Research Article
Open Access
Subtyping Patients with Myalgic Encephalomyelitis (ME) and
Chronic Fatigue Syndrome (CFS) By Course of Illness
Jamie Stoothoff *, Kristen Gleason , Stephanie McManimen , Taylor Thorpe and Leonard A. Jason
Center for Community Research, DePaul University, Chicago, IL, USA
*Corresponding author: Jamie Stoothoff , Center for Community Research, DePaul University 990 W. Fullerton Ave., Suite 3100 Chicago, IL, USA 60604-2201, Tel.: (773) 325-2018;Fax: (773) 325-4923
E-mail:
@
Received: March 22,2017; Accepted: June 08,2017; Published:June 26,2017
Citation: Jamie Stoothoff, Kristen Gleason,et.al. (2017) Subtyping Patients with Myalgic Encephalomyelitis (ME) and Chronic Fatigue Syndrome (CFS) By Course of Illness. J of Biosens Biomark Diagn 2(1):1-9 DOI: 10.15226/2575-6303/2/1/00113
Abstract
Past research has subtyped patients with Myalgic
Encephalomyelitis (ME) and Chronic Fatigue Syndrome (CFS)
according to factors related to illness onset, illness duration, and
age. However, no classification system fully accounts for the wide
range of symptom severity, functional disability, progression, and
prognosis seen among patients. This study examined whether illness
trajectories among individuals with CFS were predictive of different
levels of symptomology, functional disability, and energy expenditure.
Of the participants (N=541), the majority described their illness as
Fluctuating (59.7%), with 15.9% Constantly Getting Worse, 14.1%
Persisting, 8.5% Relapsing and Remitting, and 1.9% Constantly Getting
Better. The illness courses were associated with significant differences
in symptomology on select domains of the DSQ, functioning on select
subscales of the SF-36, and on overall levels of energy expenditure.
The significant symptomatic and functional differences between
groups suggest that subtyping patients with CFS according to illness
course is a promising method for creating more homogeneous groups
of patients.
Keywords: Myalgic Encephalomyelitis; Chronic Fatigue Syndrome; Subtypes; Illness Course;
Keywords: Myalgic Encephalomyelitis; Chronic Fatigue Syndrome; Subtypes; Illness Course;
Introduction
Subtyping Patients with Myalgic Encephalomyelitis
(ME) and Chronic Fatigue Syndrome (CFS) by Course
of Illness
Myalgic Encephalomyelitis (ME) and Chronic Fatigue
Syndrome (CFS) are debilitating illnesses, often presenting with
neurological, immunological, gastrointestinal, musculoskeletal
and hormonal symptoms [1-4]. The severity of symptoms and
levels of functional disability experienced can vary drastically
from patient to patient, suggesting there may be distinct clinical
courses that have yet to be identified. In the most extreme
cases, patients are bedbound and depend entirely on caretakers
for support. Community based studies have determined that
approximately 25% of patients are housebound and 64.3% are
on disability, with only 15.1% of patients currently employed
[5-7]. In short, those diagnosed with these illnesses represent
a heterogeneous group of individuals who experience differing
patterns of symptom severity and levels of functional disability
[8].
It is possible that combining potentially diverse patient subtypes into one sample pool may account for the inconsistent findings and the lack of reproducibility that has often plagued research related to the etiology, diagnosis, epidemiology, and treatment of ME and CFS [8]. Past studies have attempted to categorize patients based on type of illness onset [9-11], the duration of the illness, and the age of patient [12-15]. However, there is no classification system yet that fully accounts for the diversity of symptom severity, functional disability, progression, and prognosis of this illness. It is, therefore, pertinent to further explore methods of subtyping individuals with ME and CFS in order to more accurately describe the wide range of patient experiences.
