Early Systemic Therapy Crucial for Managing Prurigo Nodularis in Skin of Color

At the 2025 Fall Clinical Dermatology Conference, Mona Shahriari, MD, FAAD, an assistant clinical professor of dermatology at Yale University and the associate director of clinical trials at Central Connecticut Dermatology Research, and Shawn Kwatra, MD, PhD, a Joseph W. Burnett endowed professor and chair of dermatology at the University of Maryland School of Medicine, discussed one of dermatology’s most challenging chronic pruritic conditions, prurigo nodularis (PN), with a focus on diagnosis, pathophysiology, and management in patients with skin of color. Their session highlighted the evolving understanding of PN as a distinct inflammatory neurocutaneous disease, underscored disparities in diagnosis and treatment, and reviewed the expanding therapeutic landscape.¹

Epidemiology and Diagnostic Considerations

PN affects an estimated 0.1–0.2% of the population, though Shahriari and Kwatra noted this may be an underrepresentation due to historical underdiagnosis. The condition occurs more frequently in middle-aged females and individuals with skin of color. Both presenters emphasized that the true prevalence is likely higher as clinicians become more adept at recognizing the disease’s variable morphologies. Historically, PN was often mislabeled as neurotic excoriations or delusional parasitosis, particularly in patients with darker skin types, where erythema and secondary changes may be less visible.

Clinically, PN is characterized by firm, pruritic papules or nodules persisting for at least 6 weeks, often accompanied by evidence of chronic scratching. Lesions typically spare areas that are difficult for patients to reach, such as the mid-back. Importantly, PN should be regarded as a clinical diagnosis; biopsy findings are nonspecific and may confound diagnosis, showing hyperkeratosis, acanthosis, and dermal fibrosis.²

Pathophysiology

Kwatra outlined advances in understanding PN’s pathophysiology, emphasizing a shared inflammatory axis with other type 2–driven diseases such as atopic dermatitis (AD). Key cytokines implicated include IL-4, IL-13, and IL-31, which mediate both pruritus and cutaneous inflammation.

PN also involves fibroblast activation and collagen deposition, contributing to the nodular lesions, and neuronal sensitization, leading to chronic itch and pain. While AD primarily features epidermal barrier dysfunction and microbial dysbiosis, PN displays deeper dermal fibrosis and altered neural signaling. This distinction supports the notion that PN is a unique entity rather than a mere variant of AD. The presenters noted that patients with PN may or may not have comorbid AD, or a number of other conditions.

Disease Burden and Psychosocial Impact

The burden of PN extends far beyond the skin. Patients report intense, unrelenting itch often rated 8 to 10 on numerical rating scales. The presenters shared cases where patients described severe sleep disturbance, skin pain, and psychosocial distress. Depression, anxiety, and even relationship strain are common.

Studies indicate that PN’s impact on quality of life rivals or exceeds that of psoriasis or atopic dermatitis, with 60% of patients reporting interference with daily activities. Shahriari emphasized that pigmentary sequelae—post-inflammatory hyper- or hypopigmentation—are particularly distressing for patients with darker skin tones and should inform early therapeutic intervention, although it is not included in any current quality of life measurements.

Comorbidities and Systemic Associations

PN frequently coexists with systemic conditions, including renal insufficiency, diabetes mellitus, thyroid disease, and HIV infection. Kwatra noted emerging data suggesting that PN-associated inflammation may itself contribute to subclinical renal injury, raising the possibility that PN is not only a consequence but also a potential driver of systemic inflammation.

Treatment Evolution: From Topicals to Targeted Biologics

Traditional PN management relied heavily on topical corticosteroids, phototherapy, and antihistamines, with limited efficacy. Given the disease’s depth of inflammation and dermal fibrosis, topical therapies often fail to penetrate adequately.

The therapeutic landscape changed dramatically with the FDA approvals of dupilumab (an IL-4/IL-13 inhibitor) and nemolizumab (an IL-31 receptor inhibitor). Both agents demonstrated rapid and sustained improvements in itch and lesion clearance in pivotal phase 3 trials.

In the PRIME and PRIME2 studies, approximately 60% of dupilumab-treated patients achieved clinically meaningful itch reduction, and nearly half reached Investigator Global Assessment (IGA) scores of 0–1, indicating minimal or no lesions. Nemolizumab produced measurable itch improvement within 2 days of the first dose, with durable responses extending to 100 weeks in long-term extensions. Both drugs also significantly improved sleep quality and mental health scores with favorable safety profiles consistent with prior use in atopic dermatitis.

Management in Skin of Color

In patients with skin of color, Shahriari emphasized early systemic intervention to prevent pigmentary alteration and scarring. Post-inflammatory dyspigmentation, though often overlooked in severity indices, profoundly affects patient satisfaction and quality of life.

The speakers encouraged clinicians to maintain a low threshold for initiating systemic therapy in such populations and to incorporate counseling on pigmentary changes as part of holistic management.

Looking Ahead

Future treatments for PN may include JAK inhibitors, PDE4 inhibitors, and topical IL-31 antagonists, further broadening therapeutic options. The presenters concluded that PN exemplifies the importance of recognizing the intersection of neuroimmune dysregulation and inflammatory skin disease, particularly in underserved populations where diagnostic delay remains common.

References

1. Shahriari M, Kwatra S. Seeing clearly: A visual guide to diagnosing prurigo nodularis in skin of color. Presented at: Fall Clinical; October 23-26, 2025; Las Vegas, Nevada.

2. Mullins TB, Sharma P, Riley CA, Syed HA, Sonthalia S. Prurigo nodularis. In: StatPearls. Treasure Island (FL): StatPearls Publishing; March 1, 2024.