eMedicine Specialties > Dermatology > Bullous Diseases
Pemphigus, Drug-Induced: Treatment & Medication
Updated: Jun 11, 2007
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
Treatment
Medical Care
Withdrawal of the offending agent is the first step in treatment. Most, but not all, patients go into remission once the offending agent is stopped. Some patients may follow a chronic course identical to that of idiopathic pemphigus vulgaris. These patients require systemic corticosteroids and/or immunosuppressive therapy.
Consultations
- Burn unit consultation: For patients who have erosions involving a significant portion of the body surface area, the burn unit is helpful in providing wound care (cleansing, application of topical antibiotics, and bandaging).
Diet
Mucosal lesions may be exacerbated by eating hard or crunchy foods, such as potato chips, crackers, fresh fruits, and uncooked vegetables.
Medication
For patients in whom the disease does not resolve upon withdrawal of the offending agent, medical therapy is necessary. Generally, systemic corticosteroids or other immunosuppressants are required. Anecdotal reports support the use of alternate immunomodulating agents (eg, antimalarial drugs, rituximab, intravenous immunoglobulin, mycophenolate mofetil). Recent reports suggest targeting cholinergic drugs as antiacantholytic therapy for idiopathic pemphigus.
Corticosteroids
Systemic corticosteroids (eg, prednisone) should be initiated in patients with disease that persists after the implicated agent has been discontinued. Since most cases of drug-induced pemphigus involve an immune mechanism, the anti-inflammatory and immune modulating properties of corticosteroids are beneficial. In idiopathic pemphigus vulgaris and pemphigus foliaceus, high doses of systemic corticosteroids may be needed. This also may be necessary for cases of drug-induced pemphigus.
Prednisone (Deltasone, Orasone, Sterapred)
Initial DOC for severe or recalcitrant cases of drug-induced pemphigus. Immunosuppressant for treatment of autoimmune disorders; may decrease inflammation by reversing increased capillary permeability and suppressing PMN activity. Stabilizes lysosomal membranes and suppresses lymphocytes and antibody production. Up-regulates keratinocyte adhesion molecules desmoglein 1 and 3.
Adult
0.5-2 mg/kg/d PO; high doses (eg, 150-200 mg/d PO) may be needed; taper as condition improves; single morning dose is safer for long-term use, but divided doses have more anti-inflammatory effect
Pediatric
4-5 mg/m2/d PO or 0.05-2 mg/kg PO divided bid/qid; taper over 2 wk, as symptoms resolve
Coadministration with estrogens may decrease prednisone clearance; when used with digoxin, digitalis toxicity secondary to hypokalemia may increase; phenobarbital, phenytoin, and rifampin may increase metabolism of glucocorticoids (consider increasing maintenance dose); monitor for hypokalemia with coadministration of diuretics; postmarketing surveillance reports indicate that risk of tendon rupture may be increased in patients receiving concomitant fluoroquinolones and corticosteroids, especially elderly persons; concomitant use with amphotericin B liposome may potentiate hypokalemia; concomitant therapy with montelukast may result in severe peripheral edema; coadministered ritonavir may significantly increase serum concentrations of prednisone
Documented hypersensitivity; viral infection, peptic ulcer disease, hepatic dysfunction, connective tissue infections, and fungal or tubercular skin infections; GI disease
Pregnancy
B - Usually safe but benefits must outweigh the risks.
Precautions
Abrupt discontinuation of glucocorticoids may cause adrenal crisis; adverse effects include weight gain, cushingoid appearance, osteoporosis, avascular necrosis, increase risk of infection, peptic ulcer disease, posterior subcapsular cataract formation, psychosis, agitation, insomnia, depression, hypertension, and skin changes including atrophy, acneiform eruption, striae, poor wound healing, and hirsutism
Immunosuppressants
For patients who do not respond to moderate doses of systemic steroids or for patients in whom steroids are contraindicated. Also used as steroid-sparing agents.
