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Classical variants of specific cutaneous LE lesions are chronic discoid LE (CDLE) and subacute cutaneous LE (SCLE). CDLE and SCLE may appear at any age; however, the most common age of onset is between 20 and 40 years, with a female predominance of 3:1 in CDLE and 3-6:1 in SCLE. Nonspecific LE skin lesions such as generalized or acrolocalized vasculitis (4-30%), livedo reticularis (22-35%), and alopecia (38-78%) are frequently seen in patients with cutaneous LE. Other typical cutaneous LE subsets such as LE profundus/panniculitis, LE tumidus, urticaria vasculitis, hypertrophic LE, and bullous LE are rather rare variants. Butterfly rash and/or macular exanthema are characteristic skin lesions of systemic lupus erythematosus (SLE) rarely found in patients with cutaneous LE.

Shower PUVA is a new variant of photochemotherapy suitable for therapy of various skin disorders. Psoralen, e.g. trioxsalen-containing water recirculates in a closed shower system and wets the skin continuously. After showering, whole-body UVA irradiation (320–400 nm) is performed. In order to prove the equal distribution of photosensitivity in vivo minimal phototoxic dose (MPD) was determined in different skin areas of healthy individuals. Additionally, we investigated the accumulation of trioxsalen in psoriasis lesions under the conditions described by quantifying psoralen in scales collected after showering. In a randomized study 20 healthy volunteers (skin type I–III) took showers for 5 and 10 min in trioxsalen (0.27 mg/l)-containing water at 37°C. Immediately afterwards, MPD was tested on the inside of the upper arms and on the buttocks by using a polychromator light source (315–400 nm). The applied UVA doses were 0.06–0.75 J/cm2 with steps of 0.125 J/cm2. MPD was evaluated after 72 h. Equal distribution of photosensitivity was defined as equal MPD on the insides of the upper arm and the buttocks (±0.125 J/cm2). Skin scales of 21 patients with psoriasis were collected by scratching after showering with trioxsalen-containing water (0.27 mg/l) for 5 min. For quantification of trioxsalen in the scales HPLC was performed. An equal distribution of photosensitivity was achieved in 70% (14/20) cases after 10-min showering in trioxsalen-containing water. Showering for 5 min only revealed a 30% (6/20) rate of equal distributed photosensitivity. After 10-min shower time MPD was 0.325 J/cm2 (median; range: 0.06–0.625 J/cm2). The average amount of trioxsalen found in the scales was 2.03 ng/mg scales (range: 0.38–7.2 ng/mg). For shower PUVA using trioxsalen, 10 min shower time is recommended to achieve sufficient distribution of photosensitivity on the skin. Clinical efficacy of shower PUVA can be explained by skin accumulation of trioxsalen which enters from the aqueous phase into the upper skin layers in detectable amounts. This is the first report demonstrating the efficacy of shower PUVA which in short shower time allows an uptake of psoralen by the skin.

The proapoptotic potential of tumor necrosis factor-alpha (TNF-alpha) has been demonstrated for various cell types, whereas nuclear factor-kappaB (NF-kappaB) is known to support the transcription of prosurvival genes. In the present study, investigation of normal human melanocytes revealed induction of apoptosis after TNF-alpha treatment (100 U/ml) in only 3 out of 11 cultures analyzed, whereas 8 cultures remained largely resistant. In sensitive cultures, NF-kappaB binding activity was found increased after TNF-alpha treatment; apoptosis-resistant cells were characterized by relatively high basic NF-kappaB binding activities and did not show NF-kappaB activation after TNF-alpha treatment. Inhibition of NF-kappaB by a specific inhibitor, Bay-11, either induced apoptosis itself or resistant melanocyte cultures became sensitive to TNF-alpha treatment. No correlation was found between apoptosis sensitivity and the expression of TNF receptor-1 or the expression of Bax, Bcl-2 and Bcl-X(L). A strong correlation, however, was found regarding the pigmentation degree, as high pigmentation correlated with apoptosis resistance and sensitive melanocyte cultures were weakly pigmented. These data may indicate that in cultured melanocytes, high levels of melanogenesis lead to an increase in oxidative stress which itself causes NF-kappaB activation. NF-kappaB mediates the transcription of antiapoptotic factors which may block TNF-alpha-induced apoptosis at early steps of the signal cascade.

It has been described that treatment of cells with high dose psoralen and UVA induce the production of reactive oxygen species (ROS) leading to DNA damage. Transcription factor nuclear factor kappa B (NFkappaB) plays a crucial role in regulating not only cell growth but also cell differentiation, and ROS seem to be partly involved in these mechanisms. The aim of this research was to find out the effect of a combined treatment with trioxsalen (TMP)/UVA on NFkappaB binding activity in HaCaT keratinocytes. HaCaT keratinocytes were treated with 27 microg/l TMP. This concentration did not affect the proliferation rates, nor was it toxic, as shown by cytotoxicity assays. After treatment with TMP with or without UVA (1 J/cm(2)), NFkappaB binding activity in nuclear protein extracts was measured by electrophoretic mobility shift assays. The effect on cytokines and cytokine receptor genes was investigated using cDNA expression arrays. An inhibitory effect on NFkappaB binding activity was found between 30 and 60 min after TMP supplementation of the culture media. UVA irradiation induced a 2-fold increase in NFkappaB binding activity in TMP supplemented HaCaT keratinocytes compared with the non-irradiated control. In addition, NFkappaB binding activity was higher after UVA irradiation with TMP than in UVA irradiated cells in the absence of TMP. TGF-alpha, IL-1R, IL-2Ralpha, IL-12beta and PDGF expression was induced by UVA. However, all of them except PDGF were inhibited by combined TMP/UVA treatment. Using an inhibitor of NFkappaB activation, we found out that under these conditions, these cytokines or cytokine receptor genes are apparently not regulated by NFkappaB. Our results indicate that a combined TMP/UVA treatment of HaCaT keratinocytes induces NFkappaB binding activity, and that this is a synergistic effect. The investigated cytokines, and cytokine receptor genes do not seem to be NFkappaB regulated; however, TMP shows anti-inflammatory capacities in vitro.

