Updated S2 K guidelines for the management of bullous pemphigoid initiated by the European Academy of Dermatology and Venereology (EADV).

BACKGROUND: Bullous pemphigoid (BP) is the most common autoimmune subepidermal blistering disease of the skin and mucous membranes. This disease typically affects the elderly and presents with itch and localized or, most frequently, generalized bullous lesions. A subset of patients only develops excoriations, prurigo-like lesions, and eczematous and/or urticarial erythematous lesions. The disease, which is significantly associated with neurological disorders, has high morbidity and severely impacts the quality of life. OBJECTIVES AND METHODOLOGY: The Autoimmune blistering diseases Task Force of the European Academy of Dermatology and Venereology sought to update the guidelines for the management of BP based on new clinical information, and new evidence on diagnostic tools and interventions. The recommendations are either evidence-based or rely on expert opinion. The degree of consent among all task force members was included. RESULTS: Treatment depends on the severity of BP and patients' comorbidities. High-potency topical corticosteroids are recommended as the mainstay of treatment whenever possible. Oral prednisone at a dose of 0.5 mg/kg/day is a recommended alternative. In case of contraindications or resistance to corticosteroids, immunosuppressive therapies, such as methotrexate, azathioprine, mycophenolate mofetil or mycophenolate acid, may be recommended. The use of doxycycline and dapsone is controversial. They may be recommended, in particular, in patients with contraindications to oral corticosteroids. B-cell-depleting therapy and intravenous immunoglobulins may be considered in treatment-resistant cases. Omalizumab and dupilumab have recently shown promising results. The final version of the guideline was consented to by several patient organizations. CONCLUSIONS: The guidelines for the management of BP were updated. They summarize evidence- and expert-based recommendations useful in clinical practice.

European guidelines (S3) on diagnosis and management of mucous membrane pemphigoid, initiated by the European Academy of Dermatology and Venereology - Part I.

This guideline on mucous membrane pemphigoid (MMP) has been elaborated by the Task Force for Autoimmune Blistering Diseases of the European Academy of Dermatology and Venereology (EADV) with a contribution of physicians from all relevant disciplines and patient organizations. It is a S3 consensus-based guideline encompassing a systematic review of the literature until June 2019 in the MEDLINE and EMBASE databases. This first part covers methodology, the clinical definition of MMP, epidemiology, MMP subtypes, immunopathological characteristics, disease assessment and outcome scores. MMP describes a group of autoimmune skin and mucous membrane blistering diseases, characterized by a chronic course and by predominant involvement of the mucous membranes, such as the oral, ocular, nasal, nasopharyngeal, anogenital, laryngeal and oesophageal mucosa. MMP patients may present with mono- or multisite involvement. Patients' autoantibodies have been shown to be predominantly directed against BP180 (also called BPAG2, type XVII collagen), BP230, laminin 332 and type VII collagen, components of junctional adhesion complexes promoting epithelial stromal attachment in stratified epithelia. Various disease assessment scores are available, including the Mucous Membrane Pemphigoid Disease Area Index (MMPDAI), the Autoimmune Bullous Skin disorder Intensity Score (ABSIS), the 'Cicatrising Conjunctivitis Assessment Tool' and the Oral Disease Severity Score (ODSS). Patient-reported outcome measurements (PROMs), including DLQI, ABQOL and TABQOL, can be used for assessment of quality of life to evaluate the effectiveness of therapeutic interventions and monitor disease course.

InnOscent system: Advancing flavor analysis using an original gas chromatographic analytical device.

