Diagnostic Pitfalls in Diffuse Interstitial Lung Damage, Presentation of Clinical Cases

Case Report | DOI: https://doi.org/10.31579/2690-8794/154

Diagnostic Pitfalls in Diffuse Interstitial Lung Damage, Presentation of Clinical Cases

  • Simona-Ştefania Dobre 1
  • Petre Iacob Calistru 2
  • Mihaly Enyedi 2

1 Diagnosis and Treatment Center, Dr Victor Babes”, Bucharest, Romania

2 University of Medicine and Pharmacy “Carol Davila”, Bucharest, Romania

*Corresponding Author: © 2023, Simona-Ştefania Dobre. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Citation: Simona-Ştefania Dobre, Petre Iacob Calistru, Mihaly Enyedi, (2023), Diagnostic Pitfalls in Diffuse Interstitial Lung Damage, Presentation of Clinical Cases, Clinical Medical Reviews and Reports, 5(2); DOI:10.31579/2690-8794/154

Copyright: © 2023, Simona-Ştefania Dobre. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Received: 23 March 2023 | Accepted: 03 April 2023 | Published: 10 April 2023

Keywords: diffuse interstitial pneumopathy; sarcoidosis; pulmonary fibrosis; sars-cov2 viral infection

Abstract

Diffuse interstitial lesions of the lung parenchyma pose complex problems of positive and differential diagnosis, the etiological spectrum including:

  • Bacterial (pulmonary tuberculosis-miliary form, brucellosis), fungal (aspergillosis, histoplasmosis), parasitic (pneumocystosis, toxoplasmosis) or viral (SARS-CoV2, HIV) infections
  • Non-infectious diseases (pneumoconiosis, collagenosis/vasculitis, carcinomatosis, hypersensitivity pneumonitis, etc.).

We present three clinical cases with similar radiological images, namely diffuse interstitial lung damage, but with different diagnosis and etiologies: sarcoidosis stage III of the disease, pulmonary fibrosis after SARS-CoV2 infection, and carcinomatous lymphangitis. In all three cases, the chest computer tomography was the basic investigation in the diagnosis of the lung disease, but the diagnosis of certainty required the performance of other investigative methods.

Introduction

Interstitial lung lesions pose complex problems of positive and differential diagnosis, the etiological spectrum including:

  1. Infections: - Bacterial: tuberculosis and nontuberculous mycobacteria, brucellosis
    • Fungal: aspergillosis, histoplasmosis, cryptococcosis
    • Parasitic: Pneumocystis jiroveci echonococcosis, toxoplasmosis


 

  • Viral: HIV, SARS-CoV2 infections
  1. Exposures/ Toxins:
    • Drug inducedhypersensitivity: metotrexate, infliximab, humira, amiodarona
    • Hypersensitivity pneumonitis
    • Pneumoconiosis (aluminium, cobalt, talc, titanium

3.Vasculitis: Churg-Strauss syndrome

Wegenergranulomatosis

4.Malignancy :- Lymphoma

  • Lymfomatoid granulomatosis

5 Inflamations:- Eosinophilic granulomtosis ( pulmonary Langerhans cell histiocytosis)

  • Lymphocytic interstitial pneumonitis

- Bronchocentric granulomatosis (Usually associated with asthma and allergic bronchopulmonary aspergillosis)

In this articlewe will present 3 cases with differentdiagnoses but with similar radiological appearance. Our aim is to demonstrate that for thedifferential diagnosis of interstitial lung lesions, numerous additional procedures of greater accuracy are needed (bronchoscopy with bronchoalveolar lavage,transbronchial biopsy, transthoracic biopsy, serological and immunological analyses, microbiological investigations), which along with conventional radiography, computed tomography with contrast substance, to establish the diagnosis of certainty.

Case Report

Patient 1The first patient is a 36-year-old white female, presented on our department with a four- month history of anterior-sided chest pain with associated shortness of breath on exertion. She described the pain as a dull ache that occurred at rest and was not worsened by exertion. She also remarka chronic dry cough that she had for the prior severalyears that was not associated with illness or exercise and a 5-pound weight loss over the previous month.

Upon arrival, her vital signs were all within normal limits,and the pulmonary clinical examination revealed sibilant and sub crepitant bronchial rales bilaterally, predominantly basal, SaO2= 91-94% in atmospheric air. Also, there were no visible skin or subcutaneous lesions.

