Abstract
Palmoplantar pustulosis (PPP) is a chronic, relapsing disease with sterile pustules involving the palms and soles. The pathogenesis of PPP remains unclear and there is currently no standard treatment. We present three cases of recalcitrant PPP treated with topical 2% crisaborole cream in our clinic from October 2024 to February 2025. All of the patients had received skin biopsy to prove their diagnosis and had been treated with various treatments with limited response. After 4 weeks of topical crisaborole, their palmoplantar pustulosis area and severity index decreased from 7.2 to 2.8, 9 to 1.8, and 28.4 to 0, respectively. Given that PPP involves the skin locally, an effective topical treatment may provide a convenient, inexpensive alternative for such patients. The positive response of topical crisaborole observed in our cases also echoes the efficacy of apremilast, a systemic phosphodiesterase 4 (PDE4) inhibitor which successfully treated PPP in other reports, highlighting the potential role of PDE4 in the pathophysiology of PPP. Further studies are needed for a more comprehensive evaluation.
Keywords: Palmoplantar pustulosis, Crisaborole, Phosphodiesterase 4 inhibitor
Key Summary Points
| Palmoplantar pustulosis (PPP) is commonly considered as a subtype of psoriasis with crops of sterile pustules on the palms and soles. |
| The etiology of PPP remains unclear, and it is usually treated similarly to psoriasis vulgaris. |
| We present three biopsy-proven, recalcitrant cases of PPP successfully treated with topical 2% crisaborole cream. |
| All patients reported improved symptoms and had a decrease in their palmoplantar pustulosis area and severity index (PPPASI) after 4 weeks of topical crisaborole treatment. |
| Topical crisaborole may provide a safe and cost-effective treatment for patients with recalcitrant PPP. |
Introduction
Palmoplantar pustulosis (PPP) is a subtype of pustular psoriasis typically presenting as crops of sterile pustules on the palms and soles [1]. It is more commonly seen in Asian population, and has a female predominance in most studies. In addition to lesions on the palms and soles, there may be pustular lesions elsewhere, and concomitant plaque type psoriasis may be present, which is often referred as palmoplantar pustular psoriasis (PPPP) [2]. Thus, a clear distinction between palmoplantar psoriasis and PPP may be difficult. Arthritis, either as SAPHO (synovitis, acne, pustulosis, hyperostosis, osteitis) or PAO (pustulotic arthro-osteitis) syndrome, may be present. The etiology is unknown but associations between metal allergy, dental or tonsil infection, and thyroid diseases have been reported. Although PPP is conventionally considered as a variant of psoriasis, T helper 2 cell (Th2) skewing is recently reported as evidenced by the treatment efficacy of dupilumab, an interleukin (IL)-4 receptor alpha blocker [3]. Here, we present three cases of biopsy-proven recalcitrant PPP treated successfully with topical 2% crisaborole.
Case Presentation
From October 2024 to February 2025, three consecutive cases of PPP who had been treated with other therapies with inadequate responses or intolerable adverse effects were prescribed with topical 2% crisaborole in our clinic (Table 1). All of the patients provided written consent to publish their case details and images. The age ranged from 46 to 78 years old. Concurrent underlying diseases included hyperthyroidism and vitiligo. The male patient was the only smoker, and presented with axial joint pain involving his sternoclavicular joints, shoulders, and costosternal joints (case 3). Active arthritis was later supported by a bone scan (Fig. 1). The pathological findings were all typical for PPP, showing psoriasiform epidermal hyperplasia, parakeratosis, and neutrophil accumulation in the corneal layer with or without microabscessess. One patient had elevated IgE level (case 3) and one patient had elevated anti-thyroid peroxidase antibody (anti-TPO) (case 1). All of the patients reported improvement in symptoms and had a decrease in their palmoplantar pustulosis area and severity index (PPPASI) after 4 weeks of topical crisaborole treatment (Fig. 2).
Table 1.
