Diagnosis is Sjögren disease associated with rheumatoid arthritis, traditionally termed secondary Sjögren syndrome.
1. Definition
Sjögren disease is a chronic systemic autoimmune disease characterized by immune-mediated dysfunction and inflammation of the lacrimal and salivary glands, resulting in dry eyes and dry mouth, with possible systemic manifestations.
2. Nomenclature
1. Sjögren disease is the preferred clinical term
2. When Sjögren disease coexists with another systemic autoimmune disease meeting its own classification criteria, the term associated Sjögren disease is preferred over secondary Sjögren syndrome
3. The distinction between standalone and associated Sjögren disease is mainly useful for describing research populations and clinical context
4. In this patient, Sjögren disease occurs in association with established rheumatoid arthritis
3. Pathophysiology
1. Autoimmune activation leads to lymphocytic infiltration and dysfunction of exocrine glands
2. The characteristic salivary gland lesion is focal lymphocytic sialadenitis
3. Lacrimal and salivary gland dysfunction causes reduced tear and saliva production
4. B-cell hyperactivity contributes to production of autoantibodies, particularly anti-SSA (Ro) and anti-SSB (La)
5. Chronic immune stimulation and B-cell activation contribute to an increased risk of B-cell non-Hodgkin lymphoma
4. Clinical Features
4.1 Glandular Features
1. Keratoconjunctivitis sicca
o Dry eyes
o Burning
o Grittiness or foreign-body sensation
2. Xerostomia
o Dry mouth
o Difficulty swallowing dry foods
o Frequent need to drink water while eating
3. Recurrent or persistent salivary gland enlargement, particularly the parotid glands
4. Dental caries, periodontal disease, and oral candidiasis may occur
4.2 Other Dryness
1. Vaginal dryness and dyspareunia
2. Dry skin
3. Dryness of the upper respiratory tract
4.3 Extraglandular Manifestations
1. Fatigue
2. Arthralgia or inflammatory arthritis
3. Raynaud phenomenon
4. Cutaneous vasculitis
5. Interstitial lung disease
6. Tubulointerstitial nephritis
7. Distal renal tubular acidosis
8. Peripheral neuropathy
9. Cryoglobulinemia
10. Hypergammaglobulinemia
5. Diagnosis
5.1 Serology
1. Anti-SSA (Ro)
o The only autoantibody included as a weighted item in the 2016 ACR/EULAR classification criteria
o Carries a weight of 3 points
2. Anti-SSB (La)
o May be present, usually with anti-SSA
o Isolated anti-SSB positivity is not an independent item in the 2016 ACR/EULAR classification criteria
3. ANA
o Frequently positive but nonspecific
4. Rheumatoid factor
o Frequently positive but nonspecific
5.2 Ocular Testing
1. Schirmer test ≤5 mm in 5 minutes indicates reduced tear production
2. Ocular staining score ≥5, or van Bijsterveld score ≥4, provides objective evidence of ocular surface involvement
5.3 Salivary Assessment
1. Unstimulated whole salivary flow ≤0.1 mL/min is abnormal
2. Salivary gland ultrasonography is a useful noninvasive adjunct but is not currently one of the five items in the 2016 ACR/EULAR classification criteria
5.4 Histopathology
1. Minor labial salivary gland biopsy is particularly useful in anti-SSA-negative or diagnostically uncertain patients
2. Characteristic finding is focal lymphocytic sialadenitis
3. A focus score ≥1 per 4 mm² is considered positive
4. Biopsy findings may also provide prognostic information, including information relevant to lymphoma risk
5.5 ACR/EULAR Classification Criteria
The 2016 ACR/EULAR criteria assign:
1. Anti-SSA positivity = 3 points
2. Focal lymphocytic sialadenitis with focus score ≥1 per 4 mm² = 3 points
3. Ocular staining score ≥5 or van Bijsterveld score ≥4 = 1 point
4. Schirmer test ≤5 mm/5 minutes = 1 point
5. Unstimulated whole salivary flow ≤0.1 mL/min = 1 point
A total score of ≥4 meets the classification threshold in an appropriate patient.
