lupus eritematos cutanat subacut asociat cu lichen plan

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LUPUS ERITEMATOS CUTANAT SUBACUT ASOCIAT CU LICHEN PLAN: GENERALITÃÞI.

PREZENTARE CAZ CLINIC

SUBACUTE CUTANEOUS LUPUS ERYTHEMATOSUSASSOCIATED WITH LICHEN PLANUS: OVERVIEW.

PRESENTATION OF A CLINICAL CASE

MONICA COSTESCU*, ANA MIHAELA UNGUREANU*, OANA ANDREIA COMAN*,**, MIHAIL ALECU*, MARIA GRIGORE*, SIMONA ROXANA GEORGESCU*,**

* Spitalul Clinic de Boli Infecþioase ºi Tropicale „Dr. Victor Babeº”, Bucureºti.„Dr. Victor Babeº” Clinical Hospital of Infectious and Tropical Diseases, Bucharest

** Universitatea de Medicinã ºi Farmacie „Carol Davila”, Bucureºti.„Carol Davila” University of Medicine and Pharmacy, Bucharest.

Rezumat

Termenul de ,,lupus eritematos (LE)” se referã la unspectru de boli cu evoluþie ºi prognostic variabile. Existãtrei forme majore de LE precum: lupus eritematos cutanatcronic, lupus eritematos cutanat subacut (LECS) ºi lupuseritematos sistemic.(1) LECS implicã, în primul rând,epidermul ºi dermul superior ºi este asociat cu anticorpianti-Ro/SSA ºi fotosensibilitate; majoritatea pacienþilor nuau afectare sistemicã semnificativã.(2) Lichenul plan (LP)este o boalã idiopaticã inflamatorie a pielii, pãrului,unghiilor ºi mucoaselor ce afecteazã, în general, adulþii devârstã medie.(13) Hepatita cu virus C (HVC) reprezintã oproblemã majorã de sãnãtate publicã, fiind principala cauzãa bolilor hepatice cronice, a cirozei si a carcinomuluihepatocelular. În ultimii ani, a devenit cunoscut cã VHCinduce un spectru larg de manifestãri extrahepatice,inclusiv manifestãri cutanate, precum LP.(15)

Prezenþa LP cutanat ºi a LP oral poate fi utilizatã camarker al infecþiei cu VHC la pacienþii asimptomatici, ceeace poate duce la un diagnostic corect, un tratament precoceºi, eventual, un prognostic mai bun al infecþiei cu VHC.Sindromul de suprapunere LE/LP este o afecþiune rarã cecombinã aspecte clinice, histologice ºi imunopatologice atât

Summary

The term ,,Lupus erythematosus” (LE) refers to aspectrum of diseases that vary in their course andprognosis. The three major forms of LE are: chroniccutaneous lupus erythematosus, subacute cutaneous lupuserythematosus (SCLE) and systemic lupus erythematosus.(1) SCLE involves primarily the epidermis and upperdermis and is associated with anti-Ro/SSA autoantibodiesand photosensitivity; the majority of patients do not havesignificant systemic disesase. (2) Lichen planus (LP) is anidiopathic inflammatory disease of the skin, hair, nails andmucous membranes, seen most commonly in middle-agedadults. (13) Hepatitis C virus (HCV) represents a majorpublic health problem as a causative agent in developingchronic hepatitis, cirrhosis, and hepatocellular carcinoma.In recent years it has become known that HCV induces abroad spectrum of extrahepatic manifestations, includingsome cutaneous ones such as LP. (15) The presence ofcutaneous LP and oral lichen planus can potentially beused as a marker of HCV infection in asymptomaticpatients, leading to proper diagnosis and early treatmentand, possibly, a better prognosis of chronic hepatitis C.Lupus erythematosus/lichen planus overlap syndrome is a

CAZURI CLINICECLINICAL CASES

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DermatoVenerol. (Buc.), 58: 263-276

I. Lupus eritematos cutanat subacut

1. LUPUS ERITEMATOS - GENERALITÃÞI

Termenul de ,,lupus eritematos (LE)” sereferã la un spectru de boli cu evoluþie ºiprognostic variabile.1 Lupusul eritematos este oboalã multisistemicã ce afecteazã, în principal,pielea, dar poate determina ºi afectãri grave,multiviscerale, cu prognostic rezervat.2 În ceea cepriveºte distribuþia pe sexe, se observã opredominanþã a bolii la femei (raport femei/bãrbaþi = 9/1).3

Cauza bolii nu este pe deplin înþeleasã.Patogeneza lupusului eritematos cutanat esteinterconectatã cu cea a lupusului eritematossistemic (LES).3 Cei mai importanþi factorietiopatogenici incriminaþi sunt: genetici,hormonali ºi de mediu.

Factori genetici. Forme familiale de LES aparla 10% din pacienþi.4 Existã citate multipleasocieri cu antigene ale complexului major dehistocompatibilitate, mai frecvent cu HLA B8,DRw52, DQw1, DQw2, DR2 ºi DR3.

Factori hormonali. Aratã predominanþa boliiîn rândul femeilor. S-au constatat nivele crescuteale metaboliþilor estrogenilor, ale prolactinei ºi ometabolizare acceleratã a testosteronului.Administrarea anticoncepþionalelor orale sauterapia de substituþie cu estrogeni creºte risculdezvoltãrii bolii la persoanele predispuse genetic,în timp ce administrarea de androgeni are efectbenefic asupra bolii.5

I. Subacute cutaneous lupus erythematosus

1. LUPUS ERYTHEMATOSUS - GENERAL

The term of “lupus erythematosus” (LE)refers to a spectrum of diseases that vary in theircourse and prognosis.1Lupus erythematosus is amultisystemic disease affecting primarily theskin, but may also cause severe multivisceraldisorders, with reserved prognosis.2 In terms ofgender distribution, there is a predominance ofthe disease in women (female/male ratio = 9/1).3

The cause of the disease is not fullyunderstood. The pathogenesis of cutaneouslupus erythematosusis interconnected with thatof systemic lupus erythematosus (SLE).3 Themost important etiopathogenic factors that areincriminated are: genetic, hormonalandenvironmental.

Genetic factors. Family forms of SLE occur in10% of patients.4 There are quoted multipleassociations with antigens of the majorhistocompatibility complex, most frequently withHLA B8, DRw52, DQw1, DQw2, DR2 and DR3.

