Skin and mucous membranes lesions in systemic lupus erythematosus (SLE) significantly impair the quality of life of patients, although they are not a formidable manifestation of the disease. Skin manifestations of SLE can occur both at the onset and on the late stage of the disease. Although skin and mucous membranes lesions are clearly grouped in the latest classification criteria for SLE, verification of the diagnosis requires a multidisciplinary approach. In the etiology of SLE, environmental factors, hormonal factors, and genetic predisposition play a role. Further research will reveal differences in subtypes of cutaneous lupus erythematosus and will facilitate the development of new therapies.

Objective: to analyze preliminary data on 5-year clinical and radiographic outcomes in patients with early psoriatic arthritis (PsA) observed as part of the Treat to target (T2T) strategy.
Patients and methods. We examined 37 patients (18 men and 19 women) with early PsA who met the CASPAR criteria (2006), who received treatment according to the principles of the T2T strategy for 24 months. The mean age of the patients was 43.3±11.7 years, the median (Me) of PsA duration was 72 [60; 90] months, psoriasis – 120 [88; 180] months, follow up – 62 [51; 81] months. After completion of participation in the T2T strategy, patients were followed up in a real clinical setting. Most of the patients used methotrexate, biologic disease modifying antirheumatic drugs and non-steroidal anti-inflammatory drugs. In the dynamics after 5 years, PsA activity was determined by the DAPSA index and the achievement of the minimum disease activity (MiDA). In 16 (43%) patients, a dynamic assessment of radiographic changes in the joints of the hands and feet was performed using the Sharp quantitative method modified for PsA (m-Sharp/vanderHeijde).
Results and discussion. By 24 months of therapy (the end of the T2T study), DAPSA remission was registered in 19 (52%) patients, in the same number of cases (16%) low (LDA), moderate (MDA) and high (HDA) disease activity was noted. Me DAPSA was 3.85 [0.67; 21.76], MiDA was detected in 22 (59.5%) patients. After 5 years of observation, Me DAPSA was 7.67 [2.2; 14.5]. Remissions according to DAPSA were achieved in 13 (35%) patients, LDA – also in 13 (35%), MDA – in 5 (14%), HDA remained in 6 (16%), MiDA – in 20 (54%). No significant differences were found when comparing disease activity at 24 months (at the end of the T2T study) and after 5 years of follow-up (p=0.41). In 11 (69%) out of 16 patients after 5 years, a negative trend was recorded in the assessment of radiological progression.
Conclusion. After 5 years of follow-up, 70% of patients with PsA treated at an early stage of the disease as part of the T2T strategy achieved remission or LDA, and 54% of patients remained in MiDA. In 69% of patients, despite the achievement of remission and MiDA, there was a negative radiological dynamic in the hands and feet.

Currently, a biosimilar (BS) of rituximab (RTM) Acellbia® is widely used in Russia for the treatment of rheumatoid arthritis (RA), however, a systematic study of this drug in routine clinical practice has not been conducted.
Objective: to compare the results of the use of RTM BS (Acellbia®) and the original rituximab (oRTM) in the daily clinical practice of a large rheumatology center.
Patients and methods. The study involved 127 patients predominantly with seropositive RA, who were divided into four groups. Groups 1 and 2 included 66 bionaive patients with active RA and ineffectiveness of previous therapy. 31 patients of the 1st group received 2 infusions of oRTM at a dose of 500 mg intravenously (IV) 2 weeks apart; 35 patients of the 2nd group – 2 infusions of RTM BS at a dose of 500 mg IV 2 weeks apart. Groups 3 and 4 included 61 patients who had previously received oRTM therapy. These patients received 4 courses of oRTM treatment on average before being included in the study. 30 patients of the 3rd group continued oRTM therapy: they received 2 infusions at a dose of 500 mg IV 2 weeks apart; 31 patients of the 4th group received 2 infusions of RTM BS at a dose of 500 mg IV 2 weeks apart.
Results and discussion. During the observation period, the dynamics of the main indicators of RA activity in the 1st and 2nd groups did not differ significantly. Although the indication for rehospitalization was an exacerbation of the disease, 64.5% of patients in the 1st and 77.1% of patients in the 2nd group, preserved a 20% improvement according to the ACR criteria on re-examination. The condition of patients of the 3rd and 4th groups remained generally stable during the observation period. The change in the DAS28 index in most cases was clinically insignificant. There were no significant differences in the dynamics of inflammatory activity among patients who continued oRTM treatment and who received RTM BS.
Conclusion. The results of the study show that both the prescription of RTM to bionaive RA patients and repeated courses of treatment with RTM BS and oRTM are comparable in terms of efficacy and tolerability.

