McNabb v. Secretary of Health and Human Services

In the United States Court of Federal Claims

OFFICE OF SPECIAL MASTERS

Filed: December 2, 2025

* * * * * * * * * * * * *

DEBORAH MCNABB *

*

Petitioner, * No. 19-1185V

*

v. * Special Master Gowen

*

SECRETARY OF HEALTH *

AND HUMAN SERVICES, *

*

Respondent. *

* * * * * * * * * * * * *

Meredith Daniels, Conway Homer, P.C., Boston, MA, for petitioner.

Nina Ren, U.S. Department of Justice, Washington, D.C., for respondent.

RULING ON ENTITLEMENT1

On August 13, 2019, Deborah McNabb (“petitioner”) filed her claim in the National

Vaccine Injury Compensation Program.2 Petition (ECF No. 1). Petitioner alleges that as a result

of receiving the influenza (“flu”) vaccine on September 29, 2016, she developed Drug Reaction

with Eosinophilia and Systemic Symptoms (“DRESS”) syndrome. Id. at Preamble; see also

Petitioner’s (“Pet’r”) Brief (“Br.”) at 1 (ECF No. 48). After a review of the record, I find that

petitioner has established by preponderant evidence that she is entitled to compensation.

I. Procedural History

Petitioner filed her claim on August 13, 2019 and filed medical records to support her

claim on September 4, 2019. Pet’r Exhibits (“Exs.”) 1-22 (ECF Nos. 7—9). Respondent filed

1

Pursuant to the E-Government Act of 2002, see 44 U.S.C. § 3501 note (2012), because this decision 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

decision will be available to anyone with access to the Internet. Before the decision 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 decision 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.

the Rule 4(c) Report on May 15, 2020 recommending against compensation, asserting that

petitioner had yet to file sufficient evidence to support vaccine causation. Respondent (“Resp’t”)

Report (“Rept.”) (ECF No. 14).

Petitioner filed a response to respondent’s Rule 4(c) report on June 15, 2020 and filed an

expert report by immunologist, Dr. David Rosenstreich3, and supporting medical literature. Pet’r

Ex. 24, 26—41. Respondent filed an expert report from dermatologist, Dr. Emanual Maverakis4,

and medical literature, on April 27, 2021. Resp’t Exs. A, Resp’t Exs. A, Tabs 1-8 (ECF No. 26).

The undersigned held a Rule 5 Status Conference on October 1, 2021, after which I

ordered petitioner to file a supplemental expert report. Rule 5 Order (ECF No. 29). Petitioner

filed a supplemental expert report by Dr. Rosenstreich on December 2, 2021. Pet’r Ex. 42 (ECF

No. 31). Respondent also filed a supplemental expert report by Dr. Maverakis on March 28,

2022. Resp’t Ex. B (ECF No. 35). After unsuccessful litigative risk negotiations, petitioner filed

a motion for a ruling on the record. Pet’r Br. (ECF No. 48). Respondent filed a response to

petitioner’s brief on April 4, 2024. Resp’t Br. (ECF No. 52). Petitioner has not filed a reply.

This matter is now ripe for adjudication.

II. Legal Standard for Adjudication

The Vaccine Act was established to compensate vaccine-related injuries and deaths. §

10(a). “Congress designed the Vaccine Program to supplement the state law civil tort system as a

simple, fair and expeditious means for compensating vaccine-related injured persons. The

Program was established to award ‘vaccine-injured persons quickly, easily, and with certainty

and generosity.’” Rooks v. Sec’y of Health & Hum. Servs., 35 Fed. Cl. 1, 7 (1996) (quoting H.R.

Rep. No. 908 at 3, reprinted in 1986 U.S.C.C.A.N. at 6287, 6344).

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Dr. David Rosentreich is currently the Director of the Division of Allergy and Immunology in the Department of

Medicine at Albert Einstein College of Medicine and Montefiore Medical Center located in the Bronx, New York.

Pet’r Ex. 25 at 1. He received his medical degree from the New York University School of Medicine in 1967, and is

Board Certified in Allergy and Immunology, and is licensed to practice medicine in the State of New York. Id. at 2.

He completed his residency at Bronx Municipal Hospital Center, then worked at the National Institute of Allergy

and Infectious Disease section at the National Institutes of Health from 1969-1979. Id. at 1-2. In 1980, Dr.

Rosenstreich began as an Associate Professor at Albert Einstein College of Medicine and also became an attending

physician. Id. at 2. Dr. Rosenstreich has served as a member of the Data Safety Monitoring Board of the National

Institute of Allergy and Infectious Disease for ten years, which was responsible for approving and supervising many

types of human research studies, some involving vaccines. Pet’r Ex. 24 at 1. Additionally, Dr. Rosenstreich has

published over 200 paper in the field of Allergy and Immunology, including articles that discuss multiple

hypersensitivity disorders, including asthma, sinusitis, and urticaria. Pet’r Ex. 24 at 2; Pet’r Ex. 25. Dr.

Rosenstreich is qualified as an expert in immunology and allergy.

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Dr. Emanual Maverakis is a professor of Dermatology at the University of California, Davis Medical Center in

Sacarmento, California. Resp’t Ex. A; Resp’t Ex. D. Dr. Maverakis received his medical degree from Harvard

Medical School in 2003 and completed his residency in dermatology at University of California, Davis in 2007.

Resp’t Ex. D at 5. From 2007-2013, Dr. Maverakis was a staff physician at the Northern California Health Care

System of the Department of Veterans Affairs. Id. Dr. Maverakis became an Assistant Professor at the University

of California, Davis Medical Center in the Department of Dermatology in 2007. He is Director of Immune

Monitoring Shared Resource at the UC Davis Comprehensive Cancer Center at the University of California, Davis.

Dr. Maverakis is board certified in dermatology and preventive medicine, and he is licensed to practice medicine in

the State of California. Id. at 5. Dr. Maverakis has authored or co-authored 140 peer reviewed medical articles

focusing on immune-mediated diseases. Resp’t Ex. A at 1. Dr. Maverkais is qualified as an expert in dermatology.

2

a. Legal Standard for Fact Finding

Petitioner’s burden of proof is by a preponderance of the evidence. § 13(a)(1). A

petitioner must offer evidence that leads the “trier of fact to believe that the existence of a fact is

more probable than its nonexistence before [he or she] may find in favor of the party who has the

burden to persuade the judge of the fact’s existence. Moberly v. Sec’y of Health & Hum. Servs.,

592 F.3d 1315, 1322 n.2 (Fed. Cir. 2010).

The process for making determinations in Vaccine Program cases regarding factual issues

begins with analyzing the medical records, which are required to be filed with the petition. §

11(c)(2). Medical records created contemporaneously with the events they describe are

generally considered to be more trustworthy. Cucuras v. Sec’y of Health & Hum. Servs., 993

F.2d 1525, 1528 (Fed. Cir. 1993); but see Kirby v. Sec’y of Health & Hum. Servs., 997 F.3d

1378, 1382-83 (Fed. Cir. 2021) (clarifying Cucuras does not stand for the proposition that

medical records are presumptively accurate and complete). While not presumed to be complete

and accurate, medical records made while seeking treatment are generally afforded more weight

than statements made by petitioner after-the-fact. See Gerami v. Sec’y of Health & Hum. Servs.,

No. 12-442V, 2013 WL 5998109, at *4 (Fed. Cl. Spec. Mstr. Oct. 11, 2013) (finding that

contemporaneously documented medical evidence was more persuasive than the letter prepared

for litigation purposes), mot. for rev. denied, 127 Fed. Cl. 299 (2014). Indeed, “where later

testimony conflicts with earlier contemporaneous documents, courts generally give the

contemporaneous documentation more weight.” Campbell ex rel. Campbell v. Sec’y of Health &

Hum. Servs., 69 Fed. Cl. 775, 779 (2006); U.S. v. U.S. Gypsum Co., 333U.S. 364, 396 (1948).

The Vaccine Act requires petitioner to show by preponderant evidence that she “suffered

the residual effects or complications of such illness, disability, injury, or condition for more than

6 months after the administration of the vaccine.” § 11(c)(1)(D)(i); see Song v. Sec’y of Health

& Hum. Servs., 31 Fed. Cl. 61, 65-66 (1994), aff’d, 41 F.3d 1520 (Fed. Cir. 2014). “The term

‘residual effects…’ requires a change within the patient that is caused by the vaccine injury.”

Wright v. Sec’y of Health & Hum. Servs., 22 F.4th 999 (Fed. Cir. 2022). “ ‘Residual’ suggests

something remaining or left behind from a vaccine injury…Because vaccine injuries are somatic

conditions defined by their signs and symptoms with the patient….their residues are similarly

defined. Id. at 1005-06. The use of the words “suffered” and “complication” in association with

“residual effects in § 11(c)(1)(D)(i) “suggests that Congress contemplated residual effects to be

detrimental conditions within the patient, such as lingering or recurring signs and symptoms.”

Id. at 1006. Together, ‘residual effects’ and ‘complications’ appear to both refer to conditions

within the patient, with ‘residual effects’ focused on lingering signs, symptoms, or sequelae

characteristics of the course of the original vaccine injury, and ‘complications’ encompassing

conditions that may not be ‘essential part[s] of the disease’ or may be outside the ordinary

progression of the vaccine injury.” Id.

b. Legal Standard for Causation

To receive compensation through the Program, petitioner must prove either (1) that [he]

suffered a “Table Injury”—i.e., an injury listed on the Vaccine Injury Table—corresponding to a

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vaccine that she received, or (2) that he suffered an injury that was actually caused by a

vaccination. See §§ 11(c)(1), 13(a)(1)(A); Capizzano v. Sec’y of Health & Hum. Servs., 440 F.3d

1317, 1319-20 (Fed. Cir. 2006). Because petitioner does not allege that he suffered a Table

Injury, he must prove that a vaccine he received caused his injury. To do so, he must establish,

by preponderant evidence: (1) a medical theory causally connecting the vaccine and his injury

(“Althen Prong One”); (2) a logical sequence of cause and effect showing that the vaccine was

the reason for her injury (“Althen Prong Two”); and (3) a showing of a proximate temporal

relationship between the vaccine and her injury (“Althen Prong Three”). § 13(a)(1); Althen, 418

F.3d at 1278.

