September 2019 Pulmonary Case of the Month: An HIV Patient with a Fever

William P. Diehl IV, DO

Nicholas Villalobos, MD

Department of Internal Medicine

University of New Mexico

Albuquerque, NM USA

History of Present Illness

A 33-year old transgender male to female presented from human immunodeficiency virus (HIV) clinic for two months of fevers, intermittent shortness of breath, cough with blood streaked sputum, headache, and nausea. The clinic provider was concerned when labs showed up trending HIV viral load (3.3 million copies) and an absolute CD4 count of 57.

Past Medical History, Social History and Family History

The patient had a history of stage-III HIV diagnosed in 2014 on bictegravir, emtricitabine, tenofovir (Biktarvy) and latent tuberculosis (TB) diagnosed 2017 on isoniazid and B6. She is from Nicaragua and arrived in Albuquerque, NM in 2017. Social history is pertinent for sex trafficking and methamphetamine use.

Physical Examination

Upon admission, the patient’s vital signs were notable for a temperature of 39.2 degrees Celsius, blood pressure of 114/71 mmHg, oxygen saturation of 95% on room air with a respiratory rate of 18 breaths per minute. Physical exam was notable for an absence of rash, palpable lymphadenopathy or cachexia.

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

1. Blood cultures
2. Lumbar puncture
3. Sputum for AFB and tuberculosis
4. 1 & 3
5. All of the above

Cite as: Diehl WP IV, Villalobos N. September 2019 pulmonary case of the month: an HIV patient with a fever. Southwest J Pulm Crit Care. 2019;19(3):87-94. doi: https://doi.org/10.13175/swjpcc056-19 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

December 2018 Pulmonary Case of the Month: A Young Man with Multiple Lung Masses

Lewis J. Wesselius, MD

Department of Pulmonary Medicine

Mayo Clinic Arizona

Scottsdale, AZ USA

History of Present Illness

A 28-year-old man from Tennessee has been feeling ill with malaise and weight loss for the past 3 months. He had been in the in the Palm Springs area a few weeks prior to becoming ill. He works as a musician.

Past Medical History, Social History and Family History

He has a history of Wolf-Parkinson-White syndrome and had a prior ablation procedure at age 16. He does not smoke tobacco but does smoke marijuana occasionally. Family history is noncontributory.

Physical Examination

Physical examination was unremarkable.

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

1. Bronchoscopy with EBUS
2. Chest X-ray
3. VATS
4. 1 and 3
5. All of the above

Cite as: Wesselius LJ. December 2018 pulmonary case of the month: a young man with multiple lung masses. Southwest J Pulm Crit Care. 2018;17(6):138-45. doi: https://doi.org/10.13175/swjpcc118-18 PDF 

September 2018 Pulmonary Case of the Month: Lung Cysts

Lewis J. Wesselius, MD

Department of Pulmonary Medicine

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. 

0.50 AMA PRA Category 1 Credit(s)™

Estimated time to complete this activity: 0.50 hours

Lead Author(s): Lewis J. Wesselius, MD. 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: The University of Arizona College of Medicine-Tucson

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

Financial Support Received: None

History of Present Illness

A 67-year-old woman was referred for mild shortness of breath for several years, but worse since January 2018.  She has dyspnea on exertion after 1 block. An outside chest x-ray, electrocardiogram and echocardiogram are reported as normal. She was begun on prednisone at 40 mg/day and her symptoms improved. However, her symptoms worsened when the dose tapered to 5 mg/day. She gained 35 pounds while on the prednisone and tried a steroid inhaler therapy without benefit. She is still dyspneic after 1 block of exertion.

Past Medical History, Social History, Family History

• Her past medical history was only positive for gastroesophageal reflux for which she takes ranitidine and hypertension for which she takes lisinopril.
• She was a life-long nonsmoker.
• There was no occupational history, hot tub or bird exposures.
• Family history is noncontributory.

Physical Examination

• Her SpO2 was 94% on room air.
• Chest:  few crackles noted at right base.
• Cardiovascular: regular rate and rhythm without a murmur.
• Extremities: no edema or clubbing.

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. Measure her SpO2 after exercise
2. Reassure the patient the patient that she has hysterical dyspnea
3. Pulmonary function testing
4. 1 and 3
5. All of the above

Cite as: Wesselius LJ. September 2018 pulmonary case of the month: lung cysts. Southwest J Pulm Crit Care. 2018;17(3):85-92. doi: https://doi.org/10.13175/swjpcc101-18 PDF 

August 2018 Pulmonary Case of the Month

Arooj Kayani, MD

Richard Sue, MD

Banner University Medical Center Phoenix

Phoenix, 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): Arooj Kayani, MD. 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, 201

Financial Support Received: None

History of Present Illness

A 59-year-old woman referred because of worsening dyspnea over the past 2 months along with cough and wheezing. She has a history of chronic obstructive pulmonary disease (COPD) and is on continuous oxygen @ 2 L/min.

PMH, SH, and FH

In addition to her COPD she has a history of hypothyroidism, pneumonia, tonsillectomy, hip lipoma resection, hysterectomy, and a herniorrhaphy. She has a 30 pack-year history of smoking. She currently smokes half pack/day. No family history of lung disease or cancer.

Medications

• Fluticasone/salmeterol
• Tiotropium
• Albuterol
• Levothyroxine

Physical Examination

• Vitals: HR 79/min, BP 100/69 mmHg, RR 16/min, SpO2 92% on 2 L/min.
• General: Alert and oriented. Healthy appearing in no distress.
• Lungs: Expiratory stridor and expiratory wheezing loudest over left lung. No crackles.
• Cardiac: Regular rhythm with no murmurs. No edema.
• The remainder of physical examination was unremarkable.

Which of the following should be performed? (Click on the correct answer to proceed to the second of four pages)

1. Spirometry
2. Sputum Gram stain, AFB stain, and fungal stain with cultures
3. Thoracic CT scan
4. 1 and 3
5. All of the above

Cite as: Kayani A, Sue R. August 2018 pulmonary case of the month. Southwest J Pulm Crit Care. 2018;17(2):47-52. doi: https://doi.org/10.13175/swjpcc093-18 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 

Intralobar Bronchopulmonary Sequestration: A Case and Brief Review

Uddalak Majumdar, MD¹ 

Payal Sen, MD²

Akshay Sood, MD²

¹Cleveland Clinic Foundation, Cleveland, OH USA

²Univeristy of New Mexico, Albuquerque, NM USA

Abstract

Objective: Bronchopulmonary sequestration is a rare congenital abnormality of the lower respiratory tract, seen mostly in children but often in adults. The term implies a mass of lung tissue that has no function and lacks normal communication with the rest of the tracheobronchial tree.

Case: A 40-year-old man presented with acute onset of left flank pain for 4 hours. He was born in Yemen and emigrated to the US in 1998; at that time, he had been tested for tuberculosis which was negative. In this admission, he met systemic inflammatory response (SIRS) criteria and had basilar crackles in the left lower lobe of the lung. CT scan revealed a cavitary lesion with air-fluid level in the left lower lobe airspace. There was systemic arterial blood supply to this region arising off the celiac axis. He was diagnosed with an infected intralobar bronchopulmonary sequestration and underwent video-assisted thoracoscopic wedge resection. On follow up 3 months later, he was doing well.

Discussion: Pulmonary sequestration is a rare congenital anomaly of a mass of lung tissue, which can have cystic changes and is a very important differential diagnosis of cavities in the lung. Confirmation of diagnosis is by visualization of a systemic vessel supplying sequestrated pulmonary, and this is accomplished by contrast-enhanced CT scan, MRI or invasive angiography. 

Conclusion: The delay in diagnosis in our patient was due to falling prey to anchoring and availability biases and chasing the diagnosis of tuberculosis in a patient from Yemen with a lower lobe cavitation.

Case

History of Present Illness: A 40-year-old man with a past medical history of atrial fibrillation presented to the hospital with acute onset of left flank pain for 4 hours, fevers and chills. The pain was sharp and stabbing, pleuritic, non-radiating, and was severe with an intensity of 10/10. He denied extraneous activity or trauma earlier in the day, denied substernal pain, cough, night sweats, weight loss or change in urinary habits. He was born in Yemen and emigrated to the US in 1998; at that time, he was tested for tuberculosis (TB) which was negative. He was known to have a cavitary lesion in left lower lobe since 2005, and had undergone extensive evaluation (imaging, sputum and PPD) which showed no form of tuberculosis. He denied taking prophylactic TB treatment. Annual PPD testing had always been negative.

