John  Martinelli,  MSIII,  SGUSOM             DATE:   10/6/13  Pediatrics,  Case  3:  Heart  Transplant,  Immunosuppression          Identifying  Data:      A.A.  is  a  pleasant,  English  speaking,  3-­‐year-­‐old  African-­‐American  boy  who  presented  to  the  SBMC  ED  with  his  mother  and  father  on  the  evening  of  September  24,  2013.  He  was  subsequently  admitted  to  the  pediatric  step  down  unit  on  this  same  visit.    DOB:  6/26/10    Chief  Complaint:    A.A.’s  parents  reported  recent  swelling  of  his  left  eyelid  and  A.A.  pointing  to  his  left  eye  complaining  “my  eye  hurts”.    History  of  Present  Illness:    Beginning  four  days  prior  to  A.A.’s  ED  visit  and  admission,  he  was  observed  to  have  increasing  redness,  swelling,  pain,  and  tenderness  of  his  left  upper  eyelid.  This  continued  to  progress,  which  prompted  his  parents  to  seek  medical  care.  Upon  presentation  to  the  ED,  the  left  upper  lid  was  significantly  erythematous,  edematous,  as  well  as  tender  to  touch.  He  had  not  noticed  a  change  in  vision  or  diplopia.  There  was  no  evidence  of  extra-­‐ocular  muscle  restriction,  paresis,  paralysis,  or  nystagmus.  The  eye  did  not  appear  exophthalmic.  There  was  no  anisocoria  noted.  Conjunctival  injection  was  not  evident.  There  was  no  history  of  recent  sick  contacts,  travel,  change  in  environment,  trauma,  or  insect  bites  reported.  Prior  to  presentation,  he  was  found  to  have  a  temperature  of  101  at  home  and  101.5  recorded  in  the  ED.  He  did  not  have  any  recent  nausea,  vomiting,  diarrhea,  chest  pain,  shortness  of  breath,  or  signs  of  respiratory  distress.  Considering  A.A.’s  increasing  temperature  combined  with  his  ocular  signs  and  symptoms,  it  was  decided  to  admit  for  further  treatment  as  a  precaution  against  progressive  orbital  involvement.    Past  Medical  History:    A.A.  was  born  at  term  via  uncomplicated  cesarean  section  at  8lbs,  0oz  at  Columbia  University  with  a  prenatal  diagnosis  of  left  heart  hypoplasia.  He  was  immediately  admitted  to  the  NICU  and  underwent  his  first  cardiac  surgery  at  5  days  of  age.  Post-­‐operatively,  he  remained  in  the  NICU  for  approximately  one  month.  He  has  an  extensive  cardiac  history  and  required  a  second  procedure  at  6  ½  months  of  age.  In  December  of  2011,  he  received  a  successful  allogeneic  heart  transplant.  He  currently  has  no  signs  or  symptoms  of  rejection,  and  on  September  6,  2013  he  underwent  his  annual  heart  biopsy,  which  confirmed  no  rejection.    Subsequent  to  A.A.’s  heart  transplant,  he  did  require  temporary  speech  and  language  therapy;  however,  he  has  progressed  to  a  point  whereby  these  services  have  been  discontinued.  Currently  there  are  no  concerns  with  respect  to  reaching  his  developmental  milestones.    At  the  time  of  his  recent  biopsy,  he  was  diagnosed  with  idiopathic  autoimmune  hemolytic  anemia  for  which  he  required  a  blood  transfusion.  His  current  hemoglobin  is  now  close  to  normal  levels  and  he  continues  to  be  monitored.  He  was  also  found  to  be  neutropenic  during  this  biopsy  visit,  which  has  persisted  to  date.    He  has  had  no  other  serious  or  significant  illnesses  and  his  immunization  history  is  documented  and  up  to  date.  

