para>If signs indicate L ƒ ¶fgren syndrome (acute sarcoid with bilateral hilar lymphadenopathy, erythema nodosum [EN] and diffuse arthritis/arthralgias), it is not necessary to perform a biopsy because prognosis is good with observation alone, and biopsy would not change management. ‚
Test Interpretation
Noncaseating epithelioid granulomas without evidence of fungal/mycobacterial infection ‚
TREATMENT
- Many patients undergo spontaneous remission. It is difficult to assess disease activity and severity, however, making it challenging to develop guidelines.
- No treatment may be necessary in asymptomatic individuals, but treatment may be needed for specific indications, such as cardiac, CNS, renal, or ocular involvement.
- No treatment is indicated for asymptomatic patients with stage I " “III radiographic changes with normal/mildly abnormal lung function, although close follow-up is recommended.
- Treatment of pulmonary and skin manifestations is done on the basis of impairment. The symptoms that necessitate systemic therapy remain controversial.
- Worsening pulmonary symptoms
- Deteriorating lung function
- Worsening radiographic findings
MEDICATION
Systemic therapy is clearly indicated for hypercalcemia, cardiac disease, neurologic disease, and eye disease not responding to topical therapy. Most patients with pulmonary sarcoidosis do not require treatment with medications, as many are asymptomatic or have a spontaneous remission. ‚
First Line
- Systemic corticosteroids in the symptomatic individual (dyspnea, cough, hemoptysis) or in the individual with worsening lung function or radiographic findings
- The optimal dose of glucocorticoids is not known.
- Usually prednisone initially, 0.3 to 0.6 mg/kg ideal body weight (20 to 40 mg/day) for 4 to 6 weeks.
- If stable, taper by 5 mg/week to 10 to 20 mg/day over the next 6 weeks.
- If no relapse, 10 to 20 mg/day for 8 to 12 months
- Relapse is common.
- Higher doses (80 to 100 mg/day) may be warranted in patients with acute respiratory failure, cardiac, neurologic, or ocular disease.
- In patients with skin disease, topical steroids may be effective.
- Inhaled steroids (budesonide 800 to 1,600 Ž ¼g BID) may be of some clinical benefit in early disease with mild pulmonary symptoms.
- Contraindications: patients with known problems with corticosteroids
- Precautions: careful monitoring in patients with diabetes mellitus and/or hypertension
- Significant possible interactions: Refer to the manufacturer 's profile of each drug.
Second Line
- All alternative agents to glucocorticoids carry substantial risk for toxicity, including myelosuppression, hepatotoxicity, and opportunistic infection.
- Methotrexate: initially 7.5 mg/week, increasing gradually to 10 to 15 mg/week
- Azathioprine: 50 to 100 mg/day
- Leflunomide: 20 mg/day
- Use of immunosuppressants, such as methotrexate or azathioprine, will require regular monitoring of CBC and LFTs.
- Antimalarial agents, such as chloroquine or hydroxychloroquine
- Tumor necrosis factor antagonists, such as infliximab, have been useful in refractory cases (9)[C].
ISSUES FOR REFERRAL
May be followed by a pulmonologist, with referrals to other specialists as dictated by involvement of other organ systems. If requiring a second-line therapy, should be followed by a specialist. ‚
SURGERY/OTHER PROCEDURES
Lung transplantation in severe, refractory cases; long-term outcomes are unknown. ‚
COMPLEMENTARY & ALTERNATIVE MEDICINE
None known to be effective ‚
ONGOING CARE
FOLLOW-UP RECOMMENDATIONS
There is limited data on indications for the specific tests and optimal frequency of monitoring of disease activity. Suggestions follow. ‚
Patient Monitoring
- Patients on prednisone for symptoms should be seen q1 " “2mo while on therapy.
- Patients not requiring therapy should be seen regularly (q3mo) for at least the first 2 years after diagnosis, obtaining a thorough history and physical exam, laboratory testing tailored to sites of disease activity, PFTs, and ambulatory pulse oximetry.
- If active disease
- Every 6 to 12 months, obtain ophthalmologic exam if on hydroxychloroquine.
- Annually, CBC, creatinine, calcium, LFTs, ECG, 25-hydroxy vitamin D and 1,25 dihydroxy vitamin D, CXR, ophthalmologic examination
- Other testing per individual patient 's symptoms, including HRCT, echocardiogram, Holter monitoring, urinalysis (UA), thyroid-stimulating hormone (TSH), bone density, MRI of brain
- The serum ACE level is used by some physicians to follow the disease activity. In patients with an initially elevated ACE level, it should fall toward normal while on the therapy or when the disease resolves.
- If inactive disease, follow annually with history and physical exam, PFTs, ambulatory pulse oximetry, CBC, creatinine, calcium, liver enzymes, 1,25 dihydroxy vitamin D, EKG, ophthalmologic exam.
