Price v. Secretary of Health and Human Services

In the United States Court of Federal Claims
OFFICE OF SPECIAL MASTERS
Case No. 11-442V
Filed: October 29, 2015
[TO BE PUBLISHED]
*************************
TABITHA PRICE, as Mother and Natural *
Guardian of D.P., *
* Ruling on Entitlement; DTaP; MMR;
* Prevnar; Anaphylaxis; Neurological
Petitioner, * Injuries; Epilepsy; Seizures.
*
v. *
*
SECRETARY OF HEALTH *
AND HUMAN SERVICES, *
*
Respondent. *
*************************
Clifford Shoemaker, Shoemaker and Associates, Vienna, VA for petitioner.
Robert Paul Coleman, III, United States Department of Justice, Washington, DC, for respondent.
RULING ON ENTITLEMENT1
Gowen, Special Master:
On July 7, 2011, Tabitha Price (“petitioner”) filed a petition on behalf of her minor son
(“D.P.” or “minor child”) for compensation under the National Vaccine Injury Compensation
Program, 42 U.S.C. § 300aa-10 – 34 (2012)2 (the “Vaccine Act” or “the Program”). Petitioner
alleged that as a result of receiving Diphtheria-Tetanus-acellular-Pertussis (“DTaP”), Measles-
Mumps-Rubella (“MMR”) and Pneumococcal Conjugate (“Prevnar”) vaccines on August 4, 2008,
1
Because this published ruling contains a reasoned explanation for the action in this case, I intend
to post it on the United States Court of Federal Claims' website, in accordance with the E-
Government Act of 2002, Pub. L. No. 107-347, 116 Stat. 2899, 2913 (Dec. 17, 2002). In
accordance with Vaccine Rule 18(b), petitioner has 14 days to identify and move to delete medical
or other information, the disclosure of which would constitute an unwarranted invasion of privacy.
If, upon review, I agree that the identified material fits within this definition, I will delete such
material from public access.
2
National Childhood Vaccine Injury Act of 1986, Pub. L. No. 99-660, 100 Stat. 3755. Hereinafter,
for ease of citation, all “§” references to the Vaccine Act will be to the pertinent subparagraph of
42 U.S.C. § 300aa (2012).
1
D.P. had a severe anaphylactic reaction within two minutes of the vaccinations, which caused him
to suffer a grand mal seizure. Petitioner further alleged that several hours later D.P. experienced
more seizures and subsequently developed a seizure disorder and secondary developmental delay.
In addition to documentary evidence in the form of medical records, petitioner presented
the testimony of Yuval Shafrir, M.D., a neurologist and epileptologist. The respondent presented
the testimony of Peter Bingham, M.D., a pediatric neurologist. Both parties submitted medical
literature in support of their positions.
For the reasons stated herein, I find by preponderant evidence that: (1) the petitioner has
presented a reasonable theory as to how D.P.’s vaccinations caused an anaphylactic reaction in the
form of seizures, (2) she presented a logical cause and effect explanation relating the vaccinations
to D.P.’s anaphylaxis and seizures, and (3) the timing in this case was particularly significant.
Respondent’s contention that the seizures occurred as a result of pure coincidental onset of
idiopathic epilepsy within two minutes of receipt of the vaccines, or occurred as a result of an
unknown gastrointestinal illness, for which there was no evidence, I find to be considerably less
likely.
Accordingly, I conclude that D.P. is entitled to compensation under the National Childhood
Vaccine Injury Act.
I. BACKGROUND
A. Procedural History
Petitioner filed numerous medical records in support of her petition. See Petitioner’s
(“Pet.”) Exhibits (“Exs.”) 1-28, 41-53. On April 19, 2012, respondent filed a Rule 4(c) report
recommending against compensation. Respondent’s (“Res.”) Report at 9, docket no. 24, filed Apr.
19, 2012. Respondent argued that “petitioner [had] not offered a reliable medical opinion
demonstrating that any of [the minor’s] vaccinations either could be, or were, the cause of [the]
alleged injury.” Id. at 11. Additionally, respondent argued that “[t]he records submitted also [did]
not contain a medical theory causally connecting the vaccinations and injury, nor [did] they
provide a logical sequence of cause and effect showing that the vaccinations were the reason for
the injury, as required by Althen.” Id.; see Althen v. Sec’y of HHS, 418 F.3d 1274, 1278 (Fed. Cir.
2005).
On May 1, 2013, petitioner filed an expert report from Dr. Yuval Shafrir, along with his
curriculum vitae and medical literature. See Pet. Exs. 29-40. Thereafter, a status conference was
held on May 7, 2013, where the parties agreed to proceed with petitioner preparing a demand, in
addition to respondent filing a responsive expert report. Order, docket no. 43, filed May 8, 2013.
Petitioner filed a status report indicating her demand was conveyed to respondent on July 8, 2013.
Respondent filed a responsive expert report from Dr. Peter Bingham, along with his curriculum
vitae and medical literature on September 19, 2013. See Res. Exs. A-D.
A status conference was held on October 8, 2013, to discuss additional proceedings. The
parties agreed to proceed with an entitlement hearing and were ordered to determine a hearing
2
date. Order, docket no. 53, filed Oct. 8, 2015. A hearing order was issued on November 12, 2013,
scheduling an entitlement hearing for March 3 and 4, 2014, to take place in Washington, D.C.
before Special Master Hamilton-Fieldman. Hearing Order, docket no. 54, filed Nov. 12, 2013.
Petitioner filed pre-hearing submissions on January 7, 2014 and respondent filed her pre-hearing
submissions on January 28, 2014. However, as a result of inclement weather, the entitlement
hearing was cancelled on March 2, 2014.
Thereafter, in order to clarify conflicting evidence between the medical records and
petitioner’s assertions as to whether there was an incidence of vomiting in advance of the child’s
initial seizure, Special Master Hamilton-Fieldman ordered a fact hearing on whether the minor
child had a gastrointestinal illness prior to his vaccinations. The parties were ordered to file a joint
status report providing dates for a fact hearing, as well as any desired affidavits. See Order, docket
no. 60, filed Mar. 11, 2014. On April 11, 2014, a fact hearing was scheduled for May 20, 2014 in
Washington, D.C. See Pre-Hearing Order, docket no. 69, filed Apr. 11, 2014.
On April 10 and 14, 2014, petitioner’s counsel filed affidavits from Ann Wilson, the minor
child’s grandmother; Nancy Floyd, the minor child’s aunt; and Tabitha Price, the minor child’s
mother and petitioner in this matter. See Pet. Exs. 51-53. However, only Tabitha Price presented
testimony at the fact hearing on May 20, 2014. See Transcript of Fact Hearing, docket no. 74,
filed June 4, 2014. At the conclusion of the hearing, respondent was ordered to file a supplemental
expert report based on the testimony at the fact hearing. See Order, docket no. 72, filed May 20,
2014. Additionally, the parties were notified that any findings of fact would be incorporated in an
entitlement decision. Id.An entitlement hearing was thereafter scheduled for September 19, 2014. See Prehearing
Order, docket no. 77, filed June 30, 2014. On July 7, 2014, respondent filed a supplemental expert
report from Dr. Bingham. See Res. Ex. E. Petitioner elected not to file a responsive expert report
from Dr. Shafrir. See Pet. Status Report, docket no. 79, filed Aug. 4, 2014. On September 10,
2014, this case was reassigned to the undersigned. Subsequently, petitioner filed additional
medical literature in support of her position. See Pet. Exs. 54-59.
An entitlement hearing was held on September 19, 2014, where Dr. Shafrir testified on
behalf of petitioner and Dr. Bingham testified on behalf of respondent. See Transcript of
Entitlement Hearing, docket no. 86, filed Oct. 8, 2014. Petitioner filed a post-hearing brief on
November 7, 2014 and a reply brief on December 23, 2014. Respondent filed a post-hearing brief
on December 5, 2014. Accordingly, this case is ripe for a decision.
B. Summary of the Facts
D.P. was born prematurely on April 13, 2007 at thirty-six weeks gestation, weighing six
pounds fourteen ounces. Pet. Ex. 1 at 129. D.P. was delivered via cesarean section. Id. His
mother’s preoperative diagnoses included hypertension, failure to progress in labor, and failed
induction of labor. Id. The pregnancy was complicated by low amniotic fluid and gestational
diabetes. Id. at 30. Additionally, D.P.’s mother tested positive for a group B streptococcus
3
infection. Id. at 146. At birth, D.P.’s Apgar Scores3 were nine and nine at one and five minutes
old. Id. at 129. D.P. was discharged home with his mother after three days. Pet. Ex. 11 at 9.
Within the first year of life, D.P. had periodic issues with reflux, colic, vomiting,
conjunctival infection with obstruction of his tear duct, umbilical hernia, and various upper
respiratory infections, ear infections, and fevers. Pet. Ex. 7 at 23-50. On February 5, 2008, at ten
months of age, D.P. was brought to a pediatric gastroenterologist for an evaluation due to
gastrointestinal complaints. Id. at 112. His symptoms were described as “constipation problems
and reflux symptoms.” Id. The physician continued his Zantac prescription and deferred further
evaluation. Id.
