WORKUP	Section 5 of 11
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Lab Studies:

• CBC count with differential: Mild anemia and leukopenia are present.

• Erythrocyte sedimentation rate (ESR): Elevated ESR is observed in 80-90% of patients, often related to hypergammaglobulinemia; however, C-reactive protein (CRP) levels are usually within the reference range.

• Immunoglobulin levels: Hypergammaglobulinemia, up to several grams of immunoglobulin G (IgG), is observed in 70-80% of both pediatric and adult patients.

• Autoantibodies

• ANA and RF levels - Usually elevated

• Anti-Ro (SS-A), anti-La (SS-B)

• Autoantibodies to thyroglobulin, thyroid microsomal, mitochondrial, smooth muscle, parietal, peroxisomal, and salivary duct (often present in adults with Sjögren syndrome)

• Cryoglobulins and, occasionally, antiphospholipid antibodies

• Rose Bengal staining: The dye stains damaged corneal epithelium and indicates keratoconjunctivitis. This is not often performed in children.

• Schirmer tear test: This test is used to evaluate tear production by lacrimal glands. A strip of filter paper is placed beneath the lower lid, and wetting of the paper is measured at 5 minutes. Less than 10 mm of film is abnormal, and less than 5 mm of wetting suggests decreased tear production and sicca syndrome. This test is performed more often in pediatric patients.

Imaging Studies:

• Sialography - A sensitive and specific radiographic technique to find evidence of sialectasis (Sialography sensitivity has not been reported in the pediatric literature. These techniques are not commonly used at most pediatric centers.)

• Technetium Tc 99 pertechnetate scintigraphy - Delayed uptake in Sjögren syndrome; often correlates with pathological changes

• MRI - Visualization of the glandular parenchyma, in particular for the evaluation of cystic or solid masses (In addition, the volumetric estimate of the gland size can be determined.)

Other Tests:

• In the questionnaire of adult salivary hypofunction, positive responses to all 4 of the following questions indicate major salivary gland hypofunction (adapted from Fox, 1998).
  • Do you sip liquids to aid in swallowing dry foods?

  • Does your mouth feel dry when eating a meal?

  • Do you have difficulties swallowing any foods?

  • Does the amount of saliva in your mouth seem to be too little?

• Sialometry is the quantification of whole saliva or individual gland secretions at unstimulated (resting) or stimulated flow rates. For salivary hypofunction, the flow rate for unstimulated whole saliva is less than 0.1 mL/min, while the rate for stimulated whole saliva is less than 0.5 mL/min. The collection period is a minimum of 5 minutes and often up to 15 minutes. When secretions from the parotid gland are evaluated, the modified Carlson-Crittenden collector is placed over the Stensen duct. Isolation of the salivary gland orifices in the floor of the mouth and gentle suction are used to collect submandibular and sublingual secretions together. Besides demonstrating salivary hypofunction, these methods can be used to evaluate the effectiveness of secretogogue therapy. These procedures are not commonly used in pediatric patients.

• On sialochemistry, collected secretions can be chilled, frozen, and evaluated for electrolytes, immunoglobulins, and protein constituents. Although not diagnostic for Sjögren syndrome, a profile has been observed, including an increase in secretory levels of immunoglobulin A, lactoferrin, total protein, and sodium and chloride ions. In addition, decreased levels of lysozyme and potassium and phosphate ions are found. Although still considered experimental, these changes in salivary constituents are of unknown predictive value.

• Less than 50% of pediatric patients report ocular symptoms, whereas older patients with Sjögren syndrome more frequently report them. Ocular screening questions include the following:

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

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

• Do you use tear substitutes more than 3 times daily?

Procedures:

• Salivary gland biopsy

• The pathological findings are very useful in diagnosis and are often obtained while diagnosing juvenile primary Sjögren syndrome.

• Because of the relative ease and lack of complications, labial minor salivary gland biopsy is preferred over parotid gland biopsy, which can result in facial nerve damage. However, minor salivary gland biopsy requires sufficient expertise to ensure adequacy of tissue collection.

• In order to ensure that a representative sample has been obtained for histopathologic examination, harvesting 5-10 lobules of minor salivary glands is crucial.

