Dr. Kwatra’s Insights on Emerging Advances in Chronic Itch

As dermatologists, we recognize that chronic itch is a complex and often debilitating condition that significantly impacts our patients’ quality of life, affecting their physical health, mental well-being, and daily activities. Chronic itch can be especially challenging to diagnose and treat, particularly in patients with skin of color, who may experience unique clinical manifestations and complications. We are fortunate to have experts like Dr. Shawn Kwatra, Joseph W. Burnett Professor and Chair of Dermatology at the University of Maryland School of Medicine, who devote their clinical and research efforts to this multifaceted condition. Drawing on his extensive expertise, Dr. Kwatra delivered an outstanding, pearl-filled lecture titled “Diagnostic Playbook for Chronic Itch” that provides invaluable insights into the diagnosis and management of pruritus, particularly in diverse patient populations.

Initial Evaluation for Itch

Dr. Kwatra divided chronic itch into chronic itch with primary skin lesions and chronic itch without primary skin lesions.¹ He emphasized the importance of a thorough clinical history and assessment when encountering patients with chronic itch:

• • Duration: Differentiating between chronic and acute itch is vital.
  • Localization: Itching confined to specific areas, such as the scalp or arms, may suggest a neuropathic origin, while generalized itch could indicate systemic causes.
  • History of Atopy: Personal or family history of atopic conditions should be explored.
  • Back/Neck Pain: This may signal neuropathic or mixed pruritus, as damage to the somatosensory nervous system can result in itching.
  • Review of Systems: A comprehensive review should include B symptoms (e.g., fever, chills, night sweats) and assessment for dermographism.

Dr. Kwatra stressed the importance of a thorough systemic workup in patients presenting with chronic itch. Routine blood work including a complete blood count (CBC), comprehensive metabolic panel (CMP), HbA1c, and thyroid function tests should be part of the initial evaluation. Based on patient’s risk factors, should also consider additional work up such as HIV serology, Hepatitis B/C serologies, heavy metals in blood, vitamin D, vitamin B12, and stool ova and parasites if recent travel history and/or anal pruritus is suspected. Malignancy screening should also be considered, particularly in cases where the pruritus has been ongoing for less than 12 months, or when other systemic symptoms are present. Should malignancy be suspected screening for hematologic and hepatobiliary cancers should be pursed as they are more frequently associated with itch.

Dr. Kwatra also recommended using the WI-NRS (Worst Itch Numeric Rating Scale) to assess the severity of the itch. Studies suggest that a score greater than 7 correlates with higher inflammatory markers, which is particularly relevant in patients with skin of color (SOC), who are at risk of post-inflammatory hyperpigmentation (PIH). A WI-NRS score of 10 often indicates the need for systemic therapy.

Emerging Science and Chronic Itch in Skin of Color

The presentation explored how chronic itch manifests differently in patients with skin of color.

Dr. Kwatra stressed the importance of understanding these differences, not only for diagnosis but also for tailoring treatment plans to the specific needs of SOC patients, ensuring early and effective interventions to minimize long-term damage such as scarring and pigmentation changes.

Therapeutic Approaches for Chronic Itch²

Dr. Kwatra’s approach to treating chronic itch varies depending on the severity and underlying cause of the condition. For patients with severe itch, particularly those with high WI-NRS scores, systemic therapy may be necessary.

Topical Therapies include:

• • Corticosteroids: Effective in reducing localized inflammation.
  • Calcineurin Inhibitors (e.g., tacrolimus): Often used in cases where corticosteroids are insufficient or in sensitive areas like the face.
  • Crisaborole ointment: Useful for mild to moderate cases of atopic dermatitis.
  • Ruxolitinib: For patients with moderate to severe disease that have not responded to traditional therapies. Local response is noted within minutes to hours of application.
  • Phototherapy, specifically narrowband UVB, is another non-invasive option for patients with widespread pruritus who have not responded to topical treatments.

Systemic Therapies include:

• • Dupilumab: An IL-4 receptor antagonist used in atopic dermatitis, particularly effective in patients with high inflammatory markers or those unresponsive to topical treatments. Studies have demonstrated history of AD and elevated blood eosinophils as predictors to response to dupilumab.
  • JAK Inhibitors: Emerging treatments like upadacitinib and abrocitinib have shown promise in patients with severe atopic dermatitis who do not respond to other systemic therapies. Dr. Kwatra emphasized the need to inform patients about the black box warning associated with JAK inhibitors, which was based on data from studies in rheumatoid arthritis populations that showed an increased risk of malignancy and thromboembolism.³
  • Nemolizumab – An IL-31 monoclonal antibody recently approved for prurigo nodularis.⁴

Prurigo Nodularis and Its Unique Considerations

Prurigo nodularis (PN), characterized by intensely pruritic nodules, was another key focus of Dr. Kwatra’s presentation. PN can be particularly challenging to treat and often coexists with chronic itch of unknown origin. The diagnostic workup for PN should be similar to that of undiagnosed chronic pruritus, with thorough lab testing to rule out systemic causes.

In SOC patients, PN lesions tend to be fibrotic, and these patients may have lower eosinophil counts compared to other ethnicities. On a molecular level, the skin in SOC patients with PN may exhibit unique fibroblast species resembling those found in cancer-related fibrosis.⁵

In conclusion, Dr. Kwatra’s presentation underscored the complexity of diagnosing and managing chronic itch, particularly in patients with SOC. A thorough evaluation, including a detailed history, systemic review, and the use of tools like the WI-NRS, is critical for guiding treatment. In light of the evolving understanding of chronic itch and the availability of new treatments like JAK inhibitors, dupilumab, and nemolizumab, clinicians must stay informed about the latest therapeutic options and tailor treatment plans to the unique needs of their patients. 

References

1. 1. Roh YS, Choi J, Sutaria N, Kwatra SG. Itch: Epidemiology, clinical presentation, and diagnostic workup. J Am Acad Dermatol. 2022;86(1):1-14. doi:10.1016/j.jaad.2021.07.076
   2. Davis DMR, Drucker AM, Alikhan A, et al. Guidelines of care for the management of atopic dermatitis in adults with phototherapy and systemic therapies. J Am Acad Dermatol. 2024;90(2):e43-e56. doi:10.1016/j.jaad.2023.08.102
   3. Samuel C, Cornman H, Kambala A, Kwatra SG. A Review on the Safety of Using JAK Inhibitors in Dermatology: Clinical and Laboratory Monitoring. Dermatol Ther (Heidelb). 2023;13(3):729-749. doi:10.1007/s13555-023-00892-5
   4. Kwatra SG, Yosipovitch G, Legat FJ, et al. Phase 3 Trial of Nemolizumab in Patients with Prurigo Nodularis. N Engl J Med. 2023;389(17):1579-1589. doi:10.1056/NEJMoa2301333
   5. Belzberg M, Alphonse MP, Brown I, et al. Prurigo Nodularis Is Characterized by Systemic and Cutaneous T Helper 22 Immune Polarization. J Invest Dermatol.

This information was presented by Dr. Shawn Kwatra during the 2024 Skin of Color Update conference. The above session highlights were written and compiled by Dr. Nidhi Shah.

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