[CIS PIDD] [cis-pidd] PLEVA AND HLH?

[CIS-PIDD]

Dear all;

I have a very puzzling case I was hoping to get your opinions on.

8 year old girl, adopted, of Korean ancestry.

-4 years ago: Acutely developed a severe rash.  After path discussions amongst many centers in the US, final diagnosis was PLEVA (pityriasis lichenoides et varioliformis acuta), a very rare T cell driven skin disorder.  Treated with methotrexate to resolution.

-1 month ago:  One week of high fevers and lethargy, brought by ambulance to hospital with new onset seizures and altered mental status. Labs at the time:
WBC 2.09, ANC 490
Hgb 10.0
Plt 94k
Transaminitis AST 148, ALT 248
Fibrinogen 155
Trigs 451
Ferritin 616
Soluble IL2R 12882
Subsets (prior to any treatment, but during this acute episode): CD3 493, CD4 189. CD8 247. CD19 152. CD56 - 51.
NK Lytic Units 0.0 (note lymphopenia and low NK cell number above)



Brain MR: Multiple large, poorly marginated enhancing lesions scattered throughout the bilateral cerebral hemispheres, predominantly involving white matter.



LP:  27 WBC, with lymphocytic predominance.  Protein mildly elevated (54), glucose normal.  Fungal, aerobic, AFB cultures negative.  HSV, entero, VZV, EBV, CMV, Tb PCR negative.  JC negative.  Crypto Ag, myelin basic protein negative.



Brain stereotactic biopsy:  Marked perivascular cellular infiltrate comprised of lymphocytes, plasma cells and macrophages.  CD3 and CD5 stains show increased numbers of T-lymphocytes.   Sections show abundant macrophages, some of which demonstrate intracelullar material consistent with hemophagocytosis. There is a marked perivascular cellular infiltrate comprised of lymphocytes, plasma cells and macrophages. A CD68 stain highlights No abnormal cells.  Viral stains negative.

Bone marrow: 60-70% cellularity.  Increased amount of macrophages, showing occasional hemophagocytosis.  No malignant cells noted by morphology or flow.

ID (blood):  HIV, RPR negative.  EBV, CMV, entero, HHV6 PCR neg.  Crypto Ag neg.  VZV, WNV, mycoplasma, Erlichia, R Typhi, RMSF, typhus, borrelia, Hep B, Hep C, Parvo negative by antibodies (IgG normal at 1004).

Immuno:  ANA, RF, SSA/SSB, lupus anticoagulant, cardiolipin Ab negative.  ASO titer normal.  C3/C4 levels normal.

Our hematology service started her on HLH treatment (with intrathecals), which has improved both her systemic and CNS inflammation, and has now referred her to me for consideration of transplant.  HLH genetic panel was negative for AP3B1, BLOC1SG, CD27, ITK, LYST, MAGT1, PRF1, RAB27a, SH2D1a, SLC7A7, STX11, STXBP2, UNC13D, XIAP.  LRBA/CTLA4 studies are in process.

I am not sold this is "just HLH", especially given her previous history.  However, I am very concerned about her severe CNS presentation, and agree with hematology BMT might be in her best interest even if I don't have a definitive diagnosis.  Looks like we have a couple possible 9/10 donors.

So, with that in mind:

1.        Any diagnostic considerations?  She is on etoposide and steroids, so functional studies will likely not be very helpful.

2.       Our standard is to condition "HLH" patients on RICHI (-14 campath/flu/mel).  Would you consider alternate regimens for her given her history? Her functional status remains low from her CNS insult, so I don't think myeloablation is not in her best interest.

Thanks for your input.

Blachy


Blachy J. Dávila Saldaña, MD
Attending Physician, Division of Blood and Marrow Transplantation
Children's National Health System
Assistant Professor of Pediatrics
George Washington University School of Medicine and Health Sciences
111 Michigan Avenue, N.W.
Washington, DC 20010
Phone: 202-476-4561
Fax: 202-476-2280


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