What are the causes and treatment options for generalized itching without rash or other symptoms?

Causes of Generalized Itching Without Rash

Generalized pruritus without rash most commonly results from iron deficiency anemia, chronic kidney disease, cholestatic liver disease, or polycythemia vera, and requires systematic laboratory investigation to identify the underlying cause. 1

Primary Causes to Investigate

Disorders of Iron Metabolism

• Iron deficiency is the most common systemic cause, accounting for 25% of all patients with pruritus due to systemic disease 1
• Iron deficiency can cause generalized itching even before anemia develops, and iron replacement often leads to complete cessation of pruritus shortly after starting therapy 1
• Iron overload (haemochromatosis or hyperferritinaemia) can also cause generalized pruritus 1
• Check full blood count and ferritin levels in all patients with chronic generalized pruritus without rash 1

Renal Disease

• Uremia and chronic kidney disease are well-established causes of generalized pruritus 1, 2
• Urea and electrolytes should be part of the initial investigation 1

Hepatic Disease

• Cholestatic liver disease is a major cause, particularly primary biliary cholangitis 1, 2
• Liver function tests should be performed in all cases 1
• Consider bile acids and antimitochondrial antibodies if liver disease is suspected 3

Hematological Disorders

• Polycythemia vera presents with characteristic aquagenic pruritus (intense itching triggered by water contact) 1
• Hodgkin lymphoma classically causes pruritus, often with night sweats, fever, and weight loss 1, 4
• Non-Hodgkin lymphoma rarely causes pruritus 1
• Hematological causes account for approximately 2% of cases 1

Endocrine and Metabolic Disorders

• Thyroid disease (both hypothyroidism and hyperthyroidism) can cause generalized pruritus 2, 5
• Diabetes mellitus is an associated cause 2, 5
• Routine endocrine testing is not recommended unless clinical features suggest specific endocrinopathy 1

Malignancy

• Solid tumors can cause paraneoplastic pruritus 1, 2
• Pruritus with systemic symptoms of malignancy (weight loss, night sweats) requires tailored investigations 1

Infections

• HIV, hepatitis B, hepatitis C should be considered based on risk factors 3, 5
• Consider screening for malaria, strongyloidiasis, and schistosomiasis with appropriate travel history 1

Drug-Induced Pruritus

• Opioids are a common cause of drug-induced pruritus 1
• Medication review is essential in all cases 3
• Trial cessation of suspected medications if risk-benefit analysis is acceptable 1

Neurological and Psychological Causes

• Small fiber neuropathy can present as generalized pruritus 1
• Psychogenic pruritus (functional itch disorder) is a diagnosis of exclusion 2, 6
• Stress and emotional factors can trigger or worsen pruritus 7

Age-Related Causes

• Pruritus of elderly skin (senile pruritus) is common but requires exclusion of other causes 1, 2
• Asteatotic eczema should be excluded with a 2-week trial of emollients and topical steroids 3

Pregnancy-Associated Pruritus

• Pregnancy can cause generalized pruritus without rash 1, 6

Generalized Pruritus of Unknown Origin (GPUO)

• Represents chronic itch where no underlying cause is identified despite comprehensive workup 1, 2
• This is a diagnosis of exclusion after thorough investigation 6

Essential Diagnostic Workup

Order these investigations in all patients with chronic generalized pruritus without rash:

• Full blood count and ferritin levels (check iron studies if ferritin is borderline or patient has microcytosis) 1, 3
• Liver function tests 1, 3
• Urea and electrolytes (renal function) 1, 3
• Blood film, lactate dehydrogenase, and ESR if hematological disorder suspected 1
• HIV and hepatitis serology if risk factors present 3
• Thyroid function tests only if clinical features suggest thyroid disease 1

Critical Pitfalls to Avoid

• Do not assume antihistamines will work – only a small percentage of patients with generalized pruritus respond to H1 antihistamines, indicating non-histaminergic mechanisms 6
• Ferritin is an acute-phase protein and may be falsely elevated despite iron deficiency; check serum iron and total iron binding capacity if iron deficiency is suspected 1
• IgA deficiency can cause falsely negative tissue transglutaminase antibodies in celiac disease workup 1
• Avoid long-term sedative antihistamines except in palliative care due to potential dementia risk 3