Federal State Budgetary Educational Institution of Higher Education Volgograd State Medical University, Volgograd, Russia.
*Shchava S.N, Federal State Budgetary Educational Institution of Higher Education Volgograd State Medical University, Volgograd, Russia.
Abstract
Patients with acne often suffer from concomitant skin pathology, diseases of internal organs, take medications that can affect the course of comorbid pathology and the effectiveness of treatment with isotretinoin. Therefore, when prescribing systemic acne therapy, it is necessary to consider the concomitant pathology in patients, the use of other drugs.
This article presents the experience of treating severe forms of acne with isotretinoin Lidose in individuals with various pathologies of the skin and internal organs.
Introduction
Acne vulgaris is the most common skin disease, affecting approximately 80 to 90% of adolescents and 40 to 60% of adults. [1] Severe forms of acne can leave scars, cause psychological damage and require effective treatment, often systemic. [2] In recent years, acne sometimes develops against the background of atopic dermatitis, psoriasis and other skin diseases. Acne patients have or are diagnosed with concomitant pathology of internal organs, such as gastritis, duodenitis, colitis, etc. [3] Acne patients may take medications for diabetes mellitus, bronchial asthma and other pathologies. Systemic isotretinoin is a clinically effective acne therapy, which helps to achieve significant improvement and long-term remission in many patients, thereby improving their quality of life. In general, the safety profile of isotretinoin is favorable. Isotretinoin is used to treat severe, refractory, nodular acne. Isotretinoin targets all four major pathogenetic factors: it significantly reduces sebaceous gland size and suppresses sebum production, thereby changing the lipid composition of the skin surface, affects keratosis pilaris, prevents the proliferation of C. acnes, and inhibits inflammation. Isotretinoin is indicated for patients with multiple nodulocystic lesions and is also used to treat moderate acne that is unresponsive to other therapies. [4] The main side effects include dry skin and mucous membranes. The most serious concern is teratogenicity - isotretinoin use during pregnancy is associated with a significant risk of major birth defects in the fetus. Other potential side effects include hypertriglyceridemia, musculoskeletal pain, and changes in liver function tests. [5] Isotretinoin is lipophilic and virtually insoluble in water. Although the molecule readily crosses cell membranes, the poor solubility of conventional formulations in the aqueous environment of the intestine limits absorption and, therefore, bioavailability. The bioavailability of isotretinoin can be significantly increased by eating fatty foods. Therefore, co-administration with food is necessary for maximum absorption of the drug. The lipid component of food plays an important role in the absorption of lipophilic drugs, which is the basis for recommendations to take isotretinoin with a high-fat (50 g fat) and high-calorie (800-1000 calories) meal. Gastrointestinal absorption of regular isotretinoin is reduced by approximately 60% when taken on an empty stomach compared to when the drug is taken with a fatty meal. Patients taking isotretinoin without adequate food intake have a high risk of acne recurrence due to a 60 percent reduction in cumulative systemic exposure.[6]A number of advanced technologies have been successfully used to improve the solubility and bioavailability of isotretinoin. The first significant improvement in the isotretinoin formulation was the Lidose formulation, in which the active substance is pre-dissolved in a lipid matrix to improve absorption and markedly reduce dependence on high-fat meals.[7] Compared with the original formulation of regular isotretinoin, Lidose is significantly better absorbed when taken on an empty stomach (with water). In a pharmacokinetic study, when Lidose isotretinoin was administered to patients in the fasted state, plasma isotretinoin levels reached 66.8% of those observed when the drug was taken with a high-fat meal, compared with 39.6% for regular isotretinoin taken under the same conditions.[8] There are limited studies on the effects of isotretinoin on inflammatory bowel disease. However, there are reports from experimental and clinical studies that suggest that isotretinoin has anti-inflammatory effects that may be beneficial in IBD.[9] However, as IBD becomes more common, patients and clinicians are increasingly faced with the possibility of isotretinoin exacerbating IBD, although for patients with IBD and severe refractory nodulocystic acne, isotretinoin remains the most effective treatment option.[10] Severe acne may be associated with diabetes. Studies by Ertugrul et al. and Cai et al. conducted a systematic review and meta-analysis on insulin resistance and isotretinoin. The authors concluded that isotretinoin treatment of acne patients resulted in increased serum adiponectin levels but had no significant effect on insulin resistance. [10,11] Due to the increase in concomitant morbidity in patients with acne, as well as the simultaneous use of drugs, the effect of isotretinoin requires further study.
The aim of our work was to study the effect of systemic isotretinoin-Lidose on the course of acne in patients suffering from the disease in moderate to severe forms and having concomitant pathology.
Materials and Methods
We observed 27 patients treated with systemic isotretinoin - Lidose with moderate to severe acne and concomitant diseases. Atopic dermatitis was diagnosed in 7 patients, psoriasis vulgaris - 4, pityriasis versicolor - 2, obesity - 4, diabetes mellitus - 5, bronchial asthma (GCS-dependent) - 1, other - 4. Patients were examined for the appointment of treatment with systemic isotretinoin Lidose according to the standard scheme and additionally according to the concomitant disease. The drug was prescribed at a dose of 0.4 mg - 0.8 mg / kg of weight, depending on the clinical manifestations of acne, without adjustments for the treatment received for the concomitant nosology, the average course of therapy was 6-8 months. Patients with concomitant pathology were examined, in some cases correction was prescribed, patients with pityriasis versicolor were preliminarily prescribed antifungal therapy. Treatment of concomitant diseases was carried out according to the same scheme as before treatment with isotretinoin. All patients undergoing treatment with systemic isotretinoin were recommended to adhere to certain dietary rules: to limit the intake of fried foods, trans fats, fast food as much as possible, while preserving the "healthy" fats necessary for maximum absorption of the drug (for example, sea fish, cod liver, avocado, nuts, olive oil), to limit the intake of sugar and foods with a high glycemic index as much as possible. In order to monitor adverse reactions and effects on internal organs, a biochemical blood test (ALT, AST, total bilirubin, triglycerides, creatinine, glucose), a complete blood count were performed before, three months after the start of treatment and at the end of treatment with isotretinoin and, in some cases more often: monthly in patients with obesity and diabetes mellitus.
