Challenging Diagnostic Dilemmas in Primary Care

Syllabi/Slides for this program are a supplement to the live CME session and are not intended for other purposes.

Challenging Diagnostic Dilemmas in Primary CareHoward Libman, M.D.Professor of Medicine, EmeritusHarvard Medical School

Division of General MedicineBeth Israel Deaconess Medical Center, Boston

Does this patient have bacterial sinusitis?

https://www.hivehealthmedia.com/antibiotics-ineffective-bacterial-sinusitis

Case: It snot what she thinks it is…

38 y.o. woman with one week of URI symptoms who requests antibiotics.

Scratchy throat followed by nasal congestion; initially clear but now cloudy. Low grade fever and frontal headache.

T=99.4 F. No adenopathy. Diffuse mild sinus tenderness. Normal TMs and pharynx. Chest clear.

Why is This Important?

Most upper respiratory tract infections are not bacterial and do not require antibiotic therapy

Risks of unnecessary antibiotic therapy include side effects, toxicities, and drug resistance

Unnecessary antibiotic therapy increases the cost to patients and the healthcare system

It is important to distinguish bacterial from viral sinusitis in order to know who is at risk for complications


Effect of antibiotic prescribing in primary care on antimicrobial resistance in individual patients: systematic review and meta-analysis. BMJ. 2010;340:c2096.

Bacterial Resistance is Common after Antibiotic Exposure

Symptoms and Signs of Acute Rhinosinusitis (ARS) Nasal congestion and obstruction Facial pain or pressure that is worse when

bending forward Associated symptoms of eustachian tube

dysfunction Fever Cheek erythema and/or tenderness Nasal mucosa erythema/edema with

purulent discharge

Distinguishing Viral (AVRS) from Bacterial (ABRS)

Rhinosinusitis

Viral Bacterial Symptom Intensity

Mild to Moderate Moderate to Severe

Duration 7-10 days >10 daysFever Absent PresentNasal Discharge Clear Cloudy

ClearCloudy early in

courseFacial Pain/Pressure

Sometimes Almost always


Use of Radiologic Imaging/Bacterial Culture

Imaging is not indicated in patients with uncomplicated ARS because the findings are nonspecific

Plain films are not helpful because of their poor sensitivity and specificity

CT scan may show air-fluid levels, mucosal edema, and air bubbles within the sinuses

Culture of nasal discharge is not useful Needle aspiration of sinuses for culture is rarely indicated

Complications of ABRS

Periorbital and orbital cellulitis Meningitis Intracranial and epidural abscess Osteomyelitis of the sinus bones Septic cavernous sinus thrombosis


Antimicrobial Treatment of Acute Sinusitis Has Modest Value

1. RCT of adult patients (n=166) who met clinical criteria for acute sinusitis– Randomly assigned to 10-day course of amoxicillin

or placebo– Evaluated disease-related quality of life– No difference between groups at day 3 or at day 10– Greater symptom improvement in amoxicillin group

at day 7 2. 2012 meta-analysis of 13 randomized trials in adults

(n=2878): 13 patients (NNT, 95% CI 9-22) would need to be treated with antibiotics for one to benefit

JAMA. 2012;307:685. Clin Infect Dis. 2012;54:e72.

ACP 2016 Recommendations:

ACP 2016 Guideline: When to Suspect ABRS and Begin Antibiotics?

1. Persistent symptoms or signs of sinusitis lasting > 10 days without improvement

2. Severe symptoms or signs (high fever, purulent nasal discharge, and/or facial pain) for at least 3-4 days at beginning of illness

3. Symptoms of URI that are slowly improving but then worsen again (“double-sickening”) after 5-6 days

Pearls and Pitfalls

Acute rhinosinusitis (ARS) is much more often viral than bacterial

Most bacterial cases in adults are caused by Streptococcus pneumoniae or Moraxella catarrhalis

Bacterial ARS may be complicated by extension into the orbit, CNS, or surrounding tissues

Distinguish viral from bacterial ARS by characteristic symptoms and signs, duration and pattern of illness, fever, and facial pain/tenderness

Radiologic imaging and bacterial cultures are generally not helpful


Case: Cy Attica

74 y.o. man with leg heaviness and pain on walking three blocks relieved with rest and sitting. Gradual onset. History of intermittent LBP. PMH: HTN, DM. PE: reduced ROM lower spine, no focal neurologic findings, preserved pulses. What is his diagnosis?