The causation theory must relate to the injury alleged. The 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). Recently, in

Kottenstette, the Federal Circuit reiterated that proof of causation does not “require identification

and proof of specific biological mechanisms[.]” Kottenstette v. Sec’y of Health & Hum. Servs., --

Fed.Appx.—(Fed. Cir. June 15, 2021) (citing Knudsen v. Sec’y of Health & Hum. Servs., 35 F.3d

543, 549 (Fed. Cir. 1994). Causation “can be found in vaccine cases….without detailed medical

and scientific exposition of the biological mechanisms.” Knudsen, 35 F.3d 543, 548-49 (Fed.

Cir. 1994). It is not necessary for a petitioner to point to conclusive evidence in the medical

literature linking a vaccine to the petitioner’s injury, as long as the petitioner can show by a

preponderance of evidence that there is a causal relationship between the vaccine and the injury,

whatever the details of the mechanism may be. Moberly v. Sec’y of Health & Hum. Servs., 592

F.3d 1315, 1325 (Fed. Cir. 2010).

Petitioner cannot establish entitlement to compensation based solely on his 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 undersigned must weigh the submitted evidence and the testimony of the parties’ proffered

experts and rule in petitioner’s favor when the evidence weighs in his 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 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, 617 F.3d at 1339 (citing Terran v. Sec’y of Health & Hum.

Servs., 195 F.3d 1302, 1316 (Fed. Cir. 1999). In Vaccine Program cases, the Daubert analysis

has been used in the weighing of the scientific evidence actually proffered and heard rather than

as a tool for the pre-trial exclusion of expert testimony. Davis v. Sec'y of Health & Hum. Servs.,

94 Fed. Cl. 53, 66–67 (Fed. Cl. 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 923 (Fed. Cir. 2011). The flexible use of

the Daubert factors to determine the persuasiveness and/or reliability of expert testimony in

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Vaccine Program cases has routinely been upheld. See, e.g., Snyder v. Sec'y of Health & Hum.

Servs., 88 Fed. Cl. 706, 742–45 (2009). 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, 592 F.3d at 1325–26 (“[a]ssessments as to the reliability of expert testimony often turn

on credibility determinations”); see also Porter v. Sec'y of Health & Hum. 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”).

Close calls regarding causation must be resolved in favor of the petitioner. Althen, 418

F.3d at 1280 (holding that Congress created a system in which “close calls regarding causation

are resolved in favor of injured claimants”); Knudsen, 35 F.3d at 551 (“If the evidence (on

alternative cause) is seen in equipoise, then the government has failed in its burden of persuasion

and compensation must be awarded.”).

III. Summary of Evidence Submitted

a. Medical Records

Prior to receiving the flu vaccine on September 29, 2016, petitioner was relatively

healthy and a practicing registered nurse. Pet’r Ex. 18 at 1. On September 29, 2016, petitioner

received the flu vaccine in her left deltoid. Pet’r Ex. 1 at 1.

On October 10, 2016, petitioner went to the Steward Hospital Emergency Facility in

Quincy, MA, complaining of an “allergic reaction” that began 7 days prior as an itchy rash on

her torso and neck while in South Carolina. Pet’r Ex. 8 at 6. Petitioner stated that the rash had

spread to her back and woke up with an itchy red face with nasal congestion. Id. Additionally,

petitioner reported that her throat felt funny and her voice was altered. Id. Benadryl provided no

relief of symptoms. Id. The physical examination was positive for “diffuse maculopapular rash

all over the torso and back and minimally on the forearms and legs.” Id. at 8. Swelling was

noted on her face with erythema and papularity. Id. Petitioner was prescribed prednisone and

hydroxyzine and referred to dermatology. Id.

The same day, October 10, 2016, petitioner presented to dermatologist, Dr. Kenneth

Reed, for a rash located on her neck and trunk. Pet’r Ex. 9 at 6. Petitioner described the rash as

itchy, painful, and red, and present for one week. Id. At this appointment, petitioner told Dr.

Reed that the rash began right after she got the flu shot, but that she is not allergic to eggs. Id.

Dr. Reed agreed with the recommended treatment plan provided from the emergency room and

diagnosed petitioner with a hypersensitivity reaction with erythematous papular eruption

distributed on the trunk. Id. Dr. Reed also noted that petitioner had the flu vaccine, and this was

a “possible reaction to it.” Id. He explained, “Hypersensitivity reactions may result from a

medication, a viral illness, or even from an insect bite. Often it is difficult to determine the

cause, but in this instance, she developed a measles like eruption about 1 week after her MMR

vaccine, which is typical time onset for a vaccine related eruption.” Id. Dr. Reed instructed the

petitioner to return if her condition does not improve or if she develops additional symptoms. Id.

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Three days later, on October 13, 2016, petitioner went to urgent care for “a rash starting

10 days ago,” and “four days after flu vaccine.” Pet’r Ex. 15 at 31. The “History of Present

Illness” noted that petitioner was on a prednisone taper that started at 60 mg twice a day that had

improvement of her facial rash, but not the rash on her body. Id. Petitioner was given

Permethrin, an external skin cream to use all over her body and a referral to a dermatologist. Id.

Petitioner went back to Derm ASAP on October 18, 2016 for a follow-up and was seen by nurse

practitioner (“NP”) Cohen. Pet’r Ex. 9 at 1-3. Petitioner reported that the Permethrin had not

relieved her rash symptoms, and that the rash continued to be burning and itchy. Id. The

physical examination showed that the rash was present almost all over her body and she was

diagnosed with dermatitis that was inadequately controlled. Id. at 2. The differential diagnosis

included “hypersensitivity reaction,” and petitioner was instructed to discontinue all unnecessary

medications and give a prescription of a topical steroid lotion. Id. at 4. A biopsy of her left

forearm was taken. Id.

The biopsy result was negative for a fungal infection but was “consistent with a

hypersensitivity reaction such as arthropod assault,” as the skin biopsy showed “multifocal

parakeratosis with inflamed scale crust and underlying superficial perivascular lymphocytic

infiltrate. Pet’r Ex. 9 at 9.

On October 21, 2016, petitioner sought treatment with allergist, Dr. Karen Hsu Blatman

at Brigham and Women’s Hospital for the rash and itching that was all over her body. Pet’r Ex.

4 at 55. This appointment provides a more detailed timeline of events, and states:

[Petitioner] states that she was in South Carolina from September 22-26…[on] September

29 she believes she may have had her influenza vaccine; on October 7th, which was

Friday, two weeks ago, she started having sinus congestion, chest rash, and then she

developed some hives on her face. On Saturday and Sunday, she was having trouble with

a lot of sneezing, which then spontaneously resolved. But, the rash started to worsen. On

Monday, October 10th, she felt like her voice had changed and hat she was having some

trouble with respiratory symptoms and she describes having hives all over her face with

some swelling and she had new diffuse bumpy rash over her upper back. She was seen in

the ED in Quincy that day and was given prednisone starting at 40 mg a day, tapering for

10 days. Her last dose was three days ago, on 10/18. She was also given hydroxyzine

pruritus, but she did not feel like it was really touching the pruritus.

She was then sent to Dr. Reed, a dermatologist in Quincy. She felt like each dot felt like

there are 10 hornets trying to get out of her skin and she feels a completely and extreme

constant itch. On Thursday, Oct. 13th she was seen in urgent care in Weymouth and that

doctor thought it might be atypical scabies and was to use permethrin…she had relief for

about 15 minutes and then it started getting itchy….She once followed-up with Dr. Reed,

the dermatologist earlier this week…and had a skin biopsy done by one his nurse

practitioner, she also started using clobetasol mix and has been taking Allegra daily.

Id. at 57—8. Multiple excoriations throughout her arms and legs with ecchymoses on her right

thigh were observed. Id. at 58. Petitioner had minimal papules on her back. Id. Dr. Blatman

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ordered a complete blood count and checking serologies of IgG and total IgE. Id. at 59.

Petitioner was referred to dermatologist, Dr. Yang, the same day.

Petitioner had her appointment with dermatologist, Dr. Yang later on October 21, 2016,

where he mostly repeated petitioner’s HPI from her appointment with Dr. Blatman, but he also

noted, “Pt got flu shot in late September. On 10/7 had sinus congestion and chest rash. It later

spread to her face. On the 10th, pt had trouble breathing and the rash had spread diffusely on her

back, her face was also swollen….Pt saw a dermatologist, who gave clobetasol solution and did

biopsy. Pt states the solution is not helpful at all.” Pet’r Ex. 4 at 95. Dr. Yang observed faint

erythematous macules and papules on petitioner’s chest and back, and faint papular rash with ill-

defined erythematous in the background on her arms, along with scattered excoriated papules on

arms, abdomen, and legs. Id. at 98. Dr. Yang diagnosed petitioner with “rash, likely

hypersensitivity reaction to component of flu vaccine,” and noted that petitioner’s CBC was

remarkable for elevated eosinophils and ALT. Id. Petitioner was given a course of prednisone

60 mg to take daily and return in one week. Id. Dr. Yang also ordered labs to check petitioner’s

HHV-6 PCP.

Petitioner’s EBV IgG was negative and her HHV-6 had a positive result. Pet’r Ex. 2 at

70. On October 25, 2016, petitioner called Dr. Yang’s dermatology office because she was

“very anxious and concerned regarding her test results which were released via patient gateway.”

Pet’r Ex. 4 at 146. Dr. Emily Baumin spoke to petitioner on the phone and stated, “there [was]

some initial concern for a severe drug reaction given her initial laboratory testing and that she

was empirically treated with steroids. I explained that the HHV6 test is a virus whose

reactivation is associated with drug reaction eosinophilia systemic syndrome (“DRESS”).” Id. at

145-46.

Petitioner returned to Dr. Yang on October 28, 2016 for a follow-up of her “generalized

rash thought likely DRESS from flu shot.” Pet’r Ex. 4 at 150. Dr. Yang recounted that

petitioner’s labs were “remarkable for eosinophilia, HHV-6 of 2300 and ALT of 133,” and that

an EKG showed some nonspecific abnormalities. Id. Petitioner reported significant

improvement with the course of prednisone and TAC ointment. Id. No new lesions appeared

but her existing ones were still somewhat pruritic. Id. Dr. Yang diagnosed petitioner with

“generalized rash, thought likely DRESS from flu shot,” and he stated that petitioner’s “initial

labs remarkable for eosinophilia, HHV-6 of 2300, and ALT of 133. Repeat labs done at South

Shore show that ALT has come down to 53 and eosinophilia is resolved. Id. at 152—53.

