Sjogren’s Syndrome

Epidemiology

  • Incidence of Primary Sjogren’s Syndrome: 0.5-3%
  • Genetics
    • Familial clustering has been reported
    • Associated with HLA-Dw2 and HLA-Dw3

Etiologic Classification

  • Primary Sjogren’s Syndrome (34-50% of cases, not associated with connective tissue disease): occurs predominantly in post-menopausal females >40 y/o
  • Secondary Sjogren’s Syndrome (50-66% of cases, associated with connective tissue disease):
    • Rheumatoid Artritis (see [[Rheumatoid Arthritis]]): 15-20% of RA cases have associated Sjogren’s syndrome
    • SLE (see [[SLE]])
    • Polyarteritis Nodosa (see [[Polyarteritis Nodosa]])
    • Scleroderma (see [[Scleroderma]])
    • Mixed Connective Tissue Disease (see [[Mixed Connective Tissue Disease]])
    • Polydermatomyositis (see [[Polydermatomyositis]])

Physiology

  • Sjogren’s-Associated Vasculitis: hypersensitivity vasculitis (mostly involving the post-capillary venules within superficial dermis) with leukocytoclasis
    • Probably due to immune complex deposition
  • Autoimmune Exocrinopathy: lymphocytic infiltration of glandular (lacrimal, salivary, conjunctival, pharyngeal mucosal) and extraglandular organs

Diagnosis

  • Rheumatoid factor (RF): positive in 75-90% of cases
  • ANA: positive in 50-80% of cases
    • Anti-SS-A (Ro)(directed against RNA transcription factors): positive in 40-50% of primary cases
    • Anti-SS-B (La)(directed against RNA transcription factors): positive in 50% of cases
  • Lip Bopsy: diagnostic
  • Salivary Flow: reduced

Clinical Manifestations

Pulmonary Manifestations

(occur in 25% of cases -> however, it is often difficult to exclude the underlying connective tissue disease as the cause of lung findings in secondary Sjogren’s cases)

Interstitial Lung Disease (see [[ILD-Etiology]])

  • Epidemiology
    • Occurs in 10% of primary Sjogren’s cases
    • Occurs more often in patients with extraglandular manifestations than in those with glandular disease alone
  • Diagnosis
    • CXR/Chest CT Patterns
      • Fine Reticular or Reticulonodular Infiltrates: most common pattern
      • Normal CXR: in some cases
      • Pleural Effusion: may occur
      • Nodular Infiltrates: pattern seen in cases with pseudolymphoma (aka Nodular Lymphoid Hyperplasia), lymphoma, or amyloidosis
    • PFT’s: restriction (although minor degrees of obstruction also occur in a large proportion of cases)
      • DLCO: decreased
    • FOB-BAL: alveolitis with increased number of cells (predominantly lymphocytes)
      • Primary Sjogren’s: 50% of patients without clinical lung disease have abnormal BAL cell counts (2 subsets of patients were identified: 69% had a lymphocyte-predominant pattern with >18% lymphocytes and 25% had a mixed neutrophil and lymphocyte pattern with >4% neutrophils)
      • Patients with abnormal BAL cell counts had more severe Sjogren’s with extensive extraglandular disease (myositis, lymphadenopathy, renal , hepatic disease), higher serum IgG, higher serum ß2-microglobulin, higher prevalence of RF and ANA
      • Secondary Sjogren’s (associated with either biliary cirrhosis or con-nective tissue disease): non-smokers without clinical lung disease have increased BAL lymphocytes (patients with a neutrophilic alveolitis had a marked increase in T8 cells in BAL)
      • Primary cases also have activated alveolar macrophages (increased release of superoxide anion, etc.)
    • OLB Patterns
      • Nonspecific Interstitial Pneumonitis: most common pattern
  • Clinical
    • Some cases are asymptomatic but most present with cough, dyspnea, and bibasilar crackles
    • Extensive or progressive pulmonary fibrosis is rare (although around 7/30 cases in one 10-year study had significant decreases in DLCO)

