immune deficiency (CVID) and PSC

[Guest guest]

Lori:

You amaze me with all you know medically and how you have endured the trials you

have on behalf of your son. You are one of the best...

Dee

[Guest guest]

Hi

I have recently been told that the immunoglobulin levels in my blood

are very low. The consultant that I last saw is running a study on PSC

and immuno deficiencies - I will keep the group posted [next

appointment not until early September] with any developments. I also

ran a poll recently to see how many PSCers had, or do, suffer from

hives/allergies - although only a small number participated, 50% had

suffered from hives/allergies at some time. An interesting point that

needs to be investigated further I think?

Take care - you must be hugely busy with 3 10 year olds!

Kym [uK] PSC Feb 06

[Guest guest]

-----Original

Message-----

I also ran a poll

recently to see how many PSCers had, or do, suffer from hives/allergies -

although only a small number participated, 50% had suffered from

hives/allergies at some time. An interesting point that

needs to be investigated further I think?

I

don’t think PSC & allergies have anything to do with each other, but

that’s just MHO. Over 50% of

the population has allergies, so naturally 50% of us would too……

“If

you live in the United States,

chances are you have allergies. At least, that's the

finding from the third National Health and Nutrition Examination Survey (NHANES

III).

It

found that 54.3 percent of Americans between the ages of 6 and 59 tested positive

to one or more allergens. A positive test also means

that the person has a greater risk of asthma, hay fever

and eczema.”

From the web site: http://www.sixwise.com/newsletters/05/08/10/50_of_us_population_has_allergies_most_dont_realize_it__amp_suffer_unnecessarily__do_you.htm

Barb in Texas - Together in the Fight, Whatever it Takes!

Son Ken (33) UC 91 - PSC 99 Listed 7/21 @ Baylor Dallas

[Guest guest]

I was actually asking about something different than allergies- I was

asking about immune deficiencies- specifically common variable immune

deficiency that is often related to autoimmune problems the way I

understand it.

Lori

>

> -----Original Message-----

> I also ran a poll recently to see how many PSCers had, or do, suffer

> from hives/allergies - although only a small number participated, 50%

> had suffered from hives/allergies at some time. An interesting point

> that

> needs to be investigated further I think?

> I don't think PSC & allergies have anything to do with each other, but

> that's just MHO. Over 50% of the population has allergies, so naturally

> 50% of us would too..

> " If you live in the United States, chances are you have allergies. At

> least, that's the finding from the third National Health and Nutrition

> Examination Survey (NHANES III).

> It found that 54.3 percent of Americans between the ages of 6 and 59

> tested positive to one or more allergens. A positive test also means

> that the person has a greater risk of asthma, hay fever and eczema. "

> From the web site:

> http://www.sixwise.com/newsletters/05/08/10/50_of_us_population_has_alle

> rgies_most_dont_realize_it__amp_suffer_unnecessarily__do_you.htm

>

> Barb in Texas - Together in the Fight, Whatever it Takes!

> Son Ken (33) UC 91 - PSC 99 Listed 7/21 @ Baylor Dallas

>

[Guest guest]

Hi Lori;

From what I have read, primary immune deficiency can be associated

with sclerosing cholangitis, but in this combination the sclerosing

cholangitis is considered to be " secondary " to the " primary " immune

deficiency syndrome with which it is associated:

_____________________

Hepatology. 2006 Nov;44(5):1063-74.

Sclerosing cholangitis: a focus on secondary causes.

Abdalian R, Heathcote EJ

Department of Medicine, University Health Network, Toronto Western

Hospital, University of Toronto, Toronto, Ontario, Canada.

Secondary sclerosing cholangitis (SSC) is a disease that is

morphologically similar to primary sclerosing cholangitis (PSC) but

that originates from a known pathological process. Its clinical and

cholangiographic features may mimic PSC, yet its natural history may

be more favorable if recognition is prompt and appropriate therapy is

introduced. Thus, the diagnosis of PSC requires the exclusion of

secondary causes of sclerosing cholangitis and recognition of

associated conditions that may potentially imitate its classic

cholangiographic features. Well-described causes of SSC include

intraductal stone disease, surgical or blunt abdominal trauma, intra-

arterial chemotherapy, and recurrent pancreatitis. However, a wide

variety of other associations have been reported recently, including

autoimmune pancreatitis, portal biliopathy, eosinophillic and/or mast

cell cholangitis, hepatic inflammatory pseudotumor, recurrent

pyogenic cholangitis, primary immune deficiency, and AIDS-related

cholangiopathy. This article offers a comprehensive review of SSC.

