March 2022 Pulmonary Case of the Month: A Sore Back Leading to Sore Lungs

Lewis J. Wesselius MD¹

Brandon T. Larsen MD PhD²

Departments of ¹Pulmonary Medicine and ²Pathology

Mayo Clinic Arizona

Scottsdale, AZ USA

History of Present Illness

An 82-year-old woman from Colorado was referred because of progressive shortness of breath over the past year. Her primary care physician had prescribed Trelegy® which did not improve her dyspnea. An outside pulmonologist noted abnormal findings on her thoracic CT scan and a bronchoscopy with bronchoalveolar lavage (BAL) was preformed which was positive for Mycobacterium Avium Complex (MAC). She was treated with a 3-drug regimen (azithromycin, rifampin, ethambutol) for 6 months with mild improvement. After the treatment was stopped, she noted more dyspnea and required supplemental oxygen. She underwent a fundoplication and initially improved but a month later her shortness of breath seemed to worsen. She was started on prednisone which was tapered to 10 mg/day. She was referred to the Mayo Clinic for possible VATS lung biopsy.

Past Medical History (PMH), Social History (SH), Family History (FH)

PMH

• Hiatal Hernia/GERD
• Ulcerative Colitis
• Hypertension
• Chronic Back pain
• Prior breast implants

SH

• Former smoker (24 pack-years, quit 1988)
• Social use of alcohol, no drug use
• No exposure to birds or down
• No occupational dust exposures
• Home humidifier
• Has indoor hot tub used frequently for back pain

FH

• Unremarkable

 Medications

• Prednisone 10 mg daily
• Pantoprazole 40 mg bid
• Pregabalin 25 mg at bedtime
• Oxycodone 5 mg q 6 hours prn pain
• Ondansetron 4 mg tablet q 8hhours prn nausea

Physical examination

• BMI 31.9
• Oxygen saturation at rest 95% on 4 lpm, 88% on RA
• Chest: scattered crackles
• Cardiovascular: regular rate without murmur
• Extremities: no clubbing or edema

Which of the following should be done next? (Click on the correct answer to be directed to the second of seven pages.)

1. Pulmonary function testing
2. Open surgical lung biopsy
3. Review thoracic CT scan
4. 1 and 3
5. All of the above

Cite as: Wesselius LJ, Larsen BT. March 2022 Pulmonary Case of the Month: A Sore Back Leading to Sore Lungs. Southwest J Pulm Crit Care Sleep. 2022;24(3):36-39. doi: https://doi.org/10.13175/swjpccs011-22 PDF 

Diagnostic Challenges of Acute Eosinophilic Pneumonia Post Naltrexone Injection Presenting During The COVID-19 Pandemic

Michelle Breuer

Abdulmonam Ali, MD

SSM Health

Mount Vernon, IL USA

Introduction

Acute eosinophilic pneumonia (AEP) is a rare respiratory illness that may present with nonspecific symptoms ranging in severity from cough and dyspnea to potentially fatal acute respiratory distress syndrome. Although the exact etiology of AEP is unknown, it is thought to be a hypersensitivity reaction that can be idiopathic or caused by various infections, inhalation exposures, and medications (1).  Here we present a rare case of AEP secondary to injectable naltrexone.

Case Presentation

A 45-year-old Caucasian male with a history of alcohol use disorder presented to the emergency room with a 3-day history of progressively worsening dyspnea and dry cough. The patient was a lifelong non-smoker with an unremarkable past medical history aside from alcohol abuse and obesity (BMI 41.64 kg/m²). He denied fever or chills, orthopnea, chest pain, or symptoms suggestive of paroxysmal nocturnal dyspnea. He also denied any recent sick contacts, including exposure to COVID-19. Relevant history includes alcohol cessation 1 month before presentation. After 2 weeks of cessation, he received his first injection of naltrexone (Vivitrol®) as part of alcohol relapse prevention. Physical exam was notable for an initial SpO₂ of 69% on room air, sinus tachycardia at a rate of 121 bpm, and obesity. Chest examination exhibited decreased air entry with bilateral fine crackles on auscultation. No skin rashes or peripheral edema were appreciated, and the remaining physical exam was within normal limits. The patient was started on supplemental oxygen (6 liters/minute nasal cannula to maintain SpO2 above 90%).

