[CIS-PAGID] Autoimmune neutropenia and CVID - need advice

[Richard Wasserman]

I would worry about lymphoma or other clonal proliferation. Monoclonal
immunoglobulin production would be very unusual in the age group but I
guess anything is possible. (There could be an IgM/IgG producing clone) I'd
look at an immunoelectrophoresis and a PET scan. I'd also consider a more
extended study of her lymphocytes. I would not treat her with steroids, I
agree that you'd just be buying more trouble.

With regard to convincing her of the seriousness of her condition, perhaps
sending her for a second opinion to another major center (New York, Boston)
might be helpful.
Good luck,
Richard Wasserman

On Sun, May 20, 2012 at 1:17 PM, Hsu, Florence <ida.hsu at yale.edu> wrote:


>   Good question — I suppose it's the combination of ANC 0, apparent lack

> of response to G-CSF when tried at an outside hospital in the setting of an

> infection, and the fact that she is having some infections — certainly more

> than before, and she recently had some oral mucositis.  Now on top of it

> all, her total IgG and IgM are "normal", so it'll be even harder to

> convince her she needs IV or SCIG.

> How often have people seen IgG and IgM levels normalize in a case like

> this?  I am assuming it's the stress of her neutropenia and possibly

> infections driving a polyclonal humoral response.

>

>  Ida

>

>   From: <Kumar>, Ashish <Ashish.Kumar at cchmc.org>

> Reply-To: "pagid at list.clinimmsoc.org" <pagid at list.clinimmsoc.org>

> Date: Sunday, May 20, 2012 1:04 PM

> To: "pagid at list.clinimmsoc.org" <pagid at list.clinimmsoc.org>

>

> Subject: Re: [CIS-PAGID] Autoimmune neutropenia and CVID - need advice

>

>   What is the indication to treat this neutropenia – just the number? If

> her marrow capacity to produce neutrophils is normal, which looks like it

> is, then the risk of infection from the neutropenia is not that high.

> Treating with steroids in this situation will only add more morbidity.

> Rituximab is better tolerated and less likely to cause serious problems but

> I urge that you consider the cost-benefit ratio. In my small experience, I

> have treated patients like this with observation only  - one young woman

> has had an ANC of 0 for 3-4 years now; and no infections, granted while on

> IVIG. ****

>

> ** **

>

> Ashish Kumar****

>

> ** **

>

> *From:* pagid-bounces at list.clinimmsoc.org [

> mailto:pagid-bounces at list.clinimmsoc.org<pagid-bounces at list.clinimmsoc.org>]

> *On Behalf Of *Nacho Gonzalez

> *Sent:* Sunday, May 20, 2012 10:50 AM

> *To:* pagid at list.clinimmsoc.org

> *Subject:* Re: [CIS-PAGID] Autoimmune neutropenia and CVID - need advice**

> **

>

> ** **

>

> I have a similar patient (now 9y.o) with brain granuloma three years

> ago.She developed autoimmune neutropenia,anemia and thrombopenia. Rituxan

> worked well (Charlotte's has experience in this condition... See previous

> discussions in this mailing list). Due to chronic hepatitis and lung

> disease she is now under cyclosporine...uneventfully. So I would try with

> rituxan,works well with autoimmune citopenias refractory to steroids and

> immunoglobulins.

