# Pusateri v. Secretary of Health and Human Services

> United States Court of Federal Claims · October 21, 2024

URL: https://www.frixlaw.com/law-library/cases/10733947

## Case

- **Court:** United States Court of Federal Claims
- **Decided:** October 21, 2024
- **Precedential status:** Unpublished
- **Opinion:** Opinion
- **Judges:** Thomas L. Gowen
- **Cited by:** 0 later opinions in the Frix Law Library

## Citator (automated)

- No negative treatment found by the automated citator. That is not the same as a confirmation that the case is good law; read the citing cases.
- Full citator and citing cases: https://www.frixlaw.com/law-library/cases/10733947

## Opinion text

In the United States Court of Federal Claims
OFFICE OF SPECIAL MASTERS
Filed: September 23, 2024

*********************
VICTORIA PUSATERI, *
*
Petitioner, * No. 16-467
*
v. * Special Master Gowen
*
SECRETARY OF HEALTH *
AND HUMAN SERVICES, *
*
Respondent. *
*********************
Scott W. Rooney, Nemes, Rooney P.C., Farmington Hills, MI, for petitioner.
Catherine E. Stolar, U.S. Dept. of Justice, Washington, D.C., for respondent.

DECISION1

On April 13, 2016, Victoria Pusateri (“petitioner”) filed a petition for compensation
under the National Vaccine Injury Compensation Program.2 Petition (ECF No. 1). Petitioner
alleges that the human papillomavirus (“HPV”) vaccine administered on February 18 and April
22, 2013 significantly aggravated her immunodeficiency disorder, inflammatory bowel
condition, esophagitis, bronchitis, and alopecia areata. Petition (“Pet.”) at 2-5. Based on a full
review of the evidence including medical records and expert reports, I find that petitioner has not
established by preponderant evidence that the HPV vaccine caused or significantly aggravated
any of her conditions and the petition must be DISMISSED.

1
Pursuant to the E-Government Act of 2002, see 44 U.S.C. § 3501 note (2012), because this opinion contains a
reasoned explanation for the action in this case, I am required to post it on the website of the United States Court of
Federal Claims. The court’s website is at http://www.uscfc.uscourts.gov/aggregator/sources/7. This means the
opinion will be available to anyone with access to the Internet. Before the opinion is posted on the court’s
website, each party has 14 days to file a motion requesting redaction “of any information furnished by that party:
(1) that is a trade secret or commercial or financial in substance and is privileged or confidential; or (2) that
includes medical files or similar files, the disclosure of which would constitute a clearly unwarranted invasion of
privacy.” Vaccine Rule 18(b). “An objecting party must provide the court with a proposed redacted version of the
decision.” Id. If neither party files a motion for redaction within 14 days, the opinion will be posted on the
court’s website without any changes. Id.
2
The National Vaccine Injury Compensation Program is set forth in Part 2 of the National Childhood Vaccine
Injury Act of 1986, Pub. L. No. 99-660, 100 Stat. 3755, codified as amended, 42 U.S.C. §§ 300aa-10 to 34
(2012) (hereinafter “Vaccine Act” or “the Act”). Hereinafter, individual section references will be to 42 U.S.C. §
300aa of the Act.
I. Procedural History

Petitioner filed a petition for compensation on April 13, 2016 and her petition was
accompanied by medical records. See Pet. Exhibits (“Exs.”) 1-10, 12. On December 14, 2017,
petitioner filed expert reports from John Santoro, D.O..3, a gastroenterologist, to support her
claim that the HPV vaccines caused petitioner to have ulcerative colitis and Marc David
Glashofer, M.D, M.S.4, to support her claim that petitioner’s alopecia was caused by the HPV
vaccines. Pet. Exs. 14, 15 (ECF Nos. 57, 59).

Respondent filed the Rule 4(c) report, recommending against compensation, arguing that
“the alleged development of petitioner’s symptoms is outside the accepted timeframe to
demonstrate vaccine causation or significant aggravation,” and that petitioner’s diagnosis of
Common Variable Immune Deficiency (“CVID”) and antibiotic use provide alternative causes
for petitioner’s symptoms. Respondent (“Resp.”) Report (“Rept.”) at 6-7 (ECF No. 64).
Respondent also filed an expert report from Randy Longman, M.D.5, a gastroenterologist, who
opined that petitioner’s underlying immune deficiency and repeated exposure to antibiotics
caused the exacerbation of her colitis. Resp. Ex. A at 5 (ECF No. 63).

3
Dr. John J. Santoro was a gastroenterologist in practice with Atlantic Gastroenterology. Pet. Ex. 14. He
unfortunately passed away during the course of this litigation. Dr. Santoro served as the Medical Director of Clinical
Research at Atlantic Gastroenterology Associates and was Director of the Hepatitis Treatment Center at the same
group. Id. After completing undergraduate at LaSalle College, he attended Philadelphia College of Osteopathic
Medicine and graduated in 1978. Pet. Ex. 14A at 2. Dr. Santoro completed a residency at the University of
Medicine and Dentistry at John F. Kennedy Memorial Hospital in 1981. Id. Dr. Santoro became a Fellow of
Gastroenterology at University of Medicine and Dentistry with the NJ School of Osteopathic Medicine and with the
Kennedy Memorial Hospitals. Id. at 3. He was board certified in Internal Medicine and Gastroenterology. Id. Dr.
Santoro was licensed to practice medicine in New Jersey and Pennsylvania. Id. As of the filing of his CV, Dr.
Santoro was a Clinical Associate Professor of Medicine at Rowan University of Osteopathic Medicine. Id. at 4.
Additionally, Dr. Santoro has authored or co-authored numerous medical articles on issues that affect the
gastrointestinal tract. Id. Dr. Santoro has provided his opinion in other vaccine cases, where he has been accepted
as an expert in gastroenterology. See e.g. B.E. v. Sec’y of Health & Human Servs., No. 15-1458V, 2019 WL
1560371 (Fed. Cl. Spec. Mstr. Feb. 26, 2019). Accordingly, for the purposes of this case, Dr. Santoro is accepted as
an expert in gastroenterology for this matter.
4
Dr. Marc D. Glashofer is a dermatologist in practice with The Dermatology Group in West Orange, New Jersey.
Pet. Ex. 15A. He attended the University of Maryland for his undergraduate degree and attended the George
Washington University School of Medicine and Health Services in Washington, D.C. Id. Dr. Glashofer completed
his residency in dermatology at Tulane University School of Medicine in New Orleans, Louisiana. Dr. Glashofer is
board certified in dermatology. He serves as a peer reviewer for the Journal of Dermatologic Treatment and Journal
of Drugs and Dermatology and is on the Clinical Research Advisory Council for the National Alopecia Areata
Foundation. Id. at 3. It does not appear that Dr. Glashofer has appeared as an expert in the Vaccine Program before,
however, he is a practicing dermatologist with expertise in the field. Accordingly, Dr. Glashofer is accepted as an
expert in dermatology in this matter.
5
Dr. Randy Longman is an assistant professor of gastroenterology and hepatology at at the Jill Robrts IBD Center at
Weill Cornell Medical Center in New York. Resp. Ex. B. He received his undergraduate degree from Yale
University and then received his medical degree from Cornell Medical College and his Ph.D. in immunology from
the Rockefeller University. Id. He received his medical degree in 2007 and did his post-doctoral training in
Gastroenterology at Columbia Presbyterian Medical Center. Id. Dr. Longman completed a gastroenterology
fellowship in 2013. He is licensed to practice medicine in the state of New York. He has authored or co-authored
numerous medical articles in the field of gastroenterology. Id. at 3-5. He is well qualified to provide an expert
opinion on gastroenterology and immunology.

2
The undersigned held a Rule 5 Status Conference on April 25, 2018, when I observed
that petitioner had a pre-existing history of alopecia, but that it was possible that the ulcerative
colitis may have been caused by an immune reaction to the HPV vaccine. Rule 5 Order at 1-2. I
also observed that petitioner had a treating physician from the Children’s Hospital of Michigan,
indicate that it was a possibility that petitioner had CVID, but thought that petitioner’s
hypogammaglobulinemia would be reversed once her colitis was under control. Id. at 2; see also
Pet. Ex. 2 at 67.

After both parties filed supplemental expert reports from the gastroenterologists and
petitioner filed updated medical records, I held another Rule 5 status conference. See Resp. Ex.
G; Pet. Ex. 20. I noted that petitioner’s diagnosis appeared to be somewhat less clear, especially
as her immune deficiency continued, even after her colitis had resolved. Furthermore, I again
noted that some of petitioner’s medical records suggest that her alopecia, urticaria, warts, and
recurrent sinusitis appeared prior to the vaccinations. Rule 5 Order (ECF No. 94). I posed a
series of questions to petitioner’s experts in the Order.

Petitioner continued to supplement the record with updated medical records, which
included diagnoses from treating physicians. See Pet. Ex. 25. I held another status conference on
January 22, 2020, when I reviewed these records with the parties and observed that petitioner’s
diagnoses included CVID, alopecia areata, inflammatory bowel disease, and others. Scheduling
Order (ECF No. 108). Furthermore, petitioner was also diagnosed with “possible WHIM
syndrome,”6 and chronic urticaria and angioedema. Id. at 2; see also Pet. Ex. 26 at 2099. During
the status conference, petitioner’s counsel stated that petitioner was “narrowing” her claim,
focusing on a significant aggravation of alopecia. Scheduling Order at 2. I indicated that it
would take an additional expert report to “consider how the HPV vaccine stimulated (or
significantly aggravated) an autoimmune condition like alopecia if it is clear that petitioner did
not mount any immune response to the vaccine, as observed by Dr. Savasan. Id. I indicated that
the explanations offered by her previous expert, Drs. Santoro and Glashofer, were not supported
by the medical records, as petitioner continued to suffer from common variable immune
deficiency after her colitis resolved and her alopecia began prior to vaccination. Id.

Petitioner filed a supplemental expert report from Alan F. Cutler, M.D., another
gastroenterologist. Pet. Ex. 28 (ECF No. 119). Dr. Cutler indicated that he disagreed that
petitioner’s CVID was caused by intestinal inflammation, but that petitioner developed
gastroparesis because of the HPV vaccine. Id. at 1-2. I held another status conference with the
parties on July 27, 2021, when I recounted petitioner’s extensive medical history and indicated
that Dr. Cutler’s newest opinion that petitioner developed gastroparesis because of the HPV
vaccine had significant problems. I noted there was no evidence that petitioner had gastroparesis
and by this time petitioner’s diarrhea had resolved and her immunoglobulins remained
essentially undetectable. While both Drs. Santoro and Cutler focused on Dr. Marks’ early

6
WHIM syndrome is a congenital immune deficiency with characteristics clinical features that include Warts,
Hypogammaglobulinemia, recurrent bacterial Infections, and Myelokathexis (apoptosis of mature myeloid cells in
the marrow). Kawai, T. and Malech, H., WHIM Syndrome: Congenital Immune Deficiency Disease, 16(1) Curr.
Opin. Hematol. 20-26 (2009), doi: https://doi.org/10.1097%2FMOH.0b013e32831ac557.

3
hypothesis that the immune deficiency was caused by her diarrhea, Dr. Marks had appropriately
revised her opinion to diagnose agamaglobulanemia not caused by diarrhea.

I recommended that petitioner voluntarily dismiss her petition, however, if petitioner
intended to proceed on this matter, I set a deadline for respondent to file a motion to dismiss.
Scheduling Order (ECF No. 123).

Petitioner decided to continue to proceed with her claim. In the interim, petitioner’s
attorney filed a third motion for interim attorneys’ fees and costs. See Pet. Mot. for Interim
Attorneys’ Fees and Costs (ECF No. 126). I held another status conference in this matter, when I
indicated that “the path to demonstrating entitlement by preponderant evidence seems extremely
unlikely in this matter,” and the medical records demonstrated that petitioner had no response to
the HPV vaccine, or any other vaccines she had received. Id. at 2. Accordingly, I requested that
petitioner file a voluntary dismissal decision, but that if she continues to proceed, respondent will
file a motion for a ruling on the record.

On March 30, 2022, respondent filed a motion for a ruling on the record, requesting that
this petition be dismissed. Resp. Motion (“Mot.”) (ECF No. 139). Petitioner filed a response to
respondent’s motion on August 15, 2022. Pet. Response to Mot. (ECF No. 142). On October 6,
2022, respondent filed a reply to petitioner’s response. Resp. Reply (ECF No. 144).

This matter is now ripe for adjudication.

II. Evidence Submitted

a. Petitioner’s Medical History

i. Medical History Prior to Administration of HPV Vaccine on
February 18, 2013

Petitioner was born on October 10, 1997, at 36 weeks of gestation and weighed 5 pounds
six ounces. Pet. Ex. 2 at 120. She received her regular vaccines, including varicella, hepatitis B,
MMR, TDaP and influenza. Id. at 117. In April 2003, petitioner was admitted to the Children’s
Hospital of Michigan for vomiting and abdominal pain, which was suspicious for a right adrenal
mass. Id. at 121. During her hospitalization, she was noted to have episodic hypertension. Id.
Petitioner had a follow-up appointment with Dr. Neena Gupta on June 2, 2003, after the
hospitalization, at which she noted that petitioner had an esophagogastroduodenoscopy that
showed “mild esophagitis.” Id. It was thought that petitioner’s intermittent blood pressure
elevation was due to anxiety, and it was recommended that she have periodic blood pressure
monitoring. Id. at 122. At a follow-up appointment on July 14, 2003, petitioner’s mother
indicated that petitioner had been taken off of Zantac, and that petitioner’s abdominal pain,
nausea, vomiting, and heartburn subsided. Id. at 119. It was recommended that petitioner can go
back on Zantac if her symptoms flare up again and she can come back to the gastroenterology
clinic as needed. Id.

