In a patient with chronic pruritus, normal iron studies, and lichenified skin from scratching, what is the appropriate next diagnostic and therapeutic approach?

Chronic Pruritus with Lichenification and Normal Iron Studies

Despite normal iron levels, your chronic pruritus with lichenified skin requires a comprehensive systemic workup to identify treatable underlying causes—most commonly cholestatic liver disease, chronic kidney disease, hematologic disorders, or neuropathic mechanisms—while simultaneously initiating aggressive symptomatic management with emollients, gabapentin, and behavioral interventions to break the itch-scratch cycle.

Immediate Diagnostic Workup

Your "normal iron studies" may be incomplete or misleading. The single most critical pitfall is accepting "normal labs" without verifying that comprehensive iron studies were actually performed 1. Many patients are missed because only ferritin was checked, which can appear falsely normal in the setting of inflammation 1.

Mandatory Laboratory Panel (Order Today)

• Complete blood count with differential to screen for polycythemia vera, lymphoma, and occult anemia 2
• Comprehensive iron panel (serum iron, ferritin, transferrin saturation)—ferritin alone is insufficient 3, 1
• Liver function tests, total bilirubin, and serum bile acids to identify cholestatic disease, which characteristically causes palm/sole pruritus worse at night 2, 3
• Renal panel (urea, creatinine, electrolytes) to detect uremic pruritus 2
• Fasting glucose and hemoglobin A1c to evaluate for diabetic neuropathy 3
• Thyroid-stimulating hormone if clinical features suggest thyroid dysfunction 2

History-Directed Additional Testing

• JAK2 V617F mutation if you have aquagenic pruritus (triggered by water contact), which is pathognomonic for polycythemia vera 2, 3
• HIV and hepatitis A, B, C serologies if you have relevant risk factors or travel history 2
• Skin biopsy for persistent unexplained pruritus to evaluate for cutaneous lymphoma or small-fiber neuropathy (reduced intraepidermal nerve-fiber density) 2, 3

Immediate Symptomatic Management (Start While Awaiting Results)

First-Line Topical Therapy

• Apply high-lipid emollients liberally at least twice daily to all affected areas—this is universal first-line therapy for all pruritus and directly addresses the xerosis that lowers your threshold for itch 2, 3
• Topical menthol 1-3% or pramoxine 1% for immediate cooling relief 2, 3
• Low-potency topical corticosteroid (clobetasone butyrate 0.05%) for 2 weeks to treat any underlying asteatotic eczema contributing to lichenification 2

Systemic Therapy for Lichenified Skin

Gabapentin is your first-line systemic agent because lichenification with a burning/painful quality strongly suggests neuropathic pruritus from chronic scratching-induced nerve damage 2, 3:

• Start gabapentin 300 mg at bedtime, titrate to 300-1200 mg daily in divided doses over 1-2 weeks based on response 2, 3
• Do not use sedating antihistamines long-term due to dementia risk (Strength B) 2
• Non-sedating antihistamines (fexofenadine 180 mg or loratadine 10 mg daily) provide modest symptomatic relief but are generally ineffective for systemic causes 2

Cause-Specific Treatment Algorithms (Once Diagnosis Established)

If Iron Deficiency Confirmed (Despite "Normal" Initial Studies)

• Oral iron replacement (ferrous sulfate 325 mg daily or 65 mg elemental iron) leads to complete cessation of pruritus within days to weeks 2, 3, 4, 5
• Iron deficiency was the most common systemic cause in a prospective study of generalized pruritus 5

If Cholestatic Liver Disease (Elevated Bile Acids)

• First-line: Rifampin 150 mg twice daily (Strength A) 2, 3
• Second-line: Cholestyramine 9 g daily 2, 3
• Third-line: Sertraline 75-100 mg daily 2, 3
• Avoid gabapentin in hepatic disease—it is ineffective and contraindicated 2

If Uremic Pruritus (Elevated Creatinine)

• Broadband UVB phototherapy is the most effective treatment (Level 1+ evidence) 2, 3
• Optimize dialysis adequacy (Kt/V ≥1.6) to relieve pruritus in ~40% of patients 3
• Continue gabapentin 300-1200 mg daily as adjunct 2, 3

If Polycythemia Vera (JAK2 Mutation Positive)

• Low-dose aspirin 81 mg daily for immediate relief 2
• Paroxetine (selective serotonin reuptake inhibitor) shows >80% response rate 2
• Interferon-α for intractable cases reduces pruritus in up to 81% 2

If Neuropathic Pruritus (Small-Fiber Neuropathy on Biopsy)

• Continue gabapentin 300-1200 mg daily as primary therapy 2, 3
• Add topical lidocaine 5% or capsaicin 0.025-0.1% to lichenified areas 3
• Consider pregabalin as alternative if gabapentin fails 2, 3

Behavioral Interventions to Break the Itch-Scratch Cycle

Lichenification indicates chronic scratching has created a self-perpetuating cycle that requires behavioral modification 2, 3:

• Habit-reversal training: substitute scratching with clenching fists, applying pressure, or ice packs 2, 3
• Keep nails trimmed short and consider wearing cotton gloves at night 2, 3
• Avoid hot water and use lukewarm showers only 2, 3
• Stress-reduction techniques (cognitive behavioral therapy, relaxation exercises) to address psychological triggers 2, 3
• Patient support groups can be beneficial 2

Referral Criteria

Refer to Dermatology if:

• Pruritus persists >2-4 weeks despite first-line therapy 2, 3
• Diagnostic uncertainty remains after initial workup 2
• Lichenification progresses despite treatment 2, 3

Refer to Hepatology if:

• Liver enzymes >3× upper limit of normal, elevated bilirubin, or elevated bile acids 3

Refer to Nephrology if:

• Elevated creatinine requiring dialysis optimization 3

Refer to Neurology if:

• Small-fiber neuropathy confirmed on biopsy and refractory to gabapentin 3

Critical Pitfalls to Avoid

• Never accept "normal iron studies" without confirming that serum iron, ferritin, AND transferrin saturation were all measured—ferritin can be falsely normal with inflammation 3, 1
• Never assume antihistamines alone will control systemic pruritus—they are ineffective for cholestatic, uremic, or neuropathic causes 2, 3, 1
• Never use sedating antihistamines long-term due to dementia risk, especially in elderly patients (Strength B) 2
• Never delay comprehensive workup because 22% of generalized pruritus cases have an identifiable systemic cause, with pruritus being the initial symptom in 15% 5
• Never use gabapentin for hepatic pruritus—it is ineffective and potentially harmful 2