• At least one positive response to the ocular symptoms questions (see Other Tests)

• At least one positive response to the oral symptoms questions (see Other Tests)

• Ocular signs (positive Schirmer tear test or Rose-Bengal stain findings)

• Histopathological features on minor salivary gland biopsy findings

• Salivary gland involvement revealed by at least one testing modality (salivary scintigraphy, parotid sialography, unstimulated salivary flow)

• Anti-Ro (SS-A) or anti-La (SS-B)

• Exclusion criteria - Preexisting lymphoma, HIV, hepatitis C, sarcoidosis, graft-versus-host disease (GVHD)

• Proposed criteria for pediatric patients have not been prospectively validated. Only 76% sensitivity has been noted in compilation of retrospective patients. The clinical judgment of a pediatric rheumatologist is the criterion standard. However, the proposed pediatric criteria appear more sensitive than adult AECG criteria in classifying pediatric Sjögren syndrome. Diagnosis is based on the presence of 4 or more of the following proposed pediatric diagnostic criteria:

• Clinical symptoms
  • Oral symptoms (dry mouth, parotitis, parotid gland enlargement)

  • Ocular symptoms (recurrent conjunctivitis, keratoconjunctivitis sicca)

  • Other mucosal symptoms (recurrent vaginitis, vulvovaginitis)

  • Systemic symptoms (fever of unknown origin, noninflammatory arthralgias, hypokalemic paralysis)

• Immunologic abnormalities - Presence of anti-Ro (SS-A), anti-La (SS-B), high titer ANA, or RF

• Other laboratory finding abnormalities or additional investigations
  • Elevated serum amylase levels

  • Leukopenia, high ESR

  • Polyclonal hyperimmunoglobulinemia

  • Renal tubular acidosis

  • Histological proof of lymphocytic infiltration of salivary gland or other organs

  • Objective documentation of ocular dryness (Rose Bengal stain findings, Schirmer tear test findings)

  • Objective documentation of parotid gland enlargement (sialography findings)

• Exclusion of all other autoimmune disease

	TREATMENT	Section 6 of 11
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Medical Care:

• Xerostomia - Stimulation of salivary flow with sialagogues, such as pilocarpine (shown to be effective in increasing salivary flow in placebo-controlled randomized adult trials) or cevimeline; mechanical stimulation with sugarless chewing gum or lozenges; topical tissue hydration or lubrication from drinking water or the use of artificial saliva (These measures are supportive yet may improve quality of life in adult populations.)

• Oral hygiene

• Caries control - Good oral hygiene; diet control with attention to decreasing refined sugars, simple carbohydrates, and high-acidity foods and beverages; topical fluorides and remineralizing toothpaste and solutions to enhance remineralization of the teeth (Calcium is leeched from teeth because of reduction in saliva and interaction between simple sugars and acidogenic bacteria.)

• Oropharyngeal candidiasis - Topical and systemic antifungal agents; daily cleaning of removable oral prostheses or appliances in older patients

• Gingivitis and periodontitis - Good plaque control; use of antimicrobial agents such as chlorhexidine gluconate 0.12% oral rinse

• Keratoconjunctivitis - Artificial tears and conservation of natural tear flow

• Extraglandular or systemic manifestations - Often require immunosuppressive or disease-modifying antirheumatic drugs (DMARDs)

Surgical Care: In cases of parotid enlargement in adult patients, fine-needle aspiration (FNA) or open biopsy may be required if cystic or neoplastic disease is suspected.

Consultations:

• Ophthalmologist - To diagnose keratitis and uveitis using slit-lamp examination and for supportive care for sicca syndrome and inflammatory changes

• Dentist - Maintain salivary flow, prevent caries and periodontal disease

• Rheumatologist - For diagnosis and long-term care of adult or pediatric disease; for evaluation of extraglandular, systemic, or overlapping autoimmune disease symptoms; and to guide use of immunosuppressive medications in extraglandular manifestations

• Surgeon - For salivary gland biopsy

Diet: A nutritious well-balanced diet with the appropriate servings from the basic food groups is recommended.

• Patients should drink plenty of fluids with meals to aid in the chewing, tasting, and swallowing. If tolerated, encourage the intake of dairy products, especially low-fat milk, yogurt, and cheese. Milk provides increased oral lubrication, while cheese has a beneficial anticaries effect.