Characteristics of patients with palmoplantar pustulosis treated with topical 2% crisaborole
| No. | Patient characteristics | Clinical presentation | Examination | Concurrent treatment with topical crisaborole | Previous treatment | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age (y) | Sex | Age of onset (y) | BMI | Concurrent disease | Smoking | Baseline PPPASI | 4-week PPPASI | Axial disease | Pathology exam | IgE (IU/mL) | Anti-TPO (IU/mL) | Other exams | |||
| 1 | 56 | F | 53 | 18.2 | Hyperthyroidism | No | 7.2 | 2.8 | No | Yes | 77 | 24.41 | N/A | Nil | Azathioprine, hydroxychloroquine, steroid (systemic/topical), UVB |
| 2 | 78 | F | 75 | 17.3 | Vitiligo | No | 9 | 1.8 | No | Yes | N/A | < 3.00 | N/A | Nil | Acitretin, hydroxychloroquine, methotrexate, tofacitinib, UVB |
| 3 | 46 | M | 42 | 21.4 | Pustulotic arthro-osteitis | Yes | 28.4 | 0 | Yes | Yes | > 5000 | < 3.00 | HLA-B27(−) | Nil | Azathioprine, calcipotriene (topical), cyclosporine, methotrexate, steroid (systemic/topical), sulfasalzaine, UVB |
Anti-TPO anti-thyroid peroxidase antibody, BMI body mass index, F female, M male, PPPASI palmoplantar pustulosis area and severity index, PUVA psoralen and ultraviolet A phototherapy, UVB ultraviolet B phototherapy, y years old
Fig. 1.
Whole-body bone scan of case 3 was suggestive of active arthritis at bilateral sternoclavicular junctions and sternal angle, with suspicion of an inflammatory process involving chondral portion of right 6th rib and bilateral sacroiliac joints
Fig. 2.
Case 3. a Palmoplantar pustulosis on the palms and soles of a 42-year-old male patient. b Improvement after 4 weeks of topical 2% crisaborole treatment
Discussion
There is currently no standard treatment for PPP, and it is usually treated similarly to psoriasis vulgaris using topical corticosteroid, topical vitamin D, oral methotrexate, acitretin, cyclosporine, or photo(chemo)therapy. Guselkumab, risankizumab, and brodalumab, in time sequence, have been approved for the treatment of PPP in some countries. However, the treatments are expensive and their efficacy varies among individuals. In one meta-analysis of randomized controlled trials in PPP, guselkumab emerged as the most favored drug, followed by apremilast and brodalumab [4]. In other meta-analyses, PPP is often studied along with palmoplantar psoriasis [5–7]. More recently, successful treatments with an oral Janus kinase inhibitor (JAKi) and dupilumab have also been reported [3, 8]. These clinical findings suggest a complex pathophysiology of PPP, with not only interleukin (IL)-17 but also the IL-4/13 pathway involved.
The severity and clinical presentation of PPP often fluctuate during disease course and the diagnosis may be sometimes challenging. Additional investigations conducted at our hospital such as the bone scan for case 3 demonstrated evidence of PAO, a manifestation most often seen in patients with PPP. The presence of other features such as autoimmune thyroiditis and vitiligo also help in the differential diagnoses from other pustular lesions of the palmoplantar areas, such as pompholyx [9].
Since PPP is often a localized skin disease, topical treatment presents an appealing approach. However, currently approved drugs are administered systemically. Topical crisaborole is now approved for atopic dermatitis treatment, but its off-label use has also been reported in several other skin diseases, including psoriasis [10]. Given the success of apremilast in treating PPP [11], topical crisaborole offers an attractive alternative as both exert their effects through phosphodiesterase 4 (PDE4) inhibition. In our experience, use of topical crisaborole resulted in rapid and reproducible responses comparable to the previous treatment with less adverse effects and at a lower cost. Therefore, topical crisaborole may be a potential treatment option for patients with PPP who failed or were intolerable to other treatments.
Conclusion
Topical 2% crisaborole cream is a potentially safe and cost-effective treatment for refractory PPP that may also result in better compliance. Further studies are needed to clarify the efficacy and underlying mechanisms of topical crisaborole in PPP.
Acknowledgements
The authors thank the participants of the study. All the patients have given written informed consent to publication of their case details.
Author Contribution
Yen-Yi Sung and Tsen-Fang Tsai contributed to the manuscript draft. Tsen-Fang Tsai reviewed and edited the manuscript. Yen-Yi Sung and Tsen-Fang Tsai both contributed to the revision. All authors approved the final version.
Funding
No funding or sponsorship was received for this study or publication of this article.
Data Availability
The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.
Declarations
Conflict of Interest
Yen-Yi Sung and Tsen-Fang Tsai have no conflict of interest to declare.
Ethical Approval
All the patients have given written informed consent to publication of their case details and images.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.