Sjogren's syndrome (autoimmune epitheliitis)
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Introduction
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
- primary: autoimmune
- secondary: associated with:
Epidemiology
- female:male ratio 9:1
- predominantly postmenopausal women, although it may occur at any age, including children
- prevalence of primary Sjogren's syndrome is 0.5-1.0%
- 30% of patients with autoimmune connective tissue diseases also suffer from secondary Sjogren's syndrome
Pathology
- infiltrative inflammation of exocrine glands
- periacinal lymphocytic infiltration of minor salivary glands
- Sjogren's syndrome nuclear autoantigen(s)
- vasculitic neuropathy or epineural inflammation may occur[6]
- interstitial nephritis, RTA type 1, glomerulonephritis
* microscopy of renal biopsy[22]
Genetics
- implicated genes: MUC19
Clinical manifestations
- dryness of mucous membranes
- dry eyes (keratoconjunctivitis sicca, xerophthalmia)
- gritty eyes or an eye foreign body sensation
- dry mouth (xerostomia) & associated disorders
- dental caries
- dysphagia
- taste disturbance
- buccal & lip fissures
- impaired phonation
- dysparunia
- dryness may also affect nose, larynx, bronchial tree
- dry eyes (keratoconjunctivitis sicca, xerophthalmia)
- skin: dry skin, rash, annular erythema, cutaneous vasculitis (10-16%) (image of rash[22]
- bilateral parotid enlargement (generally mild & painless)
- extraglandular manifestations occurs in 50%
- arthralgias/arthritis (36-60%)
- Raynaud's phenomenon (37%)
- lymphadenopathy (14%)
- pulmonary involvement (14%)
- lymphocytic interstitial pneumonitis (5-9%)
- cough secondary to xerotrachea is common
- recurrent bronchopulmonary pneumonia
- chronic bronchitis, COPD
- bronchiolotis obliterans
- bronchiectasis
- rarely clinically significant
- vasculitis (7-11%)
- small & medium-sized vessels
- palpable purpura, skin ulcerations, recurrent urticaria
- glomerulonephritis
- mononeuritis multiplex
- renal involvement (5-9%)
- hepatobiliary[4]
- non-Hodgkin's lymphoma (2-6%, 44-fold increased risk)
- splenomegaly (3%)
- peripheral neuropathy, sensory & autonomic (2-27%%)
- cranial neuropathy
- small fiber neuropathy
- mononeuritis multiplex[4]
- central nervous system (2-27%)
- Raynaud's phenomenon (16%)[4]
- myositis (1%) 0) photosensitivity
- xerosis
- hematologic:
- thyroid disease (10-15%)[4]
- fatigue (70%), malaise, myalgia, low-grade fever (6%)
- case presentation[22] with dyspnea on exertion
Diagnostic criteria
Laboratory
- serology: autoantibodies
- anti-SSA/Ro Ab in serum*
- 40% of patients with Sjogren's syndrome
- 15% of patients with SLE
- anti-SSB/La Ab in serum*
- 60% of patients with Sjogren's syndrome
- 35% of patients with SLE
- < 1% of patients with rheumatoid arthritis
- positive antinuclear antibodies (ANA) &/or rheumatoid factor (RF)
- anti Sjogren's syndrome/scleroderma autoantigen 1
- autoantibodies to golgins
- autoantibodies to TNRC6A
- autoantibodies to ISCA1 (non-specific)
- other antibodies: ANXA11, SSSCA1
- anti-SSA/Ro Ab in serum*
- serum & urine protein electrophoresis
- hypergammaglobulinemia
- oligo & monoclonal immunoglobulins
- urinary free light chains
- increased erythrocyte sedimentation rate (ESR)
- complete blood count (CBC) may show leukopenia
- see ARUP consult[8]
* presence of both anti-SSA/Ro & anti-SSB/La with classic history & physical findings sufficient for diagnosis[4]
Diagnostic procedures
- Schirmer's test to document diminished lacrimation
- rose bengal dye staining of dessicated corneal tissue
- biopsy of minor salivary gland of lower lip (gold standard for diagnosis)
Radiology
- salivary scintigraphy
- parotid sialography
- chest X-ray may show patchy infiltrate[22]
* chest X-ray & CT of thorax[22]
Complications
- development of B-cell lymphoma
- 44-fold increased risk of lymphoma
- 5-15% lifetime risk of non-Hodgkin's lymphoma[16]
- diffuse large B-cell lymphoma[4]
- salivary MALT lymphomas most common[11]
