Sjögren syndrome

EPIDEMIOLOGY

• It affects primarily females during the fourth and fifth decades of life, with a female-to-male ratio of 9 : 1.

• Sjögren’s syndrome is very common, with a community prevalence of pSS ranging from 0.1% to 0.6% of all individuals.

Major Clinical Manifestations of Sjögren Syndrome

Non-Sicca Manifestations Suggestive of Sjögren Sydrome

CLINICAL FEATURES

Exocrinopathy (glandular involvement) Ocular involvement• The patient usually complains of a burning,

sandy, or scratchy sensation under the lids, itchiness, redness, and photosensitivity.

• Physical signs include dilation of the bulbar conjunctival vessels, pericorneal injection, irregularity of the corneal image, and lacrimal gland enlargement.

Oropharyngeal involvement

• Xerostomia, or dry mouth, results from markedly decreased production of saliva by the salivary glands.

• Other oral symptoms may include soreness, adherence of food to the mucosa, and dysphagia.

• Disappearance of the usual pooling of saliva in the floor of the mouth.

• Surface of the tongue becomes red and lobulated, with partial or complete depapillation.

• In advanced disease, the oral mucosa appears dry and glazed and tends to form fine wrinkles.

Cracked, peeling and atrophic appearance of the lips. Dry and fissured tongue

Dry and smooth tongue. Hyposalivation-related dental caries.

CAUSES OF XEROSTOMIA

1. Psychogenic2. Dehydration3. Diabetes mellitus4. Trauma5. Drugs Psychotherapeutic Parasympatholytic Antihypertensive6. Irradiation7. Congenital (absent or malformed glands)8. Viral infection

• Chronic or episodic swelling of the major salivary glands (parotid and submandibular glands).

• Dryness of the nose, throat, and trachea results in persistent hoarseness and chronic, nonproductive cough.

• Involvement of the exocrine glands of the skin leads to cutaneous dryness.

• Dryness of the vagina and vulva results in dyspareunia and pruritus.

primary Sjögren syndrome with enlarged parotidglands.

DIFFERENTIAL DIAGNOSIS OF PAROTIDGLAND ENLARGEMENT

Bilateral 1. Viral infection (mumps, influenza,

Epstein-Barr, coxsackievirus A, cytomegalovirus,HIV)

2. Sjögren syndrome3. Sarcoidosis4. Miscellaneous (diabetes mellitus,

hyperlipoproteinemia, hepatic cirrhosis,

5. chronic pancreatitis, acromegaly, gonadal hypofunction)

6. Recurrent parotitis of childhood

Unilateral1. Salivary gland neoplasm2. Bacterial infection3. Chronic sialadenitis4. Sialolithiasis

Extraglandular Manifestations

• Primarily generalized arthralgias, is seen in 25–75% of patients.

• Intermittent symmetric arthritis primarily affecting small joints can occur.

• Deformity and mild erosions are rare, except for those cases associated with rheumatoid arthritis.

Small-vessel vasculitis. • The vasculitis may be characterized by either a

lymphocytic vasculitis or leukocytoclastic vasculitis.

• The skin findings include palpable purpura, urticaria, and erythematous macules or papules.

Purpura as an extraglandular manifestation.

Palpable purpura on the lower extremities of a patient with primary

Sjögren syndrome

Nonvasculitic cutaneous lesions• polycyclic, photosensitive cutaneous lesions,

clinically identical to the so-called annular erythema described in Asian SS patients and subacute cutaneous lupus.

Polycyclic, photosensitive cutaneous lesions in a 67-year-old woman with primary SS and anti-Ro/SS-A antibodies.

Lungs• Bronchial/bronchiolar involvement and

interstitial disease can occur.• Anti-Ro antibody positivity is believed to be a

risk factor for pulmonary disease in SS. • Most patients do not develop progressive

pulmonary disease after 10-year follow-up.

Cardiovascular Features• Raynaud phenomenon, with a prevalence of

13%, is probably the most common vascular feature observed in primary SS.

• Vascular complications (eg, digital loss, digital pulp pitting, or fingertip infarctions) are uncommon.

Gut• Gastrointestinal involvement includes altered

esophageal motility, chronic gastritis, and less frequently, malabsorption.

• Liver function tests may be elevated in 10–20% of patients with primary SS.

Nephro-Urologic Involvement• Mild proteinuria in 28%.• Reduced creatinine clearance in 16%.• Distal renal tubular acidosis in 13%.• Interstitial renal disease, characterized by

hyposthenuria and type I (distal) tubular acidosis, and glomerulonephritis.

