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<p>​1. Bone marrow aspirates shows increased histiocytes with occasional hemophagocytosis.  It supports HLH if clinical other creteria fits the diagnosis, but the morphology is nonspecific which can be seen a variety of reactive conditions as well as lymphoid
 malignancy.<br>
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<p>2. Flow cytometry detects minute clonal B-cells.  IHC on bone marrow biopsy is pending.  <br>
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<p>3. Please check if any lymphadenopathy, or hepatosplenomegaly, if clinically indicated biopsy of nodal or extrondal lesions will help to rule out hematolymphoid malignancy.  <br>
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<font face="Arial, Helvetica, sans-serif">Mingyi Chen MD, PhD </font>
<div><font face="Arial, Helvetica, sans-serif">Associate Professor of Pathology</font></div>
<div><font face="Arial, Helvetica, sans-serif">Hematopathology</font></div>
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<p class="yiv0677231172msonormal" style="background:white"><font face="Arial, Helvetica, sans-serif">UT Southwestern Medical Center</font></p>
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<span id="yui_3_16_0_ym19_1_1475074718313_35688"><span style="font-family:Arial,Helvetica,sans-serif">BioCenter </span></span><span style="font-family:Arial,Helvetica,sans-serif">EB3.234A</span><span style="font-family:Arial,Helvetica,sans-serif">; </span><font face="Arial, Helvetica, sans-serif">2330
 Inwood Rd. </font></p>
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<span id="yui_3_16_0_ym19_1_1475074718313_35687"><font face="Arial, Helvetica, sans-serif">Dallas, Tx  75390</font></span></p>
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<span><font face="Arial, Helvetica, sans-serif">Tel: 214-648-4791</font></span></p>
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<font face="Arial, Helvetica, sans-serif">Email: mingyi.chen@utsouthwestern.edu</font></p>
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<div id="divRplyFwdMsg" dir="ltr"><font face="Calibri, sans-serif" color="#000000" style="font-size:11pt"><b>From:</b> Weina Chen<br>
<b>Sent:</b> Thursday, August 2, 2018 6:27 PM<br>
<b>To:</b> Christian Wysocki; Sita Bushan; Franklin Fuda; Mingyi Chen<br>
<b>Cc:</b> Aena Patel; Arjmand Mufti; Bonnie Prokesch; Tri Le; adult-hlh-mas@lists.utsouthwestern.edu; Jananie Ramesh; Joseph Frankl; Roohi Cheema; Whitney Blackwell; Racha Halawi; Wende Wells; Drew Bird; Dawn Klemow; Ellen Araj<br>
<b>Subject:</b> Re: [Adult-hlh-mas] [External] Re: securemail - possible HLH...previously known to most services involved here</font>
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<p>Hi Mingyi,</p>
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<p>Would you please update the BM finding in this case? </p>
<p><span style="font-family:"Calibri","sans-serif"; color:black">Thi Tuyet Tran (MRN 71419053)</span>, BM18-645?</p>
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<p>Thank you!</p>
<p>Weina</p>
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<div id="divRplyFwdMsg" dir="ltr"><font face="Calibri, sans-serif" color="#000000" style="font-size:11pt"><b>From:</b> Christian Wysocki<br>
<b>Sent:</b> Thursday, August 2, 2018 6:04 PM<br>
<b>To:</b> Weina Chen; Sita Bushan; Franklin Fuda; Mingyi Chen<br>
<b>Cc:</b> Aena Patel; Arjmand Mufti; Bonnie Prokesch; Tri Le; adult-hlh-mas@lists.utsouthwestern.edu; Jananie Ramesh; Joseph Frankl; Roohi Cheema; Whitney Blackwell; Racha Halawi; Wende Wells; Drew Bird; Dawn Klemow; Ellen Araj<br>
<b>Subject:</b> RE: [Adult-hlh-mas] [External] Re: securemail - possible HLH...previously known to most services involved here</font>
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<p class="MsoNormal"><span style="font-size:11.0pt; font-family:"Calibri","sans-serif"; color:#1F497D">Hi all,</span></p>
<p class="MsoNormal"><span style="font-size:11.0pt; font-family:"Calibri","sans-serif"; color:#1F497D">I see a note from the Heme/Onc folks that prelim read on BMBx showed hemophagocytosis…any more info?</span></p>
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<p class="MsoNormal"><b><span style="font-size:10.0pt; font-family:"Tahoma","sans-serif"">From:</span></b><span style="font-size:10.0pt; font-family:"Tahoma","sans-serif""> Weina Chen
