Hospital Medicine

Sjogren's disease

I. What every physician needs to know.

Sjogren's syndrome (SS) is described as a systemic autoimmune inflammatory exocrinopathy which affects predominately the salivary and lacrimal glands. Involvement of these glands leads to xerostomia and keratoconjunctivitis sicca deemed the sicca complex. Primary SS occurs in isolation while secondary SS is associated with other rheumatologic conditions such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and scleroderma.

Etiology is unknown with research suggesting a viral infection or environmental trigger in a person with a genetic predisposition to immune dysfunction. Exocrine gland biopsies show infiltration of mainly T cells with a smaller proportion of B cells. Extraglandular manifestations are common, affecting multiple organ systems.

II. Diagnostic Confirmation: Are you sure your patient has Sjogren's syndrome?

In 2002, the American-European Consensus Group (AECG) revised the previous European classification criteria in the continued attempt to standardize the selection criteria for patients with well defined disease. The intention of this criteria is to identify SS patients for use in research study groups.

It was not created for routine clinical diagnosis as many manifestations may be subtle or absent early in the disease process. Solely using with criteria could lead to misclassification of these patients. These criteria are useful in diagnosis, but the gold standard continues to be the clinical judgment of the expert clinician. A multidisciplinary approach is needed.

AECG classification criteria

I. Ocular symptoms: a positive response to at least on of the following questions:

  • Have you had daily, persistent, troublesome dry eyes for more than 3 months?

  • Do you have a recurrent sensation of sand or gravel in the eyes?

  • Do you use tear substitutes more than 3 times a day?

II. Oral symptoms: a positive response to at least one of the following questions:

  • Have you had a daily feeling of dry mouth for more than 3 months?

  • Have you had recurrent or persistently swollen salivary glands as an adult?

  • Do you frequently drink liquids to aid in swallowing dry food?

III. Ocular signs: objective evidence of ocular involvement defined as a positive result for at least one of the following two tests:

  • Schirmer's I test, performed without anesthesia (< 5mm in 5 minutes)

  • Rose bengal score or other ocular dye score (> 4 according to van Bijsterveld's scoring system)

IV. Histopathology: in minor salivary glands (obtained through normal-appearing mucosa) focal lymphocytic sialadenitis, evaluated by an expert histopathologist, with a focus score greater than 1, defined as a number of lymphocytic foci (which are adjacent to normal-appearing mucous acini and contain more than 50 lymphocytes) per 4mm2 of glandular tissue.

V. Salivary gland involvement: objective evidence of salivary gland involvement defined by a positive result for at least one of the following diagnostic tests:

  • Unstimulated whole salivary flow (< 1.5mL in 15 minutes)

  • Parotid sialography showing the presence of diffuse sialectasis (punctate, cavitary or destructive pattern), without evidence of obstruction in the major ducts.

  • Salivary scintigraphy showing delayed uptake, reduced concentration and/or delayed excretion of tracer.

VI. Autoantibodies: presence in the serum of the following autoantibodies:

  • Antibodies to Ro(SSA) or La(SSB) antigens, or both.

For Primary Sjogren's syndrome

In patients without any potentially associated disease, primary SS may be defined as follows:

  • The presence of any 4 of the 6 items is indicative of primary SS, as long as either item IV (Histopathology) or VI (Serology) is positive.

  • The presence of any 3 of the 4 objective criteria (III, IV, V VI)

  • The classification tree procedure represents a valid alternative method for classification, although it should be more properly used in clinical-epidemiological survey.

For Secondary Sjogren's syndrome

In patients with a potentially associated disease (for instance, another well defined connective tissue disease), the presence of item I or item II plus any 2 from among items III, IV and V may be considered as indicative of secondary SS.

Exclusion criteria

  • Past head and neck radiation treatment

  • Hepatitis C

  • Acquired immunodeficiency disease (AIDS)

  • Pre-existing lymphoma

  • Sarcoidosis

  • Graft versus host disease

  • Use of anticholinergic drugs (since a time shorter than 4-fold the half-life of the drug)

A. History Part I: Pattern Recognition:

Similar to other systemic autoimmune conditions, manifestations of SS can be vague and present in multiple organ systems. Signs and symptoms are broken down into glandular and extraglandular manifestations. The glandular component consists of the sicca complex of xerostomia and keratoconjunctivitis sicca (KCS). In addition to the symptom of dry mouth, xerostomia may present as difficulty swallowing dry food and given the lack of saliva's antimicrobial properties, an increase in dental caries, candida induced angular cheilitis and bacterial salivary gland infections.

