spp., Scopulariopsis spp., Scedosporium spp.
The pharmacokinetics of different azoles are different.Fluconazole (90%) is well absorbed from the gastrointestinal tract.For good absorption of itraconazole, a normal level of acidity is required.If the patient taking this drug has low acidity, its absorption is reduced and, as a result, its bioavailability is reduced.Absorption of itraconazole solution is higher than that of 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 removed from the body through the gastrointestinal tract.It is also secreted in small quantities by the sebaceous and sweat glands.Fluconazole is partially metabolized and mostly excreted unchanged by the kidneys (80%).
Itraconazole interacts with many medications.The bioavailability of ketoconazole and itraconazole is reduced 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 affects drug metabolism to a lesser extent.It is unacceptable to take azoles with terfenadine, astemizole, cisapride, quinidine, because lethal ventricular arrhythmias can develop.The simultaneous use of azoles and oral antidiabetic drugs requires constant monitoring of blood glucose levels, as hypoglycemia may develop.Taking indirect anticoagulants of the coumarin group and azoles may be accompanied by hypocoagulation and bleeding;therefore, hemostasis control is necessary.Itraconazole can increase the blood concentration of cyclosporine and digoxin, and fluconazole - theophylline and cause the development of toxic effects.Dosage adjustment and continuous monitoring of the drug concentration in the blood is required.The combined use of itraconazole with lovastatin, simvastatin, rifampicin, isoniazid, carbamazepine, cimetidine, clarithromycin, erythromycin is contraindicated.Fluconazole should not be used together with isoniazid and terfenadine.
Itraconazoleused for dermatomycosis (athlete's foot, trichophytosis, microsporia), pityriasis versicolor, candidiasis of the skin, nails and mucous membranes, esophagus, vulvovaginal candidiasis, cryptococcosis, aspergillosis, phaeohyphomycosis, sporotrichosis, AIDS chromomycoses, chromomycoses.
Fluconazoleused for the treatment of general candidiasis, all forms of invasive candidiasis, including in immunocompromised patients, genital candidiasis, candidiasis of the skin, appendages and mucous membranes.Recently, due to its safety and good tolerance, fluconazole is increasingly used for the treatment of patients with dermatomycosis with damage to both the skin and its appendages (nails and hair).
Amorolfineincluded in the varnish used to treat onychomycosis.The mechanism of action of amorolfine is to interfere with the synthesis of ergosterol, the main component of the fungal cell membrane.It has a fungistatic and fungicidal effect.Has a wide spectrum of action.The concentration of amorolfine in the nail plate significantly exceeded the MIC for the main pathogen dermatomycosis for 7 days.Therefore, the drug can be used no more than 1-2 times a week, which makes its use economically profitable.Contraindications: allergic reactions to amorolfine, infants and young children.Varnish as monotherapy is prescribed when no more than 1-3 nail plates are affected and no more than 1/2 of the area from the distal tip is affected.Amorolfine can also be used in combination with systemic antimycotics for more extensive nail damage.
Ciclopiroxhas a fungistatic effect.Active against dermatomycetes, fungi such as yeasts and filaments, molds, as well as some gram-negative and gram-positive bacteria.Ciclopirox (varnish) is used as monotherapy when no more than 1-3 nail plates are affected by no more than 1/2 of the area from the distal end.Ciclopirox can also be used in combination with systemic antimycotics for more extensive nail damage.Contraindications: allergic reactions to ciclopirox, infants and early children, pregnancy and breastfeeding.
List of laboratory tests recommended when prescribing systemic antifungal drugs.
- Clinical blood tests.
- General urine analysis.
- Biochemical blood tests (ALT, AST, bilirubin, creatinine).
- Ultrasound of abdominal organs and kidneys (preferred).
- Pregnancy test (preferred).