Nuclear factor-ĸB (NFĸB) is a pleiotropic transcriptional activator, which is a sensitive transcriptional factor for free radicals and activates multiple target genes. UVA is very efficient in inducing free radicals in human skin cells. L-ascorbic acid is regarded as a scavenger of UVA-induced free radicals in human keratinocytes. In epidermis, melanocytes and keratinocytes play an important protective role against skin photodamage. In the present study, we aimed to investigate the role of NFĸB on photodamage in melanocytes and keratinocytes. Normal human melanocytes (NHM) and HaCaT keratinocytes were treated with UVA (500 mJ/cm², 1,000 mJ/cm2) and/or L-ascorbic acid (100 µM, 250 µM). NFĸB binding activity was analysed by electrophoretic mobility shift assay. NFĸB binding activity was increased by UVA irradiation in HaCaT keratinocytes, but it was not affected in NHM. On the other hand, L-ascorbic acid decreased NFĸB binding activity both in UVA-irradiated and in non-irradiated NHM. In contrast, NFĸB binding activity in HaCaT keratinocytes was increased after treatment with L-ascorbic acid. In addition, L-ascorbic acid synergistically induced NFĸB binding activity with UVA irradiation. The contrary response on NFĸB binding activity in NHM and HaCaT keratinocytes indicated that the redox regulation might be different on photoprotective action in melanocytes and keratinocytes.

Die Vakuumversiegelungstechnik ist ein neues, einfach durchfuhrbares Behandlungsverfahren fur traumatische und chronische Weichteildefekte, Verbrennungen und Weichteilinfektionen. Wir setzten diese Technik erstmals zur temporaren Defektdeckung und Wundgrundkonditionierung nach der Resektion eines tief infiltrierenden Leiomyosarkoms ein. Bei der radikalen Ausraumung des Tumors mit teilweiser Entfernung der Unterarmbeugemuskulatur und einem Sicherheitsabstand von 3 cm entstand ein ausgedehnter Weichteildefekt von 12×16 cm Durchmesser. Zum temporaren Defektverschluss legten wir einen Vakuumversiegelungsverband uber 7 Tage an. Da sich das Resektat histologisch nicht als tumorfrei erwies, fuhrten wir am 7. postoperativen Tag eine Nachresektion durch und legten erneut einen Folienverband mit kontinuierlichem Sog an. Nach weiteren 7 Tagen zeigte sich der Wundgrund hervorragend granuliert, sodass die plastische Deckung des Defektes mit einem Spalthauttransplantat vom Oberschenkel erfolgen konnte. Bakterielle Infektionen oder sonstige Komplikationen unter Anlage des Vakuumversiegelungsverbandes traten nicht auf. Wesentlicher Vorteil der Vakuumversiegelungstechnik ist die schnelle Bildung eines fur die Hauttransplantation hochwertigen, gut vaskularisierten Granulationsgewebes; dazu kommen weitgehende Schmerzfreiheit auch bei Mobilisation und Schutz vor Kontaminationen.

Classic variants of cutaneous borreliosis are erythema chronicum migrans (ECM), lymphadenosis benigna cutis (LBC) and acrodermatitis chronica atrophicans (ACA). Other dermatoses have been reported in the literature as possibly linked to borreliosis. A 59-year old female patient was seen in the late phases of cutaneous borreliosis with histologically confirmed ACA. In addition, prominent livedo racemosa was seen on the legs, also showing tissue changes similar to those of ACA. Borrelia burgdorferi infection was serologically confirmed by the presence of anti-IgM and anti-IgG antibodies. The clinical spectrum of late cutaneous borreliosis should be enlarged to include livedo racemosa.

Radiation-induced acne is a rare, clinically and pathogenetically ill-defined acneiform dermatosis with special features that may occur in irradiated skin areas especially after high doses of deeply penetrating radiation. We report on a patient with an oropharyngeal carcinoma who developed severe radiation-induced acne including comedones and cysts as well as few inflammatory papules and pustules in a skin area irradiated with up to 63 gray of a 6 MeV photon beam. Acnegenic drugs may precipitate the disease; our patient was on longterm therapy with carbamazepine whose acnegenic potency is less well documented than that of testosterone or glucocorticoids. Treatment of radiation-induced acne is comedolytic; topical retinoids are especially valuable.

Contact allergy to oil of turpentine was reported to have become rare. However, the evaluation of standardized data of 45,005 patients tested 1992-1997 in 30 Dermatological Centers associated with the German-Austrian Information Network of Departments of Dermatology (IVDK) showed an increase in positive patch test reactions to turpentine from 0.5% during the years 1992-1995, up to 1.7% in 1996 and 3.1% in 1997. In particular, 17,347 patients tested in 1996-1997 were evaluated in detail by comparing 431 individuals with positive patch test reactions with the rest of the group found negative to turpentine. Using the so-called MOAHLFA index, the following characteristics were shown. Turpentine allergy (a) was found to be significantly less frequent in men and in patients with occupational dermatitis, (b) showed no difference in its association with atopic dermatitis, (c) patients with turpentine allergy had significantly less symptoms of the hands, more symptoms of the legs or in the face and (d) were significantly more often aged over 60 years. Also, patients sensitized to turpentine had increased rates of additional sensitizations. The definite reason for the increase in turpentine sensitization in the population tested here is not clear. Therefore, a detailed exposure analysis is necessary; the new increase in turpentine allergies may be due to popular topical remedies or household chemicals.