4
Petitioner had a well visit on October 28, 2004. Pet. Ex. 2 at 118. The note from this
appointment indicates that she had no speech problem and was doing well in general. Id. On
November 5, 2004, petitioner had a consultation with Dr. Robert Rhee for a “bump in the corner
of her left eye.” Id. Petitioner had 20/20 vision in both eyes, but she had a fluid-filled cyst in the
corner of her left eye. Id. Dr. Rhee recommended petitioner to Dr. Christine Nelson at the
University of Michigan, an oculoplastic surgeon for evaluation and treatment. Id. Later the
same month, petitioner had a consultation at the Eye Plastic Orbital and Facial Cosmetic Surgery
Clinic at the Kellogg Eye Center. Id. at 112. Petitioner was diagnosed with a “probable cystic
lesion of the left medial rectus area,” and it was recommended that it be removed and biopsied.
Id. On August 9, 2005, petitioner had the cyst removed from her left eye. Id. at 106.

On August 26, 2009, at age 12, petitioner was admitted to the University of Michigan
Hospital for a three-day history of frequent vomiting and diffuse, crampy, constant abdominal
pain. Pet. Ex. 2 at 95. Prior to admission, petitioner had acute onset of nausea, vomiting and
abdominal pain after camping out during a birthday party, where another child also had nausea
and vomiting. Id. Petitioner was given Visteril, which sedated her, but she continued to vomit
afterwards. The vomiting continued for three days, but only slightly less frequently. Id.
Petitioner had elevated blood pressure and generalized lymphadenopathy. Id. at 97. It was
suspected that her abdominal pain was likely due to gastroenteritis, but considered a “slightly
unusual presentation.” Id. A pelvic ultrasound showed intra-abdominal lymphadenopathy. Id.
Petitioner was discharged three days later, with diagnoses that included, “gastroenteritis,
intermittent hypertension and generalized lymphadenopathy.” Id. at 94.

On January 10, 2011, petitioner had an appointment with her pediatrician for a fever and
swollen neck. Pet. Ex. 9 at 1. Petitioner reported that her jaw hurt, and her head was congested
for a week. Id. She was diagnosed with sinusitis and given a prescription for antibiotics. Id.
Four months later, on April 12, 2011, petitioner was taken back to her primary care for “hives on
and off for one week that were on her arms, legs, and torso.” Id. She was diagnosed with
recurrent urticaria and given a course of prednisone and a prescription for Atarax, an
antihistamine. Id. Approximately two weeks later, on April 25, 2011, petitioner returned to her
primary care provider for the continued rash all over her body. Id. Petitioner was directed to
take Allegra, although her rash was not getting better. Id. The note from this appointment
indicates that her rash was going on for 3-4 weeks with “no known trigger,” and that she did not
have exposure to a cat, dog, or have hay fever. Id. Petitioner’s doctor stated that she should
begin prednisone and take Zyrtec and follow-up in 10-16 days. Id.

Petitioner returned on May 11, 2011 for the follow-up for her hives, which had gone
away and then came back. Pet. Ex. 9 at 2. Petitioner reported that she stayed with her father
who has a dog and her hives returned. Id. Petitioner was also not taking Zyrtec. She was
referred to the allergy clinic at Children’s Hospital.

On June 28, 2011, petitioner had an appointment with Dr. Sahar Faghih at the allergy and
immunology clinic at Children’s Hospital of Michigan. Pet. Ex. 2 at 87. This appointment notes
that petitioner was seen previously on May 31, 2011 for “a complaint of chronic urticaria and
sinusitis.” Id. The record indicates that she completed a course of Augmentin which alleviated
her nasal congestion and pressure, but the Zyrtec did not “significantly improve the occurrence

5
of her hives,” and that she gets them intermittently. Id. Petitioner reported that her hives began
while staying with her father who has two dogs. Id. She was diagnosed with chronic urticaria
and possible dust mite sensitivity. Id. Dr. Faghih’s plan was to do a skin test at the next
appointment. Id. However, no further records from Dr. Faghih or the Allergy and Immunology
Clinic from this time period were filed.

On October 14, 2011, petitioner received a flu shot. Pet. Ex. 9 at 3. She presented for a
sick visit on December 31, 2011 for coughing and green mucus that was present for one week
prior to the appointment. Id. She was diagnosed with sinusitis and given a prescription for
Augmentin and to use a nebulizer at home. Id. at 4.

There are limited medical records between 2011 and November 2012, when there is
another appointment with her primary care provider, when she reported that her right eye hurt
and she noticed that some of her eye lashes were falling out. Pet. Ex. 9 at 5. Petitioner’s mother
expressed some concern about a thyroid issue. Id. Petitioner was given eye drops. She
presented again on January 9, 2013, complaining that her right ear was red and painful, and she
was coughing constantly. Id. at 5. Petitioner was diagnosed with sinusitis and prescribed a
course of antibiotics. Id. She was told to follow-up in 10-14 days. Id. On January 30, 2013,
petitioner again reported coughing and congestion. Id. The nebulizer did not work and she
finished the amoxicillin. Id. Petitioner was diagnosed with acute bronchitis and rhinitis and
given another prescription for amoxicillin. Id. Petitioner returned on February 18, 2013, again
with coughing and congestion, this time her voice was hoarse, and her neck felt swollen. Id. At
this appointment, petitioner wanted to get the HPV vaccine and the vaccine was administered.
She was also diagnosed with bronchitis. Id.

ii. Interim Medical History Between February 18, 2013 and second HPV
Vaccine Administered on April 22, 2013

The next medial appointment in the medical records occurred on April 16, 2013, with Dr.
Steven Grekin, a dermatologist. At this appointment, petitioner had a plantar wart on her right
foot between the 1st and 2nd toes. Pet. Ex. 4 at 6. Importantly, this was a follow-up appointment
which suggests that petitioner had prior appointments with him, however, records from those
appointments were not filed.

Petitioner had an appointment on April 20, 2013 for a runny nose, coughing and green
discharge for five days. Pet. Ex. 2 at 3. Additionally, petitioner’s hives had returned on her arms
and legs. Id. Petitioner was diagnosed with urticaria and acute bronchitis and rhinitis. Id. She
was given a course of prednisone and Azithromycin. Id. Petitioner returned for her second HPV
vaccine on April 22, 2013. Id.

iii. Petitioner’s Medical History After April 22, 2013 to Present

Seven days after her second HPV vaccination, on April 29, 2013, petitioner returned to
her primary care physician for a follow-up of her sinus infection. Pet. Ex. 2 at 3. Petitioner had
finished her antibiotic course; however, her hives were now all over her body. Id. Petitioner
indicated that the hives were coming and going. Id. Petitioner also reported that the cough and

6
congestion was a little better while on the antibiotics, but they came back. Id. Claritin and
Zyrtec were not helpful in controlling the hives either. Id. She was prescribed a fourteen-day
course of Augmentin, another antibiotic. Id.

Petitioner returned to her pediatrician on May 1, 2013 for a follow-up and she indicated
that her hives were improving on the prednisone. Pet. Ex. 2 at 4. Her physician wrote that she
was “unable to determine cause of hives since she had been having recurring hives prior to
getting both antibiotics.” Id. at 4.

On June 12, 2013, petitioner had an appointment with her primary care physician for
coughing, hives (for three months), eye lashes and eyebrows falling out for two months, and
diarrhea for one week. Pet. Ex. 2 at 4. It was noted that petitioner had recurrent hives and that
she had an allergy evaluation, and the cause of the hives was undetermined. Id. Petitioner was
referred to an allergist for another evaluation and diagnosed with recurrent urticaria. Id. Two
weeks later, petitioner reported that she was still having diarrhea twice a day, her left ear was
plugged and she still had hives. Id.

On June 28, 2013, petitioner had a follow-up appointment with her dermatologist for the
plantar warts. Pet. Ex. 4 at 5. There was a note indicating that petitioner had concerns about her
eyelashes and eyebrows falling out for three months. Id. Petitioner also reported that she had
diarrhea for three weeks and a history of ulcerative colitis. Petitioner was diagnosed with
urticaria and alopecia eyebrow. Id.

Petitioner had a consultation at the Gastroenterology, Hepatology, and Nutrition Clinic at
Children’s Hospital of Michigan on July 10, 2013. Pet. Ex. 12A at 22. Petitioner reported that
she was having diarrhea for four weeks, up to six times a day, but decreased. Id. Petitioner also
reported abdominal pain, but the pain resolves once she has a bowel movement. Id. As part of
her medical history, it was noted that petitioner had chronic urticaria and she had been
hospitalized for vomiting when she was five. Id. The plan was for comprehensive blood work
and an upper endoscopy and colonoscopy. Id. at 24. The blood work revealed that petitioner
had extremely low levels of IgA and IgE. Id. at 32.

On July 15, 2013, petitioner had an appointment with Dr. James Fordyce. Pet. Ex. 2 at
73. The reasons for the visit were “chronic urticaria, rhinitis, ear-infection, and diarrhea.” Id.
She was diagnosed with idiopathic urticaria and chronic ear infections, along with chronic
rhinitis. Id. at 75. She was going to have her IgG, IgA, IgM, and IgE tested. Id. Regarding her
diarrhea, Dr. Fordyce considered an inflammatory process, such as Crohn’s disease or functional
bowel issues. Id. Petitioner’s blood work showed that she had nearly no IgE, IgA, IgG or IgM.
Id. at 71.

Petitioner had an endoscopy and colonoscopy on July 18, 2013. Pet. Ex. 2 at 69; Pet. Ex.
12A at 135. The endoscopy revealed a fungal infection in her esophagus, and she was given a
prescription for Diflucan. Id. The colonoscopy revealed diffuse active chronic colitis. Id. at
141. Petitioner had an appointment with gastroenterologist, Dr. Macha on July 24, 2013, to
follow-up from the colonoscopy and endoscopy. Pet. Ex. 12A at 145. Dr. Macha explained that
petitioner had Candidal esophagitis and inflammatory bowel disease, more likely Crohn’s than

7
ulcerative colitis. Id. At a follow-up with Dr. Macha on August 7, 2013, petitioner reported that
her diarrhea was improving, and her abdominal pain and nausea had resolved. Pet. Ex. 12A at
190. Dr. Macha ordered repeat blood work.

On August 5, 2013, petitioner had an appointment with immunologist, Dr. Amy Marks in
the Department of Allergy, Immunology and Rheumatology at the Children’s Hospital of
Michigan. Pet. Ex. 2 at 65. Dr. Marks wrote that petitioner was being seen for
hypogammaglobulinemia.7 Id. Petitioner reported that her hives began two years prior, and they
are chronic but sporadic. Id. Petitioner indicated that she was able to treat them with oral
antihistamines, but approximately six to eight months ago, the hives worsened. Id. at 66.
Additionally, petitioner reported a nine-week history of diarrhea. Id. Dr. Marks wrote that
petitioner had levels of IgA, IgE, IgG, and IgM that were “significantly low.” Id. Dr. Marks
diagnosed petitioner with chronic urticaria, colitis, likely Crohn’s disease,
hypogammaglobulinemia and truncal esophagitis. Id. at 67. Initially, Dr. Marks hypothesized
that petitioner’s hypogammaglobulinemia was likely secondary to her diarrhea and colitis. Id.
Because petitioner was being treated with steroids and Asacol, she wanted to retest her immune
globulins to see if there was improvement. Id. Dr. Marks also wrote that another possibility and
cause is CVID, but wrote, “However, at this time, I do believe this is a secondary
hypogammaglobulinemia that can be reversed once her colitis is under better control.” Id.
Additionally, Dr. Marks also considered whether petitioner’s chronic urticaria could “correlate
with an autoimmune disease, like Crohn’s,” and that petitioner, “likely has autoimmune
urticaria.” Id. at 68. She asked to see petitioner in October. Id.

Petitioner had a follow-up with Dr. Marks on September 25, 2013. Pet. Ex. 2 at 55.
Petitioner’s follow-up blood work once again showed no immunoglobulins, including IgG, IgA
and IgM. Pet. Ex. 2 at 55. Petitioner reported that her diarrhea had subsided, but she was
beginning to show signs of sinusitis. Id. During this visit, petitioner reported to Dr. Marks that
she was experiencing “quite severe plantar warts on her right foot, involving four of the five
toes,” and that she was experiencing flat warts on her face. Id. Dr. Marks wrote, “Again, when
looking back, the warts also started approximately two years ago, which is when [petitioner]
started becoming sick quite regularly with sinus infections, per Mom.” Id. Dr. Marks
recommended that petitioner continue a steroid taper, with her last dose being October 4th. At
this appointment, Dr. Marks wrote, “Given this constellation of symptoms, with complete
agammaglobulinemia, recurrent infections, and warts, I do have some concerns for WHIM
syndrome; however, she does not have the typical variants with abnormalities on CBC and
neutropenia that can be seen.” Id. at 56. Dr. Marks stated that it was “imperative” that petitioner
begin IVIG, given the recurrent infections and constellation of findings. Id. Dr. Marks opined
that petitioner either had “atypical agammaglobulinemia or WHIM syndrome variant.” Id.
Petitioner began receiving IVIG infusions on a monthly basis. See Pet. Ex. 17 at 33; Pet. Ex. 5 at
2; Pet. Ex. 26 at 2093.

7
Hypogammaglobulinemia is abnormally low levels of all classes of immunoglobulins in the blood.
Hyopogammaglobulinemia, Dorland’s Med. Dictionary Online,
https://www.dorlandsonline.com/dorland/definition?id=24235&searchterm=hypogammaglobulinemia (lasted visited
Sept. 22, 2024).

