[CIS PIDD] [cis-pidd] Female patient with CPAN and profound B cell lymphopenia

[Abraham, Roshini S., Ph.D.]

This case is posted on behalf of Dr. Ann Reed, Pediatrics, Mayo Clinic, Rochester.


Any comments related to this case will be greatly appreciated.



Patient is now 17 y/o young lady who at age 2 y/o developed a periorbital cellulitis.  Several months later she developed small nodules on her lower extremities and some pallor of her distal digits on her hands.  Ultimately, a biopsy showed CPAN (cutaneous polyarteritis nodosa) and she was tried on Abx prophylaxis with no improvements.  Her symptoms in the early years were mainly nodules and livedo with some systemic complaints of nausea and occasionally joint pain.  She was tried on a short course of MTX without success.  Finally, she was placed on Dapsone and Tagamet and the livedo improved and the nodules resolved and this combination of drugs controlled her CPAN for about ten years.  She was on a mg/kg dose of Dapsone and about every two and half years the CPAN would recur and we would up the Dapsone dose and after a month or two the CPAN would go back into "remission".  Her labs during this time frame were all normal except for an elevated Sed Rate and CRP.  We noted that her total WBC count dropped in 2005 to around 3,200 associated with an absolute lymphocyte count (ALC) drop but it was not addressed.  Her ALC continued to drop to its current level over the next eight years.

                In Oct of 2010, she had another flare of the CPAN and began to have more systemic complains such as nausea, headaches, joint pain and fatigue.  We increased her Dapsone to the max dose of 100 mg daily but it failed to improve her symptoms.   We reconfirmed the diagnosis of CPAN with a repeat skin bx and repeated many of the rheumatology labs in addition to a large coagulation work-up based on a the Japanese literature associating  CPAN and coagulation abnormalities; however, all of the Rheum and coag labs were normal.  She was tried her on Abx and MTX again without success.  By chance, we looked at her IgG level and it was low end normal (NOTE: IgA and IgM were also low) and that prompted checking T and B cell subsets.  Her total CD-19 B-cells were in the 3% range.  Clinically, she indeed had a lot of sinusitis as a young child but never any life threating pneumonias.  She had an appropriate immune response to Pneumovax (but according to physician at Vanderbilt she had a case report type reaction to the vaccination) and we were not able to sort out if she had PIDD or possible acquired immunodeficiency from the 10 years of Dapsone and Tagamet.  She was started on IVIG with the hopes that it would be monotherapy for both the CPAN and the immunodeficiency.  We did notice some improvement in the nodules and the systemic complaints but it was only transient.  We even tried high dose IVIG at 60 grams monthly but it only help with the CPAN for a short period of time.  Additional treatments including high dose steroids (she is steroid responsive), MMF and ultimately Dapsone and Tagamet again.  In Sept of 2012, she had a drop in her ANC to 900 and Plts to 125K along with a bump in her AST and ALT into the 100 range and it was unclear was this due to the multiple drugs or was she developing additional autoimmunity.  The counts recovered to NEAR baseline after numerous months.

Patient was seen at the NIH and summary is below:




1.      GATA-2 sequence showed no mutations

2.      BM - hyopcelluar with tri-lineage hematopoiesis

3.      BM - shows a block in early B - cell maturation

4.      BM showed no evidence of malignancy

5.     ? has a leaky form of recessive agammaglobulinemia (she still had some B-cells or plasma cells in the tissue that are making immunoglobulins)

6.      Lack of CD-20 expression in BM; therefore, questioned if Rituxan would be helpful

7.      The T-cells and few B -cells that Allie has are polyclonal

8.      T - cell function is normal

9.     possibly repeating the skin bx for immunofluorescence staining for immunoglobulins and complement and if there was no deposition on the vessels then she did not think that Rituxan would be helpful - (NOTE:  this study was done one of Allie's early skin bx's around age 4 y/o and did not show immunoglobulins or complement but this was also one of the early bx that did not have a good sample of the target lesion).

10.            The use Rapamycin or Imuran was raised

11.            They could find only one other case report of a child with CPAN and immunodeficiency in the literature from Florence, Italy.


It was decided to place her on Colchicine and Trental and initially she had some improvement in the CPAN and her systemic complains.  The summer of 2013 was somewhat uneventful with her CRP being completely in the normal range.  However, in Nov of 2013, she developed fever, greatly increased joint pain and fatigue.  Her I.D. w/u was neg but her Plts dropped to 95 K, ANC dropped to 550 along with an increased ALT and AST into the 100's and a new finding of an increased Alk Phos .  Some concern about Colchicine being the etiology of the cytopenias was raised by local physician in Tennessee.  Blood was sent to the Blood Center of Wisconsin to look for autoantibodies to plts and neutrophils.  The plts autoabs were negative but the neutrophil autoabs were questionable.  We did some further testing but Wisconsin was concerned that the Hizentra might be causing a false positive.  It was felt that the cytopenias were all related to her underlying disease process; therefore, we continued with the Colchicine and Trental and placed her on high dose steroid and her count and LFT's improved.  However, as in Sept of '12 her counts did not return to her baseline or even to her newly established baseline from the episode in Sept of 2012.  Along this time, her 10 y/o brother was dx'ed with bx proven CPAN and some abnormalities in his switch memory B-cells similar to Allie but overall CD-19 B-cell count was normal.  We elected to undergo WES - results not yet available.

The NIH had recommended that we repeat her BM at the one year mark; therefore, the BM was repeated on Dec 19th, 2013 with some of the specimen sent to the NIH for comparison to the NIH Jan '13 BM - because of her hypocelluar marrow, low B-cell and low NK cells the question of MonoMac was raised despite the negative finds of the GATA-2 mutation in Steve Holland's lab in Jan of 2013.  Dennis said that he has seen a heterogeneous clinical phenotype of pt's with GATA-2 and he has had several families with classic MonoMac but they could not find the mutation.  The hematopathologist indicated that patient's BM does not look like a classic "GATA-2/MonoMac" marrow.



Roshini S. Abraham
Mayo Clinic




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