[European Guidelines (S1) on the use of high-dose intravenous immunoglobulin in dermatology]. / Europäische Leitlinien (S1) für die Verwendung von hoch dosierten intravenösen Immunglobulinen in der Dermatologie.

BACKGROUND AND OBJECTIVES: Treatment of severe dermatological autoimmune diseases and toxic epidermal necrolysis (TEN) with high-dose intravenous immunoglobulin (IVIg) is a well-established procedure in dermatology. As treatment with IVIg is usually considered for rare clinical entities or severe cases, the use of immunoglobulin is not generally based on data from randomized controlled trials usually required for evidence-based medicine. Since the indications for the use of IVIg are rare, it is unlikely that such studies will be available in the foreseeable future. Because first-line use is limited by the high costs of IVIg, the first clinical guidelines on the use of IVIg in dermatological conditions were established in 2008 and renewed in 2011. METHODS: The European guidelines presented here were prepared by a panel of experts nominated by the European Dermatology Forum (EDF) and European Academy of Dermatology and Venereology (EADV). The guidelines were developed to update the indications for treatment currently considered effective and to summarize the evidence for the use of IVIg in dermatological autoimmune diseases and TEN. RESULTS AND CONCLUSION: The current guidelines represent consensual expert opinions and definitions on the use of IVIg reflecting current published evidence and are intended to serve as a decision-making tool for the use of IVIg in dermatological diseases.

Knowledge and Influence of Predatory Journals in Dermatology: A Pan-Austrian Survey.

The aim of this study was to assess the knowledge and influence of predatory journals in the field of dermatology in Austria. A total of 286 physicians (50.5% men) completed a questionnaire. The vast majority of subjects read scientific articles (n = 281, 98.3%) and took them into consideration in their clinical decision-making (n = 271, 98.5% of participants that regularly read scientific literature). Open access was known by 161 (56.3%), predatory journals by 84 (29.4%), and the Beall's list by 19 physicians (6.7%). A total of 117 participants (40.9%) had been challenged by patients with results from the scientific literature, including 9 predatory papers. Participants who knew of predatory journals had a higher level of education as well as scientific experience, and were more familiar with the open-access system (p < 0.001). These results indicate that the majority of dermatologists are not familiar with predatory journals. This is particularly the case for physicians in training and in the early stages of their career.

Europäische Leitlinien (S1) für die Anwendung von hochdosierten intravenösen Immunglobulinen in der Dermatologie.

HINTERGRUND UND ZIELE: Die Behandlung schwerer dermatologischer Autoimmunerkrankungen und der toxischen epidermalen Nekrolyse (TEN) mit hochdosierten intravenösen Immunglobulinen (IVIg) ist ein bewährtes therapeutisches Verfahren in der Dermatologie. Da eine IVIg-Therapie in der Regel nur bei seltenen Erkrankungen oder bei schweren Fällen in Betracht gezogen wird, stützt sich die Anwendung von Immunglobulinen zumeist nicht auf Daten aus randomisierten kontrollierten Studien, wie sie in der evidenzbasierten Medizin erforderlich sind. Da Indikationen für die Anwendung von IVIg selten sind, ist es unwahrscheinlich, dass solche Studien in absehbarer Zeit durchgeführt werden. Wegen der hohen Kosten für IVIg im First-Line-Einsatz wurden die ersten klinischen Leitlinien für die Anwendung von IVIg bei dermatologischen Erkrankungen im Jahr 2008 herausgegeben und im Jahr 2011 überarbeitet. METHODEN: Diese europäischen Leitlinien wurden von einer Gruppe durch das EDF und die EADV benannter Experten erarbeitet. Die Leitlinien wurden erstellt, um die derzeit als wirksam erachteten Behandlungsindikationen zu aktualisieren und die für die Anwendung von IVIg bei dermatologischen Autoimmunerkrankungen und TEN vorliegenden Daten zusammenzufassen. ERGEBNISSE UND SCHLUSSFOLGERUNG: Die vorliegenden Leitlinien repräsentieren die einvernehmlichen Meinungen und Definitionen von Experten zur Anwendung von IVIg, die die aktuell publizierten Daten widerspiegeln, und sollen als Entscheidungshilfe für den Einsatz von IVIg bei dermatologischen Erkrankungen dienen.

European Guidelines (S1) on the use of high-dose intravenous immunoglobulin in dermatology.

BACKGROUND AND OBJECTIVES: Treatment of severe dermatological autoimmune diseases and toxic epidermal necrolysis (TEN) with high-dose intravenous immunoglobulin (IVIg) is a well-established procedure in dermatology. As treatment with IVIg is usually considered for rare clinical entities or severe cases, the use of immunoglobulin is not generally based on data from randomized controlled trials usually required for evidence-based medicine. Since the indications for the use of IVIg are rare, it is unlikely that such studies will be available in the foreseeable future. Because first-line use is limited by the high costs of IVIg, the first clinical guidelines on the use of IVIg in dermatological conditions were established in 2008 and renewed in 2011. METHODS: The European guidelines presented here were prepared by a panel of experts nominated by the EDF and EADV. The guidelines were developed to update the indications for treatment currently considered effective and to summarize the evidence for the use of IVIg in dermatological autoimmune diseases and TEN. RESULTS AND CONCLUSION: The current guidelines represent consensual expert opinions and definitions on the use of IVIg reflecting current published evidence and are intended to serve as a decision-making tool for the use of IVIg in dermatological diseases.