These are classification criteria, not standalone diagnostic criteria. They are intended for appropriate patients with suspected Sjögren disease after relevant exclusion conditions have been considered. The criteria were formally developed and validated for primary Sjögren syndrome, so Sjögren disease associated with another autoimmune disease remains a clinical diagnosis supported by objective glandular, serologic, and histopathologic findings.
6. Complications
1. Corneal epithelial damage, ulceration, or visual complications from severe dry eye
2. Dental caries, periodontal disease, and tooth loss
3. Interstitial lung disease
4. Renal tubular acidosis and other renal involvement
5. Peripheral neuropathy
6. Cryoglobulinemic vasculitis
7. Increased risk of B-cell non-Hodgkin lymphoma, particularly marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT)
8. Features associated with increased lymphoma risk include:
o Persistent salivary gland enlargement
o Lymphadenopathy
o Palpable purpura
o Cryoglobulinemia
o Low C4
o Monoclonal gammopathy
7. Management
7.1 Dry Eyes
1. Preservative-free artificial tears, particularly when frequent application is required
2. Lubricating gels or ointments for more severe or nighttime symptoms
3. Topical cyclosporine may be considered for inflammatory dry eye under ophthalmologic supervision
4. Short courses of topical corticosteroid eye drops may be used in selected patients under ophthalmologic supervision
5. Punctal plugs may be considered in carefully selected patients, preferably after ocular surface inflammation has been controlled
6. Severe refractory disease may require specialist therapies such as autologous serum tears
7.2 Dry Mouth
1. Frequent water intake
2. Sugar-free or xylitol-containing gum or lozenges
3. Saliva substitutes
4. Regular dental review and meticulous oral hygiene
5. Appropriate fluoride therapy to reduce dental caries risk
7.3 Secretagogues
1. Pilocarpine
2. Cevimeline
3. Most useful when there is residual salivary gland function and no contraindication to muscarinic agonists
7.4 Systemic Therapy
1. Systemic immunosuppressive therapy is not routinely indicated for isolated sicca symptoms
2. Treatment should be directed toward the specific systemic manifestation and any coexisting autoimmune disease
3. A 6 to 12 month trial of hydroxychloroquine may be considered in selected patients with significant fatigue and systemic symptoms
4. Glucocorticoids should generally be reserved for specific active systemic manifestations and used at the lowest effective dose for the shortest appropriate duration
5. Conventional immunosuppressive agents, such as methotrexate, azathioprine, or mycophenolate, are not routinely indicated for uncomplicated Sjögren disease but may be used for selected organ-specific systemic manifestations
6. Rituximab may be considered in selected patients with severe systemic manifestations, such as significant vasculitis, cryoglobulinemia, or refractory organ involvement
7. In this patient, methotrexate should be managed primarily according to rheumatoid arthritis disease activity and should not be expected to reliably correct sicca symptoms
8. Key Clinical Insight
Dry eyes + dry mouth + parotid enlargement + anti-SSA positivity + reduced Schirmer test + focal lymphocytic sialadenitis = Sjögren disease
In a patient with established rheumatoid arthritis, this represents Sjögren disease associated with rheumatoid arthritis, traditionally called secondary Sjögren syndrome.
References
1. Price EJ, Benjamin S, Bombardieri M, et al. British Society for Rheumatology guideline on management of adult and juvenile onset Sjögren disease. Rheumatology (Oxford). 2025;64(2):409-439. doi:10.1093/rheumatology/keae152. PMID: 38621708.
2. Ramos-Casals M, Baer AN, Brito-Zerón MP, et al. 2023 International Rome consensus for the nomenclature of Sjögren disease. Nat Rev Rheumatol. 2025;21(7):426-437. doi:10.1038/s41584-025-01268-z. PMID: 40494962.
3. Shiboski CH, Shiboski SC, Seror R, et al. 2016 American College of Rheumatology/European League Against Rheumatism classification criteria for primary Sjögren's syndrome: a consensus and data-driven methodology involving three international patient cohorts. Arthritis Rheumatol. 2017;69(1):35-45. doi:10.1002/art.39859. PMID: 27785888.
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