The opinion
In the United States Court of Federal Claims
OFFICE OF SPECIAL MASTERS
No. 18-757V
Filed: May 28, 2024
DEREK GRACE,
Petitioner,
v.
SECRETARY OF HEALTH AND
HUMAN SERVICES,
Respondent.
Diana Lynn Stadelnikas, Magio Christopher & Toale, PA, Sarasota, FL, for petitioner
Voris Edward Johnson, U.S. Department of Justice, Washington, DC, for respondent
Decision1
On May 29, 2018, petitioner, Derek Grace, filed a petition under the National
Childhood Vaccine Injury Act, 42 U.S.C. § 300aa-10-34 (2012)2, alleging that an
influenza (“flu”) vaccination he received on November 9, 2016, caused him to develop
IgA vasculitis or Henoch-Schonlein purpura (“HSP”). (ECF No. 1, pp. 1-2; ECF No. 9,
pp. 1-2.) For the reasons set forth below, I conclude that petitioner is not entitled to an
award of compensation.
I. Applicable Statutory Scheme
Under the National Vaccine Injury Compensation Program, compensation
awards are made to individuals who have suffered injuries after receiving vaccines. In
general, to gain an award, a petitioner must make a number of factual demonstrations,
including showing that an individual received a vaccination covered by the statute;
1 Because this document contains a reasoned explanation for the action taken in this case, it must be
made publicly accessible and will be posted on the United States Court of Federal Claims' website, and/or
at https://www.govinfo.gov/app/collection/uscourts/national/cofc, in accordance with the E-Government
Act of 2002. 44 U.S.C. § 3501 note (2018) (Federal Management and Promotion of Electronic
Government Services). This means the document will be available to anyone with access to the
internet. In accordance with Vaccine Rule 18(b), Petitioner has 14 days to identify and move to redact
medical or other information, the disclosure of which would constitute an unwarranted invasion of privacy.
If, upon review, I agree that the identified material fits within this definition, I will redact such material from
public access.
2 Within this decision, all citation to § 300aa will be the relevant sections of the Vaccine Act at 42 U.S.C. §
300aa-10-34.
1
received it in the United States; suffered a serious, long-standing injury; and has
received no previous award or settlement on account of the injury. Finally – and the key
question in most cases under the Program – the petitioner must also establish a causal
link between the vaccination and the injury. In some cases, the petitioner may simply
demonstrate the occurrence of what has been called a “Table Injury.” That is, it may be
shown that the vaccine recipient suffered an injury of the type enumerated in the
“Vaccine Injury Table,” corresponding to the vaccination in question, within an
applicable time period following the vaccination also specified in the Table. If so, the
Table Injury is presumed to have been caused by the vaccination, and the petitioner is
automatically entitled to compensation, unless it is affirmatively shown that the injury
was caused by some factor other than the vaccination. § 300aa-13(a)(1)(A)-(B);
§ 300aa-11(c)(1)(C)(i); § 300aa-14(a).
In many cases, however, the vaccine recipient may have suffered an injury not of
the type covered in the Vaccine Injury Table. In such instances, an alternative means
exists to demonstrate entitlement to a Program award. That is, the petitioner may gain
an award by showing that the recipient’s injury was “caused-in-fact” by the vaccination
in question. § 300aa-13(a)(1)(A); § 300aa-11(c)(1)(C)(ii). In such a situation, of course,
the presumptions available under the Vaccine Injury Table are inoperative. The burden
is on the petitioner to introduce evidence demonstrating that the vaccination actually
caused the injury in question. Althen v. Sec’y of Health & Human Servs., 418 F.3d
1274, 1278 (Fed. Cir. 2005); Hines v. Sec’y of Health & Human Servs., 940 F.2d 1518,
1525 (Fed. Cir. 1991). In this case, petitioner’s alleged injury is not listed on the
Vaccine Injury Table relative to the flu vaccine. Petitioner must therefore meet the
burden of proof for establishing causation-in-fact.
The showing of “causation-in-fact” must satisfy the “preponderance of the
evidence” standard, the same standard ordinarily used in tort litigation.
§ 300aa-13(a)(1)(A); see also Althen, 418 F.3d at 1279; Hines, 940 F.2d at 1525.
Under that standard, the petitioner must show that it is “more probable than not” that the
vaccination was the cause of the injury. Althen, 418 F.3d at 1279. The petitioner need
not show that the vaccination was the sole cause but must demonstrate that the
vaccination was at least a “substantial factor” in causing the condition, and was a “but
for” cause. Shyface v. Sec’y of Health & Human Servs., 165 F.3d 1344, 1352 (Fed. Cir.
1999). Thus, the petitioner must supply “proof of a logical sequence of cause and effect
showing that the vaccination was the reason for the injury[,]” with the logical sequence
being supported by “reputable medical or scientific explanation, i.e., evidence in the
form of scientific studies or expert medical testimony.” Althen, 418 F.3d at 1278; Grant
v. Sec’y of Health & Human Servs., 956 F.2d 1144, 1148 (Fed. Cir. 1992). A petitioner
may not receive a Vaccine Program award based solely on his or her assertions; rather,
the petition must be supported by either medical records or by the opinion of a
competent physician. § 300aa-13(a)(1).
In what has become the predominant framing of this burden of proof, the Althen
court described the “causation-in-fact” standard, as follows:
2
Concisely stated, Althen’s burden is to show by preponderant evidence that
the vaccination brought about her injury by providing: (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 proximate temporal relationship between
vaccination and injury. If Althen satisfies this burden, she is “entitled to
recover unless the [government] shows, also by a preponderance of the
evidence, that the injury was in fact caused by factors unrelated to the
vaccine.”
