Generic selectors
Exact matches only
Search in title
Search in content
Post Type Selectors
Filter by Categories
15th National Conference of the IAOMFP, Chennai, 2006
Abstracts from current literature
Acne in India: Guidelines for management - IAA Consensus Document
Art & Psychiatry
Association Activities
Association Notes
Award Article
Book Review
Brief Report
Case Analysis
Case Letter
Case Letters
Case Notes
Case Report
Case Reports
Clinical and Laboratory Investigations
Clinical Article
Clinical Studies
Clinical Study
Conference Oration
Conference Summary
Continuing Medical Education
Cosmetic Dermatology
Current Best Evidence
Current Issue
Current View
Derma Quest
Dermato Surgery
Dermatosurgery Specials
Dispensing Pearl
Do you know?
Drug Dialogues
Editor Speaks
Editorial Remarks
Editorial Report
Editorial Report - 2007
Editorial report for 2004-2005
Fourth All India Conference Programme
From Our Book Shelf
From the Desk of Chief Editor
Get Set for Net
Get set for the net
Guest Article
Guest Editorial
How I Manage?
IADVL Announcement
IADVL Announcements
IJDVL Awards
IJDVL Awards 2018
IJDVL Awards 2019
IJDVL Awards 2020
IJDVL International Awards 2018
Images in Clinical Practice
In Memorium
Inaugural Address
Knowledge From World Contemporaries
Leprosy Section
Letter in Response to Previous Publication
Letter to Editor
Letter to the Editor
Letter to the Editor - Case Letter
Letter to the Editor - Letter in Response to Published Article
Letter to the Editor - Observation Letter
Letter to the Editor - Study Letter
Letter to the Editor - Therapy Letter
Letter to the Editor: Articles in Response to Previously Published Articles
Letters in Response to Previous Publication
Letters to the Editor
Letters to the Editor - Letter in Response to Previously Published Articles
Letters to the Editor: Case Letters
Letters to the Editor: Letters in Response to Previously Published Articles
Medicolegal Window
Miscellaneous Letter
Net Case
Net case report
Net Image
Net Letter
Net Quiz
Net Study
New Preparations
News & Views
Observation Letter
Observation Letters
Original Article
Original Contributions
Pattern of Skin Diseases
Pediatric Dermatology
Pediatric Rounds
Presedential Address
Presidential Address
Presidents Remarks
Report of chief editor
Report of Hon : Treasurer IADVL
Report of Hon. General Secretary IADVL
Research Methdology
Research Methodology
Resident page
Resident's Page
Resident’s Page
Residents' Corner
Residents' Corner
Residents' Page
Review Article
Review Articles
Reviewers 2022
Revision Corner
Self Assessment Programme
Seminar: Chronic Arsenicosis in India
Seminar: HIV Infection
Short Communication
Short Communications
Short Report
Special Article
Specialty Interface
Study Letter
Study Letters
Symposium - Contact Dermatitis
Symposium - Lasers
Symposium - Pediatric Dermatoses
Symposium - Psoriasis
Symposium - Vesicobullous Disorders
Symposium Aesthetic Surgery
Symposium Dermatopathology
Symposium-Hair Disorders
Symposium-Nails Part I
Symposium-Nails-Part II
Systematic Review and Meta-Analysis
Systematic Reviews and Meta-analyses
Systematic Reviews and Meta-analysis
Therapeutic Guideline-IADVL
Therapeutic Guidelines
Therapeutic Guidelines - IADVL
Therapy Letter
Therapy Letters
View Point
What’s new in Dermatology
View/Download PDF

Translate this page into:

doi: 10.4103/0378-6323.136828
PMID: 25035350

Treatment of pemphigus: An Indian perspective

Amrinder J Kanwar1 , Keshavamurthy Vinay2
1 Departments of Dermatology, Venereology and Leprology, School of Medical Sciences and Research, Sharda University, Greater Noida, Uttar Pradesh, India
2 Departments of Dermatology, Venereology and Leprology, Postgraduate Institute of Medical Education and Research, Chandigarh, India

Correspondence Address:
Amrinder J Kanwar
Department of Dermatology, Venereology and Leprology, School of Medical Sciences and Research, Sharda University, Greater Noida, Uttar Pradesh
How to cite this article:
Kanwar AJ, Vinay K. Treatment of pemphigus: An Indian perspective. Indian J Dermatol Venereol Leprol 2014;80:285-288
Copyright: (C)2014 Indian Journal of Dermatology, Venereology, and Leprology

