Course instructors (2 hour lecture) 1. Barbara Caffery OD, PhD, FAAO Diplomate, Cornea, Contact Lenses, and Refractive Technologies 2. Danielle Robertson, OD, PhD, FAAO, FBCLA Diplomate, Cornea, Contact Lenses, and Refractive Technologies Rheumatic Autoimmune Disease: Better joints, same old eyes? I. Autoimmune Epidemiology: 1. It is generally believed that rheumatic autoimmune diseases affect 5% of the population. The most prevalent of these diseases are RA, SS and SLE. There is a predominance of women affected by these diseases. 2. The most recent CDC analysis demonstrated that the prevalence of RA has lessened and that the prevalence of SS may be higher than previously thought in the US. This review of surveys suggests that up to 3.1 million adult Americans (approximately 1%) suffer from Sjögren s syndrome. It is also believed that 9 out of 10 of them are women. USA prevalence of all rheumatic AI diseases: 5-6% of the US population: 1% RA and SS. Mainly women. II. Autoimmunity pathophysiology: How does our body learn to destroy itself? The etiology of autoimmune diseases is still unknown. However, 2 major theories exist: a viral attack and a local loss of immune protection 1. Viral etiology: The ocular mucosal tissues are exposed to all forms of viral species. Viruses can travel from the surface to invade the lacrimal gland in SS or the finger joints in RA and could certainly cause an autoimmune response. Changes in cytokine expression of lacrimal acinar cells or synovial tissue would activate both T and B immune cells that are present in the healthy lacrimal gland. 2. Failed local immunity: Inflammation in and around the lacrimal gland or finger joints from any cause could create a breakdown in immune protection. Sjögren s syndrome and RA then, become diseases of failed local immunity as stimulated cells become antigen presenting cells. MHC class II positive epithelial cells initiate an autoimmune response by presenting their own internal proteins on their surfaces to reactive T lymphocytes and thus activate these cells at the local level. This form of inflammation has been noted in several ocular conditions including corneal transplant rejection, 1
uveitis and proliferative vitreoretinopathy. Dendritic, T and B cells also play a role in this process. 3. The risk factors for autoimmune disease include both environmental insults and genetics. 4. The microbiome: emerging evidences suggests that alterations in the normal microbiome may contribute to the pathogenesis of autoimmune diseases. III. The Management of these diseases has evolved with the understanding of the pathophysiology. a. Understanding Rheumatic Autoimmune Disease Treatments using Rheumatoid Arthritis. RA is an inflammatory arthropathy with multi-organ involvement. Affects 0.5 to 1% (similar to Sjögren s syndrome) of population-may be lessening in incidence. Arthritis is symmetrical, usually in small joints, and destructive. b. History of Treatments: Originally thought of as infective, treatments began as gold and sulpha. Then because of identified immune agents of inflammation in the blood did plasma exchange. Today treatments include: 1. NSAIDS 2. DMARDS: (disease modifying anti-rheumatic drugs) synthetic and newer JAK-2 inhibitors 3. STEROIDS: a DMARD but used differently and at any stage. 4. Biologics NSAIDS: 1. ASA salicylic acid. Inhibits cyclo-oxygenase pathway. Do not alter destruction. Also cause gastric irritation and nephrotoxicity. 2. Advil, Aleve, naproxen 2
DMARDS: 1. Prevent joint erosion and thus are disease modifying 2. All work to stop destruction of joint by reducing inflammatory cascade that degrades soft tissue, cartilage and bone. I. Glucocortocoids, prednisone, in the 1940 s started, then 1980 s low dose prescriptions. Side effects include a. increase your blood sugar level, which can trigger temporary and possibly long-term diabetes b. suppress your body s ability to absorb calcium, which can lead to osteoporosis c. increase your cholesterol and triglyceride levels d. increase your risk of ulcers and gastritis e. delay in wound healing, which requires a certain amount of inflammation f. suppress your immune system and make you more prone to infections II. Sulfasalazine: is sulpha plus salicylic acid to treat infection and inflammation. III. METHOTREXATE: trials in the 1980 s, the drug of choice. A dihydrofolate reductase inhibitor that acts as a chemotherapy agent. Shows reduced TNF alpha in synovial fluid and inhibits inflammatory cell maturation (fast dividing). Even if not effective enough it is continued with the use of biologics IV. Quinine: Hydroxychloroquine: not often in RA, more often in lupus V. Azathioprine VI. Cyclophosphamide Biologic Agents: 1. TNF Etenercept 2. TNF Infliximab 3. IL-1R Anakinra 3
