Biological therapy for dermatological manifestations of inflammatory bowel disease

Ulcerative colitis and Crohn's disease are the two forms of inflammatory bowel disease(IBD). The advent of biological drugs has significantly changed the management of these conditions. Skin manifestations are not uncommon in IBD. Among the reactive lesions(immunemediated extraintestinal manifestations), erythema nodosum(EN) and pyoderma gangrenosum(PG) are the two major cutaneous ills associated with IBD, while psoriasis is the dermatological comorbidity disease observed more often. In particular, in the last few years, anti-tumor necrosis factor(TNF)-α agents have been successfully used to treat psoriasis, especially these kinds of lesions that may occur during the treatment with biological therapies. The entity of the paradoxical manifestations has been relatively under reported as most lesions are limited and a causal relationship with the treatment is often poorly understood. The reason for this apparent side-effect of the therapy still remains unclear. Although side effects may occur, their clinical benefits are undoubted. This article reviews the therapeutic effects of the two most widely used anti-TNF-α molecules, infliximab(a fusion protein dimer of the human TNF-α receptor) and adalimumab(a fully human monoclonal antibody to TNF-α), for the treatment of the major cutaneous manifestations associated with IBD(EN, PG and psoriasis).

Extraintestinal manifestations in a large series of Italian inflammatory bowel disease patients

AIM:To investigate prevalence,type and time of onset of extraintestinal manifestations(EIMs)in a series of Italian inflammatory bowel disease(IBD)patients.METHODS:Data of 811 IBD consecutive patients,first referred to our Centre from 2000 to 2011,were retrospectively evaluated.RESULTS:Eight hundred and eleven IBD patients(437M,374 F)were studied:595 ulcerative colitis(UC)(73.4%)and 216 Crohn’s disease(CD)(26.6%).Among these,329(40.6%)showed EIMs:210 UC(35.3%)and119 CD(55.1%)(P<0.0001).Considering the time of the diagnosis of IBD,37 EIMs(11.2%)were developed before,229(69.6%)after and 63(19.2%)were simultaneous.The type of EIM were as follows:240 musculoskeletal(29.6%),in 72 CD patients and in 168 UC(P<0.0001);47 mucocutaneous(5.8%),in 26 CD and in21 UC(P=0.0049);26 ocular(3.2%),in 16 CD and in10 UC(CD 7.4%vs UC 1.7%,P=0.0093);6 hepatobiliary(0.8%);10 endocrinological(1.2%).In particular,with regards to the involvement of the musculoskeletal system,arthritis Type 1 was found in 41 CD(19%)and in 61 UC(10.2%)(P=0.0012)and Type 2 in 25 CD(11.6%)and in 100 UC(16.8%)(P=0.0012).CONCLUSION:Mucocutaneous manifestations,arthritis Type 1 and uveitis were significantly more frequent in CD than UC.The complications of the musculoskeletal system were the mostly observed ones,often with symptoms more severe than intestinal ones,confirming the need for close cooperation with rheumatologists.

Interleukin-21 triggers effector cell responses in the gut

In the gut of patients with Crohn's disease and patients with ulcerative colitis,the major forms of inflammatory bowel diseases(IBD) in humans,the tissue-damaging immune response is mediated by an active cross-talk between immune and non-immune cells.Accumulating evidence indicates also that cytokines produced by these cells play a major role in initiating and shaping this pathologic process.One such cytokine seems to be interleukin(IL)-21,a member of the common γ-chainreceptor family.IL-21 is produced in excess in the in-flamed intestine of patients with IBD mostly by activated CD4+ T helper cells co-expressing interferon-γ and follicular T helper cells.Moreover,both in vitro and in vivo studies indicate that excessive IL-21 production leads to the activation of multiple signaling pathways that expand and sustain the ongoing mucosal inflammation.In this article,we review the available data supporting the pathogenic role of IL-21 in IBD.

Involvement of interleukin-15 and interleukin-21, two γ-chain-related cytokines, in celiac disease

Celiac disease (CD), an enteropathy caused by dietary gluten in genetically susceptible individuals, is histologically characterized by villous atrophy, crypt cell hyperplasia, and increased number of intra-epithelial lymphocytes. The nature of CD pathogenesis remains unclear, but recent evidence indicates that both innate and adaptive immune responses are necessary for the phenotypic expression and pathologic changes characteristic of CD. Extensive studies of molecules produced by immune cells in the gut of CD patients have led to identification of two cytokines, namely interleukin (IL)-15 and IL-21, which are thought to play a major role in orchestrating the mucosal inflammatory response in CD. Here we review the current knowledge of the expression and function of IL-15 and IL-21 in CD.