Secondary Sjögren’s Syndrome and Rheumatoid Arthritis

Secondary Sjgrens Syndrome and Rheumatoid ArthritisSecondary Sjgrens Syndrome and Rheumatoid Arthritis Activity a case of intemperate juiceless eyeAuthorsDina Christina Janse van Rensburg, MD1, 2Catharina Cornelia Grant, PhD1, 2Audrey Jansen van Rensburg, MSc1,2Pieter Roelof Cronj, FC Ophth, MBChB3Thelani Catharina Grant, BSc Agric (Hons)1, 2AbstractPatients with Sjgrens syndrome present with a wide browse of clinical manifestations that carries a high rate of morbidity and mortality with increased risk of lymphoma development. Sjgrens syndrome is either a primary disorder, or secondary to separate autoimmune disorders e.g. rheumatoid arthritis (RA). Due to the multiple aspects of the disease and the similarity of the symptoms to other diseases, diagnosing and management of Sjgrens syndrome is challenging. Among the symptoms, Sjgren syndrome typically presents with dry eyes that may egress in mischievous ocular surface disorders such as persistent epithelial defects, and conve ntional dry eye therapy is often unsuccessful in exacting ocular signs and symptoms. We highlight the rargon case of a 50 year old woman whom disdain well controlled RA disease activity excuse manifested with severe secondary Sjgrens syndrome. It was only after autologous serum was applied as a last resort that her ocular symptoms improved.Keywords Rheumatoid arthritis, dry eyes, Sjgrens syndrome, autologous serum, inflammationIntroductionSjgrens syndrome (SS) is a general autoimmune disease affecting the exocrine glands. A lymphocytic infiltration in the salivary and lacrymal glands results in reduced secretion, jazzing to continual dryness of the mouth and eyes.1-3 SS may manifest as a primary disease presenting as a single(a) entity, or secondary in combination with other autoimmune disorders.4 The prevalence of secondary SS relates predominantly to RA5 and associates with increased disease acivity.6 It may present with a systemic component, including painful joints, dry an d itchy sunlight sensitive skin, irritable bowel, liver problems and extreme tiredness. Because of the many possible clinical pictures of SS it is a challenging diagnosis to do work and may therefore go undiagnosed for many years after the onset of symptoms.3,7-9 Dryness symptoms are amplified in patients with RA, it increases with age and are associated with the severity of illness, relating to worsened outcomes measures of the disease. Approximately 25% RA patients presents with keratoconjunctivitis sicca as the most prevailing and frequent ocular complication.5,10 Several therapies have been identified that inhibit inflammatory mediators and mechanisms in dry eye disease, however the interference of persistent epithelial defects and severe ocular dryness by means of topical tear replacement often proofs inadequate.11 In this case study we report a RA patient who regardless of well controlled discussion with a tumor necrosis factor (TNF) inhibitor, still genuine severe seconda ry SS. autologous serum drop-offs offered significant improvement of her extreme ocular surface inflammation and symptoms, when all other treatment modalities failed.Case spread abroadA 50 year old Caucasian woman was diagnosed with RA. During the course of the illness she was treated with methotrexate, folic acid, meloxicam, prednisone, sulfasalazine and leflunomide. Seven years post RA diagnosis and despite well controlled disease on adalimumab, methotrexate and folic acid, her eyes became extremely dry and highly sensitive to light. This dryness caused severe, constant discomfort and visual blurring, rendering her part incapacitated, even though her corrected vision was still normal at 6/6. She had to wear sunglasses indoors and could not drive independently. On examen of her corneas the various findings confirmed the severity of her dry eyes. These included a tear breakup time of 5 seconds bilaterally, mucus filaments, punctuate corneal straining and an some non-existing te ar meniscus indicating very little tear secretion. Evidence of previous (healed) peripheral ulcerative keratitis could be seen on the medial aspect of both corneas.These symptoms lead to the diagnosis of Sjgrens syndrome. She was treated with all possible modalities including punctum plugs and multitudes of topical medication including Cyclosporine A, with no apparent improvement. A decision was made to attempt an eye drop prepared from autologous serum. Her condition improved remarkably in the year since she started the serum.DiscussionSjgrens syndrome was first described by the eye specialist Hendrik Sjgren in 1933. It presents with a variety of symptoms, including fatigue, arthralgia, myalgia, keratoconjunctivitis sicca(dry eyes, in part known as Sicca syndrome), xerostomia (dry mouth), skin lesions, lymphoproliferative disorders, neurologic involvement, leukocytoclastic vasculitis, rhinitis, pharyngitis and laryngitis.3,9,12 In view of the wide range of severe systemic manifesta tions of the disease patients are often characterised with higher morbidity and mortality, which are in general related to an enhanced probability to develop lymphoma.3,13 Most patients with SS are middle-aged women, and symptoms mostly occur with the accompaniment of, but not exclusively to, RA.3,12Recently literature differentiates mingled with two main types of the disease The glandular (exocrine gland- localised) form that affects mainly the quality of life of the patient, and the systemic syndrome type which display extraglandular manifestations that may lead to lymphoma.3 The glandular phenomenon includes ocular symptoms (dry eyes, xerophthalmia) and literal involvement (dry mouth, xerostomia, caries and candidiasis).3 Extraglandular manifestations consist of musculoskeletal indications, Raynauds phenomenon, renal, liver and neurological involvement, vasculitis and haematologic manifestations.3,13DiagnosisSjgrens syndrome is difficult to diagnose due to the multiple aspects of the syndrome, and similarity to the symptoms caused by other diseases.3,7,8 SS is a slow progressing disorder, and on total may take approximately 