PMID: 17058222.

_________________

As I understand it, CVID is the most common form of primary immune

deficiency, but it's very heterogeneous, and can be caused by a

number of different genetic mutations:

_________________

Curr Opin Allergy Clin Immunol. 2005 Dec;5(6):504-9.

Tackling the heterogeneity of CVID.

Goldacker S, Warnatz K.

University Hospital Freiburg, Freiburg, Germany.

PURPOSE OF REVIEW: Common variable immunodeficiency is clinically the

most relevant primary immunodeficiency of the adult. Its

heterogeneity has hindered progress in the pathogenetic understanding

of the majority of common variable immunodeficiency patients. This

abstract summarizes recent aspects of the field and emphasizes the

need for a commonly accepted approach to classify common variable

immunodeficiency. RECENT FINDINGS: In the last 2 years, the first

genetic defects underlying common variable immunodeficiency,

including ICOS, TACI, BAFF-R and CD19, have been identified. The

analysis of dendritic cells demonstrated alterations in a majority of

patients in addition to the disturbed T and B-cell function. Several

changes of the adaptive immune system might be secondary to an

underlying chronic inflammatory setting possibly due to a HHV8

infection in a subgroup of patients with granulomatous disease,

autoimmune phenomena and T-cell dysfunction. The occurrence of

granulomatous inflammation is associated with a worse prognosis

compared with common variable immunodeficiency patients without

granuloma. SUMMARY: The pathogenesis of common variable

immunodeficiency includes disturbances of the adaptive as well as

innate immune system. Identified monogenic defects account for about

10% of cases, leaving the majority of defects undefined and certainly

in part epigenetic. To combine the known aspects of the pathogenesis

of common variable immunodeficiency to a conclusive picture, the

clinical and immunologic phenotyping of patients needs to be

standardized. PMID: 16264329.

_________________

CVID is very commonly associated with gastrointestinal disease

resembling inflammatory bowel disease:

_________________

Dig Dis Sci. 2007 Apr 12; [Epub ahead of print]

Gastrointestinal Manifestations in Patients with Common Variable

Immunodeficiency.

Khodadad A, Aghamohammadi A, Parvaneh N, Rezaei N, Mahjoob F,

Bashashati M, Movahedi M, Fazlollahi MR, Zandieh F, Roohi Z,

Abdollahzade S, Salavati A, Kouhi A, Talebpour B, Daryani NE

Department of Pediatrics, Division of Gastroenterology, Children's

Medical Center Hospital, Tehran University of Medical Sciences,

Tehran, Iran.

This study focuses on endoscopic and pathologic alterations of

gastrointestinal (GI) disorders of Iranian patients with common

variable immunodeficiency (CVID). Nineteen of 39 CVID patients (48%)

had GI complaints. The most common symptom was chronic diarrhea

(28%). In endoscopic examination of small intestines, 15 patients had

no abnormal finding. Duodenal biopsy revealed villous atrophy in

eight and nodular lymphoid hyperplasia in three patients. There was

no statistically significant difference between patients with and

patients without duodenal villous atrophy regarding the presence of

chronic diarrhea, anemia, and absolute CD4+T cells. In three

patients, biopsies of the colon showed chronic noncrypt-destructive

colitis. GI problems pose a high morbidity to CVID patients and are

second only to respiratory complications. CVID patients are at

increased risk of infectious and inflammatory conditions in the GI

tract. Early diagnosis of these complications improves the quality of

life and well-being of patients. PMID: 17431775.

_________________

Some recent treatments being tested include IL-12/IL-23 inhibitors:

_________________

Billich A. Drug evaluation: apilimod, an oral IL-12/IL-23 inhibitor

for the treatment of autoimmune diseases and common variable

immunodeficiency. IDrugs. 2007 Jan;10(1):53-9. PMID: 17187316

Mannon PJ, Fuss IJ, Dill S, Friend J, Groden C, Hornung R, Yang Z, Yi

C, Quezado M, Brown M, Strober W. Excess IL-12 but not IL-23

accompanies the inflammatory bowel disease associated with common

variable immunodeficiency. Gastroenterology. 2006 Sep;131(3):748-56.