Hormonal factors. They show the predom-inance of the disease in women. High levels ofestrogen metabolites, prolactin and acceleratedmetabolism of testosterone have been found.Administration of oral contraceptives or estrogenreplacement therapy increases the risk ofdeveloping the disease in genetically predis-posed persons, while administration ofandrogens has a beneficial effect on the disease.5

Environmental factors: ultraviolet rays(especially UVB, but also UVA), infections (viral

ale LE cât ºi ale LP. Majoritatea cazurilor apar la pacienþicu vârste cuprinse între 25-45 de ani, cu o uºoarãpredominanþã a sexului feminin.(29,30) Etiologia este înmare parte necunoscutã, dar existã în discuþie cauzeautoimune, virale, genetice ºi/sau medicamente care potinduce sindromul de suprapunere LE/LP precum:izoniazida, procainamida ºi acebutolol.(30) Prezentãmcazul unei paciente în vârstã de 54 de ani diagnosticatã cuLECS (2000), LP (2012) ºi HVC (2012). Aspectele clinice,opþiunile terapeutice ºi evoluþia sunt prezentate în articol.

Cuvinte cheie: lupus eritematos cutanat subacut,lichen plan, lichen plan oral, hepatitã cu virus C.

rare disorder combining the clinical, histological andimmunopathological features of both LE and LP. This is aninfrequently reported condition, the majority of casesoccurs between the ages of 25 to 45 with a slight femalepredominance. (29,30) The etiology is largely unknown,but its possibilities include an autoimmune, viral, and/orgenetic cause. Drugs that may induce LE/LP overlapsyndrome are isoniazide, procainamide, and acebutolol. (30)We present the case of a 54 years old female diagnosed withSCLE (2000), LP (2012) and HCV (2012). Clinical aspects,therapeutic choices and course are presented in the article.

Key words: subacute cutaneous lupus erythematosus,lichen planus, oral lichen planus, hepatitis C virus.

Intrat în redacþie: 10.10.2013Acceptat: 2.12.2013

Received: 10.10.2013Accepted: 2.12.2013

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Factori de mediu: razele ultraviolete (înspecial UVB, dar ºi UVA), infecþii (virale ºibacteriene), medicamente (hidralazinã, procaina-midã, izoniazidã, IECA, statine, IFN-α, D-penicilaminã, α-metildopa, terbinafine, etaner-cept ºi minociclina), fumatul (un studiu caz-control efectuat recent a raportat cã fumatorii auun risc mai mare de a dezvolta LES faþã denefumãtori sau foºti fumãtori).3

Conform clasificãrii lui Jim Gilliam, lupusuleritematos asociat cu leziuni cutanate se împarteîn: lupus eritematos cutanat acut, lupus eri-tematos cutanat subacut si lupus eritematoscronic cu variantele discoid, discoid verucos/hipertrofic, lupusul profund, lupus eritematos almucoasei, lupus tumidus ºi chilblains lupus.6

Lupusul eritematos poate afecta multiple organeºi sisteme, cel mai frecvent întâlnim afectareaarticulaþiilor, a tegumentului, hematologicã,pulmonarã, renalã ºi a sistemului nervos central.2

Asociaþia Americanã de Reumatologie (ARA)a propus un set de criterii clinice ºi de laboratorpentru diagnosticul lupusului eritematossistemic6: rash malar (eritem fix, macula-papulos,malar, respectã pliurile nazolabiale), rash discoid(plãci eritematoase cu scuame aderente ºi dopurifoliculare, cicatrici atrofice în leziunile vechi),fotosensibilitate (rash indus de luminã), ulceraþiiorale (ulceraþii orale sau nazofaringienenedureroase), artritã (artritã neerozivã, afectândcel puþin douã articulaþii), serozitã (pleuritã saupericarditã), afectare renalã (proteinuriepersistentã peste 0,5 g/zi sau cilindri celularihematici, granulari, tubulari, micºti), afectareneurologicã (convulsii sau psihozã), afectarehematologicã (anemie hemoliticã sau leucopenie<4000/µL sau limfopenie <1500/µL sautrombocitopenie <100000/µL), modificãri imuno-logice (anticorpi anti ADNdc sau anticorpi antiSm sau anticorpi antifosfolipide evidenþiaþi prin:nivel anormal anticorpi anticardiolipinã IgG sauIgM, test pozitiv anticoagulant lupic, test falspozitiv pentru lues cu duratã de cel puþin 6 luniconfirmat prin teste de referinþã), anticorpiantinucleari (titru anormal de anticorpi anti-nucleari în absenþa medicamentelor care potinduce sindromul ,,lupus-like“).7

and bacterial), drugs (hydralazine, procainamide,isoniazid, ACE inhibitors, statins, IFN-α, D-penicillamine, á-methyldopa, terbinafine,etanercept and minocycline), smoking (a recentcase-control study reported that smokers have ahigher risk of developing SLE compared to non-smokers or ex-smokers).3

According to Jim Gilliam’s classification,lupus erythematosus associated with skin lesionsis divided into: acute cutaneous lupuserythematosus, subacute cutaneous lupuserythematosus and chronic lupus erythematosuswith the following subtypes: discoid,verrucous/hypertrophic discoid, lupus profun-dus, lupus erythematosus of the mucousmembrane, lupus tumidus and chilblain lupus.6

Lupus erythematosus can affect multiple organsand systems, the most common being joint, skin,blood, lung, kidney and central nervous systemdisorders.2

The American Rheumatology Association(ARA) proposed a set of clinical and laboratorycriteria for diagnosing systemic lupuserythematosus6: malarrash (fixed, maculo-papular, malar erythema, sparing thenasolabialfolds), discoid rash (erythematous plaques withadherent scales and follicular plugging, atrophicscarring in old lesions), photosensitivity(light-induced rash), mouth ulcers (painless oral ornasopharyngeal ulcers), arthritis (nonerosivearthritis, affecting at least two joints), serositis(pleuritis or pericarditis), kidney disorder(persistent proteinuria over 0.5 g/day or hematic,granular, tubular, mixed cylinders), neurologicaldisorder (convulsions or psychosis), haema-tological disorder (haemolytic anaemia orleukopenia <4000/µL or lymphopenia < 1500/µLor thrombocytopenia < 100000/µL), immuno-logical modifications (anti-dsDNA antibodies oranti-Sm antibodies or antiphospholipid anti-bodies evidenced by: abnormal level of IgG orIgManticardiolipin antibodies, positive test forlupus anticoagulant, false positive test forsyphilis for at least 6 months confirmed byreference tests), antinuclear antibodies (ab-normal titre of antinuclear antibodies withoutmedication that can induce “lupus-like”syndrome).7

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2. LUPUSUL ERITEMATOS CUTANAT SUBACUT (LECS)

Definiþie:

LECS este o variantã a lupusului eritematos(LE) ce ocupã o poziþie intermediarã întrelupusul eritematos discoid (LED) ºi lupusuleritematos sistemic (LES). 1

Lupusul cutanat subacut implicã, în primulrând, epidermul ºi dermul superior ºi este asociatcu anticorpi anti-Ro/SSA, artralgii ºifotosensibilitate. Majoritatea pacienþilor nu auafectare sistemicã semnificativã.2

Epidemiologie:

LECS este mai puþin comun decât LED sauLES. Se caracterizeazã printr-o predominanþã asexului feminin, iar vârsta de debut este, deobicei, între 30-40 de ani. Boala poate debuta ºidupa decada a VI-a de viaþã, în special când esteindusã medicamentos.

