Transcript Clinical Slide Set. Sarcoidosis

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© Copyright Annals of Internal Medicine, 2012
Ann Int Med. 156 (9): ITC5-1.
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© Copyright Annals of Internal Medicine, 2012
Ann Int Med. 156 (9): ITC5-1.
in the clinic
Sarcoidosis
© Copyright Annals of Internal Medicine, 2012
Ann Int Med. 156 (9): ITC5-1.
Who is at risk?
 Varying incidence among ethnic groups
 African American lifetime risk: 2.4%
 White American lifetime risk: 0.85%
 More common if Scandinavian, Irish, German, W. Indian descent
 Relatively rare if Japanese, Spanish, Portugese descent
 Family history: Familial clustering in 5%-19% of cases
 Age: >80% of cases present between ages 20-40 years
 Gender: marginally more common in women
© Copyright Annals of Internal Medicine, 2012
Ann Int Med. 156 (9): ITC5-1.
Is there a role for screening?
 Screening is not recommended
 Even for family members of an index case
 Due to…
 Variable prognosis
 No evidence early diagnosis affects prognosis
© Copyright Annals of Internal Medicine, 2012
Ann Int Med. 156 (9): ITC5-1.
What symptoms and clinical findings should
prompt a clinician to consider sarcoidosis?
 Common signs and symptoms
 Cough (usually nonproductive)
 Fever and weight loss
 Chest pain (central substernal)
 Painful ankle swelling
 Painful red nodules on shins
 Eye pain or blurred vision
 Lung or thoracic lymph nodes almost always involved
 Lofgren syndrome: common presentation (fever, bilat
hilar LAD, ankle swelling, erythema nodosum)
 Uveoparotid fever: hallmark presentation
© Copyright Annals of Internal Medicine, 2012
Ann Int Med. 156 (9): ITC5-1.
Figure 1. A patient with lupus pernio sarcoidosis
Violaceous plaques and
nodules on the cheeks,
bridge of nose, and nares
Lesions responded to
treatment with prednisone
and methotrexate
© Copyright Annals of Internal Medicine, 2012
Ann Int Med. 156 (9): ITC5-1.
Physical exam in suspected sarcoidosis
 Skin lesions: Erythema nodosum, lupus pernio, sarcoid
lesions on old scars, tattoos (“Koebner phenomenon”)
 Parotid enlargement
 Lymphadenopathy
 Normal lung examination (usual)
 Hepatosplenomegaly
 Neurologic (especially VII nerve palsy): typically involves
cranial neuropathies, neuroendocrine disease parenchymal
brain disease, and peripheral, often small-fiber, neuropathy
 Eyes (red, painful): Ocular disease; uveitis, retinal vasculitis
 Cardiac: Any cardiac symptoms should raise suspicion
(particularly syncope and palpitations, CHF symptoms)
© Copyright Annals of Internal Medicine, 2012
Ann Int Med. 156 (9): ITC5-1.
CLINICAL BOTTOM LINE: Risk Factors
and Clinical Features...
 More common in distinct ethnic groups
 Symptoms
 Protean systemic and/or organ-specific
 Can affect any organ system
 Characteristic presentations
 Fever
}
 Bihilar lymphadenopathy
 Ankle swelling
 Erythema nodosum
Lofgren syndrome
 Asymptomatic bihilar lymphadenopathy
 Ocular involvement: painful red eyes indicates uveitis
 Cutaneous symptoms: erythema nodosum, lupus pernio
© Copyright Annals of Internal Medicine, 2012
Ann Int Med. 156 (9): ITC5-1.
How is sarcoidosis diagnosed? Do all
suspected cases require biopsy?
 Diagnosis of exclusion!
 Diagnosis Generally Requires:
o typical noncaseating granulomata on biopsy PLUS
o exclusion of other causes of granulomatous inflammation
(e.g., tuberculosis)
 Confident diagnosis only at 3-6 months follow-up: if
evolves in typical manner
© Copyright Annals of Internal Medicine, 2012
Ann Int Med. 156 (9): ITC5-1.
How is sarcoidosis diagnosed? Do all
suspected cases require biopsy?
