The blood of patients with familial chylomicronemia syndrome (FCS) can appear milky in color (lipemic) due to the buildup of fat in their body. Image courtesy of Akcea Therapeutics.
In many cases, the diagnosis and management of patients with rare diseases can require the participation of cardiologists in collaboration with a diverse team of other medical specialists. Examples of rare diseases that often involve cross-specialty collaboration include Duchenne muscular dystrophy, Fabry disease and familial chylomicronemia syndrome (FCS). Despite progress to increase awareness of these rare diseases, symptoms can often be associated with much more common diseases while clinician exposure to rare cases can be limited. As a result, patients often experience delayed diagnosis or misdiagnosis – often until symptoms become severe. In addition, while we are seeing encouraging progress in the clinical development of new treatments including some potentially curative therapies, it is often the case that available treatment options for rare diseases involve lifetime therapies and correlative strategies in patient monitoring and management that must involve a multidisciplinary approach to optimize compliance and long-term health.
Strategies for effective cross-specialty collaboration in the management of these types of patients has advanced through multispecialty protocol development and enabling technologies that can be shared among specialists in different locations. But the engagement of multiple specialists in the management of patients presents significant challenges. In some cases, lines of responsibility and decision-making procedures can be complex. Patients may not be well informed about the role of each specialist in their care. They may also fail to discuss relevant issues with all or the appropriate members of their care team. In recent years, progress in research coupled with the development of limited but useful management strategies for people living with FCS have reinforced both the need for and inherent advantages in a cross-disciplinary approach to care for patients with FCS as well as other rare diseases.
Journey to an FCS Diagnosis
Familial chylomicronemia syndrome is a rare genetic disease characterized by the buildup of chylomicrons (chylomicronemia), the largest lipoprotein particle, which are responsible for transporting dietary fat and cholesterol. Typically, the enzyme lipoprotein lipase (LPL) breaks down chylomicrons in the blood., However, in people living with FCS, LPL does not function properly. This inability to break down chylomicrons[1-3] leads to an increase in triglyceride (TG) levels. Normal TG levels are <150 mg/dL (or 1.7 mmol/L). With FCS, TG values can rise to 10 times this level, even with lipid-lowering medication or efforts to maintain a restricted low-fat diet. The buildup of lipids leads to several debilitating symptoms including fatigue, chronic pain, cognitive impairment, abdominal pain and potentially fatal attacks of pancreatitis. There is currently no effective therapy available for FCS.
The most severe risk for FCS patients is acute or chronic pancreatitis. Acute pancreatitis occurs in up to 70 percent of patients with FCS, with half having recurrent episodes. Up to 50 percent of patients who have an attack of pancreatitis will require an ICU admission. Episodes can occur as frequently as every few weeks or months, often resulting in pain that is self-reported by patients as excruciating and intolerable. Recurrent pancreatitis can lead to several complications and long term may lead to development of diabetes mellitus and chronic pancreatitis.
The fact that pancreatitis in the setting of elevated TG levels is associated with more common conditions, including diabetes mellitus, alcoholism, hypothyroidism, other dyslipidemias and use of certain medications, makes the diagnosis of rare conditions such as FCS challenging, even among pancreatic specialists. Evolving guidelines suggest that FCS should be considered in patients who present with pancreatitis or severe abdominal pain with high TG levels that have not responded to treatment with lipid-lowering drugs. Efforts to build broader awareness of FCS across specialties including cardiology, gastroenterology and endocrinology can play an important role in helping at-risk patients advance to a more timely diagnosis.
The Benefits of Cross-specialty Care
Optimal inpatient management of acute pancreatitis associated with severe hypertriglyceridemia typically requires a multidisciplinary approach that involves pancreatic specialists, GI surgeons, cardiologists, endocrinologists, and dieticians together with hospitalists/primary care physicians. Women who experience pancreatitis may also require support from additional specialists including OB-GYN. Management strategies involve intravenous hydration, antiemetics, analgesics, and in severe cases enteral or parenteral nutrition, ventilator and renal support, and monitoring of any secondary complications. Treatment of severe hypertriglyceridemia-induced acute pancreatitis may also include the use of plasmapheresis or insulin in the critically ill patient in the ICU.
