Palmoplantar Psoriasis


Article Author:
Alyssa Miceli


Article Editor:
George Schmieder


Editors In Chief:
Sisira Reddy
Joseph Nahas
Chokkalingam Siva


Managing Editors:
Avais Raja
Orawan Chaigasame
Khalid Alsayouri
Kyle Blair
Radia Jamil
Erin Hughes
Patrick Le
Anoosh Zafar Gondal
Saad Nazir
William Gossman
Hassam Zulfiqar
Navid Mahabadi
Hussain Sajjad
Steve Bhimji
Muhammad Hashmi
John Shell
Matthew Varacallo
Heba Mahdy
Ahmad Malik
Abbey Smiley
Sarosh Vaqar
Mark Pellegrini
James Hughes
Beenish Sohail
Hajira Basit
Phillip Hynes
Sandeep Sekhon


Updated:
6/3/2019 2:44:06 PM

Introduction

Palmoplantar psoriasis is a variant of psoriasis that characteristically affects the skin of the palms and soles. It features hyperkeratotic, pustular, or mixed morphologies. Palmoplantar pustulosis, or pustular palmoplantar psoriasis, is a possibly related dermatosis characterized by small, sterile pustules that may be a type of palmoplantar psoriasis or a distinct entity.[1] Both conditions are chronic in nature and produce significant functional disability. As such, they are associated with substantial impairment in quality of life. Though historically difficult to treat, recent studies on biologic therapies have shown promising results for the treatment of palmoplantar psoriasis.

Etiology

The exact cause palmoplantar pustulosis is unknown. However, palmoplantar psoriasis is caused by a combination of genetic and environmental factors. The most common genetic factor associated with palmoplantar psoriasis includes the human leukocyte antigen (HLA) Cw6. There may also be possible linkages to variations in the CARD14 gene and genes in the IL-19 subfamily in palmoplantar pustulosis. [2] [3] [4]Environmental triggers include smoking, irritants, friction, and manual or repetitive trauma. Paradoxically, anti-tumor necrosis factor-alpha agents have been shown to induce palmoplantar eruptions.

The majority of patients with palmoplantar pustulosis are current or former smokers. It is postulated that activated nicotine receptors in sweats glands cause an inflammatory response in this disease process. Palmoplantar pustulosis has also been linked to thyroid disease, smoking, and arthritis of the anterior thorax.

Epidemiology

Palmoplantar psoriasis affects individuals of all ages, while palmoplantar pustulosis has an average age of onset between 20 and 60 years of age. Gender specificity is unclear in palmoplantar psoriasis, although palmoplantar pustulosis shows a clear predilection for females, with a female-to-male ratio of 8:2. Though the incidence has not been determined, the palmoplantar variant of psoriasis comprises 3% to 4% of all cases of psoriasis, which affects 2% to 5% of the population.[5]

Pathophysiology

The pathogenesis of palmoplantar psoriasis is similar to psoriasis in that there is the interplay between genetic factors and antigenic triggers. The most commonly associated human leukocyte antigen in psoriasis is HLA-Cw6. Psoriasis is related to the psoriasis-susceptibility [PSORS1] locus on chromosome 6p21, though the relation of this gene in palmoplantar psoriasis remains unclear. [2]Alternatively, one study found no association between palmoplantar pustulosis and the PSORS1 locus. Other studies have shown possible linkages to variations in the CARD14 gene and genes in the IL-19 subfamily in palmoplantar pustulosis.

