Shower PUVA: a novel variant of photochemotherapy. Distribution of photosensitivity and accumulation of trioxsalen in the skin.

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 degrees 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/cm(2) with steps of 0.125 J/cm(2). 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/cm(2)). 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/cm(2) (median; range: 0.06-0.625 J/cm(2)). 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.

[Sensitization to tea tree oil in Germany and Austria. A multicenter study of the German Contact Dermatitis Group]. / Sensibilisierung auf Teebaumöl in Deutschland und Osterreich--Eine multizentrische Studie der Deutschen Kontaktallergiegruppe.

BACKGROUND AND AIM: Tea tree oil, a distillation product of the Australian tea tree (Melalence alternitolia) is increasingly used as an alternative remedy for various dermatological diseases. Tea tree oil contains several allergenic monoterpenes and sesquiterpenes. In this multicenter study it was evaluated, whether the increasing use of tea tree oil has lead to an increased frequency of sensitization in Germany and Austria which would justify its inclusion into the standard series. PATIENTS AND METHOD: For patch testing a standardized tea tree oil was used, dissolved 5% in diethylphtalate (DEP). Consecutive patients of 11 dermatological departments in Germany and Austria were tested. Readings were taken on day 2 and 3 according to the guidelines of the German Contact Dermatitis Research Group (DKG). RESULTS: 5% tea tree oil was positive in 36/3375 patients (1.1%). Sensitization frequencies showed great regional variations and ranged from 2.3% (Dortmund), 1.7% (Buxtehude), 1.1% (Essen), 0.7% (Graz), to 0% (Berlin, Vienna). 14/36 patients (38.9%) also showed a positive patch test reaction to oil of turpentine. CONCLUSION: Our results show that tea tree oil is an important contact allergen for some centers. It should be tested, if medical history suggests its previous use. Considering the great regional differences in frequencies of sensitization its inclusion into the standard series is not recommended yet.

Relevance of oral supplementation with antioxidants for prevention and treatment of skin disorders.

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.

[Antibiotic susceptibility of Neisseria gonorrhoeae isolates in Berlin]. / Antibiotikaempfindlichkeit von Neisseria-gonorrhoeae-Isolaten in Berlin.

BACKGROUND AND OBJECTIVE: Because of the increasing resistance of Neisseria gonorrhoeae, we studied the actual resistance of isolates in Berlin. PATIENTS/METHODS: 85 Neisseria gonorrhoeae isolates were collected between 1995 and 1997. Susceptibility testing was performed for penicillin G, tetracycline, spectinomycin, ceftriaxone, ciprofloxacin and azithromycin by agar dilution. RESULTS: 18.8% isolates were resistant or intermediately resistant to penicillin G (including 6 PPNG). 12.9% isolates were resistant, 43.5% intermediately resistant to tetracycline. One strain was resistant against ciprofloxacin, 4 isolates showed increased MIC values (0.06-0.5 mg/l), whereas 78 isolates were fully susceptible (< 0.007 mg/l). All isolates were susceptible to spectinomycin, ceftriaxone, and azithromycin. CONCLUSIONS: Penicillin G and tetracycline should be given only in cases of proven sensibility. Resistance against ciprofloxacin may occur, especially in isolates acquired in south-east Asia. Ceftriaxone, spectinomycin and azithromycin were active against all isolates. The actual resistance situation should be monitored.

[Shower PUVA: a new possibility for topical PUVA therapy. Phototoxicity in relation to shower time, water temperature and skin type]. / Dusch-PUVA: Eine neue Möglichkeit für die lokale PUVA-Therapie. Phototoxizität in Abhängigkeit von Duschzeit, Duschtemperatur und Hauttyp.

