Aquagenic pruritis

[Guest guest]

Dear All,

I am in a different yahoo group also that deals with an unknown

condition called Aquagenic Pruritis. It basically is an 'allergy'

for water (any kind, any temperature) which causes one to itch very

heavily after water contact for appr. an hour. Main areas of

itching are the extremeties and the trunk. Fortunately most (I

think) people who suffer from this do this mainly a part of the year

and might be related to the wearing off of a tan. Keeping a tan

updated by going to a tanning salon seems to keep the itching

somewhat in control (I just try not to get too much tan). Anyway,

in this group the liver has been discussed and someone asked about

PBC. I mentioned that I thought the itching of PBC or PSC is

different, but just would like to ask here if there are people here

with this Aquagenic Pruritis condition and if there might be a

connection.

Gerard

PS In the other group today (11-5) the thyroid was also discussed,

just as here, because several group members seemed to have this.

[Guest guest]

Hi Gerard;

I don't know of anyone in the group who suffers from the type of

pruritus that you describe (Aquagenic Pruritus). I believe that most

members have to contend with " cholestatic pruritus " :

___________________

Pruritus an important symptom of internal diseases (Acta

Dermatovenerologica Alpina, Pannonica et Adriatica Vol 9, No 3, 2000)

Cholestatic pruritus

Pruritus is a well-recognized manifestation among patients with liver

diseases and intrahepatic or posthepatic cholestasis. Hepatic

diseases leading to pruritus include primary biliary cirrhosis, B and

C viral hepatitis, primary sclerosing cholangitis, carcinoma of bile

ducts, alcoholic cirrhosis, autoimmune hepatitis and others. The

pruritus is generalized and more intense on hands, feet and around

tight-fitting clothes, while face, neck and genital area are rarely

involved (38). The pathogenesis is still poorly understood, as the

precise substance responsible for it is not known. Some authors

believe it is caused by the bile acids in the blood (cholemia) or

skin (39, 40), but there is a poor correlation between the skin

concentration of bile salts and intensity of pruritus. Recently, an

elevation of endogenous opioids was found in the blood of these

patients (41), and treatment with the opiate antagonist naloxone

improved pruritus. The itch in patients with cholemic pruritus can be

lessened by treatment with cholestyramine, phototherapy,

plasmapheresis which lower or remove the unknown circulating

pruritogen; antihistamines can be used as adjuvants. Ursodeoxycholic

acid has been used (10-15 mg/kg) with good success.

___________________

Support for the idea that a bile acid may be responsible for

cholestatic pruritus comes from the fact that rifampin (rifampicin)

can often alleviate cholestatic pruritus. It is now known that

rifampin (rifampicin) acts by activating the pregnane X receptor

(PXR) which in turn regulates a series of enzymes and transporters

that help detoxify harmful chemicals, including bile acids:

___________________

J Lipid Res. 2002 Mar;43(3):359-64.

Regulation of xenobiotic and bile acid metabolism by the nuclear

pregnane X receptor.

Kliewer SA, Willson TM.

Nuclear Receptor Discovery Research, GlaxoKline, 5 Drive,

Room V118.1B, Research Triangle Park, NC 27709, USA. sak15922@...

The nuclear pregnane X receptor (PXR; NR1I2) is an integral component

of the body's defense mechanism against chemical insult

(chemoprotection). PXR is activated by a diverse array of lipophilic

chemicals, including xenobiotics and endogenous substances, and

regulates the expression of cytochromes P450, conjugating enzymes,

and transporters involved in the metabolism and elimination of these

potentially harmful chemicals from the body. Among the chemicals that

bind and activate PXR is the toxic bile acid lithocholic acid;

activation of PXR, in turn, protects against the severe liver damage

caused by this bile acid.Thus, PXR serves as a physiological sensor

of lithocholic acid and perhaps other bile acids and coordinately

regulates genes involved in their detoxification. Interestingly, both

the antibiotic rifampicin and the herbal antidepressant St. 's

wort activate PXR and have anticholestatic properties, which suggests

that more potent, selective PXR agonists may be useful in the

treatment of biliary cholestasis or other diseases characterized by

the accumulation of bile acids or other toxins in the liver. PMID:

11893771.

