Case Puzzlers

Airways Disorders NetWork Case Puzzler - June 2011

ACCP — Thu, 23 Jun 2011 15:22:18 +0000

Teaser:

A 32-year-old white man with 3 months of fatigue and cough comes to you for evaluation. He had no fever, chills, night sweats, hemoptysis, or weight loss.

Airways Disorders NetWork Case Puzzler - June 2011

A 32-year-old white man with 3 months of fatigue and cough comes to you for evaluation. He had no fever, chills, night sweats, hemoptysis, or weight loss. Normal results of a CBC and metabolic profile were noted on the laboratory exam. The patient was found to have a mild mixed obstructive and restrictive pattern on his pulmonary function tests. Chest CT scans showed the following lesions (Figs 1, 2):

Figure 1. Patient CT scan of the chest.

Figure 2. Patient CT scan of the chest.

What do the scans show and what is your differential diagnosis?

See the Answer

The “reversed halo sign” is defined as a central ground-glass opacity surrounded by a denser crescent (forming more than three-fourths of a circle) or ring-shaped (forming a complete circle) opacity that is at least 2 mm in thickness. The term reversed halo sign was coined by Kim and colleagues in their retrospective study. In the study, a comparison was made between the high-resolution CT (HRCT) scan findings in 31 patients with biopsy-proven cryptogenic organizing pneumonia (COP) and the HRCT findings of 30 patients with organizing pneumonia due to a known cause. The study found that the reversed halo sign was seen in about 20% of patients and was considered to be a relatively specific sign for diagnosing COP by CT scan. The reversed halo sign serves an important role in the diagnosis of COP, but it has also been seen in several other medical conditions. When encountering this sign, it is important to look for nodularity, which would help differentiate active granulomatous diseases from COP. Therefore, the reversed halo sign may be considered as a nonspecific sign that is encountered in various pulmonary diseases (Fig 3), and one must always analyze the differential, symptommatology, and clinical signs before establishing a definitive diagnosis.

Figure 3. Various causes of reversed halo sign.

Case follow-up: The patient underwent transbronchial biopsies and bronchoalveolar lavage, and no specific diagnosis was made. He underwent open-lung biopsy, and the diagnosis of COP was confirmed. All culture results were negative. He responded well to corticosteroid therapy, with normalization of his CT scan and pulmonary function tests.

Recommended Reading

Kim SJ, Lee KS, Ryu YH, et al. Reversed halo sign on high-resolution CT of cryptogenic organizing pneumonia: diagnostic implications. AJR Am J Roentgenol. 2003;180(5):1251-1254.

Agarwal R, Aggarwal AN, Gupta D. Another cause of reverse halo sign: Wegener’s granulomatosis. Br J Radiol. 2007;80(958):849-850.

Kumazoe H, Matsunaga K, Nagata N, et al. “Reversed halo sign” of high-resolution computed tomography in pulmonary sarcoidosis. J Thorac Imaging. 2009;24(1):66-68.

Marchiori E, Zanetti G, Hochhegger B, Irion KL. Reversed halo sign: nodular wall as criterion for differentiation between cryptogenic organizing pneumonia and active granulomatous diseases. Clin Radiol. 2010; 65(9):770-771.

Submitted by:
Diego Maselli, MD; Pooja Desa, MD; and Jay Peters, MD, FCCP

Pulmonary Vascular Disease NetWork Case Puzzler- May 2011

ACCP — Tue, 17 May 2011 17:24:47 +0000

Teaser:

A 45-year-old man who was very active and could run up to 100 miles until 2 months prior to presentation started complaining of dyspnea on exertion, reduced exercise capacity, increased fatigue, and a dry cough.

Pulmonary Vascular Disease NetWork Case Puzzler- May 2011

Clinical presentation
A 45-year-old man who was very active and could run up to 100 miles until 2 months prior to presentation started complaining of dyspnea on exertion, reduced exercise capacity, increased fatigue, and a dry cough. He was evaluated and found to have a pulmonary embolus with near occlusion of the main pulmonary artery. He received an infusion of tissue plasminogen activator (TPA) with resolution of this clot, except for some residual clot on the right side. A regimen of enoxaparin was started and transitioned to coumadin. The patient was discharged but presented again with increasing cough 10 days after discharge. His repeat chest CT scan showed an extensive amount of proximal vessel occlusive material in the right ventricular outflow tract/main pulmonary artery extending into both main pulmonary arteries. Chest CT scan also showed small peripheral nodular lesions in the right upper lobe and right middle lobe. He underwent a second infusion of TPA. His care was then transferred to our hospital.

Medical and surgical history
Unremarkable.

Social history
No history of alcohol or tobacco abuse. No illicit drug abuse. He was married with two children and was an engineer by profession.

Current medications
Enoxaparin, docusate, iron, pantoprazole, coumadin.

Physical examination Temperature, 97.4 F; BP, 179/72; heart rate, 82 bpm; respiratory rate, 12/min; oxygen saturation, 100% on 2 L (by nasal cannula)
General: comfortable at rest; in no acute distress.
HEENT: neck, supple.
PULM: crackles in right upper lung zone; 3/6 bruit over left pulmonary artery
CV: heart sounds regular in rate and rhythm
EXT: no edema on the examination of extremities
NEURO: no focal neurologic deficits
HEP: liver ultrasound showed patent portal and hepatic veins.

Laboratory data
Sodium, 141 mEq/L; potassium, 3.9 mEq/L; BUN, 6 mg/dL; creatinine, 0.7 mg/dL; INR, 1.82; liver function test, normal; WBC, 5.5 X 10⁹/L; hemoglobin, 12.2 g/dL; platelets, 249 X 10⁹/L; D dimmer, 1.66 (0.00 – 0.40 µg/mL); brain naturetic peptide, 91 pg/mL. Hepatitis A, B, and C and HIV 1-2 were nonreactive. Lupus anticoagulant was positive; factor V Leiden, negative. Echocardiogram showed LVEF of 65% to 69%, RV size moderately enlarged, RV hypertrophy, RV function moderately decreased. No pericardial effusion was noted. Right ventricular systolic pressure was 81 mm Hg, right atrial pressure was 10 mm Hg, cardiac output was 4.9 L/min, and cardiac index was 2.4 L/min/m².

Chest CT scan
Large filling defect within main pulmonary artery and extending into right and left pulmonary arteries. The mass originates in the pulmonary outflow tract and is associated with some generalized thickening in this location. There is a mass in the right upper lobe that measures 2.3 cm, suspicious for neoplasm. There is some infiltrate present posterior to it in the posterior segment of the right upper lobe, which was considered nonspecific (Fig 1).

Figure 1. CT scan of the chest with contrast showed a large filling defect within the main pulmonary artery extending into right and left pulmonary arteries.

CT-PET scan did not show uptake in the very large filling defects that were seen on the contrast-enhanced CT scan. Mild uptake is present within a 2.2-cm nodular density in the lateral right upper lobe (Fig 2).


Figure 2. Top, CT-PET scan revealed a large filling defect in both the right and left proximal pulmonary artery that was noted to be photopenic and showed no uptake. . However, mild to moderate uptake was present in multiple areas in the periphery.	Bottom, CT-PET scan showing mild uptake in the 2.2 cm nodular density in the lateral right upper lobe.

Pulmonary angiogram
Main right and left pulmonary arteries filled with clot, with some clot extending into inferior branches of the right pulmonary artery. Peripheral branches were clear. Obstruction to right pulmonary artery was more severe than left pulmonary artery (Fig 3). Bird’s nest inferior vena cava filter was placed. Unsuccessful attempts were made to biopsy this central mass during the pulmonary angiogram procedure, as this mass could not be seen fluoroscopically, and the biopsy results revealed only blood clots.


Figure 3. Pulmonary angiogram showed main right and left pulmonary arteries filled with clot with some clot extending into inferior branches of the right pulmonary artery. Peripheral branches were clear. There was paucity of vessels in some areas in the periphery.

Cardiac MRI
Demonstrated a large filling defect in the pulmonary artery, extending from the root into both the right and left pulmonary artereries. In some locations, it appears adherent to the wall of the pulmonary artery. There is no invasion of adjacent myocardium and no extension through the wall of the pulmonary artery is seen. After contrast as administered, the majority of the mass does not appear to enhance significantly. However, there is at least one portion at the root of the pulmonary artery that appears to enhance (Fig 4).

Figure 4. Cardiac MRI revealed a large filling defect in the main pulmonary artery, extending from the root into both the right and left pulmonary arteries. In some locations, it appeared adherent to the wall of the pulmonary artery. There was no invasion of adjacent myocardium, and no extension through the wall of the pulmonary artery was seen.

Question: What is the diagnosis?

See the Answer

Answer: Pulmonary intimal sarcoma.

Clinical course
The patient successfully underwent pulmonary thromboendarterectomy, and the final diagnosis was pulmonary intimal sarcoma (Fig 5). The patient was referred to an oncologist for further management and follow-up. Following the pulmonary thromboendarterectomy, echocardiogram showed right ventricular systolic pressure of 31 mm Hg. Right ventricle was slightly enlarged with normal function and mildly enlarged right atrium. Left ventricular size and systolic function were normal. Resolution of mass in pulmonary artery with normalization of right ventricular size and almost normalized pressure. Cardiac output increased to 7.7 L/min.

Figure 5. Pulmonary thromboendarterectomy specimen.

Postpulmonary endarterectomy perfusion scan showed a dramatic interval improvement in the perfusion to the right lung.The perfusion images were essentially normal.

Postoperative hemodynamic values were as follows: pulmonary artery pressure, 27/7 mm Hg, with mean, 12 mm Hg; right atrial pressure, 8 mm Hg; cardiac output, 6.33 L/min; cardiac index, 3.07 L/min/m².

Normal oxygen saturation at rest was 99%, and, with exercise, no desaturation was noted.

Discussion
Intimal sarcoma of the pulmonary artery is a rare mesenchymal tumor that arises in large vessels and carries a poor prognosis. It usually is misdiagnosed as chronic thromboembolic disease and, in most cases like ours, the definitive diagnosis is made at surgery or at autopsy. This tumor is characterized by local growth with ability to metastasize and potential for embolization. The patient may have a long asymptomatic course that is followed by insidious onset of symptoms of right-sided failure. When the patient experiences symptoms from this tumor, the prognosis is poor, with a life expectancy of 12 to 18 months. Our patient underwent complete resection of the tumor from the pulmonary artery and its branches.

Teaching point
Pulmonary artery sarcoma can masquerade as chronic thromboembolic disease, and this should be included in the differential diagnosis, especially in the presence of pulmonary nodules.

Recommended Reading
1. Fernandez-Golfin C, Escribano P, Cortina J, et al. Management of primary pulmonary artery sarcoma: experience of a single center. Angiology. 2008;59(5):636-639.
2. Gan HL, Zhang JQ, Zhou QW, et al. Surgical treatment of pulmonary artery sarcoma [published online ahead of print April 15, 2011]. J Thorac Cardiovasc Surg.
3. Kaplinsky EJ, Favaloro RR, Pombo G, et al. Primary pulmonary artery sarcoma resembling chronic thromboembolic pulmonary disease. Eur Respir J. 2000;16(6):1202-1204.
4. Kerr KM. Pulmonary artery sarcoma masquerading as chronic thromboembolic pulmonary hypertension. Nat Clin Pract Cardiovasc Med. 2005;2(2):108-112.
5. Levy E, Korach A, Amir G, Milgalter E. Undifferentiated sarcoma of the pulmonary artery mimicking pulmonary thromboembolic disease. Heart Lung Circ. 2006;15(1):62-63.
6. Pavlidis AN, Tsoukas AS, Kallistratos MS, Hesketh G, Manolis AJ. Relapsed pulmonary sarcoma presenting as congestive heart failure [published online ahead of print April 21, 2011]. Neth Heart J.

Puzzler submitted by:
Zeenat Safdar, MD, FCCP
Assistant Professor of Medicine
Associate Director, Pulmonary Hypertension Center
Baylor College of Medicine
Houston, Texas
Steering Committee Member, Pulmonary Vascular Disease

Clinical Pulmonary Medicine NetWork Puzzler - March 2011

ACCP — Tue, 05 Apr 2011 18:15:40 +0000

Teaser:

A 64 year-old man with a history of cardiac coronary bypass surgery 1 month ago has hemoptysis. His symptoms started 1 day prior, and he described these symptoms as bright red blood clots, brought up with cough, which was also recent.

A Case of Recent Hemoptysis Postcardiac Surgery

Clinical Presentation
A 64 year-old man with a history of cardiac coronary bypass surgery 1 month ago has hemoptysis. His symptoms started 1 day prior, and he described these symptoms as bright red blood clots, brought up with cough, which was also recent. He complained of the sensation of a “lump in the throat,” which was sudden in onset. He was coughing up a clot every 1/2 to 1 h. He was taking daily aspirin, 325 mg; metoprolol; and amiodarone. The review of systems was remarkable only for dysphagia and mild pain at the thoracic incision site; the patient denied epistaxis, hematemesis, melena, nausea, vomiting, dizziness, syncope, shortness of breath, or orthopnea. He has never smoked and used to drink alcohol occasionally. He denied the use of any illicit drugs. His family history was significant for early coronary artery disease, as his father died of a myocardial infarction in his 50s.

On physical examination, the patient was not in any physical distress, and he was alert and oriented. His blood pressure was 150/87 mm Hg and pulse was 81/min. He was breathing at the rate of 18/min, with a hemoglobin oxygen saturation by pulse oximeter of 98% on room air. He was afebrile. On examination of his throat, there was no visible blood. Chest examination revealed a tender clean scar from his recent surgery and no associated abnormal breathing sounds. The rest of the physical examination results were normal.

Laboratory test results, including those for usual chemistries, thrombocytes, prothrombin time, international normalized ratio, and partial thromboplastin time, were unremarkable; RBC hemoglobin level was 11.3 g/dL. Chest radiograph did not show any abnormalities. A fiberoptic bronchoscopy on the second day of admission revealed a small amount of fresh blood above the vocal cords. Below the vocal cords, there was no source of bleeding identified.

Overnight, the patient coughed up copious amounts of blood clots. He was tachycardic and diaphoretic; his blood pressure was 102/56 mm Hg, and his pulse was 112/min. His hemoglobin level dropped to 9.6 g/dL, and he received a transfusion of 2 units of packed RBCs.

A barium transit series was obtained and is illustrated in Figure 1.

Figure 1. Barium transit study, upper esophageal phase.

Question: What is the diagnosis?

See the Answer

Answer: Zenker diverticulum, complicated by ulcer and significant mucosal hemorrhage

Clinical Course
The patient underwent a fiberoptic esophagoscopy, showing large-sized blood clots in the hypopharynx, which were removed with the endoscope. There was a large esophageal diverticulum emerging from the posterior wall of the proximal esophagus, which was filled with blood clots and obstructing the esophageal lumen distally. The esophagoscope could not be passed beyond the ostium of the diverticulum; hence, the procedure was terminated. A barium swallow study confirmed the presence of the large Zenker diverticulum. During each of the swallowing episodes, a moderate volume of the contrast bolus flowed into this diverticulum. There was no evidence of barium aspiration in the airways.

A cardiothoracic surgery consult was obtained for the excision of the diverticulum; due to its size and the hematologically and hemodynamically significant hemorrhage, the procedure was performed emergently. The excised diverticulum measured 3 x 1.5 x 2 cm and the histologic examination of the specimen revealed a centrally located ulcer in the diverticular mucosa, with focal areas of hyperemia and thickening (Fig 2). Postoperatively, no further bleeding episode was reported, and the patient was discharged home in stable condition.

Figure 2. Ulcerated Zenker diverticulum with acute and chronic inflammation (hematoxylin-eosin).

Discussion
Zenker diverticulum is an outpouching of the esophageal mucosa posteriorly, between the cricopharyngeus muscle and the inferior pharyngeal constrictor muscles. It is mainly seen in the elderly, and its prevalence in the United States is estimated to be between 0.01% and 0.11% of the population. A Zenker diverticulum carries with it a high frequency of retention of food elements within its pouch. Most commonly, Zenker diverticulum leads to the complaints of halitosis, regurgitation, aspiration, and dysphagia associated with weight loss. Bleeding in the diverticulum is exceedingly rare, and we have found only five cases reported in the medical literature. As in our case, all reported patients were taking daily aspirin.

