What is the best management approach for prurigo nodularis?

Management of Prurigo Nodularis

Start with potent topical corticosteroids (clobetasol propionate 0.05%) as first-line therapy for prurigo nodularis, combined with emollients and topical menthol preparations to break the itch-scratch cycle. 1

First-Line Treatment Approach

• Apply potent topical corticosteroids such as clobetasol propionate 0.05% directly to nodular lesions, limiting duration to avoid side effects like skin atrophy 1
• Use emollients liberally for skin barrier repair and to reduce xerosis that exacerbates pruritus 1
• Add topical menthol preparations for counter-irritant effects that provide immediate pruritus relief 1
• Consider occlusive dressings over topical corticosteroids to enhance penetration and efficacy, as combination approaches show superior response rates 2

The evidence strongly supports topical corticosteroids as foundational therapy, with all studies demonstrating varying levels of positive response 2. Cryotherapy has emerged as an effective lesion-directed option, with one comparative study showing 75-100% nodule clearance in all patients versus only 27% with clobetasol alone 3.

Second-Line Treatment Options

If first-line therapy fails after 2-4 weeks:

• Initiate non-sedating antihistamines: fexofenadine 180 mg or loratadine 10 mg daily 1
• Consider H1/H2 antagonist combination: fexofenadine plus cimetidine for enhanced antipruritic effect 1
• Add phototherapy: narrowband UVB or broadband UVB provides symptomatic relief, though relapse rates are high after discontinuation 1, 2

Phototherapy demonstrates good partial response rates in 6 of 8 studies with level 2b evidence or higher 4, making it a reasonable escalation option.

Third-Line Systemic Therapies

For refractory cases not responding to topical and phototherapy:

• Gabapentinoids for neuropathic pruritus: pregabalin 25-150 mg daily or gabapentin 900-3600 mg daily target the neural component of pruritus 1, 4
• Antidepressants: paroxetine, fluvoxamine, or mirtazapine reduce pruritus intensity through central mechanisms 1, 4
• Aprepitant (neurokinin-1 receptor antagonist) shows efficacy in reducing pruritus with level 2b evidence 1, 4

Advanced Systemic Options

Dupilumab is the most effective systemic agent with the best safety profile, reducing both pruritus and lesion appearance 5. This represents the strongest evidence for systemic therapy in recent literature.

Other systemic options include:

• Thalidomide: demonstrates good symptom response in 6 studies, but long-term use is limited by peripheral neuropathy and teratogenicity 4, 5
• Cyclosporine and methotrexate: show benefit but with level 4 evidence only 4, 5
• JAK inhibitors (baricitinib, tofacitinib): emerging evidence suggests benefit but large population studies are lacking 5

Critical Diagnostic Workup

Before initiating treatment, always investigate for underlying systemic diseases that may be driving prurigo nodularis:

• Screen for renal disease: check creatinine, BUN, and consider dialysis adequacy if applicable 1
• Evaluate for liver disease: obtain liver function tests and consider cholestatic causes 1
• Rule out lymphoma: complete blood count with differential, consider imaging if lymphadenopathy present 1
• Check iron studies: both iron deficiency and overload can cause pruritus 1

Treatments to Avoid

Do not use crotamiton cream, topical capsaicin, or calamine lotion for prurigo nodularis, as they lack significant antipruritic effect and evidence of efficacy 1, 6.

Treatment Algorithm

1. Weeks 0-4: Potent topical corticosteroids + emollients + topical menthol
2. Weeks 4-8: Add antihistamines (H1 ± H2 antagonists) and/or phototherapy if inadequate response
3. Weeks 8-12: Initiate gabapentinoids or antidepressants for neuropathic component
4. Beyond 12 weeks: Consider dupilumab or other systemic immunomodulators for refractory disease

Reassess treatment efficacy every 2 weeks; if no improvement or worsening occurs, escalate to the next treatment tier 1. The goal is complete resolution of pruritus and nodules, not just symptomatic improvement.