Clinical characteristics and associations of palmoplantar pustulosis: an observational study,

Anais

Brasileiros

de

Dermatologia

www.anaisdedermatologia.org.br

INVESTIGATION

Clinical

characteristics

and

associations

of

palmoplantar

pustulosis:

an

observational

study

夽,夽夽

Ayse

Oktem

,

Pınar

Incel

Uysal

,

Neslihan

Akdo˘

gan

,

Aslı

Tokmak

,

Basak

Yalcin

DepartmentofDermatology,AnkaraNumuneTrainingandResearchHospital,Ankara,Turkey Received14November2018;accepted16April2019

Availableonline14December2019

KEYWORDS Dermatitis; Dermatitis,allergic contact; Eccrineglands; Psoriasis Abstract

Background: Palmoplantarpustulosisisachronicandrelapsingdiseaseofthepalmsandsoles, whichischaracterizedbyscatteredclustersofpinhead-sized,sterilepustules.

Objective: The aim of the present study was to determine demographic features, co-morbidities,andrelationofpalmoplantarpustulosiswithpsoriasis.

Methods: Atotalof48patients(M/F:15/33)wereenrolledinthepresentstudy.Adetailed history regarding age of onset, palmoplantar pustulosis duration, number of recurrences, personalandfamilyhistoryofpsoriasis,accompanyingarthritis,sternoclaviculartenderness, dentalfillings,smokingstatus,andautoimmunediseasewasobtained;thorough dermatologi-calexaminationwascarriedout.Patchtestingresultsandlaboratoryinvestigationsforthyroid autoimmunitywererecorded.

Results: Thirty-five of48 patients (72.9%)were currentsmokers.Twentyofthe48 patients (41.7%)haddental fillings.Therewas notanysignificant correlationbetweenpalmoplantar pustulosisduration anddentalfilling duration(p=0.170).Psoriasiswas notdetected inany patients eitherinhistoryorindermatological examination.Nailinvolvementandjoint com-plaintswereobservedinsevenof48patients(14%)andinnineof48patients(18%),respectively. Autoimmunethyroiditiswasobservedinfourof48patients(12%).Patientswithpatchtesting positivity(12.5%ofpatients,M/F:1/5)hadnoconsiderableassociationforhistoryofexternal contactwiththesematerials.

Studylimitations: Retrospectiveanalysis.

Conclusion: Palmoplantar pustulosis appears to be adistinct entity from psoriasis.Routine thyroidfunctions test couldbeanalyzed,but patchtesting isnotrequired inpatientswith palmoplantar pustulosis. Also,patients with palmoplantar pustulosismustbe evaluated for musculoskeletalsymptomsandsigns.

©2019SociedadeBrasileira deDermatologia.PublishedbyElsevierEspa˜na,S.L.U.Thisisan openaccessarticleundertheCCBYlicense(http://creativecommons.org/licenses/by/4.0/).

夽 _{Howtocitethisarticle:OktemA,IncelUysalP,Akdo˘ganN,TokmakA,YalcinB.Clinicalcharacteristicsandassociationsofpalmoplantar}

pustulosis:anobservationalstudy.AnBrasDermatol.2020;95:15---9.

夽夽_{StudyconductedattheDepartmentofDermatology,AnkaraNumuneTrainingandResearchHospital,Ankara,Turkey.} ∗_{Correspondingauthor.}

E-mail:ayseoktem@yahoo.com(A.Oktem).

https://doi.org/10.1016/j.abd.2019.04.008

0365-0596/©2019SociedadeBrasileiradeDermatologia.PublishedbyElsevierEspa˜na,S.L.U.ThisisanopenaccessarticleundertheCC BYlicense(http://creativecommons.org/licenses/by/4.0/).

