Use of oral tofacitinib in a case of recalcitrant prurigo nodularis: A promising off-label alternative in resource-poor setup

Dear Editor,

Prurigo nodularis (PN) is a chronic, intensely pruritic dermatosis characterized by hyperkeratotic, excoriated nodules, most distributed symmetrically over the extensor surfaces. The condition is often recalcitrant to conventional therapies, and treatment remains a clinical challenge. Recent studies suggest that Janus kinase (JAK) inhibitors may offer therapeutic benefit by targeting multiple pruritogenic cytokines implicated in PN pathophysiology.^[1]

PN is driven by a complex neuroimmune loop involving inflammatory cells, proinflammatory cytokines, neuropeptides, and cutaneous neural hyperplasia, all contributing to a vicious itch-scratch cycle. Key cytokines— IL-4, IL-13, IL-31, IL-22, and IL-17—signal through the JAK-STAT (signal transducer and activator of transcription) pathway. IL-4α initiates a JAK1-dependent pruritic cascade by activating sensory neurons. IL-4 and IL-31, both Th2 cytokines, serve as critical mediators linking immune cells, the skin, and the nervous system. A systemic and cutaneous Th2 polarization is typical of PN. Previous studies have shown upregulation of STAT3 and STAT6 in lesional biopsies, implicating Th2, Th17, and Th22 pathways.^[2-4] Therefore, broader immunomodulation through JAK inhibition may be more effective than targeting single cytokines with monoclonal antibodies.

We report the case of a 62-year-old female with a 4-year history of generalized excoriated papulonodular lesions involving the upper and lower limbs (extensors >flexors) and trunk [Figure 1a and b]. She had well-controlled hypertension and diabetes and no history of atopy. Laboratory investigations – including complete blood count, eosinophil count, serum immunoglobulin, liver and renal function, thyroid profile, viral markers (human immunodeficiency virus, hepatitis B virus, and hepatitis C virus), Mantoux test, and chest X-ray – were unremarkable. Histopathology revealed compact orthokeratosis with focal parakeratosis, a prominent granular layer, irregular acanthosis, moderate lymphoplasmacytic infiltration in the papillary dermis, and vertically oriented collagen bundles [Figure 2], confirming PN.

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Figure 1:

(a) Multiple papulonodular excoriated lesions distributed on the trunk (baseline Pruritus Numerical Rating Scale (NRS) score was 10, severe), (b) Improvement in the lesions after 3 months of treatment with tofacitinib (Pruritus Numerical Rating Scale (NRS) score was 1, mild).

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Figure 2:

Epidermis shows compact orthokeratosis with focal parakeratosis, prominent granular layer, and irregular acanthosis. The papillary dermis shows moderate lymphoplasmacytic infiltrate and vertically oriented collagen bundles (Hematoxylin and eosin, ×40). Red arrow: Orthokeratosis with focal parakeratosis, Blue arrow: Prominent granular layer, Green arrow: Irregular acanthosis.

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The patient’s Pruritus Numerical Rating Scale (NRS) score was 10, dermatology life quality index (DLQI) was 22, and investigator’s global assessment–chronic nodular prurigo (IGA-CNPG) score was 4 at baseline. She had previously been treated unsuccessfully with methotrexate, thalidomide, topical corticosteroids, and antihistamines. Although biologics such as dupilumab or small-molecule immunomodulators such as abrocitinib or baricitinib were considered, the patient declined due to cost constraints.

Tofacitinib was initiated at 5 mg twice daily along with clobetasol propionate 0.05% ointment, emollients, and antihistamines. Remarkable improvement in pruritus was observed within 1 week. Over 8 weeks, nodules regressed significantly in number and size, with corresponding improvement in NRS and DLQI scores. By 12 weeks, lesions had nearly resolved, and the patient achieved an NRS of 1, DLQI of 2, and IGA-CNPG of 1. The dose was then tapered to 5 mg once daily and discontinued after 4 additional weeks. No adverse effects were reported during therapy. At 3-month follow-up, she remains in remission without recurrence.

Given its ability to inhibit JAK1 and JAK3, and subsequently IL-4, IL-13, and IL-31 signaling (through STAT3, STAT5, and STAT6), tofacitinib represents a rational and cost-effective off-label therapeutic option for PN. Although previous reports have raised concerns regarding relapse post-therapy^[5] our patient demonstrated sustained remission and tolerability [Table 1].^[6,7,8]

This case underscores the potential of tofacitinib as a viable alternative in refractory PN. Tofacitinib emerges as a promising, cost-effective option for managing refractory PN. It offers a practical alternative where biologics or selective JAK inhibitors are either inaccessible or unaffordable. In this case, rapid and sustained remission was achieved without adverse effects. Further controlled trials are needed to establish its definitive role in PN management. Controlled trials are warranted to further define its role in PN management.