Consensus statement on the diagnosis and treatment of sclerosing diseases of the skin, Part 1: Localized scleroderma, systemic sclerosis and overlap syndromes.

The term 'sclerosing diseases of the skin' comprises specific dermatological entities, which have fibrotic changes of the skin in common. These diseases mostly manifest in different clinical subtypes according to cutaneous and extracutaneous involvement and can sometimes be difficult to distinguish from each other. The present consensus provides an update to the 2017 European Dermatology Forum Guidelines, focusing on characteristic clinical and histopathological features, diagnostic scores and the serum autoantibodies most useful for differential diagnosis. In addition, updated strategies for the first- and advanced-line therapy of sclerosing skin diseases are addressed in detail. Part 1 of this consensus provides clinicians with an overview of the diagnosis and treatment of localized scleroderma (morphea), and systemic sclerosis including overlap syndromes.

[Scleromyxedema]. / Skleromyxödem.

Scleromyxedema is a rare disorder that frequently affects multiple extracutaneous organ systems and is usually associated with monoclonal gammopathy. The pathogenesis of scleromyxedema is unknown. The clinical course is chronic and progressive and can lead to marked morbidity or death. The skin findings consist of multiple waxy papules and indurated plaques. Progressive skin involvement can lead to decreased mobility of the mouth and joints. Extracutaneous manifestations occur in the musculoskeletal or cardiovascular system, in the gastrointestinal or respiratory tract, or in the kidneys. There are no approved or evidence-based treatment options available for scleromyxedema. High-dose immunoglobulins are considered the treatment of choice, followed by lenalidomide (or thalidomide) and systemic glucocorticosteroids, or in severe cases even autologous hematopoetic stem cell transplantation. Long-term maintenance treatment is usually required and close clinical follow-up is necessary as recurrence of scleromyxedema is common after withdrawal of an effective therapy.

European dermatology forum S1-guideline on the diagnosis and treatment of sclerosing diseases of the skin, Part 2: Scleromyxedema, scleredema and nephrogenic systemic fibrosis.

The term 'sclerosing diseases of the skin' comprises specific dermatological entities which have fibrotic changes of the skin in common. These diseases mostly manifest in different clinical subtypes according to cutaneous and extracutaneous involvement and can sometimes be difficult to distinguish from each other. The present guideline focuses on characteristic clinical and histopathological features, diagnostic scores and the serum autoantibodies most useful for differential diagnosis. In addition, current strategies in the first- and advanced-line therapy of sclerosing skin diseases are addressed in detail. Part 2 of this guideline provides clinicians with an overview of the diagnosis and treatment of scleromyxedema, scleredema (of Buschke) and nephrogenic systemic sclerosis (nephrogenic fibrosing dermopathy).

European Dermatology Forum S1-guideline on the diagnosis and treatment of sclerosing diseases of the skin, Part 1: localized scleroderma, systemic sclerosis and overlap syndromes.

The term 'sclerosing diseases of the skin' comprises specific dermatological entities, which have fibrotic changes of the skin in common. These diseases mostly manifest in different clinical subtypes according to cutaneous and extracutaneous involvement and can sometimes be difficult to distinguish from each other. The present guideline focuses on characteristic clinical and histopathological features, diagnostic scores and the serum autoantibodies most useful for differential diagnosis. In addition, current strategies in the first- and advanced-line therapy of sclerosing skin diseases are addressed in detail. Part 1 of this guideline provides clinicians with an overview of the diagnosis and treatment of localized scleroderma (morphea), and systemic sclerosis including overlap syndromes of systemic sclerosis with diseases of the rheumatological spectrum.

[Psoriasis vs. psoriatic arthritis : Similarities and differences in the pathophysiology]. / Psoriasis versus Psoriasisarthritis : Gemeinsamkeiten und Unterschiede in der Pathophysiologie.

