# Horvath v. Secretary of Health and Human Services

> United States Court of Federal Claims · January 3, 2019

URL: https://www.frixlaw.com/law-library/cases/4355839

## Case

- **Court:** United States Court of Federal Claims
- **Decided:** January 3, 2019
- **Precedential status:** Published
- **Opinion:** Opinion
- **Judges:** Laura D. Millman
- **Cited by:** 0 later opinions in the Frix Law Library

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## Opinion text

In the United States Court of Federal Claims
OFFICE OF SPECIAL MASTERS
No. 15-260V
Filed: December 20, 2018
To be Published

*************************************
S.E.H., *
*
Petitioner, *
* Influenza (“flu”) vaccine; mixed
v. * connective tissue disease (“MCTD”);
* failure to provide a persuasive
SECRETARY OF HEALTH * medical theory of causation
AND HUMAN SERVICES, *
*
Respondent. *
*
*************************************
Michael A. Firestone, San Mateo, CA, for petitioner.
Linda S. Renzi, Washington, DC, for respondent.

MILLMAN, Special Master

DECISION1

On March 13, 2015, petitioner filed a petition pro se under the National Childhood
Vaccine Injury Act, 42 U.S.C. § 300aa-10-34 (2012), alleging that influenza (“flu”) vaccine
administered in her left deltoid on September 20, 2012 caused her mixed connective tissue
disease (“MCTD”) whose onset was October 3, 2012 with joint pains. Pet. Preamble and ¶¶ 2, 4;
Pet. Tab 2.

On August 11, 2015, petitioner retained counsel. On January 4, 2016, petitioner filed an
amended petition, alleging in the alternative that her September 20, 2012 flu vaccination caused
significant aggravation of an underlying autoimmune disease that was asymptomatic until early
October 2012. Am. Pet. at ¶ 20.

1
Vaccine Rule 18(b) states that all decisions of the special masters will be made available to the public unless they
contain trade secrets or commercial or financial information that is privileged and confidential, or medical or similar
information whose disclosure would constitute a clearly unwarranted invasion of privacy. This means the decision
will be available to anyone with access to the Internet. When such a decision is filed, petitioner has 14 days to
identify and move to redact such information prior to the document’s enclosure. If the special master, upon review,
agrees that the identified material fits within the banned categories listed above, the special master shall redact such
material from public access. Petitioner filed a motion to redact on December 27, 2018 which the undersigned
granted on December 28, 2018.
A hearing was held on August 29, 2017. Testifying for petitioner were petitioner,
petitioner’s husband, and Dr. S. Sohail Ahmed. Testifying for respondent was Dr. Mehrdad
Matloubian.

On April 27, 2018, petitioner filed her post-hearing brief.

On August 31, 2018, respondent filed his post-hearing brief.

On November 16, 2018, petitioner filed her reply to respondent’s post-hearing brief.

Because the undersigned finds petitioner has failed to present a persuasive scientific or
medical theory to associate causally her September 20, 2012 flu vaccination with MCTD or, in
the alternative, to prove flu vaccine significantly aggravated her prior rheumatologic disease, the
undersigned dismisses this case.

FACTS

Prevaccination Records

Petitioner was born on July 17, 1955.

On October 7, 1999, petitioner received flu vaccine2 in her left deltoid. Med. recs. Ex.
16, at 1.

On February 8, 2000, petitioner saw Dr. Anjali Sagdeo, and gave a history that she
received a flu vaccination in her left arm and, since then, had pain in her left arm and difficulty
raising it.3 Med. recs. Ex. 12, at 1 (same record filed as Ex. 69, at 1). She saw a worker’s
compensation doctor. On physical examination, petitioner had tenderness in her left upper arm

2
In the 1999-2000 flu vaccine season, the trivalent flu vaccine contained A/Sydney/5/97-like virus (H3N2),
A/Beijing/262/95-like virus (H1N1), and B/Beijing/184/93-like (Yamagata lineage) virus. Update: Influenza
Activity – United States and Worldwide, 1998-99 Season, and Composition of the 1999-2000 Influenza Vaccine, 48
MORBIDITY AND MORTALITY WEEKLY REPORT (MMWR) 18:374-78 (May 14, 1999),
https://www.cdc.gov/mmwr/preview/mmwrhtml/mm4818a2.htm.
3
Petitioner’s description of left arm pain and difficulty raising her left arm a day after vaccination may have been
SIRVA (shoulder injury related to vaccine administration), which became a Table injury after March 21, 2017.
National Vaccine Injury Compensation Program: Revisions to the Vaccine Injury Table; Delay of Effective Date, 82
Fed. Reg. 34:11321 (Feb. 22, 2017). The Vaccine Injury Table is at 42 C.F.R. § 100.3(a). The Qualifications and
aids to interpretation, § 100.3(c)(10), state “SIRVA manifests as shoulder pain and limited range of motion
occurring after administration of a vaccine intended for intramuscular administration in the upper arm. The
symptoms are thought to occur as a result of unintended injection of vaccine antigen or trauma from the needle into
and around the underlying bursa of the shoulder resulting in an inflammatory reaction. SIRVA is caused by an
injury to the musculoskeletal structures of the shoulders (e.g. tendons, ligaments, bursae, etc.).” One of the
manifestations of SIRVA is “(iii) Pain and reduced range of motion … limited to the shoulder in which the
intramuscular vaccine was administered….” Id. The Vaccine Injury Table requires onset of SIRVA within 48 hours
of vaccination. Id. at (a). Petitioner’s description of her left arm pain and difficulty raising her left arm a day after
vaccination may have been SIRVA.
2
and decreased abduction. Dr. Sagdeo’s diagnosis was tendinitis4 – inflammation secondary to
injury from an intramuscular injection. Petitioner was right-handed. Dr. Sagdeo suggested she
follow up with the worker’s compensation doctor. Id.

On February 29, 2000, petitioner saw Dr. Dinesh N. Bhuva, giving a history that she
received flu vaccine in her left arm in November 1999 and, the next day, had a punched arm.
She could not sleep on the shoulder or abduct her arm. She could not pull up her pants. Her
range of motion declined. The doctor diagnosed petitioner with tendinitis. An examination for
her left shoulder pain revealed tenderness at the supraspinatus5 insertion. X-ray revealed
calcification of the supraspinatus.6 Med. recs. Ex. 69, at 2.

On March 9, 2000, petitioner saw Dr. Sagdeo, to rule out food and alcohol allergies.
Petitioner states her face got red with [the following word was redacted]. This also happened
with certain foods. Dr. Sagdeo referred petitioner to an allergist. He also diagnosed her with
hypothyroidism.7 Med. recs. Ex. 12, at 4 (same record filed as Ex. 69, at 4).

