Chronic Granulomatous Disease Presenting With Recurrent Skin Infections

A man in his early 20s presented with a 5-year history of nonhealing skin lesions, initially developing as clustered erythematous bullae forming ulcerated and impetiginized serum-crusted lesions, spread diffusely across his body at various stages of healing but sparing the palms, soles, and oral mucosa (Figures 1A and 2A ). Skin biopsy revealed dermal neutrophilic inflammation, and tissue cultures isolated Staphylococcus aureus. Neutrophil function testing revealed a moderate decrease in dihydrorhodamine-positive cells and profoundly decreased mean fluorescence intensity following stimulation with phorbol-12-myristate 13-acetate and N-formyl-methionyl-leucyl-phenylalanine, compatible with chronic granulomatous disease. Genetic testing revealed a homozygous pathogenic variant within the neutrophil cytosolic factor 1 gene encoding p47phox of the nicotinamide adenine dinucleotide phosphate oxidase complex, consistent with autosomal recessive chronic granulomatous disease.Figure 2Left lower extremity lesions on presentation (A) and follow-up (B) after treatment with interferon gamma, pioglitazone, trimethoprim-sulfamethoxazole, itraconazole, and wound care.View Large Image Figure ViewerDownload Hi-res image Download (PPT) Chronic granulomatous disease is a genetically variable condition characterized by severe recurrent infections and dysregulated inflammation due to functional mutations of the nicotinamide adenine dinucleotide phosphate oxidase complex of phagocytes needed to generate reactive oxygen species to eliminate catalase-producing bacterial and fungal organisms.1Anjani G. Vignesh P. Joshi V. et al.Recent advances in chronic granulomatous disease.Genes Dis. 2020; 7: 84-92Crossref PubMed Scopus (38) Google Scholar, 2Arnold D.E. Heimall J.R. A review of chronic granulomatous disease.Adv Ther. 2017; 34: 2543-2557Crossref PubMed Scopus (173) Google Scholar, 3Holland S.M. Chronic granulomatous disease.Hematol Oncol Clin North Am. 2013; 27 (viii): 89-99Abstract Full Text Full Text PDF PubMed Scopus (198) Google Scholar, 4van den Berg J.M. van Koppen E. Ahlin A. et al.Chronic granulomatous disease: the European experience.PLoS One. 2009; 4: e5234Crossref PubMed Scopus (546) Google Scholar While most cases are identified in childhood, adulthood presentations have become increasingly recognized.1Anjani G. Vignesh P. Joshi V. et al.Recent advances in chronic granulomatous disease.Genes Dis. 2020; 7: 84-92Crossref PubMed Scopus (38) Google Scholar, 2Arnold D.E. Heimall J.R. A review of chronic granulomatous disease.Adv Ther. 2017; 34: 2543-2557Crossref PubMed Scopus (173) Google Scholar, 3Holland S.M. Chronic granulomatous disease.Hematol Oncol Clin North Am. 2013; 27 (viii): 89-99Abstract Full Text Full Text PDF PubMed Scopus (198) Google Scholar Clinical manifestations include pulmonary, cutaneous, lymphatic, and hepatic infections. Diagnostic evaluation includes neutrophil function testing followed by confirmatory genetic testing if abnormal.3Holland S.M. Chronic granulomatous disease.Hematol Oncol Clin North Am. 2013; 27 (viii): 89-99Abstract Full Text Full Text PDF PubMed Scopus (198) Google Scholar Management involves lifelong antimicrobial prophylaxis with trimethoprim-sulfamethoxazole and itraconazole, immunomodulatory therapy with interferon gamma, and pioglitazone to restore efferocytosis.1Anjani G. Vignesh P. Joshi V. et al.Recent advances in chronic granulomatous disease.Genes Dis. 2020; 7: 84-92Crossref PubMed Scopus (38) Google Scholar The patient improved clinically with antimicrobial therapy followed by secondary prophylaxis, interferon gamma, pioglitazone, and wound care after 3 months while undergoing evaluation for allogeneic hematopoietic stem cell transplant (Figures 1B and 2B). The authors report no competing interests. The patient included in this study has provided research authorization for the confidential clinical use of information to Mayo Clinic. All authors contributed to the conception, preparation, and review of the submitted manuscript. Author Contributions: Dr Khodadadi—Conceptualization, methodology, writing/original draft preparation, writing/reviewing and editing, visualization; Dr Yetmar—Visualization, writing/reviewing and editing; Dr Montagnon—Visualization, writing/reviewing and editing, supervision.