On August 4, 2008, D.P. was seen for his fifteen-month check-up by Dr. Nora Patonay at
Conyers Pediatrics. Pet. Ex. 7 at 17. At this appointment he received DTaP, MMR and Prevnar
vaccinations. Id. at 21. At 10:20 a.m., within two minutes of his vaccinations, D.P. suffered a
seizure. Id. at 17, 20. An online VAERS report submitted by Conyers Pediatrics described the
incident as follows:
Patient given dtap #4, mmr #1, and prevnar #4. Two minutes after administration
of vaccines patient began seizing. Seizure lasted for approximately 2-3 minutes. He
was posturing and pupils were dilated, arms and legs shaking, lips and face were
blue. We did treat with 5L of oxygen. Vitals were within normal limits and stable
afterwards 128 [heart rate] and 32 resp/minute, o2 sat 98%. Valium prepared but
not needed. 911 called and patient transported to Egleston Children’s Hospital.
Id. at 20. Conyers Pediatrics documented that D.P. “became limp, turned blue, had grand mal
seizure, jerking legs [and] arms” after receiving his immunizations. Id. at 17. The medical records
further noted that oxygen was given to D.P., and in less than two minutes, his seizure stopped, and
his lips and skin turned pink. Id. After the seizure, D.P. was moaning and limp. Id. at 18.
According to petitioner, on the way to Dr. Patonay’s office, D.P. “was eating a hash brown
and choked on it. It caused him to throw up the food that he was swallowing, but he was fine after
that.” Pet. Ex. 52 at 1-2; see also Pet. Ex. 18 at 47 (an emergency room record noting mom reported
D.P. “eating a hash brown this am in [the] car and then vomited it out. She [was] not sure if he
choked as he was in the backseat with his sister. No choking sounds heard.”). Dr. Patonay noted
that D.P. had no illness at the time of his vaccinations. Pet. Ex. 7 at 21.
D.P. was transported by ambulance to Children’s Hospital of Atlanta-Egleston, with a
triage time of 11:57 a.m. Pet. Ex. 18 at 48, 176. The triage notes indicate that D.P.’s presenting
symptoms were seizure and that his respiratory effort was “easy,” his skin color and temperature
were normal for a child, he had a regular heart rate and rhythm, and he was sleeping, but arousable.
Pet. Ex. 18 at 46. The emergency department physician noted that D.P. was “back to baseline,”
3
“A numerical expression of the condition of a newborn infant, usually at 60 seconds after birth,
being the sum of points gained on assessment of the heart rate, respiratory effort, muscle tone,
reflex irritability, and color.” Dorland’s Illustrated Medical Dictionary 1682 (32d ed. 2012)
[hereafter “Dorland’s”].
4
and that neurology services indicated that “no workup [was] necessary . . . .” Id. at 48. The
physician further noted that “if there [was] another event[,] then the child will need [a] neuro clinic
appointment.” Id. D.P. was discharged at approximately 1:16 p.m. Id. at 50.
D.P.’s aunt, Nancy Floyd, brought him back to Egleston at 3:54 p.m. that same day, August
4, 2008, after D.P. suffered a second seizure in the car on the way home from the earlier hospital
visit. Pet. Ex. 18 at 210. The medical record notes:
Aunt reports that [patient] was at baseline on way home from ER smiling and
talking. He then had emesis.4 [Patient] then became fussy. Then within 15 minutes
mom [sic]5 noted that he became stiff in all four extremities with possible shaking
at the distal extremities. Eyes rolled back into head. Aunt unsure if any color
changes. Episode lasted 2-3 minutes. [Patient] very tired afterwards and not
responding. [Patient] did respond when EMS placed IV. Episode occurred around
2:45 today.
Id. at 210-11. A neurological assessment at the emergency department noted that “upon arrival to
the room, [patient was] gazing, apneic, . . . placed on non-rebreather 100%”. Id. at 85. Thereafter,
D.P. experienced a third seizure which was observed by Dr. Shroff directly. Id. at 85, 213. D.P.’s
third seizure lasted one minute, with tonic clonic movements, eye rolling, and breathing. Id. at 213.
He was given Ativan as his seizing stopped. Id. D.P. was subsequently hospitalized for several
days and experienced four more seizures in the course of his stay. Pet. Ex. 5 at 14.
Labs drawn at the time of the third seizure showed mildly low blood glucose at 57 L (range
65-100 MMOL/L), sodium at 133 L (range 136-145 MMOL/L), bicarbonate at 17 L (range 20-28
MMOL/L) and ammonia at 6 L (range 22-48 UMOL/L). Pet. Ex. 18 at 61. He was treated with a
bolus of dextrose which rapidly returned glucose level to 89 L. Id. at 83. An EEG performed on
August 5, 2008, indicated “[a]bnormal EEG with mild asymmetry of the background voltage and
frequency. The left hemisphere [was] consistently slower and lower in voltage. The right
hemisphere contain[ed] high-voltage posterior slowing.” Id. at 70. Dr. Philip Holt believed the
findings were nonspecific, but suggested diffuse neuronal dysfunction, likely more pronounced in
the left hemisphere. Id. Further, he believed the “[f]indings may be metabolic, pharmacologic,
infectious or even postictal.” Id.
A head CT scan was negative. Pet. Ex. 18 at 83. A lumbar puncture showed no organisms,
few white blood cells, and many red blood cells. Id. at 90. A brain MRI performed on August 5,
2008, noted multiple bilateral dilated perivascular spaces in the region of the basal ganglia.
However, there was “no evidence of territorial infarction, hemorrhage, mass, mass effect or
midline shift.” Pet. Ex. 9 at 42. Dr. Denis Atkinson Jr.’s impression was that the MRI findings
were normal and age appropriate. Id. Dr. Yong Park interpreted these films two years later, on
4
“Vomiting.” Dorland’s, supra note 3 at 608.
5
Petitioner’s affidavit notes that her son, D.P., was in the care of her sister, Nancy Floyd, while
she sought medical treatment at Eastside Medical Center for a spike in her blood pressure and a
headache she experienced that day. Pet. Ex. 52 at 2-3.
5
August 20, 2010, and noted a “slight left temporal horn asymmetry, but no evidence of mesial
temporal stenosis or cortical dysplasia.” Pet. Ex. 5 at 14. D.P. was discharged from Egleston on
August 7, 2008 with a diagnosis of seizure, asthma, and diarrhea. Pet. Ex. 18 at 34, 36. He was
treated with Dilantin for his seizures. Id. at 62.
On November 20, 2008, D.P. was seen at Emory Pediatric Neurology at nineteen months
of age. He was reported to be taking a small dose of Keppra, a seizure medication, by mouth twice
a day. Pet. Ex. 4 at 48. His mother reported last seeing a staring spell approximately one month
prior. Id.
On April 15, 2009, D.P. underwent an evaluation at Babies Can’t Wait upon referral from
his pediatrician due to concerns regarding his sensory response and history of seizures. Pet. Ex. 7
at 89. The evaluation noted that his seizures were well-managed, but that his mother had concerns
about his sensory issues. Id. Specifically, petitioner reported that D.P. would “often fall and shake
in response to loud noises, frustration, or concentrated tasks. He chew[ed] on non-food items and
roll[ed] his eyes when his hair [was] being washed.” Id. Also, he was a picky eater. Id. It was
determined at that time that D.P.’s “general development did not appear to be adversely impacted
by his sensory and neurological issues, as demonstrated by his scores . . . .” Id. Accordingly, he
was not eligible for early intervention support. Id. at 84. D.P. was found to have shown “average
developmental skills for his age,” based on a review of his medical records and a multidisciplinary
evaluation report. Id.
On April 21, 2009, D.P. was seen by a pediatric neurologist, Dr. Larry Olson, at Emory
Children’s Center. Dr. Olson noted that D.P.’s parents reported that “he has not had any ‘more big
events,’” but that D.P. experienced tremors in his hands and upper body “for a couple of seconds,”
and was responsive during those spells. Pet. Ex. 4 at 33. They also reported again that when water
was poured on his head in the tub, D.P.’s eyes would roll back and he would “get rowdy.” Id. at
33. He would get better when he was out of the water. Id. Dr. Olson noted that the developmental
specialist at Babies Can’t Wait found that D.P. was developmentally “‘fine,’” but that the specialist
did note sensory concerns. Id.
Dr. Olson further noted that D.P.’s family was “insistent that the vaccines have caused
[D.P] trouble with seizures and developmental delays,” and that “they [did] not want him to have
any more vaccinations.” Id. at 34. Dr. Olson recommended that they adhere to the CDC guidelines
for vaccination, but that “it [was] ultimately up to the family and the pediatrician to discuss” his
vaccination schedule. Id. He further assessed that “the spells where his eyes rolled back in the tub
are probably not reflex seizures” but that the family should attempt to videotape them for future
reference. Id. He also recommended an evaluation at Emory Autism Center and Marcus Autism
Center. Id.
