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Pemphigus Erythematosus Medication

  • Author: Rakesh Bharti, MD, MBBS; Chief Editor: William D James, MD  more...
 
Updated: Feb 18, 2016
 

Medication Summary

The goal of pharmacotherapy in pemphigus erythematosus is to reduce morbidity and to prevent complications.

Plasmapheresis and immunoadsorption have been shown to be effective in the treatment of pemphigus erythematosus. Plasmapheresis[23, 24, 25, 26] and, more recently, immunoadsorption,[27, 28, 29] are extracorporeal treatments that act rapidly on disease activity by lowering the load of the causative autoantibodies in the patient's circulation, causing a rebound of the plasma cell clone. During rebound, the plasma cells are more sensitive to chemotherapy.

In immunoadsorption, the immunoglobulins are selectively removed from the patient's plasma by adsorbing the antibodies to the matrix in a column of the immunoadsorption apparatus, after which the "cleansed" plasma is returned to the patient. Reportedly, immunoadsorption has higher efficacy and fewer adverse effects compared with plasmapheresis. In one German study,[30] immunoadsorption was effective and safe in treating resistant and severe pemphigus. However, more studies are needed to support these data.

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Corticosteroids

Class Summary

The mainstay of treatment of immunobullous diseases is steroids. Generally, high-dose steroids (ie, prednisolone, prednisone, methylprednisolone, dexamethasone), PO or IV, are effective in obtaining rapid disease control. However, high-dose and prolonged treatment with steroids often causes significant adverse effects. Screening and risk assessment of possible adverse effects (eg, diabetes, glaucoma, osteoporosis, blood pressure, history of GI bleeding) are required prior to and during treatment.

Concomitant calcium supplements and antacid drugs (eg, proton pump inhibitors) are recommended throughout therapy. A study[31] of patients with pemphigus vulgaris showed intravenous pulse combined with low-dose oral steroid therapy to be effective and associated with fewer severe adverse effects than oral high-dose steroid therapy.

To reduce the adverse effects of systemic steroids, French researchers compared the efficacy and adverse effect profile of topical steroids with that of systemic steroids in the treatment of moderate-to-severe bullous pemphigoid.[32] Topical steroids were more effective than oral therapy and were associated with far fewer severe complications. However, a 2003 report warns of the development of steroid-induced skin atrophy and striae after this regimen, and it has not been validated in other immunobullous diseases.[33]

Prednisone (Deltasone, Meticorten, Orasone, Sterapred)

 

Prednisone is an immunosuppressant for the treatment of autoimmune disorders; it may decrease inflammation by reversing increased capillary permeability and suppressing PMN activity. It stabilizes lysosomal membranes and suppresses lymphocyte and antibody production.

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Antineoplastic agents

Class Summary

These agents inhibit cell growth and proliferation and serve as steroid-sparing agents. Intravenous pulse cyclophosphamide (500 mg qd) has also been suggested as adjunctive therapy after plasmapheresis to prevent "rebound" (marked increase of antibodies compensating for the antibodies depleted by plasmapheresis).[25]

High-dose immunoablative cyclophosphamide without stem cell rescue was effective in 2 patients with resistant pemphigus. However, considering the serious adverse effects of this high-dose regimen, it should be reserved for patients who are resistant to other treatments.[34, 35, 36]

Cyclophosphamide (Cytoxan, Neosar)

 

Several regimens with cyclophosphamide have been described in the treatment of immunobullous disorders. Cyclophosphamide is a potent cytotoxic agent that can cause severe cytopenia and hemorrhagic cystitis (bladder inflammation).

Oral low-dose cyclophosphamide is usually used as a steroid-sparing agent.

Intravenous cyclophosphamide (500 mg qd for 1 d) plus low-dose oral (50 mg qd) has been combined with intravenous pulse dexamethasone (100 mg qd for 3 d) to achieve rapid disease control.

