Clinical Issues in AIP

22 Pages·2016·3.6 MB·English

Clinical Issues in AIP:
When to Suspect and How to Proceed
CME/CE
Supported by an independent educational grant from Recordati Rare Diseases.
www.medscape.org/roundtable/aip
Clinical Issues in AIP: When to Suspect and How to Proceed CME/CE
This article is a CME/CE certified activity.
To earn credit for this activity visit:
www.medscape.org/roundtable/aip
CME/CE Released: 3/25/2016; Valid for credit through 3/25/2017
Target Audience
This activity is intended for gastroenterologists, primary care physicians, emergency medicine physicians, and nurses.
Goal
The goal of this activity is to improve recognition, diagnosis, evaluation, and treatment of patients with acute intermittent
porphyria.
Learning Objectives
Upon completion of this activity, participants will be able to:
1. Identify key factors used to diagnose acute intermittent porphyria (AIP)
2. Select appropriate treatment and management strategies in patients with AIP
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Physicians - maximum of 0.50 AMA PRA Category 1 Credit(s)™
Nurses - 0.50 ANCC Contact Hour(s) (1 contact hours are in the area of pharmacology)
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Clinical Issues in AIP: When to Suspect and How to Proceed CME/CE
Faculty and Disclosures
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Angelika L. Erwin, MD, PhD
Assistant Professor of Genetics and Pediatrics, Lerner College of Medicine; Clinical Geneticist, Cleveland
Clinic, Cleveland, Ohio
Disclosure: Angelika L. Erwin, MD, PhD, has disclosed the following relevant financial relationships:
Served as an advisor or consultant for: Alexion Pharmaceuticals, Inc.
Served as a speaker or a member of a speakers bureau for: Genzyme Corporation
Dr Erwin does not intend to discuss off-label uses of drugs, mechanical devices, biologics, or diagnostics
approved by the FDA for use in the United States.
Dr Erwin does not intend to discuss investigational drugs, mechanical devices, biologics, or diagnostics
not approved by the FDA for use in the United States.
Manisha C. Balwani, MD, MS
Associate Professor, Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York,
New York
Disclosure: Manisha C. Balwani, MD, MS, has disclosed the following relevant financial relationships:
Served as an advisor or consultant for: Alexion Pharmaceuticals, Inc.; Genzyme Corporation; Recordati Rare
Diseases, Inc.
Received grants for clinical research from: Alnylam Pharmaceuticals, Inc.; Genzyme Corporation; Synageva
BioPharma

Dr Balwani does not intend to discuss off-label uses of drugs, mechanical devices, biologics, or diagnostics approved by the FDA
for use in the United States.

Dr Balwani does not intend to discuss investigational drugs, mechanical devices, biologics, or diagnostics not approved by the
FDA for use in the United States.
Editor
Susan L. Smith, MN, PhD
Lead Scientific Director, Medscape, LLC
Disclosure: Susan L. Smith, MN, PhD, has disclosed no relevant financial relationships.
CME Reviewer/Nurse Planner
Amy Bernard, MS, BSN, RN-BC
Lead Nurse Planner, Medscape, LLC
Disclosure: Amy Bernard, MS, BSN, RN-BC, has disclosed no relevant financial relationships.
Peer Reviewer
This activity has been peer reviewed and the reviewer has disclosed no relevant financial relationships.