8
Petitioner returned to Dr. Macha on October 30, 2013 for a re-evaluation. Pet. Ex. 12A at
372. Petitioner’s abdominal pain and nausea had subsided. Id. Petitioner also was having
normal bowel movements and was feeling good after two infusions of IVIG. Id. Petitioner was
continuing on Asacol and was “clinically doing well.” Id. A re-evaluation of her GI tract was
recommended after she had completed 3-4 months of IVIG treatment. Id.

On December 5, 2013, petitioner was evaluated by Dr. Sureyya Savasan, a hematologist
in the Department of Hematology and Oncology at the Children’s Hospital of Michigan. Pet. Ex.
2 at 49. Dr. Savasan noted that petitioner experienced four to six weeks of diarrhea before going
to the Gastroenterology Clinic in July 2013. Id. Additionally, she wrote that petitioner has
chronic urticaria which started two years ago and plantar warts involving the inner surfaces of
her toes for the past two years. Id. Further, petitioner reported that she had “a few warts on her
face which currently have subsided.” Id. Petitioner also reported to Dr. Savasan that she had
experienced hair loss that begun “one year ago,” and mainly involves her scalp hair, eyelashes,
and on the upper extremities. Id. Petitioner “noticed a distinct area of hair loss on the right side
of the scalp on the frontal region” and “there is a discrete area of hair loss on the left forearm
which she noticed about five to six weeks ago.” Id. Under “Past Medical History,” Dr. Savasan
recorded that petitioner “has a history of recurrent URI infections since childhood and she has
been treated with several courses of antibiotics periodically for suspected clinical sinusitis;
however, she does not have any documented bacterial or fungal infections.” Id. Dr. Savasan
also observed that petitioner has received all her immunizations, including the two HPV vaccine
doses, but “has not mounted an immune response to the vaccines.” Id. at 51. Dr. Savasan wrote
that petitioner had “almost undetectable levels of immunoglobulins, including IgG, IgA, IgM,
and IgE, her absolute neutrophil count ranged from 2,700-11,000, and her transaminase levels
normalized. Id. Dr. Savasan assessed petitioner with hypogammaglobulinemia with chronic
IVIG infusions, plantar warts, inflammatory bowel disease, history of candida esophagitis, and
alopecia areata. Id. at 53. Dr. Savasan opined that a potential diagnosis of atypical WHIM,
which was being entertained by Dr. Marks, was suspect because her neutrophil levels were
normal and she did not have any serious infections, aside from the repeated upper respiratory
infections. Id. Dr. Savasan wrote that there needed to be further evaluation of petitioner’s
“autoimmune/immunodysregulation condition,” and that additional labs were being ordered,
including T, B and NK cell subset counts, ANA, anti-microsomal antibodies, anti-smooth
antibodies, and anticardiolipin antibody screen “due to the co-existence of immunodeficiency
and autoimmunity and her clinical spectrum.” Id. at 53.8

On December 30, 2013, petitioner returned to Dr. Marks for a re-evaluation of her
hypogammaglobulinemia. Pet. Ex. 2 at 39. Petitioner reported that she was no longer having
diarrhea, but some constipation. Id. Petitioner’s IgG levels were improved, though not normal,
and she was cleared for a repeat colonoscopy in February. Id. Dr. Marks wrote that the antibody
tests ordered by Dr. Savasan may not be significant because petitioner does not produce
antibodies. Id. Dr. Marks also prescribed petitioner cefdinir for 10 to 14 days to combat acute
sinusitis. Id. at 41.

8
It was not clear if these tests were ever done as no additional records with Dr. Savasan were filed, despite having a
follow-up appointment recorded in other medical records. See Pet. Ex. 2 at 42 (noting that petitioner had a follow-
up appointment with Hematology/Oncology on January 16, 2014).

9
Petitioner had an appointment with dermatologist, Dr. Laurie Kohen at the Henry Ford
Hospital on January 3, 2014. Pet. Ex. 6 at 2. Petitioner’s “History of Present Illness” noted that
petitioner had warts on her right foot “ongoing for last 2 years,” and had “numerous liquid
nitrogen cryotherapy treatments over the years without improvement.” Id. Petitioner reported a
“3-month history of patch of hair loss on her right frontal scalp without associated erythema or
pruritus,” and that she had eyelash and eyebrow hair loss. Id. Dr. Kohen wrote that petitioner
“has been undergoing significant medical stressors as she is being worked up for an
immunodeficiency disorder due to findings of absent immunoglobulins all of which began with a
several week history of diarrhea.” Id. A “well-demarcated area of nonscarring alopecia
measuring 4.5 x 3 cm” was located on her right frontal scalp, she also had nonscarring alopecia
on her left eyebrow and left forearm. Id. at 5. Petitioner also had multiple verrucous papules in
the web spaces on her right foot. Id. Petitioner received a Kenalog injection in her scalp and
eyebrow to treat the alopecia. Id. Petitioner was also referred to Dr. Nydorf for bleomycin
injections for the verrucae. Id.

Petitioner had a follow-up appointment with dermatologist, Dr. Kohen, on February 12,
2014. Pet. Ex. 6 at 7. Petitioner reported that she had one “enlarging lesion on her frontal scalp
and a smaller patch adjacent to the larger one,” and that she had yet to use topical steroid on her
scalp. Id. She noted new hair growth in her left eyebrow, but her right eyebrow was now losing
hair. Id. Dr. Kohen administered another Kenalog injections for the scalp lesions and eyebrow
hair loss. Id. at 7.

On March 3, 2014, petitioner had a follow-up appointment with Dr. Marks. Pet. Ex. 2 at
35. Dr. Marks’s diagnosed petitioner with “primary immune deficiency agammaglobulinemia
and chronic urticaria angioedema-autoimmune type.” Id. at 37. Petitioner was to continue IVIG
infusions and continue to be treated by Dr. Kohen for her dermatological issues. Id. On March
25, 2014, petitioner underwent a follow-up colonoscopy and endoscopy. Id. at 26. Dr. Macha
wrote the “EGD demonstrated basal cell hyperplasia in the esophagus and chronic inactive
gastritis in the stomach,” and the colonoscopy demonstrated “chronic enteritis, chronic colitis
with moderate to severe activity in the cecum and ascending colon, and chronic colitis in the
transverse colon.” Id. Petitioner reported no diarrhea, but reduced bowel movements. Id. at 25.
Dr. Macha diagnosed petitioner with pancolitis that was clinically stable, and that petitioner
should continue Asacol twice daily. Id. at 27.

On June 25, 2014, petitioner had a follow-up with the gastroenterology clinic at
Children’s Hospital of Michigan. Pet. Ex. 2 at 25. Petitioner reported that she was eating a
regular diet and was not experiencing any abdominal pain, although she expressed some delayed
bowel movements. Id. It was recommended that petitioner continue Asacol twice daily and to
follow-up in four months. Id. at 27.

Petitioner had a consultation at the Cleveland Clinic on July 23, 2014 with Dr. Joan
Tamburro. Pet. Ex. 5. It was noted that petitioner experienced 12 weeks of diarrhea and it was
initially thought that she had Crohn’s. Id. at 3. Petitioner was experiencing hair loss for 9
months, but her hair loss started prior to the onset of the agammaglobulinemia. Id. The hair loss
began on her eyelashes, then progressed to her scalp, arm hair, and eyebrows. Id. Dr. Tamburro
noted that petitioner was receiving Kenalog injections by Dr. Kohen and using Lidex and

10
Rogaine. Id. Dr. Tamburro also noted that petitioner had been diagnosed with “alopecia totalis.”
Id. Additionally, Dr. Tamburro wrote that petitioner had flat warts on her face that were
spreading. Id. Dr. Tamburro diagnosed petitioner with alopecia areata, verruca plana, verruca
vulgaris, and wrote, “Likely related to agammaglobulinemia or other immune differential
(immunology considering other diagnoses),” and that she would contact Dr. Marks. Id. at 3.
Dr. Tamburro had a phone call with petitioner’s mother and Dr. Marks and indicated that a
follow-up would be beneficial. Id. at 8.

On August 27, 2014, petitioner was seen by Dr. Brian Berman at the Hematology Clinic
at Beaumont Hospital for the possibility evaluation of “possible emerging
leukopenia/neutropenia.” Pet. Ex. 3 at 4. Dr. Berman wrote:

[petitioner] was well until about three years ago when she began to develop recurrent
sinusitis. She received multiple antibiotics and never required hospitalization. At some
point thereafter, she developed a few months of non-bloody diarrhea and substantial
weight process and was placed on Asacol for many months. Her gastrointestinal
symptoms ultimately resolved. About a year ago, she was started on monthly IVIG
infusions because of very significant hypogammaglobulinemia. Subsequently she has
developed widespread alopecia…In addition, she has developed flat warts on her hand as
well as feet.

Id. Dr. Berman wrote that “there is a possibility that she has the WHIM syndrome-warts,
hypogammaglobulinemia, bacterial infections, and myelokathexis. There is also concern that
this may be a variant of common variable immunodeficiency.” Id. He explained, “Over the last
number of months, her blood cell count has been in the 4,000 range with the lowest white count
at 3,300 with an ANC of 1700. Because of the association of neutropenia with WHIM
syndrome, we’ve been asked to evaluate the [petitioner].” Id. Dr. Berman reviewed petitioner’s
labs and noted that her current white blood cell count and neutrophils are adequate and that no
interventions are necessary at this time. Id. at 5. His assessment was:

16 y.o. female with B-cell immunodeficiency, with a history of presumed autoimmune
alopecia and transient inflammatory bowel process associated with propensity toward
papilloma virus. Based on my review of the literature, the possibility of WHIM
syndrome seems very real. Not present is the persistent neutropenia usually associated
with this syndrome (which is related to myelokathexis-apoptosis of [nature] myeloid cells
in the marrow. However, syndromes of this sort may be quite variable in phenotypic
expression.

Id.
On September 22, 2014, petitioner returned to the Cleveland Clinic for a follow-up and
re-evaluation of her alopecia. Pet. Ex. 5 at 11. Dr. Bayart assessed petitioner with alopecia
areata and wrote that “alopecia areata has an unpredictable course, often characterized by periods
of hair loss and regrowth,” and suggested avoiding immunosuppressive therapies if possible. Id.
Dr. Bayart also wrote, “Alopecia areata can be triggered by vaccines (such as Gardasil), but
usually would occur in closer proximity to the vaccination [than] [petitioner’s] alopecia.” Id.

11
Petitioner continued to receive monthly infusions of IVIG and had follow-up
appointments for alopecia, warts, and gastrointestinal issues. See Pet. Ex. 17 at 10. A follow-up
appointment with Dr. Marks on September 26, 2016 indicated that petitioner had one sinus
infection and a follow-up colonoscopy showed no abnormalities. Id. at 33. Petitioner reported
that she was having “significant hair growth” and that her plantar warts had improved. Id. Dr.
Marks’ impression was “19-yo with significant immunodeficiency, agammaglobulinemia,
concern for WHIM syndrome variant, chronic urticaria,” and the plan was for petitioner to
continue to receive monthly IVIG infusions. Id. at 35. Regarding petitioner’s chronic urticaria,
Dr. Marks wrote that she reviewed the pathophysiology and characterized it as “autoimmune in
nature.” Id.

On April 21, 2017, petitioner had an appointment with Dr. Michael Cannon. Pet. Ex. 22
at 2. He recounted her medical history, noting that she was diagnosed with ileocolonic Crohn’s
disease in 2013 and agammaglobulinemia. Id. Petitioner also reported that “all of her symptoms
of hair loss started after the second inoculation for HPV,” and that a “Consultation at Cleveland
Clinic was not definite for a true association with the vaccine.” Id. Dr. Cannon noted that
petitioner “chronic urticaria starting five years prior.” Id. At the time of the appointment,
petitioner was experiencing diarrhea, bloating, and cramping. Id. Dr. Cannon noted that
petitioner’s symptoms “completely resolved on budesonide,” 9and he wanted to wean her off of
it. Id.

Petitioner transferred dermatology care to Dr. Wendy Sadoff and was assessed for
alopecia and plantar warts. Pet. Ex. 24 at 1. Dr. Sadoff wrote, “This is a 19-year-old female
who comes in for a chief complaint of skin lesions, located on the face. The lesions are flat
warts and mild in severity.” Id. Dr. Sadoff removed the flat warts and gave petitioner cream for
her face. Id. Petitioner continued treatment through 2017 Dr. Sadoff. On June 9, 2017, Dr.
Sadoff removed lesions on the right side of petitioner’s face. Id. at 5. The records indicate that
petitioner continued with Dr. Sadoff through 2019 for treatment of both flat warts and alopecia.
See generally Pet. Ex. 24.

On December 17, 2018, petitioner had an appointment with gastroenterologist, Dr. Jared
Bortman after her hospitalization for viral myocarditis where she was also found to be c.diff
positive, but negative toxin Pet. Ex. 22 at 18. Petitioner was treated with antibiotics and her
diarrhea and abdominal pain resolved and she was also taking budesonide. Id. Dr. Bortman
noted that petitioner was taking budesonide every other day and for most of 2018. Id. After
reviewing her history and performing an exam, he wrote that petitioner was “treated for C.diff
diarrhea with Vanco x 2 weeks in 7/2018. Clinically resolved. I am curious as to whether she
truly has Crohn’s disease….Will try to taper off of budesonide.” Id. at 20.