Research has distinguished between two different onset patterns: 1) sudden onset, in which symptoms appear over a few days or weeks and 2) gradual onset, in which symptoms develop over a period of months or years. Sudden onset has often been linked with viral and infectious illnesses [16], including: Epstein- Barr Virus infection (EBV) and enterovirus infections [17,18]. One study found that patients who experienced a sudden onset had poorer health outcomes than patients who described their onset as gradual [9]. Conversely, other findings suggest that patients with a sudden onset have a better prognosis than those with a gradual onset, while others have found no significant differences in prognosis between sudden and gradual onset subgroups [10-12]. With such a range of mixed results, subtyping patients by type of onset cannot fully account for the variability seen in symptom severity and the course of the illness.
Additionally, researchers have explored illness duration and current age as related factors that may impact prognosis and symptom severity. Research has found that patients with a longer illness duration (10 years or more) experienced poorer cognitive functioning compared to those with a shorter illnessduration (7 years or less) [13]. However, another study has found that the physical functioning of patients tended to improve over the course of their illness [14]. Further studies were unable to reproduce these findings and have suggested that the length of the illness experience does not have a significant effect on patient outcomes [12]. In general, older age has also predicted poorer prognosis among patients [15]. In one study, researchers sought to examine how both age and duration of illness can interact to affect illness severity and functioning. Within this sample, older patients with longer illness duration (10 years or more) displayed better mental health functioning than younger patients and older patients with shorter illness duration. However, younger patients with an illness duration of 10 years or more reported more severe immune and autonomic symptoms than older patients whose illness experience also spanned 10 years or more [16].
The categorization system developed to describe differing clinical courses in patients with Multiple Sclerosis (MS) is an illustrative example of the importance of defining subtypes of a chronic illness. The International Advisory Committee on Clinical Trials of MS has defined four distinct subtypes of illness course: clinically isolated syndrome, relapsing-remitting, primary progressive and secondary progressive. Clinically isolated syndrome describes patients who have experienced their first episode of neurological symptoms. The relapsing-remitting course is characterized by attacks of new neurologic symptoms, followed by periods of partial or complete recovery, while primary progressive describes patients who have experienced consistently worsening neurologic functioning without relapses or remissions. The final subtype, secondary progressive, describes a worsening of neurological symptoms over time, following a relapsing and remitting course [20].
Using the MS typology described above as a template, the current study explored the feasibility of a similar system of classifying differing experiences of CFS and ME symptomology. Specifically, we examined whether differing self-reported patient illness courses are predictive of different levels of symptom severity and functional disability. Further, we assessed the relationship between these illness course subtypes, maintenance of the energy envelope, illness duration, and age.
It is possible that combining potentially diverse patient subtypes into one sample pool may account for the inconsistent findings and the lack of reproducibility that has often plagued research related to the etiology, diagnosis, epidemiology, and treatment of ME and CFS [8]. Past studies have attempted to categorize patients based on type of illness onset [9-11], the duration of the illness, and the age of patient [12-15]. However, there is no classification system yet that fully accounts for the diversity of symptom severity, functional disability, progression, and prognosis of this illness. It is, therefore, pertinent to further explore methods of subtyping individuals with ME and CFS in order to more accurately describe the wide range of patient experiences.
Research has distinguished between two different onset patterns: 1) sudden onset, in which symptoms appear over a few days or weeks and 2) gradual onset, in which symptoms develop over a period of months or years. Sudden onset has often been linked with viral and infectious illnesses [16], including: Epstein- Barr Virus infection (EBV) and enterovirus infections [17,18]. One study found that patients who experienced a sudden onset had poorer health outcomes than patients who described their onset as gradual [9]. Conversely, other findings suggest that patients with a sudden onset have a better prognosis than those with a gradual onset, while others have found no significant differences in prognosis between sudden and gradual onset subgroups [10-12]. With such a range of mixed results, subtyping patients by type of onset cannot fully account for the variability seen in symptom severity and the course of the illness.