The patient worked on a ship, which travelled in the Great Lakes on the US-Canada border. He was a current smoker with a 20-pack-year smoking history. He lived at home with his wife and children. There was no history of IV drug use, prior imprisonment or homelessness. He denied being in contact with anyone with TB while in Yemen. He was sexually active with his wife and had no other sexual partners. He denied history of sexually transmitted infections.

Physical Examination:

Vital Signs: Temp – 38.3 degrees Fahrenheit, Pulse- 111/minute, RR- 18/min, BP- 151/66 mm Hg. Spo2- 90 % on Room Air.

Basilar crackles and rhonchi in the left lower lobe of the lung. No cervical or inguinal lymphadenopathy. Rest of the physical exam was normal.

Significant Laboratory Findings:

WBC elevated at 15,500/mm³ with 65 percent Neutrophils.

Lactate - 1.1 mmol/dL

Radiography:

Chest x-ray was done while in the emergency department, which revealed left basilar sub-segmental atelectasis (Figure 1).

Fig.1. Chest x-ray showing left basilar sub-segmental atelectasis without focal consolidation, large pleural effusion or pneumothorax.

Initial CT scan of abdomen and pelvis was done to rule out renal/ureteral stone. It showed a left lower lobe airspace consolidation with bronchiectasis and bronchiolectasis and a cavitary lesion with air-fluid level (Figure 2). 

Figure 2. Representative images from the CT scan in lung windows showing left lower lobe airspace consolidation concerning for an acute on chronic process.

C-reactive protein and erythrocyte sedimentation rate were normal, CRP and ESR- normal; blood cultures revealed no growth; procalcitonin 0.4 ng/mL (normal <0.15); anti-nuclear antibody – negative; Aspergillus antigen – negative; urine Legionella antigen – negative; Streptococcus pneumoniae antigen – positive.

Sputum Gram stain and acid-fast bacilli culture/stain could not be obtained because the patient did not produce any sputum.

Subsequently CT chest with IV contrast was done which showed findings compatible with a pneumonia within a left lower lobe intrapulmonary sequestration. (Figure 3).

Figure 3. Representative images from the thoracic CT chest with IV contrast. The left lower lobe demonstrates a 69 x 83 mm heterogeneous fluid collection with multiple locules of air. There was systemic arterial blood supply to this region arising off the celiac axis (arrows).

The patient was diagnosed with an infected intralobar bronchopulmonary sequestration. He was treated initially with intravenous fluids and piperacillin-tazobactam. He underwent video-assisted thoracoscopic wedge resection of infected bronchopulmonary sequestration in left lower lobe and ligation of the systemic feeding vessels from the celiac artery. Pathologic examination revealed a fibrotic lung with areas of centrilobular emphysema, bronchiolectasis, mucus pooling and microscopic honeycomb changes. Findings also showed an elastic artery, with features most suggestive of intralobar sequestration. His symptoms completely resolved after his operation.

Discussion

Bronchopulmonary sequestration is a rare congenital abnormality of the lower respiratory tract, seen mostly in children but often in adults, like in our patient (1). In 1946, Pryce coined the term "pulmonary sequestration" to describe a disconnected bronchopulmonary mass or cyst with an anomalous arterial supply (2). The term implies a mass of lung tissue that has no function and lacks normal communication with the rest of the tracheobronchial tree. This mass of non-functional lung tissue receives blood supply from the systemic circulation (3). The exact etiology is unknown and is thought to be an embryologic process error in foregut budding (4), although some have indicated a non-congenital acquired process in intralobar sequestration.

Sequestration may be intra- or extralobar based on its relation with the normal lung lobes. An intralobar sequestration (ILS), like the name suggests, is located within a normal lobe, lacks its own visceral pleura (5) and also has aberrant connections to bronchi, and lung parenchyma, or even the gastrointestinal tract, and often presents with recurrent infections (6,7). Compared to ILS, an extralobar sequestration (ELS) is located outside the normal lung and has its own visceral pleura (8), with the rare occurrence of infectious complications (9). About 75% of BPS is intralobar while 25% is extralobar (10). Bronchopulmonary sequestration is often associated with other congenital abnormalities like congenital diaphragmatic hernia, vertebral anomalies, congenital heart disease, pulmonary hypoplasia, colonic duplication, and congenital pulmonary airway malformation (11). 

Clinically, pulmonary sequestration is latent until infection leads to symptoms (12). Symptoms, like that of any pathological lung condition depend on the type, size, and location of the lesion. Sepsis and extracardiac shunting are common complications of untreated sequestration. Hemoptysis can also be a presentation. The mechanism of pneumonia is post-obstructive and usually recurrence of pneumonia leads to diagnosis. Recurrent pneumonia especially in the lower lobes should always include intralobar sequestration in the differential diagnoses. But the pathophysiology of infection and/or hemoptysis when ILS is not connected to airway is a mystery. Sometimes there is a partial or anatomically abnormal connection to the tracheobronchial tree, which can lead to poor mucus clearance, plugging and recurrent infection.

The mainstay of diagnosis is pre-operative imaging and post-operative histopathology of the resected specimen. The pathognomonic imaging characteristic is systemic vascular supply of the affected area of the lung (intra or extra-lobar), which is seen in about 80% of CT scans. Recurrent infection can lead to cystic areas within the mass (clusters of “ring shadows” on X-ray) (13). The surrounding normal lung may have air trapping and show emphysematous changes. Radiologic signs of BPS are a spectrum and represent the chronic and recurrent inflammation of the sequestrated lung: recurrent focal airspace disease, a parenchymal mass, a cavitary consolidation or mass, cystic lesions, localized bronchiectasis or adjacent emphysema. Bronchoscopy has little role in the management of BPS, which needs to be kept in mind by clinicians investigating cystic lung lesions. Identifying the systemic feeding vessel also helps with surgical planning.  

Symptomatic patients are treated with surgical excision; surgery is curative and is associated with minimal morbidity (14). Surgery is urgent in patients with significant respiratory distress but may be an elective procedure in adults or older children with less symptoms (15, 16). 

For asymptomatic patients of any age, management depends on how ‘high risk’ they are considered for developing complications. High risk patients are those with large lesions occupying >20 percent of the hemithorax, bilateral or multifocal cysts, or those with pneumothorax. In these patients, surgical resection is preferred to observation (17). On the other hand, in asymptomatic patients without these high-risk characteristics, either elective surgical resection or conservative management with observation are reasonable options (18). 

Apart from surgery, even embolization of the anomalous arterial supply has been reported to result in a complete resolution of symptoms and imaging changes to a certain in some cases (19). Since identification of vascular supply during surgery may be difficult during surgery, presurgical embolization may reduce risk of vascular complications (19). Embolization also has a more important role in hemoptysis and heart failure from shunting.

Conclusions

• Pulmonary sequestration is a rare congenital anomaly of a mass of lung tissue without a normal connection to the tracheobronchial tree and a systemic vascular supply.
• Presentation in adults is due to complication of the mass, undiagnosed in childhood. 
• Sequestrated lung can have cystic changes and is a very important differential diagnosis of the cavitation. 
• Confirmation of diagnosis is by visualization of a systemic vessel supplying sequestrated pulmonary, and this is usually accomplished by contrast-enhanced CT scan, MRI or invasive angiography.

Teaching points

This is a case of adult presentation of congenital pulmonary malformation and represents a delay in diagnosis, even though the patient’s symptoms started 10 years ago. The delay was due to falling prey to anchoring and availability biases and chasing the diagnosis of TB ten years ago in a patient from Yemen with a lower lobe cavitation. 

The feeding vessel from the celiac axis can only be demonstrated via a contrast enhanced CT, and thus, when in doubt, we should always get angiography by contrast-enhanced-CT or MRI or by invasive angiography. Had it been thought of and done 10 years ago, the patient would’ve been diagnosed and treated earlier.