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<b>Sent:</b> Wednesday, August 01, 2018 6:36 PM<br>
<b>To:</b> Sita Bushan; Franklin Fuda; Mingyi Chen<br>
<b>Cc:</b> Aena Patel; Arjmand Mufti; Christian Wysocki; Bonnie Prokesch; Tri Le; adult-hlh-mas@lists.utsouthwestern.edu; Jananie Ramesh; Joseph Frankl; Roohi Cheema; Whitney Blackwell; Racha Halawi; Wende Wells; Drew Bird; Dawn Klemow; Ellen Araj<br>
<b>Subject:</b> Re: [Adult-hlh-mas] [External] Re: securemail - possible HLH...previously known to most services involved here</span></p>
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<p class="MsoNormal">Buddy and Mingyi,</p>
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<p class="MsoNormal"> please see below regarding this BM case, performed today.<br>
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Thanks </p>
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<p class="MsoNormal">Weina</p>
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<p class="MsoNormal">Sent from my iPhone</p>
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On Aug 1, 2018, at 3:40 PM, Sita Bushan <<a href="mailto:SITA.BUSHAN@phhs.org">SITA.BUSHAN@phhs.org</a>> wrote:</p>
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<p><span style="font-family:"Calibri","sans-serif"; color:black">Hi everyone,</span></p>
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<p><span style="font-family:"Calibri","sans-serif"; color:black">I performed the bone marrow biopsy for this patient today.  Thank you.</span></p>
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<p><span style="font-family:"Calibri","sans-serif"; color:black">Sita </span></p>
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<p class="MsoNormal"><b><span style="font-size:11.0pt; font-family:"Calibri","sans-serif"; color:black">From:</span></b><span style="font-size:11.0pt; font-family:"Calibri","sans-serif"; color:black"> Aena Patel<br>
<b>Sent:</b> Wednesday, August 1, 2018 6:31 AM<br>
<b>To:</b> Arjmand Mufti; Christian Wysocki; Bonnie Prokesch; Tri Le; <a href="mailto:adult-hlh-mas@lists.utsouthwestern.edu">
adult-hlh-mas@lists.utsouthwestern.edu</a><br>
<b>Cc:</b> Jananie Ramesh; Joseph Frankl; Roohi Cheema; Racha Halawi; Dawn Klemow; Drew Bird; Whitney Blackwell; Ellen Araj; Wende Wells; Sita Bushan<br>
<b>Subject:</b> Re: [External] Re: [Adult-hlh-mas] securemail - possible HLH...previously known to most services involved here</span><span style="font-family:"Calibri","sans-serif"; color:black">
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<p class="MsoNormal"><span style="font-family:"Calibri","sans-serif"; color:black">I’m adding the current fellow (Sita Bushan) to this thread. </span></p>
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<p class="MsoNormal"><span style="font-family:"Calibri","sans-serif"; color:black">Thank you, </span></p>
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<p class="MsoNormal"><span style="font-family:"Calibri","sans-serif"; color:black">Aena Patel, PGY5</span></p>
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<p class="MsoNormal"><span style="font-family:"Calibri","sans-serif"; color:black">Hematology/Oncology Fellow</span></p>
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<p class="MsoNormal"><span style="font-family:"Calibri","sans-serif"; color:black">Pager: 972-229-0781</span></p>
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<p class="MsoNormal"><b><span style="font-size:11.0pt; font-family:"Calibri","sans-serif"; color:black">From:</span></b><span style="font-size:11.0pt; font-family:"Calibri","sans-serif"; color:black"> Arjmand Mufti <<a href="mailto:arjmand.mufti@utsouthwestern.edu">arjmand.mufti@utsouthwestern.edu</a>><br>
<b>Sent:</b> Wednesday, August 1, 2018 5:30 AM<br>
<b>To:</b> Christian Wysocki; Bonnie Prokesch; Tri Le; <a href="mailto:adult-hlh-mas@lists.utsouthwestern.edu">
adult-hlh-mas@lists.utsouthwestern.edu</a><br>
<b>Cc:</b> Jananie Ramesh; Joseph Frankl; Roohi Cheema; Racha Halawi; Aena Patel; Dawn Klemow; Drew Bird; Whitney Blackwell; Ellen Araj; Wende Wells<br>
<b>Subject:</b> [External] Re: [Adult-hlh-mas] securemail - possible HLH...previously known to most services involved here
