- Email: [email protected]
A Woman With Dyspnea, Weight Loss, and Splenic Lesions
[
CHEST Pearls
]
A Woman With Dyspnea, Weight Loss, and Splenic Lesions Jennifer S. Hanberg, BA; and Dana Dunne, MD
The patient is a 37-year-old hospital employee and current smoker with a 10 pack-year smoking history, who presented with dyspnea, chest pain, and weight loss. She was in her usual state of health until 4 months prior to admission when she developed intermittent left-sided chest pain, cough productive of scant yellow sputum, fevers, and anorexia. Initial chest radiograph was normal and her outpatient physician prescribed azithromycin, which she took without improvement. One month prior to admission, a follow-up chest radiograph revealed a left-sided upper lobe consolidation; she received a course of levofloxacin without improvement. At follow-up, given her occupation, 13.6-kg unintentional weight loss, and persistent pulmonary symptoms and infiltrate despite treatment for pneumonia, her provider referred her for admission with particular concern for exclusion of active TB. As a hospital employee with clinical exposure, she underwent annual TB screening, which was always negative. She had no known exposure to patients with TB. Her most recent travel was to the Midwestern United States, without significant outdoors exposure. Review of systems was positive for wheezing, anorexia, and arthralgias of both knees and the left ankle and wrist. There was no hemoptysis, leg swelling, visual changes, palpitations, or muscle weakness. CHEST 2020; 157(1):e13-e16 CASE PRESENTATION:
Physical Examination Findings On admission, the patient was thin and in no acute distress. She was afebrile with BP of 125/76 mm Hg, pulse rate of 67 beats/min, respiratory rate of 16 breaths/min, with 100% peripheral oxygen saturation on room air. Lung examination was remarkable for decreased breath sounds in the left upper lobe. Heart rate was regular and without murmurs. Her abdomen was benign without organomegaly appreciated. There was a nontender 1-cm left postauricular node. The rest of her examination was unremarkable.
Diagnostic Studies A broad laboratory workup was unremarkable, including serum chemistries, complete blood count, liver panel, procalcitonin, HIV Ag-Ab (fourth-generation)
AFFILIATIONS: From the Department of Internal Medicine, Yale University School of Medicine, New Haven, CT. CORRESPONDENCE TO: Dana Dunne, MD, Section of Infectious Diseases, PO Box 208056, 333 Cedar St, New Haven, CT 06520; e-mail: [email protected]
chestjournal.org
assay, and interferon-gamma release assay. Urinary histoplasma antigen and three sputum acid-fast bacilli smears were negative. Admission ECG showed sinus rhythm with a PR interval of 0.21 s. Chest CT scan confirmed the presence of a 2.9-cm left-sided upper lobe, nodular, noncavitating airspace consolidation surrouded by groud-glass opacities; this consolidation had been visualized on plain radiography prior to admission (Fig 1, Fig 2). Abdominal imaging revealed splenic hypodensities (Fig 3). Because of suspicion for malignancy vs fungal or mycobacterial infection, a bronchoscopy was performed; however, a biopsy was not performed at the time because of the apical location of the consolidation. BAL specimens were notable for
Copyright Ó 2019 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved. DOI: https://doi.org/10.1016/j.chest.2019.08.2181
e13
Figure 3 – Abdominal CT scan. The patient’s abdominal CT scan revealed multiple hypodense lesions of various sizes, some with septation.
Figure 1 – Chest radiograph. Two weeks prior to admission, the patient underwent chest radiograph.
Figure 2 – A-B, Chest CT angiography. A, Because of suspicion of pulmonary embolism, the patient underwent chest CT angiography. B, A representative slice of the mediastinum, showing adenopathy.
negative AFB smear, aspergillus antigen, nocardia and actinomyces cultures, and fungal culture. Cytology revealed abundant pulmonary macrophages and no malignant cells. Because of continued diagnostic uncertainty, a PET/CT scan was ordered, which revealed interval increase in size of the left-sided upper lobe opacity from 2.9 to 3.4 cm, and increased uptake in several mediastinal lymph nodes, the left-sided upper lobe mass, and the
e14 CHEST Pearls
Figure 4 – PET/CT scan. Hypermetabolic lesions in the left-sided upper lobe mass, splenic lesions, and scattered lymph nodes in the neck, chest, abdomen, and pelvis were observed.
spleen (Fig 4). A transbronchial biopsy and endobronchial ultrasound-guided biopsy were then performed, after which the patient was discharged from the hospital to await biopsy results.