Die Bade-PUVA ist ein seit Jahren etabliertes Therapieverfahren bei verschiedenen Dermatosen, insbesondere der Psoriasis. Als Alternative in der lokalen PUVA-Therapie wurde unter Verwendung von 3,4,5-Trimethylpsoralen (TMP) kombiniert mit einer UVA-Bestrahlung (315–400 nm) eine Dusch-PUVA entwickelt, bei der die Haut des Patienten mit Ausnahme des Kopf-Hals-Bereiches mit Psoralen-haltigem Duschwasser (TMP-Konzentration 0,27 mg/l) kontinuierlich benetzt wird. Vorteile, die eine solche Dusch-PUVA bietet, sind Raum-, Zeit- und Kostenersparnis sowie die geringere korperliche Belastung bei aufrechter Haltung des Patienten im Vergleich zur Ganzkorper-Bade-PUVA. Wirksamkeit und Praktikabilitat der Dusch-PUVA wurden an gesunden Probanden anhand der Minimalen Phototoxischen Dosis (MPD) gepruft in Abhangigkeit von der Temperatur des Duschwassers (33–38 °C), der Duschzeit (5–10 min) sowie der UVA-Bestrahlungsdosis (0,06–1,0 J/cm2). Zusatzlich wurde der Verlauf der Photosensitivitat auf TMP-behandelter Haut bis 4 h nach dem Duschen untersucht. Mit einer TMP-Konzentration von 0,27 mg/l im Duschwasser wurde eine MPD erreicht, die fur Hauttyp I–II zwischen 0,125–0,375 J/cm2 und fur Hauttyp III–IV zwischen 0,375– 1,0 J/cm2 lag. Phototoxische Reaktionen wurden bei einer Duschzeit von 5–10 min und einer Wassertemperatur von 33–38 °C beobachtet. Dabei korrelierte die Wassertemperatur umgekehrt proportional mit der MPD, jedoch zeigten sich kaum Unterschiede zwischen einer Duschzeit von 5 und 10 min. Die Photosensitivitat persistierte bis zu 2 h nach dem Duschen. Die minimalen phototoxischen Reaktionen bei Dusch-PUVA unter Anwendung von 3,4,5-Trimethylpsoralen entsprechen unter Berucksichtigung des jeweiligen Hauttyps denen einer Bade-PUVA. Diese ersten Untersuchungsergebnisse bilden die Grundlage fur die fachgerechte Anwendung der Dusch-PUVA und fur die Erarbeitung von therapeutischen Modalitaten.

Acute infection with hepatitis C virus (HCV) is often clinically inapparent, but may affect several organ systems in its chronic course. In dermatology, common diseases such as lichen planus, cryoglobulinemic vasculitis and porphyria cutanea tarda have been described in association with HCV infection. A number of other dermatologic disorders, e.g., psoriasis, chronic urticaria, chronic pruritus, pseudo-kaposi sarcoma, necrolytic migratory erythema and Behcet disease, have been associated in case reports with HCV-induced liver disease. In this study we summarize the recent literature reports, present three patients observed by our group and update the topic.

A 76-year-old female patient developed severe manifestations of a kaposi-like acroangiodermatitis (so-called Mali's disease) due to chronic venous insufficiency of the lower extremities. The patient presented with large areas of confluent, violaceous or brown-black papules on both lower legs. Histologically, proliferation of thick-walled capillaries was seen in the upper dermis consisting of fully differentiated endothelial cells, as shown by immunohistochemistry. In contrast to true Kaposi's sarcoma, human-herpes-virus-8 DNA could not be detected by polymerase-chain-reaction in this condition. We review the diagnostic criteria used to distinguish between acroangiodermatitis, also called pseudo-Kaposi's sarcoma, and the true Kaposi's sarcoma.

Pseudoscabies, i.e. infestation of human skin with animal mites may occasionally occur and should be considered in the differential diagnosis of pruritic and papular skin disease. We report here on a 52-year-old woman with pseudoscabies or canine scabies (Sarcoptes scabiei var. canis), transmitted by indirect contact with a red fox in the urban area of Berlin. Red foxes may live in unhabited areas of metropolitan large cities, i.e. in garages, car wrecks and cellars. Full remission of the prolonged and pruritic rush was seen after topical administration of lindane together with systemic corticosteroids.

Die perforierenden Dermatosen bilden eine heterogene Gruppe von Erkrankungen, die durch transepidermale Eliminationsphanomene gekennzeichnet sind. Abzugrenzen sind die primar perforierenden Dermatosen von solchen perforierenden Dermatosen, bei denen Perforation oder Elimination sekundar und als seltenes Teilsymptom bei bestehenden Dermatosen anderer Provenienz auftreten konnen. Zu den primar perforierenden Dermatosen zahlen dabei als Prototypen die Hyperkeratosis follicularis et parafollicularis in cutem penetrans (M. Kyrle), die Elastosis perforans serpiginosa und die perforierende Follikulitis. Die erworbene reaktiv perforierende Dermatose (syn. erworbene reaktiv perforierende Kollagenose) stellt zusammen mit der hereditaren, reaktiv perforierenden Kollagenose eine weitere Variante der primar perforierenden Dermatosen dar. Wir stellen hier eine 84jahrige und eine 96jahrige Patientin mit einer erworbenen reaktiv perforierenden Dermatose vor. Bei beiden Patientinnen lagen eine diabetogene und eine hyperurikamische Stoffwechsellage vor. Eine Therapie mit Allopurinol (100 mg/d) fuhrte bereits nach kurzer Dauer (1 bis 2 Wochen) zu einer weitgehenden Abheilung der disseminierten Lasionen. Uber einen Nachbeobachtungszeitraum von jeweils 6 Monaten befanden sich beide Patientinnen in Vollremission. Diese Beobachtungen belegen erneut die Existenz und Massivitat der Erkrankung und zeigen, das Allopurinol neben der bekannten urikostatischen Wirkung moglicherweise in der Haut immunologische oder differenzierungsmodulierende Effekte vermittelt.

