P3C374: “stop the bullae(ing):” Leukocyte Adhesion Deficiency Type 1 Presenting as Severe Bullous Pyoderma Gangrenosum

Introduction: Leukocyte adhesion deficiency (LAD) is a rare phagocytic disorder characterized by the absence of pus and persistent marked neutrophilic leukocytosis. These patients usually present in infancy with delayed separation of the umbilical cord, omphalitis, and necrotic infections of the skin and mucosal surfaces (5). Pyoderma gangrenosum (PG) is a rare neutrophilic dermatosis that can cause non-healing inflammatory ulcers and is often associated with underlying inflammatory diseases. We report a case of a 2-year-old male who presented with multiple non-healing ulcerative lesions consistent with PG, who was later found to have LAD type 1.

Case Description: A 2-year-old otherwise healthy African American male, presented to his primary care physician with ulcerative lesions on the scalp, neck and buttocks with general malaise, runny nose and nasal congestion. He was initially treated with outpatient oral antibiotics, but with worsening lesions, was referred to the emergency department and then admitted to the general pediatric ward. Despite broad spectrum antibiotic therapy, lesions continued to enlarge and new ulcerating lesions developed throughout the body [figure 1], worst at the site of a recent central line placement [figure 2]. Additionally, white blood count increased as high as 78.85 K/mcL. Immunoglobulin and complement levels were within normal limits. Histopathological results showed exuberant diffuse dermal neutrophilic infiltrate with surrounding edema and granulation. Dermatologic findings were correctly identified as PG. Symptoms began to resolve with a regimen of prednisone, cyclosporine, IVIG, Tacrolimus, and Infliximab. The patient was found to have absent CD11/CD18 expression and a compound heterozygote for two variants in ITGB2 gene on genetic testing, confirming the underlying diagnosis of Leukocyte Adhesion Deficiency (LAD).

Discussion: This case demonstrates a diagnostically challenging presentation of two rare pediatric conditions. LAD is a rare phagocytic disorder characterized by a defect in the trafficking of leukocytes from the blood vessels to the site of tissue injury. Prognosis for LAD depends on the severity of the disease. Mild to moderate phenotypic expression may live up to adulthood with supportive care management and antibiotics. However, for severe phenotype, (hematopoietic cell transplantation) HCT is the only corrective treatment. PG has a distinctive cutaneous ulceration with a purple edge. Half of PG cases are associated with a specific systemic disorder of rheumatologic, immunologic, or hematologic origin. The primary treatment of PG is high dose corticosteroids and careful wound care.

Conclusion: Although LAD is considered in cases of delayed separation of the umbilical stump and severe invasive infections, it should also be considered in the differential diagnosis of abnormal wound healing and recurrent skin ulcers. LAD1 is associated with severe morbidity and early mortality, thus making a timely diagnosis essential. Although rare, providers need to be able to identify PG and consider its comorbidities.