Disclosure Statement

Drs. Majumdar, Sen and Sood have no conflicts of interest or financial ties to disclose.

References

1. Landing BH, Dixon LG. Congenital malformations and genetic disorders of the respiratory tract (larynx, trachea, bronchi, and lungs). Am Rev Respir Dis. 1979 Jul;120(1):151-85. [CrossRef] [PubMed]
2. John PR, Beasley SW, Mayne V. Pulmonary sequestration and related congenital disorders. A clinico-radiological review of 41 cases. Pediatric radiology. Pediatr Radiol. 1989;20(1-2):4-9. [CrossRef] [PubMed]
3. Van Raemdonck D, De Boeck K, Devlieger H, et al. Pulmonary sequestration: a comparison between pediatric and adult patients. Eur J Cardiothorac Surg. 2001 Apr;19(4):388-95. [CrossRef] [PubMed]
4. Gezer S, Taştepe I, Sirmali M, Findik G, Türüt H, Kaya S, Karaoğlanoğlu N, Cetin G. Pulmonary sequestration: a single-institutional series composed of 27 cases. J Thorac Cardiovasc Surg. 2007 Apr;133(4):955-9. [CrossRef] [PubMed]
5. Shanti CM, Klein MD. Cystic lung disease. Semin Pediatr Surg. 2008 Feb;17(1):2-8. [CrossRef] [PubMed]
6. Stocker JT, Drake RM, Madewell JE. Cystic and congenital lung disease in the newborn. Perspect Pediatr Pathol. 1978;4:93-154. [PubMed]
7. Schwartz MZ, Ramachandran P. Congenital malformations of the lung and mediastinum--a quarter century of experience from a single institution. J Pediatr Surg. 1997 Jan;32(1):44-7. [CrossRef] [PubMed]
8. Abbey P, Das CJ, Pangtey GS, Seith A, Dutta R, Kumar A. Imaging in bronchopulmonary sequestration. Send to J Med Imaging Radiat Oncol. 2009 Feb;53(1):22-31. [CrossRef] [PubMed]
9. Houda el M, Ahmed Z, Amine K, Amina BS, Raja F, Chiraz H. Antenatal diagnosis of extralobar pulmonary sequestration. Pan Afr Med J. 2014;19:54. [CrossRef] [PubMed]
10. Frazier AA, Rosado de Christenson ML, Stocker JT, Templeton PA. Intralobar sequestration: radiologic-pathologic correlation. Radiographics. 1997 May-Jun;17(3):725-45. [CrossRef] [PubMed]
11. Kravitz RM. Congenital malformations of the lung. Pediatr Clin North Am. 1994 Jun;41(3):453-72. [CrossRef] [PubMed]
12. Hang JD, Guo QY, Chen CX, Chen LY. Imaging approach to the diagnosis of pulmonary sequestration. Acta Radiol. 1996 Nov;37(6):883-8. [CrossRef] [PubMed]
13. Hernanz-Schulman M. Cysts and cystlike lesions of the lung. Radiol Clin North Am. 1993 May;31(3):631-49. [PubMed]
14. Samuel M, Burge DM. Management of antenatally diagnosed pulmonary sequestration associated with congenital cystic adenomatoid malformation. Thorax. 1999 Aug;54(8):701-6. [CrossRef] [PubMed]
15. Haller JA, Jr., Golladay ES, Pickard LR, Tepas JJ, 3rd, Shorter NA, Shermeta DW. Surgical management of lung bud anomalies: lobar emphysema, bronchogenic cyst, cystic adenomatoid malformation, and intralobar pulmonary sequestration. Ann Thorac Surg. 1979 Jul;28(1):33-43. [CrossRef] [PubMed]
16. Al-Bassam A, Al-Rabeeah A, Al-Nassar S, Al-Mobaireek K, Al-Rawaf A, Banjer H, et al. Congenital cystic disease of the lung in infants and children (experience with 57 cases). Eur J Pediatr Surg. 1999 Dec;9(6):364-8. [CrossRef] [PubMed]
17. Parikh DH, Rasiah SV. Congenital lung lesions: Postnatal management and outcome. Semin Pediatr Surg. 2015 Aug;24(4):160-7. [CrossRef] [PubMed]
18. Singh R, Davenport M. The argument for operative approach to asymptomatic lung lesions. Semin Pediatr Surg. 2015 Aug;24(4):187-95. [CrossRef] [PubMed]
19. Eber E. Adult outcome of congenital lower respiratory tract malformations. Swiss Med Wkly. 2006 Apr 15;136(15-16):233-40. [PubMed]

Cite as: Majumdar U, Sen P, Sood A. Intralobar bronchopulmonary sequestration: A case and brief review. Southwest J Pulm Crit Care. 2018;16(6):343-9. doi: https://doi.org/10.13175/swjpcc075-18 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

1. Hardy RD, Jafri HS, Olsen K, Hatfield J, Iglehart J, Rogers BB, Patel P, et al. Mycoplasma pneumoniae induces chronic respiratory infection, airway hyperreactivity, and pulmonary inflammation: a murine model of infection-associated chronic reactive airway disease. Infect Immun. 2002 Feb;70(2):649-54. [CrossRef] [PubMed]
2. Kawai Y, Miyashita N, Kato T, Okimoto N, Narita M. Extra-pulmonary manifestations associated with Mycoplasma pneumoniae pneumonia in adults. Eur J Intern Med. 2016 Apr;29:e9-e10. [CrossRef] [PubMed]
3. Hage CA, Knox KS, Wheat LJ. Endemic mycoses: overlooked causes of community acquired pneumonia. Respir Med. 2012 Jun;106(6):769-76. [CrossRef] [PubMed]
4. Gosselt A, Olijhoek J, Wierema T. Severe asymptomatic rhabdomyolysis complicating a mycoplasma pneumonia. BMJ Case Rep. 2017 Jul 26;2017. pii: bcr-2016-217752. [CrossRef] [PubMed]
5. Khan FY, Sayed H. Rhabdomyolysis associated with Mycoplasma pneumoniae pneumonia. Hong Kong Med J. 2012 Jun;18(3):247-9. [PubMed]
6. Zimmerman JL, Shen MC. Rhabdomyolysis. Chest. 2013 Sep;144(3):1058-65. [CrossRef] [PubMed]
7. Zutt R, van der Kooi AJ, Linthorst GE, Wanders RJ, de Visser M. Rhabdomyolysis: review of the literature. Neuromuscul Disord. 2014 Aug;24(8):651-9. [CrossRef] [PubMed]
8. Allison SJ. Acute kidney injury: Macrophage extracellular traps in rhabdomyolysis-induced AKI. Nat Rev Nephrol. 2018 Mar;14(3):141. [CrossRef] [PubMed]
9. Bosch X, Poch E, Grau JM. Rhabdomyolysis and acute kidney injury. N Engl J Med. 2009 Jul 2;361(1):62-72. [CrossRef] [PubMed]
10. Giannoglou GD, Chatzizisis YS, Misirli G. The syndrome of rhabdomyolysis: Pathophysiology and diagnosis. Eur J Intern Med. 2007 Mar;18(2):90-100. [CrossRef] [PubMed]
11. Diaz MH, Winchell JM. The evolution of advanced molecular diagnostics for the detection and characterization of Mycoplasma pneumoniae. Front Microbiol. 2016 Mar 8;7:232. [CrossRef] [PubMed]
12. Lee SC, Youn YS, Rhim JW, Kang JH, Lee KY. Early serologic diagnosis of Mycoplasma pneumoniae pneumonia: An observational study on changes in titers of specific-igm antibodies and cold agglutinins. Medicine. 2016 May;95(19):e3605. [CrossRef] [PubMed]
13. Lee WJ, Huang EY, Tsai CM, Kuo KC, Huang YC, Hsieh KS, et al. Role of serum Mycoplasma pneumoniae IgA, IgM, and IgG in the diagnosis of mycoplasma pneumoniae-related pneumonia in school-age children and adolescents. Clin Vaccine Immunol. 2017 Jan 5;24(1). pii: e00471-16. [CrossRef] [PubMed]
14. Novacco M, Sugiarto S, Willi B, Baumann J, Spiri AM, Oestmann A, Riond B, et al. Consecutive antibiotic treatment with doxycycline and marbofloxacin clears bacteremia in Mycoplasma haemofelis-infected cats. Vet Microbiol. 2018 Apr;217:112-120. [CrossRef] [PubMed]
15. Valdivia L, Nix D, Wright M, Lindberg E, Fagan T, Lieberman D, Stoffer T, et al. Coccidioidomycosis as a common cause of community-acquired pneumonia. Send to Emerg Infect Dis. 2006 Jun;12(6):958-62. [CrossRef] [PubMed]
16. Wheat LJ. Approach to the diagnosis of the endemic mycoses. Clin Chest Med. 2009 Jun;30(2):379-89. [CrossRef] [PubMed]
17. Gupta N, Aragaki A, Wikenheiser-Brokamp KA, Benzaquen S, Panos RJ. Occam's razor or Hickam's dictum? J Bronchology Interv Pulmonol. 2012 Jul;19(3):216-9. [CrossRef] [PubMed]