Workup was performed and chest x-ray showed diffuse bilateral pulmonary infiltrates (Figure 1), hence, the patient was started on empiric antibiotic and steroid therapy.

Figure 1. Chest X-ray showing bilateral ground-glass opacities.

SARS-CoV-2 PCR testing was performed twice due to high clinical suspicion of COVID-19 infection (the patient was seen during the Coronavirus pandemic). Both SARS-CoV-2 tests were negative as well as the rest of the respiratory viral panel. CBC was significant for leukocytosis with an absolute peripheral eosinophil count of 0.49 x 10⁹ cells/L. Bloodwork also revealed mildly elevated troponin, d-dimer, and LDH. However, electrocardiogram showed no significant ST changes and Computerized Tomography (CT) angiography chest showed no evidence of pulmonary embolism but confirmed the chest x-ray findings of diffuse bilateral ground-glass opacities with anterolateral subpleural parenchymal sparing (Figure 2).

Figure 2. CTA chest (axial view, lung window) showing diffuse ground-glass opacities.

An echocardiogram showed an ejection fraction of 60% and normal left ventricular diastolic function. Moderate right ventricular (RV) dilation with reduced systolic function was reported and the peak RV pressure was estimated at 39 mmHg. Extensive blood testing for connective tissue disease was negative for ANCA, CCP, ANA, and cryoglobulins. Immunoglobulin E (IgE) level was within normal limits at 14KU/L (reference range < 214 KU/L).  Infectious disease serology was negative for mycoplasma, strongyloides, coccidioides, and aspergillus. HIV and hepatitis screening were also negative. Bronchoscopy with bronchoalveolar lavage (BAL) was performed and was significant for 27% eosinophils, 42% lymphocytes, 25% monocytes, 6% neutrophils (Figure 3).

Figure 3. Bronchoalveolar lavage (BAL) showing increased numbers of eosinophils.

BAL culture remained negative including mycobacterial and fungal cultures. BAL testing for Pneumocystis Jirovecii was negative as well. BAL cytology showed benign bronchial epithelial cells and inflammatory cells. No parasites were seen in BAL and fungal staining was negative.

The constellation of the above clinical, radiological, and laboratory findings was highly suggestive of acute eosinophilic pneumonia diagnosis. The patient’s methylprednisolone dose was increased to 125mg every 8 hours. Due to high FiO2 requirements and poor pulmonary reserve, the patient remained intubated after his bronchoscopy procedure. Over the following 48 hours, FiO₂ requirements improved significantly and his repeat chest x-ray showed almost complete resolution of the pulmonary infiltrates. The patient was successfully extubated to 2 liters of oxygen via nasal cannula on the third day.  Supplemental oxygen was eventually weaned off to room air. There wasn’t significant desaturation observed with the exercise trial. He was discharged home on a gradually tapering dose of oral steroids over 6 weeks. The patient was later seen at the pulmonary clinic for a follow-up visit. He was doing well and denied any significant respiratory symptoms. A follow-up chest x-ray was within normal limits (Figure 4).

Figure 4. Chest x-ray upon follow-up.

Discussion 

Acute eosinophilic pneumonia (AEP) is defined by rapid eosinophilic infiltration of the lung tissue, resulting in impaired gas exchange. Presenting symptoms are nonspecific and may include cough, progressive dyspnea, chest pain, and fever (2). Chest imaging of patients with AEP shows diffuse bilateral parenchymal infiltrates. Diagnosis can be made in the appropriate clinical and radiological context, with BAL showing at least 25% eosinophils on the fluid differential, and with no other identifiable causes (1).

The pathogenesis of AEP is not completely understood; however, it is hypothesized to involve a hypersensitivity reaction in patients with genetic susceptibility (3,4). AEP can be associated with many identifiable causes including cigarette smoke most notably, as well as other inhalants, infections, and medications. Although antibiotics and nonsteroidal anti-inflammatory drugs are among the more common inciting medications, injectable naltrexone has been implicated in several case reports (3,5,6,7).

