History and exam

Key diagnostic factors

common

fatigue

Fatigue is often the most reported complaint in people with Sjogren syndrome, but the underlying cause is unclear.[39][40] One study demonstrated that patients with primary Sjogren syndrome report more fatigue than healthy controls across all dimensions of the Multidimensional Fatigue Inventory (general, physical, and mental fatigue; reduced motivation; and reduced anxiety).[39]

dry eyes

Recurrent sensation of sand/gravel, itch, or burning in eyes. Persisting more than 3 months, multiple episodes per week. Redness of the eyes and sensitivity to light and wind are common.[2]

dry mouth

Can be associated with difficulties in chewing and swallowing food, difficulties in speaking, and altered or decreased taste acuities.[2]

Many patients carry liquids at all times and wake at night in order to drink.

Other diagnostic factors

common

vasculitis

Common cutaneous manifestations may include dry skin (xeroderma), palpable and non-palpable purpura, and/or urticaria-like lesions in around 50% of patients with Sjogren syndrome.[44]​ These symptoms may be seen as secondary to more prominent sicca symptoms; however, they can be prognostic for the risk of life-threatening conditions such as multisystem vasculitis and non-Hodgkin's lymphoma.[45]

A more unusual manifestation is vasculitis of medium-sized vessels that results in a clinical picture similar to polyarteritis nodosa with visceral involvement.[46]​​ Vasculitis is associated with the presence of anti-Ro and anti-La antibodies as well as cryoglobulins in the sera of patients.[47]

dental caries

Severe, may lead to loss of all teeth.

Appears as destruction around the necks of the teeth and even on the labial and incisal surfaces.[75]

Lower numbers of periopathogenic micro-organisms and higher cariogenic and acidophilic micro-organisms compared with control.[76]

uncommon

presence of risk factors

Key risk factors include: female gender, SLE, systemic sclerosis, rheumatoid arthritis, HLA type II, age 20s and 30s, and post-menopause.

increased oral fungal and bacterial infections

Associated with decreased salivary gland function.[63][64][65]​​​

musculoskeletal pain

Some patients may complain of musculoskeletal symptoms with joint pain, morning stiffness, and non-erosive inflammatory arthritis. Arthralgia impacts the peripheral joints in the majority of patients with primary Sjogren syndrome, but under 2% of patients are diagnosed with arthritis.[41]​ The joints in the hands and wrists are predominantly involved, but patients may also experience pain in their knees, ankles, shoulders, and metatarsophalangeal joints.[41]​ The presence of arthritis may be underdiagnosed by physical examination; ultrasound studies may detect subclinical synovitis and erosions.[42]

thyroid disease

​Evidence on the association of thyroid disease with Sjogren syndrome is variable. One longitudinal population-based study reported that the risk of Sjogren syndrome was significantly higher in women with thyroid disorders, especially women aged in their mid 40s to mid 60s.[48]​ However, an age- and sex-matched controlled study of 160 patients in primary care found no significant difference in the overall prevalence of any type of thyroid disease in women with Sjogren syndrome compared with matched controls without Sjogren syndrome.[49]

urogenital disease

Kidney involvement in the form of renal tubular acidosis can be a manifestation of interstitial kidney disease among patients with Sjogren syndrome.[56][57]​ Women with Sjogren syndrome may present with manifestations in the bladder such as dysuria, urinary frequency, nocturia, and urgency.[58]​ Gynaecological manifestations may include vulvovaginal dryness, pruritus, and dyspareunia.[59]

pulmonary disease

​Approximately 10% to 20% of patients with Sjogren syndrome have respiratory symptoms. There is evidence to suggest that the most typical pulmonary manifestations are chronic interstitial lung disease (ILD) and tracheobronchial disease. The most common presentation of ILD is non-specific interstitial pneumonia.[50]​ Other types of ILD (such as organising pneumonia, usual interstitial pneumonia, and lymphocytic interstitial pneumonitis) are rare.[50]

gastrointestinal disease

​Gastrointestinal (GI) manifestations of Sjogren syndrome may involve the whole GI tract, as well as the liver. Dysphagia, nausea, epigastric pain, and dyspepsia are common symptoms of GI manifestations.​​[51][52][53]​​​ Some evidence suggests hepatic abnormalities in patients with Sjogren syndrome, such as histological changes of primary biliary cholangitis, or autoimmune hepatitis.[54][55]

peripheral neuropathy

Small fibre peripheral neuropathy is the most common form of neuropathy among patients with Sjogren syndrome, and is associated with precipitating levels of anti-Ro60 (SSA) and anti-La (SSB).[61]​ Conversely, there is evidence that suggests a very low incidence of neuropathy; however, in this case the low incidence detected appears to be related to the fact that electrodiagnostic studies (electroencephalogram [EEG] and nerve conduction velocity) were used and these tests typically give negative results with small fibre neuropathy.[62]

corneal ulceration

Can be a consequence of dry eyes, but may require ophthalmological examination (lissamine green and fluorescein testing) to demonstrate.[69]

no saliva pool

Dry mucosa and thick opaque saliva may also be noted on examination.

enlarged salivary glands

Not always seen on examination, or may have marked episodes of swollen, painful glands.[37]

facial pain

In some cases, facial pain may be present in patients with sicca symptoms. Patients with facial pain should be asked whether they have dry eyes and dry mouth.[63]

Trigeminal neuralgia is the most common cranial neuralgia found in Sjogren syndrome patients. This condition typically happens bilaterally, is progressive, and may be characterised by numbness in the face, or paraesthesia with or without pain.[63][66]

Osteonecrosis of the jaw (ONJ) is a possible cause of facial pain, where there is a relevant clinical history. Observational data suggest a significant association between Sjogren syndrome and ONJ.[67][68]

burning mouth syndrome

Burning mouth is thought to be due to reduced salivary flow that results in secondary fungal infection and/or medication use that affects the functioning of the salivary glands.[63][64][65]

Risk factors

strong

female

The incidence rate of primary Sjogren syndrome in women is far higher than that for men, with reported estimates of 12.30 (95% CI 9.07 to 15.53) and 1.47 (95% CI 0.81 to 2.12) per 100,000 person years, respectively, and a male-to-female incidence ratio estimated at 9.29 (95% 6.61 to 13.04).[8]

systemic lupus erythematosus (SLE)

The prevalence rate for Sjogren syndrome associated with SLE has been estimated at 13.96% (95% CI 8.88 to 19.04).[9]

rheumatoid arthritis

The prevalence rate for Sjogren syndrome associated with rheumatoid arthritis has been estimated at 19.5% (95% CI 11.2 to 27.8).[9]

systemic sclerosis (scleroderma)

Significant overlap with Sjogren syndrome.[14][15]

HLA class II markers

HLA class II markers -A1, -B8, or -DR3/DQ2 haplotype are linked with susceptibility to Sjogren syndrome.[17] DR2 is also strongly associated with anti-Ro/La-positive Sjogren syndrome.

age 40 to 70

Sjogren syndrome predominantly affects middle-aged women.[11][12] The median age of evaluation for Sjogren syndrome was 56 years in one systematic review.[8]

weak

genetic inheritance

Two groups have reported identical twins with the syndrome, but the concordance of the disease among twin pairs is unknown.[30][31] While several genes have shown an association, genetic testing is not presently useful in the diagnosis.

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