Patients with KCS complain of dry eyes, photophobia, irritation, a sensation of grit in the eye or a film over the eye. Additional glandular manifestations include vaginal dryness causing dysparenuria, dry cough from xerotrachea and dry skin. Extraglandular manifestations are seen in many SS patients and can occur in nearly every organ system with a widely variable prevalence given the lack of uniform diagnostic criteria.

Vague constitutional symptoms such as fatigue, myalgia, arthralgia are common with SS. Polyarthralgia predominately affects the small joints in a manner resembling RA. It differs from RA as stiffness is less severe, usually intermittent and is non-erosive. Fatigue and myalgias can, at times, be difficult to differentiate from fibromyalgia and chronic fatigue syndrome.

Thyroid disease occurs in approximately 1/3 of SS patients. Autoimmune thyroiditis with subclinical hypothyroidism being the most common presentation. Studies suggest that these are related by independent autoimmune diseases rather than thyroid disease being an extraglandular manifestation of SS. Further investigations are necessary to further explain this association. Insufficient thyroid hormone should be repleted in the typical fashion.

Dry cough and dyspnea are the most common respiratory complaints in SS. In addition to xerotrachea, this may be a sign of interstitial lung disease (ILD) or small airways disease (SAD). The pathophysiology of lung disease in SS unknown with multiple different ILD patterns seen. Most common are non-specific interstitial pneunomia (NSIP), lymphocytic interstitial pneumonia (LIP), usual interstitial pneumonia (UIP), organizing pneumonia (OP) and primary pulmonary lymphoma. No correlation between disease duration and pulmonary manifestations has been found. Pulmonary hypertension (PH) is a rare manifestation in SS, with most common presentation being exertional dyspnea. In the reported cases of PH, all were antinuclear antibody (ANA) positive, 2/3 had Raynaud's syndrome and nearly half had ILD.

Dysphagia, nausea and epigastric pain may be a sign of esophageal dysmotility (similar to scleroderma) or atrophic gastritis. Other gastrointestinal findings include a persistent or intermittent subclinical elevation of liver function tests in the form of hepatocellular, cholestatic or a mixed picture. There is a higher than expected frequency of primary biliary cirrhosis and autoimmune hepatitis in patients with SS.

Overall, renal involvement is a latent process with the most common lesion being interstitial nephritis (IN). IN is typically seen early with SS with usual manifestation as indolent subclinical RTA type I or much less frequently RTA type II. Treatment typically consists of oral bicarbonate replacement. Pathophysiology is unknown, but biopsies have shown the lymphocytic infiltration also seen in the salivary glands.

Glomerular nephritis (GN) is less frequently seen than IN and usually presents later in the disease process. Manifestations usually include hypertension, mild proteinuria and microscopic hematuria. Outcomes are variable in GN with the potential of becoming dialysis dependent. Interstitial cystitis is also seen with presentation consisting of urinary urgency, frequency and dysuria. Whether this is a manifestation of SS or a related condition remains to be seen.

A wide spectrum of peripheral nervous system (PNS) manifestions is associated with SS. Sensory, with or without ataxia and sensorimotor neuropathies are the most common. Other neuropathies include pure autonomic and motor. Non-ataxic sensory neuropathy is the most common with the most common subtypes being pure small fiber, polyneuropathy and isolated trigeminal neuropathy. Course is usually chronic and indolent. SS patients with ataxic sensory neuropathy develop a loss of proprioception which commonly leads to becoming wheelchair bound despite normal muscle strength.

Multiple mononeuropathy is a type of sensorimotor neuropathy which has a more acute presentation of weakness and paresthesia or dysesthesia in hands and feet. Involvement of the autonomic nervous system can lead to orthostatic hypotension, increased or decreased sweating, constipation, diarrhea, urinary frequency or retention, andAdie's pupils. The range of possible symptoms of involvement is due to varied parasympathetic versus sympathetic involvement. The central nervous system (CNS) is less frequently affected and may manifest as memory disturbance, personality disorders and cognitive dysfunction in addition to relapsing-remitting symptoms which mimic MS.

