The burden of familial chylomicronemia syndrome from the patients’ perspective

ABSTRACT

Background: Familial chylomicronemia syndrome (FCS) is a rare, inherited lipid disorder characterized by high levels of plasma triglycerides and chylomicrons, which may cause life-threatening acute pancreatitis. Currently no FDA-approved treatment exists. Management is low-fat diet (<20g fat/day), which is difficult to maintain. With the restricted diet, triglycerides may remain elevated. We conducted discussions with patients and caregivers to better understand the burden of FCS from their perspectives.

Methods: A panel of FCS patients and caregivers was assembled to discuss and assess the clinical and psychosocial burden of FCS.

Results: Ten adults with FCS (median age 48 yr) and their spouses/caregivers were asked specific questions about their experiences living with FCS. Patients with FCS stated their symptoms were abdominal pain, nausea, diarrhea, constipation, bloating, and fatigue. Patients reported a median of 34 episodes of acute pancreatitis over their lifetimes; half of these led to hospitalizations, each with an average stay of 6.5 days. The psychosocial burden of FCS was primarily associated with the restricted diet, anxiety and stress of FCS.

Conclusions: Living with FCS imposes a significant clinical and psychosocial burden on patients and caregivers, who reported reduced quality of life, limited employment opportunities, socialization and increased burden on family.

KEYWORDS:

• Burden of disease
• chylomicronemia
• familial chylomicronemia syndrome
• FCS
• hypertriglyceridemia
• lipoprotein lipase deficiency
• LPLD
• quality of life

1. Introduction

Familial chylomicronemia syndrome (FCS) is a rare, inherited metabolic disorder that is characterized by the abnormal presence of hyperchylomicronemia and severe hypertriglyceridemia (HTG) [1]. The most common cause of FCS, which is an autosomal recessive disorder, is the inheritance of two alleles for a loss-of-function mutation for the gene coding for lipoprotein lipase (LPL), an enzyme that catalyzes the hydrolysis of triglyceride (TG)-rich lipoproteins [1]. More rarely, other mutations such as apo CII, GBIHBP1, or LMF-1 mutations can also be the cause of FCS Abnormal LPL function results in a decreased breakdown of TGs. As a result, chylomicrons remain intact and accumulate in the plasma of patients with FCS [2]. This accumulation of excess large chylomicrons in the plasma are presumed to be the primary cause of acute pancreatitis in FCS.

Acute pancreatitis is the most serious physical manifestation of HTG, and the risk of acute pancreatitis increases as TG levels increase. In a recent study [3], HTG-induced acute pancreatitis was defined as TG levels above 1,000 mg/dL (11.3 mmol/L) or more than 500 mg/dL (5.65 mmol/L) in patients with an history of HTG. The higher the serum TG levels, the greater the likelihood of persistent organ failure and even death [3]. Following gallstones and alcoholism, severe HTG is the third most common cause of acute pancreatitis [4], accounting for approximately 10–20% of all cases [5,6]. According to one study, in comparison with patients with normal TG levels, FCS patients had a 360-fold greater risk of acute pancreatitis, and a 23-fold greater risk compared to patients with TG values of 443–~800 mg/dL, underscoring the need to reduce TG in this population [7].

A significant relationship between plasma TG concentration and incidence of acute pancreatitis was reported with the risk of acute pancreatitis increasing 3% [8] or 4% [9] for every 100 mg/dL increase in plasma TG. This is significant for patients with FCS because they often have TGs ranging from 500 to 1500 mg/dL, which increases the risk of acute pancreatitis from 15 to 200% (assuming normal TG below 150 mg/dL) [10]. The mortality rate for HTG-induced acute pancreatitis has been reported to range from 5 to 30% [1,3,11].

Although HTG is a fairly well-accepted risk factor for cardiovascular disease, there remains ongoing debate about the atherogenecity of chylomicrons, once thought too large to cross the vascular walls. However, cases of CVD have been reported in a number of FCS patients [12,13].

As with many rare diseases, the exact prevalence of FCS is unknown. Prevalence estimates are approximately 1–2 million [14,15], but the sample for this estimate is poorly understood. In the literature and clinical practice, FCS is referred to by several different names, further complicating the estimate of the size of the FCS patient population. Some commonly used synonyms for FCS include LPL deficiency (LPLD) and type 1 hyperlipoproteinemia (Table 1).

Table 1. Nomenclature used to describe familial chylomicronemia syndrome.