During the past few years, bath PUVA has become established as an effective treatment for various dermatoses and especially for psoriasis. Using 3,4,5 trimethylpsoralen (TMP) in combination with subsequent UVA irradiation, a shower PUVA has been developed as an alternative in local PUVA therapy. This involves moistening the patient's skin - with the exception of the head and neck area - in a shower using water containing psoralen (TMP concentration 0,27 mg/l). The advantages of shower PUVA method are that time, space and cost savings are possible and that only a slight amount of physical exertion is required by the patient standing in the shower compared to immersing the whole body during bath PUVA therapy. The efficacy and practicability of shower PUVA were evaluated using the minimal phototoxic dose (MPD) for healthy volunteers assessing water temperature (33-38 degrees C), shower time (5-10 min), and UVA dose (0,06-1,0 J/cm(2)). Additionally, the time course of TMP-induced photosensitivity was observed over a period of 4 hours after the shower. Using a TMP concentration of 0,27 mg/l, the MPD for skin type I-II lay between 0,125-0,375 J/cm(2) and for skin type III-IV between 0,375-1,0 J/cm(2). Photosensitivity was induced by shower PUVA within 5-10 minutes shower time and at 33-38 degrees C water temperature. MPD exhibited an inverse correlation to temperature but no differences were apparent for shower times between 5 and 10 minutes. Photosensitivity completely disappeared within 2 hours. Minimal phototoxic doses using TMP in shower PUVA are comparable with classical bath PUVA when taking skin type into account. These results support the therapeutic use of shower PUVA using TMP.

Cutaneous mastocytosis in adults. evaluation of 14 patients with respect to systemic disease manifestations.

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.

[HIV-associated psoriasis. Clinical and histological observations in 36 patients]. / HIV-assoziierte Psoriasis. Klinische und histologische Beobachtungen an 36 Patienten.

Between 1982 and 1995, over 700 HIV-infected patients with different skin diseases were registered at the Department of Dermatology, Benjamin Franklin Medical Center, The Free University of Berlin. Thirty-six of them (approximately 5%) were diagnosed as having psoriasis. This is clearly a higher prevalence of psoriasis than in the general population (1-2%). If psoriasis lesions are not clinically seen before diagnosis of HIV infection, the disease will preferentially (approximately 80% of these cases) appear during the late stages of the infection (CD4/CD8 ratio < 0.4). Six of the 36 patients with HIV-related psoriasis (= 16%) were found to have severe disease, showing an exsudative clinical picture. In this paper we report in detail on two representative cases from this group of patients. Histological examination also revealed exsudative changes in HIV-infected patients with clinically moderate psoriasis. Immunohistochemically, HIV-related psoriasis showed a moderately decreased number of infiltrating T-cells, in contrast to psoriatic skin from non-infected patients. A marked difference was the reduced expression of the lymphocyte antigen OPD-4 in HIV-related psoriasis. Routine antipsoriatic treatment modalities in combination with systemic retinoids and phototherapy (SUP/PUVA) were successful in the treatment of severe exsudative psoriasis in HIV patients, but the course of the disease was prolonged and exacerbation was more frequent. HIV-related psoriasis was found not to influence the underlying HIV infection.

L-ascorbic acid inhibits UVA-induced lipid peroxidation and secretion of IL-1alpha and IL-6 in cultured human keratinocytes in vitro.

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.

[Clinical fluconazole and itraconazole resistance of oro-gastrointestinal candidiasis in a patient with AIDS]. / Klinische Fluconazol- und Itraconazol-Resistenz einer orogastrointestinalen Kandidose bei einem Patienten mit AIDS.

We report on a 32-year-old male patient with advanced acquired immunodeficiency syndrome (AIDS), who had severe candidiasis of the gastrointestinal tract. Treatment with fluconazole, 200 mg/day, was introduced. After oral intake of fluconazole over 5 months itraconazole 200 mg/day was given for 1 month. However, fungal infection still persisted. The antifungal activity of fluconazole, itraconazole and ketoconazole against Candida albicans was evaluated by means of the microdilution test by determining the 90% inhibitory concentration of each drugs. A high minimal inhibitory concentration (MIC) was detected for fluconazole (50 micrograms/ml) revealing fluconazole resistance. The susceptibility to itraconazole was borderline (MIC 0.125 micrograms/ml) and that to ketoconazole was markedly lowered (MIC 0.25 micrograms/ml). Plasma levels of itraconazole were also found to be lowered. In HIV patients the gastrointestinal absorption of azole derivatives is often reduced. Therefore, the clinical resistance of Candida albicans to itraconazole can be explained by reduced susceptibility after azole therapy and also by the decreased absorption of the drug in HIV patients.