• Low back pain is the most common musculoskeletal complaint among adult patients seen in primary care practice

• Specific diagnosis established in only 15-20%• Produces at least short-term impairment in 70-80%

of general population over lifetime• A small percentage of cases are not self-limited,

reflect a more serious underlying disease, and may require specific interventions

Common Patho-Anatomical Conditions

NEJM 2007;356:2239-2243.

Demographics/Epidemiology

• Most cases ages 30-60 years• Leading cause of disability in persons < 45• Comparable rates among men and women• Incidence greater among women than men in

occupations requiring heavy exertion• Men generally present at younger age• Precipitating event in only 6-28% of cases• Recurrence of occupational low back pain in

33-60% of patients within 3 years


Causes of Acute Low Back Pain

Ann Intern Med. 2002;137:586-97.

Mechanical Low Back Pain

History• Pain in back, buttock +/- thigh, often severe• Onset hours to days after new/unusual exertion• No history of major trauma, infection or malignancy• Relief of pain in supine position +/- legs flexed

Physical examination• Paravertebral tenderness/spasm• Scoliosis or loss of lumbar lordosis• No demonstrable neurologic deficits

Supporting studies• None necessary

Herniated Intervertebral Disc

History• Acute onset, severe, lancinating• Often antecedent flexion strain injury or trauma• Sciatica• Relief of pain with hip in partial flexion

Physical examination• Striking paravertebral tenderness/spasm, with

splinting in awkward postures• Evidence of radiculopathy

Supporting studies• Usually none early; if indications MRI, EMG/NCS Dermatomes


Utility of Physical Exam for Disc Herniation

Finding Sensitivity SpecificityIpsilateral SLR 0.80 0.40Crossed SLR 0.25 0.90Ankle dorsiflexors weak 0.35 0.70EHL weak 0.50 0.70Plantar flexion weak 0.06 0.95Quadriceps weak 0.01 0.99Sensory loss 0.50 0.50Decreased ankle reflex 0.50 0.60Decreased knee reflex 0.50 --

JAMA. 1992;268:760.

When to Suspect Malignancy or Infection?Physical examination•Tender spinous process(es)•Variable neurologic findings•Evidence of systemic cancer/infectionSupporting studies•Epidural process best delineated by MRI, CT +/-myelogram• LS x-rays may reveal destructive bony lesions•Bone scan sensitive for metastatic carcinoma (but not for myeloma)•ESR/CRP usually increased

N Engl J Med. 2006;355:2012.

Imaging in a Patientwith a “Red Flag” Diagnosis

Cancer or infection Spinal fracture Cauda equinaPrior CA or recent infection

Hx of significant trauma

Acute onset urinary retention

Fever > 100 F Prolonged use of corticosteroids

Loss of anal sphincter tone

Unexplained weight loss Age > 70 +/- limited trauma Saddle anesthesia

Immunosuppression Global/progressive LE weakness

Intravenous drug use

Corticosteroid useNo change or worse with restAge > 50Persistence > 1 month

Traditional “Red Flags”


Systematic Review of Red Flags

• Included 14 studies evaluating 53 red flags• Many red flags provide virtually no change in

probability of fracture or malignancy or have untested diagnostic accuracy

• Red flag with highest post-test probability for malignancy is history of malignancy (33%)

• Red flags with highest post-test probability for spinal fracture: 1) older age (9%); 2) prolonged use of corticosteroids (33%); 3) severe trauma (11%; and 4) presence of contusion/abrasion (62%)

Brit Med J. 2013;347:f7095.

