Sjogren's Syndrome

Question 1

Epidemiology

Answer 1

Affects women > men (9:1)
Onset usually age 40-60
Affects ~1% of the population
Up to 30% of autoimmune rheumatic disease patients also have Sjogrens syndrome.
Symptoms may develop over 8-10 yrs.

Question 2

Presentation

Answer 2

Dry eyes
- Gritty, sandy, worsens through day

Dry mouth

• “Food sticking to roof of mouth”
• Altered sense of taste
• Difficulty wearing dentures
• Needing liquids to swallow food
• Dental caries

Parotitis

Dry mucosal surfaces (skin, bronchi, or vagina)

Question 3

Sjogren’s syndrome is an autoimmune disorder with lymphocytic infiltration of the:

A – Endocrine glands
B – Exocrine glands
C – Adrenal glands
D – Hyaline membranes

Answer 3

B- exocrine glands

Question 4

Etiology

Answer 4

Sjogren’s syndrome is an autoimmune disorder of the exocrine glands.

Most common presenting symptoms are dry eyes and dry mouth (sicca syndrome).

Question 5

The inflammatory infiltrates in Sjogrens syndrome are characterized by:

A – NK cells
B – CD4+ T cells
C – Macrophages
D – Eosinophils

Answer 5

B - CD4+ T cells

Question 6

Pathophysiology

Answer 6

Lymphocytic infiltration of exocrine glands

Helper T cells infiltrate gland.
B and T cells are activated.
Leads to autoantibodies, IL-2 release.
Glandular cells express MHC class II molecules & may act as antigen-presenting cell → cell apoptosis.
Metalloproteinases are secreted → block interaction of glandular cells & extracellular matrix, inhibiting gland function.

Question 7

What’s going on here?

Answer 7

B cell hyperreactivity
Acetylcholine (muscarinic) receptor Ab
May interfere with neural stimulation of glandular secretion.

Question 8

Pathogenesis

Answer 8

87% of patients with Sjogrens syndrome are positive for HLA-DR52.

Possible environmental triggers (viral?) in addition to genetic disposition.

Question 9

Glands that may be Affected

Answer 9

Lacrimal
Salivary
Parotid
Vulvovaginal
Prostate/urethral
Pancreas
Sweat glands
Glands in GI tract
Bronchopulmonary glands

Question 10

Which of the following is most commonly associated with Sjogrens syndrome?

A – Anti-Ro/SSA, Anti-La/SSB
B – Antimitochondrial
C – Antihistone
D – Anti-Smith

Answer 10

A – Anti-Ro/SSA, Anti-La/SSB

Question 11

Diagnosis

Answer 11

At least 4 of 6; must include + biopsy or Ab
Dry eyes x 3 mos., tear substitutes >3x/day
Dry mouth, swollen salivary glands, needing liquids to swallow
Eye signs: Schirmer test or + vital dye staining
Oral signs: Abnormal scintigraphy or sialography findings
+ Biopsy of minor salivary gland
+ Anti-Ro/SSA or anti-La/SSB

Question 12

Diagnostic Tests

Answer 12

Schirmer test
(at least 10 mm moisture in 5 min.)

Sialogram of salivary glands

Lissamine green dye staining

Question 13

Eye Irritation

Answer 13

↓ liquid in tears
Tear hyperosmolarity
→ Inflammatory cascade & immune activation of the conjunctiva

Question 14

Additional Lab Findings

Answer 14

↑ ESR
Anemia
Leukopenia
Eosinophilia
Hypergammaglobulinemia
\+ RF
\+ ANA
Antiphopholipid Ab
Cryoglobulins

Question 15

Which of the following would mimic a diagnosis of Sjogrens syndrome?

A – Recent steroid use
B – Rheumatoid arthritis
C – History of head and neck irradiation
D – History of pancreatitis

Answer 15

History of head and neck irradiation

Question 16

Diagnostic Exclusions

Answer 16

Difficult to diagnose Sjogrens syndrome if:
Past head and neck irradiation
Hepatitis C infection
AIDS
Prior lymphoma
Sarcoidosis
Graft vs. host disease
Taking anticholinergic drugs
IgG4-related disease

Question 17

Mucous Membrane Involvement

Answer 17

Atrophic changes in upper respiratory tract
→ Nasal dryness, recurrent infection, hoarseness
Atrophic changes in vulvovaginal area
→ Pruritus, vaginitis
Dryness of anorectal area
→ Pruritus, inflammation

