eMedicine Specialties > Dermatology > Bullous Diseases
Pemphigus Herpetiformis: Treatment & Medication
Updated: Oct 15, 2008
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
- Multimedia
Treatment
Medical Care
Pemphigus herpetiformis is responsive to anti-inflammatory and immunosuppressive medications. Dapsone is the drug of choice if the patient tolerates the treatment. In severe cases that do not respond to conventional treatments (systemic corticosteroid and immunosuppressives), the physicians could also consider using a monoclonal antibody anti-CD20 (rituximab), which has specific actions against B lymphocytes. Rituximab has shown very good clinical efficacy for patients with pemphigus vulgaris, a form of pemphigus that is usually more severe than pemphigus herpetiformis.
A related article posted on Medscape is " Advances in Pemphigus Therapy."
Activity
No specific activity restrictions are indicated; however, advise patients to avoid injury during the active disease period.
Medication
Because pemphigus herpetiformis is a rare variant of pemphigus, comprehensive therapeutic studies of large numbers of patients have not taken place. The following treatment options are taken from the personal experiences of physician-investigators with a small number of patients.
In general, dapsone is the drug of choice. Other anti-inflammatory and immunosuppressive medications are also effective.
Anti-inflammatories
Since pemphigus herpetiformis lesions are characterized by prominent infiltration of inflammatory cells, anti-inflammatory medication may inhibit the functions of these cells, therefore improving disease conditions.
Dapsone (Avlosulfon)
Mechanism of action is similar to that of sulfonamides, in which competitive antagonists of PABA prevent formation of folic acid, inhibiting bacterial growth. Used alone or in conjunction with other anti-inflammatory medication or immunosuppressives for pemphigus herpetiformis.
Adult
100 mg PO qd or 50 mg PO bid
Pediatric
>10 years: 25-50 mg/d PO single dose or 25-50 mg/d PO bid; consult pediatrician before prescribing
Trimethoprim, probenecid, and folic acid antagonists (eg, pyrimethamine, methotrexate) increase levels; activated charcoal, PABA, and rifampin decrease levels; may increase hemolysis with sulfonamides and hydroxychloroquine
Absolute: Documented hypersensitivity
Relative: G-6-PD deficiency (especially in African Americans, persons of Middle Eastern heritage, Asians), significant cardiopulmonary disease, significant hematologic disease, sulfa allergy (cautious use may be attempted; cross-reactivity is relatively rare and mild)
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Perform weekly CBC counts (first mo), then perform CBC counts monthly (6 mo), then semiannually; discontinue if significant reduction in platelets, leukocytes, or hematopoiesis is seen; methemoglobin reductase deficiency, G-6-PD deficiency, or hemoglobin M because of high risk for hemolysis and Heinz body formation; patients exposed to other agents or conditions (eg, infection, diabetic ketosis) capable of producing hemolysis; peripheral neuropathy can occur (rare); phototoxicity may occur when exposed to UV light
Prednisone (Deltasone)
Immunosuppressant for treatment of autoimmune disorders; may decrease inflammation by reversing increased capillary permeability and suppressing PMN activity. Stabilizes lysosomal membranes and also suppresses lymphocytes and antibody production. Taken alone, or in conjunction with other anti-inflammatory or immunosuppressive medications, is useful for controlling pemphigus herpetiformis.
Adult
20-60 mg PO qam; taper over 2-4 wk as symptoms resolve; alternatively, 0.5-2 mg/kg/d; 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; taper over 2 wk as symptoms resolve; consult pediatrician before prescribing
Increased levels occur with ketoconazole, erythromycin, clarithromycin, estrogens, and birth control pills; decreased levels occur with aminoglutethimide, phenytoin, phenobarbital, rifampin, cholestyramine, and ephedrine; levels of potassium-depleting diuretics (potentiates potassium loss and digitalis toxicity) and cyclosporine increase; levels of isoniazid, insulin (resistance is induced), and salicylates decrease; monitor anticoagulant therapy and theophylline levels
Absolute: Systemic fungal infection, herpes simplex keratitis, hypersensitivity (usually with corticotropin, occasionally with IV forms)
Relative: Hypertension, active TB, CHF, prior psychosis, positive purified protein derivative test result, glaucoma, severe depression, diabetes mellitus, active peptic ulcer disease, cataracts, osteoporosis, recent bowel anastomosis, pregnancy
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Use lower dose in hypothyroidism, liver disease, and obesity (decreased cortisol-binding globulin [CBG] and increased free fraction of steroid); pregnancy, hyperthyroidism, and concurrent estrogen therapy may increase CBG levels; abrupt discontinuation of glucocorticoids may cause adrenal crisis; hyperglycemia, edema, osteonecrosis, myopathy, peptic ulcer disease, hypokalemia, osteoporosis, euphoria, psychosis, myasthenia gravis, growth suppression, and infections may occur with glucocorticoid use; alternate-day therapy does not prevent bone loss (appropriate monitoring and prophylaxis for osteoporosis continues to evolve)
Immunosuppressives
Pemphigus herpetiformis is an autoimmune disease; immunosuppressives are useful in suppressing autoimmune response.
