[HIV infection]. / HIV-Infektion.

The skin can be an indicator of decreased immunocompetence. Dermatological markers include new and extensive seborrheic eczema, psoriasis without a family history, widespread herpes zoster in young adults, oral hairy leucoplakia and mollusca in adults. In these cases an HIV test should be offered. During the last 15 years the clinical picture of HIV has changed dramatically. Almost every year new drugs with better efficacy, lower pill burden and less side effects have been approved. Life expectancy is close to normal in western countries. In spite of better treatment options, prevention is the key to stop the worldwide epidemic. Awareness campaigns have to account for the synergies between HIV and other sexually transmitted diseases. This poses a great challenge for dermatovenereology.

Treatment of condylomata acuminata with pegylated interferon alfa-2b in HIV-infected patients.

BACKGROUND: Interferon in a variety of topical, interlesional, and parenteral preparations has been used for condylomata acuminata (CA) in HIV negative patients. - STUDY GOALS: This open trial was initiated to determine the safety and efficacy of a new formulation of interferon, pegylated interferon-alpha2b (PEG-IFN, PegIntron in the treatment of recalcitrant CA in patients with HIV infection. - STUDY DESIGN: 22 HIV-1 infected patients in virologic steady state with clinically demonstrable anogenital CA were enrolled in this study (treatment group, n=12; control group, n=10). Patients in the treatment group received 80 microg PEG-IFN s.c. once a week for 24 weeks. Follow-up period was 6 month. The effects were assessed by a clinical scoring system (complete response; major response; minor response; stable disease; progression of disease). - RESULTS: 2 patients did not finish the study because of side effects. PEG-IFN was well accepted and completed by ten patients. Four patients revealed complete response, four patients had major response and two had minor response after PEG-IFN. In the control group, all patients showed progression of CA during the 24 weeks of this study (p < 0.001). 7/10 patients of the treatment group and 8/10 patients of the control received HAART. - While the differences of CD4 cell counts between treatment group and control group were not significant (increase of the mean CD4 cell count in the treatment group was 31.5 (75.33 without patient 1 with leucopenia under ribavirine), in the control group 69.75 CD4 cells), the HIV RNA decline in the PEG-IFN group was impressive (0.74 log subset10). Biological side effects of PEG-IFN treatment included flu-like symptoms, fatigue, local reaction, leucopenia, and increase of AST. This result makes an educated guess that PEG-IFN enhances the benefit of HAART. - CONCLUSION: PEG-IFN is an effective and safe therapy option in HIV infected individuals with CA with concomitant positive effects on the suppression of HIV-1 replication and CD4 cell count. It might be considered as an alternative in patients that have failed to standard therapies of CA and - at the same time -could improve the benefit of HAART to a great extent. This last hypothesis needs further research.

[Screening and therapy of anal intraepithelial neoplasia (AIN) and anal carcinoma in patients with HIV-infection]. / Screening und Therapie der analen intraepithelialen Neoplasie (AIN) und des Analkarzinoms bei HIV-Infektion.

Anal intraepithelial neoplasia (AIN) is a potential precursor of invasive anal carcinoma. Introduction of highly active antiretroviral therapy (HAART) in the treatment of HIV infection substantially reduced the incidence of some diseases associated with opportunistic viral infections. However, the incidence of AIN is reported to increase and HAART seems to have only little impact on the regression or progression of AIN. Paradoxically, improvement of survival in the HAART era results in an increased risk of anal cancer. The incidence of anal carcinoma amongst homosexual men is substantially higher compared to the normal population (35/100.000). This incidence is similar to the incidence of cervical cancer before screening for CIN with cervical cytology. Recent data suggest that the incidence of AIN and anal cancer is even higher among HIV-infected individuals. Both cancer entities share biologic similarities, including the association with human papillomavirus infection (HPV). Screening for CIN with cervical cytology and early treatment has resulted in a significant decline in the incidence of cervical carcinoma. Like cervical cancer, anal carcinoma may be preventable through identification and treatment of its precursors. Future efforts should focus on a screening protocol, training of clinicians in the diagnosis and treatment of AIN and anal carcinoma, and novel approaches to treatment of these lesions. This screening protocol could help to reduce anal cancer in HIV-infection as well as save limited resources in health care system.

Dermatological diseases and signs of HIV infection.