5 years from the onset of symptoms before the correct diagnosis is reached.8Sjgrens syndrome is strongly suggested in patients who present with both signs and symptoms of oral and ocular dryness and who test positive to the diagnostic criteria. From clinical experience it was found that if a patient does not suffer from both dry eyes and dry mouth, it is necessary to exclude further causes of the dry eyes by means of differential diagnoses.13A series of tests in the diagnosis of Sjgrens syndrome are outlined in Table 1. These criteria consider dryness symptoms, changes in salivary and lacrimal gland function, and systemic findings.8Table 1. Tests and criteria used to diagnose Sjgrens Syndrome8 treatmentThe aim of treatment for dry eyes is mainly to provide relief of symptoms and to prevent corneal epitheliopathy. Management of the di sease currently includes artificial bust, topical secretagogues, local immunomodulatory drops, lachrymal duct occlusion and hypotonic hyaluronic acid drops in the treatment of dry eyes.3 Different methods of treatment that may be used independently or in combination with tear supplements include systemic immunoactive drugs and calcineurin inhibitors, topical corticosteroids and topical non-steroidal anti-inflammatory drugs.3Patients with dry eyes normally respond well to these treatments that focus on optimising the ocular surface environment. Some patients, however, present with more serious ocular surface disorders, that do not react to conventional treatment, which may lead to severe visual impairment.14,15 Fujita et al.10 drew attention to the exceptionally high incidence of dry eyes in patients with RA. Their conclusions are that although RA patients with SS present with systemic personnels on dry eyes, there seems to be other local factors independently of the systemic proce ss, that disturbs the ocular surface and control the severity of dry eyes in RA patients.5,16 Due to the many local elements active in dry eyes it calls for improved new therapeutic agents for managing dry eyes without making use of systemic agents.5The various factors that contribute to a healthy ocular surface include an adequate blink reflex, normal tear production and healthy adnexae.14 Typically tears contain epitheliotrophic factors including growth factors, vitamins and fibronectin that are of vital importance to the ocular epithelial health.15 These factors support the viability, proliferation and migration of ocular surface epithelial cells.15 They are not found in pharmaceutical tear substitutes, but do however occur in blood serum. Clinical cohort studies have reported the successful useof epitheliotrophic factors in autologous serum drops to improve severe cases of dry eyes where other conventional treatments fall short.14,15Autologous serum drops was first described in 1984 as a substitute constituent free of potentially harmful substances17 applied as unpreserved artificial tears.15 It is believed that the epitheliotrophic factors in the serum are the rationale behind its success in the treatment of extremely dry eyes.15The use of autologous serum eye drops may in many cases be a last resort of treatment for SS patients who have not responded well to conventional tear replacement therapy. Even though the preparation thereof is costly and complex, it proofs a clinically effective treatment in ocular surface diseases.3,11 Being non-allergenic with biochemical properties akin to normal tears,3,18 it benefits the conjunctival epithelium supplementing essential vitamins, fibronectin, anti-proteases and growth factors. This may stimulate its proliferation and repair,11 and play an beta place in the integrity of the cornea and conjunctiva.3,11Autologous serum appears to be more effective in resistant cases. It may also play an essential role adjunct t o therapy in other ophthalmological conditions as seen in chemical injuries of the ocular surface.ConclusionSjgrens syndrome may cause marked disability in patients misfortunate from the disease, especially when secondary to RA. In this case study, despite optimal control with a TNF inhibitor the patient still presented with SS and suffered from severe xerophthalmia. All treatment modalities had failed and as a last alternative autologous eye serum was instituted. This significantly improved the severe dry eyes and persistent epithelial defects and enabled her to live a normal life.ConsentWritten informed consent was obtained from the patient for publication of this case report. A copy of the written consent is available for review.References1.Shiel W. What is rheumatoid arthritis?. 4/24/2014 Available at http//www.medicinenet.com/rheumatoid_arthritis/article.htm. Accessed June 26, 2014.2.Antero DC, Parra AGM, Miyazaki FH, Gehlen M, Skare TL. Secondary Sjgrens syndrome and disease activity of rheumatoid arthritis. Rev.Assoc.Med.Bras. 2011 05/2057(3)319-322.3.Vitali C, Palombi G, Cataleta P. Treating Sjgrens Syndrome Insights for the Clinician. Ther Adv Musculoskelet Dis 2010 062(3)155-166.4.Patel R, Shahane A. The epidemiology of Sjgrens syndrome. Clin Epidemiol 2014 07/306247-255.5.Lemp MA. Dry eye (Keratoconjunctivitis Sicca), rheumatoid arthritis, and Sjgrens syndrome. Am.J.Ophthalmol. 2005 11140(5)898-899.6.Fox RI. Sjgrens syndrome. lancet arch 2005 07/23366(9482)321-331.7.Mayo Clinic. Diseases and Conditions Sjogrens syndrome tests and diagnosis. Jul. 08, 2014 Available at http//www.mayoclinic.org/diseases-conditions/sjogrens-syndrome/basics/tests-diagnosis/con-20020275. Accessed June 25, 2014.8.Sjgrens Syndrome Foundation. Diagnosis about Sjgrens Syndrome. 2014 Available at http//www.sjogrens.org/home/ about-sjogrens-syndrome/diagnosis. Accessed June 26, 2014.9.Kruszka P, OBrian R,J. Diagnosis and management of Sjgren syndrome. Am.Fam.Physician 2009 0 3/1579(6)465-470.10.Fujita M, Igarashi T, Kurai T, Sakane M, Yoshino S, Takahashi H. Correlation between dry eye and rheumatoid arthritis activity. Am.J.Ophthalmol. 2005 11140(5)808-813.11.Cho YK, Huang W, Kim GY, Lim BS. Comparison of autologous serum eye drops with different diluents. 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