What is the diagnosis? [
157#1 CHEST JANUARY 2020
]
Diagnosis: Sarcoidosis Discussion Sarcoidosis is an uncommon granulomatous disorder with protean manifestations that may mimic infectious or malignant processes. Its onset peaks in the third to fifth decades of life, with higher incidence in women and in patients of Northern European and African descent.
differentiate from lymphoma, metastasis, or granulomatous infection. Further characterization is possible with gadolinium-enhanced MRI, which classically reveals hypoenhancement and T1 and T2 hypointensity, differentiating the lesions from infectious lesions (usually T2 hyperintense), benign tumors (usually T2 hyperintense), and malignancies (T1 and T2 isointense and usually isoenhancing). PET/CT scan, although not useful for this differentiation, can help identify involved tissues for biopsy.
Although the exact sequence of etiopathologic events remains unknown, a favored theory is that sarcoidosis is a multifactorial process requiring both genetic susceptibility and an environmental insult. This insult may take the form of presentation of a specific antigen by activated macrophages, leading to an overexuberant T-cell and macrophage response and subsequent widespread granuloma formation and systemic inflammation. Sarcoidosis most commonly involves the lungs and hilar lymph nodes, but virtually every organ system can be affected. In addition, the systemic inflammation associated with this condition can lead to nonspecific symptoms including weight loss, fatigue, fevers, and night sweats.
The clinical course of sarcoidosis is variable and difficult to predict, with two-thirds of patients experiencing spontaneous remission and between 10% and 30% experiencing chronic disease. Among patients with chronic or progressive disease, significant morbidity can result from cardiac involvement (which may lead to arrhythmia), ocular involvement (which may lead to visual impairment), neurosarcoidosis, and progressive lung fibrosis (which may become severe enough to warrant evaluation for lung transplantation). Screening for involvement of the eyes and heart is recommended with ophthalmologic evaluation and electrocardiography.
The latest formal guideline regarding the diagnosis of systemic sarcoidosis comes from the 1999 Sarcoidosis Consensus Statement, which requires a compatible clinico-radiographic picture, the presence of noncaseating granulomata on histology, and exclusion of alternative diagnoses. The statement also notes that a diagnosis of sarcoidosis is not established by the sole presence of granulomata in a single organ (eg, skin). The subjectivity of the requirement for a compatible clinical picture and reasonable degree of exclusion of alternative diagnoses, without any formal discussion of what this reasonable level might entail, has led to recent attempts to formalize the process of diagnosing sarcoidosis. However, to date, there is no widely accepted formulaic diagnostic algorithm.
Medical therapy is generally not recommended in asymptomatic cases of sarcoidosis. When patients are symptomatic or present with more advanced disease, corticosteroids, either topical or systemic, may improve lung function and symptoms. However, the impact of steroid therapy on disease progression and mortality is unclear, with little data available to evaluate long-term outcomes associated with steroid use. Steroid-sparing immunosuppressants have also been used with mixed results in patients refractory to or intolerant of steroid therapy. Overall, there remains a paucity of robust data to allow prognostication of clinical course or success of medical therapy. Clinical trials evaluating multiple therapies including hydroxychloroquine, mycophenolate mofetil, and a novel resokine pathway modulator are ongoing.
Of patients with extrapulmonary sarcoidosis, 50% to 70% exhibit abdominal involvement. Abdominal sarcoidosis is frequently asymptomatic and often discovered incidentally on imaging; case series of autopsies and fine-needle aspirates have confirmed that histologic involvement by the liver and spleen is much more common than symptomatic organomegaly, cytopenias, or organ dysfunction. In up to 33% of patients, multifocal lesions, usually asymptomatic, are seen on abdominal CT scan; these lesions are usually characterized as hypodense, and can be difficult to
chestjournal.org
Clinical Course
Flow cytometry of the BAL fluid revealed a cluster of differentiation 4 to cluster of differentiation 8 ratio of 4.2. The patient’s lymph node aspirate and left-sided upper lung biopsies revealed noncaseating granulomata. Fungal and AFB stains and cultures were negative. She was treated with oral prednisone. After 1 month of therapy, her symptoms had not yet resolved, and she continued to experience marked fatigue, dyspnea, and functional impairment.