Involvement of the spinal cord is rare with sensorimotor deficits at and distal to a spinal cord level or severe neck or back pain being the signs and symptoms. Treatment of sensory neuropathy usually involves the typical antiepileptics such as gabapentin or pregabalin. Tricyclic antidepressants are avoided given their anticholinergic side effects. Data is limited and, at times, conflicted in regard to immunomodulatory treatments in peripheral nervous system (PNS) and central nervous system (CNS) involvement.

Dermatologic findings in SS can be divided into vasculitic and non-vasculitic. Dry skin is the most common non-vasculitic manifestation with others being annular erythema, alopecia, vitiligo, cutaneous lymphoma and Raynaud's. Raynaud's phenomenon in SS appears to be more mild than in scleroderma and patients are more likely to have associated arthralgia and vasculitis. The majority of vasculitis is of the small vessels and most commonly presents with palpable purpura, erythematous maculopapules of the lower limbs or urticaria of the upper body and arms.

Less frequent findings include ulcers and nodules. Cryoglobulinemic, urticarial, or leukocytoclastic vasculitis not fitting in these two previous categories (usually hypergammaglobulinemic purpura of Waldenstrom), are the predominate histiologic types. Systemic vasculitis is rare, usually associated with cryoglobulins and is potentially life-threatening.

Multiple studies have shown an increased risk of lymphoma in SS patients. Non-Hodgkin's lymphoma, most commonly low-grade marginal B-cell lymphoma (MZBCL) and diffuse large B-cell lymphoma (DLBCL) develop at an extranodal MALT, predominately at the salivary glands. Other sites include lung, GI tract, thyroid and the lymph nodes. Independent predictors of lymphoma development include neutropenia, cryoglobulinemia, splenomegaly, lymphadenopathy, purpura, parotid gland enlargement and low C4 levels.

Anemia of chronic disease is the most common hematologic abnormality (generalized inflammation) followed by hypergammaglobulinemia (polyclonal b cell activation), cryoglobulinemia and leukopenia.

B. History Part 2: Prevalence:

Estimations of US prevalance have been variable given the heterogeneity of multiple previous classification criteria and lack of US-based studies. Current thoughts are that approximately 1% of the US population is affected. SS is seen in all races and ages with approximately a 9:1 female predominance and onset typically in the 4-6th decades of life.

C. History Part 3: Competing diagnoses that can mimic Sjogren's disease.

Differential diagnosis of one or both components of the sicca complex includes:

  • Medications

  • Sarcoidosis

  • Amyloidosis

  • Previous head and neck irradiation

  • Human immunodeficiency virus (HIV)

  • Hepatitis C Virus (HCV)

  • Dry Eye and Mouth Syndrome (DEMS)

  • Rheumatoid arthritis

  • Other rheumatologic conditions

Parotid gland enlargement can be seen with:

  • HIV

  • HCV

  • Diabetes Mellitus

  • Warthin tumors

  • MALT lymphoma

  • Mumps

  • Sarcoidosis

A painless soft non-inflammed enlargement can be seen with:

  • Alcoholism

  • Malnutrition

  • Diabetes

  • Bulimia

Differentiation of SS from these conditions relies heavily on history in addition to laboratory evaluation and potential biopsy.

D. Physical Examination Findings.

Physical exam findings can vary significantly between patients, Gross ocular exam may be normal, however, common findings include conjunctival injection and thick secretions. Oral exam findings include dry mucous membranes, decreased or absent saliva pooling, angular cheilitis, chronic erythematous candida and tooth decay.

Ear, nose and throat (ENT) exam may show nasal crusting, epistaxis, lymphadenopathy and firm, nontender parotid gland enlargement. Pulmonary crackles from ILD can be present. There are multiple potential skin findings ranging from dry skin, vitiligo and alopecia to palpable and non-palpable purpura, urticaria and Raynaud's among others. If nerve involvment is present, a sensory, motor or a combined deficit may be detectable.

