[CIS PIDD] [cis-pidd] 9 month-old girl with a novel STAT1 mutation

[CIS-PIDD]

Dear Yesim,

We do have good experience controlling enteropathy in STAT1 GOF disease with Ruxolitinib.  Ruxolitinib has also been useful in treating autoimmune cytopenias, arthritis and hepatitis in STAT1 GOF disease.  There are also patients who have less CMC after starting Ruxo.  I would encourage you to start Ruxolitinib.  It will take about 4 weeks for the diarrhea to improve and up to 3 months before the stools normalize.  I am happy to discuss this further.

Best Regards,
Lisa

Lisa Forbes, MD
Assistant Professor, Department of Pediatrics
Immunology Allergy and Rheumatology
Center for Human Immunobiology, Medical Director
Interim Medical Director, Texas Children’s Hospital Infusion Center
1102 Bates, Suite 330
Houston, TX 77030
Phone: 832-824-1319
Fax: 832-825-1260
lisa.forbes at bcm.edu
From: <cis-pidd at lyris.dundee.net<mailto:cis-pidd at lyris.dundee.net>> on behalf of CIS-PIDD
Reply-To: CIS-PIDD
Date: Thursday, November 9, 2017 at 5:09 PM
To: CIS-PIDD
Subject: [cis-pidd] 9 month-old girl with a novel STAT1 mutation

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Dear all,

I am following a 9-month-old Moroccan girl who initially presented with recurrent genital and oral candida infection and a labial abscess at 3 weeks of age. She eventually developed a rectovaginal fistula requiring multiple surgeries. Initial immunologic evaluation when I first saw her at 4 months of age was unremarkable.
At that time I also diagnosed her with FPIES to cow's milk.
She did well on prophylactic itraconazole without any recurrence of genital or oral thrush.

She had tolerated 1st dose of rota virus vaccine at 10 wks of age, but developed severe diarrhea about 10 days after the second dose (which was given by mistake).
Diarrhea persisted and became very severe requiring gut rest and TPN at age 6 months. Stool pcr study has been negative for rotavirus. She was admitted because of severe dehydration due to diarrhea (up to 60 watery BMs everyday). We switched to IV fluconazole but within a couple of days her LFTs increased to > 1000 ! So we had to stop it.

By that time we received WES report which revealed a de novo heterozygous mutation in STAT1 gene ( Variant: c.1627T >C Protein Change: p.Cys543Arg).
The functionality of this mutation was tested at Dr. Casanova's lab by GAS reporter assay which showed that this is a GOF mutation.

She went home on nystatin, TPN, and NPO. She had a PICC line. However, 10 days later she was taken to ER and diagnosed with septic shock.  PICC line culture grew candida parapsilosis. She responded to Amphothericin B very quickly. She is currently on Amphothericin B and TPN and doing well. However, she still has diarrhea when she takes anything by mouth.

Intestinal pathology was nonspecific (intraepithelial lymphocytes, mild chronic inflammation, etc).
Liver biopsy showed chronic inflammation- could be autoimmune, not clear.

At this time, I really don't want to refer her for HSCT because of the recent review which was not encouraging.

Is there any biologics we can try for this patient (such as JAK inhibitors) for her enteropathy ? Anyone has any experience?

Thanks in advance!

Yeshim



Yesim Yilmaz Demirdag, MD
Assistant Professor of Pediatrics
Columbia University Medical Center
Division of Allergy, Immunology and Rheumatology
3959 Broadway CHC7
New York, NY 10032
phone: (212) 305 2300




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