Sjogren's syndrome (SS)
SX | DX |
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
Sicca Syndrome - dry mouth & dry eyes.
2 -5% of people aged 60 and above have primary SS.
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.
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.
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
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
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
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
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.
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
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.
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.
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
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)
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.
The treatment of dry eyes & mouth is largely symptomatic and includes
artificial tears and lubricant ointments. Lubricant ointments should be instilled
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
(Cevimeline HCl) 30 mg cap tid
for dry mouth.
Cevimeline for the Treatment of Xerostomia in Patients With Sjögren
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.
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.
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.
Bennett: Cecil Textbook of Medicine, 20th ed., 1996
Frederick Vivino - The Female Patient August 1999, 24:65