Introduction

Palmoplantar pustulosis (PPP) is a chronic and relapsing diseaseof thepalms andsoles, which is characterizedby scatteredclustersofpinhead-sized,sterilepustules, primar-ily locatedon thethenar, hypothenar, or centralareas of thepalms, either in a symmetricalor asymmetrical fash-ion (Fig. 1). Although initially thought tobe a variant of psoriasis,1_{PPPisnowregardedasaseparateentityrather}

thanadiseaseonthepsoriasisspectrum.2,3_{Despitethefact}

thatsomepatientshavepsoriasiformplaquesonotherparts ofthebody,theselesionsarenotconsideredasthetypical psoriatic plaques.4 _{Eccrine sweat glands and the}

acrosy-ringiumplaythecentralroleinthepathogenesisofPPP.5,6

PPPisa diseasewithfemalepredominance. There is also awell-recognizedassociationwithsmoking.1,7 _Inaddition,

somereportsnotifythatabnormalityinthyroidfunctions7,8

andcontactsensitivity9_{areassociatedwithPPP.Theaimof}

thepresentstudywastodeterminedemographicfeatures, thefrequencyofthyroidautoimmunity,contactsensitivity, concomitantarthritis,nailinvolvement,andthepresenceof psoriaticlesionsondermatologicalexaminationinpatients withPPP.

Methods

Across-sectionalobservationalstudywasconducted.Atotal of48consecutivepatients(15menand33women)whowere diagnosedwithPPPbetweenJanuary2014andJanuary2018 andmetinclusioncriteriawereenrolledinthepresentstudy. The study was conducted according to the principles of the Declaration of Helsinki and approved by the local ethicscommittee.Writteninformedconsentwasobtained fromalltheparticipantsbeforestudyinclusion.Study inclu-sioncriteriawereasfollows:age≥18yearsandvoluntarily agreeing to participate in the study. Occupational expo-suresofparticipantsaswellasdemographicalandclinical characteristicswererecorded,includingageofonset, dura-tionofPPP,thenumberofrecurrences,personalandfamily history of psoriasis, presence of psoriatic lesions at the timeofdatacollection,accompanyingarthritisand/or ster-noclavicular joint tenderness, presence of dental filling, smokinghabits, andautoimmunediseasehistory.Foreach patient, a thorough dermatological examination was car-riedout.Inparticular,patientswerecarefullyexaminedto detectconcurrentpsoriaticlesionsintherestofthebody.

Figure1 Pustuleslocatedonnormalanderythematousskin ofpalmswithbrowndiscoloration.

Patchtesting resultsandlaboratoryinvestigationsfor thy-roidautoimmunitywererecorded.

Statisticalanalyses

Statistical analyses were performed with SPSS v. 21.0. Parametric variables are shown as means (mean±SD), and nonparametric variables are presented as medians (median±interquartilerange[IQR]). Frequenciesand per-centages were calculated for the categorical variables. Statistical comparisonsbetween normallydistributed con-tinuousvariablesandcategoricalvariableswereperformed with Student’s t-test. The Kolmogorov---Smirnov criterion wasusedfor assessmentofnormality.To compare propor-tions (qualitative variables),the chi-squared test and the Fisher’sexacttest(incaseexpectedvalueswere<5%)were employed.Mann---WhitneyUandKruskal---Wallistestswere used for comparing the non-normally distributed numeric variables.Allp-valuesweretwo-sidedanddifferenceswere consideredstatisticallysignificantifp-valueswere<0.05.

Results

Demographicandclinicalcharacteristics

Atotalof48consecutivepatients(15menand33women; mean age, 50.9±10.4 years [range: 21---65 years]) were enrolledinthepresentstudy.Therewasnosignificant asso-ciationbetweenmenandwomenfortheageofdiseaseonset (p=0.297).The median numberofrecurrences wasten in women,whileitwastwoinmen.Themediandisease dura-tion was36months in women,while it was12 months in men.The durationofPPPrangedfromoneto360months, andthenumberofrecurrencesrangedfromoneto50inthe studygroup.Thenumberofrecurrences(p=0.01)andthe durationofthedisease(p=0.01)weresignificantlyhigherin women.

