Difficulties in diagnosis and treatment of adult-onset Still's disease concurrent with pericardial effusion as a leading clinical manifestation

The paper considers a case of adult-onset Still's disease that occurred as acute pericarditis, two-spike hectic fever, and neutrophilic leukocytosis in a young man. It was difficult to establish a correct diagnosis because there were no characteristic clinical symptoms of Still's disease, such as salmon colored rash, arthralgia, and sore throat. The diagnosis of adult-onset Still's disease was verified on the basis of the classification criteria described by M. Yamaguchi et al. The special feature of the clinical case was the development of steroid resistance and the effective use of a combination of the interleukin-6 receptor blocker tocilizumab (8 mg/kg body weight, given intravenously dropwise once every four weeks) and methotrexate (15 mg/week orally). During this treatment, a sustained clinical and laboratory response was achieved, which could reduce the dose of glucocorticoids to the maintaining one

Comparative analysis of the concentrations of proinflammatory cytokines and glycosylated ferritin in patients with idiopathic recurrent pericarditis and adult-onset Still's disease

Idiopathic recurrent pericarditis (IRP) and adult-onset Still's disease (AOSD) are polygenic autoinflammatory diseases, in the pathogenesis of which pro-inflammatory cytokines from the interleukin-1 superfamily play a central role.Aim. To compare serum concentrations of proinflammatory cytokines and glycosylated ferritin (GF) in patients with IRP and AOSD during an exacerbation.Material and methods. The study included 15 patients with AOSD, 15 — IRP. The diagnosis of AOSD was established using the Yamaguchi criteria (1992). IRP was diagnosed in accordance with the 2015 European Society of Cardiology on the diagnosis and management of pericardial diseases. Blood sampling from all patients was carried out during the recurrence period prior to the anti-inflammatory therapy initiation. The serum levels of interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-18 (IL-18), procalcitonin, total ferritin and GF was assessed. The results obtained were compared with levels of biochemical parameters, high-sensitivity C-reactive protein (CRP), as well as with white blood cell (WBC) and neutrophil counts.Results. The median age in the AOSD group was 28 years, and the IRP — 55 years. An increase WBC count >10*109/L was detected in 10 and 9 patients in the AOSD and IRP groups, respectively. The concentration of CRP was increased in all patients and did not differ in the study groups (p=0,836).The highest values of ferritin and GF levels were found in the AOSD group (1416 ng/ml vs 408 ng/ml, p=0,008) and (12% vs 33,9%, p=0,067), respectively. In both groups, increased concentrations of IL-6 and IL-18 were determined. In the AOSD group, the concentration of IL-18 was higher than in the IRP group (2114 pg/ml vs 161,5 pg/ml, p<0,001). IL-6 concentrations in the study groups did not differ (33,9 pg/ml vs 24,9 pg/ml, p=0,4). IL-1β serum concentration in all subjects corresponded to normal values.Correlation analysis in the AOSD group revealed a direct relationship between the IL-18 and ferritin concentrations (rs=0,73, p=0,03).Conclusion. The study established a similar pattern of changes in inflammatory biomarkers in patients with AOSD and IRI. The most informative marker of inflammation was IL-18

Трудности диагностики и лечения болезни Стилла взрослых, протекавшей с экссудативным перикардитом в качестве ведущего клинического проявления

The paper considers a case of adult-onset Still's disease that occurred as acute pericarditis, two-spike hectic fever, and neutrophilic leukocytosis in a young man. It was difficult to establish a correct diagnosis because there were no characteristic clinical symptoms of Still's disease, such as salmon colored rash, arthralgia, and sore throat. The diagnosis of adult-onset Still's disease was verified on the basis of the classification criteria described by M. Yamaguchi et al. The special feature of the clinical case was the development of steroid resistance and the effective use of a combination of the interleukin-6 receptor blocker tocilizumab (8 mg/kg body weight, given intravenously dropwise once every four weeks) and methotrexate (15 mg/week orally). During this treatment, a sustained clinical and laboratory response was achieved, which could reduce the dose of glucocorticoids to the maintaining one.В статье рассматривается случай болезни Стилла у молодого мужчины, дебютировавшей симптомами острого перикардита, гектической двупиковой лихорадки и нейтрофильного лейкоцитоза. Установить правильный диагноз было сложно из-за отсутствия характерных клинических симптомов болезни Стилла, таких как сыпь («salmon-coloured» rash), артрит, боль в горле. Верификация диагноза болезни Стилла взрослых была выполнена на основании критериев M. Yamaguchi и соавт. Особенностями клинического случая явились развитие стероидорезистентности и эффективное применение комбинации блокатора рецептора интерлейкина 6 тоцилизумаба (8 мг/кг массы тела внутривенно капельно 1 раз в 4 нед) с метотрексатом (15 мг/нед внутрь). На фоне лечения был достигнут стойкий клинико-лабораторный ответ, позволивший снизить дозу глюкокортикоидов до поддерживающей

