Dermatology MCQ - Inflammatory Dermatoses - Sjögren syndrome

A 55-year-old woman presents with a 2-year history of severe dry eyes and dry mouth. She also reports profound fatigue and diffuse arthralgias. Serologic testing reveals a positive ANA (1:1280, speckled pattern) and positive anti-Ro/SSA antibodies. Which of the following is the most specific objective test to confirm a diagnosis of primary Sjögren syndrome?

A. Schirmer's test showing reduced tear production
B. A positive anti-La/SSB antibody test
C. A labial minor salivary gland biopsy demonstrating focal lymphocytic sialadenitis
D. The presence of subjective xerostomia reported by the patient
E. An unstimulated whole salivary flow rate of <0.1 mL/min

Correct Answer: C. A labial minor salivary gland biopsy demonstrating focal lymphocytic sialadenitis

Explanation

The diagnosis of Sjögren syndrome relies on objective confirmation of autoimmune exocrinopathy. While symptoms and serology are important, the most specific diagnostic feature is the histopathologic finding on salivary gland biopsy.

• Histopathologic Gold Standard: A labial minor salivary gland biopsy is considered the most specific test. The characteristic finding is focal lymphocytic sialadenitis, defined by the presence of dense aggregates of at least 50 lymphocytes (a "focus") per 4 mm² of glandular tissue. A focus score of ≥1 is a key objective criterion in both the ACR/EULAR 2016 classification criteria. This finding directly demonstrates the autoimmune attack on the exocrine glands.

Why other options are incorrect

• A. Schirmer's test showing reduced tear production: This is an important objective test for keratoconjunctivitis sicca (dry eyes) and is part of the diagnostic criteria. However, reduced tear production can occur from many other causes (aging, medications, other diseases), making it less specific than the biopsy.

• B. A positive anti-La/SSB antibody test: Anti-La/SSB is highly specific for Sjögren syndrome, but its sensitivity is lower than anti-Ro/SSA. It is a strong serologic marker but is not an objective test of glandular dysfunction. The biopsy remains the tissue-confirmation standard.

• D. The presence of subjective xerostomia reported by the patient: Subjective symptoms are necessary to raise clinical suspicion but are not sufficient for diagnosis, as they are non-specific and common.

• E. An unstimulated whole salivary flow rate of <0.1 mL/min: This is an objective test for xerostomia and is part of the diagnostic criteria. Like Schirmer's test, it confirms glandular hypofunction but does not specify the cause, whereas the biopsy confirms an autoimmune etiology.

Key Associations for Sjögren Syndrome

• Pathogenesis: An autoimmune disorder targeting the lacrimal and salivary glands, leading to lymphocytic infiltration and destruction. It can be primary or secondary (associated with another CTD like RA or SLE).

• Clinical Presentation: The classic triad is dry eyes (keratoconjunctivitis sicca), dry mouth (xerostomia), and parotid gland enlargement. Systemic ("extraglandular") manifestations are common and include fatigue, arthralgias/arthritis, Raynaud's phenomenon, interstitial lung disease, peripheral neuropathy, and renal tubular acidosis.

• Serology: Key antibodies are Anti-Ro/SSA (sensitive) and Anti-La/SSB (specific). A positive ANA with a speckled pattern is common. Rheumatoid Factor is often positive.

• Critical Association: There is a significantly increased risk of B-cell lymphoma, most often mucosa-associated lymphoid tissue (MALT) lymphoma, which can arise in the salivary glands or other sites. Persistent parotid enlargement, purpura, lymphadenopathy, and cryoglobulinemia are red flags for lymphoma development.

• Differential Diagnosis: Includes medication side effects (anticholinergics), other autoimmune diseases (SARCOIDOSIS, IgG4-Related Disease), viral infections (HIV, HCV), and age-related dryness.

• Management: Focuses on symptomatic relief and managing systemic complications.

  • Glandular: Artificial tears, saliva substitutes, pilocarpine/cevimeline.

  • Systemic: Hydroxychloroquine for fatigue and arthralgias. Systemic corticosteroids and immunosuppressants (e.g., methotrexate, azathioprine, mycophenolate) are used for severe extraglandular disease. Rituximab is used for refractory cases.