> Best regards,****

>

> Luis Ignacio Gonzalez Granado

> Immunodeficiencies unit

> Hospital 12 octubre

> Madrid.Spain****

>

> El 20/05/2012 16:21, "Hsu, Florence" <ida.hsu at yale.edu> escribió:****

>

> Dear all,****

>

>  ****

>

> I am looking for some advice and insight into a challenging case, I'd

> appreciate any help!****

>

>  ****

>

> We have a young woman (22 yo) under our care with history of CVID

> diagnosed incidentally at age 11 (in setting of Lyme meningitis), managed

> conservatively without IVIG (just PRN antibiotics) due to minimal infection

> history, and lost to follow-up, until she presented a fewmonths ago with

> severe neutropenia, anti-neutrophil antibody positive, ANC 0.  ****

>

> ** **

>

> She is anemic and direct Coomb’s positive now as well.  BM biopsy was

> hypercellular with prominent lymphoid aggregates and small granulomas

> consistent with CVID, FISH and cytogenetics were normal.  She had no

> significant response to an initial trial of G-CSF.****

>

>  ****

>

> Of note, this patient has been extremely resistant to therapy to date,

> refusing IVIG, as she has “managed so well” clinically without it so far,

> and quite frankly she is having a hard time accepting the fact that she has

> a serious illness that may require aggressive therapy.****

>

>  ****

>

> My first question is:  what are the best therapeutic options for the

> neutropenia?  We are considering rituximab, but the hematologists here have

> limited experience with this in the setting of AIN.  She has also been very

> resistant to IVIG, which we feel is important for her to receive prior to

> any rituximab, as that would affect her already defective humoral

> immunity.  Should we just startwith corticosteroids, and how safe is that

> without IgG coverage?****

>

>  ****

>

> Question #2:  Her IgG levels have actually increased from 388 in 2009, to

> 565 (around the onset of her neutropenia this spring), to 950 a month

> later!  We assume that this is not “normal” IgG, as she historically has

> not been able to mount a significant response to vaccinations, and recently

> had little IgG2 but elevated IgG3, would others agree?  Has anybody

> seenthis before, and does she still warrant IgG replacement (with or

> without her neutropenia)?  Recent CT done at outside hospital (in setting

> of bronchial infection at onset of neutropenia) did show mild

> mediastinal/para-aortic lymphadenopathy, splenomegaly, mild bronchiectatic

> changes, and bilateral nodular infiltrates <2cm size****

>

>  ****

>

> Question #3:  She is returning tomorrow for repeat post-vaccination titers

> (conjugated pneumococcal, meningococcal, and Tdap) – what other labs would

> you suggest we check?****

>

>  ****

>

> Thank you so much for your help!!!****

>

>  ****

>

> Sincerely, ****

>

> Ida Hsu****

>

> Section of Allergy and Immunology****

>

> Yale University School of Medicine****

>

> Phone: (203) 785-4143****

>

> Fax: (203) 785-3229****

>

> ** **

>

>  ****

>

> Her labs to date if you are interested, note that she has NEVER received

> IVIG:****

>

>  ****

>

> Vaccine history:****

>

> Meningitis vaccine – 2008, N. meningitidis IgG undetectable in 7/09****

>

> Pneumovax – 8/21/09, responded to 3/12 serotypes****

>

> Conjugated pneumococcal and meningococcal  vaccines – 1/15/10 (lost to

> follow-up, immediate post-vaccination titers not checked, but titers to

> both were all low when checked in 3/12)****

>

>  ****

>

> 8/15/97 ****

>

> IgG 466****

>

> IgA 10****

>

> IgM 8****

>

> VZV Ab negative****

>

>  ****

>

> 10/27/03****

>

> IgG 521****

>

> IgA 7****

>

> IgG1 361****

>

> IgG2 undetectable****

>

> IgG3 112****

>

> IgG4 undetectable****

>

> HIB 0.31****

>

> Tetanus <0.10****

>

> Flow – lymphopenia noted, predominantly affecting T, NK cells. CD3+ 646,

> CD4+ 405, CD8+ 189****

>

>  ****

>

> 1/3/09 ****

>

> IgG 405****

>

> IgA 10****

>

> IgM 26****

>

> WBC 2.5****

>

> ANC 1790****

>

> ALC 380****

>

> EBV VCA-IgM positive****

>

>  ****

>

> 7/31/09****

>

> IgG 492****

>

> IgA <7****

>

> IgM 21****

>

> IgE <2****

>

> Pneumococcal – all <.22 except for serotype 5 – 0.46****

>

> Neisseria meningitidis IgG – all undetectable (prev vaccinated for college)