D.P. was evaluated at the Marcus Autism Center for pervasive developmental disorder on
July 13, 2009. Pet. Ex. 3 at 3-18. Petitioner and several family members provided information for
this evaluation; additionally, the evaluators reviewed D.P.’s medical records. Id. at 3. D.P.’s family
reported that D.P.’s feeding habits changed and that he is a picky eater. Id. He had become very
clumsy and fell a lot. Id. He also “started to turn his right foot in when he walk[ed] or [ran],” which
6
contributed to his falling. Id. “When he [gets] excited he flaps his hands” and “when in a new
situation or around a lot of new people, he will shake all over.” Id.
Midway through the assessment, prior to moving to another testing room, [D.P.]
was observed to fall and was unresponsive for several seconds. Initially it appeared
as though he tripped over his grandmother’s legs, however, his grandmother
reported that he had gone limp. He appeared to quickly recover and easily
transitioned to a different testing room. However, qualitatively, his interactions
seemed to differ after this episode. For example, [D.P.] appeared more inattentive
and distractible.
Id. at 11. It was further noted that D.P.’s eye contact was not “well meshed with his requests and
smiles.” Id. at 12. He was observed to be “somewhat repetitive” and appeared fixated on a
particular toy. Id. “[H]is behavior was notably different when comparing his behavior from before
his falling episode during informal free play and after the episode during a semi-structured play
session.” Id.
D.P.’s cognitive skills were described as “being in the low end of Average and at an age
equivalent of 1 year, 10 months” (D.P. was 2 years and 2 months at this time). Id. at 13. His ability
to coordinate visual and fine motor process was noted to be markedly weak. Id. “His pre-academic
abilities, when compared to a child aged 2 years, 6 months, were found to be advanced.” Id. at 16.
He was below average for adaptive abilities, compared to other boys his age, and was in the
average range for his socialization skills. Id.
A developmental diagnosis was not made at his evaluation at Marcus Autism Center. Id. at
17. He was referred to child psychology to address behavioral difficulties noted at home, and
neurology to assess the status of his seizure control. Id. It was noted that a reevaluation at a later
date was important “given that some of the symptoms associated with an autism Spectrum
Disorder were denoted during the assessment such as atypical play and his early letter/number
knowledge.” Id. Additional recommendations included assessments in speech and language
therapy, and a special needs pre-school coordinator for his county. Id.
On August 5, 2009, D.P. was seen for follow-up with his pediatric neurologist Dr. Larry
Olson at Emory Children’s Center. Pet. Ex. 4 at 18. In his consult note to Dr. Nora Patonay, Dr.
Olson stated his impression was “presumed complex partial seizures” that persist with a frequency
of one every other day, typically around 20 seconds, with behavioral arrest, minor finger
automatisms bilaterally, often followed with brief limpness.” Id. Dr. Olson increased the dosage
of Keppra to 3 ml twice a day.
On February 1, 2010, D.P. underwent an EEG. The impression of his EEG was that the
EEG was abnormal secondary to focal slowing and sharp activity over the left frontotemporal
region suggestive of focal irritating focus. Pet. Ex. 5 at 195. On August 20, 2010, D.P. was
admitted to the Medical College of Georgia for EEG monitoring because of staring that interrupted
the flow of his activity, with unresponsiveness. Pet. Ex. 5 at 14. He was tapered off Trileptal and
experienced no convulsive seizures while off his medication. Id. at 15. It was noted however, that
after D.P. was completely off his medication they saw “epileptiform discharges that were diffuse
7
and bilateral, left greater than right.” Id. There were no EEG changes during his staring spells. Id.
The record notes that it was explained to D.P.’s parents that “while [D.P.] has a diagnosis of
epilepsy with left-sided seizure focus, the episodes of staring . . . do not appear to be breakthrough
complex partial seizures.” Id. It was recommended that D.P. continue on his Trileptal at 6 ml twice
a day and follow up in three months.
On Thursday, February 24, 2011, D.P. presented to the Egleston emergency department
for increased absence seizures since Saturday, February 18, 2011. Pet. Ex. 18 at 139. Petitioner
reported that the night before the emergency department visit, D.P. had five absence seizures, each
lasting 2 minutes or less. Id. at 140. “He [had] also been saying strange things . . . with repeating
phrases.” Id. Petitioner reported that D.P. had nausea and vomiting, as well as an approximate 101
degree fever the night before he presented to the emergency department. Id. at 139. Nausea and
vomiting were not present the day of the visit, but D.P. complained of forehead pain. Id. He was
noted to be awake, alert, happy, smiling, and playful. Id.
D.P. was discharged with a diagnosis of viral illness and seizures. Id. at 142. Petitioner was
instructed to have him follow up with a pediatrician and a neurologist. Id. It was noted that D.P.’s
“seizure threshold appear[ed] to have decreased due to his current febrile illness.” Id. “Given his
sore throat symptoms, he may develop more symptoms of an upper respiratory infection in the
next few days. He may also have more frequent seizures because of his viral illness.” Id. Ibuprofen
or Tylenol was prescribed, as needed. Id.
II. FACT RULING
Prior to the entitlement hearing before the undersigned, Special Master Hamilton-Fieldman
held a fact hearing on whether D.P.’s spit up of a hash brown from Burger King in the backseat of
his mother’s car, on the drive to the pediatrician’s office, where he received the vaccinations at
issue on August 4, 2008, was evidence of a gastrointestinal illness or more likely a spitting up or
choking on the hash brown.
At the fact hearing, Mrs. Price testified that her fourteen year old daughter and fifteen
month old son, D.P., were in the back seat of the car that day. Fact Transcript (“Fact Tr.”) at 19,
docket no. 74, filed June 4, 2014. D.P. sat in a car seat. Fact Tr. at 10. On the way to the
pediatrician’s office, they stopped at Burger King because D.P. liked the little round hash browns
they offered. Fact Tr. at 9. Mrs. Price testified that about ten minutes after leaving Burger King,
she heard D.P. cough. Fact Tr. at 10. She looked in the rear view mirror and saw him spit out the
hash brown he was eating. Fact Tr. at 10. She also saw her daughter grab a napkin and wipe away
the hash brown. Fact Tr. at 20. Her daughter then said, “[he] spit it up, he didn’t throw up.” Fact
Tr. at 20. Her daughter told her that D.P. coughed up the hash brown that he had just eaten. Fact
Tr. at 32. According to Mrs. Price, after that incident D.P. was fine. Id. They continued to the
doctor’s office. At the doctor’s office, D.P. played with a toy on the floor with his grandmother in
the waiting room. Fact Tr. at 11. Dr. Patonay examined him and said that he was growing normally
and had no illness. Fact Tr. at 11; see Pet. Ex. 7 at 21. Subsequently, D.P. suffered a seizure
immediately after receipt of DTaP, MMR and Prevnar vaccinations. Pet. Ex. 7 at 20. Dr. Patonay
noted in the VAERS report of that event that there was no illness at the time of vaccination. Id.
8
Medical records from D.P.’s emergency room visit after his seizure noted that petitioner
reported D.P. was “eating a hash brown this am in [the] car and then vomited it out. She [was] not
sure if he choked as he was in the backseat with his sister. No choking sounds heard.” Pet. Ex. 18
at 47. At the fact hearing, petitioner was cross-examined on the fact that she either used the word
“vomited” when she was describing this event, or that the word was used by the physician taking
the history. Petitioner testified that she might have said vomited because she prefers to use that
instead of “spit up” or “throw up.” Fact Tr. at 20.
At the outset of the entitlement hearing, after I had read the fact hearing transcript and
ascertained from the parties at the entitlement hearing that there would be no further testimony on
this point, I advised the parties of my conclusion that the evidence shows D.P. spit up the hash
brown that he had just eaten, and that there was no evidence of vomiting abdominal contents.
Entitlement Transcript (“Tr.”) at 52, docket no. 86, filed Oct. 9, 2014.
III. EXPERT OPINION AND CAUSATION ANALYSIS
A. Issues to be determined
Petitioner requests that I determine: (1) whether D.P. suffered an anaphylactic reaction to
the vaccines in the form of a seizure immediately after receipt of the vaccines; and (2) whether, as
a result of the seizure, D.P. suffered an encephalopathy or brain damage and has had continuing
impairment from that injury. Tr. at 53-54. Respondent requests that I determine: (1) whether the
petitioner has met her burden to show causation under Althen; or in the alternative, (2) whether
D.P.’s condition was caused by viral gastroenteritis. Id. at 53.
