The article considers the current state of the problem related to fever of unknown origin (FUO). It highlights the main stages of studying this issue with a detailed description of the classification diagnostic criteria, etiological types, and clinical signs of certain types of FUO, which have undergone changes over time. The authors present a differential diagnostic algorithm for managing patients with FUO and analyze the diagnostic value of the most significant laboratory and instrumental studies. PPP-syndrome is described as one of the possible etiological factors for FUO. The circle of the most common of FUO is denoted in patients at different ages. It is noted that rheumatic diseases are the most common cause of FUO in elderly patients.

Scleroderma systemitica (SDS) is an autoimmune connective tissue disease characterized by excessive fibrosis of the skin and viscera. SDS is prone to be chronic and progressive, is accompanied by the deterioration in quality of life and working ability and has an unfavorable prognosis. Interstitial lung disease (ILD) is one of the most common causes of death due to SDS.

The lecture deals with the clinical and laboratory instrumental features of ILD in SDS. SDS-associated ILD occurs in 65–80% of patients and is highly diverse in the degree of severity and the tendency to progression. In the majority of patients, the fibrous process in the lung occurs in the early years of the disease, is limited and progresses slowly. Severe lung damage with rapid progression develops only in 10–15% of cases. Evaluation of lung damage in SDS includes pulmonary function tests, lung diffusing capacity determination, Doppler echocardiography analysis, multispiral computed tomography (MSCT) of the chest, bronchoalveolar lavage, lung biopsy with morphological examination of its specimens, as well as right heart catheterization. The best technique for detecting ILD is MSCT, as chest radiography has a low sensitivity in the early stages of the disease. IPL is treated in accordance with the 2017 ACR/EULAR guidelines; the leading role is played by immunosuppressive drugs, such as cyclophosphamide and mycophenolate mofetil. Antifibrotic drugs (pirfenidone, nintedanib) are being tested now . 

In recent years, there has been a considerable rise in the incidence of psoriatic arthritis (PsA) and an increase in the number of cases of its severe course, which leads to the marked deterioration of quality of life (QL), to disability and early disability.

PsA is characterized by its chronic progressive course, the development of joint destruction and ankylosis, multiple intra-articular osteolysis, spondylitis and frequently accompanied by various comorbidities. The important aspects of the prevention of joint functional disorders and erosion and their successful therapy are early diagnosis of PsA in patients with psoriasis (Ps) and timely consultation with a rheumatologist.

The early use of pathogenetically sound therapy for PsA reduces the likelihood of irreversible damage to the joints, spine, and viscera in these patients. The main goal of PsA pharmacotherapy is to achieve remission or minimal activity of a disease (arthritis, spondylitis, enthesitis, dactylitis, and Ps), to slow or prevent radiological progression, to increase life expectancy, to improve QL for patients, and to lower the risk of comorbidities.

These guidelines have been worked out jointly by rheumatologists and dermatovenereologists in order to improve the diagnosis of PsA in patients with Ps and to timely initiate adequate therapy. 

Glucosamine sulfate (GS) is essential for the regeneration of cartilaginous tissue and, in addition, it has anti-inflammatory properties comparable to those of nonsteroidal anti-inflammatory drugs (NSAIDs). Clinical trials indicate the synergism between GS and NSAIDs in osteoarthritis (OA) and other joint diseases.

Objective: to estimate the degree of synergism between different combinations of GS and NSAIDs.

Material and methods. A differential chemoreactome analysis was employed to evaluate the effects of GS and seven agents from the class of NSAIDs, such as ketorolac, nimesulide, diclofenac, meloxicam, dexketoprofen, celecoxib, and etoricoxib, for estimating the degree of synergism between different combinations of GS and NSAIDs.

Results and discussion. Dexketoprofen is shown to enhance most effectively the anti-inflammatory properties of GS as compared to ketorolac that does this to a lesser extent. The drug should be practically used as follows: the most effective combination (GS + dexketoprofen (or GS + ketorolak) is taken at week 1 of treatment for rapid pain elimination; thereafter there may be a combination of GS and NSAIDs, the intake of which is associated with minimal adverse reactions for a longer time.

Conclusion. The investigation has shown that the coadministration of GS and NSAIDs is promising in treating joint diseases. 