On March 29, 2000, petitioner saw Dr. Bhuva for a recheck of her left shoulder. Id. at 4.
Petitioner’s last injection helped a lot for three weeks, but now her left shoulder hurt again. It

4
Tendinitis is “inflammation of tendons and of tendon-muscle attachments. . . .” DORLAND’S ILLUSTRATED
MEDICAL DICTIONARY 1881 (32nd ed. 2012) [hereinafter “Dorland’s”].
5
Supraspinatus tendinitis or painful arc syndrome occurs in the shoulder. The shoulder joint owes its stability to the
rotator cuff muscles—which are four small muscles located around the shoulder joint which help with movement,
but importantly their tendons stabilize the head of the humerus within the joint capsule. The tendon of one of these
muscles—the supraspinatus--commonly impinges on the acromion (the bone forming the tip of the shoulder) as it
passes between the acromion and the humeral head. The supraspinatus muscles help abduct (lift up sideways) the
arm. Any friction between the tendon and the acromion is normally reduced by the subacromial bursa—a fluid
filled sac between the supraspinatus tendon and the acromion. Arthritis can cause painful arc syndrome.
Supraspinatus tendinitis is very common and typically seen in people aged 25-60. It can also result from gradual
degeneration with wear and tear or other inflammatory disorders, such as rheumatoid arthritis. An x-ray may show
calcification. Chronic trauma and impingement may lead to osteoarthritis of the shoulder. Supraspinatus tendinitis
(painful arc syndrome), MYVMCVIRTUALMEDICALCENTRE, https://www.myvmc.com/diseases/supraspinatus-
tendinitis-painful-arc-syndrome/ (last visited November 26, 2018). The humerus is “the bone that extends from the
shoulder to the elbow.” Dorland’s at 873. “The humeral head is the ‘ball’ part of the ball and socket” making up the
shoulder. Anatomy of the shoulder (glenohumeral joint/scapulo-thoracic joint), MYVMCVIRTUALMEDICALCENTRE,
https://www.myvmc.com/anatomy/anatomy-of-the-shoulder-glenohumeral-jointscapulo-thoracic-joint/ (last visited
November 26, 2018). Painful arc syndrome is “shoulder pain occurring at a particular portion of the arc described
when the arm is abducted from the side to the fully raised position, as in inflammation of the tendons of the
supraspinatus muscle.” Dorland’s at 1842.
6
“Supraspinatus tendon calcification is thought to be due to the deposition of calcium hydroxyapatite crystals inside
the supraspinatus tendon near the greater tuberosity of the humerus insertion point, and the calcium deposits in the
supraspinatus tendon may be due to fibrosis, necrosis, tendon degeneration, or systemic non-degenerative causes.
[citation omitted].” David C. Riley et al., Emergency department diagnosis of supraspinatus tendon calcification
and shoulder impingement syndrome using bedside ultrasonography, 5 CRIT ULTRASOUND J 1-4, at 2-3 (2013).
7
Hypothyroidism is “a deficiency of thyroid activity, characterized by decrease in basal metabolic rate, fatigue, and
lethargy. . . .” Dorland’s at 907. The most common cause of hypothyroidism is Hashimoto’s thyroiditis or
autoimmune hypothyroidism, but Hashimoto’s is not the sole cause of hypothyroidism. Eren Berber, MD, Causes of
Hypothyroidism. Hashimoto’s thyroiditis is the most common cause, ENDOCRINEWEB,
https://www.endocrineweb.com/conditions/hypothyroidism/causes-hypothyroidism (last visited November 2, 2018).
3
hurt with overhead reaching. Id.

On April 4, 2000, petitioner filled out an Allergy Questionnaire for Dr. Clayton A.
Feldman. Med. recs. Ex. 12, at 1 (same record filed as Ex. 69, at 6). She said she had seasonal
hay fever, food allergy, and drug allergy. She complained of nasal congestion, itchy eyes,
swollen eyelids, dark circles under her eyes, and a sinus headache. Med. recs. Ex. 12, at 1. She
said 20 years previously, she broke out in hives after receiving sulfa. Id. at 8. She told Dr.
Feldman that she had years of sinus problems. Id. at 15. She had been getting erythema8 of the
face, nausea, and headaches in the past year. Id. at 16. Dr. Feldman’s impression was that
petitioner did not have a conventional food allergy, but food intolerances without food allergy.
Id. Her symptoms sounded like a vascular reaction, such as migraine,9 and he recommended she
eliminate foods for which she had no tolerance. Id. at 12-13 (same record filed as Ex. 69, at 16-
17).

On April 7, 2000, Dr. Feldman wrote a consultation report. Med. recs. Ex. 9, at 11.
Petitioner said she had several years of minor sinus and seasonal allergy symptoms. In the past
year, she had some concern about food allergy. She had been getting erythema of her face,
nausea, and headaches from almost any kind of alcoholic beverage. She experimented with red
and white wines, gin and tonic, and beer, and got reactions approximately 20 minutes after each.
She had a similar reaction after a mushroom omelet one month ago, but this occurred only once.
A few weeks earlier, she went on the Atkins diet for weight control, and since then her sinus
headaches disappeared. She ate meat, fish, and limited carbohydrates, and took supplements, but
no fruits, bread, pasta or sugars. She had a history of sulfa sensitivity. She had good relief from
mild seasonal hay fever with antihistamines, Sudafed,10 and topical steroids. Her physical
examination was unremarkable except for slightly thickened red nasal membranes. The RAST11
allergy testing was negative for fruits that she eliminated from her diet, including banana, lemon
apple, orange, peach, strawberry, and melon. Dr. Feldman’s impression was food intolerance
without food allergy, and minimal seasonal and perennial allergic rhinitis. Id. Dr. Feldman
stated petitioner really did not have a conventional food allergy. Her symptoms sounded like a
vascular reaction, something like a migraine. Id. at 11, 13.

On May 3, 2000, petitioner went to Dr. Bhuva for a recheck of her left shoulder. Med.
recs. Ex. 12, at 14 (same record filed as Ex. 69, at 18). She still had pain and could not do her
hair. Id.

8
Erythema is “redness of the skin produced by congestion of the capillaries.” Dorland’s at 643.
9
Migraine is “an often familial symptom complex of periodic attacks of vascular headache, usually temporal and
unilateral in onset, commonly associated with irritability, nausea, vomiting, constipation or diarrhea, and often
photophobia. Attacks are preceded by constriction of the cranial arteries, often with resultant prodromal sensory
(especially ocular) symptoms and the spreading depression of Leão; the migraines themselves commence with the
vasodilation that follows.” Dorland’s at 1166.
10
Sudafed is “trademark for preparations containing pseudoephedrine hydrochloride.” Dorland’s at 1796. It is used
as a nasal decongestant. Id. at 1542.
11
RAST is an acronym for “radioallergosorbent test.” Dorland’s at 1593.
4
On May 15, 2000, petitioner’s TSH12 of 6.16 was consistent with hypothyroidism. Med.
recs. Ex. 9, at 5.

On May 30, 2000, petitioner had an MRI to rule out rotator cuff tear as the cause of her
left shoulder pain. Id. at 9.

On June 2, 2000, petitioner saw Dr. Michael W. Su for migraine headaches. Med. recs.
Ex. 12, at 18. She had migraines triggered by certain foods: smoked foods and almonds. She
thought she had some nausea with photophobia. She also had a urinary tract infection. Id.

On October 31, 2000, petitioner saw Dr. Gary Lee to have her thyroid checked. Med.
recs. Ex. 16, at 24. She told Dr. Lee she felt exhausted over the prior week. Dr. Lee diagnosed
petitioner with hypothyroidism. Id.

On January 24, 2001, petitioner saw Dr. Joel S. Saal for an orthopedic consultation.
Med. recs. Ex. 11, at 1. Petitioner complained of low back pain and right leg hypesthesia.13 The
onset was December 15, 2000 while she was working as a nurse. She was using a slideboard to
help a patient transfer when the patient’s foot caught on the edge of the board and she reached
over to pull it up and support the foot. She went to Urgent Care and received a Demerol14
injection, Vicodin,15 and Flexeril.16 She was prescribed physical therapy twice a week and
placed on work restrictions of no bending, twisting, or lifting. She described no improvement
and each day when she would work, her pain became worse and was not relieved until she lay
down at night. She stopped working for a number of days and her symptoms improved
somewhat but still persisted and increased with any bending, lifting, or sitting for prolonged
periods of time. Petitioner was taking Flexeril and Naprosyn.17 Id. Dr. Saal diagnosed
petitioner with probable annulus18 tear, L4-L5 vs. L5-S1. Id. at 2. He suggested she supplant the
anti-inflammatory medicine with exercises. Id.

