Chronic granulomatous disease presenting with ecthyma gangrenosum in a neonate
Authors: Brea Prindaville, Amy J Nopper, Hillary Lawrence, Kimberly A Horii
Journal: Journal of the American Academy of Dermatology (2014)

To the Editor: While the primary immunodeficiency chronic granulomatous disease (CGD) frequently presents with cutaneous manifestations, associated ecthyma gangrenosum (EG) has rarely been reported. EG is an ulcerative infection, typically caused by Pseudomonas aeruginosa in immunocompromised patients. We report a 23-day-old male with EG due to Klebsiella oxytoca, who was subsequently diagnosed with CGD. This case emphasizes the importance of initiating broad antibiotic coverage and immunologic work-up in infants with EG. A 23-day-old term male presented to our institution febrile with temperature up to 39.2°C and a 1-week history of erythema of the perineum that progressed to pustules and ulcerations. Family and social histories were noncontributory. Upon admission, vancomycin and acyclovir were initiated by the pediatrics team. Because the ulcerations were not improving, a dermatology consult was initiated. Upon examination, irregularly shaped ulcerations were noted in the perineum and buttocks (Fig 1). Given concern for EG, ceftazidime was added. Wound care included gentamicin ointment and white petrolatum. Work-up was significant for leukocytosis and elevated band count. Blood cultures, herpes simplex virus polymerase chain reaction, and lesional viral cultures were negative. Bacterial wound cultures grew Klebsiella oxytoca and Enterococcus faecium, confirming a diagnosis of EG. Klebsiella oxytoca was thought to be the primary pathogen, but antibiotics also covered Enterococcus faecium. The patient's ulcerations dramatically improved within 1 week of antimicrobial therapy (Fig 2).Fig 2Ecthyma gangrenosum in neonatal chronic granulomatous disease. Dramatic healing of ulcerations following 9 days of antibiotic therapy and wound care.View Large Image Figure ViewerDownload Hi-res image Download (PPT) Diagnosis of EG prompted an immunologic investigation that was remarkable for dihydrorhodamine 123 (DHR); flow cytometric analysis showed no granulocyte oxidase activity. Work-up of the patient's mother showed oxidative abnormalities in 70% of granulocytes, confirming X-linked CGD in our patient. After diagnosis, the patient was started on prophylactic itraconazole, trimethoprim/sulfamethoxazole, and interferon-gamma. CGD is a rare primary immunodeficiency caused by defective formation of the phagocyte respiratory burst. It results in recurrent bacterial and fungal infections, which can lead to granuloma formation.1Brown K.L. Stein A. Morrell D.S. Ecthyma gangrenosum and septic shock syndrome secondary to Chromobacterium violaceum.J Am Acad Dermatol. 2006; 54: 224-228Abstract Full Text Full Text PDF PubMed Scopus (20) Google Scholar, 2Dohil M. Prendiville J.S. Crawford R.I. Speert D.P. Cutaneous manifestations of chronic granulomatous disease. A report of four cases and review of the literature.J Am Acad Dermatol. 1997; 36: 899-907Abstract Full Text PDF PubMed Scopus (51) Google Scholar, 3Song E. Jaishankar G.B. Saleh H. Jithpratuck W. Sahni R. Krishnaswamy G. Chronic granulomatous disease: a review of the infectious and inflammatory complications.Clin Mol Allergy. 2011; 9: 10Crossref PubMed Scopus (138) Google Scholar Cutaneous infections affect 60% to 70% of patients with CGD.2Dohil M. Prendiville J.S. Crawford R.I. Speert D.P. Cutaneous manifestations of chronic granulomatous disease. A report of four cases and review of the literature.J Am Acad Dermatol. 1997; 36: 899-907Abstract Full Text PDF PubMed Scopus (51) Google Scholar Inheritance of CGD is usually X-linked, but can be autosomal recessive. DHR has replaced nitroblue tetrazolium as the confirmatory test given its ability to differentiate subtypes. In our patient, EG was the presenting manifestation of CGD. EG has been reported only once previously with CGD; however, that pathogen was Chromobacterium violaceum.1Brown K.L. Stein A. Morrell D.S. Ecthyma gangrenosum and septic shock syndrome secondary to Chromobacterium violaceum.J Am Acad Dermatol. 2006; 54: 224-228Abstract Full Text Full Text PDF PubMed Scopus (20) Google Scholar EG is a rare infection, characteristically seen in immunocompromised patients. Most cases affect the buttocks and groin. EG typically arises from hematogenous seeding, but can occur with direct bacterial inoculation through skin.4Reich H.L. Williams Fadeyi D. Naik N.S. Honig P.J. Yan A.C. Nonpseudomonal ecthyma gangrenosum.J Am Acad Dermatol. 2004; 50: 114-117Abstract Full Text Full Text PDF PubMed Scopus (121) Google Scholar It begins as painless erythema that rapidly progresses to bullae and pustules. Deep ulcers eventually form with surrounding erythema.5Boisseau A.M. Sarlangue J. Perel Y. Hehunstre J.P. Taïeb A. Maleville J. Perineal ecthyma gangrenosum in infancy and early childhood: septicemic and nonsepticemic forms.J Am Acad Dermatol. 1992; 27: 415-418Abstract Full Text PDF PubMed Scopus (72) Google Scholar Pseudomonas aeruginosa classically causes EG, but other pathogens have been reported. If EG is suspected, bacterial cultures from cutaneous lesions and blood cultures should be obtained. Because significant morbidity is associated with EG, broad spectrum antimicrobial coverage should be initiated until a pathogen is identified. Early diagnosis of CGD is vital to help prevent future complications, in that antimicrobial prophylaxis is usually initiated to prevent recurrent infections. Immunotherapy with interferon-gamma may be beneficial in some cases, while definitive treatment for CGD is stem cell transplantation.3Song E. Jaishankar G.B. Saleh H. Jithpratuck W. Sahni R. Krishnaswamy G. Chronic granulomatous disease: a review of the infectious and inflammatory complications.Clin Mol Allergy. 2011; 9: 10Crossref PubMed Scopus (138) Google Scholar This case underscores the need for comprehensive immunologic evaluation of infants with EG.