Vol 27, No 6 (2024)

Resistance to systemic glucocorticosteroids in various dermatological conditions represents a serious clinical problem, often leading to treatment failure and exacerbation of the disease. The purpose of the review is to determine the relationships between association of genomic and non-genomic molecular factors and steroid resistance development in dermatoses of various etiologies. Genomic factors, including glucocorticoid receptor polymorphisms and changes in steroid metabolizing enzymes, may alter patient sensitivity to systemic glucocorticosteroids. All authors individually carried out a search of the available literature through PubMed, ScienceDirect, Wiley Online Library, Google Scholar, Cochrane Library, and MeSH using such key words "glucocorticoid receptor," and "glucocorticoid resistance," and "macrophage migration inhibitory factor," and "P-glycoprotein," and "polymorphism NR3C1," and "systemic lupus erythematosus," and "bullous pemphigoid," and "pemphigus vulgaris," and "atopic dermatitis."

Out of 23 analyzed sources, 8 studies were selected that describe various genomic and nongenomic factors potentially influencing the development of steroid resistance in a vast variety of skin conditions including pemphigus, bullous pemphigoid, atopic dermatitis, nummular eczema, localized neurodermatitis, lichen planus, and cutaneous and systemic lupus erythematosus.

We found that the mechanisms of steroid insensitivity were thoroughly studied in patients with systemic lupus erythematosus, including its cutaneous manifestations. Moreover, they differ in all these diseases. Meanwhile, the mechanisms underlying steroid resistance in other dermatological diseases are currently not fully understood. It is of a paramount importance to investigate mechanisms of steroid insensitivity and develop a panel of biomarkers which could predict steroid resistance in advance to optimize therapy of these conditions.

BACKGROUND: Toll-like receptor 7 (TLR7) plays a significant role in the development of inflammation in psoriasis. However, there are very few data on the role of different polymorphic markers of the TLR7 gene in psoriasis and psoriatic arthritis.

AIM: Study of the role of polymorphic marker rs179009 of TLR7 gene in patients with severe psoriasis.

MATERIALS AND METHODS: The study was conducted during the period of 2016–2024. The analysis of innate immunity indicators in the study group was performed by obtaining RNA in peripheral venous blood and polymorphisms of the gene recognizing marker rs179009 of the TLR7 receptor were investigated by polymerase chain reaction with TaqMan probes. To assess the area and severity of psoriatic lesions of the skin process, we used a standardised method of assessment — determination of the PASI index.

RESULTS: The main group consisted of 168 patients (100%) with psoriasis. Of these, 45 (26.8%) were women and 123 men (73.2%). The average age of the patients was 54.0±14.0 years. The mean duration of psoriasis course was 11.8±0.6 years. The mean psoriasis area and severity index (PASI) value was 17.7±7.2. When analyzing the genotypes of polymorphic marker rs179009 in the TLR7 gene in patients with psoriasis of different severity, it was revealed that heterozygote CT was significantly more frequent in patients with mild psoriasis, and homozygote CC and homozygote TT were registered at PASI >10 (p <0.05). The C allele of the studied marker was significantly more frequent in patients with late psoriasis debut and late development of psoriatic arthritis (p <0.01). In contrast, the T allele was significantly more frequent in patients with early debut of psoriasis and psoriatic arthritis (p <0.01). When analyzing the genotypes of polymorphic marker rs179009 in the TLR7 gene, the occurrence of homozygous CC and TT genotypes was also found to have statistically significant differences. The CC genotype was more frequently registered in patients with late onset of psoriasis and late onset of arthritis (p <0.05). In contrast, the TT genotype was significantly more frequently registered in patients with the debut of skin and joint process before 40 years of age (p <0.05).

CONCLUSION: In our study it was found that homozygous carriage of CC and TT genotypes of polymorphic marker rs179009 in the TLR7 gene predisposes to a more severe course of the skin process in psoriasis. Also, the presence in the patient of allele C or homozygote CC of marker rs179009 in the TLR7 gene is a predictor of late onset of the skin process and the development of arthritis. While the presence of the T allele or TT homozygote statistically significantly predisposes to early onset of psoriasis and early onset of joint symptoms with the development of psoriatic arthritis.

