1111- Hanseníase Associada a Granuloma

Recebido em 14.04.2000. / Received in April, 14 th of 2000.Aprovado pelo Conselho Consultivo e aceito para publicao em 02.04.2002. / Approved by the Consultive Council and accepted for publication in April, 2nd of 2002.* Trabalho realizado no IPAC - Instituto de Patologia Geral e Cutnea. / Work done at IPAC - Instituto de Patologia Geral e Cutnea.

1 Patologista; Mestre; Doutor em Medicina; Pesquisador Titular da Fundao Oswaldo Cruz. / Pathologist; Masters and Ph.D. in Medicine; Titular Researcher at the Fundao Oswaldo Cruz.

2 Professor Adjunto de Dermatologia da Universidade Federal da Bahia; Dermatopatologista. / Adjunct Professor of Dermatology at the Federal University of Bahia; Dermatopathologist.

3 Especialista em Dermatologia pela SBD. Mestre em Medicina. Mdica do Servio de Dermatologia do HUPES-UFBa. / Specialist in Dermatology by the Brazilian Dermatology Society (SBD). Doctor at the Service of Dermatology at HUPES-UFBa (Professor Edgar Santos University Hospital Federal University of Bahia).

4 Especialista em Dermatologia pela SBD / Specialist in Dermatology by the Brazilian Dermatology Society (SBD)

2002 by Anais Brasileiros de Dermatologia

Hansenase associada a granuloma elastoltico*

Leprosy combined with elastolytic granuloma*

Aryon de Almeida Barbosa Jr 1 Newton Sales Guimares 2 Ivonise Follador 3

Leila Santos Sarno 4 Constana Pithon Pereira 4

Resumo: So descritos dois casos de Hansenase combinados com granuloma elastoltico de clulasgigantes. Embora uma ocorrncia concomitante no possa ser excluda, uma possvel relao pato-gentica entre as duas condies postulada. possvel que um mecanismo imunolgico desempenheum papel no processo elastoltico, que poderia tambm ser causado por dano actnico na pele alteradapela Hansenase.Palavras-chave: Granuloma; hansenase

Summary: Two cases of leprosy combined with elastolytic giant cell granuloma are reported. Thougha coincidental occurrence cannot be excluded, a possible pathogenetic relationship between the twoconditions is postulated. It is possible that an immunological mechanism plays a role in the elastolyticprocess, which could also be caused by actinic damage in the skin altered by leprosy.Key Words: Granuloma; leprosy

Barbosa Jr, Guimares, Follador, Sarno & Pereira 585

An bras Dermatol, Rio de Janeiro, 77(5):585-592, set./out. 2002.

Caso Clnico / Case Report

INTRODUONos ltimos anos, houve aumento de interesse nas

doenas que apresentam degenerao do tecido elstico daderme1, apesar do sistema elstico da pele no ser bementendido. Algumas condies inflamatrias e no infla-matrias associadas elastlise da derme foram descritas.

A coexistncia de hansenase e granuloma elastol-tico de clulas gigantes, para o qual usaremos o termoLEGG (Leprosy and Elastolytic Giant Cell Granuloma),at onde chega o nosso conhecimento, no foi at hojereconhecido nem descrito.

O presente estudo documenta dois casos raros dehansenase associada ao granuloma elastoltico de clulasgigantes em reas expostas da pele e discute sua possvelrelao.

INTRODUCTIONIn recent years there has been increased interest in

diseases showing degeneration of dermal elastic tissue1, inspite of the fact that the skin elastic system is not wellunderstood. Some inflammatory and non-inflammatoryconditions associated with dermal elastolysis have beendescribed.

The coexistence of leprosy and elastolytic giant cellgranuloma, for which we use the term LEGG, so far as weare aware, has not hitherto been recognized nor described.

The present study documents two unusual cases ofleprosy combined with elastolytic giant cell granulomaon exposed areas of skin and discusses their possiblerelation.

Figura 1: Leses avermelhadascom hipopigmentao e pequena

atrofia no centro. A pele circundante mostra afinamento e

envelhecimento sugestivos deelastose solar. Paciente 1.

Figure 1: Reddish lesions withhypopigmentation and slightatrophy of the centers. The surrounding skin showsthinning and wrinkling sugges-tive of solar elastosis. Patient 1.