 Biopsy needed if:
 Presentation atypical (r/o cancer, TB, other infection)
 Systemic corticosteroids required
 Clinical course doesn’t stabilize or improve in 3-6 months
 Biopsy may not be needed if:
 Classical Lofgren syndrome, Heerfordt syndrome, or
asymptomatic BHL (high likelihood self-limited disease)
 Biopsy of erythema nodosum lesions not helpful (shows
panniculitis, not typical granuloma)
© Copyright Annals of Internal Medicine, 2012
Ann Int Med. 156 (9): ITC5-1.
How is sarcoidosis diagnosed? Do all
suspected cases require biopsy?
 Biopsy easily accessible sites preferentially:
 Unexplained skin lesions or peripheral LAD
 Otherwise: intrathoracic LAD or lung
 Transbronchial bx: yield up to 90% if radiographic
infiltrates
 Mediastinoscopy bx – 100% yield, but more invasive
 Endobronchial endoscopic US – guided or TBNA options
© Copyright Annals of Internal Medicine, 2012
Ann Int Med. 156 (9): ITC5-1.
What imaging studies should be ordered in
the evaluation of a patient with sarcoidosis?
 Chest x-ray
 Only routine imaging recommended
 Scadding staging system correlates with prognosis
 Not recommended for routine use:
 High-resolution CT
 Consider for atypical cases + differentiate from other
conditions
 CT and PET scans
 Monitor disease activity, progression, treatment response
© Copyright Annals of Internal Medicine, 2012
Ann Int Med. 156 (9): ITC5-1.
Stages of
sarcoidosis
C
A
B
D
E
© Copyright Annals of Internal Medicine, 2012
Ann Int Med. 156 (9): ITC5-1.
Are pulmonary function tests useful in
evaluating patients with sarcoidosis?
 Results often normal, even in parenchymal lung disease
 Most common abnormalities
 Restrictive ventilatory defect with reduced FVC
 Reduced DLCO
 Airflow obstruction with FEV1/FVC <70% seen in ≈16%
 Serial spirometry and measurement of DLCO can be
useful for:
 following response to therapy
 following disease progression
© Copyright Annals of Internal Medicine, 2012
Ann Int Med. 156 (9): ITC5-1.
What additional investigations
should be ordered?
 Complete blood count: anemia and leukopenia in >20%
 Renal function
 Serum calcium: hypercalcemia up to 10%
 24-h urine test calcium levels: hypercalciuria up to 30%
 Liver function tests
 Tuberculin skin test
 Total immunoglobulins
 ECG: indicated in all patients
 Neuorosarcoidosis evaluation: if unexplained neurologic
symptoms or seizures
© Copyright Annals of Internal Medicine, 2012
Ann Int Med. 156 (9): ITC5-1.
What other conditions should be
considered in the differential diagnosis?
 Infectious causes of granulomatous disease
 Lymphoma, other cancers
 ANCA-associated vasculitis
 Coccidiomycosis (can present like Lofgren syndrome)
 Alternate causes of parenchymal pulmonary infiltrates
Consider alternative diagnosis if…
Age >40 years
Weight loss >10% body weight
Crackles on lung exam
Tender lymph nodes
Positive tuberculin skin test
Asymmetrical BHL on chest x-ray
© Copyright Annals of Internal Medicine, 2012
Ann Int Med. 156 (9): ITC5-1.
When is consultation required?
 Pulmonologist: All cases of suspected disease
 Ophthalmologist: All newly diagnosed cases
 Cardiologist: Possible or confirmed cardiac sarcoidosis
 Neurologist: Possible neurosarcoidosis
© Copyright Annals of Internal Medicine, 2012
Ann Int Med. 156 (9): ITC5-1.
CLINICAL BOTTOM LINE: Diagnosis...
 Diagnosis of exclusion
 Definitive diagnosis requires 6 months follow-up
 Chest x-ray + eval for extrapulmonary involvement
 Clinical Dx: typical Lofgren syndrome, asymptomatic BHL
 Biopsy required? choose most accessible, least invasive site
 Differential diagnosis
 Cancer and infection, particularly lymphoma and TB
© Copyright Annals of Internal Medicine, 2012
Ann Int Med. 156 (9): ITC5-1.
Which patients with pulmonary
sarcoidosis require treatment?
