morfeea generalizatÃ generalized morphea filemase plastice), ca tehnician în prelucrarea...

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MORFEEA GENERALIZATÃ

GENERALIZED MORPHEA

DACIANA ELENA BRÃNIªTEANU*, ELENA CIUBOTARIU **, DOINIÞA OLINICI**, CÃTÃLINA-MARIA VOICU **, DAN FERARIU***, M. DANCIU*** D. C. BRÃNIªTEANU****

CAZURI CLINICECLINICAL CASES

Rezumat

Sclerodermia este o afecþiune a þesutului conjunctiv decauzã necunoscutã ºi cu mecanism autoimun, caracterizatãprintr-o fibrozã pronunþatã a dermului ºi atrofie epider-micã, asociatã sau nu cu atingeri viscerale. Morfeeageneralizatã este o formã particularã de sclerodermielocalizatã, ce prezintã plãci tipice de sclerodermie, extensiveºi situate la nivelul a cel puþin 4 regiuni anatomice.

Prezentãm cazul unui pacient, în vârstã de 73 ani,diagnosticat cu morfee generalizatã, confirmatã anatomo-patologic, cu serologie pozitivã pentru Borellia burgdorferi,pentru care a urmat tratament cu Doxiciclina timp de 3luni, cu negativarea ulterioarã a serologiei, aflat în prezentsub tratament imunosupresor. Examenul clinic obiectiv aevidenþiat leziuni în faze diferite de evoluþie: plãcieritemato-edematoase, localizate la nivelul coapselor , plãcicu induraþie lemnoasã centralã ºi coloraþie gãlbui ceroasã,cu periferia marcatã de un halo roºu-violaceu („lilacring”), majoritatea confluând, cu localizare la nivelultrunchiului, membrelor superioare ºi inferioare.

Întrucât la primele internãri s-au obiectivat valoricrescute ale anticorpilor antinucleari ºi ale imunogramei,datã fiind agresivitatea ºi extinderea leziunilor cutanate, s-a ridicat suspiciunea unei sclerodermii sistemice, darabsenþa fenomenului Raynaud, a afectãrii sistemice, a acro-sclerozei a pledat pentru morfee generalizatã, iniþiindu-se

SummaryScleroderma is a connective tissue disease of unknown

cause and with autoimmune mechanism, characterizedthrough a marked fibrosis of the dermis and epidermalatrophy, with or without visceral involvement. Generalizedmorphea is a particular form of localized scleroderma,presenting typical scleroderma plaques, extensive andlocated at the level of at least 4 anatomical regions.

We present the case of 73 years old patient, diagnosedwith generalized morphea, pathology confirmed, withpositive serology for Borellia burgdorferi, for which hereceived Doxycycline treatment for 3 months, with furthernegativity serology, currently being under immuno-suppressive therapy. Objective clinical examinationrevealed lesions in different stages of development:erythematous- edematous plaques, located at the level of thethighs, plaques with central wood-like induration and wax-yellowed colour, with periphery marked by a red-violaceaehalo ("lilac ring"), most of them confluence with locationon the torso, arms and legs.

Since the first admissions were objectified elevatedantinuclear antibodies and of immunogram, given theaggressiveness and extension of skin lesions, the suspicionof systemic scleroderma was raised, but the absence ofRaynaud's phenomenon, of systemic damage, ofacrosclerose pleaded for generalized morphea, initiating astepwise treatment with systemic corticosteroids, synthesis

* Disciplina Dermatologie, U.M.F. ,,Gr. T. Popa’’ Iaºi.Dermatology Discipline, U.M.F. ,,Gr. T. Popa’’ Iaºi.

** Clinica Dermatologicã, Spitalul Clinic de Urgenþe, ’’Sf.Spiridon’’ Iaºi.Dermatology Clinic, Emergency Hospital, ’’Sf. Spiridon’’ Iaºi.

