Published on 19/03/2015 by admin
Filed under Dermatology
Last modified 22/04/2025
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Sonja Molin and Thomas Ruzicka
Evidence Levels: A Double-blind study B Clinical trial ≥ 20 subjects C Clinical trial < 20 subjects D Series ≥ 5 subjects E Anecdotal case reports
Palmoplantar pustulosis (PPP) is a skin disease characterized by chronic and relapsing pustular eruptions of palms and soles. Because its clinical and genetic characteristics differ from psoriasis vulgaris, PPP probably must be considered as a separate entity.
PPP is a common disease that is often refractory to treatment and shows a high recurrence rate. Unlike psoriasis, there are no reported associations with candidate genes within the PSORS1 locus or tumor necrosis factor (TNF)-α promoter polymorphisms. Female predominance and high prevalence in smokers are characteristic. Cessation of smoking is essential for the treatment course of PPP. Consideration of comorbidities such as streptococcal or Helicobacter pylori infection, diabetes mellitus, thyroid disease, celiac disease or osteoarthropathy is necessary. Tonsillectomy can be helpful if a streptococcal focus is found. A gluten-free diet is recommended if gluten intolerance is proved. At the beginning of therapy and in patients with milder symptoms of PPP, potent topical corticosteroids are the treatment of choice and are even more effective when used under occlusion. Psoralen and ultraviolet A light (PUVA) therapy is also effective. In more severe or recalcitrant courses of disease systemic medication should be considered. The retinoid acitretin (starting dose 0.3–0.5 mg/kg body weight) is proven, but practical use in women is limited due to teratogenicity. There is evidence that the combination of PUVA with systemic retinoids is superior to the individual treatments. Low-dose cyclosporine (1–4 mg/kg daily) and methotrexate (10–25 mg once weekly) can cause improvement of PPP, but requires careful clinical and laboratory monitoring. Fumaric acid esters have also been reported to be effective.
A multitude of other therapeutic proposals for the treatment of PPP decorate the literature. Among those, the use of the retinoic acid metabolism blocking agent liarozole showed at least modest efficacy.
Reports on tumor necrosis factor (TNF)-α antagonist therapy in PPP show conflicting results, with many reports highlight initiation or aggravation of the disease. Non-TNF-α-inhibiting biologic agents such as alefacept or ustekinumab might be promising new therapeutic options especially in recalcitrant cases. Controlled clinical trials are needed to substantiate the evidence.
Screen for infection with streptococci or Helicobacter pylori
Gluten intolerance
Thyroid disease
Diabetes mellitus
Osteoarthropathy
Exclude SAPHO (synovitis, acne, pustulosis, hyperostosis, and osteitis)
Mrowietz U, van de Kerkhof PC. Br J Dermatol 2011; 164: 942–6.
Overview on comorbidities and treatment strategies for PPP, also discussing and current data on tonsillectomy and a probable ‘tonsil-palmoplantar-skin axis’.
Sáez-Rodríguez M, Noda-Cabrera A, García-Bustínduy M, Guimerá-Martín-Neda F, Dorta-Alom S, Escoda-García M, et al. Clin Exp Dermatol 2002; 27: 720.
Clearing of PPP in a patient with gastric Helicobacter pylori infection after eradication treatment with amoxicillin and clarithromycin in combination with omeprazole. No relapse of PPP during a 4-year follow-up.
Agner T, Sindrup JH, Høier-Madsen M, Hegedüs L. Br J Dermatol 1989; 121: 487–91.
In 53% of 32 patients with PPP thyroid disease was detected compared to 16% in the control group.
Mejjad O, Daragon A, Louvel JP, Da Silva LF, Thomine E, Lauret P, et al. Ann Rheum Dis 1996; 55: 177–80.
Comparison of 23 patients with PPP and 23 patients with psoriatic arthritis (PsoA). Clinical findings showed involvement of the anterior chest wall (e.g., sternoclavicular joints) in 19 out of 23 patients with PPP compared to 10 out of 23 with PsoA. Radiological signs of arthropathy were demonstrated in 11 PPP patients and four PsoA patients.
Hradil E, Gentz CF, Matilainen T, Möller H, Sanzén L, et al. Acta Derm Venereol 1988; 68: 65–73.
Increased isotope uptake in the sternocostoclavicular area found in 16 out of 73 patients with PPP who underwent skeletal scintigraphy.
Hayem G, Bouchaud-Chabot A, Benali K, Roux S, Palazzo E, Silbermann-Hoffman O, et al. Semin Arthritis Rheum 1999; 29: 159–71.
