The different types of corticosteroids used in pemphigus include oral prednisone/prednisolone in remission or maintenance therapy, dexamethasone as used in oral pulsed dosage for remission and topical application for local or mucosal disease [7, 8]. Intravenous therapy is used only in acute life-threatening situations. Table 46.2 presents the current recommendations and levels of evidence available for corticosteroid use in AIBD. A recent systematic review and meta-analysis [7] examined an RCT of 22 participants comparing low-dose (45–60 mg/day) to high-dose (120–180 mg/day) oral prednisolone in a cohort of newly diagnosed pemphigus vulgaris (PV) and pemphigus foliaceus (PF) patients [9]. Whilst the low number of participants made the study underpowered, no significant difference in the time to disease control (defined by the authors as no new lesions for 1 week and beginning of healing of existing lesions) was demonstrated [9]. Rates of ‘remission’ (defined by the authors as therapy of 15 mg prednisolone per day between the high-dose and low-dose steroid group as recorded over a 5-year period) were also not statistically different (p = 0.30) [9]. With regard to pulsed corticosteroid use, another RCT of 20 participants [10] compared the efficacy of adjuvant pulsed oral dexamethasone (300 mg/day for three consecutive days, monthly) versus placebo in newly diagnosed patients concurrently treated with prednisolone and azathioprine. Importantly, the rates of adverse outcomes were significantly higher amongst the pulsed corticosteroid cohort when compared to the continuous dosage cohort (p < 0.01) [10]. It is important to note that the patients enrolled in this study did not have severe or refractory disease and that pulsed corticosteroids may have a useful role in those particular subgroups of patients [8]. Dexamethasone was also associated with higher rates of corticosteroid-associated adverse effects [10]. This again highlights the importance of a dynamic corticosteroid regimen individualized for each patient depending on their individual disease severity, treatment response, and degree of adverse effects from therapy. Topical corticosteroid use in PV and PF has been documented in a number of case reports [11, 12], and expert recommendations state it may be useful in localized or mild disease [8]. No controlled trials exist to formally evaluate its efficacy, but typically, highly potent corticosteroids such as clobetasol propionate ointment are used [8, 13].

In the management of bullous pemphigoid (BP), potent topical preparations of high-potency steroids are used for mild to moderate disease and, depending on the country, potent topical or systemic corticosteroids for more severe disease [14]. As BP is usually a disease of the elderly, mortality of those diagnosed with BP is relatively high and has not improved compared to untreated controls despite the introduction of corticosteroids and other immunomodulating agents [14, 15]. Parker [15] suggests that as the natural history of BP is self-limiting and the majority of patients succumb to causes unrelated to their BP, adverse effects from systemic corticosteroids may actually increase the risk of mortality [15]. A recent Cochrane systematic review and meta-analysis [14] examined an RCT of 26 participants comparing high-dose (1.25 mg/kg) and low-dose (0.75 mg/kg) oral prednisolone in patients with newly diagnosed BP [16]. Fifty-one per cent of patients in the low-dose cohort compared to 64 % of high-dose cohort patients achieved disease control by day 21. No significant difference between time to disease control or overall mortality was found. A second study of 57 BP patients, comparing oral prednisolone to methylprednisolone over a 10-day period, found no significant difference in rates of control or decrease in the number of bullous lesions between the two treatment groups [17]. Self-reported pruritus scores were found to be significantly improved in the methylprednisolone cohort compared with the prednisolone cohort [17]. Examination of the methodology of the study shows that randomization and blinding were adequate, although the degree of allocation concealment was uncertain, questioning the reliability of this result. In 2002, the French bullous group lead by Pascal Joly published a landmark RCT comparing topical clobetasol propionate with oral prednisone in BP. This demonstrated a significant advantage of topical clobetasol propionate (0.05 %, 40 g/day) over oral prednisone (1 mg/kg/day) in individuals with severe bullous pemphigoid (defined as more than ten new blisters per day) in regard to overall mortality within 1 year of initiation of treatment [18]. The significance of this finding increased when multiple regression analysis took into account age and functional status. Importantly, Joly’s study also had adequate power to detect a decrease in the 1-year mortality rate in both severe and moderate disease groups. This lends credence to the suggestion that in severe BP, systemic corticosteroids may have a deleterious effect upon mortality rates when compared to topical high-potency corticosteroids. A follow-on study by the French group with 309 participants [19] found that lower doses of clobetasol propionate (0.05 %, 10–30 g/day) had non-inferior mortality rates than the standard regimen of 40 g/day in both severe and moderate disease. When adjusted for age and functional status, the authors concluded that the lower doses were more beneficial to patients with both moderate and severe disease, with lower rates of mortality or life-threatening adverse effects (including sepsis, diabetes mellitus) than the original 2002 study [14, 19]. Secondary outcomes such as time to disease control (defined as no new bullae for three consecutive days) were not significantly different between the standard and low-dose treatment groups (p = 0.56). Rates of disease relapse (defined as three new bullae daily for three consecutive days) were not significant during the period of treatment, and only significant at 12 months posttreatment with 30 % rate of relapse in the standard treatment group and 45 % rate of relapse in the low-dose treatment group (p = 0.012) [19]. Whilst the evidence may suggest that twice-daily topical corticosteroids are beneficial over oral dosing, the practicalities of application by or to elderly patients with multiple comorbidities are a significant barrier to the implementation of these recommendations.

