Non-syndromic autosomal recessive congenital ichthyosis in the Israeli population.

BACKGROUND: Autosomal recessive congenital ichthyosis (ARCI) is the term given to a complex and heterogeneous group of cornification disorders associated with mutations in at least eight distinct genes. Mutation distribution and prevalence rates are instrumental for the design of diagnostic strategies in ARCI but have not yet been systematically explored in the Israeli population. Previous data suggest that the demographic features specific to Middle Eastern populations, such as a high frequency of consanguineous marriages, may have an effect on the molecular epidemiology of genodermatoses. METHODS: We systematically assessed all families with ARCI presenting at our clinics over a period of 9 years, using a combination of homozygosity mapping, direct sequencing and PCR-restriction fragment length polymorphism assays. RESULTS: In total, 20 families with ARCI were assessed, and causative mutations were identified in 7 genes: TGM1 (30% of patients), ALOX12B (20%), ABCA12 (5%), CYP4F22 (10%), ALOXE3 (10%), LIPN (5%) and NIPAL4 (5%) Two families (10%) had mutations mapped to an ARCI-associated locus on 12p11.2-q13, while no mutation was found for one additional kindred. In the subgroup of families of Arab Muslim origin, mutations were identified most frequently in ALOX12B and TGM1 (31%), whereas the other subgroups displayed a subtype distribution very similar to that previously reported in western populations. CONCLUSIONS: The present data point to the need for population-tailored mutation screening strategies in genetically heterogeneous genodermatoses, based on the relative prevalence of the disease subsets.

Classic and iatrogenic Kaposi's sarcoma. Histopathological patterns as related to clinical course.

The histological findings in the first diagnostic biopsy of 50 patients with Kaposi's sarcoma (KS) were classified and were related to the clinical course. Forty-one patients had the "classic KS," of whom 31 had a benign course and 10 an aggressive disease. Nine patients had iatrogenically induced KS. Histologically the following subtypes were found: mixed type in 18 patients, spindle type in 16, early type in 14, and hemangiomatous and lymphangiomatous types in one each. We did not find any statistical relationship between the histological subtypes, degree of nuclear atypia, number of mitoses, and density of the inflammatory cell infiltrates in the KS lesions, and the clinical types and course of the disease. The results of this study do not support the possibility of a prognostic importance regarding the histological features of the early lesions in patients with classic or iatrogenic Kaposi's sarcoma.

Mal de Meleda keratoderma with pseudoainhum.

Pseudoainhum is an infrequent complication in the autosomal-recessive keratodermas. We describe two related families in which the diagnosis of mal de Meleda keratoderma has been confirmed by mode of inheritance and ultrastructural findings. One family member, a 9-year-old girl, developed pseudoainhum which threatened the viability of her little fingers. This responded to treatment with etretinate. The treatment dilemma posed by keratoderma-induced pseudoainhum in children, i.e. the concern over the possible skeletal toxic effects of long-term etretinate treatment vs. the risks and outcome of surgery, is discussed.

Neutral lipid storage disease with ichthyosis: serum apolipoprotein levels and cholesterol metabolism in monocyte-derived macrophages.

Neutral lipid storage disease with ichthyosis (NLSDI) is an inherited metabolic disorder characterized by accumulation of neutral lipids, in a wide variety of cells, by a still unknown mechanism. Previous studies have shown normal cholesterol content in NLSDI granulocytes, fibroblasts and skin cells. Monocyte-derived macrophages possess an additional pathway of cholesterol uptake, which is not shared by these cells and which is not regulated by intracellular cholesterol levels. This pathway is thought to play a rôle in the process of atherosclerosis. Three NLSDI patients were studied. The serum levels of triglycerides, cholesterol, high-density lipoprotein cholesterol, and apolipoproteins A-I and B were within normal limits in all three patients. The intracellular levels of free and esterified cholesterol were measured in the monocyte-derived macrophages of one patient and found to be normal, while the triglyceride concentrations were twice as high as normal. The cholesterol esterification rates, which serve as a sensitive indicator of intracellular changes in cholesteryl ester levels, were normal in the monocyte-derived macrophages of all three patients. These findings provide further evidence that cholesterol metabolism is not disturbed in NLSDI, and it may be inferred that in this respect these patients are not at increased risk for atherosclerosis.

[Brown spider bite].

The diagnosis of bite by the brown recluse spider, Loxosceles reclusus, is rarely based on absolute identification of the insect because the victims are usually bitten while sleeping or dressing. More often, the history, clinical findings and course of the bite lead to the diagnosis. For early confirmation up to 24 hours after the bite, the passive hemagglutination test can be used. For older lesions, the in-vitro lymphocyte transformation test is useful, but is available in only a few medical centers. Treatment of the bite of the brown recluse spider varies from conservative to more active approaches. Resting, local cooling, systemic antibiotics to prevent infection and mild anti-inflammatory drugs may be given. In the more active approach oral corticosteroids are added in the first 72 hours to the antibiotics, especially in massive bites with necrotic centers greater than 2 cm in diameter, or when there is systemic loxoscelism. Recently, good results have been reported with Avlosulfon (dapsone), which is claimed to cure necrotic cutaneous ulcerations, presumably by reducing the activity of polymorphonuclear leukocytes. Other treatments include specific antivenin, (of limited use because it must be administered shortly after the bite), and surgery to prevent spreading of the venom. We describe 3 cases of brown spider bite with typical clinical presentations in adults aged 20-40 years. 2 were treated with corticosteroids and antibiotics and 1 with Avlosulfon and prednisone, all within 72 hours of the bite. 2 recovered completely within a few days, but the third treated with prednisone and antibiotics, developed an ulcer which healed only after several months of treatment.(ABSTRACT TRUNCATED AT 250 WORDS)