Anais
Brasileiros
de
Dermatologia
www.anaisdedermatologia.org.br
CONTINUING
MEDICAL
EDUCATION
Update
on
parasitic
dermatoses
夽,夽夽
Alberto
Eduardo
Cox
Cardoso
a,
Alberto
Eduardo
Oiticica
Cardoso
b,∗,
Carolina
Talhari
c,d,
Monica
Santos
eaProfessorAlbertoAntunesUniversityHospital,UniversidadeFederaldeCiênciasdaSaúdedeAlagoas,Maceió,AL,Brazil bDepartmentofDermatology,UniversidadeEstadualdeCiênciasdaSaúdedeAlagoas,Maceió,AL,Brazil
cGraduateProgramoftheUniversidadedoEstadodoAmazonas,Manaus,AM,Brazil
dDepartmentofTeachingandResearch,Fundac¸ãoAlfredodaMattadeDermatologia,Manaus,AM,Brazil
eDepartmentofDermatology,UniversidadedoEstadodoAmazonas,TropicalDermatologyOutpatientClinic,Fundac¸ãoAlfredo daMattadeDermatologia,Manaus,AM,Brazil
Received19February2019;accepted19October2019 Availableonline31December2019
KEYWORDS Drugtherapy; Larvamigrans; Liceinfestations; Myiasis; Onchocerciasis; Scabies; Skindiseases, parasitic; Tungiasis
Abstract Thesearecutaneousdiseasescausedbyinsects,worms,protozoa,orcoelenterates whichmayormaynothaveaparasiticlife.Inthisreviewthemainethologicalagents,clinical aspects,laboratoryexams,andtreatmentsofthesedermatologicaldiseaseswillbestudied. ©2020SociedadeBrasileira deDermatologia.PublishedbyElsevierEspa˜na,S.L.U.Thisisan openaccessarticleundertheCCBYlicense(http://creativecommons.org/licenses/by/4.0/).
夽 How to cite this article: Cardoso AEC, Cardoso AEO, Talhari
C,SantosM.Updateonparasitic dermatoses.AnBrasDermatol. 2020;95:1---14.
夽夽StudyconductedattheUniversidadeFederaldeAlagoasand
UniversidadeEstadualdeCiênciasdaSaúdedeAlagoas,Maceió,AL, Brazil;UniversidadedoEstadodoAmazonasandFundac¸ãoAlfredo daMattadeDermatologia,Manaus,AM,Brazil.
∗Correspondingauthor.
E-mail:albertooiticica@gmail.com(A.E.O.Cardoso).
Introduction
Parasitic diseases are skin conditions caused by insects, worms,protozoa,orcoelenteratesthatmayormaynotbe parasitic.Giventherelativelyeasymovementofpeopleto differentregionsoftheplanet,knowledgeofthesediseases isbecomingincreasinglyimportant.
Thisreviewwilladdressthemainclinicaland therapeu-ticaspectsofscabies,pediculosis,myiasis,tungiasis,larva migrans,Lymedisease,andonchocerciasis.
Scabies
Scabiesis a contagiousdisease. Theetiological agentis a mite,Sarcoptesscabieivar.hominis.Recentmolecular epi-https://doi.org/10.1016/j.abd.2019.12.001
0365-0596/©2020SociedadeBrasileiradeDermatologia.PublishedbyElsevierEspa˜na,S.L.U.ThisisanopenaccessarticleundertheCC BYlicense(http://creativecommons.org/licenses/by/4.0/).
demiologicalstudieshaveshown thatscabies causedbyS. scabieivar.hominisisexclusivelyhuman(itdoesnotaffect animals),andtransmissionoccursthroughpersonalcontact, withnopredilectionforage,ethnicity,orgender. Transmis-sionbyfomiteisrare.1,2
Scabiesepidemiologyiscyclical,especiallyindeveloped countries.The intervalbetweencyclesrangesfromtento 15years,approximately.
According to studies on dust samples from infected patients’ homes, under normal environmental conditions,
S.scabieicansurviveoutsidethehostfor24---36h.1,2
Mitebiologyandmorphology
Aftermating,themaledies,andthefemalepenetratesthe epidermis,diggingfurrowstolayeggsandfeces.
In four to six weeks, females can release 40---50 eggs. Afterhatching,thehexapodlarvaeleavethefurrows.The numberofadultmitesinaninfectedindividualisestimated at12parasites.
Clinicalmanifestations
Pruritusisthemainsymptomofscabies,beingmoreintense atnight.Inmostcases,thissymptombeginsinsidiously, pro-gressivelyintensifying.Itcanaffectalmosttheentirebody; thefaceisrarelyaffected.
The characteristic lesion is linear, serpiginous, and raised,measuringafewmillimeters;atoneend,a papular-vesicularlesionmaybeobserved,describedbysomeauthors asa‘‘blackspot.’’ Theselesionsaremostoftenobserved onthelateralsurfacesofthefingers,palmarregions,hands, wrists,andfeet.
Scalpscabiesisnotcommoninadults;however,itmay accompanyorresembleseborrheicdermatitis.
Leftuntreated,erythematouspapularlesionsappearin thearmpits, breasts, penis, buttocks, interdigital spaces, waist,andfeet.
Long-termpatientsmaypresentpapular-nodular reddish-brown lesions, mainly located on the genitalia, armpits, trunk,and elbows. These lesionsare veryitchy andtheir regressionisslow,evenafterpropertreatment.These man-ifestationsarecalled nodularscabies(Fig.1).Ithadbeen assumed that there was no mite in these lesions. How-ever, recent studies have demonstrated the presence of
S. scabiei.3,4 In children, nodular scabies may simulate mastocytosis.5
In newborns and young children, the face and scalp maybeaffected,andcervicalpolymicroadenopathymaybe observed.Eczemaorhivelesionsmayhinderthediagnosis, especiallyininfants.6
Intheelderly, theskin reactiontothe presenceofthe mitemaybelesspronouncedandcauseatypicalconditions. Dorsalinjuriesmaybemistakenforsenilepruritus. Vesicob-ullouslesions,whichareclinicallyandhistologicallysimilar tobullouspemphigoid,havebeenreportedinpatientsolder than6yearswithoutdebilitatingdisease.