Petitioner was directed to continue the 60 mg of prednisone for another week and begin a steroid

taper and continue to use of the TAC ointment. Id. at 153.

Petitioner had an appointment with Dr. Nikita Fitzcharles on October 31, 2016 for a

medication review and follow-up. Pet’r Ex. 2 at 129. Petitioner reported that she had been

diagnosed with “DRESS related supposedly to receiving the most recent influenza vaccine at her

place of employment in…September.” Id. at 131. She is taking a high dose of oral prednisone

as part of her treatment and had a follow-up with her dermatologist for DRESS. Id. Petitioner

expressed concern about how the prednisone could affect her bone density and was told in the

past that she had osteopenia, and she was also worried about her triglyceride levels found in her

latest bloodwork. Id. A bone density scan was ordered to address petitioner’s concerns about

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osteopenia and petitioner was given a free glucometer as she was now in the diabetic range with

her A1C level at 7.6%. Id. at 132. Petitioner was also given a prescription of fenofibrate to

address her hyperlipidemia. Id.

Petitioner had a follow-up appointment on November 3, 2016 with dermatologist Dr.

Reed. Pet’r Ex. 9 at 9. At this appointment, petitioner reported that Dr. Yang had diagnosed her

with DRESS “probably related to the vaccination (flu) she had earlier,” and she was taking

prednisone. Id. Petitioner also stated that when she initially sought treatment with Dr. Reed, her

lesions were more localized, but by the time she went to Bringham the lesions were more

generalized and the itching was worse. Id. Petitioner was diagnosed with a hypersensitivity

reaction. Id. at 9.

Petitioner returned to Dr. Yang on November 8, 2016 for a follow-up of her DRESS

diagnosis. Pet’r Ex. 4 at 169. He wrote that her “DRESS…most likely triggered from influenza

vaccine that patient received on 9/29/2016.” Id. Dr. Yang stated that “the only other drugs at

that time was HCTZ and Synthroid, which patient had been taking for 20 years, and Lipitor,

which patient has been taking for 1.5 years; it is extremely unlikely for these to be the culprit as

DRESS usually occurs 1-8 weeks after trigger.” Id. (emphasis added). Petitioner’s rash had

resolved and her labs were returning to baseline. Id. Petitioner had begun the prednisone taper.

Id. Petitioner’s diagnosis remained, “DRESS, most likely from flu shot,” and directed petitioner

to “avoid flu vaccine in future.” Id. at 172. Dr. Yang continued petitioner on the prednisone

taper and told her to follow-up in three weeks. Id.

Petitioner had an appointment with Dr. Rajesh Garg, an endocrinologist, for her elevated

A1C levels. Pet’r Ex. 4 at 196. Petitioner thought that her elevated sugar levels was related to

the prednisone she was taking. Id. Dr. Garg noted that petitioner was “extremely anxious and

worried due to diabetes.” Id. at 200. He increased her Metformin to 1000 mg as needed and

instructed her to test her blood glucose level once daily at different times. Id. Additionally, he

ordered a C-peptide and Anti-GAD antibody tests. Id.

Petitioner had a follow-up appointment with dermatologist, Dr. Yang, on January 26,

2017. Pet’r Ex. 4 at 303. Petitioner had completed her prednisone taper successfully in

December and her repeat echocardiogram was normal. Id. However, about a week before this

appointment, petitioner woke up with itchy arms and legs, used the cream she had previously

been prescribed and the itching resolved. Id. The itching lasted two days but then resolved.

Petitioner was still concerned about her symptoms and got a repeat CBC, CMP, and EKG. Id.

Dr. Yang performed a skin inspection and noted that she had xerosis, but no skin lesions or facial

swelling. Id. at 305. He assessed her with “DRESS-most likely from flu shot, resolved. Repeat

labs remarkable for mild elevation of ALT and EKG abnormalities.” Id. Dr. Yang wrote,

“Informed patient that I am not concerned about recurrence of DRESS at this time. Elevated

ALT most likely 2/2 fenofibrate, which patient was recently started [on] for hypertension.

Patient to discuss with primary care physician about fenofibrate.” Id. He also told petitioner that

her cardiologist should review her EKG with her and determine if a further work-up is necessary.

Id. Additionally, Dr. Yang diagnosed petitioner with pruritus 2/2 xerosis and recommended she

avoid hot water and use mild soaps, and apply moisturizers while her skin was still wet. Id. at

306.

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On January 30, 2017, petitioner had an MRI of her right foot for evaluation of possible

stress fracture. Pet’r Ex. 15 at 51. The MRI found “mildly increased signal within the bone

marrow of the fifth metatarsal shaft likely the sequela of a stress related injury. No evidence for

a displaced fracture.” Id.

Petitioner had an appointment with Dr. Nikita Fitzcharles on February 3, 2017 for a

follow-up for “multiple concerns.” Pet’r Ex. 2 at 125, 127. Petitioner had a possible hairline

fracture of the 5th metatarsal after having a fall, injuring her right foot, which petitioner

associated with osteopenia and risk associated with her prolonged use of oral steroids for

treatment of her DRESS. Id. at 127. Although at this appointment, petitioner was no longer

taking steroids. Petitioner also explained that recent bloodwork showed a TSH level of 0.26 and

petitioner self-discontinued use of levothyroxine 88 mg because she was afraid from suffering a

repeat/recurrent DRESS syndrome. Id. D. Fitzcharles counseled petitioner about risks related to

osteopenia and developing osteoporosis and did not recommend that petitioner begin

bisphosphonate, and petitioner insisted on being referred to an endocrinologist. Id. at 128. Dr.

Fitzcharles also assessed petitioner with hypothyroidism and stated, “patient with history of

Graves Disease as a result of radiation therapy and subsequent development of hypothyroidism.”

Id.

Nearly five months later, on June 9, 2017, petitioner had an appointment with Dr.

Fitzcharles to review her labs. Pet’r Ex. 15 at 56. Dr. Fitzcharles explained that the most recent

labs only showed a past infection of HHV-6. Id. Petitioner also reported she has only had one

48-hour episodes in which she had itching since her DRESS diagnosis last October. Id.

Petitioner’s ankle stress fracture had healed, and petitioner reported some weight loss. Id.

Petitioner was diagnosed with Type 2 diabetes mellitus without complication and

hypothyroidism. Additionally, Dr. Fitzcharles assessed petitioner with “DRESS,” but wrote:

Symptoms of DRESS last fall, was told at that time she may have sustained damage to

the heart from the stress of the condition, referring for cardiac evaluation following

management and treatment, and possibly an echocardiogram to evaluate for any lingering

damage.

Id.

Prior to her appointment with Dr. Fitzcharles, petitioner had undergone additional blood

work. The lab test results showed petitioner had high HHV-6 antibodies, indicative of a “past

infection,” and the interpretation on the lab results stated:

In seroepidemilogy studies of the prevalence of exposure using serum screening dilutions

of 1:10, the detection of IgG antibody in a mid-life population approaches 100%. Due to

this high prevalence of HHV-6 antibody, correlation of single IgG titers with specific

diseases are of little clinical value. Evidence of acute infection or reactivation of HHV-6

is demonstrated by a significant rise or seroconversion of IgG and IgM titers.

Id.

9

On August 15, 2017, petitioner had an appointment with Dr. Isabelle Zamfirescu, an

endocrinologist, for an evaluation for type 2 diabetes and hypothyroidism. Pet’r Ex. 15 at 62.

Petitioner reported that in February 2016, she had acute pancreatitis and then in October 2016,

she developed DRESS following an adverse reaction to the flu vaccine. Id. Petitioner stated that

she was on “high dose prednisone for DRESS and Hba1c of 7.6 in 10/2016.” Id. Petitioner also

noted that she has a history of hypothyroidism and was feeling well with Synthroid 88 mg six

days a week. Id. Dr. Zamfirescu diagnosed petitioner with Type 2 diabetes that was well

controlled and petitioner was advised to cut back on testing and mild hypertriglyceridemia and

recommended a low dose of Atorvastatin. Id. at 64.

Petitioner went to cardiologist, Dr. Pranitha Reddy on August 31, 2017 for a cardiac

screening. Pet’r Ex. 12 at 1. At this appointment, petitioner reported that she had “a history of

DRESS diagnosed last fall reportedly secondary to influenza vaccine. She has been referred for

evaluation of cardiac involvement. She states that her rash almost completely resolved and she

no longer is on steroids.” Id. Petitioner also stated that her recent echocardiogram revealed a

structurally normal heart. Id. Petitioner denied a prior cardiac disease, chest pains, or

palpitations. Id. Petitioner associated the onset of her diabetes with being on steroids. Id. Dr.

Reddy performed a cardiovascular screening, diagnosed petitioner with cardiovascular risk factor

and hypertension and wrote:

1. Cardiovascular screening: DRESS syndrome has been associated with cardiac

involvement, including eosinophilic myocarditis though [petitioner] was reportedly

without cardiac symptoms during her acute phase last fall. EKGs done at the time are

not available though current echocardiogram and EKG are unremarkable. Literature

review illustrates that patients can present with fulminant myocarditis events months

after initial treatment.

Id. at 4.

Approximately 16 months later, on May 2, 2019, petitioner went to South Shore Allergy

and Asthma for an evaluation for “food allergy.” Pet’r Ex. 23 at 2. Petitioner reported that three

days ago she ate steam clams and approximately 90 minutes after eating the clams she noted

some facial flushing, and then thirty minutes after the onset of flushing, she developed loose

stools. Id. About four hours after eating the clams, petitioner developed itching on her arms and

chest and then developed hives and an erythematous bumpy rash on her thighs. Id. Petitioner’s

gastrointestinal issues resolved the next day, but she had a generalized rash. Id. She took

Benadryl at work, and by the afternoon, she had developed chills. Id. Petitioner took Benadryl

again before bed, but woke up overnight with wheezing and difficulty breathing, which resolved

after taking an albuterol. Id. Petitioner reported never having a shellfish allergy and had never

had issues with clams specifically. Id. At this appointment, petitioner also explained her allergic

reaction to the flu vaccine in October 2016, and how she was on prednisone for two months and

reported that “it took over 6 months for her eosinophil count and HPPV-6 level to normalize.”