In FCS, the involvement of different specialists can help streamline care, which includes a rigorous exercise regimen, strict low-fat diet, and screening of other family members that might be affected. Cardiologists as lipid specialists are positioned to manage TG levels while gastroenterologists can work to manage abdominal pain and other gastrointestinal symptoms. Dieticians provide the needed support to maintain a very low-fat restrictive diet. And primary care physicians work to coordinate overall care and patient access to as-needed specialty care and support services. In addition, knowledge that FCS is refractory to lipid-lowering medications such as niacin and fibrates due to the loss of lipoprotein lipase activity1 can reduce the risk of inappropriate use of these medications. Specialists from the different disciplines also have an important role in updating patients with FCS as well as each other about advances in research and opportunities to participate in clinical trials.
The Continuing Unmet Need in FCS
The importance of close collaboration among specialists is reinforced by challenges in the lack of available treatments in FCS and by advances in research that could change the treatment dynamic in the future. The only therapeutic option to manage TG levels in FCS patients is an extremely restrictive low-fat diet, limited to intake of 10 to 20 grams of fat per day. (There are 14 grams of fat in a single tablespoon of olive oil.) Most patients find this diet very difficult to maintain long term, resulting in a significant impact on their emotional health and quality of life. Compliance is further challenged by the fact that patients who adhere to a restrictive diet can still experience episodes of pancreatitis. A multidisciplinary approach in FCS can play an important role in outlining all elements of an optimal treatment strategy for each patient while reinforcing the importance of compliance despite demonstration of continued risk and sometimes limited efficacy benefit.
While potentially challenging, the effort to maintain a cross-specialty approach when caring for familial chylomicronemia syndrome and other rare disease patients can deliver significant benefits. As researchers continue to make progress in the development of new and more effective treatment options, these benefits may impact the role of each specialist. For example, treatment shown to reduce the incidence of pancreatitis could limit the level of engagement required by pancreatologists, while the need to monitor TG levels regularly could position cardiologists or lipidologists as well as primary care providers and dietitians to take a more active role. The bottom line is that with close collaboration, all members of a patient’s care team can be positioned to provide the targeted support and engage in the essential levels of communication that can continually optimize outcomes.
Editor's note: Steven D. Freedman, M.D., Ph.D., is a gastroenterologist in Boston, Mass. He serves as the chief of the division of translational research and director of The Pancreas Center at Beth Israel Deaconess Medical Center. He is also a professor of medicine at Harvard Medical School and works in the Division of Respiratory Diseases and Cystic Fibrosis Center at Boston Children’s Hospital. Freedman is a leading expert in the clinical and basic science research of diseases such as acute and chronic pancreatitis and cystic fibrosis. Dr. Freedman holds a Ph.D. from Yale University School of Medicine and an M.D. from the University of Connecticut School of Medicine. He completed his residency and fellowship in gastroenterology at Beth Israel and has remained on faculty since 1991.
1. Brahm AJ, Hegele RA. Chylomicronaemia – current diagnosis and future therapies. Nat Rev Endocrinol. 2015;11(6):352-362.
2. Gaudet D, Brisson D, Tremblay K, et al. Targeting APOC3 in the familial chylomicronemia syndrome. N Engl J Med. 2014;371(23): 2200-2206.
3. Chait A, Brunzell JD. Chylomicronemia syndrome. Adv Intern Med. 1992;37:249-273.
4. Bijvoet SM, Bruin T, Kastelein JJ. The familial hyperchylomicronaemia syndrome. Neth J Med. 1993;42(1-2):36-44.
5. Blom D. Hypertriglyceridaemia: aetiology, complications and management. JEMDSA. 2010;15(1):11-17.
6. Gaudet D, Blom D, Bruckert E et al. J Clin Lipidology 2016; 10:680.
7. CMFB Patient Comment: Pancreatitis Symptoms. Available at: http://www.medicinenet.com/pancreatitis/patient-comments-36-page3.htm.
8. Banks PA et al. Classification of acute pancreatitis--2012: revision of the Atlanta classification and definitions by international consensus. Gut 2013;62:102-111