The electrocardiogram showeda normal sinusrhythm of 82 beats per minute withoutany sign of ischemia. Laboratory tests including complete blood count, complete metabolic profile, and acute ischemia tests (Troponin, CK, CK-MB) were all negative.

Pulmonary function exploration (spirometry) revealed restrictive ventilatory dysfunction with a reductionin FEV1 by 42% and FVC by 33%, IT = 76.

Chest X-ray demonstrated hili with increased projection area, with polycyclic appearance and diffuseinterstitial nodular opacitiesin bilateral lungs (Image 1).

Image 1: Chest radiograph depicting diffuse interstitial nodular opacities throughout the lungs bilaterally with hilums increased in volume.

Intravenous contrast computed tomography of the chest revealed middle and upper lung nodularity with a perilymphatic distribution involving the central peribronchial vascular regions as well as the subpleural and fissural surfaces. (Image 2).

Image 2: Computed tomography of the chest with intravenous contrast depicting mid and upper lung nodularity with a perilymphatic distribution involving the central peribronchial vascular regions as well as subpleural and fissural surfaces.Based on the clinicaland imaging data with diffuseinterstitial damage and bilateral hilar adenopathy, pulmonarysarcoidosis was suspectedand the patient underwent bronchoscopy with bronchioloalveolar lavage and transbronchial biopsies. Bronchoalveolar lavage was negative for fungal infections, acid-fast bacilli, and malignant cells and showed lymphocyte proliferation. Transbronchial lung biopsy showed numerous well-formed, non- caseating granulomas embedded in dense hyaline sclerosis.

According to the histopathological examination with the presence of non-caseating granulomas, we diagnosed her as : Pulmonary sarcoidosis stage 2, and he started taking daily prednisone and sulfamethoxazole/trimethoprim three times a week for eight weeks. After the treatment, the symptoms decreased significantly and a chest CT showed a clear reduction in lung field shadows and an impression of reducted mediastinal lymph node enlargement.

Patient 2

The second patient,58-year-old patient, female,diagnosed with an ovarian neoplasm,operated on in 2017 and polychemotherapy with numerous therapeutic lines, presents with a dry, irritating cough, sometimes with frequent attacks in the supine position, associated with mixed dyspnea at low exertion and lying down, fatigue, weight loss significant (9 kg in 2 months).

The onset is recent, 2 months ago, with cough, to which progressive dyspnea and general asthenia were associated in the last 2weeks.

On admission, the patient's condition is serious, Pulmonary stetacustic we find the reduction of the vesicular murmur, with subcrepitant bronchial rales bilaterally basal.

The biological samplesshow anemia with hypochromia and microcytosis (Hb 8.9 g/dl),thrombocytosis 459 mil/mm3,inflammatory syndrome (CRP= 9.9 mg/dL, Ferritin > 2000 µg/L).

The antero-posterior chest X-ray highlights the accentuation of the lung pattern due to the vascularand interstitial components, minimal right basal pleural effusion (Image 3).

  
 

Image 3: Chest X-ray shows diffusely dispersed reticulonodular opacities, more pronounced in the parahilar region, predominantly peripheral Kerley B lines. Deformation of the hilum with hilar adenopathy, small fluid collection on the left, with the penetration of the fluid into the interlobar fissure.

The diagnostic assumptions included: bilateral pulmonary disseminated process: pulmonary metastases (carcinomatous lymphangitis), tuberculosis. A computertomography of the chest was performed with the contrastsubstance, which found:

Image 4: ThoracicCT in the pulmonary windowshows reticular linearinterstitial densifications, on the background of some diffuseareas in groundglass of reducedintensity, right pleuralcollection 7 mm. A lung biopsy was discussed, but based on the oncological antecedents, the medical history and the tomographic investigation, the diagnosis of pulmonary carcinomatous lymphangitis with an ovarianstarting point was established (Ovarianneoplasm with peritoneal carcinomatosis, with secondary hepatic, pancreatic, ureteral, pulmonary, lung biopsy is no longer necessary)- At the level of the chest, the presence of nodular thickenings of the interlobular septa and bronchovascular bundles (small centrilobular nodules), septal lines and polygons, bead-like thickening of the interlobular fissures, free fluid in the right pleural cavity 7 mm and hilar lymphadenopathy (Im

During the hospitalization, the general conditionwithout dynamics is maintained, the excruciating dry cough and low fever, the general asthenia progresses, the patient was taken over by the oncology servicefor specialized treatment.