Intravenous pulse cyclophosphamide (500 mg qd) has also been suggested as adjunctive therapy after plasmapheresis to prevent "rebound" (marked increase of antibodies compensating for the antibodies depleted by plasmapheresis).

More recently, high-dose immunoablative cyclophosphamide without stem cell rescue was effective in 2 patients with resistant pemphigus. However, considering the serious adverse effects of this high-dose regimen, it should be reserved for patients who are resistant to other treatments.

More studies are needed to outline the risk of adverse effects vs benefits of this regimen.

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Sulfone antibiotics

Class Summary

Dapsone's anti-inflammatory mechanism of action differs from the antibacterial mechanism of action. Suppression of neutrophils by inhibiting the halide-myeloperoxidase system is the most likely mechanism of action for anti-inflammatory effects.

Dapsone (Avlosulfon)

 

Dapsone is bactericidal and bacteriostatic against mycobacteria; its mechanism of action is similar to that of sulfonamides, where competitive antagonists of PABA prevent formation of folic acid, inhibiting bacterial growth.

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Immunosuppressants

Class Summary

These agents are effective in the treatment of autoimmune diseases. See Glied and Rico[37] and Tan et al[38] for references regarding adverse effects (eg, abnormal LFT results) related to thiopurine-methyltransferase (TPMT).

Also see the clinical guideline summary from the British Association of Dermatologists, Guidelines for prescribing azathioprine in dermatology.[39]

Azathioprine (Imuran)

 

Among the slowly acting adjuvant therapies, azathioprine is a useful and safe steroid-sparing agent, provided TPMT assay is performed prior to treatment. TPMT is an enzyme that converts azathioprine into its inactive metabolites.

If TPMT is lacking or present in a much lower concentration, patient is at high risk for bone marrow suppression and thus anemia, thrombocytopenia, and leukopenia. Therefore, analysis of TPMT levels is recommended before starting treatment.

Other adverse effects (eg, abnormal LFT results) are not reflected by this enzyme level.

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Intravenous immunoglobulins

Class Summary

IVIGs have proven beneficial in achieving rapid disease control in patients with immunobullous diseases.[40, 41, 42, 43, 44, 45]

Immune globulin intravenous (Gamimune, Gammagard, Sandoglobulin)

 

Immune globulin intravenous consists of IgG collected from a pool of thousands of blood donors (virus-free), thus providing a wide range of immunologically different IgG. Theoretically, they bind and neutralize pathogenic autoantibodies.

It is administered IV, with each cycle lasting 3-5 days, at a dose of 1-2 g/kg/cycle. Several cycles are usually required.

Cost and availability limit its use. IVIG is expensive. It is generally used in resistant and severe bullous diseases in addition to immunosuppressive therapy or as monotherapy in patients with contraindications for immunosuppressive drugs.

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Anti-inflammatory agents

Class Summary

Anti-inflammatory agents (eg, dapsone, gold, tetracyclines) are also being used to treat certain immunobullous disorders. However, they are generally used in patients with mild-to-moderate disease, with the exception of those with dermatitis herpetiformis and linear IgA disease, in whom dapsone is still first-line treatment. Dapsone can be started after glucose-6-P-dehydrogenase screening. Low levels are associated with a high risk of methemoglobinemia. When using tetracyclines, some authors have reported minocycline-induced pigmentation in patients with pemphigus and pemphigoid, with a prevalence that appears to be much higher than in persons with acne or rheumatoid arthritis.[46]

Rituximab targets a cell-specific protein and may represent a promising novel therapeutic option for refractory immunobullous diseases.[47, 48, 49, 50]

Rituximab (Rituxan)

 

Rituximab is a monoclonal anti-CD20 antibody (CD20 is a protein on the surface of lymphocytes), reported to be effective in treating resistant pemphigus foliaceous and vulgaris. It may deplete B lymphocytes (antibody-producing cells) and rapidly removes desmoglein antibodies (antibodies causing pemphigus) from circulation.

