[Cutaneous granulomatous reactions at botulinum neurotoxin A injection sites: First manifestation of systemic sarcoidosis]. / Granulomatöse Hautveränderungen an Botulinumtoxin-A-Injektionsstellen : Erstmanifestation einer systemischen Sarkoidose.

CASE REPORT: We report a case of granulomatous skin reaction after injection of an unknown botulinum neurotoxin (BoNT) A preparation. Four years after occurrence of skin lesions, systemic sarcoidosis became manifest. CONCLUSION: In addition to injection trauma, the BoNT A preparation may have acted as an immunogenic stimulus leading to cutaneous manifestation of sarcoidosis.

[Does dilution have an impact on cosmetic results with BoNT/A? Complex-protein-free BoNT/A for treatment of glabella lines]. / Beeinflusst die Verdünnung das kosmetische Ergebnis von BoNT/A? Komplexproteinfreies BoNT/A zur Behandlung der Glabellafalte.

BACKGROUND: In this 2-armed, randomized study we investigated the efficacy and tolerability of complex-protein-free botulinum neurotoxin type A (BoNT/A), applied in two different dilution volumes for treatment of glabellar lines. PATIENTS AND METHODS: 40 patients with grade 2-3 glabellar lines (Facial Wrinkle Scale) received treatment with 25U BoNT/A (Xeomin). 100U of botulinum neurotoxin were diluted in 2.5 ml (group I) or 4 ml sodium chloride solution (group II). Responders showed an improvement in the wrinkle score (independent rater) of at least one point. RESULTS. Response rates two weeks after treatment were 100% / 89.5%, at 3 months 84.2% / 64.7% and at 4 months 53.3% / 61.5% (groups I / II respectively). There was no significant difference between the two dilutions. CONCLUSION: Complex-protein-free botulinum neurotoxin type A in both dilutions effectively reduced severity of glabellar lines. There was no statistically significant difference in efficacy between the two dilutions.

[Erythema induratum Bazin. "Tuberculid" or tuberculosis?]. / Erythema induratum Bazin: "Tuberkulid" oder Tuberkulose?

A 66-year-old woman presented with erythematous nodules on both legs and told of a history of lymph node tuberculosis that had been treated with surgery and tuberculostatic therapy years before. A biopsy taken from a nodule showed nodular vasculitis. PCR for Mycobacterium tuberculosis-specific DNA on the paraffin-embedded tissue was positive. Based on the experience with our patient, positive PCR results for Mycobacterium tuberculosis-specific DNA in lesions of nodular vasculitis are discussed critically. The historical background of "tuberculids", such as erythema induratum Bazin, is elucidated.

Unusual histopathological features of cutaneous leishmaniasis identified by polymerase chain reaction specific for Leishmania on paraffin-embedded skin biopsies.

BACKGROUND: Cutaneous leishmaniasis (CL) is rare in Northern Europe and may be overlooked because colleagues have little experience with it. OBJECTIVES: To identify manifestations of CL that may escape diagnosis. METHODS: Correlation of clinical diagnosis and histopathological findings in 28 biopsy specimens taken from 19 patients with CL confirmed by polymerase chain reaction (PCR) specific for Leishmania. RESULTS: In only one patient was the clinical diagnosis CL; other diagnoses included: malignant epithelial neoplasms (5), follicular cyst (2), atypical mycobacteriosis (1), sarcoidosis (2) and lymphoma (1). Lesions were single (15) or few (4) nodules predominantly situated on the extremities or face (16). Histopathological findings were diagnostic of CL in only 10 cases. In nine cases Leishmania was not identified microscopically; histopathological diagnoses were: granulomatous dermatitis (6), lupoid rosacea (1), foreign body granuloma (1) and granuloma annulare (1). Unaltered epidermis (9), nodular infiltrates (5), numerous multinucleated histiocytes (3), palisaded granulomas with fibrinoid centres (2), sarcoidal granulomas (4) and elastophagocytosis (1) misled the histopathologists in these cases. CONCLUSIONS: CL seems often to be misdiagnosed clinically in countries where it is not endemic. Histopathologically, CL may be misinterpreted as sarcoidosis, foreign body granuloma, lupoid rosacea and granuloma annulare, especially when Leishmania is not seen microscopically. We suggest that in Northern Europe, PCR for Leishmania-specific DNA should be performed routinely in any granulomatous dermatitis presenting as a single or few nodules on the extremities or face, even when a diagnosis of CL was not considered by the referring clinician.

Gain of 11q/cyclin D1 overexpression is an essential early step in skin cancer development and causes abnormal tissue organization and differentiation.

