**4. TNF-α inhibitors in other forms of systemic vasculitis**

#### **4.1. Behcet's syndrome**

Infliximab at a dose of 5mg/kg, showed efficacy in cases with refractory uveo-retinitis with improvement of visual acuity, healing of oro-genital ulcers, healing of intestinal lesions and remission. It has also been disclosed that infliximab is a rapid and effective therapy for sightthreatening panuveitis in Behçet's disease. Infliximab administration thus leads to a rapid and effective suppression of acute ocular inflammation, and the remission of the uveitis remained for as long as 28 days after infliximab administration in all five patients. Etanercept is also now being used in refractory Behçet's disease. [33, 34, 35, 36, 37] Despite that Tumor necrosis factor therapy is not an approved therapeutic alternative in Behcet's syndrome due to lack of randomized controlled studies, yet TNF inhibition might provide a valuable alternative in Behçet's syndrome patients who were proven refractory to more commonly used treatments.

#### **4.2. Kawasaki disease**

TNF has been suggested as an important cytokine in the active phase of coronary disease in mouse models of Kawasaki disease.However, the current use of anti TNF therapy in Kawasaki remains restricted only to cases with immunoglobulin resistant disease. [38,39]

#### **4.3. Deep idiopathic small vessels cutaneous vasculitis**

Cutaneous vasculitis, is a disease with an annual incidence rate ranging from 39.6 to 59.8 per million, can be classified as primary or idiopathic; or secondary, when it presents as a mani‐ festation of connective tissue diseases, infections, drug reactions or malignancies. [41, 42] Most of the idiopathic cases are self-limited and responsive to supportive measures (limb elevation, warming, avoid standing) and nonsteroidal anti-inflammatory drugs, potent immunesuppressants are sometimes required for the management of the refractory situations. [42]

The high serum levels of the pro-inflammatory cytokines TNF-*α*, IL-1*β* observed in sera of patients with small vessels cutaneous vasculitis supports a potential role of these cytokines in the pathogenesis of such forms of vasculitis. [43] Reports support the benefit of infliximab in the treatment of some cases of deep cutaneous vasculitis as well as in difficult to treat cases who failed to respond to cyclophosphamide pulse therapy with successful tapering of oral corticosteroids [44, 45, 46] Cases of deep cutaneous vasculitis following infliximab therapy have also been reported. [47]
