Destruction of the glandular epithelium, antibodies against muscarinic receptors, impairment of neurotransmission

Difficulty chewing or swallowing, sore mouth

Oral infections and dental caries, fungal infections (pseudomembranous or erythematous mucosal lesions, fissured tongue, atrophy of filiform papillae and angular cheilitis)

Usually bilateral, firm to palpation, asymptomatic, adverse predictor of lymphoma

Sandy feeling or itchiness of the eyes

Reduced tear secretion, chronic irritation and destruction of the corneal and bulbar conjunctival epithelium (keratoconjunctivitis sicca)

Dry skin with accompanying pruritus

Dry nasal mucosa, xerotrachea, bronchitis sicca

Chronic dry cough, shortness of breath (xerotrachea/bronchitis sicca)

Dyspareunia commonly observed in premenopausal women (dysfunction of lubricative vaginal glands)

Jaccoud arthropathy (reversible hand deformities, absence of erosive lesions);7,25,26 radiographs of the hands show soft-tissue calcification (especially in association with Raynaud phenomenon)12

Milder in Sjögren syndrome compared with other autoimmune diseases; no associated vascular complications12,27,28

Increase demand for rest, associated with functional disability

Peribronchial and/or peribronchiolar mononuclear inflammation

Dry cough and shortness of breath on exertion

Pulmonary function testing: predominantly small airway obstructive pattern

Chest radiography: usually normal or ill-defined pattern of infiltrates

High-resolution computed tomography: thickened bronchial walls; pure interstitial involvement is less frequent (common types: lymphocytic interstitial pneumonia characterized by thin wall cysts on imaging, lymphocytic bronchiolitis29,30)

Lymphocytic infiltration around cholangial cells

Antimitochondrial antibodies and Sjögren syndrome: two-thirds of patients show liver enzyme abnormalities

Liver histopathology: mild intrahepatic bile duct inflammation reminiscent of primary biliary cirrhosis (stage I)14

Progression of Sjögren syndrome–associated primary biliary cirrhosis: very slow in clinical, serologic and histopathologic terms31

Interstitial nephritis-lymphocytic infiltration around renal tubular cells

Subclinical course

Distal renal tubular acidosis (hypokalemia, low specific gravity and alkaline pH of the urine, nephrocalcinosis)15,32,33

Mild chronic renal compromise34

Periepithelial lymphocytic infiltrations in thyroid, adrenals, ovaries

Suggests a subtype of Sjögren syndrome with a mild course and C4 normocomplementemia35

Associated with B-cell activating cytokines and adrenal hyporesponsiveness

Deposition of immunocomplexes in small vessels of the skin, nerves, kidney, brain as a result of B-cell hyperactivity

Most common manifestation of cutaneous vasculitis

Associated with hypocomplementemia and cryoglobulinemia conferring increased risk of lymphoma

Flat purpura can also occur in the setting of hypergammaglobulinemia

Glove–stocking distribution

Painful or burning paresthesia

Adverse predictor of lymphoma in association with hypocomplementemia, cryoglobulinemia and vasculitic lesions

Associated with systemic vasculitis, hypocomplementemia and cryoglobulinemia; adverse predictor of lymphoma and survival

Membranoproliferative and membranous glomerulonephritis are the most commonly occurring histopathologic types

Immunofluorescence showing IgM and complement deposition in renal tissues; hypertension, mild proteinuria and hematuria are the most common manifestations36

Associated with antibodies against SSA (Ro/SSA)

Multiple sclerosis-like features24,37

Antibodies against aquaporin-4 have been detected among patients with lupus and Sjögren syndrome with evidence of longitudinally extensive transverse myelitis or optic neuritis38

Chronic antigenic stimulation, genetic aberrations

Sites of involvement include minor and/or major salivary glands, stomach, lungs, nodes; involvement of bone marrow is rare

Adverse predictors of lymphoma include peripheral neuropathy, glomerulonephritis, lymphopenia, vasculitic or purpuric lesions, low C4 levels, cryoglobulinemia, germinal centres in salivary gland biopsy7,9,39,40