Poliangeíte microscópica é uma forma de vasculite sistêmica de pequenos vasos, associada aos anticorpos anticitoplasma de neutrófilos, que preferencialmente acomete vênulas, capilares e arteríolas, e que pode, entretanto, envolver artérias e veias. Está entre as vasculites sistêmicas primárias de pequenos vasos mais freqüentes, e pode ter apresentação clínica indistinguível da granulomatose de Wegener e da síndrome de Churg-Strauss. Estas vasculites de pequenos vasos são histologicamente semelhantes e podem ser diferenciadas pela presença de granulomas na granulomatose de Wegener, ou de quadro clínico-funcional de asma na síndrome de Churg-Strauss. Relata-se o caso de um paciente do sexo masculino de 66 anos com poliangeíte microscópica com hemorragia alveolar difusa como forma de apresentação clínica, com ênfase no diagnóstico diferencial com outras vasculites pulmonares de pequenos vasos.
Poliangeíte microscópica; Hemorragia alveolar; Vasculites pulmonares
Microscopic Polyangiitis is a form of Anti-Neutrophil Cytoplasmic Antibody (ANCA)- associated small-vessel vasculitis that preferentially involves venules, capillaries and arterioles and may also involve arteries and veins. It is one of the most common primary systemic small-vessel vasculitis. Its clinical presentation is not distinguishable from the Wegener’s granulomatosis (WG) and the Churg-Strauss syndrome (CSS). These types of small-vessel vasculitis are histologically similar and can be differentiated by the presence of granulomatous inflammation in WG or asthma in CSS. The case of a 66-year-old man with microscopic polyangiitis presenting with alveolar hemorrhage is reported with a discussion of the differential diagnosis of other types of pulmonary small-vessel vasculitis.
Microscopic polyangiitis; Alveolar hemorrhage; Pulmonary vasculitis
Microscopic Polyangiitis with Alveolar Hemorrhage * * Work carried out:Pneumology Service Hospital Universitário de Santa Maria, Universidade Federal de Santa Maria ; Pathology Department, Faculdade de Medicina, Universidade de São Paulo USP.
José Wellington Alves dos Santos(TE SBPT); Gustavo Trindade Michel; Carlos Eurico da Luz Pereira(TE SBPT); Vera Luiza Capelozzi; Jader Nascimento Mileto; Cleber Antonio Fiorini
Microscopic Polyangiitis is a form of Anti-Neutrophil Cytoplasmic Antibody (ANCA)-associated small-vessel vasculitis that preferentially involves venules, capillaries and arterioles and may also involve arteries and veins. It is one of the most common primary systemic small-vessel vasculitis. Its clinical presentation is not distinguishable from the Wegener's granulomatosis (WG) and the Churg-Strauss syndrome (CSS). These types of small-vessel vasculitis are histologically similar and can be differentiated by the presence of granulomatous inflammation in WG or asthma in CSS. The case of a 66-year-old man with microscopic polyangiitis presenting with alveolar hemorrhage is reported with a discussion of the differential diagnosis of other types of pulmonary small-vessel vasculitis.
Key words: Microscopic polyangiitis. Alveolar hemorrhage. Pulmonary vasculitis
Acronyms and abbreviations utilized in this paper
MP Mycroscopic polyangiitis
ANCA Anti-Neutrophil Cytoplasmic Antibody
WG - Wegener Granulomatosis
CSS Churg Strauss Syndrome
Microscopic Polyangiitis is a systemic pauci-immune necrotizing vasculitis, in general associated to ANCA Anti-Neutrophil Cytoplasmic Antibody, - which primarily affects the small vessels (capillaries, venules and arterioles) 1-4. Necrotizing glomerulitis with development of crescents and hemorrhagic pulmonary capillaritis are frequent manifestations being the most important causes of the diseases morbidity and mortality. Incidence of MP is of approximately 1:1000.000 with a slight prevalence in the male gender and a mean age of 50 years for onset of symptoms, although individuals of any age may be affected 1,3,4.