Id. Dr. Young assessed petitioner for a shellfish allergy, acute urticaria, mild intermittent

asthma, drug allergy, and drug-related rash and wrote:

10

Her constellation of symptoms, especially chills, rhinitis, wheezing, loose stools, suggest

viral syndrome; presentation for food allergy atypical in terms of symptom onset and

persistence of symptoms.

Id. at 5. Dr. Young noted that petitioner had her primary care physician order labs and asked her

to return the following Tuesday for a skin allergy test to clams. Id.

Over two years and seven months later, on May 6, 2019, petitioner called Brigham and

Women’s Hospital Dermatology Department and reported having a rash and itch all over her

body. Pet’r Ex. 22 at 62. The record states that petitioner “had clams at home on Monday after

that she started having rashes, then loose stools. No prior allergies to clams or sea food. She

feels the rash looked similar to the DRESS syndrome rash. Reports intermittent chills and fever

like when she had DRESS, she feels stress might have reactivated it.” Id.

Petitioner had an appointment with Dr. Yang on May 7, 2019, when she repeated her

symptoms after eating clams, similar to the explanation given to Dr. Young. Pet’r Ex. 22 at 26.

However, she also explained that her labs from primary care physician demonstrated high

eosinophils, mildly elevated CRP and increased HHV-6 titers, but her kidney and liver numbers

were normal. Id. Petitioner stated that she was taking Cetirizine 10 mg for the rash and the rash

has mostly resolved. Id. Petitioner inquired as to whether if her DRESS was recurring. Id. After

an examination and a review of her labs, Dr. Yang assessed petitioner with “Rash, favor

hypersensitivity reaction based on history, resolving on its own. I do not suspect DRESS at this

time.” Id. at 28 (emphasis added). He continued, stating:

Suspect hypersensitivity reaction, given distribution and timing. Discussed

pathophysiology and timing with patient. No causative agent identified, but patient will

be alert to possible causes should the rash recur in the future. Patient’s bloodwork was

reviewed in detail and I explained to her that high eosinophil and elevated CRP can be

seen with any hypersensitivity reaction.

Ordered ECG (as patient had ECG abnormalities during her previous episode of DRESS,

which I do NOT favor at this time, but patient would like repeat ECG to feel assured).

Id.

Dr. Yang called petitioner on May 10, 2019 after reviewing lab results and informed her

that her labs were “remarkable for elevated HHV-6 and eosinophils,” and he opined that

petitioner’s rash was likely due to a reactivation of HHV-6. Id. at 34; see also Pet’r Ex. 22 at 41

(lab results documenting elevated HHV-6 titers). He did not recommend any additional

treatment, given the lack of systemic involvement and quick improvement in the rash. Id.

b. Petitioner’s Expert’s Reports—Dr. David Rosenstreich

Petitioner submitted two expert reports from Dr. David Rosenstreich. Pet’r Ex. 24 & 42.

Dr. Rosenstreich reviewed petitioner’s medical history through her records and stated that she

had a history of “chronic asthma, intermittent sinusitis, hypertension and hypothyroidism

11

(following Grave’s disease and treatment with radioactive iodine in 1994)” and “chronic

osteopenia and had developed a third metatarsal stress fracture at one point.” Pet’r Ex. 24 at 4.

He also noted that petitioner had an electrocardiogram on February 14, 2016, approximately, 7

months prior to receiving the flu vaccine at issue, which had “nonspecific ST abnormalities,” and

that she also previously had abnormal liver function tests in February 2016 that resolved. Id.

Dr. Rosenstreich opined that petitioner developed Drug Reaction with Eosinophilia and

Systemic Symptoms syndrome approximately four to seven days after she received the Fluarix

vaccine on September 29, 2016. Id. He opined that petitioner “experienced a severe allergic

reaction to the influenza vaccine” and her initial symptoms included “a generalized pruritic and

painful rash, bruising, leg swelling, nasal congestion, and hoarseness.” Id. at 8. Dr.

Rosenstreich stated, “Because of associated laboratory abnormalities (eosinophilia, abnormal

liver function tests, ECG abnormalities and elevated blood levels of HHV-6 viral DNA)

suggesting a more severe, systemic inflammatory reaction, she was diagnosed by several medical

specialists as having DRESS.” Id.

Dr. Rosenstreich also stated that petitioner was initially treated with high-dose steroids

and the rash finally resolved in approximately 6 weeks, but that petitioner experienced “periodic

(every few week) relapses of rash lasting 48- hours,” and that “some of these episodes included

painful rash, chills and muscle aches, and these recurrences lasted at least until June 2017, 9

months after the initial vaccination. Id. Dr. Rosenstreich also associated petitioner’s “worsening

diabetes” as a result of her prolonged use of prednisone. Id. He noted that petitioner had an

event in May 2019 that he called a “possible DRESS relapse” which was “possibly related to

ingesting clams,” when she developed generalized urticaria, chills and fever, associated with

eosinophilia, and signs of systemic inflammation. Id. While he did not fully endorse petitioner’s

progressive leg pain and neuropathy in her left arm as to be wholly related to DRESS, Dr.

Rosenstreich stated that petitioner’s primary care physician was considering the neuropathy to

possibly related to DRES in June 2019.

In his first report, Dr. Rosenstreich described DRESS as a “drug-induced hypersensitivity

reaction whose manifestations include a skin rash, eosinophilia and involvement of other internal

organs such as the liver.” Id. at 9. The 2006 and 2019 Shiohara articles explain that DRESS

typically starts 2—3 weeks after the induction of a drug and that the “delayed onset in relation to

the introduction of the causative drug is one important feature of DRESS that can be

distinguished from other types of drug eruptions.” Pet’r Ex. 36 at 25; Pet’r Ex. 296 at 2. DRESS

typically begins with a fever shortly followed by a maculopapular rash, which may be purpuric

and symmetrically distributed on the trunk and extremities. Pet’r Ex. 29 at 3; Pet’r Ex. 36 at 4.

Both articles explain that the early phase of the cutaneous lesions are periorbital and facial

edema with pinhead-sized pustules. Pet’r Ex. 29 at 3; Pet’r Ex. 36 at 4. Cervical

lymphadenopathy is present in most patients early in the illness. Pet’r Ex. 36 at 4. Transient

5

Shiohara, T. et al., Drug Induced Hypersensitivity Syndrome (DIHS): A Reaction Induced by a Complex Interplay

among Herpesviruses and Antiviral and Antidrug Immune Responses, 55 Allerol. Internat. 1-8 (2006). [Pet’r Ex.

36].

6

Shiohara, T. & Mizukawa, Y., Drug-induced Hypersensitivity Syndrome (DiHS)/Drug Reaction with Eosinophilia

and Systemic Symptoms (DRESS): An Update in 2019, 68 Allerg. Int. 301-308 (2019). [Pet’r Ex. 29].

12

eosinophilia is often present, and may be delayed 1—2 weeks, even after elevations of liver

enzymes return to baseline. Pet’r Ex. 29 at 4. Elevation in liver enzymes occurs in

approximately 70% of DRESS patients at the acute phase and “a marked decrease in serum IgG

is typically observed in the acute phase,” and “at its nadir, around 1—2 weeks after onset, the Ig

levels may fall as low as 300-600 mg/dL.” Id. at 4. Further, HHV-6 reactivation, “as evidenced

by the significant increase in serum IgG titers to HHV-6 and the detection of HHV-6 DNA in

leukocytes can be observed in the vast majority of DRESS patients at a certain time point, 2—3

weeks after onset.” Id.

The diagnostic criteria for DRESS as set forth by RegiSCAR and the Japanese Consensus

Group (“JCG”) are the following:

DRESS Diagnostic Criteria by RegiSCAR DRESS Diagnostic Criteria by JCG

Acute Rash Maculopapular rash developing >3 weeks after

starting with a limited number of drugs

Reaction suspected drug-related Prolonged Clinic Symptoms after

Discontinuation of Drug

Hospitalization Fever

Fever (>38 degrees C) Liver abnormalities (ALT >100U/L)

Laboratory Abnormalities with at least one Leukocyte abnormalities (at least one present):

present: lymphocyte above/below normal; low leukocytosis; abnormal lymphocytosis;

platelet; eosinophilia eosinophilia (>1.5 x 10/L)

Involvement of one more internal organ Lymphadenopathy

Enlarged lymph nodes at two or more sites HHV-6 Reactivation

Pet’r Ex. 29 at 3. Important to this case, for a diagnosis of DRESS using the RegiSCAR

criterion, “the first three criteria are necessary for diagnosis, and the presence of 3 out of the

other 4.” Id. Typical treatment of DRESS is with systemic corticosteroids for approximately 6-8

weeks and then ongoing monitoring to prevent the relapse of symptoms. Pet’r Ex. 36 at 6.

Regarding petitioner’s diagnosis, Dr. Rosenstreich stated that at least three of petitioner’s

treating physicians diagnosed her with DRESS. Pet’r Ex. 24 at 10. He stated that petitioner’s

symptoms were consistent with DRESS, including the eosinophilia finding of greater than 700

K/uL, a rash covering more than 50% of her body, initial facial swelling and purpura, and liver

involvement. Id. He stated that the “finding of increased blood levels of HHV-6 DNA makes the

diagnosis of DRESS even more likely.” Id. Dr. Rosenstreich wrote, “This constellation of

findings is strong evidence that [petitioner] had experienced a powerful, systemic,

immunologic/inflammatory reaction caused by the influenza vaccination that if it was not exactly

typical DRESS, was at least-DRESS like in its manifestations and consequences.” Id. Dr.

Rosenstreich also stated that he could not be certain that the transient ECG abnormalities that

petitioner developed were DRESS-related, as she had experienced a similar event prior to the flu

vaccination, and two of petitioner’s treating cardiologists did not feel that they were significant.

Id.

13

Dr. Rosenstreich’s supplemental report addressed Dr. Maverakis’ opinion that petitioner

would not meet the criteria for DRESS. Pet’r Ex. 42. While Dr. Maverakis took issue with the

fact that petitioner did not have a fever or enlarge lymph nodes, Dr. Rosenstreich observed that

lymphadenopathy is not present in 35-46% of patients in DRESS, and that while petitioner did

not have a fever, she did present with hoarseness and congestion, consistent with DRESS. Pet’r

Ex. 42 at 3, citing Pet’r Ex. 43 at 57; see also Pet’r Ex. 29 at 3 (“they may be an upper-airway

infection-like prodrome”). Additionally, Dr. Rosenstreich referred to petitioner’s labs taken on

October 21, 2016, which showed an elevation of eosinophils of 760 K/ul, contradicting Dr.