BACKGROUND: Pemphigus is a serious life-threatening disease characterized by the formation of IgG autoantibodies against the cell membranes, leading to the formation of intraepidermal blisters.

AIM: To evaluate the effectiveness of combined therapy with intravenous immunoglobulin and plasma exchange for steroid-resistant patients with pemphigus based on the cytokine, chemokine and granulysin profiles investigation.

MATERIALS AND METHODS: The group of patients receiving systemic glucocorticoid monotherapy (Group 1; control group) consisted of 26 patients with pemphigus vulgaris. The group of steroid-resistant patients (Group 2; main group) who received combined therapy with systemic glucocorticoid, intravenous immunoglobulin (IVIg), and plasmapheresis included 15 people. The presence of steroid resistance was assessed by Murrell consensus (2008). All pemphigus patients received the initial dose of systemic glucocorticoids of 80–100 mg/day with subsequent slow tapering, according to guidelines. The treatment protocol for combined therapy included four sessions of discrete plasma exchange per week every other day. Immediately after completion of the plasma exchange cycle, IVIg was added to the ongoing treatment, with a total dose of 2 g/kg per cycle. The levels of IL-4, IL-10, IL-15, TNF-α, chemokines CXCL8, CCL11, and granulysin were assessed via ELISA method.

RESULTS: We observed some discrepancies in cytokine profiles in both groups of patients. In patients who received combined therapy, there was a statistically significant decrease in the levels of IL-4, IL-15, TNF-α compared to those in patients on systemic glucocorticoid monotherapy ― IL-4, IL-15 TNF-α (p <0.01). Notably, that the level of CCL11 in serum of steroid-resistant patients before the IVIg therapy was significantly higher (Me=51 pg/ml) compared to systemic glucocorticoid monotherapy group (Me=10 pg/ml; p <0.01). The level of granulysin after the treatment with IVIg and plasma exchange in group 2 was also significantly lower (Me=0 ng/ml) compared to the group of control (Me=2700 ng/ml respectively; p <0.01).

CONCLUSION: We found a trend towards higher serum levels of IL-4, IL-15, and CCL11 in steroid-resistant pemphigus patients who received combined therapy with IVIg and plasma exchange compared to the control group. Moreover, these cytokines can be considered as the potential biomarkers for refractory disease course, and might be used as therapeutic targets in the future. It should be also noted that the prolonged remission of patients receiving combined therapy with systemic glucocorticoid, IVIg, and plasma exchange, was on average two years.

Syphilis is an infectious human disease caused by pale treponema (Treponema pallidum), transmitted mainly by sexual intercourse and characterised by a progressive course with periodisation of clinical symptoms and lesions of the skin, mucous membranes, nervous system, internal organs and musculoskeletal apparatus, the incidence of which remains an important and urgent problem requiring medical alertness.

The current data and the main trends of syphilis morbidity in the Russian Federation for several years (from 2019 to 2023) are analyses in detail in the article. It is established that the number of new cases of the infectious disease has increased over the specified time period. The COVID-19 pandemic had a particular impact on syphilis morbidity statistics. In addition, the introduction of additional measures, such as mandatory testing of foreign citizens for dangerous infections, including syphilis, with mandatory submission of the results to the Ministry of Internal Affairs of the Russian Federation also had an impact on the statistics of morbidity.