Crusted scabies,alsoknownasNorwegian scabies, isa clinicalvarietyofscabiesthatoccursduetomite hyperin-festation;over one million parasites can be found in this condition. Currently, it is observed primarily in
immuno-Figure1 Nodularscabies---intensepruritusanderythematous papularnodularlesions.
Figure 2 Crusted scabies. Intense, constant pruritus and generalized erythematous, squamous lesions. HTLV+ patient. Personlarchive:Dr.PauloRobertoMachado.
suppressedpatients,thoseunderchemoterapy,thosewith malignant neoplasms, and transplant recipients. The fre-quency of this clinical form has increased in HIV-positive patients.7,8AustralianaboriginesandcarriersoftheHTLV1 virusarealsorelativelyfrequentlyaffected.9Clinically,itis characterizedbyhyperkeratotic,crustedlesionswith cuta-neousfissuresand thickenedanddystrophicnails(Fig.2). Secondaryinfectionsmaybeobservedinthesepatients.In thevastmajorityofcases,thepruritusisveryintense.The differentialdiagnosis ismainlymade withDarier’s disease andpsoriasis.
Figure3 Sarcoptesscabiei.Dermoscopy.Atthelowerend,a ‘‘hangglider’’-shapeddarkspot,correspondingtotheanterior segmentofthemite.
Differentialdiagnosis
Differential diagnosis is made with most pruritic condi-tions,suchasatopicdermatitis,drugrash,papularurticaria, insectbites,andpyoderma.
Diagnosis
Directexamination of thelesions should always bedone, especially in atypical cases. Two drops of mineral oil are placedonthelesions,whicharethenscarifiedwithascalpel blade or curette, removing the furrow ceiling, which is placed on a glass slide. It is then examined under the microscopeat10×and40×magnification.Themite,eggs, and/orfecesmaybeobserved.Afewdropsof30%potassium hydroxidecanbeplacedonthecollectedmaterialpriorto microscopeobservation.
PCRmaybeusefulinclinicallyatypicalcases.10
Dermoscopy can also be used to find the para-site (Fig. 3).11 Epiluminescence microscopy is another recommended method for mite visualization;12 confocal microscopyandopticalcoherencetomographymayalsobe used.13
Treatment
Inthetreatmentofscabies,itisimportantthatallhousehold residentsaretreated,inordertoavoidreinfestation.
Permethrin: a synthetic, effective, and non-toxic pyrethroidisavailableasa5%creamorlotion.Itcanbeused inchildren,adults,pregnantwomen,andnursingmothers.
Itshouldbeappliedovertheentirebody,fromneckto toe.Inchildren,itshouldalsobeappliedtothescalpand retroauricularridges.Thedrugshouldbeappliedat night-time,for twoconsecutivenights. Onthethird day, inthe morning,allbeddingshouldberemovedandwashed.
Precipitatedsulfur: recommendedat concentrations of 5---10% in petroleum jelly. It does not cause side effects. It can beused in children, pregnant women, and nursing mothers.It shouldbeapplied ontheentire bodyfor four consecutivenights,andremovedduringtheday.
Ivermectin: used systemically. It is a semi-synthetic macrocycliclactone suitable for adults andchildren over 5years.Thedoseprescribedis200g/kg,givenasasingle dose,whichmayberepeatedaftersevendays.For immuno-suppressedpatients,twodosesshouldbeusedataone-week interval.Itisthegoldstandardinthetreatmentofcrusted scabies,inwhichitisassociatedwithtopicalkeratolytics, suchas5%salicylatedpetroleumjelly.
Ivermectinmayalsobeusedtopically,at1%,inpropylene glycolorasalotion.Itshouldbeappliedontheentirebody andtheapplicationshouldberepeatedafteroneweek.14
Newmedications arecurrentlybeing investigated.The useofTinosporacordifolialotionshowedsimilarefficacyto permethrin,withnosideeffectsintreatment.15Moxidectin isanotherpromisingmedication whoseefficacyandsafety havealreadybeendemonstrated.16
Potenttopicalcorticosteroids,twotothreetimesdaily, areusedinthetreatmentofnodularscabies.Occlusionor triamcinoloneinfiltration (3---4mg/mL)can alsobeused.17 Topicalpimecrolimusandtacrolimushavebeenusedincases ofcorticosteroidresistance,withgoodresults.18Inresistant cases,obeyingthelegalrestrictions,oralthalidomideata doseof100mgdailymaybeused.
Pediculosis
HumanscanbeparasitizedbythreespeciesoftheAnoplura suborder:Pediculushumanuscapitis,theetiologicalagent of scalp pediculosis, Pediculus humanus, which causes pediculosiscorporis,andPthiruspubis,thepubiclouse.All feedonblood.
Etiologyandpathogenesis Scalppediculosis
The etiological agentis Pediculus capitis (Fig.4A). Louse salivaprobablyinducesthepruritusthatoccursonthescalp. Nymphsandadultsaredifficulttosee,buttheeggsthat attachtothehairareeasilyidentified(Fig.4B).
Wood’slightanddermatoscopycanbeusedtoaid diag-nosis.
Whenapatientreportsscalppruritus,pediculosisshould notberuledout.19
A
B
Figure4 (A)Pediculuscapitisonthescalp(Photocourtesyof Dr.DanielFranc¸a).(B)Nits,attachedtothehair.
Pediculosiscorporis
Bystingingtheskin,Pediculushumanushumanuscauses pru-ritusofvaryingintensity,leadingtoerythematousmacules, papules, scabs, and abrasions, mainly seen onthe trunk, armpits,andbuttocks.Secondaryinfection, hyperpigmenta-tion,andlichenificationmayoccur.InBrazil,thiscondition isalsotermedthe‘‘homelessdisease’’.
Thediagnosisisconfirmedbyfindingthepedicleornits inthefoldsoftheclothes.
Pediculosispúbisorpthiriasis
ThecausativeagentisPthiruspubis,whichparasitizesthe hairsof the genitoanalregion andeventually the hairsof thethighs,trunk,armpits,beard,eyelashes,eyebrows,and scalpborders.
