[Aquagenic urticaria. A case report]. / Aquagene Urtikaria. Ein Fallbericht.

A 38-year-old woman presented with recurrent episodes of urticaria after contact with water affecting the upper part of the body. We confirmed the diagnosis of aquagenic urticaria. Aquagenic urticaria is a rare form of contact urticaria with small wheals generally affecting the upper part of the body. It has to be distinguished from aquagenic pruritus. The pathogenetic mechanisms are not known in detail. Treatment with antihistamines, ultraviolet therapy or application of protective hydrophobic barrier creams could be effective.

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.

[Phlebology in German departments of dermatology. An analysis on behalf of the German Society of Phlebology]. / Phlebologie an deutschen Hautkliniken. Eine Bestandsaufnahme im Auftrag der Deutschen Gesellschaft für Phlebologie.

BACKGROUND: Phlebologic diseases have become extremely common and have major socio-economic impact. However, the percentage of dermatologists working in phlebology appears to be decreasing according to the data of the German Society of Phlebology (DGP). METHODS: To investigate the reasons for this development, we--on behalf of the DGP--sent a questionnaire to 120 German Departments of Dermatology in autumn 2012. RESULTS: In 76 returned questionnaires, the number of physicians with additional fellowship training in phlebology averaged 1.5; the average number of those who fulfill the criteria for training fellows in phlebology was 0.9. In 71.1 % of the departments there was a phlebologist. A special phlebologic outpatient clinic existed in 73.7 % of the departments. Sonography with Doppler (89.5 %) and duplex (86.8 %) was used as the most frequent diagnostic tool. For therapy, compression (94.7 %), sclerotherapy (liquid 78.9 %, foam 63.2 %, catheter 18.4 %), endoluminal thermic procedures (radio wave 28.9 %, laser 17.1 %) and surgery (especially crossectomy and stripping 67.1 %, phlebectomy of tributaries 75 %) were used. The average number of treatments was very heterogenous in the different departments. CONCLUSIONS: Phlebology definitely plays an important role in dermatology. Most departments fulfill the formal criteria for the license to conduct advanced training in phlebology. A wide spectrum of phlebological diagnostic and therapeutic procedures is available.

Hidradenitis suppurativa/acne inversa: bilocated epithelial hyperplasia with very different sequelae.

BACKGROUND: Hidradenitis suppurativa/acne inversa is a chronic, inflammatory, scarring disease in the terminal hair follicle and apocrine gland-bearing areas (skin folds). There is considerable histological evidence that perifolliculitis and follicular hyperkeratosis precede the rupture of the follicle. The timing of the epithelial hyperplasia at the infundibula of inflamed terminal follicles has not yet been clarified. OBJECTIVES: To clarify the early histopathological life of lesions ('chronology') in hidradenitis suppurativa/acne inversa, focusing on the terminal follicle structure and its surrounding tissue (hyperkeratosis, hyperplasia of follicular epithelium, perifolliculitis and rupture). METHODS: In total, 485 operative specimens obtained from 128 patients with diagnosed hidradenitis suppurativa/acne inversa (all surgically treated by wide excision) were examined histologically. Two to five histological preparations (total 485) per operation area (total 196) were prepared by multiple slicing. RESULTS: Hidradenitis suppurativa/acne inversa showed a heterogeneous histological pattern: hyperkeratosis of the terminal follicles (89%), hyperplasia of follicular epithelium (80%), pronounced perifolliculitis (68%) and follicle rupture (24%). Perifolliculitis, follicular hyperkeratosis and hyperplasia occurred prior to the rupture of the follicle. Other histological criteria were: subepidermal cellular inflammatory infiltrate (82%), epidermal psoriasiform hyperplasia (56%), pronounced acute dermal inflammation (28%), pronounced chronic dermal inflammation (49%), and involvement of apocrine glands (52%) and subcutis (31%). CONCLUSIONS: Infundibular hyperkeratosis, hyperplasia of the follicular epithelium and perifolliculitis are major histopathological characteristics of hidradenitis suppurativa/acne inversa. These apparently precede rupture of the follicle. In particular, hyperplasia of the follicular epithelium probably marks the beginning of sinus formation, which usually spreads horizontally. Psoriasiform hyperplasia of the interfollicular epidermis with subepidermal inflammatory infiltrate might be interpreted as an inflammation-driven process basically identical to that which is evident at the terminal follicle. However, it does not lead to harmful and progressive sequelae like those (rupture, sinus tracts) seen at the terminal follicles.