On May 31, 2019, petitioner sought a second opinion from Dr. Carl Lauter. Pet. Ex. 25
at 20. Dr. Lauter wrote that petitioner has a history of IBS, alopecia and agammaglobulinemia
and sought a second immunology opinion and to establish care at the immunology clinic at the
Beaumont Hospital. Id. He wrote that petitioner was in good health in 2013, except for
occasional URIs, isolated congenital cyst removed from the left medial eye corner a wart
removed from her foot. Id. He also noted that petitioner had hives five years prior to 2013 and
9
Budesonide is steroid used to treat Crohn’s Disease

12
it was “attributed to heat and sweating.” Id. Dr. Lauter wrote “she had first shot of HPV in
2/2013. In April 2013 she began having upper respiratory symptoms and hives. Two days later
she received her 2nd dose of HPV vaccine and 3 days later developed bronchitis, rhinitis,
sinusitis, hives, and swollen fingers. She did not get her 3rd dose of HPV vaccine due to her
“reactions.” Id. Dr. Lauter also wrote that “Her hives were attributed to a possible reaction to
Augmentin, however, a month later she continued to have the same symptoms along with loss of
her hair, eyebrows, eyelashes, left ear pain and plugging and new onset of non-bloody diarrhea.”
Id. Regarding her alopecia, Dr. Lauter wrote “[petitioner] denies that her diagnosis was
confirmed as “alopecia areata,” and that she had stopped injections after her hair returned, but
she developed a bald spot in November 2018. Id. at 21. Dr. Lauter observed that petitioner is
followed by Dr. Berman for her thrombocytopenia. Id. He diagnosed her with
agammaglobulinemia, CVID, viral warts, alopecia areata, thrombocytopenia, IBS (unspecified),
and others. Id. at 26. He “agreed with current total management including monthly IVIG,” and
recommended that petitioner do an HPV vaccine test and if negative, complete the HPV series.
Id. Dr. Lauter also wrote that he agrees “with referral to NIH or other major academic center
that has the ability to evaluate complex immune and genetic disorders, such as National Jewish,
Mayo Clinic, University of Cincinnati Children’s Hospital to assess case more thoroughly.” Id.

At a follow-up appointment with Dr. Sadoff, petitioner reported that she was again
experiencing hair loss, however, her verrucous lesions on her face have completely resolved.
Pet. Ex. 24 at 40. Dr. Sadoff noted that Dr. Lauter suggested petitioner participate in an NIH
trial. Id.

Petitioner saw gastroenterologist Dr. Michael Cannon on June 27, 2019 with complaints
of diarrhea. Pet. Ex. 22 at 9. Petitioner reported that she had weaned off budesonide for
approximately 6 months and was doing well until she began to have increased bowel movement
and watery stools. Id. Petitioner restarted budesonide and had “minimal improvement.” Id.
Petitioner was positive for alopecia, sinus drainage, and rhinorrhea. Id. Dr. Cannon diagnosed
petitioner with “diarrhea of presumed infectious origin.” Petitioner was positive for c.diff and
PCR toxin. Id. at 21. He also wrote that he was “in doubt of the diagnosis of Crohn’s disease,”
and that “Agammaglobulinemia does also put her at risk of infectious etiologies, most notably
small intestinal bacterial overgrowth.” Id. Petitioner was to start a course of cephalosporin for
her sinus infection and Dr. Cannon wrote that, “It will be interesting to see if it helps the diarrhea
symptoms.” Id.

Petitioner had a follow-up appointment with Dr. Cannon on September 18, 2019. Pet.
Ex. 22 at 4. At this appointment, petitioner reported that she was treated with Vancomycin after
testing positive for c.diff. Id. Petitioner indicated that she could have up to three days a week
where she experienced diarrhea five times a day. Id. Petitioner was diagnosed with “diarrhea of
presumed infectious origin,” and “indeterminate colitis,” along with CVID and alopecia. Id. at 7.
Dr. Cannon wrote, “last colonoscopy in 2016 was completely normal including small intestine. I
am in doubt of the diagnosis of Crohn’s disease. Agammaglobulinemia does also put her at risk
of infectious etiologies; most notably small intestinal bacterial overgrowth. She unfortunately
developed c.diff after [antibiotic] treatment.”

13
The most recent medical records filed by petitioner indicate that she was still receiving
IVIG infusions at Royal Oak Hospital in March 2020 See Pet. Ex. 27.

b. Expert Opinions

i. Petitioner’s Expert, Dr. Marc Glashofer’s Opinion

Dr. Marc Glashofer, offered his opinion as to how the HPV vaccine could cause a
significant aggravation of alopecia in the petitioner. Pet. Ex. 15. He stated that alopecia areata is
an autoimmune condition in which “an immune response to a component of the hair follicle
leads to loss of hair.” Id. at 4. He wrote that “There is no universally accepted cause, and no
definitive treatment.” Id.

Dr. Glashofer wrote that the purpose of vaccines is to “induce immunity by stimulating a
low-level immune response, such that a subsequent exposure to that immunogen allows the body
to recognize the threat and neutralize it with a robust response, thereby minimizing the
deleterious effects of the microorganism.” Id. He stated that during immunization, “there is the
potential that a portion of the foreign immunogen introduced may have a similar peptide
sequence or be structurally similar to a component of oneself,” and that this leads to “the body
creating an immune response, not just to the introduced antigen, but to normal components of
one’s self, thereby leading to autoimmune reactions and disease states.” Id. at 4-5. Essentially,
he endorsed a theory of molecular mimicry, pursuant to which components of the HPV vaccine
share homology between the structure of hair follicles. He theorized that the immune response to
the vaccine began to target hair follicles, thus exacerbating petitioner’s alopecia.

Dr. Glashofer referenced an article by Chu et al., to support his opinion that a vaccination
can induce alopecia areata. Pet. Ex. 15 at 4. The article is a case report of a young child who
experienced alopecia one week after receiving the third dose of the Japanese encephalitis vaccine
and then again three days after receiving the influenza vaccine. Pet. Ex. 15B at 1.10 The authors
of the article wrote that a review of VAERS case reports found “that patients with the zoster
vaccination or quadrivalent human papillomavirus vaccination had a greater risk of developing
alopecia than unexposed individuals, although the investigators did not have sufficiently detailed
clinical information in either study to ascertain whether each case of “alopecia” was alopecia
areata.” Id. The authors hypothesized that an inflammatory response to the vaccine antigens and
adjuvants could evoke T-cell mediated immune reactions, which can trigger alopecia areata in
genetically predisposed individuals. Id at 2. With respect to the case they were describing, the
authors wrote, “The occurrence of alopecia areata one week after vaccination followed by
regrowth followed by recurrence three days after a different vaccine strongly suggests a link
between vaccination and the onset of alopecia in this child, who was probably genetically
predisposed.” Id.

10
Chu, Chien-Ho, Alopecia Areata after Vaccination: Recurrence with Rechallenge, 33 Pediatric Derm. E218-19
(2016). [Pet. Ex. 15B].

14
Dr. Glashofer also referenced an article by Geier and Geier,11which examined
autoimmune adverse events after HPV vaccination as evidence that alopecia areata can be caused
by the vaccine. The Geier article found that the incidences of “serious autoimmune adverse
events,” including alopecia, “were significantly more likely,” to occur in individuals who
received the HPV-4 vaccine than controls. Pet. Ex. 15C. Geier stated that while the etiology of
autoimmune disease is “still not completely clear… genetic, immunological, hormonal, and
environmental factors are considered to be important triggers,” and that environmental triggers
can include, bacterial, viral or parasitic infections. Id. Furthermore, Geier stated that bacterial,
viral, or parasitic infections are known to induce and exacerbate autoimmune diseases, mainly by
the mechanism of molecular mimicry….it was suggested that the same mechanisms that act in
infectious invasion of the host apply equally to the host response to vaccination.” Id. at 1. The
study indicated that the time between vaccination and onset of symptoms of the adverse
autoimmune event was 6 to 55 days. Id.

Dr. Glashofer concluded his report, stating that “Based on the temporal relationship
between the vaccination and the development of the petitioner’s signs and symptoms of the
disease, there exists a logical sequence of cause and effect, showing that the vaccine resulted in
the petitioner’s injuries.” Pet. Ex. 15 at 4. He wrote that “there are no other non-vaccine
factors,” which appeared to have played a role. Id.

ii. Petitioner’s Expert, Dr. Santoro’s Opinion

In his first report, Dr. Santoro wrote that petitioner developed diarrhea within one month
after receipt of the second HPV vaccination. Pet. Ex. 14 at 6. He stated that petitioner’s initial
diarrhea was caused by the innate immune response, which failed to resolve and progressed to
inflammatory bowel disease, as a result of the later adaptive immune system response. Id. at 7.
Dr. Santoro explained that inflammatory bowel disease is an immune mediated chronic intestinal
condition that can be caused by a combination of factors, including genetics, the environment,
and an overreactive immune system. Id. at 5. Dr. Santoro wrote that there are several case
reports of ulcerative colitis after Gardasil vaccination, which is also an immune mediated chronic
intestinal condition. Id. He noted that in Morgan v. Sec’y of Health & Human Servs., “the
special master found that the petitioner and her experts presented a reasonable theory invoking
the role of both the initial innate response to the vaccine antigen (Gardasil) and of the adaptive
non-specific response as contributing to the development of ulcerative colitis.” Id. at 6; see also
Morgan v. Sec’y of Health & Human Servs., No. 13-529V, 2015 WL 9694667 (Fed. Cl. Spec.
Mstr. Dec. 10, 2015).

Dr. Santoro endorsed a theory of molecular mimicry as a cause of autoimmune disease
post-vaccination. Pet. Ex. 14 at 5. He explained molecular mimicry in general terms, stating,
“Molecular mimicry is one mechanism by which infectious agents (or other exogenous
substances such as vaccines) may trigger an immune response against autoantigens….Molecular
mimicry occurs when a pathogen expresses a protein that is remarkably similar in sequence or
shape to a protein in the host but sufficiently different to provoke an immune response. This can

11
Geier, D. & Geier, M., A case-control study of quadrivalent human papillomavirus vaccine-associated
autoimmune adverse events, 34(7) Clin. Rheumatol. 1225-1231 (2014). [Pet. Ex. 15C].

15
lead to the body creating an immune response...to normal components of one’s self, thereby
leading to an autoimmune reaction and disease.” Id.

In his second report, Dr. Santoro again wrote that the petitioner was “in excellent health
prior to receiving her first Gardasil vaccination on 2/18/2013. Petitioner received her second
HPV4 vaccination on 4/22/2013,” and then developed generalized urticaria, bronchitis, rhinitis
and finger swelling necessitating systemic corticosteroids and within one month of the vaccines
developed diarrhea, and ultimately was diagnosed with inflammatory bowel disease.” Pet. Ex.
20 at 1. He acknowledged that petitioner had significantly low IgA, IgE, IgG, and IgM, which
“would weigh against an excessive auto-immune response,” but opined that petitioner’s
hypogammaglobulinemia was secondary to her severe diarrhea and ulcerative colitis. Id.

Dr. Santoro wrote, “If [petitioner] had genetic IgG deficiency, she would have had a long
history of bronchitis, pneumonia, ear infections, and sinusitis, which is common with such a
deficiency. I did not see any extraordinary such reporting of these problems in [petitioner’s
records].” Id. at 2. He also stated that a review of petitioner’s records did not show that she had
a history of diarrhea, chronic dermatitis, allergic rhinitis, and recurrent infections, thus he did not
believe petitioner had an IgM deficiency prior to receiving the HPV vaccines. Id. Dr. Santoro
wrote, “hypogammaglobulinemia…can be seen in patients with inflammatory bowel disease,
both Crohn’s disease and ulcerative colitis.” Id. at 3. He referenced an article by Elson et al.,
which examined two patients who developed hypogammaglobulinemia secondary to Crohn’s
disease. Pet. Ex. 21.12 The authors acknowledged that “protein-losing enteropathy can be
associated with Crohn’s disease,” but noted that, “this was not the mechanism of
hypogammaglobulinemia in these cases.” Id. at 6. The authors instead found that the patients’
hypogammaglobulinemia was T-cell suppressor mediated, meaning that the T-cells inhibited the
antibody synthesis. Id.

Dr. Santoro stated that petitioner’s treating physician, Dr. Marks, “clearly stated that the
petitioner had ulcerative colitis that explained her low immune globulin levels after the onset of
[petitioner’s] ulcerative colitis.” Pet. Ex. 20 at 3. Dr. Santoro rejected respondent’s expert’s
opinion that petitioner had Common Variable Immune Disorder (“CVID”), stating that Dr.
Marks did not believe that petitioner had CVID, and asserted that petitioner’s IgG levels
improved after several rounds of IVIG and resolution of her gastrointestinal issues. Id. Dr.
Santoro stated that “petitioner does not have a general immunodeficiency disorder or CVID,”
and that it was his opinion that petitioner’s active colitis and diarrhea was the cause of
petitioner’s low levels of immunoglobulins. Id.

iii. Petitioner’s Expert, Dr. Alan Cutler’s Opinion

Petitioner also filed an expert report from another gastroenterologist, Dr. Alan Cutler.
Pet. Ex. 28. Taking a different view as to diagnosis from that of Dr. Santoro, or any of
petitioner’s treating physicians, Dr. Cutler opined that the HPV vaccine caused petitioner to have
gastroparesis, which led to erosive esophagitis. Id. at 3. He stated that without the HPV vaccine,
petitioner “would likely not have developed her upper gastrointestinal symptoms.” Id.

12
Charles O. Elson, et al., Hypogammaglobulinemia Due to Abnormal Suppressor T-Cell Activity in Crohn’s
Disease, 86 Gastroenterology 569-76 (1984). [Pet. Ex. 21].

