June 2024 Pulmonary Case of the Month: A Pneumo-Colic Association

Lewis J. Wesselius MD

Pulmonary Department

Mayo Clinic Arizona

Scottsdale, AZ USA

History of Present Illness

The patient is a 57-year-old woman who presented to the emergency department with increasing cough and shortness of breath over several days. She has a history of ulcerative colitis complicated by toxic megacolon with subsequent colectomy.

Past Medical History, Family History and Social History

• Ulcerative colitis with history of toxic megacolon (4 years prior), s/p total colectomy

• History of recent respiratory failure thought secondary to ustekinumab (Stelara).  The respiratory failure responded well to steroid therapy.

• She has a history of latent Tb treated with rifampin

• Anxiety

Medications

• Clonazepam 1.0 mg daily at bedtime

• Gabapentin 300 mg TID

• Pantoprazole 40 mg BID

• Prednisone 5 mg daily

Physical Examination

• Mild-moderate respiratory distress

• Afebrile. SpO2 87% on room air. Oxygen saturation 94% on 2 lpm supplemental oxygen.

• Chest: crackles noted at left base

• Cardiovascular: regular rhythm, no murmur

• Extremities: scarring and erythema on both ankles consistent with resolving pyoderma gangrenosum

Laboratory

• Hgb 9.7 g/dL

• White Blood Cell Count 16.9 × 109/L

• Increased neutrophils on differential

• Electrolytes, creatinine, BUN and liver function tests within normal limits

Radiology

A portable AP of the chest was performed in the emergency department (Figure 1).

Figure 1. Portable AP of chest done in emergency department.

Which of the following are appropriate next step(s)? (Click on the correct answer to be directed to the second of six pages)

1. Thoracic CT scan

2. Discharge to home on empiric antibiotics with close follow-up

3. Influenza A/B, Covid and Cocci serology

4. 1 and 3

5. All of the above

Cite as: Wesselius LJ. June 2024 Pulmonary Case of the Month: A Pneumo-Colic Association. Southwest J Pulm Crit Care Sleep. 2024;28(6):74-77. doi: https://doi.org/10.13175/swjpccs023-24PDF

December 2023 Pulmonary Case of the Month: A Budding Pneumonia

Ishan A. Patel, MD¹

Sarah Medrek, MD¹

Michael Reyes, MD²

Brannon Raney, MD³

Section of ¹Pulmonary, Critical Care, and Sleep Medicine, ²Pathology, and ³Infectious Disease

VA Albuquerque Health System

Albuquerque, NM USA

History of Present Illness

A 70-year-old man with a history of seropositive rheumatoid arthritis previously well controlled on hydroxychloroquine, methotrexate, and adalimumab was admitted to the hospital with 3 weeks of progressively worsening fatigue, night sweats, chills, and malaise. He did not describe new or worsening cough, shortness of breath, or sputum production. On the day of admission, he had intense nausea and vomiting.

PMH, SH, and FH

Prior to this admission, he was followed in Pulmonary Clinic for asymptomatic mild basilar fibrosis thought to be related to his rheumatoid arthritis and paraseptal emphysema related to prior smoking which was largely stable and unchanged over the previous two years. Previously, he smoked cigarettes at ½ pack per day for about 30 years and quit about 15 years ago. He denied any recent travel and was retired from the last 15 years from being a meat butcher. FH is noncontributory.

Physical Examination

On examination the day after admission from the ER, the patient’s temperature was 37.6C. His pulse was 79 bpm, blood pressure was 142/65 mmHg, and pulse oximetry revealed a saturation of 92% with 2 LPM nasal cannula of O2. He appeared generally weak, but alert. Pulmonary exam was unrevealing as was cardiac exam. He did not have cyanosis, clubbing, delayed capillary refill, or peripheral edema.

Laboratory

Initial blood work showed a WBC count of 7500/µL, hemoglobin level of 9.6 gm/dl, serum blood urea nitrogen of 36 gm/dl, serum creatinine of 2.49 g/dl, and serum calcium that was elevated at 12.3 mg/dl. A T-spot was obtained and was negative. Blood and sputum cultures were obtained and negative.

Radiography

Figure 1. Admission portable chest x-ray in the emergency department. To view Figure 1 in an enlarged, separate window click here.

The patient has a history of rheumatoid arthritis (RA). Which of the following patterns of interstitial lung disease (ILD) is most common in patients with RA? (Click on the correct answer to be directed to the second of seven pages)

1. Acute eosinophilic pneumonia
2. Lymphocytic interstitial pneumonitis
3. Non-specific interstitial pneumonia
4. Organizing pneumonitis
5. Usual interstitial pneumonitis

Cite as: Patel IA, Medrek SK, Reyes MD, Raney BL. December 2023 Pulmonary Case of the Month: A Budding Pneumonia. Southwest J Pulm Crit Care Sleep. 2023;27(6):62-66. doi: https://doi.org/10.13175/swjpccs048-23 PDF

September 2023 Pulmonary Case of the Month: A Bone to Pick

Lewis J. Wesselius MD

Pulmonary Department

Mayo Clinic Arizona

Scottsdale, AZ USA

History of Present Illness

A 56-year-old man presented acute onset of shortness of breath. He denied cough, fever or other symptoms

Past Medical History, Family History and Social History

• Occasional gout
• No relevant family history
• Never smoked

Medications

• Allopurinol
• Multivitamin

Physical Examination

• Other than tachypnea and mild shortness of breath, no significant abnormalities.

Chest X-ray

An AP chest X-ray was performed (Figure 1).

Figure 1. Admission chest X-ray.

Which abnormality is suggested  by the chest X-ray? (Click on the correct answer to the second of seven pages)

1. Calcified micronodules in the right lung
2. Retained secretions with atelectasis left lung
3. Right pneumothorax
4. 1 and 3
5. None. The chest X-ray is within normal limits.

Cite as: Wesselius LJ. September 2023 Pulmonary Case of the Month: A Bone to Pick. Southwest J Pulm Crit Care Sleep. 2023;27(3):26-29. doi: https://doi.org/10.13175/swjpccs037-23 PDF

June 2023 Pulmonary Case of the Month: An Invisible Disease

Lewis J. Wesselius MD

Pulmonary Department

Mayo Clinic Arizona

Scottsdale, AZ USA

History of Present Illness

A 78-year-old man presented to the Emergency Department on April 7 for shortness of breath and weakness over the last 2 weeks. He was in good health prior to an outside hospitalization March 29-April 3 for pneumonia and a possible non-ST-elevation myocardial infarction (elevated troponins). He had a bronchoscopy during his recent outside hospitalization without specific pathogen identified but was treated with antibiotics and discharged on levofloxacin. Since his hospital discharge 4 days previously he feels weaker and increasingly short of breath. He is short of breath even walking around his home. He denies fever or a productive cough.

Past Medical History, Family History and Social History

• Atrial fibrillation, s/p ablation. On Eliquis.
• Prior renal cell carcinoma, s/p resection, no recurrence
• DM Type 2
• GERD
• OSA
• Essential tremor
• Never smoked

Medications

• Apixaban
• Aspirin
• Atorvastatin
• Flecanide
• Insulin
• Levofloxacin
• Lisinopril
• Pantoprazole
• Tamsulosin

Physical Examination

• General: The patient looks comfortable and is in no distress
• Vital Signs: BP 110/62 O2 Sat 94% on room air
• CVS: Heart sounds are regular
• Lungs: Clear to auscultation
• Abdomen: Soft, nontender, bowel sounds present
• Extremities: No edema
• Neuro: Alert and oriented
• Skin: Warm and dry, no rashes

Chest X-ray

A portable chest X-ray was performed (Figure 1).

Figure 1. Portable chest X-ray obtained in the emergency department.

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

1. Arterial blood gases
2. Bronchoscopy
3. Thoracic CT scan
4. 1 and 3
5. All of the above

Cite as: Wesselius LJ. June 2023 Pulmonary Case of the Month: An Invisible Disease. Southwest J Pulm Crit Care Sleep. 2023;26(6):83-86. doi: https://doi.org/10.13175/swjpccs022-23 PDF

Kaposi Sarcoma With Bilateral Chylothorax Responsive to Octreotide

Humzah Iqbal, MD

Department of Internal Medicine, University of California San Francisco, Fresno, CA, USA

Abstract

Kaposi sarcoma (KS) is a soft tissue malignancy of the endothelial cells that can rarely invade the thoracic duct and cause bilateral chylothorax. Treatment for chylothorax includes drainage and dietary modification. However, octreotide has been reported to improve chylothorax in some pediatric and post-operative cases. We present a case in which a 9-day course of octreotide led to an improvement of non-traumatic malignant chylothorax.

Abbreviation list

• AIDS: acquired immunodeficiency syndrome
• CT: computed tomography
• HIV: human immunodeficiency virus
• KS: Kaposi sarcoma

Introduction

Kaposi sarcoma (KS) is a malignant, multifocal, highly vascularized tumor of the endothelial cells that most commonly affects the skin but may also include the lymph nodes, mucosa, and viscera (1). KS is commonly associated with human immunodeficiency virus (HIV) and can occur at any CD4 count (2). In very rare cases, Kaposi sarcoma can invade the thoracic duct and cause chylothorax (3). Chylothorax occurs when lymphatic fluid accumulates in the pleural cavity and is usually seen after damage to the thoracic duct following trauma or cardiothoracic surgery. It can also be caused by malignancy, however, bilateral chylothorax secondary to KS is rare. Treatment of chylothorax usually involves drainage of the effusion and initiation of a low-fat diet. Octreotide has been reported to improve traumatic chylothorax, but has only been reported in non-traumatic etiologies in a handful of cases (4). Here, we present a case of bilateral chylothorax associated with KS, which was successfully treated with octreotide.

Case Presentation 

A 40-year-old man with a previous diagnosis of acquired immunodeficiency syndrome (AIDS) and KS presented to the emergency department due to progressive tachypnea, dyspnea, bilateral lower extremity edema, and expansion of his KS lesions onto his legs and genital region. His vital signs were significant for a respiratory rate of 25 breaths per minute and pulse of 109 beats per minute. The patient denied recent infection, trauma, or procedures. Chest X-ray showed a large left pleural effusion with midline shift and a small right pleural effusion (Figure 1).

Figure 1. Upright chest X-ray demonstrating large left pleural effusion with midline shift and small right pleural effusion.

Computed tomography (CT) scan of the chest showed large bilateral pleural effusions with collapse of the right lower lobe and partial collapse of the upper lobes bilaterally (Figure 2).

Figure 2. Representative view from computed tomography (CT) scan (axial plane) in lung windows showing bilateral pleural effusions.

The patient developed hypoxemia and underwent thoracentesis with a total of 1.5 liters of pink, milky fluid removed (Figure 3).

Figure 3. Image of pleural fluid obtained from thoracentesis demonstrating pink, milky appearance.

