[CIS PIDD] [cis-pidd] Question from Juan Carlos Aldave

[Risma, Kimberly]

Juan Carlos and colleagues,
Last year I evaluated a teenage boy with very similar clinical picture and exact same immune abnormalities secondary to HTLV infection. Discerning whether the runaway T cell activation/proliferation is smoldering ATL seems a bit tricky- because my patient and others described in the literature have spontaneous lymphocyte proliferation due to HTLV.  
I would love to hear from our colleagues who see patients with HTLV-associated diseases more often for advice on how to discern patients with benign spontaneous lymphoproliferation vs smoldering or chronic Adult T cell leukemia. Also, are there strategies for monitoring progression? 
Interestingly my patient is also very short and was delayed in puberty (started at 17). He has interstitial lung disease, dermatitis, keratitis.  I suspect his short stature may be related to chronic inflammation but interestingly none of the pro-inflammatory cytokines were elevated in the blood. He has severe scoliosis that may be partially responsible for short stature. The latter may be secondary to a neurologic decline-- he has typical Anti Smooth muscle antibodies. I wonder if these patients are prone to other autoAb that prevent growth?
 
Kim

Kimberly Risma MD PhD
Assistant Professor, Pediatrics
Cincinnati Children’s Hospital Medical Center
Kimberly.Risma at cchmc.org


Original Message-----
From: Arturo Borzutzky [mailto:drarturo at gmail.com] 
Sent: Monday, May 05, 2014 10:59 AM
To: CIS-PIDD
Subject: Re: [cis-pidd] Question from Juan Carlos Aldave

With that story it would be reasonable to rule out STAT5b deficiency which may explain the growth hormone insensitivity and many of the other findings.A kidney biopsy is warranted with that proteinuria and hypoalbuminemia to rule out autoimmune glomerulonephritis.

Arturo Borzutzky

On 5/5/14, Sokolic, Robert (NIH/NHGRI) [E] <sokolicr at mail.nih.gov> wrote:

> With hepatosplenomegaly, lymphadenopathy, HTLV-1 positivity, and a 

> preponderance of CD4+CD45RO+ and HLA-DR+ T-cells, I would want to rule 

> out chronic or smoldering ATLL. In this case, the eosinophilia would 

> be secondary. Are the CD4+CD45RO+ cells also DR+? Would biopsy a LN or liver.

> ATLL wouldn't explain growth hormone insensitivity, so it might not 

> all fit together, but I think biopsy is indicated in any case.

> Rob Sokolic

>

> From: <Sullivan>, Kathleen

> <sullivak at mail.med.upenn.edu<mailto:sullivak at mail.med.upenn.edu>>

> Reply-To: CIS-PIDD

> <cis-pidd at lists.clinimmsoc.org<mailto:cis-pidd at lists.clinimmsoc.org>>

> Date: Monday, May 5, 2014 9:59 AM

> To: CIS-PIDD

> <cis-pidd at lists.clinimmsoc.org<mailto:cis-pidd at lists.clinimmsoc.org>>

> Subject: [cis-pidd] Question from Juan Carlos Aldave

>

> Dear professors,

>

> I evaluated this week a 16 yr-old boy with a very puzzling clinical picture.

> I describe below the clinical history.

>

> The main features are:

> - HTLV-1–induced infective dermatitis

> - Deep skin ulcer infected by Pseudomona aeruginosa and 

> Stenotrophomonas maltophilia

> - Immune abnormalities: low naive CD4+ T cells, marked T-cell 

> activation, low B-cell counts, marked eosinophilia

> - Arrest of body growth and sexual development: insensitivity to 

> growth hormone? (low GH, high IGF-1)

> - Anemia, hepatosplenomegaly

> - Marked hypoalbuminemia

>

> I would appreciate your expert insights and suggestions.

> Thank you very much.

>

>

> Lima, Peru

>

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

> May 3rd 2014

> Boy, 16 years of age

> Date of birth: August 23rd 1997

> Blood group: A Rh(+)

>

>

>

> FAMILY HISTORY:

> -       No family members with suspicion of PID.

> -       2 half-brothers and 4 half-sisters (some mother), all healthy.

> -       No consanguinity.

>

>

>

> PERSONAL HISTORY:

> -       Weight at birth=2500 g

> -       No adverse reaction to BCG.

> -       Current weight=24 kg (very low for age)

> -       Current height=126 cm (very low for age)

>

>

>

> CURRENT DISEASE:

> -       Completely healthy up to 9 years of age (weight at that time=36

> kg).

> -       From 9 years of age: abdominal erythema with blisters, desquamation

> and scaling; relapsing course with progressive expansion to all the 

> body; partial response to high-dose systemic corticosteroids. 

> Recurrent fever, general malaise.

> -       From 9 years of age: arrest of body growth and sexual development.