B. Legal Standard
The Vaccine Act established the Program to compensate vaccine-related injuries and
deaths. § 300aa-10(a). “Congress designed the Vaccine Program to supplement the state law civil
tort system as a simple, fair and expeditious means for compensating vaccine-related injured
persons. The Program was established to award ‘vaccine-injured persons quickly, easily, and with
certainty and generosity.’” Rooks v. Sec’y of HHS, 35 Fed. Cl. 1, 7 (1996) (quoting H.R. Rep. No.
908 at 3, reprinted in 1986 U.S.C.C.A.N. at 6287, 6344).
In order to prevail under the Program, a petitioner must prove either a “Table” injury or
that a vaccine listed in the Table was the cause-in-fact of an injury (an “off-Table” injury).
Petitioner alleges D.P. suffered from anaphylaxis, causing seizures, and encephalopathy. The facts
do not support the Table definition under the QAI of encephalopathy. However, after analysis of
the evidence, I have concluded that the petitioner did prove a Table Anaphylaxis—the anaphylaxis
having occurred within the required four hours of receipt of the DTaP and MMR vaccinations.6
Additionally, petitioner has proved as by preponderant evidence that D.P. suffered ongoing
seizures secondary to the anaphylactic injury and is therefore entitled to compensation.
6
The Vaccine Injury Table, 42 C.F.R ' 100.3 lists anaphylaxis or anaphylactic shock occurring
within four hours of DTaP and MMR vaccinations as table injuries.
9
An “off-Table” injury is initially established when the petitioner demonstrates, by a
preponderance of the evidence that: (1) the minor child received a vaccine set forth on the Vaccine
Injury Table; (2) he received the vaccine in the United States; (3) he sustained or had significantly
aggravated an illness, disease, disability, or condition caused by the vaccine; and (4) the condition
has persisted for more than six months. § 13(a)(1)(A).
There is no dispute but D.P. received the DTaP, MMR and Prevnar vaccines in the United
States at the office of his pediatrician on August 4, 2008 in Atlanta, Georgia. He has also continued
to experience symptoms in the form of additional seizures and a developmental delay for more
than six months.
The respondent contended that D.P. did not experience anaphylaxis, and thus this case was
presented as a cause-in-fact case. To satisfy her burden of proving causation in fact, petitioner
must establish each of the three Althen factors by preponderant evidence: (1) a medical theory
causally connecting the vaccination and the child’s injury; (2) a logical sequence of cause and
effect showing that the vaccination was the reason for the injury; and (3) a proximate temporal
relationship between vaccination and injury. Althen, 418 F.3d at 1278; see de Bazan v. Sec’y of
HHS, 539 F.3d 1347, 1351-52 (Fed. Cir. 2008); Caves v. Sec’y of HHS, 100 Fed. Cl. 119, 132
(2011), aff. per curiam, 463 Fed. Appx. 932 (Fed. Cir. 2012) (specifying that each Althen factor
must be established by preponderant evidence). The preponderance of the evidence standard, in
turn, has been interpreted to mean that a fact is more likely than not. See Moberly v. Sec’y of HHS,
592 F.3d 1315, 1322 n.2 (Fed. Cir. 2010). Proof of medical certainty is not required. Bunting v.
Sec’y of HHS, 931 F.2d 867, 873 (Fed. Cir. 1991).
The Federal Circuit in Althen noted that “while [Althen’s petition] involves the possible
link between [tetanus toxoid] vaccination and central nervous system injury, a sequence hitherto
unproven in medicine, the purpose of the Vaccine Act’s preponderance standard is to allow the
finding of causation in a field bereft of complete and direct proof of how vaccines affect the human
body.” Althen, 418 F.3d at 1280.
Once petitioner establishes each of the Althen factors by preponderant evidence, the burden
of persuasion shifts to respondent, who must show that the alleged injury was caused by a factor
unrelated to the vaccination. Knudsen v. Sec’y of HHS, 35 F.3d 543, 548 (Fed. Cir. 1994); §
13(a)(1)(B). Respondent must demonstrate that “the factor unrelated to the vaccination is the more
likely or principal cause of the injury alleged. Such a showing establishes that the factor unrelated,
not the vaccination, was ‘principally responsible’ for the injury.” Deribeaux v. Sec’y of HHS, 717
F.3d 1363, 1369 (Fed. Cir. 2013). Section 13(a)(2) specifies that factors unrelated do “not include
any idiopathic, unexplained, unknown, hypothetical, or undocumented causal factor, injury,
illness, or condition.” Close calls regarding causation must be resolved in favor of the petitioner.
Althen, 418 F.3d at 1280.
In determining whether petitioner is entitled to compensation, a special master must
consider the entire record and is not bound by any particular piece of evidence. § 13(b)(1) (stating
a special master is not bound by any “diagnosis, conclusion, judgment, test result, report, or
summary” contained in the record). Thus a special master must weigh and evaluate opposing
expert opinions, medical and scientific evidence, and the evidentiary record in deciding whether
10
petitioners have met their burden of proof. “Although Althen and Capizzano make clear that a
claimant need not produce medical literature or epidemiological evidence to establish causation
under the Vaccine Act, where such evidence is submitted, the special master can consider it in
reaching an informed judgment as to whether a particular vaccination likely caused a particular
injury . . . . Medical literature and epidemiological evidence must be viewed, however, not through
the lens of the laboratorian, but instead from the vantage point of the Vaccine Act’s preponderant
evidence standard.” Andreu v. Sec’y of HHS, 569 F.3d 1367, 1380 (Fed. Cir. 2009).
C. Expert Qualifications
1. Petitioner’s Expert, Yuval Shafrir, M.D.
Dr. Yuval Shafrir is board certified in neurology with a special qualification in child
neurology. Tr. at 57. He is also board certified in clinical neurophysiology. Id. He completed a
fellowship in pediatric epilepsy and electroencephalography (“EEG”). Tr. at 57. He testified that
he was board certified in pediatrics, but this certification “was time-limited, so he did not recertify
after 1998.” Id. He received his medical degree, magna cum laude, from the Sackler School of
Medicine in Tel Aviv in 1982. Pet. Ex. 30 at 1. After medical school, he spent several years
completing a pediatric residency in Israel and at North Shore University Hospital, a major affiliate
of Cornell University Medical College. Id. Subsequently, Dr. Shafrir completed a pediatric
neurology fellowship at Washington University in St. Louis and an epilepsy fellowship at Miami
Children’s Hospital. Id.; Tr. at 56. He worked as a pediatric neurologist at Walter Reed Army
Medical Center, then at Georgetown University Hospital, and is currently in private practice. Pet.
Ex. 30 at 1-2; Tr. at 56. At the hearing, Dr. Shafrir described himself as an epileptologist, which
he explained is someone who specializes in epilepsy in children and in EEG. Tr. at 157. He is also
an Assistant Professor in the Department of Pediatrics at the University of Maryland School of
Medicine in Baltimore, Maryland. Pet. Ex. 30 at 1. He regularly treats children with epilepsy. Tr.
at 109.
2. Respondent’s Expert, Peter Bingham, M.D.
Dr. Peter Bingham is a board certified pediatric neurologist with seventeen years post-
residency experience in general child neurology. Res. Ex. A at 1. He trained at Columbia College
of Physicians & Surgeons and did his residency at the University of Pennsylvania and Children’s
Hospital of Philadelphia. Id.; Tr. at 115. Subsequently, he performed a two-year fellowship in
neuromuscular disease and neurogenetics. Tr. at 115. Dr. Bingham continued on the faculty at the
University of Pennsylvania and then to the University of Vermont. Tr. at 115. He is licensed to
practice in the State of Vermont. Tr. at 115. He indicated that he currently reviews numerous
medical journals and has authored articles in peer-reviewed journals. Tr. at 116-17.
Dr. Bingham testified that he works at the University of Vermont and the affiliated Fletcher
Allen Hospital. Tr. at 116. He works predominately as a clinician, generally seeing child neurology
cases, both outpatient and inpatient. Tr. at 117. About twenty to twenty-five percent of his time at
the University of Vermont is devoted to research. Id. Dr. Bingham estimated that he treats
approximately twenty infants and children each week. Id. He estimated that he has treated in the
range of 1500 to 2000 patients with a seizure disorder. Id. The court granted respondent’s request
11
that Dr. Bingham be offered as an expert in the field of pediatric neurology, to which petitioner
did not object. Tr. at 117-18.
D. Althen Analysis
In this case, I have reviewed the medical records of D.P., the reports of the parties’
respective experts, all of the testimony, and the medical literature submitted. Petitioner submitted
two entire textbooks regarding allergy and anaphylaxis, among other literature. While I did not
read all of the textbooks, I have read all chapters which appear to have relevance to this matter, in
addition to the other literature submitted by both parties.7
i. Althen Prong One – Medical Theory
a. Petitioner’s Expert Dr. Shafrir
Dr. Shafrir opined that D.P. suffered a cerebral anaphylaxis as a result of receiving DTaP,
MMR and Prevnar vaccines on August 4, 2008. Tr. at 58. He testified that he considered this to be
a “focal” cerebral anaphylaxis based upon the localized abnormalities on the EEG that was done
the following day. Tr. at 60.