Althen, 418 F.3d at 1278 (citations omitted). The Althen court noted that a petitioner
need not necessarily supply evidence from medical literature supporting petitioner’s
causation contention, so long as the petitioner supplies the medical opinion of an
expert. Id. at 1279-80. The court also indicated that, in finding causation, a Program
fact-finder may rely upon “circumstantial evidence,” which the court found to be
consistent with the “system created by Congress, in which close calls regarding
causation are resolved in favor of injured claimants.” Id. at 1280.
II. Procedural History
This case was initially assigned to another special master. (ECF No. 4.) It was
reassigned to the undersigned on August 27, 2019. (ECF Nos. 36-37.)
Petitioner filed medical records and a Statement of Completion in June of 2018.
(ECF Nos. 10-12; Exs. 1-12.) In February of 2019, respondent filed a Rule 4 Report
recommending against compensation. (ECF No. 21.) In addition to contending
petitioner had not met his burden of proof under any of the Althen prongs, respondent
also asserted that his treatment with Humira may have caused his condition. (Id. at 7.)
Respondent also filed three medical articles to support this proposition. (ECF No. 22;
Exs. A-C.)
Thereafter, petitioner filed additional medical records (Ex. 13), photographs of his
rash (Ex. 14), and an affidavit regarding his alleged damages (Ex. 15). (ECF Nos. 23,
29-30.) On December 16, 2019, petitioner filed an expert report by rheumatologist
Lindsay Lally, M.D., with supporting materials. (ECF Nos. 40-41; Exs. 16-27.)
Respondent filed a responsive report by Mehrdad Matloubian, M.D., Ph.D., on June 3,
2020. (ECF No. 45; Exs. D-P.) Petitioner then filed additional medical records (Ex. 28)
and a supplemental expert report and further supporting materials (Exs. 29-31). (ECF
Nos. 49, 51.) Respondent filed a responsive supplemental expert report. (ECF No. 53;
Ex. Q.) Petitioner filed still further medical records (Exs. 32-41) and a second
supplemental report by Dr. Lally (Exs. 42-48). (ECF Nos. 54-55, 60.)
On November 22, 2021, I held a Rule 5 conference. (ECF No. 62.) I noted that
Dr. Matloubian’s opinion as stated to that point was inadequate to support respondent’s
contention that Humira was a likely cause of petitioner’s condition. (Id. at 1-2.) Instead,
I advised that my preliminary view was that the case would turn on Althen prongs one
3
and three, which I felt were interrelated. (Id. at 1.) Petitioner requested an opportunity
to file a further supplemental report, and I instructed the parties identify dates on which
to schedule an entitlement hearing. (Id. at 3.)
In June of 2022, petitioner filed a fourth report by Dr. Lally (Exs. 49-52) and
additional medical records (Ex. 53). (ECF Nos. 67-68.) Respondent filed a final report
by Dr. Matloubian in August of 2022. (ECF No. 70; Ex. R.) An entitlement hearing was
set, but then cancelled after the parties jointly requested that the case be decided on
the written record. (ECF Nos. 72-73; Order (Non-PDF), 2/16/2023.) Petitioner
explained on behalf of the parties that “[u]pon review of the evidentiary record, in
preparation for the entitlement proceedings and after discussion with Respondent’s
counsel, the parties believe the issues at question to be clear and evidentiary record to
be complete in terms of resolving the issues.” (ECF No. 73, p. 1.)
Petitioner filed his motion for a ruling on the written record on June 2, 2023.
(ECF No. 75.) Respondent filed a response on July 6, 2023, and petitioner filed his
reply on August 18, 2023. (ECF Nos. 76, 78.) Accompanying his reply, petitioner filed
updated medical records and a declaration. (ECF No. 79; Exs. 54-59.)
This matter is now ripe for resolution. I have concluded that the parties have had
a full and fair opportunity to develop the record and that it is appropriate to resolve this
case without an entitlement hearing. See Kreizenbeck ex rel. C.J.K. v. Sec’y of Health
& Human Servs., 945 F.3d 1362, 1366 (Fed. Cir. 2020) (citing Simanski v. Sec’y of
Health & Human Servs., 671 F.3d 1368, 1385 (Fed. Cir. 2012)); see also Vaccine Rule
8(d); Vaccine Rule 3(b)(2).
III. Factual History
a. Medical Records
Although I have reviewed the complete medical records filed in this case, it is not
necessary to discuss the records in detail because the operative facts are undisputed.
Petitioner received a flu vaccine on November 9, 2016, at age 48. (Ex. 1, p. 5.) He had
a longstanding prior history of psoriasis and psoriatic arthritis for which he initially
treated with methotrexate but later switched to adalimumab, which was more effective.
(See Ex. 10, p. 281.) At the time of vaccination, petitioner was taking adalimumab once
monthly. (Id. at 245.) Typically, however, it is administered once every two weeks.
(Ex. D, p. 2.)
Following the vaccination, petitioner presented to an urgent care clinic on
November 14, 2016, with a complaint of “rash since 11/9/16.” (Ex. 2, p. 3.) Petitioner
explained that after he was administered his vaccination, he “noticed a rash later that
night.” (Id.) He subsequently developed diarrhea as well as joint, muscle and
abdominal pain, though he had no fever or chills. (Id.; Ex. 5, p. 3.) At urgent care, it
was initially felt that petitioner’s rash was “probably an immune response to
vaccination.” (Ex. 5, p. 4.) He was subsequently seen at the emergency department
4
and then evaluated by a dermatologist and was ultimately diagnosed with IgA
vasculitis/Henoch Schonlein Purpura following a skin biopsy. (Ex. 10, p. 81.) As
discussed below, both parties’ experts accept this diagnosis. (See Ex. 16, p. 2; Ex. D,
p. 2.) Petitioner was started on prednisone. (Ex. 10, p. 251.)
