Use of Immunosuppressive Drugs in
Hypersensitivity and Autoimmune Diseases
1. Glucocorticoids
Glucocorticoid administration can be
life-saving in certain acute disorders, such as bronchial asthma and autoimmune
thrombocytopenic purpura and can induce significant improvement in chronic warm
autoantibody hemolytic anemia, autoimmune chronic active hepatitis, autoimmune
thrombocytopenic purpura, systemic lupus erythematosus, and a va-riety of
chronic hypersensitivity conditions. Steroids are also part of most
immunosup-pressive regimens used for preventing the rejection of transplanted
organs.
2. Cytotoxic
Agents and Cyclosporin A
Many nonneoplastic diseases either proven or
presumed to be immunologically mediated have been treated with cytotoxic drugs.
Results of controlled trials of azathioprine, methotrexate, and
cyclophosphamide suggest that these cytotoxic drugs, when given in suf-ficient
quantity, may be capable of suppressing disease activity and eliminate the need
for long-term therapy with steroids.
Methotrexate is the most effective second-line
drug for rheumatoid arthritis not con-trolled by NSAIDs. Methotrexate not only
alleviates the signs and symptoms of rheuma-toid arthritis, but also may
increase the hemoglobin and decrease the erythrocyte sedimen-tation rate (ESR)
in patients. Methotrexate is usually given in weekly oral doses.
Cyclophosphamide has been demonstrated to be
the only effective means of achiev-ing immunosuppression (and sometimes
clinical cure) in certain steroid-resistant diseases, such as Wegener’s
granulomatosis. Cyclophosphamide is also the drug of choice for the treatment
of lupus glomerulonephritis and other vasculitides. In-terestingly,
cyclophosphamide is better tolerated if given as monthly intravenous pulses
rather than daily by mouth.
Azathioprine has also been used in the
treatment of patients with SLE. Controlled studies demonstrated a number of
beneficial effects, i.e., an increase in creatinine clear-ance, a decrease in
proteinuria, and a decrease in mortality. However, a decrease in glomerular
cell proliferation has been noted in renal biopsies of SLE patients receiving
aza-thioprine and upon discontinuation of treatment severe exacerbations of the
disease have been reported.
Cyclosporin A has not been as widely used in
the treatment of autoimmune disorders as azathioprine, methotrexate, and cyclophosphamide,
with the exception of type I (insulin-dependent) diabetes and myasthenia
gravis. In these conditions, considerable clinical im-provement may be seen
while cyclosporine is being administered, but relapses occur as soon as it is
suspended.
Combinations of glucocorticoids and cytotoxic
agents have been used in most diseases that were classically treated with
glucocorticoids alone, and although controlled trials are still required to
assess overall benefit in many of these diseases, it should be stated that
their major advantage may be the possibility of reducing the dose of steroids
when such drugs are added to corticosteroid therapy—the previously mentioned
“steroid-sparing” effect.
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