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Sjogren's syndrome (autoimmune epitheliitis)

Chronic, slowly progressive autoimmune disease characterized by lymphocytic infiltration of the exocrine glands resulting in xerostomia & dry eyes. Systemic manifestations are present in 1/3 of patients. Etiology: 1) primary: autoimmune 2) secondary: associated with: a) rheumatoid arthritis b) systemic lupus erythematosus (SLE) c) autoimmune thyroiditis, Hashimoto's thyroiditis [4] d) scleroderma e) mixed connective tissue disease f) primary biliary cirrhosis g) vasculitis h) chronic active hepatitis Epidemiology: 1) female:male ratio 9:1 2) predominantly postmenopausal women, although it may occur at any age, including children 3) prevalence of primary Sjogren's syndrome is 0.5-1.0% 4) 30% of patients with autoimmune connective tissue diseases also suffer from secondary Sjogren's syndrome Pathology: 1) infiltrative inflammation of exocrine glands 2) periacinal lymphocytic infiltration of minor salivary glands 3) Sjogren's syndrome nuclear autoantigen(s) 4) vasculitic neuropathy or epineural inflammation may occur [6] 5) interstitial nephritis, RTA type 1, glomerulonephritis * microscopy of renal biopsy [22] Genetics: - implicated genes: MUC19 Clinical manifestations: 1) dryness of mucous membranes a) dry eyes (keratoconjunctivitis sicca, xerophthalmia) - gritty eyes or an eye foreign body sensation b) dry mouth (xerostomia) & associated disorders 1] dental caries 2] dysphagia 3] taste disturbance 4] buccal & lip fissures 5] impaired phonation c) dysparunia d) dryness may also affect nose, larynx, bronchial tree 2) skin: dry skin, rash, annular erythema, cutaneous vasculitis (10-16%) (image of rash [22] 3) bilateral parotid enlargement (generally mild & painless) 4) extraglandular manifestations occurs in 50% a) arthralgias/arthritis (36-60%) b) Raynaud's phenomenon (37%) c) lymphadenopathy (14%) d) pulmonary involvement (14%) 1] lymphocytic interstitial pneumonitis (5-9%) 2] cough secondary to xerotrachea is common 3] recurrent bronchopulmonary pneumonia a] chronic bronchitis, COPD b] bronchiolotis obliterans 4] bronchiectasis 5] rarely clinically significant e) vasculitis (7-11%) 1] small & medium-sized vessels 2] palpable purpura, skin ulcerations, recurrent urticaria 3] glomerulonephritis 4] mononeuritis multiplex f) renal involvement (5-9%) 1] interstitial nephritis 2] renal tubular acidosis type 1 3] glomerulonephritis h) hepatobiliary [4] - hepatomegaly, autoimmune hepatitis, biliary cirrhosis (3-20%) i) non-Hodgkin's lymphoma (2-6%, 44-fold increased risk) j) splenomegaly (3%) k) peripheral neuropathy, sensory & autonomic (2-27%%) - cranial neuropathy - small fiber neuropathy - mononeuritis multiplex [4] l) central nervous system (2-27%) 1] cerebritis 2] stroke 3] demyelinating syndrome, multiple sclerosis-like illness 4] myelopathy [4] 5] cognitive impairment m) Raynaud's phenomenon (16%) [4] n) myositis (1%) 0) photosensitivity p) xerosis q) hematologic: - anemia, leukopenia, thrombocytopenia (2-6%) - cryoglobulinemia [4] r) thyroid disease (10-15%) [4] t) fatigue (70%), malaise, myalgia, low-grade fever (6%) 5) case presentation [22] with dyspnea on exertion Diagnostic criteria: - see diagnostic criteria for Sjogren's syndrome. Laboratory: 1) serology: autoantibodies a) anti-SSA/Ro Ab in serum* 1] 40% of patients with Sjogren's syndrome 2] 15% of patients with SLE b) anti-SSB/La Ab in serum* 1] 60% of patients with Sjogren's syndrome 2] 35% of patients with SLE 3] < 1% of patients with rheumatoid arthritis c) positive antinuclear antibodies (ANA) &/or rheumatoid factor (RF) d) anti Sjogren's syndrome/scleroderma autoantigen 1 e) autoantibodies to golgins - GOLGA1, GOLGA4, GOLGB1, TRIM68, RAB11FIP5 - sera from patients with Sjogren's syndrome often contain autoantibodies that react with normal components of the Golgi complex f) autoantibodies to TNRC6A g) autoantibodies to ISCA1 (non-specific) h) other antibodies: ANXA11, SSSCA1 2) serum & urine protein electrophoresis a) hypergammaglobulinemia b) oligo & monoclonal immunoglobulins c) urinary free light chains 3) increased erythrocyte sedimentation rate (ESR) 4) complete blood count (CBC) may show leukopenia 5) see ARUP consult [8] * presence of both anti-SSA/Ro & anti-SSB/La with classic history & physical findings sufficient for diagnosis [4] Special laboratory: 1) Schirmer's test to document diminished lacrimation 2) rose bengal dye staining of dessicated corneal tissue 3) biopsy of minor salivary gland of lower lip (gold standard for diagnosis) Radiology: 1) salivary scintigraphy 2) parotid sialography - salivary flow (=< 1.5 mL in 15 min) 3) chest X-ray may show patchy infiltrate [22] * chest X-ray & CT of thorax [22] Differential diagnosis: 1) xerostomia a) viral infections b) drugs 1] psychotherapeutic drugs 2] parasympatholytic drugs 3] antihypertensives c) psychogenic d) radiation e) diabetes mellitus f) trauma 2) dry eyes a) Stevens-Johnson syndrome b) pemphigoid c) chronic conjunctivitis d) chronic blepharitis e) burns f) drugs g) neurologically impaired lacrimal gland function h) impaired eyelid function i) anesthetic cornea j) hypervitominosis A k) epithelial irregularity l) environmental - low humidity, high wind, smoke, other irritants [5] 3) bilateral parotid gland enlargement a) viral infections: mumps, influenza, Epstein-Barr virus, Coxsackie A, Cytomegalovirus, HIV1 infection b) sarcoidosis c) amyloidosis d) IgG4 disease e) chronic pancreatitis f) diabetes mellitus g) hyperlipoproteinemia h) hepatic cirrhosis i) acromegaly i) gonadal hypofunction Complications: 1) development of B-cell lymphoma a) 44-fold increased risk of lymphoma - 5-15% lifetime risk of non-Hodgkin's lymphoma [16] - diffuse large B-cell lymphoma [4] b) salivary MALT lymphomas most common [11] c) risk factors - rheumatoid factor - mixed cryoglobulinemia mononclonal - cutaneous vasculitis - low serum complement C4 2) corneal ulceration 3) renal tubular acidosis type 1 4) paraproteinemia - vasculitis associated with cryoglobulinemia type 1 5) neonatal heart block in Sjogren's syndrome patients with antianti-SSA/Ro Ab in serum &/or anti-SSB/La Ab in serum Management: 1) incurable disease 2) symptomatic relief (fluid replacement) 3) avoid drugs that diminish lacrimal & salivary gland secretions a) diuretics b) antihypertensive agents c) antidepressants 4) dry eyes - tear replacement a) Tearisol, Liquifilm, 0.5% methyl cellulose, Hypo tears b) in severe cases, may need to use every 30 min c) corneal ulceration 1] eye-patching 2] boric acid ointments d) cyclosporine ophthalmic [4] 5) dry mouth, sicca manifestations a) attention to dental care to prevent dental caries & need for dental extractions [4] b) sugar-free candy c) parasympathomimetics - cevimeline 30 mg PO TID - pilocarpine 5 mg PO TID 6) vaginal dryness: topical lubricant, propionic acid gel 7) hydroxychloroquine 200 mg PO QD a) helpful for arthralgias b) partially corrects hypergammaglobulinemia c) decreases IgG antibodies to SSB/La antigen d) decreases erythrocyte sedimentation rate (ESR) e) of no benefit for relief of xerostomia, fatigue, pain [15] 8) NSAIDs, topical glucocorticoids useful for arthralgia &/or rash [4] 9) treatment of renal, pulmonary or nervous system involvement & vasculitis a) glucocorticoids 1 mg/kg/day (high-dose) [4] b) immunosuppressive agents - cyclophosphamide, methotrexate, azathioprine, mycophenolate, rituximab [4] c) treatment of neuropathy with low-dose oral alpha-interferon or zidovudine [6] 10) prognosis a) mortality only slightly higher than general population b) lymphoma primary cause of increased mortality [4]

Interactions

disease interactions

Related

diagnostic criteria for Sjogren's syndrome lymphocytic interstitial pneumonitis Schirmer tear test sicca syndrome Sjoegren syndrome/scleroderma autoantigen 1; autoantigen p27 (SSSCA1) SSA/Ro Ab in serum SSB/La Ab in serum

Specific

Sjogren's syndrome in the elderly

General

autoimmune disease connective tissue disease; soft tissue disease

Database Correlations

OMIM 270150

References

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