Onychomycosis is the most common nail disease.
It was found that 50% of cases of changes in the nail plates are associated with mycotic infection.Epidemiological studies conducted in Russia and abroad have revealed a high incidence of onychomycosis, ranging from 2 to 13% in the general population.The risk of developing onychomycosis is highest in older patients.For example, in people over 70 years of age, the prevalence of onychomycosis of the feet may be 50% or more.This is believed to be facilitated by the slow growth of nail plates and disturbances of the peripheral and main circulation in the elderly.A high incidence of onychomycosis is also noted in patients with immunodeficiency (including AIDS patients) and in patients with diabetes mellitus.
Often patients and some doctors perceive onychomycosis as an exclusively aesthetic problem.However, this is a serious disease that occurs chronically and, in the event of immunodeficiency or decompensation of endocrine diseases, can lead to the development of extensive 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 can lead to the development of invasive mycoses.Therefore, treatment of onychomycosis is necessary and should be carried out in a timely manner.
Just a few decades ago, the treatment of onychomycosis was labor-intensive, lengthy and unpromising.Drugs for the treatment of fungal diseases of the skin and its appendages were characterized by low effectiveness and high toxicity.To achieve a positive result, long-term treatment or an increase in the dosage of medication was required, which was often accompanied by serious complications.Some treatments were potentially life-threatening for patients.For example, X-ray therapy, the use of thallium and mercury in patients led to the development of skin cancer, diseases of the brain and internal organs.
The advent of highly effective and low-toxic antimycotics has made the treatment of fungal diseases of the skin and its appendages much easier.However, the results of the use of new antifungal drugs have not been satisfactory.Controlled clinical trials have shown that the effectiveness of systemic antifungal agents is 40 to 80% after treatment and 14 to 50% after 5 years.At the same time, the effectiveness of therapy for onychomycosis increases due to the use of complex treatment methods, which involve the use of etiotropic drugs and active substances that affect the pathogenesis.In addition, as a result of clinical studies conducted in European countries, it was found that the effectiveness of the treatment of onychomycosis can be increased by an average of 15% through the combined use of systemic antifungal drugs and antifungal varnish containing amorolfine.
Treatment
To treat onychomycosis, drugs are used that differ in chemical composition, mechanism of action, pharmacokinetics and spectrum of antifungal activity.A common property is their specific effect on pathogenic fungi.This group includes 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 currently not prescribed for the treatment of onychomycosis due to low efficacy and high risk of adverse events.Amorolfine and ciclopirox-containing varnishes and solutions are used as external agents against onychomycosis.
Allylaminesare synthetic antifungals.Allylamines act primarily on dermatomycetes, while they have a fungicidal effect.Their mechanism of action is to inhibit the enzyme squalene epoxidase, which is involved 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, mycosis of the scalp, 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 and hair and is excreted in the secretions of the sweat and sebaceous glands.The absorption of terbinafine when applied topically is less than 5%, of 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.When combined with inducers (rifampicin) or inhibitors of liver microsomal enzymes (cimetidine), correction of the terbinafine dosage regimen may be necessary, since the former increase clearance and the latter decrease it.
As a result of numerous controlled multicenter comparative clinical studies, terbinafine was found to be the most effective antifungal agent in the treatment of onychomycosis.
TerbinafineUsed for extensive skin lesions, onychomycosis and 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 pathogens of onychomycosis - dermatomycetes.Contraindications to the use of allylamines are allergic reactions to drugs of the allylamine group, pregnancy, breastfeeding, age under 2 years, liver diseases with impaired liver function (increased transaminases).
Azoles- the largest group of synthetic antifungal drugs.The first systemic antimycotic from the azole group, ketoconazole, was introduced into practice in 1984, fluconazole in 1990 and itraconazole in 1992.
Azoles used as systemic drugs predominantly have fungistatic effects.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.out of.
The pharmacokinetics of different azoles are different.Fluconazole (90%) is well absorbed from the gastrointestinal tract.Normal acidity is necessary for good absorption of itraconazole.If a patient taking these medicines has low acidity, their absorption and therefore bioavailability will be reduced.The 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 excreted from the body via the gastrointestinal tract.It is also secreted in small quantities by the sebaceous and sweat glands.Fluconazole is partially metabolized and largely excreted 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 drugs.Fluconazole influences drug metabolism to a lesser extent.Taking azoles together with terfenadine, astemizole, cisapride and quinidine is unacceptable as fatal ventricular arrhythmias may occur.Concomitant use of azoles and oral antidiabetic agents requires constant monitoring of blood glucose levels as hypoglycemia may occur.Taking indirect anticoagulants of the coumarin and azole groups may be associated with hypocoagulation and bleeding;Therefore, control of hemostasis is necessary.Itraconazole can increase the blood concentration of cyclosporine and digoxin, as well as fluconazole and theophylline, causing the development of a toxic effect.Dose adjustments and constant monitoring of drug concentrations in the blood are required.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, pheohyphomycosis, sporotrichosis, chromomycosis, endemic mycoses, for the prevention of mycoses in AIDS.
