Recognizing Key Differences Between Atopic Dermatitis and Prurigo Nodularis

Although both can be characterized by intense itch, atopic dermatitis and prurigo nodularis demonstrate key differences in appearance, cytokine pathways, and diagnostic criteria. When first examining patients, prurigo nodularis presents with nodular lesions compared with erythematous patches of atopic dermatitis.^1,2 The importance of differentiating between the 2 conditions was recently discussed by Gil Yosipovitch, MD, in an interview with Dermatology Times.

Yosipovitch, professor and Stiefel Endowed Chair of medical dermatology of the Dr. Phillip Frost department of dermatology at the Miller School of Medicine at the University of Miami and director of the Miami Itch Center, is an author and study investigator of countless publications and clinical studies on atopic dermatitis, prurigo nodularis, chronic itch, and more.

Q&A With Gil Yosipovitch, MD

Gil Yosipovitch, MD

Image credit: Miller School of Medicine - University of Miami

Dermatology Times: What are the key differences in the appearance and/or lesions of prurigo nodularis vs atopic dermatitis?

Yosipovitch: The key differences between prurigo nodularis and atopic dermatitis are that prurigo nodularis lesions are firm nodular lesions that are fibrotic, usually on extensor surfaces, and can leave scars. The classical atopic dermatitis does not have nodules, is eczematous, and is mainly in flexural areas. Rarely if ever, prurigo nodularis involves the face, while atopic dermatitis commonly does.

DT: What are the prominent cytokine pathways in prurigo nodularis and atopic dermatitis?

Yosipovitch: Although in both conditions, type 2 cytokines play a major role including IL4, IL-13, and IL-31 in prurigo nodularis, the role of IL-31 in the dermis has a key role. Also, IL-22 seems to have a more robust role than in atopic dermatitis. In atopic dermatitis, thymic stromal lymphopoietin plays a more significant role as it's produced by keratinocytes. This emphasizes that in atopic dermatitis, the barrier disruption is a major key driver and the disease is more epidermal in origin, while in prurigo nodularis, it’s more of a dermal-epidermal process and the barrier damage is secondary.

DT: Regarding epidemiology, are there specific patient populations more likely to develop prurigo nodularis vs atopic dermatitis?

Yosipovitch: Prurigo nodularis is more common in the elderly and rarely will be noticed in infants. Prurigo nodularis is 3.4 times more prevalent in Black patients. Of note in prurigo nodularis, there is a higher association of comorbidities including hypertension, diabetes, chronic kidney disease, end-stage depression, central sensitization pain disorders such as interstitial cystitis, irritable bowel syndrome, and fibromyalgia. Prurigo nodularis is also more common in HIV patients. In atopic dermatitis, there is a higher association with asthma, allergic rhinitis, eosinophilic gastritis, alopecia areata, and ADHD. Clearly, atopic dermatitis is more prevalent in the younger infant population.

DT: How does your treatment approach differ when managing prurigo nodularis compared to atopic dermatitis, particularly with the development of newer biologics? 

Yosipovitch: As both conditions are predominantly associated with Type 2 inflammation, the biologics dupilumab, which targets the IL-4 receptor, and the recently approved nemolizumab targeting the IL-31 receptor are the mainstay of therapy. I believe that IL-4 and IL-13 have a more robust upstream role in atopic dermatitis than in prurigo nodularis, and I think that targeting the IL-31 receptor has a more rapid effect in prurigo nodularis than dupilumab. As prurigo nodularis could be associated with neural damage and neuropathy, using drugs targeting the neural system like GABAergic drugs and kappa opioids like butorphanol have a more effective role in prurigo nodularis than in atopic dermatitis.

Also, the use of topicals that target the neural system like the KAL cream (ketamine 10%, lidocaine 5%, and amitriptyline 5%) have a more effective role in prurigo nodularis lesions than in atopic dermatitis. As JAK/STAT inhibitors are not approved for prurigo nodularis, clearly, they are more utilized in atopic dermatitis. Although from my experience, using them off-label, they are very effective for prurigo nodularis patients. However, their safety profile is less than the targeted biologics, and therefore use in prurigo nodularis patients should be monitored more carefully. including blood tests and avoid using them when prurigo nodularis patients have too many comorbidities that can be associated with adverse effects of JAK/STATs such as thrombotic, cardiac, and metabolic disorders.

DT: What diagnostic tools or criteria do you prefer when differentiating between the 2 conditions? 

Yosipovitch: Mainly good clinical assessments as the clinical presentations are quite straightforward. We recently found that Brain Natriuretic Peptide, a neuropeptide highly associated with congestive heart failure, is a good biomarker for the severity of itch of different types including atopic dermatitis and prurigo nodularis. We think that in prurigo nodularis, it’s more robust and may be a better marker. Of note, specifically in atopic dermatitis patients with skin of color and especially younger ages, prurigo nodularis is more commonly noted and their atopic dermatitis phenotype is more like prurigo nodularis than the flexural eczema noted in White patients.

DT: How do the psychological and quality of life impact on patients compare in prurigo nodularis and atopic dermatitis, especially given the often severe itch in both?

Yosipovitch: In both diseases, there are significant psychological components, with sleep impairment in more than 90% of patients that further augments anxiety and stress. It seems in prurigo nodularis patients that there is a higher prevalence of psychological comorbidities. Therefore, a holistic approach addressing the stress and anxiety component could be added as an adjunctive to the treatment regimen. Unfortunately, only a few dermatologists as well as psychiatrists and psychologists have an interest or expertise in addressing these issues that are of prime importance to patients’ well-being.

References

1. McCann MR, Kosloski MP, Xu C, Davis JD, Kamal MA. Dupilumab: mechanism of action, clinical, and translational science. Clin Transl Sci. 2024;17(8):e13899. doi:10.1111/cts.13899
2. Fölster-Holst R, Reimer R, Neumann C, et al. Comparison of Epidermal barrier integrity in adults with classic atopic dermatitis, atopic prurigo and non-atopic prurigo nodularis. Biology (Basel). 2021;10(10):1008. Published 2021 Oct 7. doi:10.3390/biology10101008