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.

Usefulness of high-frequency ultrasonography in the evaluation and monitoring of sclerosing dermatoses: a cohort study.

BACKGROUND: Monitoring of disease activity in sclerosing dermatoses (SD) can be challenging and tools to support clinical decision-making are lacking. AIM: To analyse the impact of high-frequency ultrasonography (HFUS) on the clinical management of SD and to describe the US characteristics of disease activity. METHODS: This was a cohort study of patients with various SD [morphoea, systemic sclerosis (SS) and chronic graft-versus-host disease (cGvHD)] who underwent HFUS between January 2017 and August 2019. HFUS criteria for diagnosing active SD were increased Doppler vascularity and/or meeting all B-mode greyscale US signs of activity. Discordance in SD activity between HFUS and clinical examination was evaluated at the time of the first US assessment. Changes in patient management were instituted after HFUS were recorded. RESULTS: In total, 72 patients (31 with morphoea, 19 with SS and 22 with cGvHD), who underwent 163 HFUS sessions in total, were included. All HFUS-active morphoea lesions exhibited increased vascularity, and all HFUS-active SS exhibited dermal thickening and dermal hypoechogenicity. HFUS-active cGvHD displayed increased dermal thickness and loss of definition of the dermal-hypodermal junction, and there were signs of panniculitis in 80% of cases and of increased vascularity in 70%. Discordance in disease activity between clinical and HFUS evaluation was found in 17 (23.6%) patients. Changes in clinical management after HFUS were made for 14 (19.4%) patients: treatment discontinuation for 6 patients (42.9%), treatment initiation for 5 (35.7%), medication change for 2 (14.3%) and skin biopsy taken for 1 (7.1%). CONCLUSION: HFUS seems an efficacious support tool in the monitoring of SD activity with a notable impact on clinical management. Further studies are warranted to evaluate the impact of HFUS-supported management changes on SD outcomes.

Reactive granulomatous dermatitis as a histological pattern including manifestations of interstitial granulomatous dermatitis and palisaded neutrophilic and granulomatous dermatitis: a study of 52 patients.

BACKGROUND: Confusion exists regarding interstitial granulomatous dermatitis (IGD) and palisaded neutrophilic and granulomatous dermatitis (PNGD). OBJECTIVE: To determine whether IGD and PNGD are two different entities, or whether they must be considered as two subtypes of the same reactive pattern, and thus whether the unification of the nomenclature is necessary. METHODS: Observational retrospective multicentre study of patients with IGD and PNGD evaluated between 1999 and 2019 and review of their clinical and histological features. RESULTS: We identified 52 patients (38 women and 14 men). Clinical and histological findings of IGD were observed in 88.4% of cases. The most common cutaneous lesions were plaques/macules (IGD) or annular plaques and papules/nodules (PNGD), located mostly on the limbs and trunk. The rope sign was developed in two patients with IGD that associated autoimmune disorders. Similar associated comorbidities (75%) were found in both entities, mainly autoimmune diseases (53.8%). In IGD, the infiltrate was predominantly lympho-histiocytic. Neutrophilic infiltrates, karyorrhexis and skin lesions with limited clinical course were mainly associated with PNGD biopsies. In biopsies with a limited recurrent course, a predominant lymphocytic inflammatory infiltrate was found. Collagen degeneration was present in 75.9% of cases. The floating sign was observed only in IGD type patients (63%). Overlapping histological findings were found in one fourth of cases, especially between IGD and interstitial granuloma annulare. Interface dermatitis, apparently unrelated to drug intake, was observed in 4 cases of IGD. CONCLUSION: We support the term reactive granulomatous dermatitis to unify both the clinical and histological findings of IGD and PNGD, and the overlapping between IGD and interstitial granuloma annulare. According to this, a spectrum of histological changes will be found depending on the clinical course of the skin lesions.

Updated S2K guidelines on the management of pemphigus vulgaris and foliaceus initiated by the european academy of dermatology and venereology (EADV).

