Medication Summary
Hematopoietic stem cell transplantation (HSCT) is the only curative therapy for immunodysregulation polyendocrinopathy enteropathy X-linked (IPEX) syndrome. [29, 30] However, numerous medications are used to treat the various disease associations.
Medications should be used on an individual basis with consideration of the particular disease targeted and individual response to therapy. Diabetes is treated with replacement insulin. Thyroid disease may be treated with either replacement thyroid hormone or antithyroid medications, depending on the underlying thyroid condition. Topical steroids and anti-inflammatory medications are used to treat the dermatitis associated with IPEX syndrome. Cytopenias can be treated with granulocyte-colony stimulating factor (G-CSF), corticosteroids, or replacement blood products in more severe cases. Infections associated with IPEX syndrome usually respond to antibiotics, antiviral, or antifungal therapy. These medications can be targeted against the specific pathogen, if known.
Immunosuppressive medications are the mainstay of treatment for the enteropathy associated with IPEX syndrome. Medications that have been reported to reduce GI symptoms include high-dose corticosteroids, cyclosporin A, tacrolimus, sirolimus, infliximab, and rituximab. None of these medications have demonstrated remission, although sirolimus has demonstrated sustained symptom reduction for as long as 5 years. [6] The side effects of these medications include infectious complications, risk of malignancy, and end-organ toxicity. Because IPEX syndrome is rare, no large-scale comparative studies of these medications have been performed, and optimal dosing has not been established.
Immunomodulators
Class Summary
These agents modify immune processes that promote inflammation, without causing generalized immunosuppression.
Rituximab (Rituxan)
Antibody genetically engineered. Chimeric murine/human monoclonal antibody directed against the CD20 antigen found on surface of B-lymphocytes. It eliminates circulating CD20+ B cells with resultant reduction of autoantibody production and B cell (as an antibody presenting cells) mediated immune activation.
Infliximab (Remicade)
Chimeric IgG1k monoclonal antibody that neutralizes cytokine TNF-α and inhibits its binding to TNF-α receptor. Reduces infiltration of inflammatory cells and TNF-α production in inflamed areas. Used with methotrexate in patients that have had inadequate response to methotrexate monotherapy.
Immunosuppressant Agents
Class Summary
Selective inhibitors of T-cell lymphocytes (eg, cyclosporine) suppress early cellular response to antigenic and regulatory stimuli.
Traditionally, high-dose steroids were thought to be lympholytic, but recent studies have suggested that steroids may inhibit T-cell proliferation and T-cell–dependent gene expression of cytokines. They produce nonspecific anti-inflammatory effects and antiadhesion effects that contribute to immune suppression.
Cyclosporine (Gengraf, Neoral, Sandimmune)
An 11-amino acid cyclic peptide and natural product of fungi. Acts on T-cell replication and activity. Specific modulator of T-cell function and an agent that depresses cell-mediated immune responses by inhibiting T-cell function by blocking a Ca/calmodulin-NFAT mediated signaling pathway. Preferential and reversible inhibition of T lymphocytes in G0 or G1 phase of cell cycle suggested.
Binds to cyclophilin, an intracellular protein, which, in turn, prevents T-cell activation, transcription of T-cell cytokines, and the subsequent recruitment of activated T cells. Has about 30% bioavailability, but marked interindividual variability is noted. Specifically inhibits T-lymphocyte function with minimal activity against B cells. Maximum suppression of T-lymphocyte proliferation requires that drug be present during first 24 h of antigenic exposure.
Suppresses some humoral immunity and, to a greater extent, cell-mediated immune reactions (eg, delayed hypersensitivity, allograft rejection, experimental allergic encephalomyelitis, and graft versus host disease) for various organs.
Tacrolimus (Prograf)
Immunomodulator produced by the bacteria Streptomyces tsukubaensis. Mechanisms of action similar to cyclosporine. Primarily used in transplants but used in Behçet disease to treat uveitis.
Sirolimus (Rapamune)
Inhibits lymphocyte proliferation by interfering with signal transduction pathways. Binds to immunophilin FKBP12 to block action of mTOR. FDA approved for prophylaxis of organ rejection in patients receiving allogeneic renal allografts.
Prednisone
Prednisone or other systemic corticosteroids elicit immunosuppression for treatment of autoimmune disorders; may decrease inflammation by reversing increased capillary permeability and suppressing PMN activity. Stabilizes lysosomal membranes and also suppresses lymphocyte and antibody production.