Aspecte clinice:

LECS se caracterizeazã , iniþial, prin maculeºi/sau papule eritematoase transformându-seapoi în leziuni papulo-scuamoase psoriaziformesau plãci inelare/policiclice. O parte din pacienþipot dezvolta elemente ale ambelor variantemorfologice. Leziunile în LECS apar, pre-dominant, la nivelul zonelor expuse la soare (ex.partea superioarã a toracelui posterior, umeri,braþe, V-ul decolteului ºi, mai putin comun, faþa).Acestea se vindecã, de obicei, cu hipopigmentãrisau depigmentãri reziduale, fãrã cicatrici ºi fãrãhiperkeratozã folicularã (principalele trãsãturicare îl deosebesc de lupusul eritematos cutanatcronic). Leziunile nu sunt indurate deoarece se caracterizeazãprintr-un infiltrat inflamator superficial ºi rar.

Histopatologie:

Modificãrile sunt mai puþin pronunþate decâtîn LED. La nivelul epidermului se poate observaatrofie minimã ºi modificãri vacuolare, iar lanivelul dermului se remarcã un infiltratinflamator limfocitar rar.

Teste de laborator:

Anticorpii anti-Ro, caracteristici acestei formede lupus, sunt prezenþi într-o proporþie de 60%-

2. SUBACUTE CUTANEOUS LUPUS ERYTHEMATOSUS (SCLE)

Definition:

SCLE is an intermediary form of lupuserythematosus (LE) between discoid lupuserythematosus (DLE) and systemic lupuserythematosus (SLE).1

Subacute cutaneous lupus involves primarilythe epidermis and the upper dermis and isassociated with anti-Ro/SSA antibodies,arthralgia and photosensitivity. Most patients donot present significant systemic disorders.2

Epidemiology:

SCLE is less common than DLE or SLE. It ispredominant in females, and the onset ageusually ranges from 30 to 40 years. The diseasecan also appear after the age of 60, especiallymedication-induced.

Clinical aspects:

SCLE is initially characterised by erythe-matosus patches and/or papules that turn topsoriasi form papulosquamous lesions orannular/polycyclic plaques. Some patients candevelop elements of both morphological forms.SCLE lesions occur mainly on sun-exposed areas(e.g. upper part of posterior thorax, shoulders,arms, V neckline and, less common, on the face).They usually heal with residual hypo-pigmentation or depigmentation, withoutscarring and without follicular hyperkeratosis(main characteristics distinguishing it fromchronic cutaneous lupus erythematosus). Lesionsare not indurated as they are characterised bysuperficial and rare inflammatory infiltrate.

Histopathology:

Modifications are less evident than in DLE.The epidermis shows minimal atrophy andvacuolar modifications and the dermis showsrare lymphocytic inflammatory infiltrate.

Laboratory tests:

Anti-Ro antibodies, which are characteristic forthis form of lupus, are present at a rate of 60%-90%.Antinuclear antibodies (ANA) are positive in 60%-80% of patients, in 40% of patients anti-

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90%. Anticorpii antinucleari (ANA) sunt pozitivila 60%-80% dintre pacienþi, la un procent de 40%dintre pacienþi pot sã aparã anticorpi anti-La ºianticorpi anti-ADNdc (de obicei în titru foartemic). Factorul reumatoid este prezent la 20%dintre pacienþi. Cei cu boalã activã pot prezentasemne ale inflamaþiei (protein C reactivã,creºterea vitezei de sedimentare a hematiilor,hipergamaglobulinemie). De asemenea, se poateobserva pe hemoleucogramã: anemie, leucopenieºi trombocitopenie.1

Evoluþie ºi prognostic:

Evoluþia bolii nu este foarte clarã, se pare cã10-15% dintre pacienþi dezvoltã afectaresistemicã.8

Se ºtie cã ac. anti-Ro apar ºi în sindromulSjögren, motiv pentru care unii pacienþi cu LECSpot prezenta caracteristici ale ambelor boli, bamai mult unii pot avea manifestãri interneserioase ale sindromului Sjögren precum afectarepulmonarã ºi neurologicã.9

Pe lângã sindromul Sjögren, LECS se poatesuprapune ºi cu alte boli autoimune precum:artrita reumatoidã ºi tiroidita Hashimoto. Existãcâteva date în literaturã care vorbesc despre oasociere între LECS ºi diferite malignitãþi(neoplasme mamare, pulmonare, gastrice,uterine, hepatocelulare sau limfomHodgkin).10

Diagnostic diferenþial:

Psoriazis-ul, tinea corporis ºi dermatitaseboreicã sunt frecvent confundate cu lupusuleritematos cutanat subacut. De asemenea, se maipoate face diagnostic diferenþial cu dermato-miozita ºi cu toate formele de fotosensibilitate.

Tratament:

Rãspunsul la tratamentul cu antimalarice estemai puþin pozitiv decât în LED. 11 De obicei,corticosteroizii sunt mai eficienþi, în special cândexistã ºi afectare sistemicã. De ajutor este ºicombinaþia de antimalarice cu corticosteroizi. Înformele severe, de tranziþie cãtre LES sunt utile:azatioprina, metotrexatul ºi ciclofosfamida. Camedicaþie topicã se folosesc corticosteroizii ºiinhibitorii de calcineurinã în asociere cu cremeecran solar cu protecþie pentru UVB ºi UVA.