Objective: to evaluate the efficacy and safety of Chondroguard® in the combined (intra-articular (IA) + intramuscular (IM)) and IM injection in patients with knee osteoarthritis (OA).

Patients and methods. The study enrolled 150 patients with knee OA who were divided into two groups with 75 patients in each group. Group 1 received the drug (100 mg/ml) intramuscularly: 25 injections every other day, the first three injections at a dose of 100 mg, the fourth injection was started with a dose of 200 mg. Group 2 had five IA injections into the target joint at a daily dose of 200 mg with an interval of 3 days between injections, then 16 IM injections at 200 mg every other day. All the patients were prescribed nonsteroidal anti-inflammatory drugs (NSAIDs), such as meloxicam 15 mg. To determine the efficiency of treatment, the investigators estimated the following parameters: pain intensity on a visual analogue scale (VAS), the total WOMAC index and its components (pain, stiffness, and functional insufficiency), sensory and affective-emotional pain characteristics (for the target joint) according to McGill Pain Questionnaire (MPQ) scores. Clinical and biochemical blood tests, clinical urinalysis, coagulogram, and electrocardiography were performed in all the patients at the beginning and the end of the study.

Results and discussion. Comparison of two Chondroguard® regimens showed that by the end of treatment, the pain intensity on VAS was significantly lower in Group 2 (IA + IM administration) than in Group 1 (16.81±13.49 and 21.88±13.24, respectively; p<0.0001). Analysis revealed that there were no significant differences between Groups 1 and 2 in the changes of the overall WOMAC index and its components (pain, stiffness, and functional performance), as well as in MPQ pain scores. No serious adverse events (AEs) were recorded in the study. There were 11 AEs in 3.3% (n = 5/150) of the patients throughout the study. By its end, resolution/termination of AEs was noted in 100% of cases. There were no clinically significant pathological laboratory and ECG findings.

Conclusion. The test drug during any (IM or combined) route of administration quickly and effectively reduces pain syndrome and stiffness and improves joint functional performance and at the same time it is a safe drug. Its important advantage is a quick effect achieved by IA and IM administration. This makes it possible to reduce the dose of NSAIDs or to discontinue the latter, which is very important for OA patients with comorbidity. 

Rheumatoid arthritis (RA) therapy is aimed not only at suppressing inflammation, but also at preventing local and generalized bone loss, particularly in patients receiving glucocorticoids (GCs). Denosumab, a fully human monoclonal antibody that binds to the receptor activator of nuclear factor kappa B ligand (RANKL), prevents interaction with the receptor on osteoclasts, reduces their activity, and inhibits bone resorption is a promising drug for the treatment of secondary osteoporosis (OP).

Objective: to assess bone mineral density (BMD) in the axial and peripheral skeleton, erosive and destructive changes in the hands and feet of GC-treated patients with RA 12 months after denosumab treatment.

Patients and methods. Sixty-six postmenopausal women suffering from RA with a documented diagnosis of OP received denosumab 60 mg subcutaneously twice: at baseline and 6 months later. BMD was measured before treatment and after 12 months of follow-up, by using dual-energy X-ray absorptiometry of three sections: the lumbar spine (LI–IV), femoral neck (FN) and distal forearm (DF). A change in Sharp/van der Heijde (SvH) scores, as well as the number of erosions and narrowed articular slits, and total scores were assessed, by using hand and foot radiographs, at baseline and after 12 months.

Results and discussion. The mean age of the patients was 59.6±7.4 years; the mean duration of RA was 17.7±10.4 years. All the patients received anti-inflammatory therapy, including 34 (49.3%) patients who took GCs. In this group, pre- and posttreatment BMD in LI–IV was 0.809±0.109 and 0.849±0.117 g/cm2 , respectively (p < 0.0001); that in FN was 0.598±0.087 and 0.609±0.083 g/cm2 (p=0.045); and that in DF was 0.496±0.113 and 0.498±0.106 g/cm2, respectively (p>0.05). Regardless of the nature of anti-inflammatory therapy (with/without GCs), BMD in LI–IV and FN increased significantly DF stabilized in both patient groups. Before/after denosumab treatment, the GC (GC+) group showed a significant increase in the number of erosions up to 32.5 [13.0; 78.0] and 33.0 [13.0; 90.0] scores, respectively (p=0.043) and in the total SvH scores up to 146.5 [93.0; 221.0] and 149.0 [930; 221.0] respectively (p=0.027). There was no increase in the number of narrowed slits in the GC+ group. The number of erosions, narrowed articular slits, or the total SvH scores did not significantly change in the group of patients who did not receive GC (GC-).

