Disseminated Coccidioidomycosis Treated with Interferon-γ and Dupilumab.

We describe a case of life-threatening disseminated coccidioidomycosis in a previously healthy child. Like most patients with disseminated coccidioidomycosis, this child had no genomic evidence of any known, rare immune disease. However, comprehensive immunologic testing showed exaggerated production of interleukin-4 and reduced production of interferon-γ. Supplementation of antifungal agents with interferon-γ treatment slowed disease progression, and the addition of interleukin-4 and interleukin-13 blockade with dupilumab resulted in rapid resolution of the patient's clinical symptoms. This report shows that blocking of type 2 immune responses can treat infection. This immunomodulatory approach could be used to enhance immune clearance of refractory fungal, mycobacterial, and viral infections. (Supported by the Jeffrey Modell Foundation and the National Institutes of Health.).

Patient-reported frequency of acral surface inspection during skin examination in white and ethnic minority patients.

BACKGROUND: Acral lentiginous melanomas compose a higher proportion of melanomas and have a higher mortality in ethnic minorities than in whites. Early detection by acral surface inspection during skin examinations may lead to improved acral lentiginous melanoma outcomes. OBJECTIVE: This study compared patient-reported frequencies of acral skin examinations in ethnic and white populations. METHODS: Written surveys were collected from 1040 dermatology clinic patients. RESULTS: More whites reported performing self-skin examinations than ethnic minorities (P < .01), but there was no difference in the rates of hand (P = .7) or foot (P = .87) inspection during self-skin examination between whites and ethnic minorities. More whites (77.5%) than ethnic minorities (38.9%) reported having undergone a full-body skin examination (FBSE) from a health care provider (P < .01). During their most recent FBSE by a health care provider, more whites than ethnic minorities reported having their hands examined (P = .02), but there was no difference in reported hand inspection (P = .06) at any previous FBSE or foot inspection at any (P = .07) or the most recent (P = .59) FBSE between whites and ethnic minorities. LIMITATIONS: Single-center study using a new unvalidated survey is a limitation. CONCLUSION: Whites were found to more frequently report self-skin examination and FBSE than ethnic minorities, but significant differences in reported acral examinations were not detected.

Characterization of Kupffer cells in livers of developing mice.

BACKGROUND: Kupffer cells are well known macrophages of the liver, however, the developmental characteristics of Kupffer cells in mice are not well understood. To clarify this matter, the characteristics of Kupffer macrophages in normal developing mouse liver were studied using light microscopy and immunocytochemistry. METHODS: Sections of liver tissue from early postnatal mice were prepared using immunocytochemical techniques. The Kupffer cells were identified by their immunoreactivity to the F4/80 antibody, whereas endothelial cells were labelled with the CD-34 antibody. In addition, Kupffer cells and endothelial cells were labelled by systemically injected fluorescently labelled latex microspheres. Tissue slices were examined by fluorescence microscopy. RESULTS: Intravenous or intraperitonal injections of microspheres yielded similar patterns of liver cell labelling. The F4/80 positive Kupffer cells were labelled with both large (0.2 µm) and small (0.02 µm) diameter microspheres, while endothelial cells were labelled only with the smaller diameter microspheres. Microsphere labelling of Kupffer cells appeared stable for at least 6 weeks. Cells immunoreactive for F4/80 were identified as early as postnatal day 0, and these cells also displayed uptake of microspheres. Numbers of F4/80 Kupffer cells, relative to numbers of albumin positive hepatocytes, did not show a significant trend over the first 2 postnatal weeks. CONCLUSIONS: Kupffer cells of the developing mouse liver appear quite similar to those of other mammalian species, confirming that the mouse presents a useful animal model for studies of liver macrophage developmental structure and function.

Relapsing polychondritis with meningoencephalitis.

Relapsing polychondritis (RP) is a rare autoimmune disease of the cartilaginous structures of the body with many systemic manifestations including meningoencephalitis (ME). We present a case of a man with RP-associated ME that was responsive to steroid treatment. An updated literature review of 7 cases of RP-associated ME also is provided. Early diagnosis of this condition may be of benefit to this select population of patients, and further research regarding the prognosis, mechanisms, and treatment of RP may be necessary in the future.

Binding patterns of peptide-containing liposomes in liver and spleen of developing mice: comparison with heparan sulfate immunoreactivity.

BACKGROUND: Liposomes incorporating peptide from the Plasmodium circumsporozoite protein (CSP) accumulate rapidly and selectively in adult mouse liver. PURPOSE: The development of the liposome-binding pattern in liver and spleen was studied in relationship to the development of extracellular matrix molecules. METHODS: Liposomes were administered to mice intravascularly or applied to the surface of liver and spleen slices in vitro. Slices were analyzed immunocytochemically. RESULTS: Liposomes were found along sinusoidal borders of liver, including the basolateral border of hepatocytes. The pattern was detected in the youngest animals studied (newborn). Intensity of heparan sulfate immunoreactivity increased until adult levels were reached at 20 days. Immunoreactivity for heparan sulfate proteoglycan, but not other proteoglycans, was detected in the youngest animals, and mimicked the pattern of liposome binding. The pattern of liposome binding in the spleen, concentrated in marginal zones, was similar to the pattern of heparan sulfate immunoreactivity, and also similar to the distribution of macrophage immunoreactivity. CONCLUSION: The postnatal development of liposome binding parallels the development of heparan sulfate immunoreactivity, supporting the suggestion that peptide-containing liposomes target liver by binding to heparan sulfate proteoglycans. Specific delivery of liposomes by targeting heparan sulfate proteoglycans is an effective strategy even at early time periods.