Laantibodies and anti-dsDNA antibodies canappear (usually a very small titre). The rheumatoidfactor is present in 20% of patients. Persons withactive disease may present signs of inflammation(C-reactive protein, increased erythrocytesedimentation rate, hypergammaglobulinemia).Complete blood count may also show: anaemia,leukopenia and thrombocytopenia.1

Evolution and prognosis:

The evolution of the disease is not very clear,it appears that 10-15% of patients developsystemic involvement.8

It is known that anti-Ro antibodies appear inthe Sjögren’s syndrome, which is why somepatients suffering from SCLE can presentcharacteristics of both diseases, moreover, somecan show severe internal manifestations ofSjögren’s syndrome, such as pulmonary andneurological disorders.9

Apart from Sjögren’s syndrome, SCLE canoverlap other autoimmune diseases, such as:rheumatoid arthritis and Hashimoto’sthyroiditis. There are some literature datamentioning an association between SCLE andvarious malignancies (breast, lung, stomach,uterine, liver cancer or Hodgkin’s lymphoma).10

Differential diagnosis:

Psoriasis, tineacorporis and seborrheic der-matitis are frequently mistaken for subacutecutaneous lupus erythematosus. A differentialdiagnosis with dermatomyositis and all forms ofphotosensitivity can also be performed.

Treatment:

The reaction to the treatment with anti-malarial medication is less positive than inDLE.11Usually corticosteroids are more effective,especially when there is a systemic disorder. Thecombination of antimalarial medication withcorticosteroids is beneficial. In severe forms oftransition to SLE the following are useful:azathioprine, methotrexate and cyclophos-phamide. As topical medication, corticosteroidsand calcineurin inhibitors are used incombination with UVB and UVA sunscreens.

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II. Asociere lichen plan-hepatita C

1. LICHENUL PLAN (LP)

Termenul de lichen plan a fost introduspentru prima datã de Erasmus Wilson în 1869pentru a descrie afecþiuni denumite anterior deHebra „leichen ruber“.12 LP este o boalãidiopaticã inflamatorie a pielii, pãrului, unghiilorºi mucoaselor ce afecteazã, în general, adulþii devârstã medie. Etiologia ºi patogeneza nu suntcunoscute pe deplin, LP a fost asociat cu infecþiivirale, boli autoimune, medicamente, vaccinuri,materiale dentare. 13 Existã mai multe formeclinice de LP: inelarã/rotundã, buloasã,hipertroficã, inverstã, liniarã, ulcerativã,vulvovaginalã-gingivalã, indusã medicamentosºi folicularã.12

Lichenul plan se caracterizeazã prin apariþiaunor papule plate, unele ombilicate, mici,violacee, formã poligonalã, pruriginoase, cusuprafaþã uºor lucioasã sau transparentã, cu oreþea formatã din linii albe „striurile Wickham“,papulele pot conflua într-o placã mare. Pringrataj pot fi induse noi leziuni, dispuse liniar-fenomenul Koebner. Vindecarea se face cuhiperpigmentãri reziduale, care pot persista lunisau ani. Localizãrile predilecte sunt: zonaflexoare a antebraþelor ºi a încheieturii mâinii,faþa dorsalã a mâinilor, regiunea anterioarã agambelor, gât ºi aria presacratã. Leziunilecutanate din LP afecteazã aproximativ 1% dinpopulaþia adultã, iar leziunile orale se regãsesc la1-4% din populaþie.12 Nu existã o predispoziþie înfuncþie de rasã sau sex.

Boala are în general o evoluþie autolimitatã.Lichenul plan oral este mai recalcitrant decât celcutanat. La 15-20% dintre pacienþi remisiuneainiþialã a bolii este urmatã de recurenþe, maifrecvente în cazul lichenului plan familial.12

Histologic, leziunile din LP, se caracterizeazãprin prezenþa unui infiltrat limfocitar în bandã,dens la nivelul unui epiderm acantotic, cudistrugerea stratului de celule bazale ºihipergranulozã.

Tratamentul LP constã în aplicarea localã decorticosteroizi cu potenþã mare (+/- ocluziv) saucorticosteroizi intralezional, tacrolimus, pimecro-limus, PUVA. Tratamentul sistemic estereprezentat de medicamente de prima linieprecum: corticosteroizi (30-80 mg/zi), etretinate(10-75 mg/zi), acitretin (30 mg/zi), isotretinoin

II. Association of lichen planus and hepatitis C

1. LICHEN PLANUS(LP)

The term of lichen planus was firstintroduced by Erasmus Wilson in 1869 todescribe disorders previously referred to as“leichenruber”by Hebra.12LP is an idiopathicinflammatory disease of the skin, hair, nails andmucous membranes mainly affecting middle-aged persons.The etiology and pathogenesis arenot fully known, and LP has been associated withviral infections, autoimmune diseases, drugs,vaccines, dental materials.13 There are severalclinical forms of LP: annular/round, bullous,hypertrophic, inversus, linear, ulcerative,vulvovaginal-gingival, drug-induced andfollicular.12

Lichen planus is characterised by theappearance of flat-topped, some umbilicated,small, purple, polygonal, pruritic papules, withslightly shiny or transparent surface, with anetwork of white lines called the “Wick-hamstriae”; papules can unite into a large plaque.Scratching may induce new lesions, in a linearshape-Koebner phenomenon. Healing results inresidual hyperpigmentations which may persistfor months or years. Usual sites of occurrence:flexor area of the forearms and wrists, dorsal areaof the hands, the shins, the neck and presacralarea. Skin lesions in LP affect approximately 1%of the adult population, and oral lesions arefound in 1-4% of the population.12 There is nopredisposition according to race or gender.

The disease generally has a self-limitedevolution. Oral lichen planus is more resilientthan the cutaneous one. In 15-20% of patients,initial remission of the disease is followed byrelapses, more frequent in the case of familylichen planus.12

In terms of histology, LP lesions arecharacterised by the presence of a thick band-likelymphocytic infiltrate, anacanthotic epidermis,with destruction of the basal cell layer andhypergranulosis.

LP treatment consists in topical application ofhigh potency corticosteroids (+/- occlusive) orintralesional corticosteroids, tacrolimus, pime-crolimus, PUVA. Systemic treatment is representedby the first-line therapy, such as: corticosteroids (30-80 mg/day), etretinate (10-75 mg/day), acitretin(30 mg/day), isotretinoin (20-40 mg/day) and thesecond-line therapy, such as: cyclosporine (3-10

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(20-40 mg/zi) ºi medicamente de linia a II-aprecum: ciclosporinã (3-10 mg/kg/zi), dapsonã(200 mg/zi), hidroxiclorochinã (200-400 mg/zi).14

2. HEPATITA C

Virusul hepatitei C (VHC) este un virus ARNºi reprezintã principala cauzã a bolilor hepaticecronice, a cirozei ºi a carcinomului hepatocelular,dar ºi indicaþie pentru transplantul de ficat.

