Preliminary findings suggest hidradenitis suppurativa may be due to defective follicular support.

BACKGROUND: The initial pathology in hidradenitis suppurativa (HS)/acne inversa takes place in the folliculopilosebaceous unit (FPSU) and its surrounding tissue. The process involves follicular hyperkeratosis, inflammation and perifolliculitis. Identification of the exact origin of inflammation may shed new light on the pathogenesis and aetiology of the disease. OBJECTIVES: To study the morphology of the basement membrane zone (BMZ) in patients with HS. METHODS: In total, 65 operative specimens from 20 patients diagnosed with HS were cut stepwise. Within each specimen, the focus was set on heavily involved HS regions (centre) and clinically uninvolved regions (border). All specimens were stained with periodic acid-Schiff (PAS) to visualize the epithelial support structures of the FPSU (i.e. the BMZ), the sinus tracts (STs) and the interfollicular basement membrane (BM). The intensity of BMZ PAS staining was graded from 0 to 4+. RESULTS: Compared with the axillary skin of human controls, the sebofollicular junction in patients with HS was found to be almost devoid of PAS-positive material (grade 0/1+) in both the border and centre lesions of HS, whereas STs and BMs showed uniformly grade 2-3+ positivity irrespective of any inflammation present. The distribution of inflammatory cells around the sebofollicular junction occurred predominantly in areas of BMZ thinning. CONCLUSIONS: The BMZ PAS positivity of clinically uninvolved FPSUs of patients with HS appears to be wispy or not present at all. It is speculated that this may explain the apparent fragility of the sebofollicular junction. There is an increased concentration of inflammatory cells adjacent to these areas, while inflammatory cells are scarce in areas where the PAS-positive material is intact. It is hypothesized that the PAS gap identifies (i) areas susceptible to leakage, trauma and rupture, leading to release of materials that trigger inflammatory mediators, and (ii) the seeding of the dermis with free-living stem cells generating benign but invasive epithelialized sinuses, spreading horizontally in and below the dermis.

[Umbilical endometriosis]. / Endometriose ombilicale.

Endometriosis is defined as the presence of endometrial tissue outside the uterine cavity. Involvement of the umbilical region is rare. We present the case of a woman with ovarian endometriosis associated with extragenital umbilical endometriosis. The umbilical lesion was completely removed. We take the opportunity of this case to give a short survey with consideration to histopathological and therapeutic aspects as well as possible differential diagnostics.

[Bufexamac-induced pigmented purpuric eruption]. / Kontaktallergie durch Bufexamac unter dem Bild einer chronischen Pigmentpurpura.

We report on a case of a bufexamac-induced allergic contact dermatitis with hematogenous dissemination presenting with the clinical and histological picture of a pigmented purpuric eruption. To our knowledge this is the first report on a bufexamac-induced pigmented purpuric dermatosis. It represents a further example of the clinical variety of cutaneous side-effects caused by bufexamac.

Frequent intra-tumoural heterogeneity of promoter hypermethylation in malignant melanoma.

To investigate intra-tumoural coexistence and heterogeneity of aberrant promoter hypermethylation of different tumour suppressor genes in melanoma, we analyzed the intra-tumoural distribution of promoter methylation of RASSF1A, p16, DAPK, MGMT, and Rb in 339 assays of 34 tumours (15 melanoma primaries, 19 metastases) by methylation-specific PCR, correlation to histopathology and RASSF1A expression. We detected promoter hypermethylation of at least one gene in 74% of tumours (30%, 52%, 33%, 20%, and 40% for RASSF1A, p16, DAPK, MGMT and Rb, respectively). 70% of the cases exhibited an inhomogeneous methylation pattern (17%, 45%, 33%, 20%, and 40% for RASSF1A, p16, DAPK, MGMT and Rb, respectively). Samples from the core of the tumours represented the methylation state of the whole tumours more accurately than the periphery. Local intra-tumoural correlation was found between the promoter hypermethylation state of p16 and Rb or p16 and DAPK, or epitheloid tumour cell type and RASSF1A or p16 methylation. Mitosis rate and sex was correlated with methylation of RASSF1A. Histological results confirmed that promoter hypermethylation of RASSF1A led to aberrant expression patterns. We conclude that intra-tumoural inhomogeneity of promoter hypermethylation is frequent in melanoma and this supports the hypothesis of clonal instability during progression of melanomas. In prognosis studies, missing the intra-tumoural sample representativeness may result in a reduction of the sensitivities or specificities.

The hand-foot syndrome--a frequent secondary manifestation in antineoplastic chemotherapy.

The hand-foot syndrome (HFS) (palmoplantar erythrodysesthesia) designates acute, painful erythemas of the palms and soles of the feet caused by antineoplastic chemotherapies. The most frequent trigger substances are 5-fluoruracil and its derivates. At maximum severity, the HFS is bullous to erosive or ulcerous in character. The pathogenesis has not yet been clarified. Histologically, the HFS is characterized by a toxic keratinocyte reaction. Furthermore, there is sub-basal edema with a tendency to bullae, dilated blood and lymph capillaries and usually only mild perivascular lymphocytic infiltration. Early recognition and delineation from other differential diagnoses is prerequisite to targeted management of the disease. Depending on the severity, HFS requires dose reduction, interruption or switch in the antineoplastic chemotherapy.