12
TSH stands for “thyroid-stimulating hormone.” Dorland’s at 1902.
13
Hypesthesia or hypoesthesia is “a dysesthesia consisting of abnormally decreased sensitivity, particularly to
touch.” Dorland’s at 901.
14
Demerol is “trademark for preparations of meperidine hydrochloride.” Dorland’s at 485. Meperidine
hydrochloride is “a synthetic opioid analgesic, used as an analgesic to relieve moderate to severe pain. . . .” Id. at
1136.
15
Vicodin is “trademark for combination preparations of hydrocodone bitartrate and acetaminophen.” Dorland’s at
2055. Hydrocodone is “a semisynthetic opioid analgesic derived from codeine but having more powerful sedative
and analgesic effects.” Id. at 878.
16
Flexeril is “trademark for a preparation of cyclobenzaprine hydrochloride.” Dorland’s at 717. Cyclobenzaprine
hydrochloride is “a compound structurally related to the tricyclic antidepressants, used as a skeletal muscle relaxant
for relief of painful muscle spasms. . . .” Id. at 455.
17
Naprosyn is “trademark for preparations of naproxen.” Dorland’s at 1232. Naproxen is “a nonsteroidal anti-
inflammatory drug that is a propionic acid derivative, used in the treatment of pain, inflammation, osteoarthritis,
rheumatoid arthritis, gout, calcium pyrophosphate deposition disease, fever, and dysmenorrhea and in the
prophylaxis and suppression of vascular headache. . . .” Id.
18
Annulus is “a ring or ringlike structure. . . .” Dorland’s at 94.
5
On April 3, 2001, Dr. Saal performed a lumbar transforaminal19 selective epidural block,
in the left L5 position. Id. at 5.

On April 23, 2001, petitioner returned to Dr. Saal. Id. at 7. She had marked relief for a
short period of time following the epidural injection, but no significant change in her symptoms.
Her MRI showed only minor degenerative changes at L4-L5 with a slight annular bulge, but no
evidence of significant abnormality. Dr. Saal’s impression was probable discogenic pain, most
likely from the L4-L5 segment. Id. He suggested petitioner change where she received physical
therapy or, if that were unsuccessful, have a repeat epidural injection. In addition, he wanted
petitioner to start acupuncture. Id.

On July 26, 2001, petitioner saw Dr. Su, complaining of coughing for one month. Med.
recs. Ex. 16, at 26.

On September 21, 2001, Dr. Saal performed a lumbar intradiscal electrothermal
annuloplasty (“IDET”) on petitioner. Med. recs. Ex. 11, at 17.

On September 25, 2001, petitioner saw Dr. Harley B. Negin, complaining of headache,
and palpitations for months. Med. recs. Ex. 69, at 29.

On October 18, 2001, Dr. Saal reevaluated petitioner. Med. recs. Ex. 11, at 20. She had
no further leg pain after her IDET, but her back pain was the same. Id.

On November 29, 2001, Dr. Saal reevaluated petitioner. Id. at 21. She said she felt about
30 percent better. She had difficulty with long standing. Dr. Saal recommended a pool program.
Id. She was to remain on temporary total disability through January 30, 2002. Id.

On January 3, 2002, Dr. Saal reevaluated petitioner. Id. at 22. She was markedly
improved but still significantly symptomatic and limited. Her abdominal muscles were
extremely weak. Dr. Saal recommended progression in her physical rehabilitation program. She
was to remain on temporary total disability through March 30, 2002. Id.

On January 29, 2002, petitioner saw Dr. Su, complaining of problems with her back.
Med. recs. Ex. 69, at 30. She was continuing to undergo therapy for her back. Id.

On February 28, 2002, Dr. Saal reevaluated petitioner. Med. recs. Ex. 11, at 24. She was
improving somewhat from her flare up. The symptoms were unchanged, mostly in her back.
She took Prednisone20 and then went on Vioxx. Her physical examination showed painful
lumbar flexion and extension. Dr. Saal prescribed acupuncture and extended her total temporary
disability through April 20, 2002. Id.

19
Transforaminal is “through or across a foramen.” Dorland’s at 1952. Foramen is “a natural opening or passage,
especially one into or through a bone.” Id. at 729.
20
Prednisone is “a synthetic glucocorticoid derived from cortisone, administered orally as an anti-inflammatory and
immunosuppressant in a wide variety of disorders.” Dorland’s at 1509.
6
On April 24, 2002, Dr. Saal reevaluated petitioner. Id. at 25. She described persistent
symptoms: pressure in her low back and some symptoms in her right leg. Overall, she described
herself as 50-60 percent improved. Dr. Saal injected Marcaine21 and Decadron22 into the soft
tissue region in the right L5-S1 interspace because it was tender. Id. This decreased petitioner’s
leg pain but had no effect on the pressure sensation in her low back. Id.

On June 27, 2002, Dr. Saal reevaluated petitioner. Id. at 26. Petitioner said she was
progressively improving. She had daily symptoms, but could tolerate them. Id. She remained
on total temporary disability through August 30, 2002. Id.

On July 11, 2002, Dr. Saal gave petitioner soft tissue injections with Marcaine, Depo-
Medrol,23 and Decadron after she complained about a slight increase in symptoms when she
reduced her dosage of Vioxx. Id. at 27, 28. Her disability status remained unchanged. Id. at 27.

On August 20, 2002, Dr. Saal reevaluated petitioner. She said she did not get a good
response from the intramuscular and deep paraspinal soft tissue injections, and did not receive
lasting relief from corticosteroids. Id. at 29. Her symptoms were now back to her baseline. She
tolerated the increased level of exercise from three months ago. Dr. Saal hoped to increase her
exercise tolerance and if that did not succeed, move toward a lumbar epidural. Id.

On October 15, 2002, Dr. Saal reevaluated petitioner. Id.at 30. Petitioner said she had a
little flare up of ankle pain and secondarily back pain, worse on the right than on the left. It
occurred while she was exercising more aggressively using the treadmill and doing squatting
exercises. It was similar to what she experienced at the early onset of her low back pain
syndrome. She was concerned that this was extremity referral pain from the lumbar spine. On
physical examination, however, she had some swelling in the retro-Achilles bursa and there was
marked tenderness over this on the right greater than on the left. Dr. Saal’s impression was that
her extremity pain was secondary to pre-Achilles bursitis and her back pain flare up was due to
increasing stress from her exercises. Dr. Saal’s plan was to carry out an intensive and focused
rehabilitation program. Petitioner remained on temporary total disability until November 30,
2002. Id.

21
Marcaine is “trademark for preparations of bupivacaine hydrochloride.” Dorland’s at 1105. Bupivacaine
hydrochloride is “a homologue of mepivacaine, chemically related to lidocaine, used as a local anesthetic for
infiltration, peripheral nerve block, retrobulbar block, subarachnoid block, sympathetic block, and caudal and
epidural anesthesia.” Id. at 261.
22
Decadron is “trademark for a preparation of dexamethasone.” Dorland’s at 474. Dexamethasone is “a synthetic
glucocorticoid, 25 times as potent as cortisol: used topically on the skin and conjunctiva as an anti-inflammatory and
administered orally in replacement therapy for adrenocortical insufficiency, as an anti-inflammatory and
immunosuppressant in a wide variety of disorders, and as an antiemetic in cancer chemotherapy.” Id. at 504.
23
Depo-Medrol is “trademark for preparations of methyl-prednisolone acetate.” Dorland’s at 492. Methyl-
prednisolone is “a synthetic glucocorticoid derived from progesterone, used in replacement therapy for
adrenocortical insufficiency and as an anti-inflammatory and immunosuppressant in a wide variety of disorders.”
Id. at 1154.
7
On November 7, 2002, Dr. Saal reevaluated petitioner. Id. at 31. Petitioner’s low back
had a slight flare up from doing some hamstring strengthening exercise, but overall she was
doing fairly well. Her ankle was significantly better although somewhat symptomatic after a
local injection. Dr. Saal recommended orthotics and strengthening exercises. Petitioner
remained on temporary total disability through December 30, 2002. Id.