• Recommend avoiding dry crunchy foods because they are too difficult to swallow and may irritate the mucosa.

• Patients should avoid spicy or acidic foods and beverages.

• Patients should avoid simple carbohydrates such as sucrose and highly processed refined foods such as pastries and cookies to decrease the risk of dental caries. If sweetener substitutes are used, monitor the intake because some products may cause abdominal distress.

• Recommend that patients eat foods at moderate temperatures. Foods can be liquefied or pureed if swallowing is a problem. If increase in calories is needed because of an eating disorder, consider liquid nutritional supplements.

• Alcoholic beverages and caffeinated drinks, such as coffee, tea, or cola, increase oral dryness. Patients should avoid mouth rinses that contain alcohol because they desiccate the mucosa.

Activity:

• Discourage smoking.

• Instruct patients to avoid windy and low-humidity environments.

• The family dwelling should be well humidified.

• Support normal school attendance and functioning in patients with juvenile Sjögren syndrome.

	MEDICATION	Section 7 of 11
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Primary Sjögren syndrome usually follows a benign course, and conservative management is indicated. Therapeutic approaches may include increasing lubrication with artificial tears, stimulation of salivary flow with sugar-free gum or lozenges, and vaginal lubricants. Saliva substitutes (eg, carboxymethylcellulose) are not usually effective. Cholinergic agonists have been shown to help increase salivary secretion and are approved by the US Food and Drug Administration (FDA) for this use. Treatment of secondary Sjögren syndrome is determined by the severity of the overlapping autoimmune disorder (might include additional agents such as cyclophosphamide and mycophenolate).

Drug Category: Cholinergic agonists -- These agents stimulate salivary secretion.

Drug Name	Pilocarpine (Salagen) -- Muscarinic M3 receptor agonist.
Adult Dose	5 mg PO qid
Pediatric Dose	Not established; titrate up from doses of 2.5 mg PO bid
Contraindications	Documented hypersensitivity; uncontrolled asthma; acute iritis; narrow-angle glaucoma
Interactions	May antagonize effects of anticholinergics (eg, atropine, ipratropium bromide); coadministration with beta-adrenergic antagonists may result in cardiac conduction disturbances
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	May cause sweating, urinary frequency, dizziness, and vasodilatation (ie, flushing); use with caution and close medical supervision in patients with significant cardiovascular disease, Parkinson disease, asthma, or COPD

Drug Name	Cevimeline (Evoxac) -- Muscarinic M3 agonist. Has 40-fold less binding affinity to M2 receptors and, thus, has a theoretical benefit of less stimulation to cardiac tissues. Longer duration of action than pilocarpine.
Adult Dose	30 mg PO tid
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity; uncontrolled asthma; acute iritis; narrow-angle glaucoma
Interactions	May have additive effects when used with other cholinergic agents; concurrent use with beta-blockers may cause potential for cardiac conduction disturbances; CYP2D6 inhibitors (eg, fluoxetine, amiodarone, quinidine, ritonavir, paroxetine) or CYP3A3/4 inhibitors (eg, itraconazole, diltiazem, ketoconazole, verapamil) may increase toxicity; anticholinergic agents (eg, phenothiazines, TCAs, atropine) may decrease effects of cevimeline
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Adverse effects include sweating, nausea, and rhinitis; use with caution with close medical supervision in patients with significant cardiovascular disease, asthma, or COPD

Drug Category: Immunosuppressive agents -- These agents are used to treat extraglandular disease (ie, interstitial pneumonitis, glomerulonephritis, polyarthritis, vasculitis, pseudolymphoma, neurologic manifestations).