Various antigenic triggers can initiate palmoplantar psoriasis or pustulosis in genetically susceptible individuals. Triggers, including stress, smoking, irritants, friction, and trauma, can activate dendritic cells and T cells, causing IL-20 to be produced locally, accelerating keratinocyte proliferation. At the same time, IL-23 is released from lymph nodes, recruiting Th1 and Th17 to the lesions. T-cells produce numerous cytokines, including TNF-a, IL-17, and IL-22, which stimulate keratinocytes to proliferate and produce proinflammatory antimicrobial peptides and cytokines. Lastly, neutrophils are recruited to the epidermis and activate dermal fibroblasts.[6]

History and Physical

Patients with palmoplantar psoriasis and palmoplantar pustulosis report symptoms that may include itching, pain, and fissuring. Though spontaneous remission can occur, the persistence of flares is common.  Patients may experience exacerbations brought on by seasonal changes, household work, and detergents. In fact, palmoplantar psoriasis is more common amongst farmers, manual laborers, and housewives. Significant palmoplantar skin disease may indicate underlying joint disease. 

On physical exam, thick hyperkeratotic plaques, sterile pustules, or a mixture of morphologies may be seen in palmoplantar psoriasis.  Hyperkeratotic plaques are the most common subtype. Symmetrically distributed lesions are common, as well as erythema, fissuring, and scaling. Sites other than the hands and feet are commonly involved, with 33% of patients having up to 10% of their body surface area (BSA) involved in studies. The nails are involved up to 60% of the time, with findings including coarse pitting, subungual hyperkeratosis, and longitudinal ridging. Palmoplantar pustulosis begins as a unilateral eruption of pin-sized sterile yellow pustules. Hyperkeratosis with erythema, scaling, and fissuring is seen over time. The most common locations include the thenar, hypothenar, and central portion of the palms and soles. Palmoplantar pustulosis typically resolves with residual brown pigmentation.[7][8]

The differential diagnosis of palmoplantar psoriasis includes dyshidrotic eczema, contact dermatitis, pityriasis rubra pilaris, acquired palmoplantar keratoderma, and tinea pedis/manuum. Acrodermatitis continua of Hallopeau is a related disease to palmoplantar psoriasis that features painful, pustular, periungual and subungual lesions with an inflammatory base that is chronic and recurrent.

Evaluation

A thorough history and physical examination, including exploration of triggers and exposures are essential to the diagnosis. A potassium hydroxide preparation (KOH prep) should be performed for any scaly erythematous eruption on the palms and soles to rule out dermatophytes. A biopsy is often needed, as palmoplantar psoriasis can be indistinguishable from eczematous hand dermatitides and to also rule out tinea. Histopathologic examination of psoriatic lesions shows parakeratosis, decrease/loss of the granular layer of the epidermis, psoriasiform epidermal hyperplasia and Munro microabscesses (neutrophils in stratum corneum). In palmoplantar psoriasis, foci of parakeratosis vertically oriented alternating with orthohyperkeratosis are seen. Laboratory investigations can include c-reactive protein (CRP) and uric acid levels, both of which are elevated in the pustular variant.

Several assessment tools have been developed to help clinicians assess and measure the severity of skin disease activity and response to treatment. Palmoplantar pustulosis and palmoplantar psoriasis are monitored using the Palmoplantar Pustulosis Psoriasis Area and Severity Index (PPPASI) and the Palmoplantar Psoriasis Area and Severity Index (PPASI), respectively. The Palmar-Plantar Quality-of-Life Index is a statistically unverified assessment tool used in studies to quantify disease severity and quality of life.[9]

Treatment / Management

Historically, there has been limited data on treatment of palmoplantar psoriasis, as patients had been excluded from clinical trials of psoriasis because less than 10% of their BSA was affected. Though no standardized treatment exists for patients with palmoplantar psoriasis or palmoplantar pustulosis, increasing data on treatments, especially biologic agents, has been released in recent years. Most patients will require systemic agents given the recalcitrant nature of these skin diseases. In fact, one study reported that just 27.4% of patients showed improvement with topical agents, whereas the remaining patients required systemic treatments.[10]

First-line therapy begins with potent to superpotent topical corticosteroids applied twice daily with or without occlusion, with gradual reduction in frequency over weeks to months. Calcipotriene is often combined or alternated with potent topical corticosteroids. It is important to remember that calcipotriene should not be combined with salicylic acid, which deactivates the molecule.  First-line systemic treatment includes acitretin at a dose of 10 mg to 50 mg per day, with a maximal effect seen between three and six months after initiation of treatment. Acitretin is contraindicated in pregnancy.

