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.

Anti-BP180 autoantibody levels at diagnosis correlate with 1-year mortality rates in patients with bullous pemphigoid.

BACKGROUND: Bullous pemphigoid (BP) is the most frequent autoimmune blistering disease mainly affecting elderly patients. Among several published risk factors, a recent post hoc analysis linked anti-BP180 autoantibodies (AABs) to fatal outcomes in BP. To date, this finding has not been confirmed independently. OBJECTIVE: To investigate the potential of anti-BP180-AAB levels as a marker of prognosis and to identify a cut-off level indicative of an increased risk for early death. Secondly, to characterize parameters associated with mortality. METHODS: Retrospective, single-centre study of BP patients diagnosed between 2001 and 2012. Analyses included epidemiological and patient- and disease-specific characteristics as well as immunological parameters at diagnosis and during follow-up. Standardized mortality ratios as well as uni- and multivariate regression analyses were calculated. RESULTS: One hundred patients (56 women, 44 men) with a median age of 81 years (interquartile range 74-86) were followed up for a median of 775 days (interquartile range 162-1617). One-year mortality rates were 25.0% implying a 2.4-fold increased risk of death compared with the general population. High anti-BP180 autoantibody levels at diagnosis (CI95 1.30-2.89; P = 0.001), dementia (CI95 1.13-6.72; P =0.03), length of hospitalization (CI95 1.16-2.41; P = 0.01) and age (CI95 1.23-4.19; P = 0.009) correlated significantly with 1-year mortality. BP180-AAB concentrations of ≥61 U/mL characterized a subgroup of patients with a particular higher risk for early death compared with the general population (CI95 1.81-3.81; P < 0.0001). CONCLUSION: In bullous pemphigoid, serum concentrations of BP180 autoantibodies at diagnosis could help to identify patients at risk for death within the first year after diagnosis (cut-off value 61 U/mL).

[Digital papillary adenocarcinoma : Four case reports with brief literature review]. / Digitales papilläres Adenokarzinom : Vier Fallberichte mit kurzer Literaturübersicht.

Digital papillary adenocarcinoma is a rare but well characterized carcinoma of the sweat glands, which apart from very few exceptions is localized in acral skin. This type of sweat gland carcinoma tends to recur locally and may cause delayed metastases in a few cases. We describe the clinical findings and the broad histopathologic spectrum of four cases of this rare adnexal carcinoma and give a short summary of the literature.

Apremilast in psoriasis - a prospective real-world study.

BACKGROUND: Apremilast is a novel oral phosphodiesterase-4 inhibitor approved for psoriasis treatment. Randomized trials have documented its efficacy and safety, but data on real-world patients are scarce. OBJECTIVES: We aim to characterize psoriasis patients treated with apremilast in a real-world setting and calculate drug survival as an important measure of efficacy and compliance. METHODS: All patients with psoriasis who received apremilast between 1 April 2015 and 19 January 2017 were evaluated every 4 weeks, and we documented: age, weight, height, smoking status, family history of psoriasis, joint involvement, previous treatments, psoriasis area severity index (PASI) scores, and the onset and duration of adverse events (AE). Efficacy was analysed by PASI50, PASI75 and PASI90, reflecting the improvement of skin lesions compared to the PASI-baseline. Kaplan-Meier statistics were used for drug survival estimates. RESULTS: Forty-eight patients were included. The median apremilast drug survival was 12.5 weeks (range 1-87). Three patients (6.3%) reached PASI90, nine (18.8%) PASI75 and eight patients (16.7%) PASI50. Patient weight inversely correlated with a PASI50 response (P < 0.05, n = 37), and none of the obese patients (BMI > 30.0, n = 6) reached PASI75, compared to 32% of the non-obese patients (BMI < 30.0, n = 31). Thirty-one patients (64.6%) reported at least one AE, most frequently diarrhoea (n = 21, 43.8%), headache (n = 7, 14.6%) and joint pain (n = 5, 10.4%). CONCLUSIONS: Despite differences between real-world and trial patients, apremilast is safe and effective for the treatment of skin psoriasis in the daily practice. Up to 40% of patients will reach PASI50 or higher, but only few patients will reach PASI90. Bodyweight might affect drug efficacy.

