Investigation of gamma secretase gene complex mutations in German population with Hidradenitis suppurativa designate a complex polygenic heritage.

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic inflammatory disease affecting apocrine gland-bearing skin in the axilla, groin and under the breasts. Mutations of the gamma secretase gene complex, which is essential in the activation of Notch signalling pathways, were shown in some families with HS and in a few sporadic cases. Although an imbalance in Notch signalling is implicated in the pathogenesis, the exact mechanism of HS development is yet unknown. OBJECTIVES: We aim to investigate the genetic basis of HS by determining the presence of mutations of gamma secretase gene complex in a cohort of HS patients and by searching for a disease-causing pathogenic variant in a multi-generational HS family using parametric linkage analysis. METHODS: Thirty-eight patients clinically diagnosed with HS were included in this study. All exons and exon-intron boundaries of the genes encoding gamma secretase complex consisting of six genes: APH1A, APH1B, PSENEN, NCSTN, PSEN1 and PSEN2 were sequenced by Sanger technique. Genetic mapping with parametric linkage analysis for the patients in the family was performed with eight affected and four healthy individuals. The logarithm of odds was calculated. RESULTS: In a sporadic patient with early-onset, severe lesions in axilla and groin, a novel single-nucleotide deletion causing frameshift in exon 1 of the NCSTN gene was identified ((NM_015331.3): c.38delG, p.(Gly13Glufs*15)). The LOD score of 1.5 was never exceeded in any region of the genome, pointing towards intricate multi-genic inheritance pattern within the affected family. CONCLUSIONS: The gamma secretase gene complex mutations were rare in our cohort (3.2%). Besides, our analysis indicates a possible complex multi-genic inheritance in a seemingly autosomal dominantly inherited large HS family. Genetics of both familial and sporadic HS may be complicated in most cases, and the role of other potential genes such as autoinflammatory and modifier genes as well as environmental factors may influence the pathogenesis.

[Malignant atrophic papulosis (Köhlmeier-Degos disease). Failure to respond to interferon alpha-2a, pentoxifylline and aspirin]. / Maligne atrophische Papulose (Morbus Köhlmeier-Degos) Kein Ansprechen auf Interferon alpha-2a, Pentoxifyllin und Azetylsalizylsäure.

A 45 year old female patient presented with the cutaneous manifestations of malignant atrophic papulosis (Köhlmeier-Degos disease) for two years. The typical papules with central porcelain-white atrophy correspond histologically to wedge-shaped necrosis of the connective tissue due to thrombotic occlusion of small vessels in the corium. The pathogenesis of malignant atrophic papulosis and effective treatment modalities are unknown. A slow virus infection has been suggested by some authors. Therefore, we attempted an immune therapy with interferon alpha-2a over a period of 11 months, but failed to cause a significant effect on the appearance and progression of the skin lesions. Furthermore, we could not confirm the effectiveness of a recently reported treatment modality with pentoxifylline and aspirin administered to our patient over a period of 5 months.

[Erysipelas carcinomatosum in tubular adenocarcinoma of the stomach]. / Erysipelas carcinomatosum bei tubulärem Adenokarzinom des Magens.

Erysipelas carcinomatosum is an inflammatory infiltration of dermal lymphatic vessels by tumor cells of a metastatic adenocarcinoma mimicking common erysipelas. It is most often due to adenocarcinomas, especially breast cancer. A 51 year-old male patient developed erysipelas carcinomatosum on his right chest wall due to a tubular adenocarcinoma of the stomach.