C-Reactive Protein Response in Patients With Post-Treatment Lyme Disease Symptoms Versus Those With Myalgic Encephalomyelitis/CFS, Uhde et al, 2018

[Indigophoton]

To the Editor—There is substantial
overlap in symptoms, including fatigue,
muscle and joint pain, and cognitive and
memory deficits, between post-treatment
Lyme disease syndrome (PTLDS) and
myalgic encephalomyelitis/chronic fatigue
syndrome (ME/CFS) [1]. Increasing evi-
dence suggests a role for immunologic
and inflammatory pathways in both
PTLDS and ME/CFS [2–4]. However, in
part owing to their etiologic complexity
and the lack of established biomarkers, our
understanding of the pathways involved
and potential mechanistic differences
between the 2 conditions is very limited.

...These data provide evidence for the
likely existence of distinct inflammatory
mechanisms in ME/CFS versus PTLDS,
which may be driven in part by the poten-
tially more heterogeneous etiology of
ME/CFS symptoms in comparison with
PTLDS. The absence of a significantly
enhanced CRP response in ME/CFS, des-
pite published data suggesting activation
of various inflammatory pathways, war-
rants further examination.

https://academic.oup.com/cid/advance-article-abstract/doi/10.1093/cid/ciy299/4993827

Full text, http://sci-hub.tw/10.1093/cid/ciy299

 

[Woolie]

Seems like an interesting contribution. In a previous study, this group found higher average CRP levels in people with post-treatment Lyme disease than in healthy controls. So this study was to see if MECFS patients showed the same pattern.

The main finding was that as a group, MECFS patients (131 cases) did not have significantly higher CRP levels than controls (86 cases). The authors suggest that Post-Lyme people are probably are more homogeneous group, whereas MECFS patients are probably pretty heterogeneous (different causes and mechanisms in different people. This could be the reason for the difference in findings.

I really like how they've set out the data in the fig (see image below), this is in line with current best practice, which is to prefer figures that allow the reader to visually explore the data. Its a tiny report but its really tight.

Group differences were assessed by the analysis of covariance, using the general linear model, to account for the potential con-founding effect of age, sex, and BMI.

Its really good that they paid attention to other variables that have an effect on CRP, like age, gender and BMI. But the MECFS and control samples look like they had been matched very closely on these variables to start with. So I don't know why they needed to control for this statistically at all.

They also found no difference in the percentage of cases with a CRP of 3 or more between the MECFS patients and controls.

I'm not sure why they picked 3 as their cut-off there, because 6 is usually given as the clinical threshold in lab tests - why not focus on those at or above 6? It would seem from the figure (below) that cases with CRPs over 6 are overrepresented in the MECFS group, but of course hard to say without seeing the data: the circles don't seem to correspond to individual cases, and the sample sizes were also different - 131 MECFS cases versus 86 controls.

One last thing - given that MECFS is a diagnosis of exclusion, I wonder whether different exclusion practices might shape these sorts of figures? So in a country/clinic that does thorough testing, and only gives an MECFS diagnosis when all other markers are normal, people with an abnormal CRP might be excluded, whereas in clinics where less stringent exclusion criteria are applied, people with high CRP levels might still get diagnosed.

 

[andypants]

The absence of a significantly
enhanced CRP response in ME/CFS, des-
pite published data suggesting activation
of various inflammatory pathways, war-
rants further examination.

Very interesting. Even in the middle of an infection/visible inflammation my CRP is <1. Not helpful when seeing doctors, who just cannot fathom the possibility of these two coexisting.