Objective: to assess the relationship between laboratory biomarkers and ultrasonographic signs of inflammation in patients with rheumatoid arthritis during therapy with a rituximab (RTM) biosimilar.
Patients and methods. 20 patients with definite diagnosis of RA were examined. All patients received 2 infusions of RTM (Acellbia®), at a dose of 600 mg intravenously 2 weeks apart during therapy with methotrexate, non-steroidal anti-inflammatory drugs and glucocorticoids. Clinical and laboratory parameters were analyzed immediately before the start of therapy, and then 12 and 24 weeks after the first infusion of the drug.
Results and discussion. By the 24th week of RTM therapy, a good/moderate effect according to the EULAR criteria was registered in 17 (85%) patients; remission according to DAS28 (<2.6) was achieved in 4 (20%) patients, SDAI (≤3.3) – in 2 (10%), CDAI (≤2.8) – in 1 (5%). Prior to the start of treatment, active synovitis was detected in 13 (65%) patients by power Doppler imaging (PD), and in 20 (100%) patients by gray scale scanning. During therapy with the RTM biosimilar, a significant decrease in inflammatory changes in the joints was observed, and by the 24th week after the start of treatment, the median PD was 0.5; active inflammation persisted in 7 (35%) patients. As shown by ROC analysis, the initial level of interleukin (IL) 6 >100.0 pg/ml is associated with the persistence of inflammatory activity according to PD by the 24th week of therapy with the RTM biosimilar, while the sensitivity was 85% and the specificity was 62% (AUC 0.78, 95% CI 0.57–0.99)
Conclusion. An association was found between an increased level of pro-inflammatory cytokines, mainly IL6, and the activity of synovial inflammation according to ultrasound data. IL6 is the most promising marker for predicting persistent inflammatory activity based on the results of PD; other analyzed parameters have worse sensitivity and specificity parameters.

In the last decade, anti-neutrophil cytoplasmic antibodies (ANCA)-associated systemic vasculitis (SV) has been treated with the anti-B-cell drug, rituximab (RTM) both for induction and maintenance therapy. One of the problems of the treatment with RTM in patients with ANCA-SV is the risk of late-onset neutropenia (LON), mechanisms of development of which have not been studied enough yet.
Objective: to evaluate the incidence and outcomes of LON in patients with ANCA-SV treated with RTM.

Patients and methods. A retrospective analysis of the register of 140 patients with ANCA-SV who received RTM treatment at the V.A. Nasonova Research Institute of Rheumatology from 2009 to 2021 years. The median duration of RTM treatment was 49 (6–121) months, the median of the total RTM dose was 3.5 (0.5–9.5) grams. The duration of follow-up exceeded 6 months after the first administration of RTM.
Results and discussion. LON was detected in 16 (11.4%) patients, of which 6 suffered from Wegener's granulomatosis with polyangiitis (GPA), 4 – microscopic polyangiitis (MPA), 4 – Churg-Strauss eosinophilic granulomatosis with polyangiitis (EGPA) and 2 – undifferentiated ANCA-SV. In 8 (50%) out of 16 patients, LON developed within 2 months after the 1st course of RTM, in the remaining 8 patients, on average, after 10 (4– 15.5) months. A lethal outcome was documented in 5 (31.2%) of 16 cases of LON (1 with MPA, 3 with GPA, and 1 with EGPA) on average 2 (1.5–9) months after the 1st course of RTM, at the same time, in 4 patients LON was complicated by pneumonia, including 2 with septic shock, in another 1 case LON was combined with the development of acute myocardial infarction and progression of chronic renal failure. Overall mortality among 140 patients with ANCA-SV treated with RTM was 11.4%, while in cases with a fatal outcome, the frequency of LON reached 31.2%.
Conclusion. Thus, LON induced by RTM is a common (11%) and clinically significant consequence of B-cell depletion in patients with ANCA-SV, in every 5th case it is complicated by serious infections (including sepsis in 13%) and accounts for a significant proportion in the structure of lethal outcomes (31.2%).
Patients treated with RTM require careful monitoring of absolute neutrophil count both during the first months after initiation of anti-B-cell therapy and thereafter. In the combined administration of RTM with cytotoxic drugs (primarily cyclophosphamide) in patients with ANCA-SV, it is necessary to consider the risk of LON developing, secondary immunodeficiency, and infectious complications. During the coronavirus pandemic, one should remember that treatment with interleukin 6 inhibitors used in severe COVID-19 can also be accompanied by neutropenia and requires careful dynamic monitoring of the absolute number of neutrophils in patients with ANCA-SV treated with RTM. It is necessary to inform both patients and physicians of the risk of LON development during the treatment of RTM in ANCA-SV and other rheumatic diseases.

