Phagocyte disorders — formative SAQs

SAQ 1 (10 marks)

A three-year-old boy is admitted with a two-week history of fever, right-upper-quadrant pain, and weight loss. Ultrasound shows a 4 cm liver abscess, drained at laparotomy, from which Staphylococcus aureus grows. Over the preceding year he has had a necrotising pneumonia caused by Serratia marcescens and a persistent, granulomatous, swollen gingivitis. His full blood count is normal with a neutrophil count of 6.8 × 10⁹/L. His maternal uncle died in childhood from "constant infections." ^[4]

Question: (a) What is the most likely diagnosis and what is the single most informative clinical clue? (b) Outline the confirmatory investigation and its expected result. (c) Describe the immediate and long-term medical management. (d) Discuss the curative option and the factors that determine its timing. (10 marks) ^[5]

Model answer

(a) Diagnosis and the clinical clue (2 marks). The diagnosis is chronic granulomatous disease (CGD). The single most informative clue is not the abscess itself but the organism list — Staphylococcus aureus and Serratia marcescens are members of the CGD cluster of catalase-positive organisms, which thrive when the phagocyte respiratory burst fails. The granulomatous gingivitis and the family history of an affected maternal uncle (consistent with X-linked inheritance) reinforce the diagnosis. The normal neutrophil count is expected, because in CGD the cells are made and they arrive at the infection in normal numbers — they simply cannot kill. ^[4]

(b) Confirmatory investigation (2 marks). The decisive test is the dihydrorhodamine (DHR) 123 flow cytometry assay, which quantifies the oxidative burst after stimulation with phorbol myristate acetate. In X-linked CGD (CYBB / gp91phox) the fluorescence is virtually absent — a flat histogram. In the autosomal recessive p47phox (NCF1) form it is reduced but present, a mosaic pattern reflecting residual oxidase activity. Genetic testing with a targeted panel covering CYBB, NCF1, NCF2, CYBA, and NCF4 then confirms the molecular diagnosis and, for an affected boy with a maternal family history, identifies the CYBB mutation and triggers maternal carrier testing. ^[4]

(c) Immediate and long-term medical management (4 marks). Control the active infection aggressively with prolonged, organism-targeted intravenous therapy (an anti-staphylococcal agent guided by susceptibility), because short courses fail and recurrence is the rule in CGD; surgical drainage of the liver abscess, already performed, was essential. Withhold the live BCG vaccine and any other live bacterial vaccine, because the attenuated mycobacterium persists in a defective phagocyte and can cause local or disseminated disease. Start lifelong antimicrobial prophylaxis immediately: co-trimoxazole (approximately 5 mg/kg/day of the trimethoprim component orally once daily) against the catalase-positive bacterial cluster, plus itraconazole or posaconazole for anti-mould prophylaxis against Aspergillus. Address the inflammatory complications — the granulomatous gingivitis and any colitis or obstruction may require anti-inflammatory therapy, often corticosteroids, alongside the antimicrobials, because CGD is a disease of both infection and inflammation. ^{[5] [12]}

(d) Curative option and the timing decision (2 marks). The curative therapy is haematopoietic stem cell transplantation, which replaces the defective phagocyte lineage with healthy donor cells; a normal DHR assay after transplant confirms cure. The 712-patient multicentre cohort reported by Chiesa and colleagues established overall survival of roughly 70 to 95 percent depending on age, genotype, infection status, and donor, with the best outcomes when transplant occurs before severe infection-driven organ damage and with a matched sibling donor. The decision of when to transplant is individualised: a child with good infection control on prophylaxis may defer, while a child with recurrent severe infection or intractable inflammatory complications benefits from earlier transplant. For this boy with recurrent abscess-forming infection and granulomatous complications, transplant evaluation is warranted, beginning with HLA typing and a sibling donor search. ^[7]