Fever + Leukocytosis + Hypereosinophilia + Deranged RFTs

1. DRUG REACTION WITH EOSINOPHILIA AND SYSTEMIC SYMPTOMS (DRESS)

• Features: Fever + extensive mucocutaneous rash + lymphadenopathy + hepatitis + eosinophilia + atypical lymphocytosis + multisystem organ injury
• Renal involvement: Acute tubulointerstitial nephritis (AKI, proteinuria); biopsy shows eosinophil-rich tubulointerstitial infiltrate. DRESS is associated with interstitial nephritis in up to 40% of patients with persistent drug exposure
• Classic setting: Patient defervesces on antibiotics, then develops recurrent fever days later - this pattern is nearly diagnostic of drug-induced AIN
• Implicated drugs: Aromatic anticonvulsants (phenytoin, carbamazepine), allopurinol, antibiotics (penicillins, sulfonamides, rifampicin), NSAIDs
• Key distinction: The classic "allergy triad" of fever + rash + eosinophilia occurs in <33% of all AIN; more common with antibiotic-related AIN, rare with NSAID-related AIN
• Comprehensive Clinical Nephrology, 7th Ed., p. 416
• Goldman-Cecil Medicine, Chapter 108

2. PARASITIC/HELMINTHIC INFECTIONS

• Tietz Textbook of Laboratory Medicine, 7th Ed.
• Quick Compendium of Clinical Pathology, 5th Ed.

3. HYPEREOSINOPHILIC SYNDROME (HES) WITH ORGAN DAMAGE

• Definition: Persistent blood eosinophilia (>1.5 × 10⁹/L) for >6 months + evidence of eosinophil-induced organ damage, after excluding secondary causes
• Subtypes: Myeloproliferative HES (FIP1L1-PDGFRA fusion gene, constitutive tyrosine kinase), lymphocytic HES (IL-5 overproduction by T cells), chronic eosinophilic leukemia, idiopathic HES
• Renal involvement: Renal eosinophilic infiltration, thrombotic microangiopathy, AKI
• Cardiac overlap: Löffler endocarditis (endomyocardial fibrosis) - thrombi, restrictive cardiomyopathy
• Fever is a constitutional feature of systemic HES
• Goldman-Cecil Medicine, 2-Vol Set, p. 525

4. EOSINOPHILIC GRANULOMATOSIS WITH POLYANGIITIS (EGPA / Churg-Strauss Syndrome)

• Classic triad: Asthma + eosinophilia + systemic vasculitis
• Renal involvement: Necrotizing pauci-immune glomerulonephritis (ANCA-positive in ~40%), renal infarcts, interstitial nephritis - can cause rapidly progressive GN with renal failure
• Fever is a systemic feature of active vasculitis
• Leukocytosis accompanies active disease
• Important to distinguish from HES: vasculitis is characteristic of EGPA but NOT of HES
• Firestein & Kelley's Textbook of Rheumatology, 2-Vol Set
• Murray & Nadel's Textbook of Respiratory Medicine

5. ATHEROEMBOLIC RENAL DISEASE

• Occurs after vascular instrumentation (aortography, cardiac catheterization)
• Classic features: Peripheral eosinophilia + eosinophiluria + fever + livedo reticularis/skin ischemia + AKI
• Mimics contrast nephropathy but has a subacute progressive course
• Cholesterol crystal emboli lodge in renal arterioles → foreign body reaction → eosinophil recruitment
• Comprehensive Clinical Nephrology, 7th Ed.
• Brenner and Rector's The Kidney, 2-Vol Set

6. KIMURA DISEASE

• Predominantly in Asian patients
• Nonmalignant head/neck masses + marked eosinophilia + elevated IgE
• Renal: Membranous nephropathy, FSGS (tip lesion), or mesangial PGN → nephrotic syndrome + renal impairment
• Fever can accompany systemic disease
• Comprehensive Clinical Nephrology, 7th Ed., p. 416

7. TROPICAL INFECTIONS WITH EOSINOPHILIA + RENAL INVOLVEMENT

• Sleisenger and Fordtran's Gastrointestinal and Liver Disease

8. MALIGNANCY-ASSOCIATED

• Hodgkin lymphoma - B symptoms (fever, night sweats, weight loss) + eosinophilia (cytokine-mediated) + renal involvement (paraneoplastic GN, ureteral obstruction, drug-induced AKI from chemotherapy)
• T-cell lymphoma/leukemia - Clonal T cells secrete IL-5 → lymphocytic hypereosinophilia; organ damage common
• Colonic carcinoma - Can produce eosinophilia + paraneoplastic renal disease

9. AUTOIMMUNE / CONNECTIVE TISSUE DISEASE

Summary - Mnemonic: "PAID MATCH"

Key Investigations to Differentiate

1. Stool microscopy + serology for helminths (Toxocara IgG, Strongyloides, Schistosoma)
2. ANCA (pANCA/cANCA) - for EGPA
3. FIP1L1-PDGFRA fusion gene by FISH/PCR - for myeloproliferative HES
4. Serum tryptase + bone marrow biopsy - to exclude systemic mastocytosis (can mimic)
5. Drug history - any new drug in the past 2-12 weeks
6. Urine eosinophils (Hansel stain) - seen in drug AIN and atheroembolic disease
7. Echocardiography - to screen for Löffler endocarditis in HES
8. CT chest/abdomen/pelvis - for lymphoma, metastatic disease, parasitic cysts
9. Renal biopsy - when diagnosis is unclear; pattern (eosinophilic interstitial nephritis vs. GN vs. TMA) guides treatment