Question 18

GI Involvement

Answer 18

Dysphagia due to dry pharynx & esophagus
Acute or chronic pancreatitis
Malabsorption
Digestive symptoms due to achlorhydria
Delayed gastric emptying

Question 19

Extraglandular Involvement

Answer 19

Periepithelial Infiltration

• Interstitial nephritis/RTA
• Liver disease
• Interstitial lung disease

Extraepithelial Extraglandular

• B-cell hyperreactivity
• Hypergammaglobulinemia
• Immune complex formation
• —- Glomerulonephritis, purpura, peripheral neuropathy

Question 20

Lung Involvement

Answer 20

Airway hyperreactivity

• Cough
• Bronchiolitis
• Obstructive pattern on spirometry

Interstitial lung disease

• Several types of interstitial pneumonitis
• Restrictive pattern on spirometry

Question 21

Kidney Involvement

Answer 21

Tubulointerstitial nephritis
- Mildly increased serum creatinine
- Distal (type 1) renal tubular acidosis
↓ potassium, urine pH > 5.5, urine anion gap
- Hypokalemia
- Fanconi syndrome/proximal (type 2) RTA
- Nephrogenic diabetes insipidus

Renal calculi

Interstitial cystitis

Question 22

Liver Involvement

Answer 22

Autoimmune liver disease

Primary biliary cirrhosis

• Immune-mediated destruction of small bile ducts
• Cholestatic pattern on LFT’s
• • Antimitochondrial Ab
• • Antibody to carbonic anhydrase 11

Autoimmune hepatitis

• Hepatocellular pattern on LFT’s
• • Anti-smooth muscle Ab or + ANA

Question 23

Neuro Involvement

Answer 23

Peripheral neuropathy
- Including mononeuritis multiplex
Myelitis
Cognitive dysfunction
Cranial neuropathies
Neuromyelitis optica (can mimic MS)

Question 24

Cardiac Involvement

Answer 24

Pericarditis
Pulmonary hypertension
Autonomic dysfunction
- Associated with M3 muscarinic receptor Ab

Question 25

Skin Involvement

Answer 25

``` Dryness, pruritus ↓ Sweating Erythema annulare (Asian pts.) Cutaneous vasculitis (purpura) Raynaud phenomenon Dry hair, alopecia ```

Question 26

Other Symptoms

Answer 26

Fatigue Arthritis occurs in 42%. - Nonerosive, mild

Question 27

Tx of Sicca Symptoms

Answer 27

Hydration Symptomatic treatment Ocular - Artificial tears - Punctal plugs - Topical cyclosporine Oral - Artificial saliva - Sugar-free lozenges - Pilocarpine, cevimeline

Question 28

Sjogrens Treatment

Answer 28

Arthritis - NSAID’s - Hydroxychloroquine - Methotrexate - Short-term, low-dose corticosteroids Fatigue - Exercise

Question 29

Biological Therapies

Answer 29

TNF-α inhibitors are not used to treat sicca symptoms! For systemic symptoms – begin with standard DMARDs or high-dose corticosteroids. If no improvement, consider rituximab for: - Cryoglobulinemia/vasculitis - Renal disease - Inflammatory arthritis - Pulmonary disease - Peripheral neuropathy, especially mononeuritis

Question 30

``` Patients with Sjogrens syndrome have a highly increased risk of developing: A – Non-Hodgkin lymphoma B – Follicular thyroid cancer C – Renal cell carcinoma D – Colon cancer E – Coronary artery disease ```

Answer 30

Non-Hodgkin lymphoma

Question 31

Complications

Answer 31

Lymphoma occurs in 4.3% of Sjogrens patients (increased 18x above normal). Most commonly MALT lymphoma or other B-cell lymphomas.

Question 32

Anti-Ro/SSA is associated with which complication in babies born to women with Sjogrens syndrome? A – Neonatal thyroiditis B – Neonatal hypoglycemia C – Developmental dysplasia of the hip D – Neonatal heart block

Answer 32

Neonatal heart block

Question 33

Other Complications

Answer 33

Parotid infections - Staphylococcal, streptococcal, pneumococcal Parotid tumors Antiphopholipid Ab syndrome Neonatal lupus with congenital heart block

Question 34

Prognosis

Answer 34

Symptoms do not tend to progressively worsen. Mortality is similar to the general population. Poor prognostic indicators at diagnosis: - ↓ Complement levels - Lymphocytopenia - Cryoglobulinemia ...predictive of lymphoma, more severe disease, and increased mortality.