Spinal Stenosis

History• Back pain may vary from absent to severe• Pseudoclaudication often prominent• Pain worsens during the day, aggravated by standing, relieved by rest and trunk flexion•Weakness, bladder and bowel dysfunction• Age > 50 Physical examination•Neurologic findings vary, often multiple levels• Findings of osteoarthritis may be prominentSupporting studies• Standard radiographs; MRI or CT +/- myelography; EMG/NCS

Low Back Pain: Pearls and PitfallsACP Clinical Practice Guidelines

• Conduct focused history and exam to distinguish:– Nonspecific low back pain– Back pain potentially associated with radiculopathy

and/or spinal stenosis– Back pain associated with another potential spinal

cause• Do not obtain imaging routinely in patients with nonspecific

low back pain• Image for severe or progressive neurological deficits, when

serious underlying conditions are suspected, and in candidates for epidural injection or surgery

Ann Intern Med. 2007;147:478.

When Should Endocarditis be Suspected?

https://en.wikipedia.org/wiki/Infective_endocarditis


Case: The urgent care clinic said that I just have a virus…Mr. Lee Quivalve is a 56 y.o. man with 3 weeks of fever, decreased appetite, and fatigue. He denies chest pain and dyspnea.PMH: rheumatic heart disease. PE: T=100.2 F. COR: II/VI holesystolic murmur at apex, no gallops. Lungs: clear. Abdomen: soft, nontender, without organomegaly. Skin: no rash or lesions.


Most subacute bacterial endocarditis is nonspecific in presentation and often initially misdiagnosed

It is important to maintain an index of suspicion for this diagnosis in patients with protracted febrile illness of unclear etiology

Early diagnosis and initiation of antibiotic therapy are associated with better clinical outcomes

Risk Factors for Endocarditis

Valvular or congenital heart disease Prosthetic value Prior endocarditis Injection drug use Immunosuppression Recent dental or surgical procedure

Clinical Findings in Endocarditis

Symptoms Fever (90%) Headache Myalgias/arthralgia Abdominal pain Dyspnea Cough Pleuritic chest pain Back pain

Signs Murmur (85%) Splenomegaly Petechiae Nail splinter hemorrhages Roth spots Osler’s nodes Janeway lesions


Cutaneous and Ocular Manifestations of Endocarditis

http://www.slideshare.net/jbearth/micro-quiz-4th-yr

Complications of Bacterial Endocarditis

Cardiac (50%): Valvular insufficiency, heart failure Neurologic (40%): Embolic stroke, hemorrhage,

brain abscess Septic emboli (25%): Pneumonia/lung abscess,

infarction of kidneys and other organs Other metastatic infection: Vertebral osteomyelitis,

septic arthritis, psoas abscess Systemic immune reaction: Acute glomerulonephritis

Diagnosis and Differential Diagnosis of Bacterial Endocarditis

Symptoms often nonspecific, and differential diagnosis is broad

Consider in all patients with a protracted febrile illness, particularly if risk factors

Diagnosis suspected by symptoms and/or signs but is confirmed with blood cultures and echocardiography

Additional tests depending on clinical features Use modified Duke criteria


Blood Cultures and Echocardiography

Positive blood cultures are necessary for microbiologic diagnosis of endocarditis

Three sets detect 96-98% of organisms; separate venipuncture sites

Most pathogens detected within 48 hours; fastidious ones may take up to 5 days

Echocardiography whenever suspected TTE initially; sensitivity/specificity of 75%/100% for

detecting vegetations TEE is better for diagnosing complications (e.g.,

abscess, leaflet perforation); sensitivity of >90% for detecting vegetations

Bacteriology of Endocarditis

• Most common pathogens include Staphylococcus aureus, viridans streptococci, Streptococcus gallolyticus (bovis), HACEK organisms, and enterococci

• Less commonly Coxiella burnetii, Bartonella, Chlamydia, Legionella, Mycoplasma, and Brucella