Dr. Shafrir described his differential diagnosis, saying that whenever you have “an acute
appearance of dramatic clinical symptoms after introduction of a foreign antigen, especially with
the injection of a foreign antigen, we have to assume that the patient has anaphylaxis.” Tr. at 62
(emphasis added). As agreed by Dr. Bingham, anaphylaxis is defined as “an acute allergic
phenomenon.” Tr. at 127. Dr. Bingham opined that “there are people with all kinds of allergies
where they can have a sudden, life threatening event, from an exposure to an antigen, be it dietary
or a vaccination or sometimes it is unclear what the inciting event may be.” Tr. at 127.
The term “anaphylaxis” is more formally defined in petitioner’s exhibit 40:
Anaphylaxis is a generalized, immediate IgE-mediated hypersensitivity reaction to
a foreign antigen such as a protein, a hapten, or a polysaccharide. In susceptible
persons, initial exposure to an antigen results in the formation of specific IgE
7
Petitioner submitted the textbook, LIEBERMAN AND ANDERSON, ALLERGIC DISEASES: DIAGNOSIS
AND TREATMENT (3d ed. 2007) [hereinafter “LIEBERMAN AND ANDERSON”] as exhibit 40. The
chapters reviewed from that book include: Chapter 1, “Allergic Disease,” by Akan and Lemanske;
Chapter 5, “Anaphylaxis,” by Kagy and Blaiss; and Chapter 16, “Allergic and Allergic like
Reactions to Drugs and Other Therapeutic Agents,” by Anderson.
Petitioner also submitted the textbook, CELSO PEREIRA, ALLERGIC DISEASES- HIGHLIGHTS IN THE
CLINIC, MECHANISMS AND TREATMENT (2012) as exhibit 33. The chapters reviewed from that book
include: Chapter 7, “Anaphylaxis,” by Gelnick; Chapter 19, “Specific Immunotherapy and Central
Immune System,” by Tavares and Botelho; and Chapter 25, “Derived Products of Helminths in
the Treatment of Inflammation, Allergic Reactions and Anaphylaxis,” by Araujo and Soares.
12
antibodies to that antigen. These antibodies attach to receptors on the surface of
mast cells and basophils. This leads to changes in the cell membrane with
degranulation and release of preformed chemical mediators and generation of new
potent mediators. It is these mediators that produce the clinical symptoms of
anaphylaxis.
Pet. Ex. 40 at 61.8
Dr. Shafrir testified that this case presented an anaphylactic phenomenon producing
seizures in a child who had been previously sensitized to the gelatin in the DTaP and MMR
vaccines, as well as to the pertussis antigen itself, by earlier vaccinations. Tr. at 70. He testified
that in a patient with some underlying vulnerability, the sensitization by a prior vaccination causes
the formation of IgE antibodies, which then become attached at the Fc receptor to other immune
cells known as mast cells, which are located in the brain, as well as in the skin, the lungs, and
gastrointestinal mucosa. Tr. at 70-71. When the child is exposed to the same antigen, through a
subsequent vaccination, the previously sensitized IgE cells, attached to mast cells, cross link on
the membrane and cause the mast cells to degranulate or dump their components, including
histamines, leukotrienes, serotonin and cytokines, into the surrounding tissue in the brain, which
results in a rapid anaphylactic reaction. Tr. at 70-71, 100. He supported this theory by reference to
multiple articles regarding IgE and mast cells including the Kaigy and Blaiss chapter quoted
above.9
The two-step mechanism of IgE-mediated anaphylaxis was explained in the Alan and
Lemanske chapter in petitioner’s exhibit 40. A susceptible person who has a predisposition to
develop IgE antibodies to a specific antigen is initially sensitized by exposure to that antigen. Pet.
Ex. 40 at 13.10 Then upon subsequent exposure to the same antigen, the person can rapidly
experience symptoms ranging from rhinorrhea to death. Id. The petitioner’s expert also explained
that anaphylactic reactions are often biphasic, with symptoms recurring, despite appropriate
treatment, within two to eight hours of the initial rapidly occurring event. Id. at 65.
In this case, Dr. Shafrir noted that D.P. received his fourth DTaP vaccination and that both
the DTaP and the MMR vaccines he received on August 4, 2008 contained gelatin. According to
Dr. Shafrir, both the pertussis antigen in the DTaP and the gelatin in both vaccines have been
implicated in anaphylactic reactions to vaccines. Tr. at 64. He opined that in this case, both the
antigens in the vaccine and in the gelatin could cross the blood-brain barrier attached to IgE
receptors on the mast cells in the brain, cause a cross linking of those mast cells in the brain, and
produce the rapid release of the anaphylactic agents (histamines, leukotrienes, peptides and
8
Kagy and Blaiss, Anaphylaxis 61 (2007) in LIEBERMAN AND ANDERSON.
9
See also Katherine M. Nautiyal, Mast Cells Affect Brain Physiology and Behavior 18 (Columbia
University 2011) [Pet. Ex. 39] (indicating, among other things, that a mast cell may contain up to
1000 granules which are stored and are ready for immediate release into the surrounding tissue
upon activation by the IgE ).
10
Akan and Lemanske, Allergic Disease 13 (2007) in LIEBERMAN AND ANDERSON.
13
cytokines) in the mast cells. Tr. at 100. He testified that this reaction occurs within five minutes.
Id. He further testified that D.P.’s initial seizure occurred as a result of the aforementioned
mechanism, and that the subsequent seizures, beginning a little over four hours later, are explained
by a secondary or biphasic hypersensitivity reaction that is not the immediate anaphylactic
reaction. Id. Dr. Bingham agreed that whatever caused the initial seizure in D.P. caused all the
ones that followed. Tr. at 160.
Dr. Shafrir’s explanation of the role of IgE and mast cells in anaphylaxis is consistent with
that provided by Kagy and Blaiss:
Mast cells are marrow-derived, tissue resident cells that are essential for IgE
mediated inflammatory reactions . . . . Mast cells express on their surfaces large
numbers of high affinity Fc receptors for IgE. Therefore, the surface of each mast
cell is coated with IgE molecules that have been absorbed from the circulation and
serve as receptors for specific antigens. When antigens bind to the mast cell’s
surface IgE molecules, it undergoes activation that leads to its subsequent
degranulation and release of granule contents into the surrounding tissues. The
granules contain large amounts of histamine and other inflammatory mediators.
Histamine is a major mediator of anaphylaxis.
Pet. Ex. 40 at 61.
Dr. Shafrir’s implication of the gelatin in some vaccines including the DTaP and MMR
vaccines received by D.P. on August 4, 2008 as the most likely stimulant of the anaphylactic
reaction was supported in “Allergic and Allergic-Like Reactions to Drugs and Other Therapeutic
Agents,” by John Anderson M.D. which stated:
Although infrequent, systemic allergic reactions, do occur to vaccines. Most of
these reactions are now felt to be a result of IgE antibodies directed against porcine
gelatin used as a stabilizer in these vaccines. Gelatin is found in various amounts in
measles, mumps and rubella (MMR), varicella, rabies Japanese encephalitis,
influenza and DTP vaccines.
Pet. Ex. 40 at 304.
While acknowledging Dr. Bingham’s contention that seizures are not the most common
manifestation of anaphylaxis and are in fact relatively uncommon, Dr. Shafrir provided several
articles indicating that seizures occurred between one and two percent of anaphylactic
presentations. One of such articles, from the Communicable Disease Control Immunization
Program in British Columbia, was devoted to the discussion of anaphylactic reactions to vaccines.
See generally Pet. Ex. 54.11 That article stated that seizures occur in one to two percent of
11
BC Centre for Disease Control, Communicable Disease Control Immunology Program, Section
V – Management of Anaphylaxis in a Non-Hospital Setting (April 2013) (citing The Diagnosis
and Management of Anaphylaxis: An Updated Parameter, 115 J. of Allergy and Clinical
Immunology S483-523 (2005).
14
anaphylactic events. Id. at 3. Another article in the American Family Physician discussed the
diagnostic criteria for anaphylaxis generally and stated that seizures occur in about 1.5 percent of
the presentations. See Pet. Ex. 32 at 2.12 The aforementioned Kagy and Blaiss chapter listed
neurological symptoms of anaphylaxis, including dizziness, weakness, syncope, and seizures. Pet.
Ex. 40 at 64.
In response to cross-examination as to the presence of the most common manifestations of
anaphylaxis in D.P., which respondent’s exhibit D notes are cutaneous, respiratory and
cardiovascular in nature,13 Dr. Shafrir noted that D.P. immediately turned blue, meaning he was
cyanotic, and was emergently treated with five liters of oxygen, which signals that he could have
experienced a respiratory symptom, or his symptom could have been secondary to the seizure. Tr.
at 87-88. Dr. Shafrir noted that cyanosis is a sign of hypoxemia, a symptom commonly associated
with anaphylaxis as noted in exhibit D. Tr. at 90; see Res. Ex. D at 256. He further testified that
D.P. also collapsed and was hypotonic, additional symptoms of anaphylaxis noted in exhibit D.