Pemphigus is a chronic autoimmune epidermal blistering disorder with potentially fatal outcomes. Unfortunately, in India pemphigus occurs at a younger age as compared to western countries and tends to be more severe. A significant proportion of pemphigus patients have been less than 40 years of age. [1] It is a common disorder in India; however there is lack of population based studies and most studies are hospital based. The incidence of pemphigus among the dermatology outpatient attendees has varied widely, 0.09-1.8%. [1],[2] A clinic based study from Kerala estimated the incidence of pemphigus in Thrissur district as 4.4 per million population. [3]

Pemphigus has a considerable effect on quality of life of patients as well as their family members. With a chronic course of relapses, remissions, and a mortality rate between 5-10%, it poses a challenge for treatment. Mortality due to pemphigus which was as high as 90% decreased remarkably, with aggressive and widespread use of corticosteroids. High dose corticosteroids were once used in combination with other immunosuppressants with good improvement, but such high doses of corticosteroids were often associated with severe side effects, and was responsible for the death of nearly 10% of the patients. [4] With the aim of reducing the adverse effects of long term, high dose steroid administration, dexamethasone cyclophosphamide pulse (DCP) therapy was introduced in 1984. [5] Since then DCP or oral corticosteroids with or without adjuvant immunosuppressants have been the cornerstone of therapy for these disorders in India. [6],[7] However, there has been a constant search for newer therapeutic modalities in pemphigus, to limit the corticosteroid requirement, to achieve early and long lasting remission and for better safety profile. Currently we are at the cross roads of a shift in managing our pemphigus patients with novel targeted therapeutic agents like rituximab (chimeric monoclonal antibody against CD 20 antigen) and intravenous immunoglobulin (IVIG) being increasingly used in India. At this critical juncture it is important to have an overview on therapeutics of pemphigus in an Indian context.

The choice of therapy from the available armamentarium depends on the severity of the disease, availability and affordability of the drug or facilities, associated comorbidities and the physician′s preference. We follow a three tier approach in the management of our pemphigus patients. [8] Patients with mild disease, who may not require long term, high dose corticosteroids are managed by conventional modalities. Low dose corticosteroids (0.75-1 mg/kg/day) in combination with other steroid sparing adjuvants like azathioprine, cyclophosphamide and mycophenolate mofetil are prescribed. Depending on the treatment response, daily corticosteroids are gradually tapered and adjuvants are continued until remission is achieved. The choice of adjuvant depends mainly on efficacy, contraindications, drug interactions and affordability. Chams-Davatchi et al., [9] conducted a four arm study comparing the efficacy of prednisolone alone, prednisolone plus azathioprine, prednisolone plus mycophenolate mofetil, and prednisolone plus intravenous cyclophosphamide pulse therapy. The authors found that the efficacy of prednisolone was enhanced when used in combination with an adjuvant. The most efficacious adjuvant was azathioprine followed by cyclophosphamide. [9] A multicenter randomized, placebo-controlled trial assessing the usefulness of mycophenolate mofetil in patients with mild to moderate disease severity found it to be only marginally effective with no advantage on the primary end point. [10] The use of mycophenolate mofetil is further limited by its high cost.

The major change in the therapeutics of pemphigus was the concept of pulse therapy introduced by Pasricha and Gupta. [5] As stated earlier, this regimen revolutionized pemphigus treatment in India. Later many modifications of DCP were introduced with good efficacy and reasonable safety. [6] We prefer DCP pulse therapy in patients with moderate to severe disease or patients with mild disease who fail conventional treatment and have no contraindication for pulse therapy. However, the major drawbacks of this regimen are the long treatment duration and lack of immunological monitoring. In a study to assess the need for continuing DCPs in the consolidation phase, we observed that the DCPs had no advantage over oral cyclophosphamide. [11] Patients could be shifted directly from phase I to phase III without increase in the relapse rate. We also found that periodic direct immunofluorescence (DIF) and enzyme-linked immunosorbent assay (ELISA) of desmoglein (Dsg) 1 and Dsg3 were useful in monitoring disease activity and to predict relapse. [11] In daily practice, it is advisable to assess the immunological activity by Dsg 1 and 3 index values (or DIF if facilities for ELISA are not available) 3 monthly in patients who are in clinical remission. Patients in clinical remission, but who are immunologically active have a higher chance of relapse if treatment is stopped prematurely. Oral cyclophosphamide, 50 mg once a day should be continued until both clinical and immunological remission is obtained. Thus, with a few modifications the duration of pulse therapy could be reduced by 9 months (by eliminating phase II) and relapse rate decreased (by immunological evaluation). In patients not suited for DCP therapy, some authors have used oral mini pulse, betamethasone 5mg on two consecutive days a week. [12] However, the data on the use of this regimen appears to be limited.

