SciELO - Scientific Electronic Library Online

 
vol.50 número2Serotonin receptor (5-HT 2A) and catechol-O-methyltransferase (COMT) gene polymorphisms: Triggers of fibromyalgia?Immediate complications of 3,555 injections of anti-TNFα índice de autoresíndice de materiabúsqueda de artículos
Home Pagelista alfabética de revistas  

Servicios Personalizados

Revista

Articulo

Indicadores

Links relacionados

Compartir


Revista Brasileira de Reumatologia

versión impresa ISSN 0482-5004

Rev. Bras. Reumatol. vol.50 no.2 São Paulo marzo/abr. 2010

http://dx.doi.org/10.1590/S0482-50042010000200005 

ORIGINAL ARTICLE

 

Wegener's granulomatosis: prevalence of the initial clinical manifestations - report of six cases and review of the literature

 

 

Carlos Ewerton Maia RodriguesI; Maria Roseli Monteiro CalladoII; Christiane Aguiar NobreIII; Francisca Edwiges Araújo MouraIV; Rejane Maria Rodrigues de Abreu VieiraV; Lucas Alverne Freitas de AlbuquerqueVI; Walber Pinto VieiraVII

IRheumatologist of the Rheumatology Department of Hospital Geral de Fortaleza (HGF)
IISciences PhD from the Medical School of Universidade São Paulo (USP), São Paulo, SP, Brazil. Collaborating Professor of the Medical School of Universidade Estadual do Ceará (UECe)
IIIRheumatology Resident at HGF
IVPhysician and Preceptor of the Rheumatology Residency of HGF
VMaster's Degree in Rheumatology from USP, Ribeirão Preto, SP, Brazil
VIMedical Student at Universidade Federal do Ceará
VIIChief of the Rheumatology Department of HGF. Collaborating Professor of the Medical School of UECe

Correspondence to

 

 


ABSTRACT

OBJECTIVES: To describe the initial clinical manifestations of Wegener's Granulomatosis (WG) in Brazil.
PATIENTS AND METHODS: Retrospective analysis of six medical records of WG patients followed-up at the Rheumatology Department of Hospital Geral of Fortaleza (HGF), as well as a bibliographic survey of cases of WG in Brazil on LILACS, SciELO, and MEDLINE databases.
RESULTS: The study identified 49 patients, 15 (31%) males and 34 (69%) females. Systemic disease was observed in 35 patients (73%): 28 adults, 5 children, and 2 teenagers. Limited disease was observed in 13 adults and 1 child. The average age of onset in adults was 42.2 years (18 to 65 years). Acute clinical manifestations, with the onset of symptoms less than three months before the diagnosis, were observed in 41% (20/49) of the patients, and the insidious presentation in 59% (29/49) of the patients. The prevalence of the initial clinical manifestations in adults with systemic disease (n = 28) was 64% (18/28), upper airways, 36% (10/28), lungs, 18% (5/28), kidneys, 25% (7/28), eyes, 11% (3/28) skin, 25% (7/28), musculoskeletal, and 7% (2/28), neurological. In adults (n = 13) with limited disease, prevalent symptoms included: upper airway, 84% (10/13), eyes, 23% (3/13), and lungs, 15% (2/13).
CONCLUSION: The prevalence of the initial clinical manifestations of WG in Brazil was similar to that reported in the literature. The lack of specific symptoms may delay diagnosis cases with insidious presentation of the disease and increase the morbidity and mortality in acute disease.

Keywords: Wegener´s granulomatosis, prevalence, clinical manifestations, Brazil.


 

 

INTRODUCTION

Wegener's Granulomatosis (WG) is a necrotizing vasculitis that affects small and medium-size blood vessels with granulomata formation.1 It is one of the most common forms of systemic vasculitis, with a reported annual incidence of 10 cases per one million people1. Its causes are unknown, and it is the prototype of conditions associated with anti-neutrophilic cytoplasmic antibody (ANCA).2 It affects mainly Caucasian individuals, without gender predilection, with a mean age of onset of 41 years.3 Its clinical presentation is divided in limited and systemic;1 the latter is usually associated with more severe disease, characterized by renal involvement, which is predictive of a poor prognosis.2 The clinical presentation can vary, and it may affect several organs. The most common symptoms are related to the upper and lower airways, especially recurring bloody rhinorrhea, rhinosinusitis, and cavitary and nodular lesions in the lungs. Pulmonary manifestations are seen in 45% of the cases, on presentation, and 87%, during the course of the disease.4,5 Ocular involvement in WG can be the initial presentation in 8% to 16% of the cases.6-9