As of a follow up on November 18, 2016, petitioner’s skin lesions had improved
significantly, but he had severe abdominal pain and a CT scan suggested intestinal
inflammation. (Ex. 10, pp. 241, 136-37.) He was hospitalized from November 18, 2016
until November 22, 2016. (Id. at 556.) Petitioner reported to his rheumatologist that his
condition arose following vaccination, but the rheumatologist was more concerned that
the vasculitis could have been caused by his Humira treatment. (Id. at 565-66
(discussing case reports regarding adalimumab induced IgA vasculitis).)
By November 30, 2016, petitioner was noted to be “essentially symptom free”
after steroid treatment. (Ex. 10, p. 217.) However, he did later have some recurrent
skin lesions after tapering from his prednisone. (Id. at 196, 173.) Petitioner was later
seen at the Cleveland Clinic, where rheumatology felt petitioner’s vasculitis was either
idiopathic or secondary to his Humira treatment. (Ex. 7, p. 4.) One of the Cleveland
Clinic rheumatologists, Dr. Villa-Forte, ultimately noted the vasculitis “might still have
been caused by [H]umira – we can’t prove one way or another.” (Id. at 19.)
I have not located any instance within the medical records where any of
petitioner’s treating physicians ever attributed his condition to his flu vaccination
subsequent to his IgA vasculitis diagnosis. Nor has petitioner identified any such
notation. (ECF No. 75, pp. 3-6, 43-45; ECF No. 78, pp. 6-7.)
b. Declaration
Petitioner explains that prior to his vaccination he had an active lifestyle and a
good quality of life. (Ex. 59, p. 1.) He explains that he began noticing spots on his arms
during the evening following his vaccination. (Id.) Within a week, the spots became
painful and had spread, most severely on his legs. (Id.) Initially he went to urgent care,
but they were confused by his presentation and recommended he go to the emergency
department, which he did immediately. (Id.) Petitioner indicates he was in a constant
state of worry during his hospitalization and that “[t]hese were difficult times.” (Id. at 2.)
Even after his hospitalization he remained worried about the long-term effects of taking
large doses of steroids. (Id.) He describes recurrences of his condition as
“unpredictable and devastating” and a source of newfound worry. (Id.) He considers
himself “forever changed” and indicates he will never feel mentally and physically safe
again. (Id. at 5.)
5
IV. Expert Opinions and Qualifications
a. Petitioner’s expert, Lindsay Lally, M.D.3
Dr. Lally explains that IgA vasculitis, also known as Henoch-Schonlein Purpura,
is a form of systemic vasculitis more often seen in children than adults. (Ex. 16, p. 3.) It
has a presumed infectious trigger, which is consistent with observed increased
incidences occurring in fall and winter months. (Id.) Classic findings of the condition
include nonthrombocytopenic purpura,4 arthritis, abdominal pain, and proteinuria5 or
hematuria.6 (Id.) Skin involvement is generally most prominent on the lower
extremities. (Id.) Skin biopsy will show evidence of leukocytoclastic vasculitis with IgA
deposits in the vasculature observable on immunofluorescence. (Id.)
In petitioner’s case, he presented with a rash consistent with IgA vasculitis as
well as abdominal symptoms supportive of IgA affecting his gastrointestinal tract. He
also had findings of proteinuria and intermittent hematuria consistent with IgA vasculitis
renal involvement. (Ex. 16, p. 3.) Onset of his cutaneous lesions occurred within 24
3 Dr. Lally is a board certified rheumatologist, specializing in systemic vasculitis. (Ex. 16, p. 1; Ex. 17, p.
3.) She received her undergraduate degree from Princeton University and her medical degree from Weill
Cornell Medical College. (Ex. 17, p. 2.) She completed an internship and residency at New York
Presbyterian Hospital Weill Cornell Medical Center and a rheumatology fellowship at New York
Presbyterian Hospital and Hospital for Special Surgery. (Id.) She currently works as an Assistant
Professor of Medicine at both Weill Cornell Medical College and Hospital for Special Surgery. (Id. at 5.)
At the time her CV was filed in this case, she had written six peer-reviewed articles, six reviews, and three
chapters. (Id. at 11-12.) Dr. Lally has seen over “100 patients with various forms of small vessel
vasculitis.” (Ex. 16, p. 1.) Petitioner argues that I should place more weight on Dr. Lally’s opinion
because of her specific specialization in vasculitis. (ECF No. 75-1, pp. 8-10.) I have considered this
point, but do not find that this factor overcomes the shortcomings of petitioner’s showing under Althen as
discussed in the analysis below. Additionally, while Dr. Lally has greater specialization in vasculitis, Dr.
Matloubian is likewise a rheumatologist with the requisite clinical experience to offer his own competing
medical opinion and it must be further noted that Dr. Matloubian has added qualifications in immunology
that are particularly germane to several of his criticisms of Dr. Lally’s opinion as it pertains to Althen
prongs one and three.
4 “Purpura” refers to a group of conditions characterized by small hemorrhages in the skin or other
membrane surfaces, which may be due to blood disorders, vascular abnormalities, or trauma. Purpura,
DORLAND’S MEDICAL DICTIONARY ONLINE,
HTTPS://WWW.DORLANDSONLINE.COM/DORLAND/DEFINITION?ID=42170, (last visited May, 24, 2024).
“Nonthrombocytopenic purpura” is “purpura without any decrease in platelet count of the blood.”
Nonthrombocytopenic purpura, DORLAND’S MEDICAL DICTIONARY ONLINE,
https://www.dorlandsonline.com/dorland/definition?id=101157&searchterm=nonthrombocytopenic+purpua
(last visited May, 24, 2024).
