While palmoplantar pustulosis may share some underlying pathophysiology with plaque psoriasis and generalized pustular psoriasis, it is a distinct entity with different treatment approaches. An in-depth seminar at the 2024 Fall Clinical Dermatology Conference was held to explore emerging options for this condition.

Following this presentation, featured expert Joel M. Gelfand, MD, MSCE, was interviewed by Conference Reporter Associate Editor-in-Chief Rick Davis. Dr Gelfand’s clinical perspectives on this topic are presented here.

Palmoplantar pustulosis is a distinct entity from psoriasis, with different genetics and response to treatment from that of plaque psoriasis or generalized pustular psoriasis. Treatments that work well for plaque psoriasis and generalized pustular psoriasis often do not work for palmoplantar pustulosis.

The disease is most common in middle-aged women who are smokers. One of the strongest associations in medicine is smoking and lung cancer. The second-strongest association of smoking with any other disease that I am aware of is palmoplantar pustulosis. Understanding the connection to this population can be a starting clue to the diagnosis of palmoplantar pustulosis. It can sometimes be hard to differentiate between palmoplantar pustulosis and dyshidrotic eczema, and a skin biopsy could be helpful because the diseases require very different treatments. Dyshidrotic eczema responds well to some of the biologic therapies we use for eczema, whereas palmoplantar pustulosis does not respond to these biologics.

Palmoplantar pustulosis is variable both in how it presents and how it evolves over time. The disease often starts on 1 palm or sole. It may be limited to just the palm or the sole, or it could include both. Palmoplantar pustulosis can have acute flares or be chronic. Further, patients may experience 1 or 2 pustules per month that they can manage topically, but they may occasionally have flares with dozens of disabling pustules. There can also be spontaneous remissions for reasons that we do not fully understand.

When treating palmoplantar pustulosis, we typically start with topical therapies because that can be the easiest, fastest way to quickly control the disease. If patients have disabling involvement with many lesions or an inability to walk or use their hands, they will need systemic treatment, but we can initiate topical therapy while preparing to switch the patient to a systemic treatment.

As discussed in my session with Tina Bhutani, MD, at the 2024 Fall Clinical Dermatology Conference, I was involved in a study for which we worked with 20 academic medical centers across the United States to treat palmoplantar pustulosis. We found that more than 20 therapies are routinely tried for this disease, which is a sign of how challenging it is to treat. Some of the traditional therapies that have been used over time include cyclosporine, which can be effective but has the potential for side effects and, ideally, should not be used long-term, methotrexate, and PUVA. Acitretin, a form of vitamin A, can be helpful, but it cannot be used in women of childbearing age who may not use reliable contraception for the duration of treatment and for at least 3 years after because it can cause birth defects.

When we consider the more modern therapeutics, there are mixed data for palmoplantar pustulosis. The IL-36 inhibitor spesolimab was tested in a phase 2b trial and was found to be ineffective. There are some hints that the IL-17 inhibitor secukinumab may be helpful, but the response was variable and the primary end point was not met in the phase 3b 2PRECISE trial. Additionally, the newer IL-17 inhibitor bimekizumab has some anecdotal evidence indicating that it may be helpful.

Phase 3 data have recently emerged from Japan showing that the PDE4 inhibitor apremilast was statistically superior to placebo. We have been using apremilast off-label for palmoplantar pustulosis for years in the United States, so these data provide some support for that. There are anecdotal reports of the TYK2 inhibitor deucravacitinib showing potential benefit. IL-23 biologics have also been tried, with some evidence of guselkumab demonstrating symptom improvement vs placebo in a phase 3 clinical trial in Japan.

The clinician is tasked with managing this difficult-to-treat, disabling condition. First, we need to prepare the patient with palmoplantar pustulosis to use topicals properly. We often need to augment the topical approach because the stratum corneum is so thick in the palms and soles that it is difficult to get the medication to penetrate. Because keratolytics are needed to thin out the stratum corneum, I often use 50% propylene glycol compounded in water and instruct patients to soak their palms or feet for 5 minutes before applying topical medication (such as a class 1 steroid) under occlusion. This approach can be helpful to initially achieve control of disease. We cannot use potent topical steroids long-term because they can cause atrophy, but they can initially help get the disease under good control rapidly. Second, the patient needs to understand that the first treatment we try may not work. However, they should not give up if a treatment fails; we usually eventually find the right therapy for each individual.