CFS/ME starts most often age 10-19 & 30-39: Norwegian population study

[Simon]

Two age peaks in the incidence of chronic fatigue syndrome/myalgic encephalomyelitis: a population-based registry study from Norway 2008-2012
Bakken & co-authors, 2014

This looks like a pretty interesting study to me because of its large sample size and the results do tie in with what's generally reported ie onset is more common during adolescence and in adults in their thirties. Plus the incidence rate of 0.026% ties in with other studies (note this looks at new cases, not prevalence, which is all cases).

Background
The aim of the current study was to estimate sex- and age-specific incidence rates of chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) using population-based registry data.

CFS/ME is a debilitating condition with large impact on patients and their families. The etiology is unknown, and the distribution of the disease in the general population has not been well described.

Methods
Cases of CFS/ME were identified in the Norwegian Patient Register (NPR) for the years 2008 to 2012. The NPR is nationwide and contains diagnoses assigned by specialist health care services (hospitals and outpatient clinics).

We estimated sex- and age-specific incidence rates by dividing the number of new cases of CFS/ME in each category by the number of person years at risk. Incidence rate ratios were estimated by Poisson regression with sex, age categories, and year of diagnosis as covariates.

Results
A total of 5,809 patients were registered with CFS/ME during 2008 to 2012. The overall incidence rate was 25.8 per 100,000 person years (95% confidence interval (CI): 25.2 to 26.5).

The female to male incidence rate ratio of CFS/ME was 3.2 (95% CI: 3.0 to 3.4). [females 3x more likely to get it]

The incidence rate varied strongly with age for both sexes, with a first peak in the age group 10 to 19 years and a second peak in the age group 30 to 39 years.

Conclusions
Early etiological clues can sometimes be gained from examination of disease patterns. The strong female preponderance and the two age peaks suggest that sex- and age-specific factors may modulate the risk of CFS/ME.
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The study relies on physician-reported diagnoses from those seeing a hospital specialist:

Cases of CFS/ME were all in- and outpatients in Norwegian hospitals who were registered
with the ICD-10 code G93.3 (‘postviral fatigue syndrome/benign myalgic
encephalomyelitis’). Data from mental health care facilities were not included

The study uses the Norwegian national database - all patients are registered and doctors need to include the diagnosis code to get paid so it's kept up to date.

 

[Battery Muncher]

Not the best at judging these things, but it looks like another solid piece of research from Norway.

 

[NK17]

The fact that Norway is a small rich country with a socialized medicine system and a solid medical database creates fertile ground for this kind of studies.

I'm not the bit surprised by what they have found:
- two age/s of peak incidence
and
- predominant ratio of women affected
have been observed in other countries.

Still this study does not tells us anything about pathophysiology, nonetheless it is important and should be of help in the fights that lay ahead of us.

IMO what it does tell us is two of the reasons, among the many, why ME have been so downplayed, ridiculed and understudied. Teenagers and women in their mid thirties are not good complainers and if they do their complaints are mainly put down to psychosomatic troubles, maladaptive behavior and mid life crisis.

 

[Snow Leopard]

This is a study examining the incidence (and potentially other epidemological factors) of CFS in tertiary care.

26/100,000 person years over a life time is still a low incidence rate compared to community based studies. Suggesting that patients referral to tertiary care in Norway comprises only 5-10% of patients at most.

Figure 3 shows the estimated incidence rate per 100,000 person years for men and women
separately. After adjustment for population figures, the pattern with two age peaks is clear for
women, whereas a second peak is not evident for men.

This is interesting, but figure 3 is not displayed in the early PDF that I am looking at...

From the current results, one might hypothesize that hormonal changes increase the risk of
CFS/ME in women. The pattern may also be compatible with the hypothesis of an infectious
trigger for the condition. The age distribution observed in our study may be explained by
primary exposure to an infectious agent in adolescents (first age peak) and subsequent
reactivation of latent infection (second age peak). It has been shown that reactivation of latent
(viral) infections may be triggered by stressful events, chronic stress or pregnancy [35].

I'm wondering what thoughts @Jonathan Edwards has about this.

 

[Sidereal]

This is a study examining the incidence (and potentially other epidemological factors) of CFS in tertiary care.

26/100,000 person years over a life time is still a low incidence rate compared to community based studies. Suggesting that patients referral to tertiary care in Norway comprises only 5-10% of patients at most.

It appears that they included only cases diagnosed with G93.3 and excluded cases from psychiatric facilities? Not a good strategy when it comes to researching this "condition" IMO. We all know that the neurological diagnostic code is there in the ICD, but honestly, how many doctors actually use it? They surely missed the majority of cases that were misdiagnosed as depression, anxiety, somatoform etc., plus all the cases diagnosed with plain old nothing because the doctor does not believe there is anything wrong with the patient or thinks it's CFS but doesn't want to put anything down on the chart since it's not a real illness, only a belief, and diagnosing it might encourage the patient to think he/she is actually sick and should assume the "sick role" or even, god forbid, apply for state benefits. The bogus psych literature that says there is iatrogenic harm from giving people an ME/CFS diagnosis surely doesn't help when it comes to underestimating the prevalence of this disease.