Themainclinicalmanifestationispruritus.Thediagnosis ismadebyobservingtheparasiteintheskin,usuallywith theheadportioninsertedintothehairfollicle,ornitsstuck atthebaseofthehair.
Inadditiontoabrasions, maculaeceruleae(bluish-gray spots)canbeobservedonthethighsandtrunk,similarlyto pediculosiscorporis.
Treatment Scalppediculosis
Topicalpediculicidesremainthemaintreatment.
Permethrinshampoo1% shouldbeleftonthescalpfor 10minandthenrinsed.Piperonylbutoxide15%mayalsobe usedasshampoo.
Permethrin 5% may also be used,applied to the scalp atnight,andremovedthenextday.Thetreatmentshould berepeated afterseven to ten days,becauseduring this period,the nitshatch.Malathion(0.5%)isan organophos-phatewidelyusedintheUnitedKingdom.
Due to the increasing resistance to pyrethroids, new productshavebeendevelopedforthetreatmentof pedicu-losis.
Spinosadisaninsecticidecomposedofthenatural mix-tureoftetracyclicmacrolides,spinosynAandD.Itinterferes withnicotinicacetylcholinereceptors, producingneuronal excitationandconsequentliceparalysis,dueto neuromus-cularfatigueafterlongperiodsofhyperexcitation.Spinosad killspermethrin-susceptibleand-resistantlicepopulations. It is alsoovicidal. Spinosad is usedat a concentration of 0.9% in suspension. It was approved by the FDA in 2011 for childrenaged4yearsor older.Nosystemicabsorption wasdetected.Itshouldbeappliedfor10min,thenrinsed. Treatmentshouldberepeatedaftersevendays.20,21
5% benzyl alcohol in mineral oil was the first non-neurotoxicproductapprovedbytheFDA.Itapparentlyacts bypreventingthelousefromclosingitsbreathingspiracles, which allowsthevehicletopenetrateandobstruct them, suffocating the parasites. As this is not an ovicidal, two 10-minapplicationsshouldbeperformed,withaseven-day interval.Itis FDA approved(CategoryB)and canbeused from6monthsofageonwards.22
Anotherproduct,dimethicone(4%lotion),wasapproved in2006;it waslatermarketedasaliquidgel.Itsmode of action isstillunclear.Itmayobstructtherespiratory spir-acles,andthelicewouldthusdieofasphyxiation.Another hypothesisisthatitinhibitswaterexcretion,causing physi-ologicalstressanddeathbyparalysisorruptureofinternal organs.23Themodeofapplicationaccordingtothe accord-ingtothe presentation:thegel shouldbeappliedfor ten to 15min; the lotion, for 8h. The application should be repeatedinseventotendays.Ithasovicidalaction.24---26
Ivermectintopical0.5%lotionwasapprovedbytheFDAin 2012forthetreatmentofchildrenaged6monthsorolder.It shouldbeappliedfor10min,andrinsedimmediatelyafter. Ithasovicidalaction.27
Theuseofashampoobasedonmineraloilandsaponified oliveoilwasalsoeffective.28
Single-doseivermectin200g/kg wasalsoeffective. It shouldberepeatedafterseventotendays.
A recent study advocated the use of levamisole as a pediculicide.29
Thenitsmustberemoved.To facilitatetheremovalof nits,avinegarsolutionat50%canbeusedaswellasaformic acidsolutionat8%.
Brushesandcombsshouldbeplacedincontactwith pedi-culicidesfortento15min,andthenwashedwithhotwater.
Pediculosiscorporis
Improvedhygieneandwashingtheclothespromotehealing.
Pediculosisorpthiriasis
Itcanbetreatedwithpermethrin5%ordeltamethrin0.02% cream,appliedatnightandremovedthefollowingday.Itis recommendedtobeusedfortwoconsecutivedays, repeat-ingafterseventotendays.Sexualpartnersshouldalsobe treated.Thehabitofshaving/waxingthisareahasledtoa decreaseinthenumberofcases.
Incase ofeyelashlesions,petroleum jellycanbeused twiceadayforeightdays,mechanicallyremovingthenits.
Flea-induced
dermatosis
(pulicosis)
Thebites causehivepapulesinnon-sensitizedindividuals. When sensitizationoccurs, especiallyinchildren,the sali-varyantigeniscapableofcausinglocalanddistantlesions, causingacuteinfantpruritusandHebra’sprurigo.30
Somespeciescantransmitdisease-causingbacteria,such asplague,cat-scratchdisease,andbacillaryangiomatosis.
Corticosteroid creams and, if necessary, oral antihis-taminesareindicatedforthetreatmentoffleabites.31,32
Forprophylaxis,an insecticideshouldbeappliedtothe dwellings,andpetsshouldreceivetreatment toeliminate fleas.
Tungiasis
It is caused by Tunga penetrans, the smallestof fleas;it measures on average 1mm, and lives in dry and sandy places, especially in rural areas, in pig pens and corrals. Themain hostsofthesehematophagousfleasarepigsand humans.Afterfeeding,themaleleavesthehost; the fer-tilizedfemalepenetratestheskin,introducingitsheadand chest intotheepidermis, leavingoutthe respiratory stig-masandtheegg-layingorifice.33 Theeggsdevelopandthe abdomendilates,showingayellowishnodulewitha black-ened spot in the center (Fig. 5A). There is pruritus and eventuallypain.Theyareusuallyobservedinthenailfolds of the toes, interdigital spaces, and plantar regions.34---36 When many nearby lesionsoccur, theyresemble a honey-comb(Fig.5BandC).Secondaryinfectionsmayoccur,and the lesions serve as a gateway toother diseases.37 After theeggsarefullydeveloped,thefleabeginstoexpelthem withintwoweeks;subsequently,thefemaledies.
Treatment
The flea is removed with a needle, and an antiseptic is appliedtothe wound. In generalizedcases, oral thiaben-dazole25mg/kgisusedfortendays.38
Prophylaxisconsistsofwearingshoes.
