Last week, I was presenting online about psoriasis. Whilst I was discussing variants of the condition, I mentioned pustular psoriasis – particularly the type that exclusively affects the palms and soles of the feet which is known as palmoplantar pustulosis (PPP). For many years it has been considered to be a sub-type of psoriasis but recent literature has begun to challenge this theory suggesting PPP may be a separate disease. This article examines some of the evidence and looks at recent advances in its treatment.
PPP is characterised by erythema of the plantar surface which gradually becomes studded with sterile pustules of about 2-4mm diameter. These can coalesce to form larger lesions. Eventually, as they resolve they darken, dry out and eventually desquamate. The epidermis beneath them is fragile, erythemic and the condition is frequently accompanied by hyperkeratosis. Most patients describe how the condition relapses and remits – just like psoriasis. Interestingly, research has also shown how frequently the two conditions may co-exist [1].
If we look at the typical disease characteristics of PPP we can begin to see how much it differs from psoriasis. Firstly, PPP affects women in a ratio of 5:1. Psoriasis shows a much more balanced gender bias. The typical onset period for PPP is 30-50 years of age, whilst psoriasis shows twin peaks in the teenage years and in the 40+ age group. Only 20% of patients with PPP, show a family history of psoriasis or show psoriasis elsewhere on their body which is perhaps surprising. Nail changes can be observed in both psoriasis and PPP. A study has shown nail involvement in the latter to be in 66% of patients. Psoriasis also shares a significant number of patients with nail problems. Common to both is onycholysis but pitting and sub-ungual hyperkeratosis was much more evident in psoriasis [2].
Delving into the causation, PPP shows a strong correlation with smoking, far more than psoriasis. In fact, some studies have shown smoking rates amongst PPP patients to be up to 90% [3]. Smoking cessation, unfortunately, does little to improve the condition once triggered it would seem. Other research has highlighted how the inflammation in the plantar and palmar skin is focussed around the sweat duct possibly due to cross-reactivity within the sweat ducts in an auto-immune fashion [4]. Auto-immune diseases generally happen in pairs and studies have illustrated how many patients with PPP also have diagnosable thyroid disease [5]. Allergy is also another theory that has been put forward.
Other differences between PPP and psoriasis have been reported:
· PPP does not appear to share similar genetic susceptibilities with psoriasis.
· Psoriatic arthritis does not appear to be associated with PPP.
· Fewer nail abnormalities in patients with PPP than psoriasis
· Traditional treatments for psoriasis rarely improve PPP
Treatment
Management of PPP has continued to be a challenge for this stubborn skin condition. A Cochrane review on this topic highlighted the lack of evidence of effectiveness for most of the proposed treatment. However, perhaps there is light at the end of the tunnel for sufferers of PPP.
As with psoriasis, biological drugs may hold the key. Biological drugs are designed to target specific receptors or inflammatory cytokines associated with auto-immune disease to suppress the disease. Unlike traditional immunosuppressive drugs, they only target one or two aspects of the immune system and thereby decreasing the risk of the broader side effects. A study in Japan [6] recruited 49 patients with moderate to severe PPP and randomized them to receive Guselkumab (IL-23 inhibitor) or a placebo. The results showed a significant response in the guselkumab versus placebo group and greater clearance of their PPP. Another retrospective study collated data from patients receiving a range of biologicals (infliximab, entanercept, adalimumab and ustekinumab) for their PPP. The work concluded that biologicals could induce complete clearance, rates varied between 20% with entanercept and infliximab to 39% with ustekinumab [7]. Other drugs such as Apremilast have also shown effectiveness in treating the condition [8-10]. Moving forward as new drugs are developed at pace, we are likely to see newer biological agents brought to market, with increasing efficacy for this stubborn condition.
Please read another article which I published on this subject - available here
References
1. Andersen, Y.M.F., et al., Characteristics and prevalence of plaque psoriasis in patients with palmoplantar pustulosis. British Journal of Dermatology, 2015.
2. Kim, M., et al., Nail involvement features in palmoplantar pustulosis. The Journal of Dermatology, 2020.
3. Keiju Kobayashi, et al., Cigarette smoke underlies the pathogenesis of palmoplantar pustulosis via an IL-17A-induced production of IL-36γ in tonsillar epithelial cells. Journal of the American Academy of Dermatology, 2020:
4. Hagforsen, E., et al., Palmoplantar pustulosis: an autoimmune disease precipitated by smoking? Acta Derm Venereol, 2002. 82(5): p. 341-6.
5. Gimenez-Garcia, R., S. Sanchez-Ramon, and L. Cuellar-Olmedo, Palmoplantar pustulosis: a clinicoepidemiological study. The relationship between tobacco use and thyroid function. Journal of the European Academy of Dermatology and Venereology, 2003. 17: p. 276-279.
6. Terui, T., et al., Efficacy and Safety of Guselkumab, an Anti-interleukin 23 Monoclonal Antibody, for Palmoplantar Pustulosis: A Randomized Clinical Trial. JAMA dermatology, 2018. 154(3): p. 309-316.
7. Husson, B., et al., Efficacy and safety of TNF blockers and of ustekinumab in palmoplantar pustulosis and in acrodermatitis continua of Hallopeau. Journal of the European Academy of Dermatology and Venereology, 2020.
8. Haebich, G. and M. Kalavala, Successful treatment of refractory palmoplantar pustulosis with apremilast. Clinical and Experimental Dermatology, 2017. 42(4): p. 471-473.
9. Eto, A., M. Nakao, and M. Furue, Three cases of palmoplantar pustulosis successfully treated with apremilast. The Journal of Dermatology, 2019. 46(1): p. e29-e30.
10. Carrascosa de Lome, R., E. Conde Montero, and P. de la Cueva Dobao, Refractory palmoplantar pustulosis successfully treated with apremilast. Dermatologic Therapy, 2020.