Onychomycosis is the most common nail disease.
It has been established that 50% of cases of changes in the nail plates are associated with a mycotic infection.Epidemiological studies carried out in Russia and foreign countries revealed a high incidence of onychomycosis, which ranged from 2 to 13% in the general population.The risk of developing onychomycosis is greater in elderly patients.For example, in people over 70 years of age, the prevalence of onychomycosis of the feet may be 50% or more.It is believed that this is facilitated by the slow growth of nail plates, disorders of the peripheral and main circulation in the elderly.A high incidence of onychomycosis is also detected in patients with immunodeficiency conditions (including patients with AIDS) and in patients with diabetes mellitus.
Patients and some doctors often perceive onychomycosis as an exclusively aesthetic problem.However, this is a serious disease that occurs chronically and in cases of immunodeficiency or decompensation of endocrine diseases it can cause the development of generalized mycosis of the skin and its appendages.Onychomycosis is often accompanied by the development of serious complications such as diabetic foot, chronic erysipelas of the extremities, lymphostasis and elephantiasis.In patients receiving cytostatic or immunosuppressive therapy, the disease may cause the development of invasive mycoses.That is why treatment of onychomycosis is necessary and must be carried out in a timely manner.
Just a few decades ago, the treatment of onychomycosis was laborious, time-consuming and unpromising.Medicines used to treat fungal diseases of the skin and its annexes were characterized by low efficacy and high toxicity.To obtain a positive result, prolonged treatment or an increase in the dose of medications was required, which was often accompanied by serious complications.Some treatments were potentially fatal for patients.For example, X-ray therapy, the use of thallium and mercury led 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 greatly facilitated the treatment of fungal diseases of the skin and its appendages.However, the results of using new antimycotics were not satisfactory.Controlled clinical trials have shown that the effectiveness of systemic antimycotics after treatment is 40-80%, and after 5 years - 14-50%.At the same time, the effectiveness of therapy for onychomycosis increases with the use of complex treatment methods, which involve the use of etiotropic drugs and agents that influence pathogenesis.In addition, as a result of clinical trials carried out in European countries, it was found that the effectiveness of treating onychomycosis can be increased by an average of 15% with the combined use 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.For the treatment of onychomycosis, systemic drugs belonging to the group of azoles - itraconazole, fluconazole, as well as the group of allylamines - terbinafine are used.Currently, griseofulvin and ketoconazole are not prescribed for the treatment of onychomycosis due to low efficacy and high risk of adverse events.Varnishes and solutions containing amorolfine and ciclopirox are used as external agents for onychomycosis.
Allylaminesare synthetic antimycotics.Allylamines act mainly on dermatomycetes, although they have a fungicidal effect.The mechanism of its 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.), the causative agent of chromomycosis and some other fungi.
Indications for oral administration of terbinafine are onychomycosis, common forms of dermatomycosis of the skin, scalp mycosis, chromomycosis.Indications for external use of terbinafine and naftifine include limited skin lesions due to mycoses, pityriasis versicolor, and cutaneous 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, nails, hair and is secreted with the secretions of the sweat and sebaceous glands.The absorption of terbinafine when applied topically is less than 5%, naftifine - 4-6%.The concentration of terbinafine and naftifine in the skin and its appendages significantly exceeds the MIC for the main pathogens of dermatomycosis.Correction of the terbinafine dosage regimen may be necessary when combined with inducers (rifampicin) or inhibitors of microsomal liver enzymes (cimetidine), since the former increase its clearance and the latter reduce it.
As a result of numerous controlled multicenter comparative clinical trials, it was found that terbinafine is the most effective antimycotic in the treatment of onychomycosis.
Terbinafineused for generalized skin lesions, onychomycosis, chromomycosis;In these cases, terbinafine is prescribed orally.Terbinafine is the drug of choice in the treatment of onychomycosis, as it is most effective against the main causative agents of onychomycosis - dermatomycetes.Contraindications for the use of allylamines are allergic reactions to drugs from the allylamine group, pregnancy, breastfeeding, age under 2 years, liver diseases accompanied by impaired liver function (increased transaminases).
Azoles- the largest group of synthetic antimycotics.In 1984, the first systemic antifungal from the azoles group, ketoconazole, was introduced into practice, in 1990, fluconazole and, in 1992, itraconazole.
Azoles used as systemic medications have predominantly 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 necessary.If a patient taking these medications has low acidity, their absorption decreases and, consequently, their bioavailability decreases.The absorption of itraconazole solution is greater 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 excreted 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 excreted mainly unchanged by the kidneys (80%).
Itraconazole interacts with many medications.The bioavailability of ketoconazole and itraconazole decreases 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 medications.Fluconazole affects drug metabolism less.It is unacceptable to take azoles with terfenadine, astemizole, cisapride, quinidine, as fatal ventricular arrhythmias may occur.Concomitant use of azoles and oral antidiabetics requires constant monitoring of blood glucose levels, as hypoglycemia may occur.The use of indirect anticoagulants from the coumarin and azole group may be accompanied by hypocoagulation and bleeding;therefore, control of hemostasis is necessary.Itraconazole can increase the blood concentration of cyclosporine and digoxin, and fluconazole - theophylline and cause the development of a toxic effect.Dose adjustments and constant monitoring of drug concentrations in the blood are necessary.The combined use of itraconazole with lovastatin, simvastatin, rifampicin, isoniazid, carbamazepine, cimetidine, clarithromycin, erythromycin is contraindicated.Fluconazole should not be used 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, chromomycosis, endemic mycoses, for the prevention of mycoses in AIDS.