E. What diagnostic tests should be performed?

For the work-up of xerostomia, potential diagnostic tests include sialometry, sialography and salivary gland scintigraphy. There are multiple sialometric techniques, but the unstimulated whole salivary flow rate is part of the classification criteria. The patient is asked to emit and discard all saliva once, then over a 15 minute period, collect all saliva into a graduated cylinder.

An amount less than 1.5mL is deemed positive for xerostomia, although this is not specific to SS. This alone would satisfy the criteria showing salivary gland involvement. Sialography is infrequently performed but consists of cannulation of the main salivary duct followed by injecting a contrast material and taking plain x-rays. This should not be performed in patients with a contrast allergy and should be performed with caution if acute parotitis is present as there is a risk of rupture.

The finding ofsialectasisis suggestive, but not diagnostic, of SS. An alternative to sialography is sialo-MRI. This non-invasive, non-contrasted study can also show sialectasis. Salivary gland scintigraphy uses a 99mTc pertechnetate injection to potentially show decreased uptake and release by the submandibular and parotid glands. Both sialography and scintigraphy are potential tests to satisfy the salivary gland involvement criteria for SS.

For the work-up of keratoconjunctivitis sicca, potential tests include the Schirmer test and slit-lamp exam with ocular surface staining. The Schirmer test consists of placing a strip of filter paper into the unanesthetized bilateral lower eyelids. Eyes are closed for 5 minutes with less than 5mm of paper wetting by tears being diagnostic for xerophthalmia but is not specific to SS. Classically, the ocular stain, Rose Bengal, was used along with slit-lamp exam in attempt to detect the devitalized conjunctival and corneal surfaces seen with SS. Acceptable stain alternatives include lissamine green and fluorescein. To satisfy the criteria for objective ocular involvement, only one of these tests needs to be positive.

An additional test to help support the diagnosis of SS is a salivary gland biopsy with lymphocytic sialadenitis being the characteristic finding. Minor salivary glands from an area of normal appearing mucosa of the lower lip are removed under local anesthesia by an otolaryngologist. Greater than, or equal to, 1 focus of lymphoid tissue containing at least 50 lymphocytes per 4mm2 of glandular tissue fulfills the histopathologic classification criterion.

1. What laboratory studies (if any) should be ordered to help establish the diagnosis? How should the results be interpreted?

According to the American-European Rheumatology Group Consensus Classification Criteria, anti-SSA (Ro) and anti-SSB (La) are the only labs necessary for potential diagnosis. Positivity of one or both of these satisfies the autoantibody criterion. Other labs to aid in diagnosing include antinuclear antibody (ANA), rheumatoid factor (RF) and erythrocyte sedimentation rate (ESR).

None of these labs, including anti-Ro and anti-La, is diagnostic for SS. Positivity is also seen in multiple other rheumatologic conditions, fibromyalgia, chronic fatigue syndrome and in the normal healthy population. A complete blood count (CBC) may show anemia and leukopenia. A basic metabolic profile showing a non-anion gap metabolic acidosis and a urinalysis with proteinuria may point toward renal involvement.

Labwork ruling out the differential diagnosis includes HIV ELISA, HCV antibody and serum protein electrophoresis (SPEP).

2. What imaging studies (if any) should be ordered to help establish the diagnosis? How should the results be interpreted?

Chest X-ray (CXR) is commonly ordered in work-up of dry cough and dyspnea. CXR may not be able to detect early subtle abnormalities, conversely, CXR may be abnormal in the asymptomatic patient. The most common findings are a bilateral reticulonodular pattern predominately in the lung bases. One study found that approximately 2/3 of asymptomatic SS patients had abnormalities on high-resolution computed tomography (HRCT).

Frequent findings include ground glass and reticular opacities along with air space consolidations and small nodules. These findings are predominately subpleural in the lower lung zones with the exception of small nodules favoring the upper lung zones. Less frequent findings on HRCT include traction bronchiectasis, thin walled cysts and honeycombing. The presence of lymphadenopathy or pleural effusion should prompt further work-up for lymphoma.

III. Default Management.

Treatment of SS has centered around symptomatic control of keratoconjunctivitis sicca and xerostomia as SS is rarely organ or life-threatening.

