[CIS PIDD] [cis-pidd] Mastocytosis, CVID, or something else

Mon Sep 29 17:04:54 EDT 2014

I've seen a few patients like this with in our cohort of familial tryptasemia patients. A few have had antibody issues and a few had FPIES.  Have you checked tryptase in other family members? Any joint hyper mobility in the family? We also have  a cohort of families with dominantly inherited symptoms consistent with a mast cell activation issue (urticaria flushing, anaphylaxis/anaphylactoid issues, dysautonomia  IBS-like symptoms, anxiety/depressionetc) who don't have high tryptases. They too have a predisposition to joint hyper mobility and a number are diagnosed with EDS type III. A number of the symptoms are soft, but in aggregate and in the families it makes a phenotype. Would be worth checking into the family for the other symptoms and for serum tryptase.

Josh

Joshua D. Milner, MD Chief, Genetics and Pathogenesis of Allergy Section
Laboratory of Allergic Diseases, NIAID, NIH
NIH Building 10-CRC Room 5-3950
Bethesda, MD  20892
Lab phone: 301 827 3662
Fax: 301 480 8384
jdmilner at niaid.nih.gov
http://www.niaid.nih.gov/labsandresources/labs/aboutlabs/lad/allergicinflammation/Pages/milner.aspx

From: Brant R Ward <bward at mcvh-vcu.edu<mailto:bward at mcvh-vcu.edu>>
Reply-To: CIS-PIDD <cis-pidd at lists.clinimmsoc.org<mailto:cis-pidd at lists.clinimmsoc.org>>
Date: Friday, September 26, 2014 5:37 PM
To: CIS-PIDD <cis-pidd at lists.clinimmsoc.org<mailto:cis-pidd at lists.clinimmsoc.org>>
Subject: Re: [cis-pidd] Mastocytosis, CVID, or something else

We've not seen any immunodeficiency/recurrent infections in our mastocytosis patients.  As was pointed out, you may have a low tryptase in food reactions.  But one would expect a higher level in mastocytosis, idiopathic anaphylaxis, or anaphylaxis to an environmental allergen like dog.  You can compare to the baseline tryptase ((1.2 x baseline) + 2), or a mature/total ratio to be sure.

In addition to IPEX, was DOCK8 ruled out?  They may not keep good specific Ab titers and can have terrible allergic disease.  His IgE is a bit low, but there are reported cases with levels in the hundreds (one in the original NEJM series).

Brant Ward, MD, PhD
Assistant Professor of Medicine
Clinical Immunology
Virginia Commonwealth University

-----Nick Bennett <njb35 at cantab.net<mailto:njb35 at cantab.net>> wrote: -----
To: "CIS-PIDD" <cis-pidd at lists.clinimmsoc.org<mailto:cis-pidd at lists.clinimmsoc.org>>
From: Nick Bennett <njb35 at cantab.net<mailto:njb35 at cantab.net>>
Date: 09/25/2014 04:02PM
Subject: [cis-pidd] Mastocytosis, CVID, or something else

Hi All,

I'm looking for help with a particularly difficult case.

Now 3yo I met him a year ago - many many allergy symptoms, recurrent anaphylaxis to foods and environmental triggers. Diagnosis of FPIES with an endoscopy/biopsy showing eosinophilia and mast cells in the GI tract (by report, I've not seen that to confirm). He requires severe dietary restriction and G tube feeds to maintain weight, and that at least is ok at the moment (he had severe failure to thrive as an infant). He was unable to tolerate anything except elemental food from about 4 months of age. Interestingly his symptoms of anaphylaxis are typically hives plus a weird "gagging" that he does. I've witnessed this and it's like his orophyarnx is swelling and causing him to choke, but I don't see any outward swelling, wheezing, hypotension etc. He will get very lethargic untill it is treated.

Multiple respiratory infections requiring antibiotics, CF workup negative. Immune evaluation has previously revealed low Hib and pneumococcal titers which responded to boosting, and then (when I saw him) had dropped off considerably. I diagnosed him as a possible CVID with B cell memory issues and started IVIG. From an infection standpoint that has improved things quite a bit. He is very sensitive to the IVIG and is the only child I currently have who I've seen throw off an anaphylactoid reaction mid-infusion. For a while we second-guessed ourselves and stopped the IVIG, but he got sick again so quickly it was restarted. Memory B cells on flow about a year ago were 9.1%. The rest of his flow cytometry is otherwise unremarkable, with normal total and precentages for CD4, CD8, CD4:CD8 ratio and CD19 B Cells.

He continues to experience food and environmental allergies requiring the use of epinephrine and antihistamines at times. IgE is only 100-150 when we've checked it.

I revisited his story recently with his mother during one of the IVIG infusions and wondered about mastocytosis. I started sodium cromolyn with initially perhaps some improvement, but he since then had anaphylaxis again to dog hair (a common trigger for him) and at that time tryptase was 2, which I took personal offence to as it appeared to contradict my idea about mastocytosis! This was several weeks into the cromolyn treatment so I had expected some preventative effect if mast cell degranulation was the issue.

Any and all insight would be appreciated. He's been seen by folks at Boston and Cincinnati already so some on this list may know him.

Cheers

Bennett

--
Nicholas Bennett MA(Cantab), MBBChir, PhD, FAAP
Assistant Professor of Pediatrics
Co-Director of Antimicrobial Stewardship
Medical Director, Division of Pediatric Infectious Diseases and Immunology
Connecticut Children's Medical Center,
282 Washington Street,
Hartford, CT 06106
Office Tel: +1 860 545-9490
Office Fax: +1 860 545-9371
Cell: +1 315 395-7876
Twitter: @peds_id_doc

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