About 10–40% of patients with osteoarthritis (OA) are not satisfied with the results of total arthroplasty (TA) of large joints. At the same time, the most common complication associated with the ineffectiveness of TA is postoperative pain (PP).
Objective: to identify genes whose expression in the peripheral blood before TA is associated with an increased risk of PP developing. Patients and methods. Before TA, the blood of 50 patients with late-stage knee OA was examined; the control group consisted of 26 healthy individuals. The level of pain was assessed using the visual analog scale (VAS), the BPI short questionnaire, and the WOMAC index; the presence of neuropathic pain was assessed using the DN4 and PainDETECT questionnaires. The development of PP was determined 3 and 6 months after TA. The levels of matrix metalloproteinase protein (MMP) 9 and tissue inhibitor of metalloproteinase (TIMP) 1 were quantified by ELISA. Total RNA isolated from blood was used to determine the expression of caspase 3, MMP9, TIMP1, cathepsins K and S, tumor necrosis factor (TNF) α, interleukin (IL) 1β, and cyclooxygenase 2 genes using a quantitative real-time reverse transcriptase polymerase chain reaction.
Results and discussion. PP according to VAS ≥30 mm was noted in 17 patients. Before TA, these patients had significantly increased expression of cathepsins K and S, caspase 3, TIMP1, IL1β, and TNFα genes compared to other patients with OA. ROC analysis revealed a statistically significant relationship between the expression of these genes and the likelihood of developing pain after TA.
Conclusion. High expression of genes associated with degradation of the extracellular matrix (catepsins S and K, TIMP1), inflammation (IL1β, TNFα), and apoptosis (caspase 3) can serve as an important biomarker for the development of PP in patients with knee OA. To confirm the value of preoperative gene expression testing in predicting the onset of PP, further studies involving large cohorts of patients are needed.

The main symptoms of osteoarthritis (OA) are pain and dysfunction of the joints. Neuropathic pain (NP) occurs in more than half of patients with OA, it is refractory in nature and is the cause for seeking medical advice more frequently, poor quality of life and disability.
Objective: to evaluate the frequency of NP and its relationship with geriatric syndromes (GS) in patients with OA aged 65 years and older. Patients and methods. The subanalysis of the study EVKALIPT included 2286 patients with OA and chronic pain syndrome. All patients underwent a comprehensive geriatric assessment (CGA) and diagnostics of NP using the DN4 questionnaire.
Results and discussion. The prevalence of NP in patients with OA was 22.7%. Patients with OA and NP more often experienced pain of any localization with a large number of tender points, they had a higher frequency and intensity of pain syndrome, they more often took analgesics and noted limitations in daily life. When conducting a correlation analysis, correlations of medium strength were found between the sum of scores according to DN4 questionnaire and the pain intensity assessment on a numerical rating scale at the time of examination (r=0.26; p<0.001) and in the previous 7 days (r=0.29; p<0.001). CGA data in patients with OA and NP demonstrated worse geriatric status and a higher incidence of GS. The most common GSs were basic (81%) and instrumental (64%) dependence in everyday life, senile asthenia (70%), urinary incontinence (69%), depression (69%) and cognitive impairment (67%). Multivariate analysis showed that, in addition to age, the presence of NP was independently associated with sensory deficits, depression, falls, urinary incontinence, and bedsores (odds ratio 1.77–2.49). Patients with NP were more likely to use mobility aids, absorbent underwear, and orthotics.
Conclusion. NP was diagnosed in 22.7% of OA patients aged 65 years and older. Such patients have worse functional status, they are more often diagnosed with a number of GSs.