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<p class="MsoNormal"><span style="font-family:"Calibri","sans-serif"; color:black">*** This e-mail did not originate from a Parkland e-mail address. If you do not know or trust the sender, do not click on any links in this e-mail, open any attachments, or disclose
 any sensitive information such as your password. *** </span></p>
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<p><span style="font-family:"Calibri","sans-serif"; color:black">Hi Chris,</span></p>
<p><span style="font-family:"Calibri","sans-serif"; color:black"> </span></p>
<p><span style="font-family:"Calibri","sans-serif"; color:black">I saw her on Monday and I totally agree with this plan.  I also agree that she needs to absolutely continue antiviral therapy.</span></p>
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<p><span style="font-family:"Calibri","sans-serif"; color:black">Thanks</span></p>
<p><span style="font-family:"Calibri","sans-serif"; color:black">Arji </span></p>
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<p class="MsoNormal"><span style="font-size:10.0pt; font-family:"Tahoma","sans-serif"; color:#222222; background:white">Arjmand Mufti, MD, MRCP (UK)</span><span style="font-size:10.0pt; font-family:"Tahoma","sans-serif"; color:black"></span></p>
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<p class="MsoNormal" style="background:white"><i><span style="font-size:10.0pt; font-family:"Tahoma","sans-serif"; color:black">Assistant Professor<br>
Division of Digestive and Liver Diseases<br>
UT Southwestern Medical Center</span></i><span style="font-size:10.0pt; font-family:"Tahoma","sans-serif"; color:#222222"></span></p>
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<p class="MsoNormal" style="background:white"><b><span style="font-size:11.0pt; font-family:"Calibri","sans-serif"; color:black">From:</span></b><span style="font-size:11.0pt; font-family:"Calibri","sans-serif"; color:black"> Christian Wysocki<br>
<b>Sent:</b> Tuesday, July 31, 2018 11:43 PM<br>
<b>To:</b> Bonnie Prokesch; Tri Le; <a href="mailto:adult-hlh-mas@lists.utsouthwestern.edu">
adult-hlh-mas@lists.utsouthwestern.edu</a><br>
<b>Cc:</b> Jananie Ramesh; Joseph Frankl; Roohi Cheema; Racha Halawi; Aena Patel; Dawn Klemow; Arjmand Mufti; Drew Bird; Whitney Blackwell; Ellen Araj; Wende Wells<br>
<b>Subject:</b> Re: [Adult-hlh-mas] securemail - possible HLH...previously known to most services involved here</span><span style="font-family:"Calibri","sans-serif"; color:black">
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<p style="background:white"><span style="font-family:"Calibri","sans-serif"; color:black">Hi all, sorry I was delayed in getting back to you.</span></p>
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<p style="background:white"><span style="font-family:"Calibri","sans-serif"; color:black">I took a brief look through Mrs. Tran's case.  This certainly seems to have gotten considerably worse in the past week despite 50mg daily prednisone.  I am impressed that
 she is fevering through that, and am impressed by the extremely high soluble IL2R levels.  Those levels make me concerned for lymphoid malignancy (athough we don't have clear evidence of one). They also make me worried about her prognosis.  Not sure how the
 HBV is playing into this....I suppose it could be driving T cell activation?...</span></p>
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<p style="background:white"><span style="font-family:"Calibri","sans-serif"; color:black">Given the substantial worsening in her cell counts in the past week or so, I do wonder whether a repeat BMbx is warranted. The first one wasn't entirely normal, with polytypic
 plasmacytosis and a small clonal B cell population.....perhaps something is declaring itself.  It looks like the axillary nodes on prior CT had shrunken on the recent CT chest, probably related to steroid (which is my concern....she's been on 50mg PDN for
 a week or so now and I wonder if that will make it tough at this point to get a solid diagnosis, if this is a lymphoma or lymphoproliferative disorder). </span></p>
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<p style="background:white"><span style="font-family:"Calibri","sans-serif"; color:black">That being said, it doesn't look like we have much time to wait. 