The exact mechanism or mechanisms by which aspirin can cause mucosal ulceration or frank ulcer formation is not known. One postulated mechanism is that these acidic pills enter the diverticulum and stay with continuous contact with the mucosa, leading to a “pill-induced diverticulitis.” It is known to cause the inhibition of prostaglandin synthesis, which can account for the loss of local trophic factors. Diverticulitis, due to the stasis of food in the outpouch, is thought to be another possible mechanism, although the contribution of aspirin in this mechanism is unclear. In our case, we found no evidence of diverticulitis on the histopathology specimen.

An important aspect in the management of Zenker diverticulum is to keep in mind the risk of esophageal perforation when attempting esophageal instrumentation, such as side-viewing duodenoscope, nasogastric tube, and transesophageal echocardiogram. The endoscope should be withdrawn in the case of resistance during esophageal intubation.

Conclusions
In summary, the case presented here is of a patient with a relatively large Zenker diverticulum complicated by an ulcer and significant secondary hemorrhage. This type of presentation may pose diagnostic and therapeutic challenges to the clinician; hence, we think practitioners need to be aware of this condition.

Teaching Points

Zenker diverticulum can present as a rare cause of hemoptysis.
An ulcer in Zenker diverticulum resulting in a clinically significant bleed, in itself, is not very common.
Chronic use of aspirin is probably the most important factor in the ulcer formation.
Upper endoscopy, if attempted, to look for the cause of bleeding, should be performed very cautiously because of the risk of esophageal perforation. Barium swallow can be very helpful in the diagnosis.

Suggested Reading

Haas I, Gutman M, Paran H. Massive upper GI bleeding: a rare complication of Zenker’s diverticulum. J Postgrad Med. 2008;54(3):209-210.

Odemis B, Ataseven H, Basar O, Ertugrul I, Yukesl O, Turhan N. Ulcer in the basis of Zenker’s diverticulum mimicking esophageal malignancy. J Natl Med Assoc. 2006;98(7):1177-1180.

Kensing KP, White JG, Korompai F, Dyck WP. Massive bleeding from a Zenker’s diverticulum: case report and review of the literature. South Med J. 1994;87(10):1003-1004.

Hendren WG, Anderson T, Miller JI. Massive bleeding in a Zenker’s diverticulum. South Med J. 1990;83(3):362.

Shirazi KK, Daffner RH, Gaede JT. Ulcer occurring in Zenker’s diverticulum. Gastrointest Radiol. 1977;2(2):117-118.

Siddiq MA, Sood S, Strachan D. Pharyngeal pouch (Zenker’s diverticulum). Postgrad Med J. 2001;77(910):506-511.

Corresponding Author
Misbah Baqir, MD
602 Calibre Woods Dr NE
Atlanta, GA 30329
mbaqir@emory.edu
Phone: +01 (404) 512-9000
Fax: +01 (404) 417-1525

Co-Author
Octavian C. Ioachimescu, MD, PhD
oioachi@emory.edu
Phone: +01 (404) 321-6111 #2086
Fax: +01 (404) 417-1525

Affiliations
Emory University – Division of Pulmonary, Critical Care, Sleep Medicine
Atlanta VA Medical Center
Atlanta, Georgia

Critical Care NetWork Puzzler - September 2010

ACCP — Mon, 20 Sep 2010 14:16:45 +0000

Teaser:

A 37-year-old man with type 1 diabetes had a 2-day history of worsening nausea, vomiting, malaise, and abdominal pain that began shortly after intentionally stopping his insulin regimen.

Case Report

A 37-year-old man with type 1 diabetes had a 2-day history of worsening nausea, vomiting, malaise, and abdominal pain that began shortly after intentionally stopping his insulin regimen. He denied chest pain, shortness of breath, and recent illness. Initial vital signs were significant for tachycardia and tachypnea, and results of the physical exam were normal except for diffuse abdominal tenderness. Initial laboratory testing revealed a serum pH of 7.09, a blood glucose level of 850 mg/dL, an anion gap of 50 mEq/L (serum bicarbonate level of 6 mEq/L), and a serum troponin I (TnI) concentration of 0.33 ng/mL (normal range, 0-0.5 ng/mL). There was no evidence of ischemia on ECG. The urine drug screen result was negative for illicit substances, including cocaine. Other relevant laboratory values are noted in Table 1.

Table 1—Laboratory Values During Two Admissions for Diabetic Ketoacidosis*

	Troponin I, ng/mL	Glucose, mg/dL	BUN/Creatinine, mg/dL / mg/dL	K+, mmol/L	HCO₃^-, mmol/L	pH
Current admission	0.33	850	55 / 2.6	6.3	6	7.09
At cardiac catheterization	21.3	165	17 / 0.9	3.9
Prior admission	0.1	440	38 / 1.7	4.6	11	7.17
At cardiac catheterization	14.8	153	13 / 0.8	3.1

*BUN = blood urea nitrogen; Cr = serum creatinine; K+ = serum potassium

His past medical history included a prior ST-elevation myocardial infarction (MI) 16 months earlier during a prior episode of diabetic ketoacidosis (DKA), hypertension, hyperlipidemia and poorly controlled type 1 diabetes (hemoglobin A1c = 12.2% on prior admission, four prior hospitalizations for DKA). The patient never reported chest pain during his prior admission for MI, but ST segment elevation was observed in the inferior and precordial leads (Fig 1). Transthoracic echocardiogram showed an ejection fraction of 40% with mild global hypokinesis, and cardiac catheterization revealed normal coronary arteries during that admission.

Figure 1. ECG from 2006 admission for DKA (corresponding troponin I level approximately 4 ng/mL).

Over the next 2 days of treatment, the patient’s anion gap and hyperglycemia resolved, but his TnI concentration increased to 21.3 ng/mL. Serial ECGs remained unremarkable (Fig 2), although the patient began to complain of intermittent chest discomfort on hospital day three. Transthoracic echocardiogram findings were unchanged from the previous findings, and repeat cardiac catheterization showed no significant coronary artery disease.

Figure 2. ECG from 2007 admission for DKA (corresponding troponin I level approximately 20 ng/mL).

What is the diagnosis?

See the Answer

Hypertroponinemia due to diabetic ketoacidosis

Discussion
Cases of elevated troponin concentrations in association with DKA are not commonly reported in the literature. These patients present a diagnostic dilemma, as it is unclear whether the elevated cardiac biomarkers are an indication of acute MI or myocardial damage from other causes.

In addition to acute coronary syndrome, the differential diagnosis of an elevated TnI level is broad and includes other causes of myocardial damage, including coronary vasospasm, electrical damage from defibrillation, myocardial contusion, hypertensive emergency, myocardial strain from pulmonary embolus, cardiomyopathy, and hypoperfusion states of sepsis or acute GI bleeding. At both presentations for DKA, our patient had no other contributing factors to explain his elevated troponin level. As his DKA resolved, both his troponin levels and ECG changes normalized.

The etiology of myocardial cell damage in the setting of DKA is unclear. Possible mechanisms include the activation and perpetuation of myocardial apoptosis pathways, membrane and intracellular damage from severe acidosis, ketone bodies and high levels of free fatty acids, and excessive reactive oxygen species production. In vitro studies have shown that ketone bodies have an inhibitory effect on glucose uptake into myocytes and inhibit glucose oxidation overall. Glucose becomes the primary energy source for myocytes during times of acute stress, so this inhibitory effect may preclude myocyte damage at baseline or in the setting of increased myocardial work during a stress state. Additionally, chronic or repeated exposure to elevated levels of ketone bodies can damage the myocardial glucose uptake pathways, causing decreased uptake of glucose even in low stress states. This suggests that the diseased pathways may be affecting myocardial function, even during times of low stress, perhaps making the myocardium more vulnerable in metabolically demanding situations. Moreover, the hyperosmolar environment accompanying DKA can be marked, and it appears that transient erythrocyte swelling and decreased flexibility during this state of osmotic balance can result in transient microvascular ischemia.

Two recently published studies looked at this topic and found that 27% (26 of 96) and 10% (4 of 40) patients admitted for DKA had elevated troponin concentrations. The patients in the first retrospective study had a significant increase in mortality and adverse coronary events at 2 years of follow-up compared with patients with DKA without elevated troponins (50% vs 27.1%; hazard ratio, 2.3 [1.2-4.8] and 50% vs 28.6%; hazard ratio, 2.6 [1.3-5.3]). Only elevated troponin and age were independent predictors of increased mortality and adverse cardiac events. Patients with elevated troponin in the second study underwent echocardiography and thallium-201 scintigraphy, which showed no abnormalities.

People with diabetes represent a population at high risk for coronary artery disease and cardiovascular events. An elevated troponin level without evidence of acute coronary syndrome or MI may be more common in DKA than previously documented and serve a marker for increased risk of cardiovascular morbidity and mortality in this population. Further study is needed to determine the mechanism of elevated troponin levels in these patients and the best management of these individuals, in addition to optimal diabetic control.

Recommended Reading

Geddes J, Deans KA, Cormack A, et al. Cardiac troponin I concentrations in people presenting with diabetic ketoacidosis. Ann Clin Biochem. 2007;44(pt 4):391-393.

Kubasiak LA, Hernandez OM, Bishopric NHm Webster KA. Hypoxia and acidosis activate cardiac myocyte death through the Bcl-2 family protein BNIP3. Proc Natl Acad Sci USA. 2002;99(20)12825-12830.

Mahajan N, Mehta Y, Rose M, Shani J, Lichstein E. Elevated troponin level is not synonymous with myocardial infarction. Intl J Cardiol. 2006;111(3):442-449.

Al-Mallah M, Zuberi O, Arida M, Kim HE. Positive troponin in diabetic ketoacidosis without evident acute coronary syndrome predicts adverse cardiac events. Clin Cardiol. 2008;31(2):67-71.

Moller N, Foss AC, Gravholt CH, Mortensen UM, Poulsen SH, Mogensen CE. Myocardial injury with biomarker elevation in diabetic ketoacidosis. J Diabetes Complications. 2005;19(6):361-363.

Pelletier A, Coderre L. Ketone bodies alter dinitrophenol-induced glucose uptake through AMPK inhibition and oxidative stress generation in adult cardiomyocytes. Am J Physiol Endocrinol Metab. 2007;292(5):E1325-E1332.

Taegtmeyer H, McNulty P, Young ME. Adaptation and maladaptation of the heart in diabetes: Part 1. General concepts. Circulation. 2002;105(14):1727-1733.

Submitted by:
CPT Leslie A. Jette, MC, USA
CPT Jason D. Heiner, MC, USA
MAJ Jeremy C. Pamplin, MD
Departments of Medicine and Emergency Medicine
Madigan Army Medical Center
Tacoma, WA

Sleep NetWork Puzzler, June 2010

ACCP — Wed, 30 Jun 2010 03:30:55 +0000

Teaser:

After reading the Chapter, test your knowledge with questions from ACCP-SEEK Sleep Medicine, First Edition:

Technical Aspects of Sleep Testing

Chapter from the ACCP Sleep Medicine Board Review Course, 4th Edition
Technical Aspects of Sleep Testing

After reading the chapter, test your knowledge with these two questions from ACCP-SEEK^® Sleep Medicine: First Edition.

1. A 48-year-old man is referred to the sleep laboratory for a polysomnogram (PSG) to evaluate snoring and apneas witnessed by his wife. His BMI is 35 kg/m², and he has a neck circumference of 45 cm. A representative epoch of the PSG is shown in the figure below. Which of the following is the most likely cause of the disturbance seen in the PSG epoch?

A. Change in body position from supine to lateral.
B. Excessive sweating.
C. Slow-wave sleep.
D. A loose right-eye lead.

See the Answer.

B. Excessive sweating.

Sweat artifact is a common finding on PSG. Sweating itself is common during sleep and has many causes, including infections, cancers, rheumatologic disorders, and medications. In many cases, nocturnal sweating is idiopathic. Sleep apnea is a recognized cause of nocturnal sweating, and it may be a common cause of nocturnal sweating in sleep laboratories.

When patients undergoing PSG sweat heavily, they may disrupt the contact between the electrode and the skin, resulting in artifacts. The artifacts are usually characterized by large, slow, and somewhat chaotic or dysynchronous waves in the EEG or EOG channels. In the figure above, both the EEG channels and EOG channels are affected and demonstrate the large waves typical of this setting (choice B is correct).

Sweat artifact is corrected by cooling the patient and allowing the sweating to dissipate. In some cases, the electrode artifacts may self-correct. In other cases, a change of electrodes will be required. Sleep laboratory technologists must monitor ambient temperature in the bedroom and make adjustments for patient comfort and signal integrity when sweating is a problem.

Choice A is incorrect because a change in body position would result in movement artifact, which typically involves more than just the eye channels or EEG leads. Choice C is incorrect because slow-wave sleep would not have the fluctuating or wandering baseline seen in sweat artifact. Choice D is incorrect because changing a single electrode would not eliminate the artifacts, which are seen bilaterally.

Mahowald M. Other parasomnias. In: Kryger M, Roth T, Dement W, eds. Principles and Practice of Sleep Medicine. 4th ed. Philadelphia, PA: Elsevier, 2004; 920.

Heller C. Temperature, thermoregulation, and sleep. In: Kryger M, Roth T, Dement W, eds. Principles and Practice of Sleep Medicine. 4th ed. Philadelphia, PA: Elsevier, 2004; 294.

Chokroverty S, Thomas RJ, Bhatt M. Atlas of Sleep Medicine. Philadelphia, PA: Elsevier, 2005; 15, 18-19.

2. Which of the following would correct the artifact shown in the 30-s epoch represented in the figure below?

A. Replace the electrode at the outer canthus of the left eye.
B. Replace the electrode at the left side of the vertex.
C. Replace the electrode at the left side of the vertex.
D. Replace the electrode at the right auricular area.

See the Answer.

D. Replace the electrode at the right auricular area.

Eye movements are measured to help stage sleep. The electrical principles behind eye movements are straightforward. The eye functions as an electrical dipole, with the cornea reflecting a negative charge and the iris or sclera possessing a positive charge. As the eye globe moves in its socket, the electrodes placed just above or just below the outer canthus of each eye detect a change in charge. The electrodes are set up so that conjugate eye movements are represented as disconjugate deflections of the pen or computer readout. By convention, the left side of the head has odd numbers and the right side of the head has even numbers. In the figure above, the artifact is seen in the LEOG, C3A2, and O1A2 leads and appears in the first 25 s of the epoch by sharp, high-voltage, conjugate deflections. The first step in identifying the source of the artifact is to look for an electrode common to the leads that show the artifact. In this case, A2 is the likely culprit since it is common to all three of the channels that show the artifact. The A2 (or right auricular) lead is positioned just posterior to the right ear in the mastoid area (choice D is correct).

Replacing A1 (the outer canthus of the left eye), C3 (left side of the vertex), or O1 (left side of the occiput) will not resolve the problem since those electrodes are functioning normally (choices A, B, and C are incorrect). To note, the 2007 American Academy of Sleep Medicine scoring manual renamed the auricular location the mastoid location, so the electrode is designated as M2 rather than A2.

Chokroverty S, Thomas RJ, Bhatt M. Atlas of Sleep Medicine. Philadelphia, PA: Elsevier, 2005; 3-4.

Walczak T, Choroverty S. Electroencephalography, electromyography, and electro-oculography; general principles and basic technology. In: Chokroverty S, ed. Sleep Disorders Medicine. Boston, MA: Butterworth-Heinemann, 1999; 184-186.

Carskadon M, Rechtschaffen A. Monitoring and staging human sleep. In: Kryger M, Roth T, Dement W, eds. Principles and Practice of Sleep Medicine. 4th ed. Philadelphia, PA: Elsevier, 2004; 1359-1367.

Iber C, Ancoli-Israel S, Chesson A, et al, for the American Academy of Sleep Medicine. The AASM Manual for the Scoring of Sleep and Associated Events: Rules, Terminology and Technical Specifications. Westchester, IL: American Academy of Sleep Medicine, 2007.

Chest Infections NetWork Puzzler - June 2010

ACCP — Sun, 20 Jun 2010 17:01:16 +0000

Teaser:

A 55-year-old Caucasian woman with scleroderma presented to the hospital in February 2009 with severe dyspnea. She felt well until 1 week prior, when she developed fevers, chills, and an intermittent dry cough. She then developed severe dyspnea over 2 days and presented to a local ED. Her temperature was 104°F, and arterial blood gases drawn revealed a pH of 7.46, a Pco₂ of 32, a Po₂ of 51, and an oxygen saturation of 88% on 100% nonrebreather mask. Chest radiograph showed a left lower lobe infiltrate. The patient was started on azithromycin and ceftriaxone, as well as IV solumedrol. She was intubated 1 day later for progressive hypoxia. Tracheal aspirate showed no organisms on Gram stain, and a culture revealed mixed flora. She was transferred to a tertiary hospital.

