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wheezing or stridor🚧 施工中
wheezing or stridor
Nadia L. Bennett, MD, MSEd
CHIEF COMPLAINT
PATIENT
Mr. C is a 32-year-old man with occasional wheezing.
What is the differential diagnosis of wheezing? How would you frame the differential?
CONSTRUCTING A DIFFERENTIAL DIAGNOSIS
Wheezing and stridor are symptoms of airflow obstruction caused by the vibration of the walls of pathologically narrow airways. Wheezing is a high-pitch musical sound produced primarily during expiration by airways of any size. Stridor is a single high-pitch, inspiratory sound that is produced by large airways with severe narrowing; it may be caused by severe obstruction of any proximal airway.
Stridor is often a sign of impending airway obstruction and should be considered an emergency.
Distinguishing between wheezing and stridor is essential. Typically, patients with either wheezing or stridor describe their symptoms simply as wheezing. The physical exam will determine whether the patient actually has wheezing or stridor. Because the differential diagnosis for airway obstruction is extensive, an anatomic approach is helpful.
A. Stridor
1. Nasopharynx and oropharynx
a. Tonsillar hypertrophy
b. Pharyngitis
c. Peritonsillar abscess
d. Retropharyngeal abscess
2. Laryngopharynx and larynx
a. Epiglottitis
b. Paradoxical vocal cord movement (PVCM)
c. Anaphylaxis and laryngeal edema
d. Postnasal drip
e. Benign and malignant tumors of the larynx and upper airway
f. Vocal cord paralysis
3. Trachea
a. Tracheal stenosis
b. Tracheomalacia
c. Goiter
4. Proximal airways
a. Foreign-body aspiration
b. Ingestion or inhalation of caustic materials
c. Burn injury
B. Wheezing
1. Proximal airways: Bronchitis
2. Distal airways
a. Asthma
b. Chronic obstructive pulmonary disease (COPD)
c. Pulmonary edema
d. Pulmonary embolism
e. Bronchiectasis
f. Bronchiolitis
g. Heart failure
h. Sarcoidosis
Mr. C has been having symptoms for 1–2 years. His symptoms have always been so mild that he has never sought care. Over the last month, he has been more symptomatic with wheezing, chest tightness, and shortness of breath. His symptoms are worse with exercise and worse at night. He notes that he often goes days without symptoms.
At this point, what is the leading hypothesis, what are the active alternatives, and is there a must not miss diagnosis? Given this differential diagnosis, what tests should be ordered?
RANKING THE DIFFERENTIAL DIAGNOSIS
Figure 33-1 shows an algorithmic approach to the patient with wheezing or stridor. The presence of wheezing, chest tightness, and shortness of breath are pivotal clues that place asthma at the top of the differential diagnosis. Although asthma is by far the most likely diagnosis, other diseases that could account for recurrent symptoms of airway obstruction should be considered (Table 33-1). Allergic rhinitis can cause cough and wheezing, but it would be very unusual for it to cause shortness of breath. Vocal cord dysfunction, such as PVCM, is frequently confused with asthma and can cause recurrent stridor. COPD can also cause chronic wheezing and pulmonary symptoms.
Figure 33-1. Evaluation of the patient with wheezing or stridor.
Table 33-1. Diagnostic hypotheses for Mr. C.
On further history, Mr. C reports that he had asthma as a child and was treated for years with theophylline. He was without symptoms until he moved 2 years ago.
He reports that his symptoms are worst when he has a cold, when he jogs, and when he is around dogs or cats. His most common symptoms are chest tightness and dyspnea. Only when his symptoms are at their worst does he hear wheezing. He has never smoked cigarettes.
On physical exam he appears well. His vital signs are BP, 120/76 mm Hg; RR, 14 breaths per minute; pulse, 72 bpm; temperature, 36.9°C. His lung exam is normal without wheezes or prolonged expiratory phase. His peak flow is 550 L/min (87% of predicted).
Is the clinical information sufficient to make a diagnosis? If not, what other information do you need?
Leading Hypothesis: Asthma
Textbook Presentation
Asthma commonly presents as recurrent episodes of dyspnea, often with chest tightness, cough, and wheezing. Patients usually report stereotypical triggers (eg, allergens, cold weather, exercise) and rapid response to beta-agonist inhalers.
Asthma is a common cause of wheezing; however, the absence of wheezing by no means excludes the diagnosis of asthma.
Disease Highlights
A. Definition: The definition of asthma in the National Asthma Education and Prevention Program’s Expert Panel Report is “A chronic inflammatory disease of the airways in which many cells and cellular elements play a role.” “In susceptible individuals, this inflammation causes recurrent episodes of wheezing, breathlessness, chest tightness, and cough, particularly at night and/or in the early morning. These episodes are usually associated with widespread but variable airflow limitation that is often reversible either spontaneously or with treatment.”
B. Clinical manifestations
1. Asthma is recurrent and intermittent.
a. Most patients will have periods with no, or only mild, symptoms.
b. Patients with severe disease will have persistent symptoms.
2. Asthma usually presents during childhood but presentation as an adult is not uncommon.
3. Airway function fluctuates in people with asthma more widely than in those without the diagnosis.
a. Airway function is most commonly measured by peak expiratory flow (PEF).
b. Values are generally lowest in the morning and highest at mid-day.
c. PEF will vary by more than 20% in asthmatic patients over the course of the day.
4. Identifying exacerbating factors and timing of symptoms is important. It aids in the diagnosis of asthma (exacerbating factors are stereotypical) and in treatment (if the factors are avoidable or reversible).
a. Asthma frequently worsens at night (probably related to decreased mucociliary clearance, airway cooling, and low levels of endogenous catecholamines).
b. Asthma frequently worsens with exercise (probably related to airway cooling and drying).
c. Viral infections are a common cause of asthma exacerbations.
d. A long list of airway irritants and occupational agents may cause or exacerbate asthma by a number of mechanisms:
(1) Cigarette smoke, perfumes, exhaust
(2) Corrosive agents (ammonia)
(3) Pharmacologic agents (organophosphates)
(4) Reflex bronchoconstriction (ozone)
(5) IgE-mediated (latex)
Asthma should be in the differential diagnosis of any patient with intermittent respiratory symptoms.
C. Classification: The present classification scheme for asthma helps focus attention on the severity of the asthma and dovetails nicely with treatment considerations (Table 33-2). It should be noted, however, that by necessity this scheme simplifies asthma phenotypes and many patients do not fit well into a single category.
Table 33-2. Classification of asthma severity.
D. Exacerbations or “flares”
1. Asthma exacerbations are periods of increased disease activity identified by increased
a. Airflow obstruction
b. Symptoms
c. Medication use
2. Exacerbations may or may not be caused by an identifiable trigger.
3. Management of an exacerbation depends on an accurate assessment of the cause of the exacerbation and the risk to the patient.