e15
Clinical Pearls 1. Sarcoidosis may present with nonspecific symptoms of inflammation including anorexia, weight loss, and fatigue. It is therefore a differential consideration in patients with pulmonary involvement and syndromes that may otherwise suggest infection or malignancy.
or asymptomatic incidental lesions on abdominal imaging.
Acknowledgments Financial/nonfinancial disclosures: None declared. Other contributions: CHEST worked with the authors to ensure that the Journal policies on patient consent to report information were met.
2. Multisystem involvement is an important hallmark of sarcoidosis. Imaging abnormalities are frequently observed in the abdomen; however, these may be asymptomatic. Other systems to examine in cases of suspected sarcoidosis include the skin, eyes, and heart.
Suggested Readings
3. Sarcoidosis frequently involves the spleen, with potential manifestations of this involvement including abdominal discomfort resulting from splenomegaly, cytopenias because of hypersplenism,
Palmucci S, Torrisi SE, Caltabiano DC, et al. Clinical and radiological features of extra-pulmonary sarcoidosis: a pictorial essay. Insights Imaging. 2016;7(4):571-587.
e16 CHEST Pearls
Kimbrell OC Jr. Sarcoidosis of the spleen. N Engl J Med. 1957;257(3):128-131. Selroos O. Sarcoidosis of the spleen. Acta Med Scand. 1976;200(5): 337-340. Raber EL, Haba J, Beck P. Splenic sarcoidosis: a case report and review of the imaging findings of multiple incidental splenic lesions as the initial presentation of sarcoidosis. Can J Gastroenterol. 2011;25(9):477-478.
Bargagli E, Prasse A. Sarcoidosis: a review for the internist. Intern Emerg Med. 2018;13(3):325-331.
[
157#1 CHEST JANUARY 2020
]
CHEST Pearls
]
A Woman With Dyspnea, Weight Loss, and Splenic Lesions Jennifer S. Hanberg, BA; and Dana Dunne, MD
The patient is a 37-year-old hospital employee and current smoker with a 10 pack-year smoking history, who presented with dyspnea, chest pain, and weight loss. She was in her usual state of health until 4 months prior to admission when she developed intermittent left-sided chest pain, cough productive of scant yellow sputum, fevers, and anorexia. Initial chest radiograph was normal and her outpatient physician prescribed azithromycin, which she took without improvement. One month prior to admission, a follow-up chest radiograph revealed a left-sided upper lobe consolidation; she received a course of levofloxacin without improvement. At follow-up, given her occupation, 13.6-kg unintentional weight loss, and persistent pulmonary symptoms and infiltrate despite treatment for pneumonia, her provider referred her for admission with particular concern for exclusion of active TB. As a hospital employee with clinical exposure, she underwent annual TB screening, which was always negative. She had no known exposure to patients with TB. Her most recent travel was to the Midwestern United States, without significant outdoors exposure. Review of systems was positive for wheezing, anorexia, and arthralgias of both knees and the left ankle and wrist. There was no hemoptysis, leg swelling, visual changes, palpitations, or muscle weakness. CHEST 2020; 157(1):e13-e16 CASE PRESENTATION:
Physical Examination Findings On admission, the patient was thin and in no acute distress. She was afebrile with BP of 125/76 mm Hg, pulse rate of 67 beats/min, respiratory rate of 16 breaths/min, with 100% peripheral oxygen saturation on room air. Lung examination was remarkable for decreased breath sounds in the left upper lobe. Heart rate was regular and without murmurs. Her abdomen was benign without organomegaly appreciated. There was a nontender 1-cm left postauricular node. The rest of her examination was unremarkable.
