Sjogren Syndrome: Diagnosis and Management

Introduction

Sjogren syndrome is a chronic autoimmune disease in which lymphocytic infiltration damages the exocrine glands, most conspicuously the lacrimal and salivary glands, producing the classic sicca ('dry') symptoms of dry eyes and dry mouth. It can occur as a standalone condition (primary Sjogren syndrome) or alongside another connective tissue disease, most often rheumatoid arthritis or SLE (secondary Sjogren syndrome).¹

It predominantly affects women (around 9:1), typically presenting in the fourth to sixth decades. It is examined for two reasons: the diagnostic pattern of antibodies and bedside tests is genuinely useful and testable, and the long-term lymphoma risk is a complication that is easy to forget but important not to miss.

Aetiology and pathophysiology

Sjogren syndrome results from lymphocytic infiltration of exocrine glandular tissue, with progressive destruction of glandular architecture and replacement by fibrosis, reducing secretory function. The trigger for the autoimmune process is not fully understood but, as with the other connective tissue diseases, involves a combination of genetic susceptibility, environmental factors (viral infection has been proposed) and B-cell hyperactivity, reflected in the high titres of autoantibodies typically seen.

• Female sex - around 9:1
• Age - typically diagnosed in the 40s-60s, though it can occur at any age
• Family history of Sjogren syndrome or other autoimmune disease
• Coexisting connective tissue disease - rheumatoid arthritis, SLE, systemic sclerosis, or another autoimmune condition (secondary Sjogren syndrome)

Clinical features

Sicca symptoms

• Dry eyes (keratoconjunctivitis sicca) - a gritty, foreign-body sensation, photophobia, and in severe cases corneal damage
• Dry mouth (xerostomia) - difficulty eating dry foods without fluids, altered taste, increased dental caries and oral candidiasis
• Parotid and other salivary gland swelling - often bilateral and recurrent
• Vaginal dryness and dyspareunia
• Dry skin

Systemic and extraglandular features

Sjogren syndrome is not confined to the exocrine glands - a substantial minority of patients have systemic disease:

• Fatigue - very common and often disproportionately troublesome
• Arthralgia, typically non-erosive
• Raynaud phenomenon
• Peripheral neuropathy, including sensory neuropathy and mononeuritis
• Cutaneous vasculitis - palpable purpura, usually of the lower limbs
• Interstitial lung disease
• Distal (type 1) renal tubular acidosis - from lymphocytic infiltration of the renal interstitium, causing a hyperchloraemic metabolic acidosis and a tendency to nephrocalcinosis and renal stones
• Lymphadenopathy, which alongside persistent parotid swelling should prompt consideration of lymphoma

Examination

• Eyes - reduced tear lake, conjunctival injection, and signs of corneal damage in advanced disease
• Mouth - dry, erythematous oral mucosa, a smooth or fissured tongue, dental caries at the gum line, and reduced pooling of saliva on inspection
• Salivary glands - palpate the parotid and submandibular glands for diffuse or focal swelling, and note any asymmetry or firmness that might suggest lymphoma rather than simple glandular inflammation
• Skin - purpura of the lower limbs if cutaneous vasculitis is present
• Joints - for synovitis, which if present and erosive suggests secondary Sjogren syndrome alongside rheumatoid arthritis rather than primary disease alone

Differential diagnosis

• Age-related dry eyes/mouth - common and usually mild, without the systemic or serological features
• Medication-induced dryness - anticholinergics, antihistamines, antidepressants
• Sarcoidosis - can cause parotid and lacrimal gland enlargement (part of uveoparotid fever/Heerfordt syndrome)
• IgG4-related disease - can mimic Sjogren syndrome with salivary/lacrimal gland swelling, distinguished on biopsy and serum IgG4
• Other connective tissue diseases presenting with sicca symptoms - SLE, systemic sclerosis, rheumatoid arthritis, considered as secondary Sjogren syndrome if sicca features develop alongside them
• Lymphoma - must always be actively excluded if there is persistent, asymmetrical or hard glandular swelling

Investigations

Serology

• Anti-Ro (SSA) - present in the majority of primary Sjogren syndrome, the more sensitive of the two key antibodies
• Anti-La (SSB) - less sensitive, but its presence with anti-Ro strengthens the diagnosis
• ANA - frequently positive
• Rheumatoid factor - often positive, even in patients with no coexisting rheumatoid arthritis, reflecting the general B-cell hyperactivity of the disease
• Raised immunoglobulins (polyclonal hypergammaglobulinaemia) are common; a sudden fall in immunoglobulins or the appearance of a paraprotein/monoclonal band should raise suspicion of evolving lymphoma

Bedside and objective tests of gland function

Gold standard

Labial (minor) salivary gland biopsy, usually taken from the inner lip, showing focal lymphocytic infiltration, remains the definitive test and is used particularly when serology is negative but clinical suspicion is high (seronegative Sjogren syndrome), or when lymphoma needs to be excluded.

Management

There is no cure; management is aimed at relieving sicca symptoms, treating systemic disease where present, and screening for complications.²

Symptomatic management

• Artificial tears for dry eyes, used regularly rather than only when symptomatic
• Saliva substitutes and sugar-free chewing gum/lozenges to stimulate residual saliva production
• Pilocarpine or cevimeline - muscarinic agonists that stimulate remaining exocrine gland function where enough glandular tissue survives
• Meticulous dental care - regular dental review, fluoride use, and prompt treatment of caries, given the markedly increased risk from reduced salivary flow
• Vaginal moisturisers/lubricants for vaginal dryness

Systemic and extraglandular disease

• Hydroxychloroquine - commonly used for fatigue and arthralgia, though evidence for its benefit in Sjogren syndrome specifically is less robust than in SLE
• Immunosuppression (methotrexate, azathioprine, mycophenolate) for significant systemic organ involvement
• Rituximab - used for severe systemic disease refractory to conventional treatment, and in the setting of associated lymphoma

Complications

Beyond lymphoma and the risks in pregnancy discussed above, longstanding dry eyes can cause corneal ulceration and scarring, and severe xerostomia leads to accelerated dental disease and recurrent oral candidiasis. Distal renal tubular acidosis can cause nephrocalcinosis, renal stones and, if unrecognised, hypokalaemic paralysis. Peripheral neuropathy and vasculitis can cause lasting functional impairment.

Red flags

Prognosis

For most patients, Sjogren syndrome is a manageable, chronic condition where sicca symptoms are controlled with simple measures and quality of life, while affected by fatigue and dryness, remains reasonable. The main determinant of more serious long-term outcome is the development of significant systemic organ involvement or, in a minority, lymphoma - both reasons why regular follow-up continues even once symptoms feel well controlled.