Evidence-Based Diagnosis
A. There is no single test to diagnose asthma; the diagnosis is clinical, based on multiple findings in the history, physical exam, and spirometry.
B. Asthma is easily recognized when it presents with intermittent wheezing; in fact, the diagnosis is often made by the patient.
C. Diagnosing asthma is challenging when it presents in atypical ways. Asthma should be high in the differential diagnosis when a patient has any of the following intermittent symptoms:
1. Wheezing
2. Dyspnea
3. Cough
4. Chest tightness
D. The key points in establishing the diagnosis of asthma are:
1. Episodic symptoms of airflow obstruction
2. Reversibility of the airflow obstruction
3. Exclusion of other likely diseases
E. There are not great data on the test characteristics of various symptoms of asthma.
1. One large study interviewed nearly 10,000 healthy, community-dwelling people regarding pulmonary symptoms in the preceding 12 months.
a. 225 of these people had asthma, defined as reporting that they had asthma and that a medical professional had confirmed the diagnosis.
b. The test characteristics of the most predictive historical features are shown in Table 33-3.
Table 33-3. Test characteristics of symptoms for the diagnosis of asthma.
c. It is important to note that these test characteristics were derived in a healthy population. Specificities would be lower in a population containing patients with other cardiopulmonary diseases.
2. In another study, which used a methacholine challenge test to diagnose asthma, 90% specificity was achieved for making the diagnosis of asthma with the question, “Do you cough during or after exercise?”
F. Other clues that make the diagnosis more likely are outlined in the National Asthma Education and Prevention Program’s Expert Panel Report:
1. Diurnal variability in PEF (> 20% variability between best and worst)
2. Symptoms occur or worsen in the presence of:
a. Exercise
b. Viral infections
c. Animals with fur or hair
d. House dust mites
e. Mold
f. Smoke
g. Pollen
h. Weather changes
i. Laughing or hard crying
j. Airborne chemicals or dust
3. Symptoms occur or worsen at night.
G. There is some evidence that people with asthma describe their dyspnea differently from people with other cardiorespiratory diseases. They are more likely to refer to symptoms of chest tightness or constriction.
H. Pulmonary function tests (PFTs)
1. Spirometry is recommended for patients with suspected asthma. The results are useful both as a diagnostic test and to provide objective data to be used in determining management.
2. Figure 33-2 shows a schematic diagram of many of the lung volumes, capacities, and flows measured in PFTs.
Figure 33-2. Pulmonary function tests. ERV, expiratory reserve volume; FEF 25–75%, forced expiratory flow measured during exhalation of 25–75% of the FVC; FEV1, forced expiratory volume in 1 second; FRC, functional reserve capacity; FVC, forced vital capacity; IC, inspiratory capacity; RV, residual volume; TLC, total lung capacity; VC, vital capacity; VT, tidal volume.
3. The following all support the diagnosis of asthma:
a. Decreased forced expiratory volume in 1 second (FEV1)
b. Decreased FEV1/forced vital capacity (FVC) ratio
c. Reversibility (defined as at least a 200 mL increase in FEV1 and > 12% improvement with bronchodilators)
I. Other tests
1. Chest radiography is useful mainly in excluding other diseases.
2. Methacholine challenge
a. Useful for diagnosing (or excluding) asthma in patients who have a suspicious history but normal PFTs
b. A decrease in FEV1 of < 20% has a 95% negative predictive value.
Treatment
A. The goals of asthma therapy are to
1. Prevent chronic symptoms (dyspnea, exercise intolerance, nighttime wakening)
2. Maintain normal pulmonary function (assessed by PEF and spirometry)
3. Maintain normal levels of physical activity.
a. It can be challenging to achieve this goal.
b. Many patients become accustomed to being limited by their breathing and thus may not report that their breathing limits their activity.
4. Prevent exacerbations
B. The National Asthma Education and Prevention Program’s Expert Panel Report lists 4 components of asthma care.
1. Periodic evaluation to assess asthma severity and monitor whether asthma control is achieved and maintained. This entails accurately diagnosing the severity of patients’ symptoms at baseline and during therapy.
2. Patient education
3. Control of environmental factors and comorbid conditions that affect asthma. This may include pharmacologic and nonpharmacologic interventions for, among others, the following:
a. Tobacco use and secondhand smoke
b. Air pollution (ozone, SO2, NO2)
c. Gastroesophageal reflux disease (GERD)
d. Common allergens
e. Dander, dust, mold, insects
It is critical to control diseases and factors that exacerbate asthma in order to achieve control with the least intensive regimen possible.
4. Medication use
a. Medical therapy for asthma itself is aimed at treating the factors that cause the disease and its symptoms. The drugs are summarized in Table 33-4.
Table 33-4. Pharmacotherapy of asthma.
b. The current guidelines advocate a stepwise approach to management. Step 1 is for patients with intermittent asthma and steps 2–6 build on one another for worsening levels of persistent asthma.
(1) Step 1: Short-acting beta-2-agonists used as needed.
(2) Step 2: Low-dose inhaled corticosteroids.
(3) Step 3: Low-dose inhaled corticosteroids with long-acting beta-2-agonists. An alternative at this point is medium-dose inhaled corticosteroids.
(4) Step 4: Medium-dose inhaled corticosteroids with long-acting beta-2-agonists.
(5) Step 5: High-dose inhaled corticosteroids with long-acting beta-2-agonists with consideration of omalizumab for patients with allergies
(6) Step 6: High-dose inhaled corticosteroids with long-acting beta-2-agonists and oral corticosteroids with consideration of omalizumab for patients with allergies
c. Consideration should be given for escalating therapy whenever short-acting beta-2-agonists are being used more than twice a week.
d. Efforts should always be made to step down therapy when control is achieved.
e. Inhaled tiotropium may be beneficial for patients whose asthma is poorly controlled with inhaled corticosteroids with long-acting beta-2-agonists.
At each visit, review a patient’s medications and symptoms and make an effort to step down therapy when possible.
C. Refractory asthma: Although most cases of asthma can be well controlled, there are patients whose asthma is refractory to the standard therapy. This may be due to the inherent severity of the disease or other factors:
1. Problem with adherence to prescribed regimen. This includes poor inhaler technique (common) and poor understanding of the use of maintenance and as-needed medications.
2. Unrecognized or untreated precipitants, such as GERD, sinusitis, and allergies.
3. Incorrect diagnosis; consider other causes of chronic intermittent airway obstruction such as PVCM, COPD, or sarcoid.
4. The presence of rare diseases that can cause or worsen asthma, such as eosinophilic granulomatosis with polyangiitis (formerly Churg-Strauss syndrome) or allergic bronchopulmonary aspergillosis.
