Medication Summary
Therapy with corticosteroids—such as the glucocorticoid prednisone—is often initially prescribed. An immunosuppressive agent is also sometimes initiated, either later or simultaneously; this is particularly the case in patients for whom high-dose, long-term therapy is anticipated. Some physicians select cyclosporine as the initial therapy. Other immunosuppressives used in treatment include azathioprine, mycophenolate, cyclophosphamide, chlorambucil, and tacrolimus.
The TNF-alpha inhibitors—which include thalidomide, etanercept, infliximab, adalimumab, certolizumab, [47] golimumab, and clofazimine—are close to first-line agents in the treatment of pyoderma gangrenosum.
Corticosteroids
Class Summary
These agents have anti-inflammatory properties and cause profound and varied metabolic effects. In addition, these agents modify the body's immune response to diverse stimuli.
Prednisone
Prednisone is considered the drug of choice. It may decrease inflammation by reversing increased capillary permeability and suppressing polymorphonuclear leukocyte activity. Methylprednisolone IV may be used in some patients.
Immunosuppressants
Class Summary
These agents have immunomodulatory effects.
Cyclosporine (Sandimmune, Neoral, Gengraf)
Cyclosporine has been demonstrated to be helpful in a variety of skin disorders. An effective steroid-sparing agent, it has also been used as primary therapy in some patients.
Azathioprine (Imuran, Azasan)
Azathioprine is another drug that may be effective as a steroid-sparing agent. It antagonizes purine metabolism and inhibits the synthesis of deoxyribonucleic acid (DNA), ribonucleic acid (RNA), and proteins. Azathioprine may decrease the proliferation of immune cells, which results in lower autoimmune activity.
Mycophenolate (CellCept, Myfortic)
Mycophenolate inhibits purine synthesis and the proliferation of human lymphocytes. It may be used as a steroid-sparing agent or as a primary agent in patients who do not respond to first-line agents.
Cyclophosphamide
Cyclophosphamide is an alkylating agent that depresses B-cell and T-cell function. It is chemically related to nitrogen mustards. As an alkylating agent, the mechanism of action of the active metabolites may involve cross-linking of DNA, which may interfere with the growth of normal and neoplastic cells.
Chlorambucil (Leukeran)
Chlorambucil alkylates and cross-links strands of DNA, inhibiting DNA replication and RNA transcription. It is used as a primary or steroid-sparing agent.
Tacrolimus (Prograf, Hecoria)
Tacrolimus suppresses humoral immunity (T-lymphocyte) activity.
Blood Components
Class Summary
These agents are used to improve the clinical and immunologic aspects of the disease. They may decrease autoantibody production and increase solubilization and removal of immune complexes.
IV immunoglobulins (Octagam, Hizentra, Gammagard, Gamunex)
IV immunoglobulin neutralizes circulating myelin antibodies through anti-idiotypic antibodies; down-regulates proinflammatory cytokines, including interferon (INF)-gamma; blocks Fc receptors on macrophages; suppresses inducer T and B cells and augments suppressor T cells; blocks complement cascade; and promotes remyelination. It may increase cerebrospinal fluid (CSF) IgG (10%).
Immunomodulators
Class Summary
These agents have effects on the activity of the immune system. In current practice, TNF inhibitors are close to first-line treatment.
Infliximab (Remicade)
Infliximab is a chimeric IgG1k monoclonal antibody that neutralizes the cytokine TNF-alpha and inhibits its binding to the TNF-alpha receptor. The drug reduces infiltration of inflammatory cells and TNF-alpha production in inflamed areas.
Adalimumab (Humira)
Adalimumab is a TNF-alpha inhibitor. It is a fully human inhibitor of TNF-alpha that is administered by subcutaneous (SC) injection.
Etanercept (Enbrel)
Etanercept is a soluble p75 TNF-receptor fusion protein (sTNFR-Ig). It inhibits TNF binding to cell surface receptors, thereby decreasing inflammatory and immune responses.
Golimumab (Simponi)
Golimumab is a tumor necrosis factor (TNF)–alpha inhibitor. It decreases inflammation caused by overproduction of TNF associated with chronic inflammatory diseases. It is a fully human inhibitor of TNF-alpha that is administered by subcutaneous (SC) injection.
Certolizumab pegol (Cimzia)
Certolizumab pegol is a pegylated antitumor necrosis factor (TNF)–alpha blocker, which results in disruption of the inflammatory process. It is a fully human inhibitor of TNF-alpha that is administered by subcutaneous (SC) injection.
Ustekinumab (Stelara)
Ustekinumab is a human monoclonal antibody directed against IL-12 and IL-23, thereby interfering with T-cell differentiation and activation and subsequent cytokine cascades. It is indicated for moderate-to-severe plaque psoriasis and has been used successfully in pyoderma gangrenosum.
Thalidomide (Thalomid)
Thalidomide is an immunomodulatory agent that may suppress excessive production of TNF-alpha and may down-regulate selected cell-surface adhesion molecules involved in leukocyte migration. In patients less than 50 kg (110 lb), start at the low end of the dose regimen.
Clofazimine (Lamprene)
Clofazimine inhibits mycobacterial growth, binding preferentially to mycobacterial DNA. It has antimicrobial properties, but its mechanism of action is unknown.
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Classic, or typical, pyoderma gangrenosum. This patient did not have an associated disease, and the condition responded well to cyclosporine.
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Peristomal pyoderma gangrenosum.
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Factitial ulceration on the scalp from chronic manipulation mimicking an ulceration of pyoderma gangrenosum.