Additionally, researchers have explored illness duration and current age as related factors that may impact prognosis and symptom severity. Research has found that patients with a longer illness duration (10 years or more) experienced poorer cognitive functioning compared to those with a shorter illnessduration (7 years or less) [13]. However, another study has found that the physical functioning of patients tended to improve over the course of their illness [14]. Further studies were unable to reproduce these findings and have suggested that the length of the illness experience does not have a significant effect on patient outcomes [12]. In general, older age has also predicted poorer prognosis among patients [15]. In one study, researchers sought to examine how both age and duration of illness can interact to affect illness severity and functioning. Within this sample, older patients with longer illness duration (10 years or more) displayed better mental health functioning than younger patients and older patients with shorter illness duration. However, younger patients with an illness duration of 10 years or more reported more severe immune and autonomic symptoms than older patients whose illness experience also spanned 10 years or more [16].
The categorization system developed to describe differing clinical courses in patients with Multiple Sclerosis (MS) is an illustrative example of the importance of defining subtypes of a chronic illness. The International Advisory Committee on Clinical Trials of MS has defined four distinct subtypes of illness course: clinically isolated syndrome, relapsing-remitting, primary progressive and secondary progressive. Clinically isolated syndrome describes patients who have experienced their first episode of neurological symptoms. The relapsing-remitting course is characterized by attacks of new neurologic symptoms, followed by periods of partial or complete recovery, while primary progressive describes patients who have experienced consistently worsening neurologic functioning without relapses or remissions. The final subtype, secondary progressive, describes a worsening of neurological symptoms over time, following a relapsing and remitting course [20].
Using the MS typology described above as a template, the current study explored the feasibility of a similar system of classifying differing experiences of CFS and ME symptomology. Specifically, we examined whether differing self-reported patient illness courses are predictive of different levels of symptom severity and functional disability. Further, we assessed the relationship between these illness course subtypes, maintenance of the energy envelope, illness duration, and age.
Methods
Research Participants
The sample for the present study was derived from
multiple settings in various geographical locations. Participants
included individuals at least 18 years of age with a current
diagnosis of CFS or ME. Participants from the DePaul sample
had self-report diagnoses, while the remaining samples required
diagnoses to be confirmed by a physician. Of the 882 individuals
available, only participants with complete data on the primary
illness course variable (N = 541) were included.
The overall sample was 84.5% female and 15.5% male. Most participants identified as Caucasian/White (98.2%); 0.4% were Asian or Pacific Islander, and 1.4% indicated their race as “other.” For current work status, 62.5% reported being on disability, 17.3% reported they were working, and the remaining 20.2% were not currently employed (student, homemaker, retired, or unemployed). Most participants in this sample (55.8%) were married or living with someone; 29.1% were single and 15.1% were either divorced, separated, or widowed. In terms of education, 30.4% of participants had a high school diploma or lower level of education, 11.6% attended college for at least a year, 33.6% held a standard college degree, and 24.4% had a graduate degree. The mean age was 46.3 years (SD = 13.2).
The overall sample was 84.5% female and 15.5% male. Most participants identified as Caucasian/White (98.2%); 0.4% were Asian or Pacific Islander, and 1.4% indicated their race as “other.” For current work status, 62.5% reported being on disability, 17.3% reported they were working, and the remaining 20.2% were not currently employed (student, homemaker, retired, or unemployed). Most participants in this sample (55.8%) were married or living with someone; 29.1% were single and 15.1% were either divorced, separated, or widowed. In terms of education, 30.4% of participants had a high school diploma or lower level of education, 11.6% attended college for at least a year, 33.6% held a standard college degree, and 24.4% had a graduate degree. The mean age was 46.3 years (SD = 13.2).
DePaul Sample
The largest portion of participants for the present study
(n = 213, 39.4%) came from the DePaul convenience sample pool.
This sample was recruited through support groups, internet
forums, and by contacting past participants of DePaul studies.
Participants were English speakers at least 18 years old who
self-identified as having a CFS or ME diagnosis. Those eligible
completed informed consents and surveys either electronically,
by hard-copy, or verbally over the phone. A large majority of the
DePaul participants were female (84.2% versus 15.8% male) and
most identified as Caucasian/White (97.7%). An additional 0.4%
identified as Asian and 1.9% reported their race as “other.” The
mean age for the DePaul Sample group was 51.9 (SD = 11.3).
