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 fungal infection.Epidemiological studies conducted in Russia and abroad have revealed a high incidence of onychomycosis, which ranged from 2 to 13% in the general population.The risk of developing onychomycosis is higher in older patients.For example, in people over 70 years of age, the prevalence of onychomycosis in the feet can be 50% or more.It is believed that this is facilitated by the slow growth of nail plates and disorders of peripheral and main circulation in the elderly.A high incidence of onychomycosis is also detected in patients with immunodeficiency diseases (including patients with AIDS) and in patients with diabetes mellitus.
Onychomycosis is often perceived by patients and some doctors as an exclusively cosmetic problem.However, it 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 usually 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 can lead to the development of invasive mycoses.That is why the 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, long and unpromising.Medications used to treat fungal diseases of the skin and its appendages were characterized by low efficacy and high toxicity.To achieve a positive result, long-term treatment or an increase in the dose of the drug was necessary, which was often accompanied by serious complications.Some treatments were life-threatening 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 appearance of highly effective and low-toxic antifungal drugs has greatly facilitated the treatment of fungal diseases of the skin and its appendages.However, the results of the use of new antifungals were not satisfactory.Controlled clinical trials have shown that the effectiveness of systemic antifungals after treatment is 40 to 80%, and after 5 years - 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 etiotropic drugs and agents that influence the 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 combined use of systemic antifungals 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 is made up of azoles (itraconazole, fluconazole, ketoconazole), allylamines (terbinafine, naftifine), griseofulvin, amorolfine and cyclopirox.To treat onychomycosis, systemic drugs belonging to the azole group (itraconazole, fluconazole) and the allylamine group (terbinafine) are used.Currently, griseofulvin and ketoconazole are not prescribed for the treatment of onychomycosis due to their low efficacy and high risk of adverse events.Varnishes and solutions containing amorolfine and cyclopirox are used as external agents for onychomycosis.
AllylaminesThey are synthetic antifungals.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 skin dermatomycosis, scalp mycosis, and 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, nail plates, 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 to 6%.The concentration of terbinafine and naftifine in the skin and its appendages significantly exceeds the MIC of the main pathogens of dermatomycosis.A correction of the dosage regimen of terbinafine may be necessary when it is combined with inducers (rifampicin) or inhibitors of hepatic microsomal enzymes (cimetidine), since the former increase its clearance and the latter reduce it.
As a result of numerous controlled multicenter comparative clinical trials, terbinafine was found to be the most effective antifungal in the treatment of onychomycosis.
terbinafineused for generalized skin lesions, onychomycosis, chromomycosis;In such cases, terbinafine is prescribed orally.Terbinafine is the drug of choice in the treatment of onychomycosis, since it is more 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, lactation, children under 2 years of age, liver diseases accompanied by liver failure (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 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 onychomycosis pathogens: 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 is 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 drugs 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 via 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 may 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, since fatal ventricular arrhythmias may develop.Concomitant use of azoles and oral antidiabetics requires constant monitoring of blood glucose levels, as hypoglycemia may develop.Taking indirect anticoagulants from the coumarin and azole group 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 provoke the development of a toxic effect.Dose adjustments and constant monitoring of blood drug concentrations are required.The combined use of itraconazole with lovastatin, simvastatin, rifampicin, isoniazid, carbamazepine, cimetidine, clarithromycin and 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, pheohyphomycosis, 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 for the treatment of patients with dermatomycosis with damage to both the skin and its appendages (nails and hair).
amorolfineIt is included in the varnish used to treat onychomycosis.The mechanism of action of amorolfine is to alter the synthesis of ergosterol, the main component of the fungal cell membrane.It has fungistatic and fungicidal effects.It has a wide spectrum of action.The concentration of amorolfine in the nail plate significantly exceeds the MIC of the main pathogens of dermatomycosis for 7 days.Therefore, the drug can be applied no more than 1 to 2 times a week, which makes its use economically profitable.Contraindications: allergic reactions to amorolfine, infancy and young children.Varnish as monotherapy is prescribed when no more than 1 to 3 nail plates and no more than half of the area from the distal end are affected.Amorolfine can also be used in combination with systemic antifungals for more widespread nail damage.
ciclopiroxIt has a fungistatic effect.Active against dermatomycetes, filamentous and yeast-like fungi, molds and some gram-negative and gram-positive bacteria.Ciclopirox (varnish) is used as monotherapy when no more than 1 to 3 nail plates are affected by no more than half the area from the distal end.Ciclopirox can also be used in combination with systemic antifungals for more widespread nail damage.Contraindications: allergic reactions tociclopirox, infancy and early childhood, pregnancy and lactation.
List of laboratory tests recommended when prescribing systemic antifungal medications.
- Clinical blood test.
- General urine analysis.
- Biochemical blood test (ALT, AST, bilirubin, creatinine).
- Ultrasound of the abdominal organs and kidneys (preferred).
- Pregnancy test (preferable).
Treatment of underlying diseases.The effectiveness of the use of antifungals increases with the correction of pathological conditions that contribute to the development of onychomycosis.Before starting antifungal therapy in patients with somatic, endocrine, neurological diseases and with circulatory disorders in the extremities, it is necessary to conduct an examination to identify the main symptom complex that contributed to the development of dermatomycosis.Therefore, the main goals of pathogenic therapy are to improve microcirculation in the distal parts of the extremities, venous outflow of 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 has been established that one of the main reasons for the development of dermatomycosis is disorders of the pituitary-hypothalamic-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 achieve a faster clinical effect in the treatment of dermatomycosis.It is advisable to prescribe pathogenic therapy in dermatomycosis patients with underlying diseases before the start of etiotropic treatment and continue it throughout the treatment with antifungal drugs.
Symptomatic therapyTreatment of dermatomycosis, aimed at reducing 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.With onychomycosis, the biggest concern for patients is the deformed and significantly thickened (hypertrophied) nail plate - 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 period 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 of the area from the distal edge), topical preparations are used.It is recommended to start treatment by cleaning the affected area of the nail plate using hardware pedicure or keratolytic agents.Antifungal medications are then applied to the affected nail plate.An amorolfine solution containingciclopirox is applied to the nail plate 1 or 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 seventh 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 between 5 and 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 a systemic antifungal, nail cleaning and external therapy with antifungal drugs.To prevent reinfection, it is necessary to treat the patient's gloves and disinfect personal hygiene items (towels, 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.Adults and children weighing more than 10 kg are prescribed 250 mg per day for 6 weeks.Children over 2 years old weighing less than 20 kg are prescribed terbinafine at 67.5 mg/kg per day, from 20 to 40 kg - 125 mg/kg per day for 6 weeks.Reserve medications 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 week from the start of treatment.Itraconazole is not prescribed for the treatment of onychomycosis in children.It is recommended to take fluconazole 150 mg once a week for 3 to 6 months.
Carrying out complex therapy, consisting of taking a systemic antifungal, cleaning the nails, local use of antifungal drugs and anti-epidemiological measures, guarantees high effectiveness 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 more.For children over 2 years old 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.Fluconazole is recommended for use at a dose of 150 to 300 mg once a week for 6 to 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 toes are affected, it is recommended to perform the fourth cycle of 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 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 completely regrow, therefore, complete clinical recovery can be observed only 2 to 4 months after completing treatment with antifungal drugs.