Therapy of HIV infection has undergone significant changes since the introduction of highly-active antiretroviral therapy (HAART). Mortality and the appearance of opportunistic infections have significantly been reduced. Diseases of the skin and adjacent mucous membranes often provide the first signs for HIV infection. The spectrum of dermatologic findings related to HIV includes a variety of cutaneous and mucocutaneous disorders. The most frequent diagnoses are oral candidiasis, mollusca contagiosa, oral hairy leuokoplakia, herpes zoster and herpes simplex, seborrheic dermatitis, and Kaposi's sarcoma. Incompatibility reactions to drugs are observed on a strikingly frequent basis in HIV infection. Such severe incompatibility reactions are much more frequent in HIV patients than in the normal population. Inducers often include sulfonamides, cotrimoxazole, tuberculostatics as well as nucleoside-type reverse transcriptase inhibitors.

Bacillary angiomatosis in HIV-infected patients--an epidemiological and clinical study.

BACKGROUND: No data were available on the epidemiological and clinical characteristics of bacillary angiomatosis (BA) in Germany. OBJECTIVE: To determine epidemiological and clinical data on HIV-associated BA. METHODS: A chart review of all BA cases between 1990 and 1998 was performed in 23 German AIDS treatment units. RESULTS: A total of 21 cases of BA was diagnosed. During this period, the participating HIV centers treated about 17,000 HIV-infected patients. As a result, a BA prevalence of 1.2 cases/1,000 patients can be assumed. 19 BA were localized in the skin; in 5 cases bones and in 4 cases the liver were involved. Out of 20 patients who received antibiotic therapy, 13 had complete remission. The median time of duration up to complete remission was 32 days (9-82). During the follow-up of the 20 patients, 7 relapses were observed. CONCLUSION: BA is a rare HIV-associated disease with a prevalence of 1,2 cases/1,000 patients in the presented study.

Active syphilis in HIV infection: a multicentre retrospective survey. The German AIDS Study Group (GASG).

OBJECTIVE: To study syphilis in HIV infection focusing on immunocompromised patients with an atypical or aggressive clinical course of syphilis, inappropriate serological reactions or an unreliable response to therapy. STUDY DESIGN: A multicentre retrospective chart review using a standardised questionnaire for all patients with active syphilis. SETTINGS: Thirteen dermatological and medical centres throughout Germany, all members of the German AIDS Study Group (GASG). PATIENTS: Clinical data of 11,368 HIV infected patients have been analysed for cases of active syphilis requiring treatment. Asymptotic patients with reactive serological parameters indicating latent syphilis without a need for treatment were excluded. RESULTS: Active syphilis was reported in 151 of 11,368 HIV infected patients (1.33%, range per centre 0.3%-5.1%). Most of the 151 syphilis patients were male (93%) and belonged to the homosexual or bisexual exposure category for HIV infection (79%); another 6% were iv drug users. Among the 151 syphilis patients primary syphilis was diagnosed in 17.2%, maculopapular secondary syphilis in 29.1%, ulcerating secondary syphilis in 7.3%, neurosyphilis in 16.6% and latent seropositive syphilis without clinical symptoms but serological abnormalities indicating active syphilis in 25.2%. A history of prior treatments for syphilis was reported in 50%. At the time of syphilis diagnosis 26.5% of the patients were in CDC stage II, 33.8% in stage III and 24.5% in stage IV of HIV disease (CDC classification 1987). CD4 cell count was lowest in those with ulcerating secondary syphilis (mean 307, SD 140/microliters) and neurosyphilis (351, SD 235/ microliters). The highest CD4 count was found in patients with early primary and early secondary syphilis (444, SD 163/microliters and 470, SD 355/microliters). Inappropriate serological response to syphilis infection was found in 81 of 151 patients (54%). Remarkable findings were false negative VDRL titres (11 patients with non primary syphilis), false negative TPHA (1) or 19S-IgM-FTA-ABS-tests (16), and strongly reactive VDRL (> or = 512, 8) or TPHA titres (> or = 10 240, 47). Treatment failures were reported in at least 6 of 151 cases (4%). CONCLUSIONS: Atypical clinical and serological courses of syphilis were observed in HIV infected patients. Ulcerating secondary syphilis with general symptoms ("malignant syphilis") was 60 times more frequent than in historic syphilis series. Neurosyphilis was found in one sixth of those with active syphilis. Therefore lumbar puncture should be considered a routine in coinfections with HIV and syphilis. Treatment efficacy should be monitored carefully.

CMV-antigenemia in peripheral blood for the diagnosis of CMV disease in HIV-infected patients.

In a prospective study of HIV patients with suspected cytomegalovirus (CMV) disease (n = 144; 140 men, four women; aged 23-69 years, median 38 years; CD4 cells 0-400, median 20/microliters), 242 blood samples were examined for the presence of CMV-pp65 antigen in peripheral blood polymorphonuclear leucocytes by use of monoclonal antibodies and alkaline phosphatase-anti-alkaline phosphatase staining. All patients were thoroughly examined for existing CMV disease at first visit and during follow-up (at least 2 months or until death: 0-24 months, median 14 months). In 43/486 samples of patients with CMV disease, the antigen-test was positive and in 179/194 samples of patients without CMV disease the test was negative, resulting in a sensitivity of 90% and a specificity of 93% for the presence of CMV disease in HIV-infected patients.