D. Exacerbations
1. History
a. Duration of exacerbation
(1) Exacerbations that are very recent (hours) and mild may improve with beta-agonists alone, while more established and more severe exacerbations require corticosteroids.
(2) Because early treatment leads to better outcomes, it is important that patients monitor their own disease and know how to initiate appropriate treatment and contact their physician when necessary.
b. Precipitants
(1) Consider if there is a precipitant of the exacerbation that needs to be addressed (eg, sinusitis, allergen exposure).
(2) Consider if there is an exacerbating factor that hospital admission might alleviate (eg, house painting, recent insect extermination).
c. Severity of disease. The following patients are at risk for asthma-related death. Any patient with an exacerbation and 1 of these factors require special attention with regards to education, monitoring, and care:
(1) Previous severe exacerbations
(2) Multiple, recent emergency department visits or hospitalizations
(3) Use of more than 2 canisters of beta-agonist in the past month
(4) Current use or recent discontinuation of systemic corticosteroids
(5) Difficulty perceiving airflow obstruction
(6) Low socioeconomic status or inner-city residence
(7) Illicit drug use
(8) Comorbid medical or psychiatric disease
Any patient with risk factors for asthma-related death who presents with an asthma exacerbation requires special attention, beginning with serious consideration for hospitalization.
2. Physical exam
a. The lung exam is generally a poor marker of the severity of disease.
b. Lack of wheezing can either reflect improved or worsening airflow.
Patients whose decreased wheezing is accompanied by worsening distress, diminished breath sounds, or decreased mental status probably have worsening airflow obstruction. Conversely, a patient whose decreased wheezing is accompanied by lessened respiratory distress and normal breath sounds likely has improved airflow obstruction.
3. Other tests
a. Spirometry is crucial in determining severity of exacerbation.
(1) A mild exacerbation is defined by symptoms only with activity and a FEV1 or PEF or ≥ 70% of predicted.
(2) A moderate exacerbation includes symptoms with usual activities and a FEV1 or PEF 40–69% of predicted.
(3) In a severe exacerbation, patients have dyspnea at rest and dyspnea that interferes with conversation and a FEV1 or PEF < 40% of predicted.
Spirometry and the history of the patient’s prior exacerbations are the most important pieces of information for making admission decisions.
b. Arterial blood gases (ABGs) are useful in patients whose peak flows are not improving with treatment. ABGs during severe exacerbations should reveal a respiratory alkalosis. A respiratory acidosis (or even a normal PCO2 during a severe exacerbation) is very worrisome because it suggests severe airway narrowing and respiratory fatigue.
c. Chest radiograph is only helpful for identifying the uncommon concomitant infection or complication (eg, pneumothorax).
4. Treatment of exacerbations. Figure 33-3 is a guide to the management of asthma exacerbations.
Figure 33-3. Management of asthma exacerbation. (Adapted with permission from National Heart, Lung, and Blood Institute, National Asthma Education and Prevention Program. Expert Panel Report 3: guidelines for the diagnosis and management of asthma: full report 2007.)
MAKING A DIAGNOSIS
Mr. C was scheduled for spirometry and prescribed an albuterol inhaler. He was told to use 2 puffs as needed as well as 30 minutes before exercise or expected animal exposure. On follow-up 6 weeks later, Mr. C reported improvement in his symptoms. He was able to exercise without difficulty as long as he was using his inhalers and could spend short amounts of time around friends’ pets.
Spirometry revealed an FEV1 of 70% of predicted that normalized with albuterol.
At follow up a few months later he reported that he was using his albuterol inhaler daily to maintain his asthma control.
Have you crossed a diagnostic threshold for the leading hypothesis, asthma? Have you ruled out the active alternatives? Do other tests need to be done to exclude the alternative diagnoses?
Mr. C’s clinical history is consistent with asthma. The history of childhood asthma both makes asthma the most likely diagnosis and makes his complaint of “wheezing” more reliable. The absence of wheezing on exam certainly does not exclude the diagnosis of asthma. He has intermittent symptoms of wheezing, dyspnea, and chest tightness. The presence of exacerbating factors and the results of spirometry further raise the likelihood of asthma as the diagnosis.
Because asthma is very common and the initial treatment is benign, the treatment threshold is low. A therapeutic trial of medication is nearly always appropriate.
CASE RESOLUTION
The patient’s history and response to therapy confirms the diagnosis of asthma. The patient has no nasal symptoms that would suggest allergic rhinitis. COPD is unlikely without a smoking history. Vocal cord dysfunction will be discussed below and is also unlikely. Heart failure is unlikely given the patient’s age, the absence of a history of heart disease, and his response to bronchodilators.
Given the frequency of his use of albuterol, the patient was given low-dose inhaled corticosteroids. His symptoms subsequently improved with only rare need for albuterol. The following year, Mr. C’s symptoms worsened. His asthma was eventually controlled with higher doses of inhaled corticosteroids. He was able to wean these medications after he had carpets in his house removed.
CHIEF COMPLAINT
PATIENT
Mrs. P is a 62-year-old woman who arrives at the emergency department with shortness of breath and wheezing. She says that the symptoms have been present for 3 days. The symptoms are present both at rest and with exertion and have not improved with an albuterol inhaler.
She reports that she has had these symptoms intermittently for 6 years. When the symptoms occur, they generally last for hours to a few days. She had been diagnosed with asthma and took long- and short-acting beta-agonists and inhaled and systemic corticosteroids, before coming off all medications 1 year ago. She stopped her medications out of frustration with side effects and perceived lack of efficacy. She decided instead to treat herself with yoga and meditation. She reports no episodes since this decision.
Presently she denies cough, chest pain, fever, or rhinitis. She does report hoarseness that occurs when her breathing is bad.
At this point, what is the leading hypothesis, what are the active alternatives, and is there a must not miss diagnosis? Given this differential diagnosis, what tests should be ordered?
RANKING THE DIFFERENTIAL DIAGNOSIS
As discussed above, asthma is very common and should be considered in anyone with intermittent pulmonary symptoms. The lack of symptom improvement with a beta-agonist and the discontinuation of an aggressive asthma regimen without ill effects both argue against the diagnosis of asthma in this case. In addition, the patient’s complaint of hoarseness is atypical in asthma. (Hoarseness does sometimes occur with asthma if there is associated GERD, postnasal drip, or vocal cord myopathy caused by inhaled corticosteroids.) Determining whether her symptoms are wheezing or stridor will help narrow the diagnosis. PVCM is a syndrome of episodic adduction of the vocal cords producing stridor. The lack of response to bronchodilators and associated hoarseness are clues to this diagnosis. GERD is a very common diagnosis (see Chapter 9). It can cause and worsen asthma and can cause hoarseness via irritation of the vocal cords. It is sometimes associated with PVCM. Angioedema occurs when vascular permeability increases leading to tissue edema. Airway compromise and stridor can occur. It is usually associated with other signs such as facial swelling, tongue swelling, or hives. Table 33-5 lists the differential diagnosis.