• Distal tubular acidosis may be clinically silent, but if left untreated, significant renal tubular acidosis may lead to renal stones, nephrocalcinosis, and compromised renal function.

• Patients may present with recurrent renal colic and/or hypokalemic muscular weakness.

• Less commonly, proximal tubular acidosis with Fanconi’s syndrome may occur.

Radiograph of a patient with primary Sjögren syndrome shows

nephrocalcinosis

Neurologic Involvement• Peripheral neuropathy is the most common

neurologic involvement• Pure sensory neuropathy is recognized as a

characteristic neurologic complication of primary SS.

• SS patients may present cranial nerve involvement, mainly of the trigeminal (V), vestibulocochlear (VIII), and facial (VII) cranial pairs.

ASSOCIATION OF SJÖGREN SYNDROME WITHOTHER AUTOIMMUNE RHEUMATIC DISEASES (SECONDARY

SJÖGREN SYNDROME)

1. Rheumatoid arthritis2. Systemic lupus erythematosus3. Scleroderma4. Mixed connective tissue disease5. Primary biliary cirrhosis6. Myositis7. Vasculitis8. Thyroiditis9. Chronic active hepatitis10. Mixed cryoglobulinemia

The Laboratory Evaluation in Sjögren Syndrome

Salivary Gland Biopsy

• Minor salivary gland biopsy is a highly specific test for the diagnosis of SS.

• Focal lymphocytic sialadenitis, defined as multiple, dense aggregates of 50 or more lymphocytes in perivascular or periductal areas in the majority of sampled glands, is the characteristic histopathologic feature of SS

(a) Periductal infiltrates in minor salivary glands (×200).(b) Peritubular infiltrates in a patient with interstitial nephritis (×300).

(c) Peribronchial infiltrates in a patient with small airways disease (×200).(d) Pericholangeal infiltrates in a patient with liver involvement (×200).

Labial salivary gland biopsy specimen from a patient with primary Sjögren syndrome. Focal lymphocytic infiltrates are seen

• Measurement of the salivary flow rate, sialochemistry, sialography, or scintigraphy are done to assess oral involvement.

• Measurement of the salivary flow, with or without stimulation, is the simplest method in evaluating xerostomia, and is acceptable to patients and needs no special equipment.

Sialography showing dilated and distorted ducts (sialectasis). Staging of sialectasia: punctate (< 1 mm) (A), globular (uniform, 1–2 mm) (B), cavitary

(coalescent, > 2 mm) (C), destructive (no structure visible) (D).

Ocular tests

• The main ocular tests are the Schirmer test and rose bengal staining.

• The Schirmer test for the eye quantitatively measures tear formation via placement of filter paper in the lower conjunctival sac.

• The test can be performed with or without the instillation of anesthetic drops to prevent reflex tearing.

• The test result is positive when less than 5 mm of paper is wetted after 5 minutes

Schirmer test in a patient with Sjögren syndrome. Wetting of lessthan 5 mm/5 min of the filter paper strip is shown.

Tear secretion in the left eye and a normal function in the right eye

• Rose bengal scoring involves the placement of 2.5 mL of rose bengal solution in the inferior fornix of each eye and having the patient blink twice.

• Slitlamp examination detects destroyed conjunctival epithelium due to desiccation.

Rose bengal staining (a) in a normal volunteer

In a patient with Sjögren syndrome. Retention of the stain in the cornea is apparent.

The main immunologic markers found in primary SS are

1. Antinuclear antibodies2. Anti-Ro/SS-A3. Anti-La/SS-B antibodies 4. Rheumatoid factor 5. Hypocomplementemia6. Cryoglobulins.

• Antinuclear antibodies are the most frequently detected antibodies in primary SS (in more than 80% of cases), and titers 1:80 play a central role in differentiating SS from non-autoimmune causes of sicca syndrome.

• Anti-Ro/SS-A and La/SS-B antibodies, detected in 30–60% of patients, are closely associated with most extraglandular features, especially with cutaneous lesions, neurologic features, congenital heart block, and cytopenias.

Treatment

• The therapeutic approach is based on symptomatic replacement or stimulation of glandular secretions.

• Extraglandular involvement requires organ-specific therapy, sometimes with glucocorticoids and immunosuppressive agents, as appropriate to the level of severity.

• With regard to biological agents, recent studies have demonstrated the lack of efficacy of tumor necrosis factor inhibitors in primary SS.

• The specific target of rituximab (B cells) suggests that this agent may play a role in modifying the etiopathogenic events of patients with primary SS, a disease characterized by B-cell hyperactivity.