**8. Systemic corticosteroids**

these desmoglein ectodomains have been expressed in insect cells (MBL, Nagoya, Japan), or in human HEK293 cells (Euroimmun, Lubeck, Germany) [43]. Meta-analyses suggest that available ELISAs are highly sensitive and specific, and has a higher diagnostic accuracy than indirect immunofluorescence [44]. The quantification of these autoantibodies is useful in monitoring disease activity because the titre of circulating autoantibodies has been observed to correlate with disease activity. Specifically, the level of desmoglein-1 antibodies matches the severity of skin disease, and the level of desmoglein-3 reflects the severity of mucosal

**Figure 10.** Indirect immunofluorescence with the serum of a patient with pemphigus foliaceus and monkey oesopha‐ gus substrate reveals deposition of specific IgG in the intercellular cement space substance of the epidermis resulting

in a chicken wire appearance. There is an increased deposition in the upper layers of the epidermis.

Therapy has resulted in a drastic decline of the mortality from pemphigus rate to below 7% [24],[47]; however, mortality still occurs, predominantly iatrogenic, caused by complications of the immunosuppressive therapy [24],[47]. PF tends to have a relatively benign course compared with PV. However, mortality rates of untreated endemic PF are still very high, ranging from 40 to 60% [48],[49]. With appropriate treatment endemic PF has a mortality rate of less than 10% [48]. The mortality of PV was 75% before the introduction of corticosteroids in the early 1950s [47]. Studies that differentiate PV according to clinical phenotype have shown a lower mortality in patients with predominantly mucosal PV (1–17%) compared with those with mucocutaneous PV (34–42%)[24]. Hence, the goal of managing patients with pemphigus is inducing and maintaining remission using those evidenced-based treatments that have a

Pemphigus is a rare disease and therefore it is not surprising that only a few blinded random‐ ized controlled trials have been performed to guide treatment decisions. A 2009 Cochrane

disease [45],[46].

116 Skin Biopsy - Diagnosis and Treatment

**7. Treatment**

favourable side effect profile.

Systemic corticosteroids are currently the mainstay of treatment as they have a rapid onset of action and are effective in controlling disease and improving prognosis [52]. However significant side effects such as diabetes, osteoporosis, adrenal suppression, peptic ulceration, weight gain, increased susceptibility to infection, mood changes, proximal myopathy, Cushing's syndrome, and cataracts limit their usefulness. Adjuvant treatments have therefore been introduced as steroid sparing agents. Various corticosteroid regimens are used to treat pemphigus, the most common of which is a gradual reduction of an oral formulation [47]. In newly diagnosed patients, an initial daily dose of 0.5 mg/kg of prednisone/prednisolone, (or equivalent) appears preferable to 1 mg/kg. A randomized trial compared these two regimens in 19 patients with PV and 3 with PF followed for 5 years, with remission defined as less than 15 mg of corticosteroids per day to maintain disease control [53]. No difference was observed in remission or the incidence of complications between the high and low dose regimens. In a randomized trial that included only patients with newly diagnosed PV, pulsed oral dexame‐ thasone provided no additional benefit to the combination of oral prednisone and azathioprine with remission defined as cessation of systemic treatment [54]. Furthermore, there were an increased number of adverse events in those participants receiving pulsed dexamethasone. However, the possible benefit of high dose pulsed intravenous corticosteroids in achieving disease control and maintaining remission was suggested in a small case-controlled retro‐ spective study of patients with PV initially unresponsive to low dose of prednisone (less than 40 mg daily) [55] and an open study of new diagnosed PV patients [56]. There have no studies to date examining the effects of high dose pulsed intravenous corticosteroids in PF.

Currently no optimal regimen for corticosteroid therapy has been defined for the treatment of pemphigus despite its proven benefits. Hence in routine practice, a tailored regime is recom‐ mended. A starting dose of prednisolone 0.5 mg/kg daily is prudent that may need to be increased, until no new blister formation is observed. Such higher doses of corticosteroids including pulsed therapy may be warranted in newly diagnosed severe disease and recalci‐ trant disease but this remains to be substantiated in randomized studies.