5 “Proteinuria” refers to “excessive serum proteins in urine, such as in renal disease, after strenuous
exercise, and with dehydration.” Proteinuria, DORLAND’S MEDICAL DICTIONARY ONLINE,
https://www.dorlandsonline.com/dorland/definition?id=41409&searchterm=proteinuria (last visited May
24, 2024).
6 “Hematuria” refers to “blood (erythrocytes) in the urine.”
Hematuria, DORLAND’S MEDICAL DICTIONARY
ONLINE, https://www.dorlandsonline.com/dorland/definition?id=21814&searchterm=hematuria (last visited
May 24, 2024).
6
hours of his vaccination. (Id. at 2; Ex. 29, p. 2.) IgA vasculitis can have a relapsing
course, which petitioner did. (Ex. 29, p. 1.) Prior to onset of his IgA vasculitis, petitioner
had a history of psoriasis, which placed him at increased risk of IgA vasculitis. (Ex. 16,
p. 5.) Petitioner treated his psoriasis with adalimumab (brand name Humira), which is a
type of biologic treatment known as a “TNF inhibitor or “TNFi” because it blocks a
particular inflammatory cytokine known Tumor Necrosing Factor alpha. (Ex. 16, pp. 3-
4.) Dr. Lally observes that IgA vasculitis has rarely been reported following this type of
treatment. (Id. at 3.) However, these reports generally show that the vasculitis is self-
limited and resolves when the treatment is discounted. (Id. at 3-4; Ex. 29, pp. 1-2.)
Because petitioner continued to have a relapsing course of IgA vasculitis after
discontinuance of adalimumab, and because he had been treating with adalimumab for
a decade prior to onset of his IgA vasculitis, it is unlikely his condition was related to that
treatment. (Ex. 16, pp. 3-4; Ex. 44, p. 2.)
Dr. Lally acknowledges that the casual mechanism of IgA vasculitis is unknown
but proposes that, as an autoimmune condition, the pathogenesis involves genetic and
environmental factors interacting to lead to IgA complex formation and deposition that
then leads to recruitment of pro-inflammatory neutrophils and results in tissue
destruction. (Ex. 16, p. 4 (citing Marieke H. Heineke et al., New Insights in the
Pathogenesis of Immunoglobulin A Vasculitis (Henoch-Schonlein Purpura, 16
AUTOIMMUNITY REVS. 1246 (2017) (Ex. 21)).) Citing a case series of 13 reported cases
of IgA vasculitis following vaccination (including four cases following the flu vaccine), Dr.
Lally asserts that vaccination can be implicated as among the environmental factors
leading to IgA vasculitis, along with infections and drugs. (Id. (citing Andreas Woerner
et al., IgA Vasculitis (Henoch-Schonlein): Case Definition and Guidelines for Data
Collection, Analysis, and Presentation of Immunisation Safety Data, 35 VACCINE 1559
(2017) (Ex. 27)); see also Rachael Kantor et al., Henoch-Schonlein Purpura Post-
Vaccination in a Pediatric Patient: A Rare but Possible Adverse Reaction to Vaccine, 22
ISR. MED. ASS’N J. 654 (2020) (Ex. 45).) Although she agrees the available evidence
supporting this link is “limited,” she suggests that research has been hampered by
underreporting of the condition and the lack of a uniform disease definition. (Ex. 16, p.
4; Ex. 29, p. 1.) She notes that other forms of vasculitis have also been reported as
adverse events following vaccination. (Ex. 16, p. 4-5 (citing Caterina Bonetto et al.,
Vasculitis as an Adverse Event Following Immunization – Systematic Literature Review,
34 VACCINE 6641 (2016) (Ex. 18)).) Dr. Lally agrees that immunizations are not a
“major” etiologic factor for IgA vasculitis but contends that they may be a trigger in
“select cases.” (Ex. 29, p. 1.)
Dr. Lally suggests that, because pre-existing psoriasis is an autoimmune
condition involving T cell dysregulation and autoreactive T cells, petitioner was more
susceptible to other autoimmune conditions. (Ex. 29, p. 2 (citing Yihua Cai et al., New
Insights of T Cells in the Pathogenesis of Psoriasis, 9 CELLULAR & MOLECULAR
IMMUNOLOGY 302 (2012) (Ex. 30)).) She proposes that petitioner’s vaccination
upregulated his immune response and led to an “exuberant host response.” (Id.) This
response resulted in bystander activation whereby activated antigen presenting cells in
turn activated pre-primed autoreactive T cells that initiated the autoimmune disease,
7
ultimately leading to the inappropriate IgA production and immune complex formation
seen in IgA vasculitis. (Id.) Dr. Lally acknowledges that IgA response following
influenza vaccination is “poorly understood,” but cites a study that she indicates shows
successive exposures to influenza infection and vaccination does increase IgA
response to vaccination. (Ex. 44, pp. 2-3 (citing Rodrigo B. Abreu et al., IgA Responses
Following Recurrent Influenza Virus Vaccination, 11 FRONTIERS IMMUNOLOGY 1 (2020)
(Ex. 48)).)
Dr. Lally acknowledges that the immune process she describes typically peaks
around 7 days after an exposure. (Ex. 49, p. 1.) However, she does not agree that this
implies a brisker response is not possible. (Id.) She cites a case series of 19 IgA
vasculitis cases following Covid-19 vaccination, where the mean onset was 4 days, but
the most frequent interval was 1-2 days. (Id. (citing Hideo Hashizume et al.,
Immunoglobulin A Vasculitis Post-Severe Acute Respiratory Syndrome Coronavirus 2
Vaccination and Review of Reported Cases, 49 J. DERMATOLOGY 560 (2022) (Ex. 50)).)
