Pulmonary fibrosis predating microscopic polyangiitis by seven years
ABSTRACT A 63-year-old man, ex-smoker with renal failure of recent onset was admitted at the respiratory department with massive haemoptysis. Previous X-rays and CT scans showed pulmonary fibrosis of seven-year duration. Subsequently, he developed high fever, large haemoptysis, new infiltrates and respiratory failure despite broad-spectrum antibiotic treatment. Antineutrophilic antibodies of the perinuclear type with specificity against myeloperoxidase were detected and microscopic polyangiitis was diagnosed. Immunosuppressive treatment with methylprednisolone pulses and cyclophosphamide was started with initially favorable response, but later the patient developed a hospital-acquired pneumonia which was treated successfully with meropenem. As pulmonary haemorrhage recurred, he was transferred to intensive care for plasmapheresis which was considered the last treatment option. Unfortunately he died from septic shock.ConclusionAsymptomatic pulmonary fibrosis can predate microscopic polyangiitis by several years and is associated with unfavorable prognosis of the vasculitis. Appreciation of this finding would lead to faster diagnosis and better management of these patients.
- [Show abstract] [Hide abstract]
ABSTRACT: Microscopic polyangiitis (MPA) is one of the vasculitides that is included in the pulmonary renal syndromes. Pathologically, MPA has been defined as necrotizing vasculitis with few or no immune deposits, primarily affecting small vessels including arterioles, venules, or capillaries. Pulmonary interstitial fibrosis (PIF) as an accompanying manifestation in MPA has not been widely appreciated. In the present study, we report six cases of MPA at our institution with radiographic evidence of PIF that was apparent before any treatment was administered. All had biopsy evidence of renal disease that was consistent with MPA as well as positive serum perinuclear antineutrophilic cytoplasmic antibody titers. Hemoptysis was observed in approximately one half of the patients. As determined by CT of the chest, PIF was detected in all of the patients and was often present years before a diagnosis of MPA was made. We conclude that PIF may occur as a pulmonary manifestation of MPA. Further appreciation of this finding may lead to more data with respect to the incidence of PIF in MPA, and to a better understanding of the mechanisms that are involved in the development of this finding.Chest 02/2003; 123(1):297-301. · 7.13 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: To retrospectively analyze the clinical symptoms, laboratory findings, and outcomes in patients with microscopic polyangiitis (MPA) who were enrolled in various clinical trials conducted by the French Vasculitis Study Group. A cohort of 85 patients meeting the Chapel Hill criteria for MPA participated in the study. Seventy-one of them were included in prospective therapeutic trials. Eighty-one diagnoses were biopsy proven. In the other patients, diagnosis was based on clinical findings. Forty-seven men and 38 women, with a mean +/- SD age of 56.8 +/- 14.6 years, met the criteria for MPA. Their main clinical symptoms were renal manifestations (78.8%), weight loss (72.9%), skin involvement (62.4%), fever (55.3%), mononeuritis multiplex (57.6%), arthralgias (50.6%), myalgias (48.2%), hypertension (34.1%), lung involvement (24.7%; alveolar hemorrhage 11.8%), and cardiac failure (17.6%). The mean +/- SD serum creatinine level before treatment was 2.59 +/- 2.96 mg/dl; 47 patients had renal insufficiency (serum creatinine > 1.36 mg/dl). Eight patients underwent dialysis at the time of diagnosis, and long-term dialysis was necessary for 10 patients. Antineutrophil cytoplasmic antibodies (ANCA) were present in 38 of 51 patients (74.5%), of whom 33 had a perinuclear staining pattern (pANCA) and 5 had a cytoplasmic pattern. Antibodies to proteinase 3 were present in 4 patients and antibodies to myeloperoxidase were detected in 31, as determined by enzyme-linked immunosorbent assay. Of the 30 patients who underwent renal and celiac angiography, 4 had microaneurysms. Of the 29 patients (34.1%) who had relapses, 8 died during or after the relapse. During followup, 28 of the 85 patients (32.9%) died. The mean +/- SD duration of followup of the group was 69.9 +/- 60.6 months. Deaths were less frequent when patients had been treated with steroids and immunosuppressive drugs (13 patients [24.1%]) than with steroids alone (15 patients [48.4%]) (P < 0.01). The 5-year survival rate was 74%. This study demonstrated that MPA is a multisystemic disease in which renal symptoms are frequent, but the