Table 33-5. Diagnostic hypotheses for Mrs. P.
On further history, she reports that her present symptoms are moderate for her. Past medical history is remarkable only for depression and hypertension. Her only medication is enalapril. She has no known drug allergies. She does not smoke cigarettes.
Is the clinical information sufficient to make a diagnosis? If not, what other information do you need?
Leading Hypothesis: PVCM
Textbook Presentation
PVCM typically presents as episodic attacks of respiratory distress accompanied by wheezing or stridor or both. The respiratory distress is often accompanied by voice pathology and does not respond to traditional asthma therapy.
Disease Highlights
A. PVCM has gone by many names including vocal cord dysfunction, episodic laryngeal dyskinesia, Munchausen stridor, psychogenic stridor, and factitious asthma.
B. Most commonly occurs in younger patients (< 35 years) but can be seen in any age.
C. Female predominance
D. PVCM has been associated with a number of conditions and activities including:
1. Anxiety and other psychiatric conditions
2. Exercise
3. Airway injury (iatrogenic, inhalational)
4. GERD
5. Neurologic injury
E. The symptoms are not produced consciously.
F. During asymptomatic periods, there are no abnormalities of lung function.
1. Spirometry is normal.
2. There is none of the increased variability in airway function seen with asthma.
3. Bronchial provocation tests are normal.
Evidence-Based Diagnosis
A. Given the prevalence of asthma and the similarity of the presentation, asthma needs to be excluded in any patient in whom PVCM is suspected. This is especially true as the 2 disorders may coexist.
B. Clues to the differentiation of the diseases are:
1. The lack of exacerbating factors (eg, exercise, allergens) and diurnal variation seen with asthma.
2. The lack of response to asthma medications.
3. The occasional resolution of symptoms during sleep.
4. The presence of voice pathology during attacks.
5. The preponderance of auscultatory findings in the neck.
a. PVCM should really produce inspiratory stridor, as opposed to the predominantly expiratory wheezing heard with asthma.
b. In practice, these can be hard to differentiate.
6. A flattened inspiratory limb on flow-volume loops suggesting variable extrathoracic airway obstruction.
C. The definitive diagnosis is made during laryngoscopy.
1. There is adduction of the vocal cords during flares.
2. There is generally normal vocal cord function between flares.
Treatment
A. There are no controlled trials of treatments for PVCM.
B. Speech therapy, concentrating on laryngeal relaxation seems to be the most effective therapy.
C. Psychiatric intervention is suggested for patients with psychiatric illness.
D. Acute attacks may be quite hard to manage.
1. Helium/oxygen mixtures have been suggested to obtain better flow through the narrowed larynx though there is no evidence to support its utility.
2. Instructing the patient to lay his tongue on the floor of the mouth and breathe through pursed lips may also help.
MAKING A DIAGNOSIS
On physical exam, the patient is in mild respiratory distress. Her voice is hoarse and “squeaky.” Her vital signs are temperature, 37.1°C; pulse, 110 bpm; BP, 140/90 mm Hg; RR, 32 breaths per minute. There is inspiratory and expiratory stridor in the neck transmitted throughout the lungs.
The remainder of the physical exam was normal.
PEF is 300 L/min, 70% of predicted.
Have you crossed a diagnostic threshold for the leading hypothesis, PVCM? Have you ruled out the active alternatives? Do other tests need to be done to exclude the alternative diagnoses?
The physical exam is consistent with stridor and the presence of recurrent stridor makes PVCM likely. The other important diagnosis to consider at this point is angioedema.
Alternative Diagnosis: Angioedema
Textbook Presentation
Angioedema presents with the acute swelling of soft tissues, especially the face, lips, tongue, larynx, or foreskin. Bowel edema can result in abdominal pain. Patients nearly always have a history of angioedema or a risk factor for it.
Disease Highlights
A. The onset of angioedema is usually rapid, over minutes to hours.
B. Angioedema may be caused by:
1. Medications (angiotensin-converting enzyme [ACE] inhibitors and nonsteroidal anti-inflammatory drugs [NSAIDs] being, by far, the most common culprits)
2. Allergic reactions
3. Hereditary and acquired forms of C1-inhibitor deficiency
C. The presentation can range from mild, only sensed by the patient; to disfiguring, obvious to the casual observer; to life-threatening.
D. The diverse causes of angioedema produce symptoms by different mechanisms, have different presentations, and different treatments.
1. Histamine-related angioedema
a. Almost always accompanied by pruritus and urticaria (hives).
b. Usually related to an allergic exposure such as an insect bite or a food.
c. Urticaria can also be chronic, caused by allergy, drug effect, autoimmune phenomena, or malignancy.
2. Nonhistamine-related angioedema (caused by elevated levels of bradykinin)
a. Most commonly the result of ACE inhibitor therapy
b. Deficiency of C1-inhibitor also causes elevated bradykinin levels as well as elevated C2b levels, another cause of angioedema.
If angioedema is associated with urticaria, it is not due to ACE inhibitor therapy.
Evidence-Based Diagnosis
A. A diagnosis of angioedema is clinical, based on the recognition of angioedema and associated symptoms.
B. Angioedema most commonly presents as swelling of the lips, tongue, or both.
C. Figure 33-4 presents a useful algorithm for considering the differential diagnosis and treatment of angioedema.
Figure 33-4. Differential diagnosis and treatment of angioedema.
Treatment
A. The most critical aspect of the management of angioedema is airway stabilization.
B. All patients receive H1- and H2-blockers as well as corticosteroids.
C. Patients with airway compromise or any intraoral swelling should also receive epinephrine.
D. Patients need to be closely monitored because intubation is sometimes necessary.
E. Patients with C1-inhibitor deficiency can be treated with androgens, which increase the production of C1-inhibitor, or C1-inhibitor concentrate. Patients with C1-inhibitor deficiency should also be counseled on avoiding estrogen containing medications.
CASE RESOLUTION
A helium oxygen mixture was given to the patient briefly before laryngoscopy was performed. The findings on laryngoscopy were consistent with PVCM. The patient was counseled in the emergency department on ways to improve her airflow and symptoms subsided over the next hour. The patient spent 2 days in the hospital, experiencing only 1 mild episode of dyspnea during the period of observation.
Laryngoscopic findings can make the diagnosis of PVCM. Except for her use of an ACE inhibitor, there is little evidence to support angioedema; the patient has no facial swelling, and there are no consistent findings on laryngoscopy.