She opines that, especially considering petitioner’s underlying psoriatic condition, the
proposed mechanism could unfold within 24 hours. (Ex. 29, p. 2.) She notes that it is
possible (but unknown) that petitioner may already have had elevated circulating IgA at
the time of his vaccination due to his psoriasis. (Ex. 49, p. 1 (citing E. Maverakis et al.,
The Psoriasis Glycome: Differential Expression of Cholesterol Particle Glycans and IgA
Glycans Linked to Disease Severity, J. INVESTIGATIVE DERMATOLOGY 1 (2022) (Ex. 51);
A. Damasiewicz-Bodzek & T. Wielkoszynski, Advanced Protein Glycation in Psoriasis,
26 J. EUR. ACAD. DERMATOLOGY 172 (2012) (Ex. 52)).)
b. Respondent’s expert, Mehrdad Matloubian, M.D., Ph.D.7
Dr. Matloubian agrees that petitioner suffered IgA vasculitis that was heralded by
onset of a rash occurring the day of his vaccination. (Ex. D, pp. 5, 14.) Specifically, Dr.
Matloubian places onset between 12-16 hours post-vaccination. (Id. at 9.) Treatment
with azathioprine resolved his major symptoms, but he then continued to have
occasional mild flares. (Id. at 5.) As Dr. Lally did, Dr. Matloubian discussed literature
that suggests there could be a causal relationship between TNFi treatment and
vasculitis. (Id. at 12-13.) He disagrees that petitioner’s later flares are a reason for
either favoring vaccine-causation or eliminating adalimumab as a causal factor (Ex. D,
p. 14; Ex. R, p. 2), but ultimately opined that “I do not know what causes petitioner’s
IgA/HSP and agree with Dr. Villa-Forte’s statement on 4/23/2017 that his vasculitis
7 Dr. Matloubian is a board certified rheumatologist. (Ex. E, p. 2.) He received an undergraduate degree,
medical degree, and Ph.D. in virology/immunology from the University of California, Los Angeles. (Id. at
1.) He also completed an internship, residency, fellowship in rheumatology, and a post-doctoral
fellowship at the University of California, San Francisco. (Id.) He is currently an associate adjunct
professor at the University of California, San Francisco. (Id. at 2.) His “areas of expertise include T and B
cell responses, especially to viruses as well as factors that regulate lymphocyte circulation and
trafficking.” (Ex. D, p. 1.) his research focuses on “innate and adaptive immune responses, including
those of T and B cells, to acute and chronic viral infections.” (Id.) Dr. Matloubian has published 36 peer
reviewed articles, and two review articles. (Ex. E, pp. 10-13.) Additionally, he “actively evaluates and
treats patients with complex autoimmune diseases at a tertiary referral center.” (Ex. D, p. 1.)
8
‘might still have been caused by [H]umira – we can’t prove one way or another.’” (Ex.
D, p. 12 (quoting Ex. 7, p. 19).)
Like Dr. Lally, Dr. Matloubian explains that IgA vasculitis involves immune
complex formation and deposition in tissue and, while the cause of IgA vasculitis is not
known, as an autoimmune condition genetic and environmental factors are thought to
be implicated. (Ex. D, p. 5) In particular, infection is thought to play a role. (Id.)
However, half or more of IgA cases do not have any identified environmental factor.
(Id.) Dr. Matloubian cites a literature review that observed that a majority of studies
have failed to show a causal association between vaccination and vasculitides,
including IgA vasculitis. (Id. (citing Fatma Dedeoglu & Susan Kim, IgA Vasculitis
(Henoch-Schonlein Purpura): Clinical Manifestations and Diagnosis, UPTODATE (last
updated Nov. 1, 2019) (Ex. I)).) Dr. Matloubian suggests that Dr. Lally’s theory of
causation is essentially based on temporality alone, given that she has not cited any
literature to support her specific invocation of bystander activation. (Id. at 6.) Further,
he asserts that Dr. Lally’s single supporting citation – Bonetto, et al. – does not actually
provide meaningful support for her opinion. (Id. at 6-7 (discussing Bonetto et al., supra,
at Ex. 18).) Although the Bonetto authors noted case reports purporting to link vasculitis
to vaccination, they present reasons for questioning the significance of those case
reports and ultimately concluded based on their further literature review that the existing
literature does not support the causative link. (Id. at 7 (discussing Bonetto et al., supra,
at Ex. 18, pp. 8-9).) Dr. Matloubian cites two small studies that he indicates show
patients with psoriatic arthritis treating with TNFi do not have increased risk of adverse
events after flu vaccination. (Id. at 8 (citing A. Polachek et al., Immunogenicity and
Safety of Vaccination Against Seasonal 2012 Influenza Virus Among Patients with
Psoriatic Arthritis and Psoriasis, 33 CLINICAL & EXPERIMENTAL RHEUMATOLOGY 181 (2015)
(Ex. L); Odile Launay et al., Immunogenicity and Safety of Influenza Vaccine in
Inflammatory Bowel Disease Patients Treated or Not with Immunomodulators and/or
Biologics: A Two-Year Prospective Study, 2015 J. CROHN’S & COLITIS 1096 (2015) (Ex.
M)).)