*** Disciplina Anatomie patologicã, U.M.F. ,,Gr. T. Popa’’ Iaºi.Pathology Discipline, U.M.F. ,,Gr. T. Popa’’ Iaºi.

**** Disciplina Oftalmologie, U.M.F. ,,Gr. T. Popa’’ Iaºi.Ophtalmology Discipline, U.M.F. ,,Gr. T. Popa’’ Iaºi.

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DermatoVenerol. (Buc.), 57: 255-263

Introducere

Sclerodermia este o afecþiune a þesutuluiconjunctiv de cauzã necunoscutã ºi cu mecanismautoimun, caracterizatã printr-o fibrozã pro-nunþatã a dermului ºi atrofie epidermicã, asociatãsau nu cu atingeri viscerale. Sunt descrise douãforme de sclerodermie: sistemicã ºi localizatã(circumscrisã). Morfeea generalizatã este o formãparticularã de sclerodermie localizatã, ce prezintãplãci tipice de sclerodermie, extensive ºi situate lanivelul a cel puþin 4 regiuni anatomice. Leziunilepot fi localizate pe toatã suprafaþa corpului ( petorace, sâni, abdomen, fese ºi coapse, mai rarbraþe, mâini, gambe, cap). Prezentãm cazul unuipacient cu morfee generalizatã ºi serologiepozitivã pentru Borellia burgdorferi.

Caz clinic

Pacient în vârstã de 73 ani, din mediul urban,este consultat în Clinica de Dermatologie Iaºipentru prezenþa la nivelul tegumentului de plãcieritemato-edematoase, localizate la nivelulcoapselor ºi plãci cu induraþie lemnoasã centralãºi coloraþie gãlbui ceroasã , cu periferia marcatãde un halo roºu-violaceu („lilac ring”), culocalizare la nivelul trunchiului, membrelorsuperioare ºi inferioare. Din anamnezã reþinem cãa lucrat timp de 15 ani în mediu toxic (cianuri,mase plastice), ca tehnician în prelucrareametalelor, este fost consumator cronic de etanol,fost fumãtor timp de 40 ani pânã în urmã cu 11ani , 20 þigarete/zi. Debutul bolii a fost în urmãcu 3 luni, prin apariþia la nivelul abdomenului(Figura 1) a unor plãci eritemato-violacee, discretedematoase, asimptomatice, ce ulterior s-auextins pe torace (Figura 2, 3), membre ºi cãrorapacientul nu le-a acordat importanþã; în evoluþie,leziunile iniþiale au devenit indurate central, cu o

Introduction

Scleroderma is a connective tissue disease ofunknown cause and with autoimmunemechanism, characterized through a markedfibrosis of the dermis and epidermal atrophy,with or without visceral involvement. Aredescribed two forms of scleroderma: systemicand localized (confined). Generalized morphea isa particular form of localized scleroderma,presenting typical scleroderma plaques,extensive and located at the level of at least 4anatomical regions. Lesions may be located allover the body ( torso, breasts, abdomen, buttocksand thighs, seldom on arms, hands, legs andhead). We present the case of a patient withgeneralized morphea and positive serology forBorellia burgdorferi.

Clinical case

73 years old patient, from the urbanenvironment, is consulted at Dermatology Clinicfrom Iasi for the presence at the level of the skinof erythemato-oedematous plaques, located atthe level of the thighs and plaques with centralwood-like induration and wax-yellowed colour,with periphery marked by a halo red-violaceae("lilac ring"), located at the level of the torso, armsand legs. From the anamnesis we keep in mindthat he worked for 15 years in a toxicenvironment (cyanide, plastics) as technician inmetal processing, is a chronic ethanol consumer,ex-smoker for 40 years until 11 years ago, 20cigarettes / day . The outset of the disease was 3months ago, through the appearance oferythemato-violaceous plaques at the level of theabdomen (Figure 1), discrete edematous,asymptomatic, which later expanded to thorax(Figure 2, 3), limbs and which the patient has not

tratament etapizat cu corticoizi sistemici, antipaludice desintezã ºi imunosupresoare, cu evoluþie favorabilã.

