Introduction
Epidemiology
Pathogenesis
Environmental factors
Genetic and epigenetic factors
Epithelial cells
Innate immunity
Type I IFNs
NK cells
Acquired immunity
B cells
T cells
Clinical manifestations
Glandular manifestations
Cause | Notes |
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Sialadenosis (or sialosis) | Bilateral non-painful enlargement of the major salivary glands (typically the parotids) associated with systemic disorders (endocrine/metabolic, nutritional, drug-induced) |
Sialolithiasis | Ductal obstruction causing pain and swelling of the affected salivary gland (typically unilateral, may complicate Sjögren's syndrome) |
Infections | |
Bacterial | Usually unilateral, painful swelling due to bacterial infection (e.g., acute suppurative parotitis), bacterial sialadenitis may complicate Sjögren's syndrome |
Mycobacterial | Rare forms of extra-pulmonary tuberculosis |
Viral | Acute viral parotitis—mumps (bilateral), HIV salivary gland disease, other viruses. HCV- infected patients may have histological signs of Sjögren-like sialadenitis |
Wegener granulomatosis | May involve parotid glands (rare, bilateral or unilateral) |
Sarcoidosis | May involve parotid or lacrimal glands. Heerfordt syndrome: uveitis, fever, parotid enlargement, facial palsy |
Neoplastic (benign or malignant primary tumor) | Various histology; lymphoma (generally unilateral, may complicate Sjögren's syndrome) |
IgG4-related disease | Lymphoplasmacytic infiltrate enriched in IgG4-positive plasma cells may affect lacrimal, parotid and submandibular gland (also termed Mikulicz syndrome) |
Amyloidosis | May cause salivary gland enlargement |
Masseteric hypertrophy | Asymptomatic enlargement of one or both masseter muscles (may mimic parotid enlargement) |
Pneumoparotid | Passage of air through the parotid orifice and into the ducts in individual who increases intraoral pressure by forcefully blowing |
Drugs | Rare (iodine-based contrast medium, radioactive iodine-131, anesthetics, others) |
Cause | Notes |
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Drugs (many) | Most common cause, especially among older patients. Mainly related to anti-cholinergic and/or sympathomimetic actions (e.g., antidepressants, benzodiazepines, antispasmodic agents, beta-blockers, antihistamines, diuretics, opioids, etc.). May worsen sicca symptoms in patients with Sjögren’s syndrome |
Aging | Salivary flow and tears production decrease in an elderly patient (risk increased in subjects exposed to polytherapy) |
Neuropathic | Reduced stimulation of exocrine glands (e.g., diabetes, Parkinson’s disease, Multiple Sclerosis) |
Dehydration | Decreased saliva production (e.g., diabetes mellitus, diuretics, end-stage renal disease, impaired thirst perception, etc.) |
Surgical removal of the salivary glands | Iatrogenic cause |
Radiotherapy of the head and neck | Tear gland and/or salivary gland damage |
Smoking | Long-term smoking significantly alters saliva flow rate and salivary pH |
Alcohol abuse | Damage of mucosa and salivary glands |
Dry/windy environment | Enhance tear and saliva evaporation |
HCV sialadenitis | Can cause both salivary gland enlargement and reduced salivary production |
HIV salivary gland disease | Related with lymphocytic infiltration, use of certain antiretroviral drugs |
Stress, depression and anxiety | Influence sympathetic activity that controls saliva secretion |
Chronic graft versus host disease | Related with lymphocytic infiltration, parenchymal damage and fibrosis |
Amyloidosis | Amyloid infiltration and destruction of salivary glands |
Sarcoidosis | Granulomatous infiltration may lead to xerostomia |
General constitutional symptoms
Musculoskeletal involvement
Dermatological involvement
Respiratory tract involvement
Cardiac involvement
Nervous system involvement
Renal involvement
Gastrointestinal involvement
Associated organ-specific autoimmune disorders
Lymphoma and other hematologic disorders
Pregnancy
Diagnosis
2002 American European Consensus Group (AECG) | 2012 American College of Rheumatology (ACR) | 2016 ACR/Eular Classification Criteria |
---|---|---|
Item I. Ocular symptoms (daily, persistent, troublesome dry eyes for more than 3 months and/or recurrent sensation of sand or gravel and/or use tear substitutes more than 3 times a day) | 1. Anti-Ro/SSA and/or anti-La/SSB OR positive rheumatoid factor + ANA ≥ 1:320 | 1. Labial salivary gland biopsy (focal lymphocytic sialoadenitis a focus score ≥ 1); score 3 |
Item II. Oral symptoms (daily feeling of dry mouth more than 3 months and/or recurrently or persistently swollen salivary glands as an adult and/or need of liquids to swallow solid food) | 2. Labial salivary gland biopsy (focal lymphocytic sialoadenitis with a focus score ≥ 1) | 2. Anti-Ro/SSA positivity; score 3 |
Item III. Ocular signs (Schirmer's test no anesthesia and/or rose Bengal or other dye score (> 4 according to van Bijsterveld’s scoring system) | 3. Keratoconjunctivitis sicca (ocular staining score ≥ 3 according to Whitcher’s protocol; exclude: use of glaucoma eye drops, corneal or cosmetic eyelid surgery in the last 5 years) | 3. Ocular Staining Score ≥ 5 according to Whitcher’s protocol (or van Bijsterveld’s score ≥ 4) in at least 1 eye; score 1 |
Item IV. Histopathology (focal lymphocytic sialoadenitis in minor salivary glands with a focus score ≥ 1) | Classification (only for primary SS): individuals with signs/symptoms suggestive of SS + at least 2 of the 3 objective features | 4. Schirmer’s test < 5 mm/5 min in at least 1 eye; score 1 |
Item V. Salivary gland (unstimulated salivary flow ≤ 1.5 mL/15 min and/or parotid sialography with diffuse sialectasias without obstruction and/or salivary scintigraphy specific abnormalities | Exclusion: history of head and neck radiation treatment, HCV, AIDS, sarcoidosis, amyloidosis, GVHD, IgG4-related disease | 5. Unstimulated whole saliva flow rate (< 0.1 ml/minute, as described by Navazesh and Kumar); score 1 |
Item VI. Autoantibodies (anti-Ro/SSA and/or La/SSB) | Classification: a score ≥ 4 from the five criteria items in any patient with at least one symptom of ocular (see item I of the AECG 2002 criteria) or oral dryness (see item II of the AECG 2002 criteria, excepting “salivary glands enlargement”) or in whom there is suspicion of SS from the European League Against Rheumatism SS Disease Activity Index (ESSDAI) questionnaire (at least one domain with a positive item) | |
Classification: primary SS (any 4 of the 6 items, with positive item IV or VI OR any 3 of the 4 objective criteria (III to VI); secondary SS (potentially associated disease + presence of item I OR item II + any 2 among items III to V) | Exclusion: history of head and neck radiation treatment, HCV, AIDS, sarcoidosis, amyloidosis, GVHD, IgG4-related disease | |
Exclusion: history of head and neck radiation treatment, HCV, AIDS, preexisting lymphoma, sarcoidosis, GVHD, anticholinergic drugs |