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

Oral Corticosteroids (Strength of Recommendation B, Level of Evidence 1+; See Appendices)

Systemic corticosteroids are the best established therapy for the management of PV. Their introduction in the early 1950s resulted in a dramatic fall in mortality to an average of 30%,[9] with complete remission rates off-therapy of 13–20%.[9,59] Outcomes have continued to improve, and recent studies have shown that the rate of complete remission on low-dose corticosteroids (prednisolone 10 mg per day or less) is 52–76% at 1 year with very few deaths.[53,54,60,61]

Clinical improvement may be seen within days of starting corticosteroids and, on average, cessation of blistering takes 2–3 weeks[50,53,61–64] while full healing may take 3–8 weeks.[50,61,65] IIF titres fall with corticosteroid treatment but lag behind clinical improvement.[66]

The optimum corticosteroid dosing schedule is not known, and dosing schedules are largely empirical and based on practical experience. Early studies advocated high doses, for example initial doses of prednisolone 120–400 mg per day.[62,65] However, corticosteroid side-effects were common and dose related,[67,68] with one study estimating that up to 77% of deaths were corticosteroid related.[67] Therefore, a more moderate approach to corticosteroid therapy has been advocated. However, only one RCT has compared dosing schedules; initial therapy with low-dose prednisolone (30–60 mg per day) was compared with high-dose prednisolone (120–180 mg per day) in patients with severe pemphigus (19 with PV, three with PF) affecting > 50% of their body surface. There was no significant difference in the duration to achieve initial disease control or in relapse rates at 5 years, and there were no deaths.[63] However, it should be noted that the dose tapered more rapidly in the high-dose arm so that on average, by week 7 and thereafter, the daily corticosteroid dose was lower in the 'high-dose' arm. In contrast, a retrospective study showed benefit with higher corticosteroid doses: treatment with prednisolone 1·5 mg kg−1 led to significantly shorter times to achieve initial disease control and remission compared with prednisolone 40 mg on alternate days combined with azathioprine, although there were fewer side-effects in the low-dose arm.[60]

It is common practice worldwide to initiate treatment at prednisolone 1–2 mg kg−1 or equivalent,[51,53,54,61,69–73] with a majority of clinicians experienced in managing PV choosing 1 mg kg−1.[69] However, milder cases may be treated with more conservative corticosteroid doses such as 0·5–1 mg kg−1; tailored dosing according to disease severity is well established[9,65] and appropriate,[74] with no evidence to indicate that long-term outcomes are influenced by the intensity of initial treatment.[57,74]

If there is no response within 5–7 days, it is suggested that the dose should be increased in 50–100% increments until disease control is achieved, defined as no new lesions and the onset of healing in pre-existing ones.[9,61,65,71,75] If prednisolone doses above 1 mg kg−1 per day are required, pulsed intravenous corticosteroids should be considered. Treatment failure for oral corticosteroids has been defined by international consensus as failure to achieve disease control despite 3 weeks of prednisolone 1·5 mg kg−1 per day or equivalent.[47]

Once remission is induced and maintained with healing of the majority of lesions, both skin and oral, the dose of corticosteroids can be tapered cautiously. This includes assessing oral lesions, which are often the last to heal. The mouth and other mucosal sites must be examined in addition to the skin. Tapering before disease control is established and consolidated is not recommended. There is no established tapering schedule and those published in clinical trials vary widely,[53,54,58,61,63,71,72,75–79] with the dose by week 12 varying from 5 mg[75] to 60 mg daily.[79] The average tapering rate across these trials was 6 mg per week in the first 3 months.

A 50% reduction every 2 weeks has been suggested.[9] The GDG consensus is initially to reduce the daily dose by 5–10 mg of prednisolone every 2 weeks down to 20 mg daily, then by 2·5 mg every 2–4 weeks down to 10 mg daily and thereafter reduce slowly in increments of 1 mg. Prednisolone doses of 10 mg or less should be the aim of treatment, defined by international consensus as the minimal therapy in PV.[47]

Relapses in the short term can be managed by increasing the corticosteroid dose, although there is no consensus on the optimum way to manage relapses. They are often milder than initial disease presentation and are managed typically with lower corticosteroid doses. Various approaches to managing relapses have been suggested, including reverting to the previous corticosteroid dose at which there was disease control;[80] doubling the corticosteroid dose,[61,63,72] with 50% incremental increases thereafter until disease control;[61] increasing to prednisolone 40 mg per day, or if already greater than this, to the previous dose at which disease control was achieved;[71] and increasing prednisolone dose by 10–20 mg per day.[50,81] Relapses that are more severe should be treated with corticosteroid doses as described for the initial presentation. At the time of relapse, in addition to increasing corticosteroid dose, long-term management should also be considered, as relapses may recur when the corticosteroid doses are tapered again. It may be appropriate to add an adjuvant drug, increase the dose of an existing adjuvant or switch to an alternative, if the current adjuvant drug has been given at a sufficient dose for at least 3 months (Table 1).

It is strongly recommended that guidelines for the prevention of corticosteroid-induced osteoporosis are followed.[30,82] A prednisolone dose of ≥ 7·5 mg for at least 3 months is considered a risk factor in those aged under 40 years, and any dose for those aged over 40 years.[82] Thus, all patients with PV are at risk, assuming they are likely to exceed these limits, and bone health should be considered immediately upon commencing treatment because the rate of bone loss is most marked in the first 6 months of treatment.[83]

Summary

Systemic corticosteroids are a well-established and very effective treatment for PV. They should be used as first-line therapy.

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