[PAGID] 6 mo old with enteropathy and few B cells

[sullivak at mail.med.upenn.edu]

Talk to Troy Torgerson- I think he has a few girls with a similar phenotype 
and they just get called IPEX-like.  Only 50% of patients with an IPEX 
phenotype have FoxP3 mutations so there is definitely anotehr way to get to 
the same phenotype.

Kate Sullivan

Quoting "MacGinnitie, Andrew" <Andrew.MacGinnitie at chp.edu>:


> Our immunology service is consulting on an interesting patient I'm having

> trouble understanding and I'd appreciate any input

> 

> Patient is a 6 mo old girl transferred to our hospital after a month in an

> outside hospital for failure to thrive and diarrhea.  She developed

> Klebsiella pneumonia and respiratory failure requiring intubation which was

> the proximate cause of transfer.  Intestinal biopsy showed autoimmune

> enteropathy; liver biopsy showed some fatty changes but hepatocytes

> themselves were normal and no evidence of autoimmunity. Stool cultures all

> negative

> 

> No significant infectious history prior to the Klebsiella

> 

> PE without rash, erythema or desquamation.  Really only remarkable for small

> size, intubation and some increased breath sounds.

> 

> Immune studies to date include

> 

> CBC on transfer showed ALC of 1320, and 440 eos in setting of increased 

polys

> with left shift.  Current ALC about 2000 and eos 0, but on steroids.

> 

> Multiple IgA < or = 10; IgM all < 25

> Multiple IgGs <40.  Several g/kg of IVIG have not been very successful at

> raising the IgG level, although 2g/kg raised the level to 300 right after 

but

> down to 100 today (24 hours later) suggesting she is losing quickly.

> 

> Lymphocyte subsets include

> 

> CD3+  2489

> CD3+/CD4+ 1940

> CD3+/CD8+  577

> CD19+  46

> CD16/CD56+ 111

> 

> so very low B cells, slighly low NK and CD3CD8 cells

> 

> We also had them stain for CD45RA and CD62L and this showed  >90% of CD4

> cells were CD45RA/CD62L+ (naive)

> 

> Proliferation studies are pending as are repeat subsets.

> 

> In summary, 6 mo old girl with chronic diarrhea probably secondary to

> autoimmune enteropathy, with lack of B cells or evidence of immunoglobulin

> synthesis.

> 

> I've thought of Omenn's but she lacks characteristic skin findings, and I

> wouldn't expect a normal number of naïve T cells.  

> 

> I also considered IPEX, but she's a girl and only has autoimmunity in the 

gut

> that we can see.

> 

> Finally I thought about an autosomal recessive agammaglobulinemia with a

> second process causing the autoimmune enteropathy and protein losing

> enteropathy, but that isn't very elegant.

> 

> I'd appreciate any input on differential or further testing. 

> Immunosuppression with steroids and cyclosporine was started yesterday.

> 

> Andy

> 

> Andrew J. MacGinnitie MD PhD 

> Assistant Professor of Pediatrics 

> Division of Pulmonary Medicine, Allergy and Immunology 

> Children's Hospital of Pittsburgh 

> 3705 Fifth Ave, Pittsburgh, PA 15213 

> andrew.macginnitie at chp.edu 

> 412/692-8903 (office) 412/692-8499 (fax)

> 

> 

> 

> -----Original Message-----

> From: pagid-bounces at list.clinimmsoc.org on behalf of Kathleen E. Sullivan

> Sent: Thu 6/28/2007 7:15 AM

> To: pagid at list.clinimmsoc.org

> Subject: Re: [PAGID] Welcome to the "PAGID" mailing list

>  

> A form of LAD perhaps?

> 

> Kathleen E. Sullivan MD PhD

> Chief, Division of Allergy and Immunology

> Professor of Pediatrics

> The Children's Hospital of Philadelphia

> (p) 215-590-1697

> (f) 267-426-0363

> 

> 

> On Jun 27, 2007, at 6:41 PM, Dr Joanne Smart wrote:

> 

> > Dear All,

> >

> > Would welcome any suggestions about the following case (currently  

> > an inpatient at the Royal Children's Hospital Mebourne Australia):

> >

> > Essentially this is a 6 week old female infant born to  

> > consanguineous Afghanistan parents who presents with presumed  

> > sepsis, diarrhea, hepatosplenomegaly, exfoliating dermatitis,  

> > profound eosinophillia and thrombocytopenia.

