Kristin Technau-Hafsi

Overlap of IgA pemphigus and linear IgA dermatosis in a patient with ulcerative colitis: a mere coincidence?

IgA pemphigus and linear IgA dermatosis (LAD) are rare autoimmune bullous disorders characterized by intraepidermal or dermo-epidermal IgA deposition and blister formation, respectively. IgA pemphigus is divi-ded into different subgroups according to clinical and histological findings: a subcorneal pustular dermatosis (SPD) type and an intraepidermal neutrophilic (IEN) type (1–3). The latter is clinically characterized by flac-cid vesiculopustules forming annular lesions with central crusts, often appearing as “sunflower-like” lesions. Direct immunofluorescence demonstrates intercellular IgA de-position throughout the epidermis. Patients with the SPD type often display circulating autoantibodies of the IgA class against the desmosomal protein desmocollin 1, in contrast to IgA autoantibodies to heterogeneous antigens including desmoglein 1 or 3 in patients with the IEN type of IgA pemphigus. The subepidermal bullous dermatosis LAD presents with annular tense blisters with a “crown of jewels-like” pattern, linear IgA deposition at the ba-sement membrane zone, and circulating autoantibodies that most frequently target the soluble BP180/collagen XVII ectodomain (4). In contrast to the more common eosinophil-rich autoimmune blistering dermatoses pem -phigus vulgaris and bullous pemphigoid, the development of IgA pemphigus and LAD is based on IgA deposition in the skin, which results in neutrophil chemotaxis and subsequent blister formation (5). CASE REPORT

Palmoplantar keratodermas: clinical and genetic aspects

Palmoplantar keratodermas comprise a diverse group of acquired and hereditary disorders marked by excessive thickening of the epidermis of palms and soles. Early onset and positive family history suggest a genetic cause. While hereditary forms of palmoplantar keratoderma (PPK) may represent the sole or dominant clinical feature, they may also be associated with other ectodermal defects or extracutaneous manifestations. In recent years, much progress has been made in deciphering the genetic basis of PPK, which has led to the emergence of new disorders and syndromes. The elucidation of disease mechanisms has opened new avenues for specific therapies, increasingly sparking interest in this field. Given the high heterogeneity with respect to clinical features, genetic defects, and disease mechanisms, the classification of PPK is based on various criteria. These include extent of disease manifestations, morphology of palmoplantar skin involvement, inheritance patterns, and molecular pathogenesis. Though not always feasible, the clinical distinction of various PPK entities is based on fine‐tuned criteria or clues. Remarkably, apparently distinct disorders have been shown to be allelic, as they are caused by mutations in the same gene. By contrast, similar clinical pictures may result from mutations in different genes. Because of this complexity, mutation analysis is required to determine the precise type of PPK. The best‐defined entities are described in this review.

Biglycan expression in the melanoma microenvironment promotes invasiveness via increased tissue stiffness inducing integrin-β1 expression

Novel targeted and immunotherapeutic approaches have revolutionized the treatment of metastatic melanoma. A better understanding of the melanoma-microenvironment, in particular the interaction of cells with extracellular matrix molecules, may help to further improve these new therapeutic strategies. We observed that the extracellular matrix molecule biglycan (Bgn) was expressed in certain human melanoma cells and primary fibroblasts when evaluated by microarray-based gene expression analysis. Bgn expression in the melanoma tissues correlated with low overall-survival and low progression-free-survival in patients. To understand the functional role of Bgn we used gene-targeted mice lacking functional Bgn. Here we observed that melanoma growth, metastasis-formation and tumor-related death were reduced in Bgn−/− mice compared to Bgn+/+ mice. In vitro invasion of melanoma cells into organotypic-matrices derived from Bgn−/− fibroblasts was reduced compared to melanoma invasion into Bgn-proficient matrices. Tissue stiffness as determined by atomic-force-microscopy was reduced in Bgn−/− matrices. Isolation of melanoma cells and fibroblasts from the stiffer Bgn+/+ matrices revealed an increase in integrin-β1 expression compared to the Bgn−/− fibroblast matrices. Overexpression of integrin-β1 in B16-melanoma cells abolished the survival benefit seen in Bgn−/− mice. Consistent with the studies performed in mice, the abundance of Bgn-expression in human melanoma samples positively correlated with the expression of integrin-β1, which is in agreement with results from the organotypic invasion-assay and the in vivo mouse studies. This study describes a novel role for Bgn-related tissue stiffness in the melanoma-microenvironment via regulation of integrin-β1 expression by melanoma cells in both mice and humans.