Algorithm for detection of small-bowel metastasis in malignant melanoma of the skin.

BACKGROUND AND STUDY AIM: The aim of this study was to develop an algorithm to detect small-bowel metastasis (SBM) of melanoma by sequential laboratory parameters and pan-intestinal endoscopy (PIE) including video capsule endoscopy (VCE). PATIENTS AND METHODS: A total of 390 melanoma patients (AJCC stage I/II/III/IV, 140/80/121/49) were screened for signs of intestinal blood loss (fecal occult blood test [FOBT] or overt bleeding) in an open, multicenter, prospective study, and those who were positive underwent PIE. Independent of the presence of intestinal bleeding, all stage IV patients were offered PIE. Follow-up was obtained in 357 patients (91.5 %) for a median of 16 months. We undertook to identify possible associations between SBM and clinical and laboratory data. Survival data were analyzed with regard to clinical and laboratory data and small-bowel findings. RESULTS: Intestinal blood loss was suspected in 49 of 390 patients (12.6 %), 38 of whom (77.6 %) agreed to undergo endoscopy. In 10 patients, SBM was detected by VCE (intention-to-diagnose, 20.4 %; AJCC III, n = 2; AJCC IV, n = 8). The SBM was resected in five patients. Total detection rates of SBM were 14 of 49 patients in stage IV (28.6 %, intention-to-diagnose), 2 of 121 in stage III (1.7 %), and 0 in stage I/II. In FOBT-positive patients, SBM detection rates were 72.7 %, 14.3 %, and 0 % in tumor stages IV, III, and I/II, respectively. Positive FOBT proved to be an independent negative prognostic factor for total survival in stage III and IV melanoma. CONCLUSIONS: SBMs are frequent in advanced melanoma. In stage III patients, screening for intestinal blood loss by PIE may help to identify SBMs. In stage IV, indication for PIE should depend on the individual consequences of detecting SBM, but not on bleeding symptoms alone.

[37-year old patient with fever, diarrhea and lymphadenopathy]. / 37-jähriger Patient mit Fieber, Durchfall und Lymphknotenschwellung.

A 37-year-old homosexual man was admitted because of oropharyngeal pain, fever, diarrhea, loss of weight and lymphadenopathy since one week. Acute retroviral syndrome (ARS) in primary HIV type 1 infection was diagnosed, associated with Giardia lamblia infection. Antiinfective and combined antiretroviral treatment was established, and the general condition of the patient rapidly improved. The presented report demonstrates that in case of acute HIV-infection with diarrhea other infections should be considered, particularly with regard to enteropathogens like Giardia lamblia.

[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.

[Symptomatic cardiac metastasis. Isolated visceral manifestation of a cutaneous malignant melanoma]. / Symptomatische Herzmetastase. Solitäre viszerale Manifestation eines kutanen malignen Melanoms.

Symptomatic cardiac melanoma metastases are very rare. A 76-year-old woman was admitted because of dyspnea and intrathoracic pain 8 years after surgery of a superficial spreading melanoma and 4 years after resection of in-transit metastases. MRI and echocardiography disclosed an intracavitary right atrial mass. Histologically a cardiac melanoma metastasis was found. Unspecific cardiac symptoms in a patient with elevated risk for distant metastases of melanoma should be further investigated to discover cardiac metastasis early.

[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.

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.

Patients with lymphatic metastasis of cutaneous malignant melanoma benefit from sentinel lymphonodectomy and early excision of their nodal disease.