Virusul hepatitei C a fost prima datãrecunoscut ca o cauzã a hepatitei în anul 1975.

În 1999 World Health Organization araportat 169,7 milioane de cazuri de hepatitã cuvirus C in lume.15

Cãile de transmitere sunt reprezentate deexpunere parenteralã la material infectat printransfuzii de sânge sau injecþii cu ace nesterile,comportamentul sexual, perinatal, tatuaje.16

VHC nu este citopatic, dar rãspunsul imun algazdei în incercarea de a combate virusulreprezintã cauza leziunilor hepatice ca urmare aunei inflamaþii de lungã duratã.17 Cei mai mulþipacienþi cu infecþie acutã ºi cronicã suntasimptomatici. Infecþia cronicã se dezvoltã în 43-86% din cazuri.18 Pacienþii ºi medicii pot sã nudetecteze nicio manifestare a condiþiei pentruperioade lungi de timp, însã infecþia hepaticãcronicã ºi hepatita activã cronicã sunt boli lentprogresive ce determinã morbiditate severã.

Trecerea de la hepatitã acutã la cirozã este, decele mai multe ori, asimptomaticã, se produceîntr-o perioadã de timp cuprinsã între 20-40 deani, la aproximativ 5-25% dintre pacienþiiinfectaþi cu VHC.

Evoluþia cãtre cirozã este produsã de fibrozahepaticã progresivã, aceasta reprezentând unfactor de prognostic principal în evoluþia bolii.Pacienþii cu transaminaze crescute ºi activitatenecro-inflamatorie la biopsia hepaticã sunt multmai susceptibili sã dezvolte fibrozã. Progresiafibrozei este mai rapidã la bãrbaþi ºi la Afro-Americani, precum ºi în cazul celor cu diabet,consumatorilor de alcool, celor cu hepatitã B sauHIV. 19 Carcinomul hepatocelular apare la 1-4%dintre pacienþii cu hepatitã C.

Dezvoltarea infecþiei cronice nu estesemnalatã de dezvoltarea simptomelor. Aproxi-mativ 40-74% dintre pacienþii cu VHC dezvoltãcel puþin o manifestare extrahepaticã. (Tabel I)

mg/kg/day), dapsone (200 mg/day), hydroxy-chloroquine (200-400 mg/day).14

2. HEPATITIS C

Hepatitis Cvirus (HCV)is a RNA virus andrepresents the main cause of chronic liverdiseases, cirrhosis and hepatocellular carcinoma,but also an indication for liver transplant.

Hepatitis C virus was first recognised ascause for hepatitis in 1975.

In 1999, the World Health Organizationreported a number of 169.7 million cases ofhepatitis C worldwide.15

The disease is transmitted by parenteralexposure to infected material through bloodtransfusions or infections with non-sterileneedles, sexual behaviour, perinatal, tattoos.16

HCV is not cytopathic, but the immune responseof the patient in an attempt to fight the virusrepresents the cause of hepatic lesions followinglong-term inflammation.17Most patients withacute and chronic infection are asymptomatic.Chronic infection develops in 43-86% of cases.18

Patients and doctors may not detect anymanifestation of the condition for long periods oftime, however chronic hepatic infection andchronic active hepatitis are slowly progressingdiseases that cause severe morbidity.

The transition from acute hepatitis tocirrhosis is most often asymptomatic and takesfrom 20 to 40 years, in approximately 5-25% ofthe patients infected with HCV.

The evolution to cirrhosis is caused byprogressive hepatic fibrosis, representing a mainprognosis factor in the evolution of the disease.Patients with elevated transaminases andnecroinflammatory activity on liver biopsy aremore likely to develop fibrosis. Progression offibrosis is faster in males and Afro-Americans, aswell as in the case of diabetics, alcohol users,persons infected with hepatitis B or HIV.19

Hepatocellularcarcinoma occurs in 1-4% ofpatients with hepatitis C.

The development of chronic infection is notsignalled by development of symptoms.Approximately 40-74% of patients with HCVdevelop at least one extrahepatic manifestation.(Table I).

The diagnosis of hepatitis C is based on thepresence of serum antibodies (anti-HCV).

Diagnosticul hepatitei cu virus C se bazeazãpe prezenþa anticorpilor serici (anti-VHC).Detectarea anticorpilor anti-HCV nu permite însãdiferenþierea infecþiei acute/cronice de o infecþieîn antecedente; pentru aceasta se utilizeazãdeterminarea HCV-ARN. În infecþia recentãHVC, HCV-RNA se detecteazã de obicei, lapuþine sãptãmâni de la invazia viralã (primulmarker serologic al infecþiei HVC) ºi precede cusãptãmâni, luni, seroconversia imunologicã (apa-riþia anti-VHC).

În remisiunea spontanã a infecþiei HCVrecente (acutã), HCV-RNA se negativeazã deobicei, dupa 4-6 luni. Infecþia cronicã HCV seconsiderã prezentã dacã HVC-RNA rãmânedetectabil pentru o perioadã de cel putin 12 luni.Concentraþia HCV-RNA fluctueazã pe parcursulevoluþiei infecþiei cronice; temporar, concentraþiapoate scãdea sub nivelul de detecþie. De aceea, unrezultat negativ HCV-RNA nu exclude prezenþainfecþiei cronice sau a infectivitãþii serului. Numaidacã detectarea HCV-RNA rãmâne negativã la 3determinãri consecutive, la interval de 1 an, sepoate presupune vindecarea infecþiei HCV.

Detectarea HVC-RNA este esenþialã nunumai în diagnosticul infecþiei acute sau croniceHCV, dar ºi în stabilirea indicaþiei de tratament cuinterferon a hepatitei cronice HVC ºi înmonitorizarea rãspunsului la tratament. 20

However, detection of anti-HCV antibodies doesnot allow for differentiation of acute/chronicinfection in the history,for which HCV-RNAdetermination is used. In cases of recent infectionwith HVC, HCV-RNA is usually detected in a fewweeks after viral invasion (the first serologicmarker of HVC infection) and precedesimmunological seroconversion (occurrence ofanti-HCV)by weeks or months.

