A Patient With a Novel Leukocyte Adhesion Deficiency and Pyoderma Gangrenosum-Like Disease

What can inherited immunodeficiencies reveal about pyoderma gangrenosum?

“…Laboratory analyses typically show neutrophilia due to the inability of neutrophils to properly adhere to the vasculature 2 . We found 20 patients with LAD and associated PG and PG‐like lesions 8,10–22 . Five patients were diagnosed with PG‐like presentations due to positive bacterial cultures or absence of classic PG histopathologic findings; however, bacterial superinfections are not uncommon in PG ulcers and most patients with PG do not present with classic histologic findings 23,24 .…”

“…A challenge in understanding the pathogenesis of PG in the setting of LAD stems from the paradoxical notion that an accumulation of neutrophils can develop in the setting of defective neutrophil adhesion and function. The absence of neutrophils in PG skin biopsies in some patients with LAD suggests that PG pathogenesis may not entirely depend on neutrophils 10,16 . However, classic neutrophilic infiltrates are primarily found in the acute stages of the disease and may be absent in chronic PG ulcers, which may partially explain the biopsy results 23 …”

“…The absence of neutrophils in PG skin biopsies in some patients with LAD suggests that PG pathogenesis may not entirely depend on neutrophils. 10,16 However, classic neutrophilic infiltrates are primarily found in the acute stages of the disease and may be absent in chronic PG ulcers, which may partially explain the biopsy results. 23 Alternatively, some patients with LAD may have milder phenotypes or specific genetic variations that may preserve enough neutrophil function for the development of PG ulcers.…”

“…23 Alternatively, some patients with LAD may have milder phenotypes or specific genetic variations that may preserve enough neutrophil function for the development of PG ulcers. 10,16 For example, we found a 20-year-old male with a history of recurrent PG due to a novel variation of the ITGB2 gene, involving a c.10 + 4A > G mutation in the intron 10 splice site region that allowed partial expression of CD18. 17 The patient had two compound heterozygous ITGB2 variations, which are a known cause of LAD-1.…”