Treating xerostomia consists of patient education regarding good dental hygiene and avoidance of oral dehydration. Routine brushing, flossing and using alcohol-free fluoride mouthwash will help prevent dental caries. Avoidance of tobacco and excessive alcohol with help decrease dehydration. Artificial saliva substitutes are available but most patients favor chewing sugar-free gum and carrying water.

Pilocarpine and cevimeline are both cholinergic agents with muscarinic activity which stimulate salivary secretions. Cevimeline is more selective to the muscarinic receptors and therefore, in theory, has fewer side effects. No studies have compared these two drugs head-to-head. Goal dose for pilocarpine is 5mg four times daily and cevimeline's is 30mg three times daily. Final dose is a balance between efficacy and side-effects. It may take 6 weeks before subjective effect is seen.

Treating dry eyes consists of using artificial tear substitutes including polyvinyl alcohol, carboxymethl cellulose or hydroxypropylmethyl cellulose. Sensitivity to preservatives (usually benzalkonium chloride) may necessitate a change to a preservative free solution. Lubricating ointments may be necessary for severe cases or for overnight use. Multiple different products may have to be tried in order to find the best results.

Topical steroids, nonsteroidal anti-inflammatory drugs (NSAIDS) and cyclosporine have also been used to decrease ocular surface inflammation, however, should only be prescribed by an ophthalmologist. Other treatment modalities include punctal occlusion and eye shields. Plugs can be inserted into the inferior puncta where the majority of tears drain into the nose. Temporary or permanent plugs help decrease tear loss, an alternative involves using cautery to close the puncta permanently. Eye shields placed into glasses are an additional measure to decrease tear loss.

For the general symptoms of fatigue, myalgias and arthralgias, hydroxychloroquine has been used despite the lack of controlled prospective evidence supporting its use. Corticosteroids are typically used for severe extraglandular manifestations of SS such as ILD, glomerulonephritis, neuropathy and systemic vasculitis. Rituximab may improve vasculitis, neuropathy, glomerulonephritis and arthritis, but further studies are needed. In addition to rituximab, other agents including interferon alfa-2a, infliximab, etanercept need additional studies to determine their role in SS.

V. Transitions of Care

D. Arranging for Clinic Follow-up

N/A

1. When should clinic follow up be arranged and with whom.

The number of different providers a patient with SS should follow-up with depends on their individual manifestations. In addition to rheumatologic, dental and ophthalmologic appointments, follow-up with pulmonary, nephrology, dermatology, neurology and hematology/oncology may be necessary.

2. What tests should be conducted prior to discharge to enable best clinic first visit.

If the diagnosis if suspected but not confirmed before discharge, anti-SSA(Ro), anti-SSB(La), ANA, RF and ESR should be drawn before discharge. As there is commonly a multiple day turnaround time for some of these tests, their completion by the time of follow-up will aid in diagnosis completion.

3. What tests should be ordered as an outpatient prior to, or on the day of, the clinic visit?

Based on the initial lab abnormalities, a CBC, basic metabolic profile, ESR, liver function tests, Ig levels and CXR all may benefit the rheumatologist's or other provider's appointment. Discussion with the subspecialists before discharge can help provide a list of tests to be ordered.

What's the evidence?

Baimpa, E, Dahabreh, IJ, Voulgarelis, M, Moutsopoulos, HM. "Hematologic Manifestations and Predictors of Lymphoma Development in Primary Sjogren Syndrome: Clinical and Pathophysiologic Aspects". Medicine. vol. 88. 2009. pp. 284-293.

Kassan, SS, Moutsopoulos, HM. "Clinical Manifestations and Early Diagnosis of Sjogren Syndrome". Arch Intern Med. vol. 164. 2004. pp. 1275-84.

Minozzi, F, Galli, M, Gallottini, L, Minozzi, M, Unfer, V. "Stomatological Approach to Sjogren's Syndrome: Diagnosis, Management and Therapuetic Timing". European Review for Medical and Pharmacological Sciences. vol. 13. 2009. pp. 201-16.

Kruszka, P, O'Brian, RJ. "Diagnosis and Management of Sjogren Syndrome.". Am Fam Physician. vol. 79. 2009. pp. 472-70.