In spontaneous remission of recent (acute)HCV infection, HCV-RNA usually becomesnegative after 4-6 months. Chronic HCV infectionis considered present if HVC-RNA remainsdetectable for at least 12 months. HCV-RNAconcentration fluctuates during the evolution ofchronic infection; the concentration cantemporarily drop below the detection level.Therefore, a negative HCV-RNA result does notexclude the presence of chronic infection orserum infectivity. Only when HCV-RNAdetection remains negative in 3 consecutivedeterminations, at 1-year intervals, it may beassumed that HCV infection is healed.

HVC-RNA detection is essential not only indiagnosing acute or chronic HCV infection, butalso in establishing the treatment with interferonof chronic HVC hepatitis and in monitoring theresponse to treatment.20

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Tabel I. Manifestãrile extrahepatice ale hepatitei cu virus C

Crioglobulinemie Limfom malign

Glomerulonefritã membranoproliferativã Artritã reumatoidã cronicã

Porphyria cutanea tarda Tiroiditã cronicã

Lichen plan Diabet zaharat

Sindrom Sjögren Pneumonie interstiþialã

Miozitã Cancer oral

Miocardiopatie Ulcer cornean Mooren

Table I. Extrahepatic manifestations of hepatitis C virus

Cryoglobulinemia Malignant lymphoma

Glomerulonephritis membranoproliferative Chronic rheumatoid arthritis

Porphyria cutanea tarda Chronic thyroiditis

Lichen planus Diabetes

Sjögren’s syndrome Interstitial pneumonia

Myositis Oral cancer

Cardiomyopathy Mooren corneal ulcer

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3. ASOCIEREA LICHEN PLAN-HEPATITA C

Primul raport ce indicã o asociere între bolilehepatice cronice ºi lichenul plan a fost publicat în1978.21 Dupã identificarea genomului VHC în1989, mai multe studii au raportat coexistenþaîntre hepatita cronicã cu virus C ºi lichenul plan,în special cu lichenul plan oral, având oprevalenþã cuprinsã între 1-4% în populaþiageneralã.22 Cu toate acestea, relaþia dintrehepatita cu virus C ºi lichenul plan rãmâne unsubiect controversat. Utilizând cuvintele cheiehepatitã ºi lichen plan într-o cãutarecomputerizatã în baza de date MEDLINE, au fostgãsite 263 de citate din 1966 pânã în 2003.23 De laprimul raport pe aceastã temã, mai mult de 80 delucrãri din întreaga lume au sugerat o asociereîntre lichenul plan ºi VHC.

Deºi nu este clar cum VHC afecteazã sistemulimunitar al gazdei ce va dezvolta LP se considerã,totuºi, cã acesta joacã un rol important îndezvoltarea LP la pacienþii purtãtori de virushepatic C.24 Deoarece diagnosticarea infecþiei cuVHC în stadii incipiente este importantã, apariþiaLP poate avea un rol esenþial în acest sens, avândîn vedere cã pielea ºi cavitatea oralã sunt maiuºor de observat.

Prezenþa LP cutanat ºi a LP oral poate fiutilizatã ca marker al infecþiei cu VHC la pacienþiiasimptomatici, ceea ce poate duce la undiagnostic corect, un tratament precoce ºi, even-tual, un prognostic mai bun al infecþiei cu VHC.

III. Prezentare caz clinic

Prezentãm cazul unei paciente D.C., în vârstãde 54 de ani, fumãtoare, pensionarã, normopon-deralã (IMC=20,36 kg/m2), cu un istoric familialde accident vascular cerebral ischemic ºi unistoric medical de histerectomie (1995). Aceasta afost diagnosticatã cu lupus eritematos cutanatsubacut (2000), lichen plan cutanat (2012) confir-mat histopatologic ºi hepatitã cu virus C (2012).

Boala lupicã a debutat cu fatigabilitate,artralgii, fotosensibilitate ºi cu o erupþiediseminatã la nivelul feþei, toracelui anterior (V-ul decolteului) ºi toracelui posterior, distribuitãsimetric, polimorfã, pruriginoasã, alcãtuitã dinmacule ºi papule eritemato-scuamoase, cudimensiuni variabile, intensificatã semnificativ laexpunerea la soare, cu evoluþie de 1 an.(Fig. 1)

3. ASSOCIATION OF LICHEN PLANUS AND HEPATITIS C

The first report indicating an associationbetween chronic hepatic diseases and lichenplanus was published in 1978.21After identifyingthe HCVgenome in 1989, several studies reportedthe coexistence of chronic hepatitis C and lichenplanus, especially oral lichen planus, with aprevalence ranging from 1 to 4% of the overallpopulation.22However, the relation betweenhepatitis C and lichen planus remains a contro-versial subject. Using the keywords hepatitis andlichen planus in a computer search in theMEDLINE database, 263 quotes were found from1966 to 2003.23 Since the first report on the matter,more than 80 papers worldwide suggest anassociation between lichen planus and HCV.

Although it is not clear how HCV affects theimmune system of the patient who develops LP,itis however assumed that it plays an importantpart in developing LP in patients with hepatitis Cvirus.24Since diagnosing HCV infection in theearly stages is important, occurrence of LP mayhave an essential role in this regard, given thatthe skin and the mouth are easier to observe.

The presence of cutaneous LP and oral LP canbe used as marker of HCVinfection inasymptomatic patients, which may lead toaccurate diagnosis, early treatment and, possibly,a better prognosis of HCV infection.

III. Presentation of clinical case

We present the case of a patient D.C., aged 54,smoker, retired, with a normal weight (BMI=20.36 kg/m2), with a family history of ischemicstroke and a medical history of hysterectomy(1995). She was diagnosed with subacutecutaneous lupus erythematosus (2000), cutaneouslichen planus (2012), histopathologically con-firmed, and hepatitis C (2012).

Lupus started with fatigue, arthralgia,photosensitivity and a disseminated rash on theface, anterior thorax (V neckline) and posteriorthorax, symmetrically distributed, polymorphic,pruritic, consisting of erythematous-squamousmacules and papules of various sizes, signifi-cantly intensified by sun exposure, with 1-yearevolution. (Picture 1)

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În tot acest timp, pacienta a urmat tratamentesistemice cu corticoizi (Prednison, Medrol) ºiantimalarice de sintezã (Plaquenil), iar local cudermatocorticoizi cu potenþã micã ºi medie ºifolosirea cremelor ecran solar cu factor deprotecþie 50+. Sub tratament evoluþia a fostfavorabilã, remarcându-se ameliorarea pânã ladispariþia leziunilor cutanate, iar testeleimunologice s-au menþinut relativ constante întoþi aceºti ani. Dintre criteriile ARA, pacientaprezintã: fotosensibilitate, artritã, afectare hema-tologicã ºi ANA pozitivi.