Objective: to evaluate efficacy and safety of the use of a bioactive concentrate of small marine fish (Alflutop) in patients with vertebrogenic sciatica (SC).
Patients and methods. The study included 30 patients with persistent (more than 3 months) vetebrogenic SC who underwent inpatient treatment in the neurological department of the Republican Clinical Neurological Center (Kazan). The patients were randomized into two groups: 15 patients of the 1st group received Alflutop (2 ml intramuscularly every other day, 10 injections in total) in addition to standard therapy, and 15 patients of the 2nd group (control) received standard therapy. The effectiveness of therapy was assessed using a visual analogue scale, Roland-Morris and EQ-5D questionnaires, an index of severity and frequency of sciatica.
Results and discussion. Patients who received the study drug in addition to standard therapy showed a more rapid decrease in pain intensity, a trend towards a decrease in the severity index of sciatica, while no adverse events were recorded during the entire follow-up.
Conclusion. The inclusion of Alflutop in the traditional scheme of inpatient treatment of patients with vertebrogenic SC allows to achieve a significantly greater reduction in the intensity of the pain syndrome after 20 days and 2 months after the start of therapy.

Objective: to evaluate the efficacy and safety of the parenteral form of pharmaceutical chondroitin sulfate (CS) in neuroimmune joint damage in patients with early knee osteoarthritis (OA) in long COVID.
Patients and methods. An open prospective controlled randomized study was conducted, its duration was 50 days of active controlled therapy. The study included 82 patients (age 57–63 years, men – 29, women – 53) with clinical symptoms of early knee OA and confirmed long COVID type 2 (persistence of symptoms 4–12 weeks after infection with SARS-CoV2). The diagnosis of OA was established in accordance with the updated classification criteria for early knee OA (2018).
Patients were randomized into two groups: group 1 – the main group (n=42) and group 2 – control group (n=40). Patients in both groups received celecoxib at a dose of 200 mg with the possibility of reducing the dose to 100 mg or completely discontinuing the drug if necessary. Patients of the 1st group additionally received a parenteral form of CS (Chondroguard® solution for intramuscular and intraarticular administration, 100 mg/ml). At baseline (Day 1) and on the 50th day of the study, pain intensity was assessed in all patients using a visual analogue scale (VAS), the degree of functional impairment (FI) of the joints according to the Lequesne index, ultrasound of the knee joint was performed, CRP, D-dimer, fibrinogen, interleukin (IL) 1β, IL6 levels were studied. The presence of SARS-CoV2 was determined by polymerase chain reaction in scrapings from the mucous membrane of the nasal cavity and oropharynx, and a qualitative proteomic analysis was performed (1-2DE, MALDI-TOF/TOF-MS, PathCards database). The safety of therapy was assessed using the WHO and Naranjo scales.
Results and discussion. It was established that CS therapy was well tolerated and was accompanied by a significant decrease in pain intensity according to VAS (U-test=5.71; p<0.0001), in FI according to the Lequesne scale (U-test=6.32; p<0.0001), in manifestations of synovitis and tendinitis in the group treated with CS and celecoxib, compared with the control group. During the treatment by CS a statistically significant (p<0.0001) decrease in the level of pro-inflammatory markers in the blood serum (CRP, IL6, IL1β), D-dimer and fibrinogen was noted. Proteomic analysis showed a decrease in the blood serum of patients of the 1st group of eotaxin 1, IL8, IL15, interferon γ inducible protein 10 levels, and an increase in the expression of nerve fiber growth factor β, an antagonist of the IL1 receptor.
Conclusion. The use of pharmaceutical parenteral CS in combination with oral celecoxib in patients with early OA of the knee joint, the clinical signs of which manifested after infection with SARS-CoV2 and persisted in long COVID conditions, contributed to a decrease in the severity of pain and stiffness in the knee joint, as well as improved functional capabilities.