disease is also associated with general symptoms, arthritis, mononeuritis multiplex, and other manifestations that are also seen in various vasculitides. The rarity of abnormal angiogram findings and the high frequency of pANCA are characteristic of MPA. In most cases, the outcome is comparable with those of other systemic vasculitides, but relapses are frequent.Arthritis & Rheumatology 04/1999; 42(3):421-30. · 7.87 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: Pulmonary-renal syndrome (PRS) is a combination of diffuse pulmonary hemorrhage and glomerulonephritis. Pulmonary-renal syndrome is not a single entity and is caused by a variety of conditions, including Goodpasturés syndrome associated with autoantibodies to the glomerular and alveolar basement membranes, various forms of primary systemic vasculitis associated with serum positivity for antineutrophil cytoplasmic antibodies (ANCA), cryoglobulinemia, systemic lupus erythematosus, systemic sclerosis, antiphospholipid syndrome, environmental factors, and drugs. The majority of cases of PRS are associated with ANCAs. The antigen target in Goodpasturés syndrome is the alpha-3 chain of type IV collagen. The antigen target in PRS associated with systemic vasculitis is proteinase-3 and myeloperoxidase. Pulmonary-renal syndrome has been observed from the first to the ninth decade of life. The widespread adoption of serologic testing performed in an appropriate clinical context hopefully will limit diagnostic delay. The goals of treatment in PRS are to remove the circulating antibodies, to stop further production of autoantibodies, and to remove any antigen that stimulates antibody production. Treatment is based on plasmapheresis, steroids, and cyclophosphamide; however, infections are frequent contributors to death, and less toxic alternatives may improve outcome and prognosis resulting in a long-term survival. The degree of renal function and the percent of crescents on renal biopsy are better predictors of outcome. Renal transplantation can be safely carried out in PRS.Current Rheumatology Reports 05/2003; 5(2):107-15. · 2.45 Impact Factor
Pulmonary fibrosis predating microscopic polyangiitis by seven years
Angeliki M. Tsimogianni*, Magda Stratiki, Grigoris Stratakos, Spyros Zakynthinos, Paraskeyi Katsaounou
Department of Critical Care and Pulmonary Services, General Hospital Evangelismos, School of Medicine, National and Kapodistrian University of Athens,
45-47 Ipsilantou Street, Athens, Greece
a r t i c l e i n f o
Received 21 November 2009
Accepted 15 December 2009
a b s t r a c t
A 63-year-old man, ex-smoker with renal failure of recent onset was admitted at the respiratory
department with massive haemoptysis. Previous X-rays and CT scans showed pulmonary fibrosis of
seven-year duration. Subsequently, he developed high fever, large haemoptysis, new infiltrates and
respiratory failure despite broad-spectrum antibiotic treatment. Antineutrophilic antibodies of the
perinuclear type with specificity against myeloperoxidase were detected and microscopic polyangiitis
was diagnosed. Immunosuppressive treatment with methylprednisolone pulses and cyclophosphamide
was started with initially favorable response, but later the patient developed a hospital-acquired
pneumonia which was treated successfully with meropenem. As pulmonary haemorrhage recurred, he
was transferred to intensive care for plasmapheresis which was considered the last treatment option.
Unfortunately he died from septic shock.
Conclusion: Asymptomatic pulmonary fibrosis can predate microscopic polyangiitis by several years and
is associated with unfavorable prognosis of the vasculitis. Appreciation of this finding would lead to
faster diagnosis and better management of these patients.
? 2009 Elsevier Ltd. All rights reserved.
? To emphasize the fact that pulmonary fibrosis may predate
microscopic polyangigitis by several years.
? That patients with vasculitis may have an indolent course
initially followed by a fulminant course.
? All patients with renal failure should undergo investigations to
reveal the underlying cause.
Microscopic polyangiitis (MPA) is a rare disease with a mean age
of 50 years at presentation.1The major clinical manifestations
are:2,3Rapidly progressive glomerulonephritis, fever, rigors, weight
loss, arthralgia/myalgia, mononeuritis multiplex, pulmonary hae-
morrhage, haemoptysis or pulmonary fibrosis. The diagnosis is
based on renal/lung biopsy or on clinical symptoms ? positive
antineutrophilic cytoplasmic antibodies (ANCA) testing.2,4The
majority of patients (50–80%) are ANCA positive, usually of the
perinuclear type with activity against myeloperoxidase (MPO).