The clinical presentations of AEP can mimic SARS-CoV-2 pneumonia, community-acquired pneumonia, or ARDS; hence, a high index of clinical suspicion is essential to avoid delay in therapy. A confident diagnosis of AEP can usually be made without a lung biopsy in patients who meet the following criteria (8):

1) acute onset of febrile respiratory manifestations (≤ 1-month duration before consultation).

2) bilateral diffuse opacities on chest radiography.

3) hypoxemia, with PaO₂ on room air<60 mm Hg, and/or PaO₂/FiO₂≤300 mm Hg, and/or oxygen saturation on room air<90%.4) lung eosinophilia, with >25% eosinophils on BAL differential cell count (or eosinophilic pneumonia at lung biopsy).

5) absence of known causes of AEP, including drugs, infections, asthma, or atopic disease.

In our case, the patient has met most of the suggested criteria for diagnosing AEP in addition to the presence of a triggering factor (a clear temporal relationship between the development of symptoms and the recent naltrexone injection). However, we met with a few obstacles before making the diagnosis of AEP.  During these unprecedented times, any patient presenting with acute hypoxic respiratory failure, and/or ground-glass opacities (both are classic for SARS-CoV-2 pneumonia as well as AEP) must go through an additional screening process to rule out COVID-19, including contact and airborne infection isolation precautions in addition to the standard precautions and SARS-CoV-2 PCR testing.  

On the other hand, several recent reports of AEP presumably triggered by SARS-CoV-2 infection had been described (9-10), which was another factor that contributed to making the diagnosis of AEP more challenging in his case and kept COVID-19 high on the differential diagnosis list. Furthermore, our patient received steroids on the initial presentation which likely affected the accuracy of the total eosinophilic counts in the BAL.

AEP has a higher likelihood than chronic eosinophil pneumonia of presenting with more severe symptoms and has a greater potential of rapid progression to respiratory failure. One review study reported 30-80% of AEP patients required intensive care unit admission and another case review noted 20% of AEP patients required mechanical ventilation (4,11). Treatment includes supportive care, recognition and avoidance of identifiable triggers, and systemic corticosteroids. Most patients rapidly improve with prompt corticosteroid treatment and experience complete recovery (1,3). Relapse of AEP rarely occurs (4).

Numerous conditions can cause pulmonary eosinophilia that needs to be differentiated from AEP. Different classifications have been suggested, but we will list the broad categories and most common etiologies including chronic eosinophilic pneumonia, eosinophilic granulomatosis with polyangiitis (EGPA, previously known as Churg-Strauss), drug and toxin-induced eosinophilic lung disease, helminthic, and fungal infection-related eosinophilic lung diseases, idiopathic hypereosinophilic syndrome, neoplasms, interstitial lung disease, coccidioidomycosis, tuberculosis, and allergic bronchopulmonary aspergillosis.

In addition to AEP, several conditions are associated with elevated BAL eosinophils greater than 25%.  These conditions include chronic eosinophilic pneumonia, EGPA, tropical pulmonary eosinophilia.  Other conditions causing BAL eosinophilia, but less than 25%, include connective tissue disease, drug-induced pneumonitis, fungal pneumonia, idiopathic pulmonary fibrosis, pulmonary Langerhans cell histiocytosis, sarcoidosis.

Finally, multiple medications are implicated in drug-induced AEP, however, naltrexone is still not well recognized as a potential cause.  In a recent retrospective review, naltrexone was not included in the medication list compiled (11).

Conclusion

Injectable naltrexone, a long-acting opioid antagonist, is used for the treatment of opioid and alcohol dependence. Although rare, the use of injectable naltrexone is associated with the potentially fatal side effect of AEP. Since AEP shares many clinical attributes with other causes of acute lung injury, including community-acquired pneumonia and SARS-CoV-2 pneumonia, it can be easily overlooked. Therefore, having an accurate history and an appropriate index of suspicion is important for early detection and proper management (3).