586 Barbosa Jr, Guimares, Follador, Sarno & Pereira


RELATO DOS CASOSCaso 1: mulher branca de 50 anos, com pele fototipo

II, de Vitria da Conquista, Bahia, com longa histria epide-miolgica de contato ntimo com paciente portador de han-senase multibacilar que sofrera de hepatite medicamentosaque causou sua morte durante o tratamento para hansenase.Ela relatava uma histria de 1 ano de mculas e placas erite-mato-edematosas, no-pruriginosas, em reas de exposiosolar. O exame clnico revelou leses eritematosas mltiplascom bordas elevadas, s vezes, de aspecto anular, no tronco,rea do colo, braos, membros e lbulos da orelha (Figura1). Quase todas de aspecto infiltrado. A paciente no tinhasintomas subjetivos. As leses cutneas no apresentavamalterao de sensibilidade. No tomava nenhuma medica-o. Os exames laboratoriais de rotina, incluindo examespara HTLV I e II, foram normais. Contudo, o ndice bacterio-lgico dos esfregaos foi de 3,5. A suspeita clnica, antes dosexames laboratoriais, inclua hansenase borderline, micosefungide e lupus eritematoso.

Caso 2: mulher branca de 63 anos, de Salvador,Bahia. Desenvolveu uma leso cutnea na extremidadesuperior esquerda, que havia comeado h 2 meses. A his-tria clnica no era relevante. Aparentava estar clinica-mente bem, exceto pela presena de pequenas ppulas maldefinidas, discretamente brilhantes, com bordas irregula-res e aspecto anular na superfcie flexora do antebraoesquerdo (Figura 2). A leso media aproximadamente 7x5cm de dimetro e era da mesma cor da pele, mas mostran-do pequenas reas de hipopigmentao. Apresentavadiminuio da sensibilidade trmica. Os achados e resulta-dos dos exames de laboratrio foram negativos, ou dentrodos limites normais, inclusive o ndice bacteriolgico. Asuspeita clnica era hansenase tuberculide.

Achados PatolgicosSomente uma bipsia - bipsia

incisional em fuso - foi feita de cadapaciente. As bipsias foram fixadasem formalina a 10% por um dia.Preparados histolgicos corados comH&E e Fite-Faraco, seccionados a 5mm, foram usados para classificao edemonstrao de M.Leprae. Ademais,foram realizados exames com orcenacida e alcian blue (pH 2,5).

Caso 1: a bipsia cutnea de

CASE REPORTSCase 1: a 50-year-old white woman having sun-

reactive skin type II from Vitria da Conquista, Bahia, witha long epidemiological history of close contact with a mul-tibacillary leprosy patient, which had had medicamentoushepatitis causing death during the treatment for leprosy.

Patient with a one-year history of progressivelyspreading crops of non-pruritic, erythematous and edema-tous plaques and maculae on exposed areas of her skin.Clinical examination revealed multiple erythematouslesions with elevated borders, sometimes of annular aspecton her trunk, dcollet, arms, limbs and earlobes (Figure1). Almost all of those lesions were of infiltrated aspect. Thepatient had no subjective symptoms. The cutaneous lesionsshowed no sensibility alterations. She took no medication.Routine laboratory investigation, including tests for HTLV Iand II, was normal. However, the average Bacterial Index(BI) of skin smears was 3.5. The clinical suspicion, beforethe laboratory examinations, included Borderline Leprosy,Mycosis Fungoides and Erythematous Lupus.

Case 2: a 63-year-old white woman from Salvador,Bahia, developed a cutaneous lesion on her left upper extre-mity that had begun to develop for two months. Her medi-cal background was unremarkable. Clinically she appearedto be quite well except for the presence of ill defined slightlyshinny area with small papules and irregular edges ofannular aspect on the flexor surface of her left forearm(Figure 2). The lesion measured about 7x5 Cm in diameterand was the same color as the skin, but showing small areasof hypo pigmentation. There was local thermal sensibilitydecrease. Findings and results of laboratory examinationswere negative or within normal limits, including the BI,which was negative. The clinical suspicion was TuberculoidLeprosy.

Pathological FindingsOnly one biopsy of each

patient was taken in the form of anelliptical biopsy. The biopsies werefixed in 10% formalin for one day.H&E and Fite-Faraco stained histo-logical preparations, sectioned at 5mm were used to classify anddemonstrate M. leprae. Additi-onally, acid orcein and alcian blue(pH 2.5) stains were performed.

