A case of atezolizumab‐induced photodistributed bullous pemphigoid

Immunotherapy has revolutionized cancer therapy in recent years but is associated with unique immunologically mediated adverse effects. Immunotherapy‐induced bullous pemphigoid (BP) is an uncommon but established reaction that portends significant management implications as in most instances systemic treatment is required. We report a case of immunotherapy‐associated BP in a marked photodistribution, highlighting the diverse clinical presentations of this eruption.     

Mycophenolic acid in dermatology a century after its discovery

Mycophenolic acid was first discovered in 1913 and first used clinically in the 1970s as an immunosuppressant to prevent organ transplantation rejection. It was later used in the treatment of psoriasis. However due to its side‐effect profile and fears over its carcinogenic potential it was abandoned. From the late 1990s a prodrug, mycophenolate mofetil (MMF), was developed and more recently, enteric‐coated mycophenolate sodium (EC‐MPS), both of which have gained increasing use in the field of dermatology for a variety of skin conditions. This review discusses the pharmacology, mechanisms of action, side‐effects and current clinical applications in dermatology of MMF and EC‐MPS.     

Lichen Planus Pemphigoides Presenting Preferentially Over Preexisting Scars: A Rare Instance of Isotopic Phenomenon

An 18-year-old girl presented with multiple itchy hyperpigmented papules and plaques, along with tense blisters over the lower limbs and buttocks for last 3 months. These papules, plaques, and bullae were mostly localized to preexisting scars. The histopathological findings from papule and bulla were consistent with lichen planus (LP) and bullous pemphigoid, respectively. Direct immunofluorescence (DIF) of perilesional skin around bulla showed linear deposition of IgG and C3. Considering clinical, histopathological and DIF findings, diagnosis of LP pemphigoides (LPP) was made. The preferential localization of LPP lesions over preexisting scars was a very interesting finding in our case an extremely rare instance of the isotopic phenomenon.     

Sensitivity of indocyanine green angiography for the follow-up of active inflammatory choriocapillaropathies

BACKGROUND: Inflammatory choriocapillaropathies (choriocapillaritis) correspond to the clinical spectrum of lesions of the fundus, including acute posterior multifocal placoid pigment epitheliopathy (APMPPE), multiple evanescent white dot syndrome (MEWDS), multifocal choroiditis (MC), and other rarer entities caused by inflammatory disturbances of choriocapillaris perfusion. The aim here was to study the sensitivity of indocyanine green (ICG) angiography in investigating and following inflammatory choriocapillaropathies. PATIENTS AND METHODS: Patients with inflammatory choriocapillaropthies were included who had had a dual fluorescein and ICG angiography as well as visual field testing (Goldman or computerized perimetry) at presentation and on follow-up visits. ICG angiography was performed according to a routine angiographic protocol used for inflammatory diseases and was correlated with fundus examination, fluorescein angiography, and visual field testing. RESULTS: Three patients with MEWDS, two with APMPPE, and two with MC were included. The visual field alterations in all seven patients were well correlated with the extent of the hypofluorescent areas seen on ICG angiography, whereas they were badly correlated with fluorescein angiographic signs and their evolution. The visual field in MEWDS was particularly well correlated with the importance of peripapillary hypofluorescence seen on ICG angiography. In MC, the evolution of new lesions was well demonstrated by ICG angiography and well correlated with visual symptoms and visual fields, but was barely detected on fundus examination and by fluorescein angiography. CONCLUSIONS: ICG angiographic signs were shown to be closely correlated with visual function (visual field testing). This was not the case for either fundus examination or fluorescein angiography. ICG angiography appears as a very sensitive follow-up parameter in inflammatory choriocapillaropathies, giving morphological information on the evolution of the disease and on the response to treatment when therapy is indicated.     

Activation of coagulation in bullous pemphigoid and other eosinophil-related inflammatory skin diseases

Bullous pemphigoid (BP) is a skin disease caused by autoantibodies to hemidesmosomal proteins BP180 and BP230, with eosinophils participating in blister formation. Tissue factor (TF), the initiator of coagulation, is embodied within the eosinophil granules and exposed upon activation. We evaluated the coagulation activation in patients with BP (63), chronic urticaria (CU; 20), atopic dermatitis (AD; 14), cutaneous drug reactions (CDRs; six), psoriasis (20), dermatitis herpetiformis (DH; four) and primary cutaneous T cell lymphoma (CTCL; five), and in 40 healthy controls. Prothrombin fragment F1+2 and d-dimer (coagulation markers) were measured by enzyme-linked immunosorbent assay (ELISA) in all plasma samples and BP blister fluid. Skin TF expression was evaluated immunohistochemically in the patients and 20 controls. F1+2 and d-dimer levels were higher in BP plasma than in control plasma (P = 0·0001 for both), and dramatically high in blister fluid; both correlated positively with disease severity, esinophil counts and anti-BP180 antibodies (P = 0·006-0·0001). Plasma F1+2 and d-dimer levels were higher in the CU, AD and CDR patients than in controls (P = 0·0001 for all), but normal in the psoriasis, DH and CTCL patients. Skin TF was expressed in the BP (P = 0·0001), CU (P = 0·0001), AD (P = 0·001) and CDR patients (P = 0·01), but not in the psoriasis, DH or CTCL patients. Co-localization confocal microscopy studies confirmed eosinophils as the source of TF in 10 BP patients. The coagulation cascade is activated in BP and other eosinophil-mediated skin disorders, but not in non-eosinophil driven conditions. This hypercoagulability may contribute to inflammation, tissue damage and, possibly, thrombotic risk.     

T and B cells target identical regions of the non-collagenous domain 1 of type VII collagen in epidermolysis bullosa acquisita

Epidermolysis bullosa acquisita (EBA) is a severe immunobullous disease and is caused by IgG against type VII collagen (Col VII) of anchoring fibrils. In this study, utilizing ELISA and immunoblot, 13/15 EBA sera but 0/20 bullous pemphigoid sera and 0/30 healthy control sera showed IgG reactivity with distinct recombinant subregions of the non-collagenous domain 1 (NC1) of Col VII. In two EBA patients, IgG titers against Col VII-NC1 were grossly correlated to clinical disease activity. Moreover, Col VII-reactive T cells were identified in a representative EBA patient which recognized identical subdomains of Col VII-NC1. These findings strongly suggest that (1) the Col VII-NC1 ELISA is a powerful tool for making the diagnosis of EBA, (2) Col VII-specific IgG grossly relates to disease activity and (3) IgG reactivity is associated with T cell recognition of identical subdomains of Col VII-NC1.