What are the clinical and immunologic characteristics of bullous pemphigoid associated with transient palmoplantar keratoderma, an association that has been described very rarely?
In this case series of 6 patients, a transient palmoplantar keratoderma appeared in a severe subtype of bullous pemphigoid with a generalized, multibullous disease associated with high anti-BP180 serum titer and recurrent relapses resistant to superpotent topical corticosteroid therapy. Palmoplantar keratoderma was transient and healed in all cases following bullous pemphigoid control with additional immunosuppressive therapy.
Palmoplantar keratoderma appeared in patients with an initial severe disease and after a prolonged period of clinical activity punctuated with recurrent relapses; this transient palmoplantar keratoderma could represent a clinical maker of severe, treatment-resistant bullous pemphigoid and may potentially be associated with peculiar pathophysiological mechanisms.
Development of transient palmoplantar keratoderma (PPK) with bullous pemphigoid (BP) has only been described in 2 isolated case reports. The clinical significance and the pathophysiologic mechanisms of this association are unknown.
To examine the clinical characteristics and immunological profile of patients with BP who develop transient PPK and analyze therapeutic options and outcomes.
Design, Setting, and Participants
In this case series, patients with BP who developed acquired, transient PPK, and were treated at a single institution from January 1, 2015, through December 31, 2017, were studied.
Main Outcomes and Measures
Clinical and immunological activity of BP, treatment administrated before and after PPK appearance, and patient outcomes.
Six patients with BP and transient PPK were identified and included in the study. There were 5 women and 1 man with a mean age of 72 years. At baseline, all patients had a generalized, multibullous BP and high serum anti-BP180 antibodies (mean, 130 U/mL; range, 73-150), whereas anti-BP230 antibodies were elevated in only 1 case. The PPK appeared a mean 6.2 (range, 2-12) months after BP diagnosis, following a prolonged period of disease activity with recurrent flares. When the PPK occurred, BP was uncontrolled on therapy (mean Bullous Pemphigoid Disease Activity Index [BPDAI] score, 57; range, 34-105; mean anti-BP180 antibodies titer, 122 U/mL; range, 81-150). On administration of additional systemic immunosuppressive therapies, the PPK healed progressively in a mean 4.3 months (range, 2-9), along with BP clinical remission in 4 of 6 patients. No relationship was found between PPK occurrence and anti-BP180/230 antibodies profiles. In contrast, blister fluids collected at the time of PPK displayed a much higher level of interleukin 1β (IL-1β) compared with those collected in the absence of PKK. Expression of IL-17A, IL-17F, and IL-22 was also enhanced in the blister fluid of patients with BP who had PPK
Conclusions and Relevance
To our knowledge, this is the first report of 6 cases of BP with transient PPK with extensive immunological investigation. The PPK appeared after a prolonged period of clinical BP activity punctuated with recurrent relapses, was transient, and healed after BP control with additional immunosuppressive therapy. Enhanced expression of a particular cytokine panel in the blister fluid at time of PPK could support keratinocyte proliferation as described in patients with psoriasis. Transient PPK could represent a clinical marker of severe, treatment-resistant BP.