Chylomicronemia syndrome Chylomicronemia, familial Familial chylomicronemia Hyperchylomicronemia familial Hyperlipemia idiopathic Burger-Grutz type Hyperlipoproteinemia Type I Lipase D deficiency Lipoprotein lipase deficiency (LPLD) Burger-Grutz syndrome

Endogenous hypertriglyceridemia Familial fat-induced hypertriglyceridemia Familial hyperchylomicronemia Familial LPL deficiency Hyperlipidemia Type I (Fredrickson) Hyperlipoproteinemia Type IA Lipase D deficiency

Data from [1,16]

The most distinctive clinical feature of FCS is fasting hyperchylomicronemia that results in a milky appearance of plasma samples due to excessive lipids, called ‘latescent’ or lipemic plasma (Figure 1). Other clinical features of FCS may include eruptive xanthomas on the trunk and extremities, milky appearance of the vessels in the retina (lipaemia retinalis), recurrent abdominal pain, hepatosplenomegaly, acute pancreatitis [1], and fatigue [17]. In addition to clinical features, patients with FCS report significant impairments to quality of life. The most frequent cognitive and emotional symptoms were difficulty concentrating, ‘brain fog’, anxiety, fear, and worry [17].

Figure 1. Image of lipemic blood.

Accurate treatment and diagnosis is key for patients to receive treatment and support. An online survey of patients with FCS found that patients visit at least 5 physicians (range 1–30) before receiving a diagnosis of FCS [17]. Sixty-seven percent of patients reported receiving a misdiagnosis for their FCS symptoms [17]. A delay in FCS diagnosis puts patients at an increased risk for complications associated with FCS, including acute pancreatitis [10,14]. A recently published study using an online, anonymous survey of patients with FCS reports the lengthy journey to FCS diagnosis and the physical, psychological, and financial burden shouldered by patients [17]. What is not well understood is the overall profile of the person with FCS and how caregivers deal with this disease.

While the most acute signs and symptoms as well as comorbidities such as acute and recurrent acute pancreatitis have been well documented in this population, information related to the effects of this condition from the patients and caregivers perspectives is not well documented. We convened this panel of FCS patients and some caregivers to better understand and define the daily clinical and psychosocial burdens of FCS from the patients and caregiver perspective.

2. Patients and methods

Patients diagnosed with FCS were referred by lipid specialists or were self-identified and self-referred.

The participants (patients and caregivers) were assembled for a face-to-face panel discussion in Chicago, Illinois on 12 June 2016. Diagnosis of FCS was determined based on genetic analysis in five of the ten patients, but the actual mutation causing FCS was unknown. The remaining five patients reported receiving a clinical diagnosis by lipid specialists. Eight of the patients were accompanied by a spouse or caregiver. One caregiver of a young child with FCS attended. The patients were asked a series of prepared questions related to the clinical burden and psychosocial consequences of living with FCS (Supplemental Online Material). The questions asked were not developed from a validated instrument, as little to no research existed regarding the impact of FCS on the quality of life of patients. Instead, questions were based on advisory board proceedings with lipidologists who care for these patients and reported as common complaints. Patients were given the opportunity to ask questions, assuring understanding of questions and mitigating the need for determination of health literacy verification. Additionally, patients were generally well educated, many with advanced degrees. Follow-up discussions were conducted to further elucidate the responses the patients and caregivers provided and obtain clarifications and additional information. All responses were self-reported. At one point during the discussion, the caregivers were taken to a separate room and an identical set of questions related to the effect of FCS on relationships were asked of both patients and their spouses/caregivers separately. Responses to all questions were recorded and summarized.

3. Results

3.1. Patient summaries

A total of 10 FCS patients, six males and four females, participated in the advisory board discussion. The median age of this group of patients was 48 years, ranging from 26 to 67 years (Table 2). The first symptoms of FCS were self-reported to have appeared in the immediate postnatal period in three patients and, in one case, as a child (7 years old). The remaining six patients recounted developing symptoms of FCS as adults. The average patient-reported TGs ranged from 500 to 3100 mg/dL, which is well above the normal range [10].

Table 2. Demographics and characteristics of patients with FCS (N = 10).