Allergische Reaktionen induziert durch das Antimykotikum Nystatin sind trotz des jahrelangen weitverbreiteten Einsatzes eine Raritat. Wir konnten einen Fall beobachten, bei dem es nach oraler Nystatinanwendung zur Entwicklung einer akuten generalisierten exanthematischen Pustulose mit Allgemeinsymptomatik (Fieber, Arthralgien) kam. Die Kausalitat wurde durch eine positive Intrakutantestung mit Nystatin-haltigen Arzneimitteln gesichert. Immunhistologisch fanden sich in den Testreaktionen positive Ablagerungen von Komplement C3, wohingegen zirkulierende Immunkomplexe nicht nachweisbar waren. Immunologisch ist der beschriebene Fall am ehesten als Typ-II-Reaktion nach Coombs und Gell einzuordnen. Unter systemischer Prednisolongabe kam es innerhalb von 11 Tagen zu einer kompletten Remission. Bei 2 Probanden, die berichteten, zuvor niemals Nystatin eingenommen oder lokal angewandt zu haben, wurde ebenfalls eine Intrakutantestung mit Nystatin-haltigen Arzneimitteln durchgefuhrt, die zunachst unauffallig war. Allerdings entwickelten sich bei beiden Probanden an den Injektionsstellen nach 3 Wochen juckende erythematose Papeln. Offenbar besteht fur Nystatin ein bislang nicht bekanntes Sensibilisierungsrisiko durch die Intrakutantestung.

Von 1982 bis 1995 wurden an der Hautklinik und Poliklinik des Universitatsklinikums Benjamin Franklin der Freien Universitat Berlin uber 700 dermatologische Patienten mit HIV-Infektion registriert, von denen 36 an einer Psoriasis erkrankt waren. Damit ist die Pravalenz der Psoriasis in diesem Kollektiv HIV-infizierter Patienten mit ca. 5% deutlich hoher als in der Gesamtbevolkerung (1–2%). Liegen psoriatische Hautveranderungen bei Diagnose der HIV-Infektion nicht vor, werden sie bevorzugt (ca. 80% der Falle) erst im Rahmen einer spaten Phase der Infektion (CD4/CD8-Ratio

Background and Objective: Systemic mastocytosis is a rather rare disorder involving the skin and several other organs. The aim of this study was to analyse the extent of extracutaneous manifestations in 14 adult patients who presented with prominent cutaneous involvement within the last 5 years. Results: The cutaneous lesions were clinically diagnosed as telangiectasia macularis eruptiva perstans in 2 patients, urticaria pigmentosa of varying extent in 11 and diffuse erythrodermic mastocytosis in 1 patient. All patients had extracutaneous manifestations with involvement of one additional organ system in 6/14 cases, two in 5/14 and three in 3/14. Ten out of 14 patients suffered from generalized pruritus, and 11/14 reported mild wheal formation, while 3/14 with multi-organ involvement mentioned recurrent flushing episodes. The gastro-intestinal tract was involved in 8/14 cases with an increase in gastric and colon mucosal mast cells in 5/8 cases and gastroduodenitis in 2. Bone marrow involvement was seen in 7/13 patients, hepatosplenomegaly in 2, anaemia in 2 and thrombocytopenia in 3. The disease had a duration of 0.5–32 years, clinical symptoms remaining basically unchanged. Malignant transformation was not seen; only 1 patient developed myelodysplastic syndrome within 2 years after the first cutaneous lesions. Conclusions: Our study shows that extracutaneous involvement should be carefully considered in adult patients with cutaneous mastocytosis. Systemic multi-organ mast cell disease in adults is a long-lasting disorder with recurrent episodes of varying clinical symptomatology. However, the disease shows rather slow progression, and malignant transformation is rare. Satisfactory management is achieved by symptomatic oral drug intake.

Insektengiftallergien fuhren in Deutschland zu 10–40 Todesfallen pro Jahr. Die Einleitung und Aufrechterhaltung einer Hyposensibilisierungsbehandlung kann fur die betroffenen Kranken lebensrettend sein. Im Rahmen einer prospektiven Studie mit einem gereinigten Wespengiftpraparat an 20 Wespengiftallergikern (klinischer Schweregrad II–IV) wurden die Wirksamkeit und das Auftreten von Nebenwirkungen wahrend der einleitenden Schnellhyposensibilisierung genau dokumentiert. Die Indikation zur Behandlung wurde individuell auf Grund einer Punkteskala gestellt, mit der a) die Schwere der klinischen Symptomatik, b) die Befunde der In-vivo- und In-vitro-Diagnostik und c) das Expositionsrisiko bewertet wurden. Die Schnellhyposensibilisierung erfolgte unter stationaren Bedingungen nach einem standardisierten 8-Tage-Schema. Nach Abschlus der Behandlung vertrugen alle Patienten die angestrebte Erhaltungsdosis von 100 μg des gereinigten Wespengiftpraparates komplikationslos, auch wenn Dosen von 0,01 bis 10 μg (Median 0,2 μg) zu Lokalreaktionen bei allen Patienten fuhrten. Bei 40% der Kranken traten subjektive Nebenwirkungen (Median der Schwellendosen: 30 μg, Spannbreite 0,2–60 μg) und bei 30% objektive systemische Nebenwirkungen auf (Median der Schwellendosen 55 μg, Spannbreite 20–80 μg), doch die gesamte Nebenwirkungssymptomatik war leichten klinischen Schweregrades. Die kumulativen Tagesdosen beim Auftreten objektiver systemischer Nebenwirkungen betrugen 39 bis 210 μg (Median: 135 μg) und lagen bei 83% der Patienten oberhalb von 100 μg. Unsere prospektive Studie bestatigte, das die Schnellhyposensibilisierung mit dem gewahlten Schema zur Toleranzinduktion gegenuber dem Wespengiftpraparat wirksam ist. Die Verwendung lyophilisierter, gereinigter Praparate brachte allerdings im Hinblick auf die Nebenwirkungen keine Vorteile mit sich.