Side effects of AZT prophylaxis after occupational exposure to HIV-infected blood.

UNLABELLED: It was the objective of this study to document and evaluate AZT-induced short-term toxicity in healthy individuals. The study was designed as a longitudinal monocentric side-effect monitoring study with prospective data collection. It was carried out at the Cologne University Hospital. The study population comprised health care workers who were taking AZT prophylaxis after accidental exposure to HIV-infected blood. Fourteen individuals were included into the study; seven of them discontinued treatment prematurely, five due to severe subjective symptoms. In case of one worker AZT had to be stopped due to severe neutropenia (800 cells/microliters) with signs of upper respiratory tract infection. Four of 11 individuals taking AZT for at least 4 weeks developed neutropenia (2 WHO I, 1 WHO II, 1 WHO III). All other laboratory parameters stayed within normal range. In particular, no anemia was observed. IN CONCLUSION: Compared with other studies more neutropenias are observed. Due to side effects 50% of the workers discontinued AZT administration prematurely. The data presented herein show that AZT causes considerable side effects which must be weighed against the potential protective antiviral effect.

Antiproliferative potential of zidovudine in human keratinocyte cultures.

Because the beneficial effects of zidovudine in human immunodeficiency virus infection-associated psoriasis have recently been observed, this study focused on the drug's action on the rapidly proliferating human HaCaT keratinocyte line as an in vitro model for epidermal hyperproliferation. Cultures in log growth phase were exposed to zidovudine for 2 days. Zidovudine slowed proliferation in a dose-dependent fashion as evidenced by 50% inhibition concentrations of 33 mumol/L (cell number), 30 mumol/L (protein content), 0.9 mumol/L (protein synthesis), and 0.7 mumol/L (DNA synthesis). Significant (p less than 0.01) reduction of cell viability to 94.6% and 87.2%, as well as morphologic manifestations of cytotoxicity, were first evident after 2 days' exposure to maximal drug concentrations of 10 and 100 mumol/L, respectively. Control viability, assayed by trypan blue exclusion, was 98.0%. Direct cytotoxic plasma membrane injury could be ruled out by the absence of any increase in cytoplasmic lactate dehydrogenase release into supernatants at least during the 1 day of maximal dosage exposure. The drug-induced inhibition of proliferation was reversible within 7 days after a 2-day exposure to 100 mumol/L zidovudine. Two days of treatment with a 10 mumol/L dose did not alter the pattern and synthesis of keratins in vitro. Thus the known antipsoriatic efficacy of zidovudine might be explained, at least partly, by the drug's cytostatic potency.

[The radiotherapy of epidemic Kaposi's sarcomas in AIDS patients]. / Strahlentherapie epidemischer Kaposi-Sarkome bei AIDS-Patienten.

From August 1986 to May 1989, 15 patients suffering from Kaposi's sarcoma and serologically proven HIV infections were treated in the Department of Radiotherapy, University of Cologne, Medical Hospital. All patients were male and homosexual. Therapeutic objectives were palliation of pain and functional impairment as well as elimination of the cosmetically disturbing Kaposi's sarcoma. 68 localizations (facial skin, torso, extremities, sole of the foot, penis, oral mucosa and oropharynx) were irradiated. Depending on the individual therapy regimen, photons or high-energy electrons up to a total dose of 26 to 40 Gy, with single doses of 1.8 to 2.5 Gy were applied four to five times a week. In 66% of the cases, complete remission was achieved within the area of irradiation at the dermal or mucosal level, with at most a discrete residual pigmentation of the cluster remaining. Partial remission with at least 50% regression or a distinctive residual pigmentation was achieved in 31%. In 3% of the cases, a less than 50% regression of the Kaposi's lesions were achieved after radiotherapy. There were five local recurrences. Treatment with radiation is an effective local therapy in epidemic Kaposi's sarcoma and yields good functional and cosmetic results and also provides relief from pain.

[Preventive pentamidine inhalation of Pneumocystis carinii pneumonia in patients with immune deficiency. Preliminary evaluation of a multicenter study]. / Pentamidin-Inhalationsprophylaxe der Pneumocystis-carinii-Pneumonie bei Patienten mit Immunschwäche. Zwischenauswertung einer multizentrischen Studie.

