Use of Janus Kinase Inhibitor Treatment for Palmoplantar Pustulosis: An Evidence-Based Review

To the Editor,

Palmoplantar pustulosis (PPP) is a chronic and difficult-to-treat inflammatory condition characterized by sterile pustules on the palms and soles. ¹ There are currently no US FDA-approved targeted systemic treatments for PPP. ¹ While the use of systemic Janus kinase inhibitor (JAKi) therapy for PPP remains novel, this systematic review summarizes evidence regarding their use for this condition.

Following PRISMA guidelines, Embase and MEDLINE databases were searched using variations of specific keywords (Supplemental Table 1). Quality of evidence was assessed using Oxford Centre for Evidence-Based Medicine 2011 Levels of Evidence. After independent screening by two reviewers, 16 articles (publication date: 2016-2023) encompassing 39 patients were included (Supplemental Figure 1; Supplemental Table 2). The mean age was 46 years (range: 18-70 years) with 10 males (25.6%) and 29 females (74.4%). PPP affected both the palms and soles in 21 cases (53.8%), whereas exclusive involvement of the palms or soles was observed in two cases each (5.1% each). PPP was comorbid with SAPHO syndrome and plaque psoriasis in 61.5% (24/39) and 10.3% (4/39) of patients, respectively (Supplemental Table 2). Of the cases with documented prior treatment history, 91.9% (34/37) were refractory to systemic non-JAKi therapy.

There were 39 instances of systemic JAKi therapy use with mean treatment duration of 83.1 days (range: 7-365 days). Concomitant systemic immunosuppressives were utilized in 51.3% (20/39) of patients, with non-steroidal anti-inflammatory drugs (65%, 13/20) being most frequent (Supplemental Table 2). Tofacitinib was the most commonly used systemic JAKi (82.1%, 32/39), followed by baricitinib (12.8%, 5/39) and upadacitinib (5.1%, 2/39). Complete or partial resolution was seen using tofacitinib (complete: 53.1%, 17/32; partial: 40.6%, 13/32), baricitinib (complete: 40%, 2/5; partial: 60%, 3/5), and upadacitinib (complete: 50%, 1/2; partial: 50%, 1/2) (Supplemental Table 3). In 22 reported instances, a mean reduction of 76.8% in the Palmoplantar Pustulosis Psoriasis Area and Severity Index (PPPASI) score was observed with systemic JAKi use, including 11 cases (50%) that achieved 75% improvement in PPPASI from baseline. Systemic JAKi therapy was well tolerated with 7.7% (3/39) patients experiencing mild adverse events; none led to discontinuation (Supplemental Table 2).

Although the pathogenesis of PPP is not fully understood, interleukin (IL)−22/17, interferon (IFN)-γ, and tumour necrosis factor (TNF)-α have been found to be upregulated in skin biopsy specimens and the serum of affected patients. ² Furthermore, a recent study has demonstrated that there may be significant T-cell plasticity ranging from a Th2- to Th17-predominant phenotype. ³ Therefore, pan-cytokine inhibition via the systemic JAKi studied may explain the findings observed in this review. To date, there has been only one clinical trial completed for PPP in the setting of SAPHO syndrome, which demonstrated a mean reduction of 71% in PPPASI with tofacitinib. ⁴ These results are in keeping with our review. An additional clinical trial is currently being conducted to explore deucravacitinib use in PPP (NCT05710185). ⁵

This study is limited by sample size, lack of complete follow-up data, and potential reporting bias. Meta-analysis was not performed due to study heterogeneity. Nonetheless, we highlight evidence supporting systemic JAKi for PPP. Larger-scale studies are warranted.

Supplemental Material

Figure S1 - Supplemental material for Use of Janus Kinase Inhibitor Treatment for Palmoplantar Pustulosis: An Evidence-Based Review

Supplemental material, Figure S1, for Use of Janus Kinase Inhibitor Treatment for Palmoplantar Pustulosis: An Evidence-Based Review by Siddhartha Sood, Abrahim Abduelmula, Khalad Maliyar, Jorge R. Georgakopoulos, Asfandyar Mufti, Ronald Vender, Vimal H. Prajapati and Jensen Yeung in Journal of Cutaneous Medicine and Surgery

Supplemental Material

Table S1 - Supplemental material for Use of Janus Kinase Inhibitor Treatment for Palmoplantar Pustulosis: An Evidence-Based Review

Supplemental material, Table S1, for Use of Janus Kinase Inhibitor Treatment for Palmoplantar Pustulosis: An Evidence-Based Review by Siddhartha Sood, Abrahim Abduelmula, Khalad Maliyar, Jorge R. Georgakopoulos, Asfandyar Mufti, Ronald Vender, Vimal H. Prajapati and Jensen Yeung in Journal of Cutaneous Medicine and Surgery

Supplemental Material

Table S2 - Supplemental material for Use of Janus Kinase Inhibitor Treatment for Palmoplantar Pustulosis: An Evidence-Based Review

Supplemental material, Table S2, for Use of Janus Kinase Inhibitor Treatment for Palmoplantar Pustulosis: An Evidence-Based Review by Siddhartha Sood, Abrahim Abduelmula, Khalad Maliyar, Jorge R. Georgakopoulos, Asfandyar Mufti, Ronald Vender, Vimal H. Prajapati and Jensen Yeung in Journal of Cutaneous Medicine and Surgery

Supplemental Material

Table S3 - Supplemental material for Use of Janus Kinase Inhibitor Treatment for Palmoplantar Pustulosis: An Evidence-Based Review

Supplemental material, Table S3, for Use of Janus Kinase Inhibitor Treatment for Palmoplantar Pustulosis: An Evidence-Based Review by Siddhartha Sood, Abrahim Abduelmula, Khalad Maliyar, Jorge R. Georgakopoulos, Asfandyar Mufti, Ronald Vender, Vimal H. Prajapati and Jensen Yeung in Journal of Cutaneous Medicine and Surgery