Sarcoidosis Flashcards
What characterises sarcoidosis? Which organs are most commonly affected?
Inflammatory disease characterised by noncaseating granulomas.
- Need to rule out other diseases causing granulomas
- Need >=2 organs involved for a specific diagnosis
Organs
- Lung most common
- Liver, skin, eyes all commonly affected
Varied clinical course: 50% achieve remission in a few years, with the remainder having a chronic course lasting decades
What is the aetiology and epidemiology of sarcoidosis? Prognosis? What are the predictors of chronic disease?
Aetiology = not known
- thought to be an antigenic trigger in a genetically susceptible host
- propionibacter acnes and mycobacterium tuberculosis catalase-peroxidase are found in a higher proportion of those with sarcoidosis than controls
- Molds, insecticides, and healthcare work all associated with increased risk
Epidemiology
- Lifetime risk ~3%
- Highest prevalence in Nordic people
- African Americans in the USA have much higher prevalence: may be due to selection bias as they have disproportionate amount of pulmonary disease
- F>M; bimodal peak in young adults and ~60yrs
- 5% of cases have a relative with it, most sporadic
Prognosis
- Death or loss of organ function low
- Worst outcomes in those presenting with advanced disease, treatment often has little impact
Predictors of chronic
- - Fibrosis on CXR
- Presence of: lupus pernio, bone cysts, cardiac or neurologic (not isolated 7th nerve palsy) disease, renal calculi from hypercalcaemia
- - Requirement of corticosteroids within 6 months have >50% chance of chronic
- - <10% of those requiring no systemic therapy within 6 months require chronic
- - HLA-B13
What is the pathophysiology of sarcoidosis? Can natural history be predicted at diagnosis? What is Lofgren’s Syndrome?
Pathophysiology
- granulomata the hallmark
- local accumulation of inflammatory cells a distinct feature: initially CD4+ with accumulation of activated monocytes
- Different HLA haplotypes associated with risk of development and clinical outcomes
- T-cells necessary: HIV and few CD4s rarely develop, can then be unmasked with ART
Phenotypes
- persistent form linked with high levels of IL-8
-
Lofgren’s Syndrome = erythema nodosum, hilar adenopathy, +- periarticular arthritis. Don’t biopsy the EN, manage the arthritis with NSAIDs
- >90% have resolution within 2yrs
-
HLA-DRB1*03 found in >2/3 of Scandinavians with Lofgren’s
- >95% of HLA-DRB1*03 +ve have resolution within 2yrs
What are the proportions of organs affected by sarcoidosis?
How does cutaneous and ocular sarcoidosis present?
- *Cutaneous**
- Most common form of chronic sarcoidosis is maculopapular lesions: start purple and indurated; become confluent and infiltrative
- Eventually seen in >1/3
- Classics: erythema nodosum, maculopapular lesions, hyper/hypopigmentation, keloids, subcutaneous nodules
Lupus pernio = involvement of the bridge of nose, area under eyes, and cheeks. pathognmoic for sarcoidosis
Ocular (dedicated opthalmologic exam recommended for all)
- Frequency depends on race: >70% Japanese, <30% USA
- Mostly anterior uveitis
- >25% have posterior involvement: retinitis, pars planitis
- Posterior can be asymptomatic, or may be photophobia, blurred vision, retinal detachment
- >50% have sicca
What are the liver/hepatic, bone marrow/spleen manifestations of sarcoidosis?
Liver
- >=50% have disease using biopsy as the marker; 20-30% have biochemical evidence
- Mostly elevated ALP reflecting obstruction but can have ALT; elevated bilirubin a marker of advanced disease
- 5% have sufficiency symptoms to require specific management: intrahepatic cholestasis -> portal hypertension -> ascites/varices
- Rarely require transplant due to sarcoid as they can respond to systemic therapy
- Don’t use interferon in sarcoidosis + HCV as it can worsen granulomatous disease
Bone marrow and spleen
- Most common haematologic manifestation lymphopoenia from sequestration
- Anaemia in 20%
- BMAT shows granulomas in 1/3
- Splenomegaly in 5-10% but splenic involvement on biopsy in 60%
Is serum ACE useful in diagnosing sarcoidosis? Are any other tests useful? How is it diagnosed?
Poor sensitivity and specificity
- elevated in 60% of acute and 20% of chronic
- can aid in diagnosis
Multiple diseases can cause mild elevation
>1.5x ULN only in
- sarcoidosis
- leprosy
- Gaucher’s
- hyperthryoidism
- disseminated granulomatous infections
Imaging
- CXR used for lung involvement
- PET great for identifying other regions of granulomatous disease for biopsy
- MRI can be useful but may appear similar to malignancy or infection
Diagnosis
- Do not need biopsy for dx in Lofgrens syndrome
- Can just biopsy lung if no good sites due to high rate of involvement
Kviem-Siltzbach procedure = historical test
- Intradermal injection of tissue derived from spleen of a known sarcoidosis patient
- Biopsy at 4-6 weeks post: noncaseating granulomas highly specific for sarcoidosis
- Not used anymore due to lack of commercial reagent and large variability in specificity of locally prepared batches
What is the approach to treatment of sarcoidosis?
- Topical if possible, systemic if not
- Isolated raised LFTs or abnormal CXR probably don’t need treatment
- Hydroxychloroquine or minocycline for skin
- Glucocorticoids the medicine of choice
- Methotrexate the steroid sparing medicine of choice.
- Others: azathioprine, leflunomide, mycophenolate, cyclophosphamide
- Infliximab improves lung function in those pretreated with steroids and cytotoxic drugs
What alters calcium metabolism in sarcoidosis? Do they get renal manifestations?
Hypercalcaemia in 10% due to production of 1,25OHD (active Vit D aka calcitriol) by the granulomata
- worsened by dietary calcium and sun exposure
- responds to corticosteroids
Kidneys directly infiltrated in <5%
- Most common cause of sarcoidosis related kidney disease is hypercalcaemia
What are the possible neurologic manifestations of sarcoidosis? Musculoskeletal?
Neurological
- seen in 5-10%, can affect any region of central or peripheral nervous system
- common: cranial nerves, basilar meningitis, myelopathy, anterior hypothalamic disease (diabetes insipidus)
- cranial nerves may be isolated 7th nerve palsy (transient) or optic neuritis (usually chronic requiring therapy)
- may get seizures or cognitive changes
- often shows up on MRI and may look like MS: multiple enhancing white matter lesions
- meningeal or hypothalamic suggest neurosarcoidsosis
- extraneurologic disease suggests neurosarcoidosis
Musculoskeletal
- direct involvement of bone/muscle in about 10%
- very high percentage complain of myalgias and arthralgias
- similar to other chronic inflammatory diseases
How can cardiac sarcoidosis present?
Much more common in Japanese
Infiltration of cardiac muscle by granulomata
- CCF or arrhythmias
- in diffuse involvement can get EF <10%
- arrhythmias in patchy or diffuse involvement
- common causes of death: ventricular arrhythmias. ICD reduces cardiac death
- can get arrhythmias up to 6 months after starting successful treatment
Diagnosed on MRI or PET
