Sarcoidosis Flashcards
Sarcoidosis derives from Greek - sarco = __ ; eidos = __ ; osis = __
Definitiion: systemic inflammatory disorder of __ involving multiple organs, primarily __
Sarco = flesh ; eidos = like ; osis = condition
Non-caseating granuloma, lungs
Diagnostic criteria for sarcoidosis
- Consistent clinical and radiographic presentation
- bilateral hilar adenopathy - Histological evidence of non-caseating epitheloid granulomas in > 1 organ
- Excluded other granulomatous disease - mycobacterium, fungal, berylliosis, drugs, local reactions to tumours, lymphoma
Presumptive diagnosis can be made based on clinical and radiographic features alone
- Bilateral hilar adenopathy
- Lofgren syndrome
- Heerfordt syndrome
Epidemiology of sarcoidosis
- Frequently affects African-Americans and northern Europeans
- Women > men
- Bimodal peak - 3rd to 4th decade; 6th decade (more in women)
- Higher prevalence in first generation relatives
- Obesity has higher risk of sarcoidosis
- Reduced risk in smokers
Immunopathologic features of sarcoidosis
Causes: genetics + environment
Reports of medication induced sarcoidosis: checkpoint inhibitors, HAART, IFNs, TNF-a antagonists
- Antigen-driven activation of macrophages and T-lymphocytes
- MHC class II molecules on APC present antigen to CD4+ T helper lymphocytes resulting in amplified immune response and incerased secretion of cytokines
- Incerased tissue permeability and cell migration - Dysfunction of regulatory T cells and expansion of IL-17 and INF-g TH17 cells
- Clonal expansion of CD4+ T lymphocytes leading to persistent inflammation, non-caseating granuloma formation and fibrosis of affected organs
Manifestations in laboratory testing
1. BAL cell count: elevated lymphocytes, increased CD4/CD8 ratio (>3.5)
2. Peripheral blood lymphopenia (all sequestrated at inflammatory sites)
3. Low peripheral CD4/CD8 ratio
4. Polyclonal gammopathy
5. Autoantibody (low titre RF, ANA)
Clinical presentation of sarcoidosis
- Asymptomatic with incidental abnormal CXR (bilateral hilar adenopathy)
- 95% intrathoracic involvement, and among them 50% extrathotacic involvement
- However less than 1/2 actually has respiratory symptoms
- Skin rashes, ophthalmologic involvement
- Rarely cardiac or neurologic involvement - 2% isolated extrathoracic involvement
Respiratory tract manifestations of sarcoidosis
Entire respiratory tract from sinuses to lungs can be involved - thus a spectrum of manifestations
- Asymptomatic hilar adenoapthy
- Interstitial lung disease with alveolitis
- Pleural effusion
- Pulmonary hypertension (group V)
Symptoms and signs - non-specific
1. Dry cough
2. Dysapnoea
3. Chest pain
4. Haemoptysis
- Clubbing
- Crepitations
- +/- Wheeze (endobronchial involvement)
Chest radiography staging of sarcoidosis
- Scadding staging system
Stages are not chronologic, does not indicate chronicity and does not correlate with lung function test
Extra-thoracic clinical manifestations of sarcoidosis
A. Non-specific symptoms - disabling fatigue (commonest 50%)
B. Cutaneous involvement
1. Skin rashes (33%) - erythema nodosum, subcutaneous nodules, papules, plaques
2. Tattoo/scar sarcoidosis
3. Lupus pernio
C. Ocular involvement - bilateral
4. Anterior uveitis
5. Lacrimal gland fibrosis - dry eyes, keratoconjunctivitis
6. Proptosis
D. Joint involvement
7. Inflammatory arthritis - acute or chronic
- Acute: Lofgren syndrome: oligo/polyarticular large joint swelling (commonest: ankles)
8. Osseous sarcoidosis (asymptomatic) - Phalanges
9. Skeletal muscle sarcoid myositis (<3%)
E. Systemic organ involvement
10. Hepatosplenomegaly and ALP transaminitis
