Paradoxical psoriasis flare caused by tofacitinib in a patient with alopecia totalis

Dear Editor,

Janus kinase (JAK) inhibitors are a novel class of therapeutic agents that block cytokine signalling via the Janus kinase/signal transducer and activator of transcription (JAK-STAT) pathway, thereby modulating immune responses and cell growth.¹ In dermatology, JAK inhibitors have been increasingly used to treat conditions such as psoriasis, atopic dermatitis, and alopecia areata.¹

Common cutaneous adverse effects of JAK inhibitors include acne and viral infections such as herpes zoster.¹ By contrast, paradoxical induction of psoriasis during JAK inhibitor therapy appears to be exceedingly rare, with only a few cases reported.² Here, we report the case of an adolescent patient with alopecia totalis who developed paradoxical flare of psoriasis after tofacitinib treatment.

A 12-year-old girl presented to our outpatient clinic with hair loss since the age of 4. She had been treated with multiple topical therapies, including betamethasone dipropionate (0.05%), contact immunotherapy with diphencyprone and squaric acid dibutyl ester (SADBE), and anthralin without any significant hair regrowth. Medical history revealed that she had lesions compatible with psoriasis, which had appeared 3 years ago and recurred intermittently but were controlled with topical agents (calcipotriene, mometasone furoate, and 2% salicylic acid in a vaseline base). She had no other comorbid conditions. Dermatological examination revealed the absence of scalp and body hair as well as madarosis.

She had also received systemic therapy, first with methotrexate (15 mg/week for 6 months) and subsequently with cyclosporine (150 mg/day for 9 months), but neither produced significant hair regrowth. After this lack of efficacy, we planned to initiate JAK inhibitor therapy. Hemogram, biochemical tests, creatine kinase, hepatitis serology, quantiferon test, and chest radiography were normal, and tofacitinib (5 mg twice daily) was started.

At the fourth month of tofacitinib therapy, we noted that the patient had widespread psoriatic plaques all over her body [Figure 1a, 1b]. The Psoariasis Area and Severity Index (PASI) score was 16. She did not have a history of infection and did not use any additional medications. The lesions were considered to be induced by tofacitinib.

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Figure 1a:

At the fourth month of tofacitinib therapy. Front view showing psoriatic plaques.

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Figure 1b:

At the fourth month of tofacitinib therapy. Top-view scalp image showing alopecia and psoriatic plaques during tofacitinib therapy.

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Tofacitinib was discontinued. Narrow-band UVB phototherapy and topical treatments were started. Significant regression of the lesions was observed in the follow-up period. There was also some hair regrowth on the vertex and lateral occipital areas [Figure 2a, 2b].

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Figure 2a:

After discontinuation of tofacitinib in combination with topical treatments and narrow-band UVB phototherapy. Front view showing regression of psoriatic lesions

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Figure 2b:

After discontinuation of tofacitinib in combination with topical treatments and narrow-band UVB phototherapy. Posterior view showing partial hair regrowth.

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The development of paradoxical psoriasis during biologic therapy is a well-recognised phenomenon.² One proposed mechanism is that TNF-α inhibition leads to activation of plasmacytoid dendritic cells and increases IFN-α production, which in turn may trigger psoriatic lesions.^2,3 While paradoxical psoriasis has been reported most often with anti-TNF agents, to date only a few cases have been described in association with JAK inhibitors.

Erol et al. reported a patient with rheumatoid arthritis who developed psoriasis 3 months after initiating tofacitinib (5 mg, BID).³ In the other case, palmoplantar pustular psoriasis–like eruption occurred 5 years after starting baricitinib for rheumatoid arthritis.⁴ The precise pathogenesis of JAK inhibitor-induced psoriasis remains unclear, but Erol et al. suggested that JAK inhibitors reduce levels of multiple cytokines, including IFN-α, potentially disrupting the balance between IFN-α and IFN-γ.³

Koumaki et al. postulated that an abnormal T-cell response involving cytokines such as IL-12, IL-17, and IL-23 might lead to Palmoplantar Pustulosis (PPP)-like eruptions in patients on baricitinib.⁴ Additionally, Di Domizio et al. described a paradoxical psoriasis case during baricitinib therapy and proposed that cytokine imbalances in JAK-independent pathways, specifically, excessive IL-8 and IL-36 activity due to inhibition of IFN/IL-17 signalling could be responsible.⁵

JAK inhibitors are increasingly utilised in managing various diseases, including psoriasis. Although JAK inhibitors such as tofacitinib are used in the treatment of psoriasis, clinicians should be aware that they may also cause paradoxical psoriasis, albeit rarely. Further research on the pathophysiology of this adverse effect is needed.