Palmoplantar pustulosis is a long-lasting skin condition that causes painful, pus-filled blisters and scaly patches on the palms of the hands and soles of the feet. Though it shares some features with psoriasis, this condition presents unique challenges in treatment and daily living, affecting a person’s ability to walk comfortably or use their hands without pain.

Understanding Treatment Goals for Palmoplantar Pustulosis

When someone receives a diagnosis of palmoplantar pustulosis, the primary focus of treatment shifts toward managing symptoms and improving quality of life. This condition cannot be cured, but medical care aims to reduce the frequency and severity of flare-ups, control inflammation, and help the skin heal. Because the palms and soles are areas of the body that experience constant use and friction, even small improvements in symptoms can make a significant difference in daily activities like walking, typing, cooking, or simply holding objects.

Treatment approaches vary depending on how severe the condition is and how each person responds to different therapies. Some individuals may find relief with simple topical treatments applied directly to the skin, while others require stronger medications taken by mouth or delivered through injections. The stage of the disease matters too—early intervention with appropriate treatment can sometimes prevent the condition from worsening or spreading to larger areas of the hands and feet.

Medical societies and dermatology organizations recognize palmoplantar pustulosis as a challenging condition to treat. Standard treatments that work well for regular plaque psoriasis—a common skin condition characterized by thick, scaly patches—may not always be as effective for palmoplantar pustulosis. This has led researchers and doctors to explore new therapies specifically designed to target the unique inflammatory processes that drive this particular condition.

Beyond controlling visible symptoms, treatment also addresses the significant impact this condition has on mental and emotional wellbeing. The visible nature of pustules and cracked skin on the hands can make people self-conscious about shaking hands or engaging in social activities. Pain and discomfort from affected feet can limit mobility and independence. Therefore, comprehensive care includes not only medication but also practical advice for skin protection, lifestyle modifications, and psychological support.

Standard Treatment Options

The foundation of palmoplantar pustulosis treatment typically begins with topical medications—creams, ointments, or lotions applied directly to the affected skin. Topical corticosteroids, also called steroid creams, are among the most commonly prescribed first-line treatments. These medications work by reducing inflammation, which helps decrease redness, swelling, and the burning sensation many people experience. Examples include betnovate and clobetasol propionate, which are potent steroids that can provide relief when used correctly.^[1]

Doctors often recommend using steroid creams with a technique called occlusion, which involves covering the medicated area with plastic gloves on the hands or cotton socks on the feet. This covering helps the medication penetrate more deeply into the skin and increases its effectiveness. However, occlusion should only be done under medical supervision, as overuse of strong steroid creams can cause skin thinning and other side effects.^[2]

Another topical option is coal tar ointment, which has been used for decades to treat various skin conditions. Coal tar helps slow down the rapid production of skin cells that contributes to scaling and thickness. It can also reduce itching and help blisters heal more quickly. While effective for some patients, coal tar has a strong smell and can stain clothing, which may limit its appeal for everyday use.^[6]

For patients who do not respond adequately to topical treatments alone, phototherapy becomes an important option. This involves exposing the skin to specific wavelengths of ultraviolet light under medical supervision. One common approach is PUVA therapy, which combines a medication called psoralen with ultraviolet A light exposure. The psoralen makes the skin more sensitive to the light, allowing the treatment to work more effectively at slowing skin cell growth and reducing inflammation. PUVA can provide relief for extended periods, though multiple sessions are typically required over several weeks or months.^[6]

When topical treatments and phototherapy prove insufficient, doctors may prescribe oral medications that work throughout the body. Acitretin, a medication derived from vitamin A, is considered one of the most effective systemic treatments for palmoplantar pustulosis, especially when combined with PUVA therapy. Acitretin works by regulating skin cell growth and reducing inflammation, but it comes with important considerations. Women who are pregnant or might become pregnant cannot use this medication because it can cause severe birth defects. Men who plan to father children should also discuss the risks with their doctor. Additionally, acitretin can cause side effects such as dry skin, lips, and eyes, as well as changes in cholesterol levels that require monitoring through blood tests.^[6][5]

Fumaric acid preparations represent another oral treatment option that some patients find helpful. These medications modulate the immune system and have anti-inflammatory properties. While not as commonly used as other treatments, fumaric acid can be effective for certain individuals and may enhance the benefits of PUVA therapy when used together.