Maverakis’ opinion that petitioner did not have elevated eosinophils during the initial phase.

Pet’r Ex. 42 at 5; see also Pet’r Ex. 4 at 67. With respect to the HHV-6 finding in petitioner’s

records, Dr. Rosenstreich stated that this was not a “nonspecific finding,” but actually very

relevant to the diagnosis of DRESS, as reactivation of viruses from the Herpesviridae family,

including HHV-6, “is a known phenomenon associated with DRESS and occurs in up to 75% of

patients.” Pet’r Ex. 42 at 4. Dr. Rosenstreich’s statement is supported by the articles by

Shiohara, Lee, and Tohyama, which all explained that HHV-6 reactivation is present in a

majority of probable/definite DRESS patients. See Pet’r Ex. 29 at 2; Pet’r Ex. 43 at 7; Pet’r Ex.

47 at 1.8

DRESS is thought to be a T-cell mediated disease and the symptoms associated with

DRESS are “associated with an oligoclonal proliferation of activated CD8-T lymphocytes that

are directed against viral antigens derived from herpes viruses…and whose replication is

enhanced by the culprit drug.” Pet’r Ex. 28 at 1; see also Pet’r Ex. 24 at 9. While all of the

articles referenced indicate that a specific pathogenesis of DRESS/DiHS is not known, they all

suggest a role for T-cells that are expanded by the drug resulting in large number of cytokines

such as tumor necrosis factor (TNF-α) and IFN-ƴ, leading to symptom manifestation. Pet’r Ex.

24 at 9; see also Pet’r Ex. 43 at 5 (“Although the exact pathogenesis is not fully understood”);

Pet’r Ex. 36 at 5 (“Although several theories have been proposed, the pathomechanisms of

DIHS/DRESS remains largely unknown…The results of patch tests and LTT indicate that drug-

specific T cells are behind this syndrome.”).

Dr. Rosenstreich also contended that petitioner’s event in May 2019 after eating clams

was consistent with DRESS. Pet’r Ex. 42 at 5. Dr. Rosenstreich, referencing the Lee article,

stated that “up to 25% of cases” have relapses of DRESS that “are often associated with

concurrent reactivation of HHV-6.” Id. He conceded that petitioner’s event in May 2019 was

not a result of another drug, but by a different type of allergen, the clam protein. Id. at 5.

However, he still opined that her event in May 2019 was related to her initial influenza vaccine

reaction. Pet’r Ex. 42 at 6.

With respect to the timing of petitioner’s reaction, Dr. Rosenstreich stated that “the 4-7

days between the vaccination [and dermatological reaction] is consistent with the time it takes to

begin activating influenza antigen or drug antigen specific T lymphocytes and expanding the

7

Lee, Haur Yueh, Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), Up to Date (online) (2021).

[Pet’r Ex. 43].

8

Tohyama, K, et al., Association of Human Herpesvirus-6 Reactivation with Flaring and Severity of Drug Induced

Hypersensitivity Syndrome, 157 J. of Derm. 934-940 (2007). [Pet’r Ex. 47 at 1.

14

clone of these specific cells to a number large enough [to] cause inflammatory symptoms in the

skin and other organs.” Pet’r Ex. 24 at 11. He referenced a case report by Solak et al., where the

patient had received an influenza vaccine and 7 days later developed maculopapular skin rash,

facial edema, and eosinophilia. Pet’r Ex. 35 at 1.9 The authors stated that the allopurinol was

being used over a month “but the clinical manifestations appeared 1 week after vaccination

application. Hence, we believe that the viral antigens in the vaccine…might have contributed to

trigger the disease.” Id. at 1-2 (emphasis added). Dr. Rosenstreich also referred to a case report

by Griffin et al., describing a patient that developed DRESS seven days after receiving an

adjuvanted trivalent influenza vaccine. Pet’r Ex. 3710; see also Resp. Ex. A, Tab 3. The authors

wrote, “As an immune stimulant, it makes sense that vaccination could trigger DRESS in certain

individuals,” and that “the strong temporal relationship between vaccination, onset of symptoms,

and the absence of an alternative trigger suggests a role for adjuvanted influenza vaccine as the

precipitant of DRESS.” Pet’r Ex. 37 at 3. The authors hypothesized that “the vaccine response

could facilitate reactivation of latent herpes viruses, as have been implicated in the pathogenesis

of DRESS.” Id. Additionally, Griffin stated, “While the mechanism is unclear, we hypothesis

this could be a direct reaction to a vaccine component, or that non-specific immune activation

following vaccination could permit a reaction to medication, as postulated in previous cases…”

Id.

Dr. Rosenstreich concluded both of his reports reiterating his opinion that petitioner did

have probable DRESS that was caused by the influenza vaccine. Pet’r Ex. 24 at 11; Pet’r Ex. 42

at 6.

c. Respondent’s Expert’s Opinion—Dr. Emanual Maverakis

Dr. Maverakis, a dermatologist, opined that petitioner did not experience DRESS, and

that the influenza vaccine she received, did not caused her to suffer DRESS, nor did the flu

vaccine cause petitioner’s reactivation of HHV-6 in 2019. Resp’t Ex. A at 17.

With respect to petitioner’s diagnosis, Dr. Maverakis stated that petitioner did develop a

skin rash after receiving the flu vaccine on September 29, 2016, but that her condition was not

DRESS because it lacked clinical signs and symptoms required to make that diagnosis. Resp’t

Ex. A at 13. Dr. Maverakis, accepting the RegiSCAR diagnostic criterion for DRESS, stated that

petitioner’s score would be a 3, which is a possible or probable diagnosis of DRESS. Id. at 13-

14. Specifically, he explained that petitioner did not present with a fever or lymphadenopathy,

which are “strong arguments against DRESS.” Id. at 13. He also acknowledged that petitioner

had an abnormal liver function test, showing her ALT level was elevated in her labs on

10/21/2016, but he also observed that petitioner had elevated liver function test results in

February 2016, when she had experienced a wild-flu infection. Resp’t Ex. A at 13. In his

supplemental report, Dr. Maverakis outlined petitioner’s lab results from 2015 and 2016, prior to

the flu vaccine, which demonstrated mildly elevated ALT and ALK tests. Resp’t Ex. B at 5. He

9

Solak, B. et al., DRESS Syndrome Potentially Induced by Allopurinol and Triggered by Influenza Vaccine, BMJ

Case Rep. doi:10.1136/bcr-2016-214563 (2016). [Pet’r Ex. 35].

10

Griffin, D. et al., A Case of Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) without a Typical

Precipitant, 212 Med J. Aust. 300-301 (2020). [Pet’r Ex. 37; Resp. Ex. A, Tab 3].

15

seemingly agreed that her significant elevation in liver function tests in October 2016, could be a

sign related to a possible DRESS diagnosis, but argued that since petitioner experienced

abnormal liver function tests prior to the vaccination, the abnormal liver function test results

were not caused by the flu vaccine. Resp’t Ex. B at 4. Dr. Maverakis did not address how

petitioner’s previous abnormal liver function tests were found during the same time period she

had been reporting flu-like symptoms and then found to be positive with influenza A.

Dr. Maverakis’ initial report did include some inconsistencies with his evaluation of

petitioner’s eosinophil levels, as noted by Dr. Rosenstreich, at one time acknowledging that

petitioner had elevated levels of eosinophils, but then later stating that “eosinophilia was not

noted during her initial presentation.” Resp’t Ex. A at 13, 15. In his second report, Dr.

Maverakis clarified that petitioner’s lab from 10/21/2016 did demonstrate eosinophilia and that

petitioner’s eosinophils were elevated two more times in January 2017. Resp’t Ex. B at 4; see

also Pet’r Ex. 2 at 250, 281.

Finally, Dr. Maverakis acknowledged that petitioner experienced a rash after receipt of

the flu vaccine, he argued that the rash was not clearly consistent with DRESS. Id. at 13-14. In

his supplemental report, Dr. Maverakis conceded that there is no specific characteristics of

DRESS rashes, but he argued that petitioner’s biopsy’s interpretation was that her skin condition

was “consistent with a hypersensitivity reaction, such as to an arthropod assault,” and that

petitioner’s biopsy lacked the most commonly found histologic features seen in DRESS rashes.

Resp’t Ex. B at 5. He referenced an article by Ortonne et al., which examined the

histopathological features of DRESS rashes by reviewing skin biopsies of 50 DRESS diagnosed

patients and found that the most common dermatological manifestations were “erythroderma,

maculopapular rash, bullae/erosive lesions, pustules, and purpura.” Resp’t Ex. B, Tab 6 at 3.11

Additionally, Ortonne found that “a diffuse parakeratotic layer” was found in 84% of DRESS

patients and infiltrate was only located in the superficial dermis, with the density of

inflammatory infiltrates being low or intermediate in the majority of cases. Id. at 4. The authors

wrote:

We found that the histopathological presentation of DRESS syndrome is highly variable,

encompassing many inflammatory patterns, from a slight perivascular lymphocytic

infiltrate to a pustular, AGEP-like, EM-like, eczematous or interface dermatitis, with the

latter being the most frequent. What appeared to be a special feature was the association

of different inflammatory patterns in a single specimen, a finding that was significantly

more frequent in DRESS syndrome that in nondrug dermatoses.

Id. at 7. Despite this, Dr. Maverakis stated, “In short, the most commonly associated features of

DRESS were not noted in the biopsy of the petitioner.” Resp’t Ex. B at 6.

Dr. Maverakis discussed the elevation of HHV-6 titers in petitioner and stated that

“nearly everyone in the US population has been infected with HHV-6,” and that “reactivation is

more common during times of stress, illness, in response to acute allergic reactions, and during

immunosuppression.” Resp’t Ex. A at 14. Even though Dr. Maverakis stated in his report that

11

Ortonne, N, et al., Histopathology of Drug Rash with Eosinophilia and Systemic Symptoms Syndrome: A

morphological and Phenotypical Study, 173 Brit. J. of Derm. 50-58 (2015). [Resp’t Ex. B, Tab 6]

16

the HHV-6 reactivation finding was “non-specific,” he explained in his supplemental report that

that he meant that HHV-6 reactivation is not specific to DRESS, but can be caused by other

things, such as the use of immunosuppressants such as corticosteroids. Resp’t Ex. A at 14;

Resp’t Ex. C at 6.

