eMedicine Specialties > Dermatology > Bullous Diseases
Pemphigus, Drug-Induced: Treatment & Medication
Updated: Nov 13, 2009
- 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 clearance; when used with digoxin, digitalis toxicity secondary to hypokalemia may increase; phenobarbital, phenytoin, and rifampin may increase the metabolism of glucocorticoids (consider increasing maintenance dose); monitor for hypokalemia with coadministration of diuretics; coadministration with ritonavir may significantly increase serum concentrations of prednisone; concomitant therapy with montelukast may result in severe peripheral edema; clarithromycin may increase risk of psychotic symptoms
Postmarketing surveillance reports indicate that risk of tendon rupture may be increased in patients receiving concomitant fluoroquinolones and corticosteroids, especially elderly patients; administration of asparaginase concurrently with or before prednisone therapy may result in increased toxicity
Documented hypersensitivity; viral infection, peptic ulcer disease, hepatic dysfunction, connective tissue infections, and fungal or tubercular skin infections; GI disease
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
May unmask hypertension or diabetes or exacerbate peptic ulcer disease and tuberculosis; long-term sequelae associated with long-term steroid use include osteoporosis, cataracts, and pituitary-hypothalamic axis suppression; with high doses, patients may develop a steroid psychosis and are at increased risk of infections, particularly when oral steroids are used in conjunction with other immunosuppressants; frequently monitor patient's blood sugar level, blood pressure, and weight; monitor for Cushing syndrome
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; may increase levels of methotrexate metabolites and decrease effects of anticoagulants, neuromuscular blockers, and cyclosporine; coadministration with mycophenolate may increase toxicity; alfalfa, black Cohosh, and echinacea may reduce immunosuppressive drug effectiveness
Documented hypersensitivity; deficiency of thiopurine methyltransferase (can result in severe myelosuppression and leukopenia); history of treatment with alkylating agents
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
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; hepatotoxicity and pancreatitis reported
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; may potentiate doxorubicin-induced cardiotoxicity; may reduce digoxin serum levels and antimicrobial effects of quinolones; chloramphenicol may increase half-life while decreasing metabolite concentrations; may increase effect of anticoagulants; coadministration with high doses of phenobarbital may increase rate of metabolism and leukopenic activity; thiazide diuretics may prolong cyclophosphamide-induced leukopenia and neuromuscular blockade by inhibiting cholinesterase activity; concurrent use of NSAIDs has resulted in increases in cyclosporine levels, nephrotoxicity, and increased plasma creatinine concentrations
Concomitant use of ACE inhibitors may decrease renal function; coadministration with nevirapine and St. John's wort may reduce immunosuppressive drug effectiveness
Increased risk of infection by live vaccine; coadministration with trastuzumab may increase cardiac toxicity; coadministration with tamoxifen may increase risk of thromboembolism
Documented hypersensitivity; severely depressed bone marrow function; pregnancy; breastfeeding
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Regularly examine hematologic profile (particularly neutrophils and platelets) to monitor for hematopoietic suppression; regularly examine urine for RBCs, which may precede hemorrhagic cystitis; adverse effects include oligospermia or azoospermia, cardiomyopathy, infectious disease, interstitial pneumonia, increase risk of malignancy, possibility of increased toxicity in adrenalectomized patients
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 |
| « Previous Page | Next Page » |
References
Wolf R, Brenner S. An active amide group in the molecule of drugs that induce pemphigus: a casual or causal relationship?. Dermatology. 1994;189(1):1-4. [Medline].
Brenner S, Bialy-Golan A, Anhalt GJ. Recognition of pemphigus antigens in drug-induced pemphigus vulgaris and pemphigus foliaceus. J Am Acad Dermatol. Jun 1997;36(6 Pt 1):919-23. [Medline].
Ramseur WL, Richards F 2nd, Duggan DB. A case of fatal pemphigus vulgaris in association with beta interferon and interleukin-2 therapy. Cancer. May 15 1989;63(10):2005-7. [Medline].
Nagao K, Tanikawa A, Yamamoto N, Amagai M. Decline of anti-desmoglein 1 IgG ELISA scores by withdrawal of D-penicillamine in drug-induced pemphigus foliaceus. Clin Exp Dermatol. Jan 2005;30(1):43-5. [Medline].
Hur JW, Lee CW, Yoo DH. Bucillamine-induced pemphigus vulgaris in a patient with rheumatoid arthritis and polymyositis overlap syndrome. J Korean Med Sci. Jun 2006;21(3):585-7. [Medline].
Patterson CR, Davies MG. Pemphigus foliaceus: an adverse reaction to lisinopril. J Dermatolog Treat. Jan 2004;15(1):60-2. [Medline].
Anadolu RY, Birol A, Bostanci S, Boyvatt A. A case of pemphigus vulgaris possibly triggered by quinolones. J Eur Acad Dermatol Venereol. Mar 2002;16(2):152-3. [Medline].
Patterson CR, Davies MG. Carbamazepine-induced pemphigus. Clin Exp Dermatol. Jan 2003;28(1):98-9. [Medline].
Lin R, Ladd DJ Jr, Powell DJ, Way BV. Localized pemphigus foliaceus induced by topical imiquimod treatment. Arch Dermatol. Jul 2004;140(7):889-90. [Medline].
Azad Khan AK, Johnston HH, Truelove SC. Proceedings: Bacterial breakdown of sulphasalazine (salazopyrin). Gut. Oct 1975;16(10):832. [Medline].
Maruani A, Machet MC, Carlotti A, Giraudeau B, Vaillant L, Machet L. Immunostaining with antibodies to desmoglein provides the diagnosis of drug-induced pemphigus and allows prediction of outcome. Am J Clin Pathol. Sep 2008;130(3):369-74. [Medline].
Landau M, Brenner S. Histopathologic findings in drug-induced pemphigus. Am J Dermatopathol. Aug 1997;19(4):411-4. [Medline].
Anhalt GJ. Drug-induced pemphigus. Semin Dermatol. Sep 1989;8(3):166-72. [Medline].
Brenner S, Bialy-Golan A, Ruocco V. Drug-induced pemphigus. Clin Dermatol. May-Jun 1998;16(3):393-7. [Medline].
Brenner S, Wolf R, Ruocco V. Drug-induced pemphigus. I. A survey. Clin Dermatol. Oct-Dec 1993;11(4):501-5. [Medline].
Grando SA. Cholinergic control of epidermal cohesion. Exp Dermatol. Apr 2006;15(4):265-82. [Medline].
Mutasim DF, Pelc NJ, Anhalt GJ. Drug-induced pemphigus. Dermatol Clin. Jul 1993;11(3):463-71. [Medline].
Nguyen VT, Arredondo J, Chernyavsky AI, Kitajima Y, Pittelkow M, Grando SA. Pemphigus vulgaris IgG and methylprednisolone exhibit reciprocal effects on keratinocytes. J Biol Chem. Jan 16 2004;279(3):2135-46. [Medline].
Ruocco V, De Angelis E, Lombardi ML. Drug-induced pemphigus. II. Pathomechanisms and experimental investigations. Clin Dermatol. Oct-Dec 1993;11(4):507-13. [Medline].
Uzun S, Durdu M, Akman A, et al. Pemphigus in the Mediterranean region of Turkey: a study of 148 cases. Int J Dermatol. May 2006;45(5):523-8. [Medline].
Further Reading
Keywords
pemphigus, drug-induced pemphigus, antibiotic-induced pemphigus, medication-induced pemphigus, thiol-induced pemphigus, pyrazolone-induced pemphigus