CHIEF COMPLAINT
PATIENT
Mr. S is a 50-year-old man who arrives at the emergency department with sore throat, fever, and wheezing. He reports being well until 2 days ago when his sore throat started. Over the last 2 days, the sore throat became progressively more severe and he lost his voice. On the morning of admission, a fever of 38.0°C and wheezing developed. He was also unable to eat because of the pain. He has never had similar symptoms.
At this point, what is the leading hypothesis, what are the active alternatives, and is there a must not miss diagnosis? Given this differential diagnosis, what tests should be ordered?
RANKING THE DIFFERENTIAL DIAGNOSIS
The pivotal points in Mr. S’s presentation are the acuity of the illness and the fever. Both of these points make an infectious etiology likely. Because the symptoms are not recurrent, asthma (the most common cause of airway obstruction) is unlikely. Acute infectious causes need to be considered first. These include common conditions, such as pharyngitis, and rare but serious causes, such as epiglottitis and retropharyngeal abscess. Angioedema is possible, but the infectious symptoms (fever and pain) and the lack of visible swelling make this less likely. Aspiration of a foreign body could cause either a pneumonia or infection of the soft tissues of the neck resulting in fever. Table 33-6 lists the differential diagnosis.
Table 33-6. Diagnostic hypotheses for Mr. S.
On physical exam, Mr. S is in obvious distress. He is uncomfortable, is sitting upright, and speaks in a muffled voice. His vital signs are temperature, 38.3°C; pulse, 110 bpm; BP, 128/88 mm Hg; RR, 18 breaths per minute. Examination of the oropharynx is notable only for mild tonsillar edema without exudates. There is diffuse cervical lymphadenopathy and significant tenderness over the anterior neck. The neck is supple. Lungs are clear, but there is stridor transmitted from the neck.
Is the clinical information sufficient to make a diagnosis? If not, what other information do you need?
The patient’s physical exam clarifies the picture; Mr. S has stridor. In a patient with acute stridor and infectious symptoms, epiglottitis and retropharyngeal abscess must top the differential diagnosis.
Leading Hypothesis: Epiglottitis
Textbook Presentation
Fever and sore throat are usually the presenting symptoms. There can be evidence of varying degrees of airway obstruction including wheezing, stridor, and drooling. The disease has become significantly less common in children since the development and use of the Haemophilus influenzae B vaccine.
Disease Highlights
A. Epiglottitis is an infectious disease, classically caused by H influenzae, which causes swelling of the epiglottis and supraglottic structures.
B. Because epiglottitis can rapidly cause airway compromise, the diagnosis should always be considered an airway emergency.
C. The classic presentation is a patient with sore throat, muffled “hot potato” voice, drooling, and stridor.
D. H influenzae is cultured in only a small percentage of adult patients; respiratory viruses are the likely cause of most cases of epiglottitis.
E. Early in its course, epiglottitis may resemble pharyngitis.
Evidence-Based Diagnosis
A. The gold standard for diagnosis is visual identification of swelling of the epiglottis.
1. Otolaryngology consultation is thus mandatory if there is a suspicion for the disease.
2. Visualization can be achieved with direct or indirect laryngoscopy.
3. In patients with signs of severe disease (eg, muffled voice, drooling, and stridor), an experienced physician should perform direct laryngoscopy and be prepared to intubate the patient or perform a tracheostomy (if airway control cannot be obtained).
B. The classic symptoms of muffled voice, drooling, and stridor are seen rarely and signify imminent airway obstruction.
1. Stridor and the patient sitting in an erect posture are independent predictors of subsequent airway intervention.
2. The test characteristics of these signs for airway intervention are:
a. Stridor: Sensitivity, 42%; specificity, 94%; LR+, 7; LR−, 0.61.
b. Sitting erect at presentation: Sensitivity, 47%; specificity, 90%; LR+, 4.7; LR−. 0.59.
C. Common symptoms and signs of epiglottitis (prevalence given in parentheses)
1. Sore throat (95%)
2. Odynophagia (94%)
3. Muffled voice (54%)
4. Pharyngitis (44%)
5. Fever (42%)
6. Cervical adenopathy (41%)
7. Dyspnea (37%)
8. Drooling (30%)
9. Sitting erect (16%)
10. Stridor (12%)
D. Lateral neck films, a commonly used diagnostic tool, have a sensitivity of about 90%. The classic finding is the “thumb sign” of a swollen epiglottis.
A normal lateral neck film does not rule out epiglottitis. Laryngoscopy should be performed in a patient with a high clinical suspicion of epiglottitis, even if the neck film is normal.
Treatment
A. Airway control
1. All patients should be admitted to the intensive care unit (ICU) for close monitoring.
2. Patients with signs or symptoms of airway obstruction should be intubated electively.
3. Elective intubation is preferred because intubation in a patient with epiglottitis can be very difficult.
4. Some advocate prophylactic intubation of all patients.
B. Epiglottitis is an airway emergency.
1. Patients need to be monitored closely and not left alone until the airway is stable.
2. Patients should be accompanied to radiology or other testing.
C. Antibiotics
1. Antibiotics must be effective against H influenzae.
2. Second- or third-generation cephalosporins are usually recommended.
MAKING A DIAGNOSIS
Mr. S’s history is very concerning. His upright posture, voice changes, and stridor not only strongly suggest epiglottitis but also imminent airway closure. Foreign-body aspiration does not fit the history. Retropharyngeal abscess remains a possibility.
Given the concern for epiglottitis, lateral neck films were obtained, and an otolaryngologist was called to examine the patient’s upper airway.
Have you crossed a diagnostic threshold for the leading hypothesis, epiglottitis? Have you ruled out the active alternatives? Do other tests need to be done to exclude the alternative diagnoses?
Alternative Diagnosis: Retropharyngeal Abscess
Textbook Presentation
Retropharyngeal abscess can be seen in either children or adults. Patients usually have symptoms similar to those seen in epiglottitis but commonly have a history of a recent upper respiratory infection or trauma from recently ingested materials (bones), or procedures (pulmonary or gastrointestinal endoscopy).
Disease Highlights
A. Symptoms that suggest retropharyngeal abscess rather than epiglottitis are:
1. Patients with retropharyngeal abscesses often will sense a lump in their throat.
2. Patients are often most comfortable supine with neck extended (very different from epiglottitis).
Evidence-Based Diagnosis
A. The diagnosis of retropharyngeal abscess is made when a thickening of the retropharyngeal tissues is seen on lateral neck radiographs.
B. Radiographs are probably not 100% sensitive, so when radiographs are normal and clinical suspicion is high, CT scanning should be done to verify the diagnosis.