 

[Simon]

This is a study examining the incidence (and potentially other epidemological factors) of CFS in tertiary care.

26/100,000 person years over a life time is still a low incidence rate compared to community based studies. Suggesting that patients referral to tertiary care in Norway comprises only 5-10% of patients at most.

The best epidemiological study is probably Reyes, which found an incidence rate of 180 per 100,000 ie much higher, but then that was a US community survey, not a tertiary setting
Prevalence and incidence of chronic fatigue ... [Arch Intern Med. 2003] - PubMed - NCBI

Whats odd about the Reyes, though, is that prevalence is barely higher at 235/100k, suggesting the average case lasted little more than a year. Hadn't noticed that before, but it doesn't look right.

 

[Dolphin]

The risk for children may be artifically high due to:

The Norwegian Directorate of Health has stated thatICD-10 code G93.3 is to be used for this
disorder [2]. However, cases in the present study come from a large number of different
hospitals and the criteria used to diagnose CFS/ME might have varied. In a recent study, most
Norwegian hospitals reported that they had used either the Canadian 2003 criteria [18] or the
CDC 1994 criteria [4] when diagnosing CFS/ME in adults [19]. Pediatricians generally
reported they follow the guidelines of the Norwegian Pediatric Association [20], which
formally refer to the CDC 1994 criteria, but also recommend using a practical, clinical
definition of CFS/ME in children with otherwise unexplained severe fatigue of more than
three months duration. We cannot exclude the possibility that the relatively high incidence in
children and adolescents may be partly due to the use of a less strict case definition of
CFS/ME in young people. However, we find it unlikely that this potential over-reporting is
substantial, as pediatricians probably are restrictive in using this diagnosis.

and

According to the recommendations from the Norwegian Directorate of
Health, children with suspected CFS/ME should have the diagnosis confirmed by a
pediatrician [2]. Thus, children receiving the diagnosis of CFS/ME are routinely referred to
their local hospital for the diagnostic work-up. Complicated cases may be further referred to
regional university hospitals. After the diagnosis of CFS/ME is made, patients are typically
followed up in primary care. Adults may receive a diagnosis of CFS/ME after evaluation by a
general practitioner. However, since the diagnosis requires that other possible diagnoses are
ruled out, most patients have most likely also been seen by a specialist at a local hospital
during the diagnostic work-up.

This study was based on hospital diagnoses.

 

[Dolphin]

The best epidemiological study is probably Reyes, which found an incidence rate of 180 per 100,000 ie much higher, but then that was a US community survey, not a tertiary setting
Prevalence and incidence of chronic fatigue ... [Arch Intern Med. 2003] - PubMed - NCBI

Whats odd about the Reyes, though, is that prevalence is barely higher at 235/100k, suggesting the average case lasted little more than a year. Hadn't noticed that before, but it doesn't look right.

Here's what Reyes et al. say on this:

The 1-year incidence estimate of CFS (180 per 100 000 persons; 95% CI, 0-466 per 100 000 persons) is similar to previous estimates from a physician-based study in the United States2 and a nationwide study in Japan.12 Compared with prevalence, our incidence estimate might seem too high. However, several factors preclude making a simple and direct link between incidence and prevalence in our study. First, prevalence estimates considered the probability of CFS in the entire population (all subjects with and without exclusionary conditions), while incidence reflected the yearly rate of developing CFS among the population at risk (baseline subjects who were nonfatigued and fatigued for <6 months, without medical or psychiatric exclusions). Second, even if the denominators for incidence and prevalence were the same, the classic formula relating incidence and prevalence cannot be applied because it assumes a uniform duration of illness. In the case of CFS, disease heterogeneity makes it likely that duration of illness (ie, time to recovery) is heterogeneous. This suggestion is supported by findings from a longitudinal study24 that reported higher recovery rates for subjects with CFS who were ill for less than 5 years compared with those who were ill for a longer duration. Further studies on the clinical course of CFS and the occurrence of new cases are necessary.

 

[Gijs]

I know many people with ME who where 22, 23, 24, etc... I don''t believe this study, it is bias. ME can start anytime.

 

[Simon]

Here's what Reyes et al. say on this:

Thanks, though I don't find their explanation entirely convincing. A UK study by Luis Nacul found a much lower incidence rate of ME/CFS (in line with the Norwegian study) despite a broadly similar prevalence rate to the Reyes study:

Results The estimated minimum prevalence rate of ME/CFS was 0.2% for cases meeting any of the study case definitions, 0.19% for the CDC-1994 definition, 0.11% for the Canadian definition and 0.03% for the ECD. The overall estimated minimal yearly incidence was 0.015%. [15 per 100,000]

I guess all of these studies indicate that 'more research is needed' to clarify the situation

 

[Cheesus]

I know many people with ME who where 22, 23, 24, etc... I don''t believe this study, it is bias. ME can start anytime.

Can you say where you see the bias? Or what the motivation for bias would be?