The patient has a past history of scleroderma, diagnosed 6 months prior to admission. At that time, she presented with severe edema in her feet, legs, and hands, and also skin changes in her fingers. She has been treated with prednisone and methotrexate for 6 months. She had no history of pulmonary involvement from the scleroderma. Recently, her rheumatologist felt that her skin changes were progressing. The methotrexate was stopped, and she had her first dose of cyclophosphamide, 25 mg, around the time she developed severe dyspnea.

The patient works as an elementary school teacher. She lives in a rural area of Ohio with her husband and has dogs, cats, and goats. She has not traveled recently. She has no history of TB. She had not received prior pneumococcal or influenza vaccinations.

Home medications

Prednisone, 20 mg tid, for 6 months
Methotrexate, 20 mg weekly, for 6 months
Cyclophosphamide, 25 mg daily, started 1 day prior to presentation
Metformin
Valsartan

On examination, her blood pressure was 150/70 mm Hg, pulse was 130/min, and temperature was 101.2°F. Her ventilator settings were the following: PIP of 40, Fio₂ of 100%, PEEP of 10. She was sedated and agitated. Her lungs had some soft wheezing. She was tachycardic, with no murmurs. There was severe sclerodactyly below the elbows and in both feet.

Laboratory testing showed a WBC count of 28,000/µL (93% neutrophils) and hemoglobin level of 13.0 g/dL. Complete metabolic panel was unremarkable except for a lactate dehydrogenase level of 695 U/L (normal level is 100 to 220 U/L). Other laboratories included the following: antinuclear antibody test = 1:160, speckled pattern; sedimentation rate = 55 mm/h; C-reactive protein = 13 mg/dL; β-natriuretic peptide = normal level; and lactic acid = normal level. Figures 1 and 2 show her chest radiograph and CT scan, respectively.

Figure 1. Patient chest radiograph.

Figure 2. Patient CT scan.

Within a few hours of transfer, the patient became hypotensive and required multiple boluses of normal saline, and she started to receive pressors.

What is the most likely diagnosis?

See the Answer

Pneumocystis jiroveci pneumonia

Discussion

Given her immunocompromised status, a wide differential diagnosis was initially entertained, including ARDS and infectious and noninfectious etiologies. However, Pneumocystis pneumonia (PCP) was felt to be the most likely diagnosis, given her prolonged corticosteroid use and certain aspects of her presentation as discussed below. She was started on IV trimethoprim-sulfamethoxazole and continued receiving other antibacterial agents. Bronchoscopy with lavage confirmed Pneumocystis jiroveci pneumonia.

The following questions were raised by this case:

What is the relationship between corticosteroid use and the development of PCP in patients who are HIV negative?
Are there differences in the clinical presentation between patients with PCP who are HIV negative and HIV positive?
What are the important prognostic factors for patients with PCP who are HIV negative?

In one series from the Mayo Medical Center,¹ the clinical characteristics of 116 consecutive patients with PCP without AIDS were described. The cases were first episodes of PCP seen during the period of 1985 to 1991. The associated diseases were as follows:

Hematologic malignant disorders - 30%
Organ transplantation - 25%
Inflammatory diseases - 22%
Solid tumors - 13%
Miscellaneous - 9%

Of note, more than 90% of patients had received corticosteroids within 1 month of PCP diagnosis. The median corticosteroid dose was equivalent to 30 mg of prednisone daily. However, 25% of patients had received as little as 16 mg of prednisone daily. The median duration of therapy was 12 weeks, but 25% of patients developed PCP after 8 weeks or less of steroid therapy. Respiratory failure developed in 43%, and in-hospital mortality was 34%. In this study and others, PCP can develop when corticosteroids are being tapered, and PCP should be suspected with progressive respiratory symptoms in this setting. The authors concluded that PCP prophylaxis should be considered in patients for whom prolonged systemic corticosteroid therapy is planned. Prophylaxis has been suggested by other authors for those receiving the equivalent of 20 mg of prednisone or more for more than 1 month,² with the caveat that randomized trials are lacking.

There are some recognized differences in PCP between individuals who are HIV negative and HIV positive (Table 1). These are generalizations, and a variety of clinical presentations in both groups can be seen.

Table 1— PCP in People Who Are HIV Positive and HIV Negative

	HIV Positive With PCP	HIV Negative With PCP
Clinical Course	Insidious; better oxygenation	Abrupt onset
Pathologic Findings	Fewer neutrophils High organism burden	Many neutrophils Low organism burden
Bronchoalveolar Lavage	Higher yield	Lower yield
Mortality Rate	10-35%	30-60%

From Thomas CF and Limper AH.³

A more recent retrospective study from the Mayo Clinic⁴ examined the prognosis of 30 patients with non-HIV PCP presenting with acute respiratory failure requiring positive pressure ventilation support.Both in-hospital mortality (67%) and 6-month mortality (77%) were high. Eight patients had been receiving corticosteroids, 7 had been on chemotherapy, and 15 on a combination. All patients with a pneumothorax died. All but one had a significantly elevated LDH level (median of 563 U/L), a finding also recognized in AIDS-related PCP and noted in our case. None of the patients in this series had been on PCP prophylaxis. Factors associated with a poor prognosis were delay in intubation, longer duration of intubation, development of pneumothorax, and a high APACHE III score on day one.

The clinical features of PCP in people with underlying connective tissue diseases was described in one report.⁵ This report was published in 1994, prior to the routine use of tumor necrosis factor inhibitors and other biologic agents. In this retrospective analysis, there were a number of connective tissue diseases represented, with Wegener granulomatosis being the most common (12 patients), then systemic lupus erythematosis (six patients), polymyositis/dermatomyositis (five patients), polyarteritis nodosum (four patients), and other diseases (seven patients). Nearly 75% of patients presented with PCP during the first 8 months following the diagnosis of the connective tissue disease, similar to the patient in this case. At the time of diagnosis of PCP, 94% of patients (32 of 34) were receiving corticosteroids (mean of 1.2 mg/kg), associated in 24 cases with cytotoxic agents (cyclophosphamide, n= 19; methotrexate, n=5). Most patients were lymphocytopenic at the onset of PCP. The mean duration of prodromal symptoms was 6 days. About one-half of the patients presented with severe respiratory failure requiring ICU admission. The overall mortality was 32%, although several deaths were attributed to nosocomial ICU infections.

The notion that trimethoprim-sulfamethoxazole is contraindicated in patients receiving methotrexate is probably outdated.³ This concern is based on the potential for myelosuppression when these agents are used in combination. However, studies have shown that this combination is safe; patients receiving 25 mg of methotrexate per week could tolerate trimethoprim/sulfamethoxazole prophylaxis without significant myelosuppression.

References:

Yale SH, Limper AH. Pneumocystis carinii pneumonia in patients without acquired immunodeficiency syndrome: associated illness and prior corticosteroid therapy. Mayo Clin Proceed. 1996;71(1):5-13
Walzer PD, Smulian AG. Pneumocystis species. In: Mandell, Douglas, and Bennett’s Principles and Practice of Infectious Diseases, 7th Edition. New York, NY: Churchill Livingstone; 2009
Thomas CF, Limper AH. Pneumocystis pneumonia. New Engl J Med. 2004;350(24): 2487-2498
Festic E, Gajic O, Limper AH, Aksamit TR. Acute respiratory failure due to Pneumocystis pneumonia in patients without human immunodeficiency virus infection. Chest. 2005;128: 573-579
Godeau B, Coutant-Perronne V, Le Thi Huong D, et al. Pneumocystis carinii pneumonia in the course of connective tissue disease: report of 34 cases. J Rheumatology. 1994; 21(2):246-251

Puzzler and case report submitted by:
Sara Mekuria, MD
Resident, Internal Medicine Residency Training Program
Cleveland Clinic
Cleveland OH

Nega Ali Goji, MD
Infectious Disease Specialist
Critical Care fellow, University of Rochester Medical Center
Rochester, NY

Edited by:
Carlos M. Isada, MD, FCCP
Department of Infectious Diseases, Cleveland Clinic
Cleveland OH

Critical Care NetWork Puzzler - May 2010

ACCP — Fri, 14 May 2010 16:07:30 +0000

Teaser:

A 59 year-old man developed severe abdominal pain radiating to the back immediately following elective colonoscopy.

A 59 year-old man developed severe abdominal pain radiating to the back immediately following elective colonoscopy. No bleeding was noted endoscopically. An upright abdominal radiograph shows no free air under the diaphragm, but his abdomen becomes progressively distended and rigid. Shock ensues, which is refractory to crystalloid resuscitation. Hemoglobin level is 6.2 gm/dL.

What is the diagnosis?

See the Answer

Splenic rupture

Case report:
A 59 year-old man came to your office for an elective colonoscopy. Past medical history is significant for end-stage renal disease on hemodialysis, coronary artery disease, diabetes mellitus, and multiple polypectomies during previous uncomplicated colonoscopies. He received meperidine and midazolam for the procedure, during which four polyps were removed using routine techniques. No bleeding was noted endoscopically. The patient remained stable throughout the procedure; however, in the recovery area, he noted significant epigastric abdominal pain with radiation to the back. He developed profound hypotension with cool extremities. Initial abdominal exam was soft with diffuse tenderness to palpation and hypoactive bowel sounds; no peritoneal signs were present. He was urgently transferred to the ICU for stabilization, volume resuscitation, and ultimately, vasopressors. Initial postprocedural laboratory findings showed a hemoglobin level of 6.2 gm/dL, down from preprocedure value of 11 gm/dL. Serial abdominal exams showed increasing distention and rigidity with development of peritoneal signs. CT scan of the abdomen demonstrated a tear in the splenic capsule with extensive intraperitoneal blood (Fig 1).

Figure 1. CT scan of the abdomen.

The patient was urgently taken to the operating room for exploratory laparotomy. Continued splenic bleeding was noted, and a splenectomy was performed. The postoperative course was uncomplicated, and the patient was discharged to home on postoperative day seven.

Discussion:
Splenic rupture is a rare complication of colonoscopy¹; however, it must be considered in the differential diagnosis of a patient presenting with severe abdominal pain and shock following the procedure. The mechanism by which splenic rupture occurs is not yet fully understood, but partial splenic capsular avulsion is most commonly seen.² Increased risk for splenic injury can be derived from both procedural and patient-related factors. Procedural risk factors include excessive traction on the splenocolic ligament, the supine position, and polypectomy.³ Interestingly, many splenic injuries have occurred in reportedly “easy” colonoscopies.² Patient-related risk factors revolve around anything that increases splenocolic adhesions. These include previous abdominal surgeries, repeated colonoscopies, splenomegaly, inflammatory bowel disease, and pancreatitis.^2,4 Frequently, chest and abdominal radiographs are normal; thus, CT scan is the imaging modality of choice for both the diagnosis and extent of splenic injury.² Once the diagnosis of splenic rupture is made, conservative treatment vs surgical intervention should be determined by standard surgical algorithms based on the grade of injury.¹ Although rare, splenic rupture can be deadly and should be considered early in patients who present with abdominal pain following colonoscopy.

References

Luebke T, Baldus SE, Holscher AH, Monig SP. Splenic rupture: an unusual complication of colonoscopy. Surg Laparosc Endosc Percutan Tech. 2006;16:351-354.
Espinal EA, Hoak T, Porter JA, Slezak FA. Splenic rupture from colonoscopy: a report of two cases and review of the literature. Surg Endosc. 1997;11:71-73.
Tse CC, Chung KM, Hwang JS. Splenic injury following colonoscopy. Hong Kong Med J. 1999;5:202-203.
Al Alawi I, Gourlay R. Rare complication of colonoscopy. ANZ J Surg. 2004;74:605-606.

Puzzler and case report submitted by:

Laurie A. Hohberger, MD
Resident, Department of Internal Medicine
University of Kansas School of Medicine

Trenton D. Nauser, MD, FCCP
Assistant Professor of Medicine
Division of Pulmonary and Critical Care Medicine
University of Kansas School of Medicine

Chest Infections NetWork Puzzler

ACCP — Fri, 30 Apr 2010 05:00:00 +0000

Teaser:

An 18-year-old healthy man presented to the ED with several days of sore throat and fever.

An 18-year-old healthy man presented to the ED with several days of sore throat and fever. He was diagnosed with “strep throat” and initially responded to oral azithromycin, but 1 week later, he developed shortness of breath and came to the ED. Examination showed mild pharyngeal erythema; fullness and tenderness along the sternocleidomastoid, with multiple tender cervical lymph nodes; and decreased breath sounds in the left base. The patient’s chest radiograph showed a left basilar infiltrate, and he was started on IV antibiotics. Laboratory study results were unremarkable, except for a WBC count of 14.4 x 10⁹/L.

The patient had persistent fevers, tachycardia, hypoxia, and neck pain. The result of a chest CT scan was negative for pulmonary emboli in the proximal branches but showed the following:

A CT scan of the neck was ordered. Blood culture results were positive for a gram-negative bacillus.

Questions

What is the most likely diagnosis?
What is the identity of the gram-negative bacillus?

See the Answer

Blood culture results were positive for Fusobacterium necrophorum, an anaerobe.

This patient had Lemierre syndrome, a suppurative infection associated with jugular vein thrombophlebitis, septic emboli to the lung, metastatic abscess formation, and bacteremia with F necrophorum. This typically occurs in young, otherwise healthy adults. It is a rare but well-described complication of tonsillitis, pharyngitis, odontogenic infections, and mastoiditis.

The syndrome was described in the early 1900s by Andre Lemierre and other reseachers. In a historic article in Lancet, Lemierre described 20 patients with pharyngitis followed by anaerobic septicemia, 18 of whom died. Numerous cases have been described since then. The organism, F necrophorum, is part of the normal flora in the oral cavity, female genital tract, and some areas of the GI tract. The organism has a number of potential virulence factors, including lipopolysaccharide. Other pathogens have been associated with Lemierre syndrome, including Eikenella corrodens (a member of the HACEK group), Streptococcus pyogenes, and Arcanobacterium haemolyticum.

Histologically, there is suppurative inflammation within the wall of the vein, with thrombus and pus in the lumen. Often, there is extension to the lateral pharyngeal space and can be life threatening with involvement of the carotid sheath.

As with this patient, Lemierre syndrome usually presents initially with an exudative pharyngitis. Symptoms may improve as the infection progresses, but edema and/or pain develops in the neck. At this point, there is the acute onset of fevers, shaking chills, and pain along the sternocleidomastoid or angle of the jaw. Septic emboli occur in the majority of patients. Other complications include septic arthritis, osteomyelitis, disseminated intravascular coagulopathy, and liver abscesses. In some patients, the presentation mimics right-sided endocarditis.

A number of life-threatening complications can be seen. Cavernous sinus thrombosis can result from retrograde extension of the suppurative process. Mediastinitis can occur as a result of direct extension along the vessels, with or without airway obstruction. Carotid artery rupture has been described, with sentinel bleeding from the ear, nose, or mouth.

Diagnosis rests on both a compatible clinical presentation and imaging. CT scans of the neck typically show soft tissue edema, inflammation, and filling defects in the vein, as with our patient.

Antibiotics should be targeted against anaerobes. A number of different empiric regimens have been proposed including ampicillin-sulbactam, imipenem, ceftriaxone plus clindamycin, and others. In this case, the patient was treated with penicillin G, 24 million units per day, because the isolate was β-lactamase-negative. In the literature, treatments have varied from 2 to 14 weeks. Patients should be followed carefully, given the wide range of complications. In some instances, ligation or excision of the infected jugular vein may be necessary if sepsis is uncontrolled.

The role of anticoagulation therapy is controversial, and there are no randomized controlled trials for an evidence-based decision. In this case, the patient was given anticoagulation therapy with IV heparin, and he did well on coumadin and IV penicillin.

Submitted by:
Kennon Miller, MD
Resident, Internal Medicine Residency Training Program
Cleveland Clinic
Cleveland, OH

Alan Taege, MD
Staff, Department of Infectious Diseases
Cleveland Clinic
Cleveland, OH

Edited by:
Carlos M. Isada, MD, FCCP
Department of Infectious Diseases
Cleveland Clinic
Cleveland, OH

Occupational and Environmental Health NetWork Puzzler

ACCP — Tue, 30 Mar 2010 05:00:00 +0000

Teaser:

A 70-year-old woman complained of urinary incontinence precipitated by coughing and sneezing. Her only other active medical problems were hypertension and osteoarthritis. She exercised regularly, typically cycling 16 miles daily.