With respect to vaccine causation, Dr. Maverakis opined that the flu vaccine could not

have caused DRESS, mostly because there are no epidemiological studies that demonstrate that

the flu vaccine could cause DRESS. Resp’t Ex. A at 14 (“There are currently no population-

based studies linking DRESS to influenza vaccination.”). Dr. Maverakis acknowledged the three

case reports described the Hewitt, Griffin, and Solak, which Dr. Rosenstreich also referenced,

where DRESS followed administration of a flu vaccine, but stated that “it is not surprising, given

that by chance, DRESS should sometimes present following an unrelated influenza vaccination.”

Id. Addressing Dr. Rosenstreich’s theory of how the flu vaccine could result in DRESS, Dr.

Maverakis stated that “expanding T-cells specific to influenza will not cause DRESS….In

contrast, T-cell expansion is a very common event…Simply expanding T cells does not cause a

cutaneous eruption. In fact, there are skin resident T cells that do not circulate in the periphery

and the peripherally expanded T cells do not necessarily track to the skin.” Id. at 16. In his

rebuttal report, without actually addressing how the flu vaccine could cause DRESS, Dr.

Maverakis stated that large registries of DRESS patients have failed to find an association

between the flu vaccination and DRESS. Resp’t Ex. C at 2, citing Resp’t Ex. C, Tab 2.12

Lastly, addressing the length of petitioner’s symptoms, Dr. Maverakis conceded that

relapses of DRESS can occur, however, petitioner’s alleged “relapses” were not consistent with

the relapses described in the medical literature. Resp’t Ex. B at 7. He stated that “relapses were

most attributed to the introduction of a new medication,” and that the relapses present with facial

edema, lymphadenopathy, and atypical lymphocytes. Id. Dr. Maverakis also acknowledged that

DRESS patients could have long-term sequela, including DRESS-induced organ damage,

however, petitioner did not have any evidence of such long-term organ damage. Dr. Maverakis

disagreed that petitioner’s event in May 2019 was a DRESS relapse and noted that petitioner’s

treating physician did not characterize her event in May 2019 as a DRESS relapse. Id.; see also

Pet’r Ex. 22 at 28.

IV. Analysis

a. Diagnosis

Federal Circuit precedent establishes, in certain cases, it is appropriate to determine the

nature of an injury before engaging in Althen analysis. Broekelschen v. Sec’y of Health & Hum.

Servs., 618 F.3d 1339, 1346 (Fed. Cir. 2010). Since “each prong of the Althen test is decided

relative to the injury,” determining facts relating to the claimed injury can be significant in a case

like this. Id. Thus, prior to the inquiry of vaccine causation, the undersigned addresses whether

petitioner has established by a preponderance of the evidence that she suffered DRESS.

12

Kardaun, S.H. et al., Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS): An Original Multisystem

Adverse Drug Reaction. Results from the Prospective RegiSCAR study, 169 Brit. J. of Derm. 1071-1080 (2013).

[Resp’t Ex. C, Tab 2].

17

Respondent argues that petitioner has not established by preponderant evidence she

suffered from DRESS. Resp’t Br. at 15. But he conceded that petitioner developed a skin rash

after receipt of the flu vaccine, the diagnosis of DRESS is not supported by the medical records

and is inconsistent with the medical literature describing DRESS. Id. at 19; see also Resp’t Ex.

A at 13-15. Petitioner, however, asserts that DRESS is the appropriate diagnosis for her

condition after receipt of the flu vaccine, as diagnosed by her treating physicians and supported

by the opinion of Dr. Rosenstreich. Pet’r Br. at 29-34.

After a review of the medical records, the expert reports, and the medical literature, I find

that petitioner has established by preponderant evidence that she developed DRESS and that her

injury lasted until August 2017.

Both Drs. Rosenstreich and Maverakis reference the RegiSCAR DRESS criterion

outlined above, to diagnose and validate cases of DRESS. Resp’t Ex. A at 2; Pet’r Ex. 42 at 3;

see also Resp’t Ex. B, Tab 2. The Shiohara article explains that there is often a delay of DRESS

symptoms after introduction of the inciting drug and first symptoms are typically a

maculopapular rash with a fever. Pet’r Ex. 29 at 2. DRESS rashes initially present as “patchy

erythematous macules, pustular, target-like or eczema-like lesions,” that is “symmetrically

distributed on the trunk and extremities,” with early phase rashes are “periorbital with facial

edema with pinhead-sized pustules.” Id. at 3. Both experts agree that approximately seven days

after petitioner received the flu vaccine on September 29, 2016, she developed a rash. See Pet’r

Ex. 24 at 10; Resp’t Ex. A at 13. At petitioner’s first emergency room visit on October 10, 2016,

the rash was described as “diffuse maculopapular rash over the torso and back, and minimally on

the forearms and legs….swelling of the face with erythema and papularity.” Pet’r Ex. 8 at 8.

The same day, petitioner saw dermatologist, Dr. Kenneth Reed who described petitioner’s rash

as a “erythematous papular eruption” that distributed on her trunk and neck. Pet’r Ex. 9 at 5.

Despite Dr. Maverakis taking issue with the histologic features of petitioner’s skin biopsy later,

he conceded that petitioner’s rash would be consistent with the RegiSCAR rash criteria. Resp’t

Br. at 19.

Petitioner also presented with elevated eosinophils and abnormal liver function tests,

consistent with a DRESS diagnosis. Medical literature submitted by both parties indicate that

“transient eosinophilia was far more often present,” in DRESS cases than reported. Pet’r Ex. 29

at 4; Resp’t Ex. B, Tab 2 at 4. Further, eosinophilia may often be delayed for 1-2 weeks. Pet’r

Ex. 29 at 4. Petitioner’s labs, taken on October 21, 2016, demonstrated elevated eosinophils and

both experts acknowledged this lab finding was consistent with the DRESS RegiSCAR criteria.

See Resp’t Ex. A at 13; Pet’r Ex. 24 at 9. Additionally, petitioner’s treating dermatologist, Dr.

Geoffrey Yang, considered the elevated eosinophils in petitioner’s labs relevant to his diagnosis

that petitioner was experiencing a reaction to the flu vaccine. Pet’r Ex. 2 at 86.

Petitioner’s abnormal liver function test results are also consistent with the DRESS

diagnosis and RegiSCAR criteria. Shiohara, Kardaun, and Cho explain that the liver is

frequently affected in DRESS, resulting in elevated liver enzymes. See Pet’r Ex 29 at 4

(“elelvated liver enzymes occur in up to 70% of patients with DRESS”); Resp’t Ex. B, Tab 2 at 5

(“[m]ost frequently the reaction affected the liver”); Pet’r Ex. 44 at 4 (“Liver injury is the most

common type of organ damage and has been found in 75-94% of patients.”). Both experts

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acknowledged that petitioner’s labs on October 21, 2016 did demonstrate abnormal liver

function and abnormal liver function test results are consistent with DRESS. See Pet’r Ex. 24 at

8; Resp’t Ex. A at 13 (petitioner “was found to have a slightly elevated ALT at 133 on

10/21/2016, with the upper limit of normal being 50.”). While Dr. Maverakis attempted to

minimize petitioner’s elevated ALT finding to argue against a DRESS diagnosis because she had

previous elevated liver function test results, her previously elevated ALT level occurred while

she was found positive for the flu in March 2016, demonstrating that when petitioner’s immune

system was activated in response to flu antigens, her liver functions became abnormal.

Similarly, Dr. Yang also noted petitioner’s elevated liver function test results and wrote, “liver

involvement is concerning for systemic reaction; will monitor closely.” Id.

One area of disagreement between the experts with respect to DRESS was the relevance

of reactivation of HHV-6 in petitioner. Dr. Rosenstreich explained that DRESS “is frequently

associated with reactivation of…human herpes virus 6 (“HHV-6”).” Pet’r Ex. 24 at 8. Dr.

Maverakis characterized the HHV-6 reactivation as a “non-specific finding,” although

acknowledging that DRESS patients “will often have activation of HHV-6.” Resp’t Ex. A at 14.

Shiohara, Kardaun, and Sharma all explain that reactivation of “latent viruses,” are temporally

associated with disease severity and relapse, with HHV-6 being the most commonly identified

viral reactivation. Pet’r Ex 36 at 3 (“recent studies, including ours, suggest an intimate

relationship between HHV-6 and the development of a severe systemic hypersensitivity

syndrome or DRESS.”); Pet’r Ex. 48 at 5; Resp’t Ex. B, Tab 2 at 5 (“Reactivation of herpes

viruses, especially HHV-6, often described in DRESS and even considered a criterion for DIHS

by Japanese experts, is held responsible for a more severe and/or protracted course.”). Given the

medical literature’s association of reactivation of HHV-6 and DRESS, it does not appear that this

finding is “non-specific” but instead an important consideration for diagnosing and treating a

patient with DRESS. In this case, petitioner’s labs were remarkable for elevated HHV-6 titers

and again, her treating physician, Dr. Yang, also found her elevated HHV-6 titers was an

important factor when he diagnosed petitioner with DRESS. See Pet’r Ex. 2 at 76.

Importantly, petitioner’s treating physicians ultimately diagnosed her with DRESS based

on her clinical course and treated her accordingly. When petitioner initial sought treatment for

her rash, her physicians associated the rash she developed to the flu vaccine she had received on

September 29, 2016. See Pet’r Ex. 9 at 6 (“[Patient] just had her [flu] shot, possible reaction to

it”); Pet’r Ex. 2 at 86 (Assessment: 1. Rash, likely hypersensitivity reaction to component of flu

vaccine.). After reviewing her labs and finding elevated liver function tests, eosinophilia, and

HHV-6 reactivation, her dermatologist, Dr. Yang diagnosed petitioner with “likely DRESS from

flu shot.” Pet’r Ex. 2 at 80. On October 28, 2016, at her second appointment with Dr. Yang, he

wrote that she was presenting for a “follow-up of generalized rash, thought likely DRESS from

flu shot. Labs remarkable for eosinophilia, HHV-6 of 2300, and ALT of 133….At last visit 1

week ago, patient was started on prednisone 60 mg, along with TAC ointment.” Id. at 78. His

assessment was, “Generalized rash, though likely DRESS from flu shot.” Id. When petitioner

went back to Dr. Yang on December 2, 2016, petitioner’s HPI stated, “56-year-old female with

DM and DLP who presents to clinic today for follow-up of DRESS (prior symptoms include

facial swelling, eosinophilia, elevated ALT, and HHV-6 reactivation on PCR) most likely

triggered from influenza vaccine that patient received on 9/26/2016.” Id. at 56. Dr. Yang also

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wrote that petitioner’s other medications were not likely the culprit because she had been taking

for 1.5 years and “as DRESS usually occurs 1-8 weeks after trigger.” Id.

