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Vascular lesions with telangiectasias on visible areas, such as the face, are common in discoid lupus erythematosus (DLE); however, an efficient management of these skin lesions can sometimes be difficult. Since argon laser light is able to specifically coagulate vascular structures, it has been used in the treatment of various vascular skin malformations. Therefore, we addressed the issue whether argon laser treatment could be a therapeutic alternative for this disease. Here, we report on a patient with DLE, who suffered from long-standing erythematous, telangiectatic plaques on the face refractory to standard regimens of therapy. After 2 laser applications, a significant improvement was observed and after 5 sessions of argon laser therapy the treated skin lesions had completely resolved with an excellent cosmetic result. The patient tolerated the laser treatment well without any short-term side effects. These data indicate that argon laser therapy might be a powerful alternative approach in the treatment of vascular skin lesions of DLE.

Hyperpigmentation of the skin is often refractory to conventional therapies, but has significant cosmetic implications if located on visible areas. Because laser systems are capable of removing pigment deposits caused by selective photothermolysis, we addressed the issue of whether the Q-switched ruby laser could be a useful alternative in the treatment of nonmelanotic hyperpigmented skin lesions. We report the successful treatment of a patient with hyperpigmentation caused by iatrogenic human herpesvirus 8‐associated Kaposi’s sarcoma and a patient with hyperpigmentation caused by long-term antimalarial therapy for cutaneous lupus erythematosus. In both patients, clinical lightening of the darkly pigmented lesions was seen after a single treatment, and a significant improvement was observed after 3 laser applications. The patients tolerated the laser therapy well without any short-term side effects and did not experience either scarring or considerable textural skin changes. Histologic examination was performed before and after laser treatment to confirm the reduction of the pigment deposits. Our data indicate that treatment of nonmelanotic skin hyperpigmentation with the Q-switched ruby laser might be a safe and powerful therapeutic method. (J Am Acad Dermatol 2000;43:272-4.)

We recently reported the identification of a chemokine (CTACK), which has been renamed CCL27 according to a new systematic chemokine nomenclature. We report that CCL27 binds the previously orphan chemokine receptor GPR-2, as detected by calcium flux and chemotactic responses of GPR-2 transfectants. We renamed this receptor CCR10. Because of the skin-associated expression pattern of CCL27, we focused on the expression of CCL27 and CCR10 in normal skin compared with inflammatory and autoimmune skin diseases. CCL27 is constitutively produced by keratinocytes but can also be induced upon stimulation with TNF-α and IL-1β. CCR10 is not expressed by keratinocytes and is instead expressed by melanocytes, dermal fibroblasts, and dermal microvascular endothelial cells. CCR10 was also detected in T cells as well as in skin-derived Langerhans cells. Taken together, these observations suggest a role for this novel ligand/receptor pair in both skin homeostasis as well as a potential role in inflammatory responses.

Bei Photodermatosen, die durch photosensibilisierende Substanzen verursacht werden, ist die Reproduktion der Hautveranderungen durch EP oder MP alleine nicht moglich, da zur Provokation noch der auslosende Photosensibilisator benotigt wird [138]. Die wichtigsten Photosensibilisatoren sind in Tabelle 10 zusammengefast.

Die HV ist eine sehr seltene, narbenbildende Photodermatose mit hamorrhagischen Blasen und varioliformen Narben in lichtexponierten Arealen [96].

Der LE ist eine Autoimmunerkrankung, die sich in einem oder in mehreren Organsystemen manifestieren kann [17, 33, 34, 51, 62, 65, 69, 74, 84, 105, 112, 129, 131].

Bei der EPP handelt es sich um eine Erkrankung, der ein Defekt der Ferrochelatase zugrunde liegt [93]. Neueren Untersuchungen zur Folge gibt es auch eine zweite autosomal rezessive Form.

Die aktinische Dermatitis stellt neben der polymorphen Lichtdermatose und der Lichturtikaria einen photobiologischen Forschungsschwerpunkt der dermatologischen Klinik der Heinrich-Heine-Universitat Dusseldorf dar 11001. Ziel ist es, neue Erkenntnisse zur Pathogenese zu gewinnen und diesen Teil der Photodermatosen neu zu ordnen. In diesem Kontext ist der neue Begriff der aktinischen Dermatitis mit seinen untergeordneten Entitaten als eine Hypothese zu verstehen, die erst noch verifiziert werden mus.

Die PLD ist ein lichtprovoziertes, pruritisches, papuloses, vesikuloses oder lichenoides Exanthem [61].