Bilateral PleurX catheters (PleurX; Iskus Health; London, United Kingdom) were placed for persistent drainage. Fluid studies showed a triglyceride count of 147 mg/dL on the right side and 153 mg/dL on the left side. The patient continued to self-drain when symptomatic and drained about 600 mL of light-colored opaque fluid from each side daily. Serum albumin levels decreased to about 2.0 g/dL over the next week with concurrent development of diffuse pitting edema in all four extremities and abdomen. He was started on a high-protein, low-fat diet consuming up to 6-7 nutritional protein supplements per day with little to no improvement in his clinical state or serum protein levels. Given the patient’s poor response to treatment and persistence of his pleural effusions, a trial of octreotide was initiated. The patient was given octreotide 100 mg three times per day. About 3 days after initiating therapy, the patient refrained from draining his PleurX catheters for the first time and the frequency of draining decreased over the remainder of the week due to improvement in symptoms. The fluid was noted to be less opaque and clearer with each drainage. The patient’s tachypnea and oxygen saturation also showed improvement. After day 9 of octreotide, the treatment was discontinued and repeat pleural fluid studies showed a triglyceride count of 69 mg/dL on the right side and 89 mg/dL on the left side. With the resolution of his chylothorax and improvement in oxygenation status as well as his edema, the patient was discharged and will follow up with Oncology for continuation of his KS treatment.

Discussion

KS is known as an AIDS-defining illness that can invade a variety of tissues in the body leading to manifestations beyond the classic skin lesions. It can cause unusual neurologic, cardiac, orbital, laryngeal, endocrine, and gastrointestinal complications in rare cases (5). We present a case of bilateral chylothorax as another rare potential complication of KS. Other reported cases have presented similarly to our patient, such as a case presented by Pennington et al. (6) which also described dyspnea and hypoxemia with transient but significant improvements in ventilation with serial chest drainage as well as repeated reaccumulation of the chylothorax. In their case, however, the patient died as a result of his condition. Other cases of presumed KS-induced chylothorax have also resulted in marked nutritional deficiencies as seen in our patient (7).

Treatment of chylothorax involves therapeutic thoracentesis, a low-fat diet that is high in medium-chain triglycerides which do not pass through the thoracic duct, and surgical correction or embolization of the defect (8). Though not a standard practice, the use of octreotide has been reported to improve chylothorax in some cases. The majority of these cases have been traumatic chylothorax following cardiothoracic surgery in adults or the pediatric population, or neonates with congenital chylothorax (8). There is a paucity of literature regarding octreotide in the management of malignant and other non-traumatic causes of chylothorax in the adult population. One case has been reported by Togashi et al. (9) which describes chylothorax secondary to idiopathic fibrosing mediastinitis that was treated successfully with octreotide. The exact mechanism is unknown, but as a somatostatin analogue, it may involve a decrease in splanchnic blood flow and subsequent reduction in lymphatic flow from the gastrointestinal system and through the thoracic duct (10-11). There is no standard protocol for the administration of octreotide, however, most studies report a 1-2 week course with recognizable improvements after 2-3 days of treatment, as seen in our patient (12).

Conclusion

Bilateral chylothorax is a rare manifestation of KS that can lead to respiratory failure, malnutrition, and death. We present a case of non-traumatic, malignant chylothorax that was treated successfully with octreotide, a somatostatin analogue. Further studies are necessary to elucidate the exact mechanism of its effect on chylothorax and to establish a standardized treatment protocol for the usage of octreotide in this condition. 

References

1. Cesarman E, Damania B, Krown SE, Martin J, Bower M, Whitby D. Kaposi sarcoma. Nat Rev Dis Primers. 2019 Jan 31;5(1):9. [CrossRef] [PubMed]
2. Crum-Cianflone NF, Hullsiek KH, Ganesan A, Weintrob A, Okulicz JF, Agan BK; Infectious Disease Clinical Research Program HIV Working Group. Is Kaposi's sarcoma occurring at higher CD4 cell counts over the course of the HIV epidemic? AIDS. 2010 Nov 27;24(18):2881-3. [CrossRef] [PubMed]
3. Cherian S, Umerah OM, Tufail M, Panchal RK. Chylothorax in a patient with HIV-related Kaposi's sarcoma. BMJ Case Rep. 2019 Jan 22;12(1):e227641. [CrossRef] [PubMed]
4. Ismail NA, Gordon J, Dunning J. The use of octreotide in the treatment of chylothorax following cardiothoracic surgery. Interact Cardiovasc Thorac Surg. 2015 Jun;20(6):848-54. [CrossRef] [PubMed]
5. Pantanowitz L, Dezube BJ. Kaposi sarcoma in unusual locations. BMC Cancer. 2008 Jul 7;8:190. [CrossRef] [PubMed]
6. Pennington DW, Warnock ML, Stulbarg MS. Chylothorax and respiratory failure in Kaposi's sarcoma. West J Med. 1990 Apr;152(4):421-2. [PubMed]
7. Judson MA, Postic B. Chylothorax in a patient with AIDS and Kaposi's sarcoma. South Med J. 1990 Mar;83(3):322-4. [CrossRef] [PubMed]
8. Schild HH, Strassburg CP, Welz A, Kalff J. Treatment options in patients with chylothorax. Dtsch Arztebl Int. 2013 Nov 29;110(48):819-26. doi: 10.3238/arztebl.2013.0819. [CrossRef] [PubMed]
9. Togashi Y, Kim YH, Miyahara R, et al. Octreotide, a somatostatin analogue, in the treatment of chylothorax associated with idiopathic fibrosing mediastinitis. Tohoku J Exp Med. 2010 Sep;222(1):51-3. [CrossRef] [PubMed]
10. Katz MD, Erstad BL. Octreotide, a new somatostatin analogue. Clin Pharm. 1989 Apr;8(4):255-73. [PubMed]
11. Rosti L, De Battisti F, Butera G, et al. Octreotide in the management of postoperative chylothorax. Pediatr Cardiol. 2005 Jul-Aug;26(4):440-3. [CrossRef] [PubMed]
12. Kalomenidis I. Octreotide and chylothorax. Curr Opin Pulm Med. 2006 Jul;12(4):264-7. [CrossRef] [PubMed]

Cite as: Iqbal H. Kaposi Sarcoma With Bilateral Chylothorax Responsive to Octreotide. Southwest J Pulm Crit Care Sleep. 2022;25(5):69-72. doi: https://doi.org/10.13175/swjpccs048-22 PDF

June 2022 Pulmonary Case of the Month: A Hard Nut to Crack

Daniel Gergen MD¹

Anne Reihman MD¹

Carolyn Welsh MD^1,2

¹Department of Medicine, Division of Pulmonary and Critical Care Medicine, University of Colorado, Aurora, Colorado USA

²Eastern Colorado Veterans Affairs Medical Center, Aurora, Colorado USA

History of Present Illness: A 54-year-old man presented to clinic with chronic cough, dyspnea on exertion, unintentional weight loss, and night sweats. Seven months before, he developed dyspnea on exertion and symptoms did not improve with inhalers. Four months prior to presentation, he was treated for presumed community-acquired pneumonia of the right lower lobe. Neither symptoms nor chest radiograph improved with multiple courses of antibiotics. In the four weeks prior to presentation his symptoms progressed to the point that he was unable to walk in his house without significant dyspnea.

Review of systems: 10-pound unintentional weight loss and six weeks of night sweats.

Past Medical History, Social History and Family History: The patient had a 15-pack-year smoking history and quit 15 years prior to presentation. He had no other past medical history, surgical history, family history, nor medications.

Physical Examination: Vital signs were normal on presentation. Physical exam showed faint wheezing and decreased breath sounds over the right posterior lung fields.

Radiography: Chest radiograph demonstrated dense opacification in the superior segment of the right lower lobe (Figure 1).

Figure 1. Initial chest radiography. A: PA view. B: Lateral view.

What are diagnostic possibilities at this time?

1. Lung abscess
2. Lung cancer
3. Foreign body with post-obstructive pneumonia
4. Tuberculosis
5. 1 and 3
6. All the above

Cite as: Gergen D, Reihman A, Welsh C. June 2022 Pulmonary Case of the Month: A Hard Nut to Crack. Southwest J Pulm Crit Care Sleep. 2022;24(6):89-92. doi: https://doi.org/10.13175/swjpccs024-22 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 

March 2021 Pulmonary Case of the Month: Transfer for ECMO Evaluation

Nicholas G. Blackstone, MD

April Olson, MD

Angela Gibbs, MD

Bhupinder Natt, MD

Janet Campion, MD

University of Arizona College of Medicine – Tucson

Tucson, AZ USA

History of present illness

A 31-year-old male fire fighter with a history of recurrent “atypical pneumonia”, environmental and drug allergies, nasal polyps, asthma, and Crohns disease (not on immunosuppressants) was transferred from an outside hospital for management of acute hypoxic respiratory failure with peripheral eosinophilia. Prior to admission he reported a 2-week history of worsening dyspnea, productive cough and wheezing, prompting an urgent care visit where he was prescribed amoxicillin-clavulanate for suspected community acquired pneumonia. Despite multiple days on this medication, his symptoms significantly worsened until he was unable to lie flat without coughing or wheezing. He was ultimately admitted to an outside hospital where his labs were notable for a leukocytosis to 22,000 and peripheral eosinophilia with an absolute eosinophil count of 9700 cells/microL. His blood cultures and urine cultures were negative, and a radiograph of the chest demonstrated bilateral nodular infiltrates. With these imaging findings combined with the peripheral eosinophilia there was a concern for Coccidioidomycosis infection and he was subsequentially started on empirical fluconazole in addition to ceftriaxone and azithromycin. Bronchoalveolar lavage (BAL) was performed revealing 80% eosinophils, 14% polymorphic nuclear cells (PMNs), 4% monocytes and 2% lymphocytes, no pathogens were identified. The patient’s clinical status continued to decline despite antimicrobial therapy, and he was intubated for refractory hypoxia. At this point, the patient was transferred to our hospital for further care.

What is the most likely diagnosis in this patient? (Click on the correct answer to be directed to the second of four pages.)

1. Acute asthma exacerbation
2. Bacterial pneumonia
3. Coccidioidomycosis pneumonia
4. Eosinophilic pneumonia
5. Rocky Mountain Spotted Fever

Cite as: Blackstone NG, Olson A, Gibbs A, Natt B, Campion J. March 2021 Pulmonary Case of the Month: Transfer for ECMO Evaluation. Southwest J Pulm Crit Care. 2021;22(3):69-75. doi: https://doi.org/10.13175/swjpcc069-20 PDF

Respiratory Papillomatosis with Small Cell Carcinoma: Case Report and Brief Review

Priya Sharma

Anish Kumar

Bharath Janapati

Anil Kumar Jain

Department of Respiratory Medicine

National Institute of Tuberculosis and Respiratory Diseases

New Delhi 110030, India

Abstract

Respiratory Papillomatosis is a rare disease in which multiple exophytic squamous wart-like lesions occur within the respiratory tract. Recurrent Respiratory Papillomatosis (RRP) has the potential for malignant transformation to squamous lung cell carcinoma with a dismal prognosis. Most of the prior literature has shown malignant transformation of respiratory papillomatosis into squamous cell carcinoma. Here, we report a rare presentation of respiratory papillomatosis coexisting with small cell carcinoma and a review of relevant literature.

