What Is Palmoplantar Pustulosis and How Is It Treated?

Palmoplantar pustulosis (PPP) is a chronic inflammatory skin condition that produces crops of small, sterile pustules on the palms and soles, often alongside painful cracking and scaling. It tends to run a stubborn, relapsing course, and it is notoriously difficult to treat. Despite superficial similarities to psoriasis, PPP has enough distinct features in its genetics, immune profile, and clinical behavior that many dermatologists now consider it a separate disease. Understanding what drives it, what triggers flares, and which treatments hold real promise matters, because PPP punches well above its weight in terms of how much it disrupts daily life.

What PPP Looks and Feels Like

The hallmark of PPP is clusters of small yellow or white pustules that erupt on the thick skin of the palms and soles. These pustules are sterile, meaning they are not caused by an infection, and they tend to appear in waves. Fresh pustules emerge, dry into brown spots, and peel away, only for new ones to replace them weeks or months later. In between flares, the affected skin is often red, thickened, and cracked, which can make walking or gripping objects painful. The condition almost exclusively affects the palms and soles, though nail changes and joint pain sometimes accompany it.

PPP is relatively rare in the general population but is considerably more common in East Asian populations, particularly in Japan.¹ Women develop it more frequently than men, and it most commonly appears in middle-aged adults. Pediatric cases are extremely rare.² The condition is strongly linked to smoking, with the vast majority of patients being current or former smokers.

Is PPP Actually Psoriasis?

This is one of the longest-running debates in dermatology, and the answer depends partly on where you practice. In some classification systems, PPP is considered a localized form of pustular psoriasis. In others, it is classified as its own entity. The overlap is real: PPP and psoriasis share some clinical features, including the Köbner phenomenon (new lesions appearing at sites of skin injury), nail involvement, and joint problems. They can also occur in the same families.³

But the differences are significant. PPP has a distinct genetic background compared to plaque psoriasis. It also has unique immune features, especially its strong involvement of the IL-23/Th17 pathway and IL-36 signaling, and a different demographic profile, with higher prevalence in East Asian populations and a striking female predominance.⁴ Perhaps most telling is the treatment gap: drugs that work well for plaque psoriasis often fail in PPP, which wouldn’t be the case if they were simply two faces of the same disease. For practical purposes, treating PPP as its own condition with its own treatment considerations gives patients better results than assuming it will respond like typical psoriasis.

What Drives the Inflammation

The immune process behind PPP centers on the eccrine sweat glands, the dense network of sweat-producing structures in the palms and soles. This is a key reason the disease is so localized. Research has shown that the sweat gland duct, specifically its uppermost portion called the acrosyringium, is an active immune structure that expresses IL-17, a pro-inflammatory signaling molecule. In PPP, this area becomes a focal point for immune attack.⁵

Biopsies from PPP skin reveal elevated levels of a whole suite of inflammatory molecules, including IL-8, IL-17A, IL-22, and IL-23. Blood tests tell a similar story: patients with PPP have higher circulating levels of IL-17A, IL-17F, and IL-22 than healthy individuals, and those levels track with how severe the disease is.⁶ In simple terms, the immune system mounts an aggressive inflammatory response in and around the sweat glands, which produces those characteristic pustules.

The IL-36 pathway also appears involved, though the picture is complicated. Mutations in a gene called IL36RN, which helps regulate IL-36 inflammation, have been found in some PPP patients and linked to earlier disease onset.⁷ However, a study of Japanese patients found these mutations in only a small fraction and concluded that PPP is not strongly driven by IL36RN mutations overall.⁸ The mutations that do occur also differ between European and East Asian patients, suggesting that the genetic underpinnings of PPP vary across populations.

Smoking and PPP

If there is one environmental factor that dominates the PPP story, it is tobacco. Smoking rates among PPP patients are dramatically higher than in the general population, and the link is so consistent that many researchers consider smoking a near-prerequisite for developing the disease, though non-smokers do get it. Research into the mechanism has found that nicotine alters the expression of nicotinic acetylcholine receptors in the skin. In PPP patients, the pattern of these receptors is abnormal, suggesting an exaggerated inflammatory response to nicotine in the sweat glands.⁹

What makes this frustrating for patients is that quitting smoking does not reliably clear the disease, at least not quickly. Some patients improve after stopping, but many continue to flare for years. The damage to sweat gland immune regulation appears to outlast the habit itself. That said, smoking cessation is still recommended because it removes one of the most powerful ongoing triggers and may improve the response to treatment over time.