The aim of the present study was to evaluate the supposed photoprotective effects of ascorbic acid, acetylsalicylic acid, and indomethacin by the photo hen's egg test, a recently developed new model for phototoxicity. Therefore, in three independent experimental settings the blood vessel system of the embryo's yolk sac of 24 incubated hens' eggs (2 test groups) were exposed to 60 mJ/cm2 ultraviolet B (UVB) to induce severe phototoxic damage. Before UVB irradiation, one of these test groups was exposed additionally to one of the test substances and the other one to 0.9% sodium solution alone. To exclude plain toxic reactions, two additional test groups were exposed only to 0.9% sodium chloride solution or to one of the test substances alone. Over a test observation period of 24 h, the embryo lethality as well as the morphological changes of the yolk sac blood vessel system were observed. Ascorbic acid led to a significant and remarkable reduction of the UVB-induced damage. Acetylsalicylic acid also showed a significant but lower photoprotective capacity. In contrast, indomethacin showed no photoprotective effects in the photo hen's egg test.

Porphyria cutanea tarda (PCT) is the most frequent form of porphyria. The underlying enzymatic defect in PCT is a reduced activity of the enzyme uroporphyrinogen decarboxylase (Uro-D). Four different types of Uro-D disturbances are known. Pseudoporphyrias such as porphyria cutanea uraemica or drug-induced PCT-like skin symptoms are distinguished from PCT. Porphyrinogens such as estrogens or alcohol, or other inducers of P450 isoenzymes provoke PCT. Polymorphisms of P450 isoenzymes, iron overload and infection with hepatitis C virus play an important role in the etiopathogenesis of disease manifestation. Dominant clinical symptoms are bullae, increased cutaneous vulnerability, hypertrichosis and elastosis. Biochemically, total porphyrin levels in urine are increased with a predominance of uroporphyrin and heptacarboxylic porphyrin. Isocoproporphyrin is demonstrable in feces. Best therapeutic strategies are the oral administration of chloroquine 125 mg twice a week and repetitive bloodlettings or the combination of both.

Porphyrine sind lebenswichtige Farbstoffe, die die Grundstruktur des Ham und des Chlorophyll bilden. Die Synthese des Ham erfolgt, ausgehend von Succinyl-Coenzym A und Glycin, uber acht enzymatische Schritte. Porphyrien sind Stoffwechselerkrankungen, die auf einer verringerten Aktivitat eines dieser Enzyme beruhen (Tab.1). Das klinische Bild der jeweiligen Porphyrieerkrankung hangt davon ab, welche Porphyrinvorstufen bzw. -metaboliten sich in dem entsprechenden Gewebe anreichern. Fur die Dermatologen bedeutende Porphyrien sind die erythropoetische Protoporphyrie (EPP), die congenitale erythropoetische Porphyrie (CEP), die Porphyria variegata (PV), die hereditare Coproporphyrie (HC) und vor allem die Porphyria cutanea tarda (PCT).

Contact and photocontact allergic as well as irritant and photoirritant skin reactions represent a major problem in clinical dermatology and during the development of new pharmaceuticals. Furthermore, there is a lack ofin vitroandin vivoassays that provide a clear differentiation between allergic and irritant skin reactions. Here, we describe an integrated model to differentiate between chemical-induced allergic and irritant skin reactions by measuring objective and easy-to-determine parameters within both skin and skin-draining lymph nodes. Dose–response studies with standard contact and photocontact allergens as well as irritants and photoirritants revealed that irritants predominantly induced skin inflammation, which in turn stimulated draining lymph node cell proliferation. In contrast, the induction phase of contact or photocontact allergy was characterized by marginal skin inflammation, but a marked activation and proliferation of skin-draining lymph node cells. Therefore, a differentiation index (DI) was defined describing the relation between skin-draining lymph node cell activation (lymph node cell count index) and skin inflammation (ear swelling). A DI > 1 indicates an allergic reaction pattern whereas DI < 1 demonstrates an irritant potential of a chemical. Experiments with the contact allergen oxazolone, the photocontact allergen TCSA + UVA, the irritant croton oil, and the photoirritant 8-methoxypsoralen + UVA confirmed the predictive value of DI. Furthermore, flow cytometric analysis of lymph node-derived T- and B-cell subpopulations revealed that contact sensitizer, but not irritant, induced the expression of CD69 on the surface of I-A+cells. In conclusion, further studies with a broad range of irritants and allergens will be required to confirm general applicability.

