The skin is one of the most common extraintestinal organ system affected in patients with inflammatory bowel disease (IBD), including both Crohn's disease and ulcerative colitis. The skin manifestations associated with IBD are polymorphic and can be classified into 4 categories according to their pathophysiology: (1) specific, (2) reactive, (3) associated, and (4) induced by IBD treatment. Cutaneous manifestations are regarded as specific if they share with IBD the same granulomatous histopathological pattern: perianal or metastatic Crohn's disease (commonly presenting with abscesses, fistulas or hidradenitis suppurativa-like features) is the prototype of this setting. Reactive cutaneous manifestations are different from IBD in the histopathology but have close physiopathological links: pyoderma gangrenosum, a neutrophil-mediated autoinflammatory skin disease typically manifesting as painful ulcers, is the paradigm of this group. Among the cutaneous diseases associated with IBD, the most commonly seen are erythema nodosum, a form of panniculitis most commonly involving bilateral pretibial areas, and psoriasis, a T helper 1/T helper 17-mediated erythematous squamous inflammatory disease. Finally, the number of cutaneous adverse reactions because of IBD therapies is progressively increasing. The most frequent drug-induced cutaneous manifestations are psoriasis-like, eczema-like, and lichenoid eruptions, as well as cutaneous lupus erythematosus for biologics, and nonmelanoma skin cancer, mainly basal cell and squamous cell carcinomas for thiopurines.

Venous and arterial thromboembolism in patients with inflammatory bowel diseases

Bradykinin is a mediator of inflammation, responsible for pain, vasodilation, and capillary permeability. Bradykinin receptor 1 (B₁R) and bradykinin receptor 2 (B₂R) are G protein-coupled receptors that mediate kinin effects. The latter is constitutive and rapidly desensitized; the former is induced by inflammatory cytokines and resistant to densensitization. The distribution of bradykinin receptors in human intestinal tissue was studied in patients with inflammatory bowel disease (IBD), namely ulcerative colitis (UC) and Crohn's disease (CD). Both B₂R and B₁R proteins are expressed in the epithelial cells of normal and IBD intestines. B₁R protein is visualized in macrophages at the center of granulomas in CD. B₂R protein is normally present in the apexes of enterocytes in the basal area and intracellularly in inflammatory tissue. In contrast, B₁R protein is found in the basal area of enterocytes in normal intestine but in the apical portion of enterocytes in inflamed tissue. B₁R protein is significantly increased in both active UC and CD intestines compared with controls. In patients with active UC, B₁R mRNA is significantly higher than B₂R mRNA. However, in inactive UC patients, the B₁R and B₂R mRNA did not differ significantly. Thus bradykinin receptors in IBD may reflect intestinal inflammation. Increased B₁R gene and protein expression in active IBD provides a structural basis of the important role of bradykinin in chronic inflammation.

Inflammatory bowel diseases (IBD), Crohn’s disease and ulcerative colitis (UC) are idiopathic, intestinal and systemic inflammatory disorders which are immunologically mediated with the activation of plasma proteolytic cascades. The activation of coagulation in IBD is related to the activity and colonic extension of the disease, but may still be persistent in a quiescent stage. Factor XIII seems to be as much a coagulation factor as a connective tissue factor which may contribute to intestinal healing. Fibrinolytic capacity is reduced in systemic circulation of IBD patients. Platelets activation is a feature of IBD which contributes to a pathogenic inflammatory sequel. There is evidence that coagulation activation may in turn mediate and amplify inflammatory cascades in IBD, especially via activating PARs related pathways. The etiology of thromboembolism in IBD seems to be multifactorial but is largely attributable to the coagulation activation and platelet aggregation during systemic inflammation. Thromboembolic (TE) complications in both Crohn’s disease and UC appear to have at least 3-4 fold increased risk of developing compared to control patients. Currently, no single TE laboratory marker has a predictive value, but a recently developed endogenous thrombin potential test may have a potentially predicative value in IBD. At present, no interaction between IBD and inherited factors of thrombophilia has been found. An efficacy of heparin treatment in UC is still controversial, although heparin is safe in UC flare. Prophylactic anticoagulation against TE is currently not fully defined, however, high - risk patients should be considered for using a moderate dose of heparin.