Sjögren's Syndrome: Dry as a Desert

Therapy for Sjögren’s syndrome must be tailored to the individual patient.

In September 2011, tennis great Venus Williams gave an obscure condition a much-needed celebrity face when she announced she has Sjögren’s (SHUR-grens) syndrome (SjS). She joined approximately 4 million Americans who also have this relatively common but little-discussed autoimmune disease.

SjS attacks the exocrine (ie, moisture-producing) glands. SjS can attack any exocrine gland (eg, those in the nose, skin, lungs, and vagina), but it usually starts in 3 areas: the lacrimal glands, causing ophthalmic dryness (keratoconjunctivitis sicca); the salivary glands, causing xerostomia; and the parotid glands, causing pouch-like swelling along the jaw line.^1-3

Approximately 90% of SjS sufferers are female. SjS can occur at any age but is more likely to develop after 40 years of age.^1-3 SjS appears to have genetic contributors, but researchers postulate that genetics and environmental triggers (viral or bacterial infection that target gene expression) work together to cause it.⁴ Once SjS starts, T cells infiltrate the salivary and lacrimal glands, activating B cells. Antibody production follows, as does cytokine production, inflammation, and destruction.⁴ The B cells also generate SSA (anti-Ro) and SSB (anti-La), markers for SjS. Patients may have positive rheumatoid factor and an antinuclear antibody (ANA) titer of at least 1:320.

SjS owes its low profile to ambiguous presentations. Symptoms that mimic other disease states and cross clinical specialties make diagnosis difficult. SjS’s symptoms occur over a continuum and vary considerably. Patients who have dry mouth, for example, may have dry, cracked tongues or difficulty talking, swallowing, or chewing dry food.⁵ Patients may report a sore or burning throat, altered taste or smell, dry cough, or hoarseness. Dental decay and oral candidiasis are also likely due to less saliva.^5,6 Patients may have joint and muscle pain that is sometimes severe, migraines, severe sinusitis, or persistent and intrusive flu-like fatigue.⁷ Carpal tunnel syndrome is common among these patients. Table 1 describes symptoms that affect parts of the body other than the eyes and mouth, referred to generally as extra-glandular symptoms.

Because SjS mimics other conditions, it typically takes approximately 6 years from the first symptoms to confirm the diagnosis.⁵ Clinicians use patient history, physical examination, and laboratory work (anti-Ro: SSA or SSB) to diagnose SjS. The 2002 American-European Consensus Classification Criteria for Sjögren’s defines 6 criteria that signal SjS and guide diagnosis.^1,2,8 About three-fourths of SjS patients have positive rheumatoid factors and/or a positive ANA.^1,9

Patients with SjS have up to a 44-fold increased risk of developing lymphoma; between 2% and 10% of patients will develop lymphoma.¹⁰

Treatment

Clinicians work with patients to alleviate dryness in the eyes, mouth, and extra-glandular areas using an array of OTC artificial tears and ointments with different viscosity characteristics. Some patients develop sensitivity to preservatives in OTC products and therefore must switch to another product with an alternative preservative or select a preservative-free preparation. In the latter case, pharmacists should counsel patients about careful instillation technique to avoid contamination/eye infection by direct contact with the eye dropper and the eye itself. Ointments often blur vision and are best applied at bedtime.

Treating keratoconjunctivitis sicca with OTC products starts with tear replacement or supplementation. Many patients find relief from a prescription hydroxypropylcellulose pellet (Lacrisert) that decreases tear evaporation from the eye’s surface. Patients insert the pellets, which dissolve and form a film, between the lower eyelid and the eye once or twice daily. Adverse effects may include blurred vision, matting/stickiness of the eyelash, and ocular discomfort.¹¹

Cyclosporine ophthalmic emulsion (Restasis) can reduce lacrimal gland inflammation and preserve tear production. The approved labeling recommends 1 drop in both eyes twice daily. Common adverse effects include burning during administration, red eye, epiphora (overflow of tears due to imperfect drainage by the tear-conducting passages), a foreign body sensation, itching, and blurred vision.¹²

