PsAPASH: a rare and recent autoinflammatory syndrome associated with hidradenitis suppurativa,

AnBrasDermatol.2020;95(2):203---206

Anais

Brasileiros

de

Dermatologia

CASE

REPORT

PsAPASH:

a

rare

and

recent

autoinflammatory

syndrome

associated

with

hidradenitis

suppurativa

夽,夽夽

Raissa

de

Lima

Gadelha

,

Renata

da

Silveira

Rodrigues

Paiva

,

Esther

Bastos

Palitot

,

Joanne

Elizabeth

Ferraz

da

Costa

DepartmentofDermatology,HospitalUniversitárioLauroWanderley,JoãoPessoa,PB,Brazil

Received6November2018;accepted27February2019

Availableonline21January2020

KEYWORDS Acnevulgaris; Arthritis,psoriatic; Hidradenitis suppurativa; Pyoderma gangrenosum

Abstract Hidradenitissuppurativaisachronicinflammatoryskindisease,whichaffects1%of

thepopulation,beingmorecommoninyoung,obeseandsmokers,andmainlyaffectsarmpits

and groin, with formation ofpustules, nodules, abscesses, scars and fistulas.Recently, its

association withother autoimmunediseasessuch as psoriasis,psoriatic arthritis,pyoderma

gangrenosum,pyogenic arthritisandulcerativecolitishavebeenreported.Theseassociated

formsareusuallyresistanttostandardtreatment,withimmunobiologicalsaspromising

ther-apy.Thecaseofarareformofassociationisreported,withonlyonecasepreviouslydescribed

intheliterature:psoriasisarthritis,pyodermagangrenosum,acneandhidradenitissuppurativa.

©2020SociedadeBrasileira deDermatologia.PublishedbyElsevierEspa˜na,S.L.U.Thisisan

openaccessarticleundertheCCBYlicense(http://creativecommons.org/licenses/by/4.0/).

Introduction

Suppurativehidradenitisisachronicinflammatoryskin dis-ease with pathophysiology based on follicular occlusion of thepilosebaceousunitand innatederegulatedimmune response.1,2

夽 _{How to cite this article: Gadelha RL, Paiva RSR, Palitot EB,}

Costa JEF. PsAPASH: a rare and recent autoinflammatory syn-dromeassociatedwithhidradenitissuppurativa.AnBrasDermatol. 2020;95:203---6.

夽夽_{StudyconductedattheHospitalUniversitárioLauroWanderley,}

UniversidadeFederaldaParaíba,JoãoPessoa,PB,Brazil.

∗_{Correspondingauthor.}

E-mail:raissalimagadelha@hotmail.com(R.L.Gadelha).

Suppurative hidradenitis and acne may be essential components of the auto-inflammatory syndromes which are described: Pyoderma gangrenosum, Acne and Pyo-genic Arthritis (PAPA), pyoderma gangrenosum, acne and hidradenitis suppurativa (PASH), Pyoderma gangrenosum, Acne, Pyogenic arthritis and Hidradenitis Suppurativa (PAPASH) and Pyoderma gangrenosum, Acne and Spondy-loarthritis(PASS).Recentlyitwasaddedtothespectrumthe syndromecomposed of Psoriatic Arthritis, Pyoderma gan-grenosum,AcneandHidradenitisSuppurativa(PsAPASH)and Pyodermagangrenosum,AcneandulcerativeColitis(PAC).3

Autoinflammatorysyndromesaredefinedbyanaberrant innateimmune systemand absenceofcirculating autoan-tibodies and autoreactive T-cells and it is believed that recurrentepisodesof neutrophilicinflammation are medi-ated by interleukin 1.4 _{The symptoms are usually severe}

andmaynotrespondtostandardtreatmentsandthushave https://doi.org/10.1016/j.abd.2019.02.012

0365-0596/©2020SociedadeBrasileiradeDermatologia.PublishedbyElsevierEspa˜na,S.L.U.ThisisanopenaccessarticleundertheCC BYlicense(http://creativecommons.org/licenses/by/4.0/).