Figura 4: Bipsia cutnea daleso do antebrao (leso anu-lar). Fragmentos engolfados de

fibras elsticas so vistas nasclulas gigantes multinucleadas

entre as fibras de colgeno.H&E, 250X. Paciente 1.

Figure 4: Skin biopsy from thelesion of forearm (annularlesion). Engulfed fragments ofelastic fibers are seen withinmultinuclear giant cells amongcollagen fibers. H&E, 250X.Patient 1.



Case 1: skin biopsy from one of the lesions revealedinflammation of neurovascular bundles and skin appenda-ges. Macrophages and lymphocytes were the predominantcell-types. Large number of acid-fast bacilli (AFB) could beseen in the cytoplasm of macrophages, often with foamyaspect (Figure 3). In focal areas of the superficial and middermis, sometimes in close proximity to the marked leprosytissue reaction there was a patchy lymphohistiocytic infil-trate, with many giant cells without vacuoles nor AFB(Figure 4). Elastic fibers were less frequently found in theseinfiltrates. The few isolated bundles of fibers observed inthis area were short and thin. Fragments of elastic fiberswere demonstrated within the cytoplasm of a few of thegiant cells and macrophages. In the deep reticular dermis,the elastic fibers appeared to be normal. The diagnosis ofsubpolar lepromatous leprosy combined with elastolyticgiant cell granuloma was made.

Case 2: Histological examination of the lesionrevealed coexistence of macrophages and multinucleatedgiant cells that phagocytosed elastic fibers in the upper der-mis, causing them to disappear (Figure 5). Besides this

lesion, there was perineuralinflammation composedmainly of lymphocytes andhistiocytes (Figure 6) presenteither in the deep dermis orin the vicinity of sweat

uma das leses revelou inflamao dos feixes neurovascu-lares e anexos cutneos. Macrfagos e linfcitos eram ostipos de clulas predominantes. Podia-se ver grande nme-ro de bacilos cido-resistentes (BAAR), no citoplasma dosmacrfagos, freqentemente de aspecto espumoso (Figura3) Em reas focais da derme superficial e mdia, por vezesprximo da rea do tecido hansenaco reacional, havia uminfiltrado linfohistiocitrio com vrias clulas gigantes semvacolo nem bacilos cido-resistentes (figura 4) Estes infil-trados apresentavam menos fibras elsticas do que encon-tradas normalmente. Os poucos feixes de fibras observadosnesta rea eram curtos e finos. Foram demonstradas fibraselsticas no citoplasma de algumas clulas gigantes emacrfagos. Na derme reticular profunda, as fibras elsticaspareciam normais. Foi feito o diagnstico de hansenasevirchowiana subpolar associada ao granuloma elastolticode clulas gigantes.

Caso 2: exame histolgico da leso revelou coexis-tncia de macrfagos e clulas gigantes multinucleadasque fagocitaram as fibras elsticas da derme superior, cau-sando seu desaparecimento (Figura 5). Alm desta leso,havia inflamao perineural,composta basicamente delinfcitos e histicitos(Figura 6), presentes naderme profunda ou prximos glndulas sudorparas.

Figura 2: Leses eritematosas, levemente infiltradas no antebrao.Paciente 2. / Figure 2: Erythematous, slightly infiltrated annular

lesions on the forearm. Patient 2.

Figura 3: Macrfagos podem ser vistos em volta dos nervos commuitos bacilos cido-resistentes viveis. Colorao de Fite-Faraco,320X. Paciente 1. / Figure 3: Macrophages are seen around nerves

with many viable fast-acid bacilli. Fite-Faraco stain, 320X. Patient 1.

Figure 6: Perineural inflammatory infiltrate, composed mainly of lymphocytes and histiocytes is present in the mid-dermis. H&E 120X. Patient 2.

Figura 5: Fibras elsticas diminudas nas reas do granulo-ma de clulas gigantes da derme

media, enquanto permanecem narea da derme superficial e no

subcutneo. Colorao pala orce-na 120X. Paciente 2.



Havia escassos bacilos cido-resis-tentes demonstrveis nos feixes dosnervos, mas nenhuma proliferaode clulas de Schwann. No foramobservadas alteraes significativasna epiderme.