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 

June 2018 Pulmonary Case of the Month

Lewis J. Wesselius, MD

Department of Pulmonary Medicine

Mayo Clinic Arizona

Scottsdale, AZ USA

History of Present Illness

The patient is a 53-year-old man who presented in January 2018 for a second opinion on interstitial lung disease first diagnosed in 2011. He lives in Los Angeles and had one year of increasing dyspnea on exertion prior to diagnosis. He had an outside surgical lung biopsy and was treated with prednisone, then started on azathioprine and the prednisone tapered. He was followed regularly and had limited progression over next 7 years.  However, recently he had increasing shortness of breath.

Past Medical History, Social History, Family History

He has no significant past medical history. He is a nonsmoker and denies any significant occupational exposures.

Physical Examination

Physical examination was unremarkable without rales or clubbing.

Which of the following should be obtained at this time? (Click on the correct answer to proceed to the second of five pages)

1. Prior chest x-rays, CT scans, pulmonary function testing and lung biopsy
2. Repeat CT scan, pulmonary function testing
3. Rheumatological serologies
4. 1 and 3
5. All of the above

Cite as: Wesselius LJ. June 2018 pulmonary case of the month. Southwest J Pulm Crit Care. 2018;16(6):296-303. doi: https://doi.org/10.13175/swjpcc063-18 PDF 

April 2018 Pulmonary Case of the Month

Ashely L. Garrett, MD

Mayo Clinic Arizona

Scottsdale, AZ USA

History of Present Illness

A 74-year-old woman with known chronic obstructive pulmonary disease (COPD) presented to emergency department on 2/4/18 with dyspnea. She had been hospitalized at another hospital from 12/29/17 - 1/30/18 for a COPD exacerbation and health care associated pneumonia described as a cavitary pneumonia. She was treated with various doses of systemic steroids and antibiotics. Her course was complicated by atrial fibrillation with a rapid ventricular response. She eventually was discharged to a skilled nursing facility.

Past Medical History, Social History and Family History

She has a known history of COPD with an FEV1 of 22% of predicted and is on 2L/min of O2 by nasal cannula. There is also a history of:

• Hypertension.
• Hypercholesterolemia.
• Paroxysmal atrial fibrillation, not on anticoagulation.
• Right 4 mm PICA aneurysm

She lives in rural Kingman, AZ with some dust and outdoor bird exposure.

Family history is noncontributory.

Medications

• Alprazolam 0.25 mg p.o. b.i.d.
• Symbicort two puffs inhaled b.i.d.
• Diltiazem 120 mg p.o. q.12h
• Disopyramide 150 mg p.o. q.6h
• Furosemide 20 mg p.o. daily
• Levalbuterol 0.31 mg q.6 days p.r.n.
• Meperidine 50 mg p.r.n. pain
• Metoprolol succinate 12.5 mg p.o. b.i.d
• Prednisone 10 mg p.o. daily

Physical Examination

• Vitals: BP 110/65 mm Hg, P 130 irregular beats/min, T 37° C, Respirations 20 breaths/min
• General: Appears in mild respiratory distress
• Lungs: Distant breath sounds
• Heart: Irregular rhythm with distant tones
• Abdomen: no organomegaly, masses or tendernesses
• Extremities:  No edema

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

1. Arterial blood gases (ABGs)
2. Chest x-ray
3. Electrocardiogram
4. 1 and 3
5. All of the above

Cite as: Garrett AL. April 2018 pulmonary case of the month. Southwest J Pulm Crit Care. 2018;16(4):174-82. doi: https://doi.org/10.13175/swjpcc050-18 PDF

February 2018 Pulmonary Case of the Month

Lewis J. Wesselius, MD

Department of Pulmonary Medicine

Mayo Clinic Arizona

Scottsdale, AZ USA

History of Present Illness

A 75-year-old woman was diagnosed with a thymic carcinoid tumor in April, 2015 (Figure 1).

Figure 1. Representative image from the preoperative CT scan performed in April 2015 showing an anterior mediastinal mass (arrow).

This was treated with surgical resection followed by radiation therapy.

She began having cough and dyspnea 1 to 2 months later and in August, 2015 had a thoracic CT scan of her chest (Figure 2).

Figure 2. Representative image in lung windows from the second thoracic CT scan performed in August 2015.

Which of the following are true? (Click on the correct answer to proceed to the second of six pages)

1. Bronchoscopy should be performed
2. She should be given an empiric course of antibiotics
3. The most like diagnosis is radiation pneumonitis
4. 1 and 3
5. All of the above

Cite as: Wesselius LJ. February 2018 pulmonary case of the month. Southwest J Pulm Crit Care. 2018;16(2):55-61. doi: https://doi.org/10.13175/swjpcc020-18 PDF 

January 2018 Pulmonary Case of the Month

Lewis J. Wesselius, MD

 Departments of Pulmonary Medicine

Mayo Clinic Arizona

Scottsdale, AZ USA

History of Present Illness

A 67-year-old man from Idaho was seen in November 2017 for a second opinion. He has a history of slowly progressive dyspnea on exertion for 7 to 8 years. He has a significant smoking history of 50 pack-years, but is still smoking “a few cigarettes”.

He saw an outside pulmonologist in September 2017 and was noted to have abnormal pulmonary function testing with the primary abnormality being a low DLco. A thoracic CT Scan was reported to be abnormal with evidence of interstitial lung disease. He underwent video-assisted thorascopic surgery and the biopsies were reported to show usual interstitial pneumonitis (UIP). His pulmonologist questioned whether this was interstitial pulmonary fibrosis or UIP associated with rheumatoid arthritis.

PMH, SH and FH

He has a history of rheumatoid arthritis and had been treated with methotrexate for approximately 8 years. His methotrexate had been discontinued in September with no change in symptoms. FH is noncontributory.

Medications

Prednisone 5 mg/daily and tiotropium (these also did not change his dyspnea).

Physical Examination

• Chest:  bibasilar crackles.
• Cardiovascular:  regular rhythm without murmur.
• Ext:  no clubbing, no edema, no joint deformity noted

Which of the following are indicated at this time? (Click on the correct answer to proceed to the second of five pages)

1. Obtain a complete blood count and rheumatoid factor
2. Begin pirfenidone or nintedanib
3. Review his pulmonary function testing and radiographic studies
4. 1 and 3
5. All of the above

Cite as: Wesselius LJ. January 2018 pulmonary case of the month. Southwest J Pulm Crit Care. 2018;16(1):8-13. doi: https://doi.org/10.13175/swjpcc157-17 PDF

Diffuse Idiopathic Pulmonary Neuroendocrine Cell Hyperplasia in a Patient with Multiple Pulmonary Nodules: Case Report and Literature Review

Hasan S. Yamin, MD¹

Feras Hawarri, MD¹

Mutaz Labib, MD¹

Ehab Massad, MD²

Hussam Haddad, MD³

Departments of ¹Internal Medicine Pulmonary & Critical Care Division, ²Thoracic Surgery and ³Pathology

King Hussein Cancer Center

Amman, Jordan

Abstract

Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) is a rare pulmonary disease, where carcinoid tumorlets invade the pulmonary parenchyma and bronchioles. These nests of cells release a variety of mediators including bombesin and gastrin releasing peptide that cause heterogeneous bronchoconstriction, creating a mosaic appearance on chest imaging studies, especially on expiratory scans. Clinically patients usually have long standing symptoms of shortness of breath (SOB) and cough that are difficult to distinguish from asthma. In this article we describe a case of DIPNECH in a patient with several years’ history of SOB and cough, and review 179 cases of DIPNECH reported in the literature since 1992.

