Eight Novel Mutations Confirm the Role of AAGAB in Punctate Palmoplantar Keratoderma Type 1 (Buschke-Fischer-Brauer) and Show Broad Phenotypic Variability.

Punctate palmoplantar keratoderma (PPKP1; Buschke-Fischer-Brauer) is a rare autosomal dominant inherited skin disease characterized by multiple hyperkeratotic papules involving the palms and soles. Mutations have been found at 2 loci, on chromosomes 15q22-15q24 and 8q24.13-8q24.21. We recently identified mutations in 3 families, in the AAGAB gene on 15q, which encodes the alpha- and gamma-adaptin-binding protein p34. The current study examined 14 additional families, comprising a total of 26 affected individuals and identified 8 novel mutations in 9 families. In one family a mutation that was present only in the affected individuals was found, and in 4 other families, previously reported mutations were found (1, 2). These results confirm the role of AAGAB in PPKP1. Our findings suggest that there is no correlation with age, but with mechanical factors. No additional obvious genotype-phenotype correlation was observed, even when comparing different types of mutations. Rather, identical genotypes presented a very broad interfamilial and intrafamilial variability of phenotypes.

S1-Guidelines on UV phototherapy and photochemotherapy.

Known in part since antiquity, the salutary effects of sunlight again garnered increasing attention in the second half of the 19(th) century. The development of a device for ultraviolet irradiation of cutaneous tuberculosis by Finnsen at the onset of the twentieth century truly marked the beginning of modern phototherapy. In dermatology, treatment methods almost exclusively use wavelengths below the visible light range (ultraviolet light). Since the early 1970s, increasingly powerful artificial light sources have become available for UVB and UVA therapy as well as the combination of UVA and photosensitizers (photochemotherapy). High structural and procedural quality standards are an essential prerequisite for the implementation of effective as well as safe phototherapy. The following guidelines outline the current consensus of leading experts in the field of phototherapy with respect to indications, contraindications, and side effects of various treatment options available. Particular focus is also on adequate UV doses at the beginning and over the further course of treatment as well as on management of side effects.

S1-Leitlinie zur UV-Phototherapie und Photochemotherapie.

Die heilsame Wirkung des Sonnenlichts war teilweise schon im Altertum bekannt und fand in der zweiten Hälfte des 19. Jahrhunderts wieder zunehmend Beachtung. Den Beginn der modernen Phototherapien markiert die Entwicklung einer Apparatur zur ultravioletten Bestrahlung der Hauttuberkulose durch Finnsen zu Beginn des zwanzigsten Jahrhunderts. Zur Therapie von Hauterkrankungen finden beinahe ausschließlich die spektralen Bereiche unterhalb des sichtbaren Lichtes (ultraviolett) Anwendung. Seit den 1970er Jahren stehen zunehmend leistungsfähige künstliche Strahlenquellen bereit für die Therapie mit UVB, UVA und die Kombination von UVA mit Photosensibilisatoren (Photochemotherapie). Hohe strukturelle und prozedurale Qualitätsstandards sind unabdingbare Voraussetzung für die Durchführung einer gleichermaßen wirkungsvollen wie auch sicheren Phototherapie. Die Leitlinie formuliert den aktuellen Konsens führender Experten auf dem Gebiet der Phototherapie in Bezug auf die Indikationen für die jeweiligen Therapieverfahren, deren Gegenanzeigen und Nebenwirkungen und insbesondere für die Wahl der korrekten Dosis zu Beginn und im Verlauf einer Therapie sowie das Management von Nebenwirkungen.

Chronic hand eczema: perception and knowledge in non-affected individuals from general and dermatological practice.

Misunderstanding and stigmatisation are common problems encountered by patients with hand eczema. Various misconceptions about the disease circulate in the general population. Although hand eczema has gained more attention in dermatology during the past years, information on public perception of the disease is still lacking. The aim of our study was to investigate perception of and level of knowledge on the subject hand eczema. There were 624 patients included from 2 general medicine practices and 2 dermatological practices. A self-administered questionnaire was filled out by the participants, covering issues on history of hand eczema, level of knowledge and attitude towards a clinical photograph of hand eczema. We found that a larger proportion of individuals from dermatological practice were more familiar with hand eczema as a disease than those from general medical practice. Women knew significantly more about and had a more positive perception of the disease than men. Our results imply that the level of knowledge on hand eczema in the general public is rather low and influenced by prejudice.

Childhood lichen planus pemphigoides: report of two cases treated successfully with systemic glucocorticoids and dapsone.

We describe two boys, ages 8 and 7 years, who developed lichen planus pemphigoides. In one of the boys, a henna tattoo probably triggered the disease. Therapy with systemic glucocorticoids and dapsone was successful.

Hemophagocytic lymphohistiocytosis/cytokine release syndrome secondary to neoadjuvant pembrolizumab for triple-negative breast cancer: a case study.

As indications for immune checkpoint inhibitors for breast cancer continue to expand, rare toxicities will emerge that require careful consideration and multidisciplinary management. We report the case of a 40-year-old female receiving neoadjuvant pembrolizumab and chemotherapy for locally advanced triple-negative breast cancer who developed cytokine release syndrome (CRS)/hemophagocytic lymphohistiocytosis (HLH). CRS/HLH secondary to pembrolizumab are scarcely documented in the literature and, to our knowledge, have never been reported in the context of neoadjuvant treatment for breast cancer.