Cazul prezentat readuce în discuþie implicareaBorelliei burgdorferi în declanºarea sclerodermiei ºidificultãþile terapeutice în cazul formei generalizate demorfee.

Cuvinte cheie: sclerodermie, morfee generalizatã,Borellia burgdorferi.

antipaludiques and immunosuppressive, with favorableevolution.

The case presented brings into question theinvolvement of Borellia burgdorferi in triggeringscleroderma and therapeutic difficulties in the case ofgeneralized morphea form.

Key words: scleroderma, generalized morphea,Borellia burgdorferi.

Intrat în redacþie: 10.08.2012Acceptat: 21.09.2012

Received: 10.08.2012Accepted: 21.09.2012

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Figura 1/Figure 1

Figura 3/Figure 3

Figura 2/Figure 2

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coloraþie galben ceroasã, în timp ce noi plãci auapãrut predominant la nivelul coapselor.

Examenul dermatologic a evidenþiat leziuniîn faze diferite de evoluþie: plãci eritemato-edematoase, bine delimitate, rotunde sau ovalare,cu dimensiuni variabile (de la 2 la 4 cmdiametru), localizate la nivelul coapselor, plãcicu induraþie lemnoasã centralã ºi coloraþie gãlbuiceroasã, cu suprafaþa netedã ºi strãlucitoare,aderenþa de planurile profunde nepermiþândformarea de pliuri, cu periferia marcatã de unhalo roºu-violaceu („lilac ring”), având conturneregulat, imprecis delimitate, cu o marevarietate de dimensiuni (de la 2 cm la 6-7 cmdiametru) ºi forme (ovalare, rotunde), uneleizolate, dar majoritatea confluând, cu localizare lanivelul trunchiului, membrelor superioare ºiinferioare (Figura 4, 5, 6); la nivelul unor plãci seconstatã în centru ºi mici zone de atrofie. Lanivelul leziunilor pilozitatea este absentã ºi seremarcã o infiltraþie tegumentarã accentuatã lanivelul umerilor (în pelerinã).

Paraclinic se constatã un sindrom inflamator(VSH acceleratã, leucocitozã), valori crescute aleANA 53,2 ui/ml ( N : < 23 ui/ml), Ig A 514 mg%(N 70-400 mg%) ºi prezenþa Ac Ig M anti Borelia

given importance; evolving, the initial lesionsbecame central endured, with a wax- yellowedcolor, while new plaques appeared pre-dominantly at the level of the the thighs.

The dermatologic examination revealedlesions in different stages of development:erythemato-oedematous plaques, clearly defined,round or oval, with variable sizes (from 2 to 4 cmdiameter), located at the level of the thighs,plaques with central wood-like induration andwax-yellowed colour, with smooth and shinysurface, bound to the underlying structures, notallowing the formation of folds, the peripherymarked by a red-violaceae halo ("lilac ring") withirregular contour, imprecise defined, with a widevariety of sizes (from 2 cm to 6-7 cm diameter)and shapes (oval, round), some isolated, but mostof them confluenced, localized on the trunk, armsand legs (Figure 4, 5, 6); at the level of someplaques is found in the center small areas ofatrophy. At the level of the lesions ,pilosity isabsent and there is a pronounced skin infiltrationat the level of the shoulders (the cape).

Paraclinical is found an inflammatorysyndrome (accelerated VSH, leukocytosis),elevated values of ANA 53,2 ui/ml (N:<

Figura 4/Figure 4

Figura 5/Figure 5

23ui/ml), Ig A 514 mg% (N 70-400 mg%) and thepresence of Ac Ig M anti Borelia burgdorferi . Acanti ADN dc , Ac anti SCL -70, Ac anti SSA , Acanti SSB, Ac antiphospholipids were absent.

