Sjogren's Syndrome

[Mike Bartolatz]

Sjögren syndrome (SS) / Gougerot-Nulock-Houwer syndrome (sometimes mistyped as Sjogren, Sjoegren, or Sjogrens syndrome)
Epidemiology : female:male ratio 9:1. Prevalence : 6-27 cases every 100,000 people (peak at age 40-50)
Aetiology :
primary (RR > 3 in individuals with HLA-B8, HLA-DR2, HLA-DR3, and HLA-Dw52 haplotypes or HLA-DQA1*0501 gene)
secondary to ...
rheumatoid arthritis (70% of patients has HLA-DR4; RR = 5)
scleroderma
systemic lupus erythematosus
Pathogenesis : autoantibodies against ...
a cleavage product of 120-kDa a-fodrin (selectively expressed in salivary glands)
golgin a1
RF (50-90%)
mobilferrin / calreticulin (Ag A)
M3 AChR
IgG antibodies against T3, T4 or both (50%)
SS-A / Ro (50-90%; 95% of patients has HLA-DR2/DR3; RR = 17) => leukopenia, vasculitis
SSB / La
SSN / ABCA7
SSNA1
SSSCA1
Slowly progressive dysfunction and destruction of the salivary, lacrimal and other exocrine glands
Symptoms & signs :
exocrine glands => sicca syndrome
xerophthalmia for > 3 months (47%) due to keratoconjunctivitis sicca
xerostomia for > 3 months (42.5%) due to intermitting monolateral parotitis or bilateral parotitis (24% at onset, 60% at anamnesis)
xeronose
xeropharynx
xerotrachea
xerovaginia due to vaginitis (5%)
xeroepidermis
primary biliary cirrhosis (PBC) / primary sclerosing cholangitis (PSC) (5-10%)
extraglandular manifestations (33%)
chronic non-erosive polyarthralgia / polyarthritis / synovitis (60%; 28% at onset) causing night and morning stiffness, but rarely leading to ulnar deviation
fever / fatigue (10%)
Raynaud's phenomenon (37%; 21% at onset)
lymphadenitis (14%)
cutaneous vasculitis due to hypergammaglobulinemia (11%) =>
purpura
peripheral neuropathy due to vasculitis of vasa nervorum (2-5%) => secondary polymyositis (1-2-%)
recurrent urticaria
skin ulcers
annular erythema in UV-esposed skin
lung involvement (14%) : dry cough, nasal crustae, chronic bronchitis with dense phlegm, lymphocytary interstitial bronchitis, pleural effusion (expecially in SS secondary to SLE), pulmonary arterial hypertension
renal involvement (9%) : interstitial chronic nephritis => tubular tubuloacidosis => calculosis => nephrocalcinosis => renal failure; membranous glomerulonephritis or membranoproliferative glomerulonephritis only in patients with systemic vasculitis, essential mixed cryoglobulinemia or SLE; interstial cystitis
low malignancy, B cell, extralymphnodal (usually salivary) lymphoma (6%; 44-fold higher than in unaffected individuals)
CNS involvement : hemiparesis, sensorial deficits, transverse myelitis, aseptical meningitis, seizures, ...
peripheral neuropathy (2%)
pancreatitis
pleuritis
myositis (1%)
Clinical diagnosis is impaired when the patient has GvHD, pre-existing lymphomas, HCV, HIV-1, or sarcoidosis.
Laboratory examinations :
normal CRP
increased ESR
increased [b2 microglobulin]serum
normocytic and normochromic anemia
leukopenia
Schirmer's test
break up time
evaluation of corneal surface integrity
99mTc scintigraphy
measure of unstimulated salivary flow
parotideal sialography with hydrosoluble contrast enhancement medium : ectasia of ductuli
biopsy of minor salivary glands (inner face of lower lip) : focus score > 1
Treatment :
therapy for xerostomia
therapy for xerophthalmia
propionic acid gel to treat dyspareunia
GR agonists and antimalarial drugs
Au salts
Experimental animal models : spontaneously occuring in selected mouse strains
Web resources :
Sjögren's Syndrome Foundation (SSF)
SjS World
Sjögren's syndrome
Sjögren's syndrome at Medicine Net
Sjögren's syndrome at Mayo Clinic