Newcastle Sample
Another 18.1% of the participants (n = 98) in the
present study came from the Newcastle Sample. Individuals
18 years of age and older with a suspected CFS diagnosis were
referred to the Newcastle-upon-Tyne Royal Infirmary clinic for
a medical assessment. A physician completed a comprehensive
medical history and medical examination for each participant. All
informed consents and measures were completed by hard copy.
Most of the Newcastle Sample group (84.2%) identified as female
and 15.8% identified as male. Almost all participants from this
group identified as Caucasian (99.0%), and 1 participant selected
“other” as their primary race. The mean age was 45.7 years (SD =
14.0).
Norway 1 Sample
The Norway 1 Sample database contributed 34.4% of
the participants in the present study (n = 168). Participants living
in the suburbs of Oslo, Norway, were recruited to participate
in a CFS self-management trial program, through referrals
from healthcare professions as well as through CFS patient
organizations and education programs. Patients were required
to be 18 years of age or older, have a current CFS diagnosis,
and be physically able to attend the self-management program.
Participants completed an informed consent that included
permission to request a confirmation of their CFS diagnosis.
Within this sample of 168 individuals, 87.4% were female and
12.6% were male. Nearly all participants identified as Caucasian
(99.4%), and 1 participant identified as “other”. The mean age
was 43.4 years (SD = 11.6).
Norway 2 Sample
The final 11.5% of the sample in the present study
came from the Norway 2 Sample database. Participants from
this database were recruited from an inpatient medical facility
and an outpatient CFS/ME Center. Participants were required
to be between 18 and 65 years of age. An experienced physician
completed a comprehensive medical history interview and
medical examination for individuals suspected of having a CFS
diagnosis. In addition, a psychologist examined each individual to
rule out exclusionary conditions. All informed consent and other
study measures were completed by hard copy. Again, the majority
of participants were female (82.3%) and 17.7% were male.
Regarding race, 95.0% identified as Caucasian, 1.7% as Asian and
3.3% identified as “other.” The mean age was 34.8 years (SD =
11.7).
Illness Course Groups
Participants were placed in one of five illness
course groups based upon their response to an item asking
about the progression of their illness. This item provided the
choice of five labels: “constantly getting worse,”“constantly
improving,”“persisting (no change),”“relapsing and remitting
(having ‘good’ periods with no symptoms alternating with
symptomatically ‘bad’ periods),” and “fluctuating (symptoms
periodically get better and get worse, but never disappear
completely).”
Measures
SF-36
Participants completed the Medical Outcomes Study
36-item short-form health survey (SF-36) to measure their
current physical and mental functioning [21]. The questionnaire
measures functioning on eight subscales: Physical Functioning,
Role Physical, Bodily Pain, General Health, Social Functioning,
Mental Health, Role Emotional, and Vitality. This measure is
scored on a 100-point scale, where higher scores indicate higher
functioning, and lower scores indicate lower functioning. The
SF-36 has been found to have good internal consistency and
discriminate validity among subscales [22].
DePaul Symptom Questionnaire (DSQ)
The DePaul Symptom Questionnaire (DSQ)[7]consists of
54 self-report items assessing CFS-related symptomatology, as
well as demographic, occupational, and social history. Patients
were asked to rate the frequency of their symptoms over the
past 6 months on a 5-pt Likert scale as follows: 0 = none of the
time, 1 = a little of the time, 2 = about half the time, 3 = most
of the time, and 4 = all of their time. Patients were also asked
to rate the severity of their symptoms over the past 6 months
on a 5-pt Likert scale as follows: 0 = symptom not present, 1 =
mild, 2 = moderate, 3 = severe, and 4 = very severe. Symptom
frequency and severity were converted to a 100-point scale,
and were averaged to create one composite score for each
symptom. Symptoms were compiled into domains[23] based
on symptomology suggested by the Canadian Clinical Criteria
for ME/CFS[2] and select other symptoms categories that were
empirically identified through factor analysis [23,2,7]. The
domain composite scores were calculated by converting the frequency and severity for each symptom in the domain and
averaging them to create one score. The DSQ has proven to
have good test-retest reliability, as well as good convergent and
discriminate validity [24,25]. The DSQ has been made available
at Research Electronic Data Capture (REDCap): https://redcap.
is.depaul.edu/surveys/?s=tRxytSPVVw.
