What is the best approach to manage generalized pruritis without a rash in a patient?

Management of Generalized Pruritus Without Rash

Begin with a systematic laboratory workup to identify treatable systemic causes, prioritizing iron studies as iron deficiency is the most common reversible cause of generalized pruritus in patients with underlying systemic disease. 1

Initial Clinical Assessment

Obtain a detailed history focusing on:

• Dietary patterns (vegetarian/vegan diets suggesting iron deficiency) 1
• Sources of blood loss (gastrointestinal symptoms, menstruation) 1
• Travel history (malaria, strongyloidiasis, schistosomiasis) 1
• Complete medication review, as 20-30% of cases are drug-induced 2
• Duration of symptoms (chronic defined as >6 weeks) 1

Physical examination must assess for:

• Secondary skin changes from scratching (excoriations, lichenification) that may obscure the absence of primary dermatosis 1
• Body surface area involved 2
• Signs of systemic disease 1

Mandatory Laboratory Investigation

Order the following tests in all patients with chronic generalized pruritus without rash: 1

• Complete blood count and ferritin (most important—iron deficiency causes 25% of systemic pruritus cases) 1
• Comprehensive metabolic panel (urea, electrolytes, liver function tests) 1
• Thyroid-stimulating hormone 1
• Iron studies including serum iron and total iron binding capacity if ferritin is "normal" but clinical suspicion remains 1

Critical caveat: Ferritin is an acute-phase protein and may appear falsely normal or elevated despite true iron deficiency. 1

Consider additional testing based on clinical context: 1

• HIV and hepatitis A, B, C serology
• Bile acids and antimitochondrial antibodies if liver disease suspected
• Tissue transglutaminase antibodies if iron deficiency is unexplained (check IgA levels simultaneously as IgA deficiency causes false negatives) 1

Treatment Algorithm Based on Identified Cause

Iron Deficiency (Most Common Treatable Cause)

Initiate iron replacement if: 1

• Ferritin below 15-25 μg/L (lower limit of reference range)
• Anemia or microcytosis present without other explanation
• Clinical suspicion remains despite "normal" ferritin

Iron replacement can produce complete cessation of pruritus shortly after starting therapy. 1

Cholestatic Pruritus

Use cholestyramine for pruritus associated with partial biliary obstruction. 3 This bile acid sequestrant removes bile acids from enterohepatic circulation, reducing dermal tissue deposition that causes itch. 3

Symptomatic Management When Cause Unknown or Untreatable

For mild disease: 2

• Topical emollients applied liberally and frequently
• Mild-to-moderate potency topical corticosteroids 3-4 times daily

For moderate disease: 2

• Medium-to-high potency topical corticosteroids twice daily
• Oral antihistamines: fexofenadine 180 mg, loratadine 10 mg, or cetirizine 10 mg daily

For severe disease: 2

• High-potency topical corticosteroids with emollients
• Systemic corticosteroids: prednisone 1 mg/kg/day, tapering over at least 4 weeks

For neuropathic or mixed etiology (when systemic workup negative): 4

• Topical neuropathic agents (menthol, pramoxine, lidocaine)
• Gabapentin for neuropathic pruritus 1, 4
• Antidepressants (sertraline, doxepin, mirtazapine) 1, 4
• Opioid receptor modulators (naltrexone, butorphanol) 4

Critical Pitfalls to Avoid

Do not use sedating antihistamines (hydroxyzine) long-term, especially in elderly patients, due to dementia risk and limited efficacy for chronic pruritus. 2, 5 Despite FDA approval for pruritus 6, guidelines explicitly recommend against this practice. 2, 5

Do not delay specialist referral if: 2, 5

• Symptoms fail to improve after 4-6 weeks of appropriate therapy
• Diagnostic uncertainty exists
• Symptoms worsen despite treatment

Do not accept "normal" ferritin at face value—check serum iron and total iron binding capacity if clinical suspicion for iron deficiency remains, as ferritin elevation from inflammation can mask deficiency. 1

Special Populations

For hematologic malignancy-associated pruritus: 1

• Lymphoma: Consider cimetidine, carbamazepine, gabapentin, or mirtazapine
• Polycythemia vera: Cytoreductive therapy, aspirin, interferon-α, SSRIs, or phototherapy

For uremic pruritus: 1

• Ensure adequate dialysis
• Normalize calcium-phosphate balance
• Control parathyroid hormone
• Correct anemia with erythropoietin

For paraneoplastic pruritus from solid tumors: 1

• Paroxetine, mirtazapine, granisetron, or aprepitant