CLINICAL AND LABORATORY INVESTIGATIONS BJD British Journal of Dermatology The use of sulfasalazine and pentoxifylline (low-cost antitumour necrosis factor drugs) as adjuvant therapy for the treatment of pemphigus vulgaris: a comparative study M. El-Darouti, S. Marzouk, R. Abdel Hay, A. El Tawdy, M. Fawzy, T. Leheta, H. Gammaz* and N. Al Gendy  Departments of Dermatology and  Clinical Pathology, Faculty of Medicine, Cairo University, Cairo, Egypt *Department of Dermatology, Al Hod Al Marsoud Hospital, Cairo, Egypt Correspondence Rania M. Abdel Hay. E-mail: omleila2@yahoo.com Accepted for publication 23 March 2009 Key words pemphigus, pentoxifylline, sulfasalazine Conflicts of interest None declared. DOI 10.1111/j.1365-2133.2009.09208.x Summary Background Pemphigus vulgaris (PV) represents a potentially life-threatening auto- immune blistering disease in which IgG autoantibodies are directed against cell– cell adhesion molecules. Tumour necrosis factor (TNF)-a has been suggested to have a possible role in the mechanism underlying acantholysis. Objectives This comparative double-blinded study was carried out to estimate the use of both sulfasalazine (SSZ) and pentoxifylline (PTX) (low-cost anti-TNF drugs) as an adjuvant therapy for PV. Methods The study included 64 patients with PV: 42 patients received the full treatment regimen (with SSZ and PTX) and 22 patients followed the same regi- men except they received placebo instead of PTX and SSZ. Five healthy subjects were included as controls. Serum samples were taken to measure TNF-a levels in the control group and before starting treatment in both the patient groups and this was repeated every 2 weeks for 8 weeks; a clinical assessment was made every week for all the patients. Results The serum level of TNF-a was statistically higher in both groups of patients than in the healthy individuals. There was a statistically significant decrease in the serum levels of TNF-a in patients in group 1 compared with those in group 2 at 6 and 8 weeks. There was also a significant clinical improvement in patients in group 1 compared with those in group 2. Conclusion The use of PTX and SSZ as adjuvant therapy in the treatment of PV induced a faster and more significant decrease in the serum level of TNF-a, and this decrease was associated with rapid clinical improvement. Pemphigus vulgaris (PV) is a potentially life-threatening auto- immune blistering disease of the skin and mucous mem- branes 1 in which IgG autoantibodies are directed against cell–cell adhesion molecules. These include desmoglein (Dsg) 3 (primary antigen), Dsg 1, desmocollins, plakoglobin and collagen XVII ⁄ BP18. 2 As a consequence of the antibody bind- ing to the target antigen, keratinocytes lose their adhesion properties resulting in acantholytic blisters. The exact mecha- nism of acantholysis is unknown. Recently, tumour necrosis factor (TNF)-a has been suggested to have a possible role in the mechanism underlying the acantholysis. 3 Anti-TNF agents such as infliximab (a chimeric monoclonal antibody against TNF-a) and etanercept (a fusion protein of the TNF receptor) have been used successfully in the treatment of PV. 4,5 However, their high cost may preclude their use as adjuvant therapy, especially in developing countries. Accord- ingly the use of less-expensive anti-TNF drugs as adjuvant therapy for PV deserves study. Sulfasalazine (SSZ) and pentoxi- fylline (PTX) are known to have potent anti-TNF effects. 5–9 Sulfasalazine and its metabolite 5-aminosalicylic acid are believed to exert their benefit by inducing apoptosis of macro- phages, thereby inhibiting the production of TNF-a [as well as interleukin (IL)-1 and IL-6]. 6 PTX, a phosphodiesterase inhibitor, has a variety of immuno- modulatory properties. It inhibits the release of TNF-a along with other cytokines, 8 suppresses T- and B-cell proliferation 10 and inhibits intercellular adhesion molecule (ICAM)-1 expres- sion. 11 We hypothesized that the concomitant use of SSZ and PTX is better than either drug alone because they have differ- ent modes of actions hence providing a potent effect. We wanted to investigate if the addition of SSZ and PTX to our standard treatment of PV would induce a better response and Ó 2009 The Authors Journal Compilation Ó 2009 British Association of Dermatologists • British Journal of Dermatology 2009 161, pp313–319 313