Case Presentation: A 4-year-old girl presented for evaluation of right sided jaw swelling and dental pain for 2 months. She had seen several specialists including dentists, oral surgeons, and otolaryngologists and had been treated with antibiotics and steroids for presumed lymphadenitis with temporary improvement. However, she had return of daily pain that worsened during the day and has had night sweats for 1 week. She denied fever, fatigue, rashes, abdominal pain, nausea, vomiting, joint pain and swelling, recent travel, and exposure to tuberculosis. Her review of systems was positive for intermittent, non-bloody diarrhea for two months, complicated by multiple courses of antibiotics. She had a history of eczema but had otherwise been healthy. Physical exam was notable for marked facial asymmetry with tender right mandibular swelling and shotty cervical lymphadenopathy. Initial labs demonstrated normal blood counts and metabolic panel, CRP 11.5 (normal <10), and indeterminate QuantiFERON®-TB test. CT showed lamellar new bone formation around the majority of the right mandible and medial portion of the left mandible, consistent with chronic sclerosing osteomyelitis.
Biopsy of the right mandible demonstrated benign-appearing lamellar bone with osteoblastic rimming, fibrous medullary stroma with foci of neutrophils and plasma cells, without necrotic bone. Aerobic, anaerobic, fungal, and AFB cultures on the sample were negative.
She had two separate respiratory burst tests that were consistent with chronic granulomatous disease.Genetic testing was then sent, and the patient was homozygous for a known pathogenic mutation in NCF1. The patient has been started on prophylactic sulfamethoxazole/trimethoprim and itraconazole, and her diarrhea is currently being evaluated by pediatric gastroenterology.
Discussion: Chronic granulomatous disease (CGD) is a primary immunodeficiency that inhibits the ability of the respiratory burst in neutrophils through defects in one of any five subunits of the NADPH oxidase complex. CGD is inherited through CYBB on the X chromosome in approximately two thirds of cases, autosomal recessive mutations in NCF1 in ~20% of cases, and mutations in CYBA and NCF2, each representing 5% of cases. [1] The incidence of CGD in the United States and Europe is 1 in 200,000 to 1 in 250,000 live births. The autosomal recessive inheritance pattern is associated with less severe disease and older age of presentation [2], which is consistent with this patient’s disease course. Infections of the lung, skin, lymph nodes, and liver are the most common first manifestations of CGD.[3] Although impaired primary immunity is the most commonly identified phenotype of CGD, it is also associated with a hyperinflammatory state in the gastrointestinal and genitourinary tracts. [4,5] A recent case report described chronic recurrent multifocal osteomyelitis (CRMO) as a presenting illness for CGD that involved the long bones and was responsive to thalidomide in an 11 year old male. [6] However, no cases of CGD have been described with CRMO of the mandible as the initial presentation.
Conclusions: CRMO is a notoriously difficult diagnosis, requiring a confluence of tissue and diagnostic markers with clinical symptoms. As our laboratory initially attributed the patient’s partial oxidative burst to collection error, these patients may benefit from further genetic exploration of CGD as an underlying cause of CRMO.