Onychomycosis is the most common nail disease.
It has been established that 50% of cases of nail changes are associated with a fungal infection.Epidemiological studies conducted in Russia and abroad 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 age 70, the prevalence of onychomycosis of the feet may be 50% or higher.It is believed that this is facilitated by slow growth of nails, 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 cosmetic problem.However, it is a serious disease that manifests itself chronically and in cases of immunodeficiency or decompensation of endocrine diseases can cause the development of widespread 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 undergoing cytostatic or immunosuppressive therapy, the disease can 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 appendages were characterized by low efficacy and high toxicity.To achieve a positive result, long-term treatment or an increase in the dose of drugs was required, which was often accompanied by serious complications.Some treatments were potentially life-threatening to 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 antifungal drugs has greatly facilitated the treatment of fungal diseases of the skin and its appendages.However, the results of using the new antifungals have not been satisfactory.Controlled clinical studies have shown that the effectiveness of systemic antifungals after treatment ranges 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 influence the pathogenesis.In addition, as a result of clinical studies conducted in European countries, it was found that the effectiveness of treatment of onychomycosis can be increased by an average of 15% with the combined use of systemic antifungals and antifungal paints 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 that belong to the azole group - itraconazole, fluconazole and the allylamine group - terbinafine are used.Griseofulvin and ketoconazole are not currently prescribed for the treatment of onychomycosis due to poor efficacy and high risk of adverse events.Paints and solutions containing amorolfine and ciclopirox are used as external agents for onychomycosis.
Allylaminesthey are synthetic antifungals.Allylamines act mainly on dermatomycetes, while they have a fungicidal effect.The mechanism of their 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 the administration of terbinafine orally are onychomycosis, common forms of dermatomycosis of the skin, mycosis of the scalp, chromomycosis.Indications for the external use of terbinafine and naftifine include limited skin lesions due to mycosis, 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 sweat and sebaceous gland secretions.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.A correction of the terbinafine dosing regimen may be necessary in combination with inducers (rifampicin) or inhibitors of microsomal liver enzymes (cimetidine), since the former increase 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 widespread skin lesions, onychomycosis, chromomycosis, in these 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 of the allylamine group, pregnancy, breastfeeding, age under 2 years, liver diseases 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 predominantly fungistatic activity.An important advantage of azoles over other drugs is their broad spectrum of antifungal activity.Itraconazole is active in vitro against the majority of 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 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 drugs has low acidity, their absorption decreases and, consequently, their bioavailability decreases.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 metabolised 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 metabolised and is mainly excreted unchanged by the kidneys (80%).
Itraconazole interacts with many drugs.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 affects drug metabolism to a lesser extent.It is unacceptable to take azoles with terfenadine, astemizole, cisapride, quinidine, as fatal ventricular arrhythmias may develop.Concomitant use of azoles and oral antidiabetic drugs requires constant monitoring of blood glucose levels, as hypoglycemia may develop.Taking indirect anticoagulants of the coumarin and azole groups 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 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.
Fluconazoleused for the treatment of generalized candidiasis, all forms of invasive candidiasis, including immunocompromised patients, genital candidiasis, candidiasis of the skin, its appendages and mucous membranes.Recently, thanks to its safety and good tolerability, fluconazole is increasingly used for the treatment of patients suffering from dermatomycosis with damage to both the skin and its appendages (nails and hair).
Amorolfinait is included in the paint used to treat onychomycosis.The mechanism of action of amorolfine is to interrupt the synthesis of ergosterol, the main component of the fungal 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 for 7 days.Therefore, the drug can be applied no more than 1-2 times a week, which makes its use cost-effective.Contraindications: allergic reactions to amorolfine, childhood and young children.Varnish in 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 end is affected.Amorolfine can also be used in combination with systemic antifungals for more widespread nail damage.
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 are affected for no more than 1/2 of the area from the distal end.Ciclopirox can also be used in combination with systemic antifungals for more widespread nail damage.Contraindications: allergic reactions to ciclopirox, infancy and early childhood, pregnancy and breastfeeding.
List of laboratory tests recommended when prescribing systemic antifungal drugs.
- Clinical blood test.
- General urinalysis.
- Biochemical blood test (ALT, AST, bilirubin, creatinine).
- Ultrasound of the abdominal organs and kidneys (preferred).
- Pregnancy test (preferred).
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 the improvement of 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 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 the microcirculation and peripheral innervation.A variety of measures aimed at correcting 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 you to achieve a faster clinical effect in the treatment of dermatomycosis.It is advisable to prescribe pathogenetic therapy to patients suffering from dermatomycosis with underlying diseases before the start of etiotropic treatment and continue it during the entire course of taking antifungal drugs.
Symptomatic therapyof 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 allows you to quickly improve the condition of patients, reduce the feeling of discomfort and eliminate cosmetic defects.With onychomycosis, the greatest concern for patients is caused by deformed, significantly thickened (hypertrophic) 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 from 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 a hardware pedicure or keratolytic agents.After that, antifungal drugs 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 varnish, it is not necessary to clean the nail plate from previous layers of the preparation.The varnish is applied daily until the healthy nail plate fully grows.On the 7th day, the nail plate is cleaned using any cosmetic nail remover.There are conflicting reports in the literature on the effectiveness of this treatment method.The cure rate for patients is quoted as 5–9 to 50%.
In case of widespread damage to the finger nails, a complex of therapeutic measures should include the prescription of a systemic antifungal, cleaning of 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 (wipes, towels, nail files, graters and scrapers for treating skin and nails).
The drug of choice for the treatment of onychomycosis 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 older than 2 years 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 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 after starting therapy.Itraconazole is not prescribed for the treatment of onychomycosis in children.It is recommended to take fluconazole 150 mg once a week for 3-6 months.
Carrying out complex therapy, consisting of taking a systemic antifungal, cleaning the nails, local use of antifungal drugs and anti-epidemiological measures, ensures high efficiency in the treatment of onychomycosis of the feet.Terbinafine is prescribed to adults and children weighing more than 10 kg, 250 mg daily for 12 weeks or longer.For children older than 2 years and weighing less than 20 kg, the drug is prescribed at a dose 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 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 toes are affected, it is recommended to carry out the 4th cycle of pulsed therapy in the thirteenth week after starting therapy.Itraconazole is not used to treat onychomycosis in children.
The criteria for the mycological treatment of onychomycosis are the negative results of the microscopic and cultural examination of the nail plate.After treatment with itraconazole and terbinafine, healthy nails do not grow back completely, so complete clinical recovery can be observed only 2-4 months after the end of taking antifungal drugs.