Energy Quotient
Energy quotients were calculated from information
provided on the DSQ and used to assess how much energy
participants were expending in comparison to how much they
had available. The Energy Envelope theory suggests that patients
who monitor their activity and are mindful not to overexert
themselves will experience better health outcomes and fewer
symptoms such as Post-Exertional Malaise (PEM) [26]. Using
a Likert scale ranging from one (no energy) to 100 (pre-illness
energy level), participants were asked to rate their available and
expended energy yesterday and last week. To calculate energy
quotients for both yesterday and last week, expended energy
levels were divided by available energy levels and then multiplied
by 100. Scores over 100 indicate overextension and scores
under 100 indicate under extension. Due to multiple outliers, a
winsorizing technique was used to minimize their effect. Energy
scores within the top 5th percentile were replaced with the value
corresponding to the 95th percentile.
Statistical Analysis
A series of one-way ANOVAs were used to compare
mean differences between illness subtypes for the following
categories: SF-36 subscales, DSQ symptom items, illness duration,
age, and energy quotients. Missing data were handled using
pair wise deletion and all analyses were performed using SPSS
software (version 21). The Games-Howell post-hoc test was used
to examine significant differences between groups.
Results
Illness Course Groups
Most the sample (59.7%), described the course of their
illness as Fluctuating, with symptoms periodically alternating
between getting better and getting worse but never disappearing
completely. Constantly Getting Worse comprised the second
largest group, representing 15.9% of the sample. Similarly,
14.1% of the sample described their illness as Persisting, which
was characterized by having no changes in symptomatology.
The Relapsing and Remitting group represented 8.5% of the
total sample, and was defined by having “good” periods with
no symptoms alternating with symptomatically “bad” periods.
The remaining 1.9% of the sample described their illness as
Constantly Getting Better.
Demographics
Table 1 shows the demographic information for each
illness course subtype. A series of chi-square tests were performed
and no significant relationship was found between illness course
groups and gender, race, ethnicity, marital status, education, or
work status. In addition, a series of one-way ANOVAs determinedthe groups did not differ significantly in age at time of self-report,
age at diagnosis, or illness duration.
Table 1: Demographic information for patients in each illness subtypes (N=541)
DSQ Domain Differences
Table 2 shows the means for DSQ domain composites for
each illness course group, along with the total sample. There were
significant differences in symptom scores between groups for the
following domains: the Immune Domain (F(4, 535) = 5.3, p = .000),
the Pain Domain (F(4, 535) = 6.8, p = .000), the Post-Exertional
Malaise Domain, F(4, 535) = 18.7, p = .00, the Sleep Domain (F(4,535) = 5.1, p = .002), the Gastrointestinal Domain (F(4, 535) =
4.6, p = .001) and the Orthostatic Intolerance Domain (F(4, 535)
= 4.6, p = .001). The Constantly Getting Worse group generally
reported higher levels of symptom severity and frequency when
compared to the other groups, while the Constantly Improving
group reported lower levels of symptom severity and frequency
compared to the other groups. The remaining three groups had
intermediate scores on these domains.