Tratamento e Curso ClnicoUma vez feito o diagnstico,

foi iniciado tratamento para hanse-nase em ambos os casos. Terapiamultidrogas, como as usadas empacientes com hansenase multibacilar, foi recomendadapara a paciente do caso 1. A paciente do caso 2 recebeudose nica de quimioterapia de curta durao. Nos 12meses subseqentes, no apareceram novas leses nem foiobservada recorrncia, e ambas as pacientes mostravammelhora significativa.

DISCUSSOA degenerao das fibras elsticas ou elastlise, aspec-

to de algumas doenas cutneas, constitui um grupo de doenascaracterizadas por diminuio ou desaparecimento do tecidoelstico drmico. A elastlise foi classificada como localizadaou generalizada e pode ser congnita ou adquirida, com ou semmanifestaes sistmicas.2 Apesar da elastina principal prote-na constitutiva das fibras elsticas abranger 2% do total deprotenas da derme3, ela importante fisiologicamente, propor-cionando elasticidade pele. Existem evidncias bioqumicasde que a elastina produzida pelos fibroblastos da pele.4

Alteraes na estrutura ou metabolismo da elastina foramimplicadas em diversas doen-as cutneas adquiridas ouhereditrias. Embora a basebioqumica para as mudanasobservadas na estrutura daelastina no seja conhecida,pensa-se que a elastase umaenzima proteoltica esteja

glands. There were scanty demons-trable AFB on nerve bundles, but noSchwann cell proliferation. No sig-nificant abnormalities were obser-ved in the epidermis. The diagnosisof indeterminate leprosy combinedwith elastolytic giant cell granulo-ma was made.

Treatment and Clinical CourseOnce the diagnosis was

made, the treatment for leprosywas initiated in both cases. Multidrug Therapy (MDT), asused for multibacillary patients was recommended forpatient 1. Patient 2 received a single dose of short-termchemotherapy (ROM). No new lesions appeared in the sub-sequent twelve months, nor was recurrence observed,during this time the lesions of both patients showed markedimprovement.

DISCUSSIONElastic fiber degradation or elastolysis, a feature of

some cutaneous diseases, constitutes a group of disorderscharacterized by a decrease or disappearance of dermalelastic tissue. It has been classified as either localized orgeneralized and may be congenital or acquired with orwithout systemic manifestations.2 Although elastin, the prin-cipal protein constituent of the elastic fibers, comprisesonly about 2% of the total protein in dermis,3 it is physiolo-gically important, providing the resiliency of skin. There arebiochemical evidences that elastin is produced by skin

fibroblasts.4 Alterations inthe elastin structure or meta-bolism have been implicatedin a number of heritable andacquired cutaneous diseases.Although the biochemicalbasis for the observed chan-ges in the elastin structure is

Figure 5: Elastic fibers are dimin-ished in the areas of giant cellgranuloma of the mid-dermis,while they remain in the superficial area of the dermis andthe subcutis. Orcein stain 120X.Patient 2.

Figura 6: Infiltrado inflamatrio perineural,

composto principalmente de linfcitos e histicitos, presente

na derme mdia. H&E 120X. Paciente 2.



not known, elastasea proteolytic enzyme has beenthought to be involved in the process, sometimes stimulatedby cathepsin G.5 Moreover, the interaction of elastase withelastin depends on electrostatic forces.6 The pathogenicmechanisms of elastolysis are poorly understood. Defects insynthesis of elastic tissue, release of elastase by inflamma-tory tissue, decrease in serum copper, and immune mecha-nisms have been postulated as possible mechanisms.Although it is not clear whether inflammation is a primaryevent or if it occurs as a phenomenon secondary to the elas-tolytic process, there is some evidence that inflammation isimportant in various elastolysis.2

Dermal histiocytic and giant cell phagocytosis ofelastic tissue (elastoclasis) is seldom found in severalinflammatory dermatoses that may be considered to belongto a clinical spectrum of diseases characterized by a granu-lomatous infiltrate with elastolysis. Multinucleated giantcells containing elastic fibers are also found in annulargranuloma (then known as annular elastolytic giant cellgranuloma), actinic keratoses, persistent insect-bite reac-tions, elastosis perforans serpiginosa, granulomatoussyphilis, foreign body granuloma, keratoacanthoma, basalcell carcinoma and certain variants of cutaneous T-celldyscrasia i.e. granulomatous slack skin and mycosis fun-goides;7,8 as well in Adult T cell leukemia, 9,10 necrobiosislipoidica and senil purpura.11 Recently we have seen elasto-clasis in a cutaneous lesion from a patient with tegumentarleishmaniasis (unpublished data). Other conditions thatneed to be considered in the histopathologic differentialdiagnosis include cutaneous sarcoidosis and deep fungalinfections. All these diagnoses may be excluded in ourpatients. Our specimens showed neither epithelioid tuber-cles nor numerous lymphocytes and the pathological pro-cess also spared the subcutis.

