[PAGID] very sick baby in Australia

[Sergio Rosenzweig]

Netherton syndrome is an AR disease (SPINK5, 5q32) characterized by icthyosis, 
erythrodermia, hyper IgE and eosynophilia. Hepatosplenomegaly, recurrent infections 
and combined immunedeficiency have also been described. Molecular diagnosis is 
definitive and  light microscopy of the hair is also pathognomonic: these pts present 
trichorrhexis nodosa due to trichorrhexis invaginata (it looks like hair-into-hair 
intussusception...I can send  pictures if somebody wants!).
Sergio
PS Sorry for not being more clear the first time

Sergio D. Rosenzweig, MD, PhD
Servicio de Inmunologia
Hospital Nacional de Pediatria "J. P. Garrahan"
Buenos Aires, Argentina
srosenzweig at garrahan.gov.ar

On 28 Jun 2007 at 8:54, Conley, Mary-Ellen wrote:


> 

> Hi Serigio,

> Why don't you remind us of the most important features of Netherton syndrome and tell us why 

> you think that it might be the diagnosis in this baby. 

> A gentle reminder to all:1) sign with your full name, your institution and your city so we know who 

> you are; 2) remember to change the subject title to fit your topic. thanks

> Mary Ellen

> 

> 

> 

> 

> 

> Mary Ellen Conley, MD 

> Department of Immunology 

> St. Jude Children's Research Hospital 

> 332 N. Lauderdale 

> Memphis, TN 38105-2794 

> FAX 901-495-3977 

> TEL 901-495-2576 

> 

> 

> 

>     From: pagid-bounces at list.clinimmsoc.org [mailto:pagid-bounces at list.clinimmsoc.org] On 

>     Behalf Of Sergio Rosenzweig

>     Sent: Wednesday, June 27, 2007 7:40 PM

>     To: pagid at list.clinimmsoc.org

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

>     

>     Joanne, I would evaluate Netherton syndrome. Hair examination under light microscopy 

>     (trichorrhexis invaginata) would help on the diagnosis.

> Good luck with this difficult case,

> Sergio

> 

> Sergio D. Rosenzweig, MD, PhD

> Servicio de Inmunologia

> Hospital Nacional de Pediatria "J. P. Garrahan"

> Buenos Aires, Argentina

> srosenzweig at garrahan.gov.ar

> 

> Dr Joanne Smart <joanne.smart at rch.org.au> 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 œwasn™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:

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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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