Blog: ME/CFS onset had two peaks, which may be a clue to causes

[Ravn]

Interesting work, thanks @Simon M. It's probably as much as can be done with the available data (unless the decode data can somehow be re-analysed by age of onset subgoup)

I don’t know what to think of the results, still on the fence.

Could be mostly diagnostic bias. Doctors may just be diagnosing certain groups more because they have two stereotypes in their mind, the PVF in a teenager after mono, and the middle-aged woman unable to cope with life’s demands . Others with the same presentation may just be more likely to get a different diagnosis. I first fell ill at age 10. An initial PVF explanation was soon replaced by ‘growing pains’. A major relapse in my late 20s was (wrongly) deemed MS. Wasn’t until I hit middle age ME/CFS was even considered. Also, all the data is from Europe which makes it more likely that doctors share the same biases. Would be interesting to see if there’s a double peak in completely different cultures as well, if suitable data can be found

Or it could reflect a biological reality. Though even in this case it may still all be one and the same illness the risk of which increases with age. The first peak my just be a blip on top of the ‘normal’ age-related increase, caused by higher numbers of mono in that age group. And the decreasing case numbers in the older age groups may be due to almost everyone who’s susceptible having already succumbed. Would be interesting to see data from countries where everyone gets EBV early and consequently there isn’t much mono, would the early peak still show?

Or it could be an important clue to pathology. In which case, would it make sense to look at papers looking at major physiological changes during normal ageing, also beyond puberty and menopause, changes that might plausibly increase the likelihood of something going wrong in susceptible people? For example this paper (barely) discussed here?

 

[Jonathan Edwards]

Explanations might not be too complicated: What if the first statistical concentration at around nineteen represented EBV infection at its peak too, also known as the kissing disease.

We have discussed this at some length in the thread on two peaks already existing. EBV peak incidence does not appear to account for the first peak - it is a bit too late, even if it makes a substantial contribution to the triggering of the first peak.

The idea that stress peaks at 35 seems pretty untestable since there is no agreed definition of, or way to measure, 'stress'. I think whatever stress was one would expect it to vary across countries with variation in cultural factors. Apart from Germany being slightly different in peak time the peak seems remarkably constant. And stress does not drop off progressively with age, I can assure you!!

 

[PageofME]

We have discussed this at some length in the thread on two peaks already existing. EBV peak incidence does not appear to account for the first peak - it is a bit too late, even if it makes a substantial contribution to the triggering of the first peak.

The idea that stress peaks at 35 seems pretty untestable since there is no agreed definition of, or way to measure, 'stress'. I think whatever stress was one would expect it to vary across countries with variation in cultural factors. Apart from Germany being slightly different in peak time the peak seems remarkably constant. And stress does not drop off progressively with age, I can assure you!!

I am glad we agree on the idea that the triggers are not what will lead us to understand the pathomechanism!! I think that's the important thing here.

 

[Jonathan Edwards]

I am glad we agree on the idea that the triggers are not what will lead us to understand the pathomechanism!! I think that's the important thing here.

I didn't actually say that, I don't think. Triggers may provide essential clues. I just think we have to be careful about assuming we know the range of them. I think some proposed triggers would narrow down the possibilities quite considerably.

 

[Sasha]

I didn't actually say that, I don't think. Triggers may provide essential clues. I just think we have to be careful about assuming we know the range of them. I think some proposed triggers would narrow down the possibilities quite considerably.

Intriguing! Would you like to expand on that?

 

[Turtle]

I got a really bad A-flu at 20 which coincided with living on my own in my nice appartment.
I got mono and pneumonia at 34, the day after I moved in with my partner.
Don't get a virus or don't move?

 

[Creekside]

Would be interesting to see if there’s a double peak in completely different cultures as well, if suitable data can be found

I agree. That seems the easiest way to test the hypothesis. Surely there's some suitable data from Asian countries.

 

[Kitty]

Surely there's some suitable data from Asian countries.

