Disseminated Mycobacterium marinum infection with extensive cutaneous eruption and bacteremia in an immunocompromised patient

Mycobacterium marinum can cause fish tank granuloma (or swimming pool or aquarium granuloma) in immunocompetent patients. Dissemination of Mycobacterium marinum-infection is a rare condition which occurs mainly in immunocompromised patients and can be life-threatening. We report the case of an 87-year-old woman who was treated with oral corticosteroids for polymyalgia rheumatica for many years and developed erythema nodosum-like lesions on the right forearm and arthritis of the right wrist. By increasing the steroid dosage and adding methotrexate only short-term remission was achieved. Seven months later painful erythematous nodules occurred on all extremities which became necrotic, ulcerative and suppurative. Ziehl-Neelsen staining revealed acid-fast bacilli and Mycobacterium marinum was cultured from skin biopsies, blood, and urine. The critically ill patient was treated with clarithromycin and ethambutol resulting in a dramatic improvement of the general condition. After four months, doxycycline had to be added because of new skin lesions. This case illustrates the impact of Mycobacterium marinum infection in immunocompromised patients.

Detection of perforin and granzyme B mRNA expressing cells in lichen sclerosus

Granzyme B and perforin messenger RNA (mRNA) expression has been shown to be a specific in vivo activation marker for cytotoxic cells. The aim of this study was to assess the contribution of cell-mediated cytotoxicity in the pathogenesis of lichen sclerosus. In situ hybridization and immunohistochemistry were performed on serial tissue sections of lesional skin biopsies and normal skin as control. Immunohistochemical staining showed that the cellular infiltrate of diseased skin consisted predominantly of T cells (CD3+) and some B cells (CD20+). Among T cells CD4+ and CD8+ cells were found in about equal numbers. In normal skin samples perforin and granzyme B mRNA expressing cells were only rarely found. In contrast, in biopsies from diseased skin a high percentage of infiltrating cells expressed mRNA for perforin and granzyme B. The perforin and granzyme B expressing cells were found in the dermal infiltrate and intraepidermally in close proximity to keratinocytes suggesting in situ activation of these cells. These findings provide evidence that cell-mediated cytotoxicity plays a significant role in tissue destruction in lichen sclerosus.

Efalizumab-associated papular psoriasis

BACKGROUND: Efalizumab is a human anti-CD11a monoclonal antibody used in the treatment of patients with moderate to severe plaque psoriasis. Some of the patients develop new papular lesions during treatment, which are predominantly located in the flexural regions. OBSERVATION: Four patients with recalcitrant psoriasis undergoing treatment with efalizumab presented with erythematous, partly scaly papules and small plaques on previously unaffected areas after 4 to 10 weeks of efalizumab therapy. Tissue sections of biopsy specimens were stained with hematoxylin-eosin, and immunohistochemical staining was performed using monoclonal antibodies against CD3, CD4, CD8, T-cell-restricted intracellular antigen 1, granzyme B, neutrophil elastase, CD68, CD1a, CD11c, HLA-DR, CD25, CD20, and CD56. Histopathological and immunohistochemical examination of the lesions showed features consistent with psoriasis and activation of various leukocyte subtypes including T cells, dendritic cells, macrophages, and neutrophils. CONCLUSIONS: Papular eruptions appearing during efalizumab therapy represent new psoriatic lesions and could be referred to as efalizumab-associated papular psoriasis (EAPP). They usually do not necessitate termination of efalizumab therapy and may optionally be treated with topical corticosteroids. Dermatologists should be aware of these lesions and inform their patients accordingly.

Wegener's granulomatosis presenting as pyoderma gangrenosum

Half of the patients with Wegener's granulomatosis develop skin lesions due to the systemic vasculitis. Wegener's granulomatosis should be included in the differential diagnostic considerations for necrotic ulcers, including leg ulcers. We present a case which demonstrates the importance of histological evaluation of a skin biopsy from the margin of the ulcer for establishing the diagnosis. Antineutrophil cytoplasmic antibodies with antigen specificity for proteinase 3 (PR3-ANCA) were detected supporting the diagnosis of Wegener granulomatosis. Further evaluation showed involvement of the eyes and kidneys. The ulcer rapidly healed under treatment with cyclophosphamide and corticosteroids.

Photodynamic therapy in the treatment of actinic keratosis

The efficacy of photodynamic therapy (PDT) with 5-aminolevulinate and methyl aminolevulinate in the treatment of actinic keratosis has been demonstrated in a large number of clinical studies over the last several years. Here, we recapitulate the major findings, comparing the various photosensitizers, light sources and therapeutic regimens, and present a retrospective analysis of 142 own cases treated with 259 PDTs. In addition, we also discuss the value of PDT in comparison with cryotherapy or 5-fluorouracil. The efficacy and the low risk of side effects of PDT have resulted in a high patient preference in clinical trials.

Alopecia areata universalis elicited during treatment with adalimumab

Adalimumab is a fully humanized recombinant anti-tumour-necrosis-factor (TNF-alpha) monoclonal antibody which has been approved for rheumatoid arthritis, active ankylosing spondylitis, psoriatic arthritis and Crohn's disease. We report a case of alopecia areata (AA) universalis occurring 6 months after administration of adalimumab monotherapy in a patient with a long-standing history of psoriatic arthritis and psoriasis. The diagnosis was confirmed by a scalp biopsy which showed a peribulbar infiltrate of both CD4+ and CD8+ T cells, CD1a+ dendritic cells as well as CD68+ and CD163+ macrophages. In addition, immunofluorescence staining for TNF-alpha was found in the mononuclear cell infiltrate. This case suggests a complex role of TNF-alpha in the induction of AA.

Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization

The QT interval, an electrocardiographic measure reflecting myocardial repolarization, is a heritable trait. QT prolongation is a risk factor for ventricular arrhythmias and sudden cardiac death (SCD) and could indicate the presence of the potentially lethal mendelian long-QT syndrome (LQTS). Using a genome-wide association and replication study in up to 100,000 individuals, we identified 35 common variant loci associated with QT interval that collectively explain ∼8-10% of QT-interval variation and highlight the importance of calcium regulation in myocardial repolarization. Rare variant analysis of 6 new QT interval-associated loci in 298 unrelated probands with LQTS identified coding variants not found in controls but of uncertain causality and therefore requiring validation. Several newly identified loci encode proteins that physically interact with other recognized repolarization proteins. Our integration of common variant association, expression and orthogonal protein-protein interaction screens provides new insights into cardiac electrophysiology and identifies new candidate genes for ventricular arrhythmias, LQTS and SCD.

Der Koran und die Genealogie des Islam

Lange war man im Westen davon überzeugt gewesen, dass zwischen Religion, Gesellschaft und Staat in der Epoche der europäischen Aufklärung ein Einverständnis gefunden worden ist. Diese Sicherheit ist in den vergangenen Jahrzehnten ins Wanken geraten. Im Namen ‘des’ Islam werden Terroranschläge verübt und Kriege geführt. Von vielen Menschen wird ‘der’ Islam als eine Religion wahrgenommen, die nicht zwischen Religion und Zivilgesellschaft unterscheidet und den Friedenszustand gefährdet. Doch gibt es überhaupt ‘den’ Islam oder ‘den’ Koran? Der Islam wird oft in einer problematischen Vereinfachung auf den Koran und den Propheten Muḥammad reduziert. Daraus wird dann der Kurzschluss gezogen, der Islam lasse sich aus diesem Ursprung heraus definieren. Gegen dieses ahistorische Ursprungsdenken und die damit einhergehenden Stereotypen zu ‘dem’ Islam und ‘dem’ Koran bring Reinhard Schulze die Geschichte in Anschlag. Er verfolgt in seiner gelehrten und analytisch präzisen Studie die Geschichte der Entstehung der Schrift Koran über deren sprachliche Verfasstheit (das Arabische) und Intertexte; betrachtet die Offenbarung an Muḥammad aus historischer Perspektive und reflektiert – nicht zuletzt – über die Voraussetzungen und unhinterfragten Prämissen des wissenschaftlichen Diskurses über den Islam – so etwa im Orientalismus des 19. Jahrhunderts, in der Rede von der Religion als anthropologischer Konstante oder neurobiologischer ‘Programmierung’.

Antwort Sr. Maj. des Königs, an die Deputation der Bürger, vom zweiten Wahlbezirk, auf ihre Bitte, um Aufhebung des Belagerungs-Zustandes: Seine Majestät empfingen die Deputation ernst und sprachen Sich in kurzen Worten dahin aus ...

Welsch (Projektbearbeiter): Friedrich Wilhelm IV. lehnt die Bitte um Aufhebung des Belagerungszustandes mit der Begründung ab, er lasse sich durch nichts bestimmen, von dem, was er für gut und recht für sein Volk erachte, abzugehen und bezieht sich dabei auf den Inhalt des Liedes Nr. 205 des Porst'schen Evangelischen Kirchengesangbuches ("Gott selbsten hat dies Wort / der Wahrheit fest versiegelt ...")

European Dermatology Forum Guidelines on topical photodynamic therapy

Topical photodynamic therapy (PDT) is a widely approved therapy for actinic keratoses, squamous cell carcinoma in-situ, superficial and certain thin basal cell carcinomas. Recurrence rates are typically equivalent to existing therapies, although inferior to surgery for nodular basal cell carcinoma. PDT can be used both as a lesional or as a field therapy and has the potential to delay/reduce the development of new lesions. PDT has also been studied for its place in the treatment of, as well as its potential to prevent, superficial skin cancers in immune-suppressed patients, although sustained clearance rates are lower than for immunocompetent individuals. Many additional indications have been evaluated, including photo-rejuvenation and inflammatory and infective dermatoses. This S2 guideline considers all current and emerging indications for the use of topical photodynamic therapy in Dermatology, prepared by the PDT subgroup of the European Dermatology Forum guidelines committee. It presents consensual expert recommendations reflecting current published evidence. An unabridged version of this guideline is available online at: http://www.euroderm.org/edf/index.php/edf-guidelines.

Molecular diagnostics of myeloproliferative neoplasms

Since the discovery of the JAK2 V617F mutation in the majority of the myeloproliferative neoplasms (MPN) of polycythemia vera, essential thrombocythemia and primary myelofibrosis ten years ago, further MPN-specific mutational events, notably in JAK2 exon 12, MPL exon 10 and CALR exon 9 have been identified. These discoveries have been rapidly incorporated into evolving molecular diagnostic algorithms. Whilst many of these mutations appear to have prognostic implications, establishing MPN diagnosis is of immediate clinical importance with selection, implementation and the continual evaluation of the appropriate laboratory methodology to achieve this diagnosis similarly vital. The advantages and limitations of these approaches in identifying and quantitating the common MPN-associated mutations are considered herein with particular regard to their clinical utility. The evolution of molecular diagnostic applications and platforms has occurred in parallel with the discovery of MPN-associated mutations, and it therefore appears likely that emerging technologies such as next-generation sequencing and digital PCR will in the future play an increasing role in the molecular diagnosis of MPN. Accepted for publication 30 April 2015 doi:10.1111/ejh.12578