Histopathology exam revealed:- at the level of the abdomen- atrophic

epidermis, proper papillary dermis withmoderate collagen, papillary type vesselsat this level showing moderate edema andreduced infiltrate inflammatory lymphmonocyte (the identified issues maycorrespond to a morphea lesion) (Figure 7)

- at the level of the thigh - epidermis withatrophic areas, perifollicular there ismoderated infiltrate mononuclear inflam-matory lymph monocyte with rare plasmacells; vessels of the superficial dermispresents marked edema and reducedchronic inflammatory infiltrate (theidentified issues may correspond to amorphea type lesion - inflammatoryphase) (Figure 8).

The presence of typical lesions andhistopathology exam support the morpheadiagnosis, and the fact that the plaques are higher

burgdorferi. Ac anti ADN dc , Ac anti SCL -70 ,Ac anti SSA, Ac anti SSB, Ac antifosfolipidici aufost absenþi.

Examenul histopatologic a evidenþiat:- la nivelul abdomenului- epiderm atrofic,

derm papilar ºi propriu – zis cu moderatãcolagenizare, vasele de tip papilar de laacest nivel prezentând moderat edem ºiredus infiltrat inflamator limfomonocitar(aspectele identificate putând corespundeunei leziuni de tip morfee) (Figura 7)

- la nivelul coapsei - epiderm cu zone atrofice,perifolicular se constatã moderat infiltratinflamator mononucleat limfomonocitar,cu rare plasmocite; vasele din dermulsuperficial prezintã marcat edem ºi redusinfiltrat inflamator cronic (aspecteleidentificate putând corespunde uneileziuni de tip morfee - faza inflamatorie)(Figura 8).

Prezenþa leziunilor tipice ºi examenulhistopatologic susþin diagnosticul de morfee, iarfaptul cã plãcile sunt mai mari ca în morfeealocalizatã, au tendinþã la confluare, extinderealeziunilor la nivelul a mai mult de 4 regiuni


Figura 6/Figure 6 Figura 7/Figure 7

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anatomice, prezenþa infiltraþiei tegumentare înpelerinã pledeazã pentru diagnosticul de morfeegeneralizatã. Impresia clinicã (agresivitatea ºiextinderea leziunilor), prezenþa anticorpilorantinucleari a impus diagnosticul diferenþial cusclerodermia sistemicã , dar absenþa fenomenuluiRaynaud, a afectãrii organelor interne, aacrosclerozei orienteazã spre diagnosticul demorfee generalizatã.

Evoluþia a fost lent favorabilã, cu negativareaanticorpilor antinucleari, sub tratament etapizatcu corticoizi sistemici, antipaludice de sintezã ºiimunosupresoare, în asociere cu antiscleroase,dermatocorticoizi nefluoruraþi potenþi la nivelulleziunilor, UVA. Concomitent s-a instituittratamentul infecþiei cu Borellia burgdorferi(Doxiciclinã, 200 mg/zi, 3 luni), cu negativareaanticorpilor Ig M. Toate acestea ºi evoluþia clinicãa leziunilor (diminuarea eritemului, a graduluide infiltraþie tegumentarã, fãrã apariþia de noiplãci) orienteazã spre un prognostic favorabil,fãrã progresie cãtre sclerodermie sistemicã .

Discuþii

Morfeea generalizatã este o formã severã desclerodermie localizatã, mai des întâlnitã laadult, fiind cuprinsã în special vârsta de mijloc.Se ºtie cã este un teren genetic predispus la carese adaugã ulterior o microangiopatie, o disimu-nitate ºi un dezechilibru între sinteza ºi degra-darea colegenului. În literatura de specialitate aufost raportate cazuri de sclerodermie declanºatede: antigene infecþioase (de exemplu: Borelliaburgdorferi, virusul varicelo-zosterian, cisticer-

than in localized morphea, have a tendency toconfluence, the extent of lesions at the level ofmore than four anatomical regions, the presenceof skin infiltration in cape advocates for thediagnosis of generalized morphea. The clinicalimpression (aggressiveness and extent of lesions),the presence of antinuclear antibodies imposeddifferential diagnosis with systemic scleroderma,but the absence of Raynaud's phenomenon, thedamage of the internal organs, of the acroscleroseguided towards the diagnosis of generalizedmorphea.

