Annals Medicus
Online Indexed Medical Journal with ISSN No 2348 -3970
Vol 2; Issue 02: April 2015
CASE REPORT
Reversible interstitial lung disease with prolonged use of
nitrofurantoin
Sandeep V Nair1, Mithun C Mohan2 , Sriram R3, Midhu K4, Laiju V5
Abstract
Drug induced interstitial lung disease (DILD) is not uncommon and has a myriad of clinical patterns
from benign infiltrates to severe respiratory distress with fatal complications. Nitrofurantoin; an
antibiotic used commonly for urinary tract infection is well known to cause pulmonary toxicity. We
report a case of an elderly gentleman who was on long term use of Nitrofurantoin presenting with
respiratory symptoms and found to have DILD. The lung changes induced by the drug may be
reversible on stoppage of the drug as seen in our case.
Keywords: Nitrofurantoin, drug induced interstitial lung disease, chronic interstitial pneumonia
Introduction
Drug induced interstitial lung disease (DILD) is
well known with variable presentations ranging
from benign infiltrates to life threatening acute
respiratory distress syndrome1. The development of
DILD may be multifactorial with interdependent
mechanisms: direct dose dependent toxicity and
immune
mediated
lung
injury
targeting
pneumocytes or alveolar capillary endothelium.
Identifying the causative drug and exclusion of
mimics of the disease aids in the diagnosis of
DILD and is important for the treatment of the
condition.
Nitrofurantoin; an antibiotic of quinolone group
targeting bacterial DNA is one of the commonest
antimicrobial drugs causing DILD, resulting in
pulmonary fibrosis2. It is commonly used in
urinary tract infections with well known side effect
Corresponding Author:
Sandeep V Nair
Consultant Physician & Diabetologist Don
Bosco Hospital, North Paravoor, Kerala
Email Id :[email protected]
www.annalsmedicus.com / Vol 2 ; Issue 2; 2015 April
profile targeting multiple organ systems resulting
in gastrointestinal discomfort, pulmonary toxicity,
neuropathy,
hepatotoxicity
etc.
Urinary
discoloration causing brown urine is frequently
encountered. This can be considered harmless as
there are no clinical sequelae3.
Pulmonary toxicity of nitrofurantoin may be acute
or sub acute which may be due to hypersensitivity
reaction or chronic pulmonary reaction due to
cumulative drug dose. Chronic involvement of
lungs secondary to nitrofurantoin may manifest as
chronic interstitial pneumonia, diffuse interstitial
pneumonitis, pulmonary fibrosis, pulmonary
hemorrhage or pleural effusion. These clinical
manifestations are well known but rarely
encountered in long term use of the drug and can
cause potentially serious and even fatal pulmonary
reactions. If identified early and drug withdrawn
from use; patients may have reversal of the
symptoms and lung pathology.
Here we report a case of a 74 year old gentleman
who developed respiratory symptoms following
Page 311
over the counter use of nitrofurantoin for recurrent
urinary tract infections complicating obstructive
uropathy due to prostatic enlargement.
Case report
A 74 year old gentleman presented to the medical
OPD with chronic cough and associated
progressive exertional dyspnea. The symptoms
initiated with exertional dyspnea since 10 months
back and development of cough with little
expectoration since 5 months. He was an
electrician by profession and was not having
occupational or environmental exposure to metal
fumes or organic dusts. He had a past medical
history of systemic hypertension which was being
treated with Losartan and Atenolol. A diagnosis of
benign hypertrophy of prostate was made on
evaluation for recurrent urinary tract infections and
obstructive symptoms to micturition 2 years prior
to the presentation, for which he was prescribed
nitrofurantoin and tamsulosin. Following this the
patient lost follow up and was on over the counter
medication with both the drugs for 2 years.
On examination he was found to have tachypnea
with a rate of 24 breaths per minute at rest and no
features of respiratory failure. His vital signs were
stable with a BP under control on medications.
Chest expansion was normal for his age and no
features of obstructive lung diseases noticed on
examination. Auscultation revealed bilateral fine
inspiratory crackles predominantly at the base of
the lungs. Cardiac auscultation was normal.
Investigations revealed normal blood counts with
raised ESR (75mm in 1 hour). Renal and hepatic
functions were normal. Cardiac evaluation with
ECG and echocardiography revealed ischemic
heart disease with good left ventricular function
and no pulmonary arterial hypertension. Chest X
ray showed bilateral non homogenous opacities
involving the lower zones (Figure 1). Computed
tomography scan of the chest confirmed the
interstitial involvement in the mid and lower parts
of the lungs bilaterally, with no volume loss. No
pleural or mediastinal pathologies were noticed in
the study. The images were suggestive of diffuse
www.annalsmedicus.com / Vol 2 ; Issue 2; 2015 April
bilateral lung parenchymal disease – chronic
interstitial pneumonia (Figure 2 &3). Pulmonary
function tests, bronchoscopy and bronchoalveolar
lavage was not done in the case due to the limited
technical support in the hospital.
Patient was counseled regarding his clinical
condition and the need to stop the drug
(nitrofurantoin) was explained. He was treated with
bronchodilators and inhaled steroids. He improved
dramatically with resolution of symptoms and
signs during follow up in next 2 weeks. Clinical
examination revealed normal vesicular breath
sounds and no added auscultatory findings.
Radiological clearance of the pathology was
noticed on review X rays (Figure 4). Patient
became completely asymptomatic for the
respiratory pathology in a matter of 4 weeks and
further treatment was tailored for hypertension
control and urology consultation for urinary
symptoms.