Interstitial pulmonary fibrosis can predate the vasculitis by
some years and is possibly attributed to subclinical episodes of
alveolar haemorrhage. These patients have a worse prognosis5,6
with sepsis being the commonest cause of death. In this paper we
present a case of pulmonary fibrosis that predated the onset of
vasculitis by seven-years. The patient was asymptomatic until the
onset of vasculitis and subsequently he had a fulminant course. As
far as we know this long interval between the appearance of
pulmonary fibrosis and vasculitis onset is unusual as well as this
2. Case report
In October 2008, a 63-year-old man was admitted at the respi-
ratory department of a tertiary hospital with 2-days history of
major haemoptysis. The patient was a heavy ex-smoker (160 pack/
years) without previous respiratory complaints although his old
Chest radiographs-CTs revealed an established interstitial pattern
since 2001 compatible with pulmonary fibrosis (Figs.1 and 2). Two
months earlier the patient presented at the renal department with
renal impairment, no biopsy was done as his disease was consid-
ered end-stage and was started on renal replacement therapy, his
laboratory findings on that admission are presented in Table 1.
On clinical examination the patient looked fairly well. He had
marked clubbing and fine end-inspiratory bibasal crackles. His
* Corresponding author. Department of Critical Care and Pulmonary Services,
General Hospital ‘‘Evangelismos’’, School of Medicine, National and Kapodistrian
University of Athens, 3 Ploutarhou Str., 10675 Athens, Greece. Tel.: þ30 210
9944013; fax: þ30 210 7239127.
E-mail addresses: firstname.lastname@example.org, email@example.com (A.M. Tsimogianni).
Contents lists available at ScienceDirect
Respiratory Medicine CME
journal homepage: www.elsevier.com/locate/rmedc
1755-0017/$36.00 ? 2009 Elsevier Ltd. All rights reserved.
Respiratory Medicine CME 3 (2010) 207–210
Blood Pressure was 150/90 mmHg, Heart rate ¼ 112/min,
Temperature ¼ 36.2?C. His arterial blood gazes on air were: PaO2:
82 mmHg, PaCO2: 41 mmHg, Ph: 7.40, HCO3: 25 mmol/l. His labo-
ratory findings on present admission are shown in Table 2 and his
chest radiograph and CTs are depicted in Figs. 3 and 4.
The patient was treated conservatively and a bronchoscopy was
undertaken which revealed a small bleeding mucosal lesion in left
main bronchus and a clot obstructing the lower lingular segmental
bronchus (Fig. 5). After bronchoscopy the patient developed fever
(38.5?C) and worsening haemoptysis. Mantoux was positive at
13 mm. The lack of response to initial antibiotic treatment (3rd
generation cephalosporin) with increase in CRP to 7.5 mg/dl leaded
to upgrade his antibiotic treatment to carbapenem, linezolide and
kinolone. As an old echo was suspicious for a right-atrium mass,
a transesophageal echo was performed which was unremarkable.
Direct sputum and bronchoscopy washing specimen were negative
for acid fast bacilli as well as all sputum, blood, urine and washings
cultures. A skin-muscle-vessel biopsy was performed which did not
show any specific changes. A new chest radiograph was similar to
the admission one and a new bronchoscopy (9 days after first-one)
did not show any endobronchial lesions.
Two weeks later the patient deteriorated suddenly with the
development of acute dyspnoea, swelling of the left calf and
respiratory failure, PaO2: 52 mmHg, PaCO2: 28 mmHg, Ph: 7.51,
HCO3: 24 mmol/l (fiO2: 21%). Large haemoptysis occurred with
significant drop in haematocrit from 32% to 23% and his chest
radiograph showed new infiltrates and pleural effusions. Pulmo-
nary embolism was ruled out, fluid overload was managed and
eventually the diagnosis of pulmonary haemorrhage was made.
The serologic investigations revealed positive P-ANCA: 1:160 with
activity against myeloperoxidase (MPO: 32.5 U) and microscopic
polyangiitis was diagnosed.
The patient was started on immunosuppressive treatment with
pulse Methylprednizolone1 g for 5 days and cyclophosphamide
0.5 g/m2and subsequently Prezolon 1 mg/kg with Isoniazid
prophylaxis. He responded fairly well with progressive improve-
ment to his oxygenation and temperature although haemoptysis
continued. Unfortunately 10 days later, the patient deteriorated
again with worsening dyspnoea, fever and [ WBC: 11,180 K/ul (N:
93%), [ CRP: 8 mg/dl and radiological deterioration which was
attributed to hospital-acquired pneumonia and was started on
empirical treatment with meropenem, linezolide and colistine. A
3rd bronchoscopy was undertaken, BAL was not getting progres-
sively more haemorrhagic and was CMV (?), PCP (?), B Koch (?).
BAL culture grew: Klebsiella pneumoniae S Meropenem.
A week later, while the patient still myelosuppressed the
pulmonary haemorrhage recurred and was transferred to Intensive
Care Unit for plasmapheresis which was considered the last
Fig. 1. Routine chest radiogram of the patient in 2001.