Despite continuous advances in analytical and physiological knowledge, the comprehension of an aroma is still a challenge. Gas chromatography coupled to olfactometry (GC-O) is an efficient method to identify and estimate individual potential of odorants, but there is a gap between this individual characterization and the effective contribution of compounds in the mixture, which is due to complex chemical and perceptual interactions. Therefore, recombination and omission experiments are often performed to achieve an understanding of food aromas. In this study, a chromatographic device, developed to facilitate aroma analysis, is presented. It was configured to perform both (1) conventional analyses by GC coupled with a mass spectrometer, olfactometric port(s), and a flame ionization detector (FID), and (2) omission or recombination experiments. This dual capability is due to the singular configuration of the system using an ingenious combination of splitter and Deans switch microfluidics transfer modules, and the existence of multiple outlets. The operational status of the system was tested using a purposely simple mixture of compounds. The similarity of retention times (RT) and FID peak areas obtained for each outlet demonstrates that the multiple outlets of the system are equivalent. The reproducibility of retention times (RT) and FID peak areas obtained in switching and non-switching conditions, also demonstrates the efficiency of switching operations. The validation of the system enables multiple detectors to be connected to the outlets and complementary information can be obtained from the eluate. The connection of recovery disposals to the outlets provides fraction collection and recombination possibilities, which contribute much to the understanding of aroma-aroma interactions. As an illustration of the InnOscent system relevance for the comprehension of more complex aromas, the device was used to study the aroma of a wine made from Cabernet Franc grape variety. An olfactometric profile was efficiently produced with the device configured as a GC-MS coupled to a dual olfactometric port. The main odorant active compounds were identified. The omission approach, carried out with the system on isopropyl- and isobutyl-methoxypyrazines, demonstrates the significant contribution of these compounds to the aroma of the wine studied, despite an individual perception among the weakest of the aromagram. A similar approach can be used to evaluate the contribution of any compound to any aroma. This approach overcomes constraints of current methodologies associated to reconstituted model solutions and paves the way for a better understanding of aroma construction.

[The persistent sciatic artery aneurysm. A rare and painful buttock mass]. / Anévrisme de l'artère sciatique persistante. Une cause rare de masse fessière douloureuse.

The persistent sciatic artery is a rare cause of painful buttock mass with L5-S1 radicular signs. A 56-year-old man presents a right painful buttock mass with L5-S1 radicular symptoms for 3 years. The surgical exploration found a pulsatile vascular mass like a persistent sciatic artery aneurysm. This vascular pathology is a misunderstood embryogenesis anomaly. The treatment aims to avoid serious complications. This pathology must be known from plastic surgeon.

[Chronic necrotizing pulmonary aspergillosis following an infection by Mycobacterium malmoense]. / Aspergillose pulmonaire chronique nécrosante compliquant une pneumopathie à Mycobacterium malmoense.

Pneumonia due to Mycobacterium malmoense is rare and usually occurs in damaged lung as is the case with Aspergillus infections. We report the case of a patient who developed chronic necrotizing pulmonary aspergillosis following an infection by atypical mycobacteria. A 53-year-old woman was hospitalized because of weight loss and fever. Direct examination of sputum smear was positive for acid fast bacilli and PCR and culture led to the diagnosis of infection with M. malmoense. Treatment was begun with clarithromycin, rifampicin and ethambutol. Despite initial improvement and excellent adherence to treatment, fever and weight loss recurred 6 months later. Relapse of the mycobacterial infection was excluded and the final diagnosis was necrotizing pulmonary aspergillosis. Infection with A. fumigatus complicating the treatment of M. malmoense is unusual. The management is challenging because of strong interactions between voriconazole and rifampicin, and thus requires a multidisciplinary and specialized approach.

[Vascular ischemic lesions of the kidney in multiple trauma patients: incidence and management, a report of 7 cases]. / Lésions vasculaires ischémiques rénales chez le polytraumatisé: incidence et prise en charge à propos de 7 cas.

AIMS: Study the incidence, type and outcome of traumatic ischemic arterial lesions of the kidney in multiple trauma patients. MATERIALS AND METHODS: Retrospective study of 500 multiple trauma patients who underwent whole body 64 slice CT Scan (mean age 34 years old, sex ratio 4M/1W, mean ISS 29). RESULTS: There were seven cases of vascular lesions of the left kidney 1.4% of patients (men, median age 25 years old, mean ISS43.9). These were closed traumas with sudden deceleration and dissection of the renal artery trunk in three cases and injury to its branches in four cases with preserved excretion. Three patients died of associated injuries, including one patient who received a stent on D0. One patient underwent a nephrectomy and the three other patients were not treated which did not affect renal function or pressure (follow-up 19 months). CONCLUSION: We found a high incidence of traumatic renal dissection in multiple trauma patients. Multidetector scan appears to provide the best results for the diagnosis of these lesions as well as the many associated lesions resulting in a very poor prognosis for these patients. Treatment is not well defined and management of these lesions is often of secondary importance because of the severity of associated injuries.

Cerebrovascular disease related to COL4A1 mutations in HANAC syndrome.