Pyoderma gangrenosum during pregnancy - treatment options revisited.

BACKGROUND: Pyoderma gangrenosum (PG) is a rare, ulcerating neutrophilic dermatosis of unknown aetiology; PG during pregnancy is particularly rare. The disease is frequently associated with immune-mediated, inflammatory diseases. OBJECTIVE: Diagnosis of PG can be challenging and relies upon exclusion of other causes such as traumas, infections, vascular diseases or neoplasms. Treatment options during pregnancy are limited. METHODS: To evaluate current treatment options for PG during pregnancy, we present a case of multilocular PG during the patient's first trimester. In conjunction with a comprehensive review of previously published cases of PG during gravidity, we discuss available treatment modalities including immunosuppressants and TNFα inhibitors. RESULTS: Our patient highlights the importance of including PG as a potential differential diagnosis of cutaneous ulcers during gravidity. Treatment with systemic glucocorticoids is effective and safe for the health of the mother and the unborn. CONCLUSION: In pregnant females, it is particularly important to diagnose PG and control disease activity due to the risk of pathergy and wound healing deficiencies during delivery and post-partum. A limited number of treatment options are available to date, which require a precise risk-benefit evaluation.

Mycoplasma pneumoniae-associated mucositis--case report and systematic review of literature.

BACKGROUND: Mycoplasma pneumoniae, a bacterium known to be a common cause of pneumonia, has been documented to cause complications such as debilitating mucositis previously described as an atypical Stevens-Johnson syndrome without skin lesions. However, in the spectrum of epidermal dermatopathies, the condition is increasingly recognized as a separate entity, now termed M. pneumoniae-associated mucositis (MPAM). OBJECTIVES: We present a case of MPAM and systemically review the literature to discuss diagnostic and therapeutic options. METHODS: A systematic literature search was performed to find studies reporting MPAM in adults. We extracted and analysed patient demographics, disease symptomatology, diagnostic testing and treatment. RESULTS: Eleven articles, describing 12 patients and our own patient met the predefined criteria and were analysed. Respiratory, ocular and oral symptoms were present in all patients. Therapies predominantly included antibiotics (10 of 13) and immunosuppressive treatment (9 of 13) leading to complete resolution of symptoms in all patients. CONCLUSION: Our findings highlight that MPAM should be recognized as a distinct disease entity within the spectrum of epidermal dermatopathies. We discuss and show in our patient why M. pneumoniae IgA serum levels could prove to be more reliable diagnostic tools in the MPAM diagnosis than the widely used IgG and IgM titre levels.

Merkel cell carcinoma: mitoses, expression of Ki-67 and bcl-2 correlate with disease progression.

BACKGROUND: There are conflicting data on markers of disease progression and outcome of Merkel cell carcinoma. OBJECTIVE: We suggest to review histological and various immunohistochemical features of Merkel cell carcinoma specimens, in order to identify prognostic markers of clinical relevance. METHODS: We collected paraffin-embedded blocks from primary tumours from 26 patients diagnosed with Merkel cell carcinoma and determined the following: type and size of the tumour, number of mitoses, proliferation rate (Ki-67 antibody), (anti)-apoptosis rate (bcl-2, p53, p63 antibodies) and lymphatic vessel invasion (D2-40 antibody for podoplanin). Two authors blinded to clinical outcome, independently assessed and scored all samples. The findings were correlated with tumour progression, which was determined by local recurrence, lymph node- or distant metastases. RESULTS: During the average follow-up period of 63.4 months 12 (46%) patients had disease progression. Statistical analysis revealed Ki-67-staining (P = 0.005) as a marker of disease progression, high number of mitoses (P = 0.026) correlated with lymph node metastasis, while a tendency for increased Bcl-2 expression (P = 0.064) was found in patients with local recurrence. A higher number of invaded lymphatic capillaries showed a tendency in correlation with metastases (P = 0.072). CONCLUSION: The findings indicate that high numbers of mitoses, proliferation and survival of tumour cells as marked by Ki-67- and Bcl-2-staining, and infiltration of lymphatic vessels, might correlate with the biological behaviour of Merkel cell carcinoma.