We present a unique clinical case that demonstrates the presence of primary seropositive syphilis (perianal chancres) in a male patient with acute condylomas of the facial skin and perianal candidiasis. Initially, a coloproctologist made an incorrect diagnosis, despite the history (unprotected sexual intercourse), the characteristic clinical picture of the disease and the specific localisation of the rashes, indicating the site of the pathogen's introduction. The diagnosis was confirmed by positive results of nontreponemal test, specific treponemal tests and passive haemagglutination reaction. Pale treponema was also detected by dark-field microscopy. Due to aggravated allergological anamnesis ― intolerance to penicillin antibiotics ― specific antisyphilitic treatment with ceftriaxone was prescribed. According to the results of control analyses, the treatment was positive. Acute condylomas of the facial skin were removed by the radio wave method after complex treatment of the underlying disease. After completion of the specific treatment, it was recommended to carry out clinical and serological control once every 3 months.

On May 17^th we held our last meeting of Moscow Society of Dermatologists and Cosmetologists named after A.I. Pospelov in person within XLI Rachmanov Readings conference. There were 61 participants.

Our agenda included two clinical cases: the first one was dedicated to the PASH-syndrome as the most common manifestation of gangrenous pyoderma syndromic form; the second one was about diagnostic difficulties in mycosis fungoides. The first report was accompanied by the presentation of clinical cases of PASH syndrome (gangrenous pyoderma, Hoffmann's folliculitis, suppurative hidradenitis) in a patient aged 19 years and gangrenous pyoderma combined with suppurative hidradenitis and conglobate acne in a patient aged 32 years. The main treatment was the administration of methylprednisolone in combination with antibiotics and the addition of a cytostatic in the second clinical observation.

Two reports were presented in the scientific part of the meeting. In the first report (on the experience of using bacteriorhodopsin in patients with psoriasis vulgaris), the author demonstrated the results of his own prospective study of bacteriorhodopsin cream, noting that the fastest effect occurred on open skin areas. A special emphasis of the second report (on tattoos in the practice of a dermatologist (Fomin Clinic) was made on the absence of a list of contraindications, mandatory certification of dyes for tattooing and tattoo master's workplace, standard of preliminary laboratory tests, as well as uniform requirements for specialists performing tattooing, which determines the frequency of infectious complications after the procedure.

Leprosy is a chronic disabling disease of infectious nature caused by Mycobacterium leprae hominis and accompanied by lesion of the skin, mucous membranes, peripheral nervous system, musculoskeletal system and viscera.

According to the World Health Organization in 2018 208,641 new cases of leprosy have been registered in the world. The major share of morbidity is accounted for countries such as Angola, the Democratic Republic of the Congo, Central African Republic, India, Mozambique, Madagascar, Brazil, Nepal, United Republic of Tanzania. However, due to migration, expansion of trade and economic ties and tourism development, there have been sporadic cases of leprosy in other countries, too.

This article describes the illustration of the clinical case of 24-year-old patient S., who turned to our clinic with complaints of rashes on the skin of the face, limbs, auricles of the ears, accompanied by itching. From anamnesis: the patient lived in the Republic of Chad, Central Africa, until 2019, when he moved to Moscow and entered Moscow Institute of Technology, and lived in a dormitory. Patient hasn`t left Moscow since 2019. Comorbidity: chronic viral hepatitis B. According to the patient’s words relatives don’t have complaints. The patient reckons he fell ill about 3 years ago when he noticed rashes on his face the first time. Later on, rashes appeared on the skin of the limbs and body. Over the last year, he has experienced swelling of the hands and the feet. Starting in March 2023, he repeatedly was consulted by dermatologists and haematologists. Among the proposed diagnoses were lichen planus, multiple eruptive xanthoma, non-Langerhans cell histiocytosis (Erdheim–Chestern's disease). Treatment with topical glucocorticosteroids has proved ineffective.

Following that the patient visited V.A. Rakhmanov Department of Skin and Venereal diseases, where he was diagnosed with leprosy (multiple hemispherical elevated lepromas on the skin of the body, limbs, face and auricles of the ears, bloody nasal discharge, hypopigmented spots with loss of tactile sensitivity especially on the skin of the limbs, papular rashes on the oral mucosa) and recommended bacterioscopic examination of skin scarificates and nasal mucosa scrapings for detection of Mycobacterium leprae.