Survival and Effectiveness of Tumour Necrosis Factor-alpha Inhibitors in the Treatment of Plaque Psoriasis under Daily Life Conditions: Report from the Psoriasis Registry Austria.

This retrospective multicentre analysis from the Psoriasis Registry Austria (PsoRA) was conducted to determine drug effectiveness and survival of anti-tumour necrosis factor alpha (anti-TNF-α) agents in patients with moderate-to-severe chronic plaque psoriasis over a 9-year period. Data on 1,019 treatment cycles with adalimumab (n = 460), etanercept (n = 501), and/or infliximab (n = 58) administered to 827 patients (272 women, 555 men) were available for analysis. Compared with etanercept, adalimumab and infliximab showed superior short-term effectiveness. Intention-to-treat-calculated median drug survivals for adalimumab (1,264 days) and etanercept (1,438 days) were similar to each other (p = 0.74), but significantly superior to that of infliximab (477 days) (p = 7.0e-07 vs. adalimumab and p=2.2e-07 vs. etanercept, respectively). Their drug survival rates at 36 months were 51.6%, 56.0%, and 22.6%, respectively. Survival rates correlated significantly with effectiveness for adalimumab and etanercept, but not for infliximab.

Gemella morbillorum bacteremia after anti-tumor necrosis factor alpha as acne inversa therapy.

We present a case of fever, brain abscesses, and Gemella morbillorum bacteremia after anti-tumor necrosis factor alpha (TNF-α) therapy in a 21-year-old acne inversa patient currently taking long-term dapsone. To the best of our knowledge, this is the first report describing such a case. During antimicrobial therapy, the patient developed systemic varicella infection with severe thrombocytopenia.

[Successful therapy of sacroiliitis in SAPHO syndrome by etanercept]. / Sacroileitis im Rahmen eines SAPHO Syndroms - promptes Ansprechen auf Etanercept.

Painful, aseptic osteitis remains the major problem in the treatment of patients with SAPHO syndrome. We present a child suffering of both sacroiliitis and acne conglobata in the context of SAPHO syndrome. While acne lesions responded well to systemic isotretinoin, sacroiliitis associated pain could be controlled neither by NSAR nor by intralesional or systemic steroid injection. Worse pain limited substantially patient's mobility. This changed immediately after starting etanercept. Within a few days, pain resolved and the patient regained his mobility. This favourable response lasted for 8 months when we tried to stop etanercept under protection with the DMARD sulfazalazin. Unfortunately, within a few days, pain and immobility re-occurred requiring reinstitution of etanercept. This case demonstrates that, similar to other reports, TNF blockade is able to induce prompt and long-lasting response of SAPHO syndrome associated osteoarthritis to TNF blockade.

Diagnosis of infection with human herpes viruses in routine laboratory practice.

BACKGROUND: The potential for faster detection of human herpes viruses using PCR compared to other methods is undisputed. However, because of fear of contamination, the clinical implication of nucleic amplification methods in routine laboratories is not widespread. Herpes viruses cause a wide spectrum of diseases and can cause morbidity and mortality in immune-compromised patients. Using real-time PCR, most of the problems associated with PCR (contamination, cumbersome detection, and rather expensive tests) are solved, and a rapid, economical, and--most importantly--closed system is at hand. METHODS: We evaluated work procedures in our laboratory that enable the routine diagnosis of viral infections with high accuracy and rapid turn-around time. In parallel, inherent problems usually associated with PCR testing, especially cross-contamination could be suppressed to a minimum. The start of the work flow process begins with an automated nucleic acid extraction procedure that yields high quality DNA. A common--internally and externally controlled--PCR program for all six viruses allows rapid sample turn around. RESULTS: In all, 7500 analyses for human herpes virus infection were performed in the last 5 years. Results for various different specimens were produced within 24 h. Contamination occurred rarely and could be ameliorated easily. The use of internal controls identified rare PCR-inhibited samples. The detection limits for our assays are markedly below the clinically relevant range. CONCLUSIONS: Our workflow allowed rapid, cost-efficient, and labor saving routine diagnostic detection of viral infections.

Perforating folliculitis, angioedema, hand-foot syndrome--multiple cutaneous side effects in a patient treated with sorafenib.

A patient with clear cell renal cell carcinoma was treated with sorafenib, a multikinase inhibitor, which induced a variety of cutaneous side effects. In addition to xerosis, he developed angioedema (AE), hand-foot syndrome (HFS) and perforating folliculitis (PF). The latter three occurred in a dose-dependent manner. AE was observed at the recommended daily dose of 800 mg. Dose reduction to 400 mg prevented its recurrence. At this dose level, the patient exhibited HFS, which cleared upon further reduction of the dose. While receiving 200 mg, the patient developed PF. To the best of our knowledge, this is the first description of a case of PF during treatment with sorafenib.