The Tonsil Connection

One of the more surprising findings in PPP research, particularly in Japanese studies, is the role of the tonsils. Patients with PPP appear to have an overactive immune response to normal bacteria living in their tonsils, particularly streptococcal species. This is sometimes described as a breakdown in immune tolerance: the body’s ability to coexist peacefully with its own commensal bacteria fails, and the resulting immune activation radiates outward to the skin.¹⁰

More recent research has confirmed that the tonsils of PPP patients show enhanced Th17 and Th2 immune responses, and that Streptococcus bacteria in particular correlate with the expression of genes in these inflammatory pathways.¹¹ Multiple reports have described improvement in PPP skin lesions after tonsillectomy, particularly in Japanese patients. Tonsillectomy is not widely practiced for PPP outside of Japan, but the evidence suggests that for a subset of patients, the tonsils act as a reservoir that feeds the disease. This is especially relevant for patients who get recurrent tonsillitis alongside their PPP flares.

Metal Allergies and Other Triggers

Beyond smoking and tonsillar infection, contact allergy to metals is an underrecognized trigger. A systematic review evaluating over 500 PPP patients found that roughly a quarter had some form of allergy, and the overwhelming majority of those allergies were to metals. Among patients with confirmed metal allergy, about two-thirds saw improvement in their PPP after removing the metal source, whether that meant replacing dental fillings or avoiding jewelry.¹² This is not a universal cause, but it is worth investigating in patients who are not responding to standard treatment, particularly with patch testing for common metal allergens like nickel, cobalt, and chromium.

Getting the Diagnosis Right

PPP should be straightforward to recognize for a trained dermatologist, but in practice, diagnosis is often delayed. A registry study found that more than half of patients were initially misdiagnosed with eczema, leading to an average delay of nearly three years before the correct diagnosis was made.¹³ The confusion is understandable at a glance: the cracking, peeling, and redness of PPP can look a lot like chronic hand eczema, especially between pustule flares when the telltale pustules are absent. The key difference is that PPP produces distinct, recurrent crops of sterile pustules on a background of red, thickened skin, whereas eczema typically presents with itching, dryness, and vesicles rather than true pustules.

This diagnostic delay matters because the treatments are different. Eczema often responds to moisturizers and mild topical steroids, whereas PPP usually requires stronger interventions. Patients stuck on the wrong treatment path for years experience unnecessary suffering and may develop complications like secondary skin infections from the chronic cracking.

Associated Health Conditions

PPP does not exist in isolation. It has connections to several other health conditions that are worth being aware of. The most distinctive is SAPHO syndrome, a condition involving bone and joint inflammation (synovitis, acne, pustulosis, hyperostosis, osteitis). In some patients, PPP on the hands and feet is the first sign, with painful inflammation of the chest wall joints developing months later.¹⁴ The anterior chest wall is the most commonly affected skeletal site in PPP patients who develop bone and joint involvement.

Thyroid disorders have also drawn attention. One study found that anti-thyroid antibody levels were significantly higher in PPP patients than in controls, and the presence of thyroid abnormalities was a risk factor for PPP in initial analysis.¹⁵ Meanwhile, a separate study found high rates of elevated cholesterol and triglycerides in PPP patients, with nearly half having high LDL cholesterol and about a fifth having diabetes.¹⁶ Whether PPP directly raises metabolic risk or whether the two share upstream drivers like chronic inflammation and smoking is not fully clear, but screening for thyroid and metabolic problems is reasonable in anyone diagnosed with PPP.

Quality of Life

PPP’s impact on daily life is easy to underestimate from the outside. It affects the palms and soles, which are involved in virtually everything a person does: walking, working, cooking, exercising, shaking hands. A Swedish register study found that PPP patients reported worse quality of life than patients with plaque psoriasis when confounders were accounted for, despite PPP covering a much smaller body surface area.¹⁷ A Korean study found that average quality-of-life scores in PPP patients fell into the range that dermatologists classify as a “very large effect” on daily living, and patients with more severe disease scored significantly worse.¹⁸

The economic toll is also measurable. A Canadian population study found that medical costs for PPP patients were roughly double those for patients with standard plaque psoriasis, reflecting the frequent visits, failed treatments, and specialist referrals that come with a condition that doesn’t respond well to first-line therapies.