Discussion
Nitrofurantoin although well known to cause
pulmonary toxicity is less commonly encountered
in clinical practice with pulmonary symptoms. The
reason for the same may be due to the short term
use of the drug. Acute responses may be due to
immune mediated hypersensitivity response
mimicking drug reactions of other classes as well
and may not be attributed with special importance
to nitrofurantoin. Acute reactions may resolve on
discontinuation of the drug in 72 hours. However
the chronic pulmonary manifestations may be dose
dependant and seen on prolonged use of
nitrofurantoin. One study reported development of
symptoms of pulmonary toxicity within 6–36
months following nitrofurantoin administration in
therapeutic doses4. The diagnosis is aided by the
history of the drug intake with specific clinical
situation and radiological appearance. The history
of the drug intake would be the key to the
diagnosis as proven in this case. Our patient had
been on nitrofurantoin 200 mg / day in divided
doses for 14 months when he started having
symptoms in the form of exertional dyspnea. The
Page 312
delay in identification of the etiology led to
progressive worsening of the condition requiring
activity restriction, thus impairing his quality of
life within a span of 10 months.
The mechanisms of nitrofurantoin induced
pulmonary toxicity are not completely understood
but may be dose dependant with regards to
cumulative doses and duration of therapy. It may
present as chronic interstitial pneumonia, diffuse
interstitial pneumonitis or pulmonary fibrosis5.
Chronic interstitial pneumonia was seen in our
patient on computed tomography scan of thorax.
Other rare manifestation of pulmonary side effects
may be pleural effusion, pulmonary hemorrhage
and rarely secondary changes seen as
bronchiectasis. Clinico radiologically the condition
masquerades other forms of interstitial lung
diseases with the exception of the history as
discussed early. Eosinophilia may be more
commonly associated with acute toxicity of the
drug. Bronchoalveolar lavage usually shows a
lymphocytic reaction and may be non specific.
Pulmonary function tests may reveal a restrictive
pattern with decreased Total lung capacity (TLC),
forced vital capacity (FVC) and single breath
carbon monoxide diffusion capacity (DLCO). Anti
nuclear antibody titers in patients with DILD may
be positive in upto 25 - 60%. This emphasizes the
References
1. Matsuno O. Drug induced interstitial
lung disease: mechanisms and best
diagnostic
approaches.
Resp
Research 2012, 13:39.
2. Hainer
BL,
White
AA.
Nitrofurantoin pulmonary toxicity. J
Fam Pract 1981, 13(6): 817-823.
3. Macrobid
drug
label.
FDA.
Retrieved 21 April 2014.
4. Hardak E, Berger G, et al.
Nitrofurantoin pulmonary toxicity:
2
importance of the history taking clinical judgment,
guiding the diagnosis and judicious use of
laboratory and radiological data in managing
patients. The laboratory findings in patients with
pulmonary toxicity6 are mentioned in Table 1.
The key treatment strategy is discontinuation of the
drug and symptomatic measures. Steroid therapy
can be tried with variable results but may be
promising in patients with severe symptoms. Our
patient was treated with inhaled steroids and
bronchodilators after discontinuation of the drug
and was asymptomatic on review after a couple of
weeks. The review radiograph showed partial
clearance of the pathology as documented in our
case.
Conclusion
This case highlights the importance of clinical
history in clinching the diagnosis and judicious
interpretation of laboratory data in clinical practice.
Nitrofurantoin use in clinical history of the patient
will be the key to diagnosis with supportive
radiographic findings. The use of nitrofurantoin on
long term basis may not be safe as pulmonary
toxicity
happens
on
cumulative
doses.
Discontinuation of the drug will lead to resolution
of symptoms and radiographic findings.
Neglected threat. Curr Drug Saf.
2010 Apr;5(2):125-8.
5. Schwaiblmair M, Behr W, et al.
Drug induced interstitial lung
disease. The Open Respiratory
Medicine Journal. 2012;6:63-74.
6. B
Vahid,
B
Wildemore.
Nitrofurantoin pulmonary toxicity: A
brief review. The internet journal of
pulmonary medicine. 2005 Vol 6 (2).
Dept. of General Medicine, MES Medical College, Perinthalmanna Kerala
Dept. of General Medicine, Bosco Hospital, North Paravoor , Kerala
3, 4, 5
www.annalsmedicus.com / Vol 2 ; Issue 2; 2015 April
Page 313
Table:
Table 1: Laboratory findings in nitrofurantoin induced pulmonary toxicity
Acute
Chronic
Peripheral Blood Eosinophils > 5%
83%
44%
WBCs > 9000/mm3
52%
15%
Elevated Transaminases
23%
37%
Elevated IgG
30%
80%
ANA (titre > 1/10)
25%
60%
Figures
Figure 1: Chest X ray showing bilateral basal non
homogenous opacities.
Figure 2: CT Chest showing pulmonary infiltrates
www.annalsmedicus.com / Vol 2 ; Issue 2; 2015 April
Page 314
Figure 3: CT Chest showing infiltrates
suggesting chronic interstitial pneumonia
Figure 4: Repeat X ray after 4 weeks
showing resolution of lesion
Article Info:
Submitted on: Apr 8, 2015 at 3:39 PM
Revised version accepted on: Apr 23, 2015 at 6:19 AM
How to cite this article : Sandeep V Nair, Mithun C Mohan , Sriram.R, Midhu K, Laiju V
: Reversible interstitial lung disease with prolonged use of nitrofurantoin . Ann Med 2015; 2: Pg –311-315
www.annalsmedicus.com / Vol 2 ; Issue 2; 2015 April
Page 315