Second-line therapy begins with light therapy, including PUVA and NB-UVB or monochromatic excimer laser. Second-line systemic agents include methotrexate and cyclosporine. Methotrexate is dosed at 7.5 mg to 20 mg per week over three to six weeks. Cyclosporine can be used in immunocompetent patients with severe recalcitrant palmoplantar psoriasis. Doses start at 2.5 mg/kg to 5.0 mg/kg per day for a maximum of one year and should be decreased by 0.5 mg/kg to 1.0 mg/kg if hypertension or abnormal renal function test results are seen.  Methotrexate is contraindicated in pregnancy, while cyclosporine can be used with caution.[11]

Biologics are reserved for patients who fail or cannot complete treatment with topical or other systemic medications. Etanercept is a TNF-a inhibitor that showed a statistically significant reduction in PPPASI with 50 mg twice weekly for 24 weeks of therapy. [12]e Similarly, infliximab dosed at 5 mg/kg at weeks zero, two, and six, and then every eight weeks showed a 50% reduction in the mean surface area of the palms and soles.[13] Adalimumab treatment with 40 mg given subcutaneously (SC) every two weeks for a total of three months demonstrated improved quality of life in studies. [14] Ustekinumab is an IL-12 and IL-23 inhibitor dosed at 45 mg (less than 100 kg) or 90 mg SC (100 kg or more) every three months that resulted in complete clearance in 35% of patients at 16 weeks.  [15]Secukinumab is an IL-17A inhibitor dosed at 300 mg (90 kg or more) or 150 mg SC (<less than 90 kg) every week from baseline to week three then every four weeks. Thirty-three percent and 22.1% of patients were clear or almost clear at week 16 with 300 mg and 150 mg, respectively.[16] Ixekizumab is another IL-17A inhibitor which is dosed at 160 mg SC at week zero then 80 mg every two weeks up until week 12 then 80 mg every four weeks. PPASI 100 was achieved in 50% of patients treated with ixekizumab in studies.[17]

Enhancing Healthcare Team Outcomes

Palmoplatarpsoriasis is best managed by an interprofessional team that also includes the nurse and pharmacist. There is no cure for this disorder and at some point, drug treatment is required. The constant itching and pain and results in a poor quality of life, hence, healthcare workers should take steps to reduce triggers and educate patients on medication compliance. In addition, patients should be encouraged to discontinue smoking.

The outcomes for most patients with palmoplantar psoriasis are guarded; relapses are common and eventually most patients require the potent biological agents, which have their own adverse reactions.


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Palmoplantar Psoriasis - Questions

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A 39-year-old obese male with a history of tobacco abuse presents with a rash of several months. Physical exam reveals numerous thick, scaly plaques on the trunk and well-demarcated hyperkeratotic plaques on the palms. What is the genetic factor most commonly associated with the most likely diagnosis?



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A 44-year-old female presents with a unilateral eruption of sterile pustules on the left palm after starting etanercept for rheumatoid arthritis 4 months prior. Which of the following is true regarding the most likely diagnosis?



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A 29-year-old female presents with scaling and fissuring of her palms for 2 months duration. Histopathologic examination of a punch biopsy of the left palm reveals foci of parakeratosis alternating with orthohyperkeratosis, loss of the granular layer of the epidermis, and neutrophils in the stratum corneum. What is the first-line treatment for this disease process?



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A 47-year-old male who works as in construction presents with numerous pustules in addition to scaling and fissuring of the palms and soles. Histopathologic examination of a biopsy specimen shows parakeratosis, regular epidermal hyperplasia, and collections of neutrophils in the stratum corneum. What is the most likely diagnosis?