Treatment of basic diseases.The effectiveness of antimycotic use increases with the correction of pathological conditions that contribute to the development of onychomycosis.Before starting antimycotic therapy in patients with somatic, endocrine, neurological diseases, and with circulatory disorders in the legs, it is necessary to conduct an examination to identify the main symptom complex that contributes to the development of dermatomycosis.Therefore, the main objective of pathogenetic therapy is to improve microcirculation in the distal part of the extremities, venous outflow in the legs, normalize the level of thyroid-stimulating hormone in patients with thyroid disease, carbohydrate metabolism in patients with diabetes mellitus, etc.As a result of years of research, it has been established that one of the main reasons for the development of dermatomypothalamusicosis is the pituitary system.This leads to disruption of blood circulation in the distal end, disruption of microcirculation, and peripheral conservation.A set of measures aimed at correcting this disorder include acupuncture, transcranial electrical stimulation of the subcortical center of the brain, and the prescription of drugs that correct the function of the sympathetic and parasympathetic autonomic nervous system.All this makes it possible to achieve a faster clinical effect in the treatment of dermatomycosis.It is advisable to prescribe pathogenetic therapy in patients with dermatomycosis with an underlying disease before the start of etiotropic treatment and continue it during the entire period of taking antifungal drugs.
Symptomatic therapydermatomycosis, aimed at reducing the patient's subjective complaints and objective manifestations of the disease, cannot replace etiotropic therapy.However, its use in combination with antifungal drugs makes it possible to quickly improve the patient's condition, reduce discomfort and eliminate cosmetic defects.With onychomycosis, the biggest concern for patients is caused by the deformed nail plate, significantly thickened (hypertrophy) - onychogryphosis.To correct this condition, a hardware pedicure is used.Using a device that resembles a dental turbine, in a short period of time, altered nail areas, hyperkeratotic areas, horny masses from the skin, and calluses are mechanically removed.In this case, there was no trauma to the nail matrix, and the patient remained functional after the procedure.
For limited damage to the nail (no more than 3 nail plates and no more than 1/2 in area from the distal edge), topical preparations are used.It is recommended to start the treatment by cleaning the affected area of the nail plate using hardware pedicure or keratolytic agents.Next, antifungal medication is applied to the affected nail plate.Amorolfine solution containing ciclopirox is applied to the nail plate 1-2 times a week.Before applying the varnish, you do not need to first clean the nail plate from the previous preparation layer.Varnish is used daily until the healthy nail plate grows completely.On the 7th day, the nail plate is cleaned using any cosmetic nail polish remover.There are conflicting reports in the literature about the effectiveness of this treatment method.The percentage of cure for patients is shown from 5-9 to 50%.
In case of extensive damage to the nail plate on the fingers, a complex of treatment measures should include the prescription of systemic antimycotics, nail cleaning and external therapy with antifungal drugs.To prevent re-infection, it is necessary to treat the patient's gloves and disinfect personal hygiene items (wipes, towels, nail files, scales and scrapers for treating skin and nails).
The drug of choice for the treatment of onychomycosis of any localization is terbinafine.It is prescribed to adults and children weighing more than 10 kg, 250 mg per day for 6 weeks.Children over 2 years of age with a weight of less than 20 kg are prescribed terbinafine at a rate of 67.5 mg/kg per day, from 20 to 40 kg - 125 mg/kg per day for 6 weeks.Reserve drugs are products containing itraconazole and fluconazole.Itraconazole is used in two regimens: 200 mg daily for 3 months or 200 mg twice daily for 7 days in the first and fifth weeks from the start of therapy.Itraconazole is not prescribed for the treatment of onychomycosis in children.Fluconazole is recommended to be taken 150 mg once a week for 3-6 months.
Carrying out complex therapy, which consists of taking systemic antimycotics, cleaning the nails, local use of antifungal drugs, as well as anti-epidemiological measures, ensures high efficiency in curing foot onychomycosis.Terbinafine is prescribed to adults and children weighing more than 10 kg, 250 mg per day for 12 weeks or more.For children over 2 years old with a weight of less than 20 kg, this drug is prescribed at a rate of 67.5 mg/kg per day, from 20 to 40 kg - 125 mg/kg per day for 12 weeks.Fluconazole is recommended for use at a dose of 150-300 mg once a week for 6-12 months.Itraconazole is used in two regimens: 200 mg daily for 3 months or 200 mg twice daily for 7 days in the first, fifth and ninth weeks.If the big toe is affected, it is recommended to carry out the 4th pulse therapy in the thirteenth week from the start of therapy.Itraconazole is not used for the treatment of onychomycosis in children.
The criteria for a mycological cure for onychomycosis is a negative result of microscopic examination and culture of the nail plate.After treatment with itraconazole and terbinafine, the healthy nail plate does not grow back completely, so complete clinical recovery can be observed only 2-4 months after the end of taking antifungal drugs.