Basics
Description
A multisystem chronic granulomatous disease that has two distinct variants often differentiated by age of onset ‚
Epidemiology
- More common in the southeastern part of the United States
- Early-onset sarcoidosis/Blau syndrome
- Disease occurs before age 4 years as arthritis, uveitis, and dermatitis.
- Adult-type disease
- Diagnosed in adolescence as L ƒ ¶fgren syndrome with erythema nodosum, polyarthritis, and hilar adenopathy
- However, marked pulmonary involvement may also occur in older adolescents.
- CNS involvement (rare): seizures, cranial neuropathy, hypothalamic dysfunction
Risk Factors
Genetics
- Blacks are more commonly affected than whites; specific genetic tendencies not identified.
- Early childhood cases of arthritis, uveitis, and dermatitis may result from mutation of the CARD15/NOD2 gene " ”either spontaneous or hereditary (AD) " ”familial form, the latter also known as Blau syndrome. Some of the mutation-negative patients have systemic/visceral involvement.
Etiology
- Unknown (possibly infectious)
- Resembles pulmonary borreliosis
- Possible association with substantial dust inhalation (e.g., collapse of World Trade Center towers in New York)
Pathophysiology
T-cell " “mediated disease resulting in noncaseating epithelioid giant cell granulomas in affected organs ‚
Diagnosis
History
Prolonged malaise, fever, weight loss, rash, painful arthritis, swollen lymph nodes, chronic cough, and hematuria (can be microscopic) may be initial complaints. ‚
Physical Exam
- Peripheral lymphadenopathy is most common manifestation.
- Conjunctival injection
- Bilateral parotid gland enlargement and hepatosplenomegaly may be present.
- The arthritis, usually in the ankles, is extremely tender and boggy.
- Rash is diffuse, erythematous, and macular or plaque-like. It can also be erythema nodosum.
Diagnostic Tests & Interpretation
Lab
- CBC
- Mild anemia, leukopenia, lymphopenia
- Erythrocyte sedimentation rate (ESR) elevated
- Angiotensin converting enzyme (ACE) level
- Can be elevated
- Produced in many granulomatous diseases but is useful in cases in which index of suspicion is high
- Not a perfect screening test; however, can follow levels in response to treatment
- False positives: may be elevated in
- Miliary tuberculosis
- Biliary cirrhosis
- Lysozyme level elevation
- May be more sensitive than ACE level for detecting sarcoidosis
- May be useful to follow disease activity in proven cases, if ACE levels cannot be used
- False positives: may be elevated in
- Serum calcium and creatinine levels
- Important in baseline evaluation
- Urine test for blood
- Seen in patients with hypercalciuria
- Synovial effusion is typically mildly inflammatory.
- Biopsy of affected organ, such as peripheral lymph node, parotid gland, skin, conjunctivae, minor salivary gland, or synovium (demonstrating noncaseating granuloma), is helpful and many times diagnostic.
Imaging
- Chest radiography
- May demonstrate hilar adenopathy
- Gallium scan
- Demonstrates uptake diffusely in lungs (extremely sensitive test)
Alert
Uveitis may be occult; slit-lamp ophthalmologic evaluation is important. ‚
Differential Diagnosis
- Infection
- Tuberculosis
- Bacterial sepsis
- Mumps
- HIV
- Gonorrhea
- Lyme disease
- Pulmonary mycoses
- Tumors
- Leukemia
- Neuroblastoma
- Lymphoma
- Immunologic
- Oligoarticular juvenile idiopathic arthritis (for early-onset type)
- Systemic juvenile idiopathic arthritis
- Systemic lupus erythematosus
- Sj ƒ ¶gren disease
- Dermatomyositis
- Beh ƒ §et disease
- Crohn disease
- Immunodeficiency
- Common variable immunodeficiency
- Skin
- Granuloma annulare
- Erythema nodosum due to Streptococcus, hepatitis B, or inflammatory bowel disease (IBD)
Alert
- Pitfalls in diagnosis include not considering IBD arthritis with erythema nodosum.
- Granulomatous skin lesions can occur in both.
- Gene mutations in CARD15/NOD occur in both IBD and Blau syndrome, albeit at different regions of the same chromosome.
