[CIS PIDD] Self-resolving infant HLH?

[Blachy Davila-Saldana]

Hello all;
I was hoping you could help me with an interesting patient.   He is a 2 month old (at presentation) male, first child of Hispanic (non-consanguineous) parents, who presented to ICU with severe dehydration.  After resuscitation and transfer to the floor, he persisted with profuse, watery diarrhea requiring fluid replacement.  Subsequently, he became febrile and developed cytopenias.  Lowest hemoglobin was 4.9, lowest platelet count was 17k.  He was never leukopenic; lowest ANC was 1,300.  He had no splenomegaly but increased liver enzymes with a palpable liver edge.  Laboratories were obtained with concern for HLH. Ferritin was 2703, triglycerides 247, fibrinogen 146.  Cultures obtained were relevant for a CMV PCR in blood at 560,000.  Endoscopy done also showed changes consistent with acute CMV infection.  Bone marrow showed no malignancy and did have some evidence of hemophagocytosis.
After this, he oddly started to markedly improve on his own.   He did not receive HLH nor CMV-directed treatment, and he defervesced.  His counts recovered and his diarrhea resolved.  His CMV copies decreased to 5600.  The rest of his labs:
Soluble IL-2 8450 pg/mL
IgG 180
IgM 28
IgA 37

Lymphocyte Subsets:
Number 5920 /cu mm
CD3 5021 /cu mm
CD3%  84.8 (H)          45.0 - 75.0 %
CD4 2437 /cu mm
CD4 %  41.2               35.0 - 55.0 %
CD8  2467 (H) /cu mm
CD8 % 41.7 (H)                    10.0 - 25.0 %
CD19  619 /cu mm
CD19%  10.5 (L)            15.0 - 45.0 %
CD56+, CD3- (NK CELLS) 196 (L) /cu mm
CD56+, CD3- % (NK CELLS) 3.3            3.0 - 25.0 %
CD4/CD8 Ratio 1.0 (L)           2.0 - 5.0 Ratio

Lymphocyte stim:
Low response to Candida, Tetanus
Normal response to PHA, Con A, Pokeweed mitogen.

NK Function:
E:T ratio        % cytotoxicity
50:1                        6
25:1                        3
12:1                        0
6:1                          0
NK Lytic units 0.3
CD 16/56 +:  7%

Perforin/Granzyme:
CD 56 Bright 12%
Perforin:
% NK cells: 76%
NK cells MCF: 92  (98-181 ref)
Cd8% 19
NKT %  37
Granzyme:
% NK: 95
NK cells MCF: 629    (152-825 ref)
Cd8% 59
%NKT 95

PRF1 gene mutation analysis showed no mutations.   Mutation analysis for primary HLH (MUNC13-4, STXBP2, RAB27A, STX11) and XLP is currently underway in Cincinnati.  MUNC was just reported as no mutations identified.  He is growing and feeding well; no recurrence of fevers, diarrhea or infections has occurred (so far).  I was wondering,

-          Is there anything else I should be thinking of as mutation analysis is underway?  He worries me.  Neither he nor his smear look like Chediak-Higashi.

-          Has anyone heard of HLH on someone this young self resolving?  I could not find anything on literature.

-          Have you seen cases of secondary HLH in 2 month olds?

-          Even if no mutations are identified, should transplant still be offered?  Or should we offer it even before analysis is finished?  I find it hard to convince myself his chances of relapse are anything other than humongous.

Thanks for  your thoughts!

Blachy

Blachy J. Dávila Saldaña
PGY-6
Pediatric Hematology-Oncology Fellow
Mail Code CDRCP
3181 SW Sam Jackson Park Road
Portland OR 97231
503-494-0829


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