1. Harjot Sihota MD4 #1034

2. Introduction An autoimmune disease characterized by destruction of the lacrimal and salivary glands, resulting in the inability to produce saliva and tears. Females>Males; age range: 30-50 years

3. Symptoms/Signs Keratoconjunctivitis sicca (dry eyes) Xerostomia (dry mouth) Recurrent dental carries Mikulicz syndrome: enlargement of the salivary and lacrimal glands Alopecia Dry skin Dry respiratory tract Dry vagina Tooth decay Enlarged Parotid

4. Symptoms/Signs Extraglandular symptoms: Arthalgias/arthritis --(hydrochloroquine, methotrexate+prednisolone) Raynauds Phenomenon --(Nifedipine and gloves) Lymphadenopathy --(enlarged axillary lymphnodes) Vasculitis --(glucocorticoids, cyclophophamide,) Kidney disease Chronic hepatobiliary disease Non hodgkin lymphoma-(anti CD20+CHOP(cyclophosphamide, hydroxydaunorubicin, oncovin, prednisolone)) Rarely: splenomegaly or myositis

5. Causes Rheumatoid arthritis and other autoimmune diseases SLE Systemic sclerosis Mixed connective tissue disease Vasculitis Hashimoto’s thyroiditis Poliomyositis Primary biliary cirrhosis Chronic autoimmune hepatitis

6. Pathogenesis T and B lymphocytes invade the exocrine glands Leading to ductal epithelial cell hyperplasia Obstruction Leads to atrophy-fibrosis-hyalinization B lymphocytes infiltrate glands which create lymphoid follicles with germinal centers in the salivary glands Lymphocyte-mediated damage (type IV hypersensitivity) with fibrosis Characterized by ANA and Anti-ribonucleoprotein antibodies SS-A (Ro) SS-B (La)

7. Diagnosis blood tests: Leukopenia, anemia, increased erythrocyte sedimentation rate, autoantibodies Biopsy from lip or minor salivary glands (in buccal mucosa) Genetics tests can show association of sjogrens syndrome with HLA DR3 Dry eyes tested by doing the schirmers test (normal is 15mm) Slit-lamp examination testing the tear film breakup time Dry mouth: can test the salivary flow (less than 1.5 ml in 15 min) -salivary scintiscanning, or sialography If enlarged parotid glands are persistently firm-rule out lymphoma If painful with infection -apply local wet heat compresses, antibiotics, and analgesics

8. Management Dry eyes avoid anticholinergics, diuretics, antihistamines, antidepressants Can use artificial tears or lubricant drops like methylcellulose, hypromellose, Can stimulate lubricant: locally by cAMP, Cyclosporine 2% olive solution systemically by pilocarpine, cevimeline, **Tiny plaques or corneal transplantation. Dry mouth drink water daily to help swallowing, or we can stimulate salivary glands locally by chewing sugar free gum, or mouth wash containing carboxymethylcellulose, Also we can stimulate systemically by using drugs pilocarpine, cevimeline Can prevent tooth decay by regular dental visits and by using topical fluoride, or good oral hygeine. Dry skin can be treated with lubricants Dysparenuia can be treated with lubricants

9. Complications Increased risk of developing non-Hodgkin lymphoma Increased risk for B-cell (marginal zone) lymphoma, which presents as unilateral enlargement of the parotid gland late in disease course Stones can appear in the salivary glands which have to be removed to preserve the salivary tissue

10. Case Study A 38-year-old woman was referred to an oral surgeon for investigation of a dry mouth. She had a sister with arthritis. Examination and investigations were unremarkable except for a raised ESR (42mm/h). Six months later, she developed a mild conjunctivitis and complained of sore eyes. On testing, rheumatoid factor was now positive (Rose-Waaler titre 1/64); total serum proteins were raised (98g/l); and immunoglobulin levels showed a raised IgG of 28g/l (NR 7.2-19.0), with a slightly raised IgM of 2.8g/l (NR 0.5-2.0) and a normal IgA. Schirmer's test was performed (see Section 10.8.2). The test was markedly abnormal as only 3.5mm of the filter strip in the right eye and 1.5mm of that in the left eye became wet. She was treated with methylcellulose eye drops to prevent corneal ulceration. Over a period of many years, her rheumatoid factor titre steadily increased and ANA and antibodies to the extractable nuclear antigens Ro and La became detectable. Seven years after the development of the dry mouth and dry eyes (together known as the sicca complex), she developed a mild, bilateral non-erosive polyarthritis of her hands, wrists and knees.

11. References http://europepmc.org/abstract/MED/10493692 http://emedicine.medscape.com/article/332125- clinical http://emedicine.medscape.com/article/332125- clinical Robbins basic pathology (9 th edition)