Patient 3

Patient 3

The third case is of a 75-year-old man who presented to our clinic for fever, cough and dyspneathat started 5 days ago andwith progressive worsening of dyspnea and cough. The patient has a medical history of hypertension, dyslipidemia, grade 2 obesity and OSA with CPAP.Thepatient has not been vaccinated against SARS-CoV-2.

At presentation, body temperature was 38.5˚C, blood pressure was 140/80 mmHg, heart rate was 90 beats per minute, respiratory rate was 28 breaths per minute, and SpO2 was 87% on room air. Chest examination revealed crackles on auscultation in all lung fields.

Laboratory findings included an increased WBC count ( 13.560 /µl reference range, 4000-10000 /µl) with neutrophilia (84.8%;reference range, 50-70%)and lymphopenia (8,7%; reference range, 25-40%), elevatedCRP levels (39 mg/l; referencerange, 0-0,3 mg/l), elevated LDH levels (500 U/l; reference range, 135-225 U/l) and elevated ferritin levels (816 ng/ml; reference range, 13-150 µg/ml).

Chest radiography revealed diffuse infiltrates in both lung fields with predominantly subpleural and basal disposition, with consolidations in the right middle lung field and left lower lungfield

- with the appearance of viral interstitial pneumonia (Image 5).


 

Image 5: Chest X-Ray shows nodularinfiltrative opacities in frosted glass with a predominant subpleural and basal bilateral disposition

Thoracic computed tomography reveals areas of pulmonary condensation with a "mattedglass" appearance, associating the presence of small densifications in the band with a fibrotic appearance, with a relatively symmetrical arrangement, more importantly in the lower lobes, with a predominantly subpleural topography. (Image 6)


 

Image 6: Chest computed tomography reveals bilateral peripheral ground-glass infiltrates in both lung fields, with a predominantly peripheral and basaldisposition

Based on clinical and radiological data, COVID18 infection with interstitial lung involvement was suspected.The patient was tested by RT-PCR testing of a nasopharyngeal swab sample for SARS-CoV- 2, with positive RT-PCR result and diagnosed as organized pneumoniaassociated with COVID infection19.

The patient was hospitalized for 14 days, received specificantiviral treatment, systemiccorticosteroid therapy, oxygen therapy, with slowly favorable evolution of symptoms, with considerable improvement of oxygenation levelsand improvement of biological constants.

A chest X-ray and a CT scan at discharge showed a marked improvement of the pulmonary infiltrates previously observed. The patient returned for evaluation 3 months after discharge with no respiratory symptoms, and the follow-upchest radiograph illustrated a significant improvement in pulmonary infiltrates at the 3-month follow-up ( Image 7).


 

Image7: Comparative lung X-ray at admission and 3 monthsafter discharge - a significant regression of interstitial infiltrates was observed 3 months after discharge.

Discussions

The presented cases arouse interestthrough the issue of establishing the etiological diagnosis; early diagnosis is of great practical importance, because it allows the timelyestablishment of treatment that can stop the evolution of the pathological process.

Sarcoidosis is a multisystem inflammatory disease of unknown etiology that predominantlyaffects the lungs and intrathoracic lymph nodes. Sarcoidosis is manifested by the presence of noncaseating granulomas (NCG) in the tissuesof the affected organs. (1)

The incidence varies from 5 to 40 cases per 100,000 inhabitants, in Romania the prevalence of the disease is approximately 4 cases per 100,000 inhabitants, with a higher frequency in the femalesex and the 20-40 age group.

Chest X-ray is essential for evaluation (2). Approximately 60-70% of patients with sarcoidosis have characteristic radiological images; sarcoidosis may present with equivocal radiological aspects for this diagnosis, depending on the stage of thedisease.

CT scanning is more sensitive than radiography in detecting lymphadenopathy and early parenchymal disease, and high-resolution CT (HRCT) can identify alveolitis or active fibrosis, the resultsbeing well correlated with the yield of lung biopsy (3,4,5).

However, in most cases, the diagnosis of certainty requires bronchial biopsy with histological evidence of noncaseating granulomas, with negative special tests for mycobacteria and fungi (6,7).