Recurrent ulceronecrotic plaques and nodules with spontaneous remission

A 66-year-old patient presented with a fi ve-week history of an indolent nodule in the right axilla and an ulceronecrotic plaque in the left nuchal region, which already showed signs of regression. Both lesions had occurred within a few weeks, had rapidly increased in size and shown spontaneous ulceration. A similar nodule had occurred on the right side of the neck a few years earlier and had spontaneously healed with scar formation. Six months earlier, the patient had been diagnosed with poorly differentiated adenosquamous lung cancer, pT2b pN2(3/39) cM0, stage IIIA (UICC), which had subsequently been treated by lower lobectomy. He was in good general health and denied any B symptoms. Recent follow-up imaging studies had yielded no evidence of recurrence or metastasis related to the NSCLC (non-small-cell lung cancer).

A new clinical variant of acquired reactive perforating dermatosis-like bullous pemphigoid

Bullous pemphigoid (BP) is a blistering disorder associated with circulating autoantibodies against BP180/ collagen XVII. As part of a prodromal stage patients might present with eczematous lesions or erythematous papules and prurigo- or urticaria-like erythema without any blistering. Recent studies described four patients with clinical features resembling acquired reactive perforating dermatosis (ARPD) co-existing with BP. They initially presented with papules and nodules with a central keratotic plaque; diabetes mellitus (DM) and hemodialysis thought of being causative. This article is protected by copyright. All rights reserved.

Papulopustular lesions of the face and scalp

A 43-year-old Central European man presented with painful erythema and widespread pustules that had fi rst appeared on the nose and cheeks in March 2015, and had subsequently spread to the scalp and neck. The patient suspected an association with the rubber breathing mask he had to wear several hours a day during his job as a car painter. He denied any increased photosensitivity. His medical history showed no evidence of preexisting atopic dermatitis, allergic rhinoconjunctivitis, or asthma.

Keratosis palmoplantaris: klinische und genetische Aspekte

Zu den Palmoplantarkeratosen (PPK) gehören verschiedene erworbene und angeborene Störungen, die durch übermäßige Verdickung der Epidermis an Handflächen und Fußsohlen gekennzeichnet sind. Ein früher Ausbruch und eine positive Familienanamnese weisen auf eine genetische Ursache der PPK hin. Eine angeborene PPK kann das einzige oder das dominante klinische Merkmal darstellen oder sie kann von anderen ektodermalen Dysplasien oder extrakutanen Symptomen begleitet sein. In der letzten Zeit wurden bei der Entschlüsselung der genetischen Grundlagen der PPK deutliche Fortschritte erzielt und neue Störungen und Syndrome sind bekannt geworden. Die Aufklärung der Krankheitsmechanismen öffnet neue Wege für spezifische Therapien und macht dieses Gebiet immer interessanter. Wegen der starken Heterogenität der klinischen Merkmale, genetischen Defekte und Krankheitsmechanismen können PPK auf der Grundlage unterschiedlicher Kriterien klassifiziert werden. Dazu gehören das Ausmaß der Krankheitsmanifestationen, die Morphologie der befallenen palmoplantaren Hautbereiche, das Vererbungsmuster oder die molekulare Pathogenese. Die klinische Differenzierung zwischen den PPK‐Entitäten stützt sich auf subtile Kriterien oder Anzeichen und ist nicht immer möglich. Interessanterweise haben sich scheinbar unterschiedliche Erkrankungen als allelisch erwiesen, werden also durch Mutationen im selben Gen ausgelöst. Andererseits können ähnliche Krankheitsbilder durch Mutationen in verschiedenen Genen verursacht sein. Aufgrund dieser Komplexität muss der genaue Typ der PPK durch Mutationsanalyse bestimmt werden. Die am besten definierten Entitäten werden in diesem Übersichtsartikel beschrieben.

Vegetierende Plaques bei einem Patienten mit Anfallserkrankung

Ein 12-jähriger Junge stellte sich mit mehreren schmerzhaften nodulären Plaques an den Unterschenkeln vor, die sich in den vorangegangenen vier Wochen während eines längeren Ferienaufenthaltes in der Türkei gebildet hatten. Er war mehrfach sowohl topisch als auch systemisch antibiotisch behandelt worden, ohne eine Besserung zu erreichen. Seine Eigenanamnese ergab eine psychosomatische Retardierung unklarer Genese sowie eine schwer zu kontrollierende generalisierte Epilepsie. Die medikamentöse Therapie der Epilepsie bestand aus Lamotrigin, Levetiracetam und Kaliumbromid.

Vegetating plaques in a patient with a seizure disorder

A 12 year-old boy presented with multiple painful nodular plaques on the lower legs that had developed over the previous four weeks during a longer vacation in Turkey. He had undergone several cycles of topical and systemic antibiotics without success. His personal history revealed a developmental retardation of unknown cause and a severe seizure disorder that had been very difficult to control. His medications included lamotrigine, levetiracetam, and potassium bromide.

Pruritic intertriginous vesiculopustular eruption

A 64-year-old Turkish woman presented with progressive pr -uritic vesicles and erosions in the intertriginous areas, which she first detected during the summer months of the previous year. She reported developing more than 5 new vesicles each week that ruptured promptly after scratching and resolved le -aving hyperpigmentation but no scarring. Her general health was good and she was on no medications.