If data for China replicated, that would be very interesting. A member who translated our fact sheets into Chinese said there isn't a word for glandular fever/mono because it's so rare. Children get infected with EBV early in life, possibly due to cultural practices.

If that's correct and the double peak is still there, it might help clarify whether mono has much of an influence.

 

[Mortal Machinery]

EBV peak incidence does not appear to account for the first peak - it is a bit too late, even if it makes a substantial contribution to the triggering of the first peak.

There appears to be at least some evidence, in certain context/cultures, that first EBV infection is happening later.
Declining Epstein-Barr Virus Antibody Prevalence in College Freshmen Strengthens the Rationale for a Prophylactic EBV Vaccine, (Balfour, 2022)

Antibody prevalence decreased over 15 years from 64% to 52%.

If only 52% of college freshmen (18-19 years old) have EBV antibodies, that doesn't seem out of line with a first peak around age 19. (with some before and some after)

EBV could also be a contributor through a time-lag effect, such as is seen in MS.
Longitudinal analysis reveals high prevalence of Epstein-Barr virus associated with multiple sclerosis, Bjornevik et al (2022) | S4ME Thread

The median time from the first EBV-positive sample to MS onset was 5 years (range: 0 to 10 years), and the median time from estimated EBV seroconversion, defined as the midpoint between the last seronegative sample and the first seropositive sample, to MS onset was 7.5 years (range: 2 to 15 years).

I am not saying that EBV is the cause of ME/CFS. But it does not seem to me that the two peaks observation does anything to rule it out as a trigger or contributing factor for many.

I agree that data from other cultures for comparison would be helpful. And/or a longitudinal study for ME/CFS like the one above for MS.

 

[Jonathan Edwards]

But it does not seem to me that the two peaks observation does anything to rule it out as a trigger or contributing factor for many.

The Edinburgh data suggest that EBV triggering is a major factor in the early peak. That does not seem to be in doubt. What is confusing, though, is that it does not look as simple as that. Exposure to EBV with intimate contact would be expected to produce a pretty sharp upswing peak in late teens. The early peak starts too early (around 12) and probably peaks too early if I remember rightly. And there is a significant chunk of early onset ME/CFS thta does not seem to be EBV related.

 

[Mortal Machinery]

The early peak starts too early (around 12) and probably peaks too early

I was recalling the DecodeME graph from Simon's Blog post showing the peak for EBV triggered ME/CFS onset at age 20. To the eye, the "All EMEA countries (excluding Norway)" graph in the subject paper appears to have a similar profile for the first peak as Decode.

Then, as @Turtle mentioned, there are some who dodge EBV in childhood/adolescence and get it in their 30's. (not enough to be the second peak - just noting outliers)

As you said, it is not simple.

 

[Yann04]

I had the same question, and people shared lots of interesting thoughts in the DecodeME thread if you haven't seen it.

Cheers! Glad this is being considered.

 

[ME/CFS Science Blog]

Excellent blog, clearly written, thanks!

Perhaps not very relevant but Jason also looked at seasonal onset in his Chicago cohort and found significantly more cases where onset was in January compared to other months. Seems likely to be due to chance in my opinion (it had a low sample size of 31 Fukuda CFS patients), but perhaps others can make more sense of it.

A community-based study of seasonal variation in the onset of chronic fatigue syndrome and idiopathic chronic fatigue - PubMed

 

[Mij]

My sudden vertigo viral onset was during the first week of February. I skated on the canal in -27 C temperature without wearing a hat 4 days prior.

 

[Mortal Machinery]

Perhaps not very relevant but Jason also looked at seasonal onset in his Chicago cohort and found significantly more cases where onset was in January compared to other months. Seems likely to be due to chance in my opinion (it had a low sample size of 31 Fukuda CFS patients), but perhaps others can make more sense of it.

A community-based study of seasonal variation in the onset of chronic fatigue syndrome and idiopathic chronic fatigue - PubMed

Looks like it lines up with flu and virus season in the US.
What is odd is the gap in December. Doctors offices closed for the holidays, so no one to make a diagnosis? "Come back in January"...