A patient of the male gender, Caucasian, 66 years old and former smoker (60years/pack) sought medical care with a history of dyspneia and productive cough with scarce mucoid sputum for the past 4 months. In the last 30 days, presented with repeated episodes of hemoptysis and weight loss of 3 kg in this period. Upon admission chest X-ray disclosed diffuse infiltrate with interstitial and alveolar pattern. Blood tests disclosed anemia (hemoglobin 9.5 g/dl.) Qualitative urinalysis showed proteinuria, over 50 blood cells per field, and hyaline cylinders with inclusion of blood cells. Endogenous creatinine clearance was of 25 ml/min 1.73 m2 of body surface and 24 hours proteinuria was of 2.56g. Anti nuclear factor, LE cells trial, rheumatoid factor VDRL and testing for antibodies anti-DNA and anti-sm were negative. Echocardiogram and kidney ultrasound did not disclose changes, X-rays and CT scan of the maxillary sinuses were normal. Biopsy of the kidney carried out eight days after hospital admission showed advanced sclerosis with formation of crescents and immunofluorescence of the specimen showed few linear deposits of IgG. ANCA investigation carried out twelve days after admission by using indirect immunofluorescence was positive and disclosed a perinuclear pattern (p-ANCA). Computerized tomography of the chest showed areas with a bilateral ground glass appearance, with some confluent, dense micronodules (figure 1). The patient remained clinically stable and on the thirteenth hospital day was submitted to lung biopsy by videothoracoscopy. On the day following the procedure the patient progressed to diffuse alveolar hemorrhage and respiratory failure. Notwithstanding onset of therapy with high doses of corticosteroids (500mg/day of metylprednisolone and cyclophosphamide (150 mg/day) patient died 48 hours after worsening of the clinical picture. The histo-pathological study of the surgical specimen obtained was compatible with small vessels pauci-immune vasculitis (figure 2). Because the patient did not present histo-pathological evidence of granulomatous disease, clinical picture of asthma and had normal pulmonary function tests, diagnosis of microscopic polyangiitis was confirmed.
MP is a form of small vessels systemic vasculitis characterized by absence or scarcity of immunovascular deposits and associated with ANCA in approximately 90% of the cases 3.
Clinical manifestations are varied and not specific. Hematuria, hemoptysis, purpura, peripheral neuropathy, abdominal pain, gastrointestinal hemorrhage, sinusitis, fever, weight loss, myalgias, arthralgias are frequent manifestations 5, 6, 7. Alveolar hemorrhage occurs in up to 30% of the cases and is normally associated to extra-thoracic manifestations, mainly of the kidneys (97%). Muscle and joint complaints may arise years before the appearance of kidney and/or lung alterations. However, diffuse alveolar hemorrhage has been described as the only manifestations in patients with MP 6. When it presents with diffuse alveolar hemorrhage, the main symptoms are usually severe dyspneia (90%), cough (90%) and hemoptysis (79%) 6.
Laboratory findings often include anemia, hematuria, proteinuria, cylyndruria and loss of the renal function. Initially chest X-ray may show bilateral alveolar opacities suggestive of alveolar hemorrhage or, while the disease is progressing, diffuse reticulonodular infiltrate.6
In a study of 29 patients with MP and alveolar hemorrhage, at chest X-ray Lauque and collaborators found an alveolar pattern in 28 (97%), with bilateral involvement in 26 (90%) of the cases. In this study, computerized tomography of the thorax, carried out in 18 cases disclosed, similar to the case in question, bilateral involvement in 100% of the patients, with a prevalence of consolidations (67%) and a ground glass appearance (61%). Considering that the finding of bilateral alveolar lavage is not specific, progressively hemorrhagic bronchoalveolar lavage ands higher diffusion of carbon monoxide - DlCO - may support diagnosis
Microscopic polyangiitis has been reported as being the main cause of renal-pulmonary syndrome 8 and must be taken into account in patients with hemoptysis that present alteration of the renal function or of the urinary sediment. However, to achieve a diagnostic substantiation of MP with pulmonary involvement, other forms of vasculitis that progress with a renal pulmonary syndrome must be excluded. 2, 3, 7
The histo-pathological study attests to small vessels vasculits, although, in some cases, larger arteries may be involved. The vascular basic lesion of MP consists in a segmental vascular necrosis with neutrophils and monocytes infiltrate with scarcity or absence of immune deposits (pauci-immune). The kidney is the target organ, most often injured by MP 1, 4, 9 and is affected in approximately 90% of the cases. The most frequent renal lesion is necrotizing glomerulonephritis with formation of crescents and the glomerular lesion detected at histo-pathological exam is identical in MP, Wegeners Granulomatosis (WG) and the Churg-Strauss Syndrome (CSS).
The patient in this case presented initially with pulmonary clinical manifestations having a four months evolution, thereby presence of infectious disease as cause of the alveolar hemorrhage (i.e. leptospirosis, hantavirosis) seemed unlikely. Furthermore, upon admission the patient presented with impairment of the renal function.
ANCAs are antibodies with specificity for cytoplasm constituents of monocytes and neutrophils. It remains uncertain whether these antibodies are directly involved in the pathogenesis of vasculitis or are merely an associated phenomenon 9
ANCAs translate into a useful diagnostic marker when there is a clinical suspicion of small vessels vasculitis. 3, 5 In patients with clinical suspicion of small vessels vasculitis the test has a positive predictive value of 90%, which does not rule out histo-pathological evaluation. Nevertheless, a negative test does not completely exclude a series of diseases 10 .In patients with poor clinical evidence, the test has a negative predictive value of 99% 8. MP must be differentiated mainly from WG and CSS as they are also small vessels pauci-immune vasculitis associated to ANCA and with identical pathologic aspects. Any type of ANCA is prevalent in WG and the p-ANCA in CSS 3. In MP there is a prevalence of the p-ANCA pattern, however, the c-ANCA can also be proven 5.