FluconazoleFor 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.Due to its safety and good tolerability, fluconazole has recently been increasingly used to treat patients with dermatomycosis with damage to both the skin and its appendages (nails and hair).
Amorolfineis contained in the varnish for the treatment of onychomycosis.The mechanism of action of amorolfine is to disrupt the synthesis of ergosterol, the main component of the fungal cell membrane.It has fungistatic and fungicidal effects.Has a wide spectrum of effects.The concentration of amorolfine in the nail plate significantly exceeds the MIC for the main pathogens of 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 if no more than 1-3 nail plates are affected and no more than half of the area is affected from the distal end.For larger nail damage, amorolfine can also be used in combination with systemic antifungal agents.
Ciclopiroxhas a fungistatic effect.Active against dermatomycetes, yeast-like and filamentous fungi, molds and some gram-negative and gram-positive bacteria.Ciclopirox (varnish) is used as monotherapy when no more than 1-3 nail plates and no more than half of the area from the distal end are affected.In the case of major nail damage, Ciclopirox can also be used in combination with systemic antimycotics.Contraindications: allergic reactions to ciclopirox, infancy and young children, pregnancy and breastfeeding.
List of recommended laboratory tests when prescribing systemic antifungals.
- Clinical blood test.
- General urinalysis.
- 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 antifungal drugs 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 circulatory disorders of the extremities, an examination is necessary to identify the main symptom complex that contributed to the development of dermatomycosis.Therefore, the main goals of pathogenetic therapy are to improve microcirculation in the distal parts of the extremities, venous outflow of the extremities, normalization of 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 causes of the development of dermatomycosis is disorders of thepituitary-hypothalamic-gonadal system.This leads to circulatory disorders of the distal extremities, microcirculation disorders and peripheral innervation.A number of measures to correct these disorders include acupuncture, transcranial electrical stimulation of the subcortical centers of the brain and the prescription of drugs that correct the functioning of the sympathetic and parasympathetic autonomic nervous systems.All this allows for a faster clinical effect in the treatment of dermatomycosis.It is advisable to prescribe pathogenetic therapy to patients with dermatomycosis with underlying diseases before starting etiotropic treatment and to continue it throughout the entire course of taking antifungal drugs.
Symptomatic therapyof dermatomycosis, aimed at reducing subjective complaints of patients and objective manifestations of the disease, cannot replace etiotropic therapy.However, its use in combination with antifungal drugs allows to quickly improve the condition of patients, reduce discomfort and eliminate cosmetic defects.In onychomycosis, deformed, significantly thickened (hypertrophied) nail plates - onychogryphosis - are the biggest concern for patients.To correct this condition, hardware pedicure is used.Using a device similar to a dental turbine, altered areas of the nails, hyperkeratotic areas, horny masses on 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 nail damage (no more than 3 nail plates and no more than 1/2 area from the distal edge), topical preparations are used.It is recommended to start treatment by cleaning the affected area of the nail plate with a hardware pedicure or keratolytic agents.Antifungal medications are then applied to the affected nail plate.An amorolfine solution with 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 layers of the preparation.The varnish is applied daily until the healthy nail plate has completely grown back.On the 7th day, the nail plate is cleaned with 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 reported to be 5-9 to 50%.
With extensive damage to the nail plates on the fingers, a complex of treatment measures should include the prescription of a systemic antifungal drug, cleaning the nails and external therapy with antifungal drugs.To prevent re-infection, it is necessary to treat the patient with gloves and disinfect personal hygiene items (washcloths, towels, nail files, graters and scrapers for treating skin and nails).
The drug of choice for the treatment of onychomycoses of any location 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 old and weighing less than 20 kg are prescribed terbinafine at a dose of 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 doses: 200 mg daily for 3 months or 200 mg twice daily for 7 days in the first and fifth weeks after starting therapy.Itraconazole is not prescribed to treat onychomycosis in children.It is recommended to take fluconazole 150 mg once a week for 3-6 months.
Conducting complex therapy, consisting of taking a systemic antifungal drug, cleaning nails, local use of antifungal drugs, as well as antiepidemiological measures, ensures 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 a dosage of 67.5 mg/kg per day, from 20 to 40 kg – 125 mg/kg per day for 12 weeks.It is recommended to use fluconazole at a dose of 150-300 mg once weekly for 6-12 months.Itraconazole is used in two doses: 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 that the fourth pulse therapy be carried out in the 13th week after the start of therapy.Itraconazole is not used to treat onychomycosis in children.
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, so complete clinical recovery can be observed only 2-4 months after stopping taking antifungal drugs.