Dear Editor,

Prurigo nodularis (PN) is a chronic, debilitating dermatological condition marked by intensely pruritic nodules, often resulting in significant impairment in quality of life. While the exact etiology remains unclear, a strong link with atopic diathesis has been documented. A systematic review and meta-analysis reported a significantly higher risk of atopic dermatitis in patients with PN, showing a pooled unadjusted odds ratio of 16.85.^[1]

Recent breakthroughs in managing this challenging condition include targeted biologics, notably dupilumab and nemolizumab, which recently gained food and drug administration, United States (US-FDA) approval. While these biologics specifically inhibit Interleukin (IL)-4/-13 and IL-31, respectively, additional cytokines such as IL-17, IL-22, and thymic stromal lymphopoietin (TSLP) also play crucial roles in PN pathogenesis.^[1] Furthermore, biologics such as dupilumab and nemolizumab are not yet available in countries like India. Thus, there is an unmet need for managing PN, particularly in patients who are refractory to conventional immunomodulators such as cyclosporine. Here, we present a case of an adult female with PN unresponsive to cyclosporine, who experienced marked improvement with abrocitinib, a selective Janus kinase 1 (JAK1) inhibitor.

A 46-year-old woman presented with persistent itchy skin lesions over her back, arms, and legs lasting 2 years [Figure 1A and B]. Examination revealed numerous well-defined, erythematous to hyperpigmented papules and nodules with excoriation and mild scaling involving approximately 75% of her body surface [Figure]. She reported severe sleep disturbance due to intense itching, scoring 9 on the visual analog scale (VAS). She had a history of childhood atopic dermatitis. Routine laboratory tests, including eosinophil count and serum Immunoglobulin E levels, were normal. Histopathology demonstrated marked orthohyperkeratosis, focal parakeratosis, irregular acanthosis, reduced nerve fiber density, and a non-specific dermal infiltrate of lymphocytes, macrophages, eosinophils, and neutrophils [Figure 1C]. Based on clinical and histopathological findings, a diagnosis of PN was confirmed.

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Figure 1:

(A-E) Clinical and histopathological features of the disease. (A) Multiple discrete to grouped hyperpigmented papules and nodules distributed over the back, some showing excoriation and post-inflammatory hyperpigmentation before initiating abrocitinib. (B) Widespread involvement of the back with post inflammatory hyperpigmentation, 6 weeks after abrocitinib treatment. (C) Hematoxylin and Eosin staining (10X) showing marked orthohyperkeratosis focal parakeratosis (green arrow), marked acanthosis, prominent granular layer (white arrow) and irregular acanthosis in the epidermis. The papillary dermis displays a mild to moderate lymphoplasmacytic infiltrate (yellow arrow), along with vertically oriented collagen bundles (blue arrow). (Hematoxylin and Eosin stain, original magnification ×10). (D) Multiple discrete to grouped hyperpigmented papules and nodules distributed over the abdomen, some showing excoriation and post-inflammatory hyperpigmentation before treatment. (E) Resolved lesions and residual hyperpigmentation in the abdomen after 6 weeks of treatment with abrocitinib.

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The patient’s dermatology life quality index (DLQI) was 21, indicating substantial impairment in daily functioning and quality of life. The Investigator’s Global Assessment for Chronic Nodular Prurigo (IGA-CNPG) score was 4, reflecting severe disease with over 100 palpable, pruritic nodules. Previous treatments, including oral antihistamines, cyclosporine for more than a year, methotrexate, and multiple sessions of intralesional corticosteroid injections, provided minimal clinical improvement.

Due to inadequate response, oral abrocitinib (200 mg daily) was initiated along with topical tacrolimus, following informed consent and patient counseling. Within 1 week, pruritus significantly reduced (VAS score from 9 to 3). By 10 weeks, pruritus fully resolved (VAS score 0), and nodular lesions markedly regressed, leaving only post-inflammatory hyperpigmentation [Figure 1D and E]. The DLQI improved to 6, IGA-CNPG reduced to 1 (almost clear), and sleep quality normalized. Abrocitinib was continued for 10 weeks without dose adjustments, resulting in sustained improvement, minimal residual nodules, and no significant adverse effects. Current International Forum for the Study of Itch guidelines recommend a stepwise approach for managing chronic prurigo. Initial therapy includes topical corticosteroids, topical calcineurin inhibitors, and H1 antistamines. Second-line options involve topical capsaicin, intralesional corticosteroids, and ultraviolet phototherapy. Neuropathic pruritus responds to neuromodulators (gabapentin, pregabalin, and antidepressants), while inflammatory variants may benefit from systemic immunosuppressants (cyclosporine and methotrexate). Advanced therapies include neurokinin-1 receptor antagonists, µ-opioid receptor antagonists, biologics (dupilumab and nemolizumab), and thalidomide in selected cases.^[2] However, the recent FDA approvals of dupilumab (2022) and nemolizumab (2024) have significantly transformed PN management, positioning them frequently as first-line treatments for moderate-to-severe disease.

Nemolizumab is neither approved nor available in India, while dupilumab, though approved for atopic dermatitis, is currently not marketed. Although JAK inhibitors are not yet approved for PN, the easy availability and notable efficacy of abrocitinib in refractory AD encouraged its use in this case. In a U.S.-based phase 2 open-label trial, oral abrocitinib (200 mg/day) significantly reduced pruritus severity after 12 weeks, with peak pruritus numerical rating scale (PP-NRS) scores decreasing by 78.3% in PN patients and 53.7% in chronic pruritus of unknown origin (CPUO). Clinically meaningful itch reduction (≥4-point PP-NRS improvement) occurred in 80% of PN and 60% of CPUO patients, accompanied by substantial DLQI-based quality-of-life improvements.

Several key cytokines are implicated in the pathogenesis of PN. IL-31 significantly drives the intense pruritus characteristic of PN, while IL-4 and IL-13 promote type 2 inflammation, strongly associated with allergic disorders and critical in PN. Overproduction of IL-22 contributes to skin thickening and nodules, and IL-17 is also notably upregulated in PN lesions. TSLP, released following scratching and skin injury, further initiates and amplifies inflammation in PN.^[3] Many of these cytokines signal through the JAK–STAT pathway: IL-4 predominantly via JAK1/JAK3, IL-13 through JAK1 in combination with JAK2 or TYK2, IL-31 via JAK1/JAK2, IL-22 through JAK1/TYK2, and TSLP via JAK1/JAK2.^[4] JAK1 activation is central to most, if not all, of these cytokines. Therefore, as demonstrated by our case, selective JAK1 inhibition using abrocitinib provides a safe, effective, and potentially superior therapeutic strategy for this otherwise refractory and pathogenetically complex disorder.