10 - 68 - SJOGREN SYNDROME Flashcards
Sjogren syndrome is a chronic, multisystem autoimmune disease, characterized by chronic inflammation involving what glands?
exocrine glands
Salivary and lachrymal glands are affected predominantly, leading to dry mouth and dry eyes
Recent studies have shown that both innate and adaptive immunity contribute to the development of pSS; the what signaling pathway plays a central role in the pathogenesis of the disease?
Type 1 interferon (IFN)
SS patients with systemic manifestations are at higher risk of developing what malignancy?
Lymphoma
chronic systemic autoimmune disorder characterized by lymphocytic infiltration and destruction of exocrine glands and epithelia leading to dry mouth, dry eyes, and B lymphocyte hyperreactivity
Sjögren syndrome (SS)
this mutation has been correlated with an increased risk of lymphoma
TNFAIP3 mutation
best-defined autoantibodies in SS
anti-Ro/SSA and anti-La/ SSB antibodies.
- Anti-Ro/SSA antibodies are found in more than 70% of patients with SS but are not specific for SS and are frequently found in SLE and other autoimmune diseases, even when there is no symptom or sign of oral or ocular dryness
* Anti-La/ SSB antibodies are more specific; it is present in 50% of patients with pSS or SS/SLE but is rarely seen in other diseases.
major stimulus for saliva production
binding of acetylcholine to muscarinic acetylcholine receptors
principal symptom of SS
Oral dryness/ xerostomia
- caused by decreased saliva secretion, which is persistent and continuous throughout the day and night and can significantly compromise quality of life
It represents an important marker of more severe disease and is associated with an increased risk of lymphoma development and mortality
Palpable purpura
- does not blanch when pressure is applied to the skin, is due to dermal vasculitis with extravasation of red blood cells, and typically involves the lower extremities and buttocks
characteristic feature of caries in SS is its primary location which are what regions of the teeth?
characteristic feature of caries in SS is its primary location, at the cervical and incisal regions of the teeth
second most frequent form of cutaneous vasculitis in SS and presents as pruritic wheals with erythema
Urticarial vasculitis
- In contrast to true urticaria, individual lesions last for more than 24 hours and often resolve with hyperpigmentation.
- Biopsy of the skin lesions demonstrates a perivascular neutrophilic infiltrate, accompanied by leukocytoclasia
Its presence should raise suspicion for sarcoidosis.
Erythema Nodosum
most common peripheral nervous system manifestations of pSS, which are typically sensory
peripheral axonal polyneuropathies
most common cranial neuropathy anifestation of pSS
unilateral trigeminal neuropathy
- it usually spares the ophthalmic division, preserving the corneal reflex
These antibodies can cause congenital heart block (CHB) or neonatal lupus (NLE), characterized by an annular rash with central regression or mild atrophy in the scalp and around the eyes, as well as hepatic and hematologic abnormalities
anti-Ro/SSA, anti-La/SSB
- For the diagnosis of pSS, at least** 4 criteria **should be present, and at least one of them should be evidence of lymphocytic infiltration or the presence of autoantibodies
- Patients with a coexisting connective tissue disease are labeled secondary SS.
- Exclusions include other diseases and medications that may cause sicca symptoms
Classification Criteria for Sjögren Syndrome
involves measurement of the total saliva produced from all salivary glands in a time period of 15 min
*What is considered suggestive of SS?
Sialometry
The whole unstimulated salivary flow is considered suggestive of SS if it is <1.5mL in 15 minutes
A “stimulated” salivary flow can be measured after administration of lemon juice or citric acid, and low values are also suggestive of SS
functional study to assess saliva production by measuring the secretion of a radioisotope (99m technetium sodium pertechnetate) into the oral cavity
Salivary gland scintigraphy (SGS)
provides functional information about individual salivary glands and can potentially distinguish between decreased production and/ or decreased excretion of saliva
Salivary gland scintigraphy (SGS)
Tear production is usually measured using what test?
Schirmer test
how do you do Schirmer test?
What value is diagnostic of dry eye?
- This is performed by placing a standardized paper strip in the inferior fornix of each eye and measuring the length of filter paper that becomes wet after 5 minutes.
- The American–European classification system uses a cut-off value of 5 mm in 5 minutes, below which a diagnosis of dry eye is made
histologic hallmark of SS
Evidence of a focal, periductal infiltrate, composed of T and B lymphocytes and few plasma cells
- The degree of lymphocytic infiltration is evaluated semiquantitatively by means of a focus scoring system
Evidence of how many foci is considered indicative of SS?
one or more
a focus is considered a conglomeration of at least how many lymphocytes per 4 mm2 of glandular tissue
at least **50 lymphocytes **per 4 mm2
these structures seen in histopath are thought to be a risk factor for developing lymphoma
germinal center-like structures
classified as a high-risk disease syndrome (Type I)
Patients with l**ow complement C4 levels **and/or palpable purpura early in their disease course
- comprises ∼20% of pSS diagnoses and carries a significantly increased risk of lymphoproliferative disease;
- it also has an increased mortality rate
- Most severe extraglandular manifestations also occur in this group.
- Patients without these 2 predictors (80% of all pSS diagnoses) may be reassured that they have a lowrisk (Type II) form of pSS that carries no increased risk of death and, in general, has a more benign course, dominated by sicca symptom
two secretagogue drugs approved for dry mouth
pilocarpine (5 mg 4 times/d) and cevimeline (30 mg 3 times/d)
- Both act on muscarinic receptors and increase exocrine gland secretion.
- They are contraindicated in narrow-angle glaucoma and uncontrolled asthma
- Cholinergic side effects, such as excessive sweating, urinary frequency, flushing, and headaches, are common with both
approved by the FDA for the treatment of keratoconjunctivitis sicca
Cyclosporine 0.05% ophthalmic solution
