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CLINICAL MEDICINE

PBL #10AUTOIMMUNE DISEASE

Name:___________________________________________ Student ID#:________________

FOR THIS PBL, YOU WILL BE REQUIRED TO PROVIDE THE

INFORMATION FOR THE CATEGORIES ON PAGE 2. ANSWER ALL

AREAS LISTED WITH REGARD TO ONE OF THE AUTOIMMUNE

PROCESSES I HAVE LISTED.

PLEASE CHOOSE ONE OF THE FOLLOWING AUTOIMMUNE DISEASE

PROCESSES:

Alopecia Areata

Ankylosing SpondylitisAntiphospholipid Antibody Syndrome

Celiac Disease

Cold Agglutinin DiseaseCrohns Disease

Dermatomyositis

Goodpastures

Kawasakis DiseaseLupus

Rheumatoid ArthritisJuvenile Rheumatoid ArthritisMyasthenia Gravis

Primary Biliary Cirrhosis

Psoriatic ArthritisSjogrens Syndrome

Temporal Arteritis

Wegeners Granulomatosis

(Do me a favor and avoid Wikipedia! Please use your textbook or other medical

journals/texts/articles J)

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Autoimmune Disease:

Myasthenia Gravis

Definition: Autoimmune disease caused by a mis-communication between nerves and

muscles at the neuromuscular junction (NMJ), thus a neuromuscular transmission

disease.

Etiology:In a normal functioning NMJ, the acetylcholine (ACh) travels across the synaptic clef to

the post-synaptic membrane in order to produce a muscle action from an action potential.

In MG, the body produces antibodies that attach to the acetyl choline receptor (AChR)

reducing the binding of ACh to the AChR, thus reducing muscle contraction.Furthermore, receptor tyrosine kinase may be blocked by the antibodies, resulting in a

reduction of action potentials. In recent research, it has been found that a congenital form

of MG that is antibody negative produced against lipprotein related protein 4, thus

genetics may be a factor in some MG cases.

Incidence and Prevalence: Can occur at any age, however, is more prevalent in women

60. In the US the prevalence of MG is 14-20 per 100 000,

therefore approximately 36 000 to 60 000 cases of MG in the US.

Pathophysiology and Pathogenesis:

In the neuromuscular junction (NMJ) of an individual with MG, the post-synaptic muscle

membrane does not have sufficient number of acetyl choline receptors (AChR), in

addition to a reduced number of AChR, there are also antibodies made by the body thattarget and attach to the remaining AChR, therefore there is an overall reduction of AChR

and a lower stimulation of the muscle past this NMJ. Therefore there is a reduction

muscle action potential transmission, and therefore muscle activity down stream. It ishypothesized that the thymus has a connection to the development of MG, however, it is

unclear as to whether the thymus is the primary cause of MG or secondary to MG.

Clinical and Laboratory Manifestations:

Clinical Manifestations

1. eyes - ptosis, diplopia2. muscles - weakness in neck, arms and legs ; arms more effect than legs

3. face and throat - 15% of population affected by face and eyes; difficulty chewing and

swallowing; affected CN VII causes altered facial expression4. speech - altered speech sounding more nasal

Laboratory Manifestations

1. acetylcholine receptor antibodies in blood serum and in the nerve

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Diagnostic Indicators: (What criteria/information is required to make a clinical

diagnosis)

Ptosis and muscle weakness that improves with rest are key symptoms of MG.1. edrophonium test: edrophium chloride injection causes improvement of muslce

strength. Edrophonium prevents enzymatic breakdown of ACh.

2. Ice pack test:2 minute placement of ice pack on eye may cause sudden muscleimprovement.

3. blodo analysis: test for serum antibodies against AChR. Ab are present in 80% of MG

patients, and 50% are limited to eye symptoms only.

4. receptive nerve stimulation - repeated pulses of electricity will help diagnosis MG ifmuscle action becomes progressively weaker over time (decrement of compound muscle

action potential).

5. Imaging - CT or MRI cheks for physical abnormalities.

Treatment and Prognosis: (Please include specific pertinent pharmacologicinterventions with generic and/or brand name drugs and pharmacologic action of drug

categories as indicated)

1. cholinesterase inhibitors (ChEI): inhibit the hydrolysis of Ach at the NMJ

allowing for an accumulation of ACh at the neuromuscular end plate therefore

allowing for a more prolonged effect of ACh. Common drugs are Prostigmin

(neuostigmine bromide) or Mestinon (pyridostigmine bromide).2. Thymectomy: response to this treatment starts to work well 2-5 years post-

surgery. Response to this treatment is not predictable. This will remove the

antigens being produced by the body.3. Corticosteroids: >75% of patients treated with corticosteroids, mostly prednisone,

show relief of symptoms and show improvement within 6-8 weeks. This treatment

works best when used with patients with recent symptom onset.4. Immunosuppressant drugs: E.g. Azathioprine will inhibit T-lymphocyte dependent

immune responses to reduce the auto immunicity of the disease. Improvement

starts 1-2 months post-therapy initiation but maintain reduced symptoms for the

long run and this drug has less side effects.5. Plasma exchange: this is an acute intervention for patients who have a sudden

exacerbation of symptoms.

6. Intravenous immune globulin: this drug class down-regulates antibodies againstAChR and produce anti-idiotypic antibodies that cause relie of symptoms. Onset

of results start at week 1 and last for months. The improvement is seen from 50

100% of patients.

Bonus Question:

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Dr. Braidys mother-in-law suffers with Sjogrens syndrome. She also has required

treatment for BOOP. (True Story)

Please describe in detail what BOOP is, its treatment and its relationship to Autoimmune

disease?

BOOP stands for bronchiolitis obliterans organizing pneumonia and is a rare diseaewhere granulation tissue develops in the bronchioles, alveolar ducts, and alveoli resulting

in blockage of the alveolar lumen and bronchiolar. BOOP is a non-specific response to

various types of lung injuries (injury due to physical, medication, radiation, malignanciesetc.) The treatment includes corticosteroids which allow for rapid recovery. BOOP is

associated with various autoimmune diseases such as rheuamatoid arthritis, systemic

lupus erythematosus and at also sjogrens syndrome.

Also, what famous golf star suffers from Psoriatic Arthritis?

Phil Mickelson suffers from psoriatic arthritis

http://www.myasthenia.org/HealthProfessionals/ClinicalOverviewofMG.aspx