Smokinghabits

Thirty-fiveof48patients(72.9%)werecurrentsmokersand 13 of the patients (27.1%) were non-smokers. Among the non-smokers, 11of13hadneversmoked,while twoof 13 wereex-smokers.Theex-smokerswerenon-smokersforthe lasttwotothreeyearsandhadhadsmokinghabitsof25and 30pack-years,respectively.Themeanvalueofpack-years smokedwasfoundtobe20±13.3(3---60pack-years)inthe studygroup.Therewasastatisticallysignificantdifference betweenmenandwomeninsmokinghabits.Themeanvalue ofpack-yearswassignificantlyhigherinmalesthanfemales (p=0.044).

Dentalfilling

Twenty of the 48 of the patients (41.7%) had dental fill-ings.Therewasnosignificantdifferencebetweenmenand womenintermsofdentalfillingduration.Inaddition,there was no significant correlation between PPP duration and dentalfillingduration(p=0.170).Outof11patientswhohad dentalfillings,twoshowedpatchtestpositivitytonickel.

Occupationalexposure

Sixof48patientsreportedoccupationalexposure. Occupa-tionsofthesepatientswereasfollows;cleaningstaff(2), constructionworker(2),seamworker(1), andhairdresser (1).Patchtestingwaspositiveinallpatientswithhistoryof occupational exposure. Occupational exposurewas higher inmenthaninwomen;however,theresultsdidnotreach statisticalsignificance(26%vs.6%,p=0.067).

Psoriasisinhistoryanddermatologicalexamination Psoriasiswasnotdetectedinanypatients,eitherinhistory orindermatologicalexamination.Afamilyhistoryof psori-asisorpalmoplantar dermatitiswasrecordedin twoof 48 patients(4.2%).

Nailinvolvement

Nailinvolvementwasobservedinsevenof48patients(14%). Allpatientswithnailinvolvementhadonycholysis;threeof thesevenalsohadpitting.

Accompanyingarthritis,sternoclavicularjoint tenderness

Musculoskeletal complaints were observed in nine of 48 patients(18%).Statisticalanalysisrevealedthattherewas nosignificantdifferencebetweenmenandwomeninterms of frequency of accompanying arthritis. Palpable tender-nessof thesternoclavicular jointwasreportedby fourof 48 patients (8.3%, M/F: 1/3). One of these patients had the history of ankylosing spondylitis. Sincenone of these patientsexhibitedtypicalmanifestationssuchaspain,local swelling,orwarmth,10,11 _{imagingforradiographic changes}

wasnotperformed.Thesepatientswerenotconsideredto haveanykindofsternoclavicularjointpathology,including hyperostosis.

Five patients with musculoskeletal complaints in the presentstudyhadalreadybeenevaluatedbya rheumatolo-gistforjointinvolvement.Twohadadiagnosisofrheumatoid arthritis,two haddiagnosis of ankylosing spondylitis, and one female patient was under follow up for seroneg-ative arthritis with methotrexate therapy. Another four patientswhodidnotpreviouslyseekmedicalcarefortheir musculoskeletal complaints were seen by the rheumatol-ogy, orthopedic, andphysical medicine andrehabilitation departments.Onepatientwhosufferedfromkneepainhad thediagnosisofdiscoidmeniscus.Threepatientshadpainin thesmalljointsofthehands,whileonehadpainonlyinthe smalljointsofthelefthand,andwasfinallydiagnosedbythe orthopedicsurgeonashavingcervical diskhernia.Another twopatients, whohad been evaluatedby the rheumatol-ogy department, hadno specific diagnosis. Regarding the relation between jointinvolvementand nail involvement, intotal sevenpatients hadonycholysisandthreeofthem hadarthralgia(onepatientdiagnosedwithAS,onepatient whohada diagnosis ofseronegativearthropathy,and one patientwitharthralgiainthesmalljointsof handswitha nonspecificdiagnosis).

Figure2 Desquamationandbrowndiscolorationon erythe-matousskinofpalms.

Autoimmunediseases

Autoimmunethyroiditiswasobservedinfourof48patients (12%).Allfourpatientswerefemale.Otherautoimmune dis-easeswereobservedinsix(M/F:1/5)of48patients(12.5%). Regardingthefrequencyofautoimmunediseases,including autoimmune thyroiditis, no statistically significant differ-ence wasestablished between maleand female patients (p>0.05).