Diagnostic Studies A broad laboratory workup was unremarkable, including serum chemistries, complete blood count, liver panel, procalcitonin, HIV Ag-Ab (fourth-generation)
AFFILIATIONS: From the Department of Internal Medicine, Yale University School of Medicine, New Haven, CT. CORRESPONDENCE TO: Dana Dunne, MD, Section of Infectious Diseases, PO Box 208056, 333 Cedar St, New Haven, CT 06520; e-mail: [email protected]
chestjournal.org
assay, and interferon-gamma release assay. Urinary histoplasma antigen and three sputum acid-fast bacilli smears were negative. Admission ECG showed sinus rhythm with a PR interval of 0.21 s. Chest CT scan confirmed the presence of a 2.9-cm left-sided upper lobe, nodular, noncavitating airspace consolidation surrouded by groud-glass opacities; this consolidation had been visualized on plain radiography prior to admission (Fig 1, Fig 2). Abdominal imaging revealed splenic hypodensities (Fig 3). Because of suspicion for malignancy vs fungal or mycobacterial infection, a bronchoscopy was performed; however, a biopsy was not performed at the time because of the apical location of the consolidation. BAL specimens were notable for
Copyright Ó 2019 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved. DOI: https://doi.org/10.1016/j.chest.2019.08.2181
e13
Figure 3 – Abdominal CT scan. The patient’s abdominal CT scan revealed multiple hypodense lesions of various sizes, some with septation.
Figure 1 – Chest radiograph. Two weeks prior to admission, the patient underwent chest radiograph.
Figure 2 – A-B, Chest CT angiography. A, Because of suspicion of pulmonary embolism, the patient underwent chest CT angiography. B, A representative slice of the mediastinum, showing adenopathy.
negative AFB smear, aspergillus antigen, nocardia and actinomyces cultures, and fungal culture. Cytology revealed abundant pulmonary macrophages and no malignant cells. Because of continued diagnostic uncertainty, a PET/CT scan was ordered, which revealed interval increase in size of the left-sided upper lobe opacity from 2.9 to 3.4 cm, and increased uptake in several mediastinal lymph nodes, the left-sided upper lobe mass, and the
e14 CHEST Pearls
Figure 4 – PET/CT scan. Hypermetabolic lesions in the left-sided upper lobe mass, splenic lesions, and scattered lymph nodes in the neck, chest, abdomen, and pelvis were observed.
spleen (Fig 4). A transbronchial biopsy and endobronchial ultrasound-guided biopsy were then performed, after which the patient was discharged from the hospital to await biopsy results.
What is the diagnosis? [
157#1 CHEST JANUARY 2020
]
Diagnosis: Sarcoidosis Discussion Sarcoidosis is an uncommon granulomatous disorder with protean manifestations that may mimic infectious or malignant processes. Its onset peaks in the third to fifth decades of life, with higher incidence in women and in patients of Northern European and African descent.
differentiate from lymphoma, metastasis, or granulomatous infection. Further characterization is possible with gadolinium-enhanced MRI, which classically reveals hypoenhancement and T1 and T2 hypointensity, differentiating the lesions from infectious lesions (usually T2 hyperintense), benign tumors (usually T2 hyperintense), and malignancies (T1 and T2 isointense and usually isoenhancing). PET/CT scan, although not useful for this differentiation, can help identify involved tissues for biopsy.
Although the exact sequence of etiopathologic events remains unknown, a favored theory is that sarcoidosis is a multifactorial process requiring both genetic susceptibility and an environmental insult. This insult may take the form of presentation of a specific antigen by activated macrophages, leading to an overexuberant T-cell and macrophage response and subsequent widespread granuloma formation and systemic inflammation. Sarcoidosis most commonly involves the lungs and hilar lymph nodes, but virtually every organ system can be affected. In addition, the systemic inflammation associated with this condition can lead to nonspecific symptoms including weight loss, fatigue, fevers, and night sweats.
The clinical course of sarcoidosis is variable and difficult to predict, with two-thirds of patients experiencing spontaneous remission and between 10% and 30% experiencing chronic disease. Among patients with chronic or progressive disease, significant morbidity can result from cardiac involvement (which may lead to arrhythmia), ocular involvement (which may lead to visual impairment), neurosarcoidosis, and progressive lung fibrosis (which may become severe enough to warrant evaluation for lung transplantation). Screening for involvement of the eyes and heart is recommended with ophthalmologic evaluation and electrocardiography.
