[Disseminated cryptococcosis with extensive cutaneous involvement in AIDS]. / Disseminierte Kryptokokkose mit ausgeprägtem Hautbefall bei AIDS.

BACKGROUND: Diagnosis of an ulceratively decaying indolent papule in the skin of an AIDS patient. CASE REPORT: In a 36-year-old HIV-positive man with a CD4 lymphocyte count of 60/microliters, a diagnosis of disseminated cryptococcosis was established based on a biopsy of an ulceratively decaying indolent papule in the skin of the left side gluteal region. In additional papulopustular skin lesions of neck, upper arm, upper thigh, and rima ani, Cryptococcus neoformans var. neoformans was detected by specific culture. The Cryptococcus neoformans antigen titre in serum was 1:160. The extensive cryptococcal skin involvement was accompanied by symptoms of meningeal cryptococcosis like hearing at an abnormal sound volume, a sensation of high pressure in the head and a change of behaviour, but absence of cephalgia and stiff neck. Attention is drawn to the importance of biopsy for the differential diagnosis of the skin lesions and to the significance of a specific cultural detection of Cryptococcus neoformans in view of the therapy and epidemiology of this mycosis. Under a combination therapy, consisting of amphotericin B, flucytosine and fluconazole, a healing of the skin lesions and disappearance of the neurological symptoms followed by negative cultural and serological tests were seen. Specific comments on the epidemiology of cryptococcosis in AIDS are made. CONCLUSION: In case of doubt, papulopustular skin lesions of HIV-positive patients should be biopsied. Cryptococcosis should also be considered.

Generalised acanthosis nigricans with vitiligo.

We report on a 19-year-old woman with generalised acanthosis nigricans of the inherited type and concomitant vitiligo. Cutaneous velvety thickening of the skin with intensification of skin markings and progressive development of hyperpigmented papillomatous, verrucoid lesions in the body folds started to develop in early childhood. These hyperpigmentations were continuously replaced by a progressive vitiligo, finally leaving most of the acanthosis nigricans lesions completely depigmented. Generalised, pachyderma-like acanthosis nigricans with concomitant vitiligo is an association which to the best of our knowledge has not yet been described.

[Alopecia areata and diffuse hypotrichosis associated with Ullrich-Turner syndrome. Presentation of 4 patients]. / Alopecia areata und diffuse Hypotrichose assoziiert mit Ullrich-Turner-Syndrom. Vorstellung von 4 Patientinnen.

Gonosomal aberrations such as Turner's syndrome are frequently associated with autoimmune diseases or with serological markers for autoimmune diseases. An autoimmune origin has been suggested for alopecia areata. The simultaneous occurrence of alopecia areata and Turner's syndrome has not formerly been reported. We present here four female patients with Turner's syndrome, who also developed typical alopecia areata. In three of these cases alopecia areata first appeared during adolescence, whilst the fourth patient showed an early manifestation at the age of 10. Two of the patients had alopecia areata of the ophiasis type, while the condition was localized in one and diffuse in the fourth. In addition, two of the patients had diffuse hypotrichosis of the scalp and reduced sweat gland activity, with no other signs of ectodermal dysplasia. The third patient had not develop body hair after her childhood, except for some sparse thin hair in the axilla and in the genital area. The coincidence of alopecia areata and Turner's syndrome may indicate some genetic relationship between the two entities.

[Granulocyte colony stimulating factor (G-CSF) in treatment of patients with HIV-associated mucocutaneous Kaposi sarcoma. Successful use in virus and drug-induced leukopenia]. / Granulozyten-Koloniestimulierender Faktor (G-CSF) in der Behandlung von Patienten mit HIV-assoziiertem mukokutanem Kaposi-Sarkom. Erfolgreicher Einsatz bei virus- bzw. medikamenteninduzierter Leukopenie.

Three patients with HIV-associated Kaposi sarcoma were treated with human recombinant granulocyte colony stimulating factor (G-CSF). They had all developed leucopenia during treatment with recombinant interferon-alpha-2a, in two cases combined with vincristine. In all three patients, there was an obvious rapid stimulation after s.c. injection of 300 or 150 micrograms G-CSF per day; the white blood count reached normal values within only a few days and partial transformation to leucocytosis took place. After discontinuation of G-CSF, leucocyte counts regressed rapidly to pretreatment levels. A dose of 150 micrograms of G-CSF twice to three times per week proved to be sufficient to keep the white blood cell count in the normal range allowing the treatment necessary for Kaposi sarcoma. G-CSF therapy had no serious side effects. One of the patients developed a tumour-like infiltration in his left upper jaw, which histologically simulated Burkitt's lymphoma and which regressed spontaneously after discontinuation of the G-CSF therapy. G-CSF plays an important role in the treatment of patients with HIV-associated Kaposi sarcoma and enables combined treatment with zidovudine, interferon, and cytostatic drugs.

Elephantiasis nostras verrucosa: beneficial effect of oral etretinate therapy.