> ****

>

> HIB 3.0****

>

> Tetanus <0.10****

>

> VZV indeterminate****

>

> EBV-VCA IgG Positive****

>

> Flow cytometry - absolute decrease in T, NK, B cells.  CD3+ 568, CD4+ 349,

> CD8+ 156, CD45RA+ 225, CD45RA+ 218, NK 31, CD19+ 69****

>

>  ****

>

> 10/12/09****

>

> IgG 388****

>

> IgA <7****

>

> IgM 14****

>

> IgE <2****

>

> Pneumococcal  3/14 titers >1 - 5, 18C, 19F (post–vaccination on 8/21/09)**

> **

>

>  ****

>

> 7/24/10 ****

>

> IgG 386****

>

> IgM 16****

>

> IgA 6****

>

>  ****

>

> Outside hospital 2/27 –3/5/12:****

>

> Sputum PCP negative****

>

> Influenza A/B Ab negative****

>

> Legionella Ag negative****

>

> Parvovirus B19 IgG, IgM negative****

>

> CMV DNA negative****

>

> Strep pneumo Ag negative****

>

> IgG 418, IgA 9, IgM 280****

>

> Flow cytometry:****

>

> CD45+ lymphocytes  0.4****

>

> CD3+ 354****

>

> CD19+ 18****

>

> CD 16/56+ 17****

>

> CD4+ 285****

>

> CD8+ 59****

>

> H/S ratio 4.9 (>1)****

>

>  ****

>

> CBCs in early March:  ****

>

> WBC 0.8 – 1.3 (as low as 0.7 on 2/27)****

>

> ANC 0.1 – 0.2  (as low as 1% of 3.88 on 3/04, 3% of 4.06 on 3/04)****

>

> Hgb 10.9 – 12.2****

>

> Plts 95 – 107 (as low as 60 on 2/27)****

>

>  ****

>

> 3/07/12****

>

> IgG 565****

>

> IgM 553****

>

> IgA <7****

>

> IgE <2****

>

> IgG1 308****

>

> IgG2 16****

>

> IgG3 294 (elevated)****

>

> IgG4 <0.2****

>

> Histoplasma ID neg****

>

> Flow cytometry – marked leukopenia, lymphopenia.  Increase in CD45RO

> positive cells for age.  Marked non-specific binding of Ig to B cells.

>  CD4+ 598, CD8+ 101****

>

> HIB 1.8****

>

> Pneumococcal Abs – all low,*<*0.26****

>

> Tetanus <0.10****

>

> N meningitidis negative to A, C, Y, W-135 serogroups****

>

> HBV SAb, CoreAb, SAg  negative****

>

> HIV 1/2 negative****

>

> HCV negative****

>

> CMV PCR negative****

>

> Parvo B19 PCR negative****

>

> DAT Coombs negative****

>

> LDH 184****

>

> ACE 49****

>

> Anti-neutrophil Ab – POSITIVE.  "Neutrophil reactive antibodies (IgM only)

> and class I HLA antibodies were detected in the patient's sample.  The

> reactivity against neutrophils was still present following absorption with

> normal donor platelets (removes class I HLA antibodies)."****

>

>  ****

>

> 3/13****

>

> Vitamin B12 1076****

>

> Folic Acid 815****

>

> DAT negative****

>

>  ****

>

> 4/9/12****

>

> IgG 950****

>

> IgM 692****

>

> IgA 8****

>

> B. pertussis Ab 0.2****

>

> CBC 1.0/11.7/126, ANC 0.0****

>

>  ****

>

> 5/1/12****

>

> ABO Group/Rh B+****

>

> Ab screen negative****

>

> DAT Positive (IgG Positive, C3 Positive)****

>

> CBC 0.7/8.8/128****

>

>  ****

>

>  ****

>

> Imaging:****

>

> 2/27/12 - CT C/A/P****

>

> Mild mediastinal and para-aortic adenopathy****

>

> Moderate splenomegaly****

>

> Multiple bilateral nodular consolidations <2 cm w/centrilobular infiltrates

> ****

>

> Multiple hypodense lesions in both kidneys, up to 1.9cm, may represent

> renal carbuncle, masses, or less likely infarcts.  Bilateral renal scarring

> is noted.****

>

>  ****

>

> 5/1/12 CXR****

>

> Clustered nodular opacities in the right midlung similar to that seen on

> prior chest CT from 2/27/2012 and likely represent focal areas of bronchial

> impaction with possible developing bronchopneumonia. Mild bronchiectatic

> changes again seen bilaterally, better appreciated on the prior CT.****

>

>  ****

>   ------------------------------

>

> F. Ida Hsu, M.D.****

>

> Section of Allergy and Immunology****

>

> Yale University School of Medicine****

>

> Phone: (203) 785-4143****

>

> Fax: (203) 785-3229****

>




-- 
Richard L. Wasserman, MD, PhD
DallasAllergyImmunology
7777 Forest Lane, Suite B-332
Dallas, Texas 75230
Office (972) 566-7788
Fax (972) 566-8837
Cell (214) 697-7211
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