Drug Name	Prednisone (Deltasone, Meticorten, Orasone, Sterapred) -- Corticosteroid with salt-retention properties used for its potent anti-inflammatory effects.
Adult Dose	Up to 60-80 mg PO qd
Pediatric Dose	1-2 mg/kg/d PO
Contraindications	Documented hypersensitivity; systemic infections
Interactions	Coadministration with estrogens may decrease prednisone clearance; concurrent use with digoxin may cause digitalis toxicity secondary to hypokalemia; phenobarbital, phenytoin, and rifampin may increase metabolism of glucocorticoids (consider increasing maintenance dose); monitor for hypokalemia with coadministration of diuretics
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Long-term corticosteroid use leads to adrenal insufficiency, which may persist for months after its discontinuation; implement steroid replacement in times of stress and, during that period, avoid exposure to chickenpox and measles; long-term use may impair growth in children; electrolyte and fluid disturbances, myopathy, osteoporosis, vertebral fractures, aseptic necrosis of femoral and humeral heads, peptic ulcer, pancreatitis, esophagitis, facial erythema, skin fragility, impaired wound healing, headache, vertigo, depression, overexcitation, menstrual irregularities, cushingoid features, decreased carbohydrate tolerance, cataracts, or glaucoma may occur

Drug Category: Nonsteroidal anti-inflammatory drugs (NSAIDs) -- The use of NSAIDs in Sjögren syndrome is similar to agents used for juvenile arthritis. These agents may be used to treat polyarthritis associated with Sjögren syndrome.

Drug Name	Naproxen (Aleve, Naprosyn, Naprelan) -- For relief of mild to moderate pain. Inhibits inflammatory reactions and pain by decreasing activity of cyclooxygenase, which is responsible for prostaglandin synthesis.
Adult Dose	250-500 mg PO bid (Naprosyn); may increase to 1.5 g/d for limited periods; available in SR formulation (Naprelan)
Pediatric Dose	<2 years: Not established >2 years: 15-20 mg/kg/d PO divided bid; not to exceed adult dose
Contraindications	Documented hypersensitivity; peptic ulcer disease; recent GI bleeding or perforation; renal insufficiency
Interactions	Coadministration with aspirin increases risk of inducing serious NSAID-related adverse effects; probenecid may increase concentrations and, possibly, toxicity of NSAIDs; may decrease effect of hydralazine, captopril, and beta-blockers; may decrease diuretic effects of furosemide and thiazides; may increase PT when taking anticoagulants (instruct patients to watch for signs of bleeding); may increase risk of methotrexate toxicity; phenytoin levels may be increased when administered concurrently
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Category D in third trimester of pregnancy; acute renal insufficiency, interstitial nephritis, hyperkalemia, hyponatremia, and renal papillary necrosis may occur; patients with preexisting renal disease or compromised renal perfusion risk acute renal failure; leukopenia is rare, is transient, and usually returns to normal during therapy; persistent leukopenia, granulocytopenia, or thrombocytopenia warrants further evaluation and may require discontinuation of drug

Drug Category: Disease-modifying antirheumatic drugs (DMARDs) -- These agents are used for polyarthritis not controlled with NSAIDs. Methotrexate (MTX) has been shown to be effective in managing polyarthritis. Other DMARDs (eg, hydroxychloroquine, sulfasalazine, D-penicillamine) may be synergistic when coadministered with methotrexate.

Drug Name	Methotrexate (Folex PFS, Rheumatrex) -- Unknown mechanism of action in treatment of inflammatory reactions (although may involve adenosine receptors); may affect immune function. Ameliorates symptoms of inflammation (eg, pain, swelling, stiffness). Adjust dose gradually to attain satisfactory response.
Adult Dose	7.5 mg/wk or 2.5 mg PO/IM bid for 3 doses qwk as per use in RA
Pediatric Dose	10-15 mg/m2/wk PO/SC as a single dose; alternatively, 3 divided doses administered 12 h apart or 2 divided doses 24 h apart
Contraindications	Documented hypersensitivity; alcoholism; hepatic insufficiency; documented immunodeficiency syndromes; preexisting blood dyscrasias (eg, bone marrow hypoplasia, leukopenia, thrombocytopenia, significant anemia); renal insufficiency
Interactions	PO aminoglycosides may decrease absorption and blood levels of concurrent PO methotrexate (MTX); charcoal lowers MTX levels; coadministration with etretinate may increase hepatotoxicity of MTX; folic acid or its derivatives contained in some vitamins may decrease response to MTX; coadministration with NSAIDs may be fatal; indomethacin and phenylbutazone can increase MTX plasma levels; may decrease phenytoin serum levels; probenecid, salicylates, procarbazine, and sulfonamides, including TMP-SMZ, may increase effects and toxicity of MTX; may increase plasma levels of thiopurines
Pregnancy	X - Contraindicated in pregnancy
Precautions	Monitor CBC counts monthly and liver and renal function q1-3mo during therapy (monitor more frequently during initial dosing, dose adjustments, or when risk of elevated MTX levels, eg, dehydration); MTX has toxic effects on hematologic, renal, GI, pulmonary, and neurologic systems; discontinue upon significant drop in blood counts; aspirin, NSAIDs, or low-dose steroids may be administered concomitantly with MTX (possibility of increased toxicity with NSAIDs, including salicylates, has not been tested); may consider folic acid supplementation to avoid deficiency

