[CIS-PAGID] intestinal atresias with immune deficiency

[Green, Todd (CHP)]

Hello,

We are seeking input on the following case of a girl with a combined type picture. Thanks in advance for your time and thoughts:

2yo female born at 35 wks as part of twin (fraternal) gestation.   The patient had dilated bowel loops on fetal US.  She was treated for presumed sepsis at birth with antibiotics.  A few days later was taken to OR and found to have dozens of intestinal atresias and webs now s/p multiple OR procedures with almost no small bowel remaining, on small bowel transplant list.  Currently TPN dependent.  She has had multiple admissions with fever (15-20 episodes) and variably has had central line infections, UTIs (on 2-3 occasions), G tube site infection, and most recently fungemia (candida).  Her most severe infection was E coli sepsis leading to ARDS, from which she recovered.  She has had coag neg staph, E faecalis, E cloacae, E coli grow from blood cultures in past but on several occasions her cultures have been negative.  No history of recurrent sino-pulmonary infections, otitis media, skin infections/abcesses.  She is not on steroids or immunosuppressives.  She is on methadone and also gets some IV atarax for itching.  No family history of known immunodeficiency though her mom thinks maybe she (Mom) was on IVIG for a year or so around age 1-2.  Mom currently has no issues with infections. Patient got the Varicella vaccine and subsequently developed chicken pox.  In addition she subsequently had an episode of shingles as well.

Labs:
Albumin 1.8-3 (currently 2.3); stool output less than 500cc per day, but higher in past
QUIGS IgG 242 (Low end of normal is low-mid 400s for age), IgA 21 (nl), IgM<25

Total CD3 135 /cumm
Total CD4 108
Total CD8 21
Total B cells 85
Total CD56 54
(all decreased)

"Moderate" Cylex Response

Mitogens  (from Mayo-- expressed as max % of prolif cells) :
Viability Day 0 47.6 % (>75%)
PWM CD45 8.8 (>4.5)
PWM CD3 9.3 (>3.5)
PHA CD45 4.4 (>49.9)
PHA CD3 11.5 (>58.5)


No protective antibody titers to tetanus, diphtheria, pneumococcus; No IgG to Herpes Zoster
HIV negative

Bone marrow biopsy was normocellular and no cytogenetic abnormalities identified

Uric acid low at 0.8 (1.9-5.4)
Stool alpha 1 antitrypsin pending.
CH50  normal

We considered protein losing enteropathy but with little stool output and an albumin that is not terribly low we felt it was less likely.  In addition we expect that with PLE she would have functional antibody responses and functional T cells, which is not the case.  Overall her pattern of infections is not consistent with a humoral deficiency.  In fact you could argue that all of her infections were nosocomial in nature (line infections, UTIs, fungemia on TPN) except for her varicella after vaccination.  Interestingly, when reviewing the literature we were able to find reports (<10) of multiple intestinal atresia associated with immunodeficiency.  Most die in infancy of sepsis.  It was suggested there was a possible hereditary component as one family had 2 siblings with the condition.  Wide range of immune defects reported from functional lymphopenia to SCID like with GVHD after a blood transfusion.

She is symmetrically less than 3rd %ile for height and weight, not dysmorphic, and otherwise developing normally.

We started on IVIG, PCP prophy with IV pentamidine (shortage of IV bactrim and has no small bowel for medication absorption).  Recommended no live vaccines in the future.   Have not yet assessed ADA/PNP activity, but wondering about that as well as looking for other leaky SCID etiiologies.  Any other thoughts? She is currently on the small bowel transplant list but the transplant team is  understandably concerned she won't do well post transplant  and we all would like to clarify her immune defect if possible .  Thank you again for your help.

Best,
Todd

Todd D Green, MD
Assistant Professor of Pediatrics
Division of Pulmonary Medicine, Allergy & Immunology
Children's Hospital of Pittsburgh of UPMC
One Children's Hospital Drive
4401 Penn Avenue
Pittsburgh, PA   15224

tel 412-692-7885
fax 412-692-8499


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