Topical Crisaborole for the Treatment of Recalcitrant Palmoplantar Pustulosis: A Case Series

Dermatol Ther (Heidelb) https://doi.org/10.1007/s13555-025-01419-w CASE SERIES Topical Crisaborole for the Treatment of Recalcitrant Palmoplantar Pustulosis: A Case Series Yen‑Yi Sung · Tsen‑Fang Tsai Received: March 8, 2025 / Accepted: April 9, 2025 © The Author(s) 2025 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 stand‑ ard treatment. We present three cases of recal‑ citrant PPP treated with topical 2% crisaborole cream in our clinic from October 2024 to Febru‑ ary 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 alter‑ native for such patients. The positive response of topical crisaborole observed in our cases also echoes the efficacy of apremilast, a systemic Y.-Y. Sung · T.-F. Tsai (*) Department of Dermatology, National Taiwan University Hospital, No. 7 Chung Shan South Road, Taipei City 10048, Taiwan e-mail: T.-F. Tsai Department of Dermatology, College of Medicine, National Taiwan University Hospital and National Taiwan University, Taipei City, Taiwan phosphodiesterase 4 (PDE4) inhibitor which successfully treated PPP in other reports, high‑ lighting the potential role of PDE4 in the patho‑ physiology 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. Vol.:(0123456789) Dermatol Ther (Heidelb) 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 concomi‑ tant plaque type psoriasis may be present, which is often referred as palmoplantar pustular psoria‑ sis (PPPP) [2]. Thus, a clear distinction between palmoplantar psoriasis and PPP may be difficult. Arthritis, either as SAPHO (synovitis, acne, pus‑ tulosis, 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 thy‑ roid diseases have been reported. Although PPP is conventionally considered as a variant of pso‑ riasis, 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 suc‑ cessfully with topical 2% crisaborole. CASE PRESENTATION From October 2024 to February 2025, three con‑ secutive 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 pub‑ lish their case details and images. The age ranged from 46 to 78 years old. Concurrent underly‑ ing diseases included hyperthyroidism and viti‑ ligo. The male patient was the only smoker, and presented with axial joint pain involving his sternoclavicular joints, shoulders, and costos‑ ternal joints (case 3). Active arthritis was later supported by a bone scan (Fig. 1). The patho‑ logical findings were all typical for PPP, show‑ ing psoriasiform epidermal hyperplasia, par‑ akeratosis, 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 topi‑ cal crisaborole treatment (Fig. 2). DISCUSSION There is currently no standard treatment for PPP, and it is usually treated similarly to pso‑ riasis vulgaris using topical corticosteroid, topical vitamin D, oral methotrexate, acitre‑ tin, cyclosporine, or photo(chemo)therapy. Guselkumab, risankizumab, and brodalumab, in time sequence, have been approved for the treat‑ ment of PPP in some countries. However, the treatments are expensive and their efficacy var‑ ies 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 metaanalyses, PPP is often studied along with pal‑ moplantar psoriasis [5–7]. More recently, suc‑ cessful 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. Addi‑ tional 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, top‑ ical treatment presents an appealing approach. However, currently approved drugs are admin‑ istered systemically. Topical crisaborole is now approved for atopic dermatitis treatment, but its off-label use has also been reported in 56 78 1 2 F F 75 53 Age (y) Sex Age of onset (y) No. Patient characteristics 17.3 Vitiligo No 9 7.2 1.8 2.8 No No Smoking Baseline 4-week Axial PPPASI PPPASI disease 18.2 Hyperthy- No roidism BMI Concurrent disease Clinical presentation Yes Yes N/A 77 Pathol- IgE (IU/ ogy mL) exam Examination Table 1  Characteristics of patients with palmoplantar pustulosis treated with topical 2% c (...truncated)