Introduction

RRP is a rare disease in which multiple exophytic squamous wart-like lesions occur within the respiratory tract. RRP has the potential for malignant transformation to squamous lung cell carcinoma with a dismal prognosis. The cases of squamous cell carcinomas developing within lung papillomas have been reported and these are usually associated with HPV 11 DNA (1,2). Here we present a rare case of respiratory papillomatosis coexisting with small cell carcinoma.  

Case Report

A 47-year-old woman presented with right sided chest pain and cough for 8 months. She had history of two episodes of blood streaked sputum four months ago. She also complained of loss of appetite and weight loss. She was a former smoker (1-2 cigarettes per day for 2-3 years quitting 5 years ago) and had a history of exposure to biomass fuel while working as a farmer. On examination pallor and clubbing was noted. Chest x-ray was suggestive of hilar enlargement (Figure 1).

Figure 1. Initial chest radiography.

Contrast-enhanced CT of the chest showed homogeneously enhancing soft tissue density central lung mass that is narrowing and circumferentially encasing right main bronchus. The mass was abutting arch of aorta and the ascending aorta and circumferentially encasing and narrowing the superior vena cava and right main pulmonary artery. Subsegmental collapse of superior segment of right lower lobe was also seen with right paratracheal and pretracheal lymph node enlargement (Figure 2).

Figure 2. Representative axial image from thoracic CT scan in soft tissue windows showing the right lung mass.

Flexible optic bronchoscopy showed an endoluminal irregular mass invading distal end of trachea along with carina and right main bronchus (Figure 3).

Figure 3. Photograph taken at bronchoscopy of the endobronchial mass in the distal trachea and right main bronchus.

Endobronchial biopsy showed papillary structures with fibro vascular cores lined with cell with moderate amount of cytoplasm with enlarged nuclei with granular chromatin and inconspicuous nuclei suggestive of RPR on histopathological examination. The patient was lost to follow up. Two months later she presented with increased breathlessness. Chest x-ray showed unilateral opaque right hemithorax with mediastinum slightly shifted to right (Figure 4).

Figure 4. Repeat chest radiography taken 2 months after initial presentation.

Hyponatremia was seen on routine blood investigation. CECT chest showed a well-defined heterogeneously enhancing soft tissue mass lesion with irregular margins involving the upper and middle lobe of right lung (Figure 5).

Figure 5. Coronal view of repeat thoracic CT in soft tissue windows.

The mass was encasing the right main bronchus and distal trachea, abutting large vessel, shifting trachea towards right side with moderate pleural effusion. Sputum analysis for acid-fast bacteria and malignant cells was negative. Ultrasound of abdomen showed no abnormality. Pleural fluid analysis showed paucicellular smear on cytology with ADA 20.5U/l, Protein 2.4 mg/dl and glucose 95.1 mg/dl. The patient refused bronchoscopy but consented to an ultrasound guided trans-thoracic biopsy. Histopathology showed pulmonary tissue with infiltrating tumor and the tumor was made up of sheets of small round cells with irregular contours suggestive of small cell carcinoma. Patient refused further management and left against medical advice. She passed away 11 days later.

Discussion

The incidence of RRP is bimodal, with the juvenile-onset form typically first occurring in children aged 2 to 4 years and adult-onset RRP typically occurring in adults aged 20 to 40 years. Juvenile-onset RRP is thought to be caused from peripartum exposure through an infected birth canal (3). Risk factors for adult-onset RRP include multiple lifetime sexual partners as well as a high frequency of oral sex. There was no statistically significant difference in illicit drug use between patients with adult-onset RRP vs a control group in a study by Ruiz et al. (4). RRP affects, from the most common site to the least common site, the true vocal cord, oral cavity, trachea, bronchi, and esophagus. Only 5% of the patients had the distal involvement of the trachea, and the involvement of the lung parenchyma is very rare, which is seen in, 1% of all cases (5). Therefore, patients present most commonly with hoarseness followed by stridor, cough, and dyspnea. Risk factor for malignant conversion includes smoking, prior irradiation, HPV-6. A recent study showed the presence of E6 and E7 oncogenes and their transcripts in HPV-positive lung cancer cases that are prerequisite for cancer development, thus reinforcing further the hypothesis that HPV could be a co-factor in bronchial carcinogenesis (6).Our patient had history of smoking as the only risk factor for malignant conversion.

Progressively increased expression of p53 and pRb proteins along with a reduced expression of p21^WAF1 protein appears to be significant subsequent events in the progression to carcinoma (7). Talierco et al. (8) reported 100% of patients with adult onset RRP had concurrent HPV infection of the oral cavity; however, our patient had no evidence of oral cavity HPV infection on physical examination. Bronchoscopic pictures were suggestive of papillary lesion although association with HPV can’t be commented upon as patient refused for further testing. A literature review of RRP case reports revealed that patients usually have the diagnosis of RRP many years before evidence of malignant transformation (9-12). In contrast, our patient had evidence of malignant transformation about six months after diagnosis of respiratory papillomatosis.

DiMarco et al. (13) were the first to report the presence of the multiple RRP of the tracheobronchial tree with malignant degeneration, in 1978. One other case report showing coexistence of multiple squamous cell papilloma and carcinoma in the upper trachea with severe airway obstruction has been reported (14). A case study done in Taiwan suggests that HPV infection is an important risk factor for lung cancer among women (15).

Surgical excision of RRP is the current standard of care with objective of preserving adequate voice quality and airway patency (16). Lasers can also be employed for surgical excision of RRP. Either cutting/ablating lasers (CO2 and thallium lasers), or photoangiolytic lasers such as pulsatile (PDL) and potassium- titanil-phosphate lasers (KTP) can be used. Both KTP and PDL lasers are safe and effective for in office treatment of RRP (17). Microdebriders have distinct advantages over lasers and cold instruments because of their shorter operating time and absence of thermal injury (18). Adjuvant therapies for RRP include the usage of immunomodulators such as IFN, antivirals such as Cidofovir, Angiogenesis inhibitor (Bevacizumab) and PDL-1 inhibitor (19). The development of HPV- 1 vaccination is perhaps the most important modality in the management of RRP, by preventing infection with papilloma virus.

Conclusion

To the best of our knowledge, this is the first case report of coexisting respiratory papillomatosis with small cell carcinoma lung. Thus, coexistence of malignancy or malignant degeneration of respiratory papillomatosis is although unusual but can still occur without the associative factors. Patients with RRP should be radiographically monitored at regular intervals for pulmonary involvement and further evaluation actively pursued if any suspicion of malignancy arises.

References

1. Magid MS, Chen YT, Soslow RA, Boulad F, Kernan NA, Szabolcs P. Juvenile-onset recurrent respiratory papillomatosis involving the lung: A case report and review of the literature. Pediatr Dev Pathol. 1998 Mar-Apr;1(2):157-63. [CrossRef] [PubMed]
2. Kramer SS, Wehunt WD, Stocker JT, Kashima H. Pulmonary manifestations of juvenile laryngotracheal papillomatosis. AJR Am J Roentgenol. 1985 Apr;144(4):687-94. [CrossRef] [PubMed]
3. Kashima HK, Shah F, Lyles A, Glackin R, Muhammad N, Turner L, Van Zandt S, Whitt S, Shah K. A comparison of risk factors in juvenile-onset and adult-onset recurrent respiratory papillomatosis. Laryngoscope. 1992 Jan;102(1):9-13. [CrossRef] [PubMed]
4. Ruiz R, Achlatis S, Verma A, Born H, Kapadia F, Fang Y, Pitman M, Sulica L, Branski RC, Amin MR. Risk factors for adult-onset recurrent respiratory papillomatosis. Laryngoscope. 2014 Oct;124(10):2338-44. Epub 2014 Jun 10. [CrossRef] [PubMed].
5. Cook JR, Hill DA, Humphrey PA, Pfeifer JD, El-Mofty SK. Squamous cell carcinoma arising in recurrent respiratory papillomatosis with pulmonary involvement: emerging common pattern of clinical features and human papillomavirus serotype association. Mod Pathol. 2000 Aug;13(8):914-8. [CrossRef] [PubMed]
6. Giuliani L, Favalli C, Syrjanen K, Ciotti M. Human papillomavirus infections in lung cancer. Detection of E6 and E7 transcripts and review of the literature. Anticancer Res. 2007 Jul-Aug;27(4C):2697-704. [PubMed]
7. Lele SM, Pou AM, Ventura K, Gatalica Z, Payne D. Molecular events in the progression of recurrent respiratory papillomatosis to carcinoma. Arch Pathol Lab Med. 2002 Oct;126(10):1184-8. [CrossRef] [PubMed]
8. Taliercio S, Cespedes M, Born H, Ruiz R, Roof S, Amin MR, Branski RC. Adult-onset recurrent respiratory papillomatosis: a review of disease pathogenesis and implications for patient counseling. JAMA Otolaryngol Head Neck Surg. 2015 Jan;141(1):78-83. [CrossRef] [PubMed]
9. Martina D, Kurniawan A, Pitoyo CW. Pulmonary papillomatosis: a rare case of recurrent respiratory papillomatosis presenting with multiple nodular and cavitary lesions. Acta Med Indones. 2014 Jul;46(3):238-43. [PubMed]
10. Azadarmaki R, Lango MN. Malignant transformation of respiratory papillomatosis in a solid-organ transplant patient: case report and literature review. Ann Otol Rhinol Laryngol. 2013 Jul;122(7):457-60. [CrossRef] [PubMed]
11. Hasegawa Y, Sato N, Niikawa H, Kamata S, Sannohe S, Kurotaki H, Sasaki T, Ebina A. Lung squamous cell carcinoma arising in a patient with adult-onset recurrent respiratory papillomatosis. Jpn J Clin Oncol. 2013 Jan;43(1):78-82. Epub 2012 Oct 30. [CrossRef] [PubMed]
12. Lin HW, Richmon JD, Emerick KS, de Venecia RK, Zeitels SM, Faquin WC, Lin DT. Malignant transformation of a highly aggressive human papillomavirus type 11-associated recurrent respiratory papillomatosis. Am J Otolaryngol. 2010 Jul-Aug;31(4):291-6. Epub 2009 Jul 10.  [CrossRef] [PubMed].
13. DiMarco AF, Montenegro H, Payne CB Jr, Kwon KH. Papillomas of the tracheobronchial tree with malignant degeneration. Chest. 1978 Oct;74(4):464-5. [CrossRef] [PubMed].
14. Paliouras D, Gogakos A, Rallis T, Chatzinikolaou F, Asteriou C, Tagarakis G, Organtzis J, Tsakiridis K, Tsavlis D, Zissimopoulos A, Kioumis I, Hohenforst-Schmidt W, Zarogoulidis K, Zarogoulidis P, Barbetakis N. Coexistence of squamous cell tracheal papilloma and carcinoma treated with chemotherapy and radiotherapy: a case report. Ther Clin Risk Manag. 2015 Dec 21;12:1-4. [CrossRef] [PubMed]
15. Lin FC, Huang JY, Tsai SC, Nfor ON, Chou MC, Wu MF, Lee CT, Jan CF, Liaw YP. The association between human papillomavirus infection and female lung cancer: A population-based cohort study. Medicine (Baltimore). 2016 Jun;95(23):e3856. Erratum in: Medicine (Baltimore). 2016 Jul 18;95(28):e0916. [CrossRef] [PubMed]
16. Kim HT, Baizhumanova AS. Is recurrent respiratory papillomatosis a manageable or curable disease? Laryngoscope. 2016 Jun;126(6):1359-64. [CrossRef] [PubMed] Epub 2015 Nov 26.
17. Yan Y, Olszewski AE, Hoffman MR, Zhuang P, Ford CN, Dailey SH, Jiang JJ. Use of lasers in laryngeal surgery. J Voice. 2010 Jan;24(1):102-9. Epub 2009 May 31.  [CrossRef] [PubMed]
18. Holler T, Allegro J, Chadha NK, Hawkes M, Harrison RV, Forte V, Campisi P. Voice outcomes following repeated surgical resection of laryngeal papillomata in children. Otolaryngol Head Neck Surg. 2009 Oct;141(4):522-6. [CrossRef] [PubMed]
19. Ivancic R, Iqbal H, deSilva B, Pan Q, Matrka L. Current and future management of recurrent respiratory papillomatosis. Laryngoscope Investig Otolaryngol. 2018 Jan 14;3(1):22-34. [CrossRef] [PubMed]