• Diagnosis of these pathogens by serology or PCR testing

• Culture-negative endocarditis rarely

http://emedicine.medscape.com/article/1954887-overview#a7

Modified Duke Criteria

Major Positive BC x 2 with

typical organism Persistent positive BCs Coxiella burnetti Echo: vegetations,

abscess, partial dehiscence of prosthetic valve, new regurgitation

Minor Risk factors Fever Vascular: emboli,

infarcts, mycotic aneurysm, Janeway lesions

Immune features: GN, Osler nodes, Roth spots

Other positive BC

Diagnosis of Bacterial Endocarditis Using Modified Duke Criteria

Definite Endocarditis

Possible Endocarditis

Pathologic • Vegetation or intracardiac abscess

• Not applicable

Clinical • 2 major criteria • 1 major and 1 minor criteria

• 1 major criterion and 3 minor criteria

• 3 minor criteria

• 5 minor criteria


Pearls and Pitfalls

Consider in patients with a protracted febrile illness, particularly those with risk factors

Symptoms are generally nonspecific; fever and a murmur are the most common physical findings

May occasionally present with cardiac, neurologic, embolic, or metastatic infectious complications

Diagnosis by blood cultures and echocardiography using the modified Duke criteria

Prompt diagnosis and treatment are essential for optimal clinical outcome

Case: Ann Hedonia

31 year old woman Has lost interest in

gardening and hobbies Friends say she doesn’t

look right Distracted at work Is she depressed? Could she be suicidal?


Annual prevalence of ~ 7%; lifetime prevalence of ~ 15%

Only about half of patients diagnosed Most common cause of disability in persons

aged 20-40 Suicide in ~ 2% of patients with major

depression Suicidality is a “can’t miss” diagnosis Effective treatment exists in primary care

settings

When Should You Consider Depression? It’s more than Just Sadness: Sig ECAPS

Sleep Insomnia or sleeping too muchInterest Diminished interest or pleasure in most

activitiesGuilt Feelings of guilt or worthlessnessEnergy Loss of energy or fatigueConcentration Diminished ability to think or

concentrate, indecisivenessAppetite Increase or decrease in appetitePsychomotor Psychomotor agitation or retardationSuicide Thoughts of death or suicidal ideation


Differential Diagnosis Post-traumatic stress disorder Bipolar disorder Alcoholism or drug use (dual diagnosis) Hypothyroidism Parkinson’s disease Obstructive sleep apnea Stroke (particularly frontal lobe) Medication adverse effect (beta blockers,

corticosteroids, opiates) Alzheimer’s or other types of dementia

PHQ-9: Over the Past 2 Weeks, Have You Been Bothered by:

J Gen Intern Med. 2001;16:606.

Depression Severity

Score

Minimal 4Mild 5-9Moderate 10-14Moderately severe 15-19Severe 20-27

Operating Characteristics of PHQ-9: Score of 10 Discriminates Well

PHQ-9 Score Sensitivity %

Specificity %

LR +

≥ 9 95 84 6.0

≥10 88 88 7.1

≥11 83 89 7.8

≥12 83 92 10.2

≥13 78 93 11.1

≥14 73 94 12.0

≥15 68 95 13.6

PHQ-2: Ask Two Simple Questions

1. ‘During the past month, have you often been bothered by feeling down, depressed or hopeless?’

2. ‘During the past month, have you often been bothered by having little interest or pleasure in doing things?’

J Gen Intern Med. 1997;12:439.

Not at all 0 pointsSeveral days 1 pointMore than half the days 2 points

Nearly every day 3 points


PHQ-2 Score Probability of major depression

%

Probability of any depression %

1 15 372 21 483 38 754 46 815 56 856 79 93

PHQ-2 is Reasonably Accurate as Diagnostic Tool

Sensitivity 83% Specificity 90%

Always Screen for Suicidality After Making a Diagnosis of Depression

There are no validated risk instruments for assessing suicidality in depressed primary care patients

There is no evidence that inquiring about SI increases suicidal thoughts

Ask three questions:1. Do you ever think of hurting yourself

or taking your own life?2. Do you currently have a plan?3. What is your plan?