Treatment
Medications are used to treat active disease with clinical symptoms. ‚
- Pitfalls include overtreating asymptomatic lymphadenopathy and not detecting hypercalciuria.
Medication
- Corticosteroids may provide rapid improvement; NSAIDs/analgesics for symptom relief.
- In cases of chronic disease, immunosuppressive medications such as methotrexate can be used in addition to corticosteroids.
- The tumor necrosis factor inhibitors, specifically antibodies like infliximab and adalimumab show promising preliminary results and should be considered especially in uveitis.
- In cases of hypercalciuria/hypercalcemia, consider hydration and furosemide.
- Cyclophosphamide for neurosarcoidosis.
Ongoing Care
Follow-up Recommendations
Patient Monitoring
- Referral to rheumatologist indicated, also regular ophthalmologic assessment
- Signs to watch for:
- Climbing creatinine
- Shortness of breath
- Persistent uveal tract inflammation
- Neurologic deficit
Prognosis
- Variable in early onset. Severe organ involvement and joint and eye damage can occur " ”needs close follow-up.
- L ƒ ¶fgren syndrome can resolve after a couple of years.
- More than 40% of older children with adult-type disease have persistent pulmonary changes, but only a few will have pulmonary symptoms.
Complications
- In children, usually related to uveitis or from hypercalciuria resulting in renal injury. Lung, CNS, and ocular involvement can bring long-term defects.
- In older adolescents, pulmonary problems, such as restrictive lung disease, as well as severe growth delay, may occur.
Additional Reading
- Baumann ‚ RJ, Robertson ‚ WC Jr. Neurosarcoid presents differently in children than in adults. Pediatrics. 2003;112(6)(Pt 1):e480 " “e486. ‚ [View Abstract]
- Iannuzzi ‚ MC, Rybicki ‚ BA, Teirstein ‚ AS. Sarcoidosis. N Engl J Med. 2007;357(21):2153 " “2165. ‚ [View Abstract]
- Lindsley ‚ CB, Petty ‚ RE. Overview and report on international registry of sarcoid arthritis in childhood. Curr Rheumatol Rep. 2000;2(4):343 " “348. ‚ [View Abstract]
- Rose ‚ CD, Wouters ‚ CH, Meiorin ‚ S, et al. Pediatric granulomatous arthritis: an international registry. Arthritis Rheum. 2006;54(10):3337 " “3344. ‚ [View Abstract]
- Shetty ‚ AK, Gedalia ‚ A. Childhood sarcoidosis: a rare but fascinating disorder. Pediatr Rheumatol Online J. 2008;6:16. ‚ [View Abstract]
Codes
ICD09
- 135 Sarcoidosis
- 517.8 Lung involvement in other diseases classified elsewhere
- 713.7 Other general diseases with articular involvement
- 695.2 Erythema nodosum
ICD10
- D86.9 Sarcoidosis, unspecified
- D86.0 Sarcoidosis of lung
- D86.86 Sarcoid arthropathy
- 86.83 Sarcoid iridocyclitis
- D86.87 Sarcoid myositis
- D86.2 Sarcoidosis of lung with sarcoidosis of lymph nodes
- D86.89 Sarcoidosis of other sites
- D86.81 Sarcoid meningitis
- D86.82 Multiple cranial nerve palsies in sarcoidosis
- D86.85 Sarcoid myocarditis
- D86.1 Sarcoidosis of lymph nodes
- D86.84 Sarcoid pyelonephritis
- L52 Erythema nodosum
- D86.3 Sarcoidosis of skin
SNOMED
- 31541009 Sarcoidosis (disorder)
- 24369008 Pulmonary sarcoidosis (disorder)
- 361198004 Sarcoid arthritis (disorder)
- 234526006 Ocular sarcoidosis (disorder)
- 75403004 Cardiac sarcoidosis
- 193251003 Sarcoid myopathy
- 55941000 cutaneous sarcoidosis (disorder)
- 64757003 lymph node sarcoidosis (disorder)
FAQ
- Q: Why is therapy in childhood sarcoidosis more aggressive compared with adults?
- A: These may be 2 distinct granulomatous diseases. Early-onset sarcoidosis is a very aggressive and destructive disease requiring chronic therapy rather than a relatively short course of steroids.