Psoriasis is a chronic inflammatory skin disease with genetic and (auto)immunological backgrounds. Up to 30% of patients with psoriasis also develop a mostly oligoarticular arthritis with spinal involvement that is termed psoriatic arthritis (PsA) and shows a specific joint pattern which differs from that of rheumatoid arthritis (RA). Both Psa and psoriasis share a common main axis, the interleukin (IL) 23/IL17 pathway as well as major overlaps in the functions of tumor necrosis factor alpha (TNFalpha). Recently acquired knowledge supports the concept that in both diseases, similar genetic dispositions and molecular pathways lead to organ-specific disease patterns. In some types of PsA, genetic predisposition and the relevance of acute inflammatory reactions appear to be greater that in psoriasis, while in the latter exogenous factors and T­lymphocyte reactions in the skin seem to have a higher impact. A key difference between PsA and cutaneous psoriasis is the largely irreversible nature of inflammatory joint changes in PsA, whereas cutaneous plaques in psoriasis completely heal. The question of how interdependent both diseases are and whether immunologically primed T­lymphocytes from cutaneous lesions in PsA may transmit the disease to the synovial membranes and induce acute inflammation is not precisely known. A detailed analysis of these organ-specific differences may not only provide an explanation for the similar, but partly different efficacy of novel therapeutic strategies but may also lead to the development of personalized therapies that take into account the individually different manifestations of the diseases over time.

Adjuvant treatment with pegylated interferon α-2a versus low-dose interferon α-2a in patients with high-risk melanoma: a randomized phase III DeCOG trial.

BACKGROUND: Adjuvant treatment with interferon (IFN)-α-2a improved disease-free survival (DFS) and showed a trend for improving overall survival (OS) in melanoma. This trial was designed to examine whether PEG-IFN is superior to IFN with regard to distant metastasis-free survival (DMFS), DFS and OS. PATIENTS AND METHODS: In this multicenter, open-label, prospective randomized phase III trial, patients with resected cutaneous melanoma stage IIA(T3a)-IIIB (AJCC 2002) were randomized to receive PEG-IFN (180 µg subcutaneously 1×/week; 24 months) or IFN α-2a (3MIU subcutaneously 3×/week; 24 months). Randomization was stratified for stage, number of metastatic nodes, age and previous IFN treatment. The primary end point was DMFS; secondary end points were OS, DFS, quality of life (QoL) and tolerability. RESULTS: A total of 909 patients were enrolled (451 PEG-IFN versus 458 IFN). Neither 5-year DMFS [PEG-IFN 61.0% versus IFN 67.3%; hazard ratio (HR) 1.16, P = 0.21] nor 5-year OS (PEG-IFN 73.2% versus IFN 75.2%; HR 1.05, P = 0.70) nor 5-year DFS (PEG-IFN 57.3% versus IFN 60.9%; HR 1.09, P = 0.40) showed significant differences. Subgroup analyses in patients ± ulcerated primaries and of different tumor stages did not find differences in DMFS, OS or DFS between the treatment groups. One hundred and eighteen patients (26.2%) in the PEG-IFN and 61 patients (13.3%) in the IFN population did not receive the full dosage and length of treatment due to adverse events (P < 0.001). Leukopenia and elevation of liver enzymes were more common in the PEG-IFN arm (56% versus 23.5% LCP; 19.1% versus 9.4% AST; 33.0% versus 16.5% ALT). QoL was identical for nearly all domains. CONCLUSION: PEG-IFN did not improve the outcome over IFN. A higher percentage of patients under PEG-IFN discontinued treatment due to toxicity. CLINICAL TRIALSGOV IDENTIFIER: NCT00204529.

[Scabies in childhood and adolescence]. / Skabies im Kindes- und Jugendalter.

Scabies is a common parasitosis, occurring worldwide and at any age that impairs the quality of life of patients and their families by the itching and the stigmatization. The main aims of therapy are destroying the mites Sarcoptes scabiei var. hominis that infect the stratum corneum and reduction of the itching. This requires detailed clarification for the patients and the parents of affected children as the instructions for the use of the drugs and also the necessary additional steps are often not correctly followed. Many special features regarding the clinical symptoms and therapy in early childhood should be taken into consideration.

[Cutaneous symptoms of various vasculitides]. / Kutane Symptome der Vaskulitiden.