Fluconazoleused for the treatment of generalized candidiasis, all forms of invasive candidiasis, including in immunocompromised patients, genital candidiasis, candidiasis of the skin, its appendages and mucous membranes.Recently, due to its safety and good tolerability, fluconazole is increasingly used in the treatment of patients with dermatomycosis with lesions on both the skin and its appendages (nails and hair).
AmorolfineIt is included in the varnish used to treat onychomycosis.Amorolfine's mechanism of action is to disrupt the synthesis of ergosterol, the main component of the fungus' cell membrane.It has fungistatic and fungicidal effects.It has a broad spectrum of action.The concentration of amorolfine in the nail plate significantly exceeds the MIC for the main pathogens of dermatomycosis within 7 days.Therefore, the medicine cannot be applied more than 1 to 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 distal end area is affected.Amorolfine can also be used in combination with systemic antimycotics for more generalized nail damage.
Ciclopiroxhas a fungistatic effect.Active against dermatomycetes, yeast-like and filamentous fungi, 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 for no more than 1/2 of the distal end area.Ciclopirox can also be used in combination with systemic antimycotics for more generalized nail damage.Contraindications: allergic reactions to ciclopirox, infants and early childhood, pregnancy and lactation.
List of laboratory tests recommended when prescribing systemic antifungals.
- Clinical blood test.
- General urine analysis.
- Biochemical blood test (ALT, AST, bilirubin, creatinine).
- Ultrasound of abdominal organs and kidneys (preferred).
- Pregnancy test (preferred).
Treatment of underlying diseases.The effectiveness of the use of antimycotics 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 circulatory disorders in the extremities, it is necessary to carry out an examination to identify the main symptom complex that contributed to the development of dermatomycosis.Thus, the main goals of pathogenetic therapy are to improve microcirculation in the distal parts of the extremities, venous outflow from the extremities, normalize the level of thyroid-stimulating hormones in patients with thyroid diseases, carbohydrate metabolism in patients with diabetes mellitus, etc.As a result of many years of research, it was established that one of the main reasons for the development of dermatomycosis is disorders of the pituitary-hypothalamus-gonadal system.This leads to circulatory disorders in the distal extremities, disorders of microcirculation and peripheral innervation.A set of measures aimed at correcting these disorders includes acupuncture, transcranial electrical stimulation of the subcortical centers of the brain, and the prescription of medications that correct the functioning of the sympathetic and parasympathetic autonomic nervous system.All this makes it possible to obtain a faster clinical effect in the treatment of dermatomycosis.It is advisable to prescribe pathogenetic therapy in dermatomycosis patients with underlying diseases before starting etiotropic treatment and continue it throughout the entire course of antifungal treatment.
Symptomatic therapyof dermatomycosis, which aims to reduce patients' 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 condition of patients, reduce the feeling of discomfort and eliminate cosmetic defects.In onychomycosis, the greatest concern for patients is caused by deformed and significantly thickened (hypertrophied) nail plates - onychogryphosis.To correct this condition, hardware pedicure is used.Using a device that resembles a dental turbine, altered areas of the nails, hyperkeratotic areas, horny masses of the skin and calluses are mechanically removed in a short space of time.In this case, there is no trauma to the nail matrix and the patient remains functional after the procedure.
For limited damage to the nails (no more than 3 nail plates and no more than 1/2 area of the distal edge), topical preparations are used.It is recommended to start treatment by cleaning the affected area of the nail plate with a pedicure or keratolytic agents.Then, antifungal medications are applied to the affected nail plate.An amorolfine solution containing ciclopirox is applied to the nail plate 1-2 times a week.Before applying the varnish, it is not necessary to first clean the nail plate from the previous layers of the preparation.The varnish is applied daily until the healthy nail plate grows completely.On the 7th day, the nail plate is cleaned with any cosmetic nail polish remover.There are conflicting reports in the literature regarding the effectiveness of this treatment method.The percentage of cure of patients is indicated from 5–9 to 50%.
In case of widespread damage to the nail plates of the fingers, a set of treatment measures should include the prescription of systemic antimycotics, cleaning the nails and external therapy with antifungal drugs.To prevent reinfection, it is necessary to treat the patient's gloves and disinfect personal hygiene items (cloths, towels, nail files, graters and scrapers for skin and nail treatment).
The drug of choice for the treatment of onychomycosis of any location is terbinafine.It is prescribed for adults and children weighing more than 10 kg, 250 mg per day for 6 weeks.Children over 2 years old and weighing less than 20 kg receive terbinafine at the rate of 67.5 mg/kg per day, from 20 to 40 kg - 125 mg/kg per day for 6 weeks.Backup medicines 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.It is recommended that fluconazole be taken 150 mg once a week for 3–6 months.
Carrying out complex therapy, which consists of the use of systemic antimycotics, cleaning of nails, local use of antifungals, as well as anti-epidemiological measures, guarantees high efficiency in curing onychomycosis of the feet.Terbinafine is prescribed for adults and children weighing more than 10 kg, 250 mg per day for 12 weeks or longer.For children over 2 years old and weighing less than 20 kg, the drug is prescribed at the rate of 67.5 mg/kg per day, from 20 to 40 kg - 125 mg/kg per day for 12 weeks.It is recommended that fluconazole be used at a dose of 150–300 mg once a week for 6–12 months.Itraconazole is used in two regimens: 200 mg per day for 3 months or 200 mg twice per day for 7 days in the first, fifth and ninth weeks.If the big toes are affected, it is recommended to carry out the 4th course of pulse therapy in the thirteenth week of starting therapy.Itraconazole is not used to treat onychomycosis in children.
The criteria for mycological cure of onychomycosis are negative results of microscopic and cultural examination of the nail plate.After treatment with itraconazole and terbinafine, healthy nail plates do not grow back completely, therefore, complete clinical recovery can be observed only 2 to 4 months after stopping the use of antifungal drugs.