16
Dr. Cutler also wrote that petitioner was in excellent health prior to the receipt of the
HPV vaccine, ignoring the multiple appointments for sinusitis, bronchitis, otitis and coughing
prior to the receipt of the first vaccine. He said, “within two months of her HPV vaccine, the
petitioner developed a systemic inflammatory reaction including urticaria, bronchitis, rhinitis,
distal extremity edema, and subsequent inflammatory bowel disease.” Id. at 2. He stated,
without citation to the record, that, “petitioner describes stomach problems starting in late
February 2013,” and that she had significant weight loss, reported as 30 pounds, leading to an
investigative endoscopy and colonoscopy which revealed severe erosive esophagitis with
candida and diffuse active chronic pan-colitis. Id. Dr. Cutler wrote that, “The presentation of
significant weight loss with severe esophagitis is commonly seen in gastroparesis, which I
believe contributed to the patient’s presentation and illness.” Id. He explained that gastroparesis
is a syndrome of objectively delayed gastric emptying in the absence of mechanical obstruction.
Presenting symptoms include bloating, nausea, emesis, early satiety and epigastric discomfort
and pain.

Dr. Cutler wrote that he disagreed with Dr. Marks’ finding that petitioner had CVID
caused by intestinal inflammation. Pet. Ex. 28 at 2. Although, he did not discuss the consistent
findings of essentially nondetectable levels of IgG, IgM, IgA and IgE even well after the diarrhea
had ended.

Dr. Cutler explained that gastroparesis presents with symptoms including bloating,
nausea, emesis, feeling full, and epigastric discomfort or pain. Id. at 2. He stated that causes
include, diabetes, autoimmune, post-surgical, viral, neurological disease, or medication induced.
Id. Similarly to Dr. Santoro, Dr. Cutler opined that molecular mimicry could cause petitioner’s
gastrointestinal issues though he diagnosed gastroparesis, writing, “There is a cross-reaction
from a component of the vaccine which results in the loss of immune tolerance and thereby
inappropriate activation of the immune system cells and resulting damage to the gastrointestinal
system. An enteric neuropathy develops due to inflammation and immunologic insult to the
autonomic nervous system.” Id. at 3. He also stated that the adjuvant in the HPV vaccine could
be the cause of the autonomic nervous system insult, instead of just the antigen in the vaccine.
Id. at 2.

Referencing an article by Palmieri et al., which examined reports of neuropathy with
autonomic dysfunction after HPV vaccination, Dr. Cutler asserted that the adjuvant in the HPV
vaccine can cause an autoimmune/inflammatory syndrome induced by adjuvants often referred
to as ASIA. Id.; Pet. Ex. 30.13 The authors explained that an adjuvant is designed to enhance an
immune response to a vaccine, but the theory proposes that the “adjuvants themselves include
some pathogen-associated molecular patterns and/or create a mild tissue injury exposing some
damage-associated molecular patterns, which are recognized by the innate immune system
through specific pattern recognition.” Pet. Ex. 30 at 5. It is the immune response to both the
adjuvant and the antigen that may cause an autoimmune reaction. Id. In their case review, the
Palmieri authors found that many patients reported an “acute phase” of post-vaccination

13
Beniamino Palmieri et al., Severe Somatoform and Dysautonomic Syndromes after HPV Vaccination: Case Series
and Review of Literature, 65 Immunol. Res. 106-16 (2017). [Pet. Ex. 30].

17
symptoms, which include low-grade fever, skin rashes, muscle pain, headache, and sensorial
disturbances. Id. The acute phase onset occurred within hours or days post-vaccination, but then
subsided and patients then began experiencing recurrent or chronic symptoms. Id. The authors
explained that some other studies speculated that post-vaccination fibromyalgia, POTS or
complex regional pain syndrome, might be due to dysfunction in the sympathetic nervous system
caused by the HPV vaccine in susceptible individuals. Id. at 8. Dr. Cutler stated that, “such an
event would explain the development of gastroparesis post-HPV vaccination.” Pet. Ex. 28 at 3.

Dr. Cutler also referenced an article by Brinth et al., as evidence for causation between
the HPV vaccination and the immunologic insult to the autonomic nervous system, including
gastroparesis. Pet. Ex. 28 at 3. In the Brinth article, the authors examined autonomic functions
of patients who had reported autonomic dysfunction symptoms within the first two months of
receiving the HPV vaccine. Pet. Ex. 33.14 They found 53 patients who reported headache,
excessive fatigue, cognitive dysfunction, and widespread neuropathic pain. Id. The authors
diagnosed over half of the patients with POTS, but explained that POTS “should probably be
looked upon as a symptom secondary to another yet unidentified condition rather than as a
disease entity of its own.” Id. While the authors found “a close chronological association to the
vaccination,” they did not opine as to how the vaccine could have caused these symptoms in the
patients. Id.

iv. Respondent’s Expert, Dr. Randy Longman’s Opinion

Dr. Longman wrote two reports for respondent. Resp. Exs. A & G. His reports focused
on both of petitioner’s alleged injuries-an aggravation of her alopecia and the cause of her
gastrointestinal injury.

Dr. Longman responded to Dr. Glashofer’s report, stating, “given the underlying immune
deficiency and hypogammaglobulinemia,” in petitioner, “Gardasil stimulation of immune-
mediated molecular mimicry as suggested by Dr. Glashofer is less likely.” Resp. Ex. A at 4. Dr.
Longman accepted Dr. Glashofer’s explanation of molecular mimicry and wrote that molecular
mimicry has been “described to lead to specific autoantibody response to nerve proteins leading
to Guillain-Barré syndrome.” Id. However, “given the [petitioner’s] primary immunodeficiency
and lack of sustained titers to HBV immunization, it would be more reasonable to suspect a
decreased immune response to Gardasil vaccination rather than stimulating cross-reactive
autoimmune antibodies.” Id. at 4.

Dr. Longman explained that CVID is a primary immunodeficiency characterized by
impaired antibody production and it is the second most common immunodeficiency. Resp. Ex.
A at 3. Clinically, CVID is defined by reduced or absent serum concentrations of IgG, IgA, and
IgM. Id.; Resp. Ex. G at 2. He wrote that the designation “variable” refers to a heterogenous
group of clinical manifestations including recurrent infections, chronic lung disease, and
common gastrointestinal diseases. Id. The hallmark of CVID is the abnormalities in B cell
maturation and differentiation into antibody producing plasma cells. Resp. Ex. G at 2.

14
Louise Brinth et al., Suspected Side Effects to the Quadrivalent Human Papilloma Vaccine, 62 Dan. Med. J. 1-5
(2015). [Pet. Ex. 33].

18
He explained that “IgM is the initial version of the antibody created by the immune system
during the first exposure to antigen.” Id. As the affinity in the antibody is refined, the antibody
type will switch over from IgM to IgG….Low levels of antibodies can result either from
impaired production or increased loss of antibodies. Resp. Ex. G at 1. Impaired production
generally results from abnormalities in B cell maturation and differentiation into memory B cells
that produce antibodies. Id. Hypogammaglobulinemia can also occur due to kidney disease,
burns, or intestinal inflammation. However, in petitioner’s case, even after her inflammatory
colitis resolved, petitioner was still presenting with nearly absent or no antibodies of any class.
See Pet. Ex. 2 at 55-56; Resp. Ex. G at 1.

Dr. Longman explained that petitioner’s presentation of diarrhea which ultimately led to
her diagnosis is consistent with a CVID presentation. He explained that diagnosis is often
delayed following symptom onset. Resp. Ex. A at 5. He referenced and article by Khodadad et
al. article which examined gastrointestinal manifestations in patients with CVID and noted that,
“Some patients [with CVID] may present with GI problems as their first clinical presentation.”
Resp. Ex. D at 5.15 Additionally, the authors stated, “Between 20% and 60% of individuals
develop diarrheal disease, and chronic watery diarrhea is common in CVID.” Id. The authors
noted that “inflammatory bowel diseases appear to occur with increased frequency in patients
with CVID,” but that CVID-associated colitis is “felt to be separate from classic [irritable bowel
disease].” Id. at 5.

Additionally, an Dr. Longman cited to an article by Cunningham-Rundles and Bodian
which explained that the “clinical spectrum of CVID is quite broad, and symptoms of antibody
deficiency may not become obvious until young, middle, or even late in life.” Resp. Ex. I at 1.16
Some patients with CVID may present with classic or, more often, atypical inflammatory
gastrointestinal disease, resulting in diarrhea, malabsorption and weight loss. Id. Furthermore,
the article explained, “For unknown reasons, autoimmune diseases, particularly autoimmune
thrombocytopenia, rheumatoid arthritis, and pernicious anemia, are relatively common in this
patient group.” Id. Acute, chronic, or recurrent infections were found in almost all the cases of
CVID reported in the Rundles and Bodian article, and “almost all the patients had a history of
recurrent episodes of bronchitis, sinusitis, and/or otitis.” Id. at 2.

Dr. Longman observed that petitioner’s treating physician, Dr. Marks, initially
hypothesized that petitioner’s hypogammaglobinemia was related to her active colitis, but noted
that these numbers needed to be reversed once her colitis resolved. See Pet. Ex. 2 at 64.
Importantly, at petitioner’s second appointment with Dr. Marks on September 25, 2013 after her
diarrhea had resolved and she still had “no immunoglobulins, including IgG, IgA, as well as
IgM,” and petitioner’s mother revealed that petitioner had a two year history of chronic sinus
infections, Dr. Marks revised her opinion and diagnosed petitioner with a primary
immunodeficiency of “atypical agammaglobulinemia or WHIM syndrome variant.” Pet. Ex. 2 at
57; Resp. Ex. G at 1. Dr. Longman stated that Dr. Mark’s initial assessment of petitioner was
15
Ahmad Khodadad et al., Gastrointestinal Manifestations in Patients with Common Variable Immunodeficiency,
52 Dig. Dis. Sci. 2977-2983 (2007). [Resp. Ex. D].
16
Charlotte Cunningham-Rundles and Carol Bodian, Common Variable Immunodeficiency: Clinical and
Immunological Features of 248 Patients, 92 Clin. Immunol. 34-48 (1999). [Resp. Ex. I].

19
reasonable and after subsequent evaluation, petitioner’s disease was more consistent with a
primary immune deficiency and was treated as such with IVIG therapy. Resp. Ex. G at 2.

Dr. Longman also observed that petitioner’s experts failed to acknowledged petitioner’s
medical history, which included repeated sinus infections treated with antibiotics, chronic
urticaria, and warts. Resp. Ex. G at 2. In his first report, Dr. Longman reviewed petitioner’s
medical history in detail, chronicling the appointments where petitioner was treated for repeated
sinus infections and recurrent urticaria with antibiotics and steroids. Resp. Ex. A at 1-2. He
opined that the delay in diagnosis, the presentation of petitioner with diarrhea, and the repeated
sinus infections, are all consistent with a primary immunodeficiency, despite no family history of
an immune deficiency or identified genetic disorder to account for her primary immune
deficiency. Resp. Ex. G at 2.

With respect to Dr. Santoro’s opinion that the innate immune system’s response to the
HPV vaccine triggered petitioner’s diarrhea, Dr. Longman stated that “adverse effects of broad
systemic cytokine activation would generally trigger the characteristic biology of fever, change
in blood pressure, leukocytosis, and elevated acute phrase reactants and a general sense of
feeling unwell. These were not present in [petitioner’s] case.” Resp. Ex. A at 4. Dr. Longman
stated that the “non-specific adaptive immune response does not offer a plausible mechanism for
specific intestinal inflammation.” Id. He wrote that, “[Petitioner] tolerated the initial
vaccination without evidence of a non-specific inflammatory response.” Id. He opined that
instead of the vaccine at issue in this case, the temporal association of diarrhea with the use of
antibiotics for persistent upper respiratory infections and congestion is more plausible as a cause
of the diarrhea. Id. at 5. He wrote, “GI manifestations including inflammatory colitis commonly
occur in individuals with CVID and repeated antibiotic exposure increases the potential for
microbial exacerbation of underlying colitis.” Id.

He concluded his reports, stating “petitioner’s presentation is consistent with a primary
immune deficiency such as CVID.” Resp. Ex. G at 3. Dr. Longman wrote, “CVID is a common
primary immune deficiency that can present without family history and is frequently associated
with gastrointestinal inflammation. Therefore, it is my opinion that the petitioner has a primary
immune deficiency, likely CVID, that is causally linked to her history of intestinal
inflammation.” Id.

III. Applicable Legal Standards

To receive compensation through the Program, Petitioner must prove either (1) that she
suffered a “Table Injury”—i.e., an injury listed on the Vaccine Injury Table—corresponding to a
vaccine that she received, or (2) that she suffered an injury that was actually caused by a
vaccination. See §§ 11(c)(1), 13(a)(1)(A); Capizzano, 440 F.3d at 1319-20. Petitioner must
show that the vaccine was “not only a but-for cause of the injury but also a substantial factor in
bringing about the injury.” Moberly, 592 F.3d at 1321 (quoting Shyface, 165 F.3d at 1352-53).

In the present case, petitioner does not allege a Table injury. Instead, petitioner alleges that
she suffered an off-table significant aggravation of her pre-existing alopecia and a new
gastrointestinal injury as a result of the receipt of the HPV vaccination on February 18, 2013 and

20
April 22, 2013. Pet. Response at 21, 26. Thus, petitioner bears the burden of establishing actual
causation of the significant aggravation of these conditions.

a. Causation

Because Petitioner does not allege a Table Injury, she must prove a vaccine she received
actually caused her injury. To do so, Petitioner must establish, by preponderant evidence: “(1) a
medical theory causally connecting the vaccination and the injury; (2) a logical sequence of
cause and effect showing that the vaccination was the reason for the injury; and (3) a showing of
a proximate temporal relationship between vaccination and injury.” Althen, 418 F.3d at 1278.