În anul 2012 s-a observat apariþia unei erupþiidiseminate la nivelul gâtului, decolteului, feþei,trunchiului, antebraþelor bilateral, monomorfã,intens pruriginoasã, alcãtuitã din papule discretviolacee, unele solitare, altele cu tendinþã laconfluare, formã poligonalã, dimensiuni varia-bile, margini regulate, suprafaþã lucioasã cu oreþea formatã din linii albe ,,striurile Wickham“,cu evoluþie de 6 luni. (Fig. 2) Erupþia a debutat înlunile de varã, în urma unui stres emoþionalmajor negativ, pe fondul întreruperii bruºte aterapiei cortizonice ºi antimalarice, urmatã deexpunere solarã. Terapia fusese instituitã în urmãcu peste 2 luni.

Sub anestezie localã cu xilinã 2%, s-a practicatpunch biopsia unei leziuni localizate la nivelul

During this time the patient was undersystemic therapy with corticoids (Prednison,Medrol) and synthetic antimalarials(Plaquenil),and topical treatment with dermatocorticoids oflow and medium potency, as well as the use ofsunscreen with SPF 50+.Under treatment, theevolution was favourable, with improvement tothe disappearance of the skin lesions, theimmunological tests remaining relativelyconstant over the years. From among ARAcriteria, the patient showed: photosensitivity,arthritis, haematological disorder and positiveANA.

In 2012, a disseminated eruption occurred onthe neck, V neckline, face, thorax, both forearms,monomorphic, highly pruritic, consisting ofslightly purple papules, some isolated, otherstending to fuse, of polygonal shape and variablesizes, with regular edges, shiny surface, with anetwork of white lines - the “Wickhamstriae” andwith an evolution of 6 months. (Picture 2) Theeruption started in the summer, after a majornegative emotional stress, and on a backgroundof the sudden interruption of corticoid andantimalarial therapy, followed by sun exposure.The therapy had been started 2 months before.

Under local anaesthesia with lidocaine 2%, alesion on the right forearm was punch biopsied,

Fig. 1. Macule eritemato-scuamoase la nivelul toraceluianterior (V-ul decolteului)

Fig. 1. Squamos erythemato macules to the anterior thoraxV neckline

Fig. 2. Lichen plan cutanat antebraþ stângFig. 2. Lichen planus cutaneous left forearms

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antebraþului drept, urmatã de suturã cu fireneresorbabile ºi pansament steril. Piesa excizatã afost trimisã în serviciul de Anatomo-Patologie, învederea efectuãrii examenului histopatologic, iaraspectul histopatologic a fost compatibil cudiagnosticul de lichen plan.

Pentru aceastã afecþiune dermatologicã,pacienta a primit tratament local cu corticoizi cupotenþã medie ºi mare, iar sistemic cu anti-histaminice. În timp pruritul s-a amelioratsemnificativ, iar leziunile cutanate au dispãrut înaproximativ un an de la debut.

Este demn de reþinut cã pacienta a prezentatvalori anormal de mari ale transaminazelor chiarde la prima prezentare în clinica noastrã, în 2000,dar investigaþiile repetate pentru depistareamarkerilor hepatitelor virale au fost negative. S-astabilit diagnosticul de colecistopatie în urmainvestigaþiilor medicale, fapt care ar fi explicatparþial, în opinia noastra, valorile de douã ori maimari ale transaminazelor faþã de intervalulnormal, valori care au variat foarte puþin peparcursul a peste 10 luni de urmãrire a pacientei.Aceasta prezenta relativ frecvent vãrsãturi,senzaþie de greaþã, durere sub rebordul costaldrept, crize care se repetau la intervale deaproximativ 4-6 luni. Pacienta nu era consu-matoare de alcool.

În urma diagnosticului de lichen plan, s-adecis repetarea unor investigaþii: markerilorhepatici virali (antigenul HBs ºi anticorpii anti-HCV). Se depisteazã acticorpii anti–HCVpozitivi. Ulterior, pacienta a fost îndrumatã într-un serviciu de Boli Infecþioase, unde a primittratament cu Interferon si Ribavirinã timp de 1an, fiind în continuare dispensarizatã.

Testele de laborator efectuate includ: hemo-grama fãrã modificãri majore (uºoarã leocopenie,limfopenie ºi trombocitopenie), creºtereatransaminazelor ºi a colesterolului. Testeleimunologice au decelat: anticorpi anti ADNdcnegativi, anticorpi antinucleari pozitivi, anticorpianti Ro negativi, anticorpi anti Sm negativi, celulelupice absente, prezenþa corpilor în rozetã,complexe imune circulante negative, comple-ment seric fracþiunea C3 în limite normale.

Examenul histopatologic a evidenþiat carac-teristicile principale ale lichenului plan: fragmentde tegument cu moderatã hiperortokeratozã ºihipergranulozã; atrofie epidermalã cu ºtergereareliefului dermului papilar; marcat infiltrat

followed by suturing with non-absorbablesutures and sterile dressing. The excised piecewas sent to Anatomopathology for histopatho-logical testing, and the histopathological aspectwas compatible to the diagnosis of lichen planus.

For this dermatological disorder, the patientreceived topical treatment with medium and highpotency corticoids and systemic treatment withantihistamines. In time the pruritus improvedsignificantly and the skin lesions disappearedapproximately one year after onset.

It is worth mentioning that the patientpresented abnormally high transaminases fromthe very first presentation to our clinic in 2000,butrepeated investigations to detect viral hepatitismarkers were negative. Medical investigationsled to the diagnosis of cholecystopathy, which, inour opinion, partially explained the twice as hightransaminases compared to the normal values,which showed little variations over more than 10months of patient follow-up. She presentedrelatively frequent vomiting, nausea, pain underthe right costal margin, crises that occurredrepeatedly at 4 to 6-month intervals. The patientwas not an alcohol drinker.

After being diagnosed with lichen planus, itwas decided to repeat certain investigations ofthe viral hepatic markers (HBsantigen and anti-HCV antibodies). Anti–HCV antibodies werefound positive. After that, the patient was sent tothe department of Infectious Diseases, where shereceived treatment with Interferon and Ribavirinfor 1 year, and remained under dispensaryobservation.

