The Impact of Prurigo Nodularis

This blog series highlights conditions that have a strong impact on people of color and appears as part of Project IMPACT: Improving Medicine’s Power to Address Care and Treatment.

Prurigo nodularis (PN) is a chronic inflammatory skin disease characterized by intensely pruritic, hyperkeratotic nodules on the extremities and trunk. PN is likely a complex disease driven by both environmental and genetic factors, but the underlying mechanisms remain largely unknown. As with other itchy inflammatory skin conditions like atopic dermatitis, PN is also thought to be driven by Th2-type cytokines such as interleukin (IL)-4 and IL-13. Notably, patients with PN also have abnormally high Th22/IL-22 activity. Recent data suggest that PN is driven by both neural and immune dysregulation of itch-encoding sensory neurons, wherein predisposing dermatologic, infectious, neurologic, and psychiatric diseases associated with severe itch promote continuous scratching that then leads to the development of PN.

Recent studies estimate that PN affects between 36.7 and 148.3 per 100,000 people in the United States, with the highest prevalence among patients of color. PN is more common in middle-aged adults, with one study reporting a median age of 62 years.

PN is characterized by symptoms of severe itch for greater than 6 weeks. The itch can be episodic, sporadic, or continuous. It is often worsened by heat, sweating, or irritation from clothing.

PN is associated with systemic conditions such as chronic kidney disease, chronic hepatitis C, chronic obstructive pulmonary disease, congestive heart failure, depression, atopic dermatitis, diabetes, thyroid disease, and malignancy. Because of how commonly patients with PN suffer from these comorbidities, they also experience higher all-cause mortality than patients with other inflammatory dermatoses such as psoriasis and atopic dermatitis.

How do pigmentary demarcation lines impact people of color?

PN disproportionately affects patients of color and is reported to be 3-4 times more common in Black patients than White patients. Black patients unfortunately tend to experience a more recalcitrant presentation, with larger, firmer nodules that are more acanthotic and hyperkeratotic on histology. Black patients with PN are also more likely to experience more severe itch and a larger decline in quality of life. This itch is accompanied by greater systemic inflammation overall, with higher erythrocyte sedimentation rates, C-reactive protein, ferritin, and eosinophils.


What to look for:

Skin exam:

  • 3-mm to 2-cm firm or indurated nodules that can be dome shaped, smooth topped, or crusted
  • Nodules are distributed along extremities and trunk, most classically in a distribution of areas that are accessible for the patient to scratch themselves
  • Impetiginization of nodules is common
  • Skin of color
    • Patients with skin of color tend to present with more nodules that are often larger and firmer, with more acanthosis and hyperkeratosis on histology

Healed or regressed nodules may result in more obvious postinflammatory hyperpigmentation


  • Hypertrophic lichen planus – characterized by thick hyperkeratotic plaques often on the anterior leg; histology would reveal a lichenoid infiltrate and thereby help differentiate between PN and hypertrophic lichen planus
  • Epidermolysis bullosa pruriginosa – variant of dystrophic epidermolysis bullosa; diagnosis confirmed by the appropriate immunofluorescence studies and histologically distinct from PN
  • Multiple keratoacanthomas – unlike PN, there is an absence of pruritus and different histologic features including keratin pseudocysts
  • Acquired reactive perforating dermatoses
  • Kaposi sarcoma – unlike PN, Kaposi sarcoma is not commonly itchy; Kaposi sarcoma also can also develop on mucous membranes
  • Pemphigoid nodularis – a variant of bullous pemphigoid; diagnosis is distinguishable from PN by histological direct immunofluorescence with linear IgG and C3 along the basement membrane
  • Dermatofibromas – not commonly itchy; positive “dimple sign” or “Fitzpatrick sign” upon squeezing the lateral edges
  • Nodular scabies – patients have an exposure to scabies
  • Bullous and nonbullous impetigo – unlike in PN, the face is the most common location, especially around the nose and mouth


Diagnostic Pearls:

Suspect PN in patients for whom nodules are missing in hard-to-reach areas, such as the midback and interscapular area.

When caring for patients with PN, screen for potential co-morbid diseases such as HIV, diabetes, and chronic kidney disease.



Of note, there are currently no US Food and Drug Administration (FDA)-approved treatments for prurigo nodularis.

First line:

Supportive care

  • Symptomatic control of skin inflammation
    • Mild cleansers
    • Topical emollients, as needed
    • Calamine or camphor lotion, topically as needed
  • Minimize scratching
    • Keep nails short
    • Wear gloves at night
  • Antihistamines
    • hydroxyzine; 25 mg 3-4 times daily, orally
    • diphenhydramine; 25-50 mg 3-4 times daily, orally
  • Corticosteroids
    • betamethasone; 0.05% lotion/cream/ointment 1-2 times daily, topically
      • MAX 50 g/wk or 50 mL/wk
      • MAX duration, 2 consecutive weeks
    • clobetaso; 0.025% lotion/cream/ointment 1-2 times daily, topically
      • MAX 50 g/wk or 50 mL/wk
      • MAX duration, 2 consecutive weeks
    • flurandrenolide; 4 ?g/cm² tape, 1-2 times daily, topically

Second line:


  • narrowband ultraviolet B + topical corticosteroids
  • 2-3 times weekly for up to 10 weeks
  • psoralen plus ultraviolet A
  • 4 times weekly for up to 5 weeks


  • age < 65; titrate to 300 mg three times daily, orally:
    • 300 mg orally on day 1
    • 300 mg twice a day on day 2
    • 300 mg three times a day on day 3
    • can increase to maximum daily dose of 3600 mg
  • age ? 65; 100 mg nightly, orally

Calcineurin inhibitors

  • tacrolimus; 0.1% lotion/cream/ointment 1-2 times daily, topically
  • pimecrolimus; 1% lotion/cream/ointment 1-2 times daily, topically


  • triamcinolone; 20-40 mg/mL, intralesional

Third line:


  • methotrexate
    • 15-20 mg weekly, orally
    • 15-25 mg/m² subcutaneous injection once weekly
  •  mycophenolate mofetil; 500-1500 mg/day, orally
  • azathioprine; 50-150 mg/day, orally
  • cyclosporine; 2-5 mg/kg/day, orally
  • pregabalin; 75-600 mg/day, orally
  • butorphanol; 1 mg every 4 hours as needed, intranasally
  • naltrexone; 25-50 mg/day, orally
  • aprepitant; 80 mg/day, orally
  • thalidomide; 50-150 mg/day, orally

Calcineurin inhibitors

  • cyclosporine; 3-5 mg/kg daily, orally

Anti-IL-4/13 regimen (off-label)

  • dupilumab; 600 mg induction followed by 300 mg every 2?weeks, subcutaneous injection


About the Authors:

Chirag Vasavda is an MD/PhD student at the Johns Hopkins University School of Medicine. His research interests are in leveraging small molecules and metabolites to probe and treat diseases of itch and pain.

Shawn Kwatra is an associate professor of Dermatology at the Johns Hopkins University School of Medicine and the director for the Johns Hopkins Itch Center. His areas of clinical expertise include general dermatology, chronic pruritus, prurigo nodularis, atopic dermatitis, and dermatology for ethnic skin.


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