[PAGID] complications in XLA patient

[John Ziegler]

-

Ashish

Has XLA been confirmed by gene testing? What viral antigen, PCR testing has
he had? What screening of plasma donors was in place?

John

-----Original Message-----
From: pagid-bounces at list.clinimmsoc.org
[mailto:pagid-bounces at list.clinimmsoc.org] On Behalf Of Ashish Kumar
Sent: Friday, 13 February 2009 2:46 PM
To: Pagid
Subject: [PAGID] complications in XLA patient

I need help with a very complex patient. It's a long story so please bear
with me.

- 24 year old Vietnamese male with X-linked agammaglobulinemia
- was on monthly plasma infusions in Vietnam until 2003 when he came to the
US and was switched to IVIG (BTK mutation was confirmed as well)
- developed ulcers on legs at age 14  that spread (ulcer spanned ankle to
knee on right leg) and became chronic
- after multiple biopsies and cultures, chronic non-healing ulcers diagnosed
as pyoderma gangrenosum; immune suppression initiated 4 years ago with
prednisone+MMF with gradual but dramatic response; at one point ulcers were
completely healed
- one episode of ascites 3 years ago, with no clear etiology; fluid drained
and did not recur
- recently traveled to Vietnam for a month (large dose of IVIG prior to
departure)
- upon return, leg ulcers noted to have regressed to original state of 2003,
along with significant ascites
- evaluation including paracentesis, liver biopsy, viral PCRs reveal no
etiology; ascites fluid noted to be transudate, liver biopsy showed
neutrophil infiltration with regenerative nodular hyperplasia
- prednisone resumed for PG with mild improvement in leg ulcers; MMF not
restarted because he was noted to have low WBC and platelets (30k)
- 2 weeks later developed fever, recurrence of massive ascites followed by
profuse watery bloody diarrhea; 4 litres of bloody watery stool in a one day
- GI endoscopy showed duodenum heavily infiltrated with lymphocytes, mucosa
of duodenum completely denuded with significant apoptotic bodies
- pathology consistent with grade III-IV GVHD; also noted to have several
esophageal varisces on endoscopy although none actively bleeding
- after ascitis fluid was drained, massive splenomegaly was palpable,
confirmed by abdominal CT, which showed multiple splenic infarcts
- underwent splenectomy with normalization of platelet count; spleen
pathology just showed multiple infarcts

The ascites and splenic infarcts can be explained by portal hypertension
caused by regenerative nodular hyperplasia of liver. But what caused that -
the same dysregulated T-cells that caused the GVHD-like gut pathology? We
cannot find any infectious agents anywhere, so do we initiate immune
suppression? If so, with what - he developed watery diarrhea 2 weeks after
Prednisone was initiated (1.5 mg/Kg). In the BMT world, steroid resistant
GVHD would be treated with ATG or sometimes Infliximab/Remicaid. The
symptoms began 2-3 weeks after he returned from Vietnam, so a tropical
infection is less likely since the incubation period would be too long. He
has puzzled all the specialists - GI, tropical medicine, pathology. Any
ideas?

Thanks!

Ashish Kumar

--
Ashish Kumar, MD, PhD
Assistant Professor
Pediatric Hematology/Oncology/Blood and Marrow Transplantation University of
Minnesota 420 Delaware St. SE Minneapolis, MN 55455
Ph: 612-626-2778
Fax: 612-626-4842