Table 2: Demographic information for patients in each illness subtypes (N=541)
SF-36 Subscale Scores
Table 3 shows the means and standard deviations for
each SF-36 subscale across each illness course subtype, as well
as for the entire sample. There were significant differences
in functioning scores between groups for the following
subscales:Role Physical (F(4, 519) = 18.7, p = .000), Bodily Pain
(F(4, 519) = 9.01, p = .000), Physical Functioning (F(4, 520) =
10.01, p = .000),Vitality F(4, 520) = 11.4, p = .000), General Health
(F(4, 515) = 4.5, p = .001.), and Mental Health (F(4, 519) = 2.7, p
= .03). The Constantly Getting Worse group reported significantly
worse functioning on all subscales except the General Health and
the Role Emotional subscales.
Table 3: ANOVA results for mean (SD) differences on SF-36 subscales between illness subtypes
Energy Envelope
Table 4 displays the means and standard deviations
on reported levels of fatigue and energy for the five subtypes, as
well as for the entire sample. There were significant differences
between groups in Past Week Fatigue scores (F(4, 506) = 11.60, p
= .00) and Past Week Available Energy scores (F(4, 509) = 14.55p = .00).The Constantly Getting Worse group and the Persisting
group reported significantly more fatigue than the remaining
three groups. There was also a significant difference for Past
Week Energy Quotients between illness subtypes (F(4, 497) =
6.01, p = .00). Scores describing participants’ fatigue and energy
levels for yesterday are also shown in Table 4.
Table 4: ANOVA results for mean (SD) differences in fatigue and energy between illness subtypes
Discussion
The present study explored factors associated with differing
self-reported illness course experiences: Constantly Getting
Worse, Constantly Improving, Persisting, Relapsing and Remitting,
and Fluctuating. The findings suggest that this method of
grouping patients is a promising way to examine subtypes of CFS
with distinct patterns of symptomology and levels of functioning.
The majority of participants in our sample (59.7%) defined
the course of their illness as Fluctuating, which was described as
“symptoms periodically get better and get worse, but never disappear
completely.” In general, this group reported the third most
severe scores related to their levels of symptomology, functioning,
available energy, and fatigue. Overall, these results suggest
that the majority of participants experienced a moderate level of
illness severity when compared to other subtypes.
The Constantly Getting Worse group, representing 15.9% of the sample, demonstrated the most severe and frequent symptoms on every DSQ domain, as well as the lowest levels of functioning on the majority of SF-36 subscales. Additionally, the Constantly Getting Worse group reported overextending their personal energy envelopes to significantly higher degree compared to the average patient. In short, the illness experiences of those within this subtype seem distinctly more severe compared to the majority of patients experiencing ME or CFS.
Participants that identified with the Persisting illness course subtype comprised 14.1% of the total sample. This illness course was described to them as having no changes in symptomatology. Overall, this group did not display a consistent pattern with regards to severity of symptoms and levels of functioning. On some DSQ domains, such as the Gastrointestinal, Orthostatic Intolerance, and Neuroendocrine/Circulatory, this group reported low severity and frequency of symptoms. However, on other DSQ domains and SF-36 subscales, this group ranked behind the Constantly Getting Worse group in terms of the highest levels of symptom frequency and severity and the lowest levels of functioning. Therefore, the results indicated that this group showed a moderate to high level of severity. In fact, the only significant difference between the Persisting group and the majority group (Fluctuating) was on the Vitality subscale of the SF-36, on which the Persisting group reported lower functioning. In addition, the Persisting subtype reported significantly higher levels of fatigue, as well as less available energy when compared to the Fluctuating group. However, due to the relatively few differences that occurred between these groups, future investigation is needed to further explore the distinctive illness experience of this subtype.
Participants among the Relapsing and Remitting group represented 8.5% of the total sample. This illness course was described as involving “good” periods with no symptoms, alternat-ing with symptomatically “bad” periods. Overall, this group reported moderate levels of symptomology and functioning when compared to other groups. However, our findings do not indicate substantial differences in experiences between those in the Relapsing and Remitting group and the Fluctuating group. The only scores which significantly differed were the Mental Health subscale scores of the SF-36, on which the Relapsing and Remitting group reported higher functioning. Because of this, it is difficult to specify a distinct symptomatic profile for this group, and future research may consider combining these two subtypes. Indeed, when we repeated all analyses with the Fluctuating and Relapsing and Remitting groups combined, we found that collapsing these subtypes did not result in noticeable changes in the overall findings. Because the approach taken here was exploratory in nature, we decided that keeping these subtypes separate for now could prove to be important for future analyses. However, further examination is needed to better understand the differences between symptomology and functioning for these illness courses.
