Neutropenia, Eosinophilia & Marrow Failure Syndromes

Autoimmune neutropenia · Severe congenital neutropenia (Kostmann) · Cyclic neutropenia · Acquired neutropenia · Eosinophilia · Neutropenia secondary to marrow failure/infiltration
🩸 Key concepts: ANC <1500/microL; risk of infection severe if ANC <500. SCN (ELANE mutations), cyclic neutropenia (14-21 day cycles), autoimmune (anti-neutrophil antibodies), G-CSF therapy, eosinophilia workup, marrow infiltration (leukemia, storage diseases).

📖 Neutropenia, eosinophilia & secondary neutropenia

🧬 Severe congenital neutropenia (SCN)
Kostmann syndrome (autosomal recessive, ELANE mutations). ANC <200, recurrent severe infections, risk of MDS/AML. G-CSF responsive. HSCT may be curative.
🔄 Cyclic neutropenia
Regular 14-21 day cycles of neutropenia (ANC <200), associated with mouth ulcers, fever, infections. ELANE mutations. G-CSF reduces severity.
🛡️ Autoimmune neutropenia
Anti-neutrophil antibodies, often in infancy, mild-moderate infections, self-limited. G-CSF if severe infections. IVIG transient effect.
🩸 Acquired neutropenia & eosinophilia
Post-viral, drug-induced, nutritional (B12, folate). Eosinophilia: allergic, parasitic, drug hypersensitivity, hypereosinophilic syndromes, marrow infiltration (ALL, neuroblastoma).
🧪 Neutropenia secondary to marrow failure/infiltration
Aplastic anemia, Fanconi, leukemia, storage diseases (Gaucher, Niemann-Pick), metastatic neuroblastoma. Pancytopenia or multilineage cytopenias.
⚠️ Red flags for severe neutropenia: Recurrent fevers, severe gingivitis, perianal infections, cellulitis, septicemia. ANC <200 → high risk of bacterial/fungal infection.

🩺 Diagnostic approach to neutropenia and eosinophilia

1
Confirm neutropenia – Absolute neutrophil count (ANC) = WBC × (% segs + bands). Mild (1000-1500), moderate (500-999), severe (<500). Repeat CBC to exclude transient.
2
History & physical – Infection frequency/severity, mouth ulcers, cyclic symptoms (every 2-3 weeks), drug exposure, family history (SCN, cyclic), growth failure, organomegaly (marrow infiltration).
3
Specific tests – Serial CBC (q 2-3 weeks for cyclic). Anti-neutrophil antibodies (autoimmune). Bone marrow aspirate (maturation arrest in SCN, hypocellularity, blasts). Genetic testing (ELANE, HAX1).
4
Eosinophilia workup – Repeat smear (absolute eosinophil count). Stool for ova/parasites, IgE, allergy evaluation, autoimmune screen, bone marrow for hypereosinophilic syndrome or malignancy.
📌 Clinical pearl: Cyclic neutropenia → regular 21-day cycles (ANC nadir every 3 weeks). Oral ulcers and fever during nadir. Serial CBCs (3x/week for 6 weeks) confirm pattern.

📋 Management of neutropenia, eosinophilia & secondary neutropenia

1
Severe congenital neutropenia (SCN) – G-CSF (filgrastim) 5-20 mcg/kg/day to maintain ANC >500-1000. Monitor for MDS/AML (annual marrow). HSCT for transformation or G-CSF failure.
2
Cyclic neutropenia – G-CSF reduces severity and duration of neutropenic periods. Treat infections promptly. Good oral hygiene, antiseptic mouthwash.
3
Autoimmune neutropenia – Observation (self-limited). G-CSF if severe infections. IVIG (short-term). Treat underlying autoimmune condition.
4
Acquired neutropenia (post-viral, drug-induced) – Discontinue offending drug. Supportive care. G-CSF if prolonged severe neutropenia with infection.
5
Eosinophilia (severe or symptomatic) – Treat underlying cause (parasites, allergy). Corticosteroids for hypereosinophilic syndrome (organ damage). Imatinib for FIP1L1-PDGFRA associated.
6
Neutropenia secondary to marrow failure – Treat underlying disorder (aplastic anemia: IST or HSCT; leukemia: chemotherapy; storage disease: enzyme replacement/HSCT). G-CSF as bridge.
🚨 Emergency in neutropenia: Fever >38.5°C with ANC <500 → immediate broad-spectrum IV antibiotics, cultures, hospital admission. Avoid rectal exams/suppositories.

🧠 Reflex prompts: neutropenia syndromes & eosinophilia

🩸 Infant with recurrent fevers, omphalitis, oral ulcers, ANC 150. Bone marrow shows maturation arrest at promyelocyte stage. Diagnosis?
Severe congenital neutropenia (Kostmann syndrome). ELANE mutation. G-CSF therapy. Monitor for MDS/AML.
🔄 Child with regular episodes of fever, mouth ulcers, and neutropenia every 21 days. Most likely diagnosis?
Cyclic neutropenia. Serial CBCs show nadir every 3 weeks. ELANE mutation. G-CSF reduces severity.
🛡️ 6-month-old with mild neutropenia (ANC 600), recurrent otitis media, positive anti-neutrophil antibodies. Best management?
Autoimmune neutropenia of infancy. Usually self-limited. G-CSF if severe infections. IVIG transient effect.
🩸 Child with pancytopenia, hepatosplenomegaly, and Gaucher cells on marrow. Diagnosis?
Gaucher disease (storage disorder causing neutropenia/thrombocytopenia). Enzyme replacement therapy.
🧪 Boy with recurrent infections, ANC 200, and family history of maternal neutropenia. Gene mutation?
ELANE mutation (congenital or cyclic neutropenia). Autosomal dominant in cyclic neutropenia.
🩸 Child with absolute eosinophil count 8000, asthma, eczema, and elevated IgE. Likely cause?
Allergic/eosinophilic disorder. Rule out parasites, drug reaction, hypereosinophilic syndrome.
🩺 Most common cause of mild neutropenia in otherwise well child?
Post-viral neutropenia (self-limited, resolves in weeks). Also ethnic neutropenia (benign, ANC 1000-1500).
🧬 Which drug is first-line for severe congenital neutropenia?
G-CSF (filgrastim). Doses 5-20 mcg/kg/day to maintain ANC >500-1000.
🩸 Child with fever and neutropenia after chemotherapy. Immediate step?
Blood cultures + broad-spectrum IV antibiotics (e.g., cefepime, piperacillin-tazobactam).
🩺 Hypereosinophilic syndrome: organ damage risk includes?
Cardiac (endomyocardial fibrosis, thrombosis), neurologic, pulmonary, GI. Corticosteroids, imatinib if FIP1L1-PDGFRA positive.