Das Vena-cava-superior-Syndrom ist klinischer Ausdruck einer venosen Stauung im Ableitungsgebiet der oberen Hohlvene. Als Manifestation dieses relativ seltenen Symptomenkomplexes steht eine haufig akut entstehende Gesichtsschwellung im Vordergrund, die den Patienten zunachst zum Dermatologen fuhrt. Weitere klinische Charakteristika des Vena-cava-superior-Syndroms sind Rotung bzw. Zyanose des Gesichts, Stauung der Halsvenen und, bei langerem Bestand, Entwicklung von Kollateralvenen im Brustwandbereich. Die haufigste Ursache des Vena-cava-superior-Syndroms ist heute ein ausgepragter raumfordernder Prozes im Mediastinum, der langsam-progredient oder auch akut-subakut zur oberen Einflus-Stauung fuhrt. Die Erkrankung kann auch einen hochdramatischen, z.T. lebensbedrohlichen Verlauf nehmen, der intensiv-diagnostische bzw. intensiv-therapeutische Masnahmen erfordert. In der vorliegenden Arbeit werden drei eindrucksvolle Falle eines Vena-cava-superior-Syndrom vorgestellt, die a) durch ein Bronchialkarzinom, b) eine bihilare Sarkoidose sowie c) durch ein im Mediastinalraum metastasierendes malignes Melanom bedingt waren. Dabei wird das Krankheitsbild unter besonderer Berucksichtigung der notwendigen diagnostischen und therapeutischen Masnahmen anhand des bisherigen Schrifttums zusammenfassend dargestellt.

Epidermal homeostasis is influenced by a number of hormones and regulative growth factors that are maintained by a tightly regulated balance between cell proliferation, cell differentiation, and cell death. Vitamin D is one of those regulatory factors. It has recently been demonstrated that 1α,25-dihydroxyvitamin D 3 (1α,25(OH) 2 D 3 ) takes part in the regulation of the cell cycle by multiple and complex functions. This review discusses 1α,25(OH) 2 D 3 and its analogues in connection with the renewal of epidermal keratinocytes as well as the molecular mechanisms underlying terminal differentiation or rather programmed cell death. Furthermore, interest is focused on the possible clinical application of vitamin D 3 analogues.

Summary Scleromyxoedema, a disseminated papular and sclerotic variant of lichen myxoedematosus, is a rare disease with a chronic progressive course, and little tendency towards spontaneous remission. The treatment of scleromyxoedema has been largely ineffective. Aggressive chemotherapeutic agents have been used, often leading to therapy-related morbidity and mortality. We report a 41-year-old woman with scleromyxoedema, associated with a monoclonal gammopathy of IgG-k type, whose condition almost completely cleared with 12 monthly sessions of extracorporeal photopheresis. The patient had previously not responded to isotretinoin, and chlorambucil with prednisolone.

Recently, several reports have been describing a possible relation between Helicobacter pylori infection of the gastric mucosa and dermatological diseases. Associations have been reported for urticaria, roascea, Sjogren's syndrome and Schonlein-Henoch purpura. In this paper we review the current knowledge on Helicobacter pylori infection and its relevance for skin diseases, especially its clinical and pathophysiological aspects.

Wir berichten uber einen 32jahrigen Patienten mit fortgeschrittenem, erworbenen Immundefizienz-Syndrom (AIDS), bei dem eine schwere gastrointestinale Kandidose festgestellt wurde. Initial erfolgte eine Behandlung mit Fluconazol 200 mg/d uber5 Monate, die dann mit Itraconazol 200 mg/d uber einen weiteren Monat kombiniert wurde. Die Kandidose zeigte sich klinisch resistent auf beide Azol-Antimykotika. Die antimykotische Aktivitat von Fluconazol, Itraconazol und auch von Ketoconazol gegen Candida albicans wurde in vitro mit dem Mikrodilutionstest durch Bestimmung der 90%-Hemmkonzentration ermittelt. Eine hohe minimale Hemmkonzentration (MHK) wurde fur Fluconazol (50 μg/ml) festgestellt gleichbedeutend mit einer Fluconazol-Resistenz. Die Empfindlichkeit war gegen Itraconazol grenzwertig (MHK 0,125 μg/ml) und gegen Ketoconazol deutlich erniedrigt (MHK 0,25 μg/ml). Im Blutplasma lies sich daruber hinaus ein erniedrigter Itraconazol-Spiegel nachweisen. Bei HIV-Patienten ist die gastrointestinale Absorption von Azol-Derivaten haufig vermindert, so das sich die klinische Resistenz von Itraconazol, neben einer grenzwertig erniedrigten Empfindlichkeit von Candida albicans, auch durch eine reduzierte Absorption erklaren last.