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<p style="background:white"><span style="font-family:"Calibri","sans-serif"; color:black">If a BMBx can get done tomorrow, I think it would be a good idea to repeat. I would also like an IL18 level to be sent to Cincinnati Children's, along with a cytokine
 panel (same place - have to order them separately).  May help us down the road decide between thinks like Anakinra or Tocilizumab).</span></p>
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<p style="background:white"><span style="font-family:"Calibri","sans-serif"; color:black">My sense is that as soon as the biopsy is done, more aggressive therapies should be initiated.  An extensive infectious eval has been done.....agree with Bonnie that if
 EBV and CMV have not been repeated they should be before we get more aggressive with treatment.</span></p>
<p style="background:white"><span style="font-family:"Calibri","sans-serif"; color:black"> </span></p>
<p style="background:white"><span style="font-family:"Calibri","sans-serif"; color:black">I don't think she'll do well with etoposide right now with her severe neutropenia. 
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<p style="background:white"><span style="font-family:"Calibri","sans-serif"; color:black"> </span></p>
<p style="background:white"><span style="font-family:"Calibri","sans-serif"; color:black">As we don't yet have clear evidence for malignancy, and there have been concerns about HBV associated autoimmunity/vasculitis driving this, my proposal would be to treat
 initially with a solumedrol pulse and anakinra, essentially treating presumptively for MAS.  Hopefully that would cool this off, and if the repeat bone marrow does show malignancy, get her to a state where she could tolerate definitive treatment.  I also think
 we need to continue antivirals while doing this!</span></p>
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<p style="background:white"><span style="font-family:"Calibri","sans-serif"; color:black">What do others think of that plan?</span></p>
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<p style="background:white"><span style="font-family:"Calibri","sans-serif"; color:black">-Chris</span></p>
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<p class="MsoNormal" style="background:white"><b><span style="font-size:11.0pt; font-family:"Calibri","sans-serif"; color:black">From:</span></b><span style="font-size:11.0pt; font-family:"Calibri","sans-serif"; color:black"> Bonnie Prokesch<br>
<b>Sent:</b> Monday, July 30, 2018 9:27 AM<br>
<b>To:</b> Tri Le; <a href="mailto:adult-hlh-mas@lists.utsouthwestern.edu">adult-hlh-mas@lists.utsouthwestern.edu</a><br>
<b>Cc:</b> Jananie Ramesh; Joseph Frankl; Roohi Cheema; Racha Halawi; Aena Patel; Dawn Klemow<br>
<b>Subject:</b> Re: [Adult-hlh-mas] securemail - possible HLH...previously known to most services involved here</span><span style="font-size:10.5pt; font-family:"Cambria","serif"; color:black">
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<p class="MsoNormal" style="background:white"><span style="font-size:10.5pt; font-family:"Cambria","serif"; color:black">Hi Tri,</span></p>
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<p class="MsoNormal" style="background:white"><span style="font-size:10.5pt; font-family:"Cambria","serif"; color:black">Thanks for posting this case/alerting us all to the fact that Ms. Tran is back in the hospital. It is definitely a challenging one. I agree
 with current work up that is going on and feel like other than her known underlying hepatitis B, there is unlikely another infectious component playing a role (and definitely agree with holding off of antibiotic therapies for now especially in light of her
 prior likely DRESS). That being said, since she has been on high dose steroids for a while at this point, I think it is worth repeating EBV and CMV PCRs in the serum. I will defer discussion about length of immunosuppression and exact treatment to my immunology,
 heme, and derm colleagues. Chris and Sri, do you think she would be a candidate for etoposide? I wonder, too, if there would be any utility in repeating a bone marrow biopsy.</span></p>
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<p class="MsoNormal" style="background:white"><span style="font-size:10.5pt; font-family:"Cambria","serif"; color:black">Bonnie</span></p>
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<p class="MsoNormal" style="background:white"><b><span style="font-size:11.0pt; font-family:"Calibri","sans-serif"; color:black">From:
</span></b><span style="font-size:11.0pt; font-family:"Calibri","sans-serif"; color:black">Tri Le <<a href="mailto:TRI.LE@phhs.org" id="LPlnk358948">TRI.LE@phhs.org</a>><br>
<b>Date: </b>Sunday, July 29, 2018 at 2:35 PM<br>
<b>To: </b>"<a href="mailto:adult-hlh-mas@lists.utsouthwestern.edu" id="LPlnk499256">adult-hlh-mas@lists.utsouthwestern.edu</a>" <<a href="mailto:adult-hlh-mas@lists.utsouthwestern.edu" id="LPlnk913158">adult-hlh-mas@lists.utsouthwestern.edu</a>><br>