Recentstudieshaveshownthatlowviscositydimethicone (NYDA)appliedforsevendaysiseffectiveandsafe.39
Bedbugdermatitis(cimicidiasis)
Allcimicids(bedbugs)areblood-sucking parasitesofbirds and mammals. Two thirds of the species are bat para-sites. The genus Cimex, with the species lectularius and hemiptera,is a human parasite.Commonlyknownasbed bugs, these insects have nocturnal habitsand live in the cracksandholesoffurnitureandmattresses.Atnight, espe-ciallyatdawn,theybitehumans.Duringthemealtheyinject saliva,whichcontainsananticoagulantandanesthetic.
These bites are most commonly observed onthe face, neck,arms,andhands.Theycausehivesandpruriticlesions (Fig.6),ofteninlineararrangement.Distantsensitization injuriesmayoccur,includingbullouslesions.40,41
Bedbugsshareimportanttraitswithtriatomineinsects, butitisunclearwhetherthesesimilaritiesincludetheability to transmit Trypanosoma cruzi, which causes Chagas dis-ease.
A
B
C
Figure5 (A)Tungiasis---typicalaspect.Isolatedlesion.Note apustule,inregression,withcentralcrustedarea.(B,C) Tun-giasis.Multiplelesions,isolatedandconfluent.
Figure6 Bedbug dermatitis. Multiple,characteristic linear erythematouspapularlesionslocatedintheabdomen.
Arecentstudydemonstratedefficientandbidirectional transmissionofT.cruzibetweenhostsandbed bugs.Most bedbugsthatfedoninfectedmiceacquired theparasite; mostmice wereinfected after cohabitationwithexposed
Figure7 Furunculoidmyiasis.Ulcero-nodularlesionand eti-ologicalagent(Dermatobiahominis).
bedbugs. T.cruzi wasalsotransmittedtomice afterthe fecesofinfectedbedbugswereapplieddirectlytotheskin ofthehost.Thesefindingssuggestthatbedbugsmaybea
T.cruzivector.42
Corticosteroid cream is used for the treatment, and, dependingonthepruritus,antihistaminesmayalsobeused. Bedbugsmustbeeradicatedwiththeuseofinsecticides.
Several reports suggest an increase in the number of cases worldwide, including in Europe and the United States.43,44
Myiasis
Myiasisis characterized by the invasionof Dipteralarvae intothe skin, mucous membranes, and organs of humans andanimals.
AmongthevariousfamiliesofDiptera,thefliesare note-worthybecause,besideotherdiseases,theycausemyiasis. AccordingtotheevolutionarycycleoftheDipteraflies, myiasisisclassifiedintoprimaryandsecondary.
In patients with primary myiasis, the larvae invade healthytissues. This variety iscalled furunculoidmyiasis. Inthesecondaryform,knownascavitymyiasis,theflieslay theireggsonskinwoundsorinthemucosa.45,46
Furunculoidmyiasis
ItisobservedintropicalregionsoftheAmericancontinent, extendingfromsouthernMexicotonorthernArgentina.The life cycle of D. hominis is unique. After copulation, the femaleflies andcaptures ahematophagous Dipterafly. It lays10---50 eggs in the prey’sabdomen, without affecting itsability tofly.47 When it lands on the skin of a human or animal, the eggs hatch and larvae are released into thehostthroughthe hairfollicles or theinsectbitehole. Larvapenetrationisusuallynotnoticed.Atthelarvaentry site,anerythematous,papulous,pruritic,andpainfullesion arises.Thepapuleincreasesinsize,evolvingtoafurunculoid aspect,withminorulcerationandoutflowofserousexudate. Inthisopening,itispossibletoobservethetailofthelarva. Thelarvaefeedonhypodermicmaterialforan averageof fiveto12weeks.Afterthisperiod,thelarvaeleavethehost andfalltotheground,becomingapupa.Between60and80 days,thepupaevolvesintoawingedinsect.Thelarvacan beexposedbypressingthelesion(Fig.7).47,48
Thelarvaactivelymoves,andpatientsreporta‘‘stinging pain’’ at the site. Eventually, a secondary infection may occur,withabscess,cellulitis,andadenopathy.
Whenthe larvaleavesthenodule,the lesionregresses andheals.47,48
Thetreatmentconsistsofremovingthelarva,whichcan be done by compressingthe nodule aftera smallincision intothelesionorifice.Holeobstructionwithpetroleumjelly, andplacementofadhesivetape,preventingthelarvafrom breathing,facilitatesitsremoval.Alaytreatmentconsists of placing heated bacon over the hole of the lesion --- to breathe,thelarvapenetratesthebacon.
Secondarymyiasis
It is caused bythe larvae of fliesthat arenotmandatory parasites.Dependingonwheretheeggsarelaid,these sec-ondaryinfectionscanbecutaneousorcavitary.When eggs areaccidentallyingested,intestinalmyiasismayoccur.
Inthe cutaneous form,the flylays eggs onskin ulcer-ations. The eggs hatch andthe larvae develop. The main etiological agents are the larvae of the flies Cochliomya macellaria,C.hominivorax,andotherspeciesofthefamily SarcophagidaeandgenusLucilia.49
Thediagnosisisclinical,asthelarvaeareeasily visual-ized.Traditionally,treatmentisperformedbyremovingthe larvae after topicalapplication of ether. The use of iver-mectin1% inpropylene glycolis anothermethod thathas beenused---2hafterapplication,thelesioniscleanedand thelarvaeremoved.50
Cavitymyiasis
Inthesecases,theflylayseggsinnaturalcavities,suchas thenostrils,ear,eyesockets,andvagina.Themostsevere casesarecausedbythespeciesC.hominivorax.
The treatment ofchoice is asingledose of ivermectin 200g/kg.
Priortoivermectin,mercuryoxycyanide1%wasused.
Demodicidosis
It is caused by Demodex folliculorum,a mite, which is a holoparasiteofthehairfollicle.Thesemiteshavea prefer-enceforareaswithhighsebumproduction,suchastheface andchest.
Demodex has been frequently implicated in the etiopathogenesisofrosacea.51-54However,theinvitro resis-tanceofthemitetohighconcentrationsofmetronidazole castsdoubtontheroleoftheparasiteinthepathogenesis ofrosacea.55
Itispossiblethatthroughtheobstructionofthe follicu-larostia,Demodexcontributestotheinflammatoryreaction observedinrosacea,allowingbacterialproliferationor indu-cingmechanismsofhypersensitivitytomiteantigens.