References

1. De Giacomi F, Vassallo R, Yi ES, Ryu JH. Acute Eosinophilic Pneumonia. Causes, Diagnosis, and Management. Am J Respir Crit Care Med. 2018 Mar 15;197(6):728-736. [CrossRef] [PubMed]
2. Katz U, Shoenfeld Y. Pulmonary eosinophilia. Clin Rev Allergy Immunol. 2008 Jun;34(3):367-71. [CrossRef] [PubMed]
3. Mears M, McCoy K, Qiao X. Eosinophilic Pneumonia and Extended-Release Injectable Naltrexone. Chest. 2021;160(4): A1676 [Abstract]. [CrossRef]
4. Suzuki Y, Suda T. Eosinophilic pneumonia: A review of the previous literature, causes, diagnosis, and management. Allergol Int. 2019 Oct;68(4):413-419. [CrossRef] [PubMed]
5. Horsley R, Wesselius LJ. June 2107 Pulmonary Case of the Month. Southwest J Pulm Crit Care. 2017;14(6):255-61. [CrossRef]  
6. Esposito A, Lau B. Saved by the BAL: A Case of Acute Eosinophilic Pneumonia After Methyl-Naltrexone Injection. Chest. 2019;156(4):A2210 [Abstract]. [CrossRef]
7. Korpole PR, Al-Bacha S, Hamadeh S. A Case for Biopsy: Injectable Naltrexone-Induced Acute Eosinophilic Pneumonia. Cureus. 2020 Sep 3;12(9):e10221. [CrossRef] [PubMed]
8. Philit F, Etienne-Mastroïanni B, Parrot A, Guérin C, Robert D, Cordier JF. Idiopathic acute eosinophilic pneumonia: a study of 22 patients. Am J Respir Crit Care Med. 2002 Nov 1;166(9):1235-9. [CrossRef] [PubMed]
9. Araújo M, Correia S, Lima AL, Costa M, Neves I. SARS-CoV-2 as a trigger of eosinophilic pneumonia. Pulmonology. 2022 Jan-Feb;28(1):62-64. [CrossRef] [PubMed]
10. Murao K, Saito A, Kuronuma K, Fujiya Y, Takahashi S, Chiba H. Acute eosinophilic pneumonia accompanied with COVID-19: a case report. Respirol Case Rep. 2020 Nov 16;8(9):e00683. [CrossRef] [PubMed]
11. Bartal C, Sagy I, Barski L. Drug-induced eosinophilic pneumonia: A review of 196 case reports. Medicine (Baltimore). 2018 Jan;97(4):e9688. [CrossRef] [PubMed]
12. Salahuddin M, Anjum F, Cherian SV. Pulmonary Eosinophilia. 2021 Dec 8. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan–. [PubMed]

Cite as: Breuer M, Ali A. Diagnostic Challenges of Acute Eosinophilic Pneumonia Post Naltrexone Injection Presenting During The COVID-19 Pandemic. Southwest J Pulm Crit Care Sleep. 2022;24(2):26-31. doi: https://doi.org/10.13175/swjpccs002-22 PDF 

Severe Respiratory Disease Associated with Vaping: A Case Report

Evan Denis Schmitz MD

La Jolla, CA USA

Abstract

A case of severe respiratory disease associated with vaping cannabinoid oil is reported in a 38-year-old woman. She presented with shortness of breath and nonproductive cough. Chest x-ray and CT scan showed diffuse ground glass opacities and consolidation. Bronchoscopy showed diffuse bronchial erythema and bronchoalveolar lavage contained an increased percentage of eosinophils (59%). She was treated with high dose corticosteroids and rapidly improved.

Case Report

History of Present Illness

A 38-year-old woman complained of worsening shortness of breath and nonproductive cough for four weeks. She used to be able to climb three flights of stairs but now can barely walk ten feet. She had been treated with various forms of antibiotics, inhalers and steroids and was taking 20 mg of prednisone a day on the day of hospitalization. She also received opiates to help control her cough. She denied any hemoptysis, fever, chills, or sputum production. Because of her progressive symptoms she was hospitalized for further evaluation and management.

Past Medical History, Social History and Family History

She has a history of obesity and fibromyalgia. She has a prior history of smoking one to two packs a day for five years quitting approximately 15 years ago. Because of a family crisis she tried vaping cannabidiol (CBD) oil approximately one month prior to admission. She also resumed smoking tobacco one half a pack per day. Her family history was unremarkable.

Medications

She was taking prednisone 20 mg/day and cyclobenzaprine (Flexeril®) for her fibromyalgia. She was also taking codeine cough syrup.

Review of Symptoms

She did have some chest pain associated with her shortness of breath as well as chronic muscle aches and intermittent lower extremity edema. Her review of systems was otherwise unremarkable.

