Paeds · allergy-and-immunology
Phagocyte disorders
Also known as Chronic granulomatous disease · CGD · Leukocyte adhesion deficiency · LAD · Severe congenital neutropenia · Chédiak-Higashi syndrome · Congenital neutropenia · Innate immune deficiency
Fellowship topic on phagocyte disorders — the primary immunodeficiencies in which neutrophils and monocytes fail to kill microbes, recurrent tissue invasive infection drives the presentation, and inflammation paradoxically coexists with infection. Chronic granulomatous disease (CGD) is the prototype and the most tested: a defective NADPH oxidase prevents the respiratory burst, so catalase-positive organisms (Staphylococcus aureus, Burkholderia cepacia complex, Serratia, Nocardia, Aspergillus) survive inside phagocytes and the host responds with granulomatous inflammation that obstructs hollow viscera. X-linked gp91phox (CYBB) is the commonest genotype, autosomal recessive p47phox (NCF1) the next, and the dihydrorhodamine (DHR) flow cytometry assay is the diagnostic test. Leukocyte adhesion deficiency (LAD) presents with delayed cord separation, pus-less infection, and striking leukocytosis; severe congenital neutropenia with overwhelming bacterial sepsis in early infancy and a long-term myelodysplasia risk; Chédiak-Higashi syndrome with giant intracellular granules, partial albinism, and a fatal accelerated phase. The curative therapy for the severe forms is haematopoietic stem cell transplantation, and antimicrobial prophylaxis (co-trimoxazole and an anti-mould antifungal) is the backbone of medical management. The page owns CGD, LAD-1/2/3, congenital and cyclic neutropenia, Chédiak-Higashi, specific granule deficiency, and Shwachman-Diamond, and cross-links the combined immunodeficiency leaf for SCID and the antibody-deficiency leaf for humoral defects.
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Red flags
- A child with recurrent or persistent infection caused by Staphylococcus aureus, Burkholderia cepacia complex, Serratia marcescens, Nocardia, or invasive Aspergillus has chronic granulomatous disease until a dihydrorhodamine (DHR) flow cytometry assay proves otherwise
- Delayed separation of the umbilical cord beyond three weeks with omphalitis, periodontitis, and a markedly raised neutrophil count but no pus at infection sites is leukocyte adhesion deficiency type 1 — check CD18 expression by flow cytometry
- A granulomatous obstruction of the gastrointestinal or genitourinary tract — gastric-outlet obstruction, recurrent hydronephrosis, or Crohn-like colitis — in a child with recurrent infection is inflammatory CGD, not ordinary inflammatory bowel disease
- An infant with severe congenital neutropenia who develops new cytopenias, macrocytosis, or a monosomy 7 clone on bone marrow is evolving to myelodysplasia or leukaemia — surveillance marrow cytogenetics is mandatory
- A fair-haired child with recurrent pyogenic infection, a bleeding tendency, and giant azure granules in the neutrophils has Chédiak-Higashi syndrome, and a fever with hepatosplenomegaly marks the start of the often-fatal accelerated phase
Life stages
Care settings
Clinical exam formats
Board mappings
- General Paediatrics and Immunology: recognise the CGD phenotype — recurrent or invasive infection with Staphylococcus aureus, Burkholderia, Serratia, Nocardia, or Aspergillus — and order the dihydrorhodamine (DHR) flow cytometry assay
- Neonates and emergency: delayed cord separation with pus-less omphalitis and a high neutrophil count is leukocyte adhesion deficiency until CD18 is checked
- Renewed curriculum — Allergy & immunology (LG): CGD genotypes and the NADPH oxidase pathway, LAD-1/2/3, severe congenital neutropenia and its myelodysplasia risk, Chédiak-Higashi and the accelerated phase, and the role of haematopoietic stem cell transplantation
- Acute and critical care: antimicrobial prophylaxis, the management of inflammatory granulomatous obstruction, and transplant decision-making in CGD
- General Paediatrics / ED: suspect a phagocyte disorder from the infecting organism and the paradox of inflammation without pus; confirm with DHR or flow cytometry
- Resuscitation: treat invasive infection aggressively, start co-trimoxazole and anti-mould prophylaxis, and refer to immunology and transplant