D.folliculorumhasbeenattributedapathogenicrolein pityriasisfolliculorum,adermatological conditionwhichis predominantly observed in middle-agedwomen. This der-matosisischaracterizedbythepresenceofdiffuseerythema and folliculitis on the face. Microscopic examination evi-dencesalargenumberofmites.Topicalacaricidesareused fortreatment.51
Papular or papule-pustular eruptions on the face, trunk, and limbs observed in immunosuppressed individu-als (HIV-positive patients, children with leukemia, and a case of mycosis fungoides) have also been attributed to
Demodex.56,57
Systemic treatment with ivermectin (200g/kg body-weight, single dose) or metronidazole 250mg daily, with varyingduration,dependingontheresponse,iseffective.
Cutaneous
larva
migrans
Itisalsocalledserpiginouslineardermatitis,creeping erup-tion,grounditch,sandworm,andplumber’sitch.
Infectionoccurswhenindividualscomeintocontactwith sandorsoilcontaminatedwithdogandcatfeces.
Duringtherainyseason,thenumberofinfectedpeople increases,probably due tothe dissolution of dog and cat feces,facilitatingthehatchingofeggsandthepenetration oflarvaeintopeople’sskin.
Thediseaseoccursbyskinpenetrationoflarvalformsof dogandcatnematodesthatarelikelytopenetratetheskin, probablybyhyaluronidasesecretion.58
Ancylostomabrasiliensisisthemostcommonetiological agent.A.caninum,Uncinaria(Europeandogworms), Bunos-tomum(cattleworm),andPhebotumumstenocephalamay alsocausethedisease.
Clinicalmanifestations
The lesions are usually linear, raised, erythematous, and serpiginous (Fig. 8A). Vesicles and even blisters may also appear. The most affected areas are the feet, legs, but-tocks;itappearslessofteninotherregions,suchastheface, armpits,andpenis.Onecasewithoralmucosalesionswas described.Larvaedislocationtriggersintensepruritus.59
When eczema and secondary infectionoccur, diagnosis canbeverydifficult.Insuchcases,itisfirstrecommended touseointmentsfortheallergiccondition,andantibiotics,if necessary.Thiswillmaketheclinicalaspectoflarvamigrans moreevident.
When interdigital spacesareaffected,maceration may occur.Thisclinicalpresentationmaybeconfusedwithfoot dermatophytosis.
Hematological alterations may also occur, with eosinophilia that, in some cases, reaches 30%. In severe infestations (Fig. 8B), the larvae may invade theblood streamandtrigger Loeffler’s syndrome, charac-terized by eosinophilic pneumonia associated with blood eosinophilia.60
Treatment
Depending on the number of lesions and their location, treatmentmaybetopicalorsystemic.Inpatientswith mul-tiplelesions or involvementof hyperkeratoticareas, such asthepalmoplantarregions,systemictreatmentis recom-mended.
Albendazoleatadoseof15mg/kg/dayforthreedaysis agoodtherapeuticoption.Itsusedoesnotprevent
breast-A
B
Figure8 (A)Larvamigrans.Intensepruritus.Typical serpig-inouslesion with linearaspect.(B)Larvamigrans. Numerous lesionscausedbymultiplelarvae.
feeding,andthefetalriskiscategoryC.Thecureratevaries from77%to100%.61,62
Ivermectin,atasingledoseof200g/kg,isalso effec-tive.Dependingontheevolutioncourse,thesamedosemay berepeatedaftersevendays.63
When the number oflesions is reduced andlocated in theglabrousskin,topicaltreatmentwiththiabendazole5% ointmentmaybeindicated.
Carbonicsnoworliquidnitrogenarealsoused.64,65
Lyme
disease
Lyme disease (LD), also termed Lyme borreliosis, is a tick-borne zoonosis, mainly of the genus Ixodes, infected with spirochetes of the Borrelia burgdorferi sensu lato
complex.66 Currently, 20 species have been recognized withinthesensulatocomplex,sixrelatedtothediseasein humans:B.burgdorferistrictusensuandB.mayonii(United States);B.bavariensis,B.garinii,B.afzelli,andB.spielmanii
(Europe).67
Afzelius,inSweden,in1909,andLipschutz,inAustria,in 1913,describedthefirstcasesofpatientswith centrifugal-growingerythematousplaques,whichweretermedchronic migratory erythema (CME).68,69 In 1977, Steere et al. observed an association between CME and arthritis. The caseswerestudiedinthecityofLyme,Connecticut(USA). Since this publication, the names Lyme arthritis and LD becamepopular.Inadditiontotheassociationwith arthri-tis,Steereetal.observednon-specificsymptoms(malaise,
fatigue,headache,fever,andothermanifestations),aswell ascardiac,ophthalmic,andneurologicalalterations.70Due tothenotalwayschronicevolutionofskinlesions,in1989, Detmaretal.proposedthenamemigratoryerythema(ME), whichhasbeenwidelyadopted.71 InBrazil,thefirstcases were reported in Manaus by Talhari et al.72,73 Filgueira, Azulay,andFlorião74---76alsodescribedclinicallycompatible casesin Riode Janeiro. In1992, the firstcasesof Brazil-ian patients with joint manifestations associated with B. burgdorferiinfectionweredescribed.74
Pathogenesis
TheetiologicagentofME/LD,aspirochete,wasfirstisolated by Burgdorfer in 1982 in the intestine of Ixodes dammini
ticks.75 This spirochete is now called Borrelia burdorgeri
sensulato.Ithasbeenidentifiedinbiopsiesofskinlesions, blood,cerebrospinalfluid,synovialtissue,myocardium,and eyesofpatientswithLD.12
In the United States, mice and deer are important reservoirsofthisspirochete.Elevatedserologicaltitersfor
Borreliahave been observed in horses, cows, sheep,and cats. In Brazil, wild rodents and other mammals, such as skunks,appeartoparticipatein theepidemiologicalcycle ofLD.76
The main transmitters of the disease areIxodes ticks. In Europe, Ixodes ricinus is the most prevalent, while in theUnitedStates itis theIxodesdammini, alsoknownas
I.scapularis. InBrazil,Ambylomma cajannenseis thetick believedtoberesponsibleforthetransmissionofLD. How-ever,theparticipationofothertickspeciesisnotexcluded. Theevolutionaryformsofticksmostassociatedwith Borre-liatransmissionarenymphsandadultticks.Nymphbitesare painless,whichwouldexplainthefactthatmanyinfected patientsdonotrememberbeingbittenbyticks.77
Clinicalpicture
Thecutaneous manifestationsof LDaredividedintoearly localized(erythemamigransandlymphocytomacutis);early disseminatedinitial(MEandmultiplelymphocytomas,which maybe accompanied by alterations inother organs);and late(acrodermatitischronicaatrophicans).78
Dermatologicalmanifestations
MEisthemainearlyclinicalmanifestationofLD.Threeto 30 days after the tick bite, an enlarged papule or small erythematous plaque appears at the site of inoculation, formingaplaquewithdiscontinuousedgesandaclear, cyan-otic, and/or scaly center that expands centrifugally and mayreacha largediameter (Fig. 9).Rapidprogressionof lesions,whichmayreach20---30cmormoreindaysorweeks, is common. In most patients, these lesions are asymp-tomatic.Differentclinicalfeatureshavebeendescribedin ME:erysipeloid,erythematous,lichenoid.79Europeancases ofMEtend topresent witha smallnumberoflesionsand withoutatendencytocutaneousspread.80
InadditiontoME,anotherimportantcutaneous manifes-tationoftheearlyphaseofLDislymphocytomacutis,also
Figure9 Lymedisease.Plaquepresentingcentrifugalgrowth, with erythematous-violet borders, measuring approximately 18cm,locatedontheposteriorsurfaceofthethigh.