Physical Examination

Vital Signs: BP 137/72 mm Hg, Pulse 84 beats/min, temperature 98.8 °F, respirations 22 breaths/min, height 5’0, weight 231 lbs, SpO2 96%

General: She was morbidly obese and only able to speak in short sentences.

Mouth: Moist. Mallampati 3.

Pulmonary: Faint expiratory crackles. No wheezing.

Cardiovascular: Normal rate, regular rhythm, normal heart sounds and intact distal pulses. Exam reveals no gallop and no friction rub. No murmur heard.

Abdominal: Soft, bowel sounds normal. No distension, mass or tenderness. No rebound or guarding. Centripetal obesity.

Extremities: Normal range of motion. No edema or tenderness.

Lymphatics: No cervical or supraclavicular adenopathy.

Neurological: Alert and oriented to person, place and time.

Skin: Warm and dry. No rash, erythema or pallor. Not diaphoretic. Capillary refill within normal limits. No skin tenting.

Psychiatric: Depressed mood.

Laboratory

Pertinent findings are on her laboratory evaluation include an elevated white blood cell count of 16,850 cells/µL with an increased number of neutrophils. Her electrolytes, liver enzymes, creatinine, blood urea nitrogen and urinalysis were within normal limits.

Radiology

Her admission chest x-ray is shown in Figure 1.

Figure 1. The admission portable chest x-ray showed bilateral patchy pulmonary infiltrates.

To better define the areas of consolidation, a thoracic CT scan was performed (Figure 2).

Figure 2. Representative images in lung windows from contrast enhanced thoracic CT scan showing nonspecific patchy areas of ground glass and alveolar opacities with septal thickening involving both lungs.

Hospital Course

Echocardiography was unremarkable. Bronchoscopy with bronchoalveolar lavage was performed. She had diffuse upper and lower airway erythema and considerable coughing during the procedure. The cell differential revealed an increase in eosinophils (59%) and multiple foamy macrophages. Smears and cultures of the lavage fluid were negative for pathogens. She was treated with high dose corticosteroids (methylprednisolone 1000 mg/day). She rapidly improved over four days with her cough and shortness of breath resolving. A chest x-ray at discharge revealed improvement of the pulmonary infiltrates (Figure 3).

Figure 3. Chest x-ray on the morning of discharge showing near resolution of her pulmonary infiltrates.

Discussion

At the time of this writing (9/21/19) there have been 530 cases of lung injury associated with e-cigarette product use or vaping reported with seven deaths (1).  Nearly three fourths (72%) of cases have been male with two thirds (67%) 18 to 34 years old. Most patients have reported a history of using e-cigarette products containing tetrahydrocannabinol (THC). Many patients have reported using THC and nicotine. Some have reported the use of e-cigarette products containing only nicotine.

At present no specific e-cigarette or vaping product (devices, liquids, refill pods, and/or cartridges) or substance has been linked to all cases. It seems likely that there may be different mechanisms of lung injury from different substances. In support of this concept, the present case had high numbers of eosinophils in the bronchoalveolar lavage while other cases have shown an increase in neutrophils (2). Our patient was treated with high dose corticosteroids and did improve while on the corticosteroids. However, the time course does not establish a definite relationship between corticosteroid treatment and her improvement.

At present the CDC recommends refraining from using e-cigarette or vaping products (1). Anyone who uses an e-cigarette or vaping product should not buy these products (e.g., e-cigarette or vaping products with THC or CBD oils) off the street, and should not modify or add any substances to these products that are not intended by the manufacturer.

References

1. CDC. Outbreak of lung injury associated with e-cigarette use, or vaping. September 19, 2019. Available at: https://www.cdc.gov/tobacco/basic_information/e-cigarettes/severe-lung-disease.html (accessed 9/21/19).
2. Arizona Thoracic Society. September 2019 Arizona thoracic society notes. Southwest J Pulm Crit Care. 2019;19(3):99-100. [CrossRef]

Cite as: Schmitz ED. Severe respiratory disease associated with vaping: a case report. Southwest J Pulm Crit Care. 2019;19(3):105-9. doi: https://doi.org/10.13175/swjpcc062-19 PDF