Finally, the Constantly Improving group, comprising 1.9% of the total sample, consistently displayed a pattern of lower frequency and severity for symptoms on the DSQ and better overall functioning as demonstrated on the SF-36 subscales. Additionally, on average this group tended to expend more energy than they had available. This supports past research which suggests that some patients may be more able to overextend themselves with little consequence to their symptomology and functioning [27]. However, as only a small proportion (n = 10) of the present sample endorsed Constantly Improving as their illness trajectory, the conclusions that can be drawn about their illness experiences are limited. Nonetheless, the fact that there are so few participants within this subtype supports findings that suggest recovery from these debilitating illnesses is rare [28].
While the subtypes presented in this study provide promise in classifying more homogenous groups of patients, the approach taken had several limitations. First, it is difficult to assess participants’ illness experiences over time when using measures completed at a single time point. Items on the DSQ ask participants to rate the frequency and severity of their symptomatology over the past 6 months. Likewise, items on the SF-36 ask participants to rate their levels of functioning on a “typical day” over the past four weeks. The format of these items proves especially problematic for assessing the experiences of those within the Fluctuating and Relapsing and Remitting groups. As the nature of these groups’ illness course involves a variation in symptoms over time, when asking them to average their functioning and symptomology over time, we fail to capture a complete appreciation for the patterns of their illness.
Another limitation of the current study is that the majority of participants identified as Caucasian. This differs from the demographic distribution found in past community-based samples, which have documented higher levels of CFS diagnosis in ethnic minorities and those with lower socioeconomic status [29]. It would be important to consider whether patients from minority backgrounds differ in their illness course experiences, as studies have shown differences in patterns of symptom severity and functional status between different sociocultural samples[30]. However, the use of multiple geographically distinct collection sites was an advantage in that it lends support for the possibility of generalizing these results over multiple recruitment settings and geographic locations. Future studies should include greater ethnic and sociocultural diversity as well as consider utilizing a longitudinal design to more accurately measure each participant’s illness course. Measuring how symptoms and levels of functioning change over time would help distinguish clear patterns between subtypes and allow for further verification of the distinctiveness of these illness courses.
The Constantly Getting Worse group, representing 15.9% of the sample, demonstrated the most severe and frequent symptoms on every DSQ domain, as well as the lowest levels of functioning on the majority of SF-36 subscales. Additionally, the Constantly Getting Worse group reported overextending their personal energy envelopes to significantly higher degree compared to the average patient. In short, the illness experiences of those within this subtype seem distinctly more severe compared to the majority of patients experiencing ME or CFS.
Participants that identified with the Persisting illness course subtype comprised 14.1% of the total sample. This illness course was described to them as having no changes in symptomatology. Overall, this group did not display a consistent pattern with regards to severity of symptoms and levels of functioning. On some DSQ domains, such as the Gastrointestinal, Orthostatic Intolerance, and Neuroendocrine/Circulatory, this group reported low severity and frequency of symptoms. However, on other DSQ domains and SF-36 subscales, this group ranked behind the Constantly Getting Worse group in terms of the highest levels of symptom frequency and severity and the lowest levels of functioning. Therefore, the results indicated that this group showed a moderate to high level of severity. In fact, the only significant difference between the Persisting group and the majority group (Fluctuating) was on the Vitality subscale of the SF-36, on which the Persisting group reported lower functioning. In addition, the Persisting subtype reported significantly higher levels of fatigue, as well as less available energy when compared to the Fluctuating group. However, due to the relatively few differences that occurred between these groups, future investigation is needed to further explore the distinctive illness experience of this subtype.