called lymphadenosisbenigncutis,whichsimulatesB lym-phocyticpseudolymphoma.Clinically,itischaracterizedby asinglelumporerythematousplaque,1to5cmindiameter, usuallylocated ontheface,pinna, scrotum,or mammary areola.Lymphocytomaisoftenassociatedwithinfectionby
B.afzelliandB.garinii.81In2007,acaseofcutaneous lym-phocytomainassociationwithLDwaspublishedinBrazil.82 In this acute phase, systemic manifestations such as asthenia, arthralgia, myalgia, skin rash, adenopathy, splenomegalyandsignsofmeningealirritationmayalsobe observed. Early LD lesions may disappear without treat-ment, and manifestations of the second and third stages mayappearmonthsoryearsafterinitialinfection.Themain alterationsincludearticular,cardiac,neurological, ophthal-mological,andskininvolvement.Morerarely,latechanges mayoccurinthepresenceofMElesions.83Amongthe man-ifestations of the late, cutaneous phases, acrodermatitis chronicaatrophicans(ACA),alsoknownasPick-Herxheimer disease,ismoreassociatedwithB.afzeliiinfectionandis generallydescribedinEurope.ACAismorecommoninadults andmaymanifestfromsixmonthstoeightyearsafterthe tickbite.Clinically,itinitiateswithanerythematousplaque, evolvingwithskinatrophyandveryprominentbloodvessels, particularlyinthelowerlimbs.Thefaceandtrunkmayalso beaffected.84
Otherdermatologicaldiseasesassociatedwith Borreliainfection
B.burgdorferiinfectionhasbeenassociatedwithother der-matological diseases such as plaque scleroderma, lichen sclerosus, atrophoderma of Pasini and Pierini, cutaneous B-cell lymphoma, and granuloma annulare.85 In a study
conducted in Manaus in 2009, patients with scleroderma and atrophoderma of Pasini and Pierini were analyzed by immunohistochemistry withanti-B. burgdorferi polyclonal antibody;thepresenceofspirochetewasconfirmedin sam-plesfrombothdiseases.86
Diagnosis
The diagnosis of thedisease is based on epidemiological, clinical, and laboratory aspects. Laboratory diagnosis is basedonserologicaltests(detectionofspecificantibodies) and/or onthe findingoftheetiological agent.Inaddition to serology, it is important to conduct histopathological andimmunohistochemicaltests,culture,and,ifavailable, PCR.87
DetectionofIgMorIgGanti-B.burgdorferiantibodiesis commonlyusedforserologicaldiagnosisandepidemiological investigation. Enzyme-linkedimmunosorbent assay(ELISA) tests are most commonly used; however, they present false-positiveresultsin viewof cross-reactionswithother diseases,suchascollagenoses,leishmaniasis,andsyphilis. Thus,innon-endemic areas,for thedefinitivediagnosisit is necessarytoperforma confirmatoryexam that demon-stratesthepresenceoftheagent.88
HistopathologicalexaminationofMElesionsreveals pro-liferation and dilation of blood vessels associated with a centralinflammatory infiltrate consistingof macrophages, mast cells, neutrophils, plasma cells, lymphocytes, and rareeosinophils.ApPCRymphocyticvasculitismayalsobe observed.Inolderlesions,atrophyoftheepidermisand der-mis mayoccur, aswell asdecreased dermalinflammatory infiltrate.89
PCR has been used to detect Borrelia nucleic acid sequences, with high specificity. However, the sensitivity of this diagnostic method is variable (20---81%). In 2008, Ceraretal.demonstratedthatnested-PCR,usingthe flag-ellingene,presentedhighersensitivitythanPCR(64.6%vs.
24%).PCRpositivityishigherwhenfragmentsofcutaneous or synovialmembrane lesionsareused.Itis lesssensitive whenperformedonparaffinblocks,blood,synovialfluid,or cerebrospinalfluid.90
ThecultureusingBarbour,Stroenery,Kelly(BSK)medium or variationsthereof presents100% specificity, but witha relativelylowsensitivity.Giventhedifficultiesofthe tech-niqueandthecontaminationofthematerial,theresultsare positiveinapproximately45%ofthecases.91
In2007,throughaspecificimmunohistochemistrytestfor thedetectionof Borreliasp.,associatedwiththefloating focusmicroscopy(FFM)technique,Eisendleetal.obtained resultssuperiortonested-PCRin theidentificationof Bor-relia (96% vs. 45.2%), with similar specificity (99.4% vs.