The etiology of systemic autoimmune diseases, such as systemic lupus erythematosus (SLE) and systemic sclerosis (SSc) is still unknown. In several cases, however, xenobiotics (i.e. drugs and occupational agents) were identified as etiologic agents and associations with certain polymorphic alleles of xenobiotic-metabolizing enzymes have been reported. Cytochrome P4501A1 (CYP1A1) and N-acetyltransferase 2 (NAT-2) are xenobiotic-metabolizing enzymes of phase 1— and phase 2-metabolism, respectively. CYP1A1 may activate drugs and other chemicals to reactive metabolites. NAT-2 is the most important enzyme in acetylation of aromatic amines, and thus may be responsible for detoxification of many of these compounds. Two polymorphisms of the human CYP1A1 gene, a point mutation in the 3 ’ flanking region of the gene (MspI) and a mutation in exon 7 leading to an isoleucine-valine-exchange in the heme-binding region of the enzyme, have been described and may lead to a higher basal and inducible enzyme activity. With respect to NAT-2, several alleles which combine for the two phenotypes “fast” and “slow” acetylators have been described. We analyzed the gene frequencies of the CYP1A1 polymorphisms and the phenotypes of NAT-2 in patients suffering from idiopathic SLE or SSc. CYP1A1 polymorphisms were analyzed in genomic DNA by PCR, whereas NAT-2 phenotypes were measured by the caffeine method.

Background: Bath-PUVA is used to treat a variety of dermatoses. However, the kinetics of 8-methoxypsoralen during treatment are not completely clarified. Objective: The purpose of this study was to investigate the intensity of the phototoxic response and the persistence of phototoxicity after bath-PUVA. Methods: Twelve volunteers were exposed to UVA doses ranging from 0.5 to 40 J/cm 2 from 10 to 240 minutes after bath-PUVA treatment. The resulting phototoxic response of the skin was determined. Results: Irradiation 10 minutes after the psoralen bath led to the lowest assessed minimal phototoxic dose (MPD) of 1.42 J/cm 2 (mean, SD ± 0.29). Thereafter, the MPD increased significantly and sharply every hour. At 4 hours after the psoralen bath, UVA doses up to 40 J/cm 2 failed to induce any phototoxic erythema (MPD). Conclusion: For optimal effects, UVA irradiation has to be administered immediately after the psoralen bath; no restrictive behavior is necessary after bath-PUVA treatment. (J Am Acad Dermatol 1998;39:443-6.)

Recently, it has been shown that the immunosuppressive macrolide lactone, FK506, exerts good therapeutic efficacy in inflammatory skin diseases. The aim of this study was to analyze the influence of topical FK506 on molecular (IL-1alpha, IL-1beta, IL-2, IL-4, IL-12 p35, IL-12 p40, macrophage inflammatory protein-2 (MIP-2), granulocyte-macrophage CSF (GM-CSF), TNF-alpha, and IFN-gamma) and cellular (I-A+/CD80+, I-A+/CD54+, I-A+/CD69+, I-A+/B220+, and CD4+/CD25+) events in epidermal (EC) and local draining lymph node (LNC) cells during primary contact hypersensitivity responses. Cytokine mRNA levels for IL-1alpha, IL-1beta, GM-CSF, TNF-alpha, MIP-2, and IFN-gamma in EC and for IL-2, IL-4, IL-12 p35, IL-12 p40, and IFN-gamma in LNC were increased and resulted in significant LNC proliferation during oxazolone-induced contact hypersensitivity. Topical FK506 treatment dose-dependently suppressed oxazolone-induced LNC proliferation. This effect was correlated with decreased IL-1alpha, IL-1beta, GM-CSF, TNF-alpha, MIP-2, and IFN-gamma mRNA expression within the epidermis and decreased IL-12 p35 and p40 mRNA expression in LNC. Further analysis of the LNC cytokine pattern revealed that the production of both Thl (IFN-gamma and IL-2) and Th2 (IL-4) cytokines was dramatically impaired after topical FK506 treatment. Flow cytometric analysis showed that topical FK506 decreased the population of epidermis-infiltrating CD4+ T cells and suppressed the expression of CD54 and CD80 on I-A+ EC and LNC during hapten-induced contact hypersensitivity. Furthermore, topical FK506 profoundly impaired oxazolone-induced up-regulation of CD25 expression on CD4+ LNC and dramatically decreased hapten-induced expansion of I-A+/B220+ and I-A+/CD69+ LNC subsets. In conclusion, these results give new insights into the mechanisms of action of topical FK506 treatment.

