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.     

Comparison of reactivity and epitope recognition between sera from American and Italian patients with oral pemphigoid

Mucous membrane pemphigoid (MMP) (also known as cicatricial pemphigoid) is a rare autoimmune mucocutaneous blistering disease that affects mucous membranes derived from stratified squamous epithelium and the skin. A subset of MMP affects only the oral cavity and is referred to as the oral pemphigoid (OP). MMP and OP are characterized by subepithelial vesicles on histology and in vivo deposition of immunoglobulins and complement at the basement membrane zone (BMZ) on immunopathology. Previous studies have shown that sera of patients with MMP bind to human integrin beta4, while sera of patients with oral pemphigoid bind to the integrin alpha6 component of the heterodimer. The prognosis in MMP is grave but excellent in OP. In this study we compare the binding of sera from patients with OP from Boston, MA, USA to Naples, Italy, and attempt to identify an epitope to which the anti-integrin alpha6 human autoantibody binds. Our results indicate that the sera from Boston and Naples are identical in their reactivity. They recognize a fragment I (AA 23-462) and its subfragment IB (AA 217-462) only, in the human integrin alpha6 molecule. Blocking studies, immunoprecipitation and immunoabsorbtion studies confirm the presence of this single 245 AA region. Antibodies to subfragment IB cause BMZ separation in organ culture using normal human oral mucosa as substrate. This preliminary study indicates that patients on both continents may have similar reactivity and suggests that an intercontinental study group could be established to advance our understanding of the pathogenesis of OP and the biology of anti-alpha6 integrin autoantibodies.     

金匮肾气丸与糖皮质激素配伍治疗大疱性类天疱疮临床疗效观察

目的 观察金匮肾气丸联合糖皮质激素治疗大疱性类天疱疮的临床疗效、激素用量,探讨中西医结合方法治疗类天疱疮的可行性、安全性.方法 选择经临床及病理诊断的大疱性类天疱疮30例,随机分为2组,对照组给予泼尼松0.75 mg/(kg·d),研究组在此基础上加服金匮肾气丸1丸/次,2次/d.采用《大疱病临床研究观察表》记录患者每天新发水疱数、全身总水疱数和激素剂量等.结果 两组患者每天新发水疱数、全身总水疱数均减少,研究组较对照组水疱数减少更为明显(P＜0.01),但激素剂量和不良反应均小于对照组(P＜0.01).结论 金匮肾气丸与糖皮质激素配伍治疗类天疱疮具有疗效高、安全性高、不良反应小的特点,是值得临床推广的中西医结合治疗手段.     

Bullous pemphigoid with a prolonged prodrome

Bullous pemphigoid is an autoimmune blistering skin disease of the elderly that may be preceded by a pruritic, urticarial or eczematous eruption. We report a case of bullous pemphigoid preceded by prodromal eczematous eruptions that lasted an unusually long time of 11 years. Elderly patients with persistent pruritic or eczematous eruption of unknown etiology should be carefully followed, as bullous pemphigoid may be a potential diagnosis.     

Evidence-based management of bullous pemphigoid

Bullous pemphigoid (BP) is the most common autoimmune subepidermal bullous disease typically affecting the elderly. Although different therapeutic regimens have been proposed, a review of the evidence is needed to aid clinicians in their decision making and management. Systemic therapies such as corticosteroids and adjuvants are effective in BP but are plagued with adverse effects, and potent topical steroids are an alternative treatment. This article reviews the evidence supporting different therapeutic options in the management of BP.     

Azathioprine in the treatment of autoimmune blistering diseases

Although there are no standard guidelines for the treatment of autoimmune blistering diseases, azathioprine has shown good efficacy in acquired autoimmune blistering diseases, and is well tolerated. Side effects of azathioprine normally occur in mild variants. Severe reactions are due to reduced thiopurine S-methyltransferase (TPMT) or inosine triphosphate pyrophosphohydrolase (ITPA) activity. Therefore, screening for TPMT activity should be conducted in white patients and Africans, whereas Japanese should be screened for ITPA activity before therapy with azathioprine is started. Azathioprine is clinically meaningful for the treatment of pemphigus.     

The autoimmune blistering diseases in Australia: status and services

The exact epidemiology of autoimmune bullous disorders in Australia is unknown. This article describes the establishment of a registry and support group to serve patients with these disorders. The registry aids research in Australia by providing epidemiologic data and maintaining an up-to-date database with patient contact details. The support group caters to the needs of patients and/or caregivers. Teledermatology, diagnosis, and management of autoimmune bullous disease are briefly reviewed.