- Long Case / Structured discussion: the child with recurrent abscesses and granulomatous colitis — diagnosis of CGD, the DHR result, prophylaxis, the transplant decision, and genetic counselling for X-linked inheritance
- Communication station: explaining CGD, the danger of live BCG in some phagocyte disorders, lifelong prophylaxis, and the genetic implications for the family
- Level 2 / 3 — Immunology: phagocyte disorders as a cause of recurrent invasive bacterial and fungal infection; the respiratory burst, the DHR assay, and the curative role of HSCT
- Patient safety and quality: avoidable harm — live vaccines in severe phagocyte defects, missed bone-marrow surveillance in congenital neutropenia, and the accelerated phase of Chédiak-Higashi
- Foundation of Practice (FOP): the neutrophil and its killing pathways, the presentation of primary phagocyte defects, and the immunodeficiency warning signs
- Applied Knowledge in Practice (AKP): CGD organisms and the DHR assay, LAD and delayed cord separation, congenital neutropenia and myelodysplasia, and Chédiak-Higashi
- History-taking and management: the child with recurrent abscesses or granulomatous obstruction — diagnosis, prophylaxis, and the transplant decision
- Communication: explaining a phagocyte disorder, lifelong prophylaxis, the live-vaccine cautions, and genetic counselling to a family
- General Pediatrics Content Outline — immunodeficiency: recognise CGD, LAD, congenital neutropenia, and Chédiak-Higashi; order DHR and flow cytometry; refer for curative HSCT
- Allergy & Immunology: the NADPH oxidase pathway and CGD genotypes, neutrophil adhesion and LAD, neutropenia genetics, and transplant outcomes
- Emergency Medicine: the child with invasive catalase-positive infection or pus-less omphalitis — prophylaxis, treat aggressively, and emergent referral
- Patient Care: recognise and stabilise the child with a phagocyte disorder, prevent iatrogenic harm, and refer for curative HSCT when indicated
- Systems-Based Practice: equitable access to DHR testing, prophylaxis, and transplant, and family genetic counselling for X-linked forms
- Medical Knowledge: the respiratory burst, neutrophil adhesion, granulopoiesis, and the basis of curative therapy
- Medical Expert: phagocyte disorder diagnosis by DHR, flow cytometry, and genetic testing; protection of the child; and the transplant decision
- Health Advocate: equitable access to prophylaxis and transplant, and prevention of live-vaccine harm
- Communicator: explaining CGD, lifelong prophylaxis, the accelerated phase risk, and genetic counselling to a family
The same organ, two failures
Chronic granulomatous disease — the cell gets there but cannot kill
Leukocyte adhesion deficiency — the cell never arrives
Chronic Granulomatous Disease kills poorly, so remember the five organisms that thrive when the respiratory burst fails: Staphylococcus aureus, Burkholderia cepacia complex, Serratia marcescens, Nocardia, and Aspergillus — all catalase-positive, because the neutrophil relies on its own oxidase-generated hydrogen peroxide to fuel myeloperoxidase, and catalase-positive bugs destroy peroxide phagocyte needs. The rule of thumb: a child with recurrent or invasive infection by any of these five has CGD until the DHR assay proves otherwise. [4] [5]
Overview & Definition
Picture a three-year-old boy admitted for the third time in a year — once for a staphylococcal liver abscess that needed weeks of intravenous antibiotics, once for a necrotising pneumonia that turned out to be caused by Serratia marcescens, and now for a swollen, chronically inflamed gum that a biopsy calls granulomatous. His neutrophil count is normal, and each time the infection has produced abundant pus, yet the organisms keep recurring. The clue is the organism list itself — Staphylococcus, Serratia, and a granulomatous response — and it points straight to a phagocyte killing defect. This child has chronic granulomatous disease, and the single test that confirms it, the dihydrorhodamine flow cytometry assay, measures the oxidative burst his neutrophils cannot generate. [4] [5]