Case Presentation

A 72-year-old, non-smoking lady was admitted to the hospital in preparation for bilateral mastectomy. She recently received a diagnosis of bilateral breast invasive ductal carcinoma grade 2, estrogen receptor/progesterone receptor/human epidermal growth factor receptor 2 (HER-2) positive in the left tumor but negative in the right tumor.

Her past medical history was significant for hypertension, long standing cough and dyspnea on exertion labeled as asthma poorly responsive to nebulizers. Socially, she was a house wife with no history of occupational exposure.

The patient was found to be tachypneic (respiratory rate 22 breaths/minute) and hypoxemic (oxygen saturation 86% on room air). Heart rate and blood pressure were within normal limits. She had bilateral decreased breath sounds and diffuse expiratory wheezes.

Chest CT scan revealed diffuse mosaic pattern and multiple pulmonary nodules in both lungs suggestive of metastases (Figure 1).

Figure 1. Representative images form chest CT scan showing a diffuse mosaic pattern and multiple pulmonary nodules in both lung fields suggestive of metastases.

These lesions did not take up fludeoxyglucose (FDG) on positron emission tomography (PET) scan. Her pulmonary function tests (PFT) were unremarkable except for reduction in expiratory reserve volume (ERV) at 22%, and increased residual volume to total lung capacity ratio (RV/TLC) at 136% probably related to air trapping. Diffusion lung capacity was within normal limits.

Video assisted thoracoscopic biopsy of one of the nodules in left lower lobe was done. Pathology showed both a carcinoid tumor and tumorlets invading lung bronchioles (Figure 2A & B) and these tumorlets were positive for chromogranin (Figure 2C & D) and pancytokeratin (Figure 2 E & F).

Figure 2. A & B: histology (H&E stain) showing carcinoid tumorlets invading lung bronchioles; C & D: positive staining for chromogranin; E &F: positive staining for pancytokeratin.

A diagnosis of diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) was made, and the patient was treated with intravenous steroids and nebulizers. Her oxygen saturation improved to 94% on room air. She was later discharged on oral steroids. Her CT scan also showed no significant improvement in changes described above.

Review of the Literature

Methods

We searched PubMed for all cases of diffuse idiopathic pulmonary neuroendocrine cell hyperplasia reported in the English literature since 1992 when the entity was first described. A total of 179 patients were identified in 55 articles, in the form of case reports and case series. In this article we contribute an additional patient (1-55).

Patient Characteristics

A total of 180 patients (including our patient) were identified. There were 161 females (89.5%) and only 19 males (10.5%). Mean age at diagnosis was 57.75 years (males tended to present at a younger age of 52 years, compared to 58.4 years in females). Most patients were never smokers 52.8%, smokers/exsmokers 27.2%, and in 20% smoking status was not mentioned.

The majority of patients presented with cough (91 patients, 50.5%), followed by exertional dyspnea (81 patients, 45%), and hemoptysis (6 patients, 3.3%). Incidental imaging findings led to diagnosis in 22 patients (12.2%). Mean duration of symptoms before diagnosis was 8.25 years (Table 1).

Table 1. Patients` characteristics and presenting symptoms.

Diagnosis, Therapy and Outcome

Most patients underwent imaging with chest CT scan, the most common findings were nodules in 148 patients (82.2%), ground glass opacities/mosaic pattern in 66 patients (36.6%), and bronchial wall thickening in 37 patients (20.5%). Most patients had an abnormal spirometry: obstructive pattern (48.9%), restrictive (5%), or mixed obstructive restrictive pattern (6.7%) (Table 2).

Table 2. Spirometry and imaging.

Because of their symptoms, and spirometry findings 45 patients (25%) were labeled with another disease including asthma in 29 patients (16.1%), COPD in 12 patients (6.6%) and bronchiolitis in 4 patients (2.2%).

The diagnosis was made using surgical lung biopsy in 148 patients (82.2%), bronchoscopic biopsy in 10 patients (8 transbronchial biopsy, 2 endobronchial biopsy) (5.6%), CT-guided biopsy in 7 patients (3.9%), postmortem diagnosis in 3 patients (1.7%), post lung transplantation in 2 patients (1.1%) and clinically in 2 patients (1.1%). The diagnostic method was not mentioned in 8 patients (4.4%).

Patients received a variety of therapies including inhaled bronchodilators, inhaled or systemic steroids, and somatostatin analogues among others. Response to treatment was mentioned for 89 patients, (59 patients reported that their symptoms remained stable, 11 patients improved with treatment, while 18 patients reported symptom progression and 2 patients died. (Table 3).

Table 3. List of DIPNECH articles ordered by publication year. This table shows number of patients in each article, diagnostic method, therapy given and outcome.

Of note, 15 out of 23 patients who received a somatostatin analogue reported stable, or improvement in their symptoms (65.2%), which did not necessarily translate into improvement in air flows on spirometry (27, 29, 46, 51).

Discussion

Pulmonary neuroendocrine cell hyperplasia was described early in the previous century (56), however the significance and role of the pathologic changes were not precisely determined. It was thought that they were secondary to other lung diseases such as interstitial lung disease, bronchiectasis, cystic fibrosis, smoking exposure, or in people who live at high altitude. In addition to the previously mentioned associations, hyperplasia of pulmonary neuroendocrine cells was also thought to be a pre-neoplastic process, since the lesions can potentially progress to carcinoid tumors even without causing symptoms or airflow limitation. In 2004 the changes were recognized by WHO as one end of the spectrum of pulmonary neuroendocrine tumors.

The relationship between carcinoid tumorlets and other pulmonary diseases and its role in precipitating respiratory symptoms remains puzzling. The term DIPNECH was coined in 1992 by Aguayo (1) who described a new entity where idiopathic hyperplasia or dysplasia of pulmonary neuroendocrine cells occurred in the absence of other lung disorders. The changes were associated with physiologic and radiologic airflow limitation similar to obliterative bronchiolitis. This was the first description of pulmonary neuroendocrine hyperplasia as a primary process.

Because of similar symptoms, an obstructive pattern on pulmonary function tests, and chest imaging suggestive of air trapping, many patients receive a diagnosis of asthma for several years before the correct diagnosis is made. This similarity to other obstructive lung diseases can be explained by the pathologic changes of airway obstruction seen on biopsy. Pulmonary neuroendocrine cells, or Kulchitsky cells, are normally present in small numbers in airways, where they release a myriad of bioactive amines and peptides like serotonin, chromogranin A, gastrin-releasing peptide (GRP), and calcitonin.

Airway obstruction is believed to occur both due to physical obstruction of bronchioles by tumorlets and smooth muscle constriction caused by active mediators released. Bombesin and related peptides like gastrin releasing peptide, neuromedin B and neuromedin C are thought to cause bronchoconstriction indirectly through the release of several other bronchoconstrictors that act on smooth muscle cells (57). However, in vitro studies in guinea pig lungs suggest that bombesin may act directly by binding to specific receptors on smooth muscle cells (58).

Pulmonary neuroendocrine pathology occurs in a spectrum of three forms: hyperplasia, tumorlets and carcinoid tumors. DIPNECH is characterized by proliferation of neuroendocrine cells initially limited to the basement membrane of airways, when disease extends beyond the lumen of airway it is called carcinoid tumorlets. Tumorlets larger than 0.5 cm become carcinoid tumors and appear as nodules on chest CT scans. Diagnosis requires lung biopsy, with a surgical biopsy procedure more likely to provide diagnostic tissue than bronchoscopic transbronchial biopsies.

