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Qual o seu diagnstico? / Which is your diagnosis?

Ao Editor dos Anais Brasileiros de Dermatologia

Caso para diagnstico / Case for diagnosis

HISTRIA DA DOENA PATIENTS HISTORY

Paciente com 32 anos, do sexo feminino, branca, casada, do lar, natural da Paraba, refere h um ano e seis meses o aparecimento de leses eritematosas, reticuladas, localizadas na face, no tronco e nos membros superiores, que pioravam com a exposio solar e o estresse emocional. O exame clnico no apresentou alteraes, e no dermatolgico observaram-se leses eritematosas, com discreta infiltrao, com padro reticulado, localizadas na face, no colo, na partes anterior e posterior do trax e nos membros superiores (Figuras 1, 2 e 3). Os exames complementares realizados foram: eletroforese e imunoeletroforese de protenas, dosagem de T3, T4 e TSH, cadeias leves Kappa e lmbida ( e ), FAN e antiENA todos normais; tipagem do HLA presena do DR15 associado ao lpus eritematoso sistmico. O exame histopatolgico mostrou infiltrado inflamatrio superficial constitudo de clulas mononucleares em torno de vasos. Os feixes colgenos apresentavam-se dissociados e fragmentados (Figuras 4 e 5), entremeados por material basoflico filamentoso que se cora em azulesverdeado pelo ferro coloidal (mucina) (Figura 6). Na microscopia eletrnica observaram-se fibroblastos ativados, com vesculas do retculo endoplasmtico distentidas, aumento da deposio de glicosaminoglicanas e proteoglicanas entremeando os feixes colgenos.

Caucasian woman, 32, married, housewife, born in Paraba. Eighteen months earlier had erythematous reticulated lesions on the face, torso and upper limbs, which became worse with emotional stress and exposure to sunlight. No clinical abnormalities were found but the dermatological examination showed erythematous lesions of reticulated pattern with discreet infiltration on the face, neck, front and back of the thorax, and upper limbs (Figures 1, 2 and 3). The following supplementary tests were performed: protein electrophoresis and immunoelectrophoresis, T3, T4 and TSH dosage, Kappa and Lambda light chains, ( and ), FAN and anti-ENA all normal; type of HLA presence of DR15 associated with systemic lupus erythematosus. The histopathological tests showed superficial inflammatory infiltrate formed by mononuclear cells around the vessels. The collagen bundles were dissociated and fragmented (Figures 4 and 5), interspersed with a filamentous basophilic material that is stained greenishblue by colloidal iron (mucin) (Figure 6). Activated fibroblasts were observed under electron microscopy, with distended vesicles of the endoplasmic reticulum, increased deposition of glycoaminoglycans and proteoglycans, mixed with the collagen bundles.

Figura 1: Leses eritematosas de padro reticulado na face Figure 1: Reticulated erythematous lesions on the face An bras Dermatol, Rio de Janeiro, 75(1):93-97, jan./fev. 2000.

Figura 2: Leses eritematosas de padro reticulado no colo Figure 2: Reticulated erythematous lesions on the neck

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Figura 3: Leses eritematosas de padr~ao reticulado no membro superior esquerdo

Figure 3: Reticulated erythematous lesions on the left upper limb

O tratamento institudo foi cloroquina 250mg/dia e fotoproteo. Aps um ms de tratamento houve clareamento do eritema e melhora das leses. Com a suspenso da teraputica, as erupes recidivaram.
COMENTRIOS COMMENTS

The treatment chosen was chloroquinone 250mg/day and photoprotection. After one month of treatment the erythema eased off and the lesions improved. When the therapy was interrupted the eruptions reappeared.