The latest formal guideline regarding the diagnosis of systemic sarcoidosis comes from the 1999 Sarcoidosis Consensus Statement, which requires a compatible clinico-radiographic picture, the presence of noncaseating granulomata on histology, and exclusion of alternative diagnoses. The statement also notes that a diagnosis of sarcoidosis is not established by the sole presence of granulomata in a single organ (eg, skin). The subjectivity of the requirement for a compatible clinical picture and reasonable degree of exclusion of alternative diagnoses, without any formal discussion of what this reasonable level might entail, has led to recent attempts to formalize the process of diagnosing sarcoidosis. However, to date, there is no widely accepted formulaic diagnostic algorithm.
Medical therapy is generally not recommended in asymptomatic cases of sarcoidosis. When patients are symptomatic or present with more advanced disease, corticosteroids, either topical or systemic, may improve lung function and symptoms. However, the impact of steroid therapy on disease progression and mortality is unclear, with little data available to evaluate long-term outcomes associated with steroid use. Steroid-sparing immunosuppressants have also been used with mixed results in patients refractory to or intolerant of steroid therapy. Overall, there remains a paucity of robust data to allow prognostication of clinical course or success of medical therapy. Clinical trials evaluating multiple therapies including hydroxychloroquine, mycophenolate mofetil, and a novel resokine pathway modulator are ongoing.
Of patients with extrapulmonary sarcoidosis, 50% to 70% exhibit abdominal involvement. Abdominal sarcoidosis is frequently asymptomatic and often discovered incidentally on imaging; case series of autopsies and fine-needle aspirates have confirmed that histologic involvement by the liver and spleen is much more common than symptomatic organomegaly, cytopenias, or organ dysfunction. In up to 33% of patients, multifocal lesions, usually asymptomatic, are seen on abdominal CT scan; these lesions are usually characterized as hypodense, and can be difficult to
chestjournal.org
Clinical Course
Flow cytometry of the BAL fluid revealed a cluster of differentiation 4 to cluster of differentiation 8 ratio of 4.2. The patient’s lymph node aspirate and left-sided upper lung biopsies revealed noncaseating granulomata. Fungal and AFB stains and cultures were negative. She was treated with oral prednisone. After 1 month of therapy, her symptoms had not yet resolved, and she continued to experience marked fatigue, dyspnea, and functional impairment.
e15
Clinical Pearls 1. Sarcoidosis may present with nonspecific symptoms of inflammation including anorexia, weight loss, and fatigue. It is therefore a differential consideration in patients with pulmonary involvement and syndromes that may otherwise suggest infection or malignancy.
or asymptomatic incidental lesions on abdominal imaging.
Acknowledgments Financial/nonfinancial disclosures: None declared. Other contributions: CHEST worked with the authors to ensure that the Journal policies on patient consent to report information were met.
2. Multisystem involvement is an important hallmark of sarcoidosis. Imaging abnormalities are frequently observed in the abdomen; however, these may be asymptomatic. Other systems to examine in cases of suspected sarcoidosis include the skin, eyes, and heart.
Suggested Readings
3. Sarcoidosis frequently involves the spleen, with potential manifestations of this involvement including abdominal discomfort resulting from splenomegaly, cytopenias because of hypersplenism,
Palmucci S, Torrisi SE, Caltabiano DC, et al. Clinical and radiological features of extra-pulmonary sarcoidosis: a pictorial essay. Insights Imaging. 2016;7(4):571-587.
e16 CHEST Pearls
Kimbrell OC Jr. Sarcoidosis of the spleen. N Engl J Med. 1957;257(3):128-131. Selroos O. Sarcoidosis of the spleen. Acta Med Scand. 1976;200(5): 337-340. Raber EL, Haba J, Beck P. Splenic sarcoidosis: a case report and review of the imaging findings of multiple incidental splenic lesions as the initial presentation of sarcoidosis. Can J Gastroenterol. 2011;25(9):477-478.
Bargagli E, Prasse A. Sarcoidosis: a review for the internist. Intern Emerg Med. 2018;13(3):325-331.
[
157#1 CHEST JANUARY 2020
]