Fig. 2. HRCT in 2002.
Laboratory findings on admission in renal department.
? Hct: 27.4%, Hb: 9.4 g/dl,WBC: 6900 K/ml (N: 54%), PLT: 431.000 K/ml,
INR: 1.1, Fibrinogen: 555 mg/dl
? CRP: 1.4 mg/dl, Glu: 107 mg/dl, Urea: 239 mg/dl, Creat: 8.8 mg/dl,
Na: 127 mmol/l, K: 5.3 mmol/l, Bil: 0.38 mg/d lALP: 89 U/L, g-GT: 51 U/L,
Uric acid: 8.3 mg/dl, Ca: 7.6 mg/dl, P: 5.39 mg/dl SGOT: 28 U/L, SGPT:
15 U/L, LDH: 311 U/L, CPK: 215, CPK-MB: 21 U/L.
? Paraprotein in urine was not detected.
? Microscopic evaluation of urine: EB: 1006, Ph: 7, Protein: 2þ, Hb: 2þ
? HIV (?), HbsAg (?), anti-HCV (?)
? C3: 94 mg/dl, C4: 25.7 mg/dl
? Chest radiograph showing a reticulonodular pattern. A computed
tomography was prescribed.
A.M. Tsimogianni et al. / Respiratory Medicine CME 3 (2010) 207–210 208
treatment option. Four courses were performed with initial stabi-
lization of his condition but 13 days later he died from septic shock.
In the present paper, we presented the case of a 63-year-old
man with microscopic polyangiitis with presenting manifestation
pulmonary fibrosis followed seven-years later by end-stage renal
impairment and alveolar haemorrhage. MPA is a rare small vessel
necrotic vasculitis with mean age of 50 years at presentation,1,4as
in our case. What is actually unusual in our patient is the clinical
course, he developed first pulmonary fibrosis, seven-year later
renal failure, soon afterwards haemoptysis followed by fulminant
course of the vasculitis with alveolar haemorrhage and constitu-
tional symptoms. In the literature, several cases of pulmonary
fibrosis have been described that presented concomitantly or pre-
dated the other features of vasculitis for months or few years.5–10
The interval between fibrosis and the appearance of the other
vasculitic symptoms almost never reached 7 years. What is also
surprising is the excellent functional status of the patient who did
not pursue to further investigations in opposition to previous
reports.5,6The prominent symptom of our patient was the alveolar
haemorrhage which is a relatively unusual manifestation of
microscopic polyangiitis appearing in 12–29% of patients and is
associated with worse prognosis.1–3,11
One third of patients with MPA succumb to the disease2and
unfortunately our patient was one of them. The delayed diagnosis
could have contributed to the unfavorable outcome but looking at
the literature our patient had several adverse prognostic factors: He
presented with pulmonary fibrosis which is a poor prognostic
factor; Had end-stage renal failure when he presented to the renal
department; Had significant proteinuria; and his major symptom
was pulmonary haemorrhage which is an uncontestable poor
prognostic factor, increases the risk of death by 9 times.1–3,5He died
from sepsis, the commonest cause of death in these patients.
Making an appraisal of our patient management, we could first
criticize that no further investigations were performed when the
interstitial pattern was first noticed, possibly because he was
asymptomatic. Furthermore, when he presented at the renal
department no biopsy was done as his renal failure was considered
end-stage and biopsy could be nondiagnostic. There was also
a delay in diagnosis on present admission because initial bron-
choscopy findings leaded towards a specific endobronchial lesion
and anyway the serologic investigations in our institution take
a considerable amount of time. Subsequent bronchoscopies were
helpful as they clarified the issue and differentiated haemorrhage
from infection. Concerning the immunosuppressive treatment
prescribed it was in agreement with most protocols.1,2,4,11,12Plas-
mapheresis was performed in our patient with MPA and end-stage
renal impairment possibly late but anyway its role in patients
management is controversial as no survival benefit has been
Limitations of our report are first of all the lack of histological
confirmation of the diagnosis but in our defense MPA can be
diagnosed clinically in combination with positive MPO ANCA
testing.2,4,14Moreover the continuous haemoptysis of our patient
prevented satisfactory pulmonary function tests to be performed,
but our patient on admission had normal gas-exchange and
excellent exercise tolerance without desaturation on exertion.
In conclusion we presented a case of microscopic polyangiitis
predated byseven-year by pulmonary fibrosis. When a patient with
Laboratory findings on admission in pulmonary department.