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Contributor Information and Disclosures
Author

Rakesh Bharti, MD, MBBS Consultant Dermatologist and HIV Specialist, BDC Research Centre, India

Rakesh Bharti, MD, MBBS is a member of the following medical societies: International AIDS Society

Disclosure: Nothing to disclose.

Specialty Editor Board

David F Butler, MD Section Chief of Dermatology, Central Texas Veterans Healthcare System; Professor of Dermatology, Texas A&M University College of Medicine; Founding Chair, Department of Dermatology, Scott and White Clinic

David F Butler, MD is a member of the following medical societies: American Medical Association, Alpha Omega Alpha, Association of Military Dermatologists, American Academy of Dermatology, American Society for Dermatologic Surgery, American Society for MOHS Surgery, Phi Beta Kappa

Disclosure: Nothing to disclose.

Julia R Nunley, MD Professor, Program Director, Dermatology Residency, Department of Dermatology, Virginia Commonwealth University Medical Center

Julia R Nunley, MD is a member of the following medical societies: American Academy of Dermatology, American College of Physicians, American Society of Nephrology, International Society of Nephrology, Medical Dermatology Society, Medical Society of Virginia, National Kidney Foundation, Phi Beta Kappa, Women's Dermatologic Society

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: American Board of Dermatology<br/>Co-Editor for the text Dermatological Manifestations of Kidney Disease .

Chief Editor

William D James, MD Paul R Gross Professor of Dermatology, Vice-Chairman, Residency Program Director, Department of Dermatology, University of Pennsylvania School of Medicine

William D James, MD is a member of the following medical societies: American Academy of Dermatology, Society for Investigative Dermatology

Disclosure: Nothing to disclose.

Additional Contributors

Ponciano D Cruz, Jr, MD Professor and Vice-Chair, Paul R Bergstresser Chair, Department of Dermatology, University of Texas Southwestern Medical Center

Ponciano D Cruz, Jr, MD is a member of the following medical societies: Texas Medical Association

Disclosure: Received consulting fee from RCTS for independent contractor; Received honoraria from Mary Kay Cosmetics for consulting; Received grant/research funds from Galderma for principal investigator.

Acknowledgements

The author acknowledges the patience of his wife Prabha Bharti while carrying out work on this article and the constant pushing of his learned sons Aseem and Anshul.

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Direct immunofluorescence microscopy performed on epithelial biopsy specimen obtained from a patient with pemphigus vulgaris detects immunoglobulin G deposits at the epithelial cell surfaces.
Biopsy shows moderate epithelial hyperplasia with a suprabasal cleft that shows suprabasal acantholysis. The rest of the epithelium shows spongiosis with neutrophils. The submucosa has a moderately dense mixed perivascular infiltrate of lymphocytes and neutrophils. At places, the epithelium is missing, and the surface is covered by fibrin and necrotic inflammatory cells. Photo courtesy of Dr. Uday Khopkar.
Biopsy shows upper epidermal acantholytic blistering dermatitis involving the granular and upper spinous layer. The blister contains plasma, RBCs, and few acute inflammatory cells. The epidermis at the periphery of the blister shows mild spongiosis with neutrophils. In the roof of the blister, a few elongated acantholytic cells can be seen. Underlying dermis shows superficial and mid perivascular mixed infiltrate of neutrophils and lymphocytes. Photo courtesy of Dr. Uday Khopkar.
Biopsy shows upper epidermal acantholytic blistering dermatitis involving the granular and upper spinous layer with absence of roof of blister. The epidermis shows mild spongiosis with neutrophils. Underlying dermis shows superficial and mid perivascular mixed infiltrate of neutrophils and lymphocytes. Photo courtesy of Dr. Uday Khopkar.
Biopsy shows sparse superficial and deep perivascular infiltrate of lymphocytes. The papillary dermis is edematous and there is extravasation of RBCs. Basal layer shows vacuolization and interface infiltration by lymphocytes. Reticular dermis shows small amount of mucin. Photo courtesy of Dr. Uday Khopkar.
 
 
 
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