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Indian Journal of Dermatology, Venereology, Leprology, Vol. 70, No. 1, January-February, 2004, pp. 42-43 Letter To Editor Diabetes mellitus and immunosuppressives Bansal Ramesh Consultant Dermatologist, Rohtak, Haryana Code Number: dv04011 Sir, Immunosuppressive agents like azathioprine, cyclophosphamide, methotrexate (MTX) or cyclosporine A (CYA) are often used as adjuvants with corticosteroid therapy for patients with chronic dermatological disorders like pemphigus. Such patients may also have diabetes mellitus (DM), which is a relative contraindication for corticosteroid therapy, and may need immunosuppressive therapy. Many dermatologists hesitate to use these agents in patients with diabetes mellitus (DM). I would like to discuss this issue. Azathioprine (AZA), a synthetic purine analogue is one of the main immunosuppressive drugs used in dermatology. Its immunosuppressive effects are caused by the substitution of naturally occurring purine bases in DNA by its active intracellular metabolite 6-thioguanine in actively dividing cells.[1] AZA is effective in the treatment of autoimmune diseases at doses which don′t cause lymphopenia, leukopenia or bone marrow depression.[2] Although AZA can inhibit T-cell function,[3] patients treated with the standard immunosuppressive doses of AZA generally fail to exhibit significant suppression of cell mediated immunity despite a clinical response to therapy.[4] There is little evidence for any consistent effect of AZA on the normal humoral immune response and often AZA fails to inhibit it.[5] The fact that treatment with AZA is associated with an increased incidence of viral infections but not with an increase in bacterial infections has been taken as evidence against any major inhibition of humoral immunity.[6] Swanson et al[2] found that patients with immunologic diseases don′t become agammaglobulinemic as a result of antimetabolite therapy and that adequate levels of immunoglobulins having the usual spectrum of antiviral and antibacterial activities are maintained. He concluded that when used cautiously AZA does not result in a harmful degree of immunosuppression in patient with immunologic diseases. Sharma et al used AZA in four patients who had both parthenium dermatitis and DM and observed its corticosteroid sparing effect.[7] Cyclophosphamide (CPA) is the most potent immunosuppressant among the synthetic alkylating agents.[8] Several investigators have reported that there is no change in the relative percentage of circulating B and T cells during CPA induced lymphopenia.[5] Cyclosporine A (CYA) is a fungal metabolite with potent immunosuppressant effect without significant myelotoxicity. In three large controlled studies,[9],[10],[11] use of CYA was found to be successful in blocking or reducing the cytotoxic process in order to favor beta cell regeneration in patients newly diagnosed with insulin dependent diabetes mellitus (IDDM).[12] IDDM results from autoimmune beta cell destruction which is thought to be triggered by an infection or environmental stimulus.[13] Bansal et al suggested that lack of adequate insulin levels in DM impairs T lymphocyte activity and the elevated levels of immunoglobulins in DM could be due to subclinical infection.[14] Infections are thought to be due to incompletely defined abnormalities in phagocyte function associated with hyperglycemia, as well as diminished vascularization secondary to long-standing DM.[15],[16] Hyperglycemia probably aids the colonization and growth of a variety of organisms.[13] In view of the inconsistent effects of immunosuppressive agents on T and B cells, their use in a diabetic patient with optimal glycemic control is justified. The impaired immunity of diabetic patients does not debar them from using these agents. In spite of impaired immunity, diabetic patients have been successfully immunosuppressed by using triple therapy with CYA, AZA and prednisone for renal transplantation for many years.[17] Dermatologists can not afford to ignore these drugs in diabetic patients if they are required, particularly in situations where corticosteroids have to be given for a long duration or are contraindicated. REFERENCES
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