SEARCH FOR CLINICAL PREDICTORS OF PULMONARY HYPERTENSION IN PATIENTS WITH SYSTEMIC SCLEROSIS

Pulmonary hypertension (PH) in patients with systemic sclerosis (SSc) is associated with an unfavorable prognosis. The scope of investigations necessary to detect PH, the complexity of its diagnostic algorithms for routine use, as well as the impossibility to apply the existing algorithms for all PH variants increase the relevance of searching for novel PH predictors in patients with SSc.Objective: to reveal the relationship of capillary structural changes to the clinical and immunological subtype of SSc, disease activity, and risk for PH.Subjects and methods. The trial enrolled 57 patients with SSc. The investigators evaluated the activity of the disease, the extent of skin lesion, the fluorescent pattern and titer of antinuclear factor, and the level of N-terminal brain natriuretic propeptide. All the patients underwent nailfold videocapillaroscopy, a comprehensive assessment of external respiratory functions, and echocardiography. When there were indirect signs of PH, right heart catheterization was performed for its verification.Results and discussion. PH was detected in 10 of the 57 patients enrolled in the trial. The patients with PH were significantly older than those without PH (61±7 and 53±10 years, respectively; p=0.036); there were also differences between these groups in the semiquantitative assessment of nailfold capillary alterations (p<0.05) and in the signs of right cardiac remodeling (p <0.05). The Rodnan skin score was found to be related to right atrial area (r=0.506; p=0.019) and pulmonary artery diameter (r=0.482; p=0.027). It has been shown that age older than 60 years (p=0.001), reduced capillary bed density (p=0.033), and lower lung diffusing capacity (p=0.024) may be an additional criterion increasing the probability of PH. In localized cutaneous SSc, the Rodman skin score correlated with right atrial area (r=0.582; p=0.009), right ventricular dimensions in parasternal (r=0.517; p=0.023) and basal  (r=0.697; p=0.001) sections, and with pulmonary artery diameter (r=0.816; p<0.001).Conclusion. In localized cutaneous SSc, nailfold capillaroscopy can be used along with the Rodnan skin score to assess PH probability

PULMONARY ARTERIAL HYPERTENSION DIAGNOSTICS SPECIFICS IN SYSTEMIC SCLERODERMIA

Aim. Pulmonary arterial hypertension (PAH) in systemic sclerodermia patients (SSD) is associated with poorer outcomes. Aim of current study is to assess the prevalence of PAH associated with SSD, among patients with newly diagnosed pulmonary hypertension (PH), included to the registry of Federal Almazov North- West Medical Research Centre and to conduct the analysis of applicability of the algorithms for earlier diagnostics of PH in SSD patients.Material and methods. To comparative analysis we included patients with idiopathic PAH (iPAH) and PAH associated with SSD (SSD-PAH). All patients underwent thorough echocardiographic test (EchoCG), 6-minute walking test (6WT), spirometry. To confirm the diagnosis of PAH we applied the right chambers catheterization (RCC).Results. Totally, 33 SSD patients included complaining on dyspnea, of those 14 had verified PAH and were taking specific treatment. With PHAROS algorithm we were able to separate additional risk subgroup of 6 patients for further study. Among participants, iPAH had 44%, and SSD-PAH — 11%. Most patients in both groups had III-IV FC (WHO) of PH: 55% of iPAH and 75% of PAH-SSD. In SSD patients there were lower values of the right ventricle systolic function by EchoCG [FAC=26±7% (р=0,028); TAPSE=15±3 mm (р=0,027); TAS’V=9±2 cm/s (р=0,023)]; values of lung diffusion capacity (DLco): 46±14% vs 62±16% in iPAH group (р=0,001) and distance of 6WT: 326±105 m vs 383±106 m (р=0,041). This data correlates with foreign registers and witness serious prognosis in PAH-SSD.Conclusion. Our study demonstrated significance of novel algorithms development for earlier diagnostics of PAH and start of specific treatment according to severity of prognosis of SSD-PAH patients. Current guidelines for PAH diagnostics use DETECT algorithm as recommended for application in patients with SSD lasting for more than 3 years and DLco below 60%. We demonstrated the worth of inclusion in investigation algorithm for SSD the additional echocardiographic criteria for PH to increase specificity