Clinical presentation
A 70-year-old woman complained of urinary incontinence precipitated by coughing and sneezing. Her only other active medical problems were hypertension and osteoarthritis. She exercised regularly, typically cycling 16 miles daily.

Medical history: unremarkable

Surgical history: bilateral hip replacement

Social history
Tobacco history: 20 pack-years; quit 20 years ago
Occupational history: Retired office clerk. No history of occupational exposure to vapors, gases, dusts, fibers, or fumes.

Family history
Her father died of cancer of unknown primary site. Her mother died of chronic kidney disease. Two brothers and one sister are alive and well. Her four children are alive and well. The patient’s father worked in a dusty environment.

Current medications: hydrochlorothiazide, 25 mg daily, and lisinopril, 10 mg daily

Physical examination: normal

Allergies: none

Laboratory data
Urinalysis: microscopic hematuria
Urine cytology: negative result
IV pyelogram: normal result
Renal ultrasound: normal result
Cystoscopy: normal result

Images
An abdominal CT scan was obtained and is shown in Figure 1.

Figure 1. Abdominal CT scan showing a lower cut of the thorax.

Which of the following is seen in Figure 1?

Pleural effusion, visceral and parietal pleural plaque-like density and enhancement
Pleural effusion, osteolytic vertebral lesion
Pleural effusion, para-aortic lymphadenopathy
Pleural effusion, diffuse hepatic and splenic lesions

Correct answer: A. Pleural effusion, visceral and parietal pleural plaque-like density and enhancement

This CT axial section at the level of the lower thoracic cavity shows a left-sided pleural effusion that layers freely, pleural enhancement, and pleural-based plaque-like densities. The vertebra, liver, spleen, and lymph nodes are normal.

A CT of the thorax was obtained and is shown in Figure 2.

Figure 2. Chest CT image showing freely layering left-side pleural effusion.

Which is the most appropriate next test?

Pulmonary function tests (PFTs)
Sputum cytologic studies
Bronchoscopy
Thoracentesis
Follow-up CT scan in 3 months

Correct answer: D. Thoracentesis

The pleural fluid should be tapped in an attempt to establish a diagnosis (eg, specific infection or malignancy) or to narrow the differential diagnosis (eg, exudative vs transudative process). In this healthy and fit patient, PFTs are unlikely to be helpful. The CT findings suggest the diagnostic yield of sputum cytology or bronchoscopy would be very low. Watchful waiting with a follow-up imaging study to assess for interval change is reasonable, if the patient declines thoracentesis.

A thoracentesis was performed. Pleural fluid analysis showed a WBC count of 1,900/μL (63% monocytes/histiocytes, 35% lymphocytes, and 2% mesothelial cells) and a RBC count of 83/μL. Pleural fluid glucose level was 86 mg/dL. Pleural fluid total protein level was 42 gm/dL, consistent with an exudative effusion. Pleural fluid cytologic findings showed atypical cells suggestive of, but not diagnostic of, a malignancy.

The patient then underwent video-assisted thoracoscopic surgery, which showed diffuse pleural nodules and plaques. Two pleural biopsies were obtained. Histopathologic findings included stroma with dense collagen bands infiltrated by a homogeneous noncohesive population of plump, round epitheloid cells with pink cytoplasm and round regular nuclei. Upon staining, this population showed a strongly positive result for calretinin and negative result for TTF1, CEA, and CD15. Extensive invasion into the adjacent pulmonary parenchyma was noted.

Although this patient’s slides were unavailable, we have included a pathologic representation of the same disease in the figure below.

What is your diagnosis?

See the Answer

Diagnosis:Malignant epitheloid mesothelioma. The pleura is thickened by collagen and fibrous bands and shows infiltration, including fat infiltration, by loosely organized cords of neoplastic epithelioid cells with moderately pleomorphic nuclei and occasional prominent nucleoli.

Discussion

Malignant mesothelioma is an almost uniformly fatal disease caused by exposure to asbestos fibers. Most exposures are occupational and related to either mining and milling, or work in industries using asbestos (eg, textiles, cement, insulation, shipbuilding, pipe cutting). Unlike bronchogenic cancer related to asbestos exposure, smoking does not increase the risk of developing mesothelioma. Parietal pleura is the most frequently involved anatomic site; however, peritoneal and pericardial mesotheliomas are also seen. Dyspnea, nonpleuritic chest pain, and cough are common symptoms and signs. Patients may also present with insidious constitutional symptoms that include fever, weight loss, or fatigue. On chest radiographs, unilateral pleural thickening and pleural effusion are the most common manifestations of mesothelioma. CT findings include pleural masses, plaques, and effusions. Isolated pleural thickening without an effusion is relatively uncommon, occurring in 10 to 20% of cases; extension into the fissures is frequent, occurring in 40 to 90% of cases. Due to the relative lack of nuclear material (or acellular nature of the tumor), the diagnosis of mesothelioma is difficult. In the setting of a suspicious case for mesothelioma, it is appropriate to perform a video-assisted thoracoscopic surgical biopsy initially.

Well-differentiated cases require histologic evidence of an infiltrative pattern of growth into adjacent normal tissue. Immunohistochemical markers that differentiate malignant mesotheliomas from other thoracic malignancies include calretinin, D2-40, and CK 5/6, although a panel approach to immunohistochemistry (multiple markers for both mesothelioma and adenocarcinoma) is typically required due to the morphologic overlap between mesothelioma and pulmonary adenocarcinoma. Diagnosis is facilitated by review by an expert in thoracic pathology.

Malignant mesothelioma carries a poor prognosis with median survival of 6 to 18 months and a 5-year survival of <5%. Various treatment options include chemotherapy (cisplatin is the most common agent and is more effective when combined with pemetrexed), radiation therapy, intrapleural chemotherapy, intrapleural immunotherapy (with interferon-γ or interleukin-2) or surgery (pleurectomy or extrapleural pneumonectomy). Factors that favor longer survival include absence of 5% weight loss at the time of diagnosis, tumor extension limited to the ipsilateral parietal pleura, epitheloid cell type, good performance status, young age and platelet count <400,000/μL.

Our patient had revealed that her father worked with asbestos and brought dust-laden clothes home all through her childhood and adolescence. It is unclear whether the patient developed mesothelioma after asbestos exposure from her father’s clothes, from living near an asbestos plant, from exposure to naturally occurring asbestos, or de novo. However, given the explicit history from the patient, we are suspicious that the cause of mesothelioma was dust brought home on her father’s clothes.

A study of an Australian cohort of 2,552 women and girls who live in Wittenoon (an asbestos-mining township) found 30 mesothelioma deaths in these women who had domestic exposure (bystander) but no occupational exposure to asbestos. There was a nonsignificant increase in the risk of death from mesothelioma for women known to have lived with, or washed the clothes of, an asbestos worker (HR = 2.67, 95% CI, 0.77 to 9.21; HR = 2.61, 95% CI, 0.85 to 7.99, respectively). The Wittenoon study certainly suggests that there is a risk of malignant mesothelioma in the family members of asbestos workers.

One must remember that family members of asbestos workers are not only exposed to dust from worker’s clothes, but also are exposed to airborne asbestos, whether that asbestos is aerosolized from mining/milling or industrial processing. Further illustrating the increased risk of mesothelioma in those with occupational exposure to asbestos or in those living with asbestos workers or near an asbestos facility, Maule and colleagues studied four populations in the Casale Monferrato region of Italy, home to an asbestos cement factory. In addition to workers in the plant, Maule and colleagues studied those who used asbestos products in their homes (domestic exposure) and those who had relatives working in the plant. Additionally, they studied mesothelioma risk as a function of distance of residence (lagged 20 years) from the plant. The research found that, as expected, workers in the asbestos cement factory had an odds ratio of 7.1 (95% CI, 3.5-14.3) for development of mesothelioma, while those with domestic use of asbestos cement (eg, ceiling insulation) had an odds ratio of 1.7 (95% CI, 1.1-2.7). Those, such as the patient in this puzzler, who had a relative working in the asbestos cement factory, had a significant increase in risk of developing mesothelioma, with an odds ratio of 3.4 (CI, 1.8-6.5).

Maule and colleagues also found that there was an increased risk of mesothelioma as a function of distance of residence from the plant. Thus, even at a distance of 10 km from the plant, the odds ratio for development of mesothelioma was 4.2. When they corrected the mesothelioma risk in those with relatives working in the asbestos cement factory for distance of residence from the plant, the corrected odds ratio fell to 1.4 (95% CI, 0.7-2.9). The researchers concluded that domestic use of asbestos and having a relative work in the asbestos factory were comparatively less important risk factors than distance of residence from the factory. Interested readers are referred to the seminal work of Maule and his coworkers.

The vast majority of cases of mesothelioma are related to direct occupational exposures, and a smaller number appear, as with the patient in this puzzler, to be related to living with an asbestos worker or in proximity to an asbestos mill, mine or factory. However, one must remember that asbestos is a naturally occurring mineral, and that mesothelioma following environmental exposure to asbestos has been described in many locations, including Turkey, New Caledonia and California. Thus, while most cases of mesothelioma are related to direct or indirect industrial or mining exposures, there is a small background rate of naturally occurring mesothelioma.

Final diagnosis: Bystander asbestos exposure and malignant pleural mesothelioma

Recommended Reading

Gaissert HA, Piyavisetpat N, Mark EJ. Case records of the Massachusetts General Hospital: Case 14-2009—a 36-year-old man with chest pain, dysphagia, and pleural and mediastinal calcifications. N Engl J Med. 2009;360(18):1886-1895.

Robinson BW, Lake RA. Advances in malignant mesothelioma. N Engl J Med. 2005;353(15):1591-1603.

Yarborough CM. The risk of mesothelioma from exposure to chrysotile asbestos. Curr Opin Pulm Med. 2007;13(4):334-338.

Reid A, Heyworth J, de Klerk N, Musk AW. The mortality of women exposed environmentally and domestically to blue asbestos at Wittenoom, Western Australia. Occup Environ Med. 2008;65(11):743-749.

Reid A, Berry G, Heyworth J, de Klerk NH, Musk AW. Predicted mortality from malignant mesothelioma among women exposed to blue asbestos at Wittenoom, Western Australia. Occup Environ Med. 2009;66(3):169-174.

Rake C, Gilham C, Hatch J, Darnton A, Hodgson J, Peto J. Occupational, domestic and environmental mesothelioma risks in the British population: a case-control study. Br J Cancer. 2009;100(7):1175-1183.

Banks DE, Shi R, McLarty J, et al. American College of Chest Physicians consensus statement on the respiratory health effects of asbestos: results of a Delphi study. Chest. 2009;135(6):1619-1627.

Ferrante D, Bertolotti M, Todesco A, Mirabelli D, Terracini B, Magnani C. Cancer mortality and incidence of mesothelioma in a cohort of wives of asbestos workers in Casale Monferrato, Italy. Environ Health Perspect. 2007;115(1):1401-1405.

Bourdès V, Boffetta P, Pisani P. Environmental exposure to asbestos and risk of pleural mesothelioma: review and meta-analysis. Eur J Epidemiol. 2000;16(5):411-417.

Goldberg M, Luce D. The health impact of nonoccupational exposure to asbestos: what do we know [published online ahead of print July 16, 2009]? Eur J Cancer Prev. 2009.

Maule MM, Magnani C, Dalmasso P, Mirabelli D, Merletti F, Biggeri A. Modeling mesothelioma risk associated with environmental asbestos exposure. Environ Health Perspect. 2007;115(7):1066-1071.

Goldberg M, Luce D. Can exposure to very low levels of asbestos induce pleural mesothelioma? Am J Respir Crit Care Med. 2005;172(8):939-940.

Submitted by:
Harman S. Paintal, MBBS
US Department of Veterans Affairs
Palo Alto Health Care System Medical Service
Pulmonary Section
Stanford University School of Medicine

Richard Evans, MD, MPH, FCCP
University of Rochester School of Medicine and Dentistry

Kristin Jensen, MD
US Department of Veterans Affairs
Palo Alto Health Care System Pathology Service
Stanford University School of Medicine

John Drace, MD
US Department of Veterans Affairss
Palo Alto Health Care System Radiology Service
Stanford University School of Medicine

Ware G. Kuschner, MD, FCCP
Palo Alto Health Care System Medical Service
Pulmonary Section
Stanford University School of Medicine

Cardiovascular Medicine and Surgery NetWork Puzzler - March 2010

ACCP — Wed, 10 Mar 2010 06:00:00 +0000

Teaser:

A 68–year–old man previously diagnosed with a "heart-murmur," but otherwise considered healthy, was transferred to our hospital with a 3–day history of fever, back pain and confusion.

A 68-year-old man previously diagnosed with a "heart-murmur" but otherwise considered healthy was transferred to our hospital with a 3-day history of fever, back pain and confusion. His vital signs at arrival were the following: temperature = 102°F, blood pressure = 85/40 mm Hg, heart rate = 115/min, and oxygen saturation = 97% with room air. Figure 1 shows his chest radiograph at presentation. He was lethargic, confused, and could follow simple commands only. He demonstrated new onset of weakness in the bilateral lower extremities. His heart sound was regular with a systolic murmur. Laboratory values were within normal limits except for an elevated WBC count (20,000/µL, with left shift).

Figure 1. Chest radiograph of the patient at presentation.

What is the next step?
When should the patient undergo surgery?
What are the indications for surgery?

The patient was septic at the time of transfer. IV fluid was given. Blood culture results were sent before broad-spectrum antibiotics were started. His mental status was improved with these initial treatments. The patient underwent MRI of the brain and spine to rule out stoke. MRI showed recent stroke in the left parietal lobe (Fig 2).

Figure 2. MRI of the brain shows a small infarct.

A lower spine MRI demonstrated L3-L5 epidural abscess, which was confirmed by CT scan (Fig 3).

Figure 3. CT of the lower spine shows epidural abscess.

The patient’s blood culture grew methicillin-senstive Staphylococcus aureus (MSSA). Echocardiography showed normal ventricular function with severe mitral valve regurgitation. There was a mobile mass with a diameter of 20 mm on the posterior leaflet of the mitral valve (see videos below).

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Echocardiography shows vegetation on the posterior leaflet of the mitral valve.

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Echocardiography shows severe mitral valve regurgitation.

What is your diagnosis?

See the Answer

MSSA endocarditis, epidural abscess

Hospital course

Neurology concluded that the weakness in the patient’s feet was caused by epidural abscess compressing the spinal cord. He underwent emergent L3, L4, and L5 laminectomy and decompression of the epidural abscess. Purulent drainage was obtained and a culture of the drainage specimen grew MSSA. The thecal sac was intact and was irrigated with antibiotics solution. After laminectomy, the patient’s leg weakness was improved; however, he remained febrile and his blood culture persistently grew MSSA. Five days after laminectomy, he was taken to the OR for mitral valve surgery. Inspecting the mitral valve, there was a large vegitation on the posterior leaflet of the mitral valve, which was perforated in multiple areas. Gram stain of the vegetation was positive for gram-positive cocci, which was later found to be MSSA. The mitral valve was replaced with a tissue valve. His postoperative course was uneventful, and he was discharged to home on postoperative day 8 with 6 weeks of antibiotics treatment.

Discussion

Stabilization of the septic shock is the initial treatment of endocarditis. Investigation of the primary source of sepsis is important. Echocardiography is the most valuable diagnostic modality to diagnose endocarditis. Medical treatment with antibiotics is the first-line treatment for endocarditis. The infectious source should be controlled before cardiac surgery for endocarditis. The most important indications for surgery of endocarditis are uncontrolled heart failure due to valvular destruction (class I recommendation), perivalvular abscess or fistula formation (class I recommendation), persistent septicemia despite appropriate antibiotics treatment (class IIa recommendation), and recurrent embolic episodes (class IIa recommendation). Mobile and/or large size vegetation is another indication for surgery; however, it is a class IIb recommendation.¹

The presented case demonstrated a rare combination of epidural abscess and endocarditis. A patient with bilateral weakness of the feet, back pain, and fever should be investigated with MRI or CT scan to rule out epidural abscess.² Since spontaneous epidural abscess is rare, investigation of the primary source of infection such as endocarditis is necessary.

References

Bonow RO, Carabello BA, Chatterjee K, et al. 2008 focused update incorporated into the ACC/AHA 2006 guidelines for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to revise the 1998 guidelines for the management of patients with valvular heart disease). Endorsed by the Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons. J Am Coll Cardiol. 2008;52(13):e1-e142.
Cone LA, Hirschberg J, Lopez C, et al. Infective endocarditis associated with spondylodiscitis and frequent secondary epidural abcess. Surg Neurol. 2008;69(2):121-125.