If the dryness becomes severe, punctual occlusion surgery (closing the tear drainage system) allows the artificial tears to reside on the surface of the eye for a longer period of time.^8-10

Salivary Dryness

OTC natural saliva substitute products and moisturizing gels offer some relief from xerostomia. Two similar cholinergic prescription medications are currently available to stimulate salivary production—pilocarpine hydrochloride (Salagen) and Evoxac (cevimeline).¹³ If patients have residual salivary function, oral pilocarpine taken 3 or 4 times a day stimulates salivary muscarinic acetylcholine and stimulates saliva production.^14,15 Cevimeline is an oral cholinergic agent with increased activity at the M1 and M3 receptors, which are concentrated in the salivary glands.^16,17 Both drugs have been proved to improve xerostomia symptoms compared with placebo. Cholinergic agents can cause multiple side effects, including nausea, dyspepsia, diarrhea, excessive salivation, increased diaphoresis, headache, flushing, chills, and dizziness.^14-17

Extra-glandular Involvement: Inflammation

Patients who have rheumatic extra-glandular involvement may respond to nonsteroidal anti-inflammatory drugs, cyclooxygenase-2 inhibitors, corticosteroids, and possibly disease-modifying antirheumatic drugs. Hydroxychloroquine, azathioprine, prednisolone, methotrexate, and D-penicillamine have been employed, with inconsistent results.^18-21 Some researchers think that tumor necrosis factor a may have a role, but to date, studies have not shown a benefit. Recently, researchers have seen some success with rituximab in patients with primary SjS. It seems to improve salivary flow rate, lacrimal gland function, and possibly vasculitis, cryoglobulinemia, and peripheral neuropathy. This use is investigational.^22-24

The Pharmacist’s Role

Pharmacists can help SjS patients improve their quality of life (Online Table 2). The most important thing to remember is that therapy must be tailored to the individual patient.

Table 2: Helping Sjögren’s Patients in the Pharmacy

• Offer counseling on prescription and nonprescription medications, including moisturizing products for the skin, nose, and vagina.
• Advise patients to avoid windy or drafty environments and to wear sunglasses when outdoors.
• Discuss the benefits of indoor humidifiers.
• Remind patients to practice good oral hygiene (chewing sugarless gum, sucking on sugarless candy, staying well hydrated, visiting the dentist 3 times annually).
• Suggest that patients who work at a computer or read extensively remind themselves to blink.
• Encourage smoking cessation and advise avoiding smoky environments.
• Advise against wearing eye makeup.
• Address showering: patients can pat dry (leave beads of water on the skin) and apply an emollient on damp skin within 3 minutes.

Adapted from references 4, 6, 7, and 15.

Final Note

Venus Williams adjusted her routine and activities to effectively manage her symptoms. She is a great athlete and a great role model for patients who have SjS. She is helping to promote the Sjögren’s Syndrome Foundation’s new goal: to shorten the time to diagnose SjS by 50% by 2017.²⁵ Pharmacists can help meet that goal!

Ms. Wick is a visiting professor at the University of Connecticut School of Pharmacy. She has extensive experience with the geriatric population.

