Hepatitis B (HBV) reactivation in patients receiving biologic therapy for chronic inflammatory diseases in clinical practice.

INTRODUCTION AND AIM: Biologic treatment - particularly with the anti-TNF molecules - is frequently used in clinical practice to treat the severe form for both chronic rheumatic diseases and inflammatory bowel diseases. The immunosuppression induced by biologic therapies increases the risk of infections, including tuberculosis, as well as hepatitis B virus (HBV) reactivation may occur in inactive carriers or occult HBV infection (OBI) subjects during biologic therapy. This study aimed to update data on HBV prevalence and reactivation in patients receiving biologic therapy for either chronic rheumatic diseases or IBD, and to describe their management in clinical practice. MATERIALS AND METHODS: This study was performed in 6 Italian centers (3 Rheumatology Units and 3 Gastroenterology Units). Clinical, biochemical and virological data, as well as follow up information, were recorded and analyzed. RESULTS: 984 patients were considered, including 817 with rheumatic disease and 167 with IBD. A total of 43 showed HBV infection (38 OBI and 5 carriers) accounting for a prevalence of 4%. Among OBI patients, 1 (2.6%) case of HBV reactivation occurred in a male patient with Crohn disease. Among the 5 HBV carriers, two patients (1 with spondyloarthritis and 1 with rheumatoid arthritis) did not received HBV antiviral therapy, and both experienced flare of hepatitis at 47 and 49 months following biologic therapy starting. DISCUSSION: Data of our study highlight that guidelines on management of HBV patients treated with biologic therapies should be still implemented in clinical practice when considering that, although infrequent, HBV reactivation could be potentially life-threatening.

Vitamin D Signaling in Gastro-Rheumatology: From Immuno-Modulation to Potential Clinical Applications.

In the last decades, the comprehension of the pathophysiology of bone metabolism and its interconnections with multiple homeostatic processes has been consistently expanded. The branch of osteoimmunology specifically investigating the link between bone and immune system has been developed. Among molecular mediators potentially relevant in this field, vitamin D has been recently pointed out, and abnormalities of the vitamin D axis have been described in both in vitro and in vivo models of inflammatory bowel diseases (IBD) and arthritis. Furthermore, vitamin D deficiency has been reported in patients affected by IBD and chronic inflammatory arthritis, thus suggesting the intriguing possibility of impacting the disease activity by the administration vitamin D supplements. In the present review, the complex interwoven link between vitamin D signaling, gut barrier integrity, microbiota composition, and the immune system was examined. Potential clinical application exploiting vitamin D pathway in the context of IBD and arthritis is presented and critically discussed. A more detailed comprehension of the vitamin D effects and interactions at molecular level would allow one to achieve a novel therapeutic approach in gastro-rheumatologic inflammatory diseases through the design of specific trials and the optimization of treatment protocols.

Integrated gastroenterology and rheumatology ambulatory: an innovative approach for enteropathic spondyloarthritis early diagnosis.

Patients with inflammatory bowel disease (IBD) may develop rheumatic diseases, particularly enterophatic spondyloarthritis (ESpA). Similarly, an IBD may develop in patients with SpA. Management of these patients in a dedicated ambulatory could be advantageous. We pioneered an integrated "GastroReumatology" ambulatory where a gastroenterologist and a rheumatologist with a long-lasting expertise in IBD and spondyloarthritis, respectively, simultaneously visit those patients referred for a suspected ESpA. A total of 101 different patients with suspected or known IBD and/or a rheumatic disease were visited. A new diagnosis of ESpA was eventually achieved in 13 (12.9%) patients, and further 12 patients with an already known ESpA were referred for an appropriate management. No cases of IBD in those patients with an established rheumatic disease were observed. Early diagnosis of ESpA is possible in a "GastroReumatology" ambulatory.

New onset or worsening of psoriasis following biologic therapy: A case series.

Biologic therapies may cause so-called "paradoxical side-effects," that is, the onset or exacerbation of new symptoms/diseases for which biological treatment should be effective. Among these, psoriatic skin lesions have been described. We report a case series of ten patients with either new onset (seven cases) or worsening (three cases) of psoriasis occurring during a biologic therapy. Six patients were receiving a biologic monotherapy, while four patients were in combination treatment with methotrexate (MTX). Psoriasis remission was observed in two patients who discontinued biologic therapy. In the six patients in whom biologic therapy was not discontinued, a complete disappearance or a partial improvement of skin lesions was achieved following topic steroid therapy in two patients and three patients, respectively. In the remaining patient, psoriasis developed during Adalimumab monotherapy, which completely disappeared when the Infliximab and MTX combination was started. The potential pathogenetic mechanisms were shortly reviewed.

Vitamin D deficiency in patients with either rheumatic diseases or inflammatory bowel diseases on biologic therapy.

Vitamin D deficiency has been reported in patients with chronic inflammatory conditions, such as rheumatic and inflammatory bowel diseases (IBD). We evaluated the role of biologic therapy on vitamin D, calcium and parathormone (PTH) levels. This cross-sectional study enrolled consecutive patients with either rheumatic diseases or IBD who underwent an ambulatory visit. Patients receiving vitamin D/calcium supplementation were excluded. Vitamin D deficiency or insufficiency was diagnosed when values were <20 ng/mL and 21-29 ng/ml, respectively. Patients were sub-grouped according to biologic therapy. A multivariate analysis was performed. Two-hundred patients, including 136 with a rheumatic disease (M/F 37/99; mean age 60.7 ± 12.9 years) and 64 with IBD (M/F 41/23; Mean age 49.6 ± 13.1 years) were enrolled. Vitamin D deficiency/insufficiency was detected in as many as 63.5 % patients, being 61.8 and 67.2 % in patients with either rheumatic diseases or IBD, respectively. The prevalence of vitamin D deficiency/insufficiency was higher in those receiving biologics than other therapies (78.3 vs 43.2 %; p < 0.0001), in either rheumatic diseases (78.7 vs 41 %; p < 0.0001) or IBD (75 vs 50 %; p = 0.03) group. At multivariate analysis, only biologic therapy was independently associated with vitamin D deficit (OR 4.61; p = 0.001). Patients with vitamin D deficiency/insufficiency had hypocalcemia more frequently than controls (22.8 vs 10.9 %; p = 0.03), while PTH values did not differ significantly. This study finds that the prevalence of vitamin D deficiency/insufficiency was very high in patients with either rheumatic diseases or IBD receiving a biologic therapy.