A non-coding mutation in the 5' untranslated region of patched homologue 1 predisposes to basal cell carcinoma.

Mutations in the human homolog of the Drosophila patched gene, patched homologue 1 (PTCH-1), are responsible for most hereditary and sporadic basal cell carcinomas. Here, we present a father and daughter with a high propensity for the development of basal cell carcinoma who were heterozygous for a non-coding germline mutation in the 5' untranslated region (UTR) of PTCH-1 (insertion of a surplus CGG triplet at the site of a seven times CGG repeat). We analysed the impact of this mutation on PTCH translation using a luciferase-based reporter vector. Insertion of an eighth CGG in the 5' UTR repressed protein translation dramatically when compared to the wild-type sequence. Our results suggest that this non-coding variant in the 5' UTR represents a mutation predisposing to basal cell carcinoma.

Unilateral favre-racouchot disease: evidence for the etiological role of chronic solar damage.

Favre-Racouchot disease commonly presents as comedones, cysts and elastosis in the periocular region of older men. Its etiology has been linked to several exogenous factors. Here we present 2 patients with strictly unilateral manifestation of the disease and a corresponding history of predominantly one-sided chronic occupational sun exposure and smoking, making the case for the causative role of these two factors.

The epithelium specific cell cycle regulator 14-3-3sigma is required for preventing entry into mitosis following ultraviolet B.

BACKGROUND: Deoxyribonucleic acid damage activates cell cycle checkpoints in order to maintain genomic stability. We assessed the role of different checkpoint genes in response to ultraviolet B irradiation. METHODS: Cell lines expressing a dominant negative mutant of ataxia telangiectasia and Rad3 related (Atr) protein or overexpressing Cdc25A, cells deficient for 14-3-3σ, Nijmegen breakage syndrome (Nbs), or Ataxia telangiectasia mutated (Atm) were treated with ultraviolet B (UVB) and harvested after 12 h, 24 h, or 48 h for analysis by flow cytometry. RESULTS: Functional loss of Atm, Atr, or Nbs did not result in a significant alteration of the cell cycle profile. Overexpression of Cdc25A led to a delayed arrest at the G1/S transition in response to low doses of UVB. Loss of 14-3-3σ, a negative cell cycle regulator and downstream target of p53, caused a transient arrest at the G2/M boundary. CONCLUSIONS: Loss of 14-3-3σ sensitizes cells to UVB. After a transient cell cycle arrest, 14-3-3σ-deficient cells die by undergoing mitotic catastrophe. Cdc25A overexpression causes a delayed arrest in response to low doses of UVB. After higher doses, Cdc25A is no longer able to overrun the checkpoint. Atm, Atr, or Nbs are not essential for the checkpoint response to UVB, suggesting the existence of redundant signaling pathways.

Sensitization to common ragweed in southern Bavaria: clinical and geographical risk factors in atopic patients.

BACKGROUND: Sensitization to common ragweed (Ambrosia artemisiifolia) is associated with a variety of risk factors, which are incompletely defined. Our aim was to evaluate the association of a variety of clinical, geographical and demographical variables with ragweed sensitization and also to determine its frequency in southern Bavaria. METHODS: In this cross-sectional multicentre study, we enrolled 977 patients with a documented or suspected atopic disease or food allergy. Data were collected on aeroallergen sensitization, age, sex, type and history of allergic disease, place of residence and potential local ragweed exposure. For this last variable, county ragweed cover was taken as a surrogate variable. Relative rates were calculated with multiple additive logistic regression models. Randomly selected patients with ragweed sensitization had a conjunctival provocation test. RESULTS: According to skin prick tests, 190 patients (19.5%) were sensitized to ragweed. The frequency of this finding increased significantly with a rising number of additional sensitizations. Other less important predictors for a ragweed sensitization were male gender, mugwort sensitization, food allergy and a maximum of complaints in September or October. County of residence, extent of local ragweed cover or type of residential area were without relevance. Of 48 sensitized patients, 26 (54.2%) had a positive conjunctival provocation test. DISCUSSION: Patients with multiple sensitizations may be more readily sensitized to a new aeroallergen. Local geographic or environmental conditions are presumably of minor importance for becoming sensitized to ragweed. The frequency of ragweed allergy among sensitized patients might be high.

Cutaneous T-cell lymphoma mimicking myopathy with lipoatrophy.

Mycosis fungoides (MF) is the most common form of primary cutaneous T-cell lymphoma. Classic MF usually follows a rather benign course over many years or decades, rarely ever leading to fatal extracutaneous organ involvement. Single cases of muscular involvement have been reported. Here we describe a 42-year-old male patient with hair loss and lipoatrophy since six months diagnosed as follicular MF and with a two months history of progressive distal leg weakness. Muscle biopsy and whole body muscle MRI showed an extensive muscular and subcutaneous fatty tissue infiltration. After therapy with topical steroids and acitretin/PUVA, systemic chemotherapy (CHOP) was initiated. The patient suffered from a rapid disease progression with fatal outcome 2.5 years after the first skin lesions, displaying progressive cachexia, muscular atrophy and weakness with scapuloperoneal distribution and cardiac dysfunction. So far, extensive muscular involvement by MF mimicking a distinct muscular phenotype has not been reported.