Further, Dr. Matloubian observes that IgA is typically produced by mucosal
infections (or intranasal live vaccines) whereas the flu vaccine generally results in IgG
antibodies. (Ex. D, p, 9 (citing CLAIRE-ANNE SIEGRIST, General Aspects of Vaccination,
in VACCINE IMMUNOLOGY (Ex. O)).) In any event, Dr. Matloubian suggests that the Lee
study he cites shows that the flu vaccine results in activation of influenza specific
antibody secreting cells, but not those that make antibodies to other antigens,
suggesting bystander activation, as invoked by Dr. Lally, is unlikely to result from a flu
vaccination. (Id. at 10-11 (discussing F. Eun-Hyung Lee et al., Circulating Human
Antibody-Secreting Cells During Vaccinations and Respiratory Viral Infections are
Characterized by High Specificity and Lack of Bystander Effect, 186 J. IMMUNOLOGY
5514 (2011) (Ex. N)).) Even following the stronger immune response experienced
during infection, onset of IgA vasculitis usually occurs after one to two weeks. (Id. at 11
(citing Woerner et al., supra, at Ex. 27, p. 2).) Dr. Matloubian acknowledges that the
Abrue, et al., study cited by Dr. Lally did measure serum IgA post flu vaccination;
however, he stresses that these measurements were taken 21-28 days post-vaccination
9
and the increase was only “minor,” being less than 2-fold. (Ex. R, p. 1 (discussing
Abreu et al., supra, at Ex. 48, p. 2).) Thus, he opines that these findings are not
supportive of an exaggerated IgA response to vaccination. (Id.) To the extent Dr. Lally
cites petitioner’s preexisting psoriasis as a source of T cell dysfunction, Dr. Matloubian
indicates that such abnormalities are not unique to psoriasis and that vaccines are
recommended as safe for people with various autoimmune diseases, including
psoriasis. (Ex. Q, pp. 2-3 (citing Christien Rondaan et al., Efficacy, Immunogenicity and
Safety of Vaccination in Adult Patients with Autoimmune Inflammatory Rheumatic
Diseases: A Systematic Literature Review for the 2019 Update of EULAR
Recommendations, 5 RHEUMATIC & MUSCULOSKELETAL DISEASES OPEN 1 (2019) (Ex. J);
Johanna Westra et al., Vaccination of Patients with Autoimmune Inflammatory
Rheumatic Diseases, 11 NATURE REV. IMMUNOLOGY 135 (2015) (Ex. K); Polachek et al.,
supra, at Ex. L; Launay et al., supra, at Ex. M).) Dr. Matloubian stresses that there is no
evidence within petitioner’s own clinical history that he experienced the “exuberant”
immune response to vaccination that Dr. Lally proposes. (Ex. R, p. 1.)
Dr. Matloubian also opines that it is “extremely unlikely” that the immune process
that Dr. Lally theorizes could occur within 12-16 hours. (Ex. D, p. 9.) Dr. Matloubian
explains that circulating antibodies, including IgA, are produced by plasma cells which,
in turn, are produced by either naïve or memory B cells. (Id.) It generally takes at least
four days for plasma cells to appear in circulation after vaccination. (Id. (citing Lee et
al., supra, at Ex. N).) Even accounting for Dr. Lally’s invocation of a recall response,
this still would take 2-3 days. (Ex. Q, p. 2 (citing Ex. D, p. 10 (fig.).) It then typically
takes several more days for secreted antibody cells to accumulate. (Ex. D, p. 9.) By
invoking bystander activation, Dr. Lally’s theory seeks an alternative to this process
whereby IgA secreting plasma cells are directly stimulated to produce more IgA. (Id. at
9-10.) However, Dr. Matloubian raises several issues with this alternative. First, unlike
B cells, plasma cells do not respond strongly to stimulation by their specific antigen. (Id.
at 9.) Thus, Dr. Matloubian suggests he is not aware of any cytokine or immunologic
agent that could do this. (Id. at 10.) Second, if this were possible, it would still involve a
multi-step process whereby antigen presenting cells migrate to the lymph nodes to
produce more circulating cytokines to activate more IgA secreting plasma cells that in
turn have to accumulate to a sufficient degree to deposit in tissue and recruit
neutrophils. (Id.) Dr. Matloubian opines that it is also difficult to see how this alternative
process could unfold in 12-16 hours. (Id.) Dr. Lally’s reliance on pre-primed
autoreactive T cells does not overcome the timing issue, because T cells would still
need to activate IgA producing B cells, which would in turn need to differentiate into
plasma cells. (Ex. Q, p. 2.)
V. Analysis
As discussed above, petitioner’s burden of proof in a cause-in-fact claim is to
meet the three-part Althen test, which includes (1) a general theory of causation
implicating the vaccine as a cause of the alleged condition, (2) a logical sequence of
cause and effect implicating the vaccination as a cause of petitioner’s own condition,
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and (3) appropriate timing of onset based on the theory of causation. 418 F.3d at 1278.
In this case, the parties present issues with respect to all three Althen prongs.
a. Althen prong one
Under Althen prong one, petitioner must provide a “reputable medical theory,”
demonstrating that the vaccine received can cause the type of injury alleged. Pafford
ex rel. Pafford v. Sec’y of Health & Human Servs., 451 F.3d 1352, 1355-56 (Fed. Cir.
2006) (quoting Pafford ex rel. Pafford v. Sec’y of Health & Human Servs., No. 01-
0165V, 2004 WL 1717359, at *4 (Fed. Cl. Spec. Mstr. July 16, 2004)). Such a theory
must only be “legally probable, not medically or scientifically certain.” Knudsen ex rel.
Knudsen v. Sec’y of Health & Human Servs., 35 F.3d 543, 548-49 (Fed. Cir. 1994).
Petitioner may satisfy the first Althen prong without resort to medical literature,
epidemiological studies, demonstration of a specific mechanism, or a generally
accepted medical theory. See Andreu ex rel. Andreu v. Sec’y of Health & Human
Servs., 569 F.3d 1367, 1378-79 (Fed. Cir. 2009) (citing Capizzano v. Sec’y of Health &
Human Servs., 440 F.3d 1317, 1325-26 (Fed. Cir. 2006)). However, “[a] petitioner must
provide a ‘reputable medical or scientific explanation’ for [her] theory. While it does not
require medical or scientific certainty, it must still be ‘sound and reliable.’” Boatmon v.