Cite as: Sharma P, Kumar A, Janapati B, Jain AK. Respiratory papillomatosis with small cell carcinoma: case report and brief review. Southwest J Pulm Crit Care. 2020;21:141-6. doi: https://doi.org/10.13175/swjpcc064-20 PDF

December 2020 Pulmonary Case of the Month: Resurrection or Medical Last Rites?

Lewis J. Wesselius, MD

Department of Pulmonary Medicine

Mayo Clinic Arizona

Scottsdale, AZ USA

History of Present Illness

An 88-year-old man who has been short of breath and febrile up to 101.5° F for the past day presented on October 20, 2020. He has no known sick contacts or exposure to COVID-19.

PMH, SH, and FH

• No reported pulmonary history although he had a Xopenex MDI which he rarely used.
• Coronary artery disease with prior coronary artery bypass grafting (1978); multiple subsequent stents; chronic atrial fibrillation; pacemaker (Micra)
• Stage 3-4 CKD (creatinine 1.95)
• Chronically on warfarin

Physical Examination

• Temp 37.3, Sat 92% on RA, 95% on 2 lpm,
• Lungs: Few crackles in right upper chest
• CV: regular, no murmur
• Ext: 1 to 2+ edema (chronic, uses TED hose)

Which of the following is/are the most likely diagnosis? (Click on the correct answer to be directed to the second of seven pages)

1. Community-acquired pneumonia
2. Congestive heart failure
3. COVID-19
4. 1 and 3
5. Any of the above

Cite as: Wesselius LJ. December 2020 Pulmonary Case of the Month: Resurrection or Medical Last Rites? Southwest J Pulm Crit Care. 2020;21(6):128-37. doi: https://doi.org/10.13175/swjpcc065-20 PDF

September 2020 Pulmonary Case of the Month: An Apeeling Example

Lewis J. Wesselius, MD

Department of Pulmonary Medicine

Mayo Clinic Arizona

Scottsdale, AZ USA

History of Present Illness

A 67-year-old woman who developed a chronic nonproductive cough beginning in October 2019. After 4 weeks, she consulted her primary care physician.

PMH, SH, and FH

• She had a history of several prior pneumonias, including respiratory syncytial virus in 2018
• Irritable bowel syndrome
• Hypertension
• Prior smoker: 28 pack years, none since 1999
• FH negative

Physical Examination

Her physical examination is recorded as unremarkable other than decreased nasal flow.

Which of the following is/are common cause(s) of a chronic cough? (Click on the correct answer to be directed to the second of seven pages)

1. Cough-variant asthma
2. Gastroesophageal reflux disease
3. Upper airway cough syndrome (UACS) secondary to rhinosinus diseases
4. 1 and 3
5. All of the above

Cite as: Wesselius LJ. September 2020 pulmonary case of the month: an apeeling example. Southwest J Pulm Crit Care. 2020;21(3):56-63. doi: https://doi.org/10.13175/swjpcc048-20 PDF

June 2020 Pulmonary Case of the Month: Twist and Shout

Lewis J. Wesselius, MD¹

Staci E. Beamer, MD² 

¹Departments of Pulmonary Medicine and ²Thoracic Surgery

Mayo Clinic Arizona

Scottsdale, AZ USA

History of Present Illness

An 83-year-old man presented with a left upper lobe lung nodule. The nodule was noted on a routine follow-up chest radiograph obtained after a radical cystectomy and left nephro-ureterectomy done 9 months earlier for invasive bladder cancer as well clear cell carcinoma of left kidney. He had symptoms of a mild chronic cough but denied shortness of breath with activities of daily living.

PMH, SH, FH

• Prostate cancer, post prostatectomy in 2009. 
• Bladder cancer and left renal cell cancer resected in Jan 2019
• Post-op chemotherapy after bladder and left kidney resections
• Non-ischemic cardiomyopathy, possibly due to            chemotherapy, EF 45%
• Chronic atrial fibrillation
• Smoking history: 60 pack years, no occupational exposures

Physical Examination

Other than an irregular pulse, his physical examination was unremarkable.

Medications

• Warfarin
• Atorvastatin
• Hydrochlorothiazide
• Ramipril
• Atenolol

Radiography

The initial chest radiograph is shown in Figure 1.

Figure 1. Initial chest x-ray.

Which of the following should be done at this time? (Click on the correct answer to be directed to the second of eight pages)

1. Chest CT scan
2. Left upper lobectomy
3. Comparison to old chest x-rays
4. 1 and 3
5. All of the above

Cite as: Wesselius LJ, Beamer SE. June 2020 pulmonary case of the month: twist and shout. Southwest J Pulm Crit Care. 2020;20(6):179-87. doi: https://doi.org/10.13175/swjpcc038-20 PDF 

Case Report: The Importance of Screening for EVALI

Vanessa Josef MD, MS

George Tu, MD, FCCP

Department of Internal Medicine and Lung Center of Nevada

HCA MountainView Hospital

Las Vegas, Nevada, USA

Abstract

E-cigarette or vaping product use associated lung injury (EVALI) is an epidemic that has swept the United States by storm starting in Sept 2019. E-cigarettes or vaping was initially advertised as a “safer” alternative to smoking cigarettes when they entered the market in 2007. Only now are we are starting to see the complications of a not so harmless behavior. Many times, EVALI can present similar to community acquired pneumonia (CAP), which can cause a clinical conundrum when despite adequate antibiotic coverage, patients’ respiratory status tend to decline. Through our case report, we demonstrate and stress the importance of early screening for e-cigarette and vaping use in social history to increase clinical suspicion of EVALI and provide early intervention if a patient does not respond to CAP treatment, in hopes of identifying more cases of EVALI and igniting future research. 

Introduction

The recent outbreaks of E-cigarette or vaping product use associated lung injury (EVALI) in Sept 2019, has placed the spotlight on the dangers of vaping. EVALI is a form of acute or subacute lung injury whose pathogenesis is unknown and is thought to be a spectrum of disease, rather than a single process. It has many findings such as organizing pneumonia, diffuse alveolar damage or acute fibrinous pneumonitis that are bronchiocentric and accompanied by bronchiolitis (1). If not identified quickly, EVALI has led to non-invasive ventilation, intubation and mechanical ventilation and even death in, otherwise, healthy young adults (1). The CDC confirmed 57 deaths and 2,602 reported cases of EVALI throughout the United States from Aug 2019 to Jan 2020, all of whom were between the ages of 18-34 (2,3). The paucity of knowledge within the medical community with regards to the disease, its pathogenesis and targeted treatment puts clinicians at a disadvantage. We report a case of a 30-year-old male who presented to our hospital with complaints of flu-like symptoms who was initially thought to have community acquired pneumonia but was later diagnosed with EVALI in order to raise awareness, illustrate how crucial screening can affect patient outcome and the need for further investigations of this severe respiratory illness. 

Case Presentation

A 30-year-old Hispanic male with significant past medical history of intracranial hemorrhage secondary to arteriovenous malformation and craniotomy (2016) was admitted to our hospital in December 2019 after experiencing productive cough, subjective fevers, malaise, night sweats, dizziness, and fatigue for 3 days. He denied having any sick contacts or obtaining the flu vaccine, or any recent hospitalization. His admitting diagnosis was sepsis due to community acquired pneumonia and he was found to have acute renal failure which was pre-renal in nature.

Clinical findings on admission were as follows: body temperature 37°C, blood pressure 116/75mmHg, heart rate 129 beats/min, respiratory rate 18 breaths/min and oxygen saturation 99% on room air. Physical examination revealed diminished breath sounds on the right lower lobe upon auscultation. The patient’s breathing did not appear labored and he was able to speak full sentences. Laboratory tests revealed: white blood cell count of 13,000 x 10⁹/L with 88.8% neutrophils, BUN/creatinine was 29/1.59 (elevated compared to last admission in 2016), urine toxicology was positive for cannabinoids, urinalysis showed proteinuria of 100 and the rest of the biochemical testing were within normal ranges.

The initial chest x-ray (Figures 1 and 2) was read as interval development of interstitial type infiltrates in the perihilar and lower lobe distribution bilaterally, favoring pneumonia, compared to his pervious chest x-ray from 2016 which had no evidence of acute cardiopulmonary process (Figure 3).

Figures 1 and 2. Chest radiography (PA and lateral views) from the day of admission.

Figure 3. Chest radiograph from a previous admission in 2016 showing no acute cardiopulmonary process.

Sepsis bolus was given in the emergency department, blood cultures were drawn, and patient was started on ceftriaxone and azithromycin for community acquired pneumonia. Overnight, The patient spiked fever twice of 39°C at 2am and 4am the next morning. Antibiotics were broadened to vancomycin and piperacillin-tazobactam and blood cultures were repeated. Patient endorsed dyspnea and increased work of breathing requiring 2L nasal cannula. He remained tachycardic with his heart rate in the 110s despite adequate fluid resuscitation and antibiotic coverage. He also spiked an additional fever of 39.3°C at 8am. Arterial blood gas obtained showed pH 7.49, pCO₂ 33, pO₂ 70, HCO₃ 25 on 2L nasal cannula indicating acute hypoxic respiratory failure and respiratory alkalosis. Since renal function normalized, CT angiogram of the chest (Figure 4) was obtained. Although negative for pulmonary embolism, it showed extensive bilateral ground-glass lung opacities characteristic of pulmonary edema or pneumonia, noted predominantly in the lower and middle lung zones with sparing of the periphery.