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A 36-year-old male with palmoplantar psoriasis has failed a trial of combination topical therapy with clobetasol and calcipotriene cream. What is the first-line systemic therapy for palmoplantar psoriasis?



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Palmoplantar Psoriasis - References

References

Farley E,Masrour S,McKey J,Menter A, Palmoplantar psoriasis: a phenotypical and clinical review with introduction of a new quality-of-life assessment tool. Journal of the American Academy of Dermatology. 2009 Jun;     [PubMed]
Asumalahti K,Ameen M,Suomela S,Hagforsen E,Michaëlsson G,Evans J,Munro M,Veal C,Allen M,Leman J,David Burden A,Kirby B,Connolly M,Griffiths CE,Trembath RC,Kere J,Saarialho-Kere U,Barker JN, Genetic analysis of PSORS1 distinguishes guttate psoriasis and palmoplantar pustulosis. The Journal of investigative dermatology. 2003 Apr;     [PubMed]
Kingo K,Mössner R,Kõks S,Rätsep R,Krüger U,Vasar E,Reich K,Silm H, Association analysis of IL19, IL20 and IL24 genes in palmoplantar pustulosis. The British journal of dermatology. 2007 Apr;     [PubMed]
Coto-Segura P,González-Fernández D,Batalla A,Gómez J,González-Lara L,Queiro R,Alonso B,Iglesias S,Coto E, Common and rare CARD14 gene variants affect the antitumour necrosis factor response among patients with psoriasis. The British journal of dermatology. 2016 Jul;     [PubMed]
Khandpur S,Singhal V,Sharma VK, Palmoplantar involvement in psoriasis: a clinical study. Indian journal of dermatology, venereology and leprology. 2011 Sep-Oct;     [PubMed]
Murakami M,Hagforsen E,Morhenn V,Ishida-Yamamoto A,Iizuka H, Patients with palmoplantar pustulosis have increased IL-17 and IL-22 levels both in the lesion and serum. Experimental dermatology. 2011 Oct;     [PubMed]
Chopra A,Gill SS, Hyperkeratosis of palms and soles : clinical study. Indian journal of dermatology, venereology and leprology. 1997 Mar-Apr;     [PubMed]
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Janagond AB,Kanwar AJ,Handa S, Efficacy and safety of systemic methotrexate vs. acitretin in psoriasis patients with significant palmoplantar involvement: a prospective, randomized study. Journal of the European Academy of Dermatology and Venereology : JEADV. 2013 Mar;     [PubMed]
Bissonnette R,Poulin Y,Guenther L,Lynde CW,Bolduc C,Nigen S, Treatment of palmoplantar psoriasis with infliximab: a randomized, double-blind placebo-controlled study. Journal of the European Academy of Dermatology and Venereology : JEADV. 2011 Dec;     [PubMed]
Richetta AG,Mattozzi C,Giancristoforo S,D'Epiro S,Cantisani C,Macaluso L,Salvi M,Calvieri S, Safety and efficacy of Adalimumab in the treatment of moderate to severe palmo-plantar psoriasis: an open label study. La Clinica terapeutica. 2012;     [PubMed]
Gottlieb A,Sullivan J,van Doorn M,Kubanov A,You R,Parneix A,Hugot S,Milutinovic M, Secukinumab shows significant efficacy in palmoplantar psoriasis: Results from GESTURE, a randomized controlled trial. Journal of the American Academy of Dermatology. 2017 Jan;     [PubMed]
Menter A,Warren RB,Langley RG,Merola JF,Kerr LN,Dennehy EB,Shrom D,Amato D,Okubo Y,Reich K, Efficacy of ixekizumab compared to etanercept and placebo in patients with moderate-to-severe plaque psoriasis and non-pustular palmoplantar involvement: results from three phase 3 trials (UNCOVER-1, UNCOVER-2 and UNCOVER-3). Journal of the European Academy of Dermatology and Venereology : JEADV. 2017 Oct;     [PubMed]
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