The evolution was slowly favorable, withantinuclear antibodies negativity, under stepwisetreatment with systemic corticosteroids,synthesis antipaludiques and immunosuppres-sive, in combination with antisclerosis, non-fluorinated potent corticosteroid at the level ofthe lesions, UVA. Simultaneously was estab-lished the treatment of the infection with Borellaburgdorferi (Doxycycline, 200mg/day, 3 months)with Ig M antibodies negativity. All this and theclinical evolution of the lesions (the rednessreduction, of the degree of skin infiltration,without the appearance of new plaques) movedtowards a favorable prognosis, without pro-gression to systemic scleroderma.

DiscussionsGeneralized morphea is a severe form of

localized scleroderma, more common in adults,especially in the middle age. It is known to be agenetically predisposed ground plus a micro-angiopathy, a disimmunity and an imbalancebetween synthesis and collagen degradation. In

Figura 8/Figure 8

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cozã), factori din mediul profesional (siliciu,solvenþi organici, rãºini), factori iatrogeni(siliconii, parafinã - folosiþi în plastiile mamare,radioterapia, vaccinãri anti BCG), anumitemedicamente (bleomicina, triptofanul, bromo-criptina, penicilamina, injecþii cu vitamine B),reacþia grefã contra gazdã, diferite traumatisme.Multe studii au sugerat rolul patogenic alfactorului de creºtere TGF-β, ce stimuleazãfibroblastele în a produce glicozaminoglicani,fibronectinã ºi colagen, reduce matricea celularãºi scade predispoziþia fibroblastelor pentruapoptozã. Biopsiile cutanate au arãtat osupraproducþie de colagen, diferite izoforme aleTGF-β, prezenþa metaloproteinazei TIMP – 3,precum ºi o subpopulaþie de fibroblaºti cestimuleazã expresia colagenului tip I. Unelestudii sugereazã implicarea limfocitelor T CD4+în stimularea rãspunsului fibrotic. De asemenea,sunt implicate în patogenezã interleukina 2 ºiinterleukina 4.

Debutul bolii este lent ºi insidios, afectând cupredilecþie trunchiul. Clinic se constatã plãcitipice de sclerodermie, extensive, cu hipo- sauhiperpigmentare. Leziunile tinere prezintã edemcu sau fãrã halou eritematos. Durerea poatepreceda ocazional apariþia clinicã. Leziunileactive pot fi indurate ºi prezintã o margineeritematoasã sau violacee. În evoluþie leziuniledobândesc o induraþie lemnoasã centralã ºi ocoloraþie gãlbui ceroasã, unele plãci prezentândmici zone de atrofie.

În mod frecvent anticorpii antinucleari, Acanti ADN ºi Ac antihistone sunt pozitivi,comparativ cu alte forme de sclerodermielocalizatã, iar prezenþa autoanticorpilor ANA estecorelatã cu un tablou clinic mai sever, numãr maimare de leziuni sclerotice ºi o duratã mai mare aciclului clinic. Alte modificãri ale tablouluiparaclinic ce pot apãrea: eozinofilie, corelatã cugradul de activitate al bolii, imunoglobuline Gcrescute asociate cu perioada de activitate a bolii,factor reumatoid pozitiv.

Caracteristicile histopatologice variazã înfuncþie de cursul bolii. În leziunile tinere nu s-auobservat modificãri morfopatolologice tipice,fiind raportate vacuole ºi celule endotelialedistruse la nivelul membranei bazale. Leziunilemature dezvãluie un infiltrat inflamator formatdin limfocite, macrofage, eozinofile, mastocite ºi