Ciclosporin, also spelled cyclosporine, is an immunosuppressive medication that works by dampening the overactive immune response that drives palmoplantar pustulosis. This medication acts relatively quickly compared to some other treatments, and patients may notice improvement within weeks. However, one significant drawback is that symptoms often return shortly after stopping the medication. Long-term use of ciclosporin requires careful monitoring because it can affect kidney function and blood pressure.^[5]

The duration of treatment varies widely depending on the individual and the specific therapy being used. Topical steroids might be used intermittently during flare-ups, while systemic medications like acitretin may need to be taken for several months or even longer to maintain control of symptoms. Phototherapy typically involves multiple sessions per week for a period of several weeks, with maintenance treatments sometimes needed afterward.

Side effects are an important consideration with all treatments. Topical steroids can thin the skin if used excessively or for prolonged periods. Phototherapy carries a small risk of skin damage from UV exposure. Systemic medications can affect various body systems, requiring regular blood tests to monitor liver function, kidney function, blood counts, and cholesterol levels. Doctors work with patients to balance the benefits of treatment against potential risks and side effects.

Innovative Treatments Being Tested in Clinical Trials

Because standard treatments do not work for everyone with palmoplantar pustulosis, researchers continue to investigate new therapies that target specific parts of the immune system involved in this condition. Clinical trials are research studies that test whether new treatments are safe and effective before they become widely available to patients.

Biologic therapies represent a major area of research and treatment advancement. These are medications made from living cells that target specific proteins or cells in the immune system. Unlike traditional immunosuppressive drugs that broadly dampen immune function, biologics work more precisely on particular inflammatory pathways. Several types of biologic medications have shown promise for palmoplantar pustulosis.

TNF-alpha inhibitors are biologics that block tumor necrosis factor-alpha, a protein that promotes inflammation. Medications in this category include adalimumab, etanercept, and infliximab. These drugs are given by injection or intravenous infusion. While TNF-alpha inhibitors have proven effective for many people with psoriasis, their results in palmoplantar pustulosis have been more variable. Interestingly, in some cases, TNF-alpha inhibitors can paradoxically trigger or worsen palmoplantar pustulosis, a phenomenon called paradoxical reaction. Despite this complication in some patients, these medications do help certain individuals achieve better control of their symptoms.^[2][5]

Newer biologic treatments targeting interleukin-17 (IL-17) and interleukin-23 (IL-23) have shown even better results for palmoplantar pustulosis. These proteins play crucial roles in the inflammatory process that creates pustules and skin changes. Medications that block IL-17 include ixekizumab and bimekizumab. Those targeting IL-23 include medications that prevent this protein from activating inflammatory cells. Clinical experience and trial data suggest that anti-IL-17 and anti-IL-23 biologics can be particularly effective for people with palmoplantar pustulosis, sometimes producing dramatic improvements in pustule counts, skin thickness, pain, and overall quality of life.^[5][6]

Apremilast is an oral medication that works differently from traditional immunosuppressants. It inhibits an enzyme called phosphodiesterase-4 (PDE-4), which is involved in inflammation. By blocking this enzyme, apremilast reduces the production of inflammatory chemicals inside cells. This medication is taken as a pill twice daily and has shown good results in clinical trials for palmoplantar pustulosis. Because it works through a different mechanism than biologics, apremilast may be a good option for people who cannot take injections or who have not responded to other treatments.^[5]

An exciting area of current research focuses on the interleukin-36 (IL-36) pathway. Scientists have discovered that IL-36 proteins play a particularly important role in pustular skin conditions. Unlike the inflammation seen in typical plaque psoriasis, pustular conditions involve activation of innate immunity—the body’s first-line defense system. IL-36 isoforms are strongly implicated in this process, making them an attractive target for new treatments specifically designed for pustular disorders.^[19]

Several experimental medications targeting the IL-36 pathway are currently being evaluated in clinical trials. Spesolimab, also known by its development code BI 655130, is a monoclonal antibody that blocks the IL-36 receptor. By preventing IL-36 from binding to its receptor on cells, spesolimab interrupts the inflammatory cascade that leads to pustule formation. Early clinical trial results have been promising, with some patients experiencing rapid improvement in symptoms. Another experimental drug called ANB019 works through a similar mechanism by blocking the IL-36 receptor.^[19]

Researchers are also investigating whether blocking interleukin-1 (IL-1), another protein involved in innate immunity, might help treat palmoplantar pustulosis. IL-1 works in a related inflammatory pathway and has been implicated in the disease process.

