[CIS PIDD] [cis-pidd] Disregulatory Syndrome + masive splenomegaly + autoimmune hepatitis + cytopenias + pericarditis

Mon Jun 12 06:36:22 EDT 2017

Many thanks Mikko!!!
My best
SOLE
On Mon, Jun 12, 2017 at 02:36 CIS-PIDD <cis-pidd at lists.clinimmsoc.org>
wrote:

> Hi
>
>
>
> as mentioned, STAT3 GOF, PIK3CD… do not forget PIK3R1 either. Some other
> IPEX-like genes sound plausible too (especially considering how few
> patients have been found) , see Eleonora’s and Troy’s excellent review:
>
> Cell Mol Life Sci. <https://www.ncbi.nlm.nih.gov/pubmed/21984607> 2012
> Jan;69(1):49-58. doi: 10.1007/s00018-011-0838-8. Epub 2011 Oct 9.
>
>
>
>
>
> ATB
>
>
>
> Mikko
>
>
>
>
>
> *Mikko Seppänen*
>
> Director, Adjunct Professor, MD, PhD
>
> *Hospital District of Helsinki and Uusimaa, Children’s Hospital, Rare
> Disease Center *
>
> P.O.Box 280, 00029 HUS |Lastenlinnantie 2, Helsinki
>
> Senior Consultant
>
> *Hospital District of Helsinki and Uusimaa, Inflammation Center, Adult
> Primary Immunodeficiency Outpatient Clinic *
> mikko.seppanen at hus.fi
>
> +358 9 47180201[image:
> http://helmeias141v.hus.fi/sinfoweb/images/PointY.gif]| +358 50 4279606
> faxi +358 9 47174703
>
> www.hus.fi; www.harvinaissairaudet.fi
>
>  [image: cid:image002.jpg at 01D21E2C.7B3D60A0]
>
>
>
>
>
>
>
>
>
> *Lähettäjä:* cis-pidd at lyris.dundee.net [mailto:cis-pidd at lyris.dundee.net] *Puolesta
> *CIS-PIDD
> *Lähetetty:* 10. kesäkuuta 2017 3:32
> *Vastaanottaja:* CIS-PIDD <cis-pidd at lyris.dundee.net>
> *Aihe:* Re: [cis-pidd] Disregulatory Syndrome + masive splenomegaly +
> autoimmune hepatitis + cytopenias + pericarditis
>
>
>
> Dear Kelli and Megan, thank you for your suggestions!!
>
> Best
>
>
>
> SOLE
>
> On Fri, Jun 9, 2017 at 20:56 CIS-PIDD <cis-pidd at lists.clinimmsoc.org>
> wrote:
>
> Hi Maria,
>
>
>
> I would definitely consider STAT3 GOF - her case has many typical
> features: autoimmune enteropathy (many patients have what looks like celiac
> disease), lymphoproliferation, AI cytopenias, short stature, AI hepatitis,
> and low Tregs.  I also agree with you that other ALPS-like disorders are
> worth considering.
>
>
>
> Best,
>
>
>
> Megan
>
>
>
>
>
>
>
> Megan A. Cooper, MD, PhD
>
> Assistant Professor, Department of Pediatrics
>
> Director, Clinical Immunology
>
> Division of Rheumatology
>
> Washington University School of Medicine
>
> Cooper_m at wustl.edu
> <https://mail.wusm-pcf.wustl.edu/OWA/redir.aspx?C=BC4WUCQ_fUuap3pEPFb6hfMraGtH9tAIF1A5pvmTpRaRGtpUFcRGINZ4Nh0wtslF5e-0KwrezPc.&URL=mailto%3aCooper_m%40kids.wustl.edu>
>
> Lab website:
> http://research.peds.wustl.edu/Default.aspx?alias=research.peds.wustl.edu/Labs/Cooper_M
> <https://mail.wusm-pcf.wustl.edu/OWA/redir.aspx?C=BC4WUCQ_fUuap3pEPFb6hfMraGtH9tAIF1A5pvmTpRaRGtpUFcRGINZ4Nh0wtslF5e-0KwrezPc.&URL=http%3a%2f%2fresearch.peds.wustl.edu%2fDefault.aspx%3falias%3dresearch.peds.wustl.edu%2fLabs%2fCooper_M>
>
> (lab office) 314-286-0262
>
> (lab fax) 314-286-2895
>
>
> ------------------------------
>
> *From:* cis-pidd at lyris.dundee.net <cis-pidd at lyris.dundee.net> on behalf
> of CIS-PIDD <cis-pidd at lists.clinimmsoc.org>
> *Sent:* Friday, June 9, 2017 5:10 PM
> *To:* CIS-PIDD
> *Subject:* [cis-pidd] Disregulatory Syndrome + masive splenomegaly +
> autoimmune hepatitis + cytopenias + pericarditis
>
>
>
> Dear collegues, we would appreciate your thoughts about this case:
>
> 17 years old girl. Full term baby with recurrent acute diarrhea since
> first year of life.
>
> At the age of 3, diagnosed with celiac disease is made by biopsy and
> positive auto antibodies (MARSH III).
>
> At 4 years of age, began with splenomegaly + anemia + thrombocytopenia
> (with normal Bone marrow)
>
> At the age of 5: Nephrytic syndrome.  Due to ASMA +, liver biopsy
> suggestive of *Sclerosing cholangitis* with two normal Colangio
> resonances.
>
> At the age of 6, he started treatment with methylprednisone and
> azathioprine, suspended due to severe neutropenia at the age of 7.
>
> 10 years: duodenal video endoscopy revealed chronic duodenitis, MARSH1.