Prognostic markers of the disease includeadvanced changes on chest X-ray and the presence of extrapulmonary involvement (predominantly cardiac and neurological) and evidence of pulmonary hypertension (8)

Several studies have demonstrated that the most important marker for prognosis is the initial stage of the chest X-ray,and in stage II of the disease,as in the case of our patient,remission under oral corticosteroid therapy is in 40-70% of cases. (9,10)

In conditions of known malignancy, the presence of the symptoms of excruciating dry cough, sometimes with hemoptysis and progressive dyspnea up to respiratory failure, requires the presence of carcinomatous lymphangitis as a differential diagnosis.

The location of the primary tumor is very varied, the most common being breast cancer 33%, gastric 29%, lung 17%, ovarian adenocarcinoma 6%, pancreas 4%, prostate 3% and, more rarely, in colon cancer,larynx, melanomas, seminomes (11,12,13).

Chest X-ray shows reticulonodular, confluent, bilaterally disseminated, symmetrical opacities, septal thickenings, Kerley A and B lines, areas of subpleural edema (similar manifestations to interstitial edema), hilar and mediastinal adenopathies (20-40% of cases), pleuralfluid collections (30-50%of cases). (14)

PulmonaryHRCT, which has a clearlysuperior sensitivity comparedto chest radiography, can highlight: nodular thickening of the interlobular and peribrochovascular septa, associated with alveolar opacities, with peripheral or central distribution, often asymmetric.(15,16)

In the presented patient, ovarian adenocarcinoma was the source of pulmonary metastasis. The respiratory symptomatology given by carcinomatous lymphangitis was the cause that required medical consultation, with the diagnosis of secondary determinations in an advanced stage with reserved prognosis and low chances of survival.

Lung CT was highly suggestive for establishing the diagnosis of carcinomatous lymphangitis, showing the association of peripheral and central accentuated peribronchovascular pattern with images of asymmetric alveolar opacities.

COVID-19became a global pandemic after the first case of severe acute respiratory syndrome (SARS) coronavirus-2 (SARS-CoV-2) was reported in Wuhan, China in December 2019. While cases continueto rise, questionsabout the clinicalcourse and long-termimplications of the infection remain unanswered.

In the presenceof symptoms of acute respiratory infection associated with a picturesuggestive of interstitial lung damage, in the current epidemiological context it should be considered as a differential diagnosis with pneumonia associated with the viral infection COVID19.

Although the rRT-PCR test remains the gold standard for the diagnosis of COVID-19, the high false-negative rate limits the prompt diagnosis of this disease.[17–19).Therefore, CT scanning plays a key role in the diagnosis and management of this infectious disease. The imaging changes in COVID-19 pneumoniaare diverse: 78-80% "ground glass" opacities, 50% consolidation, interlobulation, septal thickening with fibrotic changes. (20, 21, 22).

As in the case of patient 3 presented, althoughthe clinical symptomsof COVID-19 pneumonia are the same as those of common upper respiratory tract infection, the chest CT examination had a key role in the diagnosis and management of COVID-19 pneumonia.

As medical evidence, CT diagnosis was written in “Diagnosis and Treatment of Pneumonia Infected by 2019-nCoV(implementation process 5th edition)” publishedby the National Health Commission of the People's Republicof China (23).

However, it is difficult to distinguish COVID-19 pneumonia from other viral pneumonias based on CT results alone, a positive RT-PCR test on a pharyngeal swab, confirming the diagnosis of COVID-19pneumonia.

The chest CT examination is also of great importance in monitoring the evolution of lunglesions at a distance, studies so far have shown a resolution of lesions of at least 82% in mild and moderateforms of bola and at least 76% for severe forms, at an intervalup to 1 month

post-infection. (24, 25) And in the presented case, the radiological evolution of the patient was significantly favorable, with a remission of the lesions of more than 75%, compared to the initialextension.

Despite the highly suggestive radiological image of interstitial lung damage that appears in numerous pathological entities,currently there are still limits regarding the definite establishment of a positivediagnosis, sometimes requiringlaborious and expensiveinvestigations.