PMID: 16952544.

_________________

Please let us know if the CVID diagnosis is refined!

Best regards,

Dave

(father of (21); PSC 07/03; UC 08/03)

>

> We recently found out that my son has an immune deficiency that is

for now thought to be CVID...that dx may be refined a little soon...

[Guest guest]

Thanks for all the info !! You're the best !!

I will let you know what the immunologist says about what type of

immune defciency Braden has.

Lori

>

> Hi Lori;

>

> From what I have read, primary immune deficiency can be associated

> with sclerosing cholangitis, but in this combination the sclerosing

> cholangitis is considered to be " secondary " to the " primary " immune

> deficiency syndrome with which it is associated:

> _____________________

>

[Guest guest]

Hi Lori;

I stumbled on this article today and thought that it might be of

interest to you:

Najwa Elnachef M.D., Marc Mc M.D., D. Chey M.D.,

F.A.C.G., A.G.A.F., F.A.C.P. (2007)

Successful Treatment of Common Variable Immunodeficiency Disorder-

Associated Diarrhea With Budesonide: A Case Report

The American Journal of Gastroenterology 102 (6), 1322–1325.

Abstract

PURPOSE: Common variable immunodeficiency disorder (CVID) is an

immunological disease that can present with gastrointestinal (GI)

symptoms including chronic diarrhea and abdominal pain. We report a

patient with CVID and chronic diarrhea who significantly improved with

budesonide.

METHODS: A 47-yr-old woman with CVID-associated diarrhea, steatorrhea,

abdominal pain, and bloating for several years had an exhaustive

evaluation for secondary causes of her symptoms, which was unrevealing.

At the advice of her immunologist, she attempted a course with

budesonide that significantly improved her GI symptoms. Given the

absence of literature on this treatment in CVID, we attempted to

systematically evaluate the clinical benefits after withdrawal of and

retreatment with budesonide.

RESULTS: Diarrhea, steatorrhea, abdominal pain, and bloating recurred

within 2 days of discontinuing budesonide. All parameters assessed

improved upon reinitiating budesonide. Further, serum immunoglobulin G

(IgG) levels significantly increased with treatment. No significant

side effects were observed with budesonide.

CONCLUSION: This is the first report of a patient with CVID-related

chronic diarrhea to be successfully treated with oral budesonide. This

observation provides clinicians with an effective and safe treatment

option in this difficult group of patients.

Best regards,

Dave R.

>

> Thanks for all the info !! You're the best !!

> I will let you know what the immunologist says about what type of

> immune defciency Braden has.

> Lori

[Guest guest]

Thanks again - I will definitely ask about this :-)

Lori

> >

> > Thanks for all the info !! You're the best !!

> > I will let you know what the immunologist says about what type of

> > immune defciency Braden has.

> > Lori

>

[Guest guest]

Lori, Kym and ,

I am an adult who has had cvid all my life. When I had elevated liver

function results 8 or so years ago, the hepatologist came up with PSC as a

tentative diagnosis, in the absence of other conditions that would make it

secondary.

Whether the sclerosing cholangitis is primary or secondary is neither here

nor there...it is still real and I have just spent a week in hospital having

the workup done for a transplant. It is complicated in some ways by the

cvid, but also simplified as the immune suppression after a transplant is

very much reduced by having the immune deficiency already. As the doctors

say...an interesting case.

Anything you want to know about immunoglobulins...I have been living without

them for 30+ years, ask away. I fi don't know the answer then I will know

someone who does. We are a big and knowlegable group us PIDer's.