There is a paucity of evidence from RCTs regarding treatments for mucous membrane pemphigoid (MMP), cicatricial pemphigoid (CP), and other subtypes of AIBD which contain mucous membrane involvement, most often the mouth, the eyes, and the genital areas. Expert recommendations cite topical therapies such as clobetasol propionate, betamethasone valerate, and dexamethasone mouthwashes; however, in the case of the eyes, the early stages may mimic conjunctivitis and other non-scarring processes, and if MMP is not recognized early, scarring may occur with topical only therapy [20, 21]. The only RCT related to MMP addressed the treatment of ocular involvement with dapsone or cyclophosphamide, finding that cyclophosphamide is the most effective treatment for severe ocular involvement [21]. There were no RCTs of steroid use in either MMP or EBA. Furthermore, no reliable evidence sources have been found to date to further elucidate the efficacy of topical treatments in these conditions.

Steroid use in linear IgA disease can be separated into topical and systemic regimens. Whilst potent topical steroids such as clobetasol propionate 0.05 % has been recommended for mild disease, it can also have a role in symptom control whilst the offending stimulant is removed in drug-induced disease [22]. No RCTs have been identified to date regarding the efficacy of corticosteroids in linear IgA disease, and expert recommendation quotes dapsone as a first-line agent [22, 23], with other immunosuppressive and immunomodulating agents such as mycophenolate mofetil (MMF) also having reports of successful treatment [22]. In this regard, systemic corticosteroids are only considered a useful adjunctive treatment in the setting of other therapies, and to this end, evidence of its usefulness is lacking.

Epidermolysis bullosa acquisita (EBA) is characterized by autoantibodies to collagen VII, which may present in several clinical forms, and treatment is therefore challenging. A recent Cochrane review found no RCTs of treatment modalities in EBA, although a handful of nonrandomized studies were found involving a wide variety of immunosuppressive and immunomodulating therapies [24, 25]. Due to the adverse outcomes of high-dose steroids needed to successfully control EBA, other management strategies such as intravenous immunoglobulins (IVIG) and anti-CD20 monoclonal antibodies (rituximab) have come to the fore as the mainstay of treatment in EBA [24]. Whilst prednisone/prednisolone 0.5–1.0 mg/kg/day is still included in the initial treatment regimen, recalcitrant or severe disease management concentrates on other immunomodulating therapies such as cyclosporine, plasmapheresis, and colchicine for maintenance therapy. Ishii states [25] that pulsed corticosteroids may also be useful in severe disease, although these recommendations have not been borne out in randomized trials.