Early versus delayed excision of lymph node metastases is still being assessed in malignant melanoma. In the present retrospective, multicentre study, the outcome of 314 patients with positive sentinel lymphonodectomy (SLNE) was compared with the outcome of 623 patients with delayed lymph node dissection (DLND) of clinically enlarged lymph node metastases. In order to avoid the lead-time bias, survival was generally calculated from the excision of the primary tumour. Survival curves were constructed using the Kaplan-Meier product-limit estimate. Cox's proportional hazards model was used to perform a multivariate analysis of factors related to overall survival. Compared with SLNE and early performed complete lymph node dissection, DLND yielded a significantly higher number of lymph node metastases. Median and mean tumour thickness were nearly identical in the two therapy groups. The estimated 3-year overall survival rate was 80.1+/-2.8% (+/-standard error of the mean (SEM)) in patients with positive SLNs, and 67.6+/-1.9% in patients with DLND (5-year survival rates 62.5+/-5.5 and 50.2+/-5.4%, respectively). The difference between the two survival curves was statistically significant (P=0.002). Using multifactorial analysis, SLNE (P=0.000052), American Joint Committee on Cancer (AJCC) Breslow thickness category (P<0.000001), age (P=0.01) and gender (P=0.028) were independent predictors of overall survival. The location of the primary tumour (P=0.59) was non-significant. Considering only those centres with sufficient data for epidermal ulceration, this risk factor was also significant. In cutaneous malignant melanoma, early excision of lymphatic metastases, directed by the sentinel node procedure, provides a highly significant overall survival benefit.

Low-dose oral etoposide monotherapy in adult Langerhans cell histiocytosis.

BACKGROUND: The purpose of this study was to test the disease-controlling effect of low-dose oral etoposide monotherapy in adult-onset multisystem Langerhans cell histiocytosis. There are no previous reports of low-dose etoposide monotherapy for this condition. OBSERVATIONS: A 27-year-old man with a 7-year history of multifocal chronic Langerhans cell histiocytosis presented with severe disabling ulcers in intertriginous areas. He had previously been treated with 2 different regimens of antitumoral chemotherapy; one had to be discontinued due to myelosuppression and the other had proved ineffective. We treated with oral etoposide monotherapy at 50 mg/d (22 mg/m2 per day) for 21 days. The treatment was repeated at 28-day intervals for a total of 6 cycles. A rapid initial response with subtotal diminution of the involved skin area was found. No adverse effects were observed. The clinical picture has remained stable during the 7 months following cessation of therapy. CONCLUSION: Low-dose oral etoposide treatment is an adequate therapeutic measure for prolonged disease control in adult-type Langerhans cell histiocytosis.

Prognostic factors of overall survival in patients with delayed lymph node dissection for cutaneous malignant melanoma.

To date, no study of melanoma patients who have undergone delayed lymph node dissection (DLND) has focused on the independent prognostic factors of overall survival, as calculated from surgery on the primary. Using Kaplan-Meier estimates and Cox's proportional hazard model, the significance of prognostic factors was evaluated in 173 patients who developed clinically apparent regional lymph node metastases. When calculated from excision of the primary tumour (median Breslow thickness 3.0 mm), the median survival was 38 months. When calculated from DLND, the median survival was 19 months. Multifactorial analysis revealed that the number of nodes involved at the time of DLND significantly affected both survival calculated from primary tumour excision (P = 0.0002) and survival calculated from DLND (P < 0.0001). In contrast, the well-known risk factors of primary melanoma did not significantly influence overall survival or survival after DLND. However, the remission duration between surgery on the primary and DLND clearly depended on epidermal ulceration (P = 0.001), Breslow thickness (P = 0.009) and the site of the primary melanoma (P = 0.048). Thus, in patients submitted to DLND, the risk factors of primary melanoma influence the early period of the disease, until metastatic lymph nodes become palpable. With regard to overall survival, only the extent of nodal disease determines the prognosis of these patients.

Epidermoid metaplasia in apocrine cystadenoma of the penis. An ultrastructural analysis.

Two cystadenomas occurring near the frenulum of the penis revealed a predominantly secretory pseudostratified columnar epithelium with PAS-reactive dome-shaped cytoplasmic protrusions at the luminal cellular parts. The content of secretory vacuoles was discharged into the cyst lumen by an exocytotic (eccrine) and ballooning type of extrusion. There were no indications of a real apocrine extrusion mechanism. No histogenetic derivation of these penile cystadenomas from apocrine sweat glands could be proved. An antennalike filamentous fuzzy coat on the luminal cytoplasmic membrane was most remarkable. Regionally, an epidermoid differentiation had developed. Morphologically, this process had begun just above the basal cell layer which had remained unchanged and led to the establishment of a stratified epithelium. Hyalin lamellarlike flattened cells at the luminal part displayed necrobiotic features and resembled periderm cells. There was no keratin pattern. Luminal cells of epidermoid differentiation still revealed a filamentous fuzzy coat which indicated that the undifferentiated cuboidal basal cells basically had a prospective secretory meaning and probably represented the target cells in the process of metaplasia.