<b>Cc: </b>Jananie Ramesh <<a href="mailto:JANANIE.RAMESH@phhs.org" id="LPlnk597350">JANANIE.RAMESH@phhs.org</a>>, Joseph Frankl <<a href="mailto:JOSEPH.FRANKL@phhs.org" id="LPlnk507934">JOSEPH.FRANKL@phhs.org</a>>, Roohi Cheema <<a href="mailto:Roohi.Cheema@UTSouthwestern.edu" id="LPlnk937052">Roohi.Cheema@UTSouthwestern.edu</a>>,
 Racha Halawi <<a href="mailto:RACHA.HALAWI@phhs.org" id="LPlnk727673">RACHA.HALAWI@phhs.org</a>>, Aena Patel <<a href="mailto:AENA.PATEL@phhs.org" id="LPlnk171731">AENA.PATEL@phhs.org</a>>, Dawn Klemow <<a href="mailto:Dawn.Klemow@UTSouthwestern.edu" id="LPlnk765723">Dawn.Klemow@UTSouthwestern.edu</a>><br>
<b>Subject: </b>[Adult-hlh-mas] securemail - possible HLH...previously known to most services involved here</span></p>
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<p style="background:white"><span style="font-family:"Calibri","sans-serif"; color:black">Hello members of the HLH task force,</span></p>
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<p style="background:white"><span style="font-family:"Calibri","sans-serif"; color:black">My name is Tri Le, one of the first-year hematology fellows covering CUH over the weekend. I am seeing Ms. Thi Tuyet Tran (MRN 71419053) at the request of the Foster Internal
 Medicine service. I am requesting the assistance of the HLH task force (whom I suspect is aware of this patient) for guidance regarding further workup of alternate diagnoses and consideration of more aggressive HLH-directed immunosuppression vs. macrophage
 directed therapy in this woman who previously had a possible history of HLH (did truly meet 5/8 criteria: elevated soluble IL2R at 65K, elevated ferritin in the upper 1000s, triglyceride 317, fever, and bicytopenia). However, this diagnosis was brought to
 question because the labs qualifying her for HLH criteria were not synchronous, she ultimately became relatively clinically well, and had improved with steroids for treatment of DRESS.</span></p>
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<p style="background:white"><span style="font-family:"Calibri","sans-serif"; color:black">This is an unfortunate woman who was previously hospitalized throughout most of June for an FUO workup and progressive failure to thrive. During that hospitalization,
 she was seen by multiple services (ID, rheum, heme, GI/liver, immunology, dermatology) and underwent extensive infectious and rheumatologic workup that was notable for multiple UTIs (treated) and chronic hepatitis B (on treatment with entecavir). Treatment
 of these did not yield much in the way of defervescence or functional status. Bone marrow biopsy was pursued and revealed a hypercellular marrow with small monoclonal B lymphocytosis (1.1%) nondiagnostic of malignancy, but no hemophagocytosis. Her bone marrow
 aspirate cultures were negative. Moreover, she developed a morbiliform rash with eosinophilia suspicious for DRESS. For this suspected DRESS (tenofovir vs cephalosporins), she was treated with high-dose prednisone at 1 mg/kg. With this, her rash improved and
 fevers resolved. She was then discharged to SNF. </span></p>
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<p style="background:white"><span style="font-family:"Calibri","sans-serif"; color:black">In the interim, she was in the MICU for severe sepsis related presumably to enteritis, from which she recovered with antibiotics and was discharged. She presents again
 to the hospital after a fall on 7/26/18 but is again found to be progressively pancytopenic with elevated inflammatory markers (ferritin now doubled to 15000), CRP in the 30s (albeit improved from prior when it was in the 70-100s), and intermittent fevers.</span></p>
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<p style="background:white"><span style="font-family:"Calibri","sans-serif"; color:black">She still appears to have some inflammatory process that is brewing and breaking past her steroids. I am still uncertain of what her precise diagnosis is, whether it is
 HLH or another autoinflammatory condition. We have requested that the primary team resend her  soluble IL2R and ferritin. Moreover, I have asked the primary team to consult immunology and hepatology since I believe that this is a primary dysregulation of her
 inflammatory system with possible interaction with her chronic hepatitis B. That said, we are all somewhat uncertain and hope that this task force has familiarity with her case and further insight.</span></p>
<p style="background:white"><span style="font-family:"Calibri","sans-serif"; color:black"> </span></p>
<p style="background:white"><span style="font-family:"Calibri","sans-serif"; color:black">Best,</span></p>
<p style="background:white"><span style="font-family:"Calibri","sans-serif"; color:black">Tri Le</span></p>
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