Gianotti-Crosti syndrome (GCS) is a distinct exanthematic, acrolocated eruption of childhood caused by a variety of infectious agents. Historically hepatitis B antigen positive (HBsAG+) papular acrodermatitis of childhood and HBsAg negative (HBsAg-) papulovesicular acrolocated syndrome have been distinguished. Here we characterize the spectrum of associated infectious agents in seven patients with confirmed GCS seen in our departments in the years 1994-1995. Where available, stored frozen serum samples were reanalyzed for antiviral antibodies. The mean age of the two girls and five boys was 22.5 months with a range of 8 to 53 months. None of the patients was HBsAG+. Four patients showed serologic evidence of an acute infection and one patient of a recent Epstein-Barr virus (EBV) infection. In two additional children vaccination preceded the appearance of GCS. In these two patients serologic investigations revealed no evidence of recent infection with most common viruses. Our results underline the role of viral infections other than hepatitis B in the etiology of GCS. EBV infection was the most commonly associated viral disease in our population. We agree with other authors that we should avoid using the terms papular acrodermatitis of childhood and papulovesicular acrolocated syndrome in describing HBsAg+ and HBsAg- forms of GCS.

We report a 62-year-old man with rectal cancer, two keratoacanthomas and multiple sebaceous adenomas, epitheliomas and sebaceous hyperplasia. His brother and father died from colorectal cancer. A subgroup of patients with the Muir-Torre syndrome (MTS) is allelic to the cancer family syndrome. This genetic disorder is caused by an autosomal dominant inherited germline mutation in one of the DNA mismatch repair genes. It is thought that a somatic mutation of the other allele leads to a genomic instability responsible for tumorigenesis. In the patient presented here the instability was detected in two characteristic skin lesions; sebaceous adenoma and epithelioma. The search for a causal germline mutation revealed a frameshift mutation in the mismatch repair gene hMSH2 leading to a truncated protein. A presymptomatic molecular diagnosis can be offered to the children of the patient.

Keine Erkrankung spiegelt den rasanten Fortschritt der Dermatotherapie so wider wie die Psoriasis. In den letzten Jahren wurden erfolgreich neue Phototherapieverfahren, systemische und topische Medikamente fur die Psoriasis entwickelt und eingefuhrt. In der folgenden Ubersichtsarbeit werden die wesentlichen Entwicklungen der UV-Therapie der Psoriasis diskutiert.

Die Entwicklungsgeschichte der Therapie mit Fumarsaurederivaten seit den ersten Selbstversuchen des Chemikers Dr. Walter Schweckendiek im Jahre 1959 [12] bis zur Zulassung durch das Bundesinstitut fur Arzneimittel und Medizinprodukte 1994 gehort sicherlich zu den ungewohnlichsten, die jemals eine Therapieform genommen hat.

Wie kaum ein anderes Gebiet der Dermatologie machte die Therapie der Psoriasis in den letzten Jah ren eine explosionsartige Entwicklung durch. Diese Entwicklung betrifft einerseits die Verbesserung be stehender Therapieverfahren, z.B. die Einfuhrung neuartiger Ultraviolettbestrahlungsmodalitaten und Kombinationstherapien, andererseits die Einfuh rung neuartiger Substanzgruppen fur die innerliche und auserliche Behandlung der Krankheit. Einige wesentliche Entwicklungen werden in der nachfol genden Aufstellung behandelt.

Die Diagnostik der Lichtdermatosen beruht auf Anamnese, klinischem Bild, Histopathologie und Ergebnis der Phototestungen. Laborchemische und immunologische Untersuchungen konnen zur Dia gnostik eines Lupus erythematodes oder einer Porphyrie dienen, sind aber bei den meisten primaren oder sekundaren Lichtdermatosen nicht hilfreich, da entsprechende spezifische Parameter fur diese Erkrankungen fehlen. Zusatzliche Bedeutung erlan gen Phototestungen, wenn die Patienten sich im er scheinungsfreien Intervall vorstellen, wie es bei polymorpher Lichtdermatose und Lichturtikaria die Regel ist.

