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Sarcoidosis, Pediatric

Basics

Description

- 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

- Urine test for blood - Seen in patients with hypercalciuria

- Gallium scan - Demonstrates uptake diffusely in lungs (extremely sensitive test)

- 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

- Referral to rheumatologist indicated, also regular ophthalmologic assessment - Signs to watch for: - Climbing creatinine - Shortness of breath - Persistent uveal tract inflammation - Neurologic deficit

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 syndromeDisease occurs before age 4 years as arthritis, uveitis, and dermatitis.
  • Adult-type diseaseDiagnosed in adolescence as L ƒ ¶fgren syndrome with erythema nodosum, polyarthritis, and hilar adenopathyHowever, 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

  • CBCMild anemia, leukopenia, lymphopenia
  • Erythrocyte sedimentation rate (ESR) elevated
  • Angiotensin converting enzyme (ACE) levelCan be elevatedProduced in many granulomatous diseases but is useful in cases in which index of suspicion is highNot a perfect screening test; however, can follow levels in response to treatmentFalse positives: may be elevated inMiliary tuberculosisBiliary cirrhosis
  • Lysozyme level elevationMay be more sensitive than ACE level for detecting sarcoidosisMay be useful to follow disease activity in proven cases, if ACE levels cannot be usedFalse positives: may be elevated in
  • Serum calcium and creatinine levelsImportant in baseline evaluation
  • Urine test for bloodSeen 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 radiographyMay demonstrate hilar adenopathy
  • Gallium scanDemonstrates uptake diffusely in lungs (extremely sensitive test)

Alert

Uveitis may be occult; slit-lamp ophthalmologic evaluation is important. ‚

Differential Diagnosis

  • InfectionTuberculosisBacterial sepsisMumpsHIVGonorrheaLyme diseasePulmonary mycoses
  • TumorsLeukemiaNeuroblastomaLymphoma
  • ImmunologicOligoarticular juvenile idiopathic arthritis (for early-onset type)Systemic juvenile idiopathic arthritisSystemic lupus erythematosusSj ƒ ¶gren diseaseDermatomyositisBeh ƒ §et diseaseCrohn disease
  • ImmunodeficiencyCommon variable immunodeficiency
  • SkinGranuloma annulareErythema 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 creatinineShortness of breathPersistent uveal tract inflammationNeurologic 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.