Participants among the Relapsing and Remitting group represented 8.5% of the total sample. This illness course was described as involving “good” periods with no symptoms, alternat-ing with symptomatically “bad” periods. Overall, this group reported moderate levels of symptomology and functioning when compared to other groups. However, our findings do not indicate substantial differences in experiences between those in the Relapsing and Remitting group and the Fluctuating group. The only scores which significantly differed were the Mental Health subscale scores of the SF-36, on which the Relapsing and Remitting group reported higher functioning. Because of this, it is difficult to specify a distinct symptomatic profile for this group, and future research may consider combining these two subtypes. Indeed, when we repeated all analyses with the Fluctuating and Relapsing and Remitting groups combined, we found that collapsing these subtypes did not result in noticeable changes in the overall findings. Because the approach taken here was exploratory in nature, we decided that keeping these subtypes separate for now could prove to be important for future analyses. However, further examination is needed to better understand the differences between symptomology and functioning for these illness courses.
Finally, the Constantly Improving group, comprising 1.9% of the total sample, consistently displayed a pattern of lower frequency and severity for symptoms on the DSQ and better overall functioning as demonstrated on the SF-36 subscales. Additionally, on average this group tended to expend more energy than they had available. This supports past research which suggests that some patients may be more able to overextend themselves with little consequence to their symptomology and functioning [27]. However, as only a small proportion (n = 10) of the present sample endorsed Constantly Improving as their illness trajectory, the conclusions that can be drawn about their illness experiences are limited. Nonetheless, the fact that there are so few participants within this subtype supports findings that suggest recovery from these debilitating illnesses is rare [28].
While the subtypes presented in this study provide promise in classifying more homogenous groups of patients, the approach taken had several limitations. First, it is difficult to assess participants’ illness experiences over time when using measures completed at a single time point. Items on the DSQ ask participants to rate the frequency and severity of their symptomatology over the past 6 months. Likewise, items on the SF-36 ask participants to rate their levels of functioning on a “typical day” over the past four weeks. The format of these items proves especially problematic for assessing the experiences of those within the Fluctuating and Relapsing and Remitting groups. As the nature of these groups’ illness course involves a variation in symptoms over time, when asking them to average their functioning and symptomology over time, we fail to capture a complete appreciation for the patterns of their illness.
Another limitation of the current study is that the majority of participants identified as Caucasian. This differs from the demographic distribution found in past community-based samples, which have documented higher levels of CFS diagnosis in ethnic minorities and those with lower socioeconomic status [29]. It would be important to consider whether patients from minority backgrounds differ in their illness course experiences, as studies have shown differences in patterns of symptom severity and functional status between different sociocultural samples[30]. However, the use of multiple geographically distinct collection sites was an advantage in that it lends support for the possibility of generalizing these results over multiple recruitment settings and geographic locations. Future studies should include greater ethnic and sociocultural diversity as well as consider utilizing a longitudinal design to more accurately measure each participant’s illness course. Measuring how symptoms and levels of functioning change over time would help distinguish clear patterns between subtypes and allow for further verification of the distinctiveness of these illness courses.
Conclusions
These preliminary findings demonstrate that illness
course subtypes can account for significant differences in the
experiences of patients with CFS and ME. The severity and frequency
of symptoms, levels of functioning, and utilization of energy
were shown to differ significantly between illness course
subtypes. Continuing to explore and develop the illness course
classification approach is an important step in furthering treatment
and research for this debilitating illness. Not only will this
lead to a more nuanced understanding of treatment efficacy and
prognosis, but it will allow researchers to consistently categorize
patients by illness subtype increasing the specificity of their research.
This would likely ultimately lead to more consistent findings
within the field.
Acknowledgments
This work was supported by the National Institute of Allergy
and Infectious Diseases under Grant (AI105781).
Declarations
Ethical Approval
The ethical standards of the American Psychological
Association were upheld throughout the study period. All procedures
were approved by the DePaul University Institutional
Review Board.
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