68 - Sjogren Syndrome Flashcards
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
Sjogren syndrome
Isolated SS disorder
Primary Sjogren syndrome
SS associated with other autoimmune condition
Secondary Sjogren syndrome
SS predominantly affects
Women
SS patients are most commonly diagnosed in their _____ decades of life
Fourth and fifth
Genetic loci significantly associated with pSS
HLA DQA1*0501
HLA DQB1*0201
Important transcription factor involved in upregulating the Type I IFN pathway, which is activated by toll-like receptor signals or viral infection and the production of inflammatory cytokines
IRF5
Protein involved in the Type II IFN pathway and activating the adaptive immune system
STAT4
_____ mutation has been correlated with an increased risk of lymphoma
TNFAIP3
Thought to be the first and main target in pSS
Salivary glands
The role of the salivary gland epithelial cells in pSS has been established. Studies have indicated that epithelial cells play an active role in disease pathogenesis and this is referred to as
“Autoimmune epithelitis”
Best-defined autoantibodies in SS
Anti-Ro/SSA
Anti-La/SSB
Recognizes 2 RNA-binding proteins (the 52-kDa or the 60-kDa protein)
Anti-Ro/SSA
Recognize RNA polymerase III
Anti-La/SSB
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
Anti-Ro/SSA
More specific for SS
Present in 50% of patients with pSS or SS/SLE but is rarely seen in other diseases
Anti-La/SSB
Frequently present in patients with both and primary SS
Although they lack specificity, they are markers of a systemic autoimmune response
Antinuclear antibodies
Rheumatoid factor
Major stimulus for saliva production
Binding of acetylcholine to muscarinic acetylcholine receptors
A small group of patients positive for anticentromere autoantibody (ACA) present a clinical picture similar to that of
Limited scleroderma
The ACA-positive group usually has a higher prevalence of
Raynaud phenomenon
Thyroid dysfunction
The ACA-positive group also shows a higher frequency of
Vasculitis
Peripheral neuropathy
Primary biliary cirrhosis
Positivity for antimitochondrial antibody (AMA) also has been demonstrated to be related to
Primary biliary cirrhosis
Sjogren syndrome is a multifocal autoimmune disease, with systemic involvement in _____ of patients
One-third
The characteristic feature of SS is exocrine gland dysfunction, leading to classic sicca symptoms of
Xerostomia (dry mouth)
Xerophthalmia or keratoconjunctivitis sicca (dry eyes)
Medical causes of oral dryness, such as _____, should be considered when evaluating a patient for Sjogren syndrome
Dehydration
Diabetes
Viral infections
Drug treatment
Flat, nonpalpable, blanching purpura
Characterized by polyclonal hypergammaglobulinemia and rheumatoid factor positivity
Skin biopsies reveal ruptured blood vessels with complement deposition
Hypergammaglobulinemic purpura
Y/N: Palpable purpura represents an important marker of more severe disease and is associated with an increased risk of lymphoma development and mortality
Yes
Histopathologically, palpable purpura can be divided into 2 groups
Neutrophilic inflammatory vascular disease
Mononuclear inflammatory vascular disease
Predominantly neutrophilic infiltrate, fibrinoid necrosis, occlusion of the lumen, and extravasation of red blood cells, and is indistinguishable form classical leukocytoclastic vasculitis
Neutrophilic inflammatory vascular disease
Mononuclear inflammatory infiltrate, with invasion of the blood vessel walls
Mononuclear inflammatory vascular disease
The clinical presentation of the 2 forms of palpable purpura are indistinguishable, but _____ is associated more strongly with markers of systemic autoimmunity
Neutrophilic inflammatory vascular disease
Second most frequent form of cutaneous vasculitis in SS
Urticarial vasculitis
Present as palpable purpuric lesions of the lower extremities, which may ulcerate, finally resolving within 1 to 4 weeks
Necrotizing vasculitis
Annular erythema associated with pSS is found primarily among
Asian pSS patients who have anti-Ro/SSA and anti-La/SSB antibodies
Erythematous lesion with a wide elevated border and central clearing