> -       One episode of thrush at 10 years of age while taking systemic

> corticosteroids.

> -       “Pneumonia” one year ago, required intravenous antibiotics, no

> microorganisms were isolated.

> -       One month ago, an ulcer appeared on the right buttock. The ulcer has

> expanded progressively. Culture of the secretion: Pseudomona aeruginosa.

> Blood culture: Stenotrophomonas maltophilia.

> -       No chronic or recurrent diarrhea.

>

>

>

> PHYSICAL EXAM:

> Growth delay (patient appears like a 9-year-old child).

> No development of secondary sex characteristics.

> Diffuse erythematous scaling all over the body (please see the 

> attached photographs).

> Deep ulcer of about 10 cm on the right buttock.

>

>

>

> WORK UP:

> April 10th, 2014:

> -       Hb=7.8 g/dL; platelets=438,000; WBC=7,650; neutrophils=5,620;

> lymphocytes=1,550; monocytes=240; eosinophils=200, basophils=40/mm3 

> April 25th, 2014:

> -       Hb=10.6 g/dL (after blood transfusion); platelets=645,000;

> WBC=16,470; neutrophils=3,730; lymphocytes=3,030; monocytes=570; 

> eosinophils=8,490, basophils=200/mm3

> -       Serum glucose, urea and creatinine: within normal limits

> -       C-reactive protein=2.57 mg/dL

> -       Albumin=1.63 g/dL; total bilirubin=0.39 mg/dl; lactate

> dehydrogenase=292 mg/dl; AST=30 U/L; ALT=31 U/L; β2 microglobulin=4.73 mg/L

> -       IgG=2159, IgA=373, IgM=340 mg/dL, IgE≥2000/mL

> -       IgG to CMV and toxoplasma: positive titers

> -       IgM to EBV, CMV, toxoplasma and rubella: negative

> -       Serology for HBV, HCV and HIV: negative

> -       Antibodies to HTLV: reactive 118.87 (normal values <1)

> -       Stool analysis for ova: negative.

> -       CT: mild left pleural effusion with atelectasis; no mediastinal or

> axillary lymphadenopathies; homogeneous hepatosplenomegaly; 

> retroperitoneal left para aortic lymphadenopathies.

> -       Cardiac US: normal systolic function, mild diastolic dysfunction of

> the left ventricle.

> -       Skin biopsy: hyperkeratosis with parakeratosis and microabscesses;

> psoriasiform acanthosis; edema in the papillary dermis; marked chronic 

> perivascular inflammatory infiltrate with extension to the papillary 

> dermis; abundant eosinophils; incontinentia pigmenti.

> April 30th, 2014:

> -       Hb=8.1 g/dL; platelets=585,000; WBC=15,780; neutrophils=5,210;

> lymphocytes=3,140; eosinophils=6,560/mm3

> -       ESR=45 mm/h; C-reactive protein=3.04 mg/dL

> -       Albumin=1.73 g/dL; bilirubin and liver enzymes within normal levels;

> 9 mg/dl; lactate dehydrogenase=292 mg/dl; β2 microglobulin=6.33 mg/L

> -       Vit B12 >1000 pg/mL; folic acid within normal levels.

> -       Free T3=1.64 pg/mL (normal values: 1.80-4.2)

> -       Free T4, TSH, prolactin, ACTH (8 a.m.), LH, FSH: within normal

> levels

> -       Growth hormone=11.1 ng/mL (normal levels <3)

> -       IGF-1 (somatomedin C) <25 (normal levels: 193-731)

> -       Total lymphocytes=3140

> -       CD3+ cells=2587 (21% are DR+)

> -       CD4+ cells=1878

> -       CD4+CD45RA+ T cells=10%; CD4+CD45RO+ T cells=90%

> -       CD8+ cells=647

> -       CD8+CD45RA+ T cells=65%; CD8+CD45RO+ T cells=35%

> -       TCRγδ CD3+ cells=1.3%

> -       TCRαβ DN CD3+ cells=2%

> -       CD19+ cells=104 (3.3%)

> -       CD56+ cells= 371 (11.8%)

> -       CD3+CD56+ cells= 47 (1.5%)

> -       Proteinuria=758 mg/day (normal values <150 mg/day).

> Kate Sullivan, MD PhD

> Wallace Chair of Pediatrics

> Professor of Pediatrics

> ARC 1216 Immunology CHOP

> 3615 Civic Center Blvd.

> Philadelphia, PA 19104

> (p) 215-590-1697

> (f) 267-426-0363

>

>

>

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--
Dr. Arturo Borzutzky S.
Inmunología, Alergia y Reumatología Pediátrica División de Pediatría Pontificia Universidad Católica de Chile
Tel: (56-2) 3543753
www.saluduc.cl

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