What are the causes and treatment options for generalized pruritis (itching) in an adult male that occurs both day and night?

Generalized Pruritus in Adult Males: Causes and Systematic Approach

All adult males with generalized day-and-night pruritus require immediate laboratory screening for iron deficiency, renal disease, liver disease, and hematologic malignancies, as these represent the most common life-threatening causes. 1, 2

Primary Systemic Causes to Consider

Iron Deficiency (Most Common)

• Iron deficiency is the single most common systemic cause, accounting for 25% of all pruritus cases with systemic disease 3
• Check full blood count and ferritin in all patients with chronic generalized pruritus 1, 2
• Critical pitfall: Ferritin is an acute-phase protein and may appear falsely normal or elevated despite true iron deficiency 1, 3
• If ferritin is "normal" but suspicion remains, check serum iron and total iron binding capacity 1, 3
• Iron replacement often produces complete cessation of pruritus shortly after starting therapy 3

Hematologic Malignancies (2% of cases but life-threatening)

• Night itching with weight loss, fevers, and night sweats strongly suggests lymphoma 1
• Hodgkin lymphoma is particularly associated with generalized pruritus, while non-Hodgkin lymphoma is less common 1
• Aquagenic pruritus (intense itching triggered by water contact without skin lesions) is characteristic of polycythemia vera 1
• Order full blood count, blood film, lactate dehydrogenase, and ESR 1
• If polycythemia vera suspected (raised hemoglobin/hematocrit with microcytosis, raised white cells/platelets, low ESR), test for JAK2 V617F mutation (present in 97% of cases) 1

Renal Disease (Uremic Pruritus)

• Chronic kidney disease and uremia are well-established causes 3
• Check urea and electrolytes in all patients 4, 2, 3

Hepatic Disease (Cholestatic Pruritus)

• Cholestatic liver disease, particularly primary biliary cholangitis, is a major cause 3
• Order liver function tests in all patients 4, 2, 3
• Consider bile acids and antimitochondrial antibodies if liver disease suspected 4, 2

Iron Overload

• Both hemochromatosis and hyperferritinaemia without hemochromatosis can cause generalized pruritus 1

Mandatory Initial Laboratory Workup

Order these tests in every adult male with generalized pruritus:

• Full blood count with differential 1, 2
• Ferritin level (with serum iron and TIBC if ferritin appears normal but suspicion remains) 1, 2, 3
• Liver function tests 4, 2, 3
• Urea and electrolytes 4, 2, 3
• HIV and hepatitis A, B, C serology if risk factors present 4, 2

Do NOT routinely order:

• Thyroid function tests unless clinical features suggest endocrinopathy 2, 3
• Extensive malignancy screening without specific systemic symptoms 2

Medication Review (Often Overlooked)

Perform comprehensive medication review immediately, as drug-induced pruritus is common and reversible 4, 2

• Opioids are a particularly important cause in palliative medicine 5
• Trial cessation of potentially causative medications when risk-benefit analysis permits 4, 2

Initial Symptomatic Treatment While Investigating

First-Line Therapy

• Emollients to maintain skin hydration 4, 2
• Topical doxepin 4
• Topical clobetasone butyrate or menthol preparations 4

Second-Line Therapy

• Non-sedating antihistamines (fexofenadine or loratadine) 4, 2
• Avoid sedating antihistamines except in palliative care due to dementia risk 4, 2, 3

Third-Line Therapy

• Paroxetine, fluvoxamine, or mirtazapine 4

Critical Red Flags Requiring Urgent Referral

• Night itching with weight loss, fevers, night sweats → immediate hematology referral for lymphoma workup 1
• Enlarged lymph nodes or masses → excision or ultrasound-guided core biopsy 1
• Aquagenic pruritus → hematology referral for polycythemia vera evaluation 1
• Significant hepatic impairment → hepatology referral 2

Common Pitfalls to Avoid

• Do not miss iron deficiency by relying solely on ferritin (check iron studies if suspicion remains despite "normal" ferritin) 1, 3
• Do not overlook medication review as a simple reversible cause 4, 2
• Do not use long-term sedating antihistamines outside palliative care settings 4, 2, 3
• Do not pursue extensive cancer screening without specific systemic symptoms 2
• Do not forget that systemic causes may not be immediately apparent – regular follow-up is essential 2

Special Consideration for Elderly Males

• Initiate a 2-week trial of emollients and topical steroids first to exclude asteatotic eczema before extensive workup 4, 2
• Use moisturizers with high lipid content 2
• Avoid sedating antihistamines due to dementia risk 4, 2
• Consider gabapentin if initial treatments fail 2