HHV-8 DNA in blood and the development of HIV-associated Kaposi's sarcoma in the era of HAART--a prospective evaluation.

OBJECTIVE: To explore the significance of HHV-8 viremia in HIV-positive individuals for the risk of developing Kaposi's sarcoma (KS) in the era of highly active antiretroviral therapy. METHODS: 237 HIV-positive patients were included in this prospective evaluation and followed over an average duration of 34 months. HHV-8 DNA in peripheral blood mononuclear cells (PBMCs) and CD4-lymphocytes were determined. In addition AIDS-defining conditions and antiretroviral therapy were documented of all participating subjects. RESULTS: HHV-8 DNA was detectable in PBMCs of 12.6% out of all individuals. 53.3% of these patients initially complained about KS, although 9.2% of patients without HHV-8 DNA in PBMCs were found on KS as well. Furthermore, four patients in total were observed with newly developed KS during follow up visits. None of these patients were noted with detectable HHV-8 DNA at their initial evaluation. CONCLUSIONS: Prevalence of HHV-8 DNA in PBMCs of subjects in this investigation was quite similar to former investigations. However, new diagnosed KS occurred less frequently than demonstrated in previous studies. All of those observed patients with new KS manifestations were negative for HHV-8 DNA in PBMCs at study entry. This observation differs from earlier studies which have postulated the detection of HHV-8 DNA in PBMCs as a predictive value for development of KS. Due to results as presented, a single HHV-8 DNA test in blood has no predictive value in support of predictability of KS development. With respect toto costs and to a less complicated performance antibody assays should be preferred.

Remission of a cutaneous Mycosis fungoides after topical 5-ALA sensitisation and photodynamic therapy in a patient with advanced HIV-infection.

BACKGROUND: Treatment of Mycosis fungoides (MF) in HIV-infected patients is controversially discoursed. Photodynamic therapy (PDT) after topical sensitization with 5-aminolevulinic acid (5-ALA) is a new and effective modality for treatment of skin malignancies. OBJECTIVE: In this report we describe, what is, to our knowledge, the first case of a patient with MF through advanced HIV-infection, successfully experiencing topical 5-ALA sensitization and PDT. METHODS: 5-ALA ointment was applied to plaques and held in occlusion for 4 hours. PDT was applied using the PDT 1200 irradiation source (Waldmann Medizintechnik System) with 180 J/cm superset 2. RESULTS: Complete remission of MF was achieved, after two completed cycles of photodynamic therapy. CONCLUSION: MF lesions in the presended case showed a high response to 5-ALA sensitization and PDT. This modality appeared to be very effective in treatment of MF in a HIV-infected patient and could be a valuable treatment option for cutaneous T-cell lymphoma in HIV-infected patients.

Umbilical endometriosis.

Cutaneous endometriosis is a well known but rare phenomenon. We present a case of spontaneous umbilical endometriosis. The patient revealed a polypoid, brown-blue nodule within the umbilical depression with the typical history of monthly bleeding from the umbilicus. The differential diagnoses are summarized.

How safe is oral isotretinoin?

Since oral isotretinoin (Roaccutane/Accutane) is the only therapy to address all major acne causes, it remains the most effective antiacne therapy available. Due to this unique efficacy and its potential side effects that are predictable and can be managed easily and effectively, it is widely used also in acne patients suffering from serious systemic diseases. As the primary mechanism of action of oral isotretinoin is suppression of sebaceous gland activity, mucocutaneous side effects such as dry lips, nasal passages and eyes are predictable. Pretreatment counseling and concomitant use of moisturizing agents usually manage these side effects effectively; in unusual cases of particularly poor tolerability, dose adjustments suffice. Severe side effects are rare, the most common being aches and pains requiring no therapy, aspirin or paracetamol. As with other retinoids, reliable contraception is mandatory for women of childbearing potential. Acne patients with serious concomitant systemic disease, such as insulin-dependent diabetes, epilepsy or spina bifida, transplant patients, patients with renal failure, multiple sclerosis motor neuron disease and other can also safe be treated with a standard cumulative dose of 120 mg/kg per treatment course.

Efficiency of acitretin in combination with UV-B in the treatment of severe psoriasis.