The naevus of Ota (naevus fusculocoeruleus ophthalmomaxillaris) was first described by the Japanese dermatologist M. T. Ota in 1939. It has a reported incidence of 0.2% to 1% in the Japanese population. It usually occurs in the skin innervated by the first or second branch of the trigeminal nerve. The naevus comprises dermal melanocytes and is congenital or acquired during adolescence. Commonly associated lesions include scleral melanocytosis and other ocular manifestations as well as lesions of the tympanic membrane, oral and intranasal mucosa and leptomeninges. Diseases associated with Ota's naevus in rare cases are open-angle glaucomas and melanoma. The naevus of Ota in Europeans is a rare manifestation. We report the very rare case of a bilateral naevus of Ota associated with enoral melanocytosis in a white European person.

34 Patients with subacute cutaneous lupus erythematosus (SCLE) were prospectively followed up and examined twice in 1986 – 1989 and 1990 – 1991, with a minimal interval of 2 years. The findings obtained were documented in a computerized registry and were evaluated by computer-assisted analysis. Thirty-one women and three men aged 23 – 66 years at the time of the first documentation (FD) were included in the study. The disease had lasted an average 6.5 years (from a few months to 39 years). Prominent cutaneous manifestations of SCLE were shown by 79.4% of the patients at the first visit compared to 58.8% at the second documentation (SD), whereas the incidence of acrolocalized vasculitis increased (FD 20.6%, SD 41.2%), as did that of Raynaud phenomenon (FD 20.6%, SD 26.5%). Mild extracutaneous symptomatology was found in 70.6% (FD) and in 85.3% (SD) of the SCLE patients. Arthralgia (FD 47%, SD 61.8%) and symptoms suggesting some involvement of the peripheral or central nervous system (FD 29.4%, SD 50%) were noted most frequently. Overall, during the follow-up there was a quantitative mild increase of extracutaneous symptomatology; a significant correlation between the presence of acrolocalized vasculitis and arthralgia was found. In conclusion, the prognosis of SCLE appears rather benign; fulminant courses were not observed. However, the risk of mild systemic involvement clearly increases during the prospective course of the disease, whereby acrolocalized vasculitis can be regarded as a cutaneous marker for extracutaneous manifestations.

Ultraviolet light is frequently used for cosmetic tanning of the skin. UV light is known to be carcinogenic, but this is attributed predominantly to short-wavelength UV radiation (UVB). However, new data indicate a carcinogenic role for long wavelength ultraviolet light (UVA) also. In vitro studies have demonstrated DNA-damaging effects of UVA. In animals squamous cell carcinomas and melanomas were induced by UVA alone or in combination with UVB. Reference to a possible carcinogenicity of UVA may also be derived from the therapeutic application of UVA together with psoralens (PUVA). In addition, recent epidemiological studies have associated the use of sunbeds with the development of malignant melanoma. In conclusion, the carcinogenicity of UVA in humans cannot be ruled out, but requires further validation. Long and repeated UVA exposure should be discouraged, because of the far-reaching risks involved.

Suramin has long been used in the treatment of onchocerciasis and trypanosomiasis. Recent investigations showed an antiproliferative effect of suramin on prostate carcinoma cell lines. Ongoing clinical trials have confirmed the effect of suramin on metastasizing prostate carcinoma. Five patients with metastatic prostate carcinoma resistant to classic hormonal therapy were treated with high-dose suramin. Four of the five developed a papulovesicular or maculopapular rash within 2-4 weeks of starting therapy. The rashes disappeared after discontinuation of suramin within 10 days. In tumour therapy, high dosages of suramin are used to achieve a serum level of 200-300 micrograms/ml. Therefore, a toxic reaction to suramin is suspected as the explanation for the skin rashes.

Aquagenic urticaria is a rare disorder characterized by the occurrence of pruritus and wheals after temporary contact with water. The familial occurrence of aquagenic urticaria over 3 generations is reported here in association with familial lactose intolerance, a condition in which the enzyme lactase encoded on chromosome 2, is deficient. In two patients, a young man and his mother, we verified the appearance of pruritic hives 5 to 10 minutes after contact with water of any temperature. Other types of physical urticaria were absent, and mastocytosis was excluded by extensive laboratory investigations; lactose intolerance was confirmed in both patients by H 2 -exhalation test. In these patients the clinical symptoms did not respond to antihistamines or UV-radiation therapy. Four other members of the family had wheals from water contact, two of whom had lactose intolerance. Two other members had lactose intolerance only. Although the association of aquagenic urticaria with lactose intolerance may be coincidental, attention is drawn to the fact that the 2 conditions, known to be familial, may coexist in the same family, possibly based on an association of gene loci. (J Am Acad Dermatol 2002;47:611-3.)

Schnitzler’s syndrome (SS) is characterized by the association of generalized chronic urticaria, osteocondensation and monoclonal IgM gammopathy. Nonsteroidal anti-inflammatory drugs and systemic steroids are the most promising treatments. In our patient, they were ineffective. By contrast, during the follow-up period of 18 months, interferon α2b therapy (IFN-α) relieved the patient from its urticarial lesions and bone pain. IFN-α was tried to be stopped twice: each time, relapse of urticaria was noticed and, each time, the cutaneous lesions disappeared after IFN-α had been reintroduced. Furthermore, our observation supports the idea of the interleukin (IL)-1-mediated pathogenesis of SS as IFN-α induces high levels of IL-1 receptor antagonists. IFN-α could be an alternative treatment in disabling SS resisting other drugs.

