http://www.fpnotebook.com/

SarcoidosisAka: Lupus Pernio, Lofgren's Syndrome

Epidemiology
1. Affects young adults most commonly ages 20 to 40 years
2. Prevalence in United States
  1. Most common in U.S. Blacks, Danes and Swedes
  2. Black patients: 40 per 100,000
  3. White patients: 5 per 100,000
History
1. First described by Hutchinson in 1877
Pathophysiology
1. Noncaseating granuloma formation
2. Idiopathic
  1. Underlying genetic predisposition
  2. Precipitated by trigger
    1. Infection (e.g. Mycobacteria, Borrelia Burgdorferi)
    2. Environmental exposure (e.g. Beryllium, Aluminum)
3. Common involvement sites (affects all organ systems)
  1. Lungs (>90%)
    1. Interstitial Lung Disease
  2. Lymphadenopathy: Hilar adnenopathy (>95%)
  3. Liver (50-80%)
    1. Hepatic Granulomas (86%)
    2. Hepatomegaly (20%)
    3. Increased Alkaline Phosphatase
  4. Spleen (40-80%)
  5. Skin lesions (25%)
    1. Lupus Pernio
    2. Dactylitis
  6. Eyes (20-50%)
    1. Anterior Uveitis (18%, also in Spondyloarthropathy)
    2. Posterior Uveitis (7%, Behcet's Disease)
    3. Lacrimal gland hypertrophy
    4. Conjunctival Nodules
    5. Keratoconjunctivitis (also in Sjogren's Syndrome)
    6. Proptosis (also in Wegener's Granulomatosis)
  7. Heart (5%)
    1. Tachyarrhythmias
    2. Cardiomyopathy
  8. Kidney (uncommon)
    1. Membranous Glomerulonephritis
    2. Nephrocalcinosis
    3. Nephrolithiasis
    4. Renal insufficiency
  9. Bone Marrow (4-40%)
    1. Leukopenia (28%)
    2. Eosinophilia (34%)
  10. Gastrointestinal
    1. Pancreas (6%)
    2. Stomach or esophagus
  11. Parotid Gland (5%, also seen in Sjogren's Syndrome)
  12. Skeletal muscle (4%, also seen in Polymyositis)
  13. Upper airway (3%, also in Wegener's Granulomatosis)
    1. Saddle-nose deformity
Symptoms
1. Pulmonary (presenting symptom in 40-45%)
  1. Dry cough
  2. Dyspnea
  3. Chest Pain (non-specific)
  4. Hemoptysis (rare initially)
2. Constitutional symptoms (presenting symptom in 25%)
  1. Fever (associated with hepatic granulomas)
  2. Weight loss
  3. Fatigue
  4. Malaise
Signs: Arthritis (occurs in 10-15% of cases)
1. Early joint disease (first 6 months)
  1. Duration: weeks to 3 months
  2. Common joints involved
    1. Onset in ankles
    2. Spreads to knees
  3. Involves other joints
    1. Proximal interphalangeal joint
    2. Metacarpophalangeal joint
    3. Wrist
    4. Elbow
  4. Spares axial skeleton
  5. Associated with Erythema Nodosum
  6. No XRay changes
2. Late joint disease (onset after 6 months)
  1. Common joints involved
    1. Knees
    2. Ankles
    3. Proximal interphalangeal joints
  2. Associated with chronic cutaneous sarcoidosis
  3. XRay changes (see below)
Signs: Skin changes (Lupus Pernio)
1. Initial Characteristics
  1. Papular lesions (most common)
  2. Reddish-brown to purple color (violaceous Plaques)
  3. Scaling may occur
  4. Diameter: 1 to 3 cm
2. Later Characteristics
  1. Lesions coalesce into Annular Lesions or Plaques
  2. Chronic form may show scarring and disfigurement
3. Distribution (most commonly involves face)
  1. Periorbital area
  2. Nasolabial folds
  3. Mucous membranes
  4. Ears
  5. Fingers and Toes
4. Other skin changes
  1. Dactylitis (sausage digits)
    1. Associated with chronic arthritis