On January 6, 2003, petitioner filled out a medical history for a chiropractor K. Robyn
Kubo-Manley at Willow Chiropractic, stating she had the following medical history: neck pain,
pain in her arms and legs, thyroid problems, and a lower back injury since 2000. Med. recs. Ex.
15, at 16.

On January 7, 2003, Dr. Saal reevaluated petitioner. Med. recs. Ex. 11, at 32. Petitioner
said her symptoms persisted. Her exercise tolerance had improved, but she had a persistent
limitation and inability to carry out any hip or leg extension. This caused increased back pain.
She described a 50 percent reduction in symptom level. Dr. Saal pondered the etiology of
petitioner’s persistent low back pain and thought it could be residual discogenic pain at the L5-
S1 vs. posterior element pain. He thought diagnostic therapeutic facet blocks were indicated.
Petitioner remained on full temporary disability through March 3, 2003. Id.

On January 9, 2003, petitioner saw Dr. Su, complaining of continuing problems with her
back. Med. recs. Ex. 12, at 29 (filed also as Ex. 69, at 33).

On January 28, 2003, petitioner had an MRI of her lumbar spine, to be compared to one
done March 23, 2001 which had revealed mild disc disease at the L3-L4 and L5-S1 disc levels
without evidence for herniation or transligamentous disc extrusion. Med. recs. Ex. 11, at 33. Dr.
Murray A. Solomon’s findings were there were no significant interval changes from the previous
MRI. There was mild disc disease at the L4-L5 and L5-S1 disc levels without evidence for large
herniation or transligamentous disc extrusion at either level. Id.

On February 7, 2003, petitioner saw Dr. Saal and told him she had a flare up with back
pain centrally and bilaterally from doing scissor kicks in the pool. Id. at 23. Dr. Saal increased
her Vioxx.24 Id.

On February 11, 2003, petitioner saw Dr. Su, stating that Zoloft helped her somewhat and
elevated her mood to some degree. She had an underactive thyroid. Dr. Su increased
petitioner’s dosage of Synthroid.25 Med. recs. Ex. 69, at 34.

On February 13, 2003, petitioner saw Dr. Saal complaining of low back pain. Med. recs.

24
Vioxx is “trademark for a preparation of rofecoxib.” Dorland’s at 2057. Rofecoxib is “a nonsteroidal anti-
inflammatory drug of the COX-2 inhibitors groups, used in treatment of osteoarthritis, acute pain, and
dysmenorrhea. . . .” Id. at 1652.
25
Synthroid is “trademark for a preparation of levothyroxine sodium.” Dorland’s at 1856. Levothyroxine sodium is
“the monosodium salt of L-thyroxine, the naturally occurring form of thyroxine, obtained from the thyroid gland of
domesticated food animals or prepared synthetically. It is used as replacement therapy for hypothyroidism and in
the prophylaxis and treatment of goiter and of thyroid carcinoma. . . .” Id. at 1032.
8
Ex. 11, at 35. Dr. Saal writes that her MRI scan showed no significant change compared to the
one in 2001. She had degenerative changes only at L5-S1, which had not progressed. However,
she had significant facet degenerative changes at those levels. On physical examination,
petitioner had painful extension, worse on the right than on the left as well as in the center. Dr.
Saal planned to carry out lumbar facet injections. Petitioner remained on temporary total
disability through April 30, 2003. Id.

On March 7, 2003, Dr. Saal performed a lumbar intra-articular facet block on the right
and left of L4-L5 and L5-S1. Id. at 36.

On April 3, 2003, Dr. Saal reevaluated petitioner. Id. at 39. Petitioner said she was 30
percent improved. She had marked dramatic improvement the day of the facet blocks which
lasted approximately six hours following the anesthetic injection. This strongly suggested to Dr.
Saal that facet symptoms and facet irritation played a role in generating her present pain. He
proposed advancement in physical rehabilitation. Petitioner remained on temporary total
disability through May 30, 2003. Id.

On April 24, 2003, Dr. Saal reevaluated petitioner. Id. at 40. She reported that her
marked improvement in back pain and increased exercise tolerance had begun to wear off and
she was approximately 40 percent worse than the best she had felt after the facet injections. Her
symptoms were localized across her lower back and increased with extension, which was limited
approximately 80 percent that day. Dr. Saal’s impression was that petitioner had facet-related
pain and would benefit from a median branch rhizotomy26 if median branch diagnostic blocks
were helpful. Id.

On May 23, 2003, Dr. Saal performed lumbar median nerve root blocks on the right and
left of L3, L4, and L5. Id. at 41.

On June 19, 2003, Dr. Saal reevaluated petitioner. Id. at 43. Despite her marked relief in
the corticosteroid and anesthetic phases with an intra-articular facet block, she had no or minimal
response during the anesthetic phase of the median branch block. Dr. Saal considered whether
petitioner had relative intolerance to local anesthetics since this was a low dose and volume vs. a
non-discrete facet source of her symptoms. He considered this somewhat paradoxical. His
recommendation was to repeat the median branch block with both short- and long-acting
anesthetic and with a slightly higher volume, being careful of nonspecific spread. If the block
were negative again, then petitioner was not a candidate for facet rhizotomy. However, she
could be a candidate for further discogenic treatment considering her partially significant
improvement, which was inadequate for carrying out full and usual work. Id.

On October 14, 2003, Dr. Saal performed lumbar intra-articular facet blocks on the right
and left of L4-L5 and L5-S1. Id. at 44.

On November 13, 2003, Dr. Saal reevaluated petitioner. Id. at 47. Petitioner was

26
Rhizotomy is “interruption of a cranial or spinal nerve root. . . .” Dorland’s at 1641.
9
significantly improved from where she first started but was still limited compared to normal.
She could carry out light housework and cook dinner and eat it, but she still could not do any
heavy housework, repetitive bending, stooping or lifting. Her symptoms remained in her low
back. On physical examination, she had limited lumbar extension by 50 percent and limited
forward flexion by 50 percent. Dr. Saal’s impression was that internal disc disruption and
discogenic pain were the persistent source of her symptoms. He recommended she live with
what she had or do a repeat discography. He prescribed a Lidoderm27 patch. Id. Petitioner
remained on temporary total disability through December 30, 2003. It was clear that she would
not be able to return to her full and usual job duties as a nurse. Id.

On January 8, 2004, Dr. Saal reevaluated petitioner. Id. at 48. Dr. Saal suggested a
lumbar discography to determine if the L4-L5 disc were painful or if the problem were the L5-S1
level. If that fails, she would be a candidate for a disc replacement or lumbar interbody fusion.
He prescribed four treatments of acupuncture. Petitioner was on temporary total disability
through March 1, 2004. Id.

On February 26, 2004, Dr. Saal reevaluated petitioner. Id. at 49. She reported continued
symptoms. Dr. Saal’s impression was internal disc disruption. Petitioner would continue on
temporary total disability through March 30, 2004. Id.

On March 25, 2004, petitioner saw Dr. Saal to discuss her course to date. Id. at 50. She
was somewhat worse and less functional. Dr. Saal thought petitioner was a candidate for either
disc replacement or fusion. Id. Petitioner was on temporary total disability through May 30,
2004. Id.

On May 6, 2004, Dr. Saal reevaluated petitioner. Id. at 51. She was still waiting for a
surgical consultation. Lumbar flexion on physical examination was 60 percent of normal.
Lumbar extension was 20 percent of normal. Bilateral side bending was guarded at 75 percent of
normal. Dr. Saal’s impression was internal disc disruption at multiple levels. Petitioner was
released to modified duties of no lifting greater than 10 pounds, a required posture change every
30 minutes, and no pushing or pulling greater than 50 pounds. Id.

