Clinical Features and Cytokine Pathways in Prurigo Nodularis vs Atopic Dermatitis

In a recent interview with Dermatology Times, Jason Hawkes, MD, MS, provided insights into the key differences between atopic dermatitis and prurigo nodularis, including appearance, cytokine pathways associated with each condition, patient populations, biologics use, diagnostic tools, and the psychological effect of both conditions on patients.

Hawkes, a board-certified dermatologist, co-owner, chief scientific officer, and investigator at the Oregon Medical Research Center in Portland, Oregon, emphasized that biologic treatments are transforming the management of both prurigo nodularis and atopic dermatitis, as treatments are needed to address the intense impact of itch on patients’ quality of life.

Q&A With Jason Hawkes, MD, MS

Jason Hawkes, MD, MS

Image credit: Oregon Medical Research Center

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

Hawkes: Some of the distinctive clinical features of prurigo nodularis are the symmetric distribution of lesions on easy-to-reach skin, prominent complaints of itch or other nerve-related symptoms, and skin plaques or nodules that are prone to scarring and dyschromia. These clinical features of prurigo nodularis are less common in patients with atopic dermatitis. However, these two pruritic conditions can co-occur and may have overlapping clinical features in patients.

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

Hawkes: Lesional skin biopsies in prurigo nodularis reveal significant increases in mixed immune cell and signaling pathways (eg. Th2, Th17, and Th22), similar to what is observed in atopic dermatitis. However, phase 3 clinical trials in PN suggest that type 2 inflammation is the predominant immune pathway driving the clinical manifestations of prurigo nodularis due to the dramatic skin and itch responses seen following blockade of IL-4, IL-13, and/or IL-31. In contrast, there are several reports of the development of prurigo nodularis following treatment with selective IL-17 inhibitors, such as secukinumab.

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

Hawkes: Robust translational research studies in humans support the predominant role of type 2 inflammation in the immunopathogenesis of atopic dermatitis, such as increased IFN, IL-4, IL-13, and IL-31 cytokine signaling. Other immune cell populations, such as Th17 and Th22, have been reported in atopic dermatitis and may play a more prominent role in special patient populations. Testing of novel immunotherapies that inhibit the upstream regulatory signals (eg. TSLP, OX40, and OX40L) driving T cell activation and the development of resident memory T cell populations is underway and quite promising.

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

Hawkes: Both conditions are observed in a broad range and diverse set of patient groups. Neither condition has a clear male or female predilection when controlling for other disease comorbidities or underlying health conditions. Atopic dermatitis has an increased overall prevalence compared to prurigo nodularis and most commonly presents in childhood or early adulthood. In contrast, prurigo nodularis is primarily observed in middle-aged adults, has a stronger association with Black patients, and co-occurs in individuals with underlying health conditions that are not commonly seen with atopic dermatitis, such as liver disease, renal dysfunction, malignancy, and HIV infection.

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

Hawkes: In general, the therapeutic goals are very similar for both conditions — to alleviate disease symptoms, promote healing of active skin lesions, and sustain adequate disease control with little or no disease activity with ongoing treatment. These goals are more achievable than ever due to the availability of several highly effective biologic agents that are approved for each individual condition. Our treatment approach, however, is still dependent on a variety of other factors, such as patient treatment preference, insurance approval and affordability, and disease severity (ie. mild or localized disease versus more severe or widespread disease). Further, not every atopic dermatitis or prurigo nodularis patient responds the same to a specific treatment, thus necessitating the need for multiple treatments with distinct mechanisms of action. Combination therapies, such as the use of topical treatments with systemic agents, is another way to optimize or maximize a patient's clinical response.

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

Hawkes: The diagnosis of atopic dermatitis and prurigo nodularis remains clinical. This is primarily due to the lack of specific, validated disease biomarkers or commercial clinical tests (including skin biopsies) that can consistently distinguish the two conditions and are readily accessible to practitioners. Rather, in cases where the diagnosis is clinically ambiguous, there is tremendous benefit to having access to a biologic therapy like dupilumab that is approved and effective for both conditions.

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?

Hawkes: Both chronic inflammatory conditions have a tremendous negative impact on the quality of life and pyschosocial health of our patients. This is well-documented in the clinical trial programs for atopic dermatitis and prurigo nodularis where multiple patient reported outcomes and quality of life measures are administered. However, the predominant symptoms that patients attribute to their disease is slightly different. In many patients with atopic dermatitis, the visible skin manifestations and their associated secondary findings (eg. skin pain, fissures, bleeding, etc) tend to be at the forefront; itch is often, but not always, a primary complaint in these patients. My patients with prurigo nodularis, on the other hand, tend to heavily focus on their itch and tendency to scratch or pick at their skin which is an essential component of their papulonodular lesions.