___________________

Recent results also suggest that by activating the pregnane X

receptor (PXR), rifampin (rifampicin) also inhibits the synthesis of

a key enzyme involved in bile acid synthesis:

___________________

Am J Physiol Gastrointest Liver Physiol. 2004 Aug 26 [Epub ahead of

print]

Mechanism of Rifampicin and Pregnane X Receptor (PXR) inhibition of

Human Cholesterol 7{alpha}-Hydroxylase Gene (CYP7A1) Transcription.

Li T, Chiang JY.

Department of Biochemistry and Molecular Pathology, Northeastern Ohio

Universities College of Medicine, Rootstown, OH, USA.

Bile acids, steroids and drugs activate steroid and xenobiotic

receptor, PXR (NR1I2), which induces CYP3A4 in drug metabolism, but

inhibits CYP7A1 in bile acid synthesis in the liver. Rifampicin, a

human PXR agonist, inhibits bile acid synthesis and has been used to

treat cholestatic diseases. The objective of this study is to

elucidate the mechanism by which PXR inhibits CYP7A1 gene

transcription. The mRNA expression levels of CYP7A1 and several

nuclear receptors known to regulate the CYP7A1 gene were assayed in

human primary hepatocytes by quantitative real time PCR (Q-PCR).

Rifampicin reduced CYP7A1 and small heterodimer partner (SHP, NR02B)

mRNA expression suggesting that SHP was not involved in PXR

inhibition of CYP7A1. Rifampicin inhibited CYP7A1 reporter activity

and a PXR binding site was localized to the bile acid response

element-I (BARE-I). Mammalian two-hybrid assays revealed that PXR

interacted with HNF4alpha (NR2A1) and rifampicin was required. Co-

immunoprecipitation assay confirmed PXR interaction with HNF4alpha.

PXR also interacted with peroxisome proliferator-activated receptor

gamma co-activator (PGC-1alpha), which interacted with HNF4alpha and

induced CYP7A1 gene transcription. Rifampicin enhanced PXR

interaction with HNF4alpha and reduced PGC-1alpha interaction with

HNF4alpha. Chromatin immunoprecipitation (ChIP) assay showed that

PXR, HNF4alpha, and PGC-1alpha bound to CYP7A1 chromatin, and

rifampicin dissociated PGC-1alpha from chromatin. These results

suggest that activation of PXR by rifampicin promotes PXR interaction

with HNF4alpha and blocks PGC-1alpha activation of HNF4alpha and

results in inhibition of CYP7A1 gene transcription. Rifampicin

inhibition of bile acid synthesis may be a protective mechanism

against drug and bile acid-induced cholestasis. PMID: 15331348.

___________________

I've read that aquagenic pruritus can have several different causes,

including hypereosinophilic syndrome [that benefits from UV

treatment]:

___________________

Br J Dermatol. 1990 Jan;122(1):103-6.

Aquagenic pruritus associated with the idiopathic hypereosinophilic

syndrome.

Newton JA, Singh AK, Greaves MW, Spry CJ.

Department of Dermatology, London Hospital, Whitechapel, U.K.

Patients with the idiopathic hypereosinophilic syndrome (HES) may

develop associated skin disorders. We describe a patient who had

xerosis since birth, but who first developed symptoms of aquagenic

pruritus soon after he presented with HES. Photochemotherapy with

psoralen and UVA treatment reduced his peripheral blood eosinophil

count. The good response to treatment suggests that there was a close

relationship between the dermatosis and the blood disorder. PMID:

2297496.

___________________

The bottom-line is that I don't think that there is much evidence

that there is a connection between the underlying mechanisms of

pruritus of PBC and PSC and aquagenic pruritus. I would tend to agree

with your thought that the itching of PBC or PSC is different.

I hope this answers your question?

Best regards,

Dave

(father of (19), PSC 07/03, UC 08/03)

> in this group the liver has been discussed and someone asked about

> PBC. I mentioned that I thought the itching of PBC or PSC is

> different, but just would like to ask here if there are people here

> with this Aquagenic Pruritis condition and if there might be a

> connection.

>

> Gerard

>

[Guest guest]

Dear Dave,

You certainly answered my question. Thanks again, you are such an

invaluable source of information!

Gerard

>

> I hope this answers your question?

>

> Best regards,

>

> Dave

> (father of (19), PSC 07/03, UC 08/03)