Sec’y of Health & Human Servs., 941 F.3d 1351, 1359 (quoting Knudsen, 35 F.3d at
548-49).
Dr. Lally opines that bystander activation can explain how the flu vaccine can
results in an exuberant immune response that in turn triggers an overproduction of IgA
leading to IgA vasculitis. (See Ex. 29, p. 2.) It must be stressed, however, that Dr. Lally
acknowledges that the evidence supporting any link between the flu vaccine and IgA
vasculitis is “limited” and that IgA response to the flu vaccination is “poorly understood.”
(Id. at 1; Ex. 44, p. 1.) Although there is no dispute that bystander activation is a valid
concept, Dr. Matloubian is persuasive in observing that Dr. Lally has provided no
support for her assertion that bystander activation can be invoked in this context.
Moreover, he has cited a study that shows that the flu vaccine results in activation of
influenza specific antibody secreting cells, but not those that make antibodies to other
antigens, suggesting bystander activation, as invoked by Dr. Lally, is unlikely to result
from a flu vaccination. (Ex. D, pp. 10-11 (discussing Lee et al., supra, at Ex. N).) Dr.
Lally did not rebut this point. Further, Dr. Matloubian explains that IgA is usually
produced by mucosal infection and the flu vaccine, by contrast, has been shown to
produce primarily IgG. (Id. at 9 (citing Siegrist, supra, at Ex. O, p. 3 (Table 2-2)).) Dr.
Lally cited Abrue, et al, for the proposition that the flu vaccine can produce IgA. (Ex. 44,
pp. 2-3 (citing Abrue et al., supra, at Ex. 48).) However, Dr. Matloubian is persuasive in
opining that the minor IgA findings observed in Abrue et al. are not consistent with the
type of exuberant immune response that Dr. Lally proposes would lead to an
overproduction of IgA. (Ex. R, p. 1.)
This leaves the case reports cited by Dr. Lally as the only remaining support for
her theory of causation. Dr. Matloubian has suggested reason to doubt the particular
case reports at issue, stressing that the Bonetto authors themselves did not believe a
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causal link was established despite having raised the case reports as some evidence.
(Ex. D, pp. 6-7 (citing Bonetto et al., supra, at Ex. 18, p. 3).) But in any event, though
they are some evidence, case reports are a particularly weak form of evidence. E.g.
Crutchfield v. Sec’y of Health & Human Servs., No. 09-39V, 2014 WL 1665227, at *19
(Fed. Cl. Spec. Mstr. Apr. 7, 2014) (“single case reports of Disease X occurring after
Factor Y . . . do not offer strong evidence that the temporal relationship is a causal
one—the temporal relationship could be pure random chance”), aff’d, 125 Fed. Cl. 251
(2014); see also Paluck v. Sec’y of Health & Human Servs., 104 Fed. Cl. 457, 475
(2012) (indicating that case reports “‘do not purport to establish causation definitively,
and this deficiency does indeed reduce their evidentiary value’. . . [but] ‘the fact that
case reports can by their nature only present indicia of causation does not deprive them
of all evidentiary weight.”), aff’d, 786 F.3d 1373 (Fed. Cir. 2015)). Especially given the
significant shortcomings in Dr. Lally’s reliance on bystander activation, the case reports
in evidence are inadequate to support Dr. Lally’s proposed theory.
For all these reasons, petitioner has not met his preponderant burden of proof
with respect to Althen prong one.
b. Althen prong three
The third Althen prong requires establishing a “proximate temporal relationship”
between the vaccination and the injury alleged. 418 F.3d at 1278. A petitioner must
offer “preponderant proof that the onset of symptoms occurred within a timeframe for
which, given the medical understanding of the disorder's etiology, it is medically
acceptable to infer causation-in-fact.” 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 coincide with the theory of how the relevant vaccine can cause an injury
(Althen prong one's requirement). Id. at 1352; Shapiro v. Sec’y of Health & Human
Servs., 101 Fed. Cl. 532, 542 (2011), mot. for recons. den’d after remand, 105 Fed. Cl.
353 (2012), aff’d, 503 Fed. Appx. 952 (Fed. Cir. 2013); Koehn ex rel. Koehn v. Sec’y of
Health & Human Servs., No. 11-355V, 2013 WL 3214877, at *26 (Fed. Cl. Spec. Mstr.
May 30, 2013), aff’d, 773 F.3d 1239 (Fed. Cir. 2014).
Dr. Lally has not provided any support for her assertion that bystander activation
leading to IgA vasculitis can occur in less than a single day. Instead, she has
acknowledged that the immune process underlying her opinion typically peaks after 7
days. (Ex. 49, p. 1.) She contends that this “does not imply that a brisker onset of IgA
vasculitis is not possible.” (Id.) However, Dr. Matloubian’s opinion is not based merely
on the “peak” of the immune response. He has explained in detail why the mechanisms
involved make it “extremely unlikely” that the process could result in disease within the
timeframe at issue in this case. (Ex. D, p. 9.) Dr. Lally has not rebutted Dr.
Matloubian’s detailed explanation of the multi-step immune process at all. To the extent
Dr. Lally referenced memory recall response and/or pre-existing autoimmunity as
reasons for suspecting a brisker onset, Dr. Matloubian addressed why neither concept
fundamentally changes the timing with respect to the overall multi-step immune process
at issue. (Ex. Q, p. 2 (citing Ex. D, p. 10 (fig.).)