 Wait on treatment if symptoms are mild
 Disease often resolves or remains stable
 Withhold systemic treatment 3-6 months, if possible
 Use NSAIDs for EN or ankle arthralgias
 Use inhaled steroids for dry cough
 Treat persistent, severe or worsening pulmonary symptoms
 Use oral corticosteroids
 Avoid potentially toxic Rx if likely to resolve spontaneously
 Controversial: whether to treat asymptomatic patients
with progression of pulmonary disease on chest x-ray
© Copyright Annals of Internal Medicine, 2012
Ann Int Med. 156 (9): ITC5-1.
Which patients with extra-pulmonary
sarcoidosis require treatment?
 Treat promptly: disease involving critical organ function
 Active uveitis
 Cranial nerve abnormalities
 Pituitary or hypothalamic dysfunction
 Meningitis
 Seizures or other manifestations of CNS involvement
 Cardiac dysfunction or dysrhythmias from granulomas
 Also treat…
 Symptomatic hypercalcemia or interstitial nephritis
 Disfiguring facial lesions
© Copyright Annals of Internal Medicine, 2012
Ann Int Med. 156 (9): ITC5-1.
What is the role of nonsystemic steroids?
 Pulmonary parenchymal sarcoidosis
 Inhaled corticosteroids: adjunct therapy for bronchospasm or cough
 Efficacy is uncertain & routine use not recommended
 Mild ophthalmologic disease
 Topical steroids alone
 Skin lesions
 Topical or intralesional steroids
 To reduce size and prominence, but may thin skin
 Don’t use potent fluorinated steroids on face
 Rhino-nasal sarcoidosis
 Intranasal steroids
© Copyright Annals of Internal Medicine, 2012
Ann Int Med. 156 (9): ITC5-1.
What is the role of systemic steroids for
the treatment of pulmonary sarcoidosis?
 Immunomodulatory therapy
 Effective but not FDA-approved for sarcoidosis
 Oral prednisone
 Consensus: start 20 – 40 mg / every other day
 Evaluate response after 1 to 3 months
 Continue therapy for ≥1 year (taper to lowest effective dose)
 Long-term use for sarcoidosis is controversial
 Use alternative if no response or intolerable SEs
© Copyright Annals of Internal Medicine, 2012
Ann Int Med. 156 (9): ITC5-1.
When should nonsteroidal pharmacologic
treatment be used for pulmonary sarcoidosis?
 Cytotoxic agent (methotrexate) or other immunosuppressant
 Use long-term only if induces unequivocal improvement
 Folic acid reduces myelosuppression with methotrexate
 Chloroquine or hydroxychloroquine
 Cutaneous or mucosal disease
 Control of hypercalcemia
 Those who with hyperglycemia on corticosteroids
 TNF inhibition with infliximab
 Progressive sarcoidosis (intolerant of non-responsive to
steroids & cytotoxic agents)
 Cytoxan, chlorambucil, cyclosporine
 Severe progressive sarcoidosis refractory to steroids and
less toxic immunosuppressive agents
© Copyright Annals of Internal Medicine, 2012
Ann Int Med. 156 (9): ITC5-1.
How long should pharmacologic
therapy be continued in pulmonary
sarcoidosis?
 Initial therapy with prednisone: 9 to 12 months
 Periodically attempt to taper to lowest effective dose
 Frequently treatment is required for >2 years
 Life-long treatment may be needed if repeated relapse
© Copyright Annals of Internal Medicine, 2012
Ann Int Med. 156 (9): ITC5-1.
How should extrapulmonary
sarcoidosis be treated?
 Myocardial sarcoidosis
 Corticosteroids, tapering over months or years
 Consider steroid-sparing agents
 Facial nerve palsy or other neurologic disorders
 Prednisone, tapering over months or years
 Adding cytotoxic agent may improve response
 Posterior uveitis, lacrimal, and orbital sarcoidosis
 Systemic corticosteroids; IV methylprednisolone if vision
threatened or changing rapidly
 Hypercalciuria and hypercalcemia
 Prednisone, tapering to lowest effective dose
 Alternative: hydroxychloroquine
© Copyright Annals of Internal Medicine, 2012
Ann Int Med. 156 (9): ITC5-1.
Which patients require life-long
therapy?
