Monogenic interferonopathies: Phenotypic and genotypic findings of CANDLE syndrome and its overlap with C1q deficient SLE.

OBJECTIVE: To report the clinical and genetic features of the first cases of chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature (CANDLE) syndrome in an Arab population and to compare them with patients of C1q deficient systemic lupus erythematosus (SLE). MATERIALS AND METHODS: This is a retrospective case series of patients with CANDLE syndrome and C1q deficient SLE seen at a single tertiary hospital. Medical records were reviewed for demographic data, clinical and laboratory features, histopathology and imaging findings, and response to therapeutic intervention. Descriptive data were summarized. RESULTS: Three patients from unrelated families fulfilled the clinical manifestations of CANDLE syndrome. The disease onset was within the first 4 months of age. Two patients had uncommon features including uveitis, pulmonary involvement, aseptic meningitis and global delay. Skin biopsy showed heterogeneous findings. Genomic DNA screening was homozygous for mutation in PSMB8, (NM_004159.4:c.212C>T, p.T71M) in one patient and inconclusive for the other two patients. The comparison group was three patients with familial C1q deficient SLE from three unrelated families, who were born to consanguineous parents with at least one affected sibling. They presented with extensive mucocutaneous lesions, discoid rash and scarring alopecia. They required frequent admissions due to infections. CONCLUSION: This is the first report of CANDLE syndrome in an Arab population; our patients had heterogeneous phenotypic and genetic features with overlap manifestations with C1q deficient SLE. Both are monogenic interferonopathies. However, C1q deficient SLE had more systemic inflammatory disease.

Lipodystrophia centrifugalis abdominalis infantilis: statistical analysis of 168 cases.

Lipodystrophia centrifugalis abdominalis infantilis is a localized lipodystrophic disease affecting young children. A total of 168 cases were collected from dermatology literature. Where possible, details of the data were also obtained from the authors. Most of the patients were Japanese, Korean, or Chinese in origin. The Caucasian patients were from England, Italy, France, Germany, Spain, and the United States. The male-to-female ratio was 1:1.6. The depressed lesions developed during the first 4 years of life in the groin or axilla, surrounded by a slight erythematous change. Histologically, subcutaneous fatty tissue was lost or markedly decreased in the depressed areas, and marked or moderate mononuclear cell infiltration was observed in the fatty tissue of the surrounding erythematous area. The depressed lesions extended centrifugally to involve the abdominal or chest walls. However, in most cases, such enlargement spontaneously ceased by the age of 13 years. No drugs used were effective in preventing the enlargement of depressed lesions, but more than 60% of patients showed spontaneous improvement after the cessation of enlargement. Lipodystrophia centrifugalis abdominalis infantilis is a clinically and histologically distinct lipodystrophic disease affecting young children, mostly in Asian countries, but a few in Western countries.

Ethnicity and gender differences in lipodystrophy of HIV-positive individuals taking antiretroviral therapy in Ontario, Canada.

PURPOSE: This study assessed ethnicity and gender differences in prevalence, type, and severity of antiretroviral-associated lipodystrophy in HIV-positive individuals in Ontario. METHODS: This was a cross-sectional analysis of the Ontario Cohort Study (OCS), a prospective study of HIV-positive patients in Ontario. Lipodystrophy was defined as at least 1 major or 2 minor self-reported changes of peripheral lipoatrophy and/or central lipohypertrophy. Prevalence, type, and severity were compared by ethnicity (Black, White, or Other) and gender. Univariate and multivariate logistic regression analyses identified predictors of lipodystrophy. RESULTS: Data were available for 778 participants (659 men, 119 women). There were 517 Whites, 121 Blacks, and 140 patients of Other ethnicities. In univariate analyses, Whites reported more peripheral lipoatrophy (P = .004) and abdominal lipohypertrophy (P = .04); these ethnic differences were observed in males (P = .05 and P = .03, respectively) but not females. Males reported more peripheral lipoatrophy (P = .01), whereas females had more central lipohypertrophy (P < .0001) and mixed fat redistribution (P < .0001). Multivariable regression analyses revealed Black women to be most vulnerable to lipodystrophy (P = .02), particularly lipohypertrophy (P < .0001). CONCLUSIONS: Ethnicity and gender are important factors influencing lipodystrophy. Combining lipoatrophy and lipohypertrophy into a single entity is not appropriate. Black women were most vulnerable to lipohypertrophy, which has important implications for antiretroviral therapy roll-out in Africa.

Lipodystrophia centrifugalis abdominalis infantilis in a 4-year-old Caucasian girl: association with partial IgA deficiency and autoantibodies.

We report the third case of lipodystrophia centrifugalis abdominalis outside East Asia. A 4-year-old Caucasian girl developed an area of bluish erythema on the left side of the lower abdomen which spread centrifugally to the umbilical and inguinal areas with depression of the skin resulting from the loss of subcutaneous fat, surrounded by an erythematous border. This unusual skin disease was characterized by clinical and histological examination. Laboratory tests revealed a partial IgA deficiency, antinuclear antibodies and IgG antibodies against gliadin.

Lipodystrophy studies in women.

AIDS: Several studies on women have examined the relationship between body composition and the fat redistribution associated with lipodystrophy. One study found that women with HIV, receiving protease inhibitors (PIs), were more likely to have an elevated waist-to-hip ratios (WHR) than HIV negative women. Another study on body shape showed greater increases in breast and waist sizes in women on PI treatment, but the difference was not significant enough to equate the changes to the protease inhibitor-containing regimen. Further study is needed to determine the relationship between lipodystrophy and HIV in women.^ieng