Signs: Lymphadenopathy
1. Mediastinal lymph node involvement most common
2. Peripheral Lymphadenopathy (non-tender, <5 cm)
Staging
1. Based on Chest XRay (see below)
Radiology: Chest XRay (abnormal in 90% of cases)
1. Type 0: No abnormality (<10% of cases)
2. Type I: Lymphadenopathy alone (43% of cases)
  1. Bilateral hilar Lymphadenopathy
  2. Mediastinal Lymphadenopathy
  3. Right paratracheal Lymphadenopathy
3. Type II: Adenopathy and Infiltrates (24% of cases)
  1. Lymphadenopathy as in Type I Chest XRay findings
  2. Parenchymal infiltrates
  3. Symptomatic respiratory disease presentation
4. Type III: Infiltrates alone (13% of cases)
  1. Parenchymal infiltrates
Radiology: Joint and Bone XRay in arthritis
1. Acute Arthritis not associated with XRay changes
2. Chronic Arthritis uncommonly with XRay changes
  1. Middle and distal phalanx bone destruction or cysts
  2. Trabecular changes to bone (honeycombing)
Labs: Diagnosis
1. Pulmonary Function Testing
  1. Findings consistent with Interstitial Lung Disease
2. Serum Angiotensin-converting enzyme (Serum ACE)
  1. Increased in 50-80% of Sarcoidosis patients
3. Gallium scan
  1. Panda and lambda patterns
4. Biopsy or Cytology (Gold standard)
  1. Finding
    1. Discrete noncaseating epithelioid granuloma
  2. Biopsy sites
    1. Transbronchial lung biopsy (preferred site)
    2. Bronchoalveolar lavage (CD4-CD8 ratio >3.5)
    3. Skin biopsy of lesion
    4. Palpable peripheral lymph node biopsy
    5. Salivary Gland biopsy
Labs: Additional baseline for Sarcoidosis monitoring
1. Serum Chemistry
  1. Serum Calcium
  2. Renal Function tests
  3. Liver Function Tests
  4. Urinalysis
2. Electrocardiogram
3. Ophthalmology evaluation
4. Tuberculin Skin Test
Associated Conditions
1. Erythema Nodosum (suggests better prognosis)
  1. Associated with acute arthritis (Lofgren's Syndrome)
  2. Not associated with chronic arthritis
  3. Most common associated nonspecific skin sign
Differential Diagnosis
1. Lung conditions
  1. See Interstitial Lung Disease
  2. See Hilar Adenopathy
  3. Infections
    1. Tuberculosis
    2. Coccidiodomycosis
    3. Blastomycosis
    4. Aspergillosis
    5. Histoplasmosis
    6. Pneumocystis carinii
2. Arthritic Conditions
3. Skin Differential Diagnosis
  1. See Annular Lesion
  2. See Erythema Nodosum
  3. Papular lesions similar to Sarcoidosis
    1. Granulomatous Rosacea
    2. Acne Vulgaris
  4. Plaque-type lesions similar to Sarcoidosis
    1. Psoriasis
    2. Lichen planus
    3. Nummular eczema
    4. Discoid Lupus Erythematosus
    5. Granuloma Annulare
    6. Cutaneous T-Cell Lymphoma
    7. Kaposi's Sarcoma
    8. Secondary Syphilis
  5. Reference
    1. Katta (2002) Am Fam Physician 65(8):1581
Management: Pulmonary Sarcoid
1. Indications
  1. Dyspnea
  2. Persistent cough
  3. Widespread debilitating disease
2. First-line: Systemic Corticosteroids (e.g. Prednisone)
  1. Indications
    1. Stage 2 or 3 lung changes
  2. Efficacy
    1. Short term benefit in moderate lung disease
    2. Unclear whether disease-modifying effect
  3. Protocol
    1. Start Prednisone at 20 to 40 mg per day
    2. Evaluate at 1-3 months for response
      1. No response: Taper off over 4-6 weeks
      2. Response
        
