U01.02.033 Immunodeficiencies Phagocyte dysfunction

Phagocyte dysfunction disorders are critical to understanding immunodeficiencies. These conditions lead to recurrent infections and impaired immune responses. Below is a detailed breakdown of key disorders associated with phagocyte dysfunction:

1. Leukocyte Adhesion Deficiency (Type 1)

Feature	Details
Defect	LFA-1 integrin (CD18) protein on phagocytes.
Pathophysiology	Impaired migration and chemotaxis. Autosomal recessive inheritance.
Key Clinical Findings	– Late separation of umbilical cord (>30 days). – Absent pus and dysfunctional neutrophils. – Recurrent skin and mucosal bacterial infections.
Lab Findings	– Increased neutrophils in blood. – Absence of neutrophils at infection sites. – Impaired wound healing.

2. Chédiak-Higashi Syndrome

Feature	Details
Defect	Lysosomal trafficking regulator gene (LYST).
Pathophysiology	Microtubule dysfunction in phagosome-lysosome fusion. Autosomal recessive inheritance.
Key Clinical Findings	– PLAIN mnemonic: Progressive neurodegeneration, Lymphohistiocytosis, Albinism (partial), recurrent pyogenic Infections, peripheral Neuropathy.
Lab Findings	– Giant granules in granulocytes and platelets. – Pancytopenia. – Mild coagulation defects.

3. Chronic Granulomatous Disease (CGD)

Feature	Details
Defect	NADPH oxidase deficiency.
Pathophysiology	– Reduced reactive oxygen species (e.g., superoxide). – Impaired respiratory burst in neutrophils. – X-linked form most common.
Key Clinical Findings	– Susceptibility to catalase-positive organisms.
Lab Findings	– Abnormal dihydrorhodamine test (reduced green fluorescence). – Nitroblue tetrazolium dye reduction test fails to turn blue (obsolete).

Points to Remember for Step 1

LAD Type 1: Think of delayed umbilical cord separation and absent pus with high blood neutrophils.
Chédiak-Higashi Syndrome: Recognize the PLAIN mnemonic and presence of giant granules.
Chronic Granulomatous Disease: Focus on catalase-positive organisms and diagnostic tests (e.g., dihydrorhodamine flow cytometry).

Mnemonic Summary

LAD: “Late cord separation, Absent pus, Dysfunctional neutrophils.”
Chédiak-Higashi: PLAIN (Progressive neurodegeneration, Lymphohistiocytosis, Albinism, Infections, Neuropathy).
CGD: “Catalase-positive infections and defective oxidative burst.”

Keep these features in mind to ace related questions on Step 1!

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