Longest form of CCTG microsatellite repeat in the promoter of the CD2BP1/PSTPIP1 gene is associated with aseptic abscesses and with Crohn disease in French patients.

PURPOSE: Aseptic abscesses syndrome (AA) is an inflammatory disease in which non-infectious deep abscesses develop; these respond quickly to corticosteroids. AA is associated with Crohn disease (CD) in 57% of cases and with neutrophilic dermatosis (ND) in 20%. Pyoderma gangrenosum is usually a sporadic ND. A hereditary autosomal dominant syndromic kind of pyoderma gangrenosum, the PAPA syndrome, is linked to mutations in the CD2BP1/PSTPIP1 gene. We systematically screened this gene in French AA patients. RESULTS: One microsatellite (CCTG)n with 3 alleles was identified in the promoter. The longest form (CCTG)7 was significantly more frequent in AA patients than in French controls (P = 0.0154). We also found an association of the (CCTG)7 allele with CD in French patients (P = 0.0351). This association was not found in a sample of Indian patients. CONCLUSIONS: The CCTG repeat in the PSTPIP1 promoter may play a role in the pathogenesis of AA and of CD. Further investigations are required to demonstrate the possible modulation of gene expression by the (CCTG)n motif.

Aseptic abscesses: a study of 30 patients with or without inflammatory bowel disease and review of the literature.

Aseptic abscesses (AA) are characterized by deep, sterile, round lesions consisting of neutrophil that do not respond to antibiotics but improve dramatically with corticosteroids. We report the clinical, laboratory, and radiologic characteristics and the associated conditions of 29 patients from the French Register on AA plus 1 patient from the Netherlands.The mean age of patients at AA diagnosis was 29 years (SD = 14). The main clinical manifestations of AA were fever (90%), abdominal pain (67%), and weight loss (50%). Duration of symptoms was 4.7 months on average until abscesses were discovered. The abscesses involved the spleen in 27/29 patients (93%; the thirtieth patient had a personal history of splenectomy after a trauma). In 7 they were unifocal and in the others they were multifocal, involving in addition the abdominal lymph nodes in 14 (48%), liver in 12 (40%), lung in 5 (17%), pancreas in 2 (7%), and brain in 2 (7%). They were not splenic in 3, including 2 with abdominal lymph nodes and 1 with superficial lymph nodes and testicle and lung involvement. Twenty-two patients (70%) had elevated white blood cell and neutrophil count; antineutrophil cytoplasmic autoantibodies with a perinuclear, cytoplasmic or atypical pattern (negative for antiproteinase 3 and negative for antimyeloperoxidase except for 1) were positive in 21% of the 24 patients tested. Twenty-one patients had inflammatory bowel disease (IBD), which preceded the occurrence of abscesses in 7, was concomitant in 7, and appeared secondarily in 7. Six patients had neutrophilic dermatosis (20%), 3 had relapsing polychondritis as an associated condition, and 3 others had monoclonal gammopathy of undetermined significance. Three patients had no associated condition. Splenectomy was performed in 15 (52%) patients. All patients received steroid therapy. Thirteen (43%) were given additional immunosuppressive therapy, 1 immediately and the others after a relapse, of whom 3 were also treated by anti-tumor necrosis factor-alpha agents. Mean follow-up was 7 years. Eighteen (60%) patients experienced 1 or several relapses, but there was no death related to AA. Relapses occurred on immunosuppressive therapy in 2 patients and off immunosuppressive therapy in the others while corticosteroids were being tapered. We surveyed the literature and analyzed 19 additional cases. AA is an emergent and probably underrecognized entity. It represents an apparently noninfectious inflammatory disorder involving neutrophils that responds to corticosteroid therapy. AA mainly affects patients with IBD but also affects those with other conditions, or with no other apparent disease.