Sex	Age (yrs)	Method of diagnosis	Age at onset of symptoms	Highest plasma TG value (mg/dL)	Average plasma TG value (mg/dL)
F	26	Genetic	7 yrs	3,000	700–800
M	36	Clinical	3 mo	4,800	1,200–1,800
M	37	Genetic	3 mo	2,600	500–700
M	46	Clinical	40 yrs	14,600	1,100
F	51	Genetic	20–25 yrs	4,400	1,200–1,800
F	57	Clinical	45 yrs	12,000	1,000
M	42	Clinical	8–10 yrs	27,000	1,000–2,000
M	50	Clinical	20–25 yrs	13,000	700–800
M	67	Genetic	49 yrs	9,000	2,600
F	55	Genetic	1.5 mo	26,000	3,100
Totals (Median)	48		15.5 yrs	10,500 mg/dL	1,300 mg/dL

The two most common clinical symptoms reported by patients with FCS were abdominal pain and fatigue. Other common symptoms were gastrointestinal: nausea, diarrhea, constipation, and bloating. Back pain, referred pain, headache, and fever were also reported. Most patients reported their symptoms appeared more frequently as they aged.

The total number of episodes of acute pancreatitis reported by patients with FCS across their life span (median age 48 years) ranged from 6 to 60 and included all reported cases managed at home and in the hospital (Figure 2(a)). It is notable that some patients reported they did not seek hospitalization for all episodes of acute pancreatitis ‘because I have been accused of drug and alcohol abuse by emergency room health care professionals.’ This indicates that current rates of acute pancreatitis based on hospitalization reports may underestimate the true number of episodes of acute pancreatitis for patients with FCS. Acute pancreatitis has been described as ‘severe abdominal pain’ and ‘unbearable abdominal pain’ by three patients with FCS. One caregiver noted ‘the pain becomes the family’s life. We all live around it and with it. Even if we catch it [acute pancreatitis] early, it’s still a week in the hospital.’

Figure 2. a) Impact of pancreatitis on patients with FCS (N = 10) and b) Self-Reported medical complications associated with 50% or more patients with FCS (N = 10).

Patients with FCS stated their average hospital stay was 6.5 days. The average hospital stay in the USA in 2012 was 4.5 days, with an average cost of $10,400 per stay [18]. Together, the 10 patients in this study reported approximately 180 hospitalizations for 395 episodes of acute pancreatitis and 1260 days in the hospital over their lifetime. Clearly, reducing the number of episodes of acute pancreatitis will greatly reduce the healthcare costs for patients with FCS.

The most commonly reported medical complications with FCS were pancreatitis, recurrent pancreatitis, fatty liver disease, gall bladder removed, type 2 diabetes, and liver and/or spleen enlargement (Figure 2(b)). Seventy percent (7 of 10) of patients stated their gallbladder had been removed due to misdiagnosis of gallbladder-induced pancreatitis. Additional clinical findings reported by individual patients included hypokalemia, hypocalcemia, cirrhosis of the liver, hypothyroidism, vitamin and mineral deficiencies, anemia, and gastric issues. All of the patients reported experiencing nausea and daily pain, typically abdominal, that is ‘relatively low level (1–2 on a five-point scale), but can quickly worsen.’ At times, such pain can increase to the point of being debilitating.

All of the patients with FCS who participated in the advisory board reported they followed an extremely restricted low-fat diet in an attempt to minimize symptoms of FCS. Four of the patients followed a diet with a goal of <10 g of fat per day. The remaining patients used a goal of <20–25 g of fat per day. A common remark from patients was ‘it’s the hardest diet to follow’ (Figure 3). Considering the extremely restrictive diet, finding appropriate fat-free foods and navigating social activities is difficult and satisfaction with the fat-restricted diet was reported to be low (30%). Patients were uncertain about the benefits of the diet for reducing symptoms of FCS and stated ‘the most discouraging thing is that we work our butts off [to maintain a strict diet], and we are still only treading water.’ Ninety percent (9 of 10) of the FCS patients agreed or strongly agreed that they still have symptoms of FCS while adhering to the low-fat diet.

Figure 3. Patient sentiments regarding the restricted low-fat diet for FCS (N = 10).

Eighty percent (8 of 10) of the patients indicated that compliance with the low-fat diet was difficult or very difficult, particularly when away from home. The low-fat diet also affects other members of the household and limits social interactions. One caregiver reported that her spouse was afraid to leave the house because of his sense of losing control of what he ate. She finally told him, ‘I can’t stay home for the next 30 years worrying about what you are going to eat.’

