1. Sjogren's Syndrome: Difficult Case Presentation: Rather than a zebra, I will present a common scenario that often falls in the lap of the rheumatologist (the only one who will listen to the patient) Robert Fox Scripps Memorial-Ximed robertfoxmd@mac.com

2. Ms. PT is a 47 yr female software CFO with a 15 yr history of Sjogren's She is having increasing ocular pain that now is limiting her ability to use computer and to travel on airplanes

3. Brief history 15 yr ago-dx SS with dry eyes/mouth and ANA >640 (SS-A/B+), ESR 20 Positive lip biopsy (focus score 2) Schirmer's 2 mm, Abnormal Tear Breakup time Mild KCS and no erosions on slit lamp Although her ocular and oral pain is now much more severe, her labs and ocular exam are essentially unchanged from 10 years ago. She even had a repeat lip biopsy one year ago (as part of study) and still has focus score 2

4. Current Treatment Preservative free tears (refresh) and ocular lubricant (Refresh PM) Prior punctal plugs Restasis (topical cyclosporin) Ophthalmologist has thrown up his hands

5. Key points On exam, she has blepharitis-in part from overuse of her nighttime lubricant Current Plan: Use no more than 1/8 inch lubricant to avoid plugging meibonian glands and use lid scrubs in am to remove A short course of oral doxycycline was helpful Systane is a useful tear in SS patients with blepharitis

6. Environmental Factors-1 Her work involves 10 hrs./day at computer Blink rate goes down 90% using computer Current Plan: Computer glasses and humidification of work area

7. Environmental Factors-2 She travels by airplane frequently (low humidity) and arrives with eyes in severe pain Use of lubricant or Tranquil-eye (Amazon) helps May require Lotemax (a soft steroid) for a day or two Already in Japan, eyeglass frames with small humidity pumps

8. Jinn Glasses with implanted moisture pump (currently available in Japan) Stems are water reservoir Working with designers for western face

9. Environment-3 She travels to Asia where dry, polluted, and people smoke Use of sunglasses with moisture shields can be fashionable and allow outdoor exercise (Wiley) (dryeyezone.com)dryeyezone.com Moisture shields on glasses

10. M “Moisture shield” glasses and sunglasses Available at “dryeyezone.com”

11. Moisture Shields for night or airline Dryeyezone.com

12. Things they may not tell you She had a blepharoplasty (facelift around eyes) two years ago when symptoms exacerbated This frequently leads to exposure keratitis (esp at night when poor lid apposition) Use of taping lid at night and humidifier Be alert to thyroid exophthalmia Lasik surgery is contra-indicated

13. Medications She was taking Benadryl (otc) to sleep across time zones Also some Elavil (from her friend) helped her sleep Especially at night, anticholinergic exacerbate the diurnal rhythm of decreased secretion at night Many herbal mixtures (otc) are anticholinergic

14. Although little progression of her biopsy or exam, her symptoms were dramatically increased Pain could only decrease from 9 to 6 (on scale of 10) after topical anesthetic This indicates role of nociceptive pain-literally a corneally mapped pain in prefrontal cortex as a result of chronic afferent stimuli May respond to combo low dose duloxetene (Cymbalta) plus pregabalin (Lyrica) Occasionally to low dose naltrexone

15. 1. Pain often increases with time 2. Even though objective measures of disease progression are absent Summary of issues-1

16. Summary of issues-2 This increase in pain is only partly reversed by Opthaine (topical anesthetic), so e know it is noci-ceptive (cortically mapped) New approaches by Neurologists and Pain Specialists are concentrating on mechanisms of “veto-neurons” to reverse this cortically mapped pain

17. Summary of issues-3 SS provides an interface of immunology and neurology to study the factors that relate to pain and fatigue This is the new frontier for the next decade