What is the updated protocol for diagnosis and management of secondary prurigo nodularis?

Updated Protocol for Diagnosis and Management of Secondary Prurigo Nodularis

Diagnostic Approach

Secondary prurigo nodularis requires systematic exclusion of underlying systemic causes through targeted investigations, as the condition often represents a cutaneous manifestation of internal disease rather than a primary dermatosis. 1

Clinical Diagnosis Criteria

The core diagnostic findings include:

• Firm, nodular hyperkeratotic lesions with intense pruritus lasting at least 6 weeks 1
• History or visible signs of repeated scratching, picking, or rubbing 1
• Symmetric distribution typically on extensor surfaces of extremities and trunk 2, 3

Histopathological Features (When Biopsy Indicated)

Skin biopsy should be considered for persistent unexplained cases to evaluate for cutaneous lymphoma or small fiber neuropathy 4. Key features include:

• Marked epidermal hyperplasia with pronounced hyperkeratosis and irregular acanthosis 5
• Dermal fibrosis with thickened collagen bundles and vertical arrangement of collagen fibers 5
• Dense dermal cellular infiltrates composed primarily of type 2 inflammation-associated immune cells 5

Mandatory Initial Investigations for Secondary Causes

All patients with prurigo nodularis must undergo comprehensive screening for systemic diseases, as 20-30% of generalized pruritus cases have significant underlying causes 6. The British Association of Dermatologists recommends:

• Full blood count and ferritin levels (iron deficiency is a common treatable cause) 4
• Liver function tests and serum bile acids (cholestatic liver disease is a major cause) 6, 4
• Urea, electrolytes, and creatinine (chronic kidney disease and uremia are well-established causes) 4
• Fasting glucose and glycated hemoglobin (diabetes is a common comorbidity) 6, 3
• Thyroid function tests (if clinical features suggest thyroid disease) 6, 4
• HIV and hepatitis A, B, and C serology (with appropriate risk history) 6, 4

Additional Investigations Based on Clinical Suspicion

• JAK2 V617F mutation analysis if polycythemia vera suspected (presents with aquagenic pruritus) 4
• Calcium, phosphate, and parathyroid hormone for renal-related pruritus 6
• Immunoglobulins to screen for hematological disorders 6
• CT scan of neck, thorax, abdomen, and pelvis if malignancy suspected 6
• Screening for parasitic infections (malaria, strongyloidiasis, schistosomiasis) with appropriate travel history 6

Management Protocol

Step 1: Treat Underlying Systemic Disease

Treating the underlying disease is essential and takes priority over symptomatic management 4. Specific interventions include:

• Iron replacement therapy for iron deficiency (can lead to complete cessation of pruritus shortly after treatment begins) 4
• Management of renal disease for uremic pruritus 4
• Treatment of cholestatic liver disease 4
• Control of diabetes and thyroid disorders 3
• Addressing malignancy or hematological disorders 4

Step 2: Break the Itch-Scratch Cycle

First-Line Topical Therapy

• Emollients with high lipid content (particularly important in elderly patients) 6
• Topical corticosteroids for at least 2 weeks to treat inflammatory component 6, 7
• Topical calcineurin inhibitors (demonstrated beneficial effect with level 2b evidence) 7

Avoid topical doxepin beyond 8 days and limit to 10% body surface area due to allergic contact dermatitis risk 6. Calamine lotion is not recommended as there is no literature supporting its use 6.

Phototherapy

• Phototherapy and photochemotherapy show good partial response rates with level 2b or greater evidence in 6 of 8 studies 7

Step 3: Systemic Therapy for Refractory Cases

Treatment should address both neural and immunologic components of pruritus and be tailored based on clinical presentation, comorbidities, and prior treatment response 1.

Neuromodulatory Agents (Preferred for Neuropathic Component)

• Gabapentin (particularly beneficial in elderly patients with pruritus) 6
• Pregabalin (demonstrated promising evidence in level 2b studies) 7

Antidepressants (For Psychogenic Component)

• Amitriptyline, paroxetine, or fluvoxamine (level 2b evidence for benefit) 7
• Psychotropic drugs and psychological therapy for psychogenic pruritus 4

Immunosuppressive Agents

• Cyclosporine or methotrexate (demonstrated benefit though with level 4 evidence) 7
• Thalidomide (6 studies showing good symptom response, but only 2 with level 2b evidence) 7

Step 4: Referral to Secondary Care

Refer patients to dermatology when:

• Diagnostic doubt exists 6
• Primary care management fails to relieve symptoms 6
• Patient is significantly distressed despite initial treatment 6

Critical Pitfalls to Avoid

• Do not use sedating antihistamines in elderly patients (increased fall risk) 6
• Do not prescribe nonsedating antihistamines beyond a short trial (limited evidence for GPUO) 6
• Do not assume prurigo nodularis is purely dermatological - maintain vigilance for developing systemic disease requiring reinvestigation 6
• Do not overlook psychiatric comorbidities - anxiety and depression are common and require concurrent management 3, 8

Follow-Up Protocol

GPs should regularly follow up patients where the underlying systematic cause is not evident initially, as secondary causes may manifest later 6. Reassess patients who have not responded to initial treatment after 2 weeks 6.

Disease Burden Considerations

Prurigo nodularis profoundly impacts quality of life with intense relentless itching, poor sleep, work absence, anxiety, and depression 3. Early diagnosis and identification of comorbidities facilitate better disease management and should prompt aggressive treatment 3.