According to Aguayo`s definition of DIPNECH, patients have pulmonary symptoms with radiographic and physiologic abnormalities suggestive of obstructive lung disease, but in our review 12.2% of patients had no symptoms at all, and 15.5% had normal spirometry. We believe hyperplasia, tumorlets and carcinoid tumors represent different aspects of the same disease, the occurrence of symptoms, radiologic and physiologic airflow limitation depends on the time frame at which diagnosis was made, should those patients be followed up, they could develop symptoms and airflow limitation in the future. Thus, we propose to expand the definition to include patients with no symptoms or spirometry abnormalities. However, it remains uncertain whether asymptomatic patients who are diagnosed at an earlier stage need specific treatment or not.

It is also clinically difficult to establish a causal relationship, or determine the direction of the relationship between pulmonary neuroendocrine cell hyperplasia and other concomitant lung disorders, or harmful exposures (1,59, 60). In our review 27.2% of patients were active or previous smokers, only one patient lived at high altitude (more than 2000m) (14), 29 patients had a history of previous or current malignancy including 8 lung cancers (not shown in table), 13 patients had evidence of bronchiectasis, and one patient had honeycombing on imaging. These findings are similar to data obtained from individual case reports and series (2, 6, 14, 17, 19, 22, 29, 33, 37, 46, 47 and 53).

When the diagnosis is made, therapeutic options may include observation for mild symptoms, inhaled or systemic steroids, in addition to bronchodilators, especially if patients who show reversible airway obstruction on PFT. Other potential therapies are somatostatin analogues, however more studies are needed to determine their precise role. (27, 29, 43, 46)

Conclusion

DIPNECH is a rare clinical entity that requires a high clinical suspicion. Because of clinical, spirometry, and imaging similarity to other obstructive lung diseases, and the requirement for lung biopsy to make the diagnosis, DIPNECH is probably an under-diagnosed entity, with still limited treatment options. The diagnosis should probably be considered in any patient with difficult to treat obstructive lung disease, unexplained bronchiolitis, particularly if there are multiple small lung nodules present on chest CT scan. We propose to expand the definition of DIPNECH to include patients with even no symptoms or spirometric evidence of airflow limitation, as development of these abnormalities depends on the time frame at which diagnosis is made. It is also difficult to establish a causal relationship with other concomitant lung conditions, the presence of which should not rule out a diagnosis of DIPNECH.

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40. Erdini F, Spaltro AA, Ruiu A, et al. Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) and multiple pulmonary epithelioid hemangioendothelioma (PEH): a case report. Pathologica. 2015 Mar;107(1):37-42. [PubMed]
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Cite as: Yamin HS, Hawarri F, Labib M, Massad E, Haddad H. Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia in a patient with multiple pulmonary nodules: case report and literature review. Southwest J Pulm Crit Care. 2017;15(6):282-93. doi: https://doi.org/10.13175/swjcc139-17 PDF

Necrotizing Pneumonia: Diagnosis and Treatment Options

Brian D. Skidmore, BS¹ and Veronica A. Arteaga, MD²

¹College of Medicine and ²Department of Medical Imaging

Banner-University Medical Center

University of Arizona

Tucson, AZ USA

Abstract

We present the case of a patient who was initially diagnosed with community-acquired pneumonia that was later discovered to have necrotizing changes. The case illustrates the challenges in diagnosing necrotizing pneumonia and the preferred treatment methods.

Case Presentation

History of Present Illness

The patient is a 51-year old woman who presents with right upper lobe pneumonia and a failed outpatient regimen of levofloxacin. She returned one week after being seen in the emergency department with worsening dyspnea, productive cough, and fever in addition to new symptoms of right chest pain and post-tussive emesis. The chest pain is stabbing in quality and constantly present. She denied any calf pain/swelling, previous history of deep venous thrombosis, or long trips or travels.

Physical Exam

Upon admission, blood pressure was 103/56 with a pulse of 114 and respiratory rate of 18. Her temperature was 38.1 °C (100.5 °F) but spiked at 39.5 °C (103.1 °F) and her SpO₂ was 94.0% on room air. Her breathing was unlabored and her lungs were clear to auscultation bilaterally except for crackles in the right upper lung field. The remainder of the exam was unremarkable.

Laboratory and Imaging

A chest radiograph was initially obtained and showed a right upper lobe consolidation consistent with community-acquired pneumonia (Figure 1).

Figure 1. Chest radiograph showing right upper lobe consolidation with possible volume loss.

One week later, a contrast-enhanced chest CT was performed and revealed a heterogeneously enhancing right upper lobe consolidation with cavitation and foci of air diagnostic of necrotizing pneumonia (Figure 2).

Figure 2. Contrast-enhanced chest CT showing right upper lobe pneumonic consolidation with peripheral enhancement, central necrosis, and small foci of air.

Laboratory studies revealed a markedly elevated C-reactive protein of 16.61 mg/dL and a white blood cell count of 18,000 cells/ μL. In addition, the red blood cell count, hemoglobin, and hematocrit were all reduced with values of 3,390,000 cells/ μL, 10.0 g/dL, and 31.0% respectively.

Hospital Course

A chest CT was ordered and the patient was diagnosed with necrotizing pneumonia. She was given IV vancomycin and piperacillin-tazobactam as empiric therapy. Tylenol was administered for fever management and steroids were deferred because her CURB-65 score for pneumonia severity was 0.

Attention was then given to identifying the infectious agent. Blood and respiratory cultures were obtained and a TB test was ordered. The cultures showed no growth and the TB test was negative. A bronchoalveolar lavage showed a highly neutrophilic cell count, however no pathogen was ever identified.

Given improvement with empiric therapy, during her hospital course she was discharged on oral amoxicillin and clavulanate until follow up with pulmonary in outpatient 6 weeks later. Imaging at that time showed post inflammatory changes and no evidence of infection.

Discussion

Necrotizing pneumonia is a rare complication of bacterial lung infections affecting 4% of all patients with community-acquired pneumonia (1). The infection can be patchy, segmental, or involve the entire lung. While the pathogenesis of necrotizing pneumonia is not clearly defined, most studies indicate that it is either an inflammatory response to toxins produced by the pathogen or it is the result of associated vasculitis and venous thrombosis. Patients typically present with common symptoms of pneumonia such as fever, cough, shortness of breath, and chest pain but can also rapidly develop hemoptysis, septic shock, and respiratory failure as the necrosis progresses (2). Because necrotizing pneumonia is associated with increased morbidity and mortality, it is important to distinguish it from non-necrotizing cases (3).

The diagnosis of necrotizing pneumonia may be difficult to make because of its similar presentation to non-necrotizing pneumonias and the limitations of standard chest radiographs. Chest radiographs may show an area of consolidation but are limited in identifying the extent of parenchymal disease (Figure 1) (2). Therefore, contrast-enhanced chest CT is an optimal exam for diagnosing necrotizing pneumonia. Disease may first appear as an in-homogeneously enhancing consolidation with focal areas of low attenuation (Figure 2).  Foci of air may subsequently develop in these areas of hypo-enhancing necrotic tissue indicating cavitation (4).

Laboratory studies may also be helpful in diagnosing necrotizing pneumonia. When compared to pneumonias without a necrotizing component, patients with necrotizing pneumonia show more elevated white blood cell counts and inflammatory markers (1). In one study, patients with necrotizing pneumonia had an average WBC count of 14,970/μL, an average ESR of 70 mm/h, and an average CRP of 18.8 mg/dL. Average values for patients with non-necrotizing pneumonia were significantly lower at 10,130/μL, 48 mm/h, and 11.4 mg/dL respectively (p<0.001) (3). These changes are also evident in the presented case with elevated WBC and CRP values of 18,000/μL and 16.61 mg/dL.

Necrotizing pneumonia is initially treated with intravenously administered broad-spectrum antibiotics that should target pathogens that commonly cause necrotizing changes. The most common microbes are Staphylococcus aureus, Streptococcus pneumoniae, and Klebsiella pneumoniae, however several other bacteria species may also cause necrosis (Table 1) (2).

Transition to oral antibiotics may be considered for patients that show improvement (1). A more focused treatment plan should be initiated once a specific pathogen is identified, however this is only accomplished in approximately 26% of cases (3).

Surgical resection may also be considered for patients who show no progress on antibiotic therapy and continue to decline. However the optimal timing and indications for surgery are not clearly defined. The extent of the resection should always be as conservative as possible and commonly involves debridement or segmentectomy of the damaged tissue. In cases where the parenchyma is extensively affected, lobectomy or pneumonectomy may be required (2).

