Diagnosis

Sjogren syndrome

Etiology

Cause [vy3]

• Unknown

• Multifactorial:

  • Genetic predisposition (HLA-DQB1)

  • Hormonal

  • Environmental factors (Epstein-Barr virus)

Classification [vy3]

• Primary Sjögren syndrome is a solitary process

• Secondary Sjögren syndrome accompanies another autoimmune disease (such as rheumatoid arthritis or systemic lupus erythematosus)

Pathophysiology [vy3]

1. Environmental insult in genetically predisposed individual

2. Epithelial damage --> inflammation --> triggers an aberrant autoimmune response

3. Aggregations of lymphocytes (CD4 T cells, memory cells and B cells)

4. Exocrine gland dysfunction --> Reduced tear and saliva production

5. Clinical presentation:

   • Keratoconjuntivitis sicca: Dry eyes, corneal erosions, vision loss

   • Xerostomia: Dry mouth, dental caries, dental decay, and tooth loss

   • Musculoskeletal: Arthritis (16%), arthralgia (96%), myalgia (70%), myositis (rare)

   • Dermatologic (72%): Xeroderma, eyelid dermatitis, Raynaud phenomenon, cutaneous vasculitis (purpura), cutaneous amyloidosis, and annular erythema

   • Neurologic (5%): Mild cognitive dysfunction, transverse myelitis, neuromyelitis optica, lymphocytic meningitis, cerebral vasculitis, cranial neuropathies (trigeminal, facial, or cochlear nerves), peripheral neuropathies, small fiber neuropathy, sensory ataxic neuronopathy, mononeuritis multiplex and autonomic dysfunction

   • Renal (5%): Tubulointerstitial nephritis, distal renal tubular acidosis, membranoproliferative glomerulonephritis

   • Hematologic: Cytopenias, hypergammaglobulinemia (40%), hypogammaglobulinemia, monoclonal gammopathy, cryoglobulins, leukopenia (20%), anemia (24%), thrombocytopenia (30%)

   • Pulmonary: Cough/dyspnea related to dryness, bronchiectasis, bronchiolitis, interstitial lung disease (nonspecific interstitial pneumonia, lymphocytic interstitial pneumonia, organizing pneumonia), cystic lung disease, pulmonary hypertension

   • Non-Hodgkin lymphoma: An 8.7-fold increased risk

Complications [vy3]

• Dental caries

• Oral infections

• Extraglandular manifestations

• Non-Hodgkin lymphoma

Epidemiology

Incidence per 100.000 [rzd][ocf][ypp][yfg][bea][ers][ugq]

Approach

• Blood: Anti-RO(SSA), anti-La(SSB), antinuclear anitbody, ANA, rheumatoid factor [pru]

• Schirmer test

• Salivary gland ultrasonography

• Salivary scintigraphy

• Sialometry

• Salivary gland biopsy: lymphocytic infiltrate, acinar atrophy

Diagnostic criteria [ers]

1. Ocular symptoms: dry eyes (>3 months), sensation of sand in eyes, use of tear substitutes >3/day

2. Oral symptoms: dry mouths (>3 months), swollen salivary glands, frequent drinking to aid swallowing dry food

3. Ocular signs: Schirmer´s I test (≤5mm in 5 min), Rose Bengal score

4. Histopathology: focal lymfocytic sialoadenitis

5. Salivary gland: understimulated flow ≤1.5ml in 15 min, parotid sialography showing sialectasias without obstruction, salivary scintigraphy showing delayed uptake/concentration/excretion

6. Autoantibodies: Anti-RO(SSA) and/or anti-La(SSB)

Diagnostic criteria [vy3]

Suspicion based on at least 1 of the following:

• Daily, persistent, troublesome dry eyes

• Recurrent sensation of sand or gravel in the eyes

• Regular use of tear substitutes

• Daily feeling of dry mouth

• Frequent need to drink liquids to help swallow dry food

1. Labial salivary gland biopsy showing focal lymphocytic sialadenitis (3 points)

2. Positive anti-Ro/SSA or anti-La/SSB antibodies (3 points)

3. Ocular staining score ≥5 or van Bijsterveld score ≥4 in at least 1 eye (1 point)

4. Schirmer’s test result ≤5 mm/5 minutes in at least 1 eye (1 point)

5. Unstimulated whole salivary flow rate ≤0.1 mL/minute (1 point)

   Score of ≥4 --> Sjögren syndrome

Treatment

There is no known cure for Sjögren syndrome and treatment focuses on relieving symptoms [vy3]

1. Xerophthalmia: [vy3]

   • Topical tear replacement

   • Topical corticosteroids: risks of glaucoma, cataracts, and infections

   • Topical cyclosporine or tacrolimus

2. Xerostomia: [vy3][pru]

   • Daily topical fluoride use and antimicrobial mouth rinses

   • Sugar-free chewing gums and sour lemon lozenges for salivary stimulation

   • Muscarinic agonists pilocarpine or cevimeline stimulate salivary flow

3. Systemic treatment: if moderate to severe extraglandular manifestations [vy3]

   • Glucocorticoids

   • Antimalarial medication (hydroxychloroquine)

   • Steroid-sparing immunosuppressants: methotrexate, azathioprine, mycophenolate mofetil, leflunomide, rituximab or cyclophosphamide

Differential diagnoses

Allergy, Benign tumors of salivary glands, Blepharitis, Celiac disease, Chronic sinusitis, Conjunctivitis, Diabetes mellitus, Drug side effects, Hashimotos thyroiditis, HIV, Hypovolemia, Lymphoma, Malignant tumors of salivary glands, Mumps, Parkinson's disease, Polyneuropathy, Rheumatoid arthritis, Rosacea, Sarcoidosis, Scleroderma, Sialadenitis, Systemic lupus erythematosus