Non-melanoma skin cancers, in particular keratoacanthomas (KAs) and squamous cell carcinomas (SCCs), have become highly frequent tumor types especially in immune-suppressed transplant patients. Nevertheless, little is known about essential genetic changes. As a paradigm of 'early' changes, that is, changes still compatible with tumor regression, we studied KAs by comparative genomic hybridization and show that gain of chromosome 11q is not only one of the most frequent aberration (8/18), but in four tumors also the only aberration. Furthermore, 11q gain correlated with amplification of the cyclin D1 locus (10/14), as determined by fluorescence in situ hybridization, and overexpression of cyclin D1 protein (25/31), as detected by immunohistochemistry. For unraveling the functional consequence, we overexpressed cyclin D1 in HaCaT skin keratinocytes. These cells only gained little growth advantage in conventional and in organotypic co-cultures. However, although the control vector-transfected cells formed a well-stratified and orderly differentiated epidermis-like epithelium, they showed deregulation of tissue architecture with an altered localization of proliferation and impaired differentiation. The most severe phenotype was seen in a clone that additionally upregulated cdk4 and p21. These cells lacked terminal differentiation, exhibited a more autonomous growth in vitro and in vivo and even formed tumors in two injection sites with a growth pattern resembling that of human KAs. Thus, our results identify 11q13 gain/cyclin D1 overexpression as an important step in KA formation and point to a function that exceeds its known role in proliferation by disrupting tissue organization and thereby allowing abnormal growth.

[Painful ischemia of the extremities with T-cell lymphoma]. / Schmerzhafte akrale Durchblutungsstörungen bei T-Zellymphomen.

Two years after the diagnosis of Sézary syndrome, a 50-year old female patient experienced attacks of painful ischemia of both hands and feet, leading to acral necrosis. Another 59-year old patient presented with severe pain in his feet, secondary to ischemia. This was the first symptom of a T-cell-chronic lymphocytic leukemia. Similar cases have only occasionally been described. The relationship between acral ischemia and T-cell-lymphoma is not clear but is discussed in this article.

[Syringocystadenoma papilliferum and trichoblastoma within a sebaceous nevus]. / Syringocystadenoma papilliferum und Trichoblastom innerhalb eines Naevus sebaceus.

Since birth, a 43 year-old man displayed a nevus sebaceus on the right temple. The histopathology revealed two distinct adnexal neoplasms associated with this lesion: a syringocystadenoma papilliferum and a trichoblastoma. We describe the combination of these entities in this report.

Kinetics of DNA strand breaks and protection by antioxidants in UVA- or UVB-irradiated HaCaT keratinocytes using the single cell gel electrophoresis assay.

The aim of this study was to characterize the genotoxic action of UVA and UVB in human keratinocytes by application of the single cell gel electrophoresis assay (SCGE assay). Dose dependence of DNA damage, the time course of its repair, and the influence of cellular antioxidant status were assessed. Irradiation with UVA or UVB both resulted in a dose-dependent increase in the level of DNA damage. A time course study to evaluate the repair kinetics in keratinocytes irradiated with 5 J/cm2 UVA revealed an immediate occurrence of DNA effects which subsequently disappeared within about 1 h, indicating removal of DNA lesions. This rapid repair of DNA damage is consistent with the observation that 5 J/cm2 UVA did not impair cellular viability. In contrast, exposure to 15 mJ/cm2 UVB resulted in a prolonged repair of DNA damage which lasted about 25 h. Thus, the repair kinetics of UVA- and UVB-induced DNA damage clearly differed from each other, implicating the induction of different types of DNA lesions by UVA and UVB. Neither a pretreatment with Mg-ascorbyl phosphate or D,L-alpha-tocopherol, nor depletion of endogenous glutathione altered cellular sensitivity to UVB. In contrast, the DNA damaging effects of UVA could be counteracted by a pretreatment with these antioxidants. These observations confirm that the UVA-induced effects on DNA are related to radical mediated strand breaks and DNA lesions forming alkali-labile sites. The UVB-induced effects mainly occur as a consequence of excision repair-related strand breaks. The observed repair kinetics of DNA lesions and the influence of cellular antioxidant status may help to elucidate protective mechanisms against the carcinogenic effects of UV radiation present in sunlight.

Palpable migratory arciform erythema. Clinical morphology, histopathology, immunohistochemistry, and response to treatment.

BACKGROUND: Palpable migratory arciform erythema is clinically characterized by sharply circumscribed, infiltrated erythematous patches that tend to spread irregularly, resulting in arciform morphologic features. The histopathologic features are characterized by a patchy inflammatory perivascular and periadnexal T-lymphocytic infiltrate throughout the dermis. The disease runs a chronic course and is rarely described in the literature. OBSERVATION: Three middle-aged patients of both sexes had palpable migratory arciform erythema with 1, several, or multiple lesions on the trunk. There was a dense perivascular and periadnexal, predominantly lymphocytic infiltrate of the reticular dermis without any interstitial distribution of inflammatory cells. Absence of mucin deposits and plasma cells was a striking feature. The immunohistochemical profile showed an infiltrate dominated by T cells of polyclonal origin. In addition, polyclonal B cells and histiocytes were present in small numbers. In all 3 cases, oral antibacterial treatment resulted in a complete (2 patients) or temporary (1 patient) resolution of skin lesions. CONCLUSIONS: Palpable migratory arciform erythema shows distinctive differences in clinical and pathological features and treatment in contrast to other diseases with cutaneous lymphocytic infiltrates, including lymphocytic infiltration of Jessner and Kanof. Therefore, it is likely a distinct disease entity.