204 GadelhaRLetal. devastatingphysicalandpsychologicalconsequencesforthe

affectedpatients.5

Case

report

A22year-oldfemalepatientreportedpainfullesionsinthe armpits3 yearslater withdisseminationto thegroin and breasts.Oneyearago,acnelesionsappearedinadditionto lowerlimb ulcersandscalylesionsonthe scalpappeared for3monthsandwerereferredtoourHULWDermatology service.Healsoreportedjointpainsinhands,wrists,knees andlumbarspinewithmorningstiffnessof30min.

At the examination he had Grade 2 acne onthe face; abscesses,fistulaeandfibrosisinarmpitsandgroin compa-tiblewithHurley’sGradeIIIsuppurativehidradenitis;scaly erythematousscalyplaquessuggestiveofpsoriasisand pseu-dotinhaamiantácea;andpurulentpainfulnodulesandulcers withviolaceous,protrudingandunderminedleftbreast ten-drilssuggestiveofpyodermagangrenosum(Figs.1---4).

The patient was medicated with capillary solution of salicylicacidandbetamethasonedipropionateand antise-cretoryshampoo,inadditiontoclindamycin300mgevery 8handmetformin500mgtwicedaily.

Theanatomopathologicalfragmentofthescalprevealed epidermis with psoriasiform acanthosis, paraaceratosis, hypogranulosis and intracranial microabscesses, a dermis withinflammatoryinfiltrateoftheperivascular lymphohis-tiocytic, compatible with psoriasis. Already the fragment oftheleftbreastshowedcutaneous ulcerwithdenseand diffusemixedinflammatoryinfiltrate,withabscessedfoci, focalareasofnecrosisandfrequentleukocytoclasia.

Hepresentedlaboratorytests,suchasnon-reactiveFAN, VHS 54, Negative Rheumatoid Factor, serologic tests for

Figure1 Injuriessuggestiveofhidradenitissuppurativainthe

axilla:nodules,scarsandfibrosis.

Figure2 Lesionssuggestiveofpyodermagangrenosuminthe

leftbreast:ulcerswithviolaceousandunderminedborders.

Figure3 Erythematousscalylesionsonthescalpsuggestive

ofpsoriasis.

Hepatitis B andC negative,PPD 0mm,Chest X-Ray with-out changes. Based on the CASPAR criteria, it presents a diagnosis of psoriatic arthritis (peripheral arthritis, cur-rent psoriasis and negative rheumatoid factor), and was referred to the Rheumatology department for interdisci-plinaryfollow-up.

PsAPASH:arareandrecentautoinflammatorysyndromeassociatedwithhidradenitissuppurativa 205

Figure4 Ulceratedcicatriciallesioninlowerleftlimbof

pyo-dermagangrenosum.

Figure5 Lesionsintheleftaxillapresentingimprovementof

thepictureafter2monthsofuseofAdalimumabeSC.

The patient did not present improvement with initial treatmentandthenstartedusingAdalimumabinascheme for hidradenitis suppurativa and presented an important improvement of the picture at the consultation after 2 months(Figs.5and6),evidenced bythe decreasein Sar-toriusscore(underarm,previous:55,after2months:49).

Figure6 Lesionsintheleftbreastpresentingimprovement

ofthepictureafter2monthsofuseofAdalimumabeSC.

The schedule wasperformed with4 syringes, subcuta-neously,ofAdalimumab(40mg)atweek0and2syringesat week2(inductionphase),followedby1syringeevery7days (maintenancephase).The samegoesonregular quarterly monitoringinourservice.

Discussion

Suppurativehidradenitisisachronicinflammatorydiseaseof theskin,clinicallydefinedbynodulesandrecurrentpainful abscessesthatleadtotheformationoffistulas,nodulesand scars.Itoccursin1%ofthepopulation,ismorefrequentin womenandtendstoresolveatmenopause.6

Locallyrecurringlesionsmaybeexcisedortreatedwith alaser.Disseminatedlesions,however,canbetreatedwith radicalsurgery,topicalorsystemicantibiotics(tetracycline orclindamycinwithrifampicin),oralretinoids,dapsoneand biologicalagents(adalimumabandinfliximab).Pain mana-gement,weightloss,tobaccoabstinenceandtreatmentof superinfectionsarealsoimportantrecommendationsforall patients.7

