title: Leukocyte adhesion deficiency-I with a novel intronic mutation presenting with pyoderma gangrenosum- like lesions.
abstract: Pyoderma gangrenosum (PG) is an uncommon noninfectious neutrophilic dermatosis characterized by recurrent, sterile, necrotic skin ulcers. It is commonly associated with underlying systemic disease like inflammatory bowel disease, rheumatoid arthritis and hematological malignancies. Pathogenesis of PG remains unclear though aberrant immune responses have been implicated. The diagnosis of PG is of exclusion and management is empirical with local or systemic immunosuppressive therapy. LAD-I is a rare form of autosomal recessive disorders caused by mutations of the gene ITGB2, clinically characterized by recurrent severe bacterial infection, impaired pus formation, poor wound healing and persistent neutrophilia. Though skin ulcerations are common, predominant clinical presentation as PG is unusual in LAD-I. Here we present four Indian patients with LAD-I from three unrelated families initially diagnosed as PG due to chronic recurrent skin ulcerations requiring steroids and antibiotics for healing, associated with atrophic scar formation. All these four patients had persistent neutrophilia without history of delayed cord separation and showed moderate expression of CD18 (19 to 68%) on neutrophils. Sequencing of the entire coding region and intronic splice sites of the ITGB2 gene from the genomic DNA of these patients revealed a novel common mutation IVS10+4A>G. LAD-I should be kept in mind while evaluating patients with PG especially those with persistent neutrophila in the absence of other rheumatological disorders. Diagnosis of LAD-I in these cases is extremely important for management as treating these patients without adequate antibiotic cover may prove fatal and these patients often require hematopoietic stem cell transplantation for permanent cure.
authors: Department of paediatric Immunology and Leukocyte biology, National Institute of Immunohaematology, 13 th floor, NMS Bldg, KEM Hospital, Parel, Mumbai, 400012, India, madkaikarmanisha@yahoo.co.in.
authors: Manisha
authors: M
authors: Madkaikar
authors: Khushnooma
authors: K
authors: Italia
authors: Maya
authors: M
authors: Gupta
authors: Mukesh
authors: M
authors: Desai
authors: Amita
authors: A
authors: Aggarwal
authors: Surjit
authors: S
authors: Singh
authors: Deepti
authors: D
authors: Suri
authors: Anju
authors: A
authors: Mishra
authors: Sushant
authors: S
authors: Chavan
authors: Kanjaksha
authors: K
authors: Ghosh
authors: Rishu
authors: R
authors: Sarangal
authors: Sunil
authors: S
authors: Dogra
mesh_terms: D000293:Adolescent; D018821:CD18 Antigens / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D003241:Consanguinity; D004252:DNA Mutational Analysis; D003937:Diagnosis, Differential; D005260:Female; D006801:Humans; D016130:Immunophenotyping; D007438:Introns; D007958:Leukocyte Count; D018370:Leukocyte-Adhesion Deficiency Syndrome / Q000175:diagnosis* / Q000235:genetics*; D008297:Male; D009154:Mutation; D009504:Neutrophils / Q000378:metabolism; D010641:Phenotype; D017511:Pyoderma Gangrenosum / Q000175:diagnosis*; D012883:Skin Ulcer / Q000473:pathology
chemical_list: D018821:CD18 Antigens