[CIS PIDD] [MARKETING][cis-pidd] granulomatous hepatitis of unknown etiology and low IgG and IgA -??

Wed Feb 10 00:53:13 EST 2016

Hi Tracy,

so basically you have low IgG, low IgA, normal IgM, no response to meningococcal vaccination, somewhat increased percentage of DNTs (common in CVID, see studies by C Speckmann S Ehl and co). She has granulomatous hepatitis, NRH of liver and granulomas of LN.

Your patient fulfills any used or recently suggested criteria for CVID, and phenotype is typical for gCVID, though I would love to hear naive CD4 T cell (low?), Tg/d counts (high?), B phenotyping results (hi Btrans?). This to make sure that you do not have a CID in your hands (in which case I would also look for rubella).
Granulomas are a feature of about 20 other PIDs, occasionally.

Most of the patients with this phenotype (which is not that rare a presenting phenotype) also have GLILD in lungs. She needs specifically HRCT (normal CT is not sensitive enough!!), spirometry, diffusion measured (and LFTs followed every 6-12 m) and likely at some point VATS-assisted biopsy.

You aim at troughs around 10 g/L = 1000, Entocort perorally usually helps with liver findings w/o severe systemic side effects, but you may need to treat the lungs more aggressively! The disease has a lot of natural fluctuation, close follow up of lungs is truly needed.

Serology is of course unreliable, you need to use PCR, Ag, culture, staining.

Prednisone 40 mg is too high for gCVID in my and others experience, lots of complications, opportunistic infections, even fatal.
Starting with 15-20 mg usually helps with liver and often with lungs (this is not sarcoidosis, you may want to check C Cunningham-Rundles & H Chapel's excellent article on the dg differences), but if GLILD unresponsive, see literature. Often flares held at bay with 5-7.5 mg/d at long term, but if not - again see literature.

"Gallbladder removed": many of these patients have idiopathic cholangitis, MRI and liver biopsy relook may be needed. May resemble PSC or PBC.

NRH: see literature, may develop portal hypertension!

If you feel that her problems are a bit too complicated, this is the patient I would remit to a highly experienced clinical immunologist, w/o shame. These patients really stretch all our abilities and competence!

ATB, kind regards,

Mikko

Oyl Mikko Seppänen
Harvinaissairauksien yksikkö (HAKE)

Head, Rare Disease Center,
Helsinki University Hospital (HUH)
FINLAND

phone +358 947180201
GSM +358 50 4279606
fax +358 9 47174703

CIS-PIDD <cis-pidd at lists.clinimmsoc.org<mailto:cis-pidd at lists.clinimmsoc.org>> kirjoitti 10.2.2016 kello 6.28:

Hello,

I am seeing a 29 year old female w/ recently diagnosed granulomatous hepatitis of unknown etiology (January 2016-1st admission) and low IgG (noted in current/2nd admission).  Prior to coming to university hospital, she had her gallbladder removed and her liver was knicked in Dec 2015 when she was being evaluated locally for abdominal girth.   She was transferred due to ascites and hepatosplenomegaly.

She has extensive work-up with no overt infection found except for a positive IgM antibody to brucellosis.  I saw her for the first time today.  She has had recurrent sinusitis since childhood and had T & A removed at age 17 due to recurrent strep throat.  She had ear infections but did not need PET tubes.  She had possible meningitis at age 19 and was hospitalized for 2 weeks for that and we hope to get her discharge records from that time period to learn more about that hospitalization since her memory is vague regarding this.

I am trying to determine if CVID as a potential diagnosis for the cause of her problems.  She had a biopsy of her liver that showed granulomatous hepatitis on 1/4/16 .  Her CT lung  is fine.  She does have hepatosplenomegaly.  She had LN biopsy done at OSH and the slide reviewed at our university hospital  confirmed  Numerous non-caseating granulomas effacing normal nodal architecture.

Has any folks seen granulomatous hepatits as presenting complaint for CVID or have you seen other immunodeficiency associated with granulomatous hepatitis?

Labs of interest:

Globulins 0.34 (low, nl 0.6-1) 1/29/16
IgG 194 (low, nl 634-1,700), IgA 64 (low; nl 78-436), IgM 206 (normal) - 1/23/16

IgG 201 (low, nl 634-1,700), IgA 78 (low; nl 66-436), IgM 188 (nl 45-281 ) - 1/29/16

- Brucella IgG wnl, IgM elevated- unreliable  BRUCELLA IgG 0.07, IgM 1.19 H (<1.10)

Cell markers 2/4/16: "there is a moderate lymphopenia with a relatively normal distribution of peripheral blood T and B cells. TCRalphabeta positive CD4/CD8 negative T cells are mildly increased. NKT cells are prominent. Increased T cell HLA-Dr expression indicates activation."

Post IVIG infusion:

1/30/16:
IgG = 619

Steroids started 1/30/16 for presumably sarcoidosis (as a diagnosis of exclusion).

1 week later

2/5/16:
IgG = 322
IgA = 72
IgM = 133

Tetanus IgG Ab = 1.08
Anti-A iso titer = 1:32
Anti-B iso titer = 1:64
CH50 = 70.2
FLEXITEST 1 NEISSERIA MENINGITIDIS IGG VACCINE RESPONSE, MAID
SEROGROUP A <0.5 L ug/mL
SEROGROUP C <0.5 L ug/mL
SEROGROUP Y <0.5 L ug/mL
SEROGROUP W-135 <0.5 L ug/mL

- CT with hepatosplenomegaly but otherwise normal w/o enlarged nodes to biopsy

- Pathology has reviewed lymph node from Pratville - lymph node consumed with granulomas. no normal lymph tissue.

- path report of normal peritoneum without granulomas. AFB stain negative and flow cytometry negative.

- Empirically treating for infiltrative process like sarcoid; also brucella as above concurrently with prednisone 40mg daily, Doxycycline, and Rifampin since 1/31/2016 ( Day 10 )

Thank you for your help,

Tracy Hwangpo

MD/PhD

Instructor, Division of Clinical Immunology & Rheumatology

Department of Medicine

thwangpo at uabmc.edu<https://webmail.uabmc.edu/owa/redir.aspx?C=Jvh21Y4R5Ey8El7HpI-8P70cvHtMgtIIoyupOWh-LnQ10U6acu4koIOBQhs3ZMe_AqV8kNSBks8.&URL=mailto%3athwangpo%40uabmc.edu>

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