What is the best approach to manage a patient with chronic pruritis?

Management of Chronic Pruritus

The best approach to managing chronic pruritus begins with identifying the underlying etiology through systematic evaluation, followed by targeted treatment based on whether the cause is inflammatory, neuropathic, systemic, or unknown origin, with emollients and topical therapies forming the foundation of all treatment strategies. 1

Initial Assessment and Diagnostic Workup

Clinical Evaluation

• Perform a thorough skin examination specifically looking for primary lesions (indicating dermatologic disease) versus secondary changes from scratching (excoriations, lichenification, prurigo nodularis) 2, 3
• Examine finger webs, anogenital region, nails, and scalp to identify subtle dermatoses 4
• Review all current medications to rule out drug-induced pruritus, as 20-30% of generalized pruritus cases have a significant underlying systemic cause 2

Laboratory Investigation

For all patients with chronic generalized pruritus without obvious dermatosis, obtain: 1, 2, 3, 4

• Complete blood count with differential (evaluate for hematologic malignancy)
• Comprehensive metabolic panel (assess renal and hepatic function)
• Ferritin levels (iron deficiency is a common reversible cause)
• Thyroid-stimulating hormone
• Iron studies if ferritin is borderline or anemia/microcytosis present

Additional testing based on clinical suspicion: 4

• Tissue transglutaminase antibodies if unexplained iron deficiency
• HIV screening
• Hepatitis serologies
• Chest radiography in older patients with chronic generalized pruritus to evaluate for malignancy

Treatment Algorithm by Etiology

Generalized Pruritus of Unknown Origin (GPUO)

First-line therapy: 1

• Liberal and frequent application of emollients to restore skin barrier
• Topical menthol or clobetasone butyrate for symptomatic relief
• Topical doxepin (limited to 8 days maximum, covering <10% body surface area, not exceeding 12g daily)

Second-line systemic therapy: 1

• Non-sedative antihistamines: fexofenadine 180 mg or loratadine 10 mg daily, or mildly sedative cetirizine 10 mg orally
• Consider combination H1 and H2 antagonists (e.g., fexofenadine plus cimetidine)

Third-line options: 1

• Paroxetine, fluvoxamine, or mirtazapine (antidepressants)
• Naltrexone or butorphanol (opioid receptor modulators)
• Gabapentin or pregabalin (neuropathic agents)
• Ondansetron or aprepitant (antiemetics with antipruritic properties)

Important contraindications: 1

• Do NOT use crotamiton cream or topical capsaicin in GPUO
• Do NOT use calamine lotion

Inflammatory Pruritus (Eczema, Psoriasis, Dermatitis)

Mild disease: 2

• Topical emollients applied liberally and frequently
• Mild-to-moderate potency topical corticosteroids (e.g., hydrocortisone 2.5%) applied 3-4 times daily

Moderate disease: 2, 3

• Continue emollients as foundation
• Medium-to-high potency topical corticosteroids applied twice daily
• Add oral antihistamines: fexofenadine 180 mg, loratadine 10 mg, or cetirizine 10 mg daily

Severe disease: 2

• High-potency topical corticosteroids combined with emollients
• Systemic corticosteroids: prednisone 1 mg/kg/day, tapering over at least 4 weeks
• Consider referral for systemic immunomodulators (dupilumab, methotrexate) if topical therapies fail 3

Neuropathic Pruritus

Topical neuropathic agents: 3, 5

• Menthol, pramoxine, or lidocaine preparations
• Can be used alone or combined with topical steroids for mixed etiology

Systemic neuropathic agents: 1, 3

• Gabapentin or pregabalin
• Antidepressants: sertraline or doxepin
• Opioid receptor agonist/antagonists: naltrexone or butorphanol

Referral: 1

• Patients with confirmed neuropathic pruritus should be referred to the relevant specialist for targeted treatment