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. Usually used as supplement to anti-inflammatory medication; is useful in controlling pemphigus herpetiformis.
Adult
1 mg/kg qd/bid (empiric) or by TPMT level; increase by 0.5 mg/kg q4wk until response, not to exceed 2.5 mg/kg/d
TPMT testing not entirely reliable; involves testing activity of TPMT activity in RBCs, which correlates with systemic TPMT activity; functional enzyme test has been shown to have variability between test sites, and kits may contain varying amounts of enzyme inhibitor; starting at low doses, monitoring for pancytopenia, then increasing the dose is an alternative; if clinical response is not good, patient may be a homozygote for high activity and may need increased dose; some references recommend checking before treatment in all patients
TPMT <5 U: No treatment with azathioprine
TPMT 5-13.7 U: Not to exceed 0.5 mg/kg
TPMT 13.7-19 U: Not to exceed 1.5 mg/kg
TPMT >19 U: Not to exceed 2.5 mg/kg
Pediatric
Safety and efficacy not established
Allopurinol increases risk of pancytopenia; captopril/ACE inhibitors may increase risk of anemia and leukopenia; warfarin dose may need to be increased; pancuronium dose may need to be increased for adequate paralysis; live virus vaccines and cotrimoxazole increase risk of hematologic toxicity; rifampicin may cause transplants to possibly be rejected; clozapine may increase risk of agranulocytosis
Absolute: Documented hypersensitivity, pregnancy or attempting pregnancy, clinically significant active infection
Relative: Concurrent use of allopurinol; prior treatment with alkylating agents (eg, cyclophosphamide, chlorambucil, melphalan, others [high risk of neoplasia])
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Increased risk of neoplasia; caution in liver disease and renal impairment; hematologic toxicities may occur; rarely, patients may develop fever without associated infections; measure thiopurine methyltransferase level prior to treatment; periodically monitor CBC count and liver function
Biological Response Modulator
Rituximab (Rituxan)
Genetically engineered chimeric murine/human monoclonal antibody against human CD20, a molecule present in normal and malignant B lymphocytes. Described in case reports as a promising biological treatment for B-lymphocyte–mediated diseases (eg, pemphigus vulgaris).
Adult
375 mg/m2 skin surface area IV weekly for 4 consecutive weeks, followed by monthly infusion of same dose for 4 consecutive months
Pediatric
Not established
Renal toxicity observed in combination with cisplatin
Documented hypersensitivity; documented anaphylaxis or IgE-mediated hypersensitivity reaction to murine proteins or their components
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Monitor CBC and platelet counts regularly during and few months posttreatment for occurrence of cytopenia; monitor human antichimeric antibody development (approximately 1% patients); monitor and treat associated infections (30% probability)
Severe infusion reactions have occurred, typically during the first infusion, with time to onset of 30-120 minutes; signs and symptoms may include urticaria, hypotension, angioedema, hypoxia, or bronchospasm and may require interruption of infusion; the most severe manifestations and sequelae include pulmonary infiltrates, acute respiratory distress syndrome, myocardial infarction, ventricular fibrillation, cardiogenic shock, and anaphylactic and anaphylactoid events
Factors most commonly associated with fatal outcomes are female sex, pulmonary infiltrates, and chronic lymphocytic leukemia or mantle cell lymphoma; infusions should be interrupted for severe reactions and medication and supportive care measures provided; in most cases, the infusion can be resumed at a 50% reduction in rate when symptoms have completely resolved
Tumor lysis syndrome (TLS): Rapid reduction in tumor volume followed by acute renal failure, hyperkalemia, hypocalcemia, hyperuricemia, or hyperphosphatemia has been reported within 12-24 h after the first infusion; risk greater in patients with high numbers of circulating malignant cells (>25,000/μ L) or high tumor burden; following complete resolution of TLS complications, rituximab has been tolerated when re-administered in conjunction with prophylactic therapy for TLS
Hepatitis B virus (HBV): Reactivation with related fulminant hepatitis and other viral infections
HBV reactivation with related fulminant hepatitis, hepatic failure and death have been reported in some patients with hematologic malignancies; most patients received rituximab in combination with chemotherapy; median time to diagnosis of hepatitis was approximately 4 mo after initiation of rituximab and approximately 1 mo after last dose; patients who develop viral hepatitis should have rituximab and any concomitant chemotherapy discontinued; appropriate treatment should be initiated; data regarding safety of resuming rituximab in patients who develop hepatitis subsequent to HBV reactivation is insufficient
More on Pemphigus Herpetiformis |
| Overview: Pemphigus Herpetiformis |
| Differential Diagnoses & Workup: Pemphigus Herpetiformis |
 Treatment & Medication: Pemphigus Herpetiformis |
| Follow-up: Pemphigus Herpetiformis |
| Multimedia: Pemphigus Herpetiformis |
| References |
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References
Amagai M, Tsunoda K, Suzuki H, Nishifuji K, Koyasu S, Nishikawa T. Use of autoantigen-knockout mice in developing an active autoimmune disease model for pemphigus. J Clin Invest. Mar 2000;105(5):625-31. [Medline].
