In situ immunophenotype of the inflammatory infiltrate in eosinophilic fasciitis

OBJECTIVE: Eosinophilic fasciitis (EF) is histologically characterized by a fibrous and inflammatory thickening of subcutaneous septal-fascial-perimysial collagenous scaffold. This study aims to define the immunophenotype of inflammatory cells of fascia and muscle underlying the in situ immune response in EF. METHODS: In 11 cases of EF, we determined the phenotype of inflammatory cells, expression of MHC class I and class II antigens, and C5b9 membranolytic attack complex (MAC) deposits by immunohistochemistry analysis of fascia tissue. Muscle biopsies from 9 patients with active dermatomyositis and 5 with active polymyositis were used as controls. Results. In all patients but one, the inflammatory infiltrate was mainly composed of macrophages associated with CD8+ T lymphocytes (CD4/CD8 ratio < 1) and few eosinophils. Cytotoxic properties were found in 14% of CD8+ T lymphocytes, as shown by granzyme B expression. MHC Class I antigens were overexpressed (5/7) by muscle fibers, with a paratrabecular reinforcement in 4 cases. MHC class II antigens were not expressed by muscle fibers except in one case. C5b9 MAC deposits were not detected. CONCLUSION: Our in situ characterization of inflammatory infiltrate demonstrates the predominancy of macrophages and CD8+ T lymphocytes. Some of these CD8+ lymphocytes contain granzyme B, thus suggesting a cytotoxic cellular immune response in EF, which could be triggered by infectious or environmental agents.     

Lactose malabsorption and recurrent abdominal pain in Italian children

The role of lactose malabsorption (LM) was investigated in 32 children (mean age 8.13 +/- 2.46 years) with recurrent abdominal pain (RAP). LM was detected in 75% of them by a lactose breath hydrogen test (LBHT) after a 2-g/kg (max 50-g) load. Of the 18 malabsorbers who participated in a 3-month lactose-free diet (LFD), 14 were judged "improved" and reported lower pain frequency (p less than 0.001). The malabsorbers who improved versus the not improved had comparable past lactose ingestion but were distinguishable on the basis of their lactose absorption capacity (0.36 vs. 0.81 g/kg; p less than 0.01), as subsequently determined by multiple LBHTs with 25-, 12.5-, and 6-g loads. The ratio between past lactose ingestion and lactose absorption was 1.89 in the improved and 0.55 in the not improved groups (p less than 0.01), retrospectively indicating lactose as a possible cause of the symptoms in the improved group. The reintroduction of lactose in amounts not exceeding the absorption capacity into the diet of each malabsorber who had improved with LFD caused relapse in none of the 14 subjects monitored for 2-6 months. In conclusion, LM seems an important cause of symptoms in Italian children with RAP. Assessment of the lactose absorption threshold of each subject of LBHTs provides a basis for reintroduction of "calibrated" amounts of lactose-containing foods (e.g., milk) into the diet.     

Chester-Erdheim disease: a neoplastic disorder.

Chester-Erdheim disease is a rare non-langerhans cell histiocytosis characterized by a xanthomatous infiltration of foamy macrophages. The cause and pathogenesis remain unclear. The aim of the present study was to determine whether Chester-Erdheim disease is a polyclonal reactive disease or a clonal neoplastic disorder. The clonal status of samples obtained from five patients with Chester-Erdheim disease was studied. DNA was extracted from fixed and paraffin-embedded sections after microdissection and clonal status was studied using the Xchromosome inactivation pattern of the human androgen receptor gene (HUMARA assay). One patient was homozygous for the HUMARA gene and noninformative. Three other cases were monoclonal. One was polyclonal, and this case showed a dense reactive infiltrate in association with spumous macrophages. This study suggests strongly that Chester-Erdheim disease is a monoclonal lesion consistent with neoplastic disorder. Thus, Chester-Erdheim disease may be considered as the "macrophage" counterpart of Langerhan's cell histiocytosis in the histiocytosis spectrum. Further studies are needed to establish the origin of this clonal proliferation.     

Relevance of clinical and laboratory findings in the diagnosis of cytomegalovirus encephalitis in patients with AIDS

A retrospective evaluation was conducted in patients with AIDS and an autopsy diagnosis of cytomegalovirus (CMV) encephalitis to determine the relevance of clinical and laboratory findings in establishing a diagnosis. On autopsy of 100 patients, CMV encephalitis was diagnosed in 13 patients; eight had periventricular CMV encephalitis, four micronodular CMV encephalitis, and one both conditions. Seven patients had had a CMV infection previously (6 cases of retinitis, 1 case of colitis), and at the onset of encephalitis all of them were receiving a maintenance dose of ganciclovir. Examination of the CSF showed specific changes in patients with periventricular encephalitis. CT revealed no characteristic findings, while MRI showed an increased signal intensity on T2 weighted images. CMV DMA amplification by nested PCR was performed in nine patients with CMV encephalitis; PCR was positive in eight patients whose CSF was collected during CMV encephalitis, and negative in one patient whose CSF was collected six months before death. In conclusion, some clinical findings suggest a presumptive diagnosis, especially of periventricular encephalitis, and nested PCR appears to be a reliable and rapid technique for making an antemortem diagnosis.     

Natural killer cells and lymphocyte subsets in active MS and acute inflammation of the CNS

Cerebrospinal fluid (CSF) and peripheral blood (PB) lymphocyte subsets were determined by flow cytometry (FCM) in 15 patients with active multiple sclerosis (MS) and 15 patients with acute inflammatory diseases (ID) of the central nervous system (CNS) in order to establish correlations between the two groups of diseases, as well as between the CSF and PB subsets distribution. A panel of monoclonal antibodies was applied to all the samples: Leu3 (CD4), Leu4 (CD3), Leu2 (CD8), Anti-HLA-DR, Leu11 (CD16). Statistical analysis did not show differences in CD3+ nor in CD3+ DR+ T-cells both in the CSF and PB in the two groups of patients. CD4+ cells were significantly higher in the CSF than in the PB, while CD8+, DR+ CD3- and CD16+ cells were constantly lower in the CSF without differences between the two groups of diseases.     

An evaluation of ventricular function in coronary artery disease patients using the isometric (handgrip) test (author's transl)]

Left ventricular contractile function was evaluated in twenty patients with coronary artery disease before and during handgrip by use of Vpm, VCEIO and Vmax (obtained with a simplified calculation) from high-fidelity pressure measurements. In eight patients the response to handgrip was characterized by an increase of the contractile indices accompanied by small changes of left ventricular end-diastolic pressure (not exceeding + 4 mm Hg) and was considered normal. Twelve patients who showed abnormal or pathologic reaction to isometric exercise repeated handgrip after administration of 0.4 mg of spray nitroglycerin. Thus eight patients normalized their response to exercise, while in four we observed again a pathologic reaction to handgrip. It is concluded that is a useful and simple manoeuvre for a better evaluation of left centricular function in patients with coronary artery disease; the repetition of the test after administration of nitroglycerin can be useful in identifying those patients with greatest contractile reserve.