The study does not say it happens to all patients between those ages. Just that those are the two peak age groups where you are most likely to develop ME.

 

[user9876]

Can you say where you see the bias? Or what the motivation for bias would be?

The study does not say it happens to all patients between those ages. Just that those are the two peak age groups where you are most likely to develop ME.

I suspect there is a bias towards reporting for children due to schools getting difficult if a child misses too much school.

 

[wastwater]

Im starting to wonder if ME/cfs for some might be vaccine induced EAE(experimental autoimmune encephalomyelitis)taking hold in humans and following the timings of MS.

 

[PhoenixDown]

Without meaningful subgroups, the results are diluted at best and meaningless at worse.

 

[duncan]

Strikes me as odd and counter-intuitive. But ok. So, what are the commonalities between those two age peaks? What would explain the gaps between age clusters? For instance, why the drop in incidence in the group that span 20-29? 40 - 49?

With Lyme, the canaries pretty much were children. It was they who ran through the wild tall grasses, and played on the edges of the woods, all places where ticks would wait for a ride. But over time, I'd wager the incidence of age in confirmed/reported Bb cases has smoothed out, and it's numbers pretty much are level in terms of acute cases - or so I believe (although now that I write it, I'd be curious to see how it plays today).

If the Norway numbers are representative - if - then there needs be an explanation for the peaks. I cannot help but wonder if this is not so much a profile of a patient community's characteristics, but rather a sideways view reflective of clinicians' perspectives.

 

[Forbin]

Strikes me as odd and counter-intuitive. But ok. So, what are the commonalities between those two age peaks? What would explain the gaps between age clusters? For instance, why the drop in incidence in the group that span 20-29? 40 - 49?

Pure speculation but... 10-19 is roughly the age when children and young adults are mixing with LOTS of other children/young adults. Prior to this, in US primary schools at least, students are mostly confined to a single classroom of 20-30 students (and the school population as whole is smaller than in middle/secondary school and college).

30-39 is, perhaps, when you're more likely to have children in the 10-19 age group.

So, kids 10-19 might be more likely to pick up something at school and bring it home to their 30-39 year old parents.

Maybe.

 

[eafw]

There could be all sorts of things going on here. What was the history of the 30+ patients - does this coincide with a "burnout" of high flyers or other similar accumulative stresses ?

Even ordinarily healthy people will say that by you hit your thirties things are much harder to recover from than in your twenties.

 

[Bob]

Looking at the range of ages in the graph (figure 1) in the full paper, the text/discussion that suggests that the peaks are related to hormonal changes makes a lot of sense. For males and females, the first peak is after the age of ten when puberty starts. Before that, during childhood, the rates are very low for both boys and girls, but also the rates for boys and girls are unusually similar before age 10 which seems significant. Then, in adulthood, the rates for men (unlike the rates for women) do not have a pronounced peak at 30-45 but are fairly consistent until they steadily decrease towards older age. Whereas, for women, there is the second peak that starts at roughly 30 to 35 when further hormonal changes are experienced by women.

So, to me, it looks like these peaks may relate to hormonal changes. I can't think of any other reason why the rates for men and women should be different (edit: hmm, well, except for the many other genetic differences!) and why the peaks occur when they do, and why women peak again at 30-45 but men don't.

It would be interesting to look at the childbirth data for Norway and see if that coincides with the second peak for women, but I suspect the average age for childbirth is not as late as 40 to 45, so the second peak is more likely to correspond with other hormonal changes at that age.

The peak for adolescents might be artificially high (as dolphin pointed out), but the difference in rates between childhood and adolescence seems remarkable.

Of course, this doesn't mean that hormones cause the disease, but it may mean that hormones play a role, or make people more susceptible to the disease. Or, of course, it could be another completely different factor.

 

[A.B.]

It would be interesting to look at the childbirth data for Norway and see if that coincides with the second peak for women

In Norway, the average age of the mother at the birth of her first child is 28.5 years according to this source.

Adding the average time to diagnosis for CFS (which is?) to this should get closer to the second peak range. And whatever hormonal changes occur probably don't cause CFS directly but merely increase susceptibility.

Is CFS more prevalent in mothers?

 

[duncan]

Are clinicians doling out ME/CFS diagnoses more readily to women, and specifically, to married women with multiple children because doctors, as a group, trend toward a stress model that is gender-biased? You see it less in the 20's thanks, in measure, to less perceived stress overall, and arguably less in women in parts of society's perspective (no overt career pressures yet, children just appearing towards the tail of that category), but the 30-39 group sure looks like a sweet spot. In their 30's more women are juggling multiple children and careers. Men, too, but maybe the actual incidence in men is being muted.

So in a way, yes, hormones could be involved, maybe just not in a causal role directly involving the patients. If clinicians are the gateway to data, and if that mechanism is flawed, the data that flows to the study's overseers may be skewed.

It is certainly a robust study with a population of 5,800.

I don't know if I believe that is what has happened here, but I certainly think it could. Dogma is a force of nature, and clinicians succumb to it regularly, imo.