What is the appropriate management for a patient with post-hepatitis A and E rash, facial swelling, anasarca, and an elevated Absolute Eosinophil Count (AEC) of 2500?

Management of Post-Hepatitis A and E with Rash, Facial Swelling, Anasarca, and Eosinophilia (AEC 2500)

This patient requires immediate evaluation for Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) syndrome and consideration of systemic corticosteroids, as this presentation most likely represents a severe drug-induced hypersensitivity reaction rather than a direct complication of viral hepatitis. 1, 2, 3

Immediate Diagnostic Priorities

Assess for DRESS Syndrome

• DRESS syndrome is the most critical diagnosis to establish, characterized by skin rash, eosinophilia (AEC 2500 is moderately elevated), facial swelling, and potential internal organ involvement including hepatitis 2, 3, 4
• Calculate the RegiSCAR score immediately: evaluate for fever, lymphadenopathy (>1 cm in ≥2 sites), atypical lymphocytosis, and organ involvement beyond skin and liver 2, 4
• Obtain detailed medication history from 2-8 weeks prior to symptom onset—specifically antibiotics (amoxicillin, sulfonamides), antivirals, anticonvulsants (lamotrigine), and NSAIDs 2, 3, 4
• The timing of 2-3 weeks post-medication exposure is classic for DRESS syndrome 4

Rule Out Life-Threatening Complications

• Immediately assess airway patency: examine for change in voice, loss of ability to swallow, or difficulty breathing, as facial swelling with anasarca suggests potential laryngeal involvement 5
• Check for hepatosplenomegaly, ascites, and deranged coagulation—these indicate severe hepatic involvement requiring urgent intervention 2
• Obtain chest imaging to evaluate for pulmonary infiltrates (eosinophilic pneumonitis) and pleural effusion 2, 4

Differentiate from Other Eosinophilic Conditions

• Hypereosinophilic syndrome (HES) is less likely given the acute presentation post-hepatitis, but must be excluded: HES requires AEC >1500 cells/μL with organ damage and exclusion of other causes 6
• Parasitic infections must be ruled out given the eosinophilia: obtain stool microscopy for ova and parasites (concentrated specimens), and consider strongyloides serology if there is tropical exposure history 6, 7
• EGPA (eosinophilic granulomatosis with polyangiitis) is unlikely without asthma, rhinosinusitis, or vasculitic features, but check ANCA if there is peripheral neuropathy or purpura 6

Laboratory Evaluation

Essential Immediate Tests

• Complete blood count with differential: confirm absolute eosinophil count, look for atypical lymphocytosis (supports DRESS) 2, 4
• Comprehensive metabolic panel: assess hepatic function (transaminases, bilirubin, alkaline phosphatase), renal function (creatinine—acute kidney injury occurs in severe DRESS), and albumin 2, 3
• Coagulation studies (PT/INR): deranged coagulation indicates severe hepatic dysfunction 2
• Hepatitis serology: confirm IgM anti-HAV and anti-HEV to document acute infection 1, 3

Additional Diagnostic Studies

• Skin biopsy from affected area: look for perivascular inflammatory infiltrate with eosinophils (supports drug reaction) 1, 2
• Chest CT if dyspnea or hypoxia present: bilateral interstitial infiltrates suggest eosinophilic pneumonitis 4
• Abdominal ultrasound: evaluate for hepatosplenomegaly, ascites, and lymphadenopathy 2

Treatment Algorithm

If DRESS Syndrome is Confirmed or Highly Suspected (RegiSCAR Score ≥4)

Immediately discontinue all potentially causative medications—this is the single most important intervention 2, 3, 4

Initiate High-Dose Systemic Corticosteroids

• Prednisone 1 mg/kg/day (or equivalent methylprednisolone IV if unable to take oral) for severe DRESS with organ involvement 8, 1, 2
• Continue high-dose therapy until clinical improvement (resolution of rash, normalization of eosinophil count, improvement in liver function), typically 2-4 weeks 2, 4
• Taper slowly over 8-12 weeks to prevent rebound—rapid taper causes relapse in up to 20% of cases 2

Monitor for Complications

• Daily assessment of liver enzymes, renal function, and eosinophil count during acute phase 2, 4
• Watch for secondary infections: corticosteroids suppress immunity and increase risk of bacterial, fungal, and viral infections including strongyloides hyperinfection 8
• Screen for latent tuberculosis before prolonged corticosteroid therapy if treatment extends beyond 2 weeks 8

If Parasitic Infection is Suspected

• Do NOT start empiric antiparasitic therapy until strongyloides is ruled out, as corticosteroids can cause fatal strongyloides hyperinfection and dissemination 6, 8
• If strongyloides serology is positive or high suspicion exists: treat with ivermectin 200 μg/kg daily for 2 days BEFORE starting corticosteroids 7, 8
• For other parasitic causes of eosinophilia: albendazole 400 mg plus ivermectin 200 μg/kg as single dose provides broad coverage 7

If Hepatitis A/E-Related Extrahepatic Manifestation

• This is a rare presentation: hepatitis A can cause systemic inflammatory response with rash, facial swelling, and eosinophilia 1
• Trial of prednisone 0.5-1 mg/kg/day may result in symptom resolution if drug causes are excluded 1
• However, DRESS syndrome is far more likely given the constellation of findings and should be the primary working diagnosis 2, 3

Critical Pitfalls to Avoid

• Never delay corticosteroid therapy in severe DRESS syndrome with organ involvement—mortality can reach 10% without treatment 2, 4
• Never start corticosteroids before ruling out strongyloides in patients with tropical exposure or unexplained diarrhea—this can be fatal 6, 8
• Do not use antihistamines, epinephrine, or standard allergy treatments as primary therapy—these are ineffective for DRESS syndrome 2
• Do not rechallenge with the suspected causative drug—cross-reactivity exists within drug classes (e.g., all beta-lactams if amoxicillin caused DRESS) 4
• Monitor for hepatitis B reactivation if prolonged corticosteroid therapy is required—screen hepatitis B surface antigen before extended treatment 8

Prognosis and Follow-Up

• With prompt corticosteroid therapy, expect normalization of eosinophil count and resolution of lung infiltrates within 2-4 weeks 4
• Liver function may take longer to normalize, particularly if cholestatic features are present 3
• Long-term follow-up is essential: autoimmune sequelae (thyroiditis, diabetes) can develop months after DRESS syndrome resolution 2