References

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• Thomas E, Hay EM, Hajeer A, Silman AJ. Sjögren’s syndrome: a community-based study of prevalence and impact. Br J Rheumatol. 1998;37:1069-1076.
• Wallace DJ. The New Sjögren’s Syndrome Handbook. Oxford, UK: Oxford University Press; 2005:24-32.
• Brennan MT. Sjögren’s syndrome [published online December 2013]. Oral Maxillofac Surg Clin North Am. 2014;26(1).
• National Institute of Arthritis and Musculoskeletal and Skin Diseases website. www.niams.nih.gov. Accessed December 15, 2013.
• Mengshoel AM, Norheim KB, Omdal R. Primary Sjögren’s syndrome: fatigue is an ever-present, fluctuating and uncontrollable lack of energy [published online December 10, 2013]. Arthritis Care Res.
• Sankar V, Noll JL, Brennan MT. Diagnosis of Sjögren’s syndrome: American-European and the American College of Rheumatology classification criteria. Oral Maxillofac Surg Clin North Am. 2014;26:13-22.
• Venables PJ. Sjögren’s syndrome. Best Pract Res Clin Rheumatol. 2004;18:313-329.
• Baecklund E, Smedby KE, Sutton LA, Askling J, Rosenquist R. Lymphoma development in patients with autoimmune and inflammatory disorders: what are the driving forces [published online December 10, 2013]? Semin Cancer Biol. 2013;12.
• Lacrisert: drug facts and comparisons. Facts & Comparisons [online database]. St. Louis, MO: Wolters Kluwer Health, Inc; 2013. Accessed December 15, 2013.
• Restasis: drug facts and comparisons. Facts & Comparisons [online database]. St. Louis, MO: Wolters Kluwer Health, Inc; 2013. Accessed December 15, 2013.
• Salagen: drug facts and comparisons. Facts & Comparisons [online database]. St. Louis, MO: Wolters Kluwer Health, Inc; 2013. Accessed December 15, 2013.
• Sjögren’s syndrome foundation. About Sjögren’s syndrome. www.sjogrens.org/home/about-sjogrens-syndrome. Accessed December 15, 2013.
• Vivino FB, Al-Hashimi I, Khan Z, et al. Pilocarpine tablets for the treatment of dry mouth and dry eye symptoms in patients with Sjögren syndrome: a randomized, placebo-controlled, fixed-dose, multicenter trial. P92-01 Study Group. Arch Intern Med. 1999:159:174-181.
• Evoxac: drug facts and comparisons. Facts & Comparisons [online database]. St. Louis, MO: Wolters Kluwer Health, Inc; 2013. Accessed December 15, 2013.
• Fife RS, Chase WF, Dore RK, et al. Cevimeline for the treatment of xerostomia in patients with Sjögren syndrome. Arch Intern Med. 2002;162:1293-1300.
• Fox RI, Dixon R, Guarrasi V, Krubel S. Treatment of primary Sjögren’s syndrome with hydroxychloroquine: a retrospective, open-label study. Lupus. 1996;(5, suppl 1):S31-S36.
• Skopouli FN, Jagiello P, Tsifetaki N, Moutsopoulos HM. Methotrexate in primary Sjögren’s syndrome. Clin Exp Rheumatol. 1996;14:555-558.
• ter Borg EJ, Haanen HC, Haas FJ, et al. Treatment of primary Sjögren’s syndrome with D-penicillamine: a pilot study. Neth J Med. 2002;60:402-406.
• Price EJ, Rigby SP, Clancy U, Venables PJ. A double bind placebo controlled trial of azathioprine in the treatment of primary Sjögren's syndrome. J Rheumatol. 1998;25:896-899.
• Dass S, Bowman SJ, Vital EM, et al. Reduction of fatigue in Sjögren syndrome with rituximab: results of a randomised, double-blind, placebo-controlled pilot study. Ann Rheum Dis. 2008;67:1541-1544.
• Pijpe J, van Imhoff GW, Spijkervet FK, et al. Rituximab treatment in patients with primary Sjögren's syndrome: an open-label phase II study. Arthritis Rheum. 2005;52:2740-2750.
• Meijer JM, Pijpe J, Vissink A, Kallenberg CG, Bootsma H. Treatment of primary Sjögren syndrome with rituximab: extended follow-up, safety and efficacy of retreatment. Ann Rheum Dis. 2009;68:284-285.
• SSF launches 5-Year breakthrough goal. Sjögren’s Syndrome Foundation website. www.sjogrens.org/home/about-the-foundation/breakthrough-goal-. Accessed December 15, 2013.