A 41-year-old woman presented with chronic diarrhea for 3 years associated with significant weight loss. An ileocolonoscopy showed multiple well-defined rectal ulcers (Figure 1). Biopsies revealed reactive hyperplasia of the superficial and cryptic epithelium with extensive ulceration translated by the presence of exudate, as well as epithelioid granulomas with nucleated giant cells (Figure 2). Histiocytes containing brown pigment in the cytoplasm were observed in the lamina propria. Biopsies from the colon showed mild chronic inflammatory changes with an epithelioid granuloma. Immunohistochemistry for cytomegalovirus, periodic acid-Schiff, and Ziehl-Neelsen stains were negative. Abdominopelvic computed tomography enterography showed only circumferential thickening of the rectum.
After reviewing the patient's medical history, we found that one of her children had died at the age of 9 years with a septic complication due to CGD. A cellular immunity and oxidative burst of granulocytes study showed a shortfall in the production of oxidative metabolites in 35% of granulocytes, therefore establishing the diagnosis of CGD carrier linked to chromosome X.
A repeat colonoscopy was performed due to her high risk for recurrent infections. A rectal ulcer biopsy was positive for Nocardia through polymerase chain reaction (PCR). After excluding cerebral disease, she was started on cotrimoxazole for 3 months, followed by continuous weekly prophylaxis. Forty-two days after colonic biopsies were performed, a positive cultural result for mycobacterium tuberculosis (TB) was depicted. Standard anti-TB therapy was started, consisting of isoniazid, rifampicin, ethambutol, and pyrazinamide; symptoms persisted after 12 months of treatment.
Three months after the end of antibiotics, a new colonoscopy revealed that the ulceration had extended to the proximal colonic segments. Histological evaluation showed similar histological findings to what was described initially, including pigmented histiocytes and epithelioid granulomas (Figure 3). Biopsies for Mycobacteria and Nocardia were negative; however biopsies were now positive for herpes simplex 1 PCR and Aspergillus PCR. There was no evidence of herpes viremia. Blood cultures for fungi were also negative. The patient was treated with valacyclovir and subsequently maintained prophylaxis with itraconazole. After controlling these infections, she continued to complain of diarrhea (>10 bowel movements per day) with further weight loss. The patient was reluctant to start systemic steroids, so a multidisciplinary meeting led to the initiation of infliximab 5 mg/kg with cotrimoxazole and itraconazole prophylaxis.
After 15 months of infliximab 5 mg/kg every 8 weeks, she had decreased her bowel movements to 3 per day and gained 5 kg. Subsequent laboratory tests showed consecutively normal complete blood counts, increased serum albumin, and normal C-reactive protein. During this period, the patient did not have any infectious complications. As such, anti-tumor necrosis factor (anti-TNF) therapy will be maintained indefinitely under close surveillance for the appearance of complications, especially infectious complications.