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.

Leukocyte adhesion deficiency-I caused by a novel mutation in ITGB2 presenting with pyoderma gangrenosum

“…The skin biopsy of patient 1 reported the presence of neutrophils suggesting partial neutrophil recruitment into the tissues. Similar histopathology findings have been described in patients with LAD-I and PG (Hinze et al 2010;Madkaikar et al 2015). This case report highlights the importance of considering LAD-I in patients presenting with PG, even in the absence of significant infections.…”

“…Patients with LAD-I presenting predominately with PG have been reported (Van de Kerkhof and Weemaes 1990;Bedlow et al 1998; Hinze al. 2010;Nord et al 2011;Thakur et al 2013;Madkaikar et al 2015). Similar to patient 1, most of these reported patients did not have significant infections prior to presenting with PG and therefore the diagnosis of LAD-I was often delayed.…”

An overview of the therapeutic potential of regenerative medicine in cutaneous wound healing

“…Impairment of wound healing because of the disruption of the inflammatory or the cellular (proliferative) response as described may occur because of a specific problem with that part of the healing process, such an interleukin deficiency , or can occur as part of a wider systemic illness, such as diabetes mellitus . Additionally, impaired healing might be because of senescence .…”

Type I leucocyte adhesion deficiency in Yemenian family managed with appropriate treatment: A case series

“…Patients with LAD10 phenotype show severe infection and die during infancy, while the others survive until adulthood (Deshpande et al, ). Pyoderma gangrenosum (PG) is an uncommon noninfectious neutrophilic dermatosis, characterized by recurrent, necrotic skin ulcers (Madkaikar et al, ). Its pathogenesis remains unclear though aberrant immune responses have been implicated.…”

“…Pyoderma gangrenosum (PG) is an uncommon noninfectious neutrophilic dermatosis, characterized by recurrent, necrotic skin ulcers (Madkaikar et al, 2015). Its pathogenesis remains unclear though aberrant immune responses have been implicated.…”