Laboratory tests included: complete bloodcount without major modifications (slightleukopenia, lymphopenia and thrombocy-topenia), increased levels of transaminases andcholesterol Immunological tests detected:negative dsDNA antibodies, positive antinuclearantibodies, negative antiRo antibodies, negativeanti-Sm antibodies, absent lupus cells, presenceof ring forms, negative circulating immunecomplexes, normal C3 fraction of complement.

Histopathological tests showed the maincharacteristics of lichen planus: skin fragmentwith moderate hyperorthokeratosis and hyperg-ranulosis; epidermal atrophy with loss of reteridges of papillary dermis; marked lymphocyticinflammatory infiltrate with melanophages in the

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inflamator limfocitar cu melanofage la niveluldermului subiacent, cu interesarea joncþiuniidermo-epidermice (dispoziþie „în bandã“);frecvenþi corpi Civatte predominant în epidermulinferior ºi în infiltratul inflamator.

IV. Discuþii ºi concluzii

Infecþia cu virus C nu reprezintã doar o cauzãfrecventã de boalã hepaticã cronicã precum:hepatitã, cirozã sau carcinom hepatocelular, dareste implicatã ºi în patogeneza unor boliautoimune (ex. lichen plan). Deºi nu este clar cumVHC afecteazã sistemul imunitar al gazdei ce vadezvolta LP se considerã, totuºi, cã acesta joacãun rol important în dezvoltarea LP la pacienþiipurtãtori de virus hepatic C.24

Boli precum: lichenul plan, prurigo nodu-laris, sindrom Sjögren, psoriazis, urticaria ºilimfomul cu celule B sunt frecvent întâlnite înrândul pacienþilor cu hepatitã C.25

Datele din literaturã ce aratã o legãturã întreVHC ºi lichenul plan sunt inconstante; în timp ceunele studii indicã o relaþie între aceste douã boli,altele o neagã.26 De asemenea, existã date ce aratãcã localizarea oralã a lichenului plan este maifrecvent asociatã cu hepatita C.27

Deoarece tratamentul cu antimalarice poatela unii pacienti sã inducã o erupþie lichenoidã,mai ales în condiþiile expunerii la soare, a fostimportantã efectuarea unei biopsii cutanatepentru tranºarea diagnosticului. În momentuldeclanºãrii erupþiei lichenoide/lichen plan,pacienta era sub tratament cu antimalarice.

Pentru tratamentul bolilor autoimune suntnecesari glucocorticoizi sau imunosupresoareadministrate pe cale sistemicã, însã acesttratament înrãutãþeºte evoluþia hepatitei C, motivpentru care este importantã introducereaagenþilor antivirali.

Formele de lupus eritematos ce prezintãclinic leziuni specifice de LED si LESA suntconsiderate variante mai blânde de boalã, cuevoluþie ºi prognostic în general bune. LESAevolueazã cel mai adesea cu remisiuni sirecurenþe. Aproximativ 50% dintre pacienþiîndeplinesc criteriile ARA de LES, dar în generalau un prognostic mai bun pe termen lung.28

În literaturã existã citate ºi câteva cazuri delupus eritematos (LE) suprapus cu lichenul plancutanat (LP). Aceasta este o afecþiune raportatã

underlying dermis, with involvement of thedermoepidermal junction (“band-like” distribu-tion); frequent Civatte bodies in the lowerepidermis and in the inflammatory infiltrate.

IV. Discussions and conclusions

C virus infection is not only a common cause ofchronic hepatic disease, such as: hepatitis, cirrhosisor hepatocellular carcinoma, but it is also involvedin the pathogenesis of certain autoimmune diseases(e.g.lichen planus). Although it is not clear howHCV affects the immune system of the patient whodevelops LP,it is however assumed that it plays animportant part in developing LP in patients withhepatitis C virus.24

Diseases such as lichen planus, prurigon-odularis, Sjögren’s syndrome, psoriasis, urticariaand B cell lymphoma are common in patientswith hepatitis C.25

Literature data showing a connectionbetween HCV and lichen planus are inconsistent;while some studies show a connection betweenthese two diseases, others deny it.26 Also, thereare data showing that oral lichen planus is morecommonly associated with hepatitis C.27

Since antimalarial treatment may inducelichenoid eruption in some patients, especiallywhen exposed to the sun, it was essential toperform a skin biopsy to establish the diagnosis.Upon onset of lichenoid eruption/lichen planus,the patient was under antimalarial treatment.

Autoimmune diseases require treatment withglucocorticoids or immunosuppressive medica-tion with systemic administration; however, thistreatment worsens the evolution of hepatitis C,which is why it is important to introduceantiviral agents.

The forms of lupus erythematosus presentingspecific clinical lesions of DLE and SCLE areconsidered milder forms of the disease, with agenerally good evolution and prognosis. SCLEusually evolves with remissions and relapses.Approximately 50% of patients fulfil the ARAcriteria of SLE, but generally have a betterprognosis in the long run.28

The literature also quotes several cases ofoverlapped lupus erythematosus (LE) andcutaneous lichen planus (LP). It is a rarelyreported disorder, such as only a subset ofpublished cases presented histological

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rar, în care numai un subset de cazuri publicateau prezentat caracteristici histologice ale ambelorboli.29 Majoritatea cazurilor apar la pacienþi cuvârste cuprinse între 25-45 de ani, cu o uºoarãpredominanþã a sexului feminin. Leziunilecutanate afecteazã în principal braþele, membreleinferioare, faþa ºi trunchiul. Implicarea palmo-plantarã este consideratã caracteristicã în cazulacestui sindrom de suprapunere.30 Etiologia esteîn mare parte necunoscutã, dar existã în discuþiecauze autoimune, virale, genetice ºi/saumedicamente care pot induce sindromul desuprapunere LE/LP precum: izoniazida, pro-cainamida ºi acebutolol.30

characteristics of both diseases.29 Most casesoccur in patients aged 25-45, with a slight pre-dominance in females.Skin lesions mainly affectthe arms, legs, face and torso. Palmoplantarinvolvement is considered characteristic in thecase of this overlap syndrome.30 Etiology islargely unknown, but may include autoimmune,viral and genetic causes,and/or medication thatcan induce the LE/LP overlap syndrome, such as:isoniazid, procainamideand acebutolol.30

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Conflict de interese Conflict of interestNEDECLARATE NONE DECLARED

Adresa de corespondenþã: Dr. Ana Mihaela UngureanuEmail: [email protected]

Correspondance address: Dr. Ana Mihaela UngureanuEmail: [email protected]


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