Kubota Y, Yoshino Y, Mizoguchi M. A case of herpetiform pemphigus associated with lung cancer. J Dermatol. Aug 1994;21(8):609-11. [Medline].
Palleschi GM, Giomi B. Herpetiformis pemphigus and lung carcinoma: a case of paraneoplastic pemphigus. Acta Derm Venereol. 2002;82(4):304-5. [Medline].
Marzano AV, Tourlaki A, Cozzani E, Gianotti R, Caputo R. Pemphigus herpetiformis associated with prostate cancer. J Eur Acad Dermatol Venereol. May 2007;21(5):696-8. [Medline].
Brod C, Fierlbeck G, Metzler G, Sönnichsen K, Röcken M, Schaller M. [Desmoglein 1-negative, desmoglein 3-positive pemphigus herpetiformis with involvement of oral mucous membranes]. J Dtsch Dermatol Ges. Apr 2005;3(4):280-2. [Medline].
Ishii K, Amagai M, Komai A, Ebihara T, Chorzelski TP, Jablonska S, et al. Desmoglein 1 and desmoglein 3 are the target autoantigens in herpetiform pemphigus. Arch Dermatol. Aug 1999;135(8):943-7. [Medline].
Kubo A, Amagai M, Hashimoto T, Doi T, Higashiyama M, Hashimoto K, et al. Herpetiform pemphigus showing reactivity with pemphigus vulgaris antigen (desmoglein 3). Br J Dermatol. Jul 1997;137(1):109-13. [Medline].
Verdier-Sevrain S, Joly P, Thomine E, Belanyi P, Gilbert D, Tron F, et al. Thiopronine-induced herpetiform pemphigus: report of a case studied by immunoelectron microscopy and immunoblot analysis. Br J Dermatol. Feb 1994;130(2):238-40. [Medline].
Sanchez-Palacios C, Chan LS. Development of pemphigus herpetiformis in a patient with psoriasis receiving UV-light treatment. J Cutan Pathol. Apr 2004;31(4):346-9. [Medline].
Morita E, Amagai M, Tanaka T, Horiuchi K, Yamamoto S. A case of herpetiform pemphigus coexisting with psoriasis vulgaris. Br J Dermatol. Oct 1999;141(4):754-5. [Medline].
Chan LS, Vanderlugt CJ, Hashimoto T, Nishikawa T, Zone JJ, Black MM, et al. Epitope spreading: lessons from autoimmune skin diseases. J Invest Dermatol. Feb 1998;110(2):103-9. [Medline].
Hashimoto T, Ogawa MM, Konohana A, Nishikawa T. Detection of pemphigus vulgaris and pemphigus foliaceus antigens by immunoblot analysis using different antigen sources. J Invest Dermatol. Mar 1990;94(3):327-31. [Medline].
Ishii K, Amagai M, Hall RP, Hashimoto T, Takayanagi A, Gamou S, et al. Characterization of autoantibodies in pemphigus using antigen-specific enzyme-linked immunosorbent assays with baculovirus-expressed recombinant desmogleins. J Immunol. Aug 15 1997;159(4):2010-7. [Medline].