4. IL-6R Tocilizumab 5. CD20-Bcells Rituximab 6. CTLA4 B cells Abatacept (The Jakinibs: not in frequent use-inhibits intracellular cytokine pathways.) Sialogogues: cholinergic agonists These agents are used to promote saliva production. They have also been shown to increase tear meniscus height in patients with SS. Primary side effect is increased sweating. 1. Evoxac (cevimeline HCL) 2. Salagen (pilocarpine) Clinical Thoughts: 1. When a patient presents with sore, red, inflamed eyes think about possible systemic involvement. a. Rheumatoid arthritis: Ocular examination: ocular surface staining, Schirmers, corneal staining with fluorescein, episcleritis, scleritis, uveitis, vasculitis then ask about Hx: pain and inflammation of joints, fatigue, skin rash, myalagia, morning stiffness Lab tests: RA, snit-ccp. b. Systemic Lupus Erythematosus: If you observe ocular surface stain, low Schirmers, episcleritis, scleritis, uveitis, vasculitis then ask about Hx: fatigue, pain, mylagia, arthralgia, rash butterfly Lab tests: ANA, anti-dsdna c. Ankylosing spondylitis: 4
If you observe uveitis especially in young men ask about Hx: sore lower back Lab tests: X ray and HLA-B27 d. Sjögren s Syndrome: If you observe ocular surface stain and low Schirmers then think about Hx: dry eye, dry mouth, fatigue Lab tests: Ro, La, ANA and RF. *Seronegativity does not rule out SS. **May need to do additional lab tests to rule out other common diseases that can mimic SS. Salivary gland biopsy: the pros and cons. 2. Differential Diagnoses of ocular diseases 1. dry eyes: Sjögren s: can be associated with RA, SLE, CREST 2. scleritis, episcleritis, red eyes: SS, RA, SLE and CREST, ankylosing spondylitis 3. uveitis: RA, ankylosing spondylitis, SLE 3. It is important to keep in mind that many patients present with vague symptoms that overlap with multiple autoimmune diseases. a. It is not uncommon for more than one autoimmune disease to be present. b. For many patients, it can take years before the appropriate diagnosis(es) are made. 4. Diagnosis and treatment require a multi-disciplinary team approach. Your observations are important in making a referral to family practice or rheumatology. Management of ocular diseases associated with rheumatic autoimmune diseases. 5
1. Uveitis: ALWAYS look for posterior involvement. Treat anterior uveitis with normal protocols. Topical Corticosteroids, cycloplegics, topical non-steroidal antiinflammatories. Know when systemic intervention is required and make timely referrals. 2. Dry eye: especially in Sjögren s syndrome learn to emphasize lubrication, lid care, pulsed steroids, Restasis, autologous serum. Also emphasize the importance of avoiding windy conditions, fans, heating vents, etc. as they can exacerbate symptoms and trigger RCEs. May need humidifiers and/or sleep masks/goggles. 3. Scleritis: topical steroids and referral. They may need systemic IV steroids. 4. Episcleritis: depending on the severity, watch it, lubricate it, topical steroids. Main Clinical Points: What we need to do in our eye examinations 1. A thorough history that identifies autoimmune disease. Ask about fatigue, myalgia, arthralgia, dry mouth and family history. 2. A series of questions of those patients presenting with prolonged and significant dry eye or acute red eyes that might identify autoimmune disease. Ask about fatigue, dry mouth and family history. Other systemic problems like joint pain or stiffness in addition to other exocrine symptoms. This involves digestive, pulmonary, genitourinary, etc. 3. If suspicious, a look at the hands of patients with suspected or confirmed autoimmune disease to assess joint inflammation. 4. An observation of the mouth and tongue of those patient in whom you suspect Sjögren s syndrome. Angular chelitis may be present. Ask about history of dental carries. 5. Inquire about symptoms that may suggest Raynauds. 6. Extra attention to the ocular surface and anterior chamber to assess: corneal staining with fluorescein, conjunctival staining with lissamine green or rose bengal, Schirmer testing, close observation of episclera and sclera, anterior chamber observation to rule out cell and flare. 6
7. Findings of Schirmer scores <= 5mm in 5 min in 1 eye and/or total staining scores of <= 4/9 in at least 1 eye suggests the possibility of primary or secondary Sjögren s syndrome. Assess the dry mouth status and refer where appropriate. 8. Significant peripheral corneal staining with inflammation and/or cell and flare requires immediate attention with topical and/or oral steroids. Hospitalization may be required. 9. Uveitis presentation requires careful observation and a thorough ophthalmic AND systemic workup. Take Home: 1. All sore, red and dry eyes are NOT the same. Always think systemically. Ask about fatigue, joint pain, muscle pain, rashes and dry mouth. The HISTORY is the most important tool for rheumatology and for optometry. 2. Do a proper workup every time. Tear flow and use of fluorescein and lissamine greean stain are essential for the diagnosis. 3. Patients with rheumatic auotimmune diseases deserve our attention. Ask about, red, sore, dry eyes. Watch for dry eyes, cell and flare and if present look for posterior segment involvement. 7