Puzzler and case report submitted by:
Hitoshi Hirose, MD, FCCP
Division of Cardiothoracic Surgery, Department of Surgery
Thomas Jefferson University Hospital
E-mail: genex@nifty.com

Chest Infections NetWork Puzzler - February 28, 2010

ACCP — Sun, 28 Feb 2010 06:00:00 +0000

Teaser:

A 55-year-old man presented with fevers, cough, and confusion. He has a history of an idiopathic dilated cardiomyopathy and had a cardiac transplant 3 years ago (cytomegalovirus status is donor-negative, recipient-positive).

He developed a nonproductive cough in mid-July, which worsened over 1 week. He also complained of mild headaches and loose stools. After 1 week of coughing, he became increasingly confused, and had altered speech over the past 24 hours. His wife found him difficult to arouse and called emergency medical services.

He lives in a suburban area with his wife and adult daughter. He has not traveled internationally, has no history of TB, and has not been in contact with anyone who is sick. He is a disabled truck driver.

He had been on stable immunosuppressive therapy, including tacrolimus, 2 mg po twice daily; mycophenalate, 500 mg po qd; prednisone 12.5 mg po qd; and acyclovir orally. He was taken off sulfamethoxazole and trimethoprim.

On admission, temperature = 100.3°F, pulse = 68/min, and blood pressure = 98/56 (baseline). So₂ was 87% on room air. He was disoriented, with a depressed level of consciousness. Results were negative for the head and neck exam, with no nuchal rigidity. His lungs had extensive crackles in the right upper field and throughout the left lung. His cardiac examination was unremarkable, and his neurologic examination was limited but seemed to be nonfocal. The patient would frequently wave his hands in the air.

The following laboratories were remarkable: WBC = 2.8 x 10⁹/L(baseline 7 x 10⁹ /L- 10 x 10⁹/L), Hemoglobin = 11 g/dL. Comprehsive metabolic panel showed alanine Aminotransferase = 110 U/L; otherwise normal results.

Figure 1. Chest radiograph.

The patient was started on IV vancomycin, ceftriaxone, azithromycin, and acyclovir. Lumbar puncture showed 22 WBC/mm³(23% neutrophils, 70% lymphocytes) and 3 RBC/mm³. Cerebrospinal fluid (CSF) glucose was within normal limits and CSF protein level was elevated at 74 mg/dL. Gram stain of CSF showed no organisms, and the cryptococcal antigen screen was negative. The CSF was sent for numerous molecular tests, including herpes simplex virus and cytomegalovirus polymerase chain reaction (PCR) assays.

Results of the MRI and magnetic resonance angiogram scan of the brain with contrast were normal. Bronchoscopy showed inflamed airways and moderate secretions. Gram stain showed no organisms and many polymorphonuclear cells. Results of routine cultures were negative.

The patient improved when receiving broad spectrum antibiotics. Results of bronchoalveolar lavage (BAL) fluid stains and cultures were negative for the following: pneumocystis stain, Nocardia stain and culture, Legionella direct fluorescent antibody test, respiratory viral panel, and acid-fast bacilli, fungi, herpes simplex virus, and cytomegalovirus tests.

Results of CSF molecular studies were later negative, including PCR assay for herpes simplex virus.

The patient had a slow recovery but eventually was discharged to home receiving antibiotics. A certain diagnosis was suspected, which was later confirmed.

See the Answer

Encephalitis, secondary to Legionella infection

Discussion

Cultures from the BAL fluid were later positive for Legionella micdadei. The patient was diagnosed with encephalitis secondary to legionella infection and continued receiving macrolide therapy.

This case illustrates the differential diagnosis of pneumonia with encephalitis. The patient’s clinical presentation was remarkable for a frank encephalitis with only mild inflammation in the CSF and normal brain imaging results. Recent guidelines issued by the Infectious Diseases Society of America outline the approach to patients with encephalitis, including those with accompanying respiratory symptoms. Diagnostic considerations include mycoplasma infection (although this is somewhat controversial), histoplasmosis, Q fever, influenza, and TB. In addition, Legionnaires disease has been described with prominent CNS involvement, and this was the tentative diagnosis in the case. This is an unusual complication of Legionnaires disease, but a variety of CNS manifestations have been described, including brain stem lesions, reversible corpus callosum lesions, cerebellar dysfunction, and global encephalitis.

In the immunocompromised host, the differential diagnosis of pulmonary infiltrates with encephalitis includes all of the above-mentioned infections, along with Cryptococcus neoformans, which can cause both meningitis and/or encephalitis, cytomegalovirus, Nocardia sp, and others. It should be noted that the differential diagnosis in our case is one of pulmonary infiltrates with encehalitis rather than meningitis, which has a somewhat different set of diagnostic considerations.

In our case, encephalitis from Legionella was strongly suspected despite the initial negative result for the Legionella pneumophila direct fluorescent antibody test and urinary antigen test. Most commercially available rapid systems detect L pneumophila but not other Legionella species from both respiratory specimens and urinary specimens. The L micdadei was only detected after extended incubation on enriched agar.

L micdadei is the second most common cause of Legionnaires disease. It is a pathogen that generally infects immunocompromised hosts but can cause a respiratory syndrome indistinguishable from L pneumophila in healthy hosts. Our patient made a full recovery with treatment with a macrolide.

About 1 year later, the patient relapsed with a second episode of L micdadei pneumonia and severe encephalitis, in an almost identical presentation.

Critical Care NetWork Puzzler - January 2010

ACCP — Sat, 30 Jan 2010 06:00:00 +0000

Teaser:

A 64-year-old man is transferred to the ICU for acute onset of confusion, septic shock, acute renal failure and disseminated intravascular coagulation.

A 64-year-old man is transferred to the ICU for acute onset of confusion, septic shock, acute renal failure and disseminated intravascular coagulation. He was admitted to the general medical ward 4 h prior with a soft tissue infection of the hand, noted after removing a large splinter from the area 2 days prior. Immediate surgical exploration and debridement of the deep soft tissue infection demonstrated gram-positive cocci in chains. He was placed on both clindamycin and penicillin G.

What additional therapy should be considered?

See the Answer

IV immune globulin

Case report: A 64-year-old man presents to the ED with 2 days of increasing right hand pain, fever, chills, nausea, and vomiting. While woodworking 2 days prior, he removed a large splinter from his right hand with pliers. Past medical history is significant for alcoholism.

On physical examination, temperature is 39.1°C, pulse rate is 108/min, respiratory rate is 18/min and blood pressure is 136/66 mm Hg. Neurologic, cardiopulmonary, and abdominal examinations are not revealing. The palmar aspect of the right hand is tender. Local edema, erythema, ecchymoses, and sloughing of the skin are noted.

Laboratory examination demonstrates WBC count of 22,500/μL, with 98% polymorphonuclear leukocytes, a hemoglobin of 12.6 g/dL, and a platelet count of 340,000/μL. Blood urea nitrogen, serum creatinine, and serum electrolyte levels are normal. Serum glucose level is 210 mg/dL.

Urgent surgical exploration and debridement of the wound reveals no foreign body. Gram stain of the deep tissue shows gram-positive cocci in chains. The patient is placed on both clindamycin and penicillin G and admitted to the general medical ward. Four hours after hospitalization, he develops confusion and hypotension (systolic blood pressure of 60 mm Hg). He is transferred to the ICU where IV fluid resuscitation and vasopressors are instituted. Laboratory studies now indicate acute renal failure and disseminated intravascular coagulation. Over the next 24 h, the patient develops ARDS, requiring low tidal volume mechanical ventilation support.

Discussion: The patient has streptococcal toxic shock syndrome.¹ Virtually all patients become hypotensive within 4 to 8 h of presentation, but roughly half have a normal blood pressure on initial evaluation. The vast majority has findings consistent with a soft tissue infection, such as edema, and erythema, followed by bruising and sloughing of skin. Necrotizing fasciitis and myositis indicate advanced infection. Diagnosis of streptococcal toxic shock syndrome requires isolation of group A streptococcus from a normally sterile area and hypotension, plus two or more of the following: renal impairment, coagulopathy, liver injury, ARDS, erythematous macular rash, and soft tissue infection.

Early surgical exploration and debridement of deep soft tissue group A streptococcus infection is mandatory. Clindamycin is a cornerstone of treatment. Compared with lactam antibiotics, clindamycin reduces mortality, presumably due to suppression of bacterial toxin production in addition to its antibacterial properties. Penicillin G is necessary in case of clindamycin resistance, which is rare in the United States.

Although controversial, the use of IV immune globulin in streptococcal toxic shock syndrome is supported by case reports and retrospective series. A double blind, randomized controlled trial² comparing IV immune globulin with placebo in 21 patients demonstrated a mortality rate of 10% (1 in 10) in the intervention group compared with 36% (4 of 11) in the placebo group. Although statistical significance was not reached in this study in which all patients received clindamycin and penicillin, this could be accounted for by the small sample size.

References

1. The Working Group on Severe Streptococcal Infections. Defining the group A streptococcal toxic shock syndrome: rationale and consensus definition. JAMA. 1993;269(3):390-391.
2. Darenberg J, Ihendyane N, Sjolin J, et al. Intravenous immunoglobulin G therapy in streptococcal toxic shock syndrome: a European randomized, double-blind, placebo-controlled trial. Clin Infect Dis. 2003;37(3):333-340.

Puzzler and case report submitted by:
Trenton D. Nauser, MD, FCCP
Assistant Professor of Medicine
Kansas City Department of Veterans Affairs Medical Center
University of Kansas School of Medicine

A Man With A History of Vasculitis and Wheezing

ACCP — Fri, 01 Jan 2010 06:00:00 +0000

Teaser:

A 27-year-old man was diagnosed with Wegener granulomatosis (WG) and treated with corticosteroids and cytotoxic agents.

A 27-year-old man was diagnosed with Wegener granulomatosis (WG) and treated with corticosteroids and cytotoxic agents. Remission was induced, and all medications were eventually discontinued. The patient returned for his semiannual follow-up visit 1 year later, complaining of wheezing and shortness of breath. Physical examination and radiograph did not reveal recurrence of the disease, but wheezing was heard over the chest and neck. A flow volume loop maneuver was performed:

See the Answer

The flow volume loop shows flattening of the inspiratory and expiratory loops, consistent with fixed airway obstruction. This complication occurs in up to 25% of patients with WG, most often in the subglottic area and usually independent of other manifestations of this disease. Subglottic obstruction was confirmed by bronchoscopy, and the patient underwent successful laser surgery with relief of symptoms. Prompt recognition of this complication of WG by a simple flow-volume loop leads to rapid treatment and alleviates the need for unnecessary work up.

Submitted by:
Subani Chandra, MD and Rubin Cohen, MD,
Airways Disorders Steering Committee Member

Thoracic Oncology NetWork Online Puzzler

ACCP — Fri, 21 Aug 2009 15:32:33 +0000

Teaser:

A 38-year-old man with a history of urethral and esophageal strictures, as well as smokeless tobacco use, was referred to the pulmonary clinic for a suspicious nodule in the right upper lobe seen on a CT scan. He had a history of oral squamous cell carcinoma stage III (T1N1M0) treated with wide local excision and bilateral neck dissection. Surgery was followed by one cycle of a planned three cycles of cisplatin complicated by severe pancytopenia requiring hospitalization. The patient subsequently received adjuvant radiation therapy to the neck. A follow-up CT scan demonstrated a suspicious nodule in the right upper lobe for which he was referred to a pulmonary medicine specialist. On exam, he has stable vital signs, including pulse oximetry. He has well-healed incisions on his neck and skin changes consistent with radiation therapy. His cardiac and lung examination results are normal. The only other noteworthy finding is that he has significant dystrophic fingernails. He states that he has had them all of his life.

Online Puzzler

Current Puzzler

Thoracic Oncology NetWork Online Puzzler - August 2009

ACCP — Mon, 17 Aug 2009 15:32:33 +0000

Teaser:

A 64-year-old woman comes to see you for a second opinion regarding a lung nodule. In 2002, she participated in a lung cancer screening study, which showed a 2.1 cm ground glass lung opacity in the right upper lobe. This was followed conservatively with serial CT scans performed every 6 months. The patient read in a magazine that radiation exposure from CT scans may cause cancer, and she is worried that having too many such studies performed may adversely affect her health. She is seeing you for a second opinion. She has no dyspnea. She began smoking one pack of cigarettes daily in college, but quit more than 30 years ago.

Online Puzzler

Current Puzzler
A 64-year-old woman comes to see you for a second opinion regarding a lung nodule. In 2002, she participated in a lung cancer screening study, which showed a 2.1 cm ground glass lung opacity in the right upper lobe. This was followed conservatively with serial CT scans performed every 6 months. The patient read in a magazine that radiation exposure from CT scans may cause cancer, and she is worried that having too many such studies performed may adversely affect her health. She is seeing you for a second opinion. She has no dyspnea. She began smoking one pack of cigarettes daily in college, but quit more than 30 years ago.

Figure 1. CT scan from 2002. There is a 2.1 cm ground-glass opacity in the right upper lobe, surrounding a more solid core.

Figure 2. CT scan from 2009.

Cumulatively, the CT scans show a ground-glass opacity in the right upper lobe, surrounding a central solid core. Over the intervening 7 years, the ground-glass opacity has expanded slightly. All CT scan reports are available to you, which state the opacity is stable.

While gently reassuring the patient that an opacity that has been so stable over 7 years could not possibly be harmful, you also pursue percutaneous core biopsy for the subtle change. Pathologic results showed well-differentiated neoplastic-appearing cells, spreading along the alveolar walls, without invasion into the underlying stroma.

See the Answer

Diagnoses and Discussion

Diagnosis: Bronchioalveolar carcinoma

Bronchioalveolar carcinoma (BAC) is a subtype of adenocarcinoma, first reported by Malassez¹ in a 63-year-old woman whose multiple lung nodules had "l'aspect du fromage de Roquefort" (the appearance of Roquefort cheese). He also described the classic histology of neoplastic cells growing along the alveolar walls without invasion, preserving the general alveolar architecture. In 1960, BAC was further characterized by Liebow² by its well-differentiated cytology and its propensity for multicentric development. Reports of the incidence of BAC vary between 5 to 25% of all lung cancers, depending on disparities in the application of strict pathologic criteria. The 2004 World Health Organization (WHO) criteria restrict the definition of BAC to those tumors without any evidence of stromal, pleural, or lymphatic invasion. BAC differs from such benign alveolar proliferative conditions as atypical adenomatous hyperplasia by the fact that the latter usually includes multiple cell lines (ie, both ciliated and cuboidal epithelium).

Patients with BAC may present differently than those with other histologic subtypes of lung cancer. A review³ of more than 300,000 lung cancer patients identified from the Surveillance, Epidemiology and End Results (SEER) database found that patients with BAC were more likely to have local disease and better 1-year survival (65% vs 39% for non-BAC adenocarcinoma) than those with other lung cancers. Likewise, radiographic abnormalities may be clinically silent and exist for extended periods of time before diagnosis. In one review⁴ of 105 surgically treated patients with BAC, 12% had had a stable solitary nodule for 2 to 7 years before diagnosis. Therefore, the 7-year period through which the CT scan remained relatively stable in this index patient’s case, although lengthy, is not unusual.

Among patients with ground-glass opacities on chest CT scans, an extended period of observation may be required to distinguish benignity from malignancy.

References:

Malassez L. Examen histologique d'un cas de cancer encephaloide du poumon (epithelioma). Arch Physiol Norm Pathol 1876; 3:353-372
Liebow AA. Bronchiolo-alveolar carcinoma. Adv Intern Med 1960; 10:329-358
Read WL, Page NC, Tierney RM, et al. The epidemiology of bronchioloalveolar carcinoma over the past two decades: analysis of the SEER database. Lung Cancer 2004; 45:137-142
Dumont P, Gasser B, Rouge C, et al. Bronchoalveolar carcinoma: histopathologic study of evolution in a series of 105 surgically treated patients. Chest 1998; 113:391-395

Puzzler Case Report submitted by:
Marc B. Feinstein, MD, FCCP
Thoracic Oncology NetWork Steering Committee Member

Cardiovascular Medicine and Surgery NetWork Online Puzzler - August 2009

ACCP — Wed, 05 Aug 2009 15:32:33 +0000

Teaser:

A 41-year-old woman at 17 weeks gestation was referred for resting dyspnea. On physical examination, she had a faint diastolic murmur. ECG revealed mitral stenosis with dilated left atrium and a normal ejection fraction. She had two prior documented strokes and is noncompliant with her anticoagulant medication. She is not responding to the current medical management.

