Prurigo Nodularis in Two Siblings with Response to Oral Tofacitinib

Dear Editor,

Prurigo nodularis is a chronic cutaneous condition characterized by hyperkeratotic, intensely pruritic, excoriated nodules mostly distributed on the extensor aspects of extremities.[1] There are several recent reports of successful treatment of prurigo nodularis with tofacitinib.[2,3] We report excellent treatment response to oral tofacitinib in two siblings with multiple prurigo nodularis lesions.

Two siblings, a four-year-old boy and a 10-year-old girl, presented with a two-year history of multiple severely itchy lesions on the shins. Personal and family history of atopy was positive. They had achieved all developmental milestones and received the recommended vaccines as per age. There were no systemic symptoms or any other type of skin lesions in the past. On examination, there were multiple hyperpigmented annular plaques, with diameters of the lesions ranging from 0.5 cm to 5 cm, with most of the lesions showing central depression, and multiple excoriation marks on the surface of the annular rims on both anterior shin areas [Figure 1a and 1b]. The rest of the areas did not show any abnormality. Biopsy of the lesion showed irregular acanthosis, hypergranulosis, papillomatosis with lymphocytic exocytosis in the epidermis, and perivascular lymphocytic infiltration in the superficial dermis, with a few areas showing vertically oriented collagen fibers. With a final diagnosis of prurigo nodularis, the siblings were started on oral tofacitinib (5 mg once daily and twice daily, respectively). The lesions showed almost complete resolution at the six-month follow-up [Figure 2a and 2b]. None of the children showed any adverse effects from the use of tofacitinib. During further follow-up, there was a recurrence of itching and reappearance of a few new lesions after stopping the drug for around 2 months. A more severe episode of recurrence was noted in the younger sibling, in the form of recurrence of lesions at the older sites, with very few new excoriated papules. So, the drugs were restarted and continued for another six months.

Figure 1.

(a) Multiple hyperpigmented annular hyperkeratotic plaques on the shin of both legs in the elder sibling. (b) Similar lesions in the younger sibling

Figure 2.

(a) Most of the lesions subsided with only hyperpigmentation remaining after 6 months of treatment in the elder sibling. (b) Most of the lesions subsided with only hyperpigmentation remaining after 6 months of treatment in the younger sibling

Chronic prurigo may present with a variety of skin lesions, such as papules, nodules, plaques, umbilicated papules or nodules, and linear lesions.[4] The lesions in our patients were of unusual morphology, which may result in a diagnostic dilemma. The smaller lesions were more typical and gave a clue to the diagnosis.

Prurigo nodularis involves a complex interaction between epidermal keratinocytes, nerve fibers, dermal vessels, and fibroblasts, with a dysregulation of the immune cell-neural circuit and a Th2 predominant immune response.[4] There is increased expression of nerve growth factor, matrix metalloproteinases, chemokine ligand 2, and insulin-like growth factors in the lesional skin.[4] Various cells, such as T cells, eosinophils, and mast cells, infiltrate the lesional skin and release multiple inflammatory mediators and itch-inducing substances. Activated sensory nerve fibers release neurotransmitters and aggravate pruritus, resulting in a vicious cycle of itching and scratching.[4]

Various treatment modalities include topical corticosteroids, intralesional corticosteroids, topical calcineurin inhibitors, topical analgesics (anesthetics, cryotherapy, the transient receptor potential vanilloid 1 agonist capsaicin), topical antiproliferative agents (coal tar, vitamin D derivatives like calcipotriene), ultraviolet (UV) phototherapy (e.g., narrowband ultraviolet B light, psoralen plus ultraviolet A and laser therapies (e.g., excimer laser), oral antihistamines, conventional immunosuppressants (oral corticosteroids, cyclosporine, methotrexate, azathioprine, thalidomide/lenalidomide), neuromodulating therapies (opioid modulators like naloxone, naltrexone and nalbuphine, neurokinin-1 receptor (NK1R) antagonists like aprepitant and serlopitant, antidepressants like paroxetine, fluvoxamine and duloxetine, gabapentin), and newer immunomodulating therapies (biologics like dupilumab, nemolizumab, and oral Janus kinase (JAK) inhibitors.[4]

Various cytokines involved in the pathogenesis of prurigo nodularis include IL-4, IL-13, IL-17, IL-22, and IL-31, and there is heightened expression of STAT3 and 6.[1,3] Tofacitinib is a non-selective JAK inhibitor, and results in blockage of the transcription of IL-4 and IL-31.[1] This explains the effectiveness of tofacitinib in prurigo nodularis.

There are very few reports of successful use of tofacitinib in prurigo nodularis in children. Sardana et al.[5] recommended tapering of the dose of oral tofacitinib after clinical improvement in their pediatric case; however, our cases showed recurrence of symptoms and lesions upon stoppage. To develop more clear insights into the effect of tofacitinib on long-term remission of the disease, further research is necessary to generate evidence.

Our cases required a longer duration of treatment, but the commonly observed side effects, such as derangement of liver function or lipid profile or infections, were not noted in follow-up visits, possibly because children may be more tolerant to long-term use compared to adults.

We report these cases to highlight the unusual morphology of the lesions in the siblings and that the extensive prurigo lesions responded well to tofacitinib therapy, without any adverse effects.

Declaration of patient consent

The authors certify that they have obtained all appropriate parent consent forms. In the form, a parent has given their consent for their images and other clinical information to be reported in the journal. The parent understands that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Conflicts of interest

There are no conflicts of interest.

Use of artificial intelligence (AI)

The preparation of this manuscript was carried out entirely by the authors without the use of artificial intelligence technologies.

Funding Statement

Nil.