Conclusion. Therapy with subcutaneous denosumab 60 mg 2 times yearly at semiannual intervals could significantly increase BMD in LI–IV and FN and stabilize in DF regardless of GC use. Negative changes in the number of erosions and total SvH scores were noted mainly in the GC+ group. The SvH scores for the hands and feet remained unchanged in the patients of the GC- group. 

Objective: to evaluate the economic impact of therapy with a Russian rituximab (RTM) biosimilar (Acellbia®) in patients with rheumatoid arthritis (RA) on the healthcare budget of the Russian Federation.

Material and methods. A review of literature data and economic modeling (budget impact analysis) were carried out.

Results. The use of the RTM biosimilar Acellbia® to treat patients with RA is appropriately and economically justified through drug supply within any funding source: a compulsory health insurance (CHI) system (for high-tech medical care or a diagnosis-related group); an essential medicines provision program, and a regional subsidized drug list.

Conclusion. The budget burden over the next three years, the budget burden will be reduced from 6% will be reduced from 6% in the CHI system to 13% in the regional subsidized drug list, which will bring additional more than 1.5 billion rubles. A further reduction in the price of a RTM biosimilar as a result of competitive activity and the potential emergence of other biosimilars will lead to a further rise in budget saving. 

Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most popular tool to combat pain. Unfortunately, NSAIDs can cause various adverse reactions, among these one of the most common ones is the development or destabilization of hypertension. Controlled and observational studies have shown that the use of NSAIDs is accompanied by an average 2–3 mm Hg increase in blood pressure (BP) and persistent hypertension is noted in 2–25% of patients. In addition, NSAIDs are able to reduce the efficacy of almost all classes of antihypertensive agents with the exception of calcium channel blockers. The clinical significance of NSAID-induced hypertension is determined by a considerable increase in the risk of cardiovascular accidents, such as infarction, ischemic stroke and sudden cardiovascular death. All NSAIDs (and nonselective traditional drugs and coxibs) can negatively affect BP. Therefore, when prescribing any NSAIDs, it is necessary to take into account the presence of baseline hypertension, to monitor BP regularly, and to correct antihypertensive therapy as needed. This review deals with the key aspects of the problem with NSAID-related hypertension.

Different types of panniculitis (Pn) can be one of the symptoms of rheumatic diseases (RDs). Pn is a group of heterogeneous inflammatory diseases that are characterized by subcutaneous adipose tissue (SAT) lesion and often occur with musculoskeletal and visceral involvements. There is no single concept of the etiology and pathogenesis of Pn. Infections, injures, hormonal and immune disorders, drug intake, pancreatic disease, malignant neoplasms, etc. can play a role in the development of Pn. The latter is associated with RDs in a fairly large group of patients. There have recently been reports of about 200 and 50 cases of only idiopathic lobular Pn in the world and Russian literature, respectively. There have also been publications on other types of Pn, such as erythema nodosum, eosinophilic fasciitis, superficial migratory thrombophlebitis, lupus Pn, dermatomyositis Pn, scleroderma systematica, gout, psoriatic arthritis, etc. There is now a need to study skin changes and SAT lesions in the context of RDs, which will be able to estimate the true clinical and prognostic value of Pn in RDs. Based on recent literature data, this review characterizes the main types of Pn, their clinical and histological signs, and diagnostic methods.

The paper systematizes data on the pharmacokinetics, molecular and cellular mechanisms of action of chondroprotectors (CPs), by using chondroitin sulfate (CS) and glucosamine (GA) as an example. It presents current ideas about the mechanisms of their absorption and penetration into the joint tissues during oral administration, the effect of CS on the cytoplasmic membrane of chondrocytes in osteoarthritis (OA). The paper also describes the plastic and regulatory functions of GA at the intracellular level after its penetration into the cells by glucose carriers. The combination of benefits from targeted and metabolic therapy determines the efficacy of combined CPs, the active principle of which is CS and GA.

