Palmoplantar plaque psoriasis responsive to upadacitinib: A report of two cases

Abstract

Palmoplantar plaque psoriasis is more resistant to therapy compared to other phenotypes of psoriasis. To our knowledge, there are no reports of the efficacy of Janus kinase (JAK) inhibitors for palmoplantar plaque psoriasis. Two adult females presented with more than 6-year histories of severe palmoplantar plaque psoriasis. The first patient had failed topical therapies, phototherapy, acitretin, and secukinumab. The second patient had failed topical therapies and systemic agents including alitretinoin, cyclosporine, apremilast, ustekinumab, ixekizumab, and risankizumab. Both cases were switched to upadacitinib 15 mg daily, with a complete response by 3 months of therapy and no adverse events. The first patient had slightly elevated fasting triglyceride and the second patient had elevated ALT, both of which are being monitored. This case series highlights the efficacy of upadacitinib in two patients with refractory palmoplantar plaque psoriasis. JAK1 inhibitors may be considered as third-line therapeutic options in patients with refractory palmoplantar plaque psoriasis and no contraindications to JAK inhibitors.

Introduction

Palmoplantar psoriasis encompasses both plaque and pustular varieties and tends to be more resistant to therapy than other phenotypes, suggesting a distinct pathogenesis.^1–3 While there are several recent case reports of successful treatment of palmoplantar pustular psoriasis with Janus kinase (JAK) inhibitors,^4,5 to our knowledge there are no reports of the efficacy of JAK inhibitors for palmoplantar plaque psoriasis (PPP). Herein, we report two recalcitrant cases of palmoplantar plaque psoriasis that responded quickly to upadacitinib (Figures 1 and 2).

Figure 1.

Clinical images of palmoplantar plaque psoriasis response to upadacitinib in case 1. (a) Right foot on secukinumab and acitretin, prior to upadacitinib. (b) Left foot on secukinumab and acitretin, prior to upadacitinib. (c) Right foot after 3 months of upadacitinib therapy. (d) Left foot after 3 months of upadacitinib therapy. Note that hydrocolloid dressings are present on the plantar aspect of the feet bilaterally in images Figure 1(a) and (b).

Figure 2.

Clinical images of palmoplantar plaque psoriasis response to upadacitinib in case 2. (a) Right foot on secukinumab, prior to upadacitinib. (b) Left foot on secukinumab, prior to upadacitinib. (c) Bilateral feet after 3 months of upadacitinib therapy.

Case report

Case 1 is a 61-year-old otherwise healthy female with severe PPP for 6 years. There was no history of pustulation. Lesions were very itchy and notable for painful fissures which interfered with daily activities. She had mild psoriasis elsewhere, and her past medical history was significant for cigarette smoking and moderate alcohol consumption. She failed therapy with topical agents (betamethasone dipropionate/calcipotriol, clobetasol, and tacrolimus), phototherapy (narrowband ultraviolet B and psoralen plus ultraviolet A soak), and acitretin 25 mg daily. Secukinumab 300 mg monthly was added for 12 months without any improvement. On physical examination, there were symmetric indurated erythematous plaques with thick scales and fissures on the palms and soles. Treatment was switched to upadacitinib 15 mg daily, with discontinuation of all other agents, and she reported a complete response after 3 months. There were no adverse events, and she remains on upadacitinib. Monitoring bloodwork showed normal complete blood count (CBC), alanine transaminase (ALT), and creatine kinase (CK) with slightly elevated fasting triglyceride (2.24 mmol/L).

Case 2 is a 52-year-old female with intensely itchy PPP for 9 years. There was no history of pustulation, and the feet were more affected than the hands. Her past medical history included hyperlipidemia, diverticulitis, scoliosis, and gastroesophageal reflux; she did not smoke cigarettes. Her active medications included rosuvastatin, gabapentin, and dexlansoprazole. She failed multiple therapies including topicals (betamethasone dipropionate/calcipotriol, halobetasol, clobetasol, and tacrolimus), alitretinoin, cyclosporine, apremilast, ustekinumab, ixekizumab, and risankizumab. Phototherapy was not accessible. Secukinumab 300 mg and later 450 mg monthly provided a partial response over the course of 3 years, but its efficacy waned over time. On physical examination, there were indurated and excoriated erythematous scaly plaques on the soles, with milder involvement of the palms. Her therapy was changed to upadacitinib 15 mg daily, and within 2 weeks, she noted significant improvement in itch, and by 3 months, her palms and soles were completely clear. She tolerated upadacitinib without any side effects, and monitoring blood work (CBC, CK, triglyceride) has been normal except for elevated ALT (124 U/L), which will be monitored.

Discussion

To our knowledge, this is the first reported case series supporting the efficacy of upadacitinib for the treatment of non-pustular palmoplantar psoriasis. The two patients failed topical agents, phototherapy, conventional systemic agents, and biologics and had significant morbidity from their disease. They demonstrated complete response to upadacitinib 15 mg daily within less than 3 months of therapy. Upadacitinib was well tolerated without any significant adverse events.

Although the exact pathogenesis of PPP is not clearly elucidated, it is likely multifactorial. Inflammatory states from environmental triggers such as stress, smoking, or infections can induce PPP, and several gene mutations have also been linked. ⁶ In contrast to other subtypes of psoriasis, PPP may activate multiple immune pathways, ⁷ which could explain why biologic treatments targeting specific pathways implicated in psoriasis are often ineffective in PPP.

While there is limited evidence regarding the use of JAK inhibitors in palmoplantar psoriasis, there are reports of the efficacy of JAK inhibitors in both psoriasis and psoriatic arthritis. JAKs are enzymes that activate signal transducers and activators of transcription proteins, ⁷ which in turn, regulate the gene transcription of cytokines, including those involved in psoriasis. ⁷ There are four JAKs in mammals: JAK1, JAK2, JAK3, and tyrosine kinase 2. ⁷ Upadacitinib is a selective JAK1 inhibitor that has been approved for psoriatic arthritis and atopic dermatitis but not psoriasis. ⁴ Although its mechanism of action in PPP is unclear, the effectiveness of upadacitinib in both psoriasis and PPP may serve as a clue for cytokine targets, as the pathogenesis for both diseases includes TNF-alpha, IL-17, and IFN-gamma. ⁸

In addition, it has been previously reported that the JAK1 and JAK3 inhibitors, tofacitinib, have efficacy in palmoplantar pustular psoriasis. ⁹ Since upadacitinib is a more selective inhibitor, it may be the inhibition of the JAK1 signaling pathway that specifically improves PPP lesions. This distinction could be important given that increased JAK inhibition may lead to adverse events; tofacitinib has been linked with an elevated risk of major adverse cardiovascular events, malignancy, and venous thromboembolism events. ¹⁰ Thus, upadacitinib may be preferred to tofacitinib to limit side effects from unnecessarily inhibiting JAK3. Prior to considering JAK inhibitors as therapeutic options, it is important to identify the specific comorbidities of the patient, such as smoking, and a history of malignancy or cardiovascular events. ¹⁰

This case series highlights the efficacy of upadacitinib in two patients with refractory PPP. While additional research is required to elucidate the exact mechanism of JAK inhibitors in PPP, these results suggest that JAK1 signals may play a role in the pathogenesis of PPP. Dermatologists can consider the use of JAK1 inhibitors as third-line therapeutic options in appropriate patients presenting with recalcitrant PPP and no contraindications to JAK inhibition.