The diagnosis is based on clinical manifestations, histopathological findings compatible with granulomatous necrotizing vasculitis,1 and the presence of ANCA, which, after the discovery of its association with WG by van der Woude et al.,10 allowed the earlier diagnosis and treatment of the disease.11,12 Cytoplasmic ANCA pattern has specificity for WG of up to 98% in the acute phase,13,14 and it seems that its titer is related with disease activity.15-17 Note that, despite of the clinical characteristics and immunopathologic findings, a small percentage of patients with WG can be ANCA negative.18

Due to the small number of Brazilian studies on the initial manifestations of WG, the authors conducted an extensive review of the literature, along with the experience of the Rheumatology Department of HGF in the clinical management of six patients who received the diagnosis of this disorder from June 2005 to August 2008.

 

PATIENTS AND METHODS

Patients

This is a descriptive, transversal study carried out at the Rheumatology Department of Hospital Geral de Fortaleza, through the retrospective analysis of the medical records of six patients with the diagnosis of WG, according to the 1990 criteria of the American College of Rheumatology (ACR).9 Those patients were identified among 535 patients hospitalized over a three-year period.

Review of the literature

Reports of cases of WG in Brazilian patients were searched in the SciELO (1998-2009), LILACS (1985-2009), and Medline (1966-2009) databases. Reports that included the initial clinical manifestations of WG were selected by type of publication (case reports and original studies), language (Portuguese and English), keywords (Wegener's Granulomatosis and clinical manifestations), and country of origin (Brazil). The following parameters were evaluated: gender, age, onset of clinical disease, characterized as acute (less than three months before the diagnosis) or insidious, and type of disease presentation (systemic or limited). Limited disease was defined by the absence of renal involvement. This study was approved by the Ethics Committee of the Institution, under research in humans protocol number 231946.

 

RESULTS

Table 1 shows the demographic and evolutive (gender, age, duration of the disease, and deaths), clinical, and therapeutic characteristics of the six WG patients seen at HGF. Table 2 shows the main results of laboratorial, radiological, and histopathological exams.

The number of WG patients corresponded to approximately 1% of the total number of patients admitted to the Rheumatology Service of HGF in three years. Five female and one male patients with ages between 16 and 55 years were included. Two patients evolved to death. Patient number two was being investigated for bilateral exophthalmia at the Endocrinology Department, with a diagnostic hypothesis of Grave's disease, and had been examined by an ophthalmologist who suspected of orbital pseudotumor (Figure 1A). The patient with the earlier diagnosis (after 10-day evolution) had vasculitis of the lower limbs and pulmonary bleeding (Figure 1 B). Figure 1C shows vasculitis and necrosis of the right hand of patient number one. The type of disease presentation, along with 43 Brazilian patients identified in the literature search, is listed.

 



 

Literature search identified 30 studies that reported initial manifestations of the disease19-48 (Table 3). Forty-nine WG patients, 15 (31%) males and 34 (69%) females, were diagnosed in Brazil; 35 (73%) patients, 28 adults, five children, and two adolescents, had systemic manifestations; limited disease was diagnosed in 13 adults and one child; the mean age of onset of the disease in adults was 42.2 years, ranging from 18 to 65 years. A cute clinical onset, with symptomatology for less than three months before the diagnosis, was observed in 41% (20/49) of the patients; insidious disease affected 59% (29/49) of the patients. In adults with systemic disease (n = 28), the main clinical manifestations, before and at the time of the diagnosis, are shown in Figure 2. Predominant clinical manifestations in patients with limited disease (n = 13) were related to the upper airways in 76% (10/13), eyes in 23% (3/13), and lungs in 15% (2/13) of the cases. Table 4 shows the initial presentation of WG in adults by organs and systems, comparing two Brazilian studies and an international reference.2,19-30,32,35,38-40,42,44,49,50

 

 

 

 