Significant association of PPP with axial osteitis in 120 reported cases with SAPHO syndrome.
Hagforsen E, Michaëlsson K, Lundgren E, Olofsson H, Petersson A, Lagumdzija A, et al. Acta Derm Venereol 2005; 85: 225–32.
Disturbed calcium homeostasis was found frequently in 60 PPP patients compared to control group. Association with diabetes mellitus, psychiatric disorders, and gluten intolerance was also reported.
Michaëlsson G, Kristjánsson G, Pihl Lundin I, Hagforsen E. Br J Dermatol 2007; 156: 659–66.
Laboratory investigation of 123 patients with PPP showed IgA antibodies against gliadin in 18% and antibodies against tissue transglutaminase in 10% of cases. Celiac disease was found in 6% of patients. Gluten-free diet resulted in (nearly) total clearance of skin symptoms and decrease of antibody level.
Marsland AM, Chalmers RJ, Hollis S, Leonardi-Bee J, Griffiths CE. Cochrane Database Syst Rev 2006; CD001433.
An extensive review of literature concerning PPP treatment showed proven evidence of PUVA and systemic retinoids alone or in combination, effectiveness of topical corticosteroids under occlusion, and probable benefit of low-dose cyclosporine, tetracycline antibiotics, and Grenz ray therapy.
A detailed survey of evidence based PPP treatment options including the classical publications regarding PUVA and systemic retinoids.
Kragballe K, Larsen FG. Acta Derm Venereol 1991; 71: 540–2.
Complete clearance of PPP with use of medium strength topical corticosteroid under hydrocolloid occlusion in 13 out of 19 patients in a left–right comparison with a highly potent topical corticosteroid alone (complete remission only in three out of 19 patients).
Erkko P, Granlund H, Remitz A, Rosen K, Mobacken H, Lindelöf B, et al. Br J Dermatol 1998; 139: 997–1004.
Fifty-eight PPP patients treated with cyclosporine in a daily dose of 1–4 mg/kg body weight for 12 months. Low-dose treatment showed improvement in 13 of 27 patients compared with six of 31 in the placebo group. Benefit of long-term use only supposed.
Thomsen K. Acta Derm Venereol 1971; 51: 397–400.
Satisfactory response in eight out of 25 patients receiving weekly oral doses of 25 mg methotrexate for 2 months.
Ständer H, Stadelmann A, Luger T, Traupe H. Br J Dermatol 2003; 149: 220–2.
Marked reduction of PPP Area and Severity Index (PPPASI) in 13 patients with PPP treated with fumaric acid esters for a period of 24 weeks.
Furuhashi T, Torii K, Kato H, Nishida E, Saito C, Morita A. Exp Dermatol 2011; 20: 768–70.
Significant improvement of PPPASI score after 20–30 treatments with excimer light therapy in 17 patients.
Shmidt E, Wetter DA, Ferguson SB, Pittelkow MR. J Am Acad Dermatol 2011; 67: e179–85.
In 56 patients treated with infliximab, adalimumab, or etanercept for reasons other than palmoplantar pustulosis, 45% developed this disease.
Benefit of TNF-α antagonist use in PPP is conflicting, with therapeutic efficacy, PPP initiation or aggravation is occurring.
Carr D, Tusa MG, Carroll CL, Pearce DJ, Camacho F, Kaur M, et al. J Dermatolog Treat 2008; 19: 97–100.
Reduction of palmoplantar psoriasis severity index (PSI) in 13 of 14 patients completing study participation with 16 weeks of alefacept treatment up to maximum dose of 30 mg per week. Mean improvement in PSI and PGA (Physicians Global Assessment) was statistically significant.
Gerdes S, Franke J, Domm S, Mrowietz U. Br J Dermatol 2010; 163: 1116–18.
Two out of four PPP patients treated with ustekinumab responded.
Bhushan M, Burden AD, McElhone K, James R, Vanhoutte FP, Griffiths CE. Br J Dermatol 2001; 145: 546–53.
Noticeable improvement of symptoms occurred in four out of seven patients treated with liarozole (75 mg, twice daily), a retinoic acid metabolism blocking agent, compared to one out of eight patients receiving placebo.
Liarozole has orphan drug designation for congenital ichthyosis.
Treatment of Skin Disease Comprehensive Therapeutic Strategies 4e
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Oral retinoids
PUVA
Topical corticosteroids
Cyclosporine
Methotrexate
Fumaric acid esters
Excimer light therapy (308 nm)
Liarozole
Alefacept
Ustekinumab
