What is the appropriate management for a patient with elevated eosinophils (EOS) and monocytes (MONO), and low neutrophils (NEUT), considering their age, medical history, and current medications, including potential allergies or parasitic infections?

Management of Elevated Eosinophils and Monocytes with Low Neutrophils

Begin by obtaining a detailed medication history (especially angiotensin II receptor antagonists like olmesartan, mycophenolate mofetil, and azathioprine), travel history to endemic areas, and assessment for allergic conditions, as these represent the most common reversible causes of this pattern. 1

Immediate Assessment Priorities

Rule Out Medication-Induced Enteropathy

• Olmesartan and other angiotensin II receptor antagonists can cause seronegative enteropathy with this exact pattern of eosinophilia and has led to misdiagnosis of refractory celiac disease. 1
• Mycophenolate mofetil and azathioprine also cause enteropathy that resolves with discontinuation. 1
• Immune checkpoint inhibitors can cause eosinophilia as part of immune-related adverse events. 2, 3

Assess for End-Organ Damage

• Any patient with eosinophilia presenting with evidence of end-organ damage (cardiac, pulmonary, or neurological symptoms) needs urgent medical assessment and emergency treatment consideration. 1
• Persistent eosinophilia at any level can cause significant damage to heart, lungs, and central nervous system. 1

Diagnostic Algorithm

First-Line History Elements

• Travel history to tropical/endemic areas: Assess for parasitic infections (Giardia, tropical sprue, Strongyloides stercoralis, schistosomiasis). 1
• Gastrointestinal symptoms: Diarrhea, abdominal pain, weight loss suggest enteropathy, Crohn's disease, or eosinophilic gastroenteritis. 1
• Allergic history: Asthma, eczema, hay fever, and atopy account for approximately 80% of eosinophilia cases. 2, 3
• Fever and bloody diarrhea: Suggest Crohn's disease or lymphoproliferative disorder. 1

Essential Laboratory Testing

• Complete blood count with differential, serum chemistries, vitamin B12 levels, and serum immunoglobulin levels (total IgG, IgA, IgM, and IgE). 2, 3
• Inflammatory markers: C-reactive protein and erythrocyte sedimentation rate. 1, 2, 3
• Urinalysis with protein assessment. 2
• Serum tryptase if myeloproliferative disorders suspected. 3

Infectious Workup

• Stool examination for ova and parasites plus serology for Strongyloides if gastrointestinal symptoms or travel history present. 1, 2, 3
• For returning travelers/migrants: First-line serology for helminths (commonest identifiable cause with diagnosis rates of 19-80%). 1
• Filarial investigations only if history of travel to/residence in West Africa. 1
• PCR from duodenal aspirate for Giardia if indicated. 1

Immunologic Assessment

• Low total IgG, IgA, and IgM suggest common variable immune deficiency (CVID), which presents with recurrent infections, persistent diarrhea, and absence of plasma cells on histology. 1
• Autoimmune markers (ANA, ANCA) if systemic vasculitis suspected, particularly eosinophilic granulomatosis with polyangiitis. 2, 3

Management Based on Etiology

If Parasitic Infection Suspected (Returning Traveler/Migrant)

• For asymptomatic eosinophilia in patients >24 months: Empirical treatment with albendazole 400 mg single dose plus ivermectin 200 μg/kg single dose. 1, 3
• Strongyloides requires treatment due to risk of lifelong persistence and hyperinfection syndrome with high mortality in immunocompromised patients. 1

If Medication-Induced

• Discontinue the offending medication—enteropathy typically resolves with cessation. 1

If Enteropathy Identified

• Specific treatments based on etiology (see below):
  • Giardiasis: Metronidazole 1
  • Tropical sprue: Tetracycline or doxycycline plus folic acid 1
  • CVID: Budesonide 1
  • Autoimmune enteropathy: Immunosuppression (steroids, azathioprine, infliximab) 1
  • Crohn's disease: Immunosuppression, biologic agents 1
  • Eosinophilic gastroenteritis: Dietary therapy, glucocorticoids 1

If Allergic Cause

• Treat the underlying allergic condition (asthma, atopic dermatitis, allergic rhinitis). 2, 3

Referral Criteria

Hematology Referral Required

• Eosinophilia ≥1.5 × 10⁹/L persisting for more than 3 months without evidence of end-organ damage—refer after infectious causes excluded or treated. 1, 3
• Persistent unexplained cytopenias (the low neutrophils in this case). 3
• Suspicion for myeloid/lymphoid neoplasms with eosinophilia (requires bone marrow biopsy, cytogenetics, FISH, RT-PCR for PDGFRA, PDGFRB, FGFR1, JAK2 fusion genes). 2

Gastroenterology Referral

• If gastrointestinal symptoms present with eosinophilia: Consider esophagogastroduodenoscopy with biopsy to evaluate for eosinophilic esophagitis, enteropathy, or Crohn's disease. 1
• Eosinophilic esophagitis causes tissue eosinophilia (≥15 eos/hpf) but peripheral eosinophilia occurs in only 10-50% of adults. 2, 4

Critical Pitfalls to Avoid

• Failing to obtain comprehensive medication history, particularly for olmesartan, which mimics refractory celiac disease. 1
• Missing parasitic infections in patients with travel history—Strongyloides can cause fatal hyperinfection syndrome years later. 1, 3
• Assuming allergy alone explains hypereosinophilia (≥1.5 × 10⁹/L)—this level rarely occurs from allergy and requires further workup. 5
• Not recognizing that peripheral eosinophil counts may not correlate with tissue eosinophilia—biopsy remains gold standard for conditions like eosinophilic esophagitis. 2, 4
• Overlooking common variable immune deficiency when low immunoglobulins present—this requires specific immunosuppressive management. 1

Monocytosis Considerations

While the evidence focuses primarily on eosinophilia, elevated monocytes in this context warrant:

• Evaluation for chronic inflammatory conditions (Crohn's disease, autoimmune disorders). 1
• Assessment for chronic infections, particularly in conjunction with travel history. 1
• Consideration of myeloproliferative disorders if persistent and unexplained. 3