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Family  History:    A.A.’s  mother  developed  gestational  diabetes  during  her  pregnancy  that  subsequently  resolved  post-­‐partum.  Maternal  and  paternal  grandparents  history  is  significant  for  DM  Type  II,  with  his  maternal  grandfather  also  being  recently  diagnosed  with  colon  cancer.  A.A.’s  parents  health  history  is  unremarkable.    Social  History:    A.A.  lives  at  home  with  his  mother,  father,  and  three  older  siblings.  A  5-­‐year-­‐old  sister,  14-­‐year-­‐old  sister,  and  a  19-­‐year-­‐old  brother.  Either  his  mother  or  father  is  always  present  at  home.  He  does  occasionally  attend  pre-­‐school  and  according  to  his  parents,  he  is  doing  well  and  they  have  no  concerns  at  this  time.  None  of  his  family  members  smoke  and  there  is  no  smoking  at  home.  There  are  no  pets  at  home.  He  is  able  to  tolerate  an  adult  diet,  however,  he  must  avoid  grapefruit  and  pomegranate  juice  due  to  possible  alterations  in  metabolizing  his  medication.    Medications:    Current:    Poly-­‐Vi-­‐Sol  Drops:  1ml,  Daily  Amlodipine:  1.5mg,  Daily  Ferrous  Sulfate:  15mg,  BID  Lansoprazole  3mg/ml  oral  suspension:  5ml,  Daily  Prednisone  5mg/ml  oral  solution:  3ml,  Daily  Tacrolimus  1mg  oral  capsule:  4mg,  Oral,  Daily,  AM  +  4.5mg,  Oral,  Bedtime.    Upon  Admission:    D5NS  1,000ml:  25ml/hr,  IV  NS  0.9%  Flush  3ml:  2ml,  IV  Push  Zosyn:  1480mg,  29.6ml,  IV  Piggyback,  Q8H  Vancomycin:  225mg,  45ml,  45ml/hr,  IV  Piggyback,  Q6H    Allergies:    NKA,  NKDA    Review  of  Systems  (upon  admission):    General:  Unremarkable,  except  as  documented  in  history  of  present  illness.  Skin:  Unremarkable.  Eye:  As  documented  in  history  of  present  illness,  left  eyelid  erythema,  edema,  pain,  tenderness.  HENT:  Unremarkable.  Normocephalic.    Cardiovascular:  As  documented  in  past  medical  history,  successful  heart  transplant  (2011).  Pulmonary:  Unremarkable.  Lymphatics:  Unremarkable.  Gastrointestinal:  Unremarkable.  Genitourinary:  Unremarkable.  Musculoskeletal:  Unremarkable.  Neurologic:  Unremarkable.  Hematologic:  As  documented  in  past  medical  history,  hemolytic  anemia,  neutropenia.  Endocrine:  Unremarkable.  Psychiatric:  Alert  and  oriented.  Appropriate  affect.    

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Physical  Exam  (upon  admission):    Vitals:            

BP:  110/76       Weight:  14.8  kg  HR:  113         Height:  96  cm  RR:  24         BMI:  16.1  Pulse  Ox:  100%  (RA)  T:  99.3  

 General:  Vertical  midline  surgical  scar  evident  at  sternum,  supine,  awakening  from  sleep.    Skin:  Unremarkable.    Eye:  PERRLA  (-­‐)APD.  EOM’s  full  without  restriction  OU,  (-­‐)diplopia,  orthophoric.  Confrontation                    visual  fields  full  OU.  (+)Red  reflex  OU.  Upper  lid  OS  with  localized  pre-­‐tarsal  grade  II+  erythema,                    II+  edema,  and  tenderness  to  palpation  5/10.  Anterior  segment  (penlight):  (-­‐)Conjunctival  or                    episcleral  injection/congestion  OU.  Clear  corneal  reflex  OU.    HENT:  Unremarkable.  Normocephalic.    Cardiovascular:  Regular  rate,  rhythm,  no  murmurs,  adequate  peripheral  perfusion,  no  edema.    Pulmonary:  Clear  to  auscultation  with  equal  breath  sounds  bilaterally.    Gastrointestinal:  Abdomen  non-­‐distended,  soft,  and  non-­‐tender  in  all  quadrants.    Genitourinary:  Deferred  physical  exam.    Musculoskeletal:  Adequate  equal  tone  and  strength  of  upper  and  lower  extremities.    Neurologic:  CN  II  –  XII  intact.  Speech  and  language  intact.  Normal  sensation  upper  and  lower                                                extremities.  DTR  normal  response  bilaterally.    Lymphatics:  No  lymphadenopathy  at  neck,  axilla,  groin.    Endocrine:  No  evidence  of  goiter,  myxedema,  tremor,  exophthalmos.    Psychiatric:  Alert  and  oriented.  Appropriate  affect.    Labs  (upon  admission):    WBC:  2.9     Na:  136     K:  5.2       Gl:  95  Hgb:  10.6     Cl:  102     HCO3:  22   Ca:  8.9  Platelets:  299     BUN:  18     Cr:  0.56        ALT:  39       Tbili:  0.8   ESR:  10  AST:  40       Tprotein:  7.0   CRP:  7.66  ALP:  705     Albumin:  3.8    Discussion/Differential  Diagnosis:    A.A.  is  a  3-­‐year-­‐old  boy  with  a  history  of  successful  allogeneic  heart  transplantation  performed  in  December  2011  due  to  congenital  hypoplastic  left  heart  syndrome  (HLHS).  HLHS  can  be  described  as  a  malformation  leading  to  a  diminutive  left  ventricle  incapable  of  providing  adequate  systemic  