The causation theory must relate to the injury alleged. Petitioner must provide a sound
and reliable medical or scientific explanation that pertains specifically to this case, although the
explanation need only be “legally probable, not medically or scientifically certain.” Knudsen v.
Sec’y of Health & Hum. Servs., 35 F.3d 543, 548-49 (Fed. Cir. 1994). Petitioner cannot establish
entitlement to compensation based solely on her assertions; rather, a vaccine claim must be
supported either by medical records or by the opinion of a medical doctor. § 13(a)(1). In
determining whether Petitioner is entitled to compensation, the special master shall consider all
material in the record, including “any . . . conclusion, [or] medical judgment . . . which is
contained in the record regarding . . . causation.” § 13(b)(1)(A). The special master must weigh
the submitted evidence and the testimony of the parties’ proffered experts and rule in Petitioner’s
favor when the evidence weighs in her favor. See Moberly, 592 F.3d at 1325-26 (“Finders of
fact are entitled—indeed, expected—to make determinations as to the reliability of the evidence
presented to them and, if appropriate, as to the credibility of the persons presenting that
evidence.”); Althen, 418 F.3d at 1280 (noting that “close calls” are resolved in Petitioner’s
favor).

In determining whether a 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 that a special master is not bound by any “diagnosis, conclusion, judgment, test result,
report, or summary” contained in the record). Furthermore, a petitioner is not required to present
medical literature or epidemiological evidence to establish any Althen prong. The special master
essentially must weigh and evaluate opposing evidence in deciding whether a petitioner has met
his or her burden of proof. Andreu, 569 F.3d at 1380; see also Grant v. Sec’y of Health &
Human Servs., 956 F.2d 1144, 1149 (Fed. Cir. 1992).

“Regardless of whether the burden ever shifts to the [R]espondent, the special master
may consider the evidence presented by the [R]espondent in determining whether the [P]etitioner
has established a prima facie case.” Flores v. Sec’y of Health & Hum. Servs., 115 Fed. Cl. 157,
162-63 (2014); see also Stone v. Sec’y of Health & Hum. Servs., 676 F.3d 1373, 1379 (Fed. Cir.
2012) (“[E]vidence of other possible sources of injury can be relevant not only to the ‘factors
unrelated’ defense, but also to whether a prima facie showing has been made that the vaccine
was a substantial factor in causing the injury in question.”); de Bazan v. Sec’y of Health & Hum.
Servs., 539 F.3d 1347, 1353 (Fed. Cir. 2008) (“The government, like any defendant, is permitted
to offer evidence to demonstrate the inadequacy of the [P]etitioner’s evidence on a requisite
element of the [P]etitioner’s case-in-chief.”); Pafford, 451 F.3d at 1358-59 (“[T]he presence of

21
multiple potential causative agents makes it difficult to attribute ‘but for’ causation to the
vaccination. . . . [T]he Special Master properly introduced the presence of the other unrelated
contemporaneous events as just as likely to have been the triggering event as the vaccinations.”).

In Vaccine Act cases, expert testimony may be evaluated according to the factors for
analyzing scientific reliability set forth in Daubert v. Merrell Dow Pharm., Inc., 509 U.S. 579,
594-96 (1993); see also Cedillo v. Sec’y of Health & Human Servs., 617 F.3d 1328, 1339 (Fed.
Cir. 2010) (citing Terran v. Sec’y of Health & Human Servs., 195 F.3d 1302, 1316 (Fed. Cir.
1999). In Vaccine Program cases, these factors are used in the weighing of the scientific
evidence actually proffered and heard. Davis v. Sec'y of Health & Human Servs., 94 Fed. Cl. 53,
66–67 (2010) (“uniquely in this Circuit, the Daubert factors have been employed also as an
acceptable evidentiary-gauging tool with respect to persuasiveness of expert testimony already
admitted”), aff'd, 420 F. App'x 973 (Fed. Cir. 2011). The flexible use of the Daubert factors to
determine the persuasiveness and/or reliability of expert testimony in Vaccine Program cases has
routinely been upheld. See, e.g., Snyder v. Sec'y of Health & Human Servs., 88 Fed. Cl. 706,
742-45 (2009).

When both sides offer expert testimony, a special master's decision may be “based on the
credibility of the experts and the relative persuasiveness of their competing theories.”
Broekelschen v. Sec'y of Health & Human Servs., 618 F.3d 1339, 1347 (Fed. Cir. 2010) (citing
Lampe v. Sec’y of Health & Human Servs., 219 F.3d 1357, 1362 (Fed. Cir. 2000)). However,
nothing requires the acceptance of an expert's conclusion “connected to existing data only by the
ipse dixit of the expert,” especially if “there is simply too great an analytical gap between the
data and the opinion proffered.” Snyder, 88 Fed. Cl. at 743 (quoting Gen. Elec. Co. v. Joiner,
522 U.S. 146 (1997)). Weighing the relative persuasiveness of competing expert testimony
based on a particular expert's credibility is part of the overall reliability analysis to which special
masters must subject expert testimony in Vaccine Program cases. Moberly v. Sec’y of Health &
Hum. Servs., 592 F.3d 1315, 1325-26 (Fed. Cir. 2010) (“[a]ssessments as to the reliability of
expert testimony often turn on credibility determinations”); see also Porter v. Sec'y of Health &
Human Servs., 663 F.3d 1242, 1250 (Fed. Cir. 2011) (“this court has unambiguously explained
that special masters are expected to consider the credibility of expert witnesses in evaluating
petitions for compensation under the Vaccine Act”).

b. Significant Aggravation

The Vaccine Act defines significant aggravation as “any change for the worse in a
preexisting condition which results in markedly greater disability, pain, or illness accompanied
by substantial deterioration of health.” § 300aa-33(4). The United States Court of Federal
Claims established the governing six-part test for off-Table significant aggravations in Loving.
Petitioner must prove by a preponderance of the evidence:

(1) The person’s condition prior to administration of the vaccine, (2) the person’s
current condition (or the condition following the vaccination if that is also
pertinent), (3) whether the person’s current condition constitutes a ‘significant
aggravation’ of the person’s condition prior to vaccination, (4) a medical theory
causally connecting such a significantly worsened condition to the vaccination, (5)
a logical sequence of cause and effect showing that the vaccination was the reason

22
for the significant aggravation, and (6) a showing of a proximate temporal
relationship between the vaccination and the significant aggravation.

Loving v. Sec’y of Health & Human Servs., 86 Fed. Cl. 135, 144 (2009); see also W.C. v. Sec’y of
Health & Human Servs., 704 F.3d 1352, 1357 (Fed. Cir. 2013) (adopting this test as the proper
legal standard for significant aggravation claims brought under the Vaccine Act). Loving prongs
four, five, and six are derived from the Federal Circuit’s test for off-Table actual causation cases.
See id. at 143; see also Althen v. Sec’y of Health & Human Servs., 418 F.3d 1274 (Fed. Cir.
2005).

The Federal Circuit clarified Loving prongs 3, 4, and 5 in Sharpe, further defining the
requirements for petitioners to successfully demonstrate a cause-in-fact significant aggravation
claim. Sharpe v. Sec’y of Health & Human Servs., 964 F.3d 1072 (Fed. Cir. 2020). Loving
prong three requires only a comparison of a petitioner’s current, post-vaccination condition with
her pre-existing pre-vaccination condition. Id. at 1082. A petitioner is not required to
demonstrate an expected outcome or that her post-vaccination condition was worse than such an
expected outcome. Id. at 1081.

Loving prong four requires petitioner to provide a “medical theory causally connecting
[petitioner’s] significantly worsened condition to the vaccination.” Id. at 1083 (quoting Loving,
86 Fed. Cl. at 144). In other words, a petitioner is “required to present a medically plausible
theory demonstrating that a vaccine ‘can’ cause a significant worsening” of the condition. Id.
(citing Pafford ex. rel. Pafford v. Sec’y of Health & Human Servs., 451 F.3d 1352, 1356-57 (Fed.
Cir. 2006)). A petitioner may be able to establish a prima facie case under Loving prong four
without eliminating a pre-existing condition as the cause of his significantly aggravated injury.
Id. (citing Walther v. Sec’y of Health & Human Servs., 485 F. 3d 1146, 1151 (Fed. Cir. 2007)
(noting that “the government bears the burden of establishing alternative causation . . . once
petitioner has established a prima facie case”)).

Loving prong five requires a petitioner to show “a logical sequence of cause and effect
showing that the vaccination was the reason for the significant aggravation.” Id. at 1085 (quoting
Loving, 86 Fed. Cl. at 144). In other words, petitioner must show that the vaccination “did” cause
a worsening of petitioner’s underlying disorder. Id. “The sequence of cause and effect is usually
supported by facts derived from petitioner’s medical records. Althen, 418 F.3d at 1478; Andreu
v. Sec’y of Health & Human Servs., 569 F.3d 1367, 1377 (Fed. Cir. 2009); Capizzano v. Sec’y of
Health & Human Servs., 440 F.3d 1317, 1326 (Fed. Cir. 2006). In determining causation, a
special master should consider the causation opinions of the treating providers as “treating
physicians are likely to be in the best position to determine whether ‘a logical sequence of cause
and effect shows that the vaccination was the reason for the injury’” Cappizano, 440 F.3d at
1280.

IV. Discussion

Petitioner is alleging two separate injuries caused by the HPV vaccinations she received
on February 18, 2013, and April 22, 2013. First, she is alleging that the HPV vaccines caused
her to develop gastrointestinal injuries, such as colitis and/or gastroparesis with resultant erosive
esophagitis. See Pet. Exs. 14, 20, &28. Then she is also alleging that the HPV vaccines caused a

23
significant aggravation of her pre-existing alopecia. However, the main problem with both of
petitioner’s claim is rooted in Loving Prong Five/Althen prong two.

a. Loving Prongs One-Three: Discussion and Conclusion

As summarized above, prior to receiving the HPV vaccines, petitioner had been
experiencing hair-loss. See Pet. Ex. 2 at 84, 94-102; Pet. Ex. 4. At least on one occasion,
petitioner reported to her pediatrician that her eye lashes were falling out in 2012. Pet. Ex. 9 at
5. In records that followed the administration of the HPV vaccines, she told treating doctors that
her hair loss began prior to the vaccinations. When petitioner was seen by Dr. Sureyya Savasan,
on December 5, 2013, petitioner reported she “noticed hair loss about one year ago,” and that
“[t]he hair loss mainly involves her scalp hair, eyelashes, and skin on the upper extremities.”
Pet. Ex. 2A at 402-03. Thus, petitioner’s records establish that she had alopecia prior to the HPV
vaccines administered on February 18, 2013 and April 22, 2013, satisfying Loving prong one.

Loving prong two requires a discussion of the petitioner’s “current condition (or
condition following the vaccination if that is also pertinent.” Loving, 86 Fed. Cl. At 144.
Petitioner also has demonstrated that after the vaccinations at issue, her alopecia had changed
and became more widespread. At an appointment with her pediatrician on June 12, 2013, it was
recorded that petitioner had a two-month history of eyebrows and eye lashes falling out. Pet. Ex.
2 at 4. While meeting with Dr. Savasan in December 2013, after the vaccinations, petitioner not
only reported hair loss for one year, but that more recently she had noticed a “distinct area of hair
loss on the right side of the scalp,” and a “discrete area of hair loss on the left forearm which she
noticed about five to six weeks ago.” Pet. Ex. 2A at 403. She continued to report hair loss on
different parts of her body, aside from her eyebrows and eye lashes to multiple providers and
was treated accordingly. See Pet. Ex. 5 at 3; Pet. Ex. 24 at 2. At the time petitioner filed her
responsive brief to respondent’s motion, petitioner still had a diagnosis of alopecia. See Pet. Ex.
24 at 41.17

Loving prong three requires only a comparison of a petitioner’s current or post-
vaccination condition with her pre-vaccination condition. Sharpe v. Sec’y of Health & Hum.
Servs. 964 Fed. Cir. 1072, 1082 (Fed. Cir. 2020); see also Loving, 86 Fed. Cl. at 144. The statute
defines “significant aggravation” as “any change for the worse in a pre-existing condition which
results in markedly greater disability, pain, or illness accompanied by substantial deterioration in
health.” § 33(4). As petitioner acknowledged, she had experienced some hair loss prior to
vaccination and the medical records are clear that her hair loss became more widespread after
receipt of the HPV vaccines, petitioner has demonstrated that there was a change in her hair loss
post-vaccination. Thus, petitioner has established Loving prong three. However, whether the
HPV vaccine was the cause of the change in petitioner’s alopecia is discussed below.

b. Petitioner has not established that the HPV vaccine caused her to develop
gastrointestinal injuries (colitis and/or gastroparesis with resultant erosive
esophagitis) or that it significantly aggravated her pre-existing alopecia.

1. Loving prong four/Althen prong one
17
Respondent concedes that petitioner has satisfied Loving prongs one and two. See Resp. Brief at 18, n. 17.

24
Under Althen prong one, the petitioner must set forth a medical theory explaining how
the received vaccine could have caused the sustained injury. Andreu, 569 F.3d at 1379; Pafford,
451 F.3d at 1355-56. Petitioner’s theory of causation need not be medically or scientifically
certain but it must be informed by a “sound and reliable” medical or scientific explanation.
Boatmon, 941 F.3d at 1359; see also Knudsen, 35 F.3d at 548.