Objective: to evaluate the efficacy and safety of febuxostat (Azuriks®) in the treatment of patients with gout and concomitant diseases.
Patients and methods. An observational, open-label, single-centre study of the results of febuxostat use in 85 gout patients with insufficient prior allopurinol efficacy or its intolerance. The median age of patients was 56.2 [49; 59] years, among them 83.5% were men. All patients had comorbid diseases, mainly cardiovascular pathology (76.5%) and chronic kidney disease (60%). The achievement of target values of uric acid (UA) during 4 months of urate-lowering therapy and its safety were assessed.
Results and discussion. After 4 months of therapy with febuxostat, 25% of patients reached the target values of UA. Exacerbations at an early stage of the use of urate-lowering therapy were rare and were characterized by a lesser severity of the articular syndrome. Normalization of purine metabolism was accompanied by a decrease in the laboratory activity index (CRP level) to values corresponding to the interictal period of gout. Febuxostat was well tolerated.
Conclusion. According to the data obtained, in patients with gout and concomitant diseases, febuxostat allows reaching target UA values in a short time without dose titration, while a high safety profile is noted.

Leukocytoclastic vasculitis (LCV) is a small vessel vasculitis characterized by immune complex depositions involving dermal post-capillary venules. Cutaneous small vessel vasculitis is most often idiopathic but may be aggravated by secondary causes, such as inflammatory conditions, infections, neoplasms, and drugs exposure.
Herein, we describe two patients with a long history of rheumatoid arthritis (RA) treated with methotrexate (MTX) for more than ten years, who later developed generalized LCV with pancytopenia after a viral infection, one with herpes simplex virus, and the other with SARS-CoV-2 virus. Because of the worldwide use of MTX in treatment of RA, strict follow-up and preventive measures are needed nowadays, especially during COVID-19 pandemic, in order to avoid any infection which may provoke LCV with or without systemic manifestations. So, using MTX for treating RA or other similar disorders may be considered a double-edged sword, especially during COVID-19 pandemic.

The results of gout therapy in many patients remain unsatisfactory, despite the availability of drugs and recommendations for its treatment. In addition to poor adherence to treatment by patients, medical errors and other reasons influence this situation. The article considers several clinical cases demonstrating the possibilities of a rational choice of urate-lowering therapy.

Pigmented villonodular synovitis (PVNS) is a rare disease, its diagnosis has certain difficulties. This is due to the absence of characteristic etiological factors and clinical manifestations of PVNS, as well as the insufficient level of knowledge among doctors. The article presents a review of the literature on the diagnosis and treatment of PVNS, as well as a clinical case, which peculiarity is the late diagnosis of this disease, despite the presence of its certain clinical and morphological manifestations.

Current trends in the development of personalized medicine dictate the need to interpret chronic pain as a multifactorial biopsychosocial phenomenon. A comprehensive integrated approach to the management of patients with chronic pain includes nosological diagnostics, assessment of factors that determine the persistence of pain and comorbid pathology, and the use of necessary pharmacological and non-pharmacological methods of treatment. Currently, primarily non-steroidal anti-inflammatory drugs are used for the pharmacotherapy of chronic pain, which is predominantly nociceptive in nature. Meloxicam (Movalis®), along with high efficacy, has a favorable safety profile and has proven itself in the treatment of chronic musculoskeletal pain. For chronic pain associated predominantly with neuropathy and central sensitization, the drugs of choice are tricyclic antidepressants, serotonin and norepinephrine reuptake inhibitor duloxetine, the α2δ ligands pregabalin and gabapentin.

The article discusses the clinical and diagnostic difficulties in verifying of panniculitis variants in children of different ages, including newborns. Successful diagnosis of the disease depends on a carefully collected anamnesis indicating information about previous diseases, background pathology, medications, as well as an adequate assessment of clinical symptoms, laboratory parameters and identification of typical morphological changes.

Chronic musculoskeletal pain (MSP) is the most painful manifestation of rheumatic diseases (RD), the main cause of disability, a decrease in the quality and life expectancy of patients, which determines not only the high medical, but also the social significance of this problem. The chronic nature of the pain forces patients with MSP to use analgesic therapy for a long time. At the same time, non-steroidal anti-inflammatory drugs (NSAIDs) are the first-line treatment for MSP. However, it is well known that the use of this group of drugs is associated with significant difficulties, mainly due to the comorbid pathology that is common in middle-aged and elderly people. In this regard, there are continuing attempts at searching for alternative agents for chronic MSP control, which have analgesic and anti-inflammatory activity similar to NSAIDs, but lack their side effects. Some researchers believe that diacerein can become such drug.