	FOLLOW-UP	Section 8 of 11
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Further Inpatient Care:

• Hospitalization, significant morbidities, and use of immunosuppressive medications are dictated by systemic extraglandular features.

• Overlapping symptoms of SLE include cerebritis, nephritis, and severe Raynaud phenomenon. Severe systemic manifestations may also develop without overt features of other autoimmune disorders.

Further Outpatient Care:

• Routine follow-up care by a rheumatologist, ophthalmologist, and dentist

Deterrence/Prevention:

• Caries prevention

• Personal dental plaque measures include twice-daily cleaning of the teeth with a toothbrush, using a fluoride-containing dentifrice, and daily use of dental floss; increase the number of professional cleanings to 3-4 times a year if carious lesions develop.

• Daily home use of topical fluorides, especially gel or toothpaste that contains 1.1% sodium fluoride or remineralizing gel with 0.05% sodium fluoride, sodium phosphate, and calcium carbonate, is recommended.

• If the patient has severe xerostomia, use custom fluoride trays or carriers to apply the topical fluorides.

• Use chlorhexidine gluconate oral rinse concurrently for 2-week periods when high numbers of Streptococcus mutans are found in the saliva (>1 X 10⁶/mL saliva).

• Limit the intake of sugary food and beverages between meals. Use sweetener alternatives, if tolerated, such as aspartame, saccharin, sorbitol, and xylitol.

• Prevention of oral mucosal lesions

• Chapped lips - Repeated use of water- or lanolin-based lip moisturizers (Avoid lip products that are medicated with menthol or phenol because they cause further drying.)

• Traumatic erosions and ulcers - Frequent hydration and the use of artificial saliva or oral moisturizing agents, especially under removable oral prostheses (see Diet)

• Oropharyngeal candidiasis - Good oral hygiene, frequent oral hydration and lubrication, and nightly removal and cleaning of dental prostheses (Intermittent use of topical or systemic antifungal agents may be necessary to prevent recurrent infection. If topical antifungal agents are used, consultation with a compounding pharmacist is recommended in order to formulate sucrose-free suspensions or lozenges.)

Complications:

• Adult patients have a small risk of developing lymphoma and other malignancies.

Prognosis:

• Patients with primary Sjögren syndrome usually have a good prognosis unless severe extraglandular manifestations appear. The prognosis of secondary Sjögren syndrome depends on the primary autoimmune disorder.

Patient Education:

• Because this is a chronic disease, participation in a local or national support group may be beneficial. The Sjögren's Syndrome Foundation is an example of an organization that helps individuals cope with this disease. Additional resources can be found at The Lupus Foundation of America and the Arthritis Foundation.

• For excellent patient education resources, visit eMedicine's Arthritis Center. Also, see eMedicine's patient education article Sjogren Syndrome.

	MISCELLANEOUS	Section 9 of 11
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Medical/Legal Pitfalls:

• Failure to diagnose and, thus, improve impairments of quality of life caused by sicca syndrome

• Failure to recognize that adult patients have a small risk of developing lymphoma and other malignancies

• Failure to review medication risks carefully with the patient and family prior to treatment with any new medication

• Failure to diagnose systemic extraglandular manifestations of Sjögren syndrome or presence of a primary autoimmune disorder (eg, SLE) that requires immunosuppressive agents

Special Concerns:

• Many of the symptoms associated with this disorder can seriously impair an individual's quality of life. In addition to sicca syndrome, concerns about facial appearance, depression, chronic fatigue, and joint pain must be addressed. Parotid enlargement and weight gain (if corticosteroids are used to manage the disease) may be problematic in an adolescent.

• Close attention must be paid to emotional and cognitive functioning of the adolescent coping with a chronic disease.

