Drug Induced Lung Disease (DILD) is an iatrogenic lung injury secondary to drug exposure.
It can be a debilitating and even life-threatening condition affecting the lung parenchyma,
airways,
pulmonary vasculature,
pulmonary interstitium and pleura.
Both cytotoxic and non-cytotoxic drugs including antimicrobials,
anti-inflammatory,
biologics & cardiovascular medication can cause DILD.
Patients on chemotherapy or patients with systemic inflammatory diseases are at increased risk.
The toxicity can be direct,
dose-dependent or immune-mediated.
Clinical history,
examination findings,
imaging tests and non-imaging tests aid the diagnosis.
DILD has no specific symptoms and may include shortness of breath,
cough,
dyspnoea or pleuritic chest pain.
Radiologists play a key role in diagnosing DILD by keeping a high level of suspicion and recognising the imaging pattern compatible with DILD.
Knowledge of imaging patterns associated with DILD and their histological correlates is therefore essential for a radiologist.
Pattern recognition helps in differentiating the etiological drug particularly in patients on multiple therapies.
The temporal association of clinical symptoms,
imaging features and subsequent improvement following drug cessation will strongly favour DILD.
The recurrence of symptoms and imaging findings on reintroduction of the drug makes the diagnosis of DILD even more specific.
Online access to Pneumotox (www.pneumotox.com) provides access to current information on DILD may be helpful.
High Resolution Computed Tomography (HRCT) is currently the best non-invasive method to image suspected drug-induced lung disease.
Particularly given its strong correlation with histological findings.
HRCT also helps in ruling out other differential diagnoses and monitor treatment response.
Although nonspecific,
Fluorodeoxyglucose (FDG)-positron emission tomography (PET) uptake was detected at an extremely early stage even in absence of symptoms or imaging findings on HRCT2.
The cytotoxic and non-cytotoxic drugs can damage the alveolar epithelial cells,
basement membranes or capillary endothelial cells.
The collapse of the collagen and elastic architecture of the alveolar walls may be lost in severe forms.
These contribute to the histological findings.
There are no pathognomonic imaging features of DLID,
making diagnosis challenging.
However,
there are recognised patterns.
These Imaging patterns of DILD ranges from acute diffuse alveolar damage,
to subacute hypersensitivity pneumonitis and organising pneumonia as well as chronic fibrosis (NSIP,
UIP).
Co-existing pathology may pose diagnostic challenges.
Diffuse alveolar damage (DAD) is more commonly seen with cytotoxic DILD whereas NSIP pattern is seen more commonly with non-cytotoxic DILD.
In a particular study DILD with imaging features of DAD was has been shown to have an increased mortality with imaging findings of DAD as compared with the findingsto DILD with features of of non-specific interstitial pneumonia (NSIP) or bronchiolitis obliterans with organizing pneumonia (BOOP)3.
In DAD pattern of DILD the chest radiograph (CXR) demonstrating bilateral opacification in a homogeneous or heterogeneous distribution with a mid and lower zone predominance.
High-resolution computed tomography (HRCT) findings in early DAD typically demonstrate ground-glass opacity (GGO) with early fibrosis progressing to marked architectural distortion and honeycombing.
This is commonly seen with Cyclophosphamide,
Bleomycin & Carmustine lung toxicity4.
NSIP pattern of DILD typically includes the CXR demonstrating wide spread heterogeneous opacities and High-resolution CT scans demosntrate ground-glass opacity (GGO) in a scattered or diffuse areas.
Late changes include predominantly basal distribution of fibrosis with traction bronchiectasis and honeycombing.
This pattern of lung toxicity is commonly seen with Amiodarone,
methotrexate,
or carmustine toxicity and less commonly with Gold salts and chlorambucil4.
Organizing Pneumonia (OP) pattern of DILD include the CXR demonstrating bilateral peripheral heterogeneous and homogeneous opacities with no specific zonal distribution.
HRCT demonstrates nodular consolidation,
centrilobular nodules and branching linear opacities (“tree-in-bud opacities”),
and bronchial dilatation.
This pattern of lung toxicity is commonly seen with Bleomycin,
gold salts,
cyclophosphamide,
and methotrexate4.
Both Bleomycin and Amiodarone have been most commonly studied as a cause for DILD.
Amiodarone is recognised to cause NSIP type DILD with increased lung lung parenchymal attenuation.
Increased liver parenchymal attenuation also points towards amiodarone induced DILD.
Bleomycin presents as cryptogenic organizing pneumonia,
eosinophilic hypersensitivity and most commonly,
interstitial pneumonitis,
which may progress into fibrosis5.
Bleomycin and methotrexate are cytotoxic and are the most common cause of UIP pattern of DILD,
which initially presents as patchy ground glass opacification and in later stages progresses to basal sub pleural fibrosis with honeycombing6.