> Video colonoscopy informed as nodular lymphoid hyperplasia.
>
> New liver biopsy: *Sclerosing cholangitis* with cirrhosis evolution
> (Normal colangio renonance). Recurrent thrush
>
> 12 years: Mononucleosis with (IgM + EBV). Later on time EBNA +.
>
> 14 years: In the context of increased liver enzymes and increased
> hepatosplenomegaly, Restart aziatoprine treatment. 3 months later suspended
> for neutropenia.
>
> New Bone Marrow Aspiration revealed: Hypercellularity, myeloid hyperplasia
> and megakaryocytic cells with abnormalities.
>
> At 15 years (September 2014): hospitalization due to severe
> ulcero-necrotizing periodontitis and pancitopenia with response to
> Neupogen. Oral candidiasis treated with VO Fluconazol. Common germs swab
> for herpes: Negative. (She required flexible ferules on her teeth due to
> the great gum compromise)
>
> Received IVIG  plus methylprednisolone pulses for 3 days and then MP 40 mg
> / day for thrombocytopenia.
>
> Bone Marrow: cellularity ++++. Thrombocytopenia assumed as autoinmune.
>
> At almost 16 years : weight 44 kg (percentile 3-10), Height 146.5 cm
> (<percentile 3).
>
> Abdominal ecography:  spleen 237 mm with enlarged liver. New liver Bx:
> moderate inflammatory infiltrate with lymphocyte predominance and moderate
> plasmocytes and eosinophils. Chronic moderate hepatitis - Knodell 11 (8 +
> 3). Asumed as Autoimmune hepatitis. Treatment with meprednisone 8 mg/day.
> Sclerosing cholangitis discarded.
>
> 2 episodes of periodontitis without hospitalization in the last 2 years
> and *Microsporidium* + in stool sample
>
> 2016: Ankles arthralgia. Eco Doppler: normal. New neutropenia episode with
> ankles celullitis. Rheumatology Unit discarded rheumatologic pathology up
> to date
>
> Abdominal ecography: hepatomegaly with isolated adenomegalies and
> gallstones. Cardiology evaluation: ECG with repolarization disorder. MNR:
> pericarditis
>
> Episode of adenophlegmon. Persist with splenomegaly, neutropenia and
> monocitosis. New bone marrow: myeloid hyperplasia. Flow: 1.5% of mature
> monocytes with monoblasts and pro-monocytes.
>
> New eco cardiography: Left auricle dilatation, Ventricle with normal
> diastolic function
>
> May 2017: hospitalization due to neutropenia and severe preseptal eye
> cellulitis.
>
> *Immunological work up:*
>
> ·      Hipergammaglobulinemia > 2SD (IgG, IgA and IgM). Nowadays low IgE.
>
> ·      Good response to proteic and polysaccharide antigens.
>
> ·      C3/C4: previously normal. In actual lab low with normal CH50 and
> AH50 (consumption?).
>
> ·      Autoantobodies: Positive ANA (low titer- dot pattern). Anti-Ro:
> Positive , IgA ASCA: Positive. Low titers of IgA anti-transglutaminase and
> Positive IgG anti-deaminated gliadin peptides.
>
> ·      Normal Lymphoproliferation assay with different mitogens (CFSE)
>
>   *Lymphocyte subsets:* Lymphocyte count 1.320 cells/mm3
>
> ·        CD3: 72 %  / CD4: *50% (660)* / CD8: 21% / CD20: 25.5%  / CD56: *1.6%
> (21) *(Normal dim/bright ratio)
>
> ·        Double Negative: 2 % in different opportunities
>
> ·        High Vitamine B12 dosage. Pending FASL
>
> ·        Alpha-Beta/Gamma-Delta: normal ratio
>
> ·        Low Naïve T cells with LT memory expansion. Low memory B cells
> with slightly high transitional B cells.
>
> ·        High LTCD4 Th17+ cells (in different opportunities). Low FOXp3+
> cells.
>
> ·        Normal CD25 up regulation assay.
>
> ·        Normal degranulation assay (CD107a)
>
> ·        Pending: NK cells cytotoxity assay.
>
> *Treatment*
>
> 1.      TMS 5 mg/k/dose 3 times a week
>
> 2.      Vitamin D- Calcium
>
> 3.      Meprednisone 8mg/d
>
> 4.      Omeprazol
>
> 5.      Ursodesoxicolic acid
>
> 6.      Sirolimus 1-2mg/m2/d
>
> *K-RAS / N-RAS (Possible diagnose??)*
>
> Please, we will be happy of receiving your suggestions about any
> diagnostic key and treatment.
>
> Many thanks in advance
>
> *María Soledad Caldirola*
> Biochemsit, PhD fellow
> Ricardo Gutierrez Children's Hospital
> Buenos Aires, Argentina
>
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