specialized literature were reported cases ofscleroderma triggered by: infectious antigens (eg:Borella burgdorferi, varicella-zoster virus,cysticercosis), work environment factors (silica,organic solvents, resins), iatrogenic factors(silicones, paraffin-used in breast plasty,radiotherapy, anti BCG vaccination), certainmedication (bleomycin, tryptophan, bromo-criptine, penicillamine, vitamin B injections),graft versus host reaction, various injuries. Manystudies have suggested the pathogenic role ofTGF-β, that stimulates fibroblasts to produceglycosaminoglycans, fibronectin and collagen,reduces the cellular matrix and decreasesfibroblast susceptibility to apoptosis. Skinbiopsies showed an overproduction of collagen,different isoforms of TGF-β, the presence ofmetalloproteinase TIMP – 3, and a subpopulationof fibroblasts that stimulates expression ofcollagen type I. Some studies suggest theinvolvement of T CD4 + lymphocytes in stimulat-ing the fibrotic response. There are also involvedin pathogenesis interleukina2 and interleukina4.

The outset of the disease is slow andinsidious, affecting the trunk. Clinically, arefound typical scleroderma plaques, extensive,with hypo-or hyper pigmentation. The younglesions present edema with or without erythema-tous halo. Pain may occasionally precede theclinical onset. Active lesions may be induratedand presents an erythematous or violaceaemargin. In evolution lesions acquire a centralwood-like induration and wax-yellowed colour,some plaques showing small areas of atrophy.

Frequently, the antinuclear antibodies, Acanti DNA and Ac antihistone are positive,compared to other forms of localized sclero-derma, and the presence of ANA auto antibodiesis correlated with a more severe clinical picture, amuch higher number of more sclerotic lesionsand a longer period of clinical cycle. Otherchanges of the paraclinical picture that mayoccur: eosinophilia, correlated with the activitydegree of the disease, increased G immuno-globulin associated with the activity period of thedisease, positive rheumatoid factor.

Histopathological characteristics varydepending on the course of the disease. In younglesions were not observed typical morpho-pathological changes, being reported vacuolesand endothelial cells destroyed at the level of

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celule plasmatice, localizat în derm ºi þesutsubcutanat, vizibil mai ales în zona de frontierã aprobei bioptice. Fibrele de colagen devineozinofilice ºi formeazã o reþea compactã, îngeneral paralelã cu epidermul. Totodatã au fostdepistate ºi depozite de glicozaminoglicani.

În evoluþie, pot sã aparã atrofii subcutanate ºimusculare, contracturi musculare precum ºihipo- ºi hiperpigmentãri, toate acestea având unrãsunet funcþional (dificultãþi de mobilitate),cosmetic ºi psihologic.

Multe cazuri de sclerodermie localizatã au oevoluþie autolimitatã, cu o perioadã de activitatecuprinsã între 3 ºi 5 ani, însã involuþia spontanã aleziunilor cutanate este mai puþin întâlnitã înmorfeea generalizatã.

Tratamentul urmãreºte stoparea sau înce-tinirea evoluþiei bolii. Se utilizeazã corticoterapiesistemicã sau topicã, în asociere sau nu cumetotrexat, azathrioprinã sau ciclofosfamidã.Efecte favorabile pot avea ºi calcipotriolulunguent 0,005/%, hidroxiclorochina sulfatpentru pacienþii la care biopsia cutanatã adovedit un stadiu inflamator activ. Inducereaatrofiei prin infiltrare cu triamcinolon acetonid(10 mg/ml) poate fi utilizatã în zonele în careîngroºarea pielii cauzeazã un discomfort evident.Calcitriolul (1,25 dihidroxivitamina D) utilizat îndoze de 0,5-0,75 mg/zi, timp de 3-7 luni, s-adovedit a avea un rol benefic. În diminuareasintezei de colagen se poate interveni cu D-penicilaminã în doze crescânde de la 150 la 900mg/zi. Tratamente ce s-au bucurat de succesinclud tacrolimus aplicat topic, sulfasalazina 1-4mg/zi ºi retinoizi. Eficientã este ºi fototerapiaasociatã sau nu cu psoralen, precum ºiinterferonul γ aplicat intralezional. Terapia fizicãare o mare importanþã la pacienþii cu contracturimusculare.

