What is the recommended etiological workup for a patient presenting with pruritus?

Recommended Etiological Workup for Pruritus

For patients presenting with pruritus, a systematic etiological workup should begin with basic laboratory investigations including full blood count, ferritin levels, liver function tests, and renal function tests, followed by targeted investigations based on clinical suspicion. 1

Initial Assessment

• A thorough history and physical examination should be performed to identify potential underlying causes, with special attention to the presence or absence of primary skin lesions 1, 2
• Classify pruritus as either with an underlying dermatosis or without (generalized pruritus without rash - GPWOR) 1
• Document duration (acute: <6 weeks; chronic: >6 weeks) as this affects diagnostic approach 1

Basic Laboratory Investigations for All Patients

• Full blood count and ferritin levels should be checked in all patients with chronic generalized pruritus without rash (GPWOR) 1
• Liver function tests (LFTs) should form part of the investigation of generalized pruritus of unknown origin (GPUO) 1
• Urea and electrolytes should be included in the initial workup to assess for renal dysfunction 1

Targeted Investigations Based on Clinical Suspicion

Iron Metabolism Disorders

• For suspected iron deficiency: check serum iron and total iron binding capacity if ferritin is "normal" but deficiency is still suspected 1
• For unexplained iron deficiency: test for tissue transglutaminase (TTG) antibodies to rule out celiac disease 1
• For suspected iron overload: consider liver function tests 1

Hematological Disorders

• If hematological involvement is suspected: include blood film, lactate dehydrogenase, and erythrocyte sedimentation rate 1
• For suspected polycythemia vera (especially with aquagenic pruritus): test for JAK2 V617F mutation 1
• In the absence of JAK2 mutation but with persistent suspicion of polycythemia: check serum erythropoietin level, oxygen saturation, chest X-ray, and abdominal ultrasound 1

Malignancy

• Full investigation to rule out malignancy is not routinely recommended unless there are specific systemic symptoms 1
• Consider lymphoma workup if there are B symptoms (night sweats, weight loss, fever) 1
• Skin biopsy may be indicated in persistent, unexplained pruritus to rule out cutaneous lymphoma 1

Endocrine Disorders

• Routine endocrine investigations (including thyroid function tests) are not recommended unless there are additional clinical features suggesting diabetes, thyroid disease, or other endocrinopathies 1
• Consider vitamin D level assessment as deficiency may contribute to pruritus 1

Liver and Renal Disease

• For suspected liver disease: consider bile acids and antimitochondrial antibodies in addition to standard LFTs 1
• Refer to hepatology if significant hepatic impairment is detected 1

Neuropathic Causes

• Detailed neurological investigation is only advised if clinically indicated 1
• Consider skin biopsy if small fiber neuropathy is suspected 1

Infections and Infestations

• Take a detailed travel history 1
• Consider HIV and hepatitis A, B, and C serology 1, 3
• In appropriate clinical settings, consider screening for malaria, strongyloidiasis, and schistosomiasis 1

Drug-Induced Pruritus

• Perform a comprehensive medication review 1
• Consider a trial of cessation of suspicious medications if the risk-benefit analysis is acceptable 1

Special Considerations

Elderly Patients

• Pruritus in the elderly (Willan's itch) requires special attention to xerosis but should not be assumed to be only age-related 1
• Consider bullous pemphigoid in elderly patients with unexplained pruritus, which may require skin biopsy and indirect immunofluorescence 1
• Avoid sedating antihistamines in elderly patients 1

When to Refer to Secondary Care

• Refer patients with GPUO if there is diagnostic doubt or if primary care management does not relieve symptoms 1
• Any suggestion of significant hepatic impairment should lead to referral to a hepatology center 1
• Patients with suspected polycythemia vera or lymphoma should be referred to hematology 1

Common Pitfalls to Avoid

• Assuming pruritus is solely due to dry skin without adequate investigation 1
• Failing to follow up patients with persistent unexplained pruritus, as the underlying cause may not be evident initially 1
• Overlooking drug-induced causes of pruritus 1
• Not considering malignancy in older patients with chronic generalized pruritus without primary skin lesions 2
• Performing excessive testing without clinical indication, leading to unnecessary patient anxiety and healthcare costs 1