Tr. at 91; see Res. Ex. D at 256; see also Pet. Ex. 7 at 17 (noting D.P. was transported to hospital
because was still moaning and limp after the seizure stopped). A red macular rash on D.P.’s left
lateral lower extremity with a one centimeter blanching macule was noted when D.P. returned to
Egleston Hospital after his second seizure that day. Pet. Ex. 19 at 178. Neither expert opined on
the significance of this finding.
In response to questioning about whether the peripherally administered vaccine antigens
could cross the blood-brain barrier and enter the brain causing anaphylaxis, Dr. Shafrir supplied
literature regarding bee and wasp stings. See Pet. Exs. 34-38. The literature demonstrated that a
single sting to a person who has been sensitized by a previous sting could cause a severe and life
threatening reaction in the brain by way of an immune mechanism, without evidence of other more
common symptoms of anaphylaxis, such as urticaria or respiratory symptoms. Tr. at 130. Dr.
Shafrir contrasted this scenario with a situation where the person sustained massive stings at one
time and succumbed to the effect of the venom. Tr. at 102. In a particularly cogent study from
Hungary, in which there were forty-two victims of a bee sting, thirty had central nervous system
reactions which included convulsions. The authors stated:
The pathophysiological basis for anaphylaxis is the release of histamine, serotonin
and other pharmacologically active substances by the Hymenoptera (bee or wasp)
antigens from the mast cells and circulating basophils sensitized by IgE type
homocytotropic immunoglobulins. In spite of earlier views, mast cells are present
throughout the brain.
Pet. Ex. 38 at 3.14
12
Angela W. Tang, A Practical Guide to Anaphylaxis, American Family Physician 2 (2003).
13
See Kirk H. Waibel, Anaphylaxis, 29 Pediatrics in Review 255-56 (2008) [Res. Ex. D at 255].
14
I. Meszaros, Transient Cerebral Ischemic Attack Caused by Hymenoptera Stings: the Brain as
an Anaphylactic Shock Organ, 25 European Neurology 248-52 (1986).
15
The wasp sting analogy explaining the central nervous system reaction to an antigen to
which a person was previously sensitized was also recognized in a case report of a man found in
status epilepticus after a single wasp sting. See Pet. Ex. 34 at 1.15 There were no rash or
cardiovascular symptoms. Id. However, tryptase released from mast cells supported a diagnosis of
significant anaphylaxis. Id. By history, it was found that anaphylaxis resulted from priming three
weeks earlier. Id.
Dr. Shafrir testified that other potential explanations on the differential, beside an
anaphylactic reaction to the vaccines, would include a breath holding spell, for which there was
no evidence in this case, or causation by something the child already had, for which there was also
no evidence and would be pure chance. Tr. at 60-61; see Pet. Ex. 29 at 26 (Dr. Shafrir noting that
seizures associated with a breath holding spell or vasovagal reaction would be shorter and not
associated with more seizures subsequently). He recognized that coincidence could possibly occur,
but that the chances of that in the scenario presented here would be extremely small. Id. at 108. He
said that in a situation where an extreme reaction occurs within two minutes of an injection of a
foreign antigen that is known to cause side effects and anaphylaxis, pure chance would not be a
serious consideration. Id. He testified that there are really no other mechanisms that would cause
such a “dramatic and shocking” reaction as experienced by D.P within two minutes, other than
anaphylaxis. Tr. at 73-74. In short, he maintained that D.P’s response was dramatic and
compelling, occurring just two minutes after the vaccines were administered, and that under these
circumstances, the diagnosis is anaphylaxis until proven otherwise. Tr. at 83-85. Further, the
timing of this event can be explained by his prior sensitization from earlier DTaP vaccinations,
and by exposure to the porcine gelatin from prior vaccinations; whereby, re-exposure on the day
of the event caused a rapid IgE and mast cell response causing anaphylaxis and repeated seizures
and encephalopathy. Tr. at 69-72.
Ultimately, Dr. Shafrir testified that based primarily on the clinical picture and the EEG,
D.P. suffered a brain anaphylaxis that affected the left hemisphere more than the right. Tr. at 112-
13. This resulted in an encephalopathy and epilepsy for which he continues to be treated. Id. at 59-
60. There was no evidence of a genetic cause of his epilepsy, and the hospital looked at multiple
other causes, such as infections, through blood work, cerebral spinal fluid, and stool samples. Tr.
at 112-13. The hospital ruled them out. Id. He testified that D.P.’s mildly low glucose commonly
occurs after seizures, but is not the cause. Id. at 78-80; see Pet. Ex. 47 at 89 (noting “low glucose
may have been related [to D.P.’s seizure], but an additional seizure occurred after the glucose was
corrected,” refuting any suggestion of a causal role). Dr. Shafrir further testified that the mildly
low glucose and sodium levels, as well as ketones in the urine, were likely the result of the child
not having been fed for a number of hours by the time he was re-hospitalized and his blood was
drawn. Tr. at 80-81. He testified that young children do not have much metabolic reserve and if
they are not fed, they can readily develop a low glucose level. Id.
b. Respondent’s Expert Dr. Bingham
15
Warner, et al., MRI Brain Appearances in Anaphylaxis: Novel Observation to Differentiate from
Global Hypoxic Insult, 88 Supp. S2 Journal of Neurosurg Psychiatry A21 (December 2012).
16
The heart of the parties’ disagreement is in the understanding of symptoms attributable to
an anaphylactic reaction from an injection of a foreign antigen, such as a vaccine. Dr. Shafrir and
Dr. Bingham agreed that vaccines can trigger an anaphylactic response. Tr. at 101, 148.
Dr. Bingham agreed that the timing of the initial seizure was definitely important and
demanded a detailed accounting of the associated signs and symptoms, but he did not find the
timing as compelling as Dr. Shafrir. Tr. at 125-26. Dr. Bingham believed the most common
presentations of anaphylaxis, including cutaneous, respiratory, or cardiovascular symptoms, were
not present in this case, and he did not believe that seizures could be part of an anaphylactic
phenomenon. Id. at 127-30. He opined that there was not significant medical literature associating
vaccines with epilepsy. Id. at 120, 130-31.
Dr. Bingham discussed D.P.’s low glucose (57), diarrhea, and other signs, as evidence of
a viral gastroenteritis; but also stated that these were more proximal factors, not causal factors in
the seizures. Tr. at 122-23. In other words, Dr. Bingham believed that these symptoms were
associated with the seizures but not causative. Id. at 123. He said that it was an open question as
to how viral gastroenteritis could cause seizures, but that it is seen. Id. at 123. He did not associate
the changes in blood chemistry, including low glucose, slightly low sodium, low bicarbonate, and
high specific urine gravity, to anaphylaxis. Id. at 125-27. Dr. Bingham opined that D.P. had
idiopathic complex partial epilepsy that coincidently started on the date of vaccination and that the
first seizure was most likely precipitated by viral gastroenteritis. Id. at 120. He agreed with Dr.
Shafrir that idiopathic does not mean that there is no cause. Id. It is just that the cause is not
understood. Id.
Dr. Bingham anchored his opinion in epidemiology. Tr. at 120, 167. He agreed that there
was no doubt that vaccines can cause anaphylaxis. Tr. at 148. But, he thought the epidemiology
was lacking to show that vaccines can cause epilepsy. Id. at 120. He testified that the incidence of
the onset of epilepsy is higher in children between one and fifteen months of age relative to the
incidence in later stages of life. Id. at 121. He said that the incidence of epilepsy in this age group
is about one in a thousand, and about one third of those are idiopathic and the rest have identifiable
causes. Id.
On cross-examination, Dr. Bingham was questioned about the statistical likelihood that an
idiopathic epilepsy could occur within two minutes of a vaccination. In other words, how likely
was it that the onset of epilepsy could occur within two minutes of vaccine administration in a
child of this age group without having a causal relationship to the vaccine? Tr. at 136-40. Dr.
Bingham agreed that based upon his figures of a one in a thousand incidence of epilepsy occurring
in this age group, and one third of those being idiopathic, the overall likelihood of idiopathic
epilepsy occurring during these fifteen months of age was 0.00067 percent. Id. at 139. He agreed
that there are approximately 450 days in fifteen months, 10,800 hours, and 648,000 minutes in that
same time period. Id. at 139-40. He agreed that a child would be exposed about five times to the
first two minutes after vaccine administration in that time period. Id. at 140. Based on that, he
agreed that it was plausible that the risk of the onset of idiopathic or unexplained epilepsy occurring
within two minutes of a vaccine would be 0.0000000154321 percent, or less than a one in fifty
million chance. Id. On later questioning, Dr. Bingham said that there would be three new cases of
17
epilepsy a day, and at some point one would probably occur in a doctor’s office, but he recognized
that it would be statistically rarer the more tightly defined the time period was. Id. at 166.