All of petitioner’s experts endorsed a theory of molecular mimicry as a causal mechanism
to explain how the HPV vaccine could cause an aggravation of alopecia and cause different
gastrointestinal injuries. As Dr. Santoro explained succinctly in his first report, “The goal of
vaccination is to induce immunity by stimulating a mild immune response, such that subsequent
exposure to a pathogen, allows the body to recognize the threat and neutralize it with a more
significant response, thereby minimizing deleterious effects of the microorganism.” Pet. Ex. 14
at 6. When explaining molecular mimicry, he states, “There is, however, the potential that a
portion of the foreign immunogen in the vaccine introduced may be structurally similar to a
component of oneself. This can lead to the body creating an immune response, not just to the
introduced vaccine antigen, but to normal components of oneself, thereby leading to an
autoimmune reaction and disease.” Id.

Petitioner’s dermatologic expert, Dr. Glashofer also explained, “During the process of
immunization, there is the potential that a portion of the foreign immunogen introduced may
have a similar peptide sequence or to be structurally similar to a component of one’s self. This
can lead to the body creating an immune response, not just to the introduced antigen, but to
normal components of one’s self, thereby leading to autoimmune reactions….This theory of
autoimmunity is known as molecular mimicry.” Pet. Ex. 15 at 5.

Dr. Longman accepted the petitioner’s experts’ description of molecular mimicry, stating,
“…molecular mimicry is the theoretical possibility that protein molecules from the Gardasil
vaccine can mimic self-peptides that are normally produced by the body, leading to an antigen
specific auto-immune response.” Resp. Ex. A at 3. Dr. Santoro also endorsed an innate
inflammatory response as a causal mechanism for the onset of petitioner’s diarrhea, beginning
roughly forty-four days after she received her second HPV vaccine. Pet. Ex. 14 at 8.

Molecular mimicry has been accepted as a sound and reliable theory to explain how
vaccines, including the HPV vaccine, can result in autoimmune diseases. See Salmins v. Sec’y of
Health & Human Servs., No. 11-140V, 2014 WL 1569478, at *14 (Fed. Cl. Spec. Mstr. Mar. 31,
2014) (finding that the HPV vaccine can cause Guillain-Barre syndrome through a mechanism of
molecular mimicry); Harmon v. Sec’y of Health & Human Servs., No. 12-298V, 2017 WL
2872293, at *23 (finding that molecular mimicry is a reliable causal mechanism for how the
HPV could cause a central demyelinating condition); McCulloch v. Sec’y of Health & Human
Servs., No. 09-293V, 2015 WL 3640610, at *28 (finding that molecular mimicry is a reliable
causal mechanism for how the HPV could cause a seizure disorder). Additionally, I have also
accepted that an inflammatory response to a vaccine by the innate immune system can cause
vaccine-related injuries. See Morgan v. Sec’y of Health & Hum. Servs., No. 13-592V, 2015 WL
9694667 (Fed. Cl. Spec. Mstr. Dec. 10, 2015) (finding that an innate inflammatory response to
the Gardasil vaccine caused petitioner’s ulcerative colitis). However, both theories rest on the

25
assumption that an individual’s immune system will have an immune response, innate and
adaptive, to the vaccine components. Due to the fact that petitioner has an underlying primary
immune deficiency, resulting in no immune response to vaccines she has received, including the
HPV vaccine, my determination as to causation turns on the analysis of Loving Prong
Five/Althen Prong Two.

Due to petitioner’s underlying primary immunodeficiency, the determination as to
vaccine causation turns on Loving prong five/Althen prong two. As I have concluded, as will be
discussed below, that she is unable to satisfy Loving prong five/Althen prong two. Therefore, it is
not necessary to make a Loving prong four/Althen prong one determination. See Winkler v. Sec’y
of Health & Hum. Servs., No. 18-203V, 2021 WL 6276203 (Fed. Cl. Spec. Mstr. Dec. 10, 2021),
mot. for review denied, 2022 WL 1528779, aff’d 88 F.4th 958 (Fed. Cir. 2023) see also Vaughn
ex rel. A.H. v. Sec’y of Health & Hum. Servs., 107 Fed. Cl. 212, 221-22 (2012) (finding the
special master’s failure to rule on Althen prong one was not fatal to his decision because Althen
prong two was fatal to petitioner’s claim); Hibbard v. Sec’y of Health & Hum. Servs., 698 F.3d
1355, 1364 (Fed. Cir. 2012) (“Given that [petitioner] had to show both the medical plausibility of
her theory of causation and that she suffered an injury consistent with that theory of causation,
there was no reason to require the special master to address the first question when the answer to
that question could have no possible effect on the outcome of the case.”) Even if I accepted
petitioner’s theory arguendo, I find that petitioner did not provide preponderant evidence of
logical sequence of cause and effect due to petitioner’s pre-existing primary immunodeficiency
at the time she received the two HPV vaccines in 2013, because she had no immune response to
the vaccines, innate and/or adaptive.

2. Loving Prong Five/Althen Prong Two

Under Loving Prong Five/Althen Prong Two, petitioner must prove by a preponderance
of the evidence that there is a “logical sequence of cause and effect showing that the vaccination
was the reason for the injury.” Capizzano, 440 F.3d at 1324 (quoting Althen, 418 F.3d at 1278).
This prong is sometimes referred to as the “did it cause” test; i.e. in this particular case, did the
vaccine(s) cause the alleged injury. Loving at 144.; Broekelschen, 618 F. 3d at 1345 (“Because
causation is relative to the injury, a petitioner must provide a reputable medical or scientific
explanation that pertains specifically to the petitioner’s case”). “Petitioner must show that the
vaccine was the ‘but for’ cause of the harm…or in other words, that the vaccine was the ‘reason
for the injury.’ ” Pafford, F.3d at 1356.

In this case, petitioner cannot show by preponderant evidence that the HPV vaccines she
received in 2013 was the “but-for” cause of her gastrointestinal injuries or exacerbated her pre-
existing alopecia because of her underlying primary immunodeficiency disorder.

Even though petitioner was not diagnosed with a primary immunodeficiency disease until
approximately five months post-vaccination, petitioner’s pre-vaccination medical history
included signs and symptoms consistent with a course of a primary immunodeficiency described
in the medical literature submitted in this matter, her treating physicians diagnosed petitioner
with common variable immunodeficiency disease, and her medical records revealed nearly
absent levels of antibodies of all classes.

26
The opinions of petitioner’s experts were significantly flawed in two respects. First, they
discounted frequent infections and hives in the year or more prior to her vaccination and made
conclusory statements that petitioner was healthy prior to receiving the HPV vaccines. Second,
petitioner’s experts apparently relied on Dr. Marks’ initial hypothesis that petitioner’s extremely
low immunoglobulin levels were secondary to her prolonged diarrhea while ignoring Dr. Marks’
revised and ultimate opinion that petitioner had a primary immunodeficiency and because of
petitioner’s underlying immunodeficiency disease she had mounted no immune response to the
vaccines.

Common variable immunodeficiency disease is a primary immunodeficiency disease
characterized by reduced serum immunoglobulins. Resp. Ex. I at 1. Reduced levels of of IgG
and IgA and/or IgM, normal or decreased B cell numbers, and impaired antibody response lead
to recurrent infections, noted mostly in the respiratory and gastrointestinal tracts. Resp. Ex. D at
1; see also Resp. Ex. C at 1. While the underlying cause of CVID is unknown, it is described as a
“failure in B cell differentiation, with impaired secretion of immunoglobulins, but T cell
abnormalities, including decreased lymphocyte proliferation to mitogen and antigens, deficiency
of antigen-primed T cells, and reduced production and/or expression of IL-2 and other cytokines
are common.” Resp. Ex. I at 1. There is a high prevalence of gastrointestinal complaints and
issues among CVID patients. Resp. Ex. D at 1. According to the Khodadad article, between
20% and 60% of individuals with CVID develop diarrheal disease, and chronic watery diarrhea
is common in CVID. Resp. Ex. D at 5. “Some patients with CVID present with gastrointestinal
problems as their first clinical presentation, while other develop GI complications during the
course of the disease.” Id. Furthermore, while the esophagus is not commonly involved in
CVID, some patients who are on chronic antibiotics can develop drug-induced esophagitis or
esophageal candidiasis as a side effect of the antibiotics. Id.

According to the Cunningham and Rundles article, there is approximately a 4–6-year lag
time between when symptoms initially occur and the diagnosis of CVID is made. Resp. Ex. I at
11. Because patients with CVID present with varied illnesses, including gastrointestinal issues
or recurring respiratory infections, they are treated by multiple physicians, which can delay
recognition of the antibody deficiency. Id. at 1. Standard treatment for CVID is periodic IVIG
infusions. Id. at 2.

Prior to receiving the two HPV vaccinations in 2013, between January 2011 and February
2013, petitioner was treated for multiple sinus infections and given multiple courses of
antibiotics for treatment. See Pet. Ex. 9 at 2 (January 10, 2011: diagnosed with sinusitis and
prescribed Amoxicillin for ten days); Pet. Ex. 2 at 84 (May 31, 2011: Patient is status post-
treatment of 21 days of Augmentin which she states alleviated her nasal congestion and pressure
significantly. She also states that starting Zyrtec did not seem to significantly improve the
occurrence of her hives.); Pet. Ex. 9 at 4 (December 31, 2011: 14-year old with a history of
prolonged sinus infection over the spring and summer that caused hives, took an antibiotic for 3-
4 weeks until it resolved); Pet. Ex. 9 at 6 (January 9, 2013: patient has painful right outer ear,
also coughing and congested with yellowish sinus drainage four times a day. Diagnosed with
sinusitis and was prescribed a course of Amoxicillin for ten days); Pet. Ex. 9 at 6 (January 30,
2013: patient is coughing with congestion, did not finish Amoxicillin. Diagnosed with bronchitis

27
and rhinitis, prescribed Azithromycin, an antibiotic); Pet. Ex. 9 at 7 (February 18, 2013: Horse
voice and neck feels swollen for two days, finished Z-pack); Id. at 8 (April 20, 2013: patient has
runny nose, coughing, and green discharge for five days. Diagnosed with bronchitis and rhinitis
and gave another Z-pack); see also Pet. Ex. 9 at 7 (April 29, 2013: bronchitis and rhinitis sinus
infection and hives all over body. Persistence of congestion and coughing. Given a course of
Augmentin for fourteen days).

Despite this extensive history of chronic and recurrent sinus infections, petitioner’s
experts contended that petitioner did not have recurrent infections or at least that she did not have
an extraordinary history of infections. Dr. Santoro wrote, “If the patient had a genetic IgG
deficiency, she would have had a long history of bronchitis, pneumonia, ear infections and
sinusitis, which is common with such a deficiency. I did not see any extraordinary such
reporting of these problems in [petitioner’s] records.” Pet. Ex. 20 at 3 (emphasis added). Dr.
Santoro also suggested that if there had been a historical problem that pre-dated the vaccinations,
petitioner would have already been treated with IVIG.

However, as explained by Dr. Longman and supported by the Cunningham-Rundles
article, delay in diagnosis of CVID is common because patients present with an array of illnesses
to multiple physicians. See Resp. Ex. G at 2; Resp. Ex. I at 1. Even though petitioner was not
diagnosed with a primary immunodeficiency until September 2013, prior to her diagnosis, she
was treated by multiple doctors for different issues, including urticaria, chronic sinusitis,
bronchitis, warts, and prolonged diarrhea as recounted above. In 2013, petitioner had multiple
trips to her primary pediatrician between January and July for chronic sinus infections with
prolonged treatment with antibiotics. See Pet. Ex. 9 at 7-8 (4/29/13: review bronchitis and
rhinitis, sinus infection; hives all over body; persistent congestion, cough, and sinus headache, a
little better on antibiotics but came back; still having hives over entire body; 5/1/13: Follow-up:
reaction to Augmentin? Hives all over; swollen fingers; currently on prednisone; 6/12/13:
coughing, hives for three months, diarrhea for one week, refer for allergy evaluation; 6/24/13:
still has diarrhea twice a day, left ear hurts, wax in both ears, urticaria resolved, prescribed
Azithromycin; 7/2/13: still has diarrhea, third visit since 6/12/13, refer to GI-CHM, CBC
normal).

Even with her prolonged diarrhea which began in June 2013, it was not until July 15,
2013, when allergist-immunologist Dr. James Fordyce recommended that petitioner have her
antibody levels were tested. Pet. Ex. 2 at 79. On July 19, 2013, petitioner’s antibody tests
revealed significantly low IgA (less than 8 mg/dl), significantly low IgE (less than 2 IU/ml), low
IgG serum of 70 mg/dL, and low IgM. Pet. Ex. 2 at 72. It was then petitioner was referred to
Dr. Marks of immunology for the concerning low levels of antibodies.

Petitioner’s treating physicians also acknowledged petitioner’s history of recurrent
infections when diagnosing her with a primary immunodeficiency. At petitioner’s second
appointment with Dr. Marks on September 25, 2013, petitioner’s mother reported that petitioner
had been experiencing severe warts and regular sinus infections that began two years prior. The
exact note from this appointment states:

28
She did call to my attention, which we did not discuss at our last visit, that [petitioner]
has been experiencing quite severe plantar warts on her right foot, involving four of the
five toes. In addition to this, she has been experiencing warts on her face. Again, when
looking back, the warts also started approximately two years ago, which is when
[petitioner] started becoming sick quite regularly with sinus infections, per Mom.

