2025 – PAGE 115 – ALLERGY & IMMUNOLOGY

CHRONIC BENIGN NEUTROPENIA

In chronic benign neutropenia, the ANC is chronically low. This is usually noted as an incidental finding when a CBC has been done for other reasons and typically resolves by 2 years of age. It’s not really chronic, but it is benign.

TRANSIENT NEUTROPENIA

Transient neutropenia is common after viral infections. No treatment is required.

CYCLIC NEUTROPENIA

Cyclic neutropenia is an autosomal dominant (AD) disorder that is inherited and results in neutropenia lasting for about one week every month. Frequent CBCs are required to document the cyclic nature of the neutropenia. This is usually self-limited and doesn’t require treatment, but if the patient has infections associated with it, GCSF may be given at the nadir of the cycle. Patients are prone to Clostridium perfringens infections and ORAL lesions, such as recurrent periodontitis or oral ulcerations.

MNEMONIC: “Kind of like a MENSTRUAL CYCLE for your NEUTROPHILS.” This is to help you remember that the cycle lasts for about one week, and it occurs every month.

SEVERE CONGENITAL NEUTROPENIA (AKA KOSTMANN SYNDROME)

In severe congenital neutropenia (AKA Kostmann syndrome), the ANC does not normalize and remains low. It is a rare condition but is associated with severe infections if present.

(DOUBLE TAKE) CHRONIC GRANULOMATOUS DISEASE (CGD) = SERRATIA

Chronic Granulomatous Disease (CGD) is an X-linked recessive disorder. On the boards, if you see a boy diagnosed with Serratia, he’s probably got CGD. CGD is the result of deficiency of an enzyme within neutrophils that is needed to destroy cell walls and aid in phagocytosis. Chemotaxis is intact. This is not a cell line deficiency, so there is NO LYMPHOpenia and NO NEUTROpenia. This is a functional/oxidative burst issue. The immune system is unable to destroy certain bacteria and fungi (Aspergillus, Candida, E. coli, Serratia and Staphylococcus) because they are all catalase positive organisms. The organisms/infections are usually considered to be low-grade. Patients may have liver abscesses, osteomyelitis, recurrent lymphadenitis, and recurrent skin infections. They can also have GI infections and granulomas of the skin, GI, or GU tract.

• DIAGNOSIS: The preferred test is Dihydrorhodamine Fluorescence (DHR), followed by the Nitroblue Tetrazolium (NBT) dye test.
• TREATMENT: Life-long prophylaxis with antibacterial antibiotics, anti-fungal medications and interferon-gamma. Infections should be treated early and aggressively.
• PEARL: Like the name says, it’s a “CHRONIC” condition. Children usually present by 5 years of age.
• MNEMONIC: CGD = This is an X-linked disorder, ChroniX GranulomatuX Disease. Put an X where it makes sense for you to remember this key fact.
• MNEMONIC: NEUTROphil disorder = NEUTROBLUE tetrazolium test, which tests for the NEUTROglycerin oxidative BURST.” ChroniX GranulomatuX Disease seems to be all about colors! BLUE and SERRATIA (RED)!!!

LEUKOCYTE ADHESION DEFICIENCY (AKA LEUKOCYTE ADHESION DEFECT)

In leukocyte adhesion deficiency (AKA leukocyte adhesion defect), the adhesion defect results in neutrophils being unable to leave the vasculature to get to infected areas. Look for a black, infected-looking cord stump (or other wound) without any pus/inflammation, DELAYED separation of cord, and delayed wound healing. Specific infections might include periodontitis, perirectal abscesses, skin infections/abscesses, and omphalitis.

• LABS will reveal LEUKOcytosis and NeutroPHILIA. The WBC will be HIGH even without infections (~20,000), and may be as high as 100,000 with infections.
• DIAGNOSTIC tests include a Rebuck Skin Windowor CD11/CD18 flow cytometry.
• BMT is curative, and without it patients will die by the age of one. So if the ABP presents an older child in the vignette, it is probably not LAD.