Ultimately, he said he was relying on epidemiology which has not identified a signal that
would, for example, raise the relationship between a vaccine and the onset of epilepsy from 1.00
to 1.20. Tr. at 167. He agreed that epidemiology does not tend to be effective in identifying rare
events, and that most papers would say that they were not sufficiently powered to identify a rise
from something like 100 to 110 in 100,000. Id. at 167-68. He further agreed that in fact the
identification of a rare case by epidemiology would require a study powered to identify a rise from
something on the order of 100 to 100.1. Id.
Dr. Bingham thought that the spitting up incident in the car might suggest the onset of a
gastrointestinal illness, but agreed that there was no other evidence specific for a gastrointestinal
illness, and that many viral or bacterial causes for D.P.’s seizures were ruled out by testing. Tr. at
142-44. He thought D.P.’s low glucose and sodium, measured in the afternoon of August 4, 2008
at Egleston Hospital, may have suggested a gastrointestinal illness. Id. at 122-23. But, as Dr.
Shafrir explained, a child of that age who has not eaten can have low glucose and sodium. Tr. at
80-81. Neither expert appeared to attach great significance to those results. The mildly low glucose
was rapidly corrected with a bolus of dextrose and the child indeed suffered an additional seizure
after his glucose level returned to normal. See Pet. Ex. 47 at 89.
As noted in respondent’s exhibit D, an idiopathic anaphylaxis is a diagnosis of exclusion.
Res. Ex. D at 257. Dr. Bingham essentially testified that it is not uncommon to make a diagnosis
of a viral illness caused by some pathogen when one does not know which virus, and when lab
results fail to identify a particular organism. Tr. at 161. Here, he agreed that there was no evidence
of a viral encephalitis and that multiple known bacterial or viral causes were ruled out. Tr. at 142-
44, 170.
Dr. Bingham further agreed that the petitioner’s theory that D.P. may have had a pre-
disposition to a seizure disorder that was triggered by the vaccines, and that this triggering often
involves an immune-mediated event, was logical and plausible—even though he thought that, in
medicine, there is sometimes a difference between logic and experience. Tr. at 142.
c. Analysis of Althen Prong One
Petitioner’s burden under Althen’s prong one is to present by preponderant evidence a
reliable medical theory to explain how the vaccines in question could cause the illness and injury
suffered by the petitioner’s child. See Althen, 418 F.3d at 1278. Dr. Shafrir indeed presented a
reasonable and persuasive theory that D.P. suffered a severe anaphylactic reaction to the DTaP
and MMR vaccines. In particular, he proposed that the gelatin used as a stabilizer in these two
vaccines was the likely inciting antigen. He also proposed that the pertussis antigen in the DTaP
vaccine could have had the same effect in causing an anaphylactic response. The child had been
exposed to both the gelatin and the pertussis antigen in prior vaccinations, thus likely causing him
to have primed IgE antibodies attached to mast cells in the brain.
18
While seizures are an unusual manifestation of anaphylaxis, which is itself a rare reaction
to vaccines, Dr. Shafrir’s opinion that they do occur in one to two percent of anaphylactic events
was supported in the submitted literature as described above. See Tr. at 72; Pet. Ex. 54 at 3. Dr.
Shafrir also presented a logical explanation of the mechanism giving rise to the seizures
immediately after receipt of the vaccines. He explained that anaphylactic reactions in the central
nervous system are generally caused by the triggering of degranulation of mast cells that are
present in the brain. As he testified, and as was well supported in the literature, upon exposure to
a particular antigen some people develop IgE antibodies rather than the IgG or IgM when class
switching occurs. Pet. Ex. 40 at 15-17. IgE causes that person to have an allergic response to a
subsequent exposure to that same antigen. Id. at 60-61; Tr. at 70-71. The anaphylactic, or severe
allergic response, occurs when a person is re-exposed to an antigen to which he has previously
developed IgE antibodies. Id. In this case, D.P. was in all likelihood primed by prior receipt of the
DTaP vaccine and vaccines containing porcine gelatin as a stabilizer. Tr. at 64. When he received
his fourth DTaP and MMR vaccine containing gelatin on August 4, 2008, his system had been
primed by the prior vaccinations. See Pet. Ex. 7 at 20; Tr. at 70.
Mast cells are present in numerous parts of the body including the brain. Tr. at 70-71; Pet.
Ex. 39. Their surfaces are heavily populated with Fc receptors for IgE. Tr. at 70. When a child has
been primed by prior exposure to an antigen and developed IgE antibodies to that antigen, the
surface of his mast cells are coated with the IgE antibodies to that same antigen. Id. at 70-71. When
he is re-exposed, as in this case, by a subsequent vaccination of the same type or containing the
same stabilizer, the mast cells are triggered by the IgE antibodies to respond very rapidly to the
new exposure to the antigen. Id. When triggered, the mast cells degranulate or dump hundreds of
inflammatory molecules including histamines, leukotrienes, cytokines, tryptase and others into the
surrounding tissue. Tr. at 100. Dr. Shafrir explained that D.P.’s rapid central nervous system
response was caused by the degranulation of the brain resident mast cells into the surrounding
brain tissue causing seizures. He supported this explanation by analogy to literature regarding
central nervous system anaphylactic response to wasp and bee stings. He explained, as did the
literature he provided, that a single bee or wasp sting on the periphery can cause a central nervous
system anaphylaxis when the stung person was previously stung by a bee or wasp. Tr. at 65-67.
The prior sting generated the IgE response and primed the mast cells to respond in rapid fashion
at the time of a subsequent sting. The submitted literature described victims in status epilepticus
and those that went into coma and died as a result of a single bee sting that occurred subsequent to
an earlier priming sting. Id.; see Pet. Ex. 34 at 1; Pet. Ex. 37 at 1-2. This was distinguished from
the situation where a person is stung simultaneously by many bees or wasps and succumbs to the
venom from the stings. Tr. at 102-03.
ii. Althen Prong Two – Logical Sequence of Cause and Effect
Proof of Althen prong two requires a logical explanation as to how the vaccine did cause
the injury in the petitioner. “A logical sequence of cause and effect’ means what it sounds like—
the claimant’s theory of cause and effect must be logical.” Capizzano, 440 F.3d at 1326. The proof
need not rise to the level of scientific certainty but rather to the Vaccine Act’s preponderance
standard under the system created by Congress, in which close calls regarding causation are
resolved in favor of injured claimants.’” Andreu, 569 F.3d at 1378. A treating physician may rely
on the close temporal proximity between a vaccine and an injury in concluding that there is a
19
logical sequence of cause and effect between the vaccine and the injury. Capizzano, 440 F. 3d at
1326. “Requiring epidemiologic studies . . . or general acceptance in the scientific or medical
communities . . . impermissibly raises a claimant’s burden under the Vaccine Act and hinders the
system created by Congress . . . .” Id. at 1325-26.
Differential diagnosis is a well-accepted medical methodology for determining diagnoses
and causation. It has been accepted by multiple courts under a Daubert analysis. The Third Circuit
addressed the reliability of differential diagnosis as a method for assessing causation. The court
held:
We have recognized that differential diagnosis is a technique that involves
assessing causation with respect to a particular individual, In Re Paoli R.R. Yard
PCB Litigation, 35 F.3d 717, 758 (3d Cir. 1994). Differential diagnosis is defined
for physicians as “the determination of which of two or more diseases with similar
symptoms is the one from which the patient is suffering, by a systematic
comparison and contrasting of the clinical findings.” Stedman’s Medical Dictionary
428 (25th ed. 1990). The elements of a differential diagnosis may consist of the
performance of physical examinations, the taking of medical histories, and the
review of clinical tests, including laboratory tests. A doctor does not have to employ
all of these techniques in order for the doctor’s diagnosis to be reliable. See Paoli,
35 F.3d at 759. A differential diagnosis may be reliable with less than all the types
of information set out above. See id. Indeed as we held in Paoli to the extent that
the district court concluded otherwise [i.e. that a differential diagnosis made on less
than all types of information cannot be reliable] we hold that it abused its discretion
. . . . As noted by this court in Paoli, evaluation of the patient’s medical records is
a reliable method of concluding that a patient is ill even in the absence of a physical
exam.
Kannankeril v. Terminix, 128 F.3d 802, 807-08 (3d Cir. 1997); see also Hocraffer v. Sec’y of HHS,
63 Fed. Cl. 765, 777 n. 15 (2005) (Judge Firestone noting that “[d]ifferential diagnosis or
differential etiology has been accepted as reliable under the standards set forth in Daubert [and]
by virtually every United States Court of Appeals to consider the issue” (internal citations
removed)).