Janus kinase (JAK) inhibitors represent another promising class of medications. These drugs block enzymes called Janus kinases that are involved in signaling between immune cells. JAK inhibitors can be taken orally, and some formulations are available as topical creams. While most data on JAK inhibitors for palmoplantar pustulosis come from case reports rather than large clinical trials, the early results appear encouraging and suggest this could become an important treatment option in the future.^[5]

Clinical trials typically progress through three phases. Phase I trials focus primarily on safety, testing the new treatment in a small group of people to identify what dose can be given safely and what side effects occur. Phase II trials expand to a larger group and begin to evaluate whether the treatment actually works—whether it reduces symptoms and improves the condition. Phase III trials involve even larger numbers of patients and compare the new treatment directly against current standard treatments to determine whether it offers meaningful advantages.

Trial locations vary depending on the specific study, but clinical research for palmoplantar pustulosis is conducted worldwide, including in the United States, various European countries, and other regions. Patient eligibility for trials depends on many factors including disease severity, previous treatments tried, other medical conditions, and specific criteria set by the researchers. People interested in participating in clinical trials should discuss this option with their dermatologist, who can help identify appropriate studies and determine whether enrollment might be beneficial.

Preliminary results from trials of IL-36 blockers and newer IL-17 and IL-23 inhibitors have shown reductions in pustule counts, improvements in skin appearance and texture, decreased pain and itching, and positive safety profiles. However, it’s important to remember that drugs in clinical trials are still being studied and have not yet been approved for general use. Their long-term effectiveness and safety continue to be evaluated.

Most common treatment methods

• Topical medications
  • Potent corticosteroid creams such as betnovate and clobetasol propionate to reduce inflammation and control symptoms
  • Coal tar ointment to slow skin cell production and reduce itching
  • Often used with occlusion technique involving plastic gloves or cotton socks to enhance penetration
• Phototherapy
  • PUVA therapy combining psoralen medication with ultraviolet A light exposure
  • Multiple sessions required over weeks or months
  • Can provide extended periods of symptom relief
• Oral retinoids
  • Acitretin derived from vitamin A, considered one of the most effective systemic treatments
  • Works by regulating skin cell growth and reducing inflammation
  • Particularly effective when combined with PUVA therapy
  • Requires careful monitoring and has contraindications for pregnancy
• Immunosuppressive medications
  • Ciclosporin provides relatively quick relief but symptoms often return after stopping
  • Requires monitoring of kidney function and blood pressure
  • Fumaric acid preparations offer immune modulation with anti-inflammatory effects
• Biologic therapies
  • TNF-alpha inhibitors including adalimumab, etanercept, and infliximab given by injection or infusion
  • IL-17 blockers such as ixekizumab and bimekizumab showing particularly good results
  • IL-23 inhibitors targeting specific inflammatory pathways
  • Precisely target specific immune system proteins involved in inflammation
• PDE-4 inhibitor
  • Apremilast taken as oral medication twice daily
  • Works by blocking phosphodiesterase-4 enzyme to reduce inflammatory chemical production
  • Alternative for patients who cannot take injections
• Experimental IL-36 pathway blockers
  • Spesolimab (BI 655130) blocking IL-36 receptor in clinical trials
  • ANB019 with similar mechanism targeting IL-36 pathway
  • Specifically designed for pustular conditions based on innate immunity research
  • Showing promising early results in clinical studies
• JAK inhibitors
  • Oral and topical formulations blocking Janus kinase enzymes
  • Early case reports showing encouraging results
  • Larger trials needed to establish effectiveness