Azathioprine (Imuran)
Antagonizes purine metabolism and inhibits synthesis of DNA, RNA, and proteins. May decrease proliferation of immune cells, which results in lower autoimmune activity. Useful in steroid-resistant patients. Less toxic than some other immunosuppressants. Generally, used in conjunction with low doses of systemic corticosteroids.
Prior measurement of thiopurine methyltransferase (TPMT) levels can be useful in guiding initial dose.
Adult
1-3 mg/kg/d PO/IV; alternatively, 1 mg/kg/d PO for 6-8 wk; increase by 0.5 mg/kg q4wk until response or dose reaches 2.5 mg/kg/d
Pediatric
Initial dose: 2-5 mg/kg/d PO/IV
Maintenance dose: 1-2 mg/kg/d PO/IV
Toxicity increases with allopurinol; concurrent use with ACE inhibitors may induce severe leukopenia; angiotensin-converting enzyme inhibitors, warfarin, may increase levels of methotrexate metabolites and decrease effects of anticoagulants, neuromuscular blockers, and cyclosporine; alfalfa, black cohosh, and echinacea may reduce immunosuppressive drug effectiveness
Documented hypersensitivity; history of treatment with alkylating agents; low levels of serum TPMT; pregnancy, breastfeeding
Pregnancy
D - Unsafe in pregnancy
Precautions
May cause leukopenia, thrombocytopenia, hemorrhagic cystitis, liver toxicity, nausea and vomiting, and increased risk of infection; increases risk of neoplasia; check TPMT level prior to therapy and follow liver, renal, and hematologic function; pancreatitis rarely associated; hepatotoxicity and pancreatitis may occur
Cyclophosphamide (Cytoxan, Neosar)
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 growth of normal and neoplastic cells. Effective in treating pemphigus; however, this drug also is very toxic.
Adult
1-2 mg/kg/d PO; alternatively, 2.5-3 mg/kg/d PO qid; intermittent IV pulse also has been used
Pediatric
Administer as in adults
Allopurinol may increase risk of bleeding or infection and enhance myelosuppressive effects of cyclophosphamide; may potentiate doxorubicin-induced cardiotoxicity; may reduce digoxin serum levels and antimicrobial effects of quinolones; chloramphenicol may increase half-life of cyclophosphamide, while decreasing metabolite concentrations; may increase effect of anticoagulants; coadministration with high doses of phenobarbital may increase rate of metabolism and leukopenic activity of cyclophosphamide; thiazide diuretics may prolong cyclophosphamide-induced leukopenia and neuromuscular blockade by inhibiting cholinesterase activity; may increase risk of infection by live vaccines; may increase risk of developing noncutaneous solid malignancies when coadministered with etanercept; coadministration with indomethacin may cause fluid retention; nevirapine and St. John's wort may decrease plasma concentrations of cyclophosphamide
Documented hypersensitivity; severely depressed bone marrow function; pregnancy; breastfeeding
Pregnancy
D - Unsafe in pregnancy
Precautions
Hematologic myelosuppression, primarily leukopenia, thrombocytopenia, anemia, gastrointestinal adverse effects, urologic adverse effects, and hemorrhagic cystitis may occur; encourage fluid intake; 45-fold increase in bladder cancer exists; interferes with oogenesis and spermatogenesis; may cause sterility in both sexes but may be irreversible in some patients; may increase risk of malignancy and increased risk of infections; may cause oligospermia or azoospermia, cardiomyopathy, infectious disease, or interstitial pneumonia; increased risk of malignancy; possibility of increased toxicity in adrenalectomized patients; tamoxifen may increase risk of thromboembolism
More on Pemphigus, Drug-Induced |
| Overview: Pemphigus, Drug-Induced |
| Differential Diagnoses & Workup: Pemphigus, Drug-Induced |
 Treatment & Medication: Pemphigus, Drug-Induced |
| Follow-up: Pemphigus, Drug-Induced |
| References |
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References
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Further Reading
Keywords
drug-induced pemphigus, antibiotic-induced pemphigus, medication-induced pemphigus, thiol-induced pemphigus, pyrazolone-induced pemphigus
