CLINICAL MEDICINE PBL #10

AUTOIMMUNE 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 Spondylitis Antiphospholipid Antibody Syndrome Celiac Disease Cold Agglutinin Disease Crohns Disease Dermatomyositis Goodpastures Kawasakis Disease Lupus Rheumatoid Arthritis Juvenile Rheumatoid Arthritis Myasthenia Gravis Primary Biliary Cirrhosis Psoriatic Arthritis Sjogrens Syndrome Temporal Arteritis Wegeners Granulomatosis

(Do me a favor and avoid Wikipedia! Please use your textbook or other medical journals/texts/articles J)

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 <40 years old and men >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 that target 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 is hypothesized 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, diplopia 2. 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 expression 4. speech - altered speech sounding more nasal Laboratory Manifestations 1. acetylcholine receptor antibodies in blood serum and in the nerve

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 muscle improvement. 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 if muscle 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 pharmacologic interventions 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 postsurgery. 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 against AChR 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:

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 diseae where 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, malignancies etc.) 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