Compared with the antipsoriatic retinoid etretinate, the new aromatic retinoid acitretin represents an important advance due to its rapid elimination kinetics. Since in psoriasis vulgaris retinoids are used predominantly in combination regimens, we investigated the therapeutic efficacy of acitretin and UV-B compared with placebo and UV-B in a double-blind, randomized multicenter trial in 82 patients with severe psoriasis. They were treated with 35 mg of the study medication during the first 4 weeks of therapy and 25 mg thereafter, concomitantly with UV-B irradiation in increasing energy doses. Forty patients who underwent therapy with acitretin and UV-B and 38 patients who underwent therapy with placebo and UV-B were evaluated for efficacy. The target variables--psoriasis severity index and total UV-B dose--were reported at intervals of 2 weeks over a maximum period of 8 weeks. At the end of treatment, the psoriasis severity index decrease was 79% in the acitretin and UV-B group and 35% in the placebo and UV-B group. The response rate, defined as greater than or equal to a 75% decrease of the psoriasis severity index, was 60% for the combination treatment and only 24% for the control treatment. This treatment response was achieved with markedly lower cumulative UV-B energy. The median cumulative UV-B energy applied to reach 75% clinical improvement was 11.8 J/cm2 vs 6.9 J/cm2. Side effects showed a similar pattern in both groups. Our data show that the acitretin dramatically improves the results of UV-B treatment in patients with severe psoriasis. In addition, it markedly decreases the effective cumulative UV-B dose, thereby reducing the potential long-term hazards of UV irradiation. We conclude that the acitretin plus UV-B combination treatment represents a highly effective therapeutic regimen in severe psoriasis.

[Dermatologic aspects of HIV infection]. / Dermatologische Aspekte der HIV-Infektion.

We report on the clinical course, the staging, and the theories regarding the etiopathogenesis and possible prognostic factors of Kaposi's sarcoma. In addition, we refer to the significance of viral, mycotic, and bacterial infections in HIV infection.

[The parapsoriasis-group]. / Parapsoriasis-Gruppe.

This review deals with the clinical and histological criteria of the parasporiasis-group. The advantage of a simplified classification based on clinical differences is demonstrated. Furthermore the proportion of cases is shown in which malignant transformation (non-Hodgin-Lymphomas) has been reported. Finally it is referred to careful monitoring of patients with distinct parapsoriasis-diseases.

[Experiences with high-dose cisplatin therapy in metastasized malignant melanoma]. / Erfahrungen mit der hochdosierten Cis-Platin-Therapie beim metastasierten malignen Melanom.

14 patients with advanced malignant melanoma were treated in 36 therapy cycles with cisplatin. 8 patients had been pretreated with dacarbazine and 6 had received additional BCG immunotherapy. 4 patients had been irradiated after surgical removal of lymph node metastases. All patients showed significant tumor progression. 4 patients were treated showing ultimately disseminated melanoma with widespread visceral involvement. 5 patients with lymph node metastases had been operated radically and were treated postoperatively. Cisplatin was administered as a 24-h high-dose therapy (200 mg or 120-200 mg/m2) under forced mannitol diuresis, treatment cycles were repeated monthly. Of all the patients, 1 showed complete remission of supraclavicular metastases lasting for 6 months until now. 1 patient showed an initial minor response with subsequent stabilization without appearance of additional metastases for 1 year. 2 patients who had received cisplatin postoperatively showed no reappearance of tumor growth for 8 months up until now. 11 patients showed no change or progression of disease, 6 of them had received only one therapy cycle. Under clinical conditions, side effects of cisplatin treatment can be managed satisfactorily, no irreversible kidney damage could be observed under forced diuresis. As far as the above-mentioned results are concerned, antineoplastic activity of cisplatin as to advanced malignant melanoma must be considered to be of limited benefit using cisplatin as a single-agent treatment. Improvement of results might be obtained using cisplatin in a combination therapy together with other antineoplastic agents, which at the present time are being investigated in several prospective trials.

[Ehlers-Danlos-Syndrome. Heterogeneity and molecular causes of the disease picture]. / Das Ehlers-Danlos-Syndrom. Heterogenität und molekulare Ursachen des Krankheitsbildes.

Progress in the experimental field and a deepened understanding of biological functional entities gave considerable impetus to connective tissue research. This was particularly true for the heritable connective tissue disorders, of which the Ehlers-Danlos-Syndrome is the best example. Its clinical and biochemical heterogeneity have allowed a classification of the disease into sub-groups, and the conditions for differential diagnosis and therapeutic trials were thus improved.

