Corticosteroids
Class Summary
These agents have potent immunosuppressive activity with rapid onset of action.
Prednisone (Deltasone, Sterapred)
Used to control acute symptoms and laboratory evidence of inflammation. May decrease inflammation by reversing increased capillary permeability and suppressing PMN activity. Stabilizes lysosomal membranes and also suppresses lymphocytes and antibody production.
Immunomodulators
Class Summary
IVIG is used as first-line therapy for Kawasaki disease; it decreases risk of coronary artery aneurysms.
Immune globulin, intravenous (Sandoglobulin, Gamimune, Gamunex, Gammar-P)
Multiple mechanisms. May absorb superantigens or toxins in Kawasaki disease. May saturate available Fc receptors. May block cytokines, cytokine receptors, or both. May absorb complement activation products. May down-regulate immunoglobulin synthesis. Blocks Fc receptors on macrophages. Suppresses inducer T and B cells and augments suppressor T cells. Blocks complement cascade. May increase CSF IgG (10%).
Immunosuppressant Agents
Class Summary
These agents help control inflammatory signs and symptoms.
Azathioprine (Imuran)
Imidazolyl derivative of 6-mercaptopurine. Many of biological effects are similar to those of parent compound. Both compounds are rapidly eliminated from blood and are oxidized or methylated in erythrocytes and liver. No azathioprine or mercaptopurine is detectable in urine 8 h after taken. Antagonizes purine metabolism and inhibits synthesis of DNA, RNA, and proteins. Mechanism whereby azathioprine affects autoimmune diseases is unknown. Works primarily on T cells. Suppresses hypersensitivities of cell-mediated type and causes variable alterations in antibody production. Immunosuppressive, delayed hypersensitivity, and cellular cytotoxicity tests are suppressed to a greater degree than antibody responses. Works very slowly; may require 6-12 mo of trial prior to effect. As many as 10% of patients may have idiosyncratic reaction disallowing use. Do not allow WBC count to drop below 3000/mL or lymphocyte count to drop below 1000/mL. Available in tablet form for PO administration or in 100-mg vials for IV injection
Cyclophosphamide (Cytoxan)
Cyclic polypeptide that suppresses some humoral activity. Chemically related to nitrogen mustards. Activated in the liver to its active metabolite, 4-hydroxycyclophosphamide, which alkylates the target sites in susceptible cells in an all-or-none type reaction. As an alkylating agent, the mechanism of action of the active metabolites may involve cross-linking of DNA, which may interfere with growth of normal and neoplastic cells. Biotransformed by cytochrome P-450 system to hydroxylated intermediates that break down to active phosphoramide mustard and acrolein. Interaction of phosphoramide mustard with DNA considered cytotoxic. When used in autoimmune diseases, mechanism of action is thought to involve immunosuppression due to destruction of immune cells via DNA cross-linking. In high doses, affects B cells by inhibiting clonal expansion and suppression of production of immunoglobulins. With long-term low-dose therapy, affects T-cell functions.
Methotrexate (Rheumatrex, Folex)
Antimetabolite that inhibits dihydrofolate reductase, thereby hindering DNA synthesis and cell reproduction. Effects may also be mediated by adenosine via the inhibition of aminoimidazole carboxamide ribonucleotide (AICAR) transformylase, leading to increased release of adenosine. Adjust dose gradually to attain satisfactory response.
Mycophenolate mofetil (CellCept); Mycophenolic acid (MyFortic)
Inhibits inosine monophosphate dehydrogenase and suppresses de novo purine synthesis by lymphocytes, thereby inhibiting their proliferation. Inhibits antibody production.
Two formulations are available and are not interchangeable. The original formulation, mycophenolate mofetil (MMF, Cellcept) is a prodrug that once hydrolyzed in vivo, releases the active moiety mycophenolic acid. A newer formulation, mycophenolic acid (MPA, Myfortic) is an enteric-coated product that delivers the active moiety.
Tumor Necrosis Factor Inhibitor
Class Summary
Blocks the process by which activated neutrophils adhere to endothelium and stimulate lysis of endothelial cells in the presence of TNF-alpha.
Infliximab (Remicade)
Chimeric IgG1k monoclonal antibody that neutralizes cytokine TNF-alpha and inhibits its binding to TNF-alpha receptor. Reduces infiltration of inflammatory cells and TNF-alpha production in inflamed areas.
Anti-B lymphocyte agent
Class Summary
May consider these agents for conditions refractory to other treatments.
Rituximab (Rituxan)
Chimeric IgG1-kappa monoclonal antibody directed against the CD20 antigen found on the surface of normal and malignant B lymphocytes. The Fab domain binds to CD20 antigen on B lymphocytes, and the Fc domain recruits immune effector functions to mediate B-cell lysis in vitro. Possible mechanisms of cell lysis include complement-dependent cytotoxicity (CDC) and antibody-dependent cell-mediated cytotoxicity (ADCC).
Anticoagulant
Class Summary
These agents provide immediate and long-term treatment of vascular thrombosis.
Heparin
Augments activity of antithrombin III and prevents conversion of fibrinogen to fibrin. Does not actively lyse but is able to inhibit further thrombogenesis. Prevents reaccumulation of clot after spontaneous fibrinolysis.
Provide as continuous heparin infusion to maintain aPTT at 1.5 times the control.
Enoxaparin (Lovenox)
Low molecular weight heparin. Augments activity of antithrombin III and prevents conversion of fibrinogen to fibrin. Does not actively lyse but is able to inhibit further thrombogenesis. Prevents reaccumulation of clot after spontaneous fibrinolysis.
Advantages include intermittent dosing and decreased requirement for monitoring. Heparin anti–factor Xa levels may be obtained if needed to establish adequate dosing.
Warfarin (Coumadin)
Interferes with hepatic synthesis of vitamin K–dependent coagulation factors.
Antibiotics
Class Summary
Prophylaxis for P jiroveci with cyclophosphamide therapy.
Trimethoprim-sulfamethoxazole (Bactrim, Septra)
As P jiroveci prophylaxis for patients taking cyclophosphamide. Dihydrofolate reductase inhibitor in combination with sulfonamide.
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Preferred sites of vascular involvement by selected vasculitides.
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Patient with Wegener granulomatosis and saddle-nose deformity.
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Tender erythematous nodules in cutaneous polyarteritis nodosa (PAN).
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Nodules on sole of foot in cutaneous polyarteritis nodosa (PAN).
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Necrotic lesions of polyarteritis nodosa (PAN).
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Chest radiography in Churg-Strauss syndrome (CSS) with pulmonary infiltrates.
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CT of sinuses in a patient with Wegener granulomatosis (WG) showing erosion and loss of sinus walls.
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CT chest in a patient with Churg-Strauss syndrome (CSS) showing multiple nodules.
Tables
Category |
Definition |
Localized |
Upper and/or lower respiratory tract disease without any other systemic involvement or constitutional symptoms |
Early systemic |
Any, without organ-threatening or life-threatening disease |
Generalized |
Renal or other organ-threatening disease, serum creatinine >500 μmol/L (5.6 mg/dL) |
Severe |
Renal or other vital organ failure, serum creatinine >500 μmol/L (5.6 mg/dL) |
Refractory |
Progressive disease unresponsive to glucocorticoids and cyclophosphamide |