Dr. Shafrir’s differential diagnosis of an anaphylactic reaction to the vaccinations was both
reasonable and persuasive. He provided a logical cause and effect explanation of the mast cell
mechanism that likely resulted in a central nervous system anaphylaxis in a child who received
vaccine antigens to which he had previously been exposed from prior vaccinations of the same
type. D.P. was tested for most, if not all, of the likely pathogenic organisms that could conceivably
give rise to seizures, and all were negative. While it is true that an unknown pathogen could give
rise to seizures, it seems highly unlikely that a completely unrelated organism would suddenly
become active within two minutes of a vaccine. In any event, the respondent’s burden to show
alternative cause cannot be met by suggesting an idiopathic or unknown cause. Knudsen, 35 F.3d
at 547-48 (quoting 42 U.S.C. ' 300aa-13(a)(2)).
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Dr. Shafrir utilized the process of differential diagnosis in reaching his opinion. He stated
that when a patient has a severe reaction like what D.P. experienced, within minutes of being
injected with an antigen known to cause anaphylaxis, the diagnosis is anaphylactic shock until
proven otherwise. He listed breath holding, an underlying condition, and pure chance as other
possibilities. As he stated, there was no evidence for breath holding, and while Dr. Bingham
suggested that the spitting up of the hash brown in the car on the way to the pediatrician’s office
may have been the onset of a gastrointestinal illness, the evidence shows that D.P.’s spit up was
not due to a gastrointestinal illness, but rather by choking or some similar mechanism. There was
no evidence of vomiting gastrointestinal contents. Dr. Patonay, the pediatrician who examined the
child before his vaccinations and treated him as he was seizing, noted that the child had no illness
at the time of the vaccinations. Pet. Ex. 7 at 21.
While Dr. Bingham testified that, based on his experience, he thought that D.P. suffered an
idiopathic seizure, or one without a known cause, he did acknowledge on cross-examination that
it was plausible to say that the chances of the child suffering an idiopathic event within two minutes
of receipt of a vaccine would be on the order of one in fifty million. Tr. at 140. As demonstrated
by Dr. Shafrir’s testimony and supporting literature, the likelihood of a biphasic anaphylactic
reaction to the vaccines is greater than one in fifty million, and in fact, is more likely than not. Tr.
at 137-38; see Pet. Ex. 40 at 64-65.
Although the presentation of seizures without respiratory or cutaneous symptoms is an
unusual manifestation of anaphylaxis, it was reasonably demonstrated that such response can and
likely did occur in this case. Notably, the child turned blue and was treated with five liters of
oxygen, which suggests a possible respiratory problem. Additionally, a physician noted a red rash
around the area of the vaccination itself. Pet. Ex. 19 at 178. These findings do suggest a respiratory
impairment and hint at a cutaneous symptom. I conclude that petitioner has met her burden under
prong two, as Dr. Shafrir presented and applied a reliable methodology in making his differential
diagnosis, which is supported by multiple references to the medical literature as cited above.
Additionally, the petitioner has presented adequate evidence that, as Dr. Bingham agreed,
what caused the first seizures likely caused the rest. I have concluded that D.P. has suffered from
ongoing seizures and cognitive impairments secondary to the brain injury that he suffered during
the initial anaphylactic seizure.
iii. Althen Prong Three – Temporal Relationship
Prong three of Althen requires a showing that the timing of the onset of the anaphylactic
response was reasonable. Indeed, Dr. Shafrir found that the timing was not only reasonable but
compelling, and that it was helpful in meeting the burden under prong one and two as well. I agree.
Anaphylactic reactions generally occur quite rapidly—in minutes to hours from the inciting event.
An antigen that is injected is considered to have greater anaphylactic potential than one that
otherwise comes in contact with the body. Pet. Ex. 40 at 65. In this case, the child turned blue,
went into tonic clonic seizures, and became limp or hypotonic within two minutes of receipt of the
vaccines. Pet. Ex. 7 at 17. He was treated with five liters of oxygen which returned him to a baseline
pink color, but he remained limp and moaning. Id. at 20. He was sent to the hospital where he
appeared fine, but on the way home from the hospital, he had a second seizure about four hours
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after the first. Pet. Ex. 18 at 210. This is most consistent with a biphasic anaphylactic reaction as
described in the literature. Pet. Ex. 40 at 65. Both experts agreed that vaccines can cause
anaphylactic reactions. Tr. at 148.
The timing of the onset of seizures was not only appropriate, but indeed seems compelling
in light of the IgE/mast cell mechanism, the absences of alternative reasonable causes, and the
rapid onset itself.
E. Alternative Cause
The Vaccine Act permits the respondent to present evidence of an alternative, unrelated
cause once the petitioner has made a prima facie case sufficient to satisfy the Althen prongs. Once
petitioner establishes each of the Althen factors by preponderant evidence, the burden of
persuasion shifts to respondent, who must show that the alleged injury was caused by a factor
unrelated to the vaccination. § 13(a)(1)(B); Knudsen, 35 F.3d at 548. Respondent must demonstrate
that “the factor unrelated to the vaccination is the more likely or principal cause of the injury
alleged. Such a showing establishes that the factor unrelated, not the vaccination, was ‘principally
responsible’ for the injury.” Deribeaux, 717 F.3d at 1369. Section 13(a)(2) specifies that factors
unrelated do “not include any idiopathic, unexplained, unknown, hypothetical, or undocumented
causal factor, injury, illness, or condition.”
The Federal Circuit held that “[s]ection 300aa-13(a)(2)(A) defines unrelated factors as not
including ‘any idiopathic, unexplained, unknown, hypothetical, or undocumentable cause, factor,
injury, illness, or condition.’ Since the word ‘or’ is used with both the adjectives (idiopathic,
unexplained, unknown, or hypothetical) and the nouns (cause, factor, injury, illness, or condition),
it is apparent that an unrelated factor is not an idiopathic illness, an unexplained illness, or an
unknown cause.” Koston v. Sec’y of HHS, 974 F.2d 157, 160 (Fed. Cir. 1992).
Dr. Bingham proposed that a gastroenteritis, for which he acknowledged there was no
direct evidence in this case, was a possible explanation that he favored over an anaphylactic
response to the vaccine. Tr. at 122-24. He said that it is common to diagnose a viral illness even
though lab reports do not identify a specific organism. Tr. at 161. I find that there was no evidence
of a gastrointestinal illness at the time of D.P.’s vaccinations. The post-vaccine vomiting and
diarrhea can be explained by the anaphylaxis, as noted in the literature. Kagy and Blaiss state, “the
GI tract is also regularly involved (in anaphylaxis). Diarrhea, abdominal cramps, nausea and
emesis developed in 25-30% of the patients.” Pet. Ex. 40 at 64-65.
In this case, the evidence shows that an anaphylactic reaction to the vaccines administered
on August 4, 2008 is much more likely to explain the reaction and seizures D.P. experienced, rather
than pure chance or an unknown gastrointestinal illness. The mechanism of anaphylaxis was
cogently defined by the testimony and the literature, and the timing was particularly appropriate.
The petitioner’s expert, Dr. Shafrir, noted in his expert report that an anaphylactic reaction
occurring within four hours of a DTaP or MMR vaccine is a Table injury. He went on to
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demonstrate a cause-in-fact injury because the QAI illustration of anaphylaxis did not include the
term seizure, but more generally described the most common manifestations of anaphylaxis,
including severe respiratory and cutaneous symptoms at times leading to death. In reviewing this
aid to interpretation of anaphylaxis, I conclude that the definition provided is illustrative of the
condition but not restrictive, as is for example, the definition of a table encephalopathy. The
respondent contended that the child did not suffer an anaphylaxis, but for the reasons stated above,
I have concluded that Dr. Shafrir has presented persuasive evidence that he did. Accordingly, I
find that the petitioner has presented persuasive evidence of a Table anaphylaxis together with
sequelae lasting more than six months resulting from the injury caused by the initial anaphylactic
event. As the petitioner, in responding to the respondent’s contention that the child did not
experience an anaphylactic reaction, has presented extensive and persuasive evidence, I find that
he has also proved both Table injury Anaphylaxis and a cause-in-fact injury, and is entitled to
compensation on either basis.
IV. CONCLUSION
I find that petitioner has presented a persuasive medical theory and a logical explanation
of cause and effect in this case, consistent with the theory of causation. The timing of the event
was certainly appropriate.
As the Vaccine Injury Table lists anaphylaxis within four hours of the DTaP and MMR
vaccinations, and I have concluded that D.P. suffered an anaphylactic reaction two minutes after
the vaccines were administered, and that that injury gave rise to ongoing seizures and cognitive
delay lasting more than six months, I find that the petitioner has proved his case both as a Table
injury and as an off-Table injury by a preponderance of the evidence. I therefore conclude that
petitioner presented sufficient evidence to establish causation in this Program and D.P. is entitled
to compensation.
A separate damages order will issue.
IT IS SO ORDERED.
s/ Thomas L. Gowen
Thomas L. Gowen
Special Master
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