A 56-year-old woman is evaluated during a follow-up visit for a 6-year history of Sjögren syndrome treated with low-dose hydroxychloroquine and cyclosporine eyedrops. She has had two episodes of cutaneous vasculitis, which resolved with corticosteroids.

On physical examination, temperature is 36.4 °C (97.6 °F), blood pressure is 116/64 mm Hg, pulse rate is 72/min, and respiration rate is 18/min. Oral mucous membranes are dry. There is a new firm, left parotid gland enlargement without tenderness or warmth, reported by the patient to be progressive over several months, with asymmetry of the parotid glands.

Laboratory studies at the time of diagnosis revealed elevated serum immunoglobulin levels; positive mixed monoclonal cryoglobulin levels; and positive rheumatoid factor, antinuclear antibodies, and anti-Ro/SSA antibodies.

Current laboratory studies:

Complete blood count	Normal
Alkaline phosphatase	Normal
Calcium	Normal
Rheumatoid factor	Negative
C3	Normal
C4	Decreased
Antinuclear antibodies	Positive
Anti-Ro/SSA antibodies	Positive

Which of the following is the most appropriate management?

A: Add pilocarpine
B: Add prednisone
C: Bone marrow biopsy
D: Increase hydroxychloroquine
E: Parotid gland biopsy

MKSAP Answer and Critique

The correct answer is E: Parotid gland biopsy. This item is available to MKSAP 16 subscribers as item 74 in the Rheumatology section.

Parotid gland biopsy is indicated for this patient who has Sjögren syndrome and progressive parotid swelling suggesting possible non-Hodgkin lymphoma. Patients with Sjögren syndrome have up to a 44-fold increased incidence of lymphoma, which may be confined to glandular tissue. Risk factors for the development of lymphoma include disappearance of rheumatoid factor, the presence of mixed monoclonal cryoglobulinemia, cutaneous vasculitis, and low C4 levels, all of which are seen in this patient. Although benign parotid gland swelling can occur and be unilateral or bilateral in patients with Sjögren syndrome, this patient’s high-risk profile and new asymmetric parotid enlargement should prompt a biopsy to evaluate for extranodal lymphoma in the parotid gland. Extranodal marginal zone B-cell lymphomas of the mucosa-associated lymphoid tissue (MALT) are the most common lymphomas in patients with Sjögren syndrome, and salivary glands are the most common location; other extranodal sites include the stomach, nasopharynx, skin, liver, and lungs. The risk of nodal lymphoma is also increased in Sjögren syndrome. Although benign lymphadenopathy is a common disease manifestation, the presence of new or rapidly enlarging lymph nodes may indicate development of nodal lymphoma and should prompt biopsy.

Pilocarpine is effective for reducing dry mouth symptoms but is not used to treat parotid enlargement.

Prednisone is generally used to treat inflammatory symptoms of Sjögren syndrome, including arthritis, vasculitis, and cytopenias, but does not reduce parotid swelling or treat symptoms of keratoconjunctivitis sicca and xerostomia (dry eyes and dry mouth).

Patients with Sjögren syndrome often have elevated immunoglobulin levels with monoclonal gammopathy; stability of this during the patient’s disease course, as well as normal hemoglobin, calcium, and alkaline phosphatase levels, suggests that bone marrow biopsy to evaluate for myeloma is not warranted. Extranodal lymphoma in Sjögren syndrome involves the bone marrow in less than 10% of patients.

Hydroxychloroquine is used to treat arthritis associated with Sjögren syndrome; however, it is unclear if this agent has efficacy in reducing sicca symptoms or parotid swelling.

Key Point

• Patients with Sjögren syndrome have up to a 44-fold increased incidence of lymphoma, which may be confined to glandular tissue.

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