DIET
No special diet ‚
PATIENT EDUCATION
- The American Lung Association at www.lungusa.org/lung-disease/sarcoidosis/?gclid=CPX6zuipm6MCFQxW2godISFepQ
- Sarcoidosis by Medline Plus at www.nlm.nih.gov/medlineplus/sarcoidosis.html
PROGNOSIS
- 50% of patients will have spontaneous resolution within 2 years.
- 25% of patients will have significant fibrosis, but no further worsening of the disease after 2 years.
- 25% of patients (higher in some populations, including African Americans) will have chronic disease.
- Patients on corticosteroids for >6 months have a greater chance of having chronic disease.
- Overall death rate: <5%
COMPLICATIONS
- Patients may develop significant respiratory involvement, including cor pulmonale.
- Pulmonary hemorrhage from infection with aspergillosis in the damaged lung is possible.
- Other organs, especially the heart (congestive heart failure, arrhythmias), eyes (rarely blindness), and CNS, can be involved with serious consequences. Cardiac, ocular, and CNS involvement usually manifests early on in patients with these complications of the disease.
REFERENCES
11 Baughman ‚ RP, Culver ‚ DA, Judson ‚ MA. A concise review of pulmonary sarcoidosis. Am J Respir Crit Care Med. 2011;183(5):573 " “581.22 Holmes ‚ J, Lazarus ‚ A. Sarcoidosis: extrathoracic manifestations. Dis Mon. 2009;55(11):675 " “692.33 King ‚ CS, Kelly ‚ W. Treatment of sarcoidosis. Dis Mon. 2009;55(11):704 " “718.44 Rybicki ‚ BA, Iannuzzi ‚ MC, Frederick ‚ MM, et al. Familial aggregation of sarcoidosis. A case-control etiologic study of sarcoidosis (ACCESS). Am J Respir Crit Care Med. 2001;164(11):2085 " “2091.55 Dempsey ‚ OJ, Paterson ‚ EW, Kerr ‚ KM, et al. Sarcoidosis. BMJ. 2009;339:b3206.66 Lodha ‚ S, Sanchez ‚ M, Prystowsky ‚ S. Sarcoidosis of the skin: a review for the pulmonologist. Chest. 2009;136(2):583 " “596.77 Statement on sarcoidosis. Joint Statement of the American Thoracic Society (ATS), the European Respiratory Society (ERS) and the World Association of Sarcoidosis and Other Granulomatous Disorders (WASOG) adopted by the ATS Board of Directors and by the ERS Executive Committee, February 1999. Am J Respir Crit Care Med. 1999;160(2):736 " “755.88 Tremblay ‚ A, Stather ‚ DR, Maceachern ‚ P, et al. A randomized controlled trial of standard vs endobronchial ultrasonography-guided transbronchial needle aspiration in patients with suspected sarcoidosis. Chest. 2009;136(2):340 " “346.99 Iannuzzi ‚ MC, Fontana ‚ JR. Sarcoidosis: clinical presentation, immunopathogenesis, and therapeutics. JAMA. 2011;305(4):391 " “399.
ADDITIONAL READING
- Hoang ‚ DQ, Nguyen ‚ ET. Sarcoidosis. Semin Roentgenol. 2010;45(1):36 " “42.
- Polychronopoulos ‚ VS, Prakash ‚ UB. Airway involvement in sarcoidosis. Chest. 2009;136(5):1371 " “1380.
CODES
ICD10
- D86.9 Sarcoidosis, unspecified
- D86.0 Sarcoidosis of lung
- D86.86 Sarcoid arthropathy
- D86.89 Sarcoidosis of other sites
- D86.85 Sarcoid myocarditis
- D86.84 Sarcoid pyelonephritis
- D86.82 Multiple cranial nerve palsies in sarcoidosis
- D86.87 Sarcoid myositis
- D86.81 Sarcoid meningitis
- D86.3 Sarcoidosis of skin
- D86.2 Sarcoidosis of lung with sarcoidosis of lymph nodes
- D86.1 Sarcoidosis of lymph nodes
- D86.83 Sarcoid iridocyclitis
ICD9
- 135 Sarcoidosis
- 517.8 Lung involvement in other diseases classified elsewhere
- 713.7 Other general diseases with articular involvement
SNOMED
- 31541009 Sarcoidosis (disorder)
- 24369008 Pulmonary sarcoidosis (disorder)
- 361198004 Sarcoid arthritis (disorder)
- 238675007 Sarcoidosis-induced erythema nodosum (disorder)
- 55941000 cutaneous sarcoidosis (disorder)
- 64757003 lymph node sarcoidosis (disorder)
- 193251003 Sarcoid myopathy
- 75403004 Cardiac sarcoidosis
- 234526006 Ocular sarcoidosis (disorder)
CLINICAL PEARLS
- Sarcoidosis is a noninfectious, multisystem granulomatous disease of unknown cause, typically affecting young and middle-aged adults.
- Any organ can be affected.
- Diagnosis is based on clinical findings, exclusion of other disorders, and pathologic detection of noncaseating granulomas.
- Most patients do not need systemic treatment and the disease resolves spontaneously; a few will have life-threatening progressive organ dysfunction.