Bullous pemphigoid is the most common autoimmune blistering disease and one that is associated with high morbidity and mortality. Treatment can be complicated by advanced age, comorbidities, and cognitive and/or physical limitations of the patients. Traditionally, oral corticosteroids have been used at doses of 0.5-1.5mg/kg, but it has been shown that high-potency topical corticosteroids (HPTCs) applied over the entire body have a similar effectiveness with fewer side effects,1 and so these are recommended as first-line treatment of bullous pemphigoid.2 However, use of these agents can be difficult due to lack of therapeutic adherence given the patient characteristics, logistic constraints, and adverse effects associated with systemic absorption. Among other treatment alternatives, tetracyclines have been widely used for treatment of bullous pemphigoid, thanks to their anti-inflammatory effect (Table 1), low cost, and good tolerability; however, robust evidence of their efficacy has not been available.

Recently, Williams et al.4 published the results of a randomized noninferiority clinical trial (defining an effectiveness margin of 37% as acceptable) comparing doxycycline (200mg/day, 132 patients) with prednisolone (0.5mg/kg/day, 121 patients). Both groups were allowed to apply HPTCs to cutaneous lesions only, without exceeding 30g/week, for the first 3 weeks. The mean age of the patients was 77 years and 68% had moderate or severe bullous pemphigoid. The main outcome measures were effectiveness at 6 weeks, where effectiveness was defined as having ≤3 blisters, and safety, determined by severe adverse effects at 52 weeks. In the doxycycline group, 74% achieved total control of bullous pemphigoid at 6 weeks compared with 91% in the prednisolone group (adjusted difference of 18.6% [90% CI: 11.1%-26.1%]), enabling the conclusion to be drawn that doxycycline was not inferior to prednisolone. Severe adverse effects were reported in 18% of the doxycycline group and 36% of the prednisolone group, including 3 and 11 treatment-related deaths, respectively. The recurrence rate was similar in both groups, as well as the decrease in Dermatology Quality of Life Index. Both treatments were less effective in patients with severe disease, and the use of topical corticosteroids was greater in the doxycycline group.

Despite doubts about whether the 37% limit for noninferiority of doxycycline treatment is acceptable (this limit was based on a survey of dermatologists in the United Kingdom, in which the specialists responded that they would accept up to a 25% reduction in the effectiveness of treatment provided it was accompanied by a reduction in adverse effects4), the study shows that doxycycline is highly effective, and allows adequate disease control with fewer side effects and deaths than with oral corticosteroids. Moreover, in the cost-effectiveness analysis of this study, no significant differences were found between the cost of treatment with doxycycline and with prednisolone.5

In view of the above results, we consider a reasonable therapeutic alternative is to initiate treatment for bullous pemphigoid with doxycycline and HPTC limited to cutaneous lesions, and initiate oral corticosteroids in the event of therapeutic failure.