Race for the Case answers

Answers to Winter 2020 Race for the Case by Julia Escandon Brehm, MD, PhD

A 23-year-old woman with a history of ulcerative colitis (UC) presented with a 3-week history of a pustular rash on the palms and soles that is intermittently pruritic but not painful. The patient had been on infliximab for her UC for 7 months when the rash appeared. Infliximab was stopped due to concern for a paradoxical drug-related reaction. Histopathological evaluation of a lesion on the left palm demonstrated a subcorneal bulla with neutrophils, and Periodic-acid Schiff stain was negative for fungal organisms. She was started on topical steroids and cyclosporine 100mg twice daily. After one month on this treatment regimen, the rash improved significantly but did not completely resolve. The patient has recently been started on Ustekinumab to manage her UC.

1. What is the diagnosis?
   Answer: Palmoplantar pustulosis

2. What factors support this diagnosis over a diagnosis of palmoplantar psoriasis?
   Answer: The relationship between palmoplantar pustulosis and palmoplantar psoriasis is controversial, and the two entities may exhibit many overlapping clinical and histological features. Some may argue that palmoplantar psoriasis may not be ruled out in this case or that the two diagnoses are one and the same. However, the absence of other psoriatic lesions in the acute clinical setting has been noted to favor a diagnosis of palmoplantar pustulosis over palmoplantar psoriasis. Additionally, the lack of a personal or family history of psoriasis may render palmoplantar psoriasis less likely.

3. What factor(s) in this patient’s history likely contributed to the development of this condition?
   Answer: The pathogenesis of palmoplantar pustulosis is not fully understood, but there have been several reports of palmoplantar pustulosis being elicited by the use of anti-Tumor Necrosis Factor (TNF)-alpha biologic agents. The pathophysiology behind this paradoxical reaction is unclear but may be related to an imbalance of TNF-alpha and interferon (IFN)-alpha molecules in genetically susceptible patients.

4. What information is important to elicit from this patient’s social history that is associated with the development of this condition?
   Answer: Smoking is very closely associated with palmoplantar pustulosis. It has been postulated that palmoplantar pustulosis is an autoimmune condition triggered by nicotine.

5. Name some potential treatment options.
   Answer: High-quality data demonstrating the efficacy of various treatment options for palmoplantar pustulosis are lacking. Topical corticosteroids have modest efficacy given the thicker stratum corneum of the palms and soles that inhibits penetration. Ultraviolet (UV) therapy and systemic treatments such as acitretin, methotrexate and cyclosporine have been described with variable efficacy. Anti-TNF-alpha biologics exhibit conflicting results in the treatment of palmoplantar pustulosis and have actually been associated with the onset of the condition. Apremilast and anti-interleukin (IL)-12/23 agents have been used, also with variable efficacy. Studies have demonstrated promising data for the use of anti-IL-17A agents for the treatment of palmoplantar pustulosis.

6. How is the pustular rash expected to evolve with the addition of an anti-IL-12/23 agent (Ustekinumb)?
   Answer: Case reports and series have documented the success of ustekinumab in treating palmoplantar pustulosis, so we may expect the rash to continue to improve with the addition of this biologic. The improvement of palmoplantar pustulosis with ustekinumab is thought to be related to the attenuation of T helper(Th)-17 cell activity by disruption of the IL-23/IL-17 axis. Th17 cells are thought to contribute to the development of palmoplantar pustulosis through their role in neutrophil recruitment.

References

Hegazy S, Konstantinou MP, Bulai Livideanu C, Tauber M, Uthurriague C, Paul C. Efficacy of ustekinumab in palmoplantar pustulosis. J Eur Acad Dermatol Venereol. 2018 May;32(5):e204-e206. doi: 10.1111/jdv.14718. Epub 2018 Jan 8. PMID: 29194805.

Raposo I, Torres T. Palmoplantar Psoriasis and Palmoplantar Pustulosis: Current Treatment and Future Prospects. Am J Clin Dermatol. 2016 Aug;17(4):349-58. doi: 10.1007/s40257-016-0191-7. PMID: 27113059.

Oktem A, Uysal PI, Akdoğan N, Tokmak A, Yalcin B. Clinical characteristics and associations of palmoplantar pustulosis: an observational study. An Bras Dermatol. 2020 Jan-Feb;95(1):15-19. doi: 10.1016/j.abd.2019.04.008. Epub 2019 Dec 14. PMID: 31899067; PMCID: PMC7058866.

Brunasso AMG, Massone C. Psoriasis and palmoplantar pustulosis: an endless debate? J Eur Acad Dermatol Venereol. 2017 Jul;31(7):e335-e337. doi: 10.1111/jdv.14131. Epub 2017 Feb 21. PMID: 28107592.

Related Academy resources