References

1. Nicolaou EV, Bartlett AH. Necrotizing pneumonia. Pediatr Ann. 2017;1;46(2):e65-e68. [CrossRef] [PubMed]
2. Tsai YF, Ku YH. Necrotizing pneumonia: a rare complication of pneumonia requiring special consideration. Curr Opin Pulm Med. 2012;18(3):246-52. [CrossRef] [PubMed]
3. Seo H, Cha SI, Shin KM, et al. Clinical relevance of necrotizing change in patients with community-acquired pneumonia. Respirology. 2017;22(3):551-8. [CrossRef] [PubMed]
4. Walker CM, Abbott GF, Greene RE, Shepard JO, Vummidi D, Digumarthy SR. Imaging Pulmonary Infection: Classic Signs and Patterns. AJR Am J Roentgenol. 2014;202(3) 479-92. [CrossRef] [PubMed]

Cite as: Skidmore BD, Arteaga VA. Necrotizing pneumonia: diagnosis and treatment options. Southwest J Pulm Crit Care. 2017;15(6):274-7. doi: https://doi.org/10.13175/swjpcc137-17 PDF

December 2017 Pulmonary Case of the Month

Lewis J. Wesselius, MD¹

Michael B. Gotway, MD²

Departments of ¹Pulmonary Medicine and ²Radiology

Mayo Clinic Arizona

Scottsdale, AZ USA

History of Present Illness

A 52-year-old woman from Iowa sought a second opinion for a left hilar mass. She travels to Phoenix regularly to visit family. She began feeling ill in late 2016 with cough and sputum production and was treated with multiple courses of antibiotics without improvement.

PMH, SH and FH

Past medical history is unremarkable. She is a nonsmoker. FH is noncontributory.

Physical Examination

Physical examination was normal.

Radiography

In March of this year she had chest radiograph in Phoenix which suggested left hilar adenopathy. A thoracic CT scan was performed (Figure 1).

Figure 1. Representative images from the thoracic CT scan in lung windows (A-E) and soft tissue windows (F).

Which of the following are diagnostic considerations? (Click on the correct answer to procced to the second of seven pages)

1. Lung cancer  
2. Lymphoma
3. Sarcoidosis
4. Tuberculosis
5. All of the above

Cite as: Wesselius LJ, Gotway MB. December 2017 pulmonary case of the month. Southwest J Pulm Crit Care. 2017;15(6):232-40. doi: https://doi.org/10.13175/swjpcc144-17 PDF

Treatment of Lymphoma and Cardiac Monitoring during Pregnancy

Stella Pak, MD

Yan Yatsynovich, MD 

Damian Valencia, MD

Calvert Busch, MD

Emily Vannorsdall, MD

Department of Medicine

Kettering Medical Center

Kettering, OH USA

Abstract

Limited data is available regarding fetal-maternal outcomes with chemotherapy during pregnancy, including cardiovascular toxicity and evaluation thereof. Early cardiovascular evaluation and initiation of cardioprotective therapies should be considered. Herein, we report a case of a 33-year-old woman treated with R-CHOP chemotherapy for large B-cell lymphoma found to have some degree of reversible cardiac strain.

Introduction

There are no guidelines specific for cardiotoxicity monitoring in pregnant patients undergoing chemotherapy. Pregnant patients are more vulnerable to cardiovascular complications, such as congestive heart failure, from chemotherapy as their cardiovascular system is under considerable stress from increasing physiological demands in pregnancy. With elevated cardiac output and circulatory volume from baseline, these patients do not have much cardiopulmonary reserve to compensate for cardiac strains from chemotherapy side effects (1). Therefore, it would be critical for clinicians to be aware of increased risk of cardiovascular adverse effect from chemotherapeutic agents in pregnant patients. Herein, we report a case of a 33-year-old woman treated with R-CHOP chemotherapy for large B-cell lymphoma found to have some degree of reversible cardiac strain.

Case Presentation

An otherwise healthy 33-year-old Caucasian female, G2P1 at 24 weeks gestation presented with a chief complaint of cough, chest pressure, and swelling in the neck and face. Physical exam was notable for a negative Pemberton’s sign, two lymph nodes in the right supraclavicular region measuring approximately 2 cm without axillary or groin lymphadenopathy. Cardiac exam demonstrated distant heart sounds with a faint I-II/VI systolic murmur in the left second intercostal space, without presence of bruits or lower extremity edema. Lung exam was positive for occasional wheezing in the left lower lobe. Breast exam was normal. Initial chest x-ray (Figure 1) and computed tomography (CT) scan (Figure 2) of the chest revealed a mediastinal mass (11 x 9.2 x 8.7 cm) and a moderate sized pericardial effusion.

Figure 1. Roentgenogram of chest demonstrating a large mass on left lower lobe and pericardial effusion.

Figure 2. Computerized tomography of chest revealing a large homogeneous left mediastinal mass (92.1 mm X 87.1 mm).

Follow up CT-guided biopsy yielded a diagnosis of large B-cell lymphoma. Bronchoscopy done at that time demonstrated diffuse tracheal and bronchial involvement, likely pointing to primary mediastinal derivation of the tumor. Interestingly, the patient had a history of lymph node biopsy of two areas on her right lateral neck and right medial supraclavicular node; pathology reports were consistent with granulomatous disease at that time. Due to pregnancy, baseline positron emission tomography (PET)/CT was not performed, however, the patient did undergo staging with a CT scan of the chest and abdominal/pelvic and magnetic resonance imaging (MRI), both of which were negative for metastatic disease. Bone marrow biopsy obtained was negative for malignancy as well. Dose-adjusted R-EPOCH (rituximab, etoposide, prednisone, oncovin, cyclophosphamide, hydroxydaunorubicin) was replaced with R-CHOP (rituximab, cyclophosphamide, hydroxydaunomycin, oncovin, prednisolone) due to the teratogenic effects of etoposide. Embryologic toxicity has previously been observed with etoposide including skeletal abnormalities, exencephaly, encephalocele and anophthalmia. Monitoring of cardiac function was performed before, during and after treatment. Initial echocardiogram demonstrated preserved ejection fraction (EF) of 60% with a large pericardial effusion and early signs of tamponade. No strain studies were done prior to initiation of chemotherapy. The patient had undergone a total of six cycles with a good response. Upon treatment completion fluoro-D-glucose (FDG)-PET/CT did show persistent uptake mostly in the manubrium as well as a persistent mediastinal mass with a low standardized uptake values (SUV).

The patient had initially considered radiotherapy in her post-delivery course, but given her most recent PET scan with a Deauville score of less than 4, the patient decided to avoid radiation and opted for close follow-up with repeat imaging. The Deauville 5-point scoring system is an internationally accepted point based scale used to characterize fluorodeoxyglucose (FDG) avidity of malignant tumor mass as seen on FDG positron emission tomography (PET) scan. Scores between 1 and 2 are considered negative, a score of 3 is typically paired with other studies and clinical signs to determine progression of disease, a score of 4 and 5 are considered positive for malignancy progression. Her pericardial effusion had resolved with chemotherapy.

Echocardiographic cardiac strain evaluation performed during follow-up evidenced a drop in her longitudinal strains from 22.8 to -15% just prior to delivery. Ejection fraction remained preserved at >60%. Low-dose carvedilol was considered during treatment however patient was not agreeable. The patient had an uneventful delivery and strain studies post-delivery showed a stable -15% strain. Echocardiogram performed 6 months post-chemotherapy demonstrated an ejection fraction of 72% and normalization of longitudinal strain. In the light of chemotherapy with known cardiotoxic adverse effects, as well as pregnancy strain on cardiac function, the patient did well and underwent an uneventful course.

Discussion 

The majority of data on maternal and fetal cardiotoxic effects of chemotherapy during pregnancy is based on case reports and retrospective data collection (2).

