Looking for Zebras: Nurse Practitioners Considering Rare Diseases in Their Differential Diagnoses

Learn more about acute hepatic porphyria and the other approximately 7,000 rare diseases affecting Americans.

The National Institutes for Health (NIH) and the U.S. Food and Drug Administration (FDA) jointly recognize Rare Disease Day on Feb. 28 as FDA-NIH Rare Disease Day. On NIH’s website, the announcement of this year’s joint effort states that “FDA-NIH Rare Disease Day aims to provide the rare disease community — patients, caregivers, families, patient advocate groups, researchers, clinicians, health care providers and trainees/students — with information relevant to their lived experiences, including activities by FDA and NIH that promote research and product development for this population with unmet health needs.”

On the latest episode of NP Pulse: The Voice of the Nurse Practitioner®, “Acute Hepatic Porphyria: Beware the Zebra,” nurse practitioner (NP) experts Laurie Connors, PhD, DNP, FNP-BC, AGN-BC, AOCNP, FAANP, FAAN, and Paula Tucker, PhD, DNP, FNP-BC, ENP-C, FAANP, discuss keeping rare diseases in mind during diagnosis. In their conversation, they talk about rare diseases in general but focus on acute hepatic porphyria (AHP) in particular.

Tucker explains that “As an emergency NP, I often have the privilege of caring for patients in acute conditions. Having the opportunity to provide awareness on this rare and often misunderstood condition is truly a privilege. You see, as clinicians, we're taught early on to think of horses, not zebras, particularly when we hear hoof beats. In other words, when a patient presents with symptoms, we focus on the most common and likely causes rather than rare diseases. But sometimes that approach leads us to miss something crucial, and that's exactly what happens with AHP.”

Understanding AHPs

Connors clarifies that the diseases we call AHPs “are primarily caused by a genetic variant. This occurs in one of the enzymes involved in heme biosynthesis in the liver. This may sound complicated. In simple terms, one of the enzymes in the heme pathway does not work properly. Heme is essential to our body and is necessary for the liver to function. In the liver, the heme pathway is controlled by the enzyme ALAS1. With AHP disease, what happens is there's an accumulation of ALAS1, and the enzyme is not able to keep up. This leads to an accumulation of neurotoxin intermediates — a buildup of toxins called porphyrins in the liver.”

We also know, according to Tucker, that “80% of cases occur in women between the ages of 15 and 45. This means that when a young female presents with severe unexplained abdominal pain, we need to expand our differential beyond the usual suspects like appendicitis, pancreatitis, cholecystitis, irritable bowel syndrome. If we don't, we risk overlooking a potentially life-threatening condition.” As Connors also points out, “Diagnosis is a challenge. Diagnosis is often delayed — misdiagnosis or missed diagnosis altogether. The average time from symptom onset to establishing definitive diagnosis is 15 years. Consider how many episodes this individual has experienced in order to get to that diagnosis.”

Fortunately, NPs and other health care providers have tools to treat AHP. Tucker describes the three main goals of treatment: “First, we aim to treat acute attacks, stopping symptoms and stabilizing the patient. Second, we focus on reducing the risk of future attacks, which means helping patients avoid triggers and using preventive treatments when needed. Finally, we look at pharmacotherapies to prevent attacks for patients with recurrent symptoms, along with cascade screening and genetic counseling to help family members understand their risk.”

Rare Disease Day Resources

AHP is just one of many rare diseases that, in total, affect “between 25 and 30 million Americans,” states the National Organization for Rare Diseases (NORD) website. “This equates to 1 in 10 Americans, or one on every elevator and four on every bus.” NORD also states that “Of the 7,000 known rare diseases, approximately 95% have no treatment.” NPs are uniquely equipped to care for patients with a rare disease “by removing barriers to evaluation and prioritizing communication between the patient and their care team. NPs provide accessible, affordable and high-quality care to patients with rare diseases.” Members of the American Association of Nurse Practitioners® (AANP) have access to materials like a practice brief about genetic counseling, and an NP tool and a downloadable resource on AHP.

NPs and their families everywhere can take part in raising awareness of AHP and other diseases on Rare Disease Day. The “Show Your Stripes” campaign (#ShowYourStripes) calls on advocates to wear striped clothing and then to “take a picture of your striped look and share it on social media with the hashtags #ShowYourStripes and #RareDiseaseDay to join this celebration of the many faces of rare disease.”