Pet. Ex. 2 at 56 (emphasis added). Dr. Marks opined, “Given this constellation of symptoms
with complete agammaglobulinemia, recurrent infections, and warts, I do have some concerns
for WHIM’s syndrome; however, she does not have the typical variants with abnormalities on
CBC with neutropenia that can be seen.” Id. at 57. Additionally, when petitioner was evaluated
by Dr. Brian Berman one year later, on August 27, 2014, he wrote that petitioner “was well until
three years ago when she began to develop recurrent sinusitis. She received multiple antibiotics
and never required hospitalization.” Pet. Ex. 3 at 5. The evidence that petitioner had repeated
sinus and bronchitis infections treated with antibiotics is incontrovertible and is consistent with
the diagnosis of a primary immune deficiency.

Dr. Santoro also argued that petitioner’s agammaglobulinemia was caused by
inflammatory colitis and wrote, “Dr. Mark’s opinion clearly stated that the petitioner had
ulcerative colitis that this explained her low immune globulin levels after the onset of her
ulcerative colitis and diarrhea, but not before,” and, “[Dr. Marks] was of the opinion that
[petitioner] did not have CVID.” Pet. Ex. 20 at 4. While Dr. Santoro is correct that when Dr.
Marks first met with petitioner on August 5, 2013, she considered that petitioner was losing
“immunoglobulins of all classes through her stools,” but also cautioned that she wanted to do
repeat blood work after a few weeks of treatment of colitis with Asacol to see if her levels
rebounded. See Pet. Ex. 2 at 65. When petitioner returned to Dr. Marks on September 25, 2013
and petitioner’s diarrhea had subsided, she again noted that petitioner had “no immunoglobulins,
including IgG, IgA, as well as IgM.” Id. at 56. Dr. Mark’s opined after this appointment
“atypical agammaglobulinemia or WHIM syndrome variant.” Id. At the November 4, 2013
follow-up with Dr. Marks, petitioner’s diagnosis was “primary immune deficiency, recurrent
infection, and agammaglobulinemia.” Pet. Ex. 12A at 472. At petitioner’s appointment with Dr.
Savasan in December 2013, again she had “almost undetectable levels of immunoglobulins,
including IgG, IgA, IgM, and IgE.” Pet. Ex. 2A at 405. When Dr. Berman met with petitioner,
he aptly diagnosed her with “B-cell immunodeficiency, with a history of presumed autoimmune
alopecia and transient inflammatory bowel process associated with propensity toward papilloma
virus,” and that “the possibility of WHIM syndrome seems very real.” Pet. Ex. 3 at 6. Thus, the
medical records do not support Dr. Santoro’s assertions that petitioner’s agammaglobulinemia
was secondary to her diarrhea, as her immune deficiency continued well after resolution of her
diarrhea. Ultimately, Dr.Marks, Dr.Savasan and later Dr. Lauter and Dr. Berman diagnosed
CVID and Dr. Marks and Savasan noted that petitioner had not mounted an immune response to
the vaccines that she had received also consistent with CVID.

With respect to petitioner’s alopecia, aside from her condition worsening after she
received the two HPV vaccines and that alopecia areata is considered an autoimmune condition,
petitioner’s expert, Dr. Glashofer’s opinion rested entirely on the assumption that petitioner had
a reaction to the HPV vaccine. See Pet. Ex. 15 at 5 (“…the Gardasil vaccination set off a
reaction of inducing various disease states of autoimmunity in the petitioner.”). The medical

29
literature Dr. Glashofer referenced to support his opinion did little to advance petitioner’s
argument that the HPV aggravated her alopecia. The Chu et al. article is a case report of young
child developing alopecia within one week of receiving a vaccine different from the HPV
vaccine. Pet. Ex. 15B at 3. The Geier and Geier article is a review of VAERS data of adverse
events post Gardasil vaccination, which provides evidence of increased reporting of diagnoses of
alopecia post-HPV vaccination. However, even if these articles provided any mechanistic
evidence which they do not, they suffer from the same problem as other general articles on the
subject as applied to the present case in that it does not provide any evidence of causation in a
person with a severe immune deficiency such as that suffered by the petitioner.

Petitioner also argues that Dr. Tamburro, a physician at the Cleveland Clinic, associated
the Gardasil vaccine with the onset or change in petitioner’s alopecia. Pet. Response at 26. This
mischaracterizes the medical records from Dr. Tamburro. At petitioner’s first appointment with
Dr. Tamburro on July 23, 2014, Dr. Tamburro noted that petitioner’s hair loss began prior to her
diagnosis of agmmaglobulinemia in August 2013. Pet. Ex. 5 at 3. She also noted that petitioner
had viral warts. Id. After an examination, Dr. Tamburro diagnosed petitioner with alopecia
areata, verruca plana, and verruca vulgaris and wrote, “likely related to agammaglobulinemia or
other immune differential.” Pet. Ex. 5 at 4 (emphasis added). At the follow-up appointment on
September 22, 2014, petitioner reported that her alopecia had worsened. Id. at 11. She
documented multiple spots of hair loss in the frontal, parietal and occipital areas of the head as
well on various other locations on her body. Dr. Tamburro diagnosed petitioner with alopecia
areata and noted that it has “an unpredictable course.” Id. at 12. Dr. Tamburro also wrote,
“Alopecia areata can be triggered by vaccines (such as Gardasil), but usually would occur in
closer proximity to the vaccination [than] [petitioner’s] alopecia.” Id. While Dr.Tamburro
apparently answered a question about Gardasil causation of alopecia, refencing possible general
vaccine causation, her opinion was that petitioner’s condition was more likely related to
agammaglobulinemia. This view is supported by the Cunningham-Rundles article, which notes,
“For unknown reasons, autoimmune diseases, particularly autoimmune hemolytic anemia,
autoimmune thrombocytopenia, rheumatoid arthritis, and pernicious anemia, are relatively
common in this patient group.” Resp. Ex. I at 1. Thus, the general statement of Dr. Tamburro
associating alopecia causation to vaccines is not sufficient to overcome the overwhelming
evidence that petitioner had a primary immunodeficiency disease that was more likely the cause
of her alopecia, considering she had no response to the HPV vaccine or other vaccines she had
received in the past.

Petitioner cannot show how the theories posited by her experts, which assume activation
of petitioner’s immune system, could cause autoimmune injuries, in the absence of an immune
response to the HPV vaccine. Even if I had accepted any of petitioner’s experts’ theories as to
vaccine causation of gastrointestinal disease or alopecia areata, there would be no logical
sequence of cause and effect because petitioner did not have an immune response to the HPV
vaccine, or any vaccine for that matter.

Petitioner’s bloodwork included testing for antibodies against tetanus and diphtheria,
which showed no antibodies to either antigen despite receiving multiple vaccines containing the
two antigens. Pet. Ex. 2 at 12. At petitioner’s appointment on November 3, 2013, petitioner and
her mother discussed getting a flu vaccine with Dr. Marks and Dr. Marks explained, “there is no

30
reason that we cannot give her [a flu shot], but I do not think she will amount much of a response
given her immune system at this time.” Pet. Ex. 12A at 472. On the December 6, 2013
appointment record with Dr. Savasan, the “Immunization Status,” section states, “[petitioner]
received all of her immunizations, receiving two of the three doses of Gardasil; however,
[petitioner] has not mounted an immune response to vaccines.” Pet. Ex. 2 at 46; Pet. Ex. 12A at
404. These statements by Dr. Marks and Dr. Savasan are unequivocal. Not only did petitioner
not have an immune response to the HPV vaccines or tetanus/diphtheria, she had repeated blood
work that showed immunoglobulins were undetectable. There is no evidence that petitioner had
any type of immune reaction to the HPV vaccines, either an innate or adaptive, without which it
difficult to see how the vaccine could have caused a cross reaction giving rise to any of the
various conditions claimed by petitioner particularly given that they were more likely explained
by her CVID.

Evidence of other possible sources of injury can be relevant not only for the “factors
unrelated” defense, but also as to whether prima facie showing has been made that the vaccine
was a substantial factor in causing the injury in question. Stone v. Sec’y of Health & Hum.
Servs., 676 F.3d 1373, 1379 (Fed. Cir. 2012); see e.g. de Bazan v. Sec’y of Health & Human
Servs., 538 F.3d 1347, 1353 (Fed. Cir. 2008) (“The government, like any defendant, is permitted
to offer evidence to demonstrate the inadequacy of the petitioner’s evidence on a requisite
element of petitioner’s case-in-chief.”). “In some cases, a sensible assessment of causation
cannot be made while ignoring the elephant in the room—the presence of compelling evidence
of a different cause for the injury in question.” Stone, F.3d at 1380 (citing Walther, 485 F.3d at
1151 n.4). Here, the elephant in the room is petitioner’s underlying primary immunodeficiency
disease that serves as compelling evidence of a different cause of her alleged injuries, and she
cannot show that the HPV vaccinations were the but-for cause of her gastrointestinal illnesses or
significant aggravation of her alopecia.

For the reasons discussed above, I find that petitioner has failed to provide preponderant
evidence of a local sequence of cause and effect required under Loving prong five/Althen Prong
Two.

3. Loving Prong Six/Althen Prong Three

The final Loving prong requires petitioner to establish a “proximate temporal
relationship” between the significant aggravation of his condition and the received vaccine.
Loving 86 Fed. Cl. at 144; see also Althen, 418 F.3d at 1281. That term has equated to the
phrase, “medically-acceptable temporal relationship.” Althen at 1281. A petitioner must offer
“preponderant proof that the onset of symptoms occurred within a timeframe which, given the
medical understanding of the disorder’s etiology, it is medically acceptable to infer causation.”
de Bazan v. Sec’y of Health & Human Servs., 539 F.3d 1347, 1352 (Fed. Cir. 2008). The
explanation for what is a medically acceptable timeframe must also coincide with the theory of
how the relevant vaccine can cause an injury (Althen prong one). Id. at 1352.

The explanation for what is a medically acceptable time frame must also coincide with
the theory of how the relevant vaccine can cause the injury alleged (under Althen Prong One).
Id.; Koehn v. Sec’y of Health & Hum. Servs., 773 F.3d 1239, 1243 (Fed. Cir. 2014); Shapiro, 101

31
Fed. Cl. at 542; see also Pafford, 451 F.3d at 1358. A temporal relationship between a vaccine
and an injury, standing alone, does not constitute preponderant evidence of vaccine causation.
See, e.g., Veryzer, 100 Fed. Cl. at 356 (explaining that “a temporal relationship alone will not
demonstrate the requisite causal link and that [P]etitioner must posit a medical theory causally
connecting the vaccine and injury”).

Based on petitioner’s medical records, the onset of petitioner’s gastrointestinal illness
began in or around June 6, 2013, approximately forty-four days after she received her second
HPV vaccine on April 22, 2013. Petitioner’s expert, Dr. Santoro opined that this timeframe is
medically appropriate for an innate inflammatory response to the vaccine and referenced
Morgan, an HPV-ulcerative colitis case. However, aside from the fact that petitioner’s
underlying primary immunodeficiency disease caused her to have no immune response to the
HPV vaccine, inflammatory or adaptive, the facts and expert opinion in Morgan differ
significantly from this one. The onset of petitioner’s gastrointestinal symptoms in Morgan began
six-hours after the HPV vaccination, became continuous, she needed extensive surgical resection
of her colon, and there was no alternative explanation for the onset of petitioner’s symptoms.
Morgan, 2015 WL 9694667, at *15. Further, the expert in Morgan, her gastrointestinal surgeon,
opined that the vaccine triggered an initial innate inflammatory response and that the cytokines
from the innate response signaled an adaptive immune response causing the autoimmune
condition of ulcerative colitis. Id. In contrast, the onset of petitioner’s diarrhea in this case was
forty-four days after petitioner received the second HPV vaccine on April 22, 2013 and largely
resolved with medication, which is more consistent with a gastrointestinal illnesses secondary to
a primary immunodeficiency disease. See Resp. Ex. D at 5 (“Some patients may present with GI
problems as their first clinical presentation, while other develop GI complications during the
course of the disease.”); see also Resp. Ex. C at 3 (“Often, in these patients, appearance of
Crohn’s-like inflammatory bowel disease findings in the intestine supports immunodeficiency
findings that are triggered by infections of inflammatory bowel disease etiology.”). Thus, the
onset of petitioner’s diarrhea forty-four days post-vaccination is significantly more consistent
with a condition incident to common variable immune deficiency.

The date of onset of the worsening of petitioner’s pre-existing alopecia is more uncertain
than the date of onset of her gastrointestinal illness, aside from it happening sometime after the
second HPV vaccination she received on April 22, 2013. Petitioner reported to Dr. Savasan in
December 2013 that she was experiencing hair loss on her scalp and at her appointment with Dr.
Berman, petitioner described developing “widespread alopecia” after she was started on IVIG
infusions. See Pet. Ex. 12A at 403; Pet. Ex. 3 at 5. Further, one of petitioner’s treating
physicians, Dr. Tamburro suggested that the onset of petitioner’s alopecia, or worsening of her
alopecia, occurred too long after the HPV vaccination. See Pet. Ex. 5 at 12. The medical records
would put the onset of petitioner’s alopecia becoming worse approximately four to six months
post-vaccination, which would exceed what has been considered an acceptable medical
timeframe to infer vaccination causation. Thus, petitioner has failed to satisfy Loving Prong
Six/Althen Prong Three.

32
V. Conclusion

After a careful review of the record, petitioner has failed to provide preponderant
evidence that her gastrointestinal illness or her alopecia were caused by or were significantly
aggravated by the HPV vaccines she received on February 18, 2013, and April 22, 2013.
Accordingly, petitioner’s claim is hereby DISMISSED.

IT IS SO ORDERED.

s/Thomas L. Gowen
Thomas L. Gowen
Special Master

33

---

Source: Frix Law Library, https://www.frixlaw.com/law-library/cases/10733947. Public record. Not legal advice.