We report the case of drug-induced, acrolocalized Kaposi sarcoma (KS), arising multicentrically in both palms and soles of a male patient who has had widespread psoriasis since 12 years of age. This 59-year-old man, of Mediterranean origin, was HIV antibody-negative and had received oral prednisolone treatment over 5 months for chronic obstructive lung disease (initial dose: 75 mg/d). Eight months after discontinuing oral treatment the KS nodules regressed spontaneously and finally disappeared completely without additional treatment. Light and electron microscopic investigations confirmed the diagnosis of KS, whereas laboratory tests excluded HIV infection and suggested mild immune dysfunction. The existence of HLA loci predisposing to KS and to psoriasis (A1, DR5, DR7, DR11) was characteristic for the simultaneous occurrence of these two diseases. This case report demonstrates the complex interrelationships between genetic predisposition, drugs leading to immune suppression, and the evolution of an unusual neoplasm.

disorders. Prevalence rates vary between 14 and 50 per 100,000 population (Hochberg 1997). Cutaneous LE (CLE) presumably occurs two to three times more frequently than SLE. However, exact population-based epidemiologic data are not available. In selected groups of patients with LE cared for in dermatology departments, the prevalence of patients with chronic discoid LE (DLE) varies between 42% and 72% (Kind and Goerz 1987, Tebbe and Orfanos 1987), and subacute cutaneous LE (SCLE) is found in 7%–32% of the entire collective (Molad 1987, Sontheimer et al. 1979, Tebbe and Orfanos 1987). The prognosis of SLE depends on the severity and extent of visceral involvement. Most fatalities among patients with SLE are attributable to active disease, especially to renal and central nervous system involvement, and to various infections. However, the 10-year survival rate today exceeds 80% owing to treatment with oral corticosteroids and potent immunosuppressive drugs (Drenkard and Alarcon-Segovia 2000, Gladman 1996, Swaak 1989). In general, the prognosis of CLE is regarded as more favorable than that of SLE, although prospective studies in large groups are rare. Classic variants of specific CLE lesions are DLE and SCLE. Other typical CLE subsets, such as LE profundus/panniculitis, LE tumidus, urticaria vasculitis, hypertrophic LE, and bullous LE, are rather rare variants. Butterfly rash and macular exanthema are characteristic skin lesions of SLE rarely found in patients with CLE. DLE and SCLE may appear at any age, but the most common age at onset is 20–40 years in females and males, with a female predominance of 3:1 in DLE and 3:1 to 6:1 in SCLE. Nonspecific LE skin lesions such as generalized or acrolocalized vasculitis (4%–30%), livedo reticularis (22%–35%), and alopecia (38%–78%) are frequently seen in patients with CLE (Beutner et al. 1991, Callen 1985, 1986, Molad 1987, Moschella 1989, Sontheimer 1979, Tebbe and Orfanos 1992). DLE and SCLE are generally regarded as disease variants with a better prognosis than that of SLE, and severe courses of cutaneous variants with a lethal outcome are rare. However, if mild signs of systemic manifestations, such as proteinuria and arthralgia, were registered in CLE, 14%–27% of patients with DLE and 67%–70% of patients with SCLE had extracutaneous involvement (Sontheimer 1989, Tebbe et al. 1997, Watanabe and Tsuchida 1995). It seems that ca. 5%–10% of patients with DLE will experience transition to SLE during long-term disease (Healy et al. 1995, Le Bozec et al. 1994, Millard and Rowell 1979, Rowell 1984, Schiodt 1984). In most cases, transition to SLE requires more than 5 years (Healy et al. 1995, Le Bozec et al. 1994). However, severe life-threatening manCHAPTER 14

Reactive oxygen species can cause harmful effects in keratinocytes and fibroblasts if antioxidative defence mechanisms are exhausted. Therefore, it seems to be reasonable to prove if oral supplementation with various nutrient antioxidants is useful in prevention or treatment of skin disorders especially in those mediated by UV irradiation. Betacarotene, ascorbic acid and tocopherol have been tested alone or in combination for prevention of sunburn, photodermatoses and photocarcinogenesis with divergent results. Other candidates for oral antioxidative supplementation in humans are selenium and polyphenols. However, clinical data are limited or missing up to date.

2-Chloracetophenone (CN) is widely used as tear gas by police and civilians for self-defence. It may affect the eyes, respiratory system and skin, sometimes causing serious injuries. Both irritative and allergic contact dermatitis have been described. We report three police officers who experienced accidental escape of CN from their professional tear gas canisters. All of them showed localized dermatitis at the site of contact to CN, while widespread lesions appeared after 4 days in one case. Patch tests with the original involved tear gas dissolved in acetone (at 0.1-0.0001%) indicated an allergic reaction in two patients and an irritative reaction in the third. Occupational contact dermatitis due to CN seems to occur among police officers more often than is generally known. Infrequently, extensive health problems may be caused by CN when lesions spread over the integument. Therefore, an improvement of safety measures in occupational CN gas use is needed, especially aiming at avoidance of accidental leakage of canisters.

An HIV-1 infected immunosuppressed patient (CD4+ cell counts: 382 cells/microL; viral load 94,000 copies/mL) with recurrent perianal herpes simplex virus type 2 (HSV-2) infections is described, showing an unusual exophytic tumour resembling a squamous cell carcinoma in the lateral part of the tongue. He also had persistent facial herpes infection, oral candidosis, oral hairy leukoplakia and lymphadenopathy. The presence of HSV-2 was detected by polymerase chain reaction both in smears and in a tissue biopsy taken from the involved tongue area. Treatment with brivudin, a new oral virustatic drug, led to rapid regression of the tumour.

