sarcoidosis

Question 1

what is sarcoidosis

Answer 1

Systemic disorder of unknown
cause(s) characterised by formation
of noncaseating granulomas,
affecting the lung in >90% of cases

Question 2

where can sarcoidosis affect

Answer 2

any organ: 
nervous
cvs
ocular = blindness 
lung most common

Question 3

what is the initial event that leads to granulomas

Answer 3

don’t know

Question 4

features of sarcoidosis and what the suggest

Answer 4

 Accumulation of oligoclonal T cells at sites of granuloma formation
suggest antigen-specific cell-mediated immune response
 Kveim-Siltzbach spleen extract skin tests suggest specific immune
response
 Features resemble other antigen-induced disorders, including chronic
beryllium disease, hypersensitivity pneumonitis, and mycobacterialinduced granulomatous disease

Question 5

what are the features that suggest infectious aetiology

Answer 5

other granulomatous diseases have infectious aetiology
• Epidemiological evidence suggesting clusters of disease in
environments linked with bioaerosol production
can be transmitted by transplant organs
difference in presence of microbe in sarcoid and control – organisms found most – P. acnes and micobacteria - however confidence intervals cross the non-significant line

Question 6

results of high throughput microbe genetic typing

Answer 6

o Correct any microbe for the sample in the env ie contaminants – found that overall the burden of microbe in sarcoid seems larger than in healthy control
o Couldn’t find microbes that were consistently present across the tissue
o Found fungi
o Need more work

Question 7

inconclusivity of finding microbes in sarcoid

Answer 7

heterogeneity between studies, especially the ones
on mycobacteria
only few international studies
unidentified organisms may be cause
Colonizing microbes may cause disease by their antigenic or
adjuvant properties rather than infection

Question 8

RF for sarcoidosis

Answer 8

Agricultural exposures
Insecticides
Microbial bioaerosols (work environments with mould/damp exposure)

Question 9

protective factors for sarcoid

Answer 9

cigarette smoking - develops when stop smoking

protective against granulomatous disorders

Question 10

genetic predisposition of sarcoidosis

Answer 10

familial clustering in several populations
More common in monozygotic than dizygotic twins
g associations with major histocompatibility
complex region (MHC) class II alleles
• susceptibility alleles: HLA DR 11, 12, 14, 15, 17
• protective alleles: HLA DR1, DR4
Other non HLA genes: BTNL2, IL-23R, NOTCH4, 11q13 locus in common
with other immune mediated diseases (ulcerative colitis, ank spond, RA)

Question 11

incidence of sarcoidosis

Answer 11

-Major geographical differences: prevalence highest in Northern Europe, USA, India
4x more severe and multi-organ in African-Americans than caucasians

Question 12

patterns of organ involvement

Answer 12

• Acute uveitis and erythema nodosum in Scandinavians, Irish, Puerto Ricans
• in Japanese, eye and heart frequent, no Lofgren (Lung)
• Lupus pernio more frequent in African-Americans

variation suggests gene involvement

Question 13

severity

Answer 13

more severe lung impairment and extrathoracic involvement in US AfricanAmerican, Afro-Caribbean patients

Question 14

could sarcoidosis be a family of disease

Answer 14

Lofgren’s disease has very distinct genetic associations (HLA DR3,
CCR2), demographics and clinical findings
• Different HLA associations with different organ involvement
(uveitis, cardiac)
• Different HLA associations with acute (HLA-DR3) and chronic
(HLA-DR14 and 15) disease

Question 15

pathogenesis of sarcoidosis

Answer 15

• Unknown ag – presented by APC coupled with HLA class 2 = amplification = granuloma

Question 16

explain the spread of sarcoidosis

Answer 16

Loosely-formed granulomas follow lymphatic pathways:
 bronchovascular bundles
 interlobular septa
 pleura

Question 17

diagnosis

Answer 17

no test for sarcoid
need compatible findings across investigations: clinical, XR, histology
exclude alternative ie TB
histology = non caseating granulomas
histology needed, especially if immunosuppressive treatment being considered
and/or diagnostic uncertainty (tb, lymphoma, lymphangitis)
discuss whether to do bronchoscopic histological confirmation with pt
o Aim for diagnostic probability of >95%
o Symmetrical bilateral lymphadenopathy and erythema nodosum = is sarcoid
o Calcification around LN and on both sides, on TB unilaterally only

