Chronic fatigue

[Guest guest]

Hi Chris;

I hope that some PSCers can give you some tips on how they cope with

the chronic fatigue associated with PSC. There seems to have been

little research on the exact causes of fatigue in PSC, and this is a

shame because it is a very common problem. I've been doing some

reading on fatigue lately, and have stumbled upon a possible

mechanism that I would like to share with the group.

Some fairly recent studies with chronic fatigue syndrome have

indicated that this disorder may actually be caused by a 'leaky gut'

and the translocation of a toxic molecule (lipopolysaccharide, also

called endotoxin) [produced by gram-negative bacteria in the gut]

across the intestinal barrier, which then stimulates inflammatory

cytokine production:

Maes M, Mihaylova I, Leunis JC (2007) Increased serum IgA and IgM

against LPS of enterobacteria in chronic fatigue syndrome (CFS):

indication for the involvement of gram-negative enterobacteria in the

etiology of CFS and for the presence of an increased gut-intestinal

permeability. J. Affect. Disord. 99: 237-240.

http://www.ncbi.nlm.nih.gov/pubmed/17007934

IBD is also associated with the same phenomenon:

Caradonna L, Amati L, Magrone T, Pellegrino NM, Jirillo E, Caccavo D

(2000) Enteric bacteria, lipopolysaccharides and related cytokines in

inflammatory bowel disease: biological and clinical significance.

J Endotoxin Res. 2000;6(3):205-14.

http://www.ncbi.nlm.nih.gov/pubmed/11052175

And it's also thought that " PSC may be triggered in genetically

susceptible individuals by toxic or infectious agents gaining access

to the liver via a diseased and permeable colon " :

Cullen S, Chapman R (2001) Aetiopathogenesis of primary sclerosing

cholangitis. Best Pract. Res. Clin. Gastroenterol. 15: 577-589.

http://www.ncbi.nlm.nih.gov/pubmed/11492969

If lipopolysaccharide was the main culprit in PSC, this would explain

the accumulation of lipopolysaccharide (endotoxin) in the biliary

epithelial cells of PSC patients:

Sasatomi K, Noguchi K, Sakisaka S, Sata M, Tanikawa K (1998) Abnormal

accumulation of endotoxin in biliary epithelial cells in primary

biliary cirrhosis and primary sclerosing cholangitis. J. Hepatol. 29:

409-416.

http://www.ncbi.nlm.nih.gov/pubmed/9764987

and would also explain the high prevalence of antibodies to the

endotoxin-binding bactericidal/permeability-increasing protein (BPI)

in PSC and IBD:

Schultz H, Weiss J, Carroll SF, Gross WL (2001) The endotoxin-binding

bactericidal/permeability-increasing protein (BPI): a target antigen

of autoantibodies. J. Leukoc. Biol. 69: 505-512.

http://www.ncbi.nlm.nih.gov/pubmed/11310835

Schinke S, Fellermann K, Herlyn K, Reichel PH, Fundke R, Stange EF,

Gross WL, Schultz H (2004) Autoantibodies against the

bactericidal/permeability-increasing protein from inflammatory bowel

disease patients can impair the antibiotic activity of

bactericidal/permeability-increasing protein.

Inflamm. Bowel Dis. 10: 763-770.

http://www.ncbi.nlm.nih.gov/pubmed/15626895

When antibodies to BPI build up, it becomes more difficult for the

body to counteract lipopolysaccharide, and this could contribute to a

perpetuation of inflammation in both the gut and liver.

I am sorry that this is not of much practical help to you in dealing

with the chronic fatigue associated with PSC, but I find it curious

that chronic fatigue syndrome shares this common thread with PSC and

IBD.

A prediction of this mechanism might be that a patient's level of

fatigue might be correlated with antibodies to BPI, but how many of

the group have actually been tested for this antibody?

Best regards,

Dave

(father of (22); PSC 07/03; UC 08/03)