Secondary Sjögren’s Syndrome and Rheumatoid Arthritis

secondary winding Sjgrens Syndrome and Rheumatoid ArthritisSecondary Sjgrens Syndrome and Rheumatoid Arthritis legal action a case of severe teetotal out eyeballAuthorsDina 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 range of clinical manifestations that carries a high value of morbidity and mortality with increased risk of lymphoma development. Sjgrens syndrome is either a primary disorder, or thirdhand to other autoimmune disorders e.g. rheumatoid arthritis (RA). Due to the multiple aspects of the disease and the coincidence of the symptoms to other diseases, diagnosis and centralisesing of Sjgrens syndrome is challenging. Among the symptoms, Sjgren syndrome typically presents with dry eyes that may result in severe opthalmic egress disorders such as persistent epithelial defects, and conventional dry eye therapy is oft unsuccessful in controlling ocular signs and symptoms. We highlight the rargon case of a 50 year one m(a) charr whom despite well controlled RA disease activity silent manifested with severe secondary Sjgrens syndrome. It was only later on autologous serum was applied as a last remedy that her ocular symptoms better.Keywords Rheumatoid arthritis, dry eyes, Sjgrens syndrome, autologous serum, inflammationIntroductionSjgrens syndrome (SS) is a systemic autoimmune disease bear on the exocrine secretory organs. A lymphocytic infiltration in the salivary and lacrymal glands results in reduced secretion, leading to continuous dryness of the mouth and eyes.1-3 SS may manifest as a primary disease presenting as a single entity, or secondary in combination with other autoimmune disorders.4 The prevalence of secondary SS relates preponderantly to RA5 and associates with increased disease acivity.6 It may present with a systemic compon ent, including painful joints, dry and itchy temperateness nice skin, irritable bowel, have it offr problems and extreme tiredness. Beca white plague of the many possible clinical pictures of SS it is a challenging diagnosis to make and may therefore go undiagnosed for many years after the onset of symptoms.3,7-9 dispassionateness symptoms are amplified in patients with RA, it increases with age and are associated with the severity of illness, relating to worse 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 treatment 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 treatment with a tumor necrosis factor ( tumour necrosis factor) inhibitor, still developed severe secondary SS. Autologous serum drops offered significant improvement of her extreme ocular jump inflammation and symptoms, when all other treatment modalities failed.Case ReportA 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 ca subroutined severe, constant discomfort and visual blurring, rendering her partially incapacitated, even though her corrected flock was still normal at 6/6. She had to wear sunglasses indoors and could not drive independently. On examination of her corneas the various findings confirmed the severity of her dry eyes. These allowd a tear breakup time of 5 seconds bilaterally , mucus filaments, punctuate corneal straining and an almost non-existing tear meniscus indicating very petty tear secretion. Evidence of previous (healed) peripheral ulcerative keratitis could be seen on the medial aspect of two 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 spare 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, neurological involvement, leukocytoclastic vasculitis, rhinitis, pharyngitis and laryngitis.3,9,12 In view of the wide range of severe systemic manifestations of the disease patients are often characterised with higher morbidity and mortality, which are mainly 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 amid two main oddballs 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 dis run across extraglandular manifestations that may lead to lymphoma.3 The glandular phenomenon includes ocular symptoms (dry eyes, xerophthalmia) and oral 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.3,13Diagnosi sSjgrens 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 average 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 twain signs and symptoms of oral and ocular dryness and who test positive to the diagnostic criteria. From clinical experience it was open up that if a patient does not suffer from both dry eyes and dry mouth, it is necessary to exclude come on 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 Syndrome8TreatmentThe aim of treatment for dry eyes is mainly to provide re lief of symptoms and to prevent corneal epitheliopathy. Management of the disease currently includes artificial tears, topical secretagogues, local immunomodulatory drops, lachrymal duct occlusion and hypotonic hyaluronic acid drops in the treatment of dry eyes.3 antithetic methods of treatment that may be used independently or in combination with tear supplements include systemic immuno supple 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 climb environment. Some patients, however, present with more serious ocular muster up 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 personal effects on dry eyes, there seems to be other local factors independently of the systemic process, 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 show off reflex, normal tear production and healthy adnexae.14 Typically tears contain epitheliotrophic factors including growth factors, vitamins and fibronectin that are of decisive 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 zeal thereof is costly and complex, it proofs a clinically effective treatment in ocular surface diseases.3,11 macrocosm 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 important role 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 to therapy in other ophthalmological conditions as seen in chemical injuries of the ocular surface.ConclusionSjgrens syndrome may cause marked disability in patients suffering 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.Ante ro 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 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.Kruszk a P, OBrian R,J. Diagnosis and management of Sjgren syndrome. Am.Fam.Physician 2009 03/1579(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. Curr.Eye Res. 2013 0138(1)9-17.12.ELLMAN P, Weber FP, Goodier T. A contribution to the pathology of Sjgrens disease. QJM 195120(1)33-42.13.Kassan SS, Moutsopoulos HM. Clinical manifestations and primordial diagnosis of Sjgren syndrome. Arch.Intern.Med. 2004 06/28164(12)1275-1284.14.Noble BA, Loh RSK, MacLennan S, Pesudovs K, Reynolds A, Bridges LR, et al. Comparison of autologous serum eye drops with conventional therapy in a randomised controlled crossover trial for ocular surface disease. Br.J.Ophthalmol. 2004 0588(5)647-652.15.Geerling G, Maclennan S, Hartwig D. Autologous serum eye drops for ocular surface disor ders. Br.J.Ophthalmol. 2004 1188(11)1467-1474.16.Villani E, Galimberti D, Del Papa N, Nucci P, Ratiglia R. Inflammation in dry eye associated with rheumatoid arthritis cytokine and in vivo confocal microscopy study. Innate Immun 201319(4)420-427.17.Fox RI, Chan R, Michelson JB, Belmont JB, Michelson PE. safe effect of artificial tears made with autologous serum in patients with keratoconjunctivitis sicca. Arthritis Rheum. 1984 0427(4)459-461.18.Quinto GG, Campos M, Behrens A. Autologous serum for ocular surface diseases. Arq.Bras.Oftalmol. 2008 11/2071(6)47-54.1