TOC |  Rheum   

Sjogren's syndrome (SS)                  
SX |  DX | RX     
is a chronic immunemediated inflammatory disorder characterized by lymphocytic infiltration of the lacrimal and salivary glands associated with the clinical features of keratoconjunctivitis sicca (xerophthalmia -dryness of eyes) and xerostomia (dryness of mouth).
SS exists in both a primary and secondary form (associated with other collagen disease).

Sicca Syndrome - dry mouth & dry eyes.

Prevalence:
2 -5% of people aged 60 and above have primary SS.

SX:

Ophthalmologic

• Dry eye symptoms (keratoconjunctivitis sicca), including burning, itching, or a foreign body (gritty, sandy) sensation; this is worse at the end of the day rather than on awakening. Patients also may notice blurred vision, redness of the eye, ocular discomfort, photophobia, and a mucinous discharge.

Salivary

• Dry mouth symptoms (xerostomia), may range in severity; many patients describe difficulty in chewing and swallowing, oral soreness, changes in tasting or smelling, fissures of the tongue and lips (angular cheilitis), and an increase in dental caries. Bilateral parotid and submandibular gland enlargement may be present.

Other

• Dry mucous membranes, including the nose, pharynx, tracheobronchial tree, and larynx; skin; and vulva and vagina. Involvement of pancreatic exocrine glands may lead to a decrease in pancreatic secretions and intestinal malabsorption; acute pancreatitis is rare. Dysphagia and noncardiac chest pain from gastroesophageal reflux are presumably due to decreased salivary production and, possibly, altered esophageal motility.

• Joint involvement, particularly arthralgias and nondeforming arthritis, is common.  Symmetric inflammatory polyarthritis with deformity and radiographic erosions implies the existence of rheumatoid arthritis with concomitant secondary SS rather than primary SS.

Extraglandular manifestations of SS are more common in patients with primary than secondary SS, especially those with antibodies to Ro(SS-A) and La(SS-B);

• Skin features include non-thrombocytopenic palpable purpura of the lower extremities, sometimes with leukocytoclastic vasculitis on biopsy, and photosensitive lesions indistinguishable from those of subacute cutaneous lupus erythematosus.
• Raynaud's phenomenon affects about one fifth of patients, & Small vessel vasculitis, with either a mononuclear perivascular infiltrate or leukocytoclastic changes on biopsy.
• Pulmonary features include Chronic bronchitis secondary to dryness of the tracheobronchial tree, lymphocytic pneumonitis, interstitial pulmonary fibrosis, and pseudolymphoma nodules; pleurisy and pulmonary vasculitis are rare.
• Renal involvement, due to lymphocytes infiltrating the cortex, is manifest as Tubulointerstitial nephritis, type 1 renal tubular acidosis; the finding of glomerulonephritis should raise the question of coexistent SLE or cryoglobulinemia.
• Central nervous system involvement has been recognized only over the past decade, and its true frequency varies according to definition and referral patterns. Reported features include focal and diffuse defects, including multiple sclerosis, stroke, progressive dementia, and cognitive dysfunction, and spinal cord involvement similar to transverse myelitis. Also Peripheral sensorimotor neuropathy
• Musculoskeletal:  Polymyositis, Polyarthralgias, polyarthritis
• Reticuloendothelial system:  Splenomegaly,  Lymphadenopathy and development of pseudolymphoma
• Liver involvement: Hepatomegaly, Primary biliary cirrhosis, recently, hepatitis C infection.
• Endocrine involvement: Hypothyroidism due to Hashimoto's thyroiditis, Other autoimmune endocrinopathies.

DIAGNOSIS

Ophthalmologic (Xerophthalmia)

• Keratoconjunctivitis sicca is demonstrated by decreased tear production
  Sx > 3 months plus any of the following
  Abnormal finding on Rose Bengal or fluorescein corneal staining on slit-lamp exam.
  Fluorescein tear breakup time < 10 sec
  Schirmer's test finding < 10 mm/5 min wetting
  The main differential diagnosis for the ocular findings is blepharitis; other conditions include reduced tear production after using antihistamines, diuretics, and antidepressant medications.