The skin is one of the organs most frequently involved in vasculitides. Cutaneous vasculitis may present (1) part of a systemic vasculitis (e.g., IgA vasculitis), (2) a skin-restricted or skin-dominant variant of the corresponding systemic vasculitis without clinically apparent visceral involvement (e.g., cutaneous IgA vasculitis), or (3) a vasculitis occurring exclusively in the skin (e.g., erythema elevatun diutinum). The clinical symptoms of vasculitides are markedly determined by the size of the predominantly affected blood vessels. Systemic polyarteritis nodosa is regarded as a medium vessel vasculitis and is associated with multiple skin symptoms: (1) vasculitis of digital arteries with ensuing digital infarction, (2) livedo racemosa and subcutaneous nodules, and (3) in some patients even purpura and hemorrhagic macules due to additional small vessel vasculitis. In contrast, in its skin-restricted entity (i.e., cutaneous polyarteritis nodosa), the predominant symptoms are subcutaneous nodules surrounded by livedo racemosa, often on the lower legs. Among small-vessel vasculitides palpable purpura with predilection for the legs is a nearly pathognomonic feature of immune complex vasculitis. Variations in clinical symptoms indicate additional pathophysiological mechanisms or different vascultides: (1) ANCA-associated vasculitides often also entail nodules or sometimes livedo, (2) cryoglobulinemic vasculitis additionally may present with necrosis at cold exposed areas and involvement of vessels of various size, (3) small vessel vasculitis associated with systemic lupus erythematosus or rheumatoid arthritis shows predilection for additional sites (e.g., nailfolds) and also involvement of vessels beyond postcapillary venules, (4) recurrent macular vasculitis in hypergammaglobulinemia also occurs on dependent parts, but shows numerous small hemorrhagic macules instead of palpable purpura, (5) erythema elevatum diutinum begins with brightly red to violaceous plaques at extensor sites, followed by fibrotic nodules. Consequently, cutaneous symptoms provide pivotal clues for further diagnosis and ensuing management of vasculitides.

[Common German language nomenclature for systemic sclerosis]. / Gemeinsame deutschsprachige Nomenklatur für die systemische Sklerose.

Large data bases and the projects arising from them have led to a much improved understanding of systemic sclerosis over the last decade. Serology has developed further so that more autoantibodies are available for routine testing. Capillary microscopy has become standard and relevant progress has also been made in therapy. Many diagnostic terms found in medical documentation do not adequately reflect this progress. The nomenclature is inconsistent and, therefore, confusing. The international classification of diseases (ICD) nomenclature is, from our point of view, also in need of improvement. This article aims to reestablish a common German language standard for systemic sclerosis, which reflects current knowledge and is suitable for implementation in the clinical routine.

[Systemic therapy with antibiotics. Overview of important antibiotics in dermatology]. / Systemtherapie mit Antiinfektiva. Übersicht über wichtige Antibiotika in der Dermatologie.

BACKGROUND: Systemic antibiotics are used in a targeted fashion, i.e. according to antibiogram whenever possible, otherwise in a calculated or empiric way. The pathogen to be treated can be identified sometimes by the clinical symptoms (e.g. in classical erysipelas) or by microbiological analysis. The latter requires adequate sampling methods. Due to the demographic development, which entails age-related multimorbidity and polypharmacy, criteria for the selection of the correct antibiotic not only encompass the pathogen spectrum and the tissue penetration of the drug, but also the risks for adverse events and unwanted interactions with other drugs. AIM: In this review article the mode of action, mechanisms of resistance, pharmacokinetics, adverse events, and drug interactions of the dermatologically important antibiotics are summarized, as are some relevant indications for their appropriate use in dermatology. RESULTS: For most bacterial skin and soft tissue infections beta-lactam antibiotics represent the first line therapy. They are efficacious, their adverse events are well known and defined, and they are mostly cost-effective. Penicillins G and V are recommended for classical erysipelas (caused by hemolytic streptococci). For uncomplicated soft tissue infections originating from wounds, which are mostly due to Staphylococcus aureus, the first line therapy are cephalosporins group 1 and 2, or isoxazoyl penicillins. The use of broad-spectrum antibiotics is indicated only for complicated soft tissue infections when a different spectrum of bacterial pathogens is suspected or when (multi-) resistant bacteria are supposed to be the causative organism.