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www.medscape.org/roundtable/aip
Angelika L. Erwin, MD, PhD: Hello, I am Dr Angelika Erwin. I am a clinical geneticist and an associate professor at the Lerner
Collage of Medicine at the Cleveland Clinic. Welcome to this program titled, “When to Suspect and How to Proceed Clinical Issues
in AIP.”
Joining me today is Dr Manisha Balwani, an associate professor of genetics and medicine and codirector of the Porphyria Center at
the Icahn School of Medicine at Mount Sinai in New York City.
Manisha Balwani, MD, MS: Thank you for having me, Angelika.
Dr Erwin: Acute intermittent porphyria (AIP) is 1 of 4 acute porphyrias, all of which are characterized by recurrent, acute attacks of
neurovisceral symptoms.
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Clinical Issues in AIP: When to Suspect and How to Proceed CME/CE
AIP is caused by a defect in the HMBS gene, which leads to a partial deficiency in porphobilinogen (PBG) deaminase, the third
enzyme of the heme biosynthetic pathway.[1] Alcohol use, exposure to certain medications, or other factors that increase
demand for heme lead to upregulation of heme biosynthesis in the liver. This results in increased production of certain heme
precursors — especially delta-aminolevulinic acid (ALA) and PBG.
Patients who have a partial deficiency in the PBG enzyme cannot sufficiently metabolize these heme precursors. The precursors
accumulate in the liver and cause the symptoms seen in patients with an AIP attack [hereafter referred to as “acute attack”]. Both
ALA and PBG are neurotoxic, which explains the neurologic nature of symptoms associated with AIP.
AIP is an autosomal dominant disorder. Affected persons have a 50% chance of passing the genetic mutation that causes AIP to
their children.
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www.medscape.org/roundtable/aip
Although AIP is the most common acute porphyria, it is nevertheless a rare disorder. Therefore, it is often misdiagnosed or
undiagnosed. Due to the nonspecific presentation of AIP, healthcare providers need to have a high initial index of suspicion to
recognize the classic symptoms and make the diagnosis.
Manisha, how does a patient who is experiencing an acute attack typically present to the healthcare system?
Dr Balwani: This is best illustrated using a case. A 24-year-old woman went to the emergency department (ED) after having a
tonic-clonic seizure at home. She had a recent history of abdominal pain, nausea, and vomiting, which had worsened over the
past 3 days; she also had back and chest pain. A physical examination showed her heart rate was 160 to 170 beats per minute,
indicating tachycardia. She was hypertensive and had significant proximal muscle weakness. She was afebrile. This is a classic
presentation of AIP, in which the patient arrives at the ED with severe symptoms.
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Clinical Issues in AIP: When to Suspect and How to Proceed CME/CE
AIP is much more common in women than in men. In women, AIP typically presents during the reproductive years (20 to 49 years
of age). More than 90% of patients with AIP present with severe, acute abdominal pain, which is a classic symptom of the disorder.
The pain is usually so severe that patients will rate it as a 10 on a scale of 0 to 10. Abdominal pain is often accompanied by pain in
the back, chest, or extremities, as was the case with our patient. Patients also typically have nausea and vomiting. Some patients
have constipation, but diarrhea is rare.
Acute onset of tachycardia and hypertension are also classic features of AIP and typically result from increased catecholamine
production. The appearance of hypertension in a patient who has no history of this condition may point to AIP as a diagnosis.
Patients with AIP may also experience headaches, confusion, or altered mental status. They may present with a seizure, as our
patient did.
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Severe muscle weakness is another common feature of AIP, as was seen in our patient. Muscle weakness is typically proximal, with
the upper extremities more commonly affected than the lower extremities.
Dr Erwin: In my experience, patients with muscle weakness who have very severe acute attacks can develop paralysis and
respiratory failure. If they are not treated appropriately, they can die.
Dr Balwani: That is correct. Muscle weakness can be progressive, so it is important to carefully monitor patients who present with
muscle weakness.
Dr Erwin: When patients like the woman in our case present to the ED, what are the first steps in assessing them?
Dr Balwani: The first thing to do, of course, is to stabilize the patient. The next step is to obtain a thorough patient history with the
goal of determining what might have precipitated the attack. Did the patient recently begin taking any new drugs or increase her
alcohol intake? Was anything else going on — such as fasting, dieting, surgery, or an illness — that could have precipitated the
event?
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Clinical Issues in AIP: When to Suspect and How to Proceed CME/CE
The physical examination is not always helpful. Patients typically have hypertension and tachycardia. Their abdominal pain
is neuropathic and presents differently than abdominal pain due to other causes. It is diffuse, with no tenderness, rebound
tenderness, or rigidity. Patients typically have no signs of infection.
Dr Erwin: What about laboratory test results?
Dr Balwani: Our patient had a normal complete blood count, which is what is usually seen during an acute attack. Although liver
enzymes are typically elevated during an acute attack, the increases are usually transient. The most striking laboratory feature is
hyponatremia. Our patient’s critically low sodium level of 130 mg/L is probably what caused her seizure. Hyponatremia may be a
clue to the diagnosis of AIP.
The patient was suspected of having hematuria, probably because her urine was dark or reddish in color, but her urinalysis results
were normal. Obviously, this means the patient did not have blood in her urine. The presence of porphyrins in her urine likely
turned it dark or reddish in color. Porphyrins in the urine can also provide a clue to the diagnosis. Patients should undergo a
complete gastrointestinal workup to rule out other causes of their symptoms. The results of our patient’s gastrointestinal workup
were normal.
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