Generalised Pruritus in a 55-Year-Old Female - Clinical Approach

Definition & Classification

Differential Diagnosis - Systemic Causes (Priority List)

1. Hepatobiliary (Very common at this age)

• Cholestatic liver disease - primary biliary cholangitis (PBC), primary sclerosing cholangitis, intrahepatic cholestasis
• PBC peaks in women aged 40-60; pruritus is often the presenting symptom and may precede jaundice by years
• Bile salts accumulating in skin activate itch-mediating nerve fibres (via TGR5 receptors and lysophosphatidic acid)

2. Chronic Kidney Disease (CKD-aP)

• 25-45% of haemodialysis patients suffer from pruritus
• Can be generalised or localised, fluctuating in intensity
• Antihistamines are largely ineffective (histamine is not the primary mediator)
• IL-31, peripheral opioid system dysregulation, and neuropathic mechanisms implicated
• Source: Dermatology 2-Volume Set 5e

3. Thyroid Disease

• Both hypothyroidism (dry skin-mediated) and hyperthyroidism (increased skin blood flow, sweating) can cause generalised itch
• At 55, perimenopausal thyroid dysfunction is common

4. Haematological

• Iron deficiency anaemia - one of the most common causes in women; depletion of iron-containing enzymes in skin
• Hodgkin lymphoma - pruritus is a B-symptom; may precede lymphadenopathy by months. A chest X-ray is recommended in any unexplained pruritus workup
• Polycythaemia vera - characteristic aquagenic pruritus (itching on contact with water)
• Myelodysplastic syndrome, CLL

5. Internal Malignancy (Paraneoplastic)

• Breast, pancreatic, gastric, lung carcinoma
• Pruritus may be the first sign, preceding diagnosis by months
• Effective treatment of the underlying malignancy resolves the itch
• Source: Fishman's Pulmonary Diseases and Disorders

6. Endocrine / Metabolic

• Diabetes mellitus - generalised or localised itch
• Hyperparathyroidism
• Carcinoid syndrome

7. Perimenopausal / Hormonal

• Falling oestrogen causes skin atrophy, xerosis, and altered skin barrier - a very relevant cause in a 55-year-old woman
• May co-exist with other causes

8. Drug-Induced

• Opioids, aspirin, ACE inhibitors, statins, HRT (oestrogens can cause cholestasis), antimalarials, bupropion

History - Key Points to Elicit

• Character: Continuous vs. episodic? Nocturnal (scabies, eczema)? Aquagenic (PV)?
• Distribution: Truly generalised vs. concentrated areas?
• Skin lesions: Primary eruption absent? Secondary changes (excoriations, lichenification, prurigo nodules)?
• Systemic symptoms: Fatigue, weight loss, night sweats (lymphoma/malignancy), jaundice, dark urine (hepatic), polyuria/polydipsia (diabetes), palpitations/heat intolerance (thyroid), bone pain
• Menstrual history / menopausal status
• Drug history including OTC supplements, herbal preparations
• Family history - atopy, PBC
• Alcohol use - hepatic disease

Physical Examination

1. Skin: Confirm absence of primary rash; look for secondary changes (excoriations, prurigo nodules, lichenification). Check for jaundice, pallor, scratch marks
2. Lymph nodes: Generalised lymphadenopathy (lymphoma)
3. Abdomen: Hepatosplenomegaly, ascites
4. Thyroid: Goitre, signs of hypo/hyperthyroidism
5. Eyes/nails: Pallor, leukonychia (hypoalbuminaemia)

Investigation Protocol

First-Line (Initial Workup)

Second-Line (If first-line inconclusive)

Management Principles

Red Flags Requiring Urgent Referral

• Unexplained weight loss / night sweats / fever (malignancy/lymphoma)
• Palpable lymphadenopathy or organomegaly
• Jaundice with pruritus
• Abnormal FBC (blasts, atypical lymphocytes, polycythaemia)
• Failure to respond to treatment after 6 weeks