	PICTURES	Section 10 of 11
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Caption: Picture 1. Lower facial appearance of a 14-year-old adolescent girl with Sjögren syndrome. She exhibits both parotid and submandibular gland enlargement and chapped lips.
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Caption: Picture 2. Intraoral view of a 14-year-old adolescent girl with Sjögren syndrome (see Image 1). Hyposalivation results in erythema of the mucosa, gingivitis, decalcification or white spot lesions of the teeth at the cervical margin, and dental caries with extensive restorations of the posterior teeth.
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Caption: Picture 3. Erythema of the labial mucosa with enlargement of the minor salivary glands and superficial mucoceles.
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Caption: Picture 4. The dorsal surface of the tongue demonstrates generalized atrophy of the filiform papillae, mild fissuring, and median rhomboid glossitis.
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Caption: Picture 5. A 14-year-old adolescent girl with Sjögren syndrome (see Image 1) with painful unilateral swelling of the knee and hyperpigmentation of the overlying skin.
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Caption: Picture 6. The dorsal tongue demonstrates hyperplastic candidiasis with focal erosions and a brown hairy tongue. Ulcerated fissures are observed on the corners of the mouth that represent angular cheilitis.
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Caption: Picture 7. Biopsy of the minor salivary glands of the lower lip may be useful in the diagnosis of Sjögren syndrome. A 1.5- to 2-cm incision of normal-appearing mucosa allows for the harvesting of 5 or more salivary gland lobules.
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Caption: Picture 8. Low-power photomicrograph of a minor salivary gland lobule showing multiple lymphocytic foci that are replacing the acinar structures (hematoxylin-eosin, 40 X).
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Caption: Picture 9. Intermediate-power photomicrograph demonstrating a chronic inflammatory aggregate of more than 50 lymphocytes and plasma cells with a periductal pattern. The inflammatory focus is adjacent to normal appearing acini (hematoxylin-eosin, 200 X).
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Caption: Picture 10. High-power photomicrograph of the chronic inflammatory aggregate consists of lymphocytes and plasma cells around a ductal structure (hematoxylin-eosin, 400 X).
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	BIBLIOGRAPHY	Section 11 of 11
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• Anaya JM, Ogawa N, Talal N: Sjogren's syndrome in childhood. J Rheumatol 1995 Jun; 22(6): 1152-8[Medline].
• Athreya BH, Norman ME, Myers AR, South MA: Sjogren's syndrome in children. Pediatrics 1977 Jun; 59(6): 931-8[Medline].
• Bell M, Askari A, Bookman A, et al: Sjogren's syndrome: a critical review of clinical management. J Rheumatol 1999 Sep; 26(9): 2051-61[Medline].
• Cassidy JT, Petty RE, Laxer RM: Overlap syndromes. Textbook of Pediatric Rheumatology 2005; 5th edition: 486-89.
• Chudwin DS, Daniels TE, Wara DW, et al: Spectrum of Sjogren syndrome in children. J Pediatr 1981 Feb; 98(2): 213-7[Medline].
• Cimaz R, Casadei A, Rose C, et al: Primary Sjogren syndrome in the paediatric age: a multicentre survey. Eur J Paediatr 2003; 162 (10): 661-5[Medline].
• DeGuzman M, Fishman MA, Lewis RA, et al: Chronic neurologic disease with visual, gait and bladder problems in a male teenager. J Pediatr 1998; 132: 742-47[Medline].
• Deprettere AJ, Van Acker KJ, De Clerck LS, et al: Diagnosis of Sjogren's syndrome in children. Am J Dis Child 1988 Nov; 142(11): 1185-7[Medline].