        Taper Prednisone to 5-10 mg/day
        
        Continue Prednisone for total of 12 months
    3. Consider Osteoporosis Prevention
      1. See Corticosteroid Associated Osteoporosis
  4. Reference
    1. Paramothayan (2002) JAMA 287:1301
    2. (1999) Am J Respir Crit Care Med 160:736
3. Other management options
  1. Cytotoxic agents
    1. Used as alternative or as adjunct to Prednisone
    2. Agents
      1. Methotrexate (Rheumatrex) 10-25 mg weekly
      2. Azathioprine (Imuran)
  2. Immunomodulators
    1. Chloroquine
    2. Hydroxychloroquine (Plaquenil)
  3. Thoracic surgery indications
    1. Life-threatening Hemoptysis (lung resection)
    2. End-stage pulmonary sarcoidosis (lung transplant)
Management: Extrapulmonary Sarcoid
1. Ophthalmologic Sarcoidosis: Uveitis
  1. First line: Topical Corticosteroids
  2. Refractory cases
    1. Prednisone (preferred)
    2. Methotrexate
2. Cutaneous sarcoidosis
  1. Erythema Nodosum lesions: NSAIDs
  2. Sarcoid lesions
    1. Intralesional Corticosteroids (e.g. Kenalog 5/ml)
      1. Inject lesions q2-3 weeks
    2. Other agents
      1. Doxycycline
      2. Minocycline
  3. Oral Corticosteroid indications
    1. Lupus Pernio
    2. Severe or disfiguring lesions
3. Neurosarcoidosis: Cranial or Peripheral Neuropathy
  1. First-line: Oral Corticosteroids (e.g. Prednisone)
  2. Other agents: Cyclosporine or Azathioprine
Monitoring
1. Monitoring tools at visits
  1. History and physical
  2. Chest XRay
  3. Spirometry
  4. Specific testing when indicated
2. Stage I Sarcoidosis
  1. Start with evaluations every 6 months
  2. May space visits to every 12 months if stable
  3. No follow-up if off therapy and stable for 3 years
3. Stage II to IV Sarcoidosis
  1. Start with evaluations every 3-6 months
  2. Continue visits indefinately
Prognosis
1. Overall mortality (from respiratory failure): 1-5%
2. Factors suggestive of worse prognosis
  1. Onset after age 40 years
  2. Black race
  3. Chronic Hypercalcemia
  4. Specific higher risk organ involvement
    1. Neurologic involvement
    2. Skin involvement (lupus Pernio)
    3. Cardiac involvement
    4. Eye involvement (Chronic Uveitis)
    5. Renal involvement (Nephrocalcinosis)
    6. Cystic bone lesions
    7. Involvement of nasal mucosa
    8. Progressive pulmonary fibrosis
3. Remission within 2 years
  1. Type I: 80% remission rate
  2. Type II: 30-50% remission rate
  3. Type III: <20% remission rate
References
1. Klippel (1997) Primer Rheumatic Diseases, AF, p. 325-7
2. Wilson (1991) Harrison's IM, McGraw-Hill, p.1463-9
3. Belfer (1998) Am Fam Physician 58(9):2041
4. Hsu (2001) Am Fam Physician 64(2):289
5. Wu (2004) Am Fam Physician 70:312

Sarcoidosis, lupus pernio type (C0024145)
Concepts	Disease or Syndrome (T047)
ICD9	135
English	CHBL, CHILBLAIN LUPUS, Chilblain lupus erythematosus, Lupus pernio
Spanish	lupus pernio, sabaÃ±Ã³n en lupus eritematoso, sabanon en lupus eritematoso
Credits	Derived from the NIH UMLS (Unified Medical Language System)

Sarcoidosis (C0036202)
Definition (AIR)	WHAT: Sarcoidosis: Sarcoidosis: a disorder of unknown etiology that affects many organ systems with noncaseating epithelioid cell granulomas. It has a special predilection for the lung and lymph tissues. WHY: Sarcoidosis can result in an acute arthritis commonly affecting the ankles and knees and less commonly the proximal interphalangeal joints, wrists, and elbows. The acute arthritis is symmetric and lasts for a few weeks. A less common chronic arthritis is destructive and may have dactylitis and telescoping digits. HOW: Sarcoidosis is a diagnosis of exclusion based on the clinical presentation and histology of biopsy tissue.
Definition (MSH)	An idiopathic systemic inflammatory granulomatous disorder comprised of epithelioid and multinucleated giant cells with little necrosis. It usually invades the lungs with fibrosis and may also involve lymph nodes, skin, liver, spleen, eyes, phalangeal bones, and parotid glands.
Definition (CSP)	inflammatory disease characterized by small lumps or granulomas in lymph nodes and other organs.
Concepts	Disease or Syndrome (T047)
ICD9	135
English	Benign Lymphogranulomatosis, Benign lymphogranulomatosis of Schaumann, BESNIER BOECK DIS, Besnier Boeck disease, Boeck Sarcoid, Boeck's Sarcoid, Boeck's sarcoidosis, Boecks Sarcoid, Boecks sarcoidosis, Lupus pernio of Besnier, lymphogranulomatosis, Miliary lupoid of Boeck, Sarcoidoses, Sarcoidosis, SCHAUMANN DIS, Schaumann Disease, SCHAUMANN SYNDROME, Schaumann's Disease, SCHAUMANNS DIS, Schaumanns Disease
Spanish	linfogranulomatosis benigna de Schaumann, lupoide miliar de Boeck, lupus pernio de Besnier, sarcoide de Boeck, sarcoidosis
Credits	Derived from the NIH UMLS (Unified Medical Language System)

Pulmonology Book

Approach

Miscellaneous

http://www.fpnotebook.com/

SarcoidosisAka: Lupus Pernio, Lofgren's Syndrome

Sarcoidosis, lupus pernio type (C0024145)

Sarcoidosis (C0036202)

Navigation Tree