> >

> > This occurs in the context of a sister, Karima, who died at the age  

> > of 5 months in Kentucky with a similar presentation in December  

> > 2005.  This child was a term baby with an unremarkable perinatal  

> > period.  She first became unwell at 4 weeks with vomiting and mild  

> > diarrhoea, and was found to have an abnormal lumbar puncture result  

> > (?Citrobacter meningitis from discharge summary).  She was treated  

> > with 1 week of IV antibiotics with improvement, but ongoing  

> > vomiting on discharge.  She was recalled back to the hospital after  

> > 1-2 days for a bone marrow aspirate for an apparent blood  

> > abnormality, and the parents were reassured that this "wasn't  

> > leukaemia". She was given nyastatin, metoclopramide, ranitidine and  

> > prednisolone on that occasion.

> >

> > She continued to have episodic vomiting at home 1-2x/day and  

> > deteriorated at 6 weeks of age with increasing diarrhoea, facial  

> > oedema, anuria, left focal seizures and respiratory failure. She  

> > also had a dry, erythematous and exfoliating rash on presentation,  

> > which was later thought to look like ichthyosis by her physicians.  

> > Investigations at this stage revealed hypereosinophillia, anaemia,  

> > thrombocytopenia, hyponatremia, hypocalcemia and a severe metabolic  

> > acidosis. Aspergillous grew from her endotracheal tube, and skin &  

> > bone marrow biopsy revealed was apparently inconclusive.  Further,  

> > CT brain revealed cerebellar atrophy and bilateral subdural  

> > hydromas.  Her treatment included mechanical ventilation,  

> > phenobarbitone, amphotericin B and caspofungin. Eventually with no  

> > improvement despite 6 weeks of mechanical ventilation we understand  

> > care was tragically withdrawn. The consideration at that stage was  

> > whether she could have Ommen's, or an undefined hypereosinophllic  

> > syndrome.

> >

> > Furthermore, there was apparently 14-16 maternal grandaunties and  

> > granduncles who passed away between the ages of 4 month-2 years  

> > from presentations with fever, diarrhoea and rashes. They however  

> > lived in a remote village with no medical care and it is uncertain  

> > how many in fact have treatment such as antimicrobials available.

> >

> > Zohra herself was a term baby who was initially well until day 7 of  

> > life, when she presented with fevers, irritability, poor feeding  

> > and vomiting. Her inflammatory markers were raised (CRP 105, WCC  

> > 17, neutrophils 12) and her platelet count dropped to 70 on day 5  

> > of admission, but resolved to 188 on discharge.  Lumbar puncture  

> > was attempted but unsuccessful. Stool cultures were negative. In  

> > total she received 6 days of IV flucloxacillin and gentamicin, and  

> > 3 days of IV ceftraixone.

> > She then was readmitted at 3 weeks, when she re-presented with  

> > fevers, rash and irritability, with no improvement having been  

> > treated with oral amoxicillin by her local doctor for 2 days.  Her  

> > CSF at that stage revealed 10 polymorphs, 810 red blood cells and  

> > her CRP was elevated at 79. Cultures of the CSF, urine and blood  

> > were negative, and she received 4 days of IV cefotaxime, penicillin  

> > and gentamicin before being discharged.

> >

> > She re-presented at the age of 4 weeks with vomiting and diarrhea,  

> > but this time without fevers.  No investigations were performed and  

> > she was treated for a presumed gastroenteritis with nasogastic  

> > rehydration. She was then transferred to Royal Children's Hospital  

> > Neonatal Unit for ongoing weight loss.  She had an initial severe  

> > metabolic acidosis (pH 7.09, HCO3- 3, base excess -24; anion gap  

> > 19; lactate 1.6 normal) and received fluid resuscitation and  

> > commencement of IV antibiotics.  As an inpatient she progressively  

> > became unwell with development of an exfoliating dermatitis and  

> > temperature instability.