Diante do quadro clnico e da anlise dos exames laboratoriais, o diagnstico conclusivo foi de mucinose reticulada eritematosa. Essa afeco foi descrita pela primeira vez por Steigleder,1 em 1974. Posteriormente, Quimby & Perry (1982)2 sugeriram que a mucinose reticulada eritematosa e a mucinose em placas (Perry, 1960)3 fizessem parte de um mesmo espectro: a sndrome REM, j que compartilham manifestaes clnicas e histopatolgicas semelhantes. uma forma de mucinose cutnea que se caracteriza por eritema reticulado persistente e atinge, predominantemente, as mulheres na faixa etria de 20 a 60 anos.4 doena rara e de etiologia desconhecida, mas as leses so desencadeadas e agravadas pela luz solar, localizando-se costumei-

After analysis of the clinical picture and laboratory tests, the conclusive diagnosis was eticulated erythematous mucinosis. This disease was first described by Steigleder,1 in 1974. Later on, Quimby & Perry (1982)2 suggested that the reticulated erythematous mucinosis and the plaque mucinosis (Perry, 1960)3 might be part of the same spectrum the REM syndrome since similar clinic and histopathologic manifestations are shared. It is a form of cutaneous mucinosis, characterized by a persistent reticulated erythema that attains mainly women between 20 and 60 years of age.4 It is a rare disease of unknown etiology, whose lesions are triggered and intensified by sunlight and usually located in body

Figura 4: Infiltrado inflamatrio mononuclear perivascular superficial, dissociao dos feixes colgenos com deposio de material basoflico filamentoso (HE, x10) An bras Dermatol, Rio de Janeiro, 75(1):93-97, jan./fev. 2000.

Figure 4: Superficial perivascular mononuclear inflammatory infiltrate, dissociation of the collagen bundles with deposition of filamentous basophilic material (HE, x10)

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Figura 5: Infiltrado inflamatrio mononuclear perivascular superficial, dissociao dos feixes colgenos com deposio de material basoflico filamentoso (HE, x40) Figure 5: Superficial perivascular mononuclear inflammatory infiltrate, dissociation of the collagen bundles with deposition of filamentous basophilic material (HE, x40)

Figura 6: Ferro coloidal material filamentoso corado em azul esverdeado (HE, x40) Figure 6: Colloidal iron greenish-blue stained filamentous material (HE, x40)

ramente nas reas fotoexpostas. Em geral so assintomticas, mas o prurido pode estar presente em 20% dos casos.5 A associao com doenas sistmicas vista em um quinto dos casos relatados, sendo as mais encontradas as neoplasias, tireoidopatias, diabetes mellitus, lpus eritematoso, prpura trombocitopnica idioptica, artrite e uvete.5 Pacientes com imunocomplexos circulantes e paraproteinemia monoclonal tambm foram relatados.6 Izumi et al. 7 tentaram elucidar o mecanismo da deposio de mucina por meio da resposta dos fibroblastos de pacientes com a doena a diversos modeladores exgenos. Os resultados mostraram resposta anormal dos fibroblastos ao estmulo pela interleucina 1 beta, podendo estar comprometida no metabolismo alterado do cido hialurnico. A relao entre a exposio solar e a exacerbao da doena sugere que a irradiao solar tenha significativa influncia em sua patognese. Bleehen et al.8 mostraram o desenvolvimento de eritema persistente por trs semanas aps exposio radiao UVB em dose trs vezes maior do que a eritematosa mnima, no havendo surgimento de leses novas. Morison et al. 9 usaram UVB , UVC e radiao solar simulada, conseguindo produzir uma erupo papulosa aps 28 dias de irradiao. Neste ltimo caso, a radiao UVB provocou a reao mais intensa, e a dose varivel de duas a duas e meia doses eritematosas mnimas ( DEM ) foi suficiente para reproduzir o rash. No entanto, Yamazaki et al.10 utilizaram com sucesso a luz UVB na dose 4 DEM no tratamento de um paciente com a sndrome REM, associada corticoterapia tpica oclusiva para clarear as leses remanescentes. Portanto, o papel exato da radiao UV na patognese da doena ainda permanece desconhecido.
An bras Dermatol, Rio de Janeiro, 75(1):93-97, jan./fev. 2000.

areas that are subjected to photo-exposure. They are generally asymptomatic, but pruritus may be present in 20% of the cases.5 Association with systemic diseases is found in 25% of the reported cases and the most common are neoplasias, thyroidopathies, diabetes mellitus, lupus erythematosus, idiopathic thrombocytopenic purpura, arthritis and uveitis.5 Patients with circulating immune complexes and monoclonal paraproteinemia were also reported.6 Izumi et al. 7 tried to unravel the mucin deposition mechanism via the fibroblastic response to several exogenous models of affected patients. The results showed an abnormal response of the fibroblasts to interleukin 1 beta stimulation, with a possible affection of the altered hyaluronic acid metabolism. The association of exposure to sunlight and the diseases exacerbation suggests that the solar radiation is an important feature of its pathogenesis. Bleehen et al. 8 demonstrated the development of persistent erythema for three weeks following exposure to a dose of UVB three times greater than the minimum erythematous dosage, with no occurrence of new lesions. Morison et al.9 used UVB, UVC, simulated solar radiation, and were able to produce a papular eruption after 28-days of irradiation. In this last instance the UVB radiation caused the most intense reaction and the variable dose of 2-2,5 minimum erythematous doses ( MED ) was sufficient to reproduce the rash. Yamazaki et al.,10 however, used the UVB light successfully in the 4 MED dose for the treatment of a patient with the MER syndrome associated with topic occlusive corticotherapy, to clear the remaining lesions. The exact influence of UV radiation on the pathogenesis of the disease is still unknown.

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Os aspectos histopatolgicos para o diagnstico so a deposio de mucina na derme e infiltrado inflamatrio linfoctico perivascular superficial. A colorao pelo ferro coloidal parece ser mais sensvel do que o Alcian blue para demonstrar os mucopolissacrides. Os estudos com a microscopia eletrnica mostram a presena de mucina como material reticular eltron-denso em justa proximidade s fibrilas elsticas e colgenas. 8 A imunofluorescncia direta geralmente negativa, mas casos com deposio de IgM granular e contnua ao longo da membrana basal tem sido relatados.5 Um estudo usando anticorpos monoclonais avaliou os fentipos das clulas mononucleares perivasculares do infiltrado drmico. A percentagem dessas clulas, que foram coradas pelo OKT3, OKT4 e OKT8, foi de apenas 5% do total, concluindo, ento, que essas clulas no so linfcitos T. No entanto, a constituio do infiltrado ainda no foi determinada. Os diagnsticos diferenciais mais importantes da sndrome REM so o infiltrado linfcito de Jessner, que se diferencia na histopatologia pelo infiltrado linfoctico perivascular denso sem associao com deposio de mucina; o lpus eritematoso, que, entretanto, apresenta em geral outros critrios diagnsticos e sorologia positiva; e a erupo polimorfa luz, que, alm da semelhana clnica, apresenta histopatologia similar, com infiltrado linfoctico perivascular e deposio de mucina, mas em pequena quantidade e restrita derme papilar. A opo teraputica de melhor resultado a administrao de antimalricos, que so a droga de escolha at o momento. Seu mecanismo de ao desconhecido, mas pode ser devido ao bloqueio de stios antignicos do DNA e dos mucopolissacrides cidos produzidos pelas alteraes fotoqumicas.4 Corticoterapia sistmica, betacaroteno e ciclosporina no foram efetivos para a resoluo das leses.5,11 Anti-histamnicos tambm no so teis na reduo do prurido, que est presente em alguns casos, ainda que a melhora das leses aps tratamento da doena de base associada, e at melhora espontnea so relatados.2,3

The histopathological aspects for diagnosis are the mucin deposition on the skin and the superficial perivascular limphocytic inflammatory infiltrate. The staining by colloidal iron seems to be more sensitive than the Alcian blue, to show the mucopolysaccharides. Studies done under electron microscopy evidenced the presence of mucin as a reticular electron-dense material in close proximity to the elastic and collagen fibrillae. 8 Direct immunofluorescence is generally negative, but there have been reports of cases with deposition of granular and continuous IgM along the basal membrane.5 One study employing monoclonal antibodies appraised the perivascular mononuclear cells phenotypes of the dermal infiltrate. The percentage of these cells stained with the OKT3, OKT4 and OKT8, was only 5% of the total, suggesting that those cells were not T lymphocytes. The make-up of the infiltrate, however, has not yet been determined. The most important differential diagnosis of the REM syndrome is the Jessner lymphocyte infiltrate, which is histopathologically differentiated by the dense perivascular lymphocytic infiltrate that is not associated with mucin deposition or the lupus erythematosus. But it commonly presents other diagnostic criteria and positive serology, besides the eruption at polymorphic light, which, besides the clinical similarity, also has a histopathology similar to the perivascular lymphocytic infiltrate and mucin deposition, but in small quantities and restricted to the papillary dermis. The therapeutic option for best results is the administration of antimalarials, which are the choice drugs at this moment. Its action mechanism is unknown but may be due to the blockage of DNA antigen sites and the acid mucopolysaccharides produced by the photochemical changes. 4 Systemic corticotherapy, beta-carotene and cyclosporine, were not effective for the resolution of lesions. 5,11 Antihistamines, also, are not useful to reduce pruritus, which is present in some cases, even when there is a remission of the lesions after treating the associated basic disease, despite the fact that spontaneous regressions have been reported.2,3

REFERNCIAS 1. Steigleder GK, Gartmann H, Linker U. REM syndrome: reticular erythematosus mucinosis (round- cell erythematosis), a new entity? Br J Dermatol 1974;91:191-9. 2. Quimby SR, Perry HO. Plaquelike cutaneous mucinosis: its relationship to reticular erythematous mucinosis. J Am Acad Dermatol 1982;6:856-61. 3. Perry HO, Kierland RR, Montgomery H. Plaquelike form of cutaneous mucinosis. Arch Dermatol 1960;82:980-5. 4. Astle NJ, Rasmussen J. A reticulated eruption on the chest. Arch Dermatol 1987;123:519-24. 5. Cohen PR, Rabinowitz AD, Ruszkowski RN, Deheo VA. Reticular erythematous mucinosis syndrome: review of the world literature and report of the syndrome in a prepubertal child. Pediatric
An bras Dermatol, Rio de Janeiro, 75(1):93-97, jan./fev. 2000.

Dermatol 1990;7(1):1-10. 6. Zaki I, Shall L, Millard LG. Reticular erythematous mucinosis syndrome and a monoclonal IgG kappa paraprotein Is there na association? Br J Dermatol 1993;129:347-8. 7. Izumi T, Tajima S, Harada R, Nishikawa T. Reticular erythematous mucinosis syndrome: glycosaminoglycan synthesis by fibroblasts and abnormal response to interleukin-1 beta. Dermatology 1996;192(1):41-5. 8. Bleehen SS, Slater DN, Mahood J, Church RE. Reticular erythematous mucinosis: light and electron microscopy, immunofluorescence and histochemical findings. Br J Dermatol 1982;106:9-18. 9. Morison WL, Shea CR, Parrish JA. Reticular erythematous

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mucinosis syndrome. Report of two cases. Arch Dermatol 1979;115:1340-2. 10. Yamazaki S, Katayama I, Kurumaji Y, Yokozeki H, Nishioka K. Treatment of reticular erythematous mucinosis with a large dose of ultraviolet B radiation and steroid impregnated tape. J Dermatol

1999;26:115-8. 11. Bulengo-Ransby S, Ellis CN, Griffiths CEM, Cantu-Gonzalez G, Dubin HV, Voorhees JJ. Failure of reticular erythematous mucinosis to respond to cyclosporine. J Am Acad Dermatol 1992;27:825-8.

Trabalho realizado no Servio de Dermatologia, Hospital Universitrio Pedro Ernesto UERJ. Giane Pereira Giro Teixeira Especialista em Dermatologia pela SBD. Maria de Ftima G. Scotelaro Alves Doutora em Dermatologia UFRJ. Leninha Valrio do Nascimento Professora Titular de Dermatologia, Faculdade de Cincias Mdicas UERJ. Av. 28 de setembro, 87 Rio de Janeiro RJ 20551-030 E-mail: dermhupe@uerj.br

Prezado(a) colega, A seo Qual o seu Diagnstico? procura apresentar casos clnicos que possam vir a questionar o diagnstico final da doena. Se voc tem algum artigo que se encaixe nesta seo, contribua com os Anais Brasileiros de Dermatologia, enviando-o para o nosso endereo: Av. Rio Branco, 39 / 18o andar - Centro - Rio de Janeiro - RJ - CEP: 20090-003

An bras Dermatol, Rio de Janeiro, 75(1):93-97, jan./fev. 2000.