[PAGID] Newborn with Sweet's syndrome and hypogammaglobulinaemia

[Kimberly Risma]

I have followed a little girl with a similar presentation for 8 years now.
As a young infant she had a neutrophilic panniculitis only at sites of pressure or injury (IV start sites
or pressure points in the car seat after a long trip) and nearly absent
B cells.  Over the next 2 years she developed a periodic fever, cystitis, and dermatitis that
responded beautifully to TNF blockade using Embrel and then subsequently
Remicade. She also had a chronic anemia and dramatic colitis that responded
to this therapy, with 6mp on board as well (the latter developed at 3 years of age).
 The B cell lymphopenia never resolved, although she had plenty of plasma cells in the gut upon
biopsy while having diarrhea. The bone marrow did not show any accumulation of immature
B cells to suggest a maturational arrest. We evaluated her for a TRAPS, FMF etc by genetic testing without any hits...
KR


Kimberly Risma MD, PhD
Assistant Professor
Allergy Immunology
Childrens Hospital Medical Center
3333 Burnet Ave, mlc 2000
Cincinnati, OH 45229
Kimberly.Risma at cchmc.org


>>> "John Ziegler" <John.Ziegler at SESIAHS.HEALTH.NSW.GOV.AU> 4/13/2009 7:44 PM >>>


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 gGT = 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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