Some particularities of the patients seen at HGF should be mentioned: 1) the first patient developed paresthesia in the lower limbs with electroneuromyography showing axonal mononeuropathy of the posterior tibial nerve, a rare symptom in the initial phase of WG. 2) The diagnosis of patient number two was delayed, evolving from limited to systemic disease, with indolent evolution.11This patient has saddle-nose deformity, which is seen in 3.5 to 7% of the cases.26-30 3) Patient number three was being investigated for six months for hearing loss, had indication for a cochlear implant. The patient developed a granular lesion in the extensor surface of the elbow with a biopsy report compatible with Churg-Strauss granuloma. 4) Patient number four, treated initially for tuberculosis (TB), was being followed-up for five years for WG with several acute relapses. The patient had a new relapse and, based on the small international experience,51,52 she was treated empirically with a biological agent (rituximab). Note that the diagnostic confusion with TB in patients with Wegener's Granulomatosis with pulmonary manifestations is frequently reported in areas endemic for TB.6,30 5) The last two patients had pulmonary hemorrhage, and kidney and respiratory failure, evolving to death. This illustrates the elevated morbimortality of this disease, especially in cases of systemic disease and acute presentation.53

On the evaluation of pediatric WG, which affects patients from one to 18 years of age, three cases had insidious disease, with onset of the initial symptoms more than three months before the diagnosis; two were acute cases; and the last case evolved to death five days after the onset of pulmonary-renal symptoms and positive p-ANCA, without a biopsy to confirm the diagnosis of WG or microscopic polyangiitis. A teenager had polyarthritis and purpura on the hands and sole of the feet for three years, receiving a diagnosis of leukocytoclastic vasculitis before the diagnosis of WG; the patient developed subglottic stenosis and chronic renal failure and remission of the disease after classical WG treatment for one year; the other teenager, seen at HGF, developed pulmonary hemorrhage and died 30 days later.

 

DISCUSSION

Wegener's Granulomatosis has been rarely described in Brazil. The six cases of WG diagnosed at HGF in approximately three years motivated this study.

The literature review revealed a small number of publications, encompassing only 109 Brazilian patients, demonstrating how rare this disorder is in our country; 50 of those cases were reported by the Medical School of USP (from 1985 to 2000), 10 cases by the School of Medical Sciences of UNICAMP (from 1982 to 1991), and 49 patients in this review, included in reports from 1966 to 2009. Their cases were documented in thesis, series of cases, and individual reports.

The investigation of the initial clinical manifestations of WG allowed the following observations: renal involvement, which characterizes systemic disease, has high morbimortality. The lack of specificity of the initial clinical manifestations of WG with insidious presentation gave patients enough time to seek tertiary hospitals for proper investigation, which occurred only in 29/49 (59%) patients in this study. Establishing an adequate diagnosis was difficult in the remaining patients, who had more acute presentations.

The prevalence of upper airways, pulmonary, and kidney symptoms in the initial presentation of systemic WG in adult patients was similar to that of the international literature summarized by Morrow et al.49 in 1999. In a Brazilian study by Antunes & Barbas,2 in 2005, with 50 patients followed-up from 1985 to 2000, symptoms were evaluated at the time of the diagnosis, demonstrating higher prevalence of all clinical manifestations investigated. The report of neurological symptoms in the initial phases of WG in three Brazilian adults could reflect a populational peculiarity, delayed diagnosis in Brazil, or a bias in reporting only cases considered relevant. The incidence of cutaneous manifestations (Table 4) of WG was lower in this cohort than in that of two other Brazilian studies and in the international literature. Musculoskeletal symptoms showed lower frequency, reported in less than 32% of the cases, the lower frequency in the literature. Ocular manifestations at the onset of the disease in 25% of the patients was similar to the reports of the two Brazilian studies and higher than reported by Duna et al.,6 which ranged from 8 to 16%. Those results could also reflect a bias in the documentation of Ophthalmology Departments.

Over a period of seven years, Vecchi et al.46 evaluated five Brazilian children, females, with the diagnosis of WG, demonstrating that the presentation of WG is more severe in this age group due to the high incidence of renal involvement and failure. Hypertension was seen in all five patients, and pneumopathy and hematuria were present from the onset of the symptoms in four children with systemic disease. The time between the onset of the symptoms and diagnosis ranged from 15 days to three years (mean of 18 months). Those results are similar to those reported by Akikusa et al.,54 who evaluated 25 patients with pediatric WG over a 21-year period and observed a male/female ratio of 1:4 and mean duration of symptoms before the diagnosis of two years. Constitutional symptoms were present in 100% of the patients at the onset of the disease. Glomerulonephritis was seen in 88% of the cases, upper airways involvement in 84%, pulmonary symptoms in 80%, and lung nodules and hemorrhage in 44% of the patients.