Low-dose inhalation of interleukin-2 bio-chemotherapy for the treatment of pulmonary metastases in melanoma patients.

BACKGROUND: Interleukin-2 (IL-2) treatment for patients with metastatic melanoma has shown remarkable durable responses. Systemic administration of IL-2 may cause severe side effects, whereas local administration is considered to be a safe alternative. The lungs are common sites of metastases in melanoma patients causing considerable respiratory problems. We sought to evaluate the potential antitumoral effect of a low-dose inhalative IL-2 (lh-IL-2) regimen for patients with melanoma lung metastases. In addition, we explored the prophylactic potential of Ih-IL-2 after surgical removal of lung metastases in a study carried out in an outpatient setting. METHODS: Twenty patients with American Joint Committee on Cancer stage-IV (M1b and M1c) melanoma were enrolled in this study and treated with 3 × 3 million IU inhalative IL-2 q.d. together with monthly dacarbazine bolus injections. Five patients received lh-IL-2 after surgical resection of lung metastases to prevent recurrence of the disease (prophylaxis group, N=5). All other patients were enrolled in the treatment group (N=15). Clinical evaluations were carried out monthly and radiological follow-up was performed every third month. RESULTS: Nine patients in the treatment group had a clinical benefit with partial regression (27%) or stable disease (33%). Four patients had progression of lung metastases (26.7%) and two patients were not evaluable (13.3%). In the prophylaxis group, none of the patients developed new lung metastases during lh-IL-2 therapy. The median follow-up period was 7.8 months in the treatment group and 25.7 months in the prophylaxis group. In the majority of patients, treatment was well tolerated. CONCLUSIONS: Low-dose IL-2 inhalation might offer an effective and safe treatment option for lung metastases in melanoma patients. In addition, lh-IL-2 may have a prophylactic potential to prevent recurrence in the lungs after pulmonary melanoma metastasectomy. Administration can easily be performed in an outpatient setting, thus offering an attractive treatment option.

A long-term study of a patient with anti-p200 pemphigoid: correlation of autoantibody levels with disease activity and an example of epitope spreading.

Anti-p200 pemphigoid is a rare subepidermal blistering disease associated with autoantibodies against a 200-kDa protein, reportedly corresponding to laminin γ1. However, direct evidence of the pathogenic potential of these antibodies has not been proven. For 5 years we have followed up a patient with anti-p200 pemphigoid. During this period she experienced a total of three generalized relapses. Quantifying our patient's autoantibody concentrations against laminin γ1 by enzyme-linked immunosorbent assay throughout the course of her disease we demonstrated a clear correlation with disease activity, thus providing the first evidence of the possible pathogenic role of antibodies against laminin γ1 in anti-p200 pemphigoid. Further analysis by Western blotting revealed the occurrence of additional autoantibodies against the α3 chain of laminin 332, 1·5 years after diagnosis, suggestive of intermolecular epitope spreading. Yet, the clinical appearance was unchanged and mucous membranes remained unaffected at any stage of the disease.

[IgA pemphigus of the subcorneal pustular dermatosis type. Successful therapy with a combination of dapsone and acitretin]. / IgA-Pemphigus vom Typ der subkornealen pustulösen Dermatose. Erfolgreiche Kombinationstherapie mit Dapson und Acitretin.

IgA pemphigus of the subcorneal pustular dermatosis type is a rare autoimmune blistering disease in the pemphigus spectrum. Patients are clinically characterized by extensive erythemas that primarily affect intertriginous areas. The erythematous macules are covered with numerous vesicles and pustules with occasional hypopyon formation. Histopathology shows subcorneal acantholysis with clefting and numerous neutrophils within the blister as well as in the edematous papillary dermis. IgA autoantibodies bind in vivo to keratinocytes within the upper half of the epidermis. Desmocollin 1, the autoantigen of this disease, is a member of desmosomal cadherins and is only expressed on more differentiated keratinocytes. The demonstration of circulating autoantibodies against desmocollin 1 in routine diagnosis is challenging and requires indirect immunofluorescence staining of desmocollin 1 transfected COS7 cells. We report a patient with a severe course of the disease who only responded to combined therapy with dapsone and acitretin.