Alterations in innate immunity and epithelial cell differentiation are the molecular pillars of hidradenitis suppurativa.

BACKGROUND: The large unmet need of hidradenitis suppurativa/acne inversa (HS) therapy requires the elucidation of disease-driving mechanisms and tissue targeting. OBJECTIVE: Robust characterization of the underlying HS mechanisms and detection of the involved skin compartments. METHODS: Hidradenitis suppurativa/acne inversa molecular taxonomy and key signalling pathways were studied by whole transcriptome profiling. Dysregulated genes were detected by comparing lesional and non-lesional skin obtained from female HS patients and matched healthy controls using the Agilent array platform. The differential gene expression was confirmed by quantitative real-time PCR and targeted protein characterization via immunohistochemistry in another set of female patients. HS-involved skin compartments were also recognized by immunohistochemistry. RESULTS: Alterations to key regulatory pathways involving glucocorticoid receptor, atherosclerosis, HIF1α and IL17A signalling as well as inhibition of matrix metalloproteases were detected. From a functional standpoint, cellular assembly, maintenance and movement, haematological system development and function, immune cell trafficking and antimicrobial response were key processes probably being affected in HS. Sixteen genes were found to characterize HS from a molecular standpoint (DEFB4, MMP1, GJB2, PI3, KRT16, MMP9, SERPINB4, SERPINB3, SPRR3, S100A8, S100A9, S100A12, S100A7A (15), KRT6A, TCN1, TMPRSS11D). Among the proteins strongly expressed in HS, calgranulin-A, calgranulin-B and serpin-B4 were detected in the hair root sheath, koebnerisin and connexin-32 in stratum granulosum, transcobalamin-1 in stratum spinosum/hair root sheath, small prolin-rich protein-3 in apocrine sweat gland ducts/sebaceous glands-ducts and matrix metallopeptidase-9 in resident monocytes. CONCLUSION: Our findings highlight a panel of immune-related drivers in HS, which influence innate immunity and cell differentiation in follicular and epidermal keratinocytes as well as skin glands.

[Dermatomyositis with tonsillar carcinoma. Rare presentation as paraneoplastic syndrome]. / Dermatomyositis bei Tonsillenkarzinom. Seltener Zusammenhang als paraneoplastisches Syndrom.

BACKGROUND: Malignant tumors occur in up to 15 % of patients with paraneoplastic syndromes. The temporal association between malignancy and paraneoplasia is variable. Dermatomyositis belongs to the facultative cutaneous paraneoplasia. CASE REPORT: A patient presented with a cervical swelling and preexisting dermatomyositis. Staging revealed a tonsillar carcinoma with cervical, mediastinal and bone metastasis, and meningeal carcinomatosis. Systemic intrathecal chemotherapy was initiated. CONCLUSION: Dermatomyositis has only been described four times worldwide as a paraneoplastic disease with tonsillar carcinoma. Upon occurrence of a paraneoplastic syndrome, an intensive search for tumours is required at regular intervals until the primary tumor is diagnosed.

[Cholesterol embolism syndrome after coronary angiography]. / Cholesterinemboliesyndrom nach Koronarangiographie.

Cholesterol crystal embolization (cholesterol embolism, cholesterol embolic disease) is a multiorgan disease, which is a severe iatrogenic complication from an invasive vascular procedure, such as manipulation of the aorta during angiography or vascular surgery, and after anticoagulant and fibrinolytic therapy. The diagnosis is made postmortem in two-thirds of cases. Cholesterol crystal embolism is an increasing and still underdiagnosed disease. Pathognomonic is the constellation of acral pain, nonhealing ulcerations and necrosis, livedo racemosa with intact peripheral arterial pulses and sudden onset of renal failure and arterial hypertension. Biopsy of the affected organs is essential for diagnosis. We report the case of a 66-year-old man who following coronary arteriography with PTCA and implantation of stents developed acral necrosis and cyanosis, livedo racemosa and acute irreversible renal failure.

[The umbilical metastasis. Sister Mary Joseph and her time]. / Die Nabelmetastase. Sister Mary Joseph und ihre Zeit.