BACKGROUND: COL4A1 mutations cause familial porencephaly, infantile hemiplegia, cerebral small vessel disease (CSVD), and hemorrhagic stroke. We recently described hereditary angiopathy with nephropathy, aneurysm, and muscle cramps (HANAC) syndrome in 3 families with closely localized COL4A1 mutations. The aim of this study was to describe the cerebrovascular phenotype of HANAC. METHODS: Detailed clinical data were collected in 14 affected subjects from the 3 families. MRI and magnetic resonance angiography (MRA) were performed in 9 of them. Skin biopsies were analyzed by electron microscopy in affected subjects in the 3 families. RESULTS: Only 2 of 14 subjects had clinical cerebrovascular symptoms: a minor ischemic stroke at age 47 years and a small posttraumatic hemorrhage under anticoagulants at age 48 years. MRI-MRA showed cerebrovascular lesions in 8 of 9 studied subjects (mean age 39.4 years, 21-57 years), asymptomatic in 6 of them. Unique or multiple intracranial aneurysms, all on the carotid siphon, were observed in 5 patients. Seven patients had a CSVD characterized by white matter changes (7/7) affecting subcortical, periventricular, or pontine regions, dilated perivascular spaces (5/7), and lacunar infarcts (4/7). Infantile hemiplegia, major stroke, and porencephaly were not observed. Skin biopsies showed alterations of basement membranes at the dermoepidermal junction associated with expansion of extracellular matrix between smooth vascular cells in the arteriolar wall. CONCLUSION: The cerebrovascular phenotype in hereditary angiopathy with nephropathy, aneurysm, and muscle cramps syndrome associates a cerebral small vessel disease and a large vessel disease with aneurysms of the carotid siphon. It is consistent with a lower susceptibility to hemorrhagic stroke than in familial porencephaly, suggesting an important clinical heterogeneity in the phenotypic expression of disorders related to COL4A1 mutations.

[Bullous pemphigoid in young patients: a retrospective study of 74 cases]. / Pemphigoïde du sujet jeune.

INTRODUCTION: Bullous pemphigoid usually affects elderly people. Only a few isolated cases among people younger than 65 years have been reported. OBJECTIVES: Describe the clinical and biological characteristics of patients younger than 60 years suffering from bullous pemphigoid, compare them with the usual characteristics known among elderly people and search for potential pathological associations. PATIENTS AND METHODS: Retrospective, national, multicenter study. Clinical, biological and histological characteristics were recorded with a standardised questionnaire as well as treatments and associated pathologies. RESULTS: Seventy-four cases of bullous pemphigoid diagnosed between June 1970 and March 2002 were analyzed. Mean age at the beginning of the disease was 46 +/- 11.6 years. Further explorations by indirect immunofluorescence of separated skin and/or immuno-electron microscopy and/or immunoblotting were performed for 42 patients (56.8 p. 100). Clinical characteristics among this restricted population were comparable to those found among the 32 other cases. Compared to usual data on bullous pemphigoid in elderly people, we observed a greater proportion of extensive form of disease (75 p. 100), a more frequent head and neck involvement (39.2 p. 100) and an overexpression of anti-BP180 autoantibodies (48 p. 100). Neoplasm was notified for 7 patients (9.5 p. 100), 18 (24.3 p. 100) suffered from a pathology of the basement membrane zone (6 psoriasis, 6 atopic dermatitis and 6 lichen) and 13 from neurological disease, among which 4 were bedridden. Fourty-six patients (62.2 p. 100) received drugs for the long term (mean 2.12 +/- 2.43), 4 patients were treated by PUVAtherapy and 2 by radiotherapy. DISCUSSION: Our results suggest that bullous pemphigoid among young people is more severe and more active than the usual form in the elderly. This particular form could be the result of a higher expression of anti-BP180 autoantibodies, which are considered as a marker of poor prognosis in this disease. We also found a high frequency of pathological associations and physical treatment, all responsible for damage to the basement membrane zone, which can involve auto-immunization against hemidesmosome components.

Clinical criteria for the diagnosis of bullous pemphigoid: a reevaluation according to immunoblot analysis of patient sera.