Petitioner was also treated with steroids for six weeks, consistent with the consensus

treatment for DRESS. See Pet’r Ex. 2 at 80. The Shiohara and Mizukawa paper states,

“Systemic corticosteroids have been accepted as the gold standard treatment for ameliorating

clinical symptoms of DiHS/DRESS at the acute phase….The usual dosage is prednisolone, 40-50

mg/day….tapered over 6-8 weeks to prevent the relapse of various symptoms of this syndrome.”

Pet’r Ex. 29 at 7. The 2017 Cho article also confirms the long-term use of corticosteroids for a

period of 2-3 months. Pet’r Ex. 44 at 13. Additionally, both articles suggest that a gradual taper

over a longer duration is preferred to reduce “disease flare-ups” or the development of

autoimmune long-term sequelae. Id.; See aso Pet’r Ex. 29 at 7 (“Once corticosteroids have

started, drug dose should be reduced gradually even upon resolution of clinical manifestations.

This is because patients with DiHS/DRESS are at greater risk of subsequently developing the

wide spectrum of immune reconstitution inflammatory syndrome (IRIS) ranging from CMV

disease to autoimmune disease.”).

Unfortunately, in this case, petitioner tapered her steroid use faster than what was

recommended by her physician, resulting in flare-ups occurring through August 2017. At her

appointment with Dr. Yang on December 2, 2016, he noted petitioner “decided to self-taper

faster than what we had discussed.” Pet’r Ex. 2 at 56. On January 13, 2017, petitioner reported a

two-day flare when she woke up with an itchy feeling all over her arms and legs, and she used a

cream to resolve the sensation. Pet’r Ex. 2 at 51. When she went to her primary care physician

on June 9, 2017, petitioner reported intermittent itching every few weeks and shared a photo of a

rash covering her bilateral arms and her thighs. Pet’r Ex. 2 at 123. But by August 2017, at a

cardiology appointment, her skin exam was normal. Pet’r Ex. 2 at 41. As a result of petitioner’s

self-tapering the steroids faster than what was recommended, petitioner experienced flare-ups of

her rash and itchiness through August 2017, consistent with what was described in the medical

literature. See Pet’r Ex. 43 at 7 (“…relapses or flare-ups are common after resolution of the

acute disease, occurring in up to 25 percent of cases weeks to months after resolution….Flare-

ups tend to be more common in patients treated with systemic corticosteroids and occur more

frequently on rapid tapering of corticosteroids.”).

However, the records do not support a finding that petitioner’s rash and hypersensitivity

reaction that occurred in May 2019 was related to her diagnosed DRESS that began in October

2016. On May 2, 2019, petitioner reported to allergist, Dr. Young, that she rapidly developed

facial flushing approximately 90 minutes after ingesting clams, then abdominal cramping and

loose stools, which resolved overnight. Pet’r Ex. 23 at 3. The following day, petitioner

developed hives in a “generalized distribution” and chills in the afternoon and into the evening.

Id. Petitioner took Benadryl for three days and used an albuterol inhaler, which helped relieve

some of the symptoms. Id. Petitioner first saw allergist, Dr. Young, who opined that petitioner

had a reaction to the clams, stating, “Her constellation of symptoms, especially chills, rhinitis,

wheezing, loose stools suggest viral syndrome; presentation for food allergy atypical in terms of

symptom onset and the persistence of symptoms.” Id. at 5.

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When petitioner saw Dr. Yang on May 7, 2019, he recounted her history and noted that

petitioner ingested clams and “by 5 pm noted hives throughout her body,” and she developed

wheezing and chills. Pet’r Ex. 22 at 51. Dr. Yang noted that petitioner’s blood work

demonstrated elevated eosinophils, mildly elevated CRP, and increased HHV-6 titers, but no

elevated liver or kidney results. Id. By this appointment, petitioner’s rash had “mostly resolved

and her itch had greatly improved on its own.” Id. Dr. Yang was able to visualize “excoriated

papules on [right] arm x 1 and low back x 1.” Id. at 53. He diagnosed petitioner with a “rash,

favor hypersensitivity reaction based on history, resolving on its own, I do not suspect DRESS at

this time.” Id. (emphasis added). Dr. Yang also explained, “Pt’s bloodwork was reviewed in

detail and I explained that her high eosinophil and elevated CRP can be seen with any

hypersensitivity reaction,” and that he ordered an ECG to help patient “feel reassured,” because

she had ECG abnormalities during her DRESS episode, but that he “did NOT favor” a DRESS

diagnosis at this time. Id. at 54. On May 10, 2019, Dr. Yang’s office informed petitioner that

her labs were remarkable for “HHV-6 and eosinophils,” and that petitioner’s rash is “likely due

to reactive HHV-6,” but given no systemic involvement and quick improvement,” no action was

necessary. Id. at 35. When petitioner went to her primary care physician, Dr. Fitzcharles on

May 15, 2019, he wrote that petitioner’s dermatologist, Dr. Yang, “does not think that this

current episode is a recurrence of reactive HHV-6 infection causing DRESS, but instead, as per

HHV-6 Foundation to be due to some sort of hypersensitivity reaction to unknown exposure, as

current symptoms were not caused by any specific drug or medication (previous symptoms

suspected due to preservation additives in influenza vaccine).” Pet’r Ex. 14 at 54.

Even though petitioner’s lab work from this period demonstrated elevated eosinophils

and a reactivation of HHV-6, Dr. Yang specifically stated that he did not believe that her reaction

was associated with her initial DRESS reaction. Further, her presentation of symptom was

significantly different from her initial reaction to the flu vaccine in 2016. For example, the onset

of her hives was nearly immediately after eating clams, while her rash after the flu vaccine

developed approximately seven days later; she developed gastrointestinal issues after eating the

clams, and she never experienced gastrointestinal issues after the flu vaccine in 2016; and her

rash resolved after taking Benadryl for approximately three days. Finally, even with the elevated

HHV-6 PCR finding, the test results narrative explains that, “Rises in antibody titers to HHV-6

have been detected during infection with other viruses. In seroepidemiology studies of the

prevalence of exposure using serum screening dilutions of 1:10, the detection of IgG antibody in

a mid-life population approaches 100%.” Pet’r Ex. 14 at 80. Thus, there is not sufficient

evidence to demonstrate that the event in May 2019 was a related to her initial DRESS event

occurring in October 2016 after receipt of the flu vaccination.

Based on the evidence summarized above, the undersigned finds that petitioner has

proven by preponderant evidence that suffered from DRESS following her flu vaccination and

that her symptoms lasted until August 2017.

b. Causation

1. Althen Prong One

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Under Althen prong one, petitioner must provide a “reputable medical theory,”

demonstrating that the vaccine received can cause the type of injury alleged. Pafford, 451 F.3d at

1355-56. Such theory must only be “legally probable, not medically or scientifically certain.”

Knudsen, 35 F.3d 548-49. 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 v. Sec’y of Health & Hum. Servs., 569 F.3d 1367, 1378-79

(Fed. Cir. 2009) (citing Capizzano, 440 F.3d at 1325-26). However, a “petitioner must provide a

‘reputable medical or scientific explanation’ for [her] theory.” Boatmon v. Sec’y of Health and

Hum. Servs., 941 F.3d 1351, 1359 (Fed. Cir. 2019) (quoting Moberly, 592 F.3d at 1322). While

the theory need not be medically or scientifically certain, “it must still be ‘sound and reliable’”

Id. (quoting Knudsen, 35 F.3d at 548-49). The 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, 35 F.3d at 548-

49. Causation “can be found in vaccine cases…without detailed medical and scientific

exposition of the biological mechanisms.” Knudsen, 35 F.3d at 548-49.

Dr. Rosenstreich opined that the flu vaccine can cause DRESS by activating T cells,

resulting in a multisystem inflammatory reaction. Pet’r Ex. 24 at 9. Dr. Maverakis did not

directly dispute Dr. Rosenstreich’s theory for the how the influenza vaccine could cause DRESS,

he only argued that “expanding T cells specific to influenza will not cause DRESS,” and that

there are no population-based studies linking DRESS to influenza vaccination. Resp’t Ex. A at

14; Resp’t Ex. C at 2. For the reasons discussed below, the undersigned finds that petitioner

through Dr. Rosenstreich has presented a sound and reliable theory to explain how the influenza

vaccine could cause DRESS.

The medical literature filed in this case explains that the pathogenesis of DRESS is not

fully understood, but it is thought to be a T-cell mediated hypersensitivity reaction to specific

drugs. Pet’r Ex. 43 at 4; see also Pet’r Ex. 44 at 10 (“The pathomechenisms of DRESS

syndrome are complex and largely unknown.”); Pet’r Ex. 36 at 5 (“Although several theories

have been proposed, the pathomechanisms of DIHS/DRESS remains largely unknown.”). Dr.

Rosenstreich opined that the flu vaccine activated T-cells, causing them to release inflammatory

cytokines, such as TNF-α and IFN-ƴ, resulting in the multisystem inflammatory reaction. Pet’r

Ex. 24 at 8. Additionally, the Picard et al. article found that DRESS patients had circulating

CD8+ T-cells that were activated, exhibited increased cutaneous homing markers, and secreted

large amounts of TNF-α and INF-ƴ. Pet’r Ex. 28 at 2. Further, the articled explained that the

“cutaneous and systemic manifestations of an immune response [is] mainly mediated by CD8+

T-lymphocytes directed against herpes virus antigens,” which suggests that the “culprit drug may

induce reactivation and antigenic presentation of quiescent forms of EBV or other herpes viruses

in cells such as B lymphocytes, which could secondarily trigger a multiorgan immune response

directed against herpes viruses.” Id. at 7-8.