With the availability of novel targeted therapeutic agents, patients who fail DCP/conventional treatment, and those in whom they are contraindicated or cause severe adverse effects can now be offered IVIG and/or rituximab. IVIG alone or in combination with rituximab is preferred in patients with extensive disease in whom immediate control of disease activity is required. It can also be safely used in patients in sepsis or those who are at risk of infection. We had previously reported the efficacy of rituximab in an open label study with a complete remission rate of 70%. [13] In a randomized controlled, investigator blinded trial, we recently showed that better clinical and immunological outcomes are achieved in patients treated with two doses of 1000 mg rituximab in comparison with 500 mg doses. [14] Long term data on rituximab is now available, with a complete remission rate of 80-86% after a single infusion cycle. [15],[16]

Though we are following a three tier approach, we offer rituximab treatment to all pemphigus patients irrespective of severity. Our own experience and evidence in the literature suggests that treatment with rituximab results in early remission, fewer relapses, and an overall better prognosis. [17] Many other authors also share the view of using rituximab as a first line therapy. [18],[19],[20] Ever since we started using rituximab in 2010 we were impressed by its efficacy. This was highlighted by us in an earlier editorial entitled "Rituximab in pemphigus" in this journal. [21] We are pleased to know that rituximab is also being used now at other centers in India. However, the major limitations of these agents in the Indian scenario are cost, availability, lack of expertise and limited clinical experience.

Although the cost of therapy with conventional drugs appears to be lower, the cost associated with complications of conventional therapies and their management is overlooked. Conventional treatment modalities require repeated hospital admissions and frequent hospital visits with subsequent loss of employment and income adding to the cost of therapy. A pharmacoeconomic study comparing the cost of treatment between IVIG and conventional drugs in autoimmune blistering diseases including pemphigus found that conventional treatment modalities had significant side effects, many of which were hazardous and required prolonged and frequent hospitalizations. Some of these side effects were severe enough to require discontinuation of treatment. The authors found that the mean total cost of treatment with IVIG therapy was statistically significantly less than that of conventional drugs and their complications during the entire course of the disease and on an annual basis. [22] With better clinical experience, wider acceptance of these targeted therapeutic agents may be seen in future and this may become first–line therapy.

Topical therapies are used as an adjuvant in the majority of patients, especially in the oral cavity. Various topical therapies including corticosteroids, cyclosporine, and tacrolimus have been described to be useful. Corticosteroid injections are commonly used and are considered to be the most effective topical treatment for oral pemphigus. [23] In an open label trial evaluating the role of perilesional/intralesional triamcinolone acetonide in the management of oral pemphigus, the authors found that patients treated with corticosteroid injections had earlier and higher rates of complete clinical remission and a lower total cumulative dose of oral corticosteroids. [24] Local hygiene is equally important since poor oral hygiene is associated with disease flare and persistence.

The often neglected drugs in pemphigus therapeutics are dapsone, and tetracycline and nicotinamide. They are specially useful in treating rare variants of pemphigus including pemphigus herpetiformis, IgA pemphigus and IgG/IgA pemphigus. [25] These subtypes respond dramatically to dapsone within days. They are also safe and require less vigorous monitoring than other adjuvants.

Certain special situations require mention in pemphigus therapeutics. Pregnancy and lactation severely limit the choice of treatment agents since commonly used cytotoxic drugs are contraindicated. Further, pemphigus per se can also lead to intrauterine growth restriction, premature delivery or death in addition to causing neonatal pemphigus. [26] Systemic corticosteroids are an important and safe therapeutic option in pregnancy. Unlike fluorinated corticosteroids, prednisone does not pass through the placenta and is the preferred choice. [27] It should preferably be given at doses less than 20 mg daily. [27] The other steroid sparing adjuvants that are relatively safe in pregnancy include azathioprine and IVIG. [28],[29]

Pemphigus is rare in children and in our previous study, children aged less than 15 years accounted for 3.7% of all cases. [1] A recent review of the English literature found 33 cases of childhood pemphigus (aged <12 years) and 47 cases of juvenile pemphigus (aged 12-18 years). [30],[31] Treatment modalities reported included systemic corticosteroids, azathioprine, dapsone, and IVIG. [30],[31] We have used rituximab in 10 patients of childhood and juvenile pemphigus with a complete remission rate of 80%. [32] Though early reports are encouraging, more data is required on the long term safety of rituximab in childhood pemphigus.

