What is the appropriate diagnosis and treatment for bilateral lacrimal gland enlargement?

Diagnosis and Management of Bilateral Lacrimal Gland Enlargement

Bilateral lacrimal gland enlargement most commonly indicates an inflammatory or lymphoproliferative systemic condition, with IgG4-related disease, idiopathic orbital inflammatory disease, lymphoma, and sarcoidosis being the most frequent causes requiring prompt evaluation and targeted treatment.

Diagnostic Approach

Initial Evaluation

• Assess for associated symptoms:
  • Dry eye symptoms (suggests Sjögren's syndrome)
  • Dry mouth (suggests Sjögren's syndrome)
  • Systemic symptoms (fatigue, joint pain, fever)
  • Pain (concerning for malignancy, particularly adenoid cystic carcinoma)
  • Proptosis severity and progression rate

Imaging

• MRI orbits without and with contrast is the optimal imaging modality to:

  • Characterize the extent of enlargement
  • Assess for "wedge sign" (characteristic shape)
  • Evaluate angle with orbital wall
  • Detect extra-lacrimal and extra-orbital involvement 1

• CT orbits may be useful to evaluate:

  • Bony involvement (scalloping or destruction)
  • Calcifications

Laboratory Testing

• Complete blood count
• Inflammatory markers (ESR, CRP)
• Serum ACE levels (for sarcoidosis)
• Sjögren's antibodies (anti-SSA/Ro, anti-SSB/La)
• IgG4 levels (for IgG4-related disease)
• Chest imaging (for sarcoidosis, lymphoma) 1, 2

Definitive Diagnosis

• Lacrimal gland biopsy is often necessary for definitive diagnosis to differentiate between:
  • Inflammatory conditions (non-caseating granulomas in sarcoidosis)
  • Lymphoproliferative disorders
  • Epithelial tumors 3

Differential Diagnosis

Inflammatory Conditions (60% of bilateral cases) 3

• IgG4-related disease (17.4%)

  • Often responsive to corticosteroids
  • May require immunosuppressants

• Idiopathic orbital inflammatory disease (17.4%)

  • Diagnosis of exclusion
  • Usually responsive to corticosteroids

• Sarcoidosis (9.6%)

  • Non-caseating granulomas on biopsy
  • Often associated with hilar lymphadenopathy
  • May show elevated ACE levels 1, 4

Lymphoproliferative Disorders (20% of bilateral cases) 3

• Lymphoma (13.9%)

  • More common in older patients (mean age 60)
  • May be primary or secondary to systemic lymphoma
  • Requires chemotherapy, often with monoclonal antibodies

• Sjögren's syndrome

  • Autoimmune exocrinopathy affecting lacrimal and salivary glands
  • Associated with aqueous tear deficiency
  • 5% risk of developing lymphoma 2

Infectious Causes

• Viral infections
  • Epstein-Barr virus
  • HIV/AIDS
  • Hepatitis C 5

Structural/Other (20% of bilateral cases) 3

• Lacrimal gland prolapse (11.3%)
• Metastatic disease
• Infiltrative disorders

Treatment Algorithm

1. For inflammatory conditions:

   • First-line: Systemic corticosteroids (prednisone 1mg/kg/day)
   • Monitor response within 1-2 weeks
   • For steroid-resistant cases: Consider immunosuppressants (methotrexate, azathioprine)
   • For IgG4-related disease: Consider rituximab for refractory cases

2. For lymphoproliferative disorders:

   • Refer to hematology-oncology
   • Treatment typically includes chemotherapy regimens
   • For low-grade lymphomas: Consider "watch and wait" approach in selected cases

3. For sarcoidosis:

   • Systemic corticosteroids
   • Steroid-sparing agents for long-term management
   • Monitor for multi-system involvement 4

4. For infectious causes:

   • Treat underlying infection
   • May require adjunctive anti-inflammatory therapy

Prognosis and Follow-up

The majority of patients (90.4%) with bilateral lacrimal gland disease achieve complete resolution, significant improvement with mild residual disease, or stable disease without progression 3.

Follow-up Recommendations

• Regular ophthalmologic examinations
• Repeat imaging based on clinical response
• Long-term surveillance for:
  • Disease recurrence
  • Progression
  • Development of lymphoma in patients with Sjögren's syndrome

Clinical Pearls and Pitfalls

• Pearl: Bilateral involvement strongly suggests systemic disease, particularly inflammatory conditions like IgG4-RD and sarcoidosis 2

• Pitfall: Relying solely on clinical features without biopsy can lead to misdiagnosis, as multiple conditions can present similarly 3

• Pearl: Pain is an important symptom that may indicate malignancy and warrants urgent evaluation 2

• Pitfall: Corticosteroid treatment before biopsy may mask histopathologic findings, complicating diagnosis 5

• Pearl: Age is an important factor, with lymphoma being more common in older patients (mean age 60 years) 2