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Even following infection, Dr. Matloubian suggests that onset of IgA vasculitis
usually occurs at least a week later. (Ex. D, p. 11 (citing Woerner et al., supra, at Ex.
27, p. 2).) Dr. Lally cited a case series of 19 cases of IgA vasculitis occurring after
Covid-19 vaccination. (Hashizume et al., supra, at Ex. 50, p. 1.) She stresses that the
series showed that onset most often occurred 1-2 days post-vaccination. (Ex. 49, p. 1.)
Critically, however, even if this series was sufficient to show that onset can occur more
quickly than Dr. Matloubian would accept,8 none of the reported cases had onset
occurring less than a day post-vaccination as seen in this particular case. (Hashizume
et al., supra, at Ex. 50, p. 3 (Table 1).)
For all these reasons, petitioner has not met his preponderant burden of proof
with respect to Althen prong three.
c. Althen prong two
The second Althen prong requires proof of a logical sequence of cause and
effect, usually supported by facts derived from a petitioner's medical records. Althen,
418 F.3d at 1278; Andreu, 569 F.3d at 1375–77; Capizzano, 440 F.3d at 1326-27;
Grant, 956 F.2d at 1147-48. Medical records are generally viewed as particularly
trustworthy evidence. Cucuras ex rel. Cucuras v. Sec'y of Health & Human Servs., 993
F.2d 1525, 1528 (Fed. Cir. 1993). However, medical records and/or statements of a
treating physician's views do not per se bind the special master. See § 300aa-13(b)(1)
(providing that “[a]ny such diagnosis, conclusion, judgment, test result, report, or
summary shall not be binding on the special master or court”); Snyder ex rel. Snyder v.
Sec’y of Health & Human Servs., 88 Fed. Cl. 706, 745 n. 67 (“there is nothing ... that
mandates that the testimony of a treating physician is sacrosanct—that it must be
accepted in its entirety and cannot be rebutted.”) A petitioner may support a cause-in-
fact claim through either medical records or expert medical opinion. § 300aa-13(a).
The special master is required to consider all the relevant evidence of record, draw
plausible inferences, and articulate a rational basis for the decision. Winkler v. Sec’y of
Health & Human Servs., 88 F.4th 958, 963 (Fed. Cir. 2023) (citing Hines, 940 F.2d at
1528).
For the reasons discussed above, petitioner has not preponderantly established
that the flu vaccine can cause IgA vasculitis. Nor, even assuming arguendo that it
could, has he preponderantly established that the onset of his own condition arose
within a timeframe from which vaccine causation could be inferred based on Dr. Lally’s
theory. Accordingly, he is not in a position to prevail under Althen prong two. It is also
worth noting that none of petitioner’s treating physicians opined that his IgA vasculitis
was vaccine caused and, moreover, as Dr. Matloubian observes, Dr. Lally has cited no
8 It should be noted that this case series involved a different vaccine.Some of the disagreement between
the experts as discussed under Althen prong one involves specific evidence regarding bystander
activation and IgA response specific to the flu vaccine. Accordingly, while I do not entirely discount this
case series, it cannot necessarily be assumed that what is true of the immune response to the Covid-19
vaccine would also be true of the flu vaccine given the experts’ differences under Althen prong one.
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aspect of petitioner’s own clinical history that would support the assertion that he
experienced a particular “exuberant” immune response. (Ex. R, p. 1.) Dr. Lally
speculates that petitioner’s pre-existing psoriasis may have resulted in already
circulating IgA at the time of vaccination, but acknowledges that this remains unknown.
(Ex. 29, p. 2.) She asserts that his psoriasis left him susceptible to additional
autoimmunity, but as explained in her first report, petitioner’s history of psoriasis alone
left him at a five-times greater risk of developing additional immune-mediated disease.
(Ex. 16, p. 5 (citing Yuki M.F. Andersen et al., Chronologic Order of Appearance of
Immune-Mediated Inflammatory Diseases Relative to Diagnosis of Psoriasis, 81 J. AM.
ACAD. DERMATOLOGY 1283 (2019) (Ex. 20)).) In that regard, Dr. Matloubian has stresses
that vaccination is considered safe and is recommended for patients with autoimmune
conditions. (Ex. Q, pp. 2-3.)
Further to this, respondent continues to highlight the possibility that petitioner’s
treatment with adalimumab may be a more likely explanation for his condition. (ECF
No. 76, p. 16.) Because petitioner cannot prevail in any event, it is not necessary to
resolve this question. However, I note in the interest of completeness that, regardless
of how well a causal relationship is supported by literature, Dr. Matloubian’s opinion
does not ultimately support adalimumab as a cause of petitioner’s own condition. Dr.
Matloubian indicated that “I do not know what caused petitioner’s IgA/HSP and agree
with Dr. Villa-Forte’s statement on 4/23/2017 that his vasculitis ‘might still have been
caused by [H]umira – we can’t prove one way or another.’” (Ex. D, p. 12 (quoting Ex. 7,
p. 19).) Accordingly, the outcome of this case does not turn on whether there is any
casual relationship between petitioner’s adalimumab treatment and his IgA vasculitis.
For all the reasons discussed above, petitioner has not met his preponderant
burden of proof with respect to Althen prong two.
VI. Conclusion
Petitioner has suffered and for that he has my sympathy. However, for all the
reasons discussed above, petitioner has not demonstrated by preponderant evidence
that his condition was caused by his vaccination. Accordingly, this case is dismissed.9
IT IS SO ORDERED.
s/Daniel T. Horner
Daniel T. Horner
Special Master
9 In the absence of a timely-filed motion for review of this Decision, the Clerk of the Court shall enter
judgment accordingly.
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