Figure 1: Patient M., 17 years old. Severe acne, concomitant. Bronchial asthma (GCS-dependent) before treatment.
Figure 2: Patient M., 17 years old. Severe acne, concomitant with bronchial asthma after completion of treatment with isotretinoin Lidose.
We present two clinical cases of patients with severe forms of acne and concomitant pathology.
Clinical case 1: Patient M., 17 years old. Complaints of rashes on the skin of the face, chest, back, pain. Has been ill since the age of 13. The skin pathological process is represented by numerous papules, nodes, post-inflammatory spots, open comedones, atrophic scars. Localization: face, back, chest area. (Fig. 1). The patient was repeatedly treated by a dermatovenerologist with various anti-inflammatory topical agents, antibiotics, and autohemotherapy - without effect. Suffers from bronchial asthma and uses sprays with GCS (which can maintain acne rashes), constantly takes cetirizine. The patient was examined: blood test showed ESR 31 mm/hour, leukocytes - 10.5 *109 /l, no other changes, including in the biochemical blood test, were revealed. According to the mother, elevated ESR and leukocytes were always noted, even before acne appeared. The patient was repeatedly examined by a pediatrician and these indicators were associated with bronchial asthma and taking GCS. Based on the examination, complaints and anamnesis, the diagnosis was: acne vulgaris, severe nodular-cystic form. Concomitant diagnosis: bronchial asthma. The patient's weight is 69 kg. The course dose is 6900 mg. Isotretinoin Lidose was prescribed at a dose of 0.4 mg/kg of weight, 32 mg per day (the drug Aknekutan 2 capsules of 16 mg per day), the course is 7.5 months. The patient tolerated isotretinoin well. During treatment, he noted dry lips and skin, which he lubricated with emollients. After the end of therapy with isotretinoin Lidose, he did not notice an increase in the frequency of asthma attacks or a deterioration in his health (Fig. 2).
Case 2: Patient M., 21, complains of painful formations in the facial area. He is obese (140 kg). For 4 months, he has been noticing the appearance of painful nodular elements in the beard area, for which he sought surgical treatment from a maxillofacial surgeon, as a result of which the elements were repeatedly opened. According to the patient, new formations appear regularly. The treatment with topical retinoids and antibiotics did not produce any effect. Upon examination: the skin pathological process is represented by multiple nodular-cystic, papulopustular elements, atrophic scars on the skin of the face, the chest and back areas are not affected. Diagnosis: Acne vulgaris, severe conglobate form. Concomitant diagnosis: Obesity grade 3 (morbid). (Fig. 3).During examination for the purpose of prescribing systemic isotretinoin, elevated ALT, AST, and glucose levels were detected. The patient was advised to consult a gastroenterologist and endocrinologist and was recommended to lose weight. After 3 months, the patient lost 23 kg, received a course of therapy from a gastroenterologist, was consulted by an endocrinologist, and after examination, laboratory values of ALT, AST, and blood sugar were within normal limits. Isotretinoin Lidose was prescribed, the course dose of 120 mg / kg was 14040 mg, the daily dose was 0.7 mg / kg of weight and was 80 mg (5 capsules of 16 mg of the drug Aknekutan per day, divided into 2 meals), the duration of treatment was 6 months. During isotretinoin therapy, the patient underwent a biochemical blood test, no pathology was noted. After the end of isotretinoin treatment, a pronounced effect was noted. The inflammation decreased, there was no pain, hypertrophic and atrophic scars were formed (Fig. 4). Blood parameters after completion of therapy with isotretinoin Lidose: glucose, ALT, AST, liver function tests, creatinine were within normal limits.
Figure 3: Patient M., 21 years old, diagnosis: acne vulgaris, severe conglobate form before treatment with isotretinoin
Figure 4: Patient M., 21 years old, diagnosis: acne vulgaris, severe conglobate form after completion of treatment with isotretinoin Lidose
Results and Discussion
The effect of the therapy with isotretinoin Lidose was noted in all patients. No changes in the studied blood parameters were detected. No deterioration in well-being or exacerbation of concomitant pathology was noted.
Conclusion
Isotretinoin is one of the highly effective methods of acne treatment and is actively used as a standard therapy for severe and moderate acne resistant to other types of therapy. It can be recommended to patients with concomitant skin pathology and diseases of internal organs. Given the various side effects of isotretinoin, its use requires adequate clinical assessment and monitoring of laboratory parameters by a dermatovenerologist, especially in the presence of concomitant diseases. In clinical cases under our observation, no exacerbation of concomitant pathology was detected, no deterioration in well-being was noted, but in a number of cases with altered biochemical blood test parameters before isotretinoin treatment, preliminary preparation of patients was required for a correct assessment of treatment tolerability during therapy with isotretinoin Lidose.