> > Her investigations to date reveals:

> > Full blood count

> > Normocytic anaemia (Hb 85-100g/L) - presumably partly contributed  

> > by multiple blood tests taken and haemodilution from fluid  

> > resuscitation

> > Leucocytosis (WCC 33-50x109/L) with fluctuating neutrophillia  

> > (8-12x109/L), high band count (3.2-7x109/L) and normal lymphocyte  

> > counts (7-8x109/L)

> > Profound eosinophillia (15-20x109/L)

> > Progressive thrombocytopenia (from 500 to 51x109/L)

> > Biochemistry

> > Progressive hyponatremia (142mmol/L on presentation, dropped to  

> > 124mmol/L) and hypokalemia (3mmol/L)

> > She was also hypocalcemic (1.75mmol/L) , hypomagnesemic (0.54mmol/ 

> > L) hypophosphatemic (0.65mmol/L) and hypoabluminaemic (16g/L)

> > Liver function and renal function essentially normal

> > Raised stool and renal electrolytes, raising the question of  

> > possible renal tubular acidosis

> > Cultures

> > CSF - negative culture (0 polymorphs, 1 lymphocyte, 0 erythrocytes)

> > Urine - negative culture

> > Stool - negative culture

> > Immune function

> > Antibodies

> > IgG 4.28 g/L

> > IgA <0.07 g/L

> > IgM 0.24 g/L

> > Lymphocyte markers

> > Normal on 2 occasions

> > 18/6/07 - Lymphocyte count (4.39x109/L), CD3 74%, CD4 63%, CD8 13%,  

> > CD19 24% and NK cells 3%

> > 19/6/07 - Lymphocyte count (6.8x109/L), CD3 77%, CD4 66%, CD8 12%,  

> > CD19 18% and NK cells 3%.

> > Lymphocyte proliferation to PHA

> > Done on 2 occasions

> > 18/6/07 - 15,986 to 50,657 (Control 39 to 57,241)

> > 19/6/07 - 7,595 to 17,291 (Control 17 to 56,281)

> > Neutrophil oxidative burst - normal

> > Pending - Variable Number Tandem Repeats (VNTR) and HLA typing of  

> > Zohra and her parents.

> > Other

> > Bone marrow aspirate - normal apart from non-diagnostic high  

> > eosinophills

> > Urine aminoacids - normal

> > Imaging

> > Abdominal US - no organomegaly

> > Cranial ultrasound - bilateral grade 1 supependymal haemorrhages

> >

> >  Currently she is being managed with total parental nutrition and  

> > IV meropenem and vancomycin.  She has been visited by multiple  

> > teams including rheumatology, infectious diseases, metabolic  

> > physicians, nephrology and gastroenterology.  She is scheduled to  

> > have a liver, skin and muscle biopsy soon.

> >

> >

> >

> > Zohra's lymphocyte proliferation whilst not normally is not  

> > profoundly depressed as you would expect in a child with SCID.   

> > Lack of B cells make Ommen's syndrome unlikely.  We are considering  

> > the posibilites of maternally engrafted T cells with resultant  

> > graft-versus-host disease and are currnetly awaiting results of  

> > VNTR's and HLA typing (which will also help rule out bare  

> > lymphocyte syndrome).

> >

> >

> >

> >

> >

> >

> >

> > At 12:03 AM 28/06/2007, you wrote:

> >> Welcome to the PAGID at list.clinimmsoc.org mailing list!

> >>

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> >

> > Dr Joanne Smart

> > BSc MBBS PhD FRACP

> > Clinical Immunologist

> > Department of Immunology

> > Royal Children's Hospital

> > Flemington Rd, Parkville

> > VICTORIA, AUSTRALIA 3052

> > PH: 61 3 9345 5733

> > FAX: 61 3 9345 5764

> > email: joanne.smart at rch.org.au

> 

> 

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