BACKGROUND: Pemphigus encompasses a group of life-threatening autoimmune bullous diseases characterized by blisters and erosions of the mucous membranes and skin. Before the era of immunosuppressive treatment, pemphigus was almost always fatal. Due to its rarity, only few randomized controlled therapeutic trials are available. Recently, rituximab has been approved as first-line treatment for moderate and severe pemphigus vulgaris in Europe and the United States. OBJECTIVES: The Autoimmune blistering diseases Task Force of the European Academy of Dermatology and Venereology (EADV) has initiated a throughout update of the guideline for the management of patients with pemphigus. RESULTS: The guidelines for the management of pemphigus were updated, and the degree of consent among all task force members was included. The final version of the guideline was consented by the European Dermatology Forum (EDF) and several patient organizations.

Inter-rater reliability of the BIOCHIP indirect immunofluorescence dermatology mosaic in bullous pemphigoid and pemphigus patients.

BACKGROUND: The BIOCHIP (Dermatology Mosaic 7; EUROIMMUN, Lubeck, Germany) is a novel multiplex indirect immunofluorescence (IIF) technique used in the serological diagnosis of bullous pemphigoid (BP) and pemphigus. OBJECTIVE: To validate the accuracy and inter-rater reliability (IRR) of the BIOCHIP in the diagnosis of BP, pemphigus foliaceus (PF) and pemphigus vulgaris (PV). METHODS: Sera from patients with BP (n = 38), PF (n = 8), PV (n = 23), control patients (n = 64) and healthy control volunteers (n = 39) were tested. Sera were collected and analysed during the course of the disease at 1-5 different time points. The BIOCHIP was performed for all patients, digital images were captured of each incubated field, and the images were shared with 10 dermatologists experienced in reading IF from around the world to report. There were 312 BIOCHIP slides consisting of 1872 photos in total. All patients were de-identified. Fleiss Kappa was used to estimate the IRR. RESULTS: Fleiss Kappa was computed for each category (Oesophagus, Oesophagus immunofluorescence pattern, Salt-Split Skin (SSS), SSS immunofluorescence location, BP180, BP230, Dsg 1 and Ds3). The inter-rater agreement between the 10 raters varied between fair and moderate for all categories. Those that demonstrated fair concordance included monkey oesophagus (k = 0.257, P < 0.0001), oesophagus pattern (k = 0.357, P < 0.0001), Dsg1 (k = 0.390, P < 0.0001) and BP230 (k = 0.281, P < 0.0001). Moderate agreement was demonstrated for SSS (k = 0.416, P < 0.0001), SSS immunofluorescence location (k = 0.505, P < 0.0001), Dsg3 (k = 0.437, P < 0.0001) and BP180 (k = 0.559, P < 0.0001). CONCLUSION: The BIOCHIP mosaic-based immunofluorescence test is a simple, time and effort saving test that can aid in the diagnosis and screening of BP, PV and PF. However, the level of agreement was relatively low. The authors found the most common causes to be variable levels of training, indicating the presence of a learning curve in the interpretation of the results and ambiguous staining patterns leading to incongruent results.

Effectiveness and safety of belimumab in patients with systemic lupus erythematosus in a real-world setting.

Objective: To investigate the effectiveness and safety of belimumab in patients with active systemic lupus erythematosus (SLE) in a real-life setting.Methods: All SLE patients treated with belimumab in the Department of Autoimmune Diseases of the Hospital Clinic of Barcelona were retrospectively analysed. The Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score, clinical SLEDAI-2K, levels of anti-double-stranded DNA (anti-dsDNA) antibody, complement components C3 and C4, and 50% haemolytic complement activity (CH50) were recorded at baseline and at 6, 12, and 24 months. Adverse events were also collected.Results: Twenty-three patients (100% women) were enrolled in the study. The most frequent manifestations that led to belimumab use were arthritis (91%) and skin involvement (39%). Both SLEDAI-2K and clinical SLEDAI-2K improved over time at all time-points (p < 0.005). Complement levels increased and the values of anti-dsDNA antibody decreased during treatment. The mean dose of prednisone could be tapered at all time-points and achieved maximum and significant reduction at 24 months (10.4 ± 4.8 mg/day to 4.8 ± 2.1 mg/day; p < 0.0005). Belimumab was well tolerated and only six patients (26%) experienced adverse events, all of which were classified as infections (one urinary tract infection without bacterial detection in urine culture and five viral infections). No deaths, severe infusion reactions, or hypersensitivity reactions were noted.Conclusion: In our patients with SLE, belimumab decreased disease activity and allowed tapering of the daily glucocorticoid dose with a good safety profile.