Ninety percent (9 of 10) of patients with FCS indicated they still work at least part time. However, most of the patients stated that FCS limited their job performance in some way (Figure 4). Fatigue and failure to concentrate due to pain were cited by the majority of patients. One patient had to change his occupation due to an inability to handle the physical aspects of his job. Another patient remarked ‘I went to college for firefighting but was not able to pursue this career because of fatigue and muscle pain.’ Frequent absences from the job due to symptoms of FCS resulted in more work stress upon their return. Concerns about diet and fear of acute pancreatitis limit the ability to travel, particularly internationally. Dietary issues also restrict attendance at meetings where food is served. One patient remarked ‘you can push things around on your plate and pretend to drink for only so long before someone notices.’

Figure 4. Patient reported impact of FCS on school and work (N = 10).

Symptoms of FCS have also affected the ability of patients to advance in their careers. Patients noted that the need for insurance and healthcare coverage has limited their job choices. Some patients chose not to pursue or were unable to complete graduate programs in their chosen fields due to the symptoms of FCS. One caregiver stated ‘he had to take a lot of time off during graduate school. We had to be in graduate school for 7 years due to the time off with pancreatic episodes of pain. He eventually couldn’t finish his PhD because of the illness and stopped at a master’s degree.’

In some cases, patients were unable to work in preferred careers due to the physical limitations imposed by FCS. Frequent absences may negatively impact an employee’s promotion or overall work appraisal. Patients with FCS reported they are dependent upon the good will and understanding of their employers for retaining their jobs. Similar findings were reported in a recent study [17], which found the career choice of 91% of patients with FCS was affected by the disease. In addition, this same report found patients with FCS missed an average of 30 days of work per year due to their disease [17], compared to 4.9 sick days for the average American [19,20]. The greater number of absences from work reduces work performance and puts a large burden on both patients with FCS and their employers [17].

The limitations that FCS imposes on employment also affect caregivers and households. Family vacations were reported to be limited by the need to use vacation days as sick leave. Caregivers reported using their own vacation time to care for patients during complications of FCS. Caregivers also expressed anxiety about seeing their loved ones going to work while sick to avoid missing a day of work.

Caregivers were asked about the effect of FCS on the social life of the couple or family. Caregivers reported that their social life was limited by symptoms of FCS, particularly fatigue, and the dietary restrictions imposed by this condition. Maintenance of the extremely strict low-fat diet is a preoccupation in the households of patients with FCS and failure of friends and family to understand the seriousness of FCS as a major stressor. Some caregivers have difficulty adjusting to the curtailment of social life that can result from FCS, imposing additional stress on the relationship.

Both patients and caregivers were asked to describe the effect that FCS has had on their relationship. In general, patients felt that the shared experience of FCS had drawn couples and families closer together. Several patients stated that the caregiver in the relationship has adapted to whatever lifestyle changes are necessary to deal with FCS and, in several cases, has been the point person seeking information, identifying appropriate health care personnel, and dealing with insurance companies. Four patients credited their caregivers with their survival. There was some concern by the patients that the burden imposed on caregivers is too much, and that the caregivers lack support. Two patients expressed concerns that their caregiver does not really understand their disease and sometimes acts inappropriately, particularly with regard to diet.

Caregivers comments regarding the effect of FCS on relationships were more mixed. Two caregivers felt that their relationship with the patient was unaffected or even strengthened by FCS. One caregiver stated that her spouse thought that pushing her away was better. Another stated that the spouse worried about the caregiver leaving. Another caregiver expressed concerns about the isolating effects of being a caregiver since the spouse with FCS was scared to leave the house. Two caregivers stated that they have sought outside psychological counseling to help cope with their burden. Clearly, living with someone with FCS has impacted relationships.

Both patients with FCS and caregivers were asked what any future therapy developed for FCS would do for them. Patients expressed the hope that a future therapy would reduce their pain and symptoms, improve their quality of life, and stay out of the hospital. Several patients also expressed a wish for a less stressful, more normal lifestyle that includes socialization and a more normal diet. Five of the patients hoped that any future therapy would improve their TG values and treat the underlying disease, not just the symptoms. When caregivers were asked what they hoped a future therapy could do for their loved ones, their replies echoed those of the patients.

Living with FCS is challenging. To better understand the burden of FCS on patients, we have included the experiences of two different patients with FCS.