Spontaneousremission

Spontaneousremission was recorded in 19 of 48 patients (39.5%). Men and women were almost the same with respecttofrequencyofspontaneousremission(40%vs.39%,

p>0.05).

Patchtestingresults

Patch testing was positive in 12.5% of the subjects (one man,fivewomen).Statisticalanalysisindicatedthatthere wasnosignificant differencebetween menandwomen in regard topatch testing positivity (p>0.05). Patch testing positivity was seen in five patients for nickel, and one patientwithconcomitantpositivityforBalsamofPeruand 2-methoxy-6-n-pentyl-4-benzoquinone.Patientswithpatch testingpositivityhadnoconsiderableassociationforhistory of external contactwith thesematerials. In twopatients withnickelsensitivity,dentalfillingwaspresent.

DruginducedPPP

Onepatientwasdiagnosed withankylosing spondylitis, in whomthelesionsonthepalmsandsoleswerecompatible withPPPfollowingtheetanercepttherapy.

Discussion

PPPaffects mostly females and the age of disease onset ranges from 45 to 65.1,3 _{Lesions are often accompanied}

bydesquamationandbrowndiscolorationduringregression (Fig.2).Recurrencesandspontaneousremissionsare com-mon.Pustulescan be locatedon normalor erythematous skin.Absenceofanyofpsoriaticplaques,pustuleslocated

onareasother than palmoplantar region,and/or erythro-dermaorlackofpersonal/familyhistoryofpsoriasisarethe characteristicfeaturesofthedisease.Patientswhoenrolled in the present study had neither classic plaque psoriasis lesionsnorpersonalorfamilyhistoryofpsoriasis.Ithasbeen suggestedthatPPPis anautoimmunediseasetriggeredby nicotine7,8_{;however,itiswellknownthatsmokingcessation}

doesnotalwayshaveafavorableeffectondisease progres-sion.Inthepresentstudy,asignificantratioofpatientshad an active or previous history of smoking. However, 11 of 48patients had noactive or passive exposure to tobacco smoke.

Although PPPhasbeen linked withpsoriasis and psori-aticlesionslocatedonbodyareasotherthanthepalmsand soles,1_{ithasbeenreportedthattheselesionsactuallywere}

linkedto psoriasis incorrectly; indeed,these psoriasiform lesionsdonotresembleclassicpsoriaticplaques.4_Currently,

itiswellknownthatpsoriasisandPPParealmostseparate entitieswithrespecttocytokineprofiles,clinicalfindings, andgeneticsusceptibility.12,13

Nail involvement --- including pitting, onycholysis, and dystrophy--- canbedetectedinpatientswithPPP.1,14_Seven

ofthepresentpatients(14%)hadonycholysisunrelatedwith onychomycosis; in additions, three of the seven also had pitting.

Smokingandthyroidglanddysfunctionarethe coexist-ingconditionsmostofteninvestigatedinpatientsdiagnosed withPPP,andtheassociationbetweentobaccouseandPPP iswellestablished.1,15 _{Thepresentstudyalsofounda}

con-siderable ratio of smoking, particularly in male patients. Thyroidglanddysfunction,includingautoimmune thyroidi-tis, has been reported in many clinical studies.1,16 _The

presentstudydetectedautoimmunethyroiddiseaseinfour of48patientsaselevatedanti-thyroidperoxidase antibod-ies,lowlevelsoffree-T4,andultrasonographicfindingsof Hashimoto’sthyroiditis.

Based onthe report suggesting spontaneousregression ofPPPafterremovalofdentalamalgam,9_{allpatientswere}

questioned for presence of dental fillings. There was no significant correlation betweenduration of PPPand dura-tionofdentalfilling(p=0.170).Outofthe11patientswho haddentalfilling,twopatientsshowedpatchtest positiv-itytonickelsulfate. Based ontheseresults,it is difficult to say that there is a contact sensitivity resulting from amalgam in the dental filling. Published reports indicate associationsofPPPwitharthralgiapredominantlylocatedin thehandsandfingers,16 _{psoriaticarthropathy,}17_and