- risk factors
- 44-fold increased risk of lymphoma
- corneal ulceration
- renal tubular acidosis type 1
- paraproteinemia
- vasculitis associated with cryoglobulinemia type 1
- neonatal heart block in Sjogren's syndrome patients with antianti-SSA/Ro Ab in serum &/or anti-SSB/La Ab in serum
Differential diagnosis
- xerostomia
- viral infections
- drugs
- psychotherapeutic drugs
- parasympatholytic drugs
- antihypertensives
- psychogenic
- radiation
- diabetes mellitus
- trauma
- dry eyes
- Stevens-Johnson syndrome
- pemphigoid
- chronic conjunctivitis
- chronic blepharitis
- burns
- drugs
- neurologically impaired lacrimal gland function
- impaired eyelid function
- anesthetic cornea
- hypervitominosis A
- epithelial irregularity
- environmental
- bilateral parotid gland enlargement
Management
- incurable disease
- symptomatic relief (fluid replacement)
- avoid drugs that diminish lacrimal & salivary gland secretions
- dry eyes - tear replacement
- Tearisol, Liquifilm, 0.5% methyl cellulose, Hypo tears
- in severe cases, may need to use every 30 min
- corneal ulceration
- eye-patching
- boric acid ointments
- cyclosporine ophthalmic[4]
- dry mouth, sicca manifestations
- attention to dental care to prevent dental caries & need for dental extractions[4]
- sugar-free candy
- parasympathomimetics
- cevimeline 30 mg PO TID
- pilocarpine 5 mg PO TID
- vaginal dryness: topical lubricant, propionic acid gel
- hydroxychloroquine 200 mg PO QD
- helpful for arthralgias
- partially corrects hypergammaglobulinemia
- decreases IgG antibodies to SSB/La antigen
- decreases erythrocyte sedimentation rate (ESR)
- of no benefit for relief of xerostomia, fatigue, pain[15]
- NSAIDs, topical glucocorticoids useful for arthralgia &/or rash[4]
- treatment of renal, pulmonary or nervous system involvement & vasculitis
- glucocorticoids 1 mg/kg/day (high-dose)[4]
- immunosuppressive agents
- treatment of neuropathy with low-dose oral alpha-interferon or zidovudine[6]
- prognosis
More general terms
More specific terms
Additional terms
- 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
References
- ↑ Clinical Diagnosis & Management by Laboratory Methods, 19th edition, J.B. Henry (ed), W.B. Saunders Co., Philadelphia, PA. 1996, pg 1018
- ↑ Harrison's Principles of Internal Medicine, 14th ed. Fauci et al (eds), McGraw-Hill Inc. NY, 1998, pg 1901-1904
- ↑ Mayo Internal Medicine Board Review, 1998-99, Prakash UBS (ed) Lippincott-Raven, Philadelphia, 1998, pg 829-30, 789-80
- ↑ 4.00 4.01 4.02 4.03 4.04 4.05 4.06 4.07 4.08 4.09 4.10 4.11 4.12 4.13 4.14 4.15 Medical Knowledge Self Assessment Program (MKSAP) 11,15,16,17,18. American College of Physicians, Philadelphia 1998,2009,2012,2015,2018.
Medical Knowledge Self Assessment Program (MKSAP) 19 Board Basics. An Enhancement to MKSAP19. American College of Physicians, Philadelphia 2022 - ↑ 5.0 5.1 Weiner S, In: UCLA Intensive Course in Geriatric Medicine & Board Review, Marina Del Ray, CA, Sept 12-15, 2001
- ↑ 6.0 6.1 6.2 Masdeu JC and Rodrigues-Oroz MC, Abnormalities of Posture and Movement, In: Geriatric Medicine, An Evidence-based approach 4th ed 2003
- ↑ Ramos-Casals M et al, Primary Sjogren's syndrome: new clinical and therapeutic concepts. Ann Rheum Dis 2005, 64:347 PMID: https://www.ncbi.nlm.nih.gov/pubmed/15498797
- ↑ 8.0 8.1 ARUP Consult: Sjogren Syndrome The Physician's Guide to Laboratory Test Selection & Interpretation https://arupconsult.com/content/sjogren-syndrome
- ↑ Latkany R. Dry eyes: etiology and management. Curr Opin Ophthalmol. 2008 Jul;19(4):287-91 PMID: https://www.ncbi.nlm.nih.gov/pubmed/18545008
- ↑ Comer DM, Droogan AG, Young IS, Maxwell AP. Hypokalaemic paralysis precipitated by distal renal tubular acidosis secondary to Sjogren's syndrome Ann Clin Biochem. 2008 Mar;45(Pt 2):221-5. PMID: https://www.ncbi.nlm.nih.gov/pubmed/18325192