[Standards in histopathologic diagnosis of malignant melanomas. Recommendations of the Working Group of the Central Malignant Melanoma Registry of the German Dermatologic Society]. / Standards der histopathologischen Diagnose maligner Melanome. Empfehlungen der Arbeitsgruppe des Zentralregisters Malignes Melanom der Deutschen Dermatologischen Gesellschaft.

The evaluation of melanocytic tumors represents one of the most intriguing and challenging aspects of the daily practice in dermatohistopathology. For the diagnosis of malignant melanoma and melanocytic nevi, standardized and reproducible criteria are required. In case of the diagnosis of melanoma, the histopathological report must include all important data relevant for the prognosis which may also influence the therapeutic procedure. The following paper summarizes the recommendations of the study group on malignant melanoma formed by the Deutsche Dermatologische Gesellschaft.

Autoradiographic mapping of beta-adrenoceptors in human skin.

A high density of beta 2-adrenoceptors has been found in human skin. Using autoradiographic mapping we investigated the distribution of beta 1- and beta 2-receptors in normal and diseased human skin. Cryostat sections of human skin obtained at biopsy were incubated with [125I]-iodocyanopindolol and nonspecific binding was identified by incubation of adjacent sections with 200 microM (-)-isoproterenol; beta 2-receptors were visualized using CGP 20712A and beta 1-receptors using ICI 118,551 as competing agents. The epidermis was densely labelled with an even distribution throughout all layers. Most of the beta-receptors were of the beta 2-subtype, with practically no beta 1-receptors. beta-Receptors were also localized to eccrine sweat glands, dermal blood vessels, and perivascular inflammatory cells, but there was no labelling of sebaceous glands. Topical glucocorticoids caused an increase in the density of epidermal beta-receptors. We conclude that keratinocytes and eccrine sweat glands express high densities of beta 2-receptors, suggesting that they may have a physiological role in the regulation of these cells.

[Urticaria vasculitis]. / Urtikariavaskulutis.

Fifteen cases with suspected urticarial vasculitis which were seen during the last ten years at the Department of Dermatology in Hamburg were reviewed. The cases were reevaluated after strict formulation of criteria for vasculitis (fibrin in and around small vessels, leukocytoclasis of neutrophilic granulocytes, extravasation of erythrocytes) and discussed in the context of the international literature on urticarial vasculitis. The conclusion of our study is that urticarial vasculitis is often overdiagnosed clinically if persistent urticarial lesions occur that show some erythematous changes or a hint of hemorrhage. Furthermore, urticarial vasculitis is often overdiagnosed histopathologically because some cases of urticaria were found that presented with heavy infiltration of small vessel walls with neutrophilic granulocytes. In these cases extravasation of erythrocytes, fibrin in and around vessels and leukocytoclasis is always absent. In summary urticarial vasculitis seems to be a variation of leukocytoclastic vasculitis with less extravasation of erythrocytes and not, as frequently stated, and entity of its own.

Acanthosis nigricans: a marker for hyperinsulinemia.

A 12-year-old girl developed acanthosis nigricans due to increased levels of serum insulin. Hyperinsulinemia has been recognized as the underlying cause in most cases of acanthosis nigricans. In this paper we outline a typical clinical case with special regard to the proposed pathogenesis.

[Anaphylaxis caused by latex contamination from the wrapper of the cannula plaster]. / Anaphylaxie durch Latexkontamination über die Verpackung des Braunülenpflasters.

A patient with pronounced latex allergy was admitted to hospital because of suspected drug allergy. He developed an anaphylactic reaction manifesting with skin reactions and difficulties in breathing immediately after an intravenous cannula was applied, although the doctor was wearing latex-free gloves. The envelope of the plaster with which the cannula was fixed was found to be the source of the latex responsible for the anaphylactic reaction. Latex contact with the skin was due either to latex contamination of the doctor's hands when opening the envelope or to the plaster itself. The case report demonstrates the difficulties arising both from the clinical reaction pattern of type I reactions to latex and from strict avoidance of latex-containing products and points out the necessity of latex declaration.

[Food-induced anaphylaxis in latex allergy]. / Nahrungsmittelanaphylaxie bei Latexallergie.

Contact uticaria and anaphylactic reactions to latex-containing rubber products are being recognized with increasing frequency in all kinds of medical disciplines. Recently a number of reports have been published describing anaphylactic reactions to food items in patients with latex allergy. The cases of three patients who developed anaphylactic reactions to both latex and food items are presented, and the importance of the association of latex and cross-reactivity with food items is stressed. The food items that led to anaphylactic reactions were banana and avocado; banana, avocado and buckwheat; and banana, avocado and tomato. The cross-reactivity of latex to buckwheat and tomato has not been reported before.

Acute myeloid leukemia: ecchymoses as sole clinical symptom.

Acute myeloid leukemia is a hematologic malignancy accompanied by specific skin involvement in only about 10 percent of reported cases. We present a case of acute myeloid leukemia in which a hemorrhagic disorder of the skin was the first and only clinical symptom of the disease before the patient died from cerebral hemorrhage.