Localized mainly on the faces of Asian patients
Annular erythema associated with pSS
May be triggers of the lesions of annular erythema associated with pSS
Sunlight
Cold exposure
Mental stress
Pregnancy
Annular erythema associated with pSS shares a clinical presentation with
Subacute cutaneous lupus
On histopathology of (annular erythema associated with pSS/SCLE), the dense cell infiltration is localized mainly around sweat glands, and nuclear dust can also be seen when they have vasculitis
Annular erythema associated with pSS
(Annular erythema associated with pSS/SCLE) are common in Asians, but rare in whites, whereas (annular erythema associated with pSS/SCLE) are more common in whites but rare in Asians
Annular erythema associated with pSS
SCLE
Presence of erythema nodosum should raise the suspicion for
Sarcoidosis
Probably the most common abnormality in SS
Can precede sicca symptoms by many years
Raynaud phenomenon
Raynaud phenomenon in SS is not accompanied by _____, as seen in systemic sclerosis
Telangiectasias
Although Raynaud phenomenon is usually mild in pSS, it is a marker of a subgroup with increased
Extraglandular manifestations
The absence of rheumatoid factor and anti-CCP antibodies, and the absence of erosions on radiographs would favor SS over
Rheumatoid arthritis
Thyroid dysfunction is a very common symptom, occurring in 10% to 70% of SS patients. It often presents as
Fatigue
Most common manifestation of peripheral nervous system involvement in SS
Peripheral axonal polyneuropathies, which are typically sensory
Most common form of cranial neuropathy in SS
Unilateral trigeminal neuropathy
The incidence of lymphoma in SS patients is increased _____-fold
15 to 44
Y/N: Recent studies have suggested that women with pSS may experience more complications in pregnancy than healthy controls
Yes - significant increases in the rates of spontaneous abortions, preterm deliveries, and low-body-weight infants
Anti-Ro/SSA and anti-La/SSA can cause _____ in the fetus
Congenital heart block
Neonatal lupus
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
Neonatal lupus
Involves measurement of the total saliva produced from all salivary glands in a time period of 15 min
Sialometry
The whole unstimulated salivary flow is considered suggestive of SS if it is
<1.5 mL in 15 minutes
A “stimulated” salivary flow can be measured after administration of
Lemon juice or citric acid
Functional study to assess saliva production by measuring the secretion of a radioisotope into the oral cavity
Salivary gland scintigraphy
Can potentially distinguish between decreased production and/or decreased excretion of saliva
Salivary gland scintigraphy
Imaging method based on retrograde injection of contrast media into the parotid duct
Sialography
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
Schirmer test
The American-European classification system uses a cut-off value for the Schirmer test of
5 mm in 5 minutes
Dye that preferentially stains the devitalized cornea and conjunctiva
Rose Bengal or lissamine green
The most reliable objective diagnostic feature of SS is seen on
Biopsy of the minor salivary gland
There are 2 patterns of pSS that define disease categories with very different clinical risks
Type I (High-risk) Type II (Low-risk)
Patients with _____ may be classified as high-risk disease syndrome (Type I)
Low complement C4 levels and/or
Palpable purpura early in their disease course
The high-risk disease syndrome group carries a significantly increased risk of _____; it also has an increased _____
Lymphoproliferative disease
Mortality rate
Two drugs approved for the treatment of dry mouth
Pilocarpine 5 mg 4 times/d
Cevimeline 30 mg 3 times/d
Pilocarpine and cevimeline are contraindicated in
Narrow-angle glaucoma
Uncontrolled asthma
Cholinergic side effects
Excessive sweating
Urinary frequency
Flushing
Headaches
Has been approved by the FDA for the treatment of keratoconjunctivitis sicca
Cyclosporine 0.05% ophthalmic solution
Most SS-associated lymphomas are
Low-grade B cell-lymphomas, localized to the exocrine glands