The hip joint damage (HJD) coxitis is a characteristic manifestation of ankylosing spondylitis (AS). Treatment policy for coxitis in this disease has not been worked out today. There are a few studies evaluating the efficacy of tumor necrosis factor-α (IFN-α ) inhibitors in these patients. Coxitis treatment with disease-modifying antirheumatic drugs (DMARDs) is under study.

The paper describes three clinical cases of patients with AS and coxitis, in two of whom combined therapy with nonsteroidal anti-inflammatory drugs (NSAIDs), DMARDs, and IFN-α inhibitors produced a fairly rapid positive effect in reducing inflammatory changes in HJD as evidenced by magnetic resonance imaging; moreover, there was no x-ray progression. It can be assumed that there is a so-called window of opportunity when no irreversible structural changes in HJD occur during timely initiated therapy with biological agents (BAs).

Our findings suggest that further investigations are needed to clarify the effects of DMARD and combination therapy using DMARD and BAs in combination with NSAIDs. 

The clinical picture of the symptomatic phase of antineutrophil cytoplasmic antibody-associated systemic vasculitis (ANCA-SV) can vary widely and be accompanied by joint damage, which complicates the early diagnosis of the disease. The paper presents a case of ANCA-SV with acute kidney injury, the manifestations of the symptomatic phase of which were confined to joint damage, myalgia, and Raynaud's syndrome, which led to delayed diagnosis at the stage of renal failure requiring hemodialysis (HD). Urgent adequate induction therapy could preserve kidney function, despite 10-day anuria and 5-week HD.

The paper discusses the need for a systematic detailed examination of patients with the onset of a joint inflammatory lesion, especially in those with its systemic manifestations, and the inclusion of serum ANCA tests in the standards of diagnosis in early arthritis. 

The main goal of management of patients with osteoarthritis (OA) is analgesic and anti-inflammatory therapy, deceleration of the progression of the disease, and improvement of quality of life. Fast-acting symptomatic drugs (analgesics and nonsteroidal anti-inflammatory drugs (NSAIDs)) and sustained-release structure-modifying drugs (chondroitin sulfate, glucosamine sulfate, their combination, piascledine, diacerein) are used to treat OA. The European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO)) has analyzed the proposals of a number of expert groups and elaborated a consensus on the management of patients with OA: it has recommended the use of sustained-release drugs just in early OA.

The article gives the data of comparative studies of a new Russian chondroprotector, the active ingredient of which is a bioactive extract from small sea fish, which contains alflutop. It evaluates the analgesic and anti-inflammatory effects and acute and chronic toxicity on experimental animal models and the preliminary results of therapy with the new drug in patients with OA in the large and small joints. 

The problem of fertility and pregnancy outcomes in rheumatic diseases (RDs) is discussed by both rheumatologists and obstetricians. The present paper considers the problems of reproductive function and pregnancy outcomes in patients with Behcet's disease (BD).

The study of the circulating level of anti-MЯllerian hormone (AMH) opened a new page in the evaluation of ovarian function and fertility in different diseases, including RDs. The evaluation of AMH as a marker of ovarian reserve substantially simplified its estimate and the determination of the contribution of the disease itself to patients' infertility.

Examination of the obstetric histories of patients with BD demonstrated different pregnancy outcomes. Our studies of familial aggregation in BD showed that there were large families in certain ethnic groups, which allowed us to evaluate, on the basis of obstetric histories, both reproductive function and pregnancy outcomes, and not one pregnancy, but several pregnancies, which is important in the study of fertility.

Data on the impact of pregnancy on BD, and vice versa, are scarce and contradictory; described as both an exacerbation of BD during gestation and improvement of disease symptoms. There is evidence for an exacerbation of BD in the third trimester of pregnancy only in the women who had painful genital ulcers. At the same time, a number of works have not reveal the impact of either BD on the outcome of gestation or that of pregnancy on the course of BD.

It is concluded that there is a need for further investigations of fertility, pregnancy and its outcomes in BD.