100%). The FFMconsists ofexamining the slide in several planes simultaneously: horizontal and vertical, advancing andretractingtheobjectiveofthemicroscope,with magni-ficationsofupto400×underbrightillumination.According to the authors, these simultaneous movements facilitate thedetectionofBorrelia.92 In2010,usingthissame tech-nique, Talhari et al. demonstrated, for the first time in Brazil,thepresenceofBorreliainMEpatientsfromManaus, using immunohistochemistry with anti-Borrelia polyclonal antibody,andobservationbyFFM.93
Treatment
The treatment of this disease is made according to the stageandclinicalmanifestationpresented.Inadultpatients withlocalizedLD,includingMEcaseswithoutspecific neu-rological manifestations, the recommended treatment is doxycycline (100mg, 2× daily), amoxicillin (500mg, 3× daily),orcefuroximeaxetil(500mg,2×daily)for14days. Forchildren and patients with doxycycline hypersensitiv-ity, amoxicillin at a dose of 500mg or 50mg/kg/day, 3× dailyisused;cefuroxime500mgor30mg/kg/day,2×daily can also be used for the same period. Joint manifesta-tionsandcasesofatrophicacrodermatitisaretreatedwith the same antibiotics for 28 days. In cases of meningitis and other manifestations of early neurological LD, intra-venous (IV)ceftriaxone 2g/day or IVcrystalline penicillin G at a dose of 18 to 24 million IU daily for 14 days is recommended. For the treatment of chronic erosive arthritis,sulfasalazine,chloroquine,methotrexate,and cor-ticosteroidsarerecommended.80,94
Onchocerciasis
Onchocerciasis, also known as ‘‘river blindness,’’ is a chronic,non-contagiousparasiticdiseasecharacterizedby thepresenceofskinlesions,andoften,severeophthalmic lesions.It is caused by the filarial nematode Onchocerca volvulus.95
According to the World Health Organization (WHO), 198 million people areat risk of infection in 31 endemic countries.96 Onchocerciasisis the secondleading causeof infectious blindness worldwide. Approximately 99% of O. volvulus-infected individuals live in sub-Saharan African countries, while the remaining patients live in Yemen, Sudan,andtheAmericas.Inthe latter,onchocerciasishas been endemicin six countries:Brazil,Colombia, Ecuador, Guatemala,Mexico,andVenezuela.96
Currently,theonlyonchocerciasisfocusintheAmericas recognizedbyWHOistheborderregionbetweenVenezuela andtheBrazilianstatesofRoraimaandAmazonas,inhabited bymembersoftheYanomamitribe.96
Since1974,theOnchocerciasisControlProgram, devel-oped by the WHO and funded by the World Bank and theUnitedNations,haspromotedvector controland iver-mectintreatment of onchocerciasis (usedbythe program since 1987) in 33 African countries.95 In 2016, over 133 million people living in risk areas received treatment for onchocerciasis.97
In1990,theOnchocerciasisEliminationProgramforthe Americas,similartotheAfrican model,wasimplemented toeliminatethediseaseinthethirteenendemicregionsof theAmericas.96Sincethen,patientshavebeentreatedwith ivermectintwoorfourtimesayear.InNovember2017,the diseasewas considered eliminatedin 11 of 13 areas with activetransmissionofO.volvulus.96
Pathogenesis
TransmissionofO.volvulusoccursthroughthebiteofinsects ofthe genus Simulium. These are found in greater abun-dancenearthebanksofriverbanks,hencethename‘‘river
Figure 10 Onchocerciasis. Intense pruritus, presence of lichenification,exulcerations,andhyperpigmentation.Patient from the Infectious Disease Clinic, Ibadan, Nigeria (personal archive:Prof.Dr.SinésioTalhari).
blindness.’’95 Microfilariaecanbetransmittedbydifferent speciesofSimulium.InBrazil,themainspeciesareS. guya-nense,S.incrustatum,andS.oyapockense.98
Humansarethemainhostsofthedisease.Bystingingan infectedhuman,hematophagousfemalesingest microfilar-iae,whichaftertwotothreeweeksbecomeinfectivelarvae. Afteraperiodofsixto12months,theselarvaedevelopinto adultworms;malesmeasure2---4cminlengthandfemales, 40---50cm.Adultworms,maleandfemale,tendtolodgein interstitialspacesandadiposetissue,forming onchocerco-mas.Theymateinthesesites.Aftermating,females give rise tomicrofilariae, which migrate to connective tissue, superficialdermis, andtheocular globe.Each femalecan generateapproximatelyonemillion microfilariaeperyear, whichliveupto2.5years.Adultfemalescanlivebetween nineand16years.99
Clinicalpicture
Intheintegument,themostcommonandearly manifesta-tionofonchocerciasisischronic,constantpruritusthatmay simulatescabies(Fig.10A).Areaswithabrasions, lichenifi-cation,andhyperpigmentationarefrequent.Thiscondition isknownaslizardskin.100,101
Latedepigmentation and acromy secondary to chronic pruritusarefrequent,especiallyinthelowerlimbs(termed leopardskin). Atrophymayoccurinthelatestagesofthe disease,whichmaybemild(Fig.10B)orverypronounced, leadingtoenlargementofthescrotumandinguinalhernia. Inguinal hernias are termed hanging groin (Fig. 11).101,102 In some cases,lesions arelimited to a certainskin area, especiallyontheleg,thigh,andglutealregion.This condi-tionisknownassowda.Onchocercomasarepainless,firm, roundedorelongated,andvaryinsize(0.5---10cmin diame-ter).Theselesionsareusuallylocatedinthepelvis,lateral surfacesofthechest,andlowerlimbsinAfricanpatients;In theAmericas,onchocercomasaremainlyseenonthescalp, arms,andchest.100
The mainophthalmic lesionsarekeratitis,iridocyclitis, cataract,choroidoretinal lesions,post-neuritic optic atro-phy,andamaurosis.Amaurosisproducedbyonchocerciasis isextremelycommoninAfrica,resultingingreat socioeco-nomiclosses.95,101
A
B
Figure11 A.Onchocerciasis.Presenceofatrophy,commonin patientswithlongcourse.NativeBrazilianfromtheYanomami tribe(personalarchive:Prof.Dr.SinésioTalhari).B. Onchocer-ciasis.Observetheclassicaspectofthe‘‘hanginggroin’’due tolongevolution.Thereisalsoscrotumelongation(secondary tocutaneousatrophy),andtherearenodulesintheiliaccrest andleftgroin---probablyonchocercomas.NativeBrazilianfrom theYanomamitribe(personalarchive:Prof.Dr.SinésioTalhari).