Fox, RI, Liu, QY. "Sjogren's Syndrome in Dermatology". Clinics in Dermatology. vol. 24. 2006. pp. 393-413.

Venables, PJ. "Management of Patients Presenting with Sjogren's Syndrome". Best Practice & Research Clinical Rheumatology. vol. 20. 2006. pp. 791-807.

Chin, RL, Latov, N. "Central Nervous Manifestations of Rheumatologic Diseases". Current Opinion in Rheumatology. vol. 17. 2005. pp. 91-9.

Sene, D, Jallouli, M, Lefaucheur, J, Saadoun, D, Costedoat-Chalumeau, N, Maisonobe, T, Diemert, M, Musset, L, Haroche, J, Piette, J, Amoura, Z, Cacoub, P. "Peripheral Neuropathies Associated with Primary Sjogren Syndrome". Medicine. vol. 90. 2011. pp. 133-8.

Schlenker, c, Halterman, T, Kowdley, KV. "Rheumatologic Disease and the Liver". Clin Liver Dis. vol. 15. 2011. pp. 153-64.

Kaufman, I, Schwartz, D, Caspi, D, Paran, D. "Sjogren's Syndrome- not just Sicca: Renal Involvement in Sjogren's Syndrome.". Scand J Rheumatol. vol. 37. 2008. pp. 213-8.

Venables, PJW. "Sjogren's Syndrome". Best Practice & Research Clinical Rheumatology. vol. 18. 2004. pp. 313-29.

Parambil, JG, Myers, JL, Lindell, RM, Matteson, EL, Ryu, JH. "Interstitial Lung Disease in Primary Sjogren Syndrome". Chest. vol. 130. 2006. pp. 1489-95.

Mahoney, EJ, Spiefel, JH. "Sjogren's Disease". Otolaryngol Clin N Am. vol. 36. 2003. pp. 733-45.

Fox, RI, Stern, M, Michelson, P. "Update in Sjogren Syndrome". Current Opinion in Rheumatology. vol. 12. 2000. pp. 391-8.

Ramos-Casals, M, Tzioufas, AG, Stone, JH, Siso, A, Bosch, X. "Treatment of Primary Sjogren Syndrome- A Systematic Review". JAMA. vol. 304. 2010. pp. 452-60.

Larche, MJ. "A Short Review of the Pathogenesis of Sjogren's Syndrome". Autoimmunity Reviews. vol. 5. 2006. pp. 132-5.

Bowman, SJ. "Sjogren's Syndrome". Medicine. vol. 38. 2009. pp. 105-8.

Vitali, C, Bombardieri, S, Jonsson, R, Moutsopoulos, HM, Alexander, EL, Carsons, SE, Daniels, TE, Fox, PC, Fox, RI, Kassan, SS, Pillemer, SR, Talal, N, Weisman, MH. "Classification Criteria for Sjogren's Syndrome: A Revised Version of the European Criteria Proposed by the American-European Consensus Group". Ann Rheum Dis. vol. 61. 2002. pp. 554-8.

Mavragani, CP, Moutsopoulos, HM. "The Geoepidemiology of Sjogren's Syndrome". Autoimmunity Reviews. vol. 9. 2010. pp. A305-10.

Helmick, CG, Felson, DT, Lawrence, RC, Gabriel, S, Hirsch, R, Kwoh, CK, Liang, MH, Kremers, HM, Mayes, MD, Merkel, PA, Pillemer, SR, Reveille, JD, Stone, JH. "Estimates of the Prevalance of Arthritis and Other Rheumatic Conditions in the United States Part I". Arthritis & Rheumatism. vol. 58. 2008. pp. 15-25.

Pillemer, SR, Matteson, EL, Jacobsson, LTH, Martens, PB, Melton, J, O'Fallon, M, Fox, PC. "Incidence of Physician-Diagnosed Primary Sjogren Syndrome in Residents of Olmstead County, Minnesota". Mayo Clin Proc.. vol. 76. 2001. pp. 593-9.