Figure 4. CT angiography of the chest in lung windows, almost 24hrs after presentation to the emergency department.

Pulmonology was consulted. Upon further questioning it was discovered the patient has been vaping CBD oil and THC for about 5 years. He vapes approximately 1-2 dabbed cartridges per week which he normally obtains from a dispensary and his friends. The last time he vaped was 3 days prior to admission. He denied smoking tobacco, having a history of childhood asthma. He was started on methylprednisolone 40mg IV BID. Because his temperature became mildly elevated at 37.9°C in the afternoon, it was decided to take him for a bronchoalveolar lavage (BAL) the following day.

Respiratory viral panel, urine Legionella and urine Streptococcus pneumoniae, HIV 4^th generation screen, sputum culture and blood cultures were all negative. Procalcitonin was 3.88 ng/ml. BAL cytology revealed non-specific pulmonary macrophages, benign bronchial epithelial cells, and mucus. It was negative for fungal organisms, cytomegalovirus, Mycoplasma, tuberculosis, Pneumocystis jirovecii, Legionella, and malignant cells. Gram stain was negative as well. 

No other events occurred during the rest of his hospital course. Extensive counseling provided regarding cessation of vaping, which the patient expressed he will no longer do. His respiratory symptoms improved with the start of steroids and he was discharged on hospital day 6 with Augmentin and a 10-day prednisone taper.

Discussion

Currently, EVALI is a diagnosis of exclusion, rather than part of the initial screening for patients who present to the hospital with respiratory complaints. During our team’s initial assessment of the patient, vaping was not asked based off the reported history, imaging studies, and labs obtained by the emergency department because it appeared to be a straightforward case of sepsis secondary to community acquired pneumonia (CAP). However, despite adequate antibiotic coverage with ceftriaxone and azithromycin our patient continued to spike high fevers overnight. He did not have any risk factors for MRSA or Pseudomonas that would call for broad empiric coverage when he was first admitted based off the IDSA 2019 guidelines for treating CAP (7).

Despite sepsis fluid resuscitation, our patient remained tachycardic where his heart rate ranged between 110-120s. CT angiogram of the chest to rule out pulmonary embolism could not be done when he was admitted due to acute renal failure. A ventilation-perfusion scan would not be an appropriate study at the time due to patient’s abnormal chest x-ray. Thus, the details of the lung parenchyma could not be appreciated at the time of admission. With his continual fever spikes, we ordered the following labs to try and identify the type of infection, the possibility of a superimposed infection or resistance to the current antimicrobial regimen and if the patient was immunocompromised: flu antigens, urine Legionella and Streptococcus pneumoniae, respiratory viral panel (adenovirus, human metapneumovirus, influenza A & B, parainfluenza 1, 2 & 3, RSV, rhinovirus), HIV 4^th generation screen, sputum culture, procalcitonin and repeat blood cultures. That same morning, his antibiotics were broadened to vancomycin and piperacillin-tazobactam.

Since the patient endorsed increased work of breathing and required 2L nasal cannula when he was initially on room air when he first arrived, pulmonary embolism (PE) had to be ruled out. With his renal function back to normal, we were able to get the CT angiogram of the chest which was negative for PE but showed the largely affected parenchyma. Pulmonology was consulted because of the irregular findings and sudden decline. Based off the peripheral sparing which is characteristic for EVALI and his urine toxicology testing positive for cannabinoids, further questioning about his social history was obtained. The patient’s admission to vaping THC and CBD oil for several years and that he obtains his cartridges from dispensaries and his friends, increased the suspicion for EVALI. Based on the current literature and reports from the CDC, EVALI is largely associated with the use of THC and products obtained from informal sources such as family/friends, dealers or online sellers (1). Many times, these unregulated products contain vitamin E acetate, which is currently thought to be the culprit ingredient igniting the destruction of lung parenchyma (4). The answer remains unclear if the cause of EVALI is an inhalation injury and/or is there an intrinsic reaction sparked by the chemical reactions between the various products that causes tissue injury.

He was immediately started on methylprednisolone 40mg IV BID, based on the recommended dosing of intravenous steroids of 1mg/kg (6). However, the patient’s temperature started to rise again despite the initiation of empiric antibiotics and steroids on the same day. BAL was performed the next morning to rule out infection, malignancy or any other structural issues and only revealed non-specific pulmonary macrophages, benign bronchial epithelial cells, and mucus. The patient clinically improved with the continued regimen of vancomycin, piperacillin-tazobactam and methylprednisolone IV.

There have been notable case reports with regards to EVALI that illustrate its various presentations and some of the barriers that make it difficult to diagnose. Salzman et al. (8) presented a case of a 27-year-old Caucasian female who developed acute eosinophilic pneumonia associated with electronic cigarettes. CBC at the time of admission showed WBC of 24,400 with 47% eosinophils. Although she admitted to vaping both nicotine and THC products for at least three years, three months prior to admission, she was vaping exclusively JUUL pods with nicotine blueberry and mint flavors. Her symptoms were severe enough that she required a one day stay in the ICU. She was treated with oral prednisone 50mg daily for a total of 5 days and oral doxycycline 100mg BID with improvement in her symptoms. This brings up the question whether her prior vaping history already jeopardized her lung parenchyma thus putting her at higher risk for developing EVALI.

In Schmitz’ (9) case report of a 38-year-old obese female with fibromyalgia on chronic prednisone (20mg daily), she admits to having started vaping CBD oil one month prior to admission. On BAL she was found to have diffuse upper and lower airway erythema with significant coughing, elevated eosinophil count (59%) and foamy macrophages which is associated with EVALI. She was started on methylprednisolone 1000mg daily, without antibiotics and experienced rapid improvement within a couple of days.

Works and Stack (5) discussed the case of a 20-year-old male who had several hospital admissions due to complaints of productive cough, high grade fever, gastrointestinal symptoms of diarrhea/nausea and 20lb unintentional weight loss over 3 weeks. The patient initially was treated at another hospital with ceftriaxone, levofloxacin and azithromycin and did not complete the course of antibiotics because they left against medical advice since they did not experience any improvement. On admission, the patient was found to have a very high leukocytosis with WBC of 44,800 and was not started immediately on empiric antibiotics. Instead, he was started on prednisone 1mg/kg and Bactrim after the BAL failed to yield an infectious cause. The patient was also noted to have obtain his THC cartridges from an outside source, like our patient.

Panse’s (10) case of a 25-year-old male who previously smoked 1-2packs per day and quit 6 months prior to admission was not forthcoming about vaping. Both CT scans showed multifocal ground-glass opacities with features of small airway obstruction. He underwent bronchoscopy and transbronchial biopsy which did not provide enough information to make a diagnosis. A video-assisted thorascopic lung biopsy was performed and showed acute and organized lung injury with interstitial edema, type II pneumocyte hyperplasia, alveolar fibrin deposition, acute fibrinous pneumonitis, lipid-laden macrophages and foci of organizing pneumonia consistent with EVALI. This is a prime example of how omission of vaping history delays diagnosis, leads to invasive procedures and although it did not happen in this particular situation, can result in death (10). Unlike the patient in Panse’s case, our patient easily admitted to vaping. Non-disclosure of medically relevant information such as vaping, is a problem clinicians will run into especially since it is a key piece of information needed to diagnose EVALI. Many patients withhold information from their doctors, especially those that they may find embarrassing, feel that they will be judge or lectured, or not wanting to hear about associated harm. Quantifying how many patients are withholding information or how many cases are not being accounted for because the person does not want to admit they are vaping would be difficult.

Formal diagnostic criteria for EVALI has not been agreed upon which can be attributed to the various forms of lung injury. We were able to diagnose our patient based of the suggested criteria of e-cigarette or vaping in the previous 90 days, lung opacities on chest x-ray or CT, exclusion of infection, and the absence of alternative diagnosis (cardiac, neoplastic or rheumatologic) (1). In a case series by Kalininskiy et al. (12), the University of Rochester Medical Center (Rochester, New York, USA) created a clinical practice algorithm to allow for the rapid identification of suspected EVALI based on history, clinical presentation and chest imaging, which is similar to the CDC however it focuses on vaping activity from the past 30 days rather than 90 days.

Currently, the treatment of EVALI is empiric antibiotics for community acquired pneumonia, systemic glucocorticoids in those with worsening symptoms, and supportive therapy with supplemental oxygen (6). In our case, the patient improved with the combination of vancomycin, piperacillin-tazobactam and methylprednisolone. The efficacy of systemic glucocorticoids is still unknown (1). However, it still remains unclear whether it was the combination of those specific antibiotics in conjunction with steroids, the combination of vancomycin and piperacillin-tazobactam only or solely systemic glucocorticoids. Since CAP is more common, it should not be overlooked and go untreated. Further investigation needs to be done for more targeted therapy.

The long-term effects of EVALI in those who were treated are still not well known. It is currently recommended for repeat imaging to determine if the treatment regimen was successful. However, many patients are lost to follow-up, as was the case for our patient due to lack of insurance.

Our case report illustrates how crucial early identification of EVALI affects patient care. It is imperative clinicians screen for the disease to prevent further complications. We recommend the following screening criteria: although the population greatly affected by the EVALI epidemic have been predominantly males between the ages of 18-34 (37% of the cases reported to the CDC as of Jan 14, 2020 are age 18-24, and 24% are 25-34, with a 66% male predominance) it should include all those who vape or use e-cigarettes regardless of age or gender as illustrated with the aforementioned case reports (13). Patients who presents with respiratory symptoms, especially if they are similar to pneumonia, such as dyspnea, increased work of breathing, fevers/chills, productive cough, chest pain, pleurisy, hemoptysis, and noted hypoxemia should be asked more than just smoking history with regards to cigarettes. They should be asked about prior E-cigarettes usage or vaping in the past, when was the last use, what kind of products were used and were they concentrated/dabbed and where it was obtained. Clinical suspicion should be increased if patients admit to THC or CBD use, but nicotine, flavorings and additives should not be disregarded. Urine drug screen should be ordered if there is a strong clinical suspicion, and the patient is denying prior THC use. EVALI has also been associated with gastrointestinal symptoms of abdominal pain, diarrhea, and nausea/vomiting. It is important to rule out infectious causes, by asking about sick contacts, recent hospitalizations, history of HIV and use of immunologic agents that can cause one to be immunocompromised. Patients should be screened about airway diseases such as asthma, COPD, and interstitial lung disease since they could have already caused chronic changes to lung parenchyma. There is still so much that the medical community does not know about EVALI. Further investigations still need to be pursued to improve the medical community’s diagnosis and treatment of this serious respiratory epidemic.