Although Baluff in 1854 and Nelaton in 1860 had already described umbilical metastases, the best known description of the metastasis of carcinomas to this site as "trouser button navel" was published in 1928 by William James Mayo (1861-1939), son of William Worrall Mayo (1815-1911), the founder of the Mayo Clinic in Rochester, Minnesota, This phenomenon is supposed to have been pointed out to Mayo by his long-serving head surgical nurse Sister Mary Joseph (1856-1939). The English surgeon Hamilton Bailey, in his famous textbook "Physical Signs in Clinical Surgery" in 1949, coined the term "Sister Joseph's nodule" for an umbilical metastasis. The expression has become widely accepted and used. Sister Mary Joseph, daughter of Irish immigrants, belonged to the 3rd order of the Holy Francis, was distinguished for her skills, intelligence and devotion to nursing which was also her calling. She worked for many decades at the world-famous Mayo Clinic and taught generations of young nurses. In recent years, the original surgical building at Saint Mary's Hospital has been named "Joseph Building" in her memory. Among the numerous eponyms occurring in the dermatology and the medicine, the association with the name of a nurse represents beyond doubt a special feature.

[Acquired epidermolysis bullosa with a highly varied clinical picture and successful treatment with mycophenolate mofetil]. / Epidermolysis bullosa acquisita mit facettenreichem klinischen Bild und erfolgreicher Mycophenolatmofetiltherapie.

A 60-year-old woman with epidermolysis bullosa acquisita (EBA) presented with a highly variable clinical picture. First she developed oral erosions and ulcers covered with shaggy epithelial rests. Later she developed pustular and target lesions as well as tense cutaneous blisters. Clinically the alterations were strongly suggestive of aphthae or a pustular dermatosis. Histological and immunological examinations revealed subepidermal blister formation, neutrophilic infiltration, linear deposition of IgG and C3 at the basement membrane in the direct immunofluorescence and the evidence of circulating IgG-antibodies against basement membrane (monkey esophagus) in the indirect immunofluorescence. Thus our working diagnosis was a pustular or nodular form of bullous pemphigoid, as a linear IgA dermatosis was excluded. Indirect immunofluorescence using NaCl-separated primate skin localized the basement membrane antibodies in the base of the artificial blister, while immunoblotting of dermal extracts disclosed binding of serum antibodies to a 290-kDa protein. Bullous systemic lupus erythematosus was excluded, leading to the definitive diagnosis of EBA. The clinical variability of this disease is well known; the polymorphic picture in our patient with erosions, pustules, target lesions and blisters is unique in the literature. The similarity in histology and immunofluorescence of the clinically quite different lesions is another unexpected event. Also the speedy response to therapy with the immunosuppressive agent mycophenolate mofetil has only been described once before. The patient remains in remission after 6 months. Because of the poor response to therapy in most cases, the significant skin lesions are a source of physical as well as emotional distress. Additional complications include stenosis of trachea or bronchi injure.

[Transthoracic-transabdominal resection of esophageal carcinoma]. / Ein Beitrag zur transthorakalen-transabdominalen Resektion des Oesophaguskarzinoms.

54 patients suffering from esophageal cancer have been treated in a period from 1990 to 1994. In 29 cases curative resection was possible, corresponding to a resection rate of 54%. Average age of resected patients was 62 years. According to pTNM-classification the stages T1 and T2 amounted to 45%, T3 and T4 to 55%. Lymphatic node metastases were discovered with an incidence of 55%. In patients treated conservatively more unfavourable stage distributions and increased rates of lymphatic node metastasis were shown. Transthoracal-transabdominal esophageal resection was preferred as curative management. Lethality amounted to 13.8%. In 3 of 4 lethal cases after resection autopsy confirmed absence of tumor. Lethal complications were two respiratory insufficiencies, one suture line dehiscence and one alcoholic delirium. Survival rates were calculated by life-table-method. We consider the transthoracal-transabdominal esophageal resection as an acceptable therapeutic option in esophageal cancer offering a real chance of enduring curing.