The ultrastructure of mycobacterium marinum granuloma in man.

3 biopsies of 3-5 week-old nodular lesions in 2 patients with so-called swimming-pool (aquarium-) granuloma have been examined by electron microscopy. The cytohistological spectrum simultaneously comprises acute exudative as well as chronic proliferative phenomena. Epithelioid cells and collagen producing fibroblasts are already conspicious in 3 week-old granuloma. According to the cytological composition the Mycobacterium marinum granuloma represents a high-turnover granuloma with immunogenic origin. It is comparable to mycobacterial diseases in the presence of well developed cell mediated immunity (Lupus vulgaris, tuberculoid leprosy). Degrading mycobacteria have been rarely detected in phagocytes and are compared with viable bacilli in macrophages of experimentally infected mice. Curved and annular parallel membranes ("worm-like structures") in the cytoplasm of transformed macrophages and in fibroblasts presumably originate from the membranes of endoplasmic reticulum. Cord-like structures with transverse bands (periodicity 170-180 A) in the lumen of RER of some fibroblasts are interpreted as intracellularly aggregated collagen precursors.

Ultrastructural detection of Haemophilus ducreyi in biopsies of chancroid.

During an endemic appearance of chancroids (26 cases) in Berlin (West) coccobacilli were disclosed in biopsies by electron microscopy. The bacteria were aggregated predominantly in groups in the extracellular space. Their cell wall is approximately 120 A thick and trilaminar as in Gram-negative bacteria. Concerning the cell wall structure and the cytoplasmic composition, the detected coccobacilli are identical to culturally grown Haemophilus ducreyi obtained from chancroids.

Actinic elastosis in black skin. A light- and electronmicroscopic study.

In 9 otherwise dermatologically normal South African Balck volunteers (1--72 years old), sunlight-exposed and non-exposed skin has been examined by light- and electronmicroscopy with special references to age-dependent and actinic alteration of dermal structures. Two 72 year old Blacks exhibited typical dermal elastosis: in 1 case to a marked extent and already detectable by lightmicroscopy, in the other case only to a mild degree. In contrast, only age-related elastic fibers were revealed in the lower dermis of sunlight-exposed skin and in all dermal layers of unexposed skin. These observations are contradictory to the general view that actinic elastosis does not occur in Blacks. The elastotic material is obviously a de-novo synthesized and secreted pathological product of chronically UV-altered fibroblasts.

Increase in types IV and VI collagen in cherry haemangiomas.

The capillaries in cherry haemangiomas show perivascular hyalinized sheaths. In order to clarify the nature of this sheath material, the extracellular matrix of cherry haemangiomas from 20 normal volunteers (age range 30-64 years) was investigated using immunohistochemical and electronmicroscopical methods. Antibodies against collagen types III, IV and VI and laminin were used. Hyaluronic acid was visualized using the hyaluronic acid binding region of the cartilage proteoglycan as ligand. Electronmicroscopically, the sheaths contained multilaminated basement membrane-like material, collagen fibres 20-25 nm thick with a periodicity of 67 nm and broad-banded aggregates with a periodicity of 100 nm (zebra bodies or fibrous long-spacing fibres). Immunohistochemically, type IV collagen was stained throughout the whole sheath material. Staining for laminin was more confined to the endothelial side of the sheath. Intense staining for type III collagen and hyaluronic acid was found in the connective tissue of the subpapillary layer and between the cherry haemangioma capillaries. Much weaker staining for type III collagen and no staining for hyaluronic acid were found invariably in an area 4-10 microns thick directly around the capillaries. Both sheath material and intercapillary connective tissue of the haemangiomas showed pronounced staining for collagen type VI. Immunogold staining revealed that type VI collagen was localized to microfibrils 5-6 nm thick and to the broad-banded aggregates with 100 nm periodicity. These findings further underline the assumption that the broad-banded aggregates consist of type VI collagen.