In the first evaluation of an uncontrolled multicenter study on inhalative pentamidine prophylaxis (300 mg pentamidine-isethionate monthly) of pneumocystis carinii pneumonia in immunocompromised patients, 48 patients (all 48 patients HIV1-infected, 36 without preceding pneumocystis carinii pneumonia (primary prophylaxis), twelve after pneumocystis carinii pneumonia (secondary prophylaxis); age 20 to 68 years (median 38); 45 male, two female, one unknown; 22 patients AIDS) were observed for 0 to 8.5 months (mean 4 +/- 2 months, intended observation time twelve months). No proven pneumocystis carinii pneumonia was found in the observed patients. One patient was treated with cotrimoxazole because of a suggested pneumocystis carinii pneumonia-relapse, which could not be proven. Out of seven (14.6%) patients, whose therapy was discontinued, three patients died, three refused further therapy, one patient had a relapse of a cerebral toxoplasmosis. Six patients (12.5%) reported adverse reactions (cough, metallic or bitter taste, slight nausea). New opportunistic infections appeared in four patients (8.3%).

[Skin changes in drug-dependent patients]. / Hautveränderungen bei Drogenabhängigen.

In parenteral drug abuse, cutaneous manifestations are very common. A variety of skin lesions are indicators of a possible drug addiction: obliteration of peripheral veins and hyperpigmentation of the overlying skin, punched-out scars due to subcutaneous injection, persistent edema following thrombophlebitis, and excoriations due to heroin pruritus. Infectious and non-infectious complications may be accompanied by typical skin alterations, such as ecthyma in sepsis caused by Pseudomonas aeruginosa, multiple ulcers due to embolic infarct, or hypersensitivity reactions mediated by an immunological process. A variety of serious complications may develop at the injection sites: abscesses, gangrene, necrosis, or necrotizing fasciitis. These examples show that the dermatologist is in many ways involved in the care for addicted patients. In addition, these patients frequently suffer from sexually transmitted diseases or blood-borne infections; HIV-infection is rapidly spreading in this group. We now face new problems of differential diagnosis, especially since constitutional symptoms of HIV-infection may mimic symptoms of drug abuse and vice versa. Moreover, immunological alterations similar to those in HIV patients may even occur in drug addicts who are not infected with the virus.

Major histocompatibility complex class I to III allotypes in patients with AIDS-related complex/Walter-Reed 5, disseminated Kaposi's sarcoma and in normal controls. The ARC-IVIG Study Group.

In HIV-infected patients major histocompatibility complex (MHC) class I and II (= HLA-A, B, C, DR) association has been controversial. Of the MHC class III coded complement components C2, BF, C4A/C4B especially C4 allotypes appear of major immunogenetic relevance for their potential differences in virus neutralizing potency and immune complex formation. In the present study 29 patients with AIDS-related complex and Walter-Reed 5 ARC/WR5), 35 patients with disseminated Kaposi's sarcoma (KS), and 160 HIV-negative control individuals were compared for MHC class I to III allotypes. Diagnosis of ARC and KS (WR criteria) was done by clinical and laboratory parameters, MHC testing, by standard procedures. An increase in frequency (p less than or equal to 0.05) was observed between ARC/WR5 patients and controls for HLA-B35/CW4, DRW14, a decrease for B16, CW6/DR7. However, values were not significant if corrected for the number of tested antigens. No significant differences were seen between KS and ARC patients or controls for class III allotypes, nor for previously reported associations, e.g. for B8, DR2, DR3, and especially DR5, including the DR5 splits DRW11, 12. The results indicate the lack of a strong MHC association with the investigated antigens in West German Caucasoids, and support the hypothesis of ethnic dependence of HIV-related diseases. The HLA-B35/CW4 increase, also associated with the duplicated C4 A*3 A*2 and the silent C4B*Q0, was more pronounced in ARC patients with progression to AIDS-OI. The increased frequency of C4B*Q0 alleles in these patients was thought to be secondary to a hypothetical increase in 'converted' and dysregulated C4 genes not seen to be associated in this study.

Cellular immunologic parameters in HIV-positive patients with AIDS-related complex and intravenous immunoglobulin therapy.

In a randomized double-blind longitudinal study with 30 HIV-1-positive patients with AIDS-related complex or stage Walter-Reed 5 disease, the effectiveness of intravenous immunoglobulin (IVIG) was tested for correcting eventual immune dysregulation. Although the IVIG-treated patients showed an improvement of their clinical score, no significant changes were observed in lymphocyte phenotypes, activation markers, immunoglobulins and subclasses, lymphocyte turnover or in indicators of acute inflammation. Since severe bacterial infections or autoimmune processes usually leading to IVIG therapy were not prevalent in the patients of the study, such therapy should probably be reserved for later stages of the disease. HIV-1 antigen expression in blood lymphocytes remained uninfluenced by IVIG treatment.