Elastoclasis may occur non-specifically, at least insome cases, in sun-protected areas, as well as in sun-expo-sed skin.12 Elastic tissue phagocytosis may be, however, asecondary event in several inflammatory dermatoses, withdegradation of the elastic fibers that are present within theinfiltrate.7,13 Alternatively, the primary event might be thegranulomatous inflammatory reaction directed againstelastic fibers, with actinic damage14 or not.15 However, theprocess of elastolysis by multinucleated giant cells has notyet been elucidated and is still uncertain. In elastolyticgiant cell granuloma, collagen fibers are not affected.16

Elastic fibers are, however, digested by histiocytes and mul-tinucleated giant cells, therefore, in the post reactive centralzone, the collagen fibers are intact and the elastic fibers areabsent.14,17,18,19 Yanagihara et al, 1987,16 suggested that theelastolytic process in this disease proceeds in two steps: anextracellular digestion and an intracellular digestion of theelastic fibers.

The purely descriptive term elastolytic giant cellgranuloma (EGCG), was introduced to overcome inade-quacies in the previous terminology.15 The lack of unifor-

envolvida no processo, s vezes, estimulada por catepsina G.5

Alm do mais, a interao de elastase com elastina depende deforas eletrostticas.6 Os mecanismos patognicos da elastliseso pouco conhecidos. Defeitos na sntese do tecido elstico,liberao de elastase por tecido inflamatrio, diminuio dosnveis sricos de cobre e mecanismos imunolgicos so postu-lados como possveis mecanismos. Apesar de no estar claro sea inflamao um evento primrio ou se ocorre como fenme-no secundrio ao processo elastoltico, existem algumas evidn-cias de que a inflamao importante em vrias elastlises.2

Histiocite drmica e fagocitose das clulas gigantes dotecido elstico (elastoclasia) so eventualmente achados emvrias dermatoses inflamatrias, que se pode considerar quepertenam a um espectro clnico de doenas caracterizadaspor infiltrados granulomatosos com elastlise. Clulas gigan-tes multinucleadas contendo fibras elsticas tambm soencontradas no granuloma anular (ento conhecido como gra-nuloma anular de clulas gigantes elastolticas), ceratose act-nica, reao persistente picada de insetos, elastose perfuran-te serpiginosa, sfilis granulomatosa, granuloma de corpoestranho, queratoacantoma, carcinoma basocelular e certasvariantes de discrasia de clulas T, i.e.pele laxa granulomato-sa e micose fungide;7,8 como tambm, leucemia de clulas Tdo adulto, 9,10 necrobiose lipodica e prpura senil.11

Recentemente vimos elastoclasia em uma leso cutnea deum paciente com leishmaniose tegumentar (dados no publi-cados). Outras condies que precisam ser consideradas nodiagnstico diferencial histopatolgico incluem sarcodosecutnea e infeces profundas por fungos. Todos estes diag-nsticos podem ser excludos nas nossas pacientes. Nossosespcimes no mostraram tubrculos epiteliides nem linfci-tos numerosos e o processo patolgico poupou o subcutneo.

Elastoclasia pode ocorrer de forma no especifica, aomenos em alguns casos, em reas protegidas do sol, assimcomo, em reas da pele expostas ao sol.12 A fagocitose do teci-do elstico pode ser, no entanto, evento secundrio em vriasdermatoses inflamatrias, com degenerao das fibras elsticasque se encontram presentes no infiltrado. 7,13 Alternativamente, possvel que o evento primrio seja a reao inflamatria gra-nulomatosa dirigida contra as fibras elsticas, com dano actni-co 14 ou no. 15 No entanto, o processo de elastose por clulasgigantes multinucleadas ainda no foi elucidado e permaneceincerto. No granuloma elastoltico de clulas gigantes, as fibrasde colgeno no so afetadas.16 Todavia, as fibras elsticas sodigeridas por histicitos e clulas gigantes multinucleadas, epor essa razo, as fibras de colgeno na zona central ps-reati-va esto intactas e as fibras elsticas encontram-se ausen-tes.14,17,18,19 Yanaguihara e colegas, em 1987,16 sugeriram que,nessa doena, o processo elastoltico age em duas etapas: umadigesto extracelular e uma intracelular das fibras elsticas.

