What can I do about persistent itching?

Management of Persistent Itching

For persistent itching without an obvious rash, start with a systematic diagnostic workup including full blood count, ferritin, liver function tests, urea and electrolytes, and thyroid function tests to identify treatable underlying causes, then initiate empiric treatment with emollients and non-sedating antihistamines while awaiting results. 1, 2

Initial Diagnostic Approach

Essential Laboratory Testing

• Check full blood count and ferritin levels in all patients with chronic generalized pruritus, as iron deficiency is a reversible cause that responds to iron replacement therapy 1, 2
• Obtain liver function tests, urea and electrolytes to screen for hepatic and renal causes, which account for significant proportions of secondary pruritus 1, 2
• Consider bile acids and antimitochondrial antibodies if liver disease is suspected based on initial screening 2
• Perform thyroid function testing only if clinical features suggest endocrinopathy, as routine endocrine screening has low yield 1, 3

Critical History Elements

• Ask specifically about water-triggered itching (aquagenic pruritus), which suggests polycythemia vera and warrants JAK2 mutation testing 1
• Inquire about night sweats, fever, and weight loss, as this triad strongly suggests lymphoma requiring lymph node evaluation 1, 4
• Review all medications including over-the-counter and herbal products, as drug-induced pruritus occurs in 12.5% of cutaneous drug reactions 1, 5
• Document travel history and HIV risk factors to screen for infectious causes including hepatitis, schistosomiasis, and strongyloidiasis 1, 2

First-Line Treatment Strategy

Immediate Symptomatic Management

• Apply emollients liberally and frequently to maintain skin hydration, as this addresses xerosis-related pruritus 2, 3
• Use topical hydrocortisone 2.5% or triamcinolone 0.1% for inflammatory components, applied 3-4 times daily to affected areas 6, 3
• Consider topical menthol or pramoxine for neuropathic components, which can be combined with topical steroids 2, 3

Oral Antihistamine Therapy

• Start with non-sedating antihistamines first: fexofenadine 180 mg daily or loratadine 10 mg daily, as these avoid cognitive side effects 1, 2, 3
• Avoid long-term sedating antihistamines (like hydroxyzine) except in palliative care settings due to dementia risk 1, 2
• Consider combining H1 and H2 antagonists (e.g., fexofenadine plus cimetidine) if monotherapy fails 1

Cause-Specific Treatment Algorithms

Iron Deficiency Pruritus

• Replace iron immediately when ferritin is low (typically <15-25 μg/L), as this leads to complete cessation of pruritus in many cases 1, 2
• Test for tissue transglutaminase antibodies if iron deficiency is unexplained, and refer to gastroenterology for possible celiac disease 1

Uremic Pruritus (Kidney Disease)

• Optimize dialysis parameters first, including normalizing calcium-phosphate balance and controlling parathyroid hormone 2
• Initiate broadband UVB phototherapy as the treatment of choice with clinical significance demonstrated in meta-analysis 1, 2
• Avoid cetirizine and long-term sedative antihistamines in this population except for palliative care 2

Hepatic/Cholestatic Pruritus

• Start rifampicin as first-line treatment for cholestatic itch 2
• Use cholestyramine as second-line if rifampicin is ineffective or not tolerated 2
• Consider sertraline as third-line, followed by naltrexone or nalmefene as fourth-line options 2
• Do not use gabapentin for hepatic pruritus, as evidence does not support efficacy 2

Polycythemia Vera-Associated Pruritus

• Prescribe aspirin 300 mg daily, which effectively relieves pruritus in many PV patients 1, 2
• Consider cytoreductive therapy, interferon-alpha, or SSRIs as additional options 1, 2
• Refer for phototherapy (NB-UVB or BB-UVB) if pharmacologic options fail, though relapse is common after stopping 1, 2

Lymphoma-Associated Pruritus

• Treat the underlying lymphoma definitively, as this invariably resolves the pruritus 1, 4
• For symptomatic management during treatment, use cimetidine, gabapentin, carbamazepine, or mirtazapine 1, 2, 4
• Reserve oral corticosteroids for incurable lymphoma as palliative therapy 1, 4
• Consider BB-UVB for Hodgkin lymphoma or NB-UVB for non-Hodgkin lymphoma for temporary relief 1, 2

Second-Line Systemic Therapies

When First-Line Treatments Fail

• Try selective serotonin reuptake inhibitors: paroxetine or fluvoxamine, which modulate central itch perception 1, 2, 3
• Consider mirtazapine, an antidepressant with antihistaminic properties effective for multiple pruritus types 1, 2, 3
• Use gabapentin or pregabalin for neuropathic components, particularly in localized pruritus suggesting nerve involvement 1, 2, 3
• Trial naltrexone for opioid receptor modulation, especially in cholestatic and drug-induced pruritus 1, 2
• Consider ondansetron or aprepitant (neurokinin-1 receptor antagonists) for refractory cases 1, 2

Special Populations and Situations

Drug-Induced Pruritus

• Attempt medication cessation if risk-benefit analysis permits, as this is the definitive treatment 1, 2
• For opioid-induced pruritus that cannot be stopped, use naltrexone as an opioid antagonist 1, 2
• Be aware that indomethacin 25 mg three times daily may help HIV-associated pruritus, though gastric intolerance is common 1

Elderly Patients

• Exclude asteatotic eczema with a 2-week trial of intensive emollients and topical steroids before extensive workup 2
• Avoid sedating antihistamines due to increased fall risk and cognitive impairment 2

Pruritus of Unknown Origin (After Negative Workup)

• Combine topical neuropathic agents with immunomodulatory therapy: menthol or pramoxine plus topical steroids 2, 3
• Consider psychosocial interventions: education on trigger avoidance, relaxation techniques, cognitive restructuring, and habit reversal training 1
• Refer to psychology or psychiatry if significant psychosocial morbidity develops, as anxiety and depression occur in one-third of chronic pruritus patients 1

Critical Pitfalls to Avoid

• Do not perform routine endocrine screening unless clinical features suggest specific endocrinopathy, as yield is extremely low 1
• Do not use long-term sedative antihistamines outside palliative care due to dementia risk and limited efficacy 1, 2
• Do not overlook medication review, as 12.5% of drug reactions present with pruritus without rash 1
• Do not miss scabies, which can present with severe pruritus and minimal skin signs, especially in immunocompromised patients 1
• Do not delay skin biopsy if pruritus persists unexplained, as cutaneous lymphoma rarely presents with normal-appearing skin 1

When to Refer to Dermatology

• Refer when first-line topical and oral therapies fail (approximately 10% of patients) for consideration of systemic immunomodulators like dupilumab or methotrexate 3
• Refer for phototherapy when pharmacologic options are exhausted or contraindicated 1, 2
• Refer urgently if lymphoma or malignancy suspected based on constitutional symptoms or abnormal laboratory findings 1, 4