Larger View

Online Puzzler

1. What is the next step?
2. Should the pregnancy be terminated?
3. Should she receive life-long anticoagulant therapy?

See the Answer

Invisible left atrial thrombus

The patient was known to have rheumatic mitral stenosis since 1992. Her first two pregnancies were uneventful. Prior to this pregnancy, she was noncompliant with her anticoagulant medication and had two documented strokes.

A transthoracic echocardiogram (TTE) revealed severe mitral stenosis, depressed left ventricular ejection fraction, elevated filling pressures, and severe pulmonary hypertension. No intracardiac thrombus was detected. Due to a high index of suspicion for an intracardiac clot, a plan was made for her to have a transesophageal echocardiogram (TEE).

She underwent a 2D and 3D TEE to assess her mitral valve suitability for transcutaneous balloon valvuloplasty. Severe mitral stenosis with mean gradient of 12 mm Hg and a mitral valve area of 0.6 cm¹ was noted (Fig 1). Also revealed was a large organized left atrial (LA) thrombus extending from the LA appendage to the LA anterolateral and posterior walls, with significant spontaneous echo contrast within the cavity (Fig 2).

Due to unfavorable prognosis of mitral stenosis with the symptom of severe dyspnea, the patient was advised to have the pregnancy terminated and opted to do so. A week after a successful and uncomplicated induction, she underwent surgical mitral valve replacement with a St. Jude mitral prosthesis (size 31 mm), thrombus evacuation, left atrial appendage ligation, and a maze procedure. At surgery, the presence of an LA thrombus in the anterolateral and posterior septal surfaces was confirmed. Her postoperative course was uneventful, and she was discharged receiving coumadin and with an international normalized ratio within therapeutic range.

At the time of open heart surgery, the TEE findings were confirmed. TTE, however, fails to identify LA thrombi in up to 50% of cases.^{1, 2, 3, 4} TEE, in contrast, provides higher resolution images of the LA appendage and body. It is more accurate in identifying, localizing, and quantifying LA thrombi. 3D TEE provides vivid details of complex spatial intracardiac anatomy, as noted in this case (Figs 3-5).

References

Bansal RC, Heywood JT, Applegate PM, et al. Detection of left atrial thrombi by two-dimensional echocardiography and surgical correlation in 148 patients with mitral valve disease. Am J Cardiol 1989; 15; 64:243-246
Okyay K, Cengel A, Tavil Y. Images in cardiology: a giant left atrium with two huge thrombi without embolic complications. Can J Cardiol 2007; 23:1088
Parekh A, Jaladi R, Sharma S, et al. Images in cardiovascular medicine: the case of a disappearing left atrial appendage thrombus--direct visualization of left atrial thrombus migration, captured by echocardiography, in a patient with atrial fibrillation, resulting in a stroke. Circulation 2006; 114:e513-e514
Agoston I, Xie T, Tiller FL, et al. Assessment of left atrial appendage by live three-dimensional echocardiography: early experience and comparison with transesophageal echocardiography. Echocardiography 2006; 23:127-132

Submitted by:
Jun R. Chiong MD, MPH, FCCP
Mirvat Alasnag, MD
Ramesh Bansal, MD

Contact information:
Loma Linda University Medical Center
11234 Anderson Street, Suite 2426
Loma Linda, CA 92354
Tel: (909) 558-9730
Fax: (909) 558-0903
E-mail: jchiong@llu.edu

Interventional Chest/Diagnostic Procedures (IC/DP) NetWork Online Puzzler - August 2009

ACCP — Wed, 05 Aug 2009 15:32:33 +0000

Teaser:

A 42-year-old African-American man with a history of HIV presented with a 3-week history of dry cough, fatigue, muscle weakness, and discoordination. He reported occasional subjective fevers, nocturnal sweats, and weight loss.

Interventional Chest/Diagnostic Procedures (IC/DP) NetWork

Online Puzzler

Clinical presentation:
A 42-year-old African-American man with a history of HIV presented with a 3-week history of dry cough, fatigue, muscle weakness, and discoordination. He reported occasional subjective fevers, nocturnal sweats, and weight loss.

Past medical/surgical history:
HIV: Diagnosed 4 years ago, currently not receiving treatment
Hand surgery

Social history:
26 pack-year history of tobacco use
Recent crack cocaine use, no IV drug abuse
Previous incarceration

Family history:
Noncontributory

Allergies:
No known drug allergies

Physical exam:

Temperature = 97.9°F, HR = 80, BP = 99/56, RR = 12/min, room air Spo₂ = 99%
General: thin man, no distress
CVS: regular rate and rythmn, no gallops
Pulm: dry rales at bilateral upper lung zones, minimal expiratory wheeze
Abdomen: soft, nontender, normoactive bowel sounds
Lymph: no adenopathy
Extremities: no clubbing or cyanosis

Pulmonary function testing:
Moderate obstruction with mildly reduced Dlco

Diagnostic testing:
Chest radiograph and CT scan of the chest (Fig 1, 2)

Figure 1. Patient chest radiograph.

Figure 2. Representative images from CT scan imaging.

Bronchoscopy revealed an intact and normal-appearing oropharynx and vocal cords without significant mucosal abnormalities. The right bronchial tree was normal in appearance without evidence of endobronchial masses or lesions. A bronchoalveolar lavage of the right upper lobe apical subsegment was performed with adequate return. Evaluation of the left bronchial tree revealed a large gray lingular mass (Fig 3) associated with hyperemia but without bleeding. The endoluminal mass was debulked without incident.

Figure 3. Verrucous lingular endobronchial mass.

See the Answer

Puzzler Answer

Diagnosis: Endobronchial aspergilloma^1-3
Nontuberculous mycobacterial (Mycobacterium avium-intracellulare) infection

Clinical course: The patient was admitted with a presumptive diagnosis of TB and initially placed in respiratory isolation. He continued to have significant dry cough and daily fevers. Over the next several days following the bronchoscopy, his symptoms improved. Results of the lavage and biopsy showed Mycobacterium avium complex but no evidence of active TB. The endobronchial mass seen on bronchoscopy was determined to be an endobronchial aspergilloma on histologic evaluation (Fig 4, 5). The patient was subsequently discharged to his home with treatment for Mycobacterium avium complex. The endobronchial aspergilloma was not treated with antifungal therapy, as there was no evidence of invasiveness.

Figure 4. Results of biopsy of the lingular endobronchial mass, revealing hyphal elements of Aspergillus (periodic acid-Schiff, original magnification x 100).

Figure 5. Results of biopsy of the lingular endobronchial mass, revealing hyphal elements of Aspergillus (periodic acid-Schiff, original magnification x 400).

Take-home points:

Endobronchial aspergillomas are a rare but reported cause of endobronchial masses.
An endobronchial aspergilloma may present as a bronchogenic carcinoma.⁴
Although endobronchial aspergillomas are more likely diagnosed in patients who are immunosuppressed, they have been reported in otherwise healthy patients.⁵
Fungal endobronchial disease is likely underrecognized and caused by numerous pathogens.⁶
It may simulate other entities such as endobronchial TB.⁷

References

Agca M, Arinc S, Yilmaz A, et al. A case of endobronchial aspergilloma. Mikrobiyol Bul 2008; 42:157-161
Kim JS, Rhee Y, Kang SM, et al. A case of endobronchial aspergilloma. Yonsei Med J 2000; 41:422-425
Tamaki S, Danbara T, Natori H, et al. A resected case of endobronchial aspergilloma due to Aspergillus restrictus (author’s transl). Nihon Kyobu Shikkan Gakkai Zasshi 1980; 18:464-469
Osinowo O, Softah A-L, Zahrani K, et al. Pulmonary aspergilloma simulating bronchogenic carcinoma. Indian J Chest Dis Allied Sci 2003; 45:59-62
Dar KA, Shah NN, Bhargava R, et al. Endobronchial aspergilloma in a 30-year-old man. J Bronchol 2007; 14:207-209
Karnak D, Avery RK, Gildea TR, et al. Endobronchial fungal disease: an under-recognized entity. Respiration 2007; 74:88-104
Rad MH, Milani M. Primary endobronchial actinomycosis simulating endobronchial tuberculosis in a patient with diabetes mellitus. Tuberk Toraks 2007; 55:186-190

Puzzler submitted by:
Raju Thakor, MD, Interventional Chest/Diagnostic Procedures NetWork Member
Mark E. Lund, MD, FCCP, Vice-Chair, Interventional Chest/Diagnostic Procedures NetWork

Affiliate NetWork Online Puzzler - July 2009

ACCP — Wed, 08 Jul 2009 16:00:27 +0000

Teaser:

Clinical presentation The patient is a 76-year-old African-American man referred for evaluation of shortness of breath and cough. His shortness of breath had progressively worsened over the last 2 months. He also had a history of productive cough with clear sputum for 2 months.

Online Puzzler

Clinical presentation
The patient is a 76-year-old African-American man referred for evaluation of shortness of breath and cough. His shortness of breath had progressively worsened over the last 2 months. He also had a history of productive cough with clear sputum for 2 months.

Review of systems
No hemoptysis. No orthopnea or paroxysmal nocturnal dyspnea. No fever, chills, night sweats, or weight loss. The patient complained of feeling fatigued for several months.

Past medical and surgical history

Myelofibrosis diagnosed with bone marrow biopsy in 2000. The patient was initially treated with hydroxyurea for thrombocytosis, but this was discontinued due to severe anemia.
Prostate cancer diagnosed in 2001 with Gleason 3+4, T2aN0M0 and treated with Zoladex and radiation therapy
Hypertension
Diabetes mellitus

Social history
The patient retired after working in the post office. He quit smoking in 1979 and had a prior 25 pack-year smoking history. He has no history of alcohol or drug abuse. He has no history of exposure to animals and has not traveled recently.

Family history
None contributory

Allergies
None

Current medications

Finasteride
Simvastatin
Glyburide, metformin
Felodipine, losartan, hydrochlorothiazide
Allopurinol
Aspirin

Physical examination
BP = 124/78; heart rate = 71; respiratory rate = 18; temperature = 98.2; oxygen saturation on room air = 90%
HEENT: Sinuses are nontender; anicteric sclera
PULM: Basal crackles on inspiration
CV: Regular, with no audible murmurs, rubs, or gallops. No loud P2
ABD: Splenomegaly 3 cm below left costal margin
EXT: No cyanosis, clubbing, or edema

Labs

WBC count = 6900 μL; hemoglobin = 9.5 g/dL; platelet count = 720 x 10³/μL
Electrolytes within normal limits
Coagulation profile: normal
BNP: 34 pg/mL
Liver function tests: normal, except albumin of 3.2 g/dL
TSH: Normal
EKG: Sinus rhythm with no acute ST-T changes

Chest radiographs
The patient’s chest radiographs are shown in Figures 1 and 2.

Figure 1. Chest radiograph, anteroposterior view.

Figure 2. Chest radiograph, lateral view.

Pulmonary function tests
The patient’s pulmonary function test results are shown in Figure 3.

A
B
C
D

Figure 3. Pulmonary function tests. A, Lung volumes. B, Spirometry results. C, Diffusing capacity. D, Flow.

Due to the patient’s hypoxemia and restrictive pattern with low diffusion capacity seen on pulmonary function tests, a CT scan of the chest was done (Fig 4).

A
B
C

Figure 4. CT chest. A, B, Interstitial infiltrates. C, Mediastinal adenopathy.

Connective tissue workup was done which yielded negative restults. HIV test results were negative. Additional testing revealed an elevated LDH of 1970 U/L. Flexible bronchoscopy was performed and no endobronchial lesions were seen. A transbronchial needle aspiration was done at station 4R, and a transbronchial lung biopsy was done in the right upper lobe.

The tissue specimens were examined histologically and are shown in Figures 5, 6, 7, and 8.

Figure 5. Pathologic findings of lung tissue showing thickened interstitium with cellular infiltrate (hematoxylin-eosin, original x 40).

Figure 6. Pathologic findings of lung tissue showing megakaryocyte in interstitium (hematoxylin-eosin, original x 100).

Figure 7. Pathologic findings of lung tissue showing erythroid precursor cell and immature myeloid cell (hematoxylin-eosin, original x 400).

Figure 8. Pathologic findings of lung tissue showing myeloid precursors and megakaryocyte (hematoxylin-eosin, original x 400).

See the Answer

Diagnosis: Extramedullary hematopoiesis

Clinical course
Subsequently, a mediastinoscopy was performed with biopsy of 4R lymph nodes, which also revealed extramedullary hematopoiesis. Bone marrow biopsy was performed which showed replacement of marrow with fibrosis and no hematopoietic cells. All culture results from bronchoalveolar lavage and biopsy were negative.

Take-Home Points:

Extramedullary hematopoiesis usually presents during the sixth to seventh decades of life, most commonly in patients with myelofibrosis.¹
Thoracic involvement is rare but can present as hemothorax, interstitial fibrosis, pulmonary hypertension, or mediastinal adenopathy. Dyspnea is the most common presenting complaint in pulmonary extramedullary hematopoiesis.
Technetium-99m-colloid scintigraphy could be useful in diagnosing extramedullary hematopoiesis.²
There is no clear consensus in the treatment of pulmonary extra-medullary hematopoiesis, although many strategies, including steroids, hydroxyurea, and low-dose whole lung radiation, have been tried.³

References

Koch CA, Li CY, Mesa RA, et al. Nonhepatosplenic extramedullary hematopoiesis: associated diseases, pathology, clinical course and treatment. Mayo Clin Proc 2003; 78:1223-1233
Bowling MR, Cauthen CG, Perry CD, et al. Pulmonary extramedullary hematopoiesis. J Thorac Imaging 2008; 23:138-141
Chunduri S, Gaitonde S, Ciurea SO, et al. Pulmonary extramedullary hematopoiesis in patients with myelofibrosis undergoing allogeneic stem cell transplantation. Haematologica 2008; 93:1593-1595

Submitted by:
Suryakanta Velamuri, MBBS, FCCP
Steering Committee Member, Affiliate NetWork

Airways Disorders NetWork Online Puzzler

ACCP — Wed, 01 Jul 2009 15:32:33 +0000

Teaser:

The patient is a 57-year-old African-American man with a history of well-controlled asthma treated with mometasone. He had a positive PPD test in the 1970s and presented to the pulmonary clinic for evaluation of chronic, progressive cough and abnormal chest imaging. The patient’s cough began approximately 2 months ago. His cough was initially nonproductive but progressed to become productive with thick, tenacious yellow-green sputum. He denied any weight loss, fevers, chills, or hemoptysis.

See the Answer

Puzzler Answer and Case Report

An ABG. In this case, ABG showed: pH 7.35, paCO2 46 mmHg, paO2 324 mmHg. Methemoglobin reading was 38%.

Methemoglobinemia

CASE REPORT: a 35 year old Caucasian man was admitted for elective fusion of C5-C6, C6-C7 with an allograft and plating due to pain and left arm weakness. Past medical history was significant for exercise-induced asthma, gastroesophageal reflux disease, fibromyalgia, depression, and long-term narcotic use for his chronic neck pain. Medications on admission were quetiapine, sertraline, montelukast, gemfibrozil, omeprazole, otodolac, lortab, fentanyl patch, and cyclobenzaprine as needed. Following the procedure he received a patient-controlled infusion of morphine, valium, and oxycodone as needed in addition to his out-patient medications.

He was noted to have increasing oxygen requirements over the next several days. On hospital day 3 he complained of chest pain and shortness of breath, and was noted to have perioral and peripheral cyanosis. Pulse oximetry showed an oxygen saturation of 80%. The patient was placed on oxygen through a non rebreather mask. Basic metabolic panel, complete blood count, EKG and chest radiograph were all within normal limits. An arterial blood gas showed pH 7.35, paCO2 46 mmHg, paO2 324 mmHg, with a methemoglobin level of 38%. A bottle of benzocaine spray was noted at his bedside.

The patient was transferred to the intensive care unit and a single dose of methylyne blue 1 mg/kg was administered with rapid resolution of his symptomatic methemoglobinemia. He was discharged from the hospital without further complications.