On June 22, 2004, Dr. Saal saw petitioner for a long discussion after her consultation
with Dr. Hsu. Id. at 52. Dr. Hsu recommended she have lumbar discography to determine what
levels are painful and if there were a disc that could be treated with an IDET and if so to carry
that out. If that procedure failed, she was a candidate for lumbar disc replacement surgery.
Petitioner continued to have functionally limiting, impairing discogenic pain. Low back pain
daily limited her ability to sit, stand, walk, or do any lifting or carrying. She remained on
temporary total disability through August 1, 2004. Id.

On December 23, 2004, Dr. Saal wrote what he called his final report. Id. at 53.

27
Lidoderm is “trademark for a preparation of lidocaine.” Dorland’s at 1034. Lidocaine is “a drug having
anesthetic, sedative, analgesic, anticonvulsant, and cardiac depressant activities, used as a local anesthetic, applied
topically to the skin and mucous membranes.” Id.
10
Petitioner decided against aggressive surgery. Id. Petitioner described constant minimal to
slight pain that became moderate with prolonged sitting of longer than 20 to 30 minutes, standing
in one spot for longer than 15 minutes, or doing repetitive bending, stooping, or heavy lifting.
Id. at 54. Rest and ice offered relief as did anti-inflammatory medication. Physical examination
showed a 25 percent decrease in lumbar forward flexion and a 50 percent decrease in lumbar
extension. She had full bilateral lateral side bending. She could carry out her duties as a nurse if
accommodations were made for postural changes and she was precluding from heavy lifting and
repetitive bending. Id.

On February 3, 2005, Dr. Saal reevaluated petitioner. Id. at 56. She decided she did not
want to live with her back condition and needed to do something else. Dr. Saal’s impression was
discogenic pain. Petitioner was ready to undergo surgery. Id.

On March 24, 2005, Dr. Saal reevaluated petitioner. Id. at 57. She reported her
symptoms unchanged. Id. He recommended another IDET. Id. at 58.

On June 7, 2005, Dr. Saal reevaluated petitioner. Id. at 61. Her symptoms were
unchanged. He recommended a lumbar discography. Id. Petitioner was to be off work until
August 10, 2005. Id. at 62.

On August 9, 2005, Dr. Saal reevaluated petitioner. Id. at 63. She continued to complain
of functionally limiting low back pain. A recent MRI of her bilateral ankles showed evidence of
adhesion of the peritendinous sheath around the Achilles tendon with a recommendation of
treatment with saline by Dr. Fred Orcutt or potentially surgery. Dr. Saal recommended
discography. Id. Petitioner was off work until October 1, 2005. Id. at 64.

On September 20, 2005, Dr. Saal reevaluated petitioner. Id. at 65. Her symptoms
remained the same. She still had sitting and bending pain and had difficulty carrying out
intensive therapeutic exercises because of a flare up of her symptoms. He recommended she
return to modified duty with no lifting greater than 25 pounds and no repetitive bending,
stooping, or twisting. She required postural changes every 30 minutes. She could push only 100
pounds and pull only 50 pounds. Id.

On December 13, 2005, Dr. Saal reevaluated petitioner. Id. at 67. She reported her
symptoms were somewhat worse. They were in her low back and bilateral heels. A new MRI
scan did not show significant abnormalities. She had undergone a number of laboratory tests so
that Dr. Orcutt28 could exclude the possibility that she had rheumatic disease or multiple
myeloma.29 She had a loss of thigh circumference. Id. Petitioner was to be off work until

28
The undersigned cannot find any records from Dr. Orcutt filed in this case. On November 5, 2018, the
undersigned ordered petitioner to file them, but petitioner filed a status report on November 15, 2018, stating that
Dr. Fred Orcutt, an orthopedic surgeon, retired and all reports from 2010 and earlier were unavailable. Petitioner
filed exhibit 120, a statement from the medical group to which Dr. Orcutt previously belonged, to that effect.
29
Multiple myeloma is “a disseminated type of plasma cell dyscrasia characterized by multiple bone marrow tumor
foci and secretion of an M component, associated with widespread osteolytic lesions resulting in bone pain,
pathologic fractures, hypercalcemia, and normochromic normocytic anemia. . . .” Dorland’s at 1219.
11
January 30, 2006. Id. at 68.

On February 9, 2006, Dr. Saal reevaluated petitioner. Id. at 69. She reported a marked
increase in the level of pain in her legs, worse in the past two weeks. She had difficulty sleeping
at night. She underwent a new MRI scan and an EMG study. On physical examination, positive
straight leg raising on both sides at 60 degrees caused leg and back pain. Dr. Saal’s impression
was referred pain into the lower extremities related to a degenerative painful disc that has disc
disruption/annulus tear at L5-S1. Id. Petitioner was to be off work until April 1, 2006. Id. at 70.

On March 9, 2006, Dr. Saal reevaluated petitioner. Id. at 71. She had improvement in
her leg pain with use of Lyrica.30 Id.

On March 29, 2006, petitioner noted neck and arm pain intermittently with numbness in
her right hand three fingers (3rd, 4th, and 5th digits) since 2003. Med. recs. Ex. 15, at 18. She
had had neck and arm pain for six months. Id. at 15.

On March 30, 2006, Dr. Saal reevaluated petitioner. Med. recs. Ex. 11, at 72. Her
symptoms remained the same. She was on total temporary disability through May 5, 2006. Id.

On April 25, 2006, Dr. Saal reevaluated petitioner. Id. at 73. She continued to complain
of the same symptoms. She went off Lyrica because of weight gain. She had returned to work
with no lifting greater than 20 pounds, no pushing or pulling greater than 40 pounds and only
occasional bending, no climbing, and no prolonged standing. Postural changes were required
every thirty minutes. Id.

On April 3, 2007, Dr. Saal reevaluated petitioner. Id. at 75. Petitioner said she had made
a 75-80 plus percent improvement. She could tolerate sitting and standing for hours. Her back
pain was less intense. Dr. Saal opined she could return to her full and usual work duties. Id.

On November 21, 2007, petitioner complained of left shoulder pain that had been
bothering her for 2-3 months. Med. recs. Ex. 14, at 49. It was not getting better despite
chiropractic treatment, upper body strengthening, anti-inflammatories, and swimming two to
four times a week. On physical examination, petitioner was tender anteriorly overlying the
biceps tendon. The doctor sent petitioner to another doctor for an injection. Id.

On March 3, 2008, petitioner saw Dr. Mary Regan at Samaritan Family Practice,
complaining of one month of aching in her fingers and thumbs bilaterally and head and chest
congestion for three days. Id. at 45. Petitioner needed a work note since she missed the last
several days due to cold/flu. Petitioner was seeing a chiropractor but that seemed to be making
her worse. Petitioner had intermittent pain on her right side. Dr. Regan questioned whether

30
Lyrica is “trademark for a preparation of pregabalin.” Dorland’s at 1088. Pregabalin is “a derivative of ƴ-
aminobutyric acid (GABA) having anticonvulsant and antinociceptive effects, used in the treatment of neuropathic
pain in diabetic neuropathy and postherpetic neuralgia. . . .” Id. at 1509. “Antinociceptive” means “blocking or
reducing sensitivity to painful stimuli. . . .” Id. at 108.
12
petitioner’s fingers were slightly swollen. She noted that petitioner had a family history of
rheumatoid arthritis in her grandmother. Id. Petitioner’s physical examination was
unremarkable except for mild nasal congestion. Dr. Regan diagnosed petitioner with upper
respiratory infection, cervical pain, and hand pain. She referred petitioner for testing to see if she
had a positive ANA31 and rheumatoid factor (“RF”).32 Id. Petitioner had a positive ANA of
1:160. Id. at 20. Dr. Regan noted petitioner might have a rheumatic disorder, discussed this with
petitioner, and referred her to a rheumatologist.33 Id.