3.2. Patient experiences with FCS

Patient 1 is a 26-year-old woman who states she was diagnosed with FCS at 5 weeks of age. Patient 1 recalls her TG levels average 700–800 mg/dL, and have ranged from 400 to 30,000 mg/dL. She characterizes FCS as having been relatively mild throughout her childhood. However, she reports her day-to-day symptoms were exacerbated during college, when she experienced severe fatigue. On a daily basis, Patient 1 describes enduring a dull ache in her mid-abdomen and nausea. Starting from an early age, she recounts 30 episodes of pancreatitis for which she has been hospitalized, and has managed one case at home. Her medical complications include nonalcoholic fatty liver disease, type 2 diabetes, splenomegaly, peripheral vein scarring, and low K/Ca levels. To manage FCS, Patient 1 describes following a strict diet of fewer than 20 g of fat per day. She notes this restricted diet is very difficult to maintain and unsatisfying; even on this diet she reports symptoms that impact her quality of life. She has a degree in dietetics and works full-time as a nutritionist. She has consulted with numerous dieticians and reports feeling frustrated because her dietitian’s understanding of the nutritional requirements of FCS is inadequate. She expressed her frustration with the diet by saying, ‘… It’s not just no or low fat diets [that patients need] – sugar matters!’ Patient 1 would like to pursue a more fulfilling career, but her concerns regarding healthcare benefits make her apprehensive about taking the ‘next step.’ In her daily life, FCS causes strain in her relationship with her boyfriend because he is constantly monitoring her diet. If a therapy existed for FCS, she hopes it would allow her to ‘stay out of the hospital’, and alleviate daily symptoms of fatigue and back pain.

Patient 2 is a 46-year-old man who first reported abdominal pain and constipation at 40 years of age (Figure 5(a)). He recounts his condition was diagnosed as acute pancreatitis and he states his TGs average 1,100 mg/dL, and have ranged from 200 to 14,600 mg/dL. He remarks his disease has progressed rapidly, aggressively, and unpredictably. On a daily basis, Patient 2 reports experiencing significant temperature fluctuations, flushing, fatigue, back pain, and headaches. He relates his symptoms are more frequent and often ‘unbearable,’ to the extent that he states he has been hospitalized 16 times in the past 9 months and receives regular plasmapheresis therapy. He reports 40 hospitalizations for a total of 40–50 episodes of pancreatitis, each hospitalization is about 5 days. He notes he ‘bypasses the emergency room whenever possible’ because he has been accused of drug and alcohol abuse by emergency room healthcare professionals. Patient 2 is happy he has been able to identify a strong medical team that consists of a primary care physician and a lipidologist. He believes this team is critical as his medical complications include nonalcoholic fatty liver disease, type 2 diabetes, gallbladder removal surgery, cysts on pancreas, neuropathy in his feet, cataracts, glaucoma, and a slow-moving gastric system. He reports managing FCS by eating less than 10 g of fat each day. He is frustrated because adherence to the strict diet does not correlate with episodes of pancreatitis. For example, he notes chicken seems to be a ‘trigger food’ for him. Patient 2 relates that FCS has affected his quality of life and personal identity. He grew up in a self-described ‘blue-collar home’ where men worked and provided for their families. He says he is often depressed because he is unable to perform in this role. He has been on disability from his former roles in manufacturing and building for the past 2 years. If a therapy existed for FCS, Patient 2 hopes it would eliminate the substantial pain he feels on a daily basis. He ‘… would do anything to get back [his] previous quality of life.’ His wife is his caregiver and is a strong source of moral support for him. She is the primary breadwinner and has advocated for a diagnosis, argued with payers, and fought for more information about FCS.

Figure 5. a) Profile of patient 2 with FCS and b) Statements from patients with FCS.

4. Discussion

This qualitative observational study found that the clinical and psychosocial burdens of FCS reduce the quality of life, social interactions, and limit employment opportunities of patients. This study extends the report of an online survey [17] to provide a better understanding of the factors that contribute to a reduced quality of life from the perspective of patients with FCS and their caregivers. Currently, there is no FDA-approved therapy indicated for the treatment of FCS. Management strategies to control symptoms associated with FCS have traditionally focused on aggressively restricting dietary consumption of fat and simple carbohydrates, abstinence from alcohol, as well as the avoidance of drugs known to raise TG levels such as thiazides, beta-blockers, and estrogen. Traditional lipid-lowering therapies such as fish oil, fibrates, and niacin are only minimally effective in the FCS population as in large part they reduce plasma TG levels by reducing hepatic output of very low-density lipoproteins (VLDL) and/or by enhancement of LPL activity [14,21]. It was evident from the patients’ and caregivers’ statements that much of the psychosocial burden of FCS is a direct result of following the strict diet and not knowing if/when patients will experience debilitating symptoms (i.e. pancreatitis, fatigue, abdominal pain) of FCS (Figure 5(b)). Adherence to the strict diet is reported to be very difficult, especially when eating outside of the house. Ninety percent of the participants indicated they consistently live with the anxiety, fear, and knowledge that even when they follow the strict diet they may still experience symptoms that impact their quality of life. TG levels frequently remain high even when patients with FCS adhere to the strict diet. These findings corroborate previous work [17], which reported patients experienced anxiety/fear/worry; out of control/powerless; and feeling sad/down/blue/depressed and socially isolated due to FCS.