Elephantiasis nostras verrucosa is characterized by chronic secondary, non-filarial lymphoedema due to recurrent lymphangitis, dermal fibrosis, and epidermal changes consisting of hyperkeratotic, verrucous and papillomatous lesions. Histologically, there is pseudoepitheliomatous hyperplasia. Therapeutic efforts should aim to reduce lymph stasis, which will also lead to improvement of the cutaneous changes. In this study, rapid disappearance of the hyperkeratotic and verrucous lesions, remarkable flattening of the papillomatous nodules and improvement of lymphoedema occurred in three obese patients treated with etretinate in an initial dose of 0.6-0.75 mg/kg/day for 4-6 weeks. Monitoring of plasma concentrations of etretinate, acitretin and 13-cis-acitretin by HPLC revealed sufficient short-time absorption (4 h) and bioavailability of the drug (30 days; two out of three patients). Long-term maintenance therapy in one patient produced a remarkable improvement in the lymphoedema; another patient relapsed after discontinuation of the etretinate and responded again after this was reintroduced. In the third patient treatment was withdrawn because of an increase in triglycerides, but improvement persisted 6 months later. The clinical side-effects of oral retinoid therapy were moderate and well tolerated.

Negative staining EM for the detection of Epstein-Barr virus in oral hairy leukoplakia.

The performance of two different EM techniques applied for the detection of Epstein-Barr Virus (EBV) in oral hairy leukoplakia (HL) was assessed, i.e. the conventional two-step method of negative staining (CNS) and negative staining after Airfuge enrichment (ANS). Scrape specimens from the lateral borders of tongue of 66 HIV-positive patients with or without HL, of 3 patients with infectious mononucleosis and of 10 HIV-negative patients were evaluated. While CNS resulted in virus detection only in 25% of clinically diagnosed HL cases, EBV was detected by ANS in 85% of clinically suspected cases of HL. Scrape specimens of individuals negative for HIV were negative in EM while 2 of 3 mononucleosis patients were positive without clinical evidence for HL. Due to this high sensitivity the method of negative staining after Airfuge enrichment appears to be useful in the diagnosis of HL. The finding of EBV in clinically normal oral mucosa in HIV-seropositive individuals is interesting and indicates that EBV expression may precede the clinical appearance of HL.

MHC-antigens: constituents of the envelopes of human and simian immunodeficiency viruses.

Immunoelectron microscopy was applied to study the antigenic make-up of human and simian immunodeficiency viruses (HIV, SIV) grown in cells expressing either MHC class I (Molt-3) or MHC class I and II (H9) antigens. A variety of antibodies directed against the surface glycoprotein gp120 of HIV and against MHC class I and II antigens were employed. Consistent with earlier observations on the loss of HIV envelope components, gp120 was only weakly demonstrable on the mature virion. MHC class I determinants were present regularly in small amounts on HIV and SIV. Class II antigens, e.g. HLA-DR were found in high density on HIV and SIV grown in H9 cells, but were absent, as expected, on virus grown in Molt-3 cells. These cellular surface antigens are constituents of the virion. The presence of MHC class II antigens in virus preparations used for diagnostic purposes might explain some of the false positive results in HIV serology. Possible biological implications of these virus associated cellular antigens for the pathogenicity of HIV are discussed.

Comparative immunoelectron microscopy with monoclonal antibodies on yellow fever virus-infected cells: pre-embedding labelling versus immunocryoultramicrotomy.

To study the intra- and extracellular distribution of yellow fever virus 17D (YFV)-specific antigens, pre-embedding immunoelectron microscopy (IEM) and IEM on ultrathin frozen sections were carried out comparatively using monoclonal antibodies (MAB) and YFV-infected cells. In addition, three electron-dense marker systems (IgG-ferritin and IgG-gold and protein A-gold) were compared for their efficiency in detecting bound MAB. Pre-embedding immuno-labelling was performed in microtest plates followed by in situ embedding and immunocryoultramicrotomy was performed using pellets of sucrose-infused cells. In both procedures, cells were prefixed with different concentrations of glutaraldehyde (GA). In pre-embedding IEM virus-specific antigens could be detected on the envelopes of extracellular virions with YFV-neutralizing MAB. Using immunocryoultramicrotomy, neutralizing MAB bound to intracellular mature virions as well as to viral antigens incorporated into cytoplasmic membranes. A concentration of 1% GA destroyed antigenicity entirely, while with 0.25% and 0.1% GA immunoreactivity was retained for more than 3 mth. Some highly reactive MAB labelled antigen significantly in pre-embedding IEM, when used at concentrations of 1 ng/ml. Immunocryoultramicrotomy was 10-100 times less sensitive. On cryosections colloidal gold was the marker of choice, due to the fact that it showed less nonspecific sticking to intracellular components and that it was easily detectable on highly contrasted cryosections. Owing to their higher sensitivity, IgG-ferritin conjugates were preferred in pre-embedding IEM.