11. Bilateral parotid enlargement, xerostomia
12. Neurological involvement in 5%
- Unilateral facial nerve palsy commonest, or any regions of brain and spinal cord
- Aseptic meningitis, encephalopathy, mass lesion
- Peripheral and small fibre neuropathy
13. Cardiac sarcoidosis in 5%
- Myocarditis, ventricular arrhythmias and conduction defectgs
14. Diabetes insipidus - HPA axis involvement
15. Sarcoidosis
16. Rarely affects kidney and GI tract
F. Haematologic involvement
16. Anaemia of chronic disease
17. Peripheral leukopenia (with organ/BAL leukocytosis and elevated CD4/CD8 ratio)
Definitive and Supportive Investigations for sarcoidosis
Definitive investigations
1. Clinical features
2. CXR - bilateral hilar adenopathy
3. Biopsy of affected organ(s) with cell count and CD4/CD8 ratio
Supportive investigations
4. Elevated serum ACE x2 ULN (40-90%) - correlates with active pulmonary disease and normalise with therapy
(Produced by epitheloid and macrophages by ACE-inducing factor released by T cells)
- DDx: TB, coccidiodomycosis, Gaucher, hypersensitivity pneumonitis, silicosis, asbestosis, leprosy, hyperthyroidism, lung cancer, DM, genetic polymorphism
- Suppressed by ACEi
5. Elevated serum lysozme (70-80%)
Correlating rheumatologic manifestations of sarcoidosis vs differentials
- Arthritis - Lofgren syndrome (25%)
DDx: RA, gonococcal arthritis, rheumatic fever, SLE, gout, spondyloarthropathies - Parotid gland enlargement (5%)
DDx: Sjogren’s syndrome, IgG4-RD - Upper airway disease (5-10%) - sinusitis, saddle nose deformity
Ddx: granulomatosis polyangitis - Anterior and posterior uveitis (20-30%)
DDx: spondyloarthropathy, Behcet - Proptosis (rare)
DDx: GPA, IgG4-RD - Myositis (3%)
Ddx: polymyositis - Mononeuritis multiplex, facial nerve palsy (1-2%)
Ddx: systemic vasculitis, Lyme disease
Lofgren’s syndrome is a triad of __ (3)
Also associated with __ and __
Joint involvement usually __, duration ________
ACE level may be __, and if so are likely to have _____ arthritis
DDx: __ - to be excluded by serologies, urine antigen, cultures
Overall prognosis: ___
Triad of acute arthritis/periarthritis, erythema nodosum, bilateral hilar adenopathy
Associated with fever and uveitis
Joint involvement: arthritis/periarthritis of ankles
Duration self limiting, either resolves within weeks or persists up to 3 months
ACE level elevated - high likelihood of recurrent/persistent arthritis
Ddx: acute histoplasmosis
Overall prognosis: >90%
Heerfordt syndrome is also known as __
Tetrad of __ (5)
Mostly occur in __ (sex) and has a poor prognosis
Treatment with __ and __
Uveoparotid fever
Tetrad of: fever, parotid enlargement, uveitis, arthritis, facial nerve palsy
Occurs in males, poor prognosis
Treatment with mod dose corticosteroids, IST
Comparison of acute and chronic sarcoid arthritis
How common does skeletal muscle sarcoidosis present?
How do they present clinically?
Sarcoid myopathy occurs in patients with multiorgan involvement
Mosty patients usually asymptomatic
Symptomatic:
1. Nodular myositis rarest - MRI dark star pattern in musculotendinous junctions
2. Acute granulomatous inflammatory myositis is rare, and indistinguishable from polymyositis
3. Chronic myositis (commonest) - insidious proximal symmetric muscle weakness and wasting, +/- neurogenic atrophy from granulomatous infiltration of nerves
Only acute myositis responds well to setroids
Osseous sarcoidosis
3-13%, asymptomatic
Involves: phalanges of hands and feet, +/- axial bones
(spares MCPJ, MTPJ, wrists)
Features on radiography:
1. Trabecular pattern
2. Osteolysis
3. Cysts/punched out lesions
Imaging
1. Bone scans
2. MRI and PET-CT