Disclaimer

This research was supported (in whole or in part) by HCA and/or an HCA affiliated entity. The views expressed in this publication represent those of the author(s) and do not necessarily represent the official views of HCA or any of its affiliated entities.

References

1. Layden JE, Ghinai I, Pray I, et al. Pulmonary illness related to e-cigarette use in Illinois and Wisconsin - final report. N Engl J Med. 2020 Mar 5;382(10):903-16. [CrossRef] [PubMed]
2. Centers for Disease Control. Outbreak of lung injury associated with the use of e-cigarette, or vaping, products. January 17, 2020.Available at: https://www.cdc.gov/tobacco/basic_information/e-cigarettes/severe-lung-disease.html#key-facts (accessed 3/10/20).
3. Ellington S, Salvatore PP, Ko J, et al. Update: product, substance-use, and demographic characteristics of hospitalized patients in a nationwide outbreak of e-cigarette, or vaping, product use-associated lung injury - United States, August 2019-January 2020. MMWR Morb Mortal Wkly Rep. 2020 Jan 17;69(2):44-9. [CrossRef] [PubMed]
4. Blount BC, Karwowski MP, Shields PG, et al. Vitamin E acetate in bronchoalveolar-lavage fluid associated with EVALI. N Engl J Med. 2020 Feb 20;382(8):697-705. [CrossRef] [PubMed]
5. Works K, Stack L. E‐cigarette or vaping product‐use‐associated lung injury (EVALI): A case report of a pneumonia mimic with severe leukocytosis and weight loss. JACEP Open. 2020;1-3. [CrossRef]
6. Triantafyllou GA, Tiberio PJ, Zou RH, et al. Vaping-associated acute lung injury: a case series. Am J Respir Crit Care Med. 2019 Dec 1;200(11):1430-1. [CrossRef] [PubMed]
7. Metlay JP, Waterer GW, Long AC, et al. Diagnosis and treatment of adults with community-acquired pneumonia. an official clinical practice guideline of the American Thoracic Society and Infectious Diseases Society of America. Am J Respir Crit Care Med. 2019 Oct 1;200(7):e45-e67. [CrossRef] [PubMed]
8. Salzman GA, Alqawasma M, Asad H. Vaping associated lung injury [EVALI]: an explosive United States epidemic. Mo Med. 2019 Nov-Dec;116(6):492-6. [PubMed]
9. Schmitz ED. Severe respiratory disease associated with vaping: a case report. Southwest J Pulm Crit Care. 2019;19[3]:105-9.[CrossRef]
10. Panse PM, Feller FF, Butt YM, Gotway MB. February 2020 imaging case of the month: an emerging cause for infiltrative lung abnormalities. Southwest J Pulm Crit Care. 2020;20(2):43-58. [CrossRef]
11. Levy AG, Scherer AM, Zikmund-Fisher BJ, Larkin K, Barnes GD, Fagerlin A. Prevalence of and factors associated with patient nondisclosure of medically relevant information to clinicians. JAMA Netw Open. 2018 Nov 2;1(7):e185293. [CrossRef] [PubMed]
12. Kalininskiy A, Bach CT, Nacca NE, Ginsberg G, Marraffa J, Navarette KA, McGraw MD, Croft DP. E-cigarette, or vaping, product use associated lung injury (EVALI): case series and diagnostic approach. Lancet Respir Med. 2019 Dec;7(12):1017-26. [CrossRef] [PubMed]
13. Centers for Disease Control. Outbreak of lung injury associated with the use of e-cigarette, or vaping, products. February 5, 2020. Available at:  https://www.cdc.gov/tobacco/basic_information/e-cigarettes/severe-lung-disease.html#map-cases (accessed 3/10/20).

Cite as: Josef V, Tu G. Case report: the importance of screening for EVALI. Southwest J Pulm Crit Care. 2020;20(3)87-94. doi: https://doi.org/10.13175/swjpcc012-20 PDF 

March 2020 Pulmonary Case of the Month: Where You Look Is Important

Richard A. Robbins, MD

Anselmo Garcia, MD

Arizona Chest and Sleep Medicine

Phoenix, AZ USA

History of Present Illness

A 47-year-old woman was seen for the first time in our clinic. She had approximately a two-year history of gradually increasing shortness of breath to the point where she could only climb one flight of stairs. In addition, she has a history of a cough sometimes productive and sometimes nonproductive. She did hear herself wheeze intermittently.

PMH, SH, and FH

She has a past medical history of gastroesophageal reflux disease (GERD). She was a nonsmoker and had no occupational exposure. Her aunt has a history of asthma.

Physical Examination

Her physical examination was normal and her lungs were clear.

Which of the following is appropriate at this time?

1. Reassurance
2. Treat empirically for post-nasal drip
3. Treat empirically with albuterol
4. Treat empirically with omeprazole
5. None of the above

Cite as: Robbins RA, Garcia A. March 2020 pulmonary case of the month: where you look is important. Southwest J Pulm Crit Care. 2020;20(3):76-83. doi: https://doi.org/10.13175/swjpcc013-20 PDF

December 2019 Pulmonary Case of the Month: A 56-Year-Old Woman with Pneumonia

Lewis J. Wesselius, MD

Department of Pulmonary Medicine

Mayo Clinic Arizona

Scottsdale, AZ USA

History of Present Illness

A 56-year-old woman complained of 6 weeks of increasing cough and shortness of breath. She had been treated for pneumonia with antibiotics, but when she failed to improve, she was begun on prednisone. She was receiving oxygen at 4 L/min by nasal cannula at the time she was seen.

PMH, SH, and FH

Her past medical history, social history and family were unremarkable other than a previous history of silicone breast implants. She was a nonsmoker.

Physical Examination

Her physical examination showed bibasilar crackles but was otherwise unremarkable.

Radiography

Her chest x-ray is shown in Figure 1.

Figure 1. Patient’s chest x-ray taken 6 weeks after the beginning of her illness.

Which of the following should be done at this time? (Click on the correct answer to be directed to the second of seven pages)

1. Coccidioidomycosis serology
2. Sputum gram stain and culture
3. Thoracic CT scan
4. 1 and 3
5. All of the above

Cite as: Wesselius LJ. December 2019 Pulmonary case of the month: a 56-year-old woman with pneumonia. Southwest J Pulm Crit Care. 2019;19(6):149-55. doi: https://doi.org/10.13175/swjpcc067-19 PDF

June 2019 Pulmonary Case of the Month: Try, Try Again

Lewis J. Wesselius, MD

Department of Pulmonary Medicine

Mayo Clinic Arizona

Scottsdale, AZ USA

History of Present Illness

A 53-year-old woman from presented with a 3-year history of shortness of breath. She was diagnosed with pneumonia in 2016, but even after treatment with antibiotics, continued to require supplemental oxygen. A CT-guided biopsy of a lung nodule was performed but there were no diagnostic findings. A surgical lung biopsy at another hospital was done but the report is unavailable. She had been diagnosed with possible scleroderma and treated with mycophenolate for 3 months and then azathioprine. 

Past Medical History, Social History and Family History

Aside from her history as in the HPI she has a remarkably negative past medical history. She does not smoke. Family history is noncontributory.

Physical Examination

• HEENT:  negative
• Chest:  Fine crackles at both lung bases
• Cardiovascular: regular rhythm, no murmur
• Skin:  skin thickening on fingers and distal forearms, but not elsewhere.  No pitting, ulcerations or calcinosis

Radiology

A chest x-ray was performed (Figure 1).

Figure 1. PA chest radiography done on presentation.

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

1. Obtain previous radiography and biopsy reports
2. Pulmonary function testing
3. Thoracic CT scan
4. 1 and 3
5. All of the above

Cite as: Wesselius LJ. June 2019 pulmonary case of the month: Try, try again. Southwest J Pulm Crit Care. 2019;18(6):144-51. doi: https://doi.org/10.13175/swjpcc026-19 PDF

March 2019 Pulmonary Case of the Month: A 59-Year-Old Woman with Fatigue

Lewis J. Wesselius, MD¹

Michael B. Gotway, MD²

¹Department of Pulmonary Medicine and ²Department of Radiology

Mayo Clinic Arizona

Scottsdale, AZ USA

History of Present Illness

A 59-year-old woman from Kingman, Arizona had a one-year history of fatigue with some shortness of breath. For this reason, she saw her primary care physician.

Past Medical History, Social History and Family History

She has no significant past medical history. She does not smoke. Family history is noncontributory.

Physical Examination

Physical examination was unremarkable.

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

1. Chest x-ray
2. Complete blood count
3. Electrolytes, blood urea nitrogen and creatinine
4. Liver panel
5. All of the above

Cite as: Wesselius LJ, Gotway MB. March 2019 pulmonary case of the month: A 59-year-old woman with fatigue. Southwest J Pulm Crit Care. 2019;18(3):52-7. doi: https://doi.org/10.13175/swjpcc008-19 PDF 

Co-Infection with Nocardia and Mycobacterium Avium Complex (MAC) in a Patient with Acquired Immunodeficiency Syndrome

Zahira Babwani DO

Kenneth Wojnowski Jr DO

Sunil Kumar MD

Broward Health Medical Center

Fort Lauderdale, FL USA

Abstract

We present a case in which a patient with acquired immunodeficiency syndrome (AIDS) and nocardiosis was found to have co-infection with Mycobacterium avium complex (MAC). Despite the fact that MAC is a known colonizer of the pulmonary system, ​ it is possible to have co-infection and a high degree of suspicion is necessary to ensure prompt treatment of both organisms. We wish to describe how radiologic findings were instrumental in guiding our differential diagnosis.

Case Report

History of Present Illness​: A 64-year-old man with history of alcohol and tobacco abuse presented with a chronic, productive cough for 5-6 months. Associated symptoms included shortness of breath and 30-pound weight loss. He denied all other symptoms.

Physical Exam​: Pertinent positives revealed temporal wasting, poor dental hygiene, oral thrush and diffuse rhonchi bilaterally. Initial vital signs were within normal limits.

Laboratory and Radiology​: Pertinent laboratory findings revealed leukocytosis with a left shift. Viral respiratory polymerase chain reaction (PCR) testing was negative. Human immunodeficiency virus (HIV) testing was positive with a CD4 count of 46 cells/mm³. QuantiFERON gold testing was negative. Sputum cultures, acid-fast bacilli (AFB) and blood cultures were obtained. Bronchoalveolar lavage (BAL) was performed with no evidence of Pneumocystis jirovecii (PJP). Chest X-ray (CXR) and computed tomography (CT) of the chest (Figure 1) revealed a multifocal right lung abscess with complex pleural fluid, empyema, nodular cavitary lesion in the left lower lobe and hilar lymphadenopathy.

Figure 1. Panel A: initial chest X-ray shows a complex infiltrate and effusion in the right lung. There is a cavitary lesion with air-fluid level vs lung abscess on the right. A nodule or consolidation is present in the left lung base. Panel B: A representative image from the initial CT of the chest showing a multifocal right lung abscess and complex pleural fluid.