Treatment
A. Retropharyngeal abscesses are usually polymicrobial.
B. Treatment is both medical and surgical.
1. Surgical drainage should be accomplished as soon as possible.
2. Many antibiotics have been suggested. Coverage of gram-positive organisms and anaerobes make clindamycin a common choice.
CASE RESOLUTION
The patient’s lateral neck radiograph showed probable acute epiglottitis with a thumb sign. An otolaryngologist visualized an inflamed and edematous epiglottis and, given the patient’s symptoms and severity of the visualized airway obstruction, placed an endotracheal tube. Mr. S was admitted to the ICU and treated with a second-generation cephalosporin. Cultures of the blood and epiglottis were negative.
The patient’s infection was diagnosed on the lateral neck radiographs. Intubation was necessary because the patient had signs and symptoms of airway obstruction. The obstruction was visualized on laryngoscopy.
CHIEF COMPLAINT
PATIENT
Mrs. A is 52-year-old woman who comes to your office with shortness of breath and wheezing. She reports that her symptoms have been present for about 2 years. She reports almost constant, mild dyspnea that is worst with exercise or when she has a cold. Only rarely does she feel “nearly normal.” She also complains of a mild cough productive of clear sputum. She does not feel that her cough is much of a problem as it is significantly better since she stopped smoking 2 years ago.
At this point, what is the leading hypothesis, and what are the active alternatives? What other tests should be ordered?
RANKING THE DIFFERENTIAL DIAGNOSIS
The pivotal points in this case are the patient’s chronic dyspnea, wheezing, and smoking history. COPD and asthma should be high in the differential diagnosis. Heart failure is also a possibility. The patient’s smoking history is a risk factor for coronary disease, the most common cause of heart failure. As noted in Chapter 15, Dyspnea, heart failure frequently complicates COPD or is misdiagnosed as the pulmonary disease, especially when a patient presents with dyspnea. Bronchiectasis could cause symptoms of dyspnea, cough, and sputum production, but the patient’s sputum production seems to be a minor symptom (rather than a predominant symptom as is usually the case in bronchiectasis). Tuberculosis should probably be considered in the differential, since it can cause chronic cough and dyspnea. Given the chronic nature of the symptoms, if tuberculosis were the cause, weight loss and other constitutional signs would be expected. Table 33-7 lists the differential diagnosis.
Table 33-7. Diagnostic hypotheses for Mrs. A.
Mrs. A reports a 60 pack-year history of smoking. She stopped 2 years ago, after smoking 2 packs a day for 30 years, when her chronic cough began to worry her. She reports that she still coughs but only rarely brings up sputum.
She has not experienced fever, chills, weight loss, or peripheral edema. She does say that when her breathing is bad, it is worse when lying down. She has never had symptoms consistent with paroxysmal nocturnal dyspnea.
Orthopnea is a very nonspecific symptom. It is found in many types of cardiopulmonary disease.
Is the clinical information sufficient to make a diagnosis? If not, what other information do you need?
Leading Hypothesis: COPD
Textbook Presentation
Presenting symptoms of COPD include progressive dyspnea, decreased exercise tolerance, cough, and sputum production. The onset is usually slow and progressive with occasional acute exacerbations. A long smoking history is present in almost all patients with COPD who live in industrialized countries.
Disease Highlights
A. COPD is defined in the WHO/NHLBI Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease (GOLD) as a “disease state characterized by airflow limitation that is not fully reversible. The airflow limitation is usually both progressive and associated with an abnormal inflammatory response of the lungs to noxious particles or gases.”
B. COPD should be considered in any patient with a smoking history who has pulmonary complaints. These complaints can be:
1. Mild (smokers’ cough or lingering colds)
2. Moderate (chronic cough, sputum production, and dyspnea)
3. Severe (activity-limiting dyspnea with life-threatening exacerbations)
C. COPD can also be seen in patients without a smoking history but with significant exposure to secondhand smoke, occupational dust and chemicals and, especially in less developed countries, indoor air pollution from cooking stoves.
D. Because of the wide variation in disease course, it is impossible to give an average amount of exposure necessary to cause disease.
1. Pulmonary symptoms usually develop after about 10 years of exposure.
2. Airflow obstruction may develop later.
E. Emphysema and chronic bronchitis are currently being used less as descriptors of types of COPD.
1. Emphysema is a pathologic term not accurately correlating with its general clinical usage.
2. Chronic bronchitis is the presence of mucus production for most days of the month, 3 months of a year, for 2 successive years. This symptom does not suggest the airflow obstruction that causes the morbidity in COPD.
3. Due to the overlap and lack of specificity of these 2 terms, COPD should be used as the diagnostic term.
F. The GOLD staging system is often used to classify patients based on their symptoms and level of risk of exacerbations. The system uses symptom severity and exacerbation risk to classify COPD.
1. Symptoms, based on the Modified Medical Research Council (MMRC) dyspnea scale:
a. Grade 0: “I only get breathless with strenuous exercise.”
b. Grade 1: “I get short of breath when hurrying on level ground or walking up a slight hill.”
c. Grade 2: “On level ground, I walk slower than people of the same age because of breathlessness, or have to stop for breath when walking at my own pace.”
d. Grade 3: “I stop for breath after walking about 100 yards or after a few minutes on level ground.”
e. Grade 4: “I am too breathless to leave the house or I am breathless when dressing.”
2. Combined assessment
a. Group A is at low risk and is less symptomatic: ≤ 1 exacerbation/year, and grade 0–1 symptoms
b. Group B is at low risk but is more symptomatic: ≤ 1 exacerbation/year, and ≥ grade 2 symptoms
c. Group C is at high risk but has few symptoms: ≥ 2 exacerbations/year, and grade 0–1 symptoms
d. Group D is at high risk and has many symptoms: ≥ 2 exacerbations/year and ≥ grade 2 symptoms
G. The BODE index, a widely available clinical decision rule, takes into account other patient features, such as body mass index and 6-minute walk distance, to give a 4-year mortality.
Evidence-Based Diagnosis
A. The diagnosis of COPD is based on history, physical exam, and ancillary tests (primarily PFTs).
B. History
1. Important aspects of the history are:
a. Chronic cough
b. Lingering colds
c. Sputum production
d. Dyspnea
e. Decreased exercise tolerance
2. Other important historical features that argue for airflow limitation include:
a. Smoking history ≥ 70 pack-years: sensitivity, 40%; specificity, 95%; LR+, 8.0; LR–, 0.63.
b. Sputum production > ¼ cup: sensitivity, 20%; specificity, 95%; LR+, 4; LR–, 0.84.