Traditional Treatment Options

Standard management of mild to moderate PPP relies on potent topical corticosteroids, phototherapy (especially PUVA, which combines a light-sensitizing medication with UV-A light), and acitretin, an oral retinoid. These approaches can control symptoms for a time, but they have not proven adequate for long-term control of more extensive disease.¹⁹ That gap between short-term suppression and lasting remission is a defining frustration of PPP.

Among systemic treatments, cyclosporine tends to produce the fastest clearance. A comparative trial pitting cyclosporine against methotrexate and acitretin found that cyclosporine brought the most rapid resolution of lesions, though acitretin provided a longer period of remission after treatment was stopped. Methotrexate fell behind both on speed and durability.²⁰ Cyclosporine’s effect appears to relate to its ability to tamp down IL-23 and TNF-alpha, key drivers of PPP inflammation.²¹ The downside is that cyclosporine carries risks with prolonged use, including kidney toxicity and high blood pressure, so it is usually reserved for short bursts rather than indefinite maintenance.

Biologic and Targeted Therapies

The biologics revolution that transformed plaque psoriasis treatment has been slower to pay off for PPP. TNF-alpha inhibitors, the first class of biologics used for psoriasis, have had inconsistent results in PPP. But newer drugs targeting IL-17 and IL-23 have shown more promise. A comprehensive review of biologics for PPP found that secukinumab (which blocks IL-17A) and guselkumab (which blocks IL-23) have shown better results than other biologics in clinical trials.²² Guselkumab is one of the few biologics to have undergone a dedicated phase 3 trial specifically for PPP, and serum biomarker data from that trial showed that it reduced the elevated IL-17 and IL-22 levels associated with disease activity.²³

Spesolimab, an antibody targeting the IL-36 receptor, has been an intriguing prospect because IL-36 signaling is elevated in PPP. An early pilot trial showed that PPP severity declined faster in patients receiving spesolimab than placebo, suggesting a potential treatment effect.²⁴ However, a larger follow-up dose-finding trial failed to meet its primary goal of demonstrating a clear dose-response relationship, though some improvements were seen in secondary measures and in non-Asian patients specifically.²⁵ That ethnic variation in response is a recurring theme in PPP trials and likely reflects the different genetic and immunological subtypes of the disease across populations.

The Microbiome Inside “Sterile” Pustules

One of the more thought-provoking recent findings is that the pustules of PPP, long described as sterile, actually contain bacterial DNA. Genetic sequencing of pustule contents has identified a diverse microbiome including members of several major bacterial groups. Smokers with PPP had notably higher levels of Staphylococcus bacteria in their pustules compared with non-smokers.²⁶ Whether these bacteria are actively contributing to the disease or are bystanders that colonize inflamed tissue is not yet clear, but the finding opens up new questions about whether manipulating the skin’s microbial environment could be therapeutic. It also adds another layer to the smoking connection, since tobacco use is known to alter the body’s microbiome in multiple locations.

Combined with the tonsillar microbiome research showing that Streptococcus correlates with Th17 gene expression in PPP tonsils, a picture is forming in which bacteria at distant sites may feed a cycle of immune activation that ultimately plays out in the palms and soles. This is still early-stage science, but it could eventually change how clinicians approach PPP, with interventions aimed at the microbiome rather than just suppressing the downstream inflammation.

Why PPP Is So Hard to Treat

Several features conspire to make PPP one of dermatology’s more stubborn conditions. The thick skin of the palms and soles limits how well topical treatments can penetrate. The disease runs a chronic, relapsing course that outlasts most short-term treatment regimens. And the immune mechanisms appear to differ between patients, and even between ethnic groups, which means a drug that works in one trial population may fail in another. The spesolimab trials illustrated this neatly, with benefits appearing in non-Asian patients but not reaching significance in the overall group.

There is also the challenge that PPP trials tend to have high placebo response rates, making it harder to demonstrate drug efficacy even when a drug is genuinely active. The natural waxing and waning of the disease means some patients will improve on their own during a trial, which washes out the drug’s signal statistically. Researchers have been rethinking how PPP trials should be designed, including using stricter enrollment criteria to ensure participants have active, severe disease at the start.

For patients navigating this landscape, the practical takeaway is that finding the right treatment often involves trial and error. A combination approach, such as a potent topical steroid plus phototherapy, or a systemic medication paired with trigger avoidance (quitting smoking, treating focal infections, investigating metal allergies), tends to give better results than any single therapy alone. Patch testing for metal allergies and screening for thyroid abnormalities are low-risk investigations that can occasionally uncover a modifiable factor that makes a real difference in disease control.