What are the differential diagnoses and treatment options for a patient presenting with a pruritic rash?

Differential Diagnoses for Pruritic Rash

The differential diagnosis for a pruritic rash must be systematically approached by first ruling out primary dermatoses, then investigating drug-induced causes, systemic diseases, infections, and finally considering neuropathic or psychogenic etiologies when no cause is identified. 1

Primary Dermatological Conditions

• Eczematous dermatitis (atopic dermatitis, contact dermatitis, xerosis): Most common cause, particularly in winter months with dry skin leading to secondary eczematous changes 2
• Urticaria: Intensely pruritic wheals with lifetime prevalence of 20%, often self-limited but can persist chronically 3
• Autoimmune bullous dermatoses: Consider if blistering is present; requires skin biopsy with direct immunofluorescence 4
• Cutaneous lymphoma: Must be considered if rash persists despite adequate treatment for 2 weeks or in elderly patients with unexplained persistent pruritus 4, 1

Drug-Induced Pruritus

• Review all medications systematically, especially in polypharmacy patients, as drug-induced pruritus is extremely common 4, 1
• Immune checkpoint inhibitor therapy: Can cause pruritic rash in cancer patients, graded by body surface area involvement 4
• Opioid-induced pruritus: Treat with naltrexone as first-line if cessation impossible 4
• Chloroquine-induced: Consider prednisolone 10 mg or niacin 50 mg 4
• Trial cessation of suspected medications when risk-benefit analysis permits 4

Systemic Disease-Associated Pruritus

Hematological Disorders

• Polycythemia vera: Check complete blood count; if elevated hemoglobin/hematocrit, send JAK2 V617F mutation analysis 4
• Iron deficiency or overload: Obtain ferritin level; treat with iron replacement or venesection respectively 4, 1
• Hodgkin and non-Hodgkin lymphoma: Consider if persistent unexplained pruritus; may require skin biopsy to rule out cutaneous involvement 4

Hepatic Disease

• Cholestatic pruritus: Check liver function tests, bile acids, and antimitochondrial antibodies; refer to hepatology if significant impairment 4
• Treatment: Rifampicin first-line, cholestyramine second-line, sertraline third-line before naltrexone 4
• Avoid gabapentin in hepatic pruritus 4

Renal Disease

• Uremic pruritus: Check urea and electrolytes as part of initial workup 4
• Management: Ensure adequate dialysis, normalize calcium-phosphate balance, control parathyroid hormone, correct anemia with erythropoietin 4
• Avoid cetirizine (not effective) and long-term sedating antihistamines (dementia risk) 4

Endocrine/Metabolic

• Do not routinely check thyroid function unless additional clinical features suggest endocrinopathy, diabetes, or renal disease 4, 1
• Vitamin D deficiency: Consider supplementation in generalized pruritus without rash 4

Malignancy

• Solid tumors: Paraneoplastic pruritus can be the presenting feature of squamous cell lung cancer and other malignancies 5
• Do not perform full malignancy workup routinely; tailor investigations only if systemic symptoms suggest specific cancers 4
• Treatment: Paroxetine, mirtazapine, granisetron, or aprepitant for paraneoplastic pruritus 4

Infectious/Parasitic Causes

• Obtain travel history and consider HIV, hepatitis A/B/C serology if risk factors present 4
• Screen for malaria, strongyloidiasis, and schistosomiasis in appropriate clinical contexts 4

Neuropathic Pruritus

• Localized pruritus suggests neuropathic cause (e.g., brachioradial pruritus, notalgia paresthetica) 6
• Consider skin biopsy to confirm small fiber neuropathy if suspected 4
• Refer to neurology for detailed investigation only if clinically indicated 4
• Treatment: Gabapentin 900-3600 mg daily or pregabalin 25-150 mg daily 2

Psychogenic/Functional Itch Disorder

• Consider in distressed patients after ruling out organic causes 4
• Psychosocial interventions: Education on trigger avoidance, relaxation techniques, cognitive restructuring, habit reversal training 4
• Referral to liaison psychiatry or psychology may be helpful in individual cases 4

Chronic Pruritus of Unknown Origin (CPUO)

• Diagnosis of exclusion after comprehensive workup reveals no identifiable cause 6
• Often generalized and chronic, requiring long-term multimodal management 1, 6

Critical Diagnostic Pitfalls

• Perform skin biopsy if lesions persist after 2 weeks of adequate topical treatment or if cutaneous lymphoma, autoimmune bullous disease, or lichenoid reactions are suspected 4, 1
• Reevaluate thoroughly if no response to optimal management after 2 weeks, considering alternative diagnoses 1, 2
• Severe chronic pruritus can cause debilitating psychological distress, behavioral disorders, and social/occupational withdrawal 1