The most common clinical symptoms reported by the patients in the advisory board were abdominal pain and fatigue, which they experience frequently. Some patients interviewed also experienced diarrhea, constipation, bloating, back pain, referred pain, headache, and fever. These common symptoms agree with those reported by patients in an online survey [17]. All patients reported experiencing daily nausea and low-level abdominal pain that could quickly worsen and sometimes become debilitating. Most patients felt the frequency of their symptoms have increased as they have gotten older.

There are limitations to this study. First, only a small group of people with FCS were interviewed. All data were self-reported, and not independently verified. The study was unstructured and the methodology was qualitative. Last, participants were recruited through physicians and by word of mouth. It is possible there is some selection bias including the selection of only patients that had experienced acute pancreatitis as a part of the patient panel; and the patients and caregivers willing to participate in this discussion suffered more than average from FCS. Nevertheless, this survey provides the first face-to-face look into the effects of FCS on the lives of patients and their caregivers.

Due to the heterogeneous nature of FCS and the limited guidance in the literature on diagnostic criteria, it is not surprising that physicians who encounter FCS may not be familiar with diagnosing this rare condition. Patients are often misdiagnosed and journey through multiple physicians prior to receiving a diagnosis of FCS [17]. A majority of patients from the advisory board (70%) indicated their gallbladder was removed due to misdiagnosis of gallbladder-induced pancreatitis.

Patients also reported that friends and family often do not understand the seriousness of FCS or have difficulty adjusting to the curtailment of social life that can result from FCS, imposing additional stress on these relationships. Such comments indicate a need to provide patients with educational tools for their friends, family, and the broader community about FCS as a chronic, lifelong disease that has considerable clinical and psychosocial burdens. One avenue for patient and caregiver support is through groups such as the FCS Foundation [22], LPLD Alliance (UK) [23], and the National Organization for Rare Disorders (NORD) [24].

In summary, our interviews and discussions with patients with FCS and caregivers indicate that the more symptoms each patient experiences, the more FCS affects their ability to function and all aspects of their quality of life including social life, family life, schooling, career choices, employment opportunities, and career advancement. Above all, patients with FCS state they want less pain, better control of the symptoms of their disease, and fewer hospitalizations. These factors will decrease their stress and enable them to have a more normal lifestyle that includes socialization, opens up career possibilities and allows them to eat a more normal diet. Patients and caregivers hope that any new therapy would improve both the clinical symptoms of FCS as well as the quality of life of patients, particularly with regard to socialization and diet.

5. Conclusions

FCS and its associated symptoms impose considerable clinical and psychosocial burdens on patients that reduce their quality of life and limit employment and social opportunities, as summarized in Table 3. Acute pancreatitis is the most serious complication of FCS, which causes debilitating pain, anxiety and frequent hospitalizations that disrupt patients’ lives. Abdominal pain and fatigue are the most common clinical symptoms associated with FCS. Much of the psychosocial burden of FCS is associated with the strict diet and lifestyle changes imposed by this condition, which limits socialization and increases the burden on caregivers and the family. Patients with FCS want better control of the symptoms of their disease and a more normal lifestyle. There is a need for an effective method to control the symptoms of FCS and reduce the clinical and psychosocial burdens of this condition.

Table 3. Factors contributing to a reduced quality of life in patients with FCS.