Concluzie

Morfeea generalizatã este o formã severã desclerodermie localizatã, între factorii trigger unrol important avându-l Borellia burgdorferi, iaralegerea unei terapii eficiente poate fi de multeori dificilã.

basic membrane. Mature lesions reveal aninflammatory infiltrate composed of lympho-cytes, macrophages, eosinophils, mast cells andplasma cells located on the dermis and sub-cutaneous tissue, especially noticeable at theborder of the biopsy sample. Collagen fibersbecame eosinophilic and form a compact net-work, generally parallel to the epidermis. Therewere also detected deposits of glycosamino-glycans.

In evolution, may occur subcutaneous andmuscle atrophies , muscle contractions and alsohypo-and hyper pigmentation, all of them havinga functional echo (mobility difficulties), cosmeticand psychological.

Many cases of localized scleroderma have aself-limiting evolution, with a period of activitybetween 3 to 5 years, but spontaneous involutionof skin lesions is less common in generalizedmorphea.

The treatment aims to stop or slow theprogression of the disease. It is used systemic ortopical corticosteroid, with or without metho-trexate, azathrioprin or cyclophosphamide.Beneficial effects can also have calcipotriolointment 0.005/%, hydroxychloroquine sulfatefor patients where skin biopsy showed an activeinflammatory stage. Inducing atrophy by infil-tration with triamcinolone acetonide (10 mg/ml)can be used on the areas where the thickening ofthe skin caused obvious discomfort. Calcitriol(1,25 dihydroxyvitamin D) used in doses of 0.5-0.75 mg/day for 3-7 months, has been shown tohave a beneficial role. In reducing collagensynthesis can interfere with D-penicillamine inincreasing doses from 150 up to 900 mg/day.Treatments that were successful include tacro-limus applied topically, sulfasalazine 1-4 mg/dayand retinoids. Phototherapy associated or notwith psoralen and interferon γ applied intra-lesional is very effective. Physical therapy is veryimportant in patients with muscle contractures.

Conclusion Generalized morphea is a severe form of

localized scleroderma, among the trigger factorsa significant role having Borella burgdorferi, andthe choice of an effective therapy can often bedifficult.

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Bibliografie/Bibliography1. Rook, Arthur et al. - Textbook of Dermatology, seventh edition, Blackwell Publishing, 2004, 56.812. Habif, Thomas P. – Clinical Dermatology, Fourth Edition, 2004, Chapter 173. Fitzpatrick, T. B. et al. – Dermatology in General Medicine, Seventh Edition 2008, 543 4. Bucur, Ghe. and collaborators – Dermato-Venereal Diseases, Encyclopedia, 2002, 664 5. Þolea, Ion – Clinical Dermatovenereology , second edition, Craiova University Medical Publishing, 228 6. Hunter J, Savin J, Dahl M – Clinical dermatology, third edition, Blackwell Publishing, 20027. English SC, John – General Dermatology An Atlas of Diagnosis and Management, Clinical Publishing, 20078. Hertl Michael - Autoimmune Diseases of the Skin - Pathogenesis, diagnosis, Management. Second, revised and

enlarged edition, 20059. Elder D, Elenitsas R, et al. – Lever’s histopathology of the skin, second edition, 10. Smoller B, Hiatt K – Dermopathology: The Basics, Springer, 200911. Bolognia JL, Jorizzo JL, Rapini RP – Dermatology e-dition, Text with Continually Updated Online Reference, Ed.

Elsevier, 2008

Conflict de interese Conflict of interestNEDECLARATE NONE DECLARED

Adresa de corespondenþã: Disciplina Dermatologie, U.M.F. ,,Gr. T. Popa’’ IaºiStr. Universitãþii nr. 16

Correspondance address: Dermatology Discipline, U.M.F. ,,Gr. T. Popa’’ IaºiUniversity Street no. 16

morfeea generalizatÃ generalized morphea filemase plastice), ca tehnician în prelucrarea...

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