The case report by Hewitt, which described a female patient developing DRESS four

days after receiving the H1NI vaccine, also endorsed the mechanism of T-cell expansion as a

result of the influenza vaccination as the cause of DRESS in the patient. Pet’r Ex. 24 at 3. Even

though the patient in the Hewitt case report was also taking sulphasalazine, a known causative

agent of DRESS, the patient had been taking that medication for 12 months and it was only after

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the introduction of the flu vaccine did the patient develop DRESS. Id. at 3. Respondent also

filed the case report by Griffin et al., which described an 80-year old male that developed

DRESS seven days after receiving the influenza vaccine. Resp’t Ex. A, Tab 3. The authors of

this care report wrote that the patient’s DRESS, “was likely triggered by influenza vaccination.”

Id. at 1. Griffin reiterated that “[t]he pathophysiology of DRESS remains unclear, but it involves

an aberrant T-lymphocyte response to an antigen, including drugs and infection.” Id. at 2.

Further, the case report states, “As an immune stimulant, it makes sense that vaccination could

trigger DRESS in certain individuals.” Id. The authors hypothesized that patient’s DRESS

“could be a direct reaction to a vaccine component, or that non-specific immune activation

following vaccination could permit a reaction to medication.” Id.

Dr. Maverakis only characterizes Dr. Rosenstreich’s theory that the influenza vaccine

caused a non-specific T-cell activation as “speculative” in both of his reports and does little to

refute the theory posited by petitioner. See Resp’t Ex.A at 16; Resp’t Ex. B at 7. Instead, he

argued unpersuasively that there are no large-scale population studies that link the influenza

vaccine to DRESS, and only a limited number of case reports describing DRESS post-

vaccination. Resp’t Ex. C at 2. However, the medical literature filed by both parties establishes

that the pathogenesis of DRESS if not fully understood and the lack of such research does not

defeat petitioner’s claim. Moreover, petitioner need not demonstrate a theory by scientific

certainty to show that a theory is sound and reliable. See Knudsen, 35 F.3d at 549 (explaining

that “to require identification and proof of specific biological mechanisms would be inconsistent

with the purpose and nature of the vaccine compensation program.”). Further, lack of

epidemiological studies is not dispositive. “Requiring epidemiologic studies….or general

acceptance in the scientific communities…impermissibly raises a claimant’s burden under the

Vaccine Act.” Andreu, 569 F.3d at 1378 (quoting Capizzano, 440 F.3d at 1325-26).

Instead, the medical literature described above supports Dr. Rosenstreich’s theory for

how the flu vaccine can cause DRESS, and accordingly petitioner has demonstrated Althen prong

one by preponderant evidence.

2. Althen Prong Two

Under 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). “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, 451 F.3d at 1356 (internal citations omitted).

In evaluating whether this prong is satisfied, the opinions and views of the vaccinee’s

treating physicians are entitled to some weight. Andreu, 569 F3d at 1367; Capizzano, 440 F.3d

at 1326 (“[M]edical records and medical opinion testimony are favored in vaccine cases, as

treating physicians are likely to be in the best position to determine whether a ‘logical sequence

of cause and effect show[s] that the vaccination was the reason for the injury.’ ” (quoting Althen,

418 F.3d at 1280)). Medical records are generally viewed as trustworthy evidence, since they are

created contemporaneously with the treatment of the vaccinee. Cucuras, 993 F. 2d at 1528.

While the medical records and opinions of treating physicians must be considered, they are not

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binding on the special master. § 13(b)(1)(B) (specifically stating that the “diagnosis, conclusion,

judgment, test result, report, or summary shall not be binding on the special master or court.”).

A petitioner need not make a specific type of evidentiary showing, i.e. “epidemiologic

studies, rechallenge, the presence of pathological markers o/r genetic predisposition, or general

acceptance in the scientific or medical communities to establish a logical sequence of cause and

effect.” Capizzano, 440 F.3D at 1325. Instead, a petitioner may satisfy their burden by

presenting circumstantial evidence and reliable medical opinions. Id. at 1325-26.

Petitioner has demonstrated by preponderant evidence a logical sequence of cause and

effect establishing that the flu vaccine she received on September 29, 2016 the cause of her

developing DRESS. Importantly, as discussed above, the undersigned found that petitioner

preponderantly established that she developed DRESS and that her symptoms continued until

August 2017. Additionally, petitioner proffered a sound and reliable mechanism of vaccine

causation.

Moreover, petitioner’s various treating physicians provide circumstantial evidence in

support of vaccine causation. On October 10, 2016, dermatologist, Dr. Kenneth Reed, assessed

petitioner with a “hypersensitivity reaction: erythematous popular eruption distributed on the

trunk; pt just had her flu shot, possible reaction to it.” Pet’r Ex. 9 at 6 (emphasis added). Dr.

Yang, petitioner’s treating dermatologist at Brigham and Women’s Dermatology Department,

diagnosed petitioner with “rash, likely hypersensitivity reaction to component of flu vaccine,”

after his first appointment with her on October 21, 2016. Pet’r Ex. 2 at 90. After reviewing her

labs, which were remarkable for elevated eosinophils and liver test results, and HHV-6 titers, Dr.

Yang revised his diagnosis of petitioner to “Generalized rash, thought likely DRESS from flu

shot,” and he also noted that petitioner had been on “HCTZ and Synthroid…and Lipitor” for a

long period of time that those drug were “extremely unlikely [to be] the culprit, as DRESS

usually occurs 1-8 weeks after trigger.” Pet’r Ex. 2 at 69, 75. At petitioner’s third appointment

on November 8, 2016 with Dr. Yang, he again revised his diagnosis of petitioner to “DRESS,

most likely from flu shot,” and in describing petitioner’s history, he wrote, “…pleasant 56-year

old female with DM and DLP who presents today for a [follow-up] of DRESS (prior symptoms

include facial swelling, eosinophilia, elevated ALT, and HHV-6 reactivation on PCR)most likely

triggered from influenza vaccine that patient received on 9/29/16.” Id. at 69 (emphasis added).

Most importantly, Dr. Yang explicitly explained that petitioner’s other drugs were not likely the

cause of her developing DRESS, as she had been on them for a long-period of time. These

statements, individually and collectively, constitute circumstantial evidence that petitioner’s

treating physicians associated the flu vaccine she received on September 29, 2016 with the

development of her DRESS.

Dr. Maverakis acknowledged that petitioner developed a rash approximately one week

after the flu vaccine, along with eosinophilia, abnormal liver function tests, and HHV-6

reactivation, but opined that it was a possible combination of petitioner’s age and a history of

elevated IgE that caused her “pruritic skin eruptions.” Resp’t Ex. A at 14. Aside from

suggesting that it was not the flu vaccine that caused petitioner to develop a rash, and other signs

and symptoms consistent with DRESS, he does not suggest an alternative cause for the sudden

onset of these symptoms approximately seven days post-vaccination.

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As petitioner has provided a sound and reliable mechanism to explain how the flu vaccine

could cause DRESS, petitioner developed DRESS in the manner described in the medical

literature, and her treating physicians associated her condition to the flu vaccine, petitioner has

provided preponderant evidence of a logical sequence of cause and effect establishing that the flu

vaccine caused her DRESS, and has satisfied Althen prong two.

3. Althen Prong Three

Althen prong three requires petitioners to establish a “proximate temporal relationship”

between the vaccination and the injury alleged. Althen, 418 F.3d at 1281. That term has been

defined as a “medically acceptable temporal relationship.” Id. Petitioners 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, 539 F.3d at 1352. The explanation for what is a medically

acceptable timeframe must also coincide with the theory of how the relevant vaccine can cause

the injury alleged (under Althen prong one). Id.; 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 a causal link and that petitioner must posit a medical

theory causally connecting the vaccine and injury.”).

Dr. Rosenstreich opined that the onset of petitioner’s DRESS, approximately 4–7-day

post-vaccination is consistent with “the time it takes to begin activating influenza antigen or drug

antigen specific T lymphocytes and expanding the clone of these specific cells to a number large

enough to cause inflammatory symptoms in the skin and other organs.” Pet’r Ex. 24 at 11. The

three case reports where patients developed DRESS after the flu vaccine all developed their

symptoms between 4-7 days post-vaccination. See Resp’t Ex. A, Tab 3 at 1 (patient received the

flu vaccine 7 days prior to DRESS symptom onset); Pet’r Ex. 34 at 1 (onset of rash,

lymphadenopathy, and fever 4 days post-H1N1 vaccination); Pet’r Ex. 35 at 2 (onset of

maculopapular skin rash, facial edema, and dysuria seven days after receiving an influenza

vaccine). Additionally, the medical literature describing DRESS explains that usually there is a

delay of symptom onset between receipt of the “offending drug” and symptoms. See Pet’r Ex.

43 at 4 (“The latency phase (from drug initiation to onset of reaction) typically ranges from two

to eight weeks.”); Pet’r Ex. 29 at 3 (Th disease usually starts abruptly with maculopapular

morbilliform exanthema with fever….2-3 weeks after the introduction of the culprit drug.”).

Dr. Maverakis agreed that petitioner’s rash began one week post-vaccination, however,

since the majority of his opinion was focused on petitioner’s diagnosis, he did not provide an

opinion as to whether the development of her rash occurred in a medically acceptable timeframe

for her symptoms to begin. See Resp’t Ex. A at 2; Resp’t Ex. B at 2 (“a temporal relationship

between her rash and an influenza vaccine a few days prior is not sufficient evidence to

conclude…that the vaccine caused her skin rash.”).

Petitioner received the influenza vaccine on September 29, 2016 and she went to the

emergency department on October 10, 2016 stating that she developed a “rash seven days ago,”

25

that was on her back and torso and developed to facial edema and “papularity.”). Pet’r Ex. 6 at

20. Petitioner consistently reported this timeframe of symptom onset to her providers, who

associated the onset of her rash to the flu vaccine. See Pet’r Ex. 6 at 33-36; Pet’r Ex. 2 at 59-62.

The onset of petitioner’s symptoms and the symptoms she experienced was consistent

with the three case reports where patients developed DRESS symptoms 4-7 days post-

vaccination. Additionally, the delayed onset of her symptoms was consistent with the DRESS

diagnosis, as described in the medical literature, and supported by her treating physicians.

Therefore, the undersigned finds that petitioner has preponderantly established Althen prong

three.

V. Conclusion

In accordance with the above, petitioner has established by preponderant evidence that

she is entitled to compensation, having demonstrated that the flu vaccine she received on

September 29, 2016 was the cause-in-fact of her developing DRESS from which she suffered

through August 2017. A separate damages order will be issued.

IT IS SO ORDERED.

s/Thomas L. Gowen

Thomas L. Gowen

Special Master

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