Penny T (in Australia)

> Hi Lori;

>

> From what I have read, primary immune deficiency can be associated

> with sclerosing cholangitis, but in this combination the sclerosing

> cholangitis is considered to be " secondary " to the " primary " immune

> deficiency syndrome with which it is associated:

[Guest guest]

hi Penny-

Thanks for your response. How long have you known about the CVID ? My

son's doctor said things are 'signifigantly behind' in the US as far

as recognizing and diagnosing immune deficiencies. I have thought

about less need for immunosuppressants post transplant too. I thought

it was really interesting that the immunologist brought up liver

consequences even before I had a chance to talk about them. I know the

CVID makes things more complicated but not real clear on how yet- we

haven't had the 2nd immunologist appt yet to talk about

treatments.What have you been treated with for the CVID and the PSC ?

thanks in advance for any help or insight you may have :-)

Lori

lucky mom blessed with wonderfully wild 10 year old triplets

-- In

, " Penny " wrote:

>

> Lori, Kym and ,

> I am an adult who has had cvid all my life. When I had elevated liver

> function results 8 or so years ago, the hepatologist came up with

PSC as a

> tentative diagnosis, in the absence of other conditions that would

make it

> secondary.

> Whether the sclerosing cholangitis is primary or secondary is

neither here

> nor there...it is still real and I have just spent a week in

hospital having

> the workup done for a transplant. It is complicated in some ways by the

> cvid, but also simplified as the immune suppression after a

transplant is

> very much reduced by having the immune deficiency already. As the

doctors

> say...an interesting case.

> Anything you want to know about immunoglobulins...I have been living

without

> them for 30+ years, ask away. I fi don't know the answer then I will

know

> someone who does. We are a big and knowlegable group us PIDer's.

>

> Penny T (in Australia)

>

[Guest guest]

Lori,

I was diagnosed with CVID at the age of 9 due to repeated chest and sinus

infections. I lived on abx constantly as a child. When I turned 24 I started

IVIG infusions, and have been having them ever since (every three weeks

35gr). I am now 42 with two healthy children aged 10 and 11, and a very

understanding and loving (although domestically useless) husband! They have

kept me well for the past 20 years, although recent liver problems are now

affecting me.

For the PSC, I have been on 1.5gr urso (for about 8 years we think), and

recently started on Questran for the itch.

As I was primarily an immune patient, not many drs had seen liver

problems...but there appears to be an increasing number of connections.

I will email you some links if you like, for cvid info and support.

Keep in touch,

Penny T (in Australia)

> hi Penny-

> Thanks for your response. How long have you known about the CVID ? My

> son's doctor said things are 'signifigantly behind' in the US as far

> as recognizing and diagnosing immune deficiencies. I have thought

> about less need for immunosuppressants post transplant too. I thought

> it was really interesting that the immunologist brought up liver

> consequences even before I had a chance to talk about them. I know the

> CVID makes things more complicated but not real clear on how yet- we

> haven't had the 2nd immunologist appt yet to talk about

> treatments.What have you been treated with for the CVID and the PSC ?

> thanks in advance for any help or insight you may have :-)

>

[Guest guest]

Hi Penny;

Whether you have PSC in association with CVID might make a difference

here in the U.S. in terms or recruitment to the North American STOPSC

Registry. CVID is an exclusion criterion for this registry:

https://web.emmes.com/study/psc/about/about.html

Exclusion criteria:

None of the following may be present if the patient is to be eligible

for enrollment in the study:

- A diagnosis of large duct PSC, small duct PSC, AIH, or PSC/AIH

overlap more than five years prior to evaluation for eligibility

- Infectious exposure known to cause cholangitis/cholangiopathy (HIV

cholangiopathy, pyogenic cholangitis)

- Serologic or histologic evidence of other liver disease (alcoholic,

toxin/drug-induced, genetic, or autoimmune liver disease, except AIH)

- Positive HIV/HCV/HBV by PCR

- Cystic fibrosis

- Primary immunodeficiency (SCID, CVID, XLA)

- Prior biliary surgery or bile duct trauma

- Primary choledocholithiasis

- Ischemic bile duct strictures secondary to hepatic artery injury

(chemotherapy infusion, radiation)

- Bile duct or gallbladder neoplasm, excluding Cholangiocarcinoma

associated with PSC

- Congenital bile duct abnormalities (Caroli's Disease, congenital

hepatic fibrosis)

- Primary Biliary Cirrhosis

- Autoimmune Hepatitis without PSC (Adult participants only)

- AIH presenting as fulminant liver failure (Pediatric participants

with AIH only).

______________________

So the researchers here seem to think that SC associated with CVID

might be different from PSC.

Best regards,

Dave R.

> Whether the sclerosing cholangitis is primary or secondary is

neither here nor there...