[Systemic therapy with anti-infective agents. Principles of rational use of systemic antibiotics in dermatology]. / Systemtherapie mit Antiinfektiva. Grundlagen zum rationalen Einsatz systemischer Antibiotika in der Dermatologie.

BACKGROUND: Antibiotics are frequently prescribed and extremely valuable drugs, because they are curative. However, their often incorrect use is the main reason for the increase of multiresistant pathogens. Inappropriate prescription of broad spectrum antibiotics for skin and soft tissue infections favors the selection and spread of multiresistant bacteria not only in the skin, but also in remote visceral organs (e.g. in the intestines), due to their systemic distribution and effects in the body (so-called collateral damage). For this reason basic knowledge and special prudence when using antibiotics are just as desirable as an awareness of responsibility for the public welfare. AIM: This article intends to convey basic knowledge on the indications and selection of suitable antibiotics as well as on the development of bacterial resistance and it gives recommendations for allergological procedures when patients report alleged drug reactions to antibiotics. RESULTS: Systemic antibiotics for soft tissue infections are indicated when the infection spreads within the tissue so that it is no longer accessible for local antiseptics. In addition to the clinical symptoms, important parameters are high blood sedimentation rates (BSR) and high levels of C-reactive protein (CRP), leukocytosis with neutrophilia and fever (not always present in elderly or immunosuppressed patients). Certain constellations, such as the presence of severe underlying diseases, perfusion disorders or a particular localization (e.g. infection of the face) may necessitate early or parenteral administration. There is no need for systemic administration of antibiotics for uncomplicated wounds without soft tissue infections. Due to their curative effects, the decisive criterion for the use of antibiotics is their sufficient antimicrobial efficacy at the site of infection. An inappropriate administration increases both the selection pressure and costs of treatment and can have fatal consequences in serious situations. In dermatological patients the beta-lactam antibiotics penicillin V, penicillin G and cephalosporins of groups 1 and 2 are the antibiotics most commonly indicated for skin and soft tissue infections. If the patient's history arouses the suspicion of incompatibility to these antibiotics, allergological diagnostics should be carried out in order to avoid as often as possible the alternative use of antibiotics which result in more undesired effects and development of resistance.

[Persistent and recurrent skin and soft tissue infections by Staphylococcus aureus. Impact of the small colony-variant (SCV) phenotype and of Panton-Valentine leukocidin (PVL)-positive S. aureus isolates]. / Chronisch rezidivierende Infektionen der Haut und Weichgewebe durch Staphylococcus aureus. Klinische Bedeutung des Small-colony-variant (SCV)-Phänotyps und von Panton-Valentine-Leukozidin (PVL)-positiven S.-aureus-Isolaten.

Staphylococcus aureus is one of the major pathogens causing chronic skin and soft tissue infections. Particularly isolates producing Panton-Valentine leukocidin (PVL) comprising methicillin-susceptible and community-associated methicillin-resistant S. aureus (CA-MRSA) have been associated with more aggressive and persistent or relapsing courses. Beyond classical resistance mechanisms, functional resistance as shown by the small colony-variant (SCV) phenotype could be also responsible for treatment failures, despite the administration of antibiotics tested in vitro as susceptible. Also this phenotype has been associated with chronic courses of infections often with multiple exacerbations. Due to their ability to persist intracellularly, SCVs are protected from host defense and antibiotic treatment if only extracellularly active agents are administered. Reduced growth, abnormal colony morphology and changes in the metabolism of the SCVs aggravate drastically their identification, differentiation and susceptibility testing. The diagnostic and therapeutic challenges of PVL-positive and SCV isolates necessitate close collaboration with microbiological and infectious disease specialists.

Skin metastases in metastatic uveal melanoma: GNAQ/GNA11 mutational analysis as a valuable tool.