DISCUSSION: Methhemoglobinemia was first described with nitrate pollution in the well water of New York in 1949.[1] In the following decades it was noted to be associated with hereditary G6PD deficiency.[2,3] It was first described in 1977 with the use of cetacaine spray (a topical anesthetic).[4] Methemoglobinemia results from the oxidation of ferrous (Fe2+ to ferric (Fe3+)which results in an increased O2-binding affinity shifting the oxygen dissociation curve to the left, thus decreasing O2 delivery. Clinical effects at high levels can result in cardiac arrythmias and ischemia, metabolic acidosis, coma, and even death. Treatment involves 1% methylene blue 1-2 mg/kg IV and supportive care.[5]

[1] Wood IR, Well water methemoglobinemia, NY State J Med 1949;49(21):2576.
[2] Lecks HI, Methemoglobinemia in infancy, Am J Dis Child 1950;79(1):117-23.
[3] Codounis A, Hereditary methemoglobinemia, Sang 1951;22(7):525-42.
[4] Douglas WW, Fairbanks VF, Methemoglobinemia induced by a topical anesthetic spray (cetacaine), Chest 1977;71(5):587-91.
[5] Mokhlesis B, Corbridge T, Toxicology in the critically ill patient, Clin Chest Med 2003;24(4):689-711.

Puzzler and case report submitted by:
Antonio Salud II, M.D. Pulmonary Critical Care Fellow University of Utah Health Sciences Salt Lake City, UT
Reviewed by:
MAJ Alexander Niven, MC, USA, FCCP Director, Respiratory Care Services Madigan Army Medical Center Tacoma, WA	John Shigeoka, M.D. Chief, Pulmonary Section - SLC VAMC Professor of Clinical Medicine - University of Utah Salt Lake City, UT

Sleep Medicine NetWork Online Puzzler

ACCP — Tue, 26 May 2009 15:32:33 +0000

Teaser:

After reading the Chapter, test your knowledge with questions from ACCP-SEEK Sleep Medicine, First Edition:

Narcolepsy and Idiopathic Hypersomnia

Narcolepsy and Idiopathic Hypersomnia
Chapter taken from the ACCP Sleep Medicine 2008 Board Review Course.

After reading the Chapter, test your knowledge with questions from ACCP-SEEK Sleep Medicine, First Edition:

1) Which one of the following statements is true regarding narcolepsy due to medical conditions?

A. The diagnosis requires the presence of reduced or absent CSF hypocretin-1 levels.
B. It has been described in association with suprasellar tumors.
C. Symptoms are typically refractory to stimulant therapy.
D. The presence of cataplexy is an almost universal finding.

See the Answer.

1) Which one of the following statements is true regarding narcolepsy due to medical conditions?

B is CORRECT. It has been described in association with suprasellar tumors.

Narcolepsy due to medical conditions is a rare complication of various neurologic disorders. Several case reports have described narcolepsy in association with neurosarcoidosis, head trauma, diencephalic stroke, suprasellar tumors, CNS infections, paraneoplastic syndromes associated with anti-Ma-2 antibodies, Neiman-Pick type C disease, and as a complication of suprasellar surgery (choice B is correct). It has also been described in association with diffuse neurodegenerative disorders, including multiple sclerosis, Parkinson disease, and multiple system atrophy. In general, the majority of these cases have been associated with lesions affecting the diencephalon and/or brain stem. Hypothalamic involvement in the diencephalon is important, in that the posterior and lateral hypothalamus are the sites of hypocretin-producing neurons that are thought to play a major role in the majority of patients with idiopathic narcolepsy. While associated cataplexy has been described with this syndrome, it is by no means a universal finding (choice D is incorrect).

As is the case for primary narcolepsy, the diagnosis of secondary narcolepsy requires at least one of the following: (1) a definite history of cataplexy; (2) in the absence of definite cataplexy, a mean sleep latency on the multiple sleep latency test (MSLT) < 8 min and two or more sleep onset REM periods; or (3) hypocretin-1 levels of <110 pg/mL (or < 30% of normal control values). As per the diagnostic criteria, reduced CSF hypocretin-1 levels have been demonstrated in some cases of narcolepsy due to medical conditions, but this is not a universal finding, even in patients with significant destruction of their hypothalamus. In addition, measurement of CSF hypocretin-1 is not readily available. Therefore, reduced or absent hypocretin-1 levels are not necessary to make a diagnosis (choice A is incorrect). Patients with neurodegenerative diseases associated with sleep-disordered breathing should have their sleep-disordered breathing adequately treated prior to making this diagnosis.

The diagnosis of narcolepsy due to medical conditions should be considered in patients who present with typical symptoms of narcolepsy with known precipitating diseases, as noted above, or in those patients who present in an atypical fashion. Specifically, patients who present with characteristic symptoms at older or very young ages should be considered for evaluation of abnormalities of the diencephalon. The median age of symptom onset in typical narcolepsy is 16 years, with 90% of patients presenting with symptoms by 33 years of age. Our patient presented with narcolepsy symptoms at the uncharacteristic age of 65 years old. Many patients who present with this form of narcolepsy will also present with other neurologic complaints and/or endocrine abnormalities resulting from hypothalamic dysfunction.

The treatment of narcolepsy due to other medical conditions has been focused on interventions that may resolve the underlying medical disorder, as well as the use of stimulants and anticataplectic agents. While not a universal finding, most case reports demonstrate significant improvements in symptoms of daytime sleepiness and cataplexy with the use of stimulants and various antidepressants (choice C is incorrect). One case report of neurosarcoidosis demonstrated complete resolution of narcoleptic symptoms with low-dose whole-brain irradiation, after high-dose steroids were ineffective at improving the patient’s symptoms.

Marcus CL, Trescher WH, Halbower AC, et al. Secondary narcolepsy in children with brain tumors. Sleep 2002; 25:427-431

Castriotta RJ, Wilde MC, Lai JM, et al. Prevalence and consequences of sleep disorders in traumatic brain injury. J Clin Sleep Med 2007; 3:349-356

Scammell TE, Nishino S, Mignot E, et al. Narcolepsy and low CSF orexin (hypocretin) concentration after a diencephalic stroke. Neurology 2001; 56:1751-1753

Rubinstein I, Gray TA, Moldofsky H, et al. Neurosarcoidosis associated with hypersomnolence treated with corticosteroids and brain irradiation. Chest 1988; 94:205-206

American Academy of Sleep Medicine. The international classification of sleep disorders: diagnostic and coding manual. 2nd ed. Chicago, IL: AASM, 2005

2) A 24-year-old woman presents with several years of excessive daytime sleepiness associated with bilateral lower extremity weakness precipitated by laughter. Her typical bedtime is 10:30 pm, with a subjective total sleep time of 8 h on most nights. She has no medical problems and takes no medications. Following an overnight polysomnogram with relatively normal results, an MSLT demonstrates a mean sleep latency of 3 min, with three sleep onset rapid eye movement (REM) periods out of four nap trials, supporting a diagnosis of narcolepsy. Therapy with modafinil, 200 mg taken each morning, is initiated and later increased to 400 mg taken each morning. After 4 weeks of therapy, she continues to have significant residual daytime sleepiness, as well as cataplexy.

Which of the following could you recommend to better treat the patient’s symptoms?

A. Increase modafinil from once-a-day to twice-a-day dosing.
B. Add methamphetamine.
C. Add sodium oxybate.
D. Add methylphenidate SR.

See the Answer.

Which of the following could you recommend to better treat the patient’s symptoms?

C is CORRECT. Add sodium oxybate.

Because narcolepsy is a chronic disease, without known cures, treatment is focused on therapies that improve or relieve symptoms. Sodium oxybate is the only treatment that has been demonstrated in several randomized clinical trials to significantly improve all of the core symptoms of narcolepsy, including daytime sleepiness, objective alertness, cataplexy, insomnia, disrupted sleep, and quality of life (choice C is correct). Sodium oxybate is derived from γ-hydroxybutyrate. The precise mechanisms of action responsible for its clinical outcomes in narcolepsy are unknown. Sodium oxybate is supplied as a liquid and is prescribed in doses between 3 and 9 g per night. It is prescribed in equally divided doses due to a short half-life of 2 to 3 h, with an initial dose taken at bedtime and a second dose taken 2.5 to 4 h later. Doses may be titrated up 1.5 g per night every 2 to 4 weeks, depending on the symptomatic response. Side effects may include dizziness, vomiting, sleep walking, confusion, and enuresis. At higher doses, it can also act as a respiratory suppressant and should not be used with other sedatives, including alcohol. Initial studies with sodium oxybate focused on the treatment of cataplexy. Sodium oxybate has been demonstrated in several randomized controlled trials to reduce episodes of cataplexy in a dose-dependent fashion over periods of 4 to 8 weeks. These improvements in cataplexy symptoms have been observed to persist for up to 12 months in observational studies, without the development of tolerance to any specific dose. Importantly, there are no significant withdrawal symptoms upon discontinuing the drug. Status catiplecticus, commonly observed upon discontinuing other REM suppressant medications used for cataplexy, typically does not occur upon stopping sodium oxybate. Early trials evaluating sodium oxybate for cataplexy also demonstrate significant reductions in subjective daytime sleepiness compared with placebo. Two randomized placebo-controlled trials have specifically evaluated the use of sodium oxybate for symptomatic improvement in daytime sleepiness in patients with narcolepsy. Sodium oxybate at doses of 6 and 9 g per night results in significant improvements in daytime sleepiness, as defined by the Epworth Sleepiness Scale, when added to concomitant baseline stimulant use. Significant improvements in objective alertness, as defined by the Maintenance of Wakefulness Test, are also seen with sodium oxybate in the 9-g dose range when used in combination with other stimulants. When used as the sole agent, sodium oxybate at doses of 6 and 9 g per night results in improvements in subjective sleepiness and daytime alertness similar to those with 200 to 400 mg per day of modafinil. Finally, the combination of sodium oxybate and modafinil appears to result in an additive effect on these sleepiness parameters when compared with placebo, though statistically the combination of these two drugs was no better than either one used alone. Based on these data, sodium oxybate is currently the only drug FDA approved for the treatments of both cataplexy and daytime sleepiness in patients with narcolepsy. Modafinil has been demonstrated in randomized trials to significantly improve symptoms of daytime sleepiness but has not been demonstrated to have any significant effects on cataplexy (choice A is incorrect). Amphetamines and methylphenidate, while used for the treatment of daytime sleepiness, have not been evaluated in randomized trials and have not demonstrated any efficacy in the treatment of cataplexy (choices B and D are incorrect). These agents are considered second-line therapies to both modafinil and sodium oxybate due to their potential significant sympathomimetic side effect profiles.

US Xyrem Multicenter Study Group. Sodium oxybate demonstrates long-term efficacy for the treatment of cataplexy in patients with narcolepsy. Sleep Med 2004; 5:119-123

Xyrem International Study Group. A double-blind, placebo-controlled study demonstrates sodium oxybate is effective for the treatment of excessive daytime sleepiness in narcolepsy. J Clin Sleep Med 2005; 1:391-397

Black J, Houghton W. Sodium oxybate improves daytime sleepiness in narcolepsy. Sleep 2006; 29:939-946

Billiard M, Bassetti C, Dauvilliers Y, et al. ENFS guidelines on the management of narcolepsy. Eur J Neurol 2006; 13:1035-1048

Dauvilliers Y, Arnulf I, Mignot E. Narcolepsy with cataplexy. Lancet 2007; 369:499-509

Cardiovascular Medicine and Surgery NetWork Online Puzzler - May 2009

ACCP — Wed, 06 May 2009 15:32:33 +0000

Teaser:

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Online Puzzler

A 50-year-old man of Indian descent with a past medical history only significant for multiple myeloma was admitted to our hospital for complaints of fatigue, increasing dyspnea, and bilateral lower extremity edema, which had been progressive for the past 2 months. The multiple myeloma had been refractory to treatment with considerable progression since the diagnosis was made 3 years earlier. Over the years, he had been treated with pulse steroids and chemotherapy (CDEP: cyclophosphamide, dexamethasone, etoposide, cisplatin), followed by a peripheral stem cell transplant and then maintenance steroids. His disease continued to progress with refractory cytpopenias and extensive bone involvement. Within the year prior to this admission, he was also treated with thalidomide and, more recently, bortezomib. Despite the multitude of therapies he underwent, his myeloma remained unresponsive. On exam, he appeared to be in congestive heart failure with findings of tachycardia. Rales were heard halfway up the lung fields bilaterally, and he had a jugular venous pulse at 12 cm, ascites, and 3+ bilateral lower extremity edema, as well as scrotal edema. Laboratory values demonstrated bicytopenia with a hematocrit concentration of 27 mg/dL and a platelet count of 10 x 109 cells/L. His chemistry panel was remarkable for a BUN value and creatinine level of 55 mg/dL and 1.0 mg/dL, respectively, and a calcium level of 12.2 mg/dL. It was notable that his albumin concentration was not significantly depleted at 3.6 mg/dL. The ECG obtained in the ED demonstrated sinus rhythm with a rate of 93 bpm, normal voltage, and a left atrial abnormality. His chest radiograph was consistent with congestion. He was directly admitted to workup a new diagnosis of congestive heart failure. A two-dimensional echocardiogram with Doppler showed a left atrium that was mildly dilated, normal left ventricular wall thickness, preserved systolic function with an ejection fraction of 65%, normal diastolic function, and a right ventricular systolic pressure of 42 mm Hg. Despite aggressive diuresis, including a furosemide drip at 20 mg/h, his status continued to decline, and he went on to require mechanical ventilation support due to respiratory failure. Below is an MRI taken of the abdomen and pelvis 1 month prior to his hospitalization.

What is his diagnosis and what is the pathophysiology?

See the Answer

Diagnoses and Discussion

Summary of findings:

Interval increase in diffuse bone marrow replacement throughout the pelvis and proximal femora.
Only small areas of residual fatty marrow in greater trochanters and femoral heads bilaterally.
An L5 compression fracture, which is stable.
Diffuse enhancement consistent with extensive disease.

Diagnosis:

A left and right heart catheterization subsequently demonstrated no evidence of coronary artery disease, but the hemodynamic values on the right heart catheterization showed the following:

RA 18 mm Hg; RV 58/3 (22) mm Hg; PA 49/15 (32) mm Hg; PCWP (32) mm Hg; LV 86/11 (24) mm Hg; AO 74/49 (61) mm Hg

Fick Output - estimated (L/min) 15.17; Fick Index - estimated (L/min/m2) 8.67;
SVR -(dynes•sec•cm-5) 227

RA - right atrium; RV - right ventricle; PA - pulmonary artery; PCWP - pulmonary capillary wedge pressure; LV - left ventricle; AO - aorta

Based on these findings, he was subsequently diagnosed with high-output cardiac failure secondary to multiple myeloma. The scant literature available, which describes this phenomenon, would suggest that the best way to treat this condition is by treating the underlying malignancy. We subsequently initiated lenalidomide (an immunomodulatory derivative similar to thalidomide that was approved in June 2006 for the treatment of refractory multiple myeloma) and pulse dexamethasone in conjunction with IV diuresis. Within 48 h, we began to see a brisk diuresis with a net fluid balance of negative 5 L. One week later, he had diuresis of an additional 15 L and was subsequently extubated. Unfortunately, 1 week later, he developed a massive upper GI bleed, which was likely precipitated by his persistent thrombocytopenia. He sustained a cardiac arrest and could not be resuscitated.

Teaching point:
Multiple myeloma is one of many conditions that can precipitate a high output state leading to congestive heart failure. Other conditions that can do the same include anemia, arteriovenous (AV) fistulas, thyrotoxicosis, beriberi, Paget disease, polycythemia vera, pregnancy, and liver disease. The pathophysiology behind high output failure and multiple myeloma is controversial and not completely understood. Current data support the theory of innumerable, small, diffuse AV fistulas in the setting of lytic bone involvement leading to this state. In a study by McBride and colleagues,1 extensive bone involvement was the only variable that predicted which myeloma patients would go on to develop a high output state. As to whether or not extensive bone involvement leads to AV fistulas, Inanir and colleageus2 examined 11 patients with myeloma and high output failure and assessed the degree of AV shunting in the pelvis by injecting technetium Tc 99m-macroaggregated albumin bubbles into the femoral artery. Patients with the greatest shunting ratios had the highest cardiac outputs (r=0.79 p=0.004). Treatment options that have been tried with some success include transcatheter embolization and chemotherapy. Both treatments have shown improvement in hemodynamics, although the number of subjects studied is very small. In conclusion, high output failure should be kept in mind as one of the cardiac complications of multiple myeloma.