Risk Factors for Suicide (1)

History of previous suicide attempts Underlying psychiatric disorder Hopelessness Not married Sexual minority Unskilled occupation Military service

Risk Factors for Suicide (2)

Chronic medical diseases Chronic pain Childhood adversity Family history of suicide Rural residence Firearms in the home Antidepressant therapy (young adults)


“Yes, I have a plan to commit suicide”’How to Assess for Imminent Risk: Are the means of committing suicide

available or readily accessible? What is the lethality of the plan? What is the likelihood of rescue? Have preparations been made (gathering

pills, changing wills, suicide note, purchase of a gun)?

What is the strength of intent to carry out the plans?

History of binge drinking? Source: UpToDate

Depression: Pearls and Pitfalls

Depression is morbid and underdiagnosed in primary care settings

Consider depression if loss of interest, guilt, distractible

Remember differential diagnosis of PTSD, alcoholism/drug use, medication side effect

Screen in clinical practice with PHQ-2 Always inquire about suicidal ideation, contract

for safety, and document this discussion

Case: Mr. Pickwick

42 year old man Notes poorer memory

for one year Distractable Cannot multitask as

well as before What is the diagnosis?


20-30% of U.S. men and 10-15% of women have at least mild obstructive sleep apnea (OSA) defined as AHI > 5

High rates are paralleling obesity epidemic Untreated OSA can decrease work productivity,

cause daytime sleepiness, reduce quality of life, and increase the risk for traffic accidents

Effective management exists for this condition


When Should You Consider OSA?

Snoring Witnessed apneas Morning headaches Attentional deficits and poor short-term memory Resistant hypertension Cor pulmonale (JVP elevation, edema) Night sweats

Secondary Causes of Hypertension: OSA More Common than Other Diagnoses Combined!

Obstructive sleep apnea Cushing’s syndrome Renal artery stenosis Primary aldosteronism Pheochromocytoma Chronic kidney disease Coarctation of the aorta Thyroid or parathyroid disease

Differential Diagnosis of OSA

Insomnia Central sleep apnea Periodic leg movements of sleep Narcolepsy Neuromuscular disease of chest wall Attention deficit disorder Gastroesophageal reflux disease Nocturnal panic attacks Other medical conditions causing chronic fatigue

Which Aspects of History and Physical Exam are Most Useful to

Make Diagnosis (AHI > 10)?Feature Sensitivity Specificity LR+ LR-HistoryHypertension 74% 45% 1.3 0.60Nocturnal gasping 52% 84% 3.3 0.57A.M. headache 22% 85% 1.5 0.92Witnessed apnea 80% 42% 1.4 0.47Daytime sleepiness 50% 61% 1.3 0.81ExamMallampati 3 or 4 55% 65% 1.6 0.68Pharyngeal narrowing

67% 53% 1.4 0.63

Rational Clinical Exam JAMA. 2013;310:731.


Mallampati Classification

Class 1: Soft palate, uvula, pillars visibleClass 2: Soft palate and base of uvula visibleClass 3: Only soft palate visibleClass 4: Only hard palate visible

Clinical Prediction Rules

STOP-BANG STOP Epworth Sleepiness Scale (ESS) Sleep apnea clinical score (SACS) Berlin questionnaire (reference

standard in research studies)

STOP-BANG Clinical Prediction Rule

1. Do you snore loudly?2. Do you often feel tired,

fatigued, or sleepy?3. Has anyone observed

apneas during sleep?4. High blood pressure?5. BMI > 356. Age > 507. Neck circumference > 40

cm8. Male gender

Total score ≥ 3 High risk of OSA Sensitivity 87% Specificity 31%Total score 5-8 High risk for moderate to severe OSA (AHI > 10)

www.stopbang.ca

Pearls and Pitfalls

OSA has become more common in association with the increased prevalence of obesity

Maintain a high index of suspicion for diagnosis Consider OSA in scenarios beyond patients

experiencing snoring or daytime somnolence– Nocturnal gasping or Mallampati class 3 or 4– Resistant hypertension

Make use of available clinical prediction rules

Challenging Diagnostic Dilemmas in Primary Care

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