Question 18

how many stages of sarcoid are there

Answer 18

4

done on XR

Question 19

stage 1 sarcoid

Answer 19

Bilateral hilar (+ Rt paratracheal) lymph nodes 
Symmetrical

Question 20

stage 2

Answer 20

Bilateral hilar (+ Rt paratracheal) nodes
 Parenchymal disease - ie white lung elargement

Question 21

stage 3

Answer 21

Parenchymal disease

No BHL/mediastinal nodes

Question 22

stage 4

Answer 22

fibrosis and scarring

upper lobe/hilar pulled up, trachea pulled to R by upper lobe fibrosis

Question 23

why is staging important

Answer 23

gives broad cohort outcomes, however
Cannot distinguish between active inflammation, fibrosis and
inactive disease
• Large variability within scorers on stage IV; trivial vs end stage lung
fibrosis
• Some pts will present at stage 1 – most will stay here, some will present at stage ¾ - sometimes see switch – but can stick with the stage you present with

Question 24

broad cohort outcomes of the stages

Answer 24

1 = good 
2 = progression in one third at 5
years
3 =  progression in two thirds at 5
years
4 =  overt fibrotic disease, significant mortality

Question 25

diagnosis with bronchoscopy and biopsy

Answer 25

in stage 1 or 2: EBUS-TBNA/EUS-TBNA • (with rapid onsite cytology if available) (80% diagnostic yield) +- TBBx (90%) ``` stage 3/4 BAL: Lymphocytosis: 25-30% • +/- CD4/CD8 ratio (>4 highly specific) • Microbiological sampling • EBBx-TBBx (90%) ```

Question 26

course of most pts

Answer 26

benign

Question 27

epidemiology of progressive pulmonary fibrosis

Answer 27

``` significant minority of people have it Approximately 8-10% of sarcoidosis patients will have shortened life expectancy; of these roughly 70% due to pulmonary involvement ```

Question 28

CT appearance of progressive pulmonary fibrosis

Answer 28

fibrotic changes with traction bronchiectesis | airway pulled apart by fibrosis and ground glass

Question 29

predictors of mortality in pulmonary sarcoidosis

Answer 29

age fibrosis on HRCT >20% ie extensive disease pul HTN

Question 30

what do you need to determine about the fibrosis and why

Answer 30

``` Is the fibrotic disease stable or progressive? • Aim of treatment is to prevent progression of fibrosis, but avoid toxicity in stable fibrosis • Ongoing active inflammation likely to lead to further progression of fibrosis therefore need measures of disease activity ```

Question 31

what are the measures of disease activity

Answer 31

``` HRCT patterns • FDG-PET • -Bronchoalveolar lavage: lymphocytosis • -Serum markers: inflammatory markers, ACE, IL2R, chitotriosidase, 24- hour urinary calcium • -Serial Lung Function Tests ```

Question 32

can you assess reversibility with CT

Answer 32

o Nodular sarcoids – reversible, agglomerates of sarcoid glomeroma therefore active – reversible o Ground glass – grey attenuation of parenchyma - mostly irreversible – cant determine if still inflamm o Irreversible – UIP pattern with honeycombing so CT cant always distinguish

Question 33

Use of FDG-PET to determine stable/progressive

Answer 33

FDG-PET/CT correlates with other markers of disease activity ie BAL and serum inflamm markers • PET activity correlated with more severe lung function impairment and extensive CT changes, including fibrosis most have extra-thoracic PET positivity too ie still inflammation in fibrotic changes therefore treatment with anti-TNF (infliximab) = improvement

Question 34

monitoring pulmonary sarcoidosis

Answer 34

Change in symptoms of breathlessness/cough Lung function: change in FVC, FEV1 by ≥10%; DLCO ≥15% (ATS/ERS criteria) • (isolated drop in DLCO suggesting pulmonary vascular involvement) chest Xray • chest HRCT better correlated with lung function changes • (FDG-PET to assess ongoing activity when disease not responding to treatment) serum biomarker changes worsening in >1 domain will increase the liklihood that the changes are real

Question 35

what is the major complication of sarcoidosis

Answer 35

chronic pulmonary aspergillosis o 5-10% from chronic sarcoid suffering from CPA – all had advanced disease, high prev pul htn, treat with long term anti-fungal- death caused by advanced sarcoid, rather than massive haemoptysis – although concern in cavitating lesions full of fungus o More common fungi exposure

Question 36

what are the indications for management of sarcoid

Answer 36

major loss of quality of life (fatigue that is life changing, skin disease, joint pains – may not danger from internal organ though) danger from disease

Question 37

treatment options for QOL

Answer 37

discuss with pt if dont treat - NSAIDs for joint pains as needed if do: Low dose prednisolone • Hydroxycloroquine • Less likely to use methotrexate or azathioprine (immunosuppressants), except for particular cases

Question 38

death in sarcoid

Answer 38

<10% of patients have a shortened life expectancy • Respiratory failure and cardiac failure/arrhythmias the most common

Question 39

risk stratification in sarcoid

Answer 39

• Integration of clinical, functional and imaging features to assess likelihood of progression of pulmonary sarcoidosis • In cardiac disease, we need markers of accurate early diagnosis to prevent loss of function and fatal arrhythmias

Question 40

how do you identify pts at risk of progression of fibrosis and so which to treat

Answer 40

• Severity of pulmonary fibrosis: • Irreversible changes present • Integration of symptoms, lung function and imaging Which lung function thresholds ? Lung function: • FVC <60% • DLCO <50% • Major airflow obstruction Longitudinal behaviour - if function dropping and symptoms increasing need to treat

Question 41

describe cardiac sarcoid

Answer 41

