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

[Nacho Gonzalez]

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

>

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