A novel homozygous mutation in PVRL4 causes ectodermal dysplasia-syndactyly syndrome 1.

Ectodermal dysplasias (EDs) are a group of hereditary disorders defined by alterations in two or more ectodermal structures. One recently described rare entity is the autosomal recessive inherited ectodermal dysplasia-syndactyly syndrome 1 (EDSS1). Homozygous and compound heterozygous missense and nonsense mutations in the poliovirus receptor related-4 (PVRL4) gene, encoding cell adhesion molecule nectin-4, have been identified as causal for EDSS1. We here report a consanguineous family with a 2-year-old girl featuring EDSS1, including slowly progressive alopecia on the head, pili torti-like twisted hairs in trichoscopy, widely spaced, peg-shaped and conical teeth, proximal syndactyly with fusion of the 2nd to 4th toes, and generalized dry skin. There was no palmoplantar hyperkeratosis and sweating appeared normal to slightly enhanced, especially on the head. Using exome sequencing, we identified the novel homozygous nonsense mutation c.229C>T (p.Gln77Ter) in PVRL4.

Prospective, randomized, multicenter, double-blind placebo-controlled trial comparing adjuvant interferon alfa and isotretinoin with interferon alfa alone in stage IIA and IIB melanoma: European Cooperative Adjuvant Melanoma Treatment Study Group.

PURPOSE: The combination of interferon alfa (IFNalpha) and isotretinoin has shown a direct antiproliferative effect on human melanoma cell lines, but it remained unclear whether this combination is more effective than IFNalpha alone in patients with metastatic melanoma. We evaluated safety and efficacy of IFNalpha and isotretinoin compared with IFNalpha alone as adjuvant treatment in patients with primary malignant melanoma stage IIA and IIB. PATIENTS AND METHODS: In a prospective, randomized, double-blind, placebo-controlled trial, 407 melanoma patients in stage IIA (301 patients) and IIB (106 patients) were randomly assigned to either IFNalpha and isotretinoin (isotretinoin group; 206 patients) or IFNalpha and placebo (placebo group; 201 patients) after excision of the primary tumor. IFNalpha was administered three times a week at a dose of 3 million units subcutaneously for 24 months. Isotretinoin at a dose of 20 mg for patients < or = 73 kg, 30 mg for patients greater than 73 kg, or placebo daily for 24 months. RESULTS: A scheduled interim analysis revealed no significant differences in survival rates, with the isotretinoin group and the placebo group showing 5-year disease-free survival rates of 55% (95% CI, 46% to 65%) and 67% (95% CI, 59% to 75%), respectively, and overall 5-year survival rates of 76% (95% CI, 67% to 84%) and 81% (95% CI, 74% to 88%), respectively. The trial was stopped for futility. CONCLUSION: The addition of isotretinoin to an adjuvant treatment of low-dose IFNalpha in patients with stage IIA and IIB melanoma had no significant effect on disease-free or overall survival and is therefore not recommended.

Atopic dermatitis with increased severity along a line of Blaschko.

Several primarily symmetric skin diseases may, on rare occasions, manifest themselves more prominently along the embryonic migration pathways of cutaneous cell clones. Loss of heterozygosity along these lines of Blaschko resulting in hemizygosity or homozygosity of alleles predisposing for the disease is the most likely explanation for this phenomenon. Here, we report a case of severe Blaschko linear atopic dermatitis superimposed on a milder symmetric eruption of atopic eczema in a 36-year-old man with personal and familial history of allergy. Continuous transition of linear atopic eczema to linear vesicular (dyshidrotic) plantar eczema demonstrates the relationship between these two entities. Individuals such as our patient offer an opportunity to identify intraindividual genetic variations marking loci involved in the pathogenesis of atopy and atopic eczema.

[Clinical practise guideline of the special interest group in allergy of the ÖGDV - Drug provocation testing in the diagnosis of cutaneous drug reactions]. / Leitlinie der Arbeitsgruppe Allergologie der ÖGDV - Provokationstestungen zur Abklärung von unerwünschten Arzneireaktionen an Haut und Schleimhäuten.

Nowadays, clinical and evidence based guidelines are considered one of the major efforts to improve patient care in medical practices as well as hospital settings. In the literature, clinical guidelines have been defined as "systematically developed statements to assist practitioner and patient decisions about appropriate healthcare for specific clinical circumstances", which promote both clinically effective standards and cost-effective care. Despite controversial discussion about the clinical impact of guidelines, they may provide workable recommendations that may thus be important for improving the individual patient's care. Adverse drug reactions (drug allergies, drug hypersensitivities) often represent a major hazard for the affected patient, and a definite diagnosis is important for further drug therapies in most cases. In this context, any diagnostic procedure must be preceded by an individual risk-benefit assessment. Drug provocation testing is regarded as the gold standard, but this kind of testing should be performed in accordance with established criteria and, in the vast majority of cases, in a hospital setting. In this paper we present a clinical guideline for drug provocation testing in Austria.