BACKGROUND: We previously proposed a set of 4 clinical criteria for the diagnosis of bullous pemphigoid (BP) that consisted of age greater than 70 years, absence of atrophic scars, absence of mucosal involvement and absence of predominant bullous lesions on the neck and head. These results have been challenged because direct immunoelectron microscopy (IEM), which was used as the standard diagnostic criterion in our initial study, does not identify the different antigens of the basement membrane zone. OBJECTIVE: To reassess the validity of these clinical criteria for the diagnosis of BP using immunoblot analysis of patient sera as the main diagnostic criterion, in order to precisely identify the antigens recognized by patient sera. METHODS: One hundred and eighty-nine sera from patients with various subepidermal autoimmune blistering diseases (AIBDs) were tested by immunoblotting using dermal and epidermal extracts. IEM was used as a complementary diagnostic procedure in a few patients whose serum recognized BPAG2 exclusively or was negative in immunoblotting. RESULTS: 142 patients (75%) had at least 3 of the 4 clinical diagnostic criteria. Sera from patients who lacked the set of BP clinical criteria were more frequently immunoblot negative (34%) than sera from patients who had the criteria (18%; p = 0.025). BPAG1 was more frequently recognized by sera from patients with the set of BP clinical criteria (78%) than by sera from patients without the criteria (45%; p = 5.10(-4)). In contrast, BPAG2 was recognized by a great number of sera from patients who lacked the criteria of BP (71%), which was in accordance with the presence of numerous patients with cicatricial pemphigoid in this group. Among patients with various subepidermal AIBDs, the diagnosis of BP could be made with a sensitivity of 86%, a specificity of 90% and an excellent prognostic positive value over 95%, if 3 of these clinical criteria were present. CONCLUSION: These results confirm the interest of this set of clinical criteria for the rapid diagnosis of BP.

[Dapsone-induced sensory peripheral neuropathy]. / Polynévrite sensitive induite par la dapsone (Disulone).

INTRODUCTION: Peripheral neuropathy is a rare complication of dapsone therapy. CASE-REPORT: A 74 year-old woman was treated with dapsone, 50 mg per day, for a linear IgA dermatosis. One month later, the disease was controlled but the patient complained of a sensory peripheral neuropathy, which was documented on electromyographic studies. Dapsone was stopped and symptoms resolved within 24 hours. Three months after the beginning of linear IgA dermatosis, a colic adenocarcinoma was revealed by an acute occlusive syndrome. After surgical resection of the tumor, remission of linear IgA dermatosis was obtained with salazopyrine. DISCUSSION: This is a rare side effect of dapsone therapy. Twenty-one cases have been previously reported. In most cases, there was a pure motor or mixed neuropathy. Dapsone therapy was then stopped or decreased. Recovery usually occurs within one year after dapsone therapy is discontinued.

[Treatment of pemphigus vulgaris by azathioprine and low doses of prednisone (Lever scheme)]. / Traitement du pemphigus vulgaire par le protocole Lever faible.

INTRODUCTION: The so-called "Lever scheme" therapeutic regimen has been proposed in the borderline forms of pemphigus to reduce the side effects of systemic corticosteroids. PATIENTS AND METHODS: A retrospective study was conducted in 8 hospital centers. The criteria for inclusion were the clinical diagnosis of pemphigus, confirmed by histological examination and direct immunofluorescence and first line therapy using the "Lever scheme" protocol, combining 40 mg of prednisone on alternate days and 100 mg/day of azathioprine. RESULTS: Twenty-two patients, seen between January 1990 and December 2000 were included in the study. Eighteen patients (82 p. 100) exhibited complete healing of their cutaneous-buccal lesions after a mean delay of 4.3 months. The lesions of 4 patients did not heal. Three of these patients died: a bed-ridden patient, a patient exhibiting a metastatic bronchial carcinoma and a hypertensive patient who died following a hemorrhagic cerebral vascular accident. Twelve patients (54 p. 100) were weaned off treatment after a mean duration of 2.9 years. Five severe adverse events were observed: one pneumonia, 2 unbalanced diabetes, one hepatitis and one pulmonary embolism. DISCUSSION: This study showed that the healing of the cutaneous-buccal lesions was obtained using the "Lever scheme" in 18 cases out of 22 (82 p. 100). The delay to healing was relatively long in view of the delayed effect of azathioprine. This limits the use of the "Lever scheme" protocol to non-extensive and/or early stage pemphigus. The severe adverse events occurred in low-weight patients in whom the dose related to weight was the highest. Hence the doses of azathioprine and prednisone should be adapted to patients' body weight.