What is the diagnosis and treatment for a patient presenting with itching and rashes over the body, elevated C-Reactive Protein (CRP), eosinophilia, and elevated Erythrocyte Sedimentation Rate (ESR)?

Diagnosis and Treatment of Itching, Rashes, Elevated CRP, Eosinophilia, and Elevated ESR

Most Likely Diagnosis

The most likely diagnosis is Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) syndrome, which requires immediate identification and withdrawal of the causative medication. 1

Your laboratory values show:

• CRP 13 mg/L (elevated, indicating active inflammation)
• Absolute eosinophil count 558 cells/mm³ (elevated, normal <500)
• ESR 20 mm/h (mildly elevated for men >20, women >30) 2

This triad of rash, eosinophilia, and elevated inflammatory markers is characteristic of DRESS syndrome, which is a severe drug hypersensitivity reaction. 1, 3

Immediate Actions Required

1. Medication Review and Withdrawal

• Immediately review all medications started within the past 2-12 weeks, as DRESS typically develops 2-8 weeks after drug initiation 1
• Common culprits include: anticonvulsants (phenytoin, carbamazepine, lamotrigine), allopurinol, sulfonamides, antibiotics (minocycline, vancomycin), and acetazolamide 1, 3
• Stop the suspected offending drug immediately - this is the only undisputed treatment for DRESS syndrome 1

2. Assess for Systemic Organ Involvement

• Check liver function tests (AST, ALT, bilirubin) - hepatitis occurs in 50-60% of DRESS cases 1
• Check renal function (creatinine, BUN) - nephritis can occur 1
• Examine for lymphadenopathy - present in most DRESS cases 1
• Monitor for fever - typically present in DRESS syndrome 1

3. Rule Out Other Critical Diagnoses

Giant Cell Arteritis/Polymyalgia Rheumatica (less likely given age and presentation):

• ESR 20 mm/h is too low for GCA (ESR >40 mm/h has 93.2% sensitivity for GCA) 2, 4
• However, if patient is >50 years with new headache, jaw claudication, or visual symptoms, urgent evaluation is needed 4

Chronic Spontaneous Urticaria:

• CRP elevation correlates with urticaria activity and antihistamine resistance 5
• Consider if rash is primarily urticarial (wheals lasting <24 hours) 5

Eosinophilic Esophagitis (if dysphagia present):

• Peripheral eosinophilia occurs in 20-100% of children and 10-50% of adults with EE 6
• Blood eosinophils >0.24 × 10⁹/L suggest tissue eosinophilia 7

Diagnostic Workup

Essential Laboratory Tests

• Complete blood count with differential - assess for leukocytosis, atypical lymphocytes 4
• Comprehensive metabolic panel - liver enzymes, creatinine, electrolytes 4
• Serum albumin - low albumin can falsely elevate ESR 4
• Lactate dehydrogenase (LDH) - elevated in DRESS syndrome 1
• Blood cultures if fever present - rule out infection 4

Additional Tests Based on Clinical Presentation

• Skin biopsy - shows interface dermatitis with eosinophils in DRESS 1
• Chest X-ray - if respiratory symptoms present 4
• Viral serologies (HHV-6, EBV, CMV) - reactivation common in DRESS 1

Treatment Algorithm

For DRESS Syndrome (Most Likely)

Step 1: Drug Withdrawal

• Discontinue all non-essential medications immediately 1
• Do not rechallenge with the suspected drug - can be fatal 1

Step 2: Systemic Corticosteroids (Controversial but Often Used)

• Consider prednisone 0.5-1 mg/kg/day if severe organ involvement present 1
• The use of systemic corticosteroids remains controversial, but many experts use them for severe cases 1
• Taper slowly over 6-12 weeks - rapid taper can cause relapse 1

Step 3: Supportive Care

• Topical corticosteroids for skin rash 1
• Antihistamines for pruritus 1
• Monitor organ function weekly during acute phase 1

For Chronic Spontaneous Urticaria (If Urticarial Rash)

Step 1: Second-Generation Antihistamines

• Start with standard dose (e.g., cetirizine 10 mg daily, loratadine 10 mg daily) 5
• Up-dose to 4 times standard dose if inadequate response after 2 weeks 6

Step 2: If Antihistamines Fail

• Consider omalizumab (anti-IgE therapy) 5
• Higher CRP levels predict antihistamine resistance 5

For Other Causes

If Eosinophilic Esophagitis suspected (dysphagia, food impaction):

• Refer to gastroenterology for endoscopy with biopsy 6
• Allergy evaluation - high rate of atopy in EE patients 6

If Parasitic Infection suspected (travel history, myalgias):

• Stool ova and parasites × 3 8
• Serologic testing for Strongyloides, Toxocara, Sarcocystis 8
• Consider albendazole if parasitic infection confirmed 8

Critical Pitfalls to Avoid

• Do not dismiss mild eosinophilia - absolute eosinophil count >500 is abnormal and requires investigation 6, 7
• Do not continue suspected drugs - DRESS can be fatal if drug exposure continues 1
• Do not use procalcitonin to rule out DRESS - it can be markedly elevated in DRESS, mimicking sepsis 3
• Do not assume infection - eosinophilia with rash suggests drug reaction or allergic process, not bacterial infection 1, 3
• Do not stop corticosteroids abruptly if started - DRESS can relapse with rapid taper 1

Monitoring Strategy

• Repeat CBC, CRP, liver enzymes weekly until normalized 1
• CRP normalizes faster than ESR during treatment response 2
• Symptoms may persist for months even after drug withdrawal 1, 8
• Watch for late complications - autoimmune thyroiditis, diabetes can develop months after DRESS 1