Lymphocytic Interstitial Infiltration of Lung

  • Epidemiology: all of these reside on a spectrum of lymphoproliferative disorders of the lung
  • Pseudolymphoma (aka Nodular Lymphoid Hyperplasia)
    • Frequently reported
    • Diffuse or focal nodular lymphocytic infiltration with formation of lymphoid follicles
    • Some cases have lymphadenopathy or salivary gland enlargement
    • Tends to occur in cases with Sicca syndrome alone (and regresses with Corticosteroids + Cytoxan)
    • May rarely evolve into frank lymphoma
  • Lymphocytic Interstitial Pneumonia (see [[Lymphocytic Interstitial Pneumonia]])
    • Most common form of diffuse lung disease in Sjogren’s syndrome
    • Diffuse lymphocytic infiltration (with or without histiocytes and multinucleated giant cells), predominantly around bronchioles
  • Primary Pulmonary Lymphoma (see [[Primary Pulmonary Lymphoma]])
    • aka Mucosa-Associated Lymphoid Tissue (MALT)-Associated Lymphoma
    • The prevalence of lymphoma is increased 40-50-fold in Sjogren’s
    • Variable clinical presentation: ranges from diffuse interstitial infiltrates to nodular masses (often peri-hilar in location)
      • Nodular pattern is the most common type
    • May regress spontaneously and responds to steroids

Cryptogenic Organizing Pneumonia (see [[Cryptogenic Organizing Pneumonia]])

  • Occurs less commonly in Sjogren’s syndrome than in RA or polydermatomyositis
  • Usually responds to corticosteroids

Dessication of Tracheobronchial Tree

  • Dried nasal passages (50% of cases/altered smell, epistaxis, septal perforation)
  • Atrophic rhinitis
  • Xerostomia (altered taste/Eustachian tube obstruction with otitis media)
  • Xerotrachea (25% of cases: chronic dry cough with bronchoscopic evidence of inflammed bronchial mucosa
  • Chronic bronchitis (cough with tenacious sputum)
  • Atelectasis
  • Middle lobe syndrome
  • Recurrent bronchopneumonia (due to secretions)

Amyloidosis (see [[Amyloidosis]])

  • May produce nodular infiltrates

Pulmonary Vasculitis

  • Epidemiology: rare
  • Vasculitis is usually confined to skin (palpable purpura predominantly of LE, nodules, ulcers) but may progress to polyarteritis nodosa-like syndrome

Pulmonary Hypertension (see Pulmonary Hypertension, [[Pulmonary Hypertension]])

  • Epidemiology: uncommon

Pleural Disease (see [[Pleural Effusion-Exudate]])

  • Epidemiology
    • Reported in cases with associated connective tissue disease and associated with atelectasis or recurrent pneumonia
  • Clinical
    • Pleurisy
    • Pleural Thickening
    • Pleural Effusion: exudative

Obstructive Airways Disease (see [[Obstructive Lung Disease]])

  • Physiology: due to mononuclear cell infiltration around small airways
  • 40-60% of primary/secondary Sjogren’s cases have bronchial hyperresponsiveness
  • PFT’s: high prevalence of small airways dysfunction
  • May increase risk of bronchopeumonia
  • Progression to severe BO is rare (unless due to associated RA)

Follicular Bronchiolitis (see [[Follicular Bronchiolitis]])

  • Epidemiology
    • May be more common in secondary Sjogren’s syndrome
  • Diagnosis
    • PFT’s: obstruction
    • FOB: BAL lymphocytosis
    • Chest CT:
      • Centrilobular Nodules with Peripheral Tree-In-Bud Pattern: characteristic of bronchiolar disease
      • Ground-Glass Opacities:
      • Mediastinal Adenopathy: also seen in LIP and Nodular Lymphoid Hyperplasia

Rheum Manifestations

  • xxx

Ocular Manifestations

  • Keratoconjunctivitis Sicca Syndrome: triad of dry eyes (with or without lacrimal gland enlargement), xerostomia (with or without salivary gland enlargement), and presence of connective tissue disease (usually RA) may also occur
    • Typically seen in females >40 y/o
  • Positive Shirmer Test:
  • Rose Bengal Score >3:

GI Manifestations

  • xxx

Neuro Manifestations

  • xxx

Prognosis

  • BAL lymphocytosis predicts a relatively good prognosis
  • Secondary Sjogren’s cases (with an associated connective tissue disease) with neutrophilic alveolitis by BAL have poorer outcome with clinical deterioration if untreated

Treatment

  • Steroids/Cyclophosphamide: patients with ILD with LIP and BOOP histologies tend to respond better to these therapies
    • Pseudolymphoma responds to these agents

References

  • Launay D, Hachulla E, Hatron PY, Jaïs X, Simonneau G, Humbert M. Pulmonary arterial hypertension: a rare complication of primary Sjögren syndrome: report of 9 new cases and review of the literature. Medicine (Baltimore) 2007;86:299 –315