Hospital Course: ​After admission, the patient was started on broad spectrum antimicrobials with vancomycin and piperacillin-tazobactam. A thoracentesis was performed due to right sided pleural effusion which yielded 65 cc of thick, purulent, green fluid. Thoracotomy with complete decortication of the right lung was performed with biopsies of the abscesses. Two 32-French chest tubes were placed due to the presence of multiple intraparenchymal lung abscesses, loculations, and empyema. Biopsy and pleural fluid cultures grew gram positive, beaded organisms which were later identified as nocardia, with no evidence of MAC or Mycobacterium tuberculosis (MTB). The patient was started on amikacin, meropenem and trimethoprim-sulfamethoxazole for newly diagnosed pulmonary nocardiosis. MAC prophylaxis was initiated due to his low CD4 count. After initiation of therapy for nocardiosis, three sputum AFB cultures began to stain positive. Since nocardiosis stains weakly positive for AFB, we initially did not suspect non-tuberculous Mycobacteria (NTM). Repeat CT scan of the chest (Figure 2) revealed ground glass opacities, nodular densities and both mediastinal and hilar lymphadenopathy.

Figure 2. Panel A: after initiation of treatment for nocardiosis, improvement of right empyema and cavitary lesion with bilateral patchy airspace disease right greater than left. Panel B: CT of the chest after initiation of treatment for nocardiosis, prominent lymph nodes in the hilar regions and mediastinum. less cavitation than the previous study. There are innumerable ground glass and nodular densities throughout both lungs, right greater than left.

Suspicion for active MAC co-infection was raised, the prophylactic dose of azithromycin was increased to the treatment dose, and ethambutol was initiated. After three weeks of intravenous amikacin, meropenem and trimethoprim-sulfamethoxazole the patient showed considerable improvement in his respiratory symptoms and was transitioned to oral trimethoprim-sulfamethoxazole for outpatient treatment of nocardiosis with continuation of ethambutol and clarithromycin for MAC.

Discussion

The Mycobacterium Avium Complex ​(MAC) is a Non-tuberculous mycobacterium (NTM) that is commonly found in patients with HIV and a CD4 count of less than 50. The diagnosis of NTM is challenging due to the fact that the organism is a known colonizer of the pulmonary system (1) ​. Supportive radiologic evidence is needed to distinguish colonization from active infection (2).

Common CT findings of nocardiosis include ground glass opacities, lung nodules, cavitation, pleural effusion and masses (3)​. The presence of mediastinal and hilar lymphadenopathy is the most common finding in immunosuppressed patients with MAC infection but is not​ a usual feature of pulmonary nocardiosis (3,4) ​. Our​ patient’s repeat CT scan showed mediastinal and hilar lymphadenopathy with improvement of cavitary lesions which suggests improvement of CT findings related to nocardiosis, but persistent findings related to NTM (5). This led us to believe that the patient was appropriately treated for nocardiosis, but with an underlying presence of active MAC infection that presented with atypical radiographic findings. As per the American Thoracic Society (ATS) guidelines for NTM pulmonary infection (6)​ ​, this patient’s pulmonary symptoms, radiological evidence on the chest CT, and positive AFB cultures from at least two separate expectorated sputum samples lends credibility to MAC as a true active infection in the setting of nocardiosis and AIDS. The patient was appropriately placed on clarithromycin and ethambutol as an outpatient, and our suspicions were confirmed for MAC with no evidence of MTB by PCR testing 5 weeks after initial AFB smears were collected.

Co-infection with Nocardiosis and MAC may be underestimated since they both often develop in immunocompromised hosts. MAC, along with other NTM species account for 20% of mycobacterium pulmonary infections in HIV infected patients (5)​. Nocardia accounts for less than 3% of pulmonary infections in HIV infected patients (5)​. A high degree of clinical suspicion is imperative to promptly treat infection with both organisms.

References

1. Young J, Balagopal A, Reddy NS, Schlesinger LS. Differentiating colonization from infection can be difficult Nontuberculous mycobacterial infections: Diagnosis and treatment. Patient Care. 2007. Available at: http://www.patientcareonline.com/infection/differentiating-colonization-infection-can-be-difficult-nontuberculous-mycobacterial-infections (accessed 10/3/18).
2. Trinidad JM, Teira R, Zubero S, Santamaría JM.Coinfection by Nocardia asteroides and Mycobacterium avium- intracellulare in a patient with AIDS. Enferm Infecc Microbiol Clin. 1992 Dec;10(10):630-1. [PubMed]
3. Kanne JP, Yandow DR, Mohammed TL, Meyer CA. CT findings of pulmonary nocardiosis. AJR Am J Roentgenol. 2011 Aug;197(2):W266-72. [CrossRef] [PubMed]
4. Erasmus JJ, McAdams HP, Farrell MA, Patz EF Jr. Pulmonary nontuberculous mycobacterial infection: radiologic manifestations. Radiographics. 1999 Nov-Dec;19(6):1487-505. [PubMed]
5. Benito N, Moreno A, Miro JM, Torres A. Pulmonary infections in HIV-infected patients: an update in the 21st century. Eur Respir J. 2012 Mar;39(3):730-45. [CrossRef] [PubMed]
6. Griffith DE, Aksamit T, Brown-Elliott BA, et al. An official ATS/IDSA statement: diagnosis, treatment, and prevention of nontuberculous mycobacterial diseases. Am J Respir Crit Care Med. 2007 Feb 15;175(4):367-416. [CrossRef] [PubMed]

Cite as: Babwani Z, Wojnowski K Jr, Kumar S. Co-Infection with Nocardia and Mycobacterium avium complex (MAC) in a patient with acquired immunodeficiency syndrome. Southwest J Pulm Crit Care. 2019;18(1):22-5. doi: https://doi.org/10.13175/swjpcc123-18 PDF

July 2018 Pulmonary Case of the Month

Anjuli M. Brighton, MB, BCh, BAO

Mayo Clinic Arizona

Scottsdale, AZ USA

Pulmonary Case of the Month CME Information

Completion of an evaluation form is required to receive credit and a link is provided on the last page of the activity. 

0.25 AMA PRA Category 1 Credit(s)™

Estimated time to complete this activity: 0.25 hours

Lead Author(s): Anjuli M. Brighton, MB. All Faculty, CME Planning Committee Members, and the CME Office Reviewers have disclosed that they do not have any relevant financial relationships with commercial interests that would constitute a conflict of interest concerning this CME activity.

Learning Objectives: As a result of completing this activity, participants will be better able to:

1. Interpret and identify clinical practices supported by the highest quality available evidence.
2. Establish the optimal evaluation leading to a correct diagnosis for patients with pulmonary, critical care and sleep disorders.
3. Translate the most current clinical information into the delivery of high quality care for patients.
4. Integrate new treatment options for patients with pulmonary, critical care and sleep related disorders.

Learning Format: Case-based, interactive online course, including mandatory assessment questions (number of questions varies by case). Please also read the Technical Requirements.

CME Sponsor: University of Arizona College of Medicine at Banner University Medical Center Tucson

Current Approval Period: January 1, 2017-December 31, 2018

Financial Support Received: None

History of Present Illness

An 81-year-old gentleman was admitted for syncope. He had felt unwell for one month. His recent illness started with the “flu”. He had lingering productive cough, low volume hemoptysis and felt very fatigued. After a coughing episode he apparently lost consciousness and was taken to the emergency department.

Past Medical History, Social History and Family History

He has a past medical history of hypertension, glaucoma, diverticulosis and COPD. He was taking only antihypertensives including a diuretic. He has a 30 pack-year history of smoking but quit 10 years ago.

Physical Examination

• Normotensive
• Tachypneic
• SpO2 96% on 2L NC
• Afebrile
• Diffuse wheezing, diminished at L base
• Irregularly irregular heart rate

Which of the following are indicated at this time? (Click on the correct answer to be directed to the second of six pages)

1. Chest x-ray
2. Complete blood count (CBC)
3. Electrocardiogram (EKG)
4. 1 and 3
5. All of the above

Cite as: Brighton AM. July 2018 pulmonary case of the month. Southwest J Pulm Crit Care. 2018;17(1):1-6. doi: https://doi.org/10.13175/swjpcc073-18 PDF 

Sharpening Occam’s Razor – A Diagnostic Dilemma

Payal Sen, MD¹

Uddalak Majumdar, MD²

Patrick Rendon, MD¹

Ali Imran Saeed, MD¹

Akshay Sood, MD¹

¹University of New Mexico

Albuquerque, NM US

²Cleveland Clinic Foundation

Cleveland, OH USA

Abstract

Objective: Physicians often search for Occam’s Razor, that is, to have a single diagnosis explain all clinical manifestations in an individual patient. Herein, we describe a case which was significant for a dual clinical diagnosis, thus proving that Occam’s razor may not always hold true. 

Case Summary: A 22-year-old Caucasian man presented with 4 days history of fever, and dry cough. Chest x-ray revealed a right middle lobe pneumonia. Mycoplasma IgM antibody titer was significantly elevated (>1:320), using the rapid diagnosis enzyme-immunoassay (EIA) test, and clinical course was complicated by rhabdomyolysis. He was treated with oral azithromycin for 5 days. The patient however returned to the ER in 2 weeks with similar symptoms and repeat chest x-ray revealed a persistent right middle lobe infiltrate. Endobronchial biopsy revealed necrotizing granulomatous inflammation which stained positive for Histoplasma capsulatum. Serum complement fixation antibody test for Histoplasma demonstrated an elevated titer of 1:64. The patient was diagnosed to have an ‘atypical pneumonia due to sub-acute Histoplasma capsulatum and acute Mycoplasma Pneumoniae infections, complicated by rhabdomyolysis.’

Discussion: This case is unusual because the patient had an acute community-acquired atypical pneumonia from Mycoplasma pneumoniae, complicated by rhabdomyolysis, and also had subacute Histoplasma pneumonia. Physicians often search for Occam’s Razor. However, following Hickam’s dictum, we made the unusual diagnosis of concomitant lung infection in an immunocompetent host with Mycoplasma pneumoniae and Histoplasma capsulatum. 

Conclusion: This was an immunocompetent patient who ran a complex, protracted, and unusual course of community acquired pneumonia. Often, the pursuit of additional or alternative diagnoses may require repeated and multiple invasive diagnostic sampling. Occam’s razor may not always hold true.

Introduction

Occam's razor proposes that the simplest explanation is usually the correct one. However, in the science of medicine, simple solutions may be elusive. Often there is an incredibly complex constellation of symptoms co-occurring with one another, thereby confounding the scientific community. We described the diagnostic conundrums in managing our patient who ran a complex protracted course of community acquired pneumonia.

Case

A 22-year-old Caucasian male college student with no significant past medical history, initially presented to the University hospital in New Mexico, United States, with 4 days’ history of fever, dry cough, and dyspnea. He had recently returned from a family vacation in Illinois and had spent several weeks fishing on the Mississippi river. Review of systems was negative for chest pain, headache, fever, chills, or night sweats. He denied any sick contacts. He did not smoke and did not use recreational drugs. His grandfather, who had been a heavy cigar smoker, had died of lung cancer.