On that same date, March 3, 2008, Dr. Keith Fraker did x-rays on petitioner’s cervical
spine for persistent neck pain. Id. at 2. Petitioner had degenerative change at the C5-C6 level
with anterior and posterior spurring and disc space narrowing. C6 and C7 appeared to be fused,
which Dr. Fraker assumed to be a congenital anomaly. He noted degenerative changes over the
facet joints and joints of Luschka.34 There might be some neural foraminal encroachment at the
C5 level, especially on the right. He noted calcification within the ligamentum nuchae and some
reversal of the normal cervical curve. Id.

On March 5, 2008, petitioner’s erythrocyte sedimentation rate (“ESR”)35 was normal, her
rheumatoid factor serum was negative, but her antinuclear antibody (“ANA”) was positive at
1:160 with a homogeneous pattern.36 Id. at 20.

31
Antinuclear antibodies (ANA) are “antibodies directed against nuclear antigens; ones against a variety of different
antigens are almost invariably found in systemic lupus erythematosus and are frequently found in rheumatoid
arthritis, scleroderma (systemic sclerosis), Sjögren syndrome, and mixed connective tissue disease. Antinuclear
antibodies may be detected by immunofluorescent staining. Serologic tests are also used to determine antibody
titers against specific antigens.” Dorland’s at 101.
32
Rheumatoid factor (“RF”) are “antibodies directed against antigenic determinants, i.e., Gm, in the Fc region of the
IgG class of immunoglobulins; these are found in the serum of about 80 percent of persons with classical or definite
rheumatoid arthritis, but only about 20 percent of those with juvenile rheumatoid arthritis. Rheumatoid factors may
be of the IgM, IgG, or IgA classes of immunoglobulins, although serologic tests measure only IgM. Rheumatoid
factors also occur in other connective tissue diseases and infectious diseases, such as Sjögren syndrome, systemic
lupus erythematosus, sarcoidosis, subacute bacterial endocarditis, hepatitis A, and leprosy.” Dorland’s at 676.
33
The undersigned cannot find any rheumatology records from 2008. In an Order dated November 5, 2018, the
undersigned ordered petitioner to file them, but petitioner filed a status report on November 15, 2018, stating the
rheumatologist, Dr. Carter V. Multz of the Arthritis Care Center in San Jose, was dead. Petitioner filed as exhibit
119 an obituary of Dr. Multz, stating his date of death was August 7, 2013.
34
Joints of Luschka are “a series of jointlike structures at the lateral edges of the vertebral bodies from vertebra C3
to T1, forming small spurlike lips at the upper surface, covered with cartilage, and containing a capsule filled with
fluid. They are considered by some to be true diarthrodial joints, and by others to be degenerative spaces of the
intervertebral disks filled with extracellular fluid and lined by a membrane formed by fibrocytes. They are frequent
sites of spur formation. Called also uncovertebral j’s.” Dorland’s at 973.
35
Erythrocyte sedimentation rate (“ESR”) is “the rate at which erythrocytes precipitate out from a well-mixed
specimen of venous blood, measured by the distance the top of the column of erythrocytes falls in a given time
interval under specified conditions; an increase in rate is usually due to elevated levels of plasma proteins, especially
fibrinogen and immunoglobulins, which decrease the zeta potential on erythrocytes by dielectric shielding and thus
promote rouleau formation. It is increased in monoclonal gammopathy, hypergammaglobulinemia due to
inflammatory disease, hyperfibrinogenemia, active inflammatory disease, and anemia.” Dorland’s at 1594. Rouleau
formation is “the aggregation of erythrocytes in structures resembling piles of coins, caused by adhesion of their flat
surfaces.” Id. at 733.
36
“ANAs are used to diagnose systemic lupus erythematosus (SLE) and other autoimmune diseases.” Kathleen D.
13
On March 12, 2008, petitioner saw MR (presumably “Mary Regan”) at Samaritan Family
Practice, complaining that her head and ear congestion persisted. Id. at 44. Petitioner said she
could not “shake this cold.” Id. Dr. Regan diagnosed petitioner with sinusitis and prescribed
Augmentin.37 Id.

On May 20, 2009, Dr. Saal reevaluated petitioner. Med. recs. Ex. 11, at 77. Petitioner
was taking Cymbalta38 and discontinued Zoloft.39 She lived a full and active lifestyle. Id.

On September 22, 2009, petitioner saw a doctor (“TK”) at Samaritan Family Practice,
stating she fell in the lobby of a Las Vegas hotel on September 18, 2009 and landed on her right
hip and right elbow and arm. Med. recs. Ex. 14, at 37. She had a stiff neck and lower back with
slight numbness in her arms and legs, but no weakness. The doctor diagnosed cervical and
lumbar strain, recommended rest, ice, and heat, and referred petitioner for physical therapy. Id.

On October 14, 2009, petitioner received flu vaccine40 in her left deltoid from Dr.
Joceliza G. Chaudhary at Samaritan Family Practice. Id. at 35. This occurred during petitioner’s
office visit for a urinary tract infection and allergic rhinitis. Id. at 36. Petitioner did not have a
reaction to the October 14, 2009 flu vaccination.

On November 20, 2009, petitioner saw a doctor (“MR” presumably Mary Regan) at
Samaritan Family Practice, complaining of a sore throat and bilateral ear pain for three days, and
99.4 degree temperature two hours previously. Id. at 34. One week earlier, she developed body

Pagana & Timothy J. Pagana, MOSBY’S MANUAL OF DIAGNOSTIC AND LABORATORY TESTS, ch. 2, at 80 (6th ed.
2018). ANA has fluorescent patterns in cells. Id. at 82. “Different patterns are associated with a variety of
autoimmune disorders.” Id. MOSBY’S states a positive ANA with a homogeneous pattern is associated with SLE
and MCTD. Id. It also says that a positive ANA with a speckled pattern is associated with SLE, scleroderma, RA,
MCTD, Sjögren syndrome, and polymyositis (“PM”). Id. As for anti-RNP antibodies, they are associated with
MCTD, SLE, and progressive systemic sclerosis (scleroderma). Id. at 81. MCTD is associated with ANA, anti-
RNP antibodies, RF, and ssDNA. Id. Petitioner tested negative in 2008 and 2012 for RF. Petitioner tested negative
in 2012 for ssDNA.
37
Augmentin is “trademark for combination preparations of amoxicillin and clavulanate potassium.” Dorland’s at
179. Amoxicillin is “a semisynthetic derivative of ampicillin effective against a broad spectrum of gram-positive
and gram-negative bacteria; used especially in the treatment of infections due to susceptible strains of Haemophilus
influenzae, Escherichia coli, Proteus mirabilis, Neisseria gonorrhoeae, streptococci (including Streptococcus
faecalis and S. pneumonia), and nonpenicillinase-producing staphylococci.” Id. at 65.
38
Cymbalta is “trademark for a preparation of duloxetine hydrochloride.” Dorland’s at 457. Duloxetine
hydrochloride is “a serotonin-norepinephrine reuptake inhibitor, used for the treatment of major depressive disorder
and the relief of pain in diabetic neuropathy. . . .” Id. at 572.
39
Zoloft is “trademark for preparations of sertraline hydrochloride.” Dorland’s at 2092. Sertraline hydrochloride is
“a selective serotonin reuptake inhibitor, used to treat depressive, obsessive-compulsive, and panic disorders. . . .”
Id. at 1699.
40
In the 2009-2010 flu season, the trivalent flu vaccine contained A/Brisbane/59/2007-like virus (H1N1),
A/Brisbane/10/2007-like virus (H3N2), and B/Brisbane/60/2008-like virus (B/Victoria lineage). Update: Influenza
Activity – United States, September 28, 2008—April 4, 2009, and Composition of the 2009—10 Influenza Vaccine,
58 MORBIDITY AND MORTALITY WEEKLY REPORT (MMWR) 14:369-74 (April 17, 2009),
https://www.cdc.gov/mmwr/preview/mmwrhtml/mm5814a4.htm.
14
aches, and fever which resolved in 3-4 days. Three days earlier, she developed sinus pain with
discharge, sore throat, and hoarseness. She wanted Vicodin for sleep. Dr. Regan diagnosed
petitioner with an upper respiratory infection and pharyngitis. She prescribed Vicodin. Id.