- ↑ 11.0 11.1 Voulgarelis M, Moutsopoulos HM. Mucosa-associated lymphoid tissue lymphoma in Sjogren's syndrome: risks, management, and prognosis. Rheum Dis Clin North Am. 2008 Nov;34(4):921-33, PMID: https://www.ncbi.nlm.nih.gov/pubmed/18984412
- ↑ Ramos-Casals M, Tzioufas AG, Stone JH, Siso A, Bosch X. Treatment of primary Sjogren syndrome: a systematic review. JAMA. 2010 Jul 28;304(4):452-60 PMID: https://www.ncbi.nlm.nih.gov/pubmed/20664046
- ↑ Thanou-Stavraki A, James JA. Primary Sjogren's syndrome: current and prospective therapies. Semin Arthritis Rheum. 2008 Apr;37(5):273-92. Epub 2007 Aug 21. PMID: https://www.ncbi.nlm.nih.gov/pubmed/17714766
- ↑ Whitcher JP, Shiboski CH, Shiboski SC et al A simplified quantitative method for assessing keratoconjunctivitis sicca from the Sjogren's Syndrome International Registry. Am J Ophthalmol. 2010 Mar;149(3):405-15. PMID: https://www.ncbi.nlm.nih.gov/pubmed/20035924
- ↑ 15.0 15.1 Gottenberg J-E et al. Effects of hydroxychloroquine on symptomatic improvement in primary Sjogren syndrome: The JOQUER randomized clinical trial. JAMA 2014 Jul 16; 312:249 PMID: https://www.ncbi.nlm.nih.gov/pubmed/25027140
- ↑ 16.0 16.1 Jonsson MV, Theander E, Jonsson R. Predictors for the development of non-Hodgkin lymphoma in primary Sjogren's syndrome. Presse Med. 2012 Sep;41(9 Pt 2):e511-6 PMID: https://www.ncbi.nlm.nih.gov/pubmed/22867948
- ↑ Delaleu N, Jonsson MV, Appel S, Jonsson R. New concepts in the pathogenesis of Sjogren's syndrome. Rheum Dis Clin North Am. 2008 Nov;34(4):833-45 PMID: https://www.ncbi.nlm.nih.gov/pubmed/18984407
- ↑ Shiboski SC, Shiboski CH, Criswell L et al American College of Rheumatology classification criteria for Sjogren's syndrome: a data-driven, expert consensus approach in the Sjogren's International Collaborative Clinical Alliance cohort. Arthritis Care Res (Hoboken). 2012 Apr;64(4):475-87. PMID: https://www.ncbi.nlm.nih.gov/pubmed/22563590
- ↑ Solans-Laque R, Lopez-Hernandez A, Bosch-Gil JA et al Risk, predictors, and clinical characteristics of lymphoma development in primary Sjogren's syndrome. Semin Arthritis Rheum. 2011 Dec;41(3):415-23 PMID: https://www.ncbi.nlm.nih.gov/pubmed/21665245
- ↑ Theander E, Henriksson G, Ljungberg O et al Lymphoma and other malignancies in primary Sjogren's syndrome: a cohort study on cancer incidence and lymphoma predictors. Ann Rheum Dis. 2006 Jun;65(6):796-803 PMID: https://www.ncbi.nlm.nih.gov/pubmed/16284097
- ↑ Theander E, Manthorpe R, Jacobsson LT. Mortality and causes of death in primary Sjogren's syndrome: a prospective cohort study. Arthritis Rheum. 2004 Apr;50(4):1262-9. PMID: https://www.ncbi.nlm.nih.gov/pubmed/15077310
- ↑ 22.0 22.1 22.2 22.3 22.4 22.5 Mogabgab ON, Osman NY, Wei K, Batal I, Loscalzo J. CLINICAL PROBLEM-SOLVING. A Complementary Affair. N Engl J Med. 2016 Jan 7;374(1):74-81 PMID: https://www.ncbi.nlm.nih.gov/pubmed/26735996 (images of rash, chest X-ray, CT of thorax, microscopy of renal biopsy)
- ↑ Duffles Amarante GB, Zotin MC et al Renal tubular dysfunction in patients with primary Sjogren syndrome. Clin Nephrol. 2014 Mar;81(3):185-91. PMID: https://www.ncbi.nlm.nih.gov/pubmed/24424087
- ↑ Mariette X, Criswell LA Primary Sjogren's Syndrome N Engl J Med 2018; 378:931-939. March 8, 2018 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/29514034 <Internet> http://www.nejm.org/doi/full/10.1056/NEJMcp1702514
- ↑ Baer AN, Walitt B. Sjogren Syndrome and Other Causes of Sicca in Older Adults. Clin Geriatr Med. 2017 Feb;33(1):87-103. Review. PMID: https://www.ncbi.nlm.nih.gov/pubmed/27886700 Free PMC Article
- ↑ Giovelli RA, Santos MC, Serrano EV, Valim V. Clinical characteristics and biopsy accuracy in suspected cases of Sjogren's syndrome referred to labial salivary gland biopsy. BMC Musculoskelet Disord. 2015 Feb 15;16:30. PMID: https://www.ncbi.nlm.nih.gov/pubmed/25887888 Free PMC Article
- ↑ National Institute of Arthritis and Muscluloskeletal and Skin Diseases (NIAMS) Sjogren's Syndrome: https://www.niams.nih.gov/health-topics/sjogrens-syndrome
Patient information
Sjogren's syndrome patient information