Figure 12 Onchocerciasis. Observe two microfilariae (Onchocerca volvulus). Directexamination insaline solution. 40×magnification(personalarchive:Prof.Dr.SinésioTalhari).
Diagnosis
Thediagnosisofonchocerciasisisbasedontheobservation of microfilariae or the adult worm through direct exam-ination. The procedure is simple and performed without anesthesia: the skin is pinched between the thumb and forefinger to preventbleeding duringmaterial collection. A superficial fragment of skin is collected. The skin sam-ple obtained is placed in saline solution and divided into smallpieceswiththeaidoftwoscalpels.Microfilariae detec-tionisdone underthemicroscope withoutanystainingat 40---50×magnification(Fig.12).101O.volvulusmayalsobe seenbyhistopathologicalexaminationoftheskinlesionsand ophthalmic examination. The usual techniques of biopsy, 10% formalin fixation, and hematoxylin-eosin staining are employed.101,102 The microfilariae canbe identifiedbyslit lamp examination.101,102 Recently, immunologicalmethods have been used to identify specific anti-onchocerca
anti-bodies(ELISAandimmunofluorescence)andonchocercaDNA (PCR).103
Treatment
Treatmentis primarilyoral ivermectin,atasingledoseof 150g/kg,everysixmonths.Thisisamicrofilaricidaldrug and does not eliminateadult worms, which remain alive, producingnewmicrofilariae.95Arandomizedcontrolledtrial suggests that the use of ivermectin every three months wouldeliminatemorefemaleadultparasites,further redu-cingO.volvulustransmission.104
Authors’
contributions
AlbertoEduardoCoxCardoso:Approvalofthefinalversion of the manuscript;conception and planning of thestudy; elaboration andwriting ofthe manuscript;criticalreview oftheliterature;criticalreviewofthemanuscript.
AlbertoEduardoOiticica Cardoso:Approvalofthefinal versionofthemanuscript;conceptionandplanningof the study;criticalreviewofthemanuscript;criticalreviewof themanuscript.
Carolina Talhari: Approval of the final version of the manuscript;conception andplanning of the study; elabo-rationandwritingofthemanuscript;criticalreviewofthe literature;criticalreviewofthemanuscript.
Monica Santos: Approval of the final version of the manuscript;conception andplanning of the study; elabo-rationandwritingofthemanuscript;criticalreviewofthe literature;criticalreviewofthemanuscript.
Financial
support
Nonedeclared.
Conflicts
of
interest
Nonedeclared.
CME
Questions
1.Ivermectin,whenusedinthesystemictreatmentof scabies,shouldbeusedatthefollowingdose: a)100mcg/kg,insingledose.
b)200mcg/kg,inasingledose. c)200mcg/kg,forsevendays. d)20mcg/kg,forsevendays.
2.ImmunosuppressedindividualswheninfectedwithS.scabiei var.hoministendtodevelop:
a)Nodularscabies. b)Bullousscabies. c)Scabbyscabies. d)Classicalscabies.
3.Inscalppediculosis,themainsymptomandclinicalfindings are:
a)Scalpabrasionsandpruritus.
b)Pruritusandpresenceofeggs(nits)onthehair. c)Pruritusandbloodcrustsonthescalp.
d)Pruritusandcervicaladenopathy.
4.Infurunculoidmyiasis,thetreatmentconsistsof: a)Ivermectin-200mcg/kg,orally,threetimesaweek. b)Albendazole-singledoseof400mg.
c)Thiabendazole-25mg/kg,forfivedays. d)Larvaeremoval.
5.Amongthedrugsbelow,whichoneisnotusedtotreat cutaneouslarvamigrans?
a)Ivermectin-200mcg/kg.
b)Albendazole-400mgsingledoseor15mg/kg/dayforthree dayswhenthepatientweighsover60kg.
c)Azithromycin-500mg/day,forfivedays. d)Thiabendazole-25mg/kgforfivedays.
6.Inpubicpediculosisorphthiriasis,whatisthemainfinding toconfirmthediagnosis:
a)Itchinginthegenitalregion.
b)Adenopathyofthegangliaintheinguinalregion. c)Findingtheparasiteintheskinwiththeheadinsertedin
thehairfollicleorthenitsadheredtothehairbase. d)Findingbluishgrayspotsinthegenitalregion.
7.Theevolutionaryformsoftickmostoftenassociatedwith transmissionofBorreliabudorgeriare:
a)Larvaeandadultticks. b)Nymphsandadultticks. c)Eggsandnymphs. d)Nymphsandlarvae.
8.Regardingmigratoryerythema,indicatethecorrect statement:
a)Itappearsthreetofivedaysaftertickbite.
b)Lesionsprogressslowlyandmayreachupto30cmin diameter.
c)Inmostpatients,migratoryerythemaisasymptomatic. d)Histopathologicalexaminationistypicalandconfirmsthe
diagnosis.
9.Regardingtheclinicalmanifestationsofonchocerciasis,the expressionssowdaandlizardskinrefer,respectively,to: a)Depigmentationandlateacromy.
b)Depigmentationandlichenification. c)Upperlimbinjuriesandlichenification. d)Limitedlimbinjuriesandlichenification. 10.Regardingthetreatmentofonchocerciasiswith
ivermective,indicatethecorrectstatement: a)Thedrugismicrofilaricidal.
b)Itshouldbeadministeredweeklyfor6months. c)Itshouldbeadministeredeverysixmonthsfor3years. d)Iteliminatesadultworms.
Answers:
Actinickeratoses:reviewofclinical,dermatoscopic,and therapeuticaspects.AnBrasDermatol.2019;94(6):637---657.
1.b 3.d 5.a 7.b 9.a
2.c 4.b 6.c 8.b 10.c
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