American College of Rheumatology. Recommendations for the prevention and treatment of glucocorticoid-induced osteoporosis. American College of Rheumatology Task Force on Osteoporosis Guidelines. Arthritis Rheum. Nov 1996;39(11):1791-801. [Medline].
Ahmed AR, Spigelman Z, Cavacini LA, Posner MR. Treatment of pemphigus vulgaris with rituximab and intravenous immune globulin. N Engl J Med. Oct 26 2006;355(17):1772-9. [Medline].
Amagai M, Klaus-Kovtun V, Stanley JR. Autoantibodies against a novel epithelial cadherin in pemphigus vulgaris, a disease of cell adhesion. Cell. Nov 29 1991;67(5):869-77. [Medline].
Barranco VP. Mixed bullous disease. Arch Dermatol. Aug 1974;110(2):221-4. [Medline].
DeMento FJ, Grover RW. Acantholytic herpetiform dermatitis. Arch Dermatol. Jun 1973;107(6):883-7. [Medline].
Dias M, dos Santos AP, Sousa J, Maya M. Herpetiform pemphigus. J Eur Acad Dermatol Venereol. Jan 1999;12(1):82-5. [Medline].
Huhn KM, Tron VA, Nguyen N, Trotter MJ. Neutrophilic spongiosis in pemphigus herpetiformis. J Cutan Pathol. Jun 1996;23(3):264-9. [Medline].
Jablonska S, Chorzelski TP, Beutner EH, Chorzelska J. Herpetiform pemphigus, a variable pattern of pemphigus. Int J Dermatol. Jun 1975;14(5):353-9. [Medline].
Kuhl KA, Shofer FS, Goldschmidt MH. Comparative histopathology of pemphigus foliaceus and superficial folliculitis in the dog. Vet Pathol. Jan 1994;31(1):19-27. [Medline].
Maciejowska E, Jablonska S, Chorzelski T. Is pemphigus herpetiformis an entity?. Int J Dermatol. Nov 1987;26(9):571-7. [Medline].
Mahoney MG, Wang Z, Rothenberger K, Koch PJ, Amagai M, Stanley JR. Explanations for the clinical and microscopic localization of lesions in pemphigus foliaceus and vulgaris. J Clin Invest. Feb 1999;103(4):461-8. [Medline].
Micali G, Musumeci ML, Nasca MR. Epidemiologic analysis and clinical course of 84 consecutive cases of pemphigus in eastern Sicily. Int J Dermatol. Mar 1998;37(3):197-200. [Medline].
Nickoloff BJ, Karabin GD, Barker JN, Griffiths CE, Sarma V, Mitra RS, et al. Cellular localization of interleukin-8 and its inducer, tumor necrosis factor-alpha in psoriasis. Am J Pathol. Jan 1991;138(1):129-40. [Medline].
O'Toole EA, Mak LL, Guitart J, Woodley DT, Hashimoto T, Amagai M, et al. Induction of keratinocyte IL-8 expression and secretion by IgG autoantibodies as a novel mechanism of epidermal neutrophil recruitment in a pemphigus variant. Clin Exp Immunol. Jan 2000;119(1):217-24. [Medline].
Robinson ND, Hashimoto T, Amagai M, Chan LS. The new pemphigus variants. J Am Acad Dermatol. May 1999;40(5 Pt 1):649-71; quiz 672-3. [Medline].
Santi CG, Maruta CW, Aoki V, Sotto MN, Rivitti EA, Diaz LA. Pemphigus herpetiformis is a rare clinical expression of nonendemic pemphigus foliaceus, fogo selvagem, and pemphigus vulgaris. Cooperative Group on Fogo Selvagem Research. J Am Acad Dermatol. Jan 1996;34(1):40-6. [Medline].
Schröder JM. Cytokine networks in the skin. J Invest Dermatol. Jul 1995;105(1 Suppl):20S-24S. [Medline].
Seitz CS, Staegemeir E, Amagai M, Rose C, Bröcker EB, Zillikens D. Pemphigus herpetiformis with an autoimmune response to recombinant desmoglein 1. Br J Dermatol. Aug 1999;141(2):354-5. [Medline].
Shimizu K, Hashimoto T, Wang N, Watanabe K, Ohata Y, Kikuchi A, et al. A case of herpetiform pemphigus associated with autoimmune hemolytic anemia: detection of autoantibodies against multiple epidermal antigens. Dermatology. 1996;192(2):179-82. [Medline].
Further Reading
Keywords
pemphigus herpetiformis, pemphigus, herpetiform pemphigus
