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: email@example.com, firstname.lastname@example.org (A.M. Tsimogianni).
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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) 207–210208
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) 207–210209
pulmonary fibrosis develops clinical manifestations from other Download full-text
systems he should undergo appropriate investigations to exclude
an underlying autoimmune disease/vasculitis.
Conflict of interest statement
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Fig. 5. Bronchoscopy showing clot in the lower segmental lingular bronchus.
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