• Fox PC, Brennan M, Pillemer S, et al: Sjogren's syndrome: a model for dental care in the 21st century. J Am Dent Assoc 1998 Jun; 129(6): 719-28[Medline].
• Fox RI, Michelson P: Approaches to the treatment of Sjogren's syndrome. J Rheumatol Suppl 2000 Dec; 61: 15-21[Medline].
• Fox RI, ed: Sjogren's syndrome. Rheum Dis Clin North Am 1992; 18:3: entire volume.
• Garcia-Carrasco M, Ramos-Casals M, Rosas J, et al: Primary Sjogren's Syndrome: Clinical and Immunologic Disease Patterns in a Cohort of 400 Patients. Medicine 2002; 81: 270-280[Medline].
• Houghton K, Malleson P, Cabral D, et al: Primary Sjogren's syndrome in children and adolescents: are proposed diagnostic criteria applicable? J Rheumatol 2005 Nov; 32(11): 2225-32[Medline].
• Jonsson R, Haga H-J, Gordon TP: Sjogren's syndrome. In: Koopman's Textbook of Arthritis and Allied Health Conditions. 14th ed. Philadelphia, Pa: Lippincott, Williams, & Wilkins; 2001: 1736 - 59.
• Kobayashi I, Furuta H, Tame A, et al: Complications of childhood Sjogren syndrome. Eur J Pediatr 1996 Oct; 155(10): 890-4[Medline].
• Leerdam CM, Martin HC, Isaacs D: Recurrent parotitis of childhood. J Paediatr Child Health 2005; 41 (12): 631-4[Medline].
• Mannoussakis MN, Georgopoulou C, Zintzara E, et al: Sjogren's syndrome associated with systemic lupus erythematosus: clinical and laboratory profiles and comparison with primary Sjogren's syndrome. Arthritis Rheum 2004; 50 (3): 681-3[Medline].
• McGuirt WF Jr, Whang C, Moreland W: The role of parotid biopsy in the diagnosis of pediatric Sjogren syndrome. Arch Otolaryngol Head Neck Surg 2002 Nov; 128(11): 1279-81[Medline].
• Nikitakis NG, Rivera H, Lariccia C, et al: Primary Sjogren syndrome in childhood: report of a case and review of the literature. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2003 Jul; 96(1): 42-7[Medline].
• Pessler F, Emery H, Dai L, et al: The spectrum of renal tubular acidosis in paediatric Sjogren syndrome. Rheumatology (Oxford) 2006 Jan; 45(1): 85-91[Medline].
• Ramon-Casals M, Font J: Primary Sjogren's syndrome: current and emergent aetiopathogenic concepts. Rheumatology (Oxford) 2005; 44: 1354-1367[Medline].
• Ramos-Casals M, Cervera R, Font J, et al: Young onset of primary Sjögren's syndrome: clinical and immunological characteristics. Lupus 1998; 7(3): 202-6[Medline].
• Ramos-Casals M, Tzioufas AG, Font J: Primary Sjogren's syndrome: new clinical and therapeutic concepts. Ann Rheum Dis 2005 Mar; 64(3): 347-54[Medline][Full Text].
• Reveille JD, Arnett FC: The immunogenetics of Sjogren's syndrome. Rheum Dis Clin North Am 1992 Aug; 18(3): 539-50[Medline].
• Rhodus NL: Sjogren's syndrome. Quintessence Int 1999 Oct; 30(10): 689-99[Medline].
• Siamopoulou-Mavridou A, Drosos AA, Andonopoulos AP: Sjogren syndrome in childhood: report of two cases. Eur J Pediatr 1989 Apr; 148(6): 523-4[Medline].
• Stiller M, Golder W, Döring E, Biedermann T: Primary and secondary Sjogren's syndrome in children--a comparative study. Clin Oral Investig 2000 Sep; 4(3): 176-82[Medline].
• Suzuki K, Matsumoto M, Nakashima M, et al: Effect of cevimeline on salivary components in patients with Sjogren syndrome. Pharmacology 2005 May; 74(2): 100-5[Medline].
• Tzioufas AG, Moutsopoulos HM: Sjogren syndrome. In: Klippel J, Dieppe P, eds. Rheumatology. 2nd ed. St. Louis, Mo: Mosby; 1998: 7.32.1-7.32.12.
• van der Reijden WA, Vissink A, Veerman EC, Amerongen AV: Treatment of oral dryness related complaints (xerostomia) in Sjogren's syndrome. Ann Rheum Dis 1999 Aug; 58(8): 465-74[Medline][Full Text].
• Williams FM, Cohen PR, Jumshyd J, Reveille JD: Prevalence of the diffuse infiltrative lymphocytosis syndrome among human immunodeficiency virus type 1-positive outpatients. Arthritis Rheum 1998 May; 41(5): 863-8[Medline].

Sjogren Syndrome excerpt