Is it Time to Re-evaluate the Treatment of Pemphigus?

October 2012 | Volume 11 | Issue 10 | Original Article | 1200 | Copyright © October 2012

Pemphigus vulgaris, foliaceous, and vegetans are potentially fatal, autoimmune, vesiculobullous mucocutaneous diseases. In order to prevent potentially fatal infection and other complications, most patients with pemphigus require treatment with systemic corticosteroids and immunosuppressive agents, although these medications often cause chronic and serious adverse effects. Many case reports and several trials have documented remissions and clinical improvement in cases of pemphigus recalcitrant to standard therapy, who were treated with either intravenous immunoglobulin (IVIG) or rituximab, alone or in combination with each other. Collectively, the body of evidence from these reports is large enough to spark consideration of these treatments early in the management of pemphigus. Among the potential benefits of a therapeutic strategy that includes these biologic agents are more rapid induction of remission, prevention of corticosteroid-related adverse effects, and decreased cost of therapy. Considering the outcomes from recent trials with these novel therapies, reevaluation of the best-practice treatment of pemphigus seems prudent and timely.

J Drugs Dermatol. 2012;11(10):1200-1206.


By 1970, systemic corticosteroids, the mainstay therapy of patients with pemphigus vulgaris, had reduced the disease's mortality rate from nearly 100% to approximately 24%.1 The addition of “adjuvant,” corticosteroid-sparing immunosuppressant agents (ISA), coupled with advances in the management of complications, further reduced mortality below 10%.2 However, even with co-administration of immunosuppressive adjuvants, prolonged high doses of systemic corticosteroids are often required. Complications of conventional therapy have become the main causes of death in pemphigus.1-3 Although the evidence for biologic agents in the treatment of this disease is limited to case reports, case series and open-label trials, there is enough efficacy and safety profile data on these agents to consider reappraisal of the conventional treatment of pemphigus vulgaris.

Conventional Therapy

The treatment for pemphigus is largely empirical with no universal consensus on corticosteroid dosing. The British Association of Dermatologists recommends treatment with prednisone doses of 40 mg to 60 mg daily, and higher doses (60 mg to 100 mg daily) for undefined “more severe cases.” 4 If an adequate therapeutic response has not been achieved within 5 to 7 days after initiation of corticosteroid treatment, the dose is then increased in 50% to 100% increments until the disease is controlled, as manifested by healing of erosions and suppressed formation of vesicles or bullae.2,4 Once disease remission is induced and maintained, the corticosteroid dose is reduced by 50% every two weeks.2 It is interesting that, despite limitations in size and study design, a randomized- controlled trial that compared doses of 1 mg per kg (120 mg to 180 mg per day) and 0.5 mg per kg (45 mg to 60 mg per day) of oral prednisone in 22 cases of severe pemphigus demonstrated no significant difference either in the treatment duration needed to attain disease remission or the 5-year relapse rate.5
Pemphigus patients develop numerous complications directly related to systemic corticosteroids. A 20-year review of over 100 patients with pemphigus reported increased rates of infections, thromboembolic events and psychosis associated with doses of prednisone higher than 120 mg per day.1 Chronic corticosteroid administration was associated with long-term morbidity that included radiographically diagnosed osteoporosis in 29% of cases, gastrointestinal adverse events in 11%, psychiatric events in 33%, and diabetes in 41%.1 Pemphigus cases invariably require high doses, which cause adverse effects that not only produce symptoms, but can reduce life span. Between 10% and 40% of persons on high-dose corticosteroid therapy develop overt diabetes mellitus, which may appear in the first six weeks of therapy,6 and approximately 20% of cases become newly hypertensive. While the risk of corticosteroid-related complications is lower at doses equivalent to 10 mg of prednisone daily, due to variability in the response of individuals to corticosteroids, complications can develop at relatively low doses. Between 30% and 50% of patients treated with long-term therapy without prophylaxis develop osteoporosis. In women, bone density in the lumbar spine is reduced between 20% to 50% with prolonged daily corticosteroid doses equivalent to 30 mg of prednisone and 10% to 20% with daily doses of 10 mg or less. Observational studies suggest that up to half of patients treated with chronic corticosteroids develop fractures, which are often asymptomatic.7 Even after only one year of treatment, the incidence of new fractures can be as high as 17%.8 In a retrospective cohort study comparing patients on long-term corticosteroids to healthy persons, the risk of fractures was found to be increased by 1.55-fold for daily prednisone doses lower than 2.5 mg and 2.59-fold for doses between 2.5 mg to 7.5 mg.9 Because bone density is most significantly decreased within the first 6 to 12 months of therapy, the duration of corticosteroid treatment should be limited to less than a year7 and preventive