C. Physical exam
1. The physical exam is useful mainly in patients with more advanced disease.
2. No findings are sensitive enough to exclude a diagnosis of COPD.
3. The test characteristics for some of the physical exam findings are listed in Table 33-8.
Table 33-8. Test characteristics for physical exam findings in COPD.
The absence of wheezing does not rule out, or even significantly decrease the likelihood of, COPD.
D. Combinations of historical features, signs and symptoms are most effective in diagnosing COPD.
1. There are many decision rules that aid in the diagnosis of COPD.
2. The combination of > 55 pack-year smoking history, wheezing on auscultation, and patient reported wheezing diagnoses airflow obstruction (LR+, 156).
3. The absence of cigarette smoking is the most effective test to rule out airflow obstruction (LR–, 0.18)
E. Spirometry
1. Spirometry should be done in all patients with suspected COPD and respiratory symptoms.
2. Because the results of spirometry are part of the information required to make a diagnosis of COPD, test characteristics cannot be calculated.
3. Although not formally incorporated into the GOLD staging, airflow limitation is considered important. GOLD recommends using postbronchodilator FEV1 after a patient meets a threshold of FEV1/FVC of < 0.7.
a. Mild: FEV1 ≥ 85% of predicted
b. Moderate: FEV1 > 50% to < 85% of predicted
c. Severe: FEV1 ≥ 30% to ≤ 50% of predicted
d. Very severe: FEV1 < 30% of predicted
4. Typically, PFTs in COPD reveal:
a. Increased total lung capacity secondary to decreased elastic recoil
b. Increased functional residual capacity and residual volume secondary to air trapping
c. Decreased FEV1 and FVC due to airflow obstruction
d. Decreased DLCO secondary to destruction of the oxygen/Hb interface.
F. Other tests
1. Spirometry with bronchodilator response is recommended to rule out asthma. Patients with completely reversible airflow obstruction likely have asthma.
2. Chest radiograph is generally not useful in diagnosing COPD.
a. Some findings are suggestive
(1) Upper lobe bullous disease (uncommon but nearly diagnostic)
(2) Flattened diaphragm on the lateral chest radiograph
(3) Large retrosternal air space
(4) Hyperlucency of the lungs
(5) Diminished distal vascular markings
b. Chest radiography is always recommended to rule out other causes of symptoms.
G. ABG measurement is recommended in patients with FEV1 < 40% predicted or right-sided heart failure.
H. Testing for alpha-1-antitrypsin deficiency (a rare cause of COPD) is recommended in patients:
1. In whom COPD develops before age 45 years
2. Who do not have a smoking history or suspicious exposure
In general, any patient with a smoking history who complains of chronic cough, sputum production, or dyspnea should be considered to have COPD if no other diagnosis can be made. Additional testing can be used to establish the diagnosis and assess severity.
Treatment
A. Management of stable disease
1. Nonpharmacologic and preventive therapy
a. Smoking cessation and avoidance of other inhaled toxic agents
Smoking cessation is more effective than any pharmacotherapy at preserving lung function in patients with COPD.
b. Exercise programs, if allowable from a cardiovascular standpoint
c. Vaccination against influenza and pneumococcal pneumonia
2. Pharmacologic
a. Patients with symptoms and an FEV1 < 60% of predicted benefit most from therapy. These patients should be prescribed bronchodilator inhalers, such as long-acting beta-agonist or anticholinergic inhalers.
b. Patients with less severe disease may benefit from treatment, especially as needed bronchodilators.
c. Combination therapy with both long-acting beta-agonist and anticholinergic inhalers may improve outcomes in patients who do not get a sufficient response with monotherapy.
d. Inhaled corticosteroids
(1) Use remains somewhat controversial
(2) There is some evidence that inhaled corticosteroids, used with long-acting beta-agonists or anticholinergics, decrease symptoms and reduce the frequency of exacerbations. This is probably most true in patients with some reversible airway obstruction on spirometry.
(3) They do not seem to affect the rate of decline in pulmonary function and may increase rates of pneumonia.
e. Home oxygen is recommended for persons with chronic hypoxia or cor pulmonale.
f. Patients who have exacerbations despite optimal therapy benefit from antibiotic prophylaxis, usually with azithromycin.
B. Management of exacerbations
1. Evaluation
a. Patients who are likely to have the worst outcomes have low baseline FEV1, PaO2, pH, and high PCO2. Discharge of such patients from an emergency department should only be done with great care.
b. Exacerbating factors
(1) Factors that may have led to the COPD exacerbation should be sought and addressed during treatment.
(2) Historical evidence of infection or exposure (air pollution, ozone) should be sought.
(3) All patients should have a chest radiograph to look for pneumonia.
(4) As discussed in Chapter 15, Dyspnea, if a cause of the exacerbation is not found, consideration should be given to pulmonary embolism and heart failure.
c. Unlike in the assessment of asthma exacerbations, spirometry is of little value in making admission decisions.
2. Therapy
a. Anticholinergic and beta-agonist inhalers should be given to all patients.
b. Systemic corticosteroids are effective when given for up to 2 weeks. For uncomplicated COPD exacerbations, a 5-day course of corticosteroids is typically given. There is no evidence that inhaled corticosteroids are effective.
3. Antibiotics are effective for more severe exacerbations.
4. Oxygen therapy is beneficial.
a. Oxygen does carry a risk of hypercapnia and respiratory failure.
b. The development of respiratory failure is somewhat predictable.
c. The following equation identifies patients who are at high risk for CO2 retention and for requiring mechanical ventilation: pH = 7.66 − 0.00919 × PaO2. If the calculated pH is greater than the patient’s true pH, he or she is at high risk for being intubated. Sensitivity is ∼ 80%.
If a patient with a COPD exacerbation requires oxygen, it should be provided and not withheld for fear of causing CO2 retention. If respiratory failure does ensue, it is caused by COPD and not by the physician who administered the oxygen.
5. Noninvasive positive pressure ventilation (eg, bilevel positive airway pressure) decreases rates of intubation, length of stay, and in-hospital mortality in patients with severe exacerbation.
6. Mucolytics, theophylline, and chest physiotherapy have no role in the treatment of COPD exacerbations.
MAKING A DIAGNOSIS
On the physical exam, Mrs. A appears well. Her vital signs are normal. The only findings on lung exam are decreased breath sounds, a prolonged expiratory phase, and scant expiratory wheezing. Her chest radiograph is normal. Some of the results of her PFTs are shown in Table 33-9.
Have you crossed a diagnostic threshold for the leading hypothesis, COPD? Have you ruled out the active alternatives? Do other tests need to be done to exclude the alternative diagnoses?
Table 33-9. Pulmonary function test results for Mrs. A.
The combination of her smoking history, reported wheezing, and wheezing on auscultation indicates airflow obstruction. The remainder of her history and physical exam support the diagnosis of COPD, and the chest radiograph does not argue for another diagnosis.