Once diagnosis of small vessels pauci-immune vasculitis has been established, associated to the ANCAs, the sequence of diagnostic investigation must be determination of a specific diagnosis 2.3.11. By definition, patients with MP have no granulomatous inflammation in the lungs or in other organs. The presence of small vessels granulomatous inflammation must be indicative of WG or CSS 2. When the patient has vasculitis associated together with evidence of necrotizing granulomatous inflammation, peripheral eosinofilia, clinical history and functional tests agreeing with asthma, the proper diagnosis is CSS. If the patient does not present evidence of granulomatous inflammation or asthma, the correct diagnosis is MP. Clinical findings such as nodules or pulmonary cavities or destructive bone lesions in the upper airways may be used as evidence of granulomatous inflammation instead of requiring tissue confirmation 9. Diagnosis of MP is Therefore by exclusion.
In the case of clinical suspicion of vasculitis, mainly when the patient exhibits alveolar hemorrhage and renal dysfunction, onset of treatment cannot be delayed. High doses of corticosteroids (metylprednisolone 7mg/kg/day) and cyclophosphamide (n 2 mg/kg/day) are the elected treatment to induce remission of MP 3, 4, 5. After remission of the disease doses of the corticosteroids are reduced until withdrawal which usually takes place in three to five months. Cyclophosphamide is continued for 6 to 12 months and can be replaced by azatiprine after remission. Morbidity and mortality depend directly on the early instatement of therapy 5. Early mortality in MP increases in presence of small vessels vasculitis involving the lungs, which in this case only became evident after worsening of the clinical picture. More than 25% of the patients die during the first episode of diffuse alveolar hemorrhage such as in the reported case. notwithstanding adequate treatment. In those that survive, response to treatment is good, but recurring episodes may be expected. Pulmonary fibrosis and obstructive pulmonary disease have been described as chronic complications of recurring episodes of diffuse alveolar hemorrhage 7.
Submitted for publication on May/5/03.
Approved after review on July/30/03
- 1. Savage CO, Winearls CG, Evans DJ, Reis AJ, Lockwood CM. Microscopic polyarteritis: presentation, pathology and prognosis. Q J Med 1985; 56:467-83.
- 2. Jennette JC, Falk RJ, Andrassy K, Bacon PA, Churg J, Gross WL, et al. Nomenclature of systemic vasculitis: the proposal of an international consensus conference. Arthritis Rheum 1994;37:187-92.
- 3. Jennette JC, Falk RJ. Small vessel vasculitis. N Engl J Med 1997;337:1512-23.
- 4. Guillevin L, Durand-Gasselin B, Cevallos R, Grayraud M, Lhote F, Callard P, et al. Microscopic polyangiitis: clinical and laboratory findings in eighty-five patients. Arthritis Rheum 1999;42:421-30.
- 5. Jennette JC, Thomas DB, Falk RJ. Microscopic polyangiitis (microscopic polyarteritis). Semin Diag Pathol 2001;18:3-13.
- 6. Lauque D, Cadranel J, Lazor R, Pourrat J, Ronco P, Guillevin L, et al. Microscopic polyangiitis with alveolar hemorrhage. A study of 29 cases and review of the literature. Medicine 2000;79:222-33.
- 7. Marvin IS, Kevin KB. Small vessel vasculitis of the lung. Thorax 2000;55:502-10.
- 8. Niles JL, Bottinger EP, Saurina GR, Kelley KJ, Pan G, Collins AB, et al. The syndrome of lung hemorrhage and nephritis is usually an ANCA-associated condition. Arch Intern Med 1996;156:440-5.
- 9. Jennette JC, Falk RJ. The pathology of vasculitis involving the kidney. Am J Kidney Dis 1994;24:130-41.
- 10. Lim LCL, Taylor JG, Schmitz JL, Folds JD, Wilkman AS, Falk RJ, et al. Diagnostic usefulness of antineutrophil cytoplasmic autoantibody serology: Comparative evaluation of commercial indirect fluorescent antibody kits and enzyme immunoassays kits. Am J Clin Pathol 1999;111:363-9.
- 11. Sorensen SF, Slot O, Tvede N, Petersen J. A prospective study of vasculitis patients collected in a five year period: evaluation of the Chapel Hill nomenclature. Ann Rheum Dis 2000;59:478-82.
CorrespondingJosé Wellington Alves dos SantosRua Venâncio Aires 2020/403, CentroZip Code 97010-004, Santa Maria, RSTel (55) 220 8585
Work carried out:Pneumology Service Hospital Universitário de Santa Maria, Universidade Federal de Santa Maria; Pathology Department, Faculdade de Medicina, Universidade de São Paulo USP.
Publication in this collection
08 June 2004
Date of issue
05 May 2003
07 July 2003