Systemic Disease-Associated Pruritus

Uraemic Pruritus

Optimize underlying condition first: 1

• Ensure adequate dialysis
• Normalize calcium-phosphate balance
• Control parathyroid hormone to accepted levels
• Correct anemia with erythropoietin
• Use simple emollients for xerosis

Specific treatments: 1

• BB-UVB phototherapy is the most effective treatment (Strength A recommendation)
• Consider capsaicin cream, topical calcipotriol, or oral gabapentin
• Auricular acupressure or aromatherapy may provide benefit
• Avoid cetirizine (not effective) and long-term sedative antihistamines

Hepatic/Cholestatic Pruritus

Treatment hierarchy: 1

1. First-line: Rifampicin (Strength A recommendation)
2. Second-line: Cholestyramine
3. Third-line: Sertraline
4. Fourth-line: Naltrexone or nalmefene
5. Fifth-line: Dronabinol, phenobarbitone, propofol, or topical tacrolimus

Adjunctive therapies: 1

• BB-UVB or combined UVA/UVB phototherapy
• Transcutaneous electrical nerve stimulation
• Do NOT use gabapentin in hepatic pruritus

Iron Deficiency Pruritus

Iron replacement therapy resolves pruritus in many cases, often shortly after commencement 1

Lymphoma-Associated Pruritus

Treatment options: 1

• Cimetidine, carbamazepine, gabapentin, or mirtazapine
• Oral corticosteroids for incurable lymphoma
• BB-UVB for Hodgkin lymphoma; NB-UVB for non-Hodgkin lymphoma

Polycythemia Vera Pruritus

Multiple effective options: 1

• Cytoreductive therapy, aspirin, interferon-α
• SSRIs, PUVA, UVB phototherapy
• Cimetidine or atenolol

Drug-Induced Pruritus

Opioid-Induced Pruritus

First-choice treatment: 1

• Naltrexone (Strength B recommendation) if cessation of opioid therapy is impossible
• Methylnaltrexone as alternative

Alternative agents: 1

• Ondansetron, droperidol, mirtazapine, or gabapentin

Postoperative Pruritus

• Diclofenac 100 mg rectally 1

Chloroquine-Induced Pruritus

• Prednisolone 10 mg, niacin 50 mg, or combination 1
• Dapsone may relieve itch 1

Psychogenic/Functional Pruritus

Psychosocial interventions: 1

• Education on trigger avoidance and treatment application
• Lifestyle interventions and relaxation techniques
• Cognitive restructuring and behavior modification including habit reversal training
• Patient support groups
• Consider referral to social workers, liaison psychiatry, or psychologists

Phototherapy: 1

• NB-UVB may benefit patients with psychogenic pruritus

Critical Pitfalls to Avoid

Antihistamine Use

Sedative antihistamines (e.g., hydroxyzine, diphenhydramine) should only be used short-term or in palliative care settings due to increased dementia risk with long-term use, particularly in elderly patients 1, 6, 7, 8

• Hydroxyzine is FDA-approved for pruritus at 25 mg three to four times daily for adults 8
• However, effectiveness beyond 4 months has not been established 8

Topical Corticosteroid Use

Limit topical steroid use to 2 weeks maximum to prevent skin atrophy and other adverse effects from prolonged application 6, 7

• For anal pruritus specifically, use 1% hydrocortisone ointment 3-4 times daily for maximum 2 weeks 7

Referral Timing

Do not delay dermatology referral if: 2

• Symptoms worsen despite treatment
• No improvement after 4-6 weeks of appropriate therapy
• Diagnostic uncertainty exists
• Primary care management fails to relieve symptoms 1

Special Populations

Elderly Patients

• Consider a 2-week trial of emollients combined with topical steroids to exclude asteatotic eczema 6, 7
• Avoid long-term sedative antihistamines due to dementia risk 1, 6, 7

Patients with Skin Breakdown

• Optimize wound healing by maintaining skin hydration with frequent emollient application 2
• Protect broken skin from further trauma 2
• Consider skin biopsy if autoimmune disease suspected or diagnosis unclear 2