Internal Medicine Correlations and Clinical Scenarios (CCS) USMLE Step 3

CASE 3: Sjögren Syndrome

Setting: office

CC:My eyes are always dry and my joints hurt.”

VS: normal

HPI: A 50-year-old woman comes to the office with several months of increasing dryness of her mouth and eyes. Her eyes are “burning” and “itching” and sometimes feels like she has a grain of sand in them. She feels like she has “dry cotton” in her mouth. She has joint pain in her knees and ankles.

Tear production is neutrally mediated through acetylcholine.

PMHX:

Image Primary biliary cirrhosis

Image Hypothyroidism

Medications:

Image Levothyroxine

Image Artificial tears

PE:

Image Head, ears, eyes, nose, throat (HEENT): several lost teeth, dental caries present

What is the greatest stimulant to saliva production?

a. Acetylcholine

b. Epinephrine

c. Norepinephrine

d. Nicotinic receptors

Answer a. Acetylcholine

Saliva production is the only part of the body in which the sympathetic and parasympathetic nervous system both lead to increased production of a substance. The greatest stimulant, however, by far, is acetylcholine. The acetylcholine receptors in the salivary glands are muscarinic receptors not nicotinic receptors.

Nicotinic Receptors

• Neuromuscular junction

• Autonomic ganglia

• Central nervous system (CNS)

Which test is most likely to be positive in Sjögren syndrome?

a. Antinuclear antibody (ANA)

b. Anti-SSA (Ro)

c. Anti-SSB (La)

d. RF

e. Anti-Jo

Answer a. Antinuclear antibody (ANA)

Although the ANA test has no specificity for Sjögren syndrome, it is the test most commonly found to be positive. Ninety-five percent of patients with Sjögren syndrome should be positive for ANA, this means the ANA has an enormously strong negative predictive value for the disorder.

Initial Orders:

Image ANA

Image Anti-SSA (Ro)

Image Anti-SSB (La)

Image RF

Image Schirmer test

Saliva pH is high to neutralize acid in the mouth.

Acid destroys tooth enamel.

Saliva has IgA to protect against infection.

Lactoferrin in saliva binds iron to “starve” bacteria of this essential nutrient.

Continue artificial tears and saliva. Sugar-free sour candy is useful to increase saliva production because the sour taste receptors are stronger than sweet, salt, umami, and bitter taste receptors in producing the highest volume of saliva.

Normal saliva volume is 1 to 2 liters a day.

More Acetylcholine = More Saliva

Acetylcholine will

• Increase bicarbonate content

• Increase volume

• Decrease sodium reabsorption

Reports:

Image ANA, anti-SSA (Ro), anti-SSB (La), RF: all positive

Image Schirmer test: decreased tear production

• Saliva is needed for taste and smell.

• Saliva is hypotonic.

Patients with Sjögren syndrome will lose their teeth because of multiple dental caries. Replacing saliva with artificial saliva and stimulating salivary flow is important.

Orders:

Image Artificial tears and saliva

Image Pilocarpine

Image Cevimeline

Image Fluoride oral treatments

How can salivary acetylcholine be increased?

Pilocarpine = Muscarinic Receptor Agonist

Cevimeline = Acetylcholine Analogue

What is the most specific test of Sjögren syndrome?

a. Anti-SSA

b. Lip biopsy

c. Schirmer test

d. Anti-SSB

Answer b. Lip biopsy

Lip biopsy shows the foci of lymphoid cells in salivary gland tissue in the accessory salivary glands. This is more specific than any serologic test.

The pilocarpine, cevimeline, and artificial tears improve symptoms immediately. The patient returns in a week because dry eyes still bother her.

Orders:

Image Cyclosporine eyedrops

Image Counseling about possible development of lymphoma

Cyclosporine:

• Inhibits lymphocyte activation

• Immunosuppressant

• Calcineurin inhibitor

Saliva

• Seventh and ninth cranial nerve control

• Slower Flow = More Sodium Reabsorption

Cevimeline is more active at the M1 and M3 receptors of the salivary and lacrimal glands.

Cevimeline is less active at the cardiac acetylcholine receptors.

Which of these impairs taste perception in Sjögren syndrome?

a. Loss of amylase and lipase

b. Loss of salivary protease

c. Increased lysozyme

d. Increased lactoperoxidase

Answer a. Loss of amylase and lipase

Salivary amylase and lipase break down enough starch and fat to increase taste perception of food. There is no normal salivary protease. Lysozyme and lactoperoxidase are decreased, but they kill bacteria and have nothing to do with taste perception.

Adverse Effects of Pilocarpine and Cevimeline

• Diarrhea

• Bronchospasm

• Bradycardia

Mechanism of Adverse Effect

• Overstimulation of muscarinic receptors

The patient’s symptoms of oral dryness and eye dryness are improved. There is little therapy for the joint pain.

Orders:

Image Educate and advise the patient to avoid cola, coffee, and tea.

Image Order a dental evaluation.

Image Educate and advise the patient regarding diligent oral care.

• Acid destroys teeth.

• The pH of cola is pH 2.5.

• Bacteria make acid.



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