Effect of low-fat diet Compliance with the diet is difficult; particularly when not at home Diet affects other members of the household and limits socialization Satisfaction with the diet is low Patients are not convinced that the diet is beneficial for reducing symptoms Financial cost of purchasing fat-free foods Burden of time required to research fat-free options and prepare fat-free meals

Effect of FCS on jobs and careers Fatigue and inability to concentrate due to pain can limit performance Frequent job absences can impede promotion Concerns about diet limit the ability to travel on the job Need for healthcare and insurance limits job opportunities Symptoms of FCS limit ability of patients to train for or perform work in a preferred career

Effect of FCS on social life Fatigue and dietary lifestyle considerations associated with FCS limit social life Failure of friends and family to understand the seriousness of FCS is a major irritant Some caregivers have difficulty adjusting to a reduced social life

Key issues

• Familial Chylomicronemia Syndrome (FCS) is a rare, inherited metabolic disorder that is characterized by the abnormal presence of hyperchylomicronemia and severe hypertriglyceridemia.

• Management of FCS is through an extremely restrictive, low-fat diet.

• The clinical burden of FCS includes chronic abdominal pain and pancreatitis. Acute pancreatitis causes debilitating pain, anxiety, loss of employment, and hospitalizations.

• The psychosocial burden of FCS is primarily due to diet, stress and anxiety.

• We conducted interviews with 10 FCS patients (6 male, 4 female; median age 48 years) and their caregivers to better understand the enormous daily clinical and psychosocial burdens of FCS from the patients perspective.

• The average patient-reported triglycerides ranged from 500 to 3100 mg/dL. The highest values of patient-reported plasma triglycerides ranged from 2,600 to 27,000 mg/dL.

• All of the patients with FCS reported following reduced-fat diets: four patients followed a diet of <10g fat/day and the remaining patients used <20-25g fat/day. Eighty percent of patients indicated that compliance with the low-fat diet was difficult or very difficult. Ninety percent of patients agreed or strongly agreed that symptoms of FCS persist while adhering to the low-fat diet.

• The most common symptoms reported by patients with FCS were abdominal pain and fatigue. All of the patients reported experiencing nausea and daily pain, which can be debilitating.

• The median number of episodes of acute pancreatitis reported by patients with FCS was 34, which resulted in average hospital stays of 6.5 days for each episode of acute pancreatitis.

• FCS reduces the quality of life of patients and limits employment opportunities. Nine of the ten patients with FCS indicated they work at least part time. Most patients stated that FCS limited their job performance due to fatigue and failure to concentrate because of pain. Some patients chose not to pursue or were unable to complete graduate programs or work in their chosen fields due to the symptoms of FCS. Frequent absences from work are sometimes viewed negatively when patients with FCS are considered for promotion. Patients are dependent upon the good will and understanding of their employers for retaining their jobs.

• Caregivers reported that their social life was limited by symptoms of FCS, particularly fatigue, and dietary restrictions.

• Patients with FCS want better control of their symptoms and a more normal lifestyle.

Declaration of interest

A Brown has received Speaker Honoraria from Amgen, Merck, Regeneron, and Sanofi, been on the Advisory Board for Akcea, Amgen, Astra Zeneca, Kowa, Merck, Pfizer, Regeneron, Sanofi, and received a modest honorarium for participating in the faculty panel discussion at the Chicago Patient Advisory Board. A Gelrud received honorarium for consulting and speaker fees from AbbVie and Akcea Therapeutics. He also has received a research grant from Dompe and royalties from UpToDate, and he received a modest honorarium for participating in the faculty panel discussion at the Chicago Patient Advisory Board. A Gilstrap, A Hsieh and K Williams are employees of Akcea Therapeutics. A Gwosdow is a medical writer who received payment from Akcea Therapeutics. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Acknowledgments

First and foremost we acknowledge and thank the patients and caregivers who participated in the Chicago Patient Advisory Board meeting. Without their contributions this publication would not be possible. We appreciate the participation of Joyce Ross from the National Lipid Association and Tricia Mullins (formerly of Global Genes) for their attendance and contribution to the patient meeting. We thank Kim Clark (Akcea Therapeutics) for writing the cases.

Writing support was provided by Andrea Gwosdow, Ph.D. of Gwosdow Associates Science Consultants, LLC and Joe Melton, who was employed by Med Val. All writing support was funded by Akcea Therapeutics.

The Chicago Patient Advisory Board meeting was funded by Akcea Therapeutics. Patients and caregivers were not paid to attend the Chicago Patient Advisory Board meeting; travel expenses for patients and caregivers were provided by Akcea Therapeutics.

Supplemental data

Supplemental data for this article can be accessed here.

Additional information

Funding

This article was funded by Akcea Therapeutics.