O termo descritivo granuloma elastoltico de clulasgigantes (EGCG) foi introduzido para suprir inadequaesna terminologia anterior.15 A falta de uniformidade na termi-nologia pode ser atribuda superposio de caractersticasclnicas e histopatolgicas 20 e incerteza quanto etiologia.



As caractersticas histolgicas incluem infiltrao granulo-matosa por muitas clulas gigantes (freqentemente comformao de corpos asterides), histicitos, linfcitos, clu-las epiteliides ocasionais, e ausncia de necrobiose. O teci-do elstico parece desaparecer nas bordas do granuloma, eencontra-se absolutamente ausente no centro deste. O granu-loma elastoltico de clulas gigantes (ECGC) uma doen-a incomum que pode no ser prontamente reconhecidapelos no iniciados. Reconhec-lo nesta regio do mundo especialmente importante porque pode ser diagnosticadoerroneamente como hansenase tuberculide. , portanto,til reconhecer o padro da elastlise granulomatosa, paraque no seja confundida com outras dermatites granuloma-tosas. Conseqentemente, um componente adicional doalgoritmo de diagnstico, na abordagem da dermatite granu-lomatosa, determinar se a fagocitose das fibras elsticas uma caracterstica proeminente da resposta histiocitria.8

O interesse especial nos casos apresentados que osachados clnicos, incluindo a localizao e os achadospatolgicos, so raros. No caso da paciente 2, o aspecto cl-nico da leso, correspondente ao granuloma elastolticosuperficial, induziu o mdico a suspeitar de hansenasetuberculide. amplamente reconhecido que o diagnsticode hansenase muitas vezes difcil. Porm, a coexistnciade hansenase e granuloma elastoltico de clulas gigantespode ser fonte de preocupao e pode representar um desa-fio maior para os patologistas. Apesar de diagnosticada ahansenase, ainda assim, poderia ser erroneamente classifi-cada. A aparncia granulomatosa da leso, com clulasgigantes elasto-fagocitrias, pode sugerir o diagnstico dehansenase paucibacilar (tuberculide ou dimorfa tuber-culide) e, com isso, induzir a tratamento no apropriado.

At onde sabemos, no h descrio clinico-patolgi-ca de casos similares com o diagnstico de elastoclasia. Rueda& Rodriguez relataram, em 1979,21 um grupo de 16 pacientes,de ambos os sexos, com hansenase virchowiana com clulasgigantes, alguns deles com corpos asterides. Apesar de teremse referido a estes casos como hansenase virchowiana declulas gigantes, e de no terem demonstrado, atravs decolorao para fibras elsticas, a incorporao de fibras els-ticas drmicas no citoplasma dos histicitos e das clulasgigantes, provvel, de acordo com um membro da nossaequipe - AABJr -, que pelo menos alguns destes pacientes seencaixem no mesmo padro clinico-patolgico do LEGG.

As fibras elsticas da derme de pacientes com hanse-nase apresentam traos caractersticos, dependendo do tipode hansenase, perodo de durao da condio ativa e estru-turas drmicas destrudas.22 A questo que surge saber se aassociao de hansenase com granuloma elastoltico declulas gigantes mais do que simples coincidncia.Embora a possibilidade de que as duas leses tenham ocor-rido por acaso no possa ser totalmente excluda, o granulo-ma elastoltico de clulas gigantes raro, e a ocorrnciasimultnea com hansenase na mesma leso cutnea sugereuma relao mais ntima. As duas pacientes apresentavam

mity in terms of terminology can be attributed to an over-lap of clinical and histopathological features20 and uncer-tainty with regard to its etiology. Its histologic featuresinclude granulomatous infiltration by many giant cells(often with asteroid body formation), histiocytes,lymphocytes, scattered epithelioid cells, and no necrobio-sis. Elastic tissue appears to disappear at the borders ofthe granuloma and is totally absent in the center. EGCG isan uncommon entity that may not be readily recognized bythe uninitiated. The recognition of this disease in thisregion of the world is especially important since it may bemisdiagnosed as tuberculoid leprosy. It is therefore usefulto recognize the pattern of granulomatous elastolysis, lestit be confused with other forms of granulomatous dermati-tis. Accordingly, an additional component of the diagnosticalgorithm in approaching granulomatous dermatitis is todetermine whether elastic fiber phagocytosis is a promi-nent feature of the histiocytic response.8

