Authors Sarah Kiel, MD, Jared Chiarchiaro, MD Division of Pulmonary, Allergy, and Critical Care Medicine University of Pittsburgh Medical Center, Pittsburgh, PA
Case
A previously healthy 74-year-old man presents with 2 years of
progressive dyspnea on exertion and a persistent dry cough increasing in
frequency and intensity over the same time period. He reports minimal
tobacco use, 1 pack year accumulated 40 years prior. He reports no
inhalational exposures through travel, environment, occupation, hobbies
or pets. He mentions occasional thigh weakness and difficulty rising
from a seated position, but denies any inflammatory arthralgias, rashes,
Raynaud’s phenomena, sicca, reflux symptoms, or family history of
autoimmune disease. Physical exam reveals a resting oxygen saturation
of 92% on room air, no cyanosis, clubbing, or edema in extremities, and
inspiratory crackles throughout the bases bilaterally. Recent serologic
testing reveals no significant results from the following tests:
antinuclear antibodies, myositis panel including anti-jo-1 antibody,
anti-cyclic citrullinated peptide, rheumatoid factor, anti-Ro/SSA,
anti-La/SSB antibodies. Pulmonary function tests (PFTs) demonstrate a
restrictive pattern with reduced diffusing capacity for carbon monoxide.
Representative CT images shown below.
Images (Fig 1A and 1B)
Question
Based on the information given, what further evaluation should be undertaken?
A. Bronchoscopy with transbronchial biopsies B. Bronchoscopy with bronchoalveolar lavage (BAL) C. VATS biopsy D. No further evaluation is indicated
Answer
Answer: D. No further evaluation is indicated
Discussion
Traditionally, the diagnosis of idiopathic pulmonary fibrosis (IPF)
is made via surgical lung biopsy. However, the clinical presentation and
presence of specific radiographic findings are usually sufficient to
make the diagnosis. High resolution CT (HRCT) images consistent with a
UIP pattern of fibrosis are highly specific for the histopathologic
correlate of IPF (1,2). The CT images depicted (Figs. 2A-B) demonstrate a
typical UIP pattern characterized by: subpleural honeycombing (black
outline), a predominantly basal distribution (red arrows), reticular
pattern, traction bronchiectasis (blue arrows), and paucity of ground
glass opacities (2). Most important is the paucity of ground glass
opacities; their presence should prompt further evaluation and
consideration for a diagnosis other than UIP (3). In the setting of a
high pretest probability based on HRCT and clinical presentation,
surgical lung biopsy is confirmatory but does not significantly change
diagnosis or management and is associated with risks including
procedural mortality (1.7%), respiratory infection (6.5%), and potential
IPF exacerbation (6%) (3). As such, patients with a typical clinical
presentation and a typical UIP pattern by HRCT, without identifiable
exposure or other etiology, can be diagnosed with IPF without biopsy or
BAL based on the 2018 ATS/ERS/JRS/ALAT clinical practice guidelines.
Given the risk associated with invasive diagnostic work up, it
becomes imperative to recognize the differences between the four
categories of HRCT imaging: typical for UIP, probable UIP, indeterminate
for UIP, and features consistent with alternative diagnosis.
Recommendation for more invasive work up would be indicated for the
latter two categories. A probable UIP CT pattern remains the same as a
typical UIP pattern in terms of a basal and subpleural heterogenous
reticular distribution, and presence of peripheral traction
bronchiectasis. However, honeycombing is often absent. In cases with a
probable UIP pattern radiographically, 82-94% of cases will demonstrate a
probable or definite UIP histopathological pattern on surgical lung
biopsy (4). An indeterminate radiographic UIP pattern is often more
diffuse in its interstitial markings without the expected basal and
subpleural distribution. CT features that should prompt the
pulmonologist to consider an alternative diagnosis to UIP include: upper
lung or mid-lung fibrosis, subpleural sparing, any consolidation or
extensive ground glass opacities, mosaicism (green arrows), and diffuse
nodules or cysts (Figs. 3A-B). In multiple studies concerning fibrotic
ILDs, the use of multidisciplinary evaluation with experienced
clinicians, radiologists, and pathologist may change an ILD diagnosis in
up to 20-50% of cases with an increase in diagnostic confidence (2).
The two most common missed diagnoses for IPF by imaging are chronic
hypersensitivity pneumonitis (HSP) and non-specific interstitial
pneumonia (NSIP). Chronic HSP often demonstrates an upper to mid-lung
distribution, mosaic attenuation or air trapping, and centrilobular
nodules which aid in distinguishing it from a typical UIP pattern. NSIP
often requires a surgical lung biopsy for diagnosis and radiographically
may demonstrate subpleural sparing, a feature atypical for UIP.
(Fig 2A and 2B)
(Fig. 3A and 3B)
References:
Chung JH, Chawla A, Peljto AL, et al. CT scan findings of probable
usual interstitial pneumonitis have a high predictive value for
histologic usual interstitial pneumonitis. Chest 2015; 147(2): 450–9.
Lynch DA, Sverzellati N, Travis WD, et al. Diagnostic criteria for
idiopathic pulmonary fibrosis: a Fleischner Society White Paper. Lancet
Respir Med 2018; 6(2): 138–53.
Raghu G, Remy-Jardin M, Myers JL, et al. Diagnosis of idiopathic
pulmonary fibrosis. an official ATS/ERS/JRS/ALAT clinical practice
guideline. Am J Respir Crit Care Med 2018;198(5): e44–e68.
Raghu G, Lynch D, Godwin JD, et al. Diagnosis of idiopathic pulmonary
fibrosis with high-resolution CT in patients with little or no
radiological evidence of honeycombing: secondary analysis of a
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