Oral (Xerostomia)

• Sx > 3 months plus any of the following
  Abnormal salivary gland scan findings
  Loss of glistening of the tongue or mucous membranes
  Markedly decreased sublingual pool
  Whole-mouth unstimulated salivary flow rate < 0.3 mL/min
  The major diagnostic tool is the labial salivary gland biopsy; the characteristic finding is focal lymphocytic infiltration. This is measured semiquantitatively by the number of foci, defined as 50 or more round cells, and a score of greater than one focus per 4 sq mm of tissue is diagnostic of SS.
  The biopsy is also useful in excluding other conditions that can cause xerostomia and bilateral glandular enlargement, including sarcoidosis, amyloidosis, hemochromatosis, and DILS.

Laboratory

• Abnormalities in the complete blood count are common and include normochromic, normocytic anemia, leukopenia, and an elevated erythrocyte sedimentation rate; these are all nonspecific.
  Rheumatoid factor is present in 60-90% of patients, especially with secondary SS.
  ANA (> 1:160) are present in over three quarters of patients, and antibodies to Ro(SS-A) in 40-60% and La(SS-B)  in 20-40% of patients with primary SS, respectively.
  Other immunologic abnormalities include a polyclonal hyperglobulinemia and positive tests for  cryoglobulins; these cryoglobulins may contain monoclonal IgMK proteins.

Differential Diagnosis of Sicca Syndrome (dry mouth & eyes)

• Sjogren's syndrome
• Medication-related dryness,
• Mouth breathing
• Others: Amyloidosis, chronic sialadenitis, diabetes mellitus, eosinophilia-myalgia syndrome, graft-versus-host disease, , multiple sclerosis, radiation injury, sarcoidosis, salivary diffuse infiltrative lymphocytosis syndrome (HIV-related), silicone breast implant disease, type 5 hyperlipidemia.

TREATMENT

The treatment of dry eyes  & mouth is largely symptomatic and includes

• artificial tears and lubricant ointments. Lubricant ointments should be instilled at bedtime.
• saliva substitutes, stimulating salivary flow from functioning acinar tissue with Salagen tab (pilocarpine hydrochloride ) 5 mg three times daily,
  the most common side effects are increased sweating and gastrointestinal intolerance.
• Evoxac (Cevimeline HCl) 30 mg cap tid for dry mouth.  
  Cevimeline for the Treatment of Xerostomia in Patients With Sjögren Syndrome
  Therapy with cevimeline, 30 mg 3 times daily, seems to be well tolerated and to provide substantive relief of xerostomia symptoms. Although both dosages of cevimeline provided symptomatic improvement, 60 mg 3 times daily was associated with an increase in the occurrence of adverse events, particularly gastrointestinal tract disorders.     Arch Intern Med. June 10, 2002;162:1293-1300
• treating oral candidiasis with nystatin or clotrimazole vaginal troches three times daily, and
• aggressively managing dental caries through both prevention and treatment.

Patients with extraglandular manifestations such as rashes and arthralgias are usually treated with systemic corticosteroids or hydroxychloroquine (5-7 mg/kg per day) may prove helpful.

Patients with secondary SS should receive appropriate therapy for their associated connective tissue disease. Patients with lymphoma should be treated in consultation with an oncologist.

More refractory symptoms of arthritis may respond to low-dose weekly methotrexate (7.5-15 mg/week) in the presence of folic acid supplementation. Leflunomide, another disease-modifying antirheumatic drug, was recently approved for use in rheumatoid arthritis. This drug may have use in Sjögren syndrome as it was very effective in animal models of autoimmune disease including Sjögren syndrome.Also, inhibitors of TNF may prove useful in modulating the immune response.

In patients with life-threatening vasculitis, high-dose corticosteroids and parenteral cyclophosphamide may be required.

PROGNOSIS

The ophthalmologic and oral manifestations of SS are generally nonprogressive. Patients with primary SS are at increased risk of developing lymphoproliferative disorders, including non-Hodgkin's lymphoma; in one study, the relative risk was estimated to be greater than 40. Patients with splenomegaly, bilateral parotid enlargement, and a history of radiation treatment to shrink these enlarged glands were at especially high risk. The lymphomas are B cell-derived.

Young women with primary SS, especially those with antibodies to Ro(SS-A), should be counseled about the increased risk of delivering a child with neonatal SLE and congenital complete heart block; such women when pregnant should be followed closely by an obstetrician expert in high-risk pregnancies.

Ref:
Bennett: Cecil Textbook of Medicine, 20th ed., 1996
Frederick Vivino - The Female Patient August 1999, 24:65

10272000

Ref:

• Patient Info (ARA)
• Sjogren Syndrome 4/ 2000 - Medscape