[Papules on the dorsal interphalangeal joints and an unspecific immunostimulating agent]. / Papeln über den dorsalen Interphalangealgelenken und ein unspezifisches Immunstimulans.

We report the case of an 8-year-old girl with skin eruptions on both hands that were thought to be of viral origin and, therefore, had been treated with an unspecific immunostimulating agent, containing large amounts of inosine. Under this therapy, which is - despite contrasting knowledge - still thought to be harmless and without serious side effects in the opinion of many physicians and especially medical laymen, the girl's condition worsened rapidly. Diagnosis of juvenile dermatomyositis was made. Because inosine is able to enhance T-cell proliferation and reverse immunosuppression in vitro, both mechanisms may have aggravated the disease course in our patient, once the autoimmune process of dermatomyositis has been initiated.

Delayed motor learning and psychomotor slowing in HIV-infected children.

OBJECTIVE: To find out whether HIV-associated subclinical psychomotor slowing is present in HIV-infected children despite effective highly active antiretroviral therapy (HAART). PATIENTS AND METHODS: An electrophysiological motor test battery shown to sensitively describe HIV-associated CNS disease in adults (tremor peak frequency []TPF], most rapid alternating movements [MRAM], reaction time [RT] and contraction time [CT]) was performed in 17 HIV seropositive (+) right-handed children. Results were compared to 16 HIV seronegative (-) children. RESULTS: HIV (-) children showed slower frequencies (TPF, MRAM) and longer RT and CT than (-) adults. They showed a significant correlation (p = 0.0263) between RT (right = dominant hand) and age. HIV (+) children showed significant prolongations of RT (right hand) and CT (both hands) compared to HIV (-) children. RT right hand did not accelerate with age in HIV (+) children. CT were significantly prolonged in 10 children with detectable HIV plasma viral burden and normal in 7 children with no detectable HIV plasma viral load. There was no correlation between CT and CD 4 cell counts. CONCLUSIONS: Despite effective HAART, electrophysiological motor testing in HIV (+) children reveals significant subclinical CNS dysfunction, especially in children with insufficient viral load suppression.

Apoptosis in T-lymphocyte subsets in human immunodeficiency virus-infected children measured immediately ex vivo and following in vitro activation.

Phosphatidylserine molecules are translocated to the outer plasma membrane of lymphocytes undergoing apoptosis and can be detected by the binding of fluorochrome-conjugated annexin V. Using the annexin V assay, we examined CD4 and CD8 T cells from human immunodeficiency virus (HIV)-infected children for apoptosis upon isolation or following in vitro culture. Immediate ex vivo analysis or overnight culture showed significantly higher levels of apoptosis in CD8 cells than in CD4 cells. Following culture with the activating stimulus phytohemagglutinin or anti-CD3 monoclonal antibody, we observed an increase in the percentage of apoptotic CD4 cells, whereas there was no change in the rate of CD8 cell death. These results demonstrate that in HIV-infected children, CD8 apoptosis may occur at a greater rate than CD4 apoptosis in vivo; greater CD4 depletion may be observed due to more efficient mechanisms for peripheral lymphocyte replacement in the CD8 compartment. Furthermore, our data suggest that CD8 lymphocytes may be maximally activated in vivo, a condition which may lead to the exhaustion of CD8-mediated immunity. These findings clarify the differences between the CD4 and CD8 apoptotic responses to HIV.

CD28 expression in pediatric human immunodeficiency virus infection.

Increased apoptosis of lymphocytes represents a key event of immune destruction in HIV infection. In this study it was investigated at which stage of the disease and in which T lymphocyte subpopulation (CD4+ or CD8+) protection against apoptosis may be lost as measured by decreased CD28 expression. In 26 HIV-infected and 20 healthy children, as well as 10 infants exposed to HIV, expression of CD28 and the apoptosis-related marker CD95 was studied by fluorescence-activated cell sorting analysis. According to established Centers for Disease Control and Prevention definitions, children were divided into three immunologic categories. In the CD8 population, patients in category 1 already showed a markedly decreased mean CD28 (36.2%+/-16.1 SD) and increased CD95 expression (48.8+/-24.1%), compared with the age-matched control group (67.7+/-14.4%, 15.8+/-8.9%). In the CD4 population, mean CD28 and CD95 expression was not altered in category 1 patients. Of the exposed children, the child with the lowest CD28 expression on CD8 cells was determined later to be infected with HIV. Significant immunophenotypical alterations are observed in early stage pediatric HIV infection, which may indicate an early loss of protection against apoptosis in the CD8+ T cell population.