JAK/STAT pathway in pathology of rheumatoid arthritis (Review).

Rheumatoid arthritis (RA) is classified as an inflammatory, chronic autoimmune and disabling disease based on the intricate interplay between environmental and genetic factors. With a prevalence ranging from 0.3 to 1%, RA is the most prevalent inflammatory joint disease observed in adults. Disruption of immune tolerance becomes evident when abnormal stimulation of the innate and adaptive immune system occurs. This cascade of events causes persistent joint inflammation, proliferative synovitis and, ultimately, damage of the underlying cartilage as well as the subchondral bone, leading to permanent joint destruction, deformity and subsequent loss of function. With cytokines being the key to a multitude of biological processes, including inflammation, hematopoiesis and overall immune response, one must inevitably look at the main pathways through which a significant number of those molecules exert their function. Janus kinase/signal transducers and activators of transcription (JAK/STATs) represent one such pathway and, recently, JAK inhibitors (JAKinibs) have shown promise in the treatment of several inflammatory diseases, including RA. This narrative review focuses on the intricate signaling pathways involved as well as on the clinical aspects and safety profiles of JAKinibs approved for the treatment of RA.

Correlations between infection patterns and eye damage in reactive arthritis.

The purpose of the study was to correlate the infectious patterns (urogenital, enteral) with ocular manifestations, such as conjunctivitis or acute anterior uveitis in reactive arthritis (ReA). The transversal, observational study was conducted in the Clinic of Rheumatology, University of Medicine and Pharmacy of Craiova, Romania, during the period 2012-2015, and included 112 patients. They were divided into three groups, as follows: Group I (52 ReA cases), Group II (30 other spondyloarthritis cases), Group III (40 osteoarthritis cases). Ophthalmologic screening was performed, together with the detection of human leukocyte antigen B27 (HLA-B27) and the infectious trigger. Within Group I, 42 (80.76%) patients presented genitourinary infections (78.57% Chlamydia trachomatis, 21.43% Ureaplasma urealyticum), 10 (19.23%) patients presented enteral infections (Yersinia enterocolitica and Salmonella). Compared with the other two groups, the patients from the first group were documented with more conjunctivitis episodes. Although anterior uveitis is more common in ankylosing spondylitis (AS), in the present study more cases were identified in Group I (11.9%) than in Group II (6.67%) and no case were recorded in Group III. Most of patients from Group I were HLA-B27 positive. The etiologic profile of ocular manifestations in ReA is dominated by genitourinary infections - C. trachomatis and U. urealyticum, respectively. Cases of recurring uveitis are associated with elevated levels of anti-immunoglobulin A (IgA).

Behçet's disease with rapidly progressive bilateral optic neuropathy and avascular femoral neck necrosis. Literature review and management update.

Behçet's disease is a multi-systemic vasculitis of small arteriolar and venular vessels, which shows a wide range of clinical manifestations, such as oral and genital aphthosis, erythema nodosum, panuveitis, complex gastrointestinal disorders, the early onset of neurological involvement being a negative prognostic factor in evolution. We present the case of a 36-year-old patient, who was admitted in the Clinic of Rheumatology for recurrent-neglected oral aphthosis, recurrent erythema nodosum, left hip pain, reduction of visual acuity of the right eye, weight loss, profuse sweating, marked fatigability. From the personal history was retained avascular necrosis of right femoral head, with arthroplasty at this level, human leukocyte antigen-B51 (HLA-B51) positive. Ophthalmological evaluation reveals severe bilateral optic neuropathy, with confirmation of neuro-Behçet's disease (NBD) diagnosis, in a Neuro-Ophthalmological Center, based on cerebral nuclear magnetic resonance and cerebrospinal fluid analysis. Associated corticosteroid therapy with Azathioprine was initiated, with no signs of activity and progression of the disease in evolution. The case provides a necessary upgrade of the therapeutic strategies specific to the NBD pattern, emphasizing the importance of the multidisciplinary approach of a patient with complex pathology.

Bone turnover markers in postmenopausal osteoporosis and their correlation with bone mineral density and menopause duration.

BACKGROUND: Biochemical bone turnover markers (BTMs) estimates the bone remodeling process, being valuable in the personalized approach of osteoporotic patients. AIM: The aim of the study was to evaluate the correlation between biochemical BTMs and bone mineral density (BMD), depending on menopause period, in postmenopausal osteoporotic women, compared to postmenopausal women without osteoporosis. PATIENTS, MATERIALS AND METHODS: The study included 149 untreated postmenopausal women, divided into three groups: group 1 (65 osteoporotic women with less than 10 years of menopause), group 2 (44 osteoporotic patients, with over 10 years of menopause), and the control group with 40 postmenopausal women without osteoporosis. RESULTS: All BTMs levels were higher in the groups with osteoporosis, than in the control group. Lumbar BMD values correlated positively with deoxypyridinoline (DPD) and negatively with bone-specific isoform of alkaline phosphatase (BAP), tartrate-resistant acid phosphatase band 5b (TRAP 5b), osteocalcin (OC) and cross-linked N-telopeptides of type I collagen (NTX). Serum estradiol levels correlated positively with spine BMD in the whole study group (r=0.508, p=0.001). BTMs correlated positively with each other. Osteoporotic women with longer period of menopause presented significantly higher values of resorption markers (NTX and TRAP 5b), compared to the group with menopause duration less than 10 years. At a cutoff value of 12 µg∕L, BAP presented 82.4% sensitivity and 62.5% specificity. CONCLUSIONS: Our study showed that BTMs correlated negatively with lumbar BMD and positively with each other. Resorption markers levels increase with duration of estradiol deprivation period.