British Association of Dermatologists' Guidelines for the Management of Pemphigus Vulgaris 2017

K.E. Harman; D. Brown; L.S. Exton; R.W. Groves; P.J. Hampton; M.F. Mohd Mustapa; J.F. Setterfield; P.D. Yesudian

Disclosures

The British Journal of Dermatology. 2017;177(5):1170-1201. 

In This Article

General Principles of Management

PV is an uncommon and potentially life-threatening disease requiring immunosuppressive treatment. It should be managed by secondary-care physicians experienced in the treatment of autoimmune mucocutaneous diseases. The management of active oral PV with systemic therapies should be approached in the same way as the management of active skin disease and could be managed by dermatologists where oral medicine expertise is not available.

The management of PV can be considered in two main phases: induction of remission and maintenance of remission.

Remission Induction

In remission induction the initial aim of treatment is to induce disease control, defined as new lesions ceasing to form and established lesions beginning to heal.[47] Corticosteroids are the most effective and rapidly acting treatment for PV, hence they are critical in this phase. Using corticosteroids, disease control typically takes several weeks to achieve (median 3 weeks).[50] During this phase the intensity of treatment may need to be built up rapidly to suppress disease activity. Although adjuvant drugs are often initiated during this phase, their immediate therapeutic benefit is relatively limited because of their slower onset. They are rarely used alone to induce remission in PV.

After disease control is achieved there follows a consolidation phase during which the drug doses used to induce disease control are continued. The end of this consolidation phase is defined arbitrarily as being reached when 80% of lesions have healed, both mucosal and skin, and there have been no new lesions for at least 2 weeks.[47] This phase may be relatively short, but could be considerably longer if there is extensive cutaneous ulceration. Healing of oral ulceration tends to take longer than that for skin, with the oral cavity often the last site to clear in those with mucocutaneous PV. The end of the consolidation phase is the point at which most clinicians would begin to taper treatment, usually the corticosteroid dose. Premature tapering of corticosteroids, before disease control is established and consolidated, is not recommended.

Remission Maintenance

After induction there follows a maintenance phase during which treatment is gradually reduced (see section 11·3), in order to minimize side-effects, to the minimum required for disease control. The ultimate goal of treatment should be to maintain remission on prednisolone 10 mg daily or less, with 10 mg being the dose designated arbitrarily as 'minimal therapy' by international consensus.[47] PV is a chronic disease, and in one study 36% of patients required at least 10 years of treatment.[51]

Systemic corticosteroids are the most important element of remission induction and consolidation. In general, adjuvant drugs are slower in onset than corticosteroids. Their main role is in remission maintenance. Adjuvant drugs are combined commonly with corticosteroids with the aim of increasing efficacy and reducing maintenance corticosteroid doses and subsequent corticosteroid side-effects. Although mortality and complete remission rates have improved since the introduction of adjuvant drugs, this is in comparison with historical controls. Until 2017 there had been no prospective, high-quality controlled studies that demonstrated conclusively the presumed benefits of adjuvant drugs in PV.[52] Therefore, some authorities have not used adjuvant drugs unless there were contraindications or side-effects of corticosteroids, or if tapering the corticosteroids dose was associated with repeated relapses.[9] Some trials demonstrated lower cumulative corticosteroid doses, but without a difference in primary disease outcome measures, for azathioprine, cyclophosphamide and mycophenolate mofetil,[53–55] which we believe is a clinically relevant outcome. A systematic review and meta-analysis, which included 10 trials and pooled adjuncts together, concluded that they were not beneficial for achieving remission but collectively decreased risk of relapse by 29%.[55] Despite this sparsity of evidence, it was commonly believed that adjuvant drugs were likely to be beneficial, as proven in other areas of autoimmunity, and most centres use them as standard practice. In 2017, the first RCT conclusively demonstrating the benefit of an adjuvant drug was published: rituximab combined with short-term prednisolone showed superior efficacy to prednisolone alone, with rates of complete remission of PV, off all treatment, of 89% compared with 28% at 2 years.[45]

An overview of PV management, with the aim of providing a brief reference for the clinical setting, is summarized in Table 1, and a more detailed description follows.

Treatment Withdrawal

Withdrawal of treatment is a realistic aim, with one study reporting rates of complete remission off-therapy of 38%, 50% and 75% achieved in 3, 5 and 10 years from diagnosis, respectively.[56] Another study reported that 59% of patients were off treatment after a mean treatment duration of 3 years and this outcome was not associated with initial disease severity.[57] However, withdrawal of treatment should be cautious and not done prematurely; relapse rates are high initially, with 47% of successfully treated patients relapsing in one trial when treatment was stopped after 1 year.[58]

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