The phagocyte disorders are the primary immunodeficiencies in which neutrophils and monocytes — the innate effector cells that migrate into infected tissue, ingest microbes, and kill them with reactive oxygen species and granule enzymes — fail at one of these steps. The 2024 IUIS classification, led by Poli and colleagues, groups them under congenital defects of phagocyte number or function, and the field divides cleanly along three mechanistic axes: a failure of killing (CGD, the largest group), a failure of adhesion and migration (leukocyte adhesion deficiency), and a failure of production or granule packaging (severe congenital neutropenia, cyclic neutropenia, Chédiak-Higashi, specific granule deficiency). Each axis produces a recognisable clinical phenotype, and recognising the phenotype is how the diagnosis is made at the bedside. [1] [2]
What unifies these disorders, and what the examination tests, is that the recurrent infection they cause is driven by a predictable cluster of organisms and by a paradoxical tissue response. In CGD the catalase-positive bacteria and Aspergillus survive because the respiratory burst fails; the host responds with granulomatous inflammation that can obstruct the gut or urinary tract. In LAD the neutrophils cannot migrate, so infection smoulders without pus while the neutrophil count climbs. In congenital neutropenia the marrow simply cannot make enough neutrophils, and the child presents with overwhelming bacterial sepsis. Understanding why each disease produces its particular fingerprint is the key to recognising all of them. [3] [4]
The clinical task has two halves. The first is recognition and protection — suspect a phagocyte disorder from the organism list or the bedside paradox, confirm with the DHR assay or flow cytometry, and start prophylaxis and infection surveillance. The second is the curative decision — haematopoietic stem cell transplantation for the severe forms, particularly CGD and LAD, in which the transplant replaces the defective phagocyte lineage with healthy donor cells. The 712-patient multicentre cohort reported by Chiesa and colleagues established that transplant works across genotypes and ages, making the decision not whether to transplant but when and with what donor. A candidate who diagnoses CGD but does not know the organism cluster, the DHR assay, or the transplant evidence fails the question. [4] [7]
References12ShowHide
- [1]Poli MC; Aksentijevich I; Bousfiha AA; Cunningham-Rundles C; Hambleton S; Klein C; Morio T; Picard C Human inborn errors of immunity: 2024 update on the classification from the International Union of Immunological Societies Expert Committee. J Hum Immun, 2025.PMID 41608114
- [2]Tangye SG; Al-Herz W; Bousfiha A; Cunningham-Rundles C; Franco JL; Holland SM; Klein C; Morio T The Ever-Increasing Array of Novel Inborn Errors of Immunity: an Interim Update by the IUIS Committee. J Clin Immunol, 2021.PMID 33598806
- [3]Bousfiha A; Jeddane L; Picard C; Ailal F; Bobby Gaspar H; Al-Herz W; Chatila T; Crow YJ The 2017 IUIS Phenotypic Classification for Primary Immunodeficiencies. J Clin Immunol, 2018.PMID 29226301
- [4]Holland SM Chronic granulomatous disease. Hematol Oncol Clin North Am, 2013.PMID 23351990
- [5]Arnold DE; Heimall JR A Review of Chronic Granulomatous Disease. Adv Ther, 2017.PMID 29168144
- [6]Kuhns DB; Hsu AP; Sun D; Lau K; Fink D; Griffith P; Shapiro RA; Malech HL NCF1 (p47(phox))-deficient chronic granulomatous disease: comprehensive genetic and flow cytometric analysis. Blood Adv, 2019.PMID 30651282
- [7]Chiesa R; Wang J; Blok HJ; Hazelaar S; Neven B; Moshous D; Friedacher K; Köglmeier J; Qasim W Hematopoietic cell transplantation in chronic granulomatous disease: a study of 712 children and adults. Blood, 2020.PMID 32614953
- [8]van de Vijver E; van den Berg TK; Kuijpers TW Leukocyte adhesion deficiencies. Hematol Oncol Clin North Am, 2013.PMID 23351991
- [9]Hanna S; Etzioni A Leukocyte adhesion deficiencies. Ann N Y Acad Sci, 2012.PMID 22276660
- [10]Skokowa J; Dale DC; Touw IP; Zeidler C; Welte K Severe congenital neutropenias. Nat Rev Dis Primers, 2017.PMID 28593997
- [11]Talbert ML; Malicdan MCV; Introne WJ Chediak-Higashi syndrome. Curr Opin Hematol, 2023.PMID 37254856
- [12]Shearer WT, Fleisher TA, Buckley RH, et al. Recommendations for live viral and bacterial vaccines in immunodeficient patients and their close contacts. J Allergy Clin Immunol, 2014.PMID 24582311