The diversity of clinical manifestations and type of disease onset (indolent or fulminant) represents a constant diagnostic challenge for rheumatologists. We observed that the prevalence of the initial clinical manifestations of WG in Brazil was similar to that reported in the literature. Note that the lack of specificity of the symptoms could delay the diagnosis, in cases with insidious presentation, and increase morbimortality, in Initial clinical manifestations of Wegener's granulomatosis acute presentations. This indicates the importance of further studies on rare rheumatic diseases, such as WG and other systemic vasculitis, in Brazil. Those studies could facilitate the knowledge of populational peculiarities in each region of the country and compare them to data in the international literature.

 

REFERENCES

1. Stone JH. Wegener granulomatosis. In current rheumatology diagnosis & treatment, 2nd ed. United States of America, Lange Medical Books/McGrawHill; 2007.         [ Links ]

2. Antunes T, Barbas CSV. Granulomatose de Wegener. J Bras Pneumol 2005; 31(1):21-6.         [ Links ]

3. Klippel JH, Dieppe PA. Rheumatology, v. 2, 2nd ed. United States of America. Mosby International; 1998.         [ Links ]

4. Fauci AS, Haynes BF ,Katz P, Wolff SM. Wegener's granulomatosis: prospective clinical and therapeutic experience with 85 patients for 21 years. Ann Intern Med 1983; 98:76-85.         [ Links ]

5. Cordier JF, Valeyne D, Guillevin L, Loire R, Brechot JM. Pulmonary Wegener's granulomatosis: a clinical and imaging study of 77 cases. Chest 1990; 97(4):906-12.         [ Links ]

6. Duna GF, Galperin C, Hoffman GS. Wegener's granulomatosis. Rheum Dis Clin North Am 1995; 21(4):949-86.         [ Links ]

7. Koldingsnes W, Nossent H. Epidemiology of Wegener's Granulomatosis in Nothern Norway. Arthritis Rheum 2000; 43(11):2481-7.         [ Links ]

8. Cid MC. New developments in the pathogenesis of systemic vasculitis. Curr Opin Rheumatol 1996; 12(1):1-11.         [ Links ]

9. Bloch DA, Michel BA, Hunder GC, McShane DJ, Arend WP, Calabrese LH et al. The American College of Rheumatology 1990 Criteria for the Classification of Wegener's Granulomatosis. Arthritis Rheum 1990; 33(8):1101-7.         [ Links ]

10. van der Woude FJ, Rasmussen N, Lobatto S. Autoantibodies against neutrophils and monocytes: tool for diagnosis and marker of disease activity in Wegener's granulomatosis. Lancet 1985; 1:425-9.         [ Links ]

11. Halpern ASR. Vasculites sistêmicas na população geriátrica. Einstein 2008; 6 (supl 1):S55-63.         [ Links ]

12. Falk RJ, Jennette JC. Antineutrophil cytoplasmic autoantibodies with specificity for myeloperoxidase in patients with systemic vasculitis and idiopathic necrotizing and crescentic glomerulonephritis. N Engl J Med 1988; 318:1651-7.         [ Links ]

13. Nölle B, Specks U, Ludemann J, Rohrbach MS, DeRemec RA, Gross WL. Anticytoplasmatic autoantibodies: their immunodiagnostic value. Ann Intern Med 1989; 111(1):28-40.         [ Links ]

14. Homer RJ. Antineutrophil. Cytoplasmic. Antibodies as Markers for Systemic Autoimmune Disease. Clin Chest Med 1998; 19(4):627-39.         [ Links ]

15. Seo P, Stone JH. Large-vessel vasculitis. Arthritis Rheum 2004; 51:128.         [ Links ]

16. Jayne D, Rasmussen N, Andrassy K. A randomized trial of maintenance therapy for vasculitis associated with antineutrophil cytoplasmic autoantibodies. N Engl J Med 2003; 349(1):36-44.         [ Links ]

17. Hoffman GS. Wegener's granulomatosis. Curr Opin Rheumatol 1993; 5(1):11-7.         [ Links ]

18. Jennette CJ, Falk RJ. Small-vessel vasculitis. N Engl J Med 1997; 337:1512-23.         [ Links ]

19. Correa JC, Azevedo AG, Rubens J, Rocha G. Granulomatose de Wegener: análise de dois casos. J Bras Med 1985; 48(6):34-8.         [ Links ]

20. Azevedo LS, Ianhez LE, Sabbaga E, Saldanha LB. Granulomatose de Wegener e transplante renal. Rev Hosp Clin Fac Med Univ São Paulo 1985; 40(2):94-8.         [ Links ]