Variants of intensification of immunosuppressive therapy of rheumatoid arthritis

Objective. To assess influence of different treatment intensification regimens on clinico- laboratory parameters of activity and quality of life of pts with rheumatoid arthritis (RA). Material and methods. 40 RA pts of group 1 received pulse-therapy with methotrexate (MT) and dexamethasone (DM), 20ptsofgroup 2 received pulse-therapy with methylprednisolone (MP) and cyclophosphane (CP). After that all pts continued treatment with disease modifying antirheumatic drugs. Pts were examined at baseline, 1 and 6 months after completion of therapy intensification cycle. Results. At 1 month tender and swollen joint counts decrease in group 1 was more prominent than in group 2. After 6 months significant decrease of all disease activity measures was maintained in group 1 but not in pts received CP and MP. Conclusion. Pulse therapy with MT and DM provided more prolonged decrease of RA clinico-laboratory activity than treatment with MP and CP. Group 1 pts also showed significant increase of quality of life. None method of intensive treatment caused severe adverse events

ANTI-HETEROGENEOUS NUCLEAR RIBONUCLEOPROTEIN B1 (ANTI-RA33) ANTIBODIES IN RHEUMATOID ARTHRITIS AND SYSTEMIC SCLEROSIS

Anti-heterogeneous nuclear ribonucleoprotein (RNP) autoantibodies (AAbs) are encountered in many autoimmune rheumatic diseases (ARDs). The potential diagnostic value of the RA33 AAb complex consisting of RNP A2 and alternative domains of the splicing proteins RNP B1 and RNP B2 is now of interest to rheumatologists. Subjects and methods. The authors studied the frequency of anti-RNP B1 AAbs in 300 patients with systemic ARDs, including those with rheumatoid arthritis (RA), ankylosing spondylitis (AS), systemic lupus erythematosus (SLE), systemic sclerosis (SSc), and Sjö gren's syndrome (SS) and in 53 people without ARDs, who constituted a control group. Serum anti-RNP B1 AAbs were assessed by enzyme immunoassay. Results and discussion. The frequency of anti-RNP B1 AAbs in patients with ARDs was much higher than that in the control group: 170/300 (56.6%) and 8/53 (13%) patients, respectively. Anti-RNP B1 AAbs were detected in 78.5% (113/144) of the patients with RA; 40.3% (23/57) of those with AS, in 67.5% (27/40) of those with SSc, in 36.4% (16/44) of those with SLE, and in 13.3% (2/15) of those with SS. The diagnostic sensitivity of the marker for RA was 78.5%, its diagnostic specificity was 84.9%; the likelihood ratio of positive and negative results was 5.24 and 0.24, respectively. In the patients with RA, the level of anti-RNP B1 AAbs significantly correlated with that of C-reactive protein and erythrocyte sedimentation rate, while in those with SSc the detection of anti-RNP B1 AAbs was related to the rigidity of the vascular wall and the presence of hypertension. The frequency of anti-RNP B1 AAbs among the RA patients seronegative for rheumatoid factor and anti-cyclic citrullinated peptide antibodies was 15.4%. Conclusion. Anti-RNP B1 AAs are a useful laboratory marker (with the upper limit of the normal range being 3.3 U/ml), but are of limited value in the diagnosis of RA. Anti-RNP B1 AAbs may be regarded as an additional diagnostic marker for RA

VASCULAR WALL STIFFNESS IN PATIENTS WITH ANKYLOSING SPONDYLITIS: RESULTS OF A MULTICENTER STUDY

Objective: to study some vascular wall stiffness parameters in patients with ankylosing spondylitis (AS) without clinically manifest cardio­ vascular diseases. Subjects and methods. One hundred and six patients with AS and 21 healthy volunteers without cardiovascular diseases who were matched for age, gender, and cardiovascular risk were examined at two centers. Cardiovascular risk and vascular wall stiffness (augmentation index and pulse wave propagation velocity (PWPV)) were assessed by oscillography. Results. Vascular wall stiffness was comparable in the patients with AS (at both centers) and in the healthy individuals. PWPV was 7.45 (5.4–8.71) m/sec in the AS patients (n = 106) and 8.53 (6.28–9.5) m/sec in the healthy individuals (n = 21); the aortic augmentation in­ dex was 15.6 (7.9–31.1) and 21.1 (10.2–24) %, respectively; p > 0.05 for all. Correlation analysis revealed associations between aug­ mentation index, age, blood pressure, disease activity (BASDAI) and spine mobility (BASMI) scores. Conclusion. The vascular wall stiffness did not differ between AS patients without cardiovascular diseases and cardiovascular risk­matched healthy individuals. Its parameters were related to age, blood pressure, and disease activity (BASDAI) and axial skeleton immobility (BASMI) indices