Her PFTs also support the diagnosis. Most importantly, there is an irreversible decrease in airflow. The low DLCO (carbon monoxide diffusing capacity), suggests loss of a portion of the Hb/air interface. She falls into GOLD, group C: high risk and few symptoms.
Asthma and heart failure, the alternative diagnoses, are very unlikely. The irreversibility of the airway disease makes asthma less likely. Heart failure remains a much less likely possibility because it is not supported by the PFTs or chest film. The lack of purulent sputum essentially excludes bronchiectasis, the other remaining diagnosis.
Alternative Diagnosis: Bronchiectasis
Textbook Presentation
Dyspnea and chronic, purulent sputum production are often present in patients with bronchiectasis. There is often a history of a chronic infection that has led to airway damage and dilatation.
Disease Highlights
A. Chronic sputum production is the hallmark of bronchiectasis.
B. The disease is caused by the combination of an airway infection and an inability to clear this infection because of impaired immunity or anatomic abnormality (congenital or acquired). Bronchiectasis can be the result of common (viral infection) or rare (Kartagener syndrome) diseases.
1. Pertussis and tuberculosis were the classic causes of bronchiectasis.
2. Some of the common causes now are:
a. Postviral, often with lymphadenopathy causing airway obstruction
b. Aspergillus fumigatus, mainly in association with allergic bronchopulmonary aspergillosis
c. Mycobacterium avium complex infection, usually causing middle lobe disease
d. Cystic fibrosis
e. HIV
C. The most common bacteria isolated from the sputum of people with bronchiectasis are H influenzae, Pseudomonas aeruginosa, and Streptococcus pneumoniae.
D. Complications of the disease include hemoptysis and rarely amyloidosis due to the chronic inflammation.
Evidence-Based Diagnosis
A. The diagnosis of bronchiectasis depends on recognizing the clinical symptoms (chronic sputum production) and demonstrating airway damage and dilatation, usually by high-resolution CT scanning.
B. Symptoms and their prevalence
1. Dyspnea and wheezing, 75%
2. Pleuritic chest pain, 50%
C. Signs and their prevalence
1. Crackles, 70%
2. Wheezing, 34%
D. Differentiation of bronchiectasis from COPD can sometimes be difficult because both may present with cough, sputum production, dyspnea, and airflow limitation. Important points in the differentiation are as follows:
1. Sputum production is heavy and chronic in bronchiectasis, while it is only truly purulent in COPD during exacerbations.
**2.**There is usually a smoking history associated with COPD.
3. Spirometry is not helpful since bronchiectasis can cause both airflow limitation and airway hyperreactivity.
4. Imaging (CT scan) will show diagnostic airway changes in bronchiectasis. In COPD, imaging may or may not demonstrate parenchymal destruction.
Treatment
A. Antibiotics are used both to treat flares of disease and to suppress chronic infection.
B. Pulmonary hygiene
1. Chest physiotherapy
2. Oscillatory positive expiratory pressure (PEP) devices
3. There may be a role for bronchodilators, mucolytics, and anti-inflammatory medication.
C. Surgery is mainly used to treat airway obstruction, to remove destroyed and chronically infected lung tissue, and to treat life-threatening hemoptysis.
CASE RESOLUTION
Mrs. A is given a tiotropium inhaler, and she reports mild improvement in her symptoms. A month later, a long-acting beta-agonist inhaler is added. This regimen produces better control of her symptoms. Four months later, she arrives at the emergency department with acute worsening of her symptoms at the time of an upper respiratory tract infection. She is admitted with an exacerbation of COPD.
REVIEW OF OTHER IMPORTANT DISEASES
Sarcoidosis
Textbook Presentation
When lung symptoms predominate, a patient in his 20s or 30s presents with dyspnea, cough, and/or wheezing. The clinical presentation may be indistinguishable from asthma. Because sarcoidosis is a multisystem disease, it may also present with symptoms caused by skin, eye, heart, or neurologic involvement. It is also occasionally diagnosed based on chest film findings in a patient without symptoms of sarcoidosis.
Disease Highlights
A. Sarcoidosis is a multisystem inflammatory disease.
B. The etiology of sarcoidosis is unknown. It is the result of a cell-mediated immune reaction that causes noncaseating granulomas. It is generally thought that, for a patient to develop sarcoidosis, he must have a genetic predisposition and then be exposed to certain triggering antigens.
C. The most commonly effected organs are the lungs, skin, eyes, heart, and CNS
1. The lungs are affected in 90% of patients
a. Common findings are asymptomatic hilar lymphadenopathy, restrictive lung disease with a decreased DLCO, and obstructive lung disease.
b. Patients may present with dyspnea, cough, chest pain or wheezing.
2. Symptoms of skin involvement are widely variable and occur in about 30% of patients.
3. Any part of the eye can be affected by sarcoid and about 25% of patients with sarcoidosis have eye involvement.
4. Cardiac sarcoidosis
a. Often not clinically apparent but commonly found on autopsies.
b. Cardiac sarcoid can cause syncope, heart failure, or sudden death.
c. Sarcoidosis is a common cause of “idiopathic” 2nd or 3rd degree AV block in pts ≤ 60.
5. Neurosarcoidosis
a. Cranial nerve involvement is most common.
b. Other common presentations of neurosarcoidosis are ataxia, cognitive dysfunction, headache, and seizures.
c. Sarcoidosis also can affect the pituitary gland or spinal cord.
Evidence-Based Diagnosis
A. The diagnosis of sarcoidosis is made when there is appropriate clinical suspicion and histologic evidence of noncaseating granulomas.
B. Biopsy
1. Any accessible lesion can be biopsied. Lymph nodes and skin biopsies are most commonly used.
2. Transbronchial biopsy has a diagnostic yield of 85%.
C. When patients present with Löfgren syndrome (erythema nodosum, hilar adenopathy, and polyarthralgias), the diagnosis of sarcoidosis is generally considered certain without biopsy.
D. The Siltzbach classification system is often used to describe sarcoidosis.
1. Stage 0: normal appearance at chest radiography
2. Stage 1: lymphadenopathy on chest radiography
3. Stage 2: lymphadenopathy and parenchymal lung disease
4. Stage 3: parenchymal lung disease only
5. Stage 4: pulmonary fibrosis
E. ACE levels are insensitive and nonspecific and should not be used for diagnosing sarcoidosis.
Treatment
A. Most patients with sarcoidosis do not require treatment.
B. When patients with sarcoidosis do require treatment, it is generally because their disease is clinically active.
C. Corticosteroids remain the mainstay of treatment.
D. Methotrexate and infliximab are also considered effective and are used in patients who require long-term therapy.
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