21. Santiago NM, Santiago CB, Queiroz AC. Granulomatose de Wegener. J Pneumol 1987; 13(2):119-23.         [ Links ]

22. Pedrini H, Fernandes SR, Billis A. Glomerulonefrite granulomatosa com necrose papilar renal em granulomatose de Wegener. J Bras Nefrol 1998; 10(2):75-8.         [ Links ]

23. Pacheco BEM. Granulomatose de Wegener. Rev Imagem (São Paulo) 1988; 10(1):33-5.         [ Links ]

24. Fernandes SR, Moreira HN, Marques Neto JF, Gusmão RJ, Samara AM. Perfuração de septo nasal na granulomatose de Wegener. Folha Med 1992; 104(5):161-5.         [ Links ]

25. Fernandes SR, Furuie SH, Amstalden EM. Granulomatose de Wegener e condrite de pavilhão auricular. Rev Bras Reumatol 1994; 34(4):203-5.         [ Links ]

26. Esteves J, Justo DM, Raskin R, Edelweiss MI, Hemb R. Episclerite como primeira manifestação de Granulomtose de Wegener: relato de caso e revisão de literatura. Rev AMRIGS 1994; 38(2):117-9.         [ Links ]

27. Nascimento VMV, Miranda NE, Branco BC, Sousa Leão A. Granulomtose de Wegener. JBM 1997; 72(6):93-101.         [ Links ]

28. Furtado RN, Maia MB, Azevedo E, Franco M, Andrade LEC. Comprometimento renal e ocular como manifestações iniciais de granulomatose de Wegener. Rev Bras Reumatol 1997; 37(6):343-7.         [ Links ]

29. Skare TL, Zappi DM. Massa intracardíaca em provável caso de granulomatose de Wegener. Arq Bras Cardiol 1998; 71(4):609-11.         [ Links ]

30. Matozo TM, Nakayama R, Ferreira RG, Ota JS, Pereira CA. Granulomatose de Wegener com comprometimento endobrônquico. J Pneumol 1998; 24(3):150-2.         [ Links ]

31. Fernandes NC, Castilho M, Paes C, Maceira J. Granulomatose de Wegener localizada com manifestação ocular: relato de caso. An Bras Dermatol 1998; 73(2):107-10.         [ Links ]

32. Cachapuz JCB, Pereira JCB. Granulomatose de Wegener. Pulmão RJ 1999; 8(2):137-45.         [ Links ]

33. Azevedo FH, Correia CC, Lins O, Coutinho O, Almeida P, Vidal CH. Neuropatia vasculítica na granulomatose de Wegener: relato de caso. Arq Neuropsiquiatr 2001; 59(2A):270-1.         [ Links ]

34. Neviani CB, Carcalho HA, Hossamu C, Aisen S, Nadalin W. Radiation therapy as na option for upper airway obstruction due to Wenener's granulomatosis. Otolaryngol Head Neck Surg 2002; 126(2):195-6.         [ Links ]

35. Rezende CE, Rodrigues RE, Yoshimura R, Uvo IP, Rapoport PB. Granulomatose de Wegener: relato de caso. Rev Bras Otorrinolaringol 2003; 69(2):261-5.         [ Links ]

36. Souza LJ, Gabriel Júnior A, Gicovate Neto C, Bastos DA, Siqueira EW. Granulomatose de Wegener e mononeurite múltipla. Rev Soc Bras Clin Med 2003; 1(5):137-40.         [ Links ]

37. Gomides AP, Costa GL ,Pena CR, Rosário EJ, Guimarães PN, Pádua PM. Paquimeningite hipertrófica e parotidite: manifestações raras da granulomatose de Wegener. Rev Bras Reumatol 2004; 44(4):308-12.         [ Links ]

38. Guidolin F, Magro CE, Bezerra Neto F, Skare TL. Granulomatose de Wegener e estenose subglótica: descrição de caso. Rev Bras Otorrinolaringol 2004; 70(3):419-22.         [ Links ]

39. Ghanem RC, Chang N, Aoki L, Santo RM, Matayoshi S. Vasculitis of the lacrimal sac wall in Wegener granulomatosis. Ophthal Plast Reconstr Surg 2004; 20(3):254-7.         [ Links ]