Treating pemphigus is akin to walking a tightrope. The therapeutic efficacy of any drug has to be balanced against its potential toxicity and systemic immunosuppression. No individual drug is uniformly effective in all patients. Effective therapy for pemphigus lies in combining various agents to maximize efficacy and minimize side effects. Corticosteroids continue to play a central role in pemphigus therapeutics while we continue our search for safe and effective adjuvants.

Kanwar AJ, Ajith AC, Narang T . Pemphigus in North India. J Cutan Med Surg. 2006;10:21-5.
[Google Scholar]
Mascarenhas MF, Hede RV, Shukla P, Nadkarni NS, Rege VL . Pemphigus in Goa. J Indian Med Assoc. 1994;92:342-3.
[Google Scholar]
Kumar KA . Incidence of pemphigus in Thrissur district, south India. Indian J Dermatol Venereol Leprol. 2008;74:349-51.
[Google Scholar]
Lever WF, Schaumburg-Lever G . Immunosuppressants and prednisone in pemphigus vulgaris: Therapeutic results obtained in 63 patients between 1961 and 1975. Arch Dermatol. 1977;113:1236-41.
[Google Scholar]
Pasricha JS, Gupta R. Pulse therapy with dexamethasone- cyclophosphamide in pemphigus. Indian J Dermatol Venereol Leprol. 1984;50:199-203.
[Google Scholar]
Kaur S, Kanwar AJ . Dexamethasone-cyclophosphamide pulse therapy in pemphigus. Int J Dermatol. 1990;29:371-4.
[Google Scholar]
Kanwar AJ, De D . Pemphigus in India. Indian J Dermatol Venereol Leprol. 2011;77:439-49.
[Google Scholar]
Tsuruta D, Kanwar AJ, Vinay K, Fukuda S, Koga H, Dainichi T, et al. Clinical and immunologic characterization in 26 Indian pemphigus patients. J Cutan Med Surg. 2013;17:321-31.
[Google Scholar]
Chams-Davatchi C, Esmaili N, Daneshpazhooh M, Valikhani M, Balighi K, Hallaji Z, et al. Randomized controlled open-label trial of four treatment regimens for pemphigus vulgaris. J Am Acad Dermatol. 2007;57:622-8.
[Google Scholar]
Beissert S, Mimouni D, Kanwar AJ, Solomons N, Kalia V, Anhalt GJ . Treating pemphigus vulgaris with prednisone and mycophenolate mofetil: A multicenter, randomized, placebo-controlled trial. J Invest Dermatol. 2010;130:2041-8.
[Google Scholar]
Parmar NV, Kanwar AJ, Minz RW, Parsad D, Vinay K, Tsuruta D, et al. Assessment of the therapeutic benefit of dexamethasone cyclophosphamide pulse versus only oral cyclophosphamide in phase II of the dexamethasone cyclophosphamide pulse therapy: A preliminary prospective randomized controlled study. Indian J Dermatol Venereol Leprol. 2013;79:70-6.
[Google Scholar]
Mahajan VK, Sharma NL, Sharma RC, Garg G . Twelve-year clinico-therapeutic experience in pemphigus: A retrospective study of 54 cases. Int J Dermatol. 2005;44:821-7.
[Google Scholar]
Kanwar AJ, Tsuruta D, Vinay K, Koga H, Ishii N, Dainichi T, et al. Efficacy and safety of rituximab treatment in Indian pemphigus patients. J Eur Acad Dermatol Venereol. 2013;27:e17-23.
[Google Scholar]
Kanwar AJ, Vinay K, Sawatkar GU, Dogra S, Minz RW, Shear NH, et al. Clinical and immunological outcomes of high and low dose rituximab treatments in pemphigus patients: A randomized comparative observer blinded study. Br J Dermatol. 2014;170:1341-9.
[Google Scholar]
Heelan K, Al-Mohammedi F, Smith MJ, Knowles S, Lansang P, Walsh S, et al. Durable Remission of Pemphigus With a Fixed-Dose Rituximab Protocol. JAMA Dermatol. 2014 [In press].