On March 11, 2010, petitioner saw a doctor (“JH”) at Samaritan Family Practice,
complaining of hot flashes and sweating. Id. at 29. She stated she was ready to stop smoking.
She wanted to stop taking Cymbalta, which she had taken for back pain which had now resolved.

On January 20, 2011, petitioner saw a doctor (“TK”) at Samaritan Family Practice to
evaluate her thyroid. Id. at 28. She had been fatigued for 1-2 months. She had had right
shoulder pain and trouble lifting her arm for 2-3 months. She had trouble sleeping on her right
side. She requested physical therapy and the doctor referred her for it. Id.

On March 17, 2011, petitioner saw a doctor at Samaritan Family Practice, complaining of
foot and shoulder pain. Med. recs. Ex. 14, at 27. She needed a referral for physical therapy
again. She did not go to physical therapy when referred before and the last referral expired. Her
palpitations resolved and she discontinued Sudafed. The doctor diagnosed petitioner with right
foot pain, right shoulder strain, hypothyroidism, and neuropathy. Id.

On April 8, 2011, petitioner saw a doctor (“TH”) at Samaritan Family Practice because
she had a rash on her stomach since the day before and a burning sensation. Id. at 26. The
doctor diagnosed dermatitis, probably due to sitting in a hot tub while wearing an old swimsuit.
Id.

On June 15, 2011, petitioner saw a doctor (“TK”) at Samaritan Family Practice for two
reasons: (1) she had sliced her pinkie finger the prior evening, and (2) her right shoulder had
been painful for nine months. Id. at 25.

On January 26, 2012, petitioner saw Dr. Jing Qing Xu as a new patient. Med. recs. Ex. 3,
at 1. Dr. Xu was at Kaiser Permanente Medical Group in San Jose, CA. Id. Petitioner had
chronic pain syndrome and shoulder joint pain. Dr. Xu prescribed Cymbalta for chronic pain
syndrome. Id. at 3. Petitioner had chronic left shoulder pain. Id. Petitioner was on
levothyroxine for hypothyroidism, Benicar,41 and Cymbalta. Id.

On March 16, 2012, Dr. Xu called petitioner. Id. at 20. She said over the prior three to
four days, she had been feeling acid reflux, burped a lot, and felt something stuck in her
esophagus. She had been taking ranitidine.42 Dr. Xu diagnosed petitioner with GERD43 and
prescribed Omeprazole,44 told her to avoid citrus, and advised walking and stress reduction. Id.

41
Benicar is “trademark for a preparation of olmesartan medoxomil.” Dorland’s at 208. Olmesartan medoxomil is
“a selective angiotensin receptor antagonist used as an antihypertensive . . . .” Id. at 1319.
42
Ranitidine is “a histamine H2 receptor antagonist, which inhibits gastric secretion.” Dorland’s at 1592.
43
GERD is “gastroesophageal reflux disease.” Dorland’s at 772.
44
Omeprazole is “a proton pump inhibitor used in the treatment of dyspepsia, gastroesophageal reflux disease, and
gastric hypersecretory conditions. . . .” Dorland’s at 1319.
15
On August 13, 2012, petitioner saw Dr. Xu, telling Dr. Xu that she had pain in her left
arm and right shoulder intermittently for a long time. Id. at 33. Dr. Xu diagnosed petitioner with
impingement syndrome of the shoulder. Id. In Dr. Xu’s progress notes, the doctor says that
petitioner has complained of pain intermittently in both shoulders. Id. at 34. Petitioner had
positive kiss elbow signs. Id. Petitioner worked as a registered nurse at the Intensive Care Unit,
pushing carts around. Dr. Xu’s diagnosis was impingement syndrome of the shoulders. Id.

Postvaccination Records

On September 20, 2012, petitioner received flu vaccine45 in her left deltoid. Med. recs.
Ex. 16, at 2.

On October 3, 2012, petitioner saw Dr. Xu complaining of still having pain in her joints,
knees, hands, and lower back, but her shoulder pain was improving. Med. recs. Ex. 3, at 37. Dr.
Xu diagnosed petitioner with chronic sinusitis and osteoarthritis of the hand. Id. at 36. Both her
hands had slight swelling. Id. at 37. Cyclic citrullinated peptide (“CCP”)46 for rheumatoid
arthritis was negative at 5 (being less than 20). Id. at 40. RF factor was negative at 10.3
(reference range less than 14.0). Id. C-reactive protein (“CRP”)47 was negative at 0.4 (reference
range less than 0.5). Id. at 41. Petitioner’s Nuclear AB Panel testing on October 3, 2012 (Ex. 3,
at 41) was negative for all of the following: dsDNA antibody48; Sjögrens49-A (anti-SS-A)
antibody and –B (anti-SS-B) antibody; Smith IgG; chromatin (nucleosomal) antibody;
ribosomal P antibody; centromere antibody; Sm antibody+RNP antibody; Scl-70 antibody; and
Jo-1 antibody. Id. Her RNP antibody was positive at 1.2 (when the normal result is less than
1.0). Id.

On October 15, 2012, petitioner had a positive ANA of 2+ with homogeneous staining

45
In the 2012-2013 flu season, the trivalent flu vaccine contained A/California/7/2009-like virus (pH1N1),
A/Victoria/361/2011-like virus (H3N2), and B/Wisconsin/1/2010-like virus (B/Yamagata lineage). Update:
Influenza Activity – United States, 2011-12 Season and Composition of the 2012-13 Influenza Vaccine, 61
MORBIDITY AND MORTALITY WEEKLY REPORT (MMWR) 22:414-20 (June 8, 2012),
https://www.cdc.gov/mmwr/preview/mmwrhtml/mm6122a4.htm. The “p” before the “H” (hemagglutinin) stands
for “pandemic.” Robert P. de Vries et al., Evolution of the Hemagglutinin Protein of the New Pandemic H1N1
Influenza Virus: Maintaining Optimal Receptor Binding by Compensatory Substitutions, 87 J VIROL 24: 13868-877,
13868 (2013).
46
Cyclic citrullinated peptide (“CCP”) is “a synthetic, citrulline-containing peptide with a cyclic structure, used in
assays for rheumatoid arthritis; the presence of antibodies to this peptide is highly specific for rheumatoid arthritis.”
Dorland’s at 1408.
47
C-reactive protein (“CRP”) is “a globulin that forms a precipitate with the somatic C-polysaccharide of the
pneumococcus in vitro; it is the most predominant of the acute phase proteins.” Dorland’s at 1532.
48
Anti-dsDNA antibody is “a type of antinuclear antibody specific for double-stranded DNA, found in the serum of
patients with systemic lupus erythematosus.” Dorland’s at 100.
49
Sjögren syndrome is “a symptom complex of unknown etiology, usually occurring in middle-aged or older
women, marked by the triad of keratoconjunctivitis sicca with or without lacrimal gland enlargement, xerostomia
with or without salivary gland enlargement, and the presence of a connective tissue disease, usually rheumatoid
arthritis but sometimes systemic lupus erythematosus, scleroderma, or polymyositis. An abnormal immune response
has been implicated.” Dorland’s at 1848.
16
and a titer of 1:320. Id. at 45. Her ESR was normal. Id. at 46.