Registry data seems to suggest that the incidence of toxic side effects is not significantly increased during pregnancy and in the current literature there is no mention of an increased frequency of heart failure or left ventricular dysfunction during pregnancy (3-5). A study by Van Calsteren et al. (6), suggested that serum levels of chemotherapy, including anthracyclines, measured in pregnant women, were lower compared with those in nonpregnant women although the differences were not statistically significant. Despite the lower serum levels, cardiotoxicity might have a more significant impact on the maternal cardiovascular system in a context of increased hemodynamic loading. The use of cardiotoxic medications during pregnancy requires further attention, however no standard cardiac follow-up protocols are currently in place (7).

There may be a need for clinical cardiac assessments and an echocardiographic functional evaluation, including cardiac strain monitoring, prior to starting chemotherapy and repeat echocardiographic evaluation prior to every dose. If changes in cardiac function are observed, less cardiotoxic treatments might be considered or cardioprotective agents could be used. In this particular patient population, baseline echocardiography with strain study is crucial. Evidence of abnormal strain study during any part of the treatment should prompt initiation of cardioprotective therapy as per standards of the current heart failure guidelines. In addition, we suggest consideration for close cardiac follow-up monitoring, including a repeat echocardiogram study at 12 months post completion of chemotherapy/radiotherapy treatment. It is still unclear whether prophylactic therapy with cardioprotective agents would be safe and beneficial in these patients. Though we may be able to extrapolate data from trials performed on non-pregnant patients undergoing therapy and apply it to this particular niche of patients. The 2013 ACC/AHA heart failure guidelines state that it may be reasonable to evaluate those who are receiving (or who have received) cardiotoxic chemotherapy agents for left ventricular dysfunction as well as use echocardiographic techniques or biomarkers to identify increased heart failure risk in those receiving chemotherapy (8). In addition, the 2012 European Society of Medical Oncology (ESMO) guidelines stress on importance of serials cardiac function monitoring at baseline, 3, 6 and 9 months during treatment and then at 12 and 18 months after initiation of treatment (9).

Today, there is still no clear consensus with regards to cardioprotective therapy in patients exposed to cardiotoxic agents. As of 2016, the ACC/AHA guidelines did not reflect any change in recommendations in this particular field. Risk-stratification and prophylactic cardioprotective therapy remain an ultimate goal in pregnant patients undergoing chemotherapy, but how that should be done is still being studied. Early cardiology involvement and possible early initiation of prophylactic heart failure therapy should be considered.

References

1. Fadol AP, Lech T, Bickford C, Yusuf SW. Pregnancy in a patient with cancer and heart failure: challenges and complexities. J Adv Pract Oncol. 2012 Mar;3(2):85-93. [PubMed]
2. Gziri MM, Amant F, Debiève F, Van Calsteren K, De Catte L, Mertens L. Effects of chemotherapy during pregnancy on the maternal and fetal heart. Prenat Diagn. 2012 Jul;32(7):614-9. [CrossRef] [PubMed]
3. Cardonick E, Dougherty R, Grana G, Gilmandyar D, Ghaffar S, Usmani A. Breast cancer during pregnancy: maternal and fetal outcomes. Cancer J. 2010;16(1):76-82. [CrossRef] [PubMed]
4. Van Calsteren K, Heyns L, De Smet F, et al. Cancer during pregnancy: an analysis of 215 patients emphasizing the obstetrical and the neonatal outcomes. J Clin Oncol. 2010 Feb 1;28(4):683-9. [CrossRef] [PubMed]
5. Cardonick E, Iacobucci A. Use of chemotherapy during human pregnancy. Lancet Oncol. 2004 May;5(5):283-91. [CrossRef] [PubMed]
6. Van Calsteren K, Verbesselt R, Ottevanger N, et al. Pharmacokinetics of chemotherapeutic agents in pregnancy: a preclinical and clinical study. Acta Obstet Gynecol Scand. 2010 Oct;89(10):1338-45. [CrossRef] [PubMed]
7. Ewer MS, Ewer SM. Cardiotoxicity of anticancer treatments: what the cardiologist needs to know. Nat Rev Cardiol. 2010 Oct;7(10):564-75. [CrossRef] [PubMed]
8. Yancy CW, Jessup M, Bozkurt B, et al. 2013 2013 ACCF/AHA guideline for the management of heart failure: executive summary: a report of the American College of Cardiology Foundation/American Heart Association Task Force on practice guidelines. Circulation. 2013 Oct 15;128(16):1810-52. [CrossRef] [PubMed]
9. Curigliano G, Cardinale D, Suter T, et al. Cardiovascular toxicity induced by chemotherapy, targeted agents and radiotherapy: ESMO Clinical Practice Guidelines. Ann Oncol. 2012 Oct;23 Suppl 7:vii155-66. [CrossRef] [PubMed]

Cite as: Pak S, Yatsynovich Y, Valencia D, Bushch C, Vannorsdall E. Treatment of lymphoma and cardiac monitoring during pregnancy. Southwest J Pulm Crit Care. 2017;15(4):154-8. doi: https://doi.org/10.13175/swjpcc106-17 PDF 

October 2017 Pulmonary Case of the Month

Eric A. Jensen, MD

Department of Radiology

Mayo Clinic Arizona

Scottsdale, AZ USA

History of Present Illness

A 56-year-old woman presented with 3 days of non-productive cough, low-grade fever and severe right-sided pleuritic chest pain.

Past Medical History, Social History and Family History

She was diagnosed with coccidioidomycosis 5 years previously. She reports that she has had pneumonia every 6 to 12 months since her diagnosis with valley fever. She does not smoke. Family history is noncontributory.

Physical Examination

Her vital signs were unremarkable and she was afebrile but did cough frequently during the examination. Her lungs were clear and the rest of the physical examination was unremarkable.

Chest Radiography

She brings in two prior chest x-rays, one from 2011 (Figure 1, Panels A & B) and another from 2012 (Figure 1, Panel C).

Figure 1. Chest radiograph from 2011 (A & B) and from 2012 (C).

Which of the following best describes the chest x-rays? (Click on the correct answer to proceed to the second of five pages)

1. A repeat chest x-ray should be performed
2. A right lower lobe mass is present which appears to have enlarged from 2011 to 2012
3. There is a right lower posterior lung density
4. 1 and 3
5. All of the above

Cite as: Jensen EA. October 2017 pulmonary case of the month. Southwest J Pulm Crit Care. 2017;15(4):125-30. doi: https://doi.org/10.13175/swjpcc115-17 PDF

September 2017 Pulmonary Case of the Month

Lewis J. Wesselius, MD

Department of Pulmonary Medicine

Mayo Clinic Arizona

Scottsdale, AZ USA

History of Present Illness

A 67-year-old woman with history of chronic lymphocytic leukemia (CLL) was referred due to a 6-week history severe cough. Her CLL had recently relapsed and she was begun on ibrutinib (a small molecule drug that binds permanently to Bruton's tyrosine kinase) in addition to acyclovir, sulfamethoxazole/trimethoprim and allopurinol.

Past Medical History, Social History and Family History

Her CLL was initially diagnosed in 2009 and had responded to fludarabine, cyclophosphamide, and rituximab. She had no other chronic medical diseases. She smoked ½ pack per day but quit with the development of her cough. Family history was noncontributory.

Physical Examination

Her vital signs were unremarkable and she was afebrile but did cough frequently during the examination. There were shoddy small lymph nodes noted in both supraclavicular and axillary areas. Lungs were clear and the rest of the physical examination was unremarkable.

Laboratory Evaluation

Her complete blood count revealed her to be mildly anemic with a hemoglobin of 9.0 g/dL, an elevated white count of 33,700 cells/mcL with 88% lymphocytes, and a low platelet count of 60,000 cells/mcL. Her electrolytes were within normal limits and her blood urea nitrogen was 20 mg/dL, creatinine 1.1 mg/dL and uric acid 7.1 mg/dL.

Chest Radiography

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

Figure 1. Initial chest x-ray.

Which of the following is true? (Click on the correct answer to proceed to the second of five pages)

1. A pulmonary nodule is present in the left upper lobe (LUL)
2. Ibrutinib is well known to cause a chronic cough
3. Pneumonia is unlikely since she is afebrile
4. 1 and 3
5. All of the above

Cite as: Wesselius LJ. September 2017 pulmonary case of the month. Southwest J Pulm Crit Care. 2017;15(3):94-9. doi: https://doi.org/10.13175/swjpcc108-17 PDF