Conclusions

The common feature of all the presented cases is the monomorphic radiological appearance which contrasts with the etiological polymorphism. The differential diagnosis of interstitial lunglesions is often laborious, involving numerous procedures: imaging(conventional radiography, computed tomography with contrast material), bronchoscopy with bronchoalveolar lavage, transbronchial biopsy, transthoracic biopsy, serological and immunological tests,microbiological investigations. Conventional lung radiography remainsone of the basic methods in the diagnosis of lung diseases, but sometimes requires the addition of otherinvestigative methods with higher accuracy,aimed at guidingthe diagnosis with certainty.

References

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S Munshi

Dr.Tania Muñoz, My experience as researcher and author of a review article in The Journal Clinical Cardiology and Interventions has been very enriching and stimulating. The editorial team is excellent, performs its work with absolute responsibility and delivery. They are proactive, dynamic and receptive to all proposals. Supporting at all times the vast universe of authors who choose them as an option for publication. The team of review specialists, members of the editorial board, are brilliant professionals, with remarkable performance in medical research and scientific methodology. Together they form a frontline team that consolidates the JCCI as a magnificent option for the publication and review of high-level medical articles and broad collective interest. I am honored to be able to share my review article and open to receive all your comments.

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Tania Munoz

“The peer review process of JPMHC is quick and effective. Authors are benefited by good and professional reviewers with huge experience in the field of psychology and mental health. The support from the editorial office is very professional. People to contact to are friendly and happy to help and assist any query authors might have. Quality of the Journal is scientific and publishes ground-breaking research on mental health that is useful for other professionals in the field”.

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George Varvatsoulias

Dear editorial department: On behalf of our team, I hereby certify the reliability and superiority of the International Journal of Clinical Case Reports and Reviews in the peer review process, editorial support, and journal quality. Firstly, the peer review process of the International Journal of Clinical Case Reports and Reviews is rigorous, fair, transparent, fast, and of high quality. The editorial department invites experts from relevant fields as anonymous reviewers to review all submitted manuscripts. These experts have rich academic backgrounds and experience, and can accurately evaluate the academic quality, originality, and suitability of manuscripts. The editorial department is committed to ensuring the rigor of the peer review process, while also making every effort to ensure a fast review cycle to meet the needs of authors and the academic community. Secondly, the editorial team of the International Journal of Clinical Case Reports and Reviews is composed of a group of senior scholars and professionals with rich experience and professional knowledge in related fields. The editorial department is committed to assisting authors in improving their manuscripts, ensuring their academic accuracy, clarity, and completeness. Editors actively collaborate with authors, providing useful suggestions and feedback to promote the improvement and development of the manuscript. We believe that the support of the editorial department is one of the key factors in ensuring the quality of the journal. Finally, the International Journal of Clinical Case Reports and Reviews is renowned for its high- quality articles and strict academic standards. The editorial department is committed to publishing innovative and academically valuable research results to promote the development and progress of related fields. The International Journal of Clinical Case Reports and Reviews is reasonably priced and ensures excellent service and quality ratio, allowing authors to obtain high-level academic publishing opportunities in an affordable manner. I hereby solemnly declare that the International Journal of Clinical Case Reports and Reviews has a high level of credibility and superiority in terms of peer review process, editorial support, reasonable fees, and journal quality. Sincerely, Rui Tao.

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Rui Tao

Clinical Cardiology and Cardiovascular Interventions I testity the covering of the peer review process, support from the editorial office, and quality of the journal.

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Khurram Arshad

Clinical Cardiology and Cardiovascular Interventions, we deeply appreciate the interest shown in our work and its publication. It has been a true pleasure to collaborate with you. The peer review process, as well as the support provided by the editorial office, have been exceptional, and the quality of the journal is very high, which was a determining factor in our decision to publish with you.

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Gomez Barriga Maria Dolores

The peer reviewers process is quick and effective, the supports from editorial office is excellent, the quality of journal is high. I would like to collabroate with Internatioanl journal of Clinical Case Reports and Reviews journal clinically in the future time.

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Lin Shaw Chin

Clinical Cardiology and Cardiovascular Interventions, I would like to express my sincerest gratitude for the trust placed in our team for the publication in your journal. It has been a true pleasure to collaborate with you on this project. I am pleased to inform you that both the peer review process and the attention from the editorial coordination have been excellent. Your team has worked with dedication and professionalism to ensure that your publication meets the highest standards of quality. We are confident that this collaboration will result in mutual success, and we are eager to see the fruits of this shared effort.

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Maria Dolores Gomez Barriga