The special interest of the presented cases is that theclinical findings, including the localization and the patho-logical findings, were uncommon. In patient 2, the clinicalaspect of the lesion, corresponding to the superficial elas-tolytic granuloma, induced the clinician to suspect ofTuberculoid Leprosy. It is widely recognized that the diag-nosis of leprosy is often difficult. But the coexistence ofleprosy and elastolytic giant cell granuloma (LEGG), couldbe a source of worry and may pose further a challenge forpathologists. In spite of the recognition of leprosy, onecould well misinterpretate the leprosy form. The granulo-matous appearance of the lesion, with elastophagocytosinggiant cells, might suggest a diagnosis of paucibacillaryleprosy (tuberculoid or borderline tuberculoid) and so indu-ce to inappropriate treatment.

To our knowledge, there are no clinico-pathologicaldescriptions of similar cases with the recognition of elasto-clasis. Rueda & Rodriguez reported, in 1979,21 a group of16 patients of both sexes, having lepromatous leprosy withgiant cells, some of which containing asteroid bodies.Although they referred to these case as Giant CellLepromatous Leprosy, and the incorporation of dermalelastic fibers into the cytoplasm of the histiocytes and giantcells was not demonstrated by means of elastica staining,according to one of us (AABJr), it is likely that at least someof these patients could also be fitted into the same clinico-pathological picture of LEGG.

The dermal elastic fibers of leprosy patients hadcharacteristic features, depending on the types of leprosy,duration periods of active condition and destroyed der-mal strutures.22 The question that arises is as to whetherthe association of leprosy with elastolytic giant cell gra-nuloma is more than just coincidental. Although the pos-sibility that the two lesions occurred per chance cannottherefore be altogether excluded, elastolytic giant cellgranuloma is uncommon and the co-occurence withleprosy in the same cutaneous lesion suggests a more inti-



mate relationship. The two patients presented with diffe-rent but well-defined forms of leprosy each. This diseaseis well known for cursing with immunologic abnormali-ties. Although the underlying ethiopathogenesis of LEGGhas not been established and the series presented issmall, the detection of LEGG in both patients stronglysuggests that the immunologic system does play a role inthe pathogenesis of this elastolytic disorder.Inflammatory infiltrates, especially leukocytes andmacrophages, are associated with elastase activity.23,24

Since inflammatory infiltrate, found in all cases ofleprosy, is composed not only by macrophages, but also ofsubstantial numbers of T-lymphocytes with the predomi-nance of the CD8 subset,25 one must question the natureof LEGG. It is therefore reasonable to assume, at least inour cases, that LEGG is not primary at all, but rather itrepresents an unusual elastolytic disorder that is secon-dary to an inflammatory process in which immunologicmechanisms are involved. The annular configuration ofthese lesions thus resulted from elastolytic activity ofinfiltrating inflammatory cells in the center and periphe-ral spreading of the active process.

Therefore, other factors such as actinic damage tothe skin altered by leprosy, in view of the history of prolon-ged sun exposure of our two patients, seemed to predispo-se the dermis to elastic fiber alteration or contribute to theabnormal elastic fiber catabolic processes. Generallyspeaking, it is unknown whether sunlight and/or any otherfactors may initiate the essential degeneration of the elas-tic fibers, which are then recognized as foreign bodies andphagocytized by histiocytes, or if these factors may inducea deviation of the foreign body recognition mechanismand/or an activation of the phagocytosis function of thehistiocytes to cause phagocytosis of their own elasticfibers. A photoallergic drug reaction seems improbable,both patients took no drugs, and the pathologic findings donot support this possibility. It remains to be determinedwhether these observations reflect the altered structure orloss of elastin seen histologically in aging skin. However,we are unable to provide a satisfactory explanation for theetiology of our patients dermatologic process. The mecha-nisms that govern this association and whether they are ofany biological significance in the pathogenesis of leprosyare uncertain. q

