Treatment Approach for Prurigo Nodularis
Start with high-potency topical corticosteroids combined with antipruritic agents, then escalate systematically to phototherapy, gabapentinoids, and immunomodulators if symptoms persist beyond 2-4 weeks, as all current treatments remain off-label in the absence of FDA-approved therapies. 1
Initial Diagnostic Confirmation
Before initiating treatment, confirm the diagnosis requires three core findings: firm nodular lesions, pruritus lasting at least 6 weeks, and documented history or physical signs of repeated scratching, picking, or rubbing. 1 Complete a thorough review of systems to identify potential systemic diseases (renal disease, hepatic disorders, hematologic conditions, malignancy) that may drive the pruritic component. 1 Assess disease severity including both disease burden and pruritus intensity using standardized scales. 1
First-Line Topical Therapy (Weeks 1-4)
Begin with high-potency topical corticosteroids applied 3-4 times daily for up to 7 days maximum to control active inflammation, using triamcinolone 0.1% as an effective option. 2 Combine this with emollients applied at least once daily to restore skin barrier function, preferring oil-in-water creams or ointments over alcohol-containing lotions. 2 Add topical calcineurin inhibitors (tacrolimus, pimecrolimus) as steroid-sparing agents, which have demonstrated beneficial effects in systematic reviews. 3
For additional symptomatic relief, incorporate menthol 0.5% preparations or capsaicin cream to address the neural component of pruritus. 2, 3 Topical calcipotriol has also shown benefit in level 2b evidence studies. 3
Systemic Antipruritic Therapy (Concurrent with Topicals)
Address both neural and immunologic components of pruritus simultaneously. 1 For daytime management without sedation, prescribe fexofenadine 180 mg daily or loratadine 10 mg daily. 2 If pruritus interferes with sleep, add hydroxyzine 25-50 mg at bedtime, but avoid sedating antihistamines in elderly patients due to cognitive impairment and dementia risk. 2, 4
For neuropathic pruritus that persists despite initial therapy, escalate to gabapentin 900-3600 mg daily or pregabalin 25-150 mg daily, which have demonstrated promising evidence in level 2b studies. 2, 3 Alternatively, consider antidepressants: paroxetine, fluvoxamine, or amitriptyline have shown benefit in systematic reviews. 3, 4
Second-Line Phototherapy (Weeks 4-8)
If topical and oral antipruritic therapy fails after 2-4 weeks, initiate phototherapy or photochemotherapy. 1 Six of eight reports investigating these modalities achieved level 2b evidence or greater with good partial response rates. 3 Both narrowband UVB and PUVA have demonstrated efficacy for prurigo nodularis. 3
Third-Line Immunomodulators (Weeks 8+)
For refractory cases, escalate to systemic immunomodulators targeting the immunologic dysregulation driven by T-lymphocytes, mast cells, eosinophils, and inflammatory cytokines. 5
Thalidomide has been studied in six reports showing good symptom response, with two achieving level 2b evidence or greater. 3 However, use requires careful risk-benefit assessment given its teratogenicity and neuropathy risks.
Cyclosporine and methotrexate have demonstrated benefit in four combined studies, though evidence remains level 4. 3 These represent reasonable options when other therapies fail.
Neurokinin-1 receptor antagonists (aprepitant) have shown promising evidence in level 2b studies and represent an emerging therapeutic option. 3
Critical Pitfalls to Avoid
Never use topical capsaicin or calamine lotion beyond initial trials, as evidence supporting their efficacy is limited. 2 Do not apply topical doxepin for more than 8 days or on more than 10% body surface area due to contact dermatitis and systemic toxicity risks. 2 Avoid crotamiton cream, which has no significant antipruritic effect versus vehicle. 2
Do not use sedating antihistamines long-term except in palliative care settings, as they predispose to dementia. 4 In elderly patients specifically, exclude asteatotic eczema with a 2-week trial of emollients and topical steroids before pursuing aggressive systemic therapy. 4
Reassessment Protocol
Reassess after 2 weeks if no improvement occurs to investigate for underlying systemic disease such as polycythemia vera, hepatic disease, or uremic conditions. 2 If symptoms persist beyond 4 weeks of appropriate therapy, regrade toxicity and escalate treatment accordingly. 6 Treatment selection must be tailored based on clinical presentation, comorbidities, response to prior treatments, and individual patient needs, as all current therapies remain off-label. 1