Background: Merkel cell carcinoma (MCC) is an uncommon primary neuroendocrine skin tumor most often seen in the elderly. The clinical course varies. Treatment is controversial and few data on drug sensitivity are available. Objective: We evaluated the clinical course and treatment of 10 MCC patients and determined MCC chemosensitivity. Methods: Clinical records as well as laboratory and histopathologic data from 10 patients with MCC treated in our department were examined. Chemosensitivity to various chemotherapeutic agents and interferons of MCC cells from four patients was determined in a soft agar clonogenic assay. Results: MCC behaved as an aggressive tumor with early and frequent local relapses (4 of 10 patients at a 2.2-month average), regional (4 of 10 patients at 2.5 months), and distant metastases (5 of 10 patients 9.6 months after excision of the primary tumor). In all but one patient, regional metastases preceded distant ones. Metastatic spread was associated with an average survival of 21 months from the initial diagnosis. Long-term survival (53+ and 65+ months) was observed in two women. Wide excision of the primary tumor, alone or combined with adjuvant chemotherapy and radiotherapy, was the most effective treatment. In advanced disease, chemotherapy and radiotherapy were not able to induce long-term remission. In vitro assays for MCC drug sensitivity revealed cisplatin, doxorubicin, and vindesine to be the most active. Conclusion: MCC has a poor prognosis in advanced stages; therefore the primary tumor should be aggressively treated. The in vitro clonogenic assay may help to identify the chemosensitivity profile of MCC and to optimize chemotherapy protocols.

We investigated the antioxidative effect of L-ascorbic acid on lipid peroxidation and on secretion and mRNA expression of IL-1alpha and IL-6 after UVA irradiation (20 J/cm2) in cultured human keratinocytes. Lipid peroxidation was measured by (i) high performance liquid chromatography with UV detection of malondialdehyde (MDA) at 256 nm and (ii) spectrometric measurement of thiobarbituric acid-reactive substances (TBARS). To evaluate UV-induced cytotoxicity, we assessed cell membrane damage by measuring lactate dehydrogenase (LDH) release. UVA-induced lipid peroxidation in cultured human keratinocytes was inhibited by ascorbic acid in a concentration-dependent manner: MDA protein equivalent was reduced by 47% (10(-6)), compared to keratinocytes not exposed to L-ascorbic acid (p < 0.05), and the TBARS showed a concentration-dependent decrease of 49% (10(-6) M) in L-ascorbic acid-supplemented cultures compared to controls (p < 0.05). LDH release was decreased by 45% in L-ascorbic acid-supplemented keratinocyte cultures, indicating protection against cell death (p < 0.05). L-Ascorbic acid was able to downregulate IL-1alpha mRNA expression in both UVA-irradiated and nonirradiated cells; however, IL-6 mRNA expression remained unaffected. The secretion of these cytokines was reduced nearly to normal in the presence of L-ascorbic acid. These findings indicate a major cell-protective effect of L-ascorbic acid on UVA-induced lipid peroxidation and the secretion of pro-inflammatory cytokines by UVA-irradiated human keratinocytes.

Together with antihistamines, various antibiotics including penicillin, tetracycline, and others have been empirically used to treat chronic urticaria in an attempt to eliminate an underlying focal infection. On the basis of this knowledge, we posed the question as to whether Helicobacter pylori infection could be an underlying cause of chronic urticaria. H. pylori infection can easily be diagnosed with high sensitivity and specificity with the [13C]-urea breath test.l, 2 The present study was performed to investigate the possible role of H. pylori in patients with chronic urticaria. We screened an unselected series of patients for infection and investigated whether specific treatment against the pathogen could cure the urticaria.

A cutaneous metastatic angiosarcoma was diagnosed in a 79-year-old woman 19 years after radiotherapy for a carcinoma of the uterine cervix. The diagnosis was confirmed by immunohistochemical staining (factor VIII-related antigen and BMA 120) and electron microscopic examination. Surgical treatment of the large tumour, which was situated in the gluteal region, was not feasible, but electron beam therapy resulted in complete remission. However, a further metastasis occurred in the inguinal region, and management by total excision, radiotherapy, and interferon-alpha treatment was unsuccessful. The patient died 28 months after the initial diagnosis of the neoplasm.

Summary An immunohistochemical analysis of skin biopsies was performed in 18 patients with cutaneous lupus erythematosus (LE), using the alkaline phosphatase and monoclonal anti-alkaline phosphatase method (APAAP). The study group was subdivided on the basis of clinical criteria into 10 patients with chronic discoid LE (CDLE) and eight patients with subacute cutaneous LE (SCLE). Using a panel of monoclonal antibodies the following results were obtained: (i) ICAM-1 was expressed on epidermal keratinocytes, dermal inflammatory cells, and endothelial cells in most biopsies, whereas LFA-1 was confined to the dermis. Attachments between keratinocytes or endothelial cells and activated T lymphocytes via ICAM-1/LFA-1 may be a possible mechanism of target/effector recognition in cutaneous LE. (ii) HLA-DR was expressed on epidermal keratinocytes and cells of the dermal infiltrate, but not on endothelial cells. HLA-DR+ cells probably function as antigen-presenting cells, leading to major histocompatibility complex-restricted cellular cytotoxicity in cutaneous LE. (iii) Interleukin 2 receptor expression on dermal inflammatory cells was weak, indicating non-specific activation of T lymphocytes. (iv) The dermal inflammatory cells were T lymphocytes, mainly of the helper/inducer subtype. B lymphocytes were rarely found in the dermis. In general, no significant immunohistochemical differences were found between CDLE and SCLE, suggesting that these variants represent clinical subtypes rather than different pathogenetic entities.