Onychomycosis is the most common nail disease.
It has been found that 50% of cases of changes in the nail plates are associated with a mycotic infection.Epidemiological studies conducted in Russia and abroad show a high incidence of onychomycosis, which varies from 2 to 13% in the general population.The risk of developing onychomycosis is highest in older patients.For example, in people over the age of 70, the prevalence of onychomycosis of the feet can be 50% or more.It is believed that this is facilitated by the slow growth of nail plates, disorders of peripheral and main blood circulation in the elderly.A high incidence of onychomycosis is also found in patients with immunodeficiency conditions (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 is chronic and in cases of immune deficiency or decompensation of endocrine diseases can lead to the development of widespread mycosis of the skin and its appendages.Onychomycosis is often accompanied by the development of severe complications such as diabetic foot, chronic erysipelas of the extremities, lymphostasis and elephantiasis.In patients receiving cytostatic or immunosuppressive therapy, the disease can cause the development of invasive mycoses.That is why the treatment of onychomycosis is necessary and should be carried out in a timely manner.
Only a few decades ago, the treatment of onychomycosis was laborious, lengthy and unpromising.Medicines used to treat fungal diseases of the skin and its appendages are characterized by low efficiency and high toxicity.To achieve a positive result, long-term treatment or an increase in the dose of drugs is required, which is often accompanied by severe complications.Some treatments are potentially 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 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 the use of new antifungals were not satisfactory.Controlled clinical trials show that the effectiveness of systemic antifungals after treatment is from 40 to 80%, and after 5 years - from 14 to 50%.At the same time, the effectiveness of the treatment of onychomycosis increases with the use of complex treatment methods, which include the use of etiotropic drugs and agents that affect pathogenesis.Also, 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
Medicines that differ in chemical composition, mechanism of action, pharmacokinetics and spectrum of antifungal activity are used to treat onychomycosis.A common property for them is the 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 are used that belong to the group of azoles - itraconazole, fluconazole, as well as to the group of allylamines - terbinafine.Currently, griseofulvin and ketoconazole are not prescribed for the treatment of onychomycosis due to low effectiveness and high risk of side effects.Varnishes and solutions containing amorolfine and ciclopirox are used as external means for onychomycosis.
Allylaminesare synthetic antifungals.Allylamines act primarily on dermatomycetes, while having a fungicidal effect.The mechanism of their 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, hair and is secreted with the secretions of the sweat and sebaceous glands.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.It may be necessary to adjust the dosage regimen of terbinafine when it is combined with inducers (rifampicin) or inhibitors of microsomal liver enzymes (cimetidine), since the former increase its clearance, and the latter decrease it.
As a result of numerous controlled multicenter comparative clinical studies, it was established that terbinafine is the most effective antifungal 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, as it is most effective against the main causative agents of onychomycosis - dermatomycetes.Contraindications to 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).
Azole- 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 mainly fungistatic action.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.A normal level of acidity is necessary for good absorption of itraconazole.If the patient taking these drugs has low acidity, their absorption decreases and therefore their bioavailability decreases.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 through the gastrointestinal tract.It is also secreted in small amounts 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 drugs.Fluconazole affects the metabolism of the drug to a lesser extent.It is unacceptable to take azoles with terfenadine, astemizole, cisapride, quinidine, as lethal ventricular arrhythmias can develop.The simultaneous use of azoles and oral antidiabetic drugs requires constant monitoring of blood sugar levels, as hypoglycemia may develop.Taking indirect anticoagulants from the coumarin and azole group can 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 the concentration of the drug 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.
Itraconazoleit is used 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.
fluconazoleit is used to treat 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 tolerance, fluconazole is increasingly used to treat patients with dermatomycosis with damage to both the skin and its appendages (nails and hair).
Amorolfineis included in a varnish used to treat onychomycosis.The mechanism of action of amorolfine is to disrupt the synthesis of ergosterol, the main component of the cell membrane of fungi.It has a fungistatic and fungicidal effect.It has a wide range of action.The concentration of amorolfine in the nail plate significantly exceeded 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 economically profitable.Contraindications: allergic reactions to amorolfine, infants and young children.Lacquer as monotherapy is prescribed when no more than 1-3 nail plates and no more than 1/2 of the area from the distal end are 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, as well as some gram-negative and gram-positive bacteria.Ciclopirox (lacquer) is used as monotherapy when no more than 1-3 nail plates are affected at 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 recommended laboratory tests when prescribing systemic antifungal drugs.
- Clinical blood test.
- General analysis of urine.
- Biochemical blood test (ALT, AST, bilirubin, creatinine).
- Ultrasound of abdominal organs and kidneys (preferred).
- Pregnancy test (preferred).
Treatment of the main diseases.The effectiveness of the use of antimycotics increases with the correction of the 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 limbs, it is necessary to conduct a study to identify the main complex of symptoms that contributed to the development of dermatomycosis.Thus, the main goals of pathogenetic therapy are improving microcirculation in the distal parts of the limbs, venous outflow of the limbs, normalizing 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 are disorders of the pituitary-hypothalamus-gonadal system.This leads to disorders of blood circulation in the distal limbs, disorders of microcirculation and peripheral innervation.The complex of measures aimed at correcting these disorders includes acupuncture, transcranial electrical stimulation of the subcortical centers of the brain and prescription of drugs that correct the functioning of the sympathetic and parasympathetic autonomic nervous systems.All this makes it possible to achieve a faster clinical effect in the treatment of dermatomycosis.It is recommended to prescribe pathogenetic therapy in patients with dermatomycosis with concomitant diseases before the start of etiotropic treatment and to continue it during the entire course of taking antifungal drugs.
Symptomatic therapyof dermatomycosis, aimed at reducing the subjective complaints of patients and the objective manifestations of the disease, cannot replace etiotropic therapy.However, its use in combination with antifungal drugs allows rapid improvement of patients' condition, reduction of discomfort and elimination of cosmetic defects.In onychomycosis, the biggest worry for patients is caused by deformed, significantly thickened (hypertrophied) nail plates - onychogryphosis.To correct this condition, a hardware pedicure is used.With an apparatus similar to a dental turbine, changed areas of the nails, hyperkeratotic areas, horny skin formations 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.
In case of limited nail damage (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 the treatment by cleaning the affected area of the nail plate using a hardware pedicure or keratolytic agents.Antifungal drugs are then 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, it is not necessary to first clean the nail plate of the previous layers of the preparation.The varnish is applied daily until the healthy nail plate has fully grown.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.Patient cure rates have been shown to range from 5–9 to 50%.
In the case of widespread damage to the nail plates of the fingers, the complex of treatment measures should include the prescription of a systemic antifungal agent, cleaning of the nails and external therapy with antifungal drugs.To prevent re-infection, it is necessary to treat the patient's gloves and disinfect personal hygiene items (towels, towels, nail files, plans and scrapers for the treatment of 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 at 250 mg per day for 6 weeks.Children older than 2 years weighing less than 20 kg are prescribed terbinafine at the rate of 67.5 mg / kg per day, from 20 to 40 kg - 125 mg / kg per day for 6 weeks.Replacement 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 during the first and fifth weeks of starting 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.
The implementation of complex therapy, consisting of a systemic antifungal agent, nail cleaning, local use of antifungal drugs, as well as anti-epidemiological measures, ensures high effectiveness in the treatment of 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 of age with a weight of 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 to be used 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 during the first, fifth, and ninth weeks.If the big toes are affected, it is recommended to conduct the 4th course of pulse therapy at the thirteenth week from the start of 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 completely, so complete clinical recovery can be observed only 2-4 months after the end of taking antifungal drugs.