Acta Demato-Venereologica 98-2CompleteContent | Page 28

SHORT COMMUNICATION Biological and Clinical Response to Omalizumab in a Patient with Bullous Pemphigoid Sébastien MENZINGER 1 , Gürkan KAYA 1 , Enno SCHMIDT 2 , Lionel FONTAO 3 and Emmanuel LAFFITTE 1 1 Department of Dermatology and 3 Laboratory Medicine, University Hospital of Geneva, 1205 Geneva, Switzerland, and 2 Department of Dermatology, University of Lübeck, Lübeck, Germany. E-mail: [email protected] Accepted Nov 13, 2017; Epub ahead of print Nov 13, 2017 Bullous pemphigoid (BP) is an autoimmune blistering disease, with auto-antibodies (autoAb) that target 2 com- ponents of the hemidesmosome: BP180, thought to be the major antigen, and BP230. The majority of IgG autoAb in patients with BP react with the 16 th non-collagenous (NC16A) domain of BP180 (1). In patients with BP, IgE is frequently elevated and specific IgE autoAb, reacting with BP180, and BP230 have been described (2). Several studies have reported variable, but usually high, frequencies of IgE anti-BP180 NC16A domain and IgE anti-BP230 antibodies in the serum of patients with BP and a possible correlation between IgE anti-BP180 levels and disease activity (3–6). The pathogenicity of IgE autoAb in BP remains elu- sive. It is likely that IgE binding to Fc-epsilon receptors (FcεR) on mast cells or eosinophils leads to inflammation and pruritus, causing the urticarial prodromal phase often seen in BP (7, 8). However, 2 studies showed no corre- lation between an urticarial/erythematous phenotype of BP and high levels of serum IgE autoAb (3, 4). In vitro, IgE autoAb act in a FcR-independent manner through direct binding to keratinocyte antigens, which trigger interleukin (IL)-6 and IL-8 release by keratinocytes and a decrease in hemidesmosomes (9). This may ultimately contribute to the weakening of the adhesive strength at the dermal–epidermal junction (DEJ) seen in BP. We report here a case of severe BP in a patient having both IgE and IgG anti-BP180 and BP230 autoAb, which was treated successfully with omalizumab, a humanized monoclonal antibody that binds to the receptor-binding portion of IgE. 284 Fig. 1. Clinical picture and laboratory findings. (a) Patient’s right leg with blisters and erosions. Direct immunofluorescent microscopy of the patient’ skin (perilesional skin) at disease onset, demonstrating (b) linear IgE and (c) IgG deposition at the dermal–epidermal junction (DEJ). (d) Negative control. Ten months after disease onset, (f) IgG, but not (e) IgE, was still found at the DEJ. Highly anti-IgE stained cells, presumably mast cells, in the dermis (b, e) arrowhead. (Scale bar 20 µm). (g) Characterization of IgG and IgE autoAb by immunoblotting analysis of normal human keratinocytes extract. In our patient’s sera (BP1), IgG reactivity was found, at 0 and 10 months with a high molecular mass antigen similar to BP230 (5E) and to BP control serum reactive to BP230 in enzyme-linked immunoassay (ELISA) (BP2). Patient’s sera, but not BP2, also contain IgE autoAb recognizing a 230 kDa antigen. No IgG or IgE reactivity was found at 180 kDa. No specific reactivity was found in the serum from a healthy donor normal human serum (NHS), arrowheads denote unspecific reactivity found in all sera. *Probable reactivity with BP230 proteolytic products. doi: 10.2340/00015555-2845 Acta Derm Venereol 2018; 98: 284–286 CASE REPORT A 76-year-old woman with mul- tiple comorbidities (dementia, chronic renal failure, ischaemic cardiopathy, gastro-duodenal ulcer, osteoporosis) presented with an intense pruritic disease that had been present for several weeks, with diffuse eczematous patches, excoriations, crusts and tense blisters (Fig. 1). Blood tests revealed elevated eosinophil count and high levels of total IgE (Table I). A lesional skin biopsy showed spongiosis and subepidermal blister with accumulation of eosinophils in the blister cavity and the underlying dermis. Direct im- munofluorescence (DIF) micro­ scopy disclosed linear deposits of IgG, IgE, and C3 at the DEJ (Fig. 1). Circulating IgG and IgE reacting with the epidermal side of 1M NaCl split normal human skin were detected by indirect IF microscopy. High serum levels of anti-BP180 NC16A IgG and IgE, and anti-BP230 IgG were found by enzyme-linked im- munoassay (ELISA) (Table I). By immunoblotting with extract of cultured normal human kera- tinocyte, IgG and IgE antibodies reacted exclusively with BP230 (Fig. 1). These findings sug- gested that IgE autoAb targeting DEJ antigens were implicated in This is an open access article under the CC BY-NC license. www.medicaljournals.se/acta Journal Compilation © 2018 Acta Dermato-Venereologica.