Suppurativehidradenitisassociatedwith autoinflamma-torysyndromesisoftensevere(HurleyII,III)anddoesnot respondtomanyoftheusualtreatments.8

Because of the likely common pathogenesis involving IL-1-inducedinflammation,collectiveexperimentstodate indicatethatIL-1andTNF-targetedtherapiesrepresentthe most successful treatment solution for prolonged remis-sion.TNF-blockingagents,adalimumabandinfliximab,have achieved good control of suppurative hidradenitis lesions and,thus,reinforcetheroleofaderegulatedinnateimmune responseinthediseasepathogenesis.3

Theautoinflammatory syndromecomposedofthe asso-ciationofpsoriaticarthritis,pyodermagangrenosum,acne

206 GadelhaRLetal. and hidradenitis suppurativa (PsAPASH) was described in

2015 and there was no other similar description in the literature.7 _{As in the case described, our patient was}

treatedwithAdalimumabandpresentedinremissionofthe disease.

No genetic mutation associated with PsAPASH has yet beenidentified,buttheothersyndromesareassociatedwith thegeneticmutationinthecodingregionofPSTPIP1aswell aswithincreasedrepetitionsofCCTGinthepromoterregion ofPSTPIP1,leadingtoitsderegulationandpredispositionto cutaneousneutrophilicinflammation.9

Thus,itisveryimportantthatdermatologistsknowabout autoinflammatorysyndromichidradenitis,includingtypical lesionsofpyodermagangrenosum,hidradenitissuppurativa, psoriasis and acne, and laboratory findings suggestive of systemicinflammation toestablish clinicalprevalenceand earlytreatment.7

Financial

support

Nonedeclared.

Authors’

contributions

Raissa de Lima Gadelha: Statistical analysis; conception andplanning of thestudy; elaboration andwriting of the manuscript;obtaining, analysis, andinterpretation of the data;intellectualparticipationinthepropaedeuticand/or therapeuticconductofthestudiedcases;criticalreviewof theliterature;criticalreviewofthemanuscript.

Renata da Silveira Rodrigues Paiva: Approval of the final version of the manuscript; effective participation in research orientation; intellectual participation in the propaedeutic and/or therapeutic conduct of the studied cases.

EstherBastosPalitot:Approvalofthefinalversionofthe manuscript;effectiveparticipationinresearchorientation; intellectualparticipationinthepropaedeuticand/or thera-peuticconductofthestudiedcases.

Joanne Elizabeth Ferraz da Costa: Approval of the final version of the manuscript; effective participation in research orientation; intellectual participation in the propaedeutic and/or therapeutic conduct of the studied cases.

Conflicts

of

interest

Nonedeclared.

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3.VinkelC,ThomsenSF.Autoinflammatorysyndromesassociated with hidradenitis suppurativa and/or acne. Int J Dermatol. 2017;56:811---8.

4.LeuenbergerM,BernerJ,DiLuccaJ,FischerL,KaparosN, Con-radC,etal. PASS syndrome:anIL-1-driven autoinflammatory disease.Dermatology.2016;232:254---8.

5.MurphyB,MorrisonG,PodmoreP.Successfuluseofadalimumab totreatpyodermagangrenosum,acneandsuppurative hidradeni-tis(PASHsyndrome)followingcolectomyinulcerativecolitis.Int JColorectalDis.2015;30:1139---40.

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8.Join-LambertO,DuchateletS,DelageM,MiskinyteS,Coignard H,LemarchandN,etal.Remissionofrefractorypyoderma gan-grenosum, severe acne, and hidradenitis suppurativa (PASH) syndromeusingtargetedantibiotictherapyin4patients.JAm AcadDermatol.2015;73Suppl.1:S66---9.

9.MarzanoAV,IshakRS,ColomboA, CaroliF,CrostiC.Pyoderma gangrenosum,acneandsuppurativehidradenitissyndrome fol-lowingbowelbypasssurgery.Dermatology.2012;225:215---9.