pustu-loticarthro-osteitis(Sonozakisyndrome).18 _However,some

findingsfromthesestudiesaredebatable.Forexample,in theretrospectivestudyofBecheretal.17_{inwhichpsoriatic}

arthropathy was reported in 12.3% of patients, a signifi-cant proportion of patients had family history of plaque psoriasis or concurrent plaque psoriasis. For this reason it is difficult to conclude there is a link between psori-aticarthropathyandPPP.Sternocostoclavicularhyperostosis (SCCH),whichpresentswithswellingandpainofthe stern-oclavicularjoint,wasreportedfirstlyinaJapanesepatient withPPP.Afterthiscasereport,Sonozakitermedthis clini-calentityaspustuloticarthro-osteitis(Sonozakisyndrome, PAO).19 _{Duetofrequentassociation betweenPPPand}

pus-tuloticarthro-osteitis,theysuggestedthatSCCHmightbea musculoskeletalmanifestationofPPP.Inthepresentstudy

noneofthepatientswithPPPhadclinicalfindingsorhistory ofSCCH.

It is well known that psoriatic nail disease, especially crumbling and onycholysis, are related with susceptibil-itytodistalinterphalangeal(DIP)arthritisinpatientswith psoriasis.20 _{Oneofthepresentpatientswhosufferedfrom}

arthralgiainthesmalljointsofthehandsalsohad onychol-ysis,butshedidnothaveobjectiveclinicalfindingsofDIP arthritis.Inthiscontext,theauthorsbelievethatnailand jointinvolvementshouldbeevaluatedamongPPPpatients infuturestudieswithlargersamplesize.

Positivityofpatchtestingwithallergens,especiallywith metals,wasreportedinPPPpatients.Inthesecasereports, positivityofpatchtestingiscorrelatedwithdentalfillings including nickel, cobalt, and zinc.9,21,22 _{Removal of}

den-tal fillingsled tothe regressionof PPPlesionsinsporadic case reports.9 _{It isalways importanttorelate patch}

test-ingresults tohistory andclinical findings.Itis difficultto say one of the etiopathogenic factorsfor PPPis systemic contactsensitivitybecauseofthelackoflargecase-control studies.Inthepresentseries,twopatientshadbothnickel positivityanddentalfillings;however,thedurationofdental fillingwasnotcompatiblewithPPPdiseaseduration.

Conclusion

Somefindingsofthepresentstudy---includingfemale pre-dominance, high prevalence of smoking habits, and nail involvement --- are compatible with the literature. Based on the increasing evidenceand the data presented here, PPPappearstobeadistinctentityfrompsoriasis.Ofnote, the available studies clinicallydescribing PPPare limited andcontroversial.Thepresentstudydidnotfinda correla-tionbetweenPPPandpsoriasis.Accordingtotheseresults, the triggeringrole ofcontactsensitivity inthe etiopatho-genesis of PPP is unclear and patch testing may not be requiredinpatientswithPPP.Routinethyroidfunctiontests couldbeanalyzedinpatientsdiagnosedwithPPPduetothe highprevalenceofthyroidfunctionabnormalityinpatients with PPP. Also, patients with PPP must be evaluated for musculoskeletalsignsandsymptoms.Itisunclearwhether typicalPPPisassociatedwithpsoriaticarthritisoranyother inflammatoryarthropathies.Inordertoclarifythis,arthritic symptomsshouldbeinvestigatedinlargepatientsgroups.

Financial

support

Nonedeclared.

Authors’

contribution

AyseOktem:Approvalofthefinalversionofthemanuscript; elaboration and writing of the manuscript; effective par-ticipation in research orientation; critical review of the literature.

PınarIncelUysal: Statisticalanalysis; effective partici-pationinresearchorientation.

NeslihanAkdo˘gan:Conceptionandplanningofthestudy; criticalreviewoftheliterature.

AslıTokmak:Elaborationandwritingofthemanuscript; obtaining,analyzing,andinterpretingthedata.

Basak Yalcin: Approval of the final version of the manuscript;criticalreviewofthemanuscript.

Conflicts

of

interest

Nonedeclared.

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