[CIS PIDD] [cis-pidd] Opinion on GLILD

CIS-PIDD cis-pidd at lists.clinimmsoc.org
Mon Jul 31 10:08:13 EDT 2017 

Dear Juthaporn,
Sirolimus (or MMF) might be a good idea in this syndrome as both agents spare steroids and seem to work in many patients with LRBA-def/CHAI disease, at least in part. I am treating a 13yo with GLILD and AI cytopenia with sirolimus as single agent (plus SCIG for hypogamma) and the granulomata in the lungs resolved. Ultimately, however, ideally supported by a genetic diagnosis, I think I would at least search for a donor.
Did you exclude IPEX? What's his IgE?
Best
Markus

Markus G. Seidel, M.D. | Professor of Translational Pediatric Hematology and Immunology | Div. of Pediatric Hematology-Oncology | Dept. of Pediatric and Adolescent Medicine | Medical University Graz | Auenbruggerpl. 34/2 | A-8036 Graz | Austria | T. 0043 316 385 80215<tel:0043%20316%20385%2080215>| F. 0043 316 385 13717<tel:0043%20316%20385%2013717> | Secr. 0043 316 385 13485<tel:0043%20316%20385%2013485> | sent from my mobile phone | please excuse typos and terseness

Am 24.07.2017 um 17:37 schrieb CIS-PIDD <cis-pidd at lists.clinimmsoc.org<mailto:cis-pidd at lists.clinimmsoc.org>>:

Juthaporn
In my opinion, the presence of fibrosis on biopsy and a reduction of DLco (not sure how reduced) indicates that the GLILD is progressive and clinically relevant. The optimal choice for the treatment of GLILD is not known. Among the medications that have been used include steroids, TNF-blockers, abatacept (in LRBA or CTLA deficiency) and rituximab w either azathioprine or MMF. As we are a referral center for GLILD, we have seen numerous patients that have failed corticosteroids==we have seen that steroids may improve disease temporarily but it recurs w taper or cessation of steroids. In talking w some of my European colleagues, they apparently have had better luck w steroids. We currently use rituximab and either azathioprine or MMF (depending on TPMT genotype, presence of liver disease and ability to tolerate one or the other) and have induced stable remissions in most patients regardless of whether a monogenic cause was found including CTLA4 haploinsufficiency. The regimen has proven to be quite safe as well. Hope this is helpful. Good luck
Jack

John M. Routes, MD
Chief, Section of Allergy and Clinical Immunology
Professor of Pediatrics, Medicine, Microbiology and Immunology
Department of Pediatrics
Children's Hospital of Wisconsin
Medical College of Wisconsin
9000 W. Wisconsin Ave.
Milwaukee, WI  53226-4874

Phone: 414-266-6061
Fax: 414-266-6437
Email: jroutes at mcw.edu<mailto:jroutes at mcw.edu>


On 7/24/17, 9:02 AM, "Cowan, Juthaporn" <jcowan at toh.ca<mailto:jcowan at toh.ca>> wrote:

   The wedge biopsies from the RUL, RML, and RLL demonstrate similar histological findings, although more prominent in the lower love. Predominant findings are that of follicular bronchiolitis with occasional, scattered, mostly ill-defined, non necrotizing granulomata. Immunological stains demonstrate a reactive follicular lymphoid infiltrate with an admixture of both CD4, CD8, B lymphocytes. There appear to be a relatively paucity of plasma cells in relation to the degree of inflammation as demonstrated on cd138, kappa and lambda immunisations. No EBV EBER positive cells identified.
   There are parenchyma fibrosis and nodules.

   Thank you very much for your interest in this case. I am looking forward to hearing from you.
   Juthaporn

   Sent from my iPhone

On Jul 22, 2017, at 3:35 PM, Routes, John <jroutes at mcw.edu<mailto:jroutes at mcw.edu>> wrote:

Please provide complete PFTs-also can you provide a better description of the CT findings
Was there remodeling and/or fibrosis on lung bx?


Sent from my iPhone and because I have fat fingers the message will likely contain misspelled words, poor punctuation and other errors.

On Jul 21, 2017, at 3:29 PM, CIS-PIDD <cis-pidd at lists.clinimmsoc.org<mailto:cis-pidd at lists.clinimmsoc.org><mailto:cis-pidd at lists.clinimmsoc.org>> wrote:

Dear all,

I would appreciate your input on a case of young man who is 35 years old, Caucasian, father of two healthy daughters.

He has - recurrent sinopulmonary tract infections for years
           - AIHA off and on 10 years ago but seems to stable now
           - ITP in 2013
           - Pulmonary nodules waxing and waning since 2007
           - Hypothyroidism
           - Cerebellar mass 2015 (pathology - small vessel angiitis/vasculitis with an associated parenchymal mixed inflammatory infiltrate, no neoplasm, no virus, fungus, AFB, bacteria or spirochetes but a single cell positive for EBV) Patient had diplopia with decreased motor strength of hand initially but gradually improving on his own. Mass still persists though.
            - Chronic diarrhea, colon biopsy showed acute cryptitis and crypt abscesses with almost complete absence of plasma cells in colonic mucosa in 2016. Negative parasites.
            - Splenomegaly
            - IgG 1.2 g/L, IgA < 0.1 g/L, IgM 0.3 g/L -  on SCIG since 2015 and infection free
            - Eczema - intermittent

Genetic testing for CTLA4 (sanger) and LRBA negative. (A panel of gene testing was done at Dr. Rosenzweig's lab).

He is quite well in general (only mild DLCO on pulmonary function test) but the most recent CT showed possible GLILD. Open lung Bx was pursued and confirmed GLILD.

Questions
1. Should we treat his GLILD? If so, with what?
2. Even though we do not know the molecular cause of his phenotypes, should we do BMT since he is quite well now before he has more complications?

Juthaporn Cowan MD, PhD, FRCPC
Assistant Professor
Division of Infectious Diseases, Department of Medicine
Department of Biochemistry, Microbiology, and Immunology
University of Ottawa & The Ottawa Hospital
Associate Scientist
The Ottawa Hospital Research Institute
Tel 613-737-8899 ext 79617
Fax 613-737-8352


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