``` o Should screen for involvement in all o Ask about presence of symptoms Palpations, disproportionate breathless, syncope, presyncope ECG abnormalities Echo if find things = furtehr imaging ```

Question 42

ECG abnormalities in cardiac sarcoid

Answer 42

``` AV block, frequent premature ventricular ectopics, non-sustained/sustained ventricular tachycardia, LBBx or RBBx, Q waves, axis deviation ```

Question 43

echo abnormalities in cardiac sarcoid

Answer 43

``` reduced LVEF, regional wall abnormalities, wall thinning or thickening, ventricular aneurysms ```

Question 44

further investigations used if suspect cardiac sarcoidosis

Answer 44

cardiac MRI FDG-PET alongside resting myocardial perfusion scan PET tends to be more sensitive than MRI: however, whether isolated PET positivity has prognostic significance remains to be established

Question 45

treatment of sarcoidosis

Answer 45

o Toxicity of steroid very diff high dose compared to low dose o Second line immunosuppression o Corticosteroids – mainstay of treatment – moderates doses o High dose long term = methylprednisolone o Aim is to go as low as possible – maintain improvement and objective lung func improvement o 2nd line – methotrexate, azathioprine +- hydroxychloroquine  Used if low dose steroids not sufficient to allow control or need corticosteroid spearing – comorb (obesity, dm, osteoporosis), intolerance o Biologics  3rd agent – once pt has failed steroid and 2nd line  Active and progressive disease despite non conventional or Toxicity or lack of tolerability to conventional treatments

Question 46

steroid regieme in sarcoidosis

Answer 46

• Corticosteroids remain mainstay of treatment: • Induction • Moderate dose oral prednisolone (20-40 mg od) • Or in selected cases with severe disease • High dose iv methylprednisolone treatment (1 Gr x 3) followed by 20 mg od, then tapered • Maintenance • Low dose 7.5-10 mg od

Question 47

PET

Answer 47

CT pick up radioactive glucose – injected into vein – goes to more active site ie inflammation or cancer- light up – wont tell sarcoid, just that there is positivity

Question 48

honeycomb pattern

Answer 48

parallel lines of cysts that have walls end stage fibrosis often seen in usual interstitial pneumonitis - pattern that defines idiopathic pul fibrosis also in sarcoid happens because disruption of architecture -dialtion of airways, formation of aberrent airways and cystic spaces

Question 49

why is the hilar pulled up in stage 4 sarcoid

Answer 49

all granulomatous disease go to apices because done with things inhaling eg hypersensitivity pneumonitis – fibrosis which retracts the lung and therefore pulls up the hilar

Question 50

presentation of sarcoid

Answer 50

o Non-specific o Extra-pul involvemenht help – erythema nodosum – painfulnothces on shin o Classic skin lesions elsewhere o Young pts o Fatigue – incredible o Joint pain – ankles most commonly involved o Cough, breathlessness – XR will show one of the stages

Question 51

what is TBNA

Answer 51

endobronchial aspirate – US guided – go with bronchoscopy and fine needle to biopsy LN of mediastinum