sjogren's disease Flashcards
overview: general concepts of sjogren’s syndrome
systemic autoimmune disease that attacks exocrine glands (glands with ducts)
often presents with dry eyes and dry mouth from desctruction of salivary and lacrimal glands
5% develop lymphoma
Epi of sjogren’s syndrome
second most common autoimmune disorder
female:male 9:1
onset in 4th-6th decade
60% associated with another autimmune disease like SLE, RA
What is the most important cytokine in the pathogenesis of sjogren’s syndrome?
TNF-alpha
What is the role of salivary gland epithelial cells in the pathogensis of sjogren’s syndrome?
epithelial cells play a roll in acquired immunity and in innate immunity. They act as antigen presenting cells, secrete pro-inflammatory cytokines, and secrete BAFF and lymphoattractant molecules- all promote acquired immunity. They also express toll like receptors, which are important for innate immunity. If they apoptose, they release many antigens. In Sjogren’s syndrome, they promote autoimmune epithelitis
what is some histo and lab findings that might be seen in sjogren’s
germinal center like structures in 1/3 of salivary glands coincide with incr. titers of rheumatoid factor and incr. IgG levels.
also see high IL-17, INF-alpha, and BAFF molecules
How do B cells become activated in sjogren’s
IFN-alpha in combination with BAFf promotes B cell activation
What is oligomonoclonal hyperactivity in the context of sjogren’s?
1/3 of pts have mixed cryoglobulins. oligoclonal B cell expansions are seen early and is the most consistent immunoregulatory aberration in Sjogren’s. It may develop into malignant monoclonal prolif.
What are the important auto-antibodies in Sjogrens?
RF, ANA, anti-Ro, anti-La
What is the histopathology of Sjogren’s
focal lymphocytic infiltrate around glandular ducts. Infiltrates are mostly made of T cells, with some activated B cells and plasma cells.
Diagnostic criteria for sjogren’s
positive anti-Ro and anti-La or (RF and ANA)
labial salivary gland biopsy with focal lymphocyti sialadentitis
keratoconjunctivitis on occular exam
need 2/3 criteria
clinical findings in sjogrens (systemic): neuro, skin, gland, lung
excretory gland dysfunction: sicca and salivary gland enlargement
hypergammaglobulinemic purpura
central and peripheral neuro problems. most often predominantly sensory neuropathy (hearing loss and CNS demyelination are rare)
palpable purpura and raynaud’s
pulmonary disease (esp. interstitial lung disease and recurrent pneumonias)
Manifestations of sicca in sjogren’s
ocular dryness with corneal injury possible; oral dryness with dysphagia, dental carries, and thrush, nasal dryness and epistaxis, vaginal dryness (yeast infections and dyspareunia
Overview of evaluation for sjogrens
rose bengal/fluorescein: opthamology. the dye should go away- if it is retained, it suggests lack of lacrimation
biopsy of minor salivary gland
serylogy tests
consider dental eval and eval for renal tubular acidosis
(schirmer test of ocular dryness now outdated)
clinical findings in sjogrens (systemic): MSK, general, GI and GU
nephropathy, esp. renal tubular acidosis (distal RTA with hypercalcuria- may see calcium on renal xray)
MSK probs, usually w/o joint deformities or erosisons
debilitating fatigue.
lymphoma
dysparunia and vaginal dryness
Can cause intestinal malabsorptio and is associated with PRIMARY BILIARY CIRRHOSIS
Lymphoma in sjogren’s
lymphoma risk is 6X that of controls
usually B cell lymphoma- even though sjogren’s is predominantly a T cell disease, we get b cell lymphoma from the oligoclonal factors.
may present as unilateral salivary gland adenopathy or swelling
Risk is about 5% in 10 yrs
many types seen, but most common is MALT- but MALT can progress to disseminated or high grade disease.
accounts for most deaths in Sjogren’s
