Claire Duretz1, Frank Antonicelli2,3, Céline Muller2, Nina Antonicelli2, Julie Plee1, Manuelle Viguier1,2, Philippe Bernard1,2. 1. Department of Dermatology, Reims University Hospital, University of Reims Champagne-Ardenne, Reims, France. 2. Laboratory of Dermatology, Faculty of Medicine, EA 7509, University of Reims Champagne-Ardenne, Reims, France. 3. Department of Biological Sciences, Immunology, UFR Odontology, University of Reims Champagne-Ardenne, Reims, France.
Abstract
Importance: 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. Objective: 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. Results: 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.
Importance: 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. Objective: 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. Results: 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.
Authors: Pascal Joly; Jean-Claude Roujeau; Jacques Benichou; Catherine Picard; Brigitte Dreno; Emmanuel Delaporte; Loic Vaillant; Michel D'Incan; Patrice Plantin; Christophe Bedane; Paul Young; Philippe Bernard Journal: N Engl J Med Date: 2002-01-31 Impact factor: 91.245
Authors: Dedee F Murrell; Benjamin S Daniel; Pascal Joly; Luca Borradori; Masayuki Amagai; Takashi Hashimoto; Frédéric Caux; Branka Marinovic; Animesh A Sinha; Michael Hertl; Philippe Bernard; David Sirois; Giuseppe Cianchini; Janet A Fairley; Marcel F Jonkman; Amit G Pandya; David Rubenstein; Detlef Zillikens; Aimee S Payne; David Woodley; Giovanna Zambruno; Valeria Aoki; Carlo Pincelli; Luis Diaz; Russell P Hall; Michael Meurer; Jose M Mascaro; Enno Schmidt; Hiroshi Shimizu; John Zone; Robert Swerlick; Daniel Mimouni; Donna Culton; Jasna Lipozencic; Benjamin Bince; Sergei A Grando; Jean-Claude Bystryn; Victoria P Werth Journal: J Am Acad Dermatol Date: 2011-11-05 Impact factor: 11.527
Authors: Julie Plée; Sébastien Le Jan; Jérôme Giustiniani; Coralie Barbe; Pascal Joly; Christophe Bedane; Pierre Vabres; François Truchetet; François Aubin; Frank Antonicelli; Philippe Bernard Journal: Sci Rep Date: 2015-12-14 Impact factor: 4.379