On October 31, 2012, petitioner saw Dr. Jan Jingyang Lin, a rheumatologist, complaining
of joint pain in her hands, knees, and toes with prolonged morning stiffness for many months.50
(This would place onset of petitioner’s pain and prolonged morning stiffness before the flu
vaccination which was just six weeks earlier than petitioner’s October 31, 2012 visit to Dr. Lin.)
Med. recs. Ex. 13, at 96-99. Dr. Lin was at Kaiser Permanente Medical Group in San Jose, CA.
Med. recs. Ex. 3, at 48. Petitioner had a history of redness of face and nasal bridge and chin, dry
eyes and mouth, and extreme fatigue. On physical examination, she had bilateral proximal-
interphalangeal (“PIP”) and metacarpal-phalangeal (“MCP”) joint tenderness, ulnar deviation,
and bilateral knee tenderness. Dr. Lin’s diagnosis was MCTD.51 She started petitioner on
hydroxychloroquine52 and prednisone. Id. at 47-64. Dr. Lin tested petitioner for cardiolipin
antibody53 and for lupus anticoagulant, both of which were negative. Id. at 62. However,
petitioner’s cardiolipin IgG was 28, which was high since the normal range is 1-14, and her
cardiolipin IgM was 15, which was also high since the normal range is 1-11. Id. at 63. Dr. Lin
had petitioner undergo chest x-rays to look for interstitial lung disease, and the result was
normal. Id. at 64. Her ESR and CRP on October 31, 2012 were normal. Id. at 58, 59.
Petitioner’s C3 and C4 complement levels were normal. Id. at 60.

On January 7, 2013, petitioner saw Dr. Lin. Her joint symptoms had resolved on
steroids, but returned while she was on hydroxychloroquine. She complained of muscle pains.
Her joint tenderness remained. She mentioned her joints were swollen. Dr. Lin prescribed
methotrexate (“MTX”).54 Id. at 67-70.

50
Subsequently, on June 19, 2015, two years and seven and one-half months after October 31, 2012, Dr. Lin
“corrected” this history at the urging of petitioner by writing a request on June 7, 2015 that Dr. Lin change the onset
date of her joint pains to “several weeks.” Med. recs. Ex. 10, at 1. But on June 19, 2015, Dr. Lin changed the onset
of petitioner’s joint pains not to “several weeks” but to “two months since August 2012.” Med. recs. Ex. 108, at 11.
This still placed onset before the September 20, 2012 flu vaccination. On January 5, 2016, three years and two
months after petitioner saw Dr. Lin on October, 31, 2012, Dr. Lin “corrected” this initial history a second time at the
urging of petitioner to reflect an onset of “four weeks since the end of September 2012.” Med. recs. Ex. 108, at 11.
Now, the onset was after the September 20, 2012 flu vaccination.
51
Mixed connective tissue disease (“MCTD”) is “a disorder combining features of scleroderma, myositis, systemic
lupus erythematosus, and rheumatoid arthritis, and marked serologically by the presence of antibody against
extractable nuclear antigen.” Dorland’s at 539.
52
The trademark for hydroxychloroquine sulfate is Plaquenil. Dorland’s at 1456. Hydroxychloroquine sulfate is “a
4-aminoquinoline compound with antiprotozoal and anti-inflammatory properties, used for suppression and
treatment of malaria, for suppression of lupus erythematosus, and as an anti-inflammatory disease-modifying
antirheumatic drug in treatment of rheumatoid arthritis. . . .” Id. at 881.
53
Anticardiolipin antibody is “an antibody directed against cardiolipin, seen with increased frequency in systemic
lupus erythematosus; its presence correlates with increased risk for thrombotic events.” Dorland’s at 100.
54
Methotrexate (“MTX”) is “a folic acid antagonist that acts by inhibiting synthesis of DNA, RNA, thymidylate,
and protein; used as an antineoplastic in treatment of a wide variety of malignancies, including acute lymphocytic,
meningeal, and acute myelocytic leukemia; gestational choriocarcinoma; chorioadenoma destruens; hydatidiform
mole; carcinoma of the breast, lung, and head and neck; non-Hodgkin lymphomas; mycosis fungoides; and
osteosarcoma. . . . It is also used as an antipsoriatic and antiarthritic in the treatment of severe, recalcitrant,
disabling psoriasis and severe rheumatoid and psoriatic arthritis.” Dorland’s at 1151.
17
On March 4, 2013, petitioner saw Dr. Lin. On physical examination, petitioner had
swollen joints. Dr. Lin increased petitioner’s dosage of MTX and tapered her steroids. Id. at 74-
83. Dr. Lin rechecked petitioner’s ESR and CRP on March 4, 2013. They were normal. Id. at
80. Dr. Lin also rechecked petitioner’s cardiolipin IgG and IgM on March 4, 2013 and they were
both normal. Id. at 82-83.

On May 14, 2013, petitioner’s CRP was slightly elevated at 0.7 when the normal range is
at or below 0.5. Id. at 87. Her ESR was still normal. Id. Petitioner’s C4 complement was high
at 45.6 when the normal range is 10.0 to 40.0. Id. at 88. Petitioner’s C3 complement was also
high at 202 when the normal range is 83 to 180. Id. at 89.

On May 15, 2013, petitioner saw NP Cynthia A. Liu, in gynecology. Id. at 90. Petitioner
told NP Liu that she had been diagnosed with RA, lupus, and Sjögren’s. Id. at 91. She
complained of chronic pain mostly in her knees and hands, but stated “everything hurts.” Id.
She complained of frequent hot flashes and sweating. Id. NP Liu noted petitioner had been
diagnosed with GERD on March 16, 2012. Id. at 93.

On May 17, 2013, petitioner saw Dr. Lin. Petitioner complained of pain in her PIP and
MCP joints with swelling. She had skin thickness on her fingers resembling sclerodactyly.55 Dr.
Lin prescribed tumor necrosis factor (“TNF”)-inhibitor therapy for her inflammation
(etanercept).56 Id. at 98-101.

On May 30, 2013, petitioner saw Dr. Yuhjung John Tsai, an allergist, who noted she had
an allergic reaction to flu vaccinations in 1999 and 2012. Id. at 107, 109. Dr. Tsai was at Kaiser
Permanente Medical Group at San Jose, CA. After petitioner’s flu vaccination on October 7,
2009,57 she had a large bruise and mass on her shoulder extending down the left arm with
development of frozen shoulder the following week. Id. at 107. She started having migraines
afterwards. In six months, her symptoms improved and she did not have any more migraines.
She did not receive any more flu vaccinations until the county medical director indicated in
August 2012 the importance of receiving flu vaccine. After her 2012 flu vaccination, in October,
she developed weakness and shortness of breath with no previous history of rheumatoid
conditions. She saw a rheumatologist Dr. Lin who diagnosed MCTD. Id. She told Dr. Tsai that
she had quit smoking one month earlier, or April 2013. Id. at 109. Dr. Tsai advised petitioner to

55
Sclerodactyly is “localized scleroderma of the digits, as in acrosclerosis.” Dorland’s at 1679. Acrosclerosis is “a
type of systemic scleroderma of the hands and feet, especially the digits (sclerodactyly), as well as the face and
neck, in combination with Raynaud phenomenon.” Id. at 21. Raynaud phenomenon is “intermittent bilateral
ischemia of the fingers, toes, and sometimes ears and nose, with severe pallor and often paresthesias and pain,
usually brought on by cold or emotional stimuli and relieved by heat; