Souza, Lcio, Palma, Frana, Azevedo & Cavalcanti

Caso Clnico / Case Report

Acne fulminans: relato de dois casos clnicos * Acne fulminans: two case reports *
Ana Elisabete Simes de Sousa1 Luciana Vianna Lcio2 Srgio Palma3 Emmanuel Rodrigues de Frana4 Ceclia Azevedo5 Silvana Cavalcanti6

Resumo: A acne fulminans um tipo raro e grave de acne vulgar, de etiologia desconhecida, que acomete principalmente jovens do sexo masculino. Inicia-se de modo sbito e est associada a manifestaes sistmicas importantes. Os autores descrevem dois casos clnicos de acne fulminans e fazem uma reviso de seus aspectos clnicos e fisiopatolgicos, e do tratamento, com o intuito de obter melhor entendimento do curso clnico e prognstico dessa doena. Palavras-chave: Acne vulgar; teraputica. Summary: Acne fulminans is a rare type of acne vulgaris, of unknown etiology, involving mainly young males. Onset is abrupt and is related to important systemic manifestations. The authors describe two clinical cases of acne fulminans and its clinical aspects, physiopathologic features and treatment are reviewed, leading to a better understanding of the clinical course and prognosis of this disease. Key words: Acne vulgaris; therapeutics.

INTRODUO A acne fulminans uma forma rara, exuberante e grave de acne vulgar, de incio agudo, acometendo principalmente adolescentes do sexo masculino.1 Caracteriza-se pelo aparecimento de leses inflamatrias dolorosas, em geral no dorso e trax, que rapidamente se tornam ulcerativas e curam deixando cicatriz. Acompanha-se de manifestaes clnicas sistmicas, tais como febre, astenia, mialgias, artralgias, e laboratoriais (anemia, leucocitose com neutrofilia e aumento da velocidade de hemossedimentao). Sua etiopatognese desconhecida, embora evidncias apontem para um possvel fenmeno imunomediado.2 Os autores apresentam dois casos clnicos de acne fulminans.

INTRODUCTION Acne fulminans is a rare, exuberant and serious form of acne vulgaris, presenting acute onset, that mainly involves male adolescents.1 It is characterized by the appearance of painful inflammatory lesions located in general on the back and thorax. These rapidly become ulcerated and leave scars on healing. They are accompanied by systemic manifestations, such as: fever, asthenia, myalgia, arthralgia and laboratorial manifestations (anemia, leukocytosis with neutrophilia and an increased erythrocyte sedimentation rate). Its etiopathogenesis remains unknown, although evidence points to a possibly immunomediated phenomena.2 The authors present two clinical cases of acne fulminans.

Recebido em 08.06.2000. / Received in June, 08th of 2000. Aprovado pelo Conselho Consultivo e aceito para publicao em 30.01.2001. / Approved by the Consultive Council and accepted for publication in January, 30st of 2001. * Trabalho realizado no Servio de Dermatologia da Faculdade de Cincias Mdicas de Pernambuco. / Work done at Dermatology Service of the Pernambuco Faculty of Medical Sciences. Mdica dermatologista. / Doctor, dermatologist. Livre-Docente; Doutor em Dermatologia. Professor Adjunto; Chefe do Servio. / Professor; Ph.D Dermatology, Professor; Head of Service. 5 Preceptora de Dermatologia. / Preceptor of Dermatology. 6 Professora Auxiliar de Dermatologia. / Assistent Professor of Dermatology.
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2001 by Anais Brasileiros de Dermatologia.

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Souza, Lcio, Palma, Frana, Azevedo & Cavalcanti

Figura 1 A: Leses ulcerocrostosas na face Figure 1A: Ulcerative and crusted lesions in the face

Figura 1 B: Leses ulcerocrostosas no tronco Figure 1 B: Ulcerative and crusted lesions in the trunk

RELATO DOS CASOS Caso n. 1 E.E.S., de 16 anos, do sexo masculino, natural e procedente de Caruaru, PE, apresentava histria prvia de acne na face h um ano, tendo realizado tratamento com medicaes tpicas sem melhora. H dois meses evoluiu com piora sbita do aspecto das leses e sua disseminao; simultaneamente, apresentava febre, astenia e artralgia. Ao exame dermatolgico observava-se a presena de leses ulcerocrostosas, exuberantes e exsudativas, localizadas na regio da face e tronco, e em menor quantidade nos membros superiores e inferiores (figuras 1 A e B, e figura 2). Quanto aos exames complementares, o hemograma evidenciou leucocitose (13.200) com desvio esquerda e velocidade de hemossedimentao elevada; o fator antinuclear foi negativo; a bioqumica, normal, e a radiografia do trax no mostrou alteraes. Cultura de secreo da leso cutnea foi positiva para Enterococcus faecalis, e a bipsia da pele mostrou quadro histopatolgico compatvel com o diagnstico de acne fulminans: presena de infiltrado inflamatrio misto (composto por neutrfilos e linfcitos) com envolvimento perivascular e perifolicular (Figura 3 A). Aps a confirmao do diagnstico, o paciente foi medicado com eritromicina 500mg de seis em seis horas por 10 dias e prednisona na dose diria de 60mg por via oral durante cerca de oito semanas, apresentando melhora do quadro clnico, com remisso da febre e involuo das leses dermatolgicas.

CASE REPORTS Case 1 E.E.S., male, 16 years of age, born and resident in Caruaru, Pernambuco State, presented a prior history of acne in the face for one year and attempted topical medications without improvement. Two months ago, this coursed with a sudden exacerbation and dissemination of the lesions; while simultaneously presenting fever, asthenia and arthralgia. At the dermatological exam, exuberant and exudative ulcerative and crusted lesions were observed localized on the face and trunk and to a lesser degree along the upper and lower members (Figures 1A and B and figure 2 ). Regarding the complementary exams: hemogram showed leukocytosis (13,200) with a left deviation and elevated erythrocyte sedimentation rate; antinuclear factor was negative; normal biochemistry; and chest radiography showed no alterations. Culture of secretion from the lesion tested positive for Enterococcus faecalis and skin biopsy showed a histopathological picture compatible with a diagnosis of acne fulminans: presence of a mixed inflammatory infiltrate (composed of neutrophiles and lymphocytes) with perivascular and perifollicular involvement (Figure 3 A). Following confirmation of the diagnosis, the patient was medicated with 500mg erythromycin every six hours for 10 days and 60mg/day oral prednisone for approximately eight weeks. He presented an improvement in the clinical picture, with normalization of the fever and involution of the dermatological lesions.

Case 2 Caso n. 2
R.O.B., de 16 anos, do sexo

masculino, natural e procedente de Recife, PE, queixava-se de pstulas na face (Figura 3 B) e tronco h dois meses, associadas a febre, dores

R.O.B., aged 16 years, male, born and resident in Recife, Pernambuco State, complaining for two months of pustules in the face (Figure 3 B) and trunk, associated

Figura 2: Leses ulcerocrostosas nos membros inferiores

Figure 2: Ulcerative and crusted lesions in the inferior members

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Souza, Lcio, Palma, Frana, Azevedo & Cavalcanti

B
Figura 4: Placas eritmato-crostosas e exsudativas no tronco Figure 4: Exudative, erythematous and crusted plaque in the trunk

Figura 3 A: Infiltrado inflamatrio composto por neutrfilos e linfcitos, com envolvimento perivascular e perifolicular Figure 3 A: Inflammatory infiltrate comprised of neutrophiles and lymphocytes, with perivascular and perifollicular involvement Figura 3 B: Leses inflamatrias na face / Figure 3 B: Inflammatory lesions in the face

articulares e perda de oito quilos de peso corporal. H cerca de duas semanas, surgiram placas eritmato-crostosas e exsudativas localizadas no tronco (Figura 4), membros superiores (Figura 5) e inferiores. O hemograma evidenciou discreta leucocitose (12.000) com neutrofilia e velocidade de hemossedimentao elevada. Os exames sorolgicos para sfilis (VDRL e FTA-abs) e Aids (ELISA para HIV-1 e HIV-2) foram negativos. A pesquisa micolgica das leses foi negativa; o teste de Mantoux mostrou-se no reator, e a radiografia do trax foi normal. O exame histopatolgico da pele demonstrou as alteraes caractersticas da doena: presena de infiltrado celular drmico perivascular e perianexial composto por neutrfilos e eosinfilos (Figura 6). Aps a confirmao do diagnstico, o paciente foi submetido a antibioticoterapia oral (tetraciclina 500mg de seis em seis horas por 30 dias), ao uso de glicocorticide sistmico (prednisona 40mg por dia durante dois meses), associados ao tratamento tpico com perxido de benzola a 5%. Trs semanas depois apresentou melhora clnica das leses.

with fever, articular pain and loss of eight kilos of body weight. Approximately two weeks previously, erythematous and crusted and exudative plaque appeared, located in the trunk (Figure 4) and upper (Figure 5) and lower members. Hemogram showed discreet leukocytosis (12,000) with neutrophilia and elevated erythrocyte sedimentation rate. Serological exams for syphilis (VDRL and FTA-abs) and Aids (ELISA for HIV-1 and HIV-2) were negative. Mycological test of the lesions was negative; mantoux test showed no reactivity, and the chest x-ray was normal. Histopathological exam of the skin demonstrated the disease's characteristic alterations: presence of perivascular and periadnexal dermal cellular infiltrate comprising of neutrophiles and eosinophiles (Figure 6). After diagnostic confirmation, the patient was submitted to oral antibiotic therapy (500mg tetracycline every six hours for 30 days) and to systemic glucocorticoid (40mg prednisone once daily for two months), associated to topical treatment with 5% benzoyl peroxide. Three weeks later he presented clinical improvement of the lesions.

Figura 5: Placas eritmatocrostosas e exsudativas no membro superior direito An bras Dermatol, Rio de Janeiro, 76(3):000-000, mar./abr. 2001.

Figure 5: Exudative, erythematous and crusted plaque in the right upper member

Souza, Lcio, Palma, Frana, Azevedo & Cavalcanti

Figura 6: Infiltrado celular drmico perivascular e perianexial, composto por neutrfilos e eosinfilos

Figure 6: Perivascular and periadnexal dermal cellular infiltrate, comprised of neutrophiles and eosinophiles

DISCUSSO A acne vulgar entidade bastante comum, que acomete cerca de 85% dos adolescentes.3 Na maioria dos casos, a doena discreta, e os pacientes no procuram o dermatologista. A acne fulminans uma entidade devastadora e rara, representada por acne ulcerativa febril com incio sbito e sintomas sistmicos, que acomete principalmente adolescentes brancos do sexo masculino,4 como nos casos referidos. Sua etiopatognese permanece obscura, com provveis mecanismos inflamatrios e imunolgicos revelados por hipergamaglobulinemia, depleo do sistema complemento, presena de complexos imunes circulantes.2 Reaes de hipersensibilidade celular retardada ao Propionibacterium acnes esto aumentadas durante o curso da acne inflamatria grave e podem estar envolvidas em sua patognese.5 Altos nveis de testosterona durante a puberdade podem ser uma importante causa da acne fulminans e podem explicar por que essa doena acomete quase exclusivamente adolescentes do sexo masculino, como nos casos relatados. Acne ulcerativa foi observada em trs garotos que fizeram tratamento a longo prazo para alta estatura com altas doses de testosterona.6 Acne fulminans tambm pode ser induzida pela isotretinona; as doses e os intervalos entre a medicao e as manifestaes agudas variam. Seu curso e tratamento no so diferentes da acne fulminans comum.7 No entanto, esse raro efeito adverso do tratamento com a isotretinona precisa ser mais bem elucidado. Clinicamente, caracteriza-se por erupo papulonodular, eritematosa, na face e no tronco, que rapidamente progride para leses ulcerativas, crostosas, exuberantes e exsudativas, com tendncia confluente, deixando cicatrizes. Acompanha-se com freqncia de sinais e sintomas sistmicos (febre, astenia, mal-estar, artralgia, mialgia) e alteraes laboratoriais (anemia, leucocitose com neutrofilia, aumento da velocidade de hemossedimentao), tendo sido as mesmas manifestaes encontradas nos pacientes aqui relatados. A ocorrncia de leses sseas rara, mas bem reconhecida, e bipsias sseas so freqentemente realizadas para descartar malignidade ou infeco.1 Embora paream ser transitrias, causam desconforto considervel ao
An bras Dermatol, Rio de Janeiro, 76(3):000-000, mar./abr. 2001.

DISCUSSION Acne vulgaris is a common entity, that involves some 85% of adolescentes.3 In most cases the disease is discreet and the individuals do not consult a dermatologist. Acne fulminans is a devastating and rare entity, represented by feverish ulcerative acne with sudden onset and systemic symptoms that mainly involves Caucasian male adolescents,4 as in the cases described above. Its etiopathogenesis remains unknown, though probably involving inflammatory and immunological mechanisms as revealed by hypergammaglobulinemia, depletion of the complement system, presence of circulating immune complexes.2 Tardive cellular hypersensitivity reactions to Propionibacterium acnes increases during the course of serious inflammatory acne and may be involved in its pathogenesis.5 High testosterone levels during puberty could be an important cause of acne fulminans and may explain why the disease almost exclusively involves male adolescents, as in the case reports. Ulcerative acne was observed in three boys undergoing long-term therapy for tall stature with elevated doses of testosterone.6 Acne fulminans can also be induced by the isotretinoin; although the doses and period between medication and acute manifestations vary. Its clinical course and treatment do not differ from common acne fulminans.7 However, this rare side effect triggered by isotretinoin therapy requires further elucidation. Clinically, it is characterized by papulonodular erythematous eruptions in the face and trunk that quickly progress to exuberant, exudative and crusted ulcerative lesions, which tend to confluence and leave scars. It is frequently accompanied by systemic signs and symptoms (fever, asthenia, indisposition, arthralgia and myalgia) and laboratorial alterations (anemia, leukocytosis with neutrophilia and increased erythrocyte sedimentation rate), i.e. presenting the same manifestations found in the patients described in the case reports. The occurrence of bone lesions is rare, but well recognized, and bone biopsy is frequently performed to discard the hypothesis of malignancy or infection.1 Although apparently transitory, they cause considerable discomfort to the patient. Radiographic exams

Souza, Lcio, Palma, Frana, Azevedo & Cavalcanti

paciente. Os exames radiogrficos no so definidos nem podem mostrar a presena de reas osteolticas nos ossos dolorosos.8 Nos dois casos em discusso os pacientes no relataram queixas sseas. Histopatologicamente, caracteriza-se pela presena de infiltrado inflamatrio drmico composto por neutrfilos e linfcitos, de localizao perivascular e perifolicular, compatveis com o resultado das bipsias dos pacientes em questo. Pode tambm apresentar-se como vasculite leucocitoclstica. O regime teraputico necessrio inclui o uso de glicocorticides sistmicos ou intralesionais (para a preveno de novas crises), alm de antibiticos orais. Tratamento similar foi preconizado para os pacientes aqui relatados. Os glicocorticides sistmicos melhoram rapidamente as leses da pele e os sintomas sistmicos, embora esses tendam a recidivar quando sua dosagem diminuda. Devem, portanto, ser mantidos por perodo varivel de dois a quatro meses e, em seguida, lentamente reduzidos.9 O uso do retinide sinttico oral tem revolucionado o manuseio da acne grave resistente ao tratamento. A isotretinona tambm benfica para esses pacientes, mas provavelmente no o tratamento de escolha e deve ser iniciada aps o uso do corticide.3 Ela age como potente antiinflamatrio em adio a sua conhecida funo de sebosttico e, provavelmente, tem efeito no padro de queratinizao folicular.10,11 Embora o prognstico aps o tratamento seja satisfatrio, as leses cutneas geralmente deixam cicatrizes e milia.12 CONCLUSO Acne fulminans doena grave, extremamente rara no Brasil, com etiopatogenia ainda no totalmente elucidada. Estudos recentes mostraram que a combinao de glicocorticides e antibiticos sistmicos constitui tratamento efetivo nos estgios precoces da doena, mas a isotretinona tem sido necessria para seu controle a longo prazo.13 Neste trabalho, os autores relatam dois casos clnicos de acne fulminans em adolescentes do sexo masculino, com leses dermatolgicas exuberantes e boa resposta teraputica aps a administrao de antibitico e corticide sistmicos. Por ser doena de incio e evoluo rpidos, deve-se enfatizar a importncia do diagnstico e tratamento precoces, com o objetivo de diminuir sua morbidade significativa.

are not defined nor show the presence of osteolytic regions in the painful bones.8 In the two cases under discussion the patients did not report bone complaints. In histopathological terms, it is characterized by the presence of inflammatory dermal infiltrate, comprising of neutrophiles and lymphocytes, with a perivascular and perifollicular location. This is compatible with the results from the biopsies of the patients in question. It can also present as leukocytoclastic vasculitis. The required therapeutic regimen includes the use of systemic or intralesional glucocorticoids (to prevent new crises) in association with oral antibiotics. Similar treatment was provided for the patients in the above case reports. Systemic glucocorticoids quickly improve the skin lesions and systemic symptoms, although these tend to relapse when the dosage is decreased. Thus they should be maintained for a period varying from two to four months and, soon after, slowly reduced.9 The use of oral synthetic retinoid has been revolutionizing the management of serious acne that is resistant to treatment. Isotretinoin is also beneficial for these patients, but it is probably not the treatment of choice and should be initiated after use of corticoid.3 The drug acts as a potent anti-inflammatory in addition to its sebostatic function and, probably, affects the follicular keratinization pattern.10,11 Although the prognostic after treatment is satisfactory, the cutaneous lesions usually leave scars and milia.12 CONCLUSION Acne fulminans is a serious disease that is extremely rare in Brazil, with etiopathogenesis still no totally clarified. Recent studies have shown that the combination of glucocorticoids and systemic antibiotics constitutes an effective treatment in the early stages of the disease, but isotretinoin has proved to be necessary for its long-term control.13 In this work, the authors describe two clinical cases of acne fulminans in male adolescents, with exuberant dermatological lesions and good therapeutic response after antibiotic management and systemic corticoid. Since it is a disease with a sudden onset and rapid clinical course, the importance of its diagnosis and precocious treatment must be emphasized, with the objective of reducing its significant morbidity.

REFERNCIAS / REFERENCES 1. Gordon PM, Farr PM, Milligan A. Acne fulminans and bone lesions may present to other specialties. Pediatr Dermatol 1997;14(6):446-8. 2. Goldstein B, Chalker DK, Lesher JL Jr. Acne fulminans. South Med J 1990;83(6):705-8. 3. Tan BB, Lear JT, Smith AG. Acne fulminans and erithema nodosum during isotretinoin-therapy responding to dapsone. Clin Exp Dermatol 1997;22(1):26-7.

4. Allison MA, Dunn CL, Person DA. Acne fulminans treated with isotretinoin and "pulse" corticosteroids. Pediatr Dermatol 1997;14(1):39-42. 5. Karvonen SL, Rasanen L, Cunliffe WJ, Holland KT, Karvonen J, Reunala T. Delayed hipersensitivity to Propionibacterium acnes in patients with severe nodular acne and acne fulminans. Dermatology 1994;189(4):344-9. 6. Traupe H, von Muhlendahl KE, Bramswig J, Happie R. Acne of the fulminans type following testosterona therapy in three

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excessively tall boys. Arch Dermatol 1998;124(3):414-7. 7. Joly P, Prost C, Gaudemar M, Revuz J. Acne fulminans triggered by isotretinoin therapy. Ann Dermatol Venereol 1991;118(5):369-72. 8. Jemec GB, Rasmussen I. Bone lesions of acne fulminans. Case report and review of the literature. J Am Acad Dermatol 1989;20(2Pt2):353-7. 9. Karvonen SL. Acne fulminans: report of clinical findings and treatment of 24 patients. J Am Acad Dermatol 1993;28(4):572-9. 10. Plewig G, Wagner A. Anti-inflamatory effects of 13-cisretinoic acid. An in vivo study. Arch Dermatol Res

1981;270(1):89-94. 11. Strauss JS, Stranieri AM. Changes in long-term sebum production from isotretinoin therapy. J Am Acad Dermatol 1982;6:751. 12. Kurokawa S, Tokura Y, Nham NX et al. Acne fulminans coexisting with pyoderma gangrenosum-like eruptions and posterior scleritis. J Dermatol 1996;23(1):37-41. 13. Karvonen SL, Vaalasti A, Kautiainen H, Reunala T. Systemic corticosteroid and isotretinoin treatment in cystic acne. Acta Derm Venereol 1993;73(6):452-5.

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An bras Dermatol, Rio de Janeiro, 76(3):000-000, mar./abr. 2001.