Nature of collagen in dermatofibrosarcoma protuberans.

The nature of collagen from 2 cases of dermatofibrosarcoma protuberans was studied. For this purpose, the tumor tissue was carefully separated from adjacent normal dermis. The collagen types comprised in the tumor were identified by CM-cellulose chromatographic and SDS-gel electrophoretic analysis of the component alpha-chains. Semiquantitative evaluation of the relative type III content was established by separation of the cyanogen bromide peptides on gels of 12% polyacrylamide in SDS. These studies showed that dermatofibrosarcoma protuberans contains alpha 1(I)-, alpha 2-, and alpha 1(III)-chains as well, and corresponding type I- and type III-related CNBr peptides. Comparing the collagen from dermatofibrosarcoma protuberans to that of normal skin, the relatively increased type III content in the case of dermatofibrosarcoma protuberans becomes apparent.

Collagen in the cellular and fibrotic stages of scleroderma.

The collagen in localized and systemic scleroderma skin was studied by light microscopy with silver impregnation (50 patients), electron microscopy (14 patients), and immunofluorescence microscopy using specific antibodies against Type I and Type III collagens (12 patients). In the cellular stage, the dermis and adipose tissue revealed perivascular or diffuse cellular infiltrates (mostly lymphocytes, plasma cells, and macrophages), accompanied by deposition of Type III collagen. The lower dermis also showed an increase in Type III collagen. In the fibrotic stage, the papillary layer showed a reduction and/or clumping of Type III collagen as compared to normal skin. The lower dermis and the adipose tissue revealed compact collagen consisting exclusively of Type I collagen or a mixture of Type I and Type III collagen. The pattern of Type III collagen distribution was similar to that of reticulin, thus suggesting that at least some reticulin fibrils may represent Type III collagen.

Collagen polymorphism in pathologic human scars.

The collagen type composition of normal and pathologic scars was examined in comparison with normal skin from the same individual. Particular care was taken to separate scar tissue from adjacent normal dermis. After urea extraction, the tissue specimens were cleaved with cyanogen bromide. The presence of the dermal collagen types I and III was deduced from the electrophoretic distribution patterns of the CNBr peptides in 12% SDS-polyacrylamide gels. The intensity of the type III specific peptide bands correlates with the type III content of the samples. Using this method, the presence of both type I and III collagen can be proved in normal as well as pathologic scars. The type III content in older normal scars is slightly increased, whereas the type III content of pathologic scars is significantly increased in comparison with the type III content of normal skin. The electrophoretic CNBr peptide distribution pattern of pathologic scar tissue is almost the same as that of fetal skin. Both are clearly different from the peptide pattern of normal adult skin.

Dermal architecture and collagen type distribution.

The human dermis consists of two morphologically different layers. A loose meshwork of thin collagenous fibres is characteristic for the adventitial dermis with includes the papillary and the periadnexal dermis. Thick, coarse collagen bundles are the main feature of the reticular dermis. Two different collagens, type I and type III occur in the dermis as shown previously by biochemical analyses. Antibodies specific for type I collagen or type III collagen and their corresponding precursors were used in indirect immunofluorescence tests to localize the various collagens in frozen sections of normal adult skin. Whereas type I collagen is found in all dermal layers, the main part of type III collagen can be found within the adventitial dermis. Antibodies against the precursor of type I collagen stain only a bandlike region immediately beneath the epidermis. Antibodies against the precursor of type III collagen stain the same regions as antibodies against the helical part of type III collagen.

SDS-polyacrylamide gel electrophoretic determination of type I and type III collagen in small skin samples.

A sodium dodecylsulfate-polyacrylamide electrophoretic method, which in contrast to other biochemical procedures, e.g. differential salt precipitation or ion exchange chromatography and molecular sieve chromatography, is applicable to smallest amounts of protein, is shown to be suitable for the determination of the collagen types from small skin samples, such as routine skin biopsies. After urea extraction, the tissue samples are cleaved with cyanogen bromide. The resulting CNBr peptides derived from the different alpha-chains are resolved in 12% SDS-polyacrylamide gels. Densitometric profiles of the gel electrophoretic patterns correspond to the collagen type content of the tissue specimens. Comparing fetal to adult skin, the higher content of type III collagen in the case of fetal skin can be demonstrated.