Medication Summary
The goal of pharmacotherapy is to reduce morbidity and to prevent complications. Combination therapy in a stepladder regimen is needed in many cases to improve disease control.
Antibiotics
Class Summary
Therapy must be comprehensive and cover all likely pathogens in the context of the clinical setting.
Dapsone (Avlosulfon)
Recommended as first-line agent for treatment of ocular cicatricial pemphigoid (OCP) if inflammatory activity is not severe, disease is not rapidly progressive, and patient is not glucose-6-phosphate dehydrogenase deficient. A response usually is observed within 4 weeks of initiation of therapy. Has both antimicrobial and anti-inflammatory activity. Mechanisms by which it influences inflammatory and immune systems are not clear. Able to penetrate bacterial cells and have both bactericidal and bacteriostatic activity against Mycobacterium leprae. Believed to mediate anti-inflammatory effects in cicatricial pemphigoid by a variety of mechanisms. Evidence suggests that dapsone stabilizes lysosomal membranes, decreasing release of contents, and interferes with myeloperoxidase halide-mediated cytotoxic system of neutrophils. May inhibit Arthus reaction and adjuvant-induced arthritis in a manner similar to that of corticosteroids and indomethacin.
Immunosuppressive agents
Class Summary
Inhibit cell growth and proliferation.
Methotrexate (Folex, Rheumatrex)
Chemical structure analogous to that of folic acid. Prevents conversion of dihydrofolate to tetrahydrofolate by competitively and irreversibly binding to enzyme dihydrofolate reductase. Tetrahydrofolate is an essential cofactor in production of 1-carbon units critical to synthesis of purine nucleotides and thymidylate. Less rapid, partially reversible competitive inhibition of thymidylate synthetase occurs within 24 h after methotrexate administration. Net effect is inhibition of DNA synthesis, DNA repair, RNA synthesis, and cell division at specific stages of the cell cycle.
Has little effect on resting cells. Exerts cytotoxic actions in actively proliferating tissues such as malignant cells, fetal cells, cells of GI tract, urinary bladder, buccal mucosa, and bone marrow. By inhibiting DNA synthesis in immunologically competent cells, methotrexate has some activity as immunosuppressive agent. Both B and T cells are affected, and primary and secondary antibody responses can be suppressed when administered during antigen encounter. To date, no controlled data in humans or animals indicate that methotrexate is carcinogenic.
Azathioprine (Imuran)
Prodrug quickly metabolized in liver to active form, 6-MP, which in turn interferes with purine metabolism and ultimately with DNA, RNA, and protein synthesis.
Shown to suppress both B and T lymphocytes. Effective in suppressing mixed lymphocyte reaction in vivo and recirculating T lymphocytes that are in the process of homing. Also can suppress development of monocyte precursors and thus participation of K cells (which themselves are derived from monocyte precursors) in antibody-dependent cytotoxicity reactions.
Reduce dose by 25% if allopurinol is administered concomitantly, since allopurinol interferes with metabolism of 6-MP8.
Cyclophosphamide (Cytoxan, Neosar)
Belongs to nitrogen mustard family of alkylating agents. Prodrug that must be converted in vivo by hepatic microsomal cytochrome P-450 mixed function oxidase system into its active metabolites, phosphoramide mustard and 4-hydroxy-cyclophosphamide. Products act through nucleophilic substitution reactions resulting in formation of covalent cross linkages (alkylation) with DNA, thereby mediating their major immunosuppressive activity.
At clinical doses, has profound effect on lymphoid cells. Both B- and T-cell function are depressed, although with acute administration of high doses of drug, B cells appear to be more affected.
It is preferred that patients take total daily dose in morning and maintain adequate oral fluids throughout rest of day, in an effort to induce frequent voiding. In this way, risk of hemorrhagic cystitis from prolonged contact of bladder mucosa with cyclophosphamide metabolites is minimized.
Intravenous administration of cyclophosphamide offers certain advantages overoral
administration and is useful in the following clinical situations: (1) permits rapid induction in patients with severe ocular inflammatory involvement; (2) avoids prolonged bladder exposure, allowing larger doses, yet less frequent dosing in patients with hemorrhagic cystitis induced from oral intake; and (3) induces only transient neutropenia, making intercurrent infections less likely
Mycophenolate mofetil (CellCept)
Has been shown useful in moderate OCP in several recent studies. Has generally been well tolerated and, in these studies, has been as effective (possibly more effective) as more traditional therapies, including dapsone, sulfasalazine, and azathioprine, with less toxicity.
Systemic steroids
Class Summary
To reduce inflammatory response; however, these are not useful drugs for this disease because of the necessity for long-term usage and the adverse effects. Reserve their use for the severely inflamed eyes that do not readily respond to immunosuppression alone.
Prednisone (Deltasone, Orasone, Meticorten)
Immunosuppressant that may decrease inflammation by reversing increased capillary permeability and suppressing PMN activity.
Aminosalicylic acid derivative
Class Summary
Used to reduce inflammation.
Sulfasalazine (Azulfidine, En-Tabs)
Sulfonamide derivative with anti-inflammatory properties. Decreases inflammatory response and systemically inhibits prostaglandin synthesis.
Immunomodulators
Class Summary
Interfere with cytokine actions responsible for inflammation. Some anecdotal reports and case series of OCP treatment with anti-TNF-alpha have been described with favorable results.
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. Reported in anecdotal case reports
Etanercept (Enbrel)
A recombinant human TNF-alpha receptor protein fused with Fc portion of IgG1 that binds to TNF-alpha, thereby neutralizing the effects of TNF-alpha. Reported in anecdotal reports and case reports.
Monoclonal antibodies
Class Summary
Found to be effective for OCP in uncontrolled small studies.
Rituximab (Rituxan)
Genetically engineered chimeric murine/human monoclonal antibody directed against the CD20 antigen found on the surface of B lymphocytes.
Immunoglobulins
Class Summary
Used in cases resistant to conventional treatment.
Immune globulin intravenous (Gamimune, Gammagard, Sandoglobulin, Gammar-P)
Contains the pooled immunoglobulin G (IgG) immunoglobulins from the plasma of approximately a thousand or more blood donors. Acts by modulation of complement activation; suppression of idiotypic antibodies; saturation of Fc receptors on macrophages; and suppression of various inflammatory mediators, including cytokines, chemokines, and metalloproteinases.
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Ocular cicatricial pemphigoid, stage II. Note the fornix foreshortening.
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Ocular cicatricial pemphigoid, stage III. Note the symblepharon.
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Ocular cicatricial pemphigoid, stage IV. Note the ankyloblepharon and ocular surface keratinization.
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Corneal neovascularization with ulceration and stromal thinning after persistent epithelial defect in a patient with ocular cicatricial pemphigoid.