40. Larrubia AFG, Keiralla LCB, Cardoso MB, Matos AC, TeixeiraCO, Teixeira MAB. Granulomatose de Wegener associada a tireoidite de Hashimoto: correlação anátomo-clínica em caso com necropsia. Rev Cienc Med (Campinas) 2004; 13(3):273-9.         [ Links ]

41. Monteiro ML, Borges WI, do Val Ferreira Ramos C, Lucato LT, Leite CC. Bilateral optic neuritis in wegener granulomatosis. J Neuroophthalmol 2005; 25(1):25-8.         [ Links ]

42. Schmidt L, Burkiewicz CJ, Silva MB, Skare TL. Esclerite como manifestação inicial de granulomatose de Wegener: descrição de caso. Rev Bas Reumatol 2007; 47(2):145-7.         [ Links ]

43. Gomides APM, Rosário EJ, Borges HM, Vignoli MA, Pádua PM, Sousa RCA. Perda auditiva neurossensorial em pacientes com granulomatose de Wegener: relato de três casos e revisão de literatura. Rev Bras Reumatol 2006; 46(3):234-6.         [ Links ]

44. Pereira IC, Zacharias LC, Zagui R, Santo R, Matayoshi S. Granulomatose de Wegener: relatos de casos. Arq Bras Oftalmol 2007; 70(6):1010-5.         [ Links ]

45. Scalcon MRR, Pereira IA, Rachid Filho A, Paiva ES. Manifestação otológica localizada em paciente com granulomatose de Wegener. Rev Bras Reumatol 2008; 48(4):253-5.         [ Links ]

46. Vecchi AP, Silva CAA, Liphaus BL, Campos LMMA, Fujimura MD, Groszmann VHKK et al. Granulomatose de Wegener na faixa etária pediátrica: relato de cinco casos e revisão da literatura. Rev Bras Reumatol 2001; 41(6):337-46.         [ Links ]

47. Blanco Filho F, Ernesto LC, Rosa MA, Stuginski LA, Zlochevsky ER, Blanco F. Rapidly progessive antineutrophil cytoplasmic autoantibodies associated with pulmonary-renal syndrome in a 10-year-old girl. São Paulo Med J 2001; 119(1):29-32.         [ Links ]

48. Machado MC, Melo EC, Sá PM, Silva DA, G Júnior AR, Brasil OO. Estenose subglótica como manifestação clínica da granulomatose de Wegener em adolescentes: relato de caso e revisão de literatura. Rev Bras Otorrinolaringol 2003; 69(5):709-13.         [ Links ]

49. Morrow J, Nelson L, Watts R, Isenberg D. Autoimmune rheumatic disease, 2nd ed, New York: Oxford Univerity Press; 1999.         [ Links ]

50. Fernandes SRM, Samara AM. Granulomatose de Wegener: análise clínica e histopatológica. Rev Bras Reumatol 1991; 31(6):218-22.         [ Links ]

51. Ferraro AJ, Day CJ, Drayson MT, Savage CO. Effective therapeutic use of rituximab in refractory Wegener's granulomatosis. Nephrol Dial Transplant 2005; 20(3):622-5.         [ Links ]

52. Stone JH. Vasculitides C. The antineutrophil cytoplasmic antibodyassociated vasculitedes: Wegener's granulomatosis, microscopic polyangiitis, and the Churg-Strauss Syndrome. In: Primer on the Rheumatic Diseases. 13th ed, New York: Springer; 2007.         [ Links ]

53. Gordon M, Luqmani RA, Adu D, Greaves I, Richards N, Michael J et al. Relapses in patients with a systemic vasculitis. Q J Med 1993; 86(12):779-89.         [ Links ]

54. Akikusa JD, Schneider R, Harvey EA, Hebert D, Thorner PS, Laxer RM et al. Clinical features and outcome of pediatric Wegener's granulomatosis.Arthritis Rheum 2007; 57(5):837-44.         [ Links ]

 

 

Correspondence to:
Carlos Ewerton Maia Rodrigues
Rua Doutor Gilberto Studart, 955, apartamento 801
CEP: 60190-750. Papicu - Fortaleza - CE
Tel.: 55-85-3265-7266, 55-85-8891-1796
E-mail: carlosewerton@hotmail.com

Received on 06/01/2009
Approved on 01/20/2010
We declare no conflict of interest

 

 

Rheumatology Department of Hospital Geral de Fortaleza

Creative Commons License Todo el contenido de esta revista, excepto dónde está identificado, está bajo una Licencia Creative Commons