Introduction In the present study, we analysed in detail nuclear autoantibodies and their associations in systemic sclerosis (SSc) patients included in the German Network for Systemic Scleroderma Registry. Methods Sera of 863 patients were analysed according to a standardised protocol including immunofluorescence, immunoprecipitation, line immunoassay and immunodiffusion. Results Antinuclear antibodies (ANA) were detected in 94.2% of patients. In 81.6%, at least one of the autoantibodies highly associated with SSc or with overlap syndromes with scleroderma features was detected, that is, anti-centromere (35.9%) or anti-topoisomerase I (30.1%), followed in markedly lower frequency by antibodies to PM-Scl (4.9%), U1-ribonucleoprotein (U1-RNP) (4.8%), RNA polymerases (RNAPs) (3.8%), fibrillarin (1.4%), Ku (1.2%), aminoacyl-transfer RNA synthetases (0.5%), To (0.2%) and U11-RNP (0.1%). We found that the simultaneous presence of SSc-associated autoantibodies was rare (1.6%). Furthermore, additional autoantibodies were detected in 55.4% of the patients with SSc, of which anti-Ro/anti-La, anti-mitochondrial and anti-p25/p23 antibodies were most frequent. The coexistence of SSc-associated and other autoantibodies was common (43% of patients). SSc-associated autoantibodies disclosed characteristic associations with clinical features of patients, some of which were previously not acknowledged. Conclusions This study shows that five autoantigens (that is, centromere, topoisomerase I, PM-Scl, U1-RNP and RNAP) detected more than 95% of the known SSc-associated antibody responses in ANA-positive SSc patients and characterise around 79% of all SSc patients in a central European cohort. These data confirm and extend previous data underlining the central role of the determination of ANAs in defining the diagnosis, subset allocation and prognosis of SSc patients. peerReviewed

Topical calcineurin inhibitors are licensed for the treatment of atopic dermatitis; however, the efficacy of tacrolimus in cutaneous lupus erythematosus (CLE) has only been shown in single case reports.In a multicenter, randomized, double-blind, vehicle-controlled trial, we sought to evaluate the efficacy of tacrolimus 0.1% ointment for skin lesions in CLE.Thirty patients (18 female, 12 male) with different subtypes of CLE were included, and two selected skin lesions in each patient were treated either with tacrolimus 0.1% ointment or vehicle twice daily for 12 weeks. The evaluation included scoring of clinical features, such as erythema, hypertrophy/desquamation, edema, and dysesthesia.Significant improvement (P.05) was seen in skin lesions of CLE patients treated with tacrolimus 0.1% ointment after 28 and 56 days, but not after 84 days, compared with skin lesions treated with vehicle. Edema responded most rapidly to tacrolimus 0.1% ointment and the effect was significant (P.001) in comparison to treatment with vehicle after 28 days. Clinical score changes in erythema also showed remarkable improvement (P.05) after 28 days, but not after 56 and 84 days. Moreover, patients with lupus erythematosus tumidus revealed the highest degree of improvement. None of the patients with CLE demonstrated any major side effects.The study was limited by the small sample size.Explorative subgroup analyses revealed that topical application of tacrolimus 0.1% ointment may provide at least temporary benefit, especially in acute, edematous, non-hyperkeratotic lesions of CLE patients, suggesting that calcineurin inhibitors may represent an alternative treatment for the various disease subtypes.

Irradiation with suberythemal doses of either UV-A or UV-B yielded an increase in the amount of stratum corneum lipids extracted from the lumbar skin area of 20 volunteers. These lipids were quantified after separation by high-performance thin-layer chromatography. Ten subfractions in the ceramide region were separated; two of them (fractions 7a and 7b) were only detectable after UV-A or UV-B irradiation. Improvement of barrier function after UV irradiation of human skin with suberythemal doses may be related to an increase in the stratum corneum ceramides.

Photosensitivity is an important characteristic feature of several forms of lupus erythematosus (LE), and induction of skin lesions by UV-A and UV-B irradiation has been proved to be an optimal model for evaluating light sensitivity in patients with this disease. Because lupus erythematosus tumidus (LET) has rarely been documented in the literature and is often difficult to differentiate from other photodermatoses such as polymorphous light eruption, we performed photoprovocation tests in 60 patients with LET according to a standardized protocol. Areas of uninvolved skin on the upper back were irradiated with single doses of UV-A (100 J/cm2) and/or UV-B (1.5 minimal erythema dose) daily for three consecutive days. Interestingly, patients with LET are more photosensitive than those with subacute cutaneous lupus erythematosus, and in our study experimental phototesting revealed characteristic skin lesions in 43 patients (72%). Because of the latency period in developing positive phototest reactions, it might be difficult for these patients to link sun exposure with their skin lesions. Furthermore, our data revealed a positive correlation of antinuclear antibodies and positive provocative phototest reactions in these patients as seen for other forms of LE. In conclusion, the high incidence of positive phototest reactions in correlation with the clinical findings, history of photosensitivity and antinuclear antibodies enable the classification of LET as the most photosensitive type of LE.