formas de hansenase diferentes, porm, bem definidas. Estadoena conhecida por cursar com alteraes imunolgicas.Apesar da etiopatognese subjacente do LEGG, em ambasas pacientes, no ter sido estabelecida, e a srie apresentadaser pequena, a deteco de granuloma elastoltico de clulasgigantes, em ambas as pacientes, sugere que o sistema imu-nolgico tem papel importante na patognese desta dis-funo elastoltica. Infiltrados inflamatrios, especialmenteleuccitos e macrfagos, esto associados atividade daelastase.23,24 Devido ao fato do infiltrado inflamatrio, encon-trado em todos os casos de hansenase, ser composto noapenas de macrfagos, como tambm de substancial quan-tidade de linfcitos T, com predominncia da subdivisoCD8,25 deve-se questionar a natureza do granuloma elastol-tico de clulas gigantes. Da, razovel assumir, pelo menosnos nossos casos, que o granuloma elastoltico de clulasgigantes no seja, de fato, primrio, mas que represente umadisfuno elastoltica rara que seria secundria a um proces-so inflamatrio no qual os mecanismos imunolgicos esta-riam envolvidos. Portanto, a configurao anular destasleses resultaram da atividade elastoltica do infiltrado declulas inflamatrias no centro e periferia do processo ativo.

Outros fatores, tais como dano actnico pele alteradapela hansenase, diante da histria prolongada de exposiosolar de nossas duas pacientes, pareceu predispor a derme aalteraes das fibras elsticas ou contribuir para o processocatablico anormal das fibras elsticas. De modo geral, no sesabe se a luz solar e/ou outros fatores iniciam a degeneraoessencial das fibras elsticas, que so ento reconhecidascomo corpos estranhos e fagocitadas pelos histicitos, ou seestes fatores induzem a alteraes no mecanismo de reconhe-cimento de corpos estranhos e/ou a ativao da funo defagocitose dos histicitos que causam fagocitose de suas pr-prias fibras elsticas. Uma reao fotoalrgica a drogas pare-ce improvvel, j que nenhuma das pacientes tomava drogas,e os achados patolgicos no confirmam tal possibilidade.Resta ser determinado se estas observaes refletem a estrutu-ra alterada ou perda da elastina vista histologicamente na peleenvelhecida. Todavia, no conseguimos chegar a uma expli-cao satisfatria para a etiologia do processo dermatolgicode nossas pacientes. Os mecanismos que governam esta asso-ciao so incertos, assim como, no se sabe se eles tmalgum significado biolgico na patognese da hansenase.q

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17. OBrien JP. Actinic granuloma: an annular connective disor-der affecting sun and heat damaged (elastotic) skin. ArchDermatol 1975;111:460-6. 18. Schwarz T, Lindlbauer R, Gschnait F. Annular elastolyticgiant cell granuloma. J Cutan Pathol 1983; 10(5): 321-6 19. Moreno A, Salvatella N, Guix M, DeMoragas JM. Actinicgranuloma, an ultrastructural study of two cases. J Cutan Pathol1984; 11: 179-83.20. McGrae JD. Actinic granuloma. A clinical, histopathologicaland immunocytochemical study. Arch Dermatol 1986; 122:43-7.21. Rueda LA, Rodriguez G. Lepra Lepromatosa Gigantocitria.IX Congresso Iberolatinoamericano de Dermatologia, SesionClinico-patologica, 24-29 novembro 1979, p. 73-7, Medellin,Colombia.22. Namisato M, Kameyama K, Yajima M. The dermal connec-tive tissue of leprosy patients. Part 1. The elastic fibers and theskin appendages. Nippon Rai Gakkai Zasshi 1994, 63(3):65-74.23. Janoff A. Mediators of tissue damage in leukocyte lysosomes:X. Further studies on human granulocyte elastase. Lab Invest1970; 22:228-36.24. Oikarinen AL. Zone JJ, Ahmed AR Kiistala U, Uitto J.Demonstration of collagenase and elastase activities in the blisterfluids from bullous skin diseases: comparison between dermatitisherpetiformis and bullous pemphigoid. J Invest Dermatol 1983;81:261-6.25. Gonzalez ACO, Silva TC, Barbosa Jr AA, Sadigursky M.Immunohistologic appraisal of infiltrating cells in skin biopsiesfrom young patients clinically suspected of having various formsof leprosy. An bras Dermatol, Rio de Janeiro, 74(4):365-71, 1999.

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1111- Hanseníase Associada a Granuloma