McBride W, Jackman JD Jr, Grayburn PA. Presence and clinical characteristics of high cardiac output state in patients with multiple myeloma. Am J Med 1990; 89:21-24
Inanir S, Haznedar R, Atavci S, et al. Arteriovenous shunting in patients with multiple myeloma and high-output failure. J Nucl Med 1998; 39:1-3
Sanchez FW, Chuang VP, Skolkin MD. Transcatheter treatment of myelomatous AV shunting causing high-output failure. Cardiovasc Intervent Radiol 1986; 9:219-221
McBride W, Jackman JD Jr, Gammon RS, et al. High-output cardiac failure in patients with multiple myeloma. N Engl J Med 1988; 319:1651-1653

Puzzler and case report submitted by:
Jason Robin, MD
Fellow in Cardiology, Feinberg School of Medicine, Northwestern University, Chicago, IL

Reviewed by:
Dan Fintel, MD, FCCP
Steering Committee Member, Cardiovascular Medicine and Surgery NetWork
Professor of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL

Interventional Chest/Diagnostic Procedures (IC/DP) NetWork Online Puzzler - May 2009

ACCP — Wed, 06 May 2009 15:32:33 +0000

Teaser:

A 31-year-old African-American man reported to the ED with a 3-week history of productive cough, fever, chills, and pleuritic chest pain. He reported multiple episodes of pneumonia and bronchitis over the last several years. He also had been treated for asthma over the same time period.

Interventional Chest/Diagnostic Procedures (IC/DP) NetWork

Online Puzzler

Larger View

Figure 1.Chest radiograph showing pneumonia on the left side.

Larger View

Figure 2. CT scan showing left-upper-lobe pneumonia and metallic density in area of left main bronchus.

Larger View

Figure 3. Bullet in left main bronchus.

Larger View

Figure 4. Distal left main bronchus after bullet removal.

Clinical presentation
A 31-year-old African-American man reported to the ED with a 3-week history of productive cough, fever, chills, and pleuritic chest pain. He reported multiple episodes of pneumonia and bronchitis over the last several years. He also had been treated for asthma over the same time period.

Review of systems
Dyspnea with moderate exertion and night sweats. There was no hemoptysis.

Past medical and surgical history
Asthma, recurrent pneumonias, and a gunshot wound to the chest 9 years prior.

Social history
Patient denies alcohol or tobacco use. At a recent incarceration 6 weeks prior, patient had a negative result on PPD test.

Family history
Noncontributory.

Allergies
None.

Medications
Albuterol metered-dose inhaler, two inhalations every 4 h, as needed.

Physical examination
Temperature=104 F; BP=114/57 mm Hg; heart rate=132 bpm; respiratory rate=16/min; oxygen saturation on room air=93%

General: no distress with frequent coughing

HEENT: no oral lesions; halitosis

PULM: decreased breath sounds and crackles present on the left

CV: tachycardia, with a regular rhythm and no murmur

Lymph: no lymphadenopathy

ABD: soft, nontender, no hepatosplenomegaly

EXT: no edema or clubbing

Neurologic: nonfocal

Pulmonary function tests
None.

See the Answer

Puzzler Answer and Case Report

Diagnosis
Endobronchial bullet causing asthma-like symptoms and recurrent pneumonia for several years.

Clinical course
The patient was taken to the operating room and underwent flexible bronchoscopy through an endotracheal tube. The right main bronchus was normal, and the distal left main bronchus was completely obstructed by an intact bullet (Fig 3). A 16-mm retrieval basket was placed around the bullet, which was removed in one unit with the bronchoscope and endotracheal tube with a moderate amount of force. Upon reintubation with the bronchoscope, there was a small amount of granulation tissue in the distal left main bronchus and a mucosal, ulcer-type lesion with no visible communication through the airway wall (Fig 4). A moderate amount of purulent secretions was suctioned out. The patient was discharged the next day to complete a course of levofloxacin and metronidazole, uneventfully.

The patient reported that 9 years prior, he had been shot in the right shoulder with the bullet traversing his right lung into the mediastinum. At that time, he was told that the bullet should not be removed do to its location.

Key points

The bullet likely migrated into the airway sometime after the injury, as evidenced by closure of the airway wall around the bullet.
Given the patient's history of recurrent pneumonias and asthma, the bullet had likely been in the airway for several years.
Although rare, 'wandering' foreign bodies in the thorax and mediastinum can migrate over time into other structures, such as the airway or blood vessels.
Long-term inclusion of foreign bodies may mimic asthma, as well as cause recurrent or nonresolving pneumonia.
A retrieval basket is an effective tool for foreign body removal.

References

Ledgerwood AM. The wandering bullet. Surg Clin North Am 1977; 57:97-109
Langer D, Petermann C, Lübbers H, et al. Relapsing pneumonia due to a migrating intrathoracic foreign body in a World War II veteran shot 53 years ago. J Intern Med 1999; 245:405-407
Bocca X, Gil L, Garrido S, et al. Management of a penetrating gunshot wound of the trachea and bullet extraction using bronchoscopy. J Bronchol 2005; 12:28-30

Puzzler and case report submitted by:
Ray Wes Shepherd, MD, FCCP
Assistant Professor of Medicine
Interventional Pulmonology, Pulmonary and Critical Care
Virginia Commonwealth University Medical Center
Richmond, VA

Thoracic Oncology NetWork Online Puzzler - March 2009

ACCP — Wed, 25 Mar 2009 15:32:33 +0000

Teaser:

A 62-year-old woman comes to your practice for evaluation of a cough and abnormal CT scan. Biopsy of a 3.5 cm lung mass 2 years ago was diagnostic of non-small lung cancer, stage IB. She underwent lobectomy, but not chemotherapy, with improvement in the mass. Eight months ago, evaluation of neck pain showed a metastatic lesion in the thoracic spine, which was managed with local radiation to the thoracic spine. Over the past month, the patient has been experiencing coughing and low-grade fevers, which have been refractory to azithromycin prescribed by her primary care physician. A CT scan was obtained, which is shown in Figure 1.

Figure 1. CT scan.
Click for Larger View

Online Puzzler

Current Puzzler
A 62-year-old woman comes to your practice for evaluation of a cough and abnormal CT scan. Biopsy of a 3.5 cm lung mass 2 years ago was diagnostic of non-small lung cancer, stage IB. She underwent lobectomy, but not chemotherapy, with improvement in the mass. Eight months ago, evaluation of neck pain showed a metastatic lesion in the thoracic spine, which was managed with local radiation to the thoracic spine. Over the past month, the patient has been experiencing coughing and low-grade fevers, which have been refractory to azithromycin prescribed by her primary care physician. A CT scan was obtained, which is shown in Figure 1.

You perform a bronchoscopy, which demonstrates nonspecific inflammation. No malignant cells are present. Special stains for microorganisms and cultures show negative results to date. After a trial of prednisone, both her clinical and radiographic findings improve after several weeks.

See the Answer

Diagnoses and Discussion

Diagnosis: Radiation-induced bronchiolitis obliterans with organizing pneumonia (BOOP)

Radiation represents one of the key modalities of lung cancer management. It is employed with curative intent when patients cannot undergo surgical resection and employed with palliative intent to manage focal symptomatic metastases (ie, pain from a bone metastasis or malignant airway obstruction). This modality is associated with a number of potential complications. Radiation pneumonitis and radiation fibrosis are the most common adverse sequelae, and they may occur any time the lung lies within the radiation field. The risk of radiation pneumonitis is proportional to the volume of lung receiving radiation, the dose of radiation, as well as the presence or absence of concurrent chemotherapy. Clinical findings often manifest 6 weeks to 6 months after radiation begins and may include coughing, fevers, chest pain (sometimes pleuritic), and dyspnea. Chest radiographs may be normal, or they may manifest dense alveolar infiltrates within the radiation field, often with a sharp line separating the radiation field from surrounding normal lung that does not conform to anatomic barriers, such as pleura (straight-line sign).

Radiation-induced bronchiolitis obliterans with organizing pneumonia (BOOP), a more rare complication of radiation, was first reported in the 1990s among breast cancer patients.¹ It may occur 5 to 10 months after radiation therapy, its time course overlapping that of radiation pneumonitis. Radiation-induced BOOP is distinguished from cryptogenic organizing pneumonia (COP) by the fact that COP is idiopathic by definition. However, the pathologic findings of BOOP and COP are indistinguishable; organizing pneumonia is typically shown with prominent lymphocytes and plasma cells. Intraluminal polypoid plugs of connective tissue may or not be present. Chronic fibrotic changes, such as honeycombing on CT scans, are unusual. Symptoms and signs are similar to those of radiation pneumonitis, including cough, crackles, and fever. Unlike radiation pneumonitis, pulmonary infiltrates are not limited to the radiation field. Infiltrates are usually patchy and alveolar, often with air bronchograms, such as in the example here. They may be diffuse or nodular in extent. Transbronchial biopsy specimens rarely obtain sufficient tissue to confirm BOOP; therefore, the diagnosis rests on excluding other possibilities and/or surgical lung biopsy. The treatment of choice is systemic steroids.

This case represents radiation-induced BOOP subsequent to radiation the patient received for bone metastasis.

References:

Bayle JY, Nesme P, Bejui-Thivolet F, et al. Migratory organizing pneumonitis “primed” by radiation therapy. Eur Respir J 1995; 8:322-326

Puzzler Case Report submitted by:
Marc B. Feinstein, MD, FCCP
Member of the Thoracic Oncology NetWork Steering Committee

Home Care NetWork Online Puzzler

ACCP — Sun, 01 Mar 2009 06:00:00 +0000

Teaser:

A 63-year-old retired radiologist was on vacation in Atlantic City. He had a mild upper respiratory tract infection approximately 1 week earlier. While in his hotel room, he noted the acute onset of orthopnea. He went to a local emergency room. In the ED, he reported orthopnea and dyspnea when bending over, but he could walk about two blocks on level ground. He denied cough, fever, wheezing, or sputum production. Review of systems was only notable for bilateral shoulder pain.

Online Puzzler

Clinical presentation
A 63-year-old retired radiologist was on vacation in Atlantic City. He had a mild upper respiratory tract infection approximately 1 week earlier. While in his hotel room, he noted the acute onset of orthopnea. He went to a local emergency room. In the ED, he reported orthopnea and dyspnea when bending over, but he could walk about two blocks on level ground. He denied cough, fever, wheezing, or sputum production. Review of systems was only notable for bilateral shoulder pain.

Past medical history
His past history included Hansen disease treated in the 1950s, prostate cancer, coronary disease, and diabetes.

Social history
He is originally from the Philippines, married, has three grown children, and no history of tobacco use.

Family history
Heart disease and diabetes

Medications
Medications included atenolol, finasteride, irbesartan, aspirin, metformin, ezetimibe/simvastatin, and fluoxetine

Physical examination

Vital signs: BP = 130/80 mm Hg; heart rate = 80 bpm; respiratory rate = 30/min
Appears comfortable but dyspneic when supine
HEENT: negative
Neck: No JVD, + use of accessory muscles
Chest: small lung volumes, no diaphragm movement, clear
Heart: reg, no murmurs/gallops
Abd: + abdominal paradox
Ext: negative
Neuro: CN intact, strength 5/5, DTRs 2+

Figure 1.Chest radiograph.

The chest radiograph was read as showing bibasilar atelectasis (Fig 1). The patient was treated with moxifloxacin for 10 days for a presumed pneumonia or bronchitis. His symptoms did not improve; after 1 month, he went to a pulmonologist.

Pulmonary function tests
Upright FVC = 1.31 (30%); FEV₁ = 0.85 (27%); FEV₁/FVC = 78. His supine FVC was 0.4 L. TLC = 3.18 (52%); RV = 1.84 (104%); MIP = -33 (30%); MEP = 164 (81%)

Diaphragm fluoroscopy was performed that showed no inspiratory movement of the diaphragm. Nerve conduction studies of the phrenic nerve showed markedly reduced compound muscle amplitude consistent with phrenic nerve injury.

See the Answer

Puzzler Answer and Case Report

Diagnosis
Brachial neuritis (also known as cervical amyotrophy, Parsonage-Turner syndrome, neuralgic amyotrophy, idiopathic diaphragm paralysis)

This syndrome was first described in the 1940s by Spillane¹ in 46 soldiers that developed brachial neuritis while convalescing from other infections. The classic presentation is the acute onset of pain in the shoulder or scapula. This pain resolves over 3 to 14 days, while weakness develops over 4 to 5 days with rapid signs of muscle atrophy. It often affects only one side of the diaphragm, but is bilateral in approximately 15% of cases. The syndrome has been reported to occur after a variety of precipitating factors, including surgery to remote parts of the body, vaccinations, and many infections.

Treatment
Fortunately, the majority of cases improve spontaneously. However, this usually occurs over 1 or 2 years. Supportive care with mechanical ventilation works well as treatment. This patient was prescribed home noninvasive positive pressure ventilation support with an inspiratory pressure of 20 cm H₂O and an expiratory pressure of 5 cm H₂O. The patient slept comfortably when supported by noninvasive ventilation. At the 6-month follow-up, his FVC had improved by 350 mL, he could lay flat for 15 s, and he could walk on a treadmill for 30 min.

This case illustrates a cause of bilateral diaphragm paralysis that is frequently not considered. Patients generally respond well to noninvasive ventilation support while awaiting phrenic nerve recovery.

Reference

Spillane JD. Localized neuritis of the shoulder girdle: a report of 46 patients in the MEF. Lancet 1943; 2:532-535

Puzzler and case report submitted by:
Noah Lechtzin, MD, FCCP
Vice-Chair, Home Care NetWork

Cardiovascular Medicine and Surgery NetWork Online Puzzler - December 2008

ACCP — Wed, 03 Dec 2008 16:52:19 +0000

Teaser:

A 66-year-old woman with hypertension, osteoarthritis, hypertensive heart disease, and chronic persistent atrial fibrillation presents to the ED with 1 week of progressive fatigue, exertional dyspnea, and nausea. For over 1 year, management of her conditions has included a daily regimen of enalapril,10 mg, bid, digoxin, 0.25 mg, chlorthalidone, 25 mg, warfarin, 5 mg, and verapamil (time-released), 240 mg. She takes aspirin as needed for joint discomfort. She was feeling well 1 month ago when seen in the clinic.

EKG graph

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Online Puzzler

Her physical exam shows bradycardia, mild hypotension (compared to baseline), and mild systemic venous congestion.

Laboratory values are pending. Her ECG is shown.

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Diagnoses and Discussion

Diagnoses:

Atrial fibrillation with a complete heart block and junctional bradycardia escape rhythm.
Digitalis toxicity due to a reduced glomerular filtration rate (GFR) (interaction of the angiotensin enzyme converting [ACE] inhibitor with a nonsteroidal antiinflammatory drug [NSAID]) plus inhibited digitalis secretion from the verapamil interaction.

Discussion:

Excretion of digoxin is approximately 80 to 85% renal, with filtration as the predominant mechanism. The drug is also actively secreted through the renal tubules, yet this mechanism can be inhibited by other drugs, including verapamil, quinidine, and amiodarone. Most physicians are aware of the combined effect of ACE inhibitors and NSAIDs in causing azotemia, but they sometimes forget that aspirin, at analgesic/antiinflammatory doses, has similar effects; the combination dilates efferent and afferent arterioles, critically reducing transglomerular filtration pressure and the excretion of any drug normally filtered in significant amounts. Although the impact of inhibited tubular secretion of digoxin by other drugs is not clearly more common in the presence of azotemia, it often makes otherwise tolerable glomerular clearance levels inadequate, reducing one major alternative excretion pathway.

Laboratory values for the patient included a serum creatinine level of 4.0 mg/dL (estimated GFR of 25 mL/min), serum CO2 concentration of 15 mEq/L, and serum potassium concentration of 6.2 mEq/L (both from reduced GFR and from the digoxin itself, which inhibits real sodium-potassium-dependent adenosine triphosphatase [ATPase] and can raise potassium levels as a consequence of toxicity).

The patient underwent emergency hemodialysis but remained in complete heart block. Digoxin-specific Fab fragments were then administered with recovery of normal conduction. With discontinuation of the verapamil, enalapril and aspirin, the patient fully recovered in 72 h and was discharged to go home with a near baseline renal function and a ventricular rate of 80 bpm.

Puzzler and case report submitted by:
Stephen A. Geraci, MD, FCCP
Chair, Cardiovascular Medicine and Surgery NetWork
Professor and Vice Chair, Internal Medicine
University of Mississippi School of Medicine
Chief, Medical Service GV (Sonny) Montgomery VAMC
Jackson, Mississippi