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circulation.  His  post-­‐operative  course  has  continued  to  prove  positive  with  respect  to  rejection,  cardiopulmonary  failure,  infection,  as  well  as  numerous  additional  possible  complications.    At  the  time  of  his  most  recent  heart  biopsy  in  September  2013,  A.A.  reportedly  presented  with  significantly  decreased  hemoglobin  and  hematocrit  levels,  along  with  additional  laboratory  indicators  pointing  to  autoimmune  hemolytic  anemia.  The  etiology  of  the  autoimmune  mechanism  was  not  determined,  however,  a  drug  trigger  is  suspected.  He  was  given  a  single  blood  transfusion  with  an  appropriate  response.    Understanding  the  need  for  immunomodulation  post-­‐transplant  creates  an  additional  area  of  concern  regarding  infection,  be  it  nosocomial,  community,  or  atypical  opportunistic  infection.  His  current  immunosuppressive  therapy  includes  prednisone  in  addition  to  tacrolimus.  Tacrolimus  is  a  macrolide  that  has  been  found  to  reduce  IL-­‐2  cytokine  levels  produced  by  T-­‐Cells,  thereby  assisting  in  the  prevention  of  organ  rejection.  In  addition,  although  rare,  several  studies  have  shown  a  correlation  between  tacrolimus  and  neutropenia  post  transplant.  There  have  also  been  reports  of  neutropenia  being  associated  with  prolonged  prednisone  therapy.  A.A.’s  WBC  count  of  2.9  is  perhaps  indicative  of  tacrolimus  and/or  prednisone  associated  neutropenia.    His  labs  on  this  current  admission  show  a  Hgb  of  10.6  (age  normal  10.5  –  12.7)  suggesting  recovery  from  his  hemolytic  anemia.  However,  of  note,  both  his  ESR  and  CRP  levels  were  elevated  at  10  and  7.66  respectively  (age  normal  ESR  1  –  8,  CRP  0  –  1.2),  perhaps  signifying  persistent  autoimmune  activity.  Also  on  this  admission,  his  ALP  level  was  found  to  be  markedly  elevated  at  705  (age  normal  115  –  391),  which  may  be  interpreted  as  a  normal  variant.  However,  elevated  ALP  in  the  presence  of  normal  liver  function  tests  (ALT/AST/Tbili/Tprotein/Albumin)  as  shown  in  this  case  has  been  recognized  in  various  pathologies  including  bone,  cardiac  failure,  as  well  as  prolonged  corticosteroid  therapy.  This  ALP  elevation  may  therefore  be  representative  of  his  cardiac  history  and/or  current  prednisone  therapy.    Considering  A.A.’s  transplant  history  requiring  ongoing  immunomodulation  therapy,  and  concurrent  with  persistent  neutropenia,  the  predilection  for  acute,  chronic,  or  progressive  complicated  infection  must  constantly  be  assessed.  Therefore,  his  presentation  to  the  ED  with  ocular  signs  and  symptoms  characteristic  of  pre-­‐septal  cellulitis  required  more  aggressive  in-­‐patient  care  versus  typical  outpatient  oral  pharmacotherapy.    Assessment:    

1. S/P  Allogeneic  Heart  Transplantation  (December  2011),  successful  post-­‐operative  course.  2. Idiopathic  Autoimmune  Hemolytic  Anemia  (September  2013),  s/p  single  blood  transfusion  

with  recovering  hemoglobin  and  hematocrit  levels.  3. Persistent  Idiopathic  Neutropenia  (current  admission).  4. Pre-­‐Septal  Cellulitis  OS  upper  lid  (current  admission),  (-­‐)  evidence  of  orbital  

progression/orbital  cellulitis.    Plan:    

1. Continue  care  with  cardiac  team  at  Columbia  University.  2. Monitor  CBC  at  Columbia  for  continued  improvement  of  hemoglobin,  hematocrit.  3. Advised  cardiac  team  at  Columbia  of  persistent  diminished  WBC  count/neutropenia  and  

increased  infection  risk.  ?Consider  future  therapy  modification.  4. Admitted  to  pediatric  step-­‐down  unit  at  SBMC.  Efficacious  response  to  IV  antibiotic  therapy  

with  significant  resolution  of  cellulitis,  no  progression  to  orbital  cellulitis.  Discharged  on  9/26/13  with  transition  to  PO  clindamycin  and  omnicef  for  10  days.  Advised  to  return  to  ED  if  signs  or  symptoms  return.