Uffmann, M, Kiener, HP, Bankier, AA, Baldt, MM, Zontsich, T, Herold, CJ. "Lung Manifestation in Asymptomatic Patients with Primary Sjogren Syndrome: Assessment with High Resolution CT and Pulmonary Function Tests". Journal of Thoracic Imaging. vol. 16. 2001. pp. 282-9.

Parke, AL. "Pulmonary Manifestations of Primary Sjogren's Syndrome". Rheum Dis Clin N Am. vol. 34. 2008. pp. 907-20.

Skopouli, FN. "Kidney Injury in Sjogren's Syndrome.". Nephrol Dial Transplant. vol. 16. 2001. pp. 63-4.

Mandel, L, Surattanont, F. "Bilateral Parotid Swelling: A Review". Oral Surg Oral Med Oral Path Oral Radiol Endod. vol. 93. 2002. pp. 221-37.

Soy, M, Piskin, S. "Cutaneous Findings in Patients with Primary Sjogren's Syndrome". Clin Rheumatol. vol. 26. 2007. pp. 1350-2.

Chai, J, Logigian, EL. "Neurological Manifestations of Primary Sjogren's Syndrome". Curr Opin Neurol. vol. 23. 2010. pp. 509-13.

Birnbaum, J. "Peripherla Nervous System Manifestations of Sjogren Syndrome". Curr Opin Neurol. vol. 23. 2010. pp. 509-13.

Machando, LM, Castro, RS, Fontes, BM. "Staining Patterns in Dry Eye Syndrome: Rose Bengal Versus Lissamine Green". Cornea. vol. 28. 2009. pp. 732-4.

Jara, LJ, Navarro, C, Brito-Zeron, MD, Garcia-Carrasco, M, Escarcega, RO, Ramos-Casals, M. "Thyroid Disease in Sjogren's Syndrome". Clinical Rheumatology. vol. 26. 2007. pp. 1601-6.

Goules, A, Masouridi, S, Tzioufas, AG, Ioannidis, JP, Skopouli, A, Fotini, N, Moutsopoulos, HM. "Clinically Significant and Biopsy-Documented Renal Involvement in Primary Sjogren's Syndrome". Medicine. vol. 79. 2000. pp. 241-9.

Leppilahti, M, Tammela, TL, Huhtala, H, Kiilholma, P, Leppilahti, K, Auvinen, A. "Interstitial Cystitis-Like Urinary Symptoms Among Patients wtih Sjogren's Syndrome: A Population-Based Study in Finland". Am J of Med. vol. 115. 2003. pp. 62-5.

Skopouli, FN, Barbatis, C, Moutsopoulos, HM. "Liver Involvment in Primary Sjogren's Syndrome". Br J Rheumatol. vol. 33. 1994. pp. 45-8.

Garcia-Carrasco, M, Siso, A, Ramos-Casals, M, Rosas, J, de la Red, G, Gil, V, Lasterra, S, Cervera, R, Font, J, Ingelmo, M. "Raynaud's Phenomenon in Primary Sjogren's Syndrome. Prevalance and Clinical Characteristics in a Series of 320 Patients". Journal of Rheumatology. vol. 29. 2002. pp. 726-30.

Ramos-Casals, M, Anaya, J, Garcia-Carrasco, M, Rosas, J, Bove, A, Claver, G, Diaz, L, Herrero, C, Font, J. "Cutaneous Vasculitis in Primary Sjogren Syndrome. Classification and Clinical Significance of 52 Patients". Medicine. vol. 83. 2004. pp. 96-106.

You must be a registered member of ONA to post a comment.

Sign Up for Free e-newsletters

Regimen and Drug Listings

GET FULL LISTINGS OF TREATMENT Regimens and Drug INFORMATION

Bone Cancer Regimens Drugs
Brain Cancer Regimens Drugs
Breast Cancer Regimens Drugs
Endocrine Cancer Regimens Drugs
Gastrointestinal Cancer Regimens Drugs
Genitourinary Cancer Regimens Drugs
Gynecologic Cancer Regimens Drugs
Head and Neck Cancer Regimens Drugs
Hematologic Cancer Regimens Drugs
Lung Cancer Regimens Drugs
Other Cancers Regimens
Rare Cancers Regimens
Skin Cancer Regimens Drugs