[Google Scholar]
Cianchini G, Lupi F, Masini C, Corona R, Puddu P, De Pita O . Therapy with rituximab for autoimmune pemphigus: Results from a single-center observational study on 42 cases with long-term follow-up. J Am Acad Dermatol. 2012;67:617-22.
[Google Scholar]
Leventhal JS, Sanchez MR . Is it time to re-evaluate the treatment of pemphigus? J Drugs Dermatol. 2012;11:1200-6.
[Google Scholar]
Cho YT, Lee FY, Chu CY, Wang LF . First-line Combination Therapy with Rituximab and Corticosteroids is Effective and Safe for Pemphigus. Acta Derm Venereol. 2014;94:472-73.
[Google Scholar]
Craythorne EE, Mufti G, DuVivier AW . Rituximab used as a first-line single agent in the treatment of pemphigus vulgaris. J Am Acad Dermatol. 2011;65:1064-5.
[Google Scholar]
Nigam R, Levitt J . Where does rituximab fit in the treatment of autoimmune mucocutaneous blistering skin disease? J Drugs Dermatol. 2012;11:622-5.
[Google Scholar]
Kanwar AJ, Vinay K . Rituximab in pemphigus. Indian J Dermatol Venereol Leprol. 2012;78:671-6.
[Google Scholar]
Daoud YJ, Amin KG . Comparison of cost of immune globulin intravenous therapy to conventional immunosuppressive therapy in treating patients with autoimmune mucocutaneous blistering diseases. Int Immunopharmacol. 2006;6:600-6.
[Google Scholar]
Bystryn JC, Rudolph JL . Pemphigus. Lancet. 2005;366:61-73.
[Google Scholar]
Mignogna MD, Fortuna G, Leuci S, Adamo D, Dell'Aversana Orabona G, Ruoppo E . Adjuvant triamcinolone acetonide injections in oro-pharyngeal pemphigus vulgaris. J Eur Acad Dermatol Venereol. 2010;24:1157-65.
. Adjuvant triamcinolone acetonide injections in oro-pharyngeal pemphigus vulgaris. J Eur Acad Dermatol Venereol. 2010;24:1157-65.'>[Google Scholar]
Kanwar AJ, Vinay K, Saikia UN, Koga H, Teye K, Tsuruta D, et al. IgG/IgA pemphigus reactive with desmoglein 1 with additional undetermined reactivity with epidermal basement membrane zone. Indian J Dermatol Venereol Leprol. 2014;80:46-50.
[Google Scholar]
Kanwar AJ, Dhar S . Pemphigus in pregnancy: Fetal risk. Int J Gynaecol Obstet. 1993;42:176-7.
[Google Scholar]
Braunstein I, Werth V . Treatment of dermatologic connective tissue disease and autoimmune blistering disorders in pregnancy. Dermatol Ther. 2013;26:354-63.
[Google Scholar]
Kardos M, Levine D, Gurcan HM, Ahmed RA . Pemphigus vulgaris in pregnancy: Analysis of current data on the management and outcomes. Obstet Gynecol Surv. 2009;64:739-49.
[Google Scholar]
Ahmed AR, Gurcan HM . Use of intravenous immunoglobulin therapy during pregnancy in patients with pemphigus vulgaris. J Eur Acad Dermatol Venereol. 2011;25:1073-9.
[Google Scholar]
Mabrouk D, Ahmed AR . Analysis of current therapy and clinical outcome in childhood pemphigus vulgaris. Pediatr Dermatol. 2011;28:485-93.
[Google Scholar]
Asarch A, Gurcan HM, Ahmed AR . A current review of juvenile pemphigus vulgaris: Analysis of data on clinical outcomes. Am J Clin Dermatol. 2010;11:21-33.
[Google Scholar]
Vinay K, Kanwar AJ, Sawatkar G U, Dogra S, Ishii N, Hashimoto T. Successful use of rituximab in the treatment of childhood and juvenile pemphigus. J Am Acad Dermatol. 2014 [In press].
[Google Scholar]

Fulltext Views

PDF downloads
Show Sections