BACKGROUND: Uveal melanomas represent 3.1% of all melanomas, with a high potential of metastatic disease of up to 50%, where the median survival time is 6 months. Though liver metastases dominate as the primary site for metastasis, the existence of primary skin metastases is still under discussion but has been reported in only a few studies. OBJECTIVES: We present two cases in which patients with a known history of uveal melanoma developed melanoma skin metastases. METHODS: Mutational analysis was performed to clarify the origin of the metastases (uvea or skin). RESULTS: The analyses revealed GNA11 mutations, which are typical for uveal melanoma. These cases strongly suggest the skin to be the primary site of uveal melanoma. CONCLUSIONS: Knowledge about the mutational status of uveal melanomas opens the opportunity for future targeted therapies that directly interact with the mutation and its activated signal cascades. First trials in uveal melanoma have shown promising results with MEK inhibitors.

[Skin manifestations of different forms of vasculitis]. / Hautmanifestationen der verschiedenen Vaskulitiden.

The skin not only represents the organ which often reveals the first signs of systemic vasculitis, but also the organ which is most frequently involved in vasculitis. These diseases encompass systemic vasculitides and those which appear to involve the skin only. Among those vasculitides restricted to the skin, some are yet typically associated with other systemic diseases, such as nodular vasculitis, which often occurs during infections by M. tuberculosis, or erythema elevatum diutinum in patients with gammopathy. The type and localization of skin lesions give valuable indications as to the type of vasculitis. Subcutaneous nodules which ulcerate and are surrounded by livedo racemosa are suggestive of polyarteritis nodosa, a palpable purpura with predilection for the lower legs is almost pathognomonic for immune complex vasculitis (e.g. IgA vasculitis or cutaneous leukocytoclastic vasculitis), hemorrhagic papules and necrotic plaques which occur in acral areas after cooling indicate cryoglobulinemic vasculitis, hemorrhagic papules and macules which develop in patients who start to feel worse and develop fever should arouse suspicion of septic vasulitis, while the simultaneous presence of ulcerating nodules and hemorrhagic papules without predilection for the lower legs will suggest ANCA-associated vasculitis. The different morphology of the cutaneous signs of the various vasculitides depends to a large extent on the size of the vessels primarily involved. In this review the cutaneous signs of vasculitides will be presented with reference to the revised nomenclature of the Chapel Hill Consensus Conference from 2012.

Inhibition of benzalkonium chloride-induced skin inflammation in mice by an indol-1-ylpropan-2-one inhibitor of cytosolic phospholipase A2 α.

BACKGROUND: Irritant contact dermatitis (ICD) is a frequent and often underrated problem for which the major efficacious therapy is still local glucocorticoids, although they have known adverse effects due to their wide spectrum of action. A more focused therapeutic strategy would be the inhibition of a key enzyme for biosynthesis of the lipid mediators, cytosolic phospholipase A(2) α (cPLA(2) α), in ICD. We are analysing the pharmacological and biological effects of a selective cPLA(2) α inhibitor. OBJECTIVES: To examine the usefulness of the potent and selective cPLA(2) α inhibitor 3-(5-carboxypentanoyl)-1-[3-(4-octylphenoxy)-2-oxopropyl]indole-5-carboxylic acid (compound 1) for therapy of inflammatory skin disorders. METHODS: We examined clinical and cellular effects of a selective cPLA(2) α inhibitor (compound 1) on ICD in mice. RESULTS: Topical application of the compound significantly reduced ear swelling after induction by the irritant benzalkonium chloride. Concomitantly, compound 1 inhibited the accumulation of granulocytes as well as the expression of inflammatory proteins such as tumour necrosis factor-α, interleukin-1ß and macrophage inflammatory proteins 1α and 1ß in the ear tissue. In primary murine keratinocytes, the benzalkonium chloride-induced expression of these proteins was also downregulated after treatment with compound 1 in vitro. CONCLUSIONS: Compound 1 is a well-aimed agent for the treatment of nonspecific skin inflammation as it selectively inhibits cPLA(2) α and as it acts on an early stage of skin inflammation after its elicitation.