? FBC: Hct: 32.9%, Hb: 10,6 g/dl,WBC: 5.560 K/ml (N: 59%),
PLT: 287.000 K/ml.
? INR: 1.1, Fibrinogen: 555 mg/dl, ESR: 56 mm/1 h
? Biochemistry: CRP: 1.1 mg/dl, Glu: 92 mg/dl, Urea: 105/mg/dl,
Creat: 6.4 mg/dl, Na: 131 mmol/l, K: 5.3 mmol/l, Bil: 0.34 mg/dl
ALP: 82 U/L, g-GT: 22 U/L, SGOT: 21 U/L, SGPT: 5 U/L, LDH: 406 U/L,
CPK: 143, CPK-MB: 56 U/L, Trop: 0.02, proBNP: >35 000,Caþ: 7.8 mg/dl
SACE: 35.1 mg/dl, C3: 82 mg/dl, C4: 29 mg/dl.
? Urine microscopy: Active sediment, EB: 1006, Ph: 7, Protein: 2þ, Hb: 2þ
? 24hour urine protein: 2.2 g
SACE; serum ACE.
Fig. 3. Admission chest radiogram (12/10/2008).
Fig. 4. Chest CT scan on admission (12/10/08).
A.M. Tsimogianni et al. / Respiratory Medicine CME 3 (2010) 207–210 209
pulmonary fibrosis develops clinical manifestations from other
systems he should undergo appropriate investigations to exclude
an underlying autoimmune disease/vasculitis.
Conflict of interest statement
1. Collins C, Quismoro Jr F. Pulmonary involvement in microscopic polyangiitis.
Curr Opin Pulm Med 2005 Sep;11(5):447–51 [Review].
2. Guillevin L, Durand-Gasselin B, Cevallos R, et al. Microscopic polyangiitis.
Clinical and laboratory findings in eighty-five patients. Arthritis Rheum
3. Lhote F, Cohen P, Ge ´ne ´rau T, et al. Ann Med Interne (Paris) 1996;147(3):165–77.
4. Ozaki S. ANCA-associated vasculitis: diagnostic and therapeutic strategy.
Allergol Int 2007;56:87–96.
5. Eschun GM, Mink SN, Sharma S. Pulmonary interstitial fibrosis as a presenting
manifestation in perinuclear antineutrophil cytoplasmic antibody microscopic
polyangiitis. Chest 2003;123:297–301.
6. Becker-Merok A, Nossent JC, Ritland N. Fibrosing alveolitis predating micro-
scopic polyangiitis. Scand J Rheumatol 1999;28(4):254–6.
7. Birnbaum J, Danoff S, Askin FB, et al. Microscopic polyangiitis presenting as
a ‘‘pulmonary-muscle’’ syndrome: is subclinical alveolar haemorrhage the
mechanism of pulmonary fibrosis? Arthritis Rheum 2007;56(6):2065–71.
8. Ando Y, Okada F, Matsumoto S, et al. Thoracic manifestation of myeloperox-
idase-antineutrophil cytoplasmic antibody (MPO-ANCA)-related disease. CT
findings in 51 patients. J Comput Assist Tomogr 2004;28(5):710–6.
9. Mansi IA, Opran A, Sondhi D, et al. Microscopic polyangiitis presenting as
idiopathic pulmonary fibrosis: is anti-neutrophilic antibody testing indicated?
Am J Med Sci 2001 Mar;321(3):201–2.
10. Foulon G, Deleval P, Vaylere D, et al. ANCA associated lung fibrosis: analysis of
17 patients. Respir Med 2008 Oct;102(10):1392–8. Epub 2008 Jul 18.
11. Papiris S, Manali E, Kalomenidis I, et al. Bench-to-bedside review: pulmo-
nary-renal syndromes-an update for the intensivist. Crit Care 2007;11:
12. Jara L, Vera-Lastra O, Calleja M. Pulmonary-renal vasculitic disorders: differ-
ential diagnosis and management. Curr Rheumatol Rep 2003;5:107–15.
13. Guillevin L, Pagnoux Ch. Indications of plasma exchanges for systemic vascu-
litides. Ther Apher Dial 2003 Apr;7(2):155–60 [Review].
14. Nabakayashi K, Hashimoto H. Microscopic polyangiitis. In: Hashimoto H, editor.
Clinical manual for vasculitis. Tokyo: Research Group of Intractable Vasculitis,
Ministry of Health, Labor and Welfare of Japan; 2002. p. 24–6.
Fig. 5. Bronchoscopy showing clot in the lower segmental lingular bronchus.
A.M. Tsimogianni et al. / Respiratory Medicine CME 3 (2010) 207–210210