[Plaques opalines: a rare form of secondary syphilis of the oral mucous membrane]. / Plaques opalines : Eine seltene Manifestation der Sekundärsyphilis an der Mundschleimhaut.

A 37 year old woman presented with a 4-month history of "plaques opalines" of the oral mucosa complaining of a rough feeling in her mouth and burning when swallowing. On the basis of clinical, histological and serological details and especially the presence of generalized indolent lymphadenopathy, the diagnosis of secondary syphilis was made. Although plaques opalines are a relatively rare manifestation of secondary syphilis, they can occasionally be the only sign and are important in the differential diagnostic considerations of gray-white mucosal lesions, especially with current continuing rise of syphilis incidence in Central Europe.

[Angioedema in hereditary deficiency of complement factor 1 esterase inhibitor and alpha 1-antitrypsin]. / Angioödeme bei familiärem Mangel von Komplement-Faktor-1-Esterase-Inhibitor und alpha(1)-Antitrypsin.

HISTORY AND CLINICAL FINDINGS: A 15-year-old girl had suffered from episodic, sometimes threatening angioedema of the face, nasopharyngeal space and distal extremities beginning at age 13. EXAMINATIONS: A C1-esterase inhibitor (C1-INH) deficiency was revealed protein-chemically and functionally. There was also an alpha (1)-antitrypsin (AAT) deficiency with heterocygotic phenotype PiMZ. The combination of C1-INH and AAT deficiency was also found in the patient's mother and brother. THERAPY AND COURSE: Under 8-month therapy with 200 mg/d danazol per os (reduction of the dosis in the last month to 100 mg/d), there was no further edema, the C1-INH concentration normalized and there was also an increase in C1-INH function. During the observation period, use of the emergency set with C1-INH concentrate was not required. CONCLUSIONS: This is the first reported case of angioedema in combination of two hereditary enzyme defects C1-INH deficiency (autosomal-dominant genetics) and AAT deficiency (autosomal-recessive). In addition to a survey of current literature, the current state of diagnostics and therapy of the hereditary angioedema is presented.

[Human cowpox/catpox infection. A potentially unrecognized disease]. / Kuh-/Katzenpocken-Infektion beim Menschen. Ein potenziell verkanntes Krankheitsbild.

HISTORY AND ADMISSION FINDINGS: A 36-year-old woman initially noticed a red spot, about pea-sized, with a central pimple over the right eyebrow and a swollen submandibular lymph node. A pressure-sensitive, 4 cm large, node developed out of this small spot, with a central, black, tightly-adhering crust bearing several varioliform vesicles around its edge. In addition to swelling of the right half of the face, the patient had a fever up to 39.5 degrees C, general malaise, nausea and vomiting. Various antibiotics were ineffective. The woman was hospitalized with a diagnosis of facial erysipelas. She owned a cat which had developed a purulent nodule on a forepaw a few days before onset of the patient's disease. LABORATORY TEST: ESR and CRP were moderately elevated, no leukocytosis and blood cultures were sterile. Wound smears showed colonization with Klebsiella pneumoniae and Enterobacter cloacae. DIAGNOSIS, TREATMENT AND COURSE: The patient's general condition improved under initially calculated antibiotic dosages, which was later adapted to the measured resistance. The black-crusted nodes became larger, however, and incision was performed on the 8 th day after hospitalization, under the suspicion of fluctuation. However, no pus was removed, but there was massive inflammatory infiltration of the soft tissue. Examination of samples of skin and part of the crust revealed orthopox virus (cowpox virus). Spontaneous healing followed within 3 weeks, leaving only a small scar. CONCLUSIONS: This was a cowpox virus in the sense of a zoonosis transmitted by the cat. In Germany, now that smallpox has been eradicated, the clinical presentation of infections with the orthopox virus, which are closely related to variola virus, are too little recognized. Atopic and immunocompromised patients are at risk of a cutaneous dissemination with a more severe course of the infectious illness; even a lethal outcome has been reported in Germany.

[Merkel cell carcinoma]. / Merkel-Zell-Karzinom.

Merkel cell carcinoma (cutaneous neuroendocrine carcinoma) is an uncommon, highly malignant, neuroendocrine skin tumour. Typically, the primary is a fast-growing tough dermal nodule that is characterized histologically by uniform round cells with a small cytoplasmic rim. The tumour cells express the cytokeratins 8, 18, 19, 20, neurofilament, synaptophysin, chromogranin, and neuron-specific enolase. A high frequency of local recurrences (25-77%) and lymph-node metastases (50%) are characteristic features of Merkel cell carcinoma. The 5-year survival rate is 30-74%. Merkel cell carcinomas are highly radiosensitive. Thus, besides surgical methods, radiation should be included into the treatment concept in every stage. We present four cases of Merkel cell carcinoma with different courses for a review-like discussion of this disease giving instructions for rapid diagnosis and effective therapy.

Treatment with cyclosporin A in a patient with Omenn's syndrome.

Unless treated with haematopoetic stem cell transplantation, Omenn's syndrome, a rare variant of severe combined immunodeficiency, is associated with a fatal outcome. We describe a male infant showing all the typical features of Omenn's syndrome, who was successfully treated with cyclosporin A to improve clinical condition prior to haematopoetic stem cell transplantation.