His vital signs were significant for a body temperature of 100.6° Fahrenheit, respiratory rate of 32 breaths per minute, pulse rate of 94 bpm, blood pressure of 130/82 millimeters of mercury, and pulse oximetry of 90 percent on room air. Physical examination demonstrated that he was in mild respiratory distress. Chest auscultation revealed decreased breath sounds over the right mid to lower lung field. The rest of his physical examination was otherwise unremarkable. 

His laboratory tests revealed a normal complete blood count with a hematocrit of 40.5%, white blood cell count of 8,200 cells per microliter, and platelet count of 263,000 per microliter.  His electrolyte levels showed a serum sodium of 136 mEq per liter, potassium of 3.4 mEq per liter, chloride of 100 mEq per liter, bicarbonate of 21 mEq per liter, blood urea nitrogen of 15 mg/dL and creatinine of 0.9 mg/dL. His blood glucose was normal at 98 mg/dL. His urine analysis revealed 3+ blood without red blood cells. His liver function tests demonstrated an elevated aspartate aminotransferase at 244 units per liter, elevated alanine aminotransferase at 72 units per liter, with normal total bilirubin, albumin, and alkaline phosphatase levels. His serum creatinine kinase (CK) was highly elevated at 26,000 units per liter (normal reference range 39-308 units per liter). His arterial blood gas at rest on room air at an elevation of 5500 feet above sea level showed acute respiratory alkalosis with a normal alveolar arterial gradient with a pH of 7.57, PaCO2 of 28 mmHg, PaO2 of 77 mmHg, and bicarbonate of 22 mEq per liter.  His mycoplasma IgM antibody titer was significantly elevated (> 1:320) using the rapid diagnosis enzyme-immunoassay (EIA) test. Anti-mycoplasma pneumoniae IgA was also elevated. The urinary legionella and pneumococcal antigen levels, sputum culture, blood cultures, and urine toxicology screen were negative. Chest radiograph revealed a right middle and lower lobe pneumonia (Figure 1). 

Figure 1. CXR revealed right mid and lower lobe pneumonia.

The patient was diagnosed with sepsis secondary to Mycoplasma pneumoniae infection of the lungs, with the added complication of rhabdomyolysis. He was treated with intravenous followed by oral azithromycin 500 mg daily for 5 days and given intense hydration therapy. Within 48 hours, his low-grade fever subsided, CK decreased to 1000 units per liter, and the patient felt better. He was then discharged on Day 3 of hospitalization.

The patient however returned to the emergency department 2 weeks after discharge with persistent cough, chest discomfort, and loss of wellbeing. Repeat chest radiograph revealed a persistent right lower lobe infiltrate. Computed tomography (CT) scan of the chest revealed a right lower lobe consolidation with surrounding nodular opacities with a possible endobronchial lesion in the right lower lobe (Figure 2).

Figure 2. Panel A: Coronal view of thoracic CT scan showing right lateral basilar segment consolidation. Panel B: Axial view showing consolidation in the right lower lobe with surrounding nodular opacities.

He underwent bronchoscopy which revealed a mass-like endobronchial lesion in the lateral basilar segmental bronchus of the right lower lobe (Figure 3).

Figure 3. Bronchoscopy revealing a mass-like endobronchial lesion in a lateral segmental bronchus of the right lower lobe.

Endobronchial biopsy revealed necrotizing granulomatous inflammation and stained positive for the yeast form of Histoplasma capsulatum.  Serum complement fixation antibody test for Histoplasma demonstrated an elevated titer of 1:64. Acid fast bacilli were not seen on smear or culture and cytology and histopathology tests did not reveal malignancy.

The patient was diagnosed with an atypical pneumonia due to sub-acute Histoplasma capsulatum and acute Mycoplasma Pneumoniae infections, complicated by rhabdomyolysis. The mycoplasma infection and rhabdomyolysis had already been treated and resolved. For the subacute pulmonary histoplasmosis, the patient was treated with 10 weeks of oral itraconazole. Post treatment clinic follow-up revealed resolution of symptoms and radiological abnormalities.

Discussion

Mycoplasma pneumoniae is a common causative pathogen for community-acquired pneumonia in both children and adults (1).  Apart from respiratory tract symptoms, it is associated with a variety of extra-pulmonary manifestations (2). Recognizing this association can lead to timely diagnosis and treatment of both the mycoplasma infection and its complications. In this case report, we also want to highlight the fact that infection with endemic mycoses can often be mistaken for community acquired pneumonias, and thus having a high index of suspicion for fungal infection is very important, even in immunocompetent patients (3), to prevent a delay in treatment. Physicians often search for Occam’s Razor, i.e., to have a single diagnosis explain all clinical manifestations in an individual patient. This case is significant because of a dual clinical diagnosis, thus proving that Occam’s razor may not always hold true in an individual patient.

Mycoplasma infection can cause several unusual extra-pulmonary manifestations such as hemolytic anemia, immune thrombocytopenic purpura, transverse myelitis, Guillain-Barre syndrome, acute hepatitis and arthritis (4). Another lesser known complication of mycoplasma infection is rhabdomyolysis (5). Rhabdomyolysis is a syndrome caused by injury to the skeletal muscles, thereby resulting in leakage of myoglobin into blood (6). The classic triad of mycoplasma infection consists of myalgias, pigmenturia, and generalized muscle weakness, but this classic triad is seen in less than 10 percent of infected patients (7). Acute renal failure due to acute tubular necrosis as a result of mechanical obstruction by myoglobin is the most common complication, in particular if the serum CK level is >16,000 IU/l, which may be as high as 100,000 IU/l (8). In addition to mycoplasma infection, more common causes of rhabdomyolysis are trauma, immobilization, and recreational drug and alcohol use (9). 

Other organisms known to cause rhabdomyolysis are Influenza A and B virus, Coxsackie virus, Epstein-Barr virus, Primary Human Immunodeficiency virus, Legionella species, Staphylococcus aureus, and Streptococcus pyogenes (9). With respect to Mycoplasma pneumoniae infection, a possible mechanism for rhabdomyolysis is the induction of inflammatory cytokines, such as tumor necrosis factor-alfa (TNF-α) and interleukin-1 (IL-1), which may cause proteolysis of skeletal muscles (10). 

The rapid and reliable diagnosis of Mycoplasma pneumoniae (Mp) enables the correct and prompt use of antibiotics. Methods for identifying Mp infection include culture, molecular detection of pathogen specific antigen or nucleic acid, and serological analysis (11). Each of these methods has its pros and cons. Culture is the definitive method for diagnosis and is critical for monitoring trends in epidemiology but is slow and requires specialized media and trained personnel (11). Although molecular methods for nucleic acid or antigen detection have emerged as the primary techniques for identification of MP pneumoniae in surveillance programs, adoption of these methods is still lagging behind in USA.

Serologic analysis can prove to be problematic due to poor sensitivity and specificity, and the inability to characterize the specific Mp strain. Having said that, most physicians in the United States continue to rely on serological testing in concordance with the IDSA guidelines (11). It is well known that a single serologic test is of limited value in the early diagnosis of mycoplasma pneumoniae since there are often no IgM antibodies in the early stage of infection, and these IgM antibodies may persist long after the infection (12). However, if these IgM antibodies are present along with anti-Mycoplasma pneumoniae IgA, it is usually indicative of recent primary mycoplasma pneumoniae infection (13). A single high Mp-specific antibody titer (> 1:320) has been regarded as a diagnostic marker of mycoplasma pneumoniae, although it is present in only about 30 percent of the patients (12). Since our hospital relies on serological testing, we tested for the specific Mycoplasma pneumoniae IgM and IgA, both of which were positive. The MP-specific antibody titer was also greater than 1:320, thus signifying it indeed was early MP infection.

Symptoms of Mp infection generally resolve within 3–4 weeks after disease onset but can be shortened with antibiotic therapy; macrolides and doxycycline are the mainstay of this treatment (14). The mainstay for the prevention of pigment-induced acute kidney injury is the correction of volume depletion, prevention of intratubular cast formation, and the treatment of the underlying cause of rhabdomyolysis (4). This is done by aggressive fluid resuscitation resulting in increased renal blood flow and thus increasing the urinary flow with consequential wash out of partially obstructing tubular casts (4). Physicians will be served well to watch out for mycoplasma associated rhabdomyolysis in patients with atypical pneumonia and manifestations like myalgia, elevated aminotransferase levels, and myoglobinuria. 

Moving on to the second teaching point, endemic mycoses like coccidioidomycosis, histoplasmosis, and blastomycosis are often overlooked causes for community acquired pneumonia, particularly when immunocompetent patients travel out of the endemic zones (15). Often, testing is not even performed until the patient has failed to improve on antibacterial therapy. Delays in recognition, diagnosis and proper treatment may lead to disastrous outcomes (3). Performance of fungal antigen testing on bronchial washings or lavage fluid may improve the sensitivity for diagnosis over microscopic examination and the speed of diagnosis over culture even though isolation of the fungus by culture remains the gold standard method for definitive diagnosis (16). In this case, our patient was previously treated as mycoplasma pneumonia, thus leading to prolonged symptom course from histoplasmosis.

This case is unusual because the patient had an acute community-acquired atypical pneumonia from Mycoplasma pneumoniae, complicated by rhabdomyolysis, and also had subacute Histoplasma pneumonia. Physicians often search for Occam’s Razor, a principle from philosophy that when presented with competing hypothetical answers to a problem, one should select the one that makes the fewest assumptions.  Countering

Occam’s Razor, Dr. John Hickam said “Patients can have as many diseases as they damn well please!” (17). Following Hickam’s dictum, we made the unusual diagnosis of concomitant lung infection in an immunocompetent host with Mycoplasma pneumoniae and Histoplasma capsulatum.

Conclusion

With this case report, the authors wish to highlight two important teaching points. The first being that rhabdomyolysis is a serious but treatable extrapulmonary complication of Mycoplasma pneumoniae infection of the lungs. Having a high index of suspicion can limit treatment delay for rhabdomyolysis caused by mycoplasma infection and will therefore limit consequential morbidity like renal insufficiency. The second point that the authors wish to emphasize is that endemic fungal infection can often be mistaken for bacterial and viral community-acquired pneumonia in an immunocompetent host, particularly when they present with symptoms outside the endemic zone, thus delaying timely management. Hence one should have a high suspicion for fungal infection in immunocompetent hosts with unusual presentations such as history of travel to endemic zone, chronicity of symptoms, lack of response to therapy for community-acquired pneumonia, nodular lung lesions, and endobronchial abnormalities.

References

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Cite as: Sen P, Majumdar U, Rendon P, Saeed AI, Sood A. Sharpening Occam's razor-a diagnostic dilemma. Southwest J Pulm Crit Care. 2018;16(6):324-31. doi: https://doi.org/10.13175/swjpcc061-18 PDF