[PAGID] Newborn with Sweet's syndrome and hypogammaglobulinaemia

[Notarangelo, Luigi]

Dear John:

A very interesting case. I would wait to see T cell function first and I would also investigate T-cell repertoire. Hypomorphic RAG mutations in mice havbe been associated with extreme neutrophilia (not necessarily with eosinophilia). The low albumin levels indicate protein loss presdumably through the skin, however the very low number of B cells and absence of IgM makes me think that the hypogamma is not entirely due to protein loss.
A bone marrow examination would be important, and I would suggest that you also look at B cell development by flow in the bone marrow.
Just to be on the safe side, I assume that metabolic examinations are normal?

Best regards

Gigi


Luigi D. Notarangelo, M.D.
Jeffrey Modell Chair of Pediatric Immunology Research in Boston
Director, Research and Molecular Diagnosis Program on Primary Immunodeficiencies
Division of Immunology, Children's Hospital
Professor of Pediatrics and Pathology, Harvard Medical School
Karp Building, 9th floor, Rm 09210
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Boston, MA 02115
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On 4/13/09 7:44 PM, "John Ziegler" <John.Ziegler at SESIAHS.HEALTH.NSW.GOV.AU> wrote:

We are looking for ideas about a 1 month old boy with

1) Neonatal Sweet's syndrome
2) Hypogammaglobulinemia
3) Hepatosplenomegaly
4) Thrombocytopenia

This is the first child of well unrelated Chinese parents, born in Sydney by vaginal delivery after a pregnancy complicated by hyperemesis.  Mum had no medications during pregnancy, there were no infectious symptoms and the antenatal infectious screening was negative.   There is no family history of skin disease or immune deficiency and no deaths in early childhood.

He presented with a mild vesicular rash a few minutes after birth, and the rash progressed over the next 3 weeks.  The distribution is head, arms, legs, scrotum and upper thorax, and the appearance is of elevated lesions with deep dermal infiltration and necrotic overlying skin.  Biopsy demonstrated panniculitis with extensive neutrophilic leukocytoclasis throughout the dermis and subcutaneous tissue.  This neutrophilic dermatosis was thought to be consistent for Sweet's syndrome, however, the young age and panniculitis are atypical. The rash was associated with a mild peripheral blood neutrophilia which reached 11,000, a significant monocytosis = 4.1 (0.3- 1.2), CRP =179 and ESR = 90.  Associated with this is ongoing thrombocytopenia with platelet counts between 41-65,000.  There is moderate splenomegaly 7.3 cm (upper limit normal 5 cm) but no Howell Jolly bodies on the blood film, and unfortunately the attempted bone marrow biopsy was an insufficient sample.  He has hepatomegaly 7.0 cm (normal 4-6) with raised *GT = 400 and low albumin = 22, but with relatively normal AST and ALT. ANA was -ve in the baby and has not yet been determined in the mother.

He has had a negative infection screen thus far, including for direct viral detection of HSV, VZV, CMV and Enterovirus from a variety of fluids.  No organisms were grown on MC&S, other than a sensitive E. coli on eye swab from a pussy eye, while gram/ fungal stain from the skin biopsy were negative (cultures of biopsy were not performed).

He was treated with steroids and seemed to have some initial response but despite 1 mg/Kg prednisolone continues to develop new skin lesions.

He was also found to be hypogammaglobulinaemic with no IgA or IgM and IgG of 2.3, and 1% of B-cells.  He is now being treated with IVIG and we are awaiting a response.  T cells were normal in number; T cell function has not yet been assessed.

Has anyone seen a neutrophilic dermatosis at birth in an immunodeficient child?  Other than congenital infection, what mechanisms might be involved?  If this is a PID, other than XLA what possibilities should be considered?



Summary of investigations:

FBC/ CBC

Hb              100 (Holding up)
Lymphocytes:    4.1 @ presentation, currently 1.3 on steroids.
Monocytes:      Highest = 4.1 (0.3 - 1.2), now normal range on steroids.
Neutrophils:    Highest = 11, prior to steroids.

Immunoglobulins (@1 month of age)

IgG                             2.30    g/L         1.7 - 5.8
IgA                             <0.06   g/L        0.00 - 0.50
IgM                             <0.05   g/L        0.19 - 0.95
IgE                     <5      IU/ml      0 - 1.5

Lymphocyte subsets (@1 month of age)
Lymphocytes                     3.6     X10^9/L     3.8 - 7.6

CD3                             3.28    x10^9/L     2.3 - 7.0
CD3                             91      %

CD4                             1.91    x10^9/L     1.7 - 5.3
CD4                             53      %

CD8                             1.37    x10^9/L     0.4 - 1.7
CD8                             38      %

CD19                            0.04    x10^9/L     0.6 - 1.9
CD19                           1       %

NK CELLS                0.14    x10^9/L     0.2 - 1.4
NK CELLS                  4       %



Dr Paul Gray and A/Prof. John B. Ziegler
Department of Immunology & Infectious Diseases
Sydney Children's Hospital
High St., Randwick NSW 2031
Australia
T: (02) 93821515
F: + 61 + 2 93821580
E: j.ziegler at unsw.edu.au

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