 Patients with repeated relapse
 80% relapse, often within 2 years of tapering corticosteroids
 10 mg prednisone daily or every other day prevents relapse
 No evidence for similar long-term, low-dose cytotoxic agents
© Copyright Annals of Internal Medicine, 2012
Ann Int Med. 156 (9): ITC5-1.
What other pharmacologic therapies
are available?
 Antimicrobial: bronchiectasis from chronic sarcoidosis
 Antifungal: hemoptysis associated with aspergilloma
 Vitamin D, calcium, nasal calcitonin, and bisphosphonates:
osteoporosis related to steroid therapy
 NSAIDs: musculoskeletal symptoms and pain from EN
 Ketoconazole (600-800 mg/day): hypercalcemia
 Pulmonary hypertension therapy- Rx of unproven benefit and
requires expert evaluation
© Copyright Annals of Internal Medicine, 2012
Ann Int Med. 156 (9): ITC5-1.
What nonpharmacologic interventions
should be considered?
 Rehabilitation program for advanced lung disease
 Oxygen therapy for hypoxemia at rest or with exercise
 Vaccination for pneumococcal pneumonia and influenza
 Pacemaker or implantable defibrillator for cardiac
sarcoidosis
© Copyright Annals of Internal Medicine, 2012
Ann Int Med. 156 (9): ITC5-1.
Which patients should be referred
for organ transplantation?
Patients with…
 Severe functional impairment
 Severe end organ damage
 Progressive deterioration despite appropriate medical Rx
Ideal time for lung transplantation is imprecise
 Refer before condition deteriorates to point when survival
time is less than time on waiting list
© Copyright Annals of Internal Medicine, 2012
Ann Int Med. 156 (9): ITC5-1.
How should sarcoidosis be monitored?
 Intensive longitudinal clinical surveillance for ≥ 5 years
 Track organ system involvement
 Regular spirometry; repeat oximetry to adjust oxygen
 Consider repeat chest imaging if clinical deterioration occurs
 Annual blood tests and EKG & Holter monitoringa
 Target signs and symptoms that frequently occur
 Those affecting pulmonary system, eyes, skin
 Refer patient to opthamologist
 Ocular involvement may be asymptomatic
© Copyright Annals of Internal Medicine, 2012
Ann Int Med. 156 (9): ITC5-1.
When should patients with sarcoidosis
be hospitalized?
 Respiratory failure
 Onset of cardiac symptoms (particularly syncope)
 Symptomatic hypercalcemia
 New or progressive neurologic disease
 Acute vision loss
 Acute renal failure
 Severe treatment side effects
© Copyright Annals of Internal Medicine, 2012
Ann Int Med. 156 (9): ITC5-1.
What is the prognosis of patients with
sarcoidosis?
 Resolution: ≥50%
 Persistent fibrosis: 25%
 May cause symptoms but no progression
 Chronic progressive disease: 25%
 Fatal: 5% (usually pulmonary/cardiac impairment)
 Predictors of good prognosis
 EN; stage 1 CXR; asymptomatic presentation
 Predictors of poor prognosis
 Lupus pernio; cardiac, neurologic, or bone involvement;
nephrolithiasis
© Copyright Annals of Internal Medicine, 2012
Ann Int Med. 156 (9): ITC5-1.
What education do patients with
sarcoidosis require?
 Information on organ involvement
 Information on symptoms to be alert for
 Treatment risks and possible side effects
 Measures to counteract toxicity of medications
 Prognostic information
© Copyright Annals of Internal Medicine, 2012
Ann Int Med. 156 (9): ITC5-1.
CLINICAL BOTTOM LINE: Treatment...
 Observe for 3-6 months before therapy, if possible
 Spontaneous remission can occur
 1st-line Rx, when warranted: prednisone 9-12 months
 Treat promptly
 Symptomatic neurologic, cardiac, or eye sarcoidosis or
symptomatic hypercalcemia
 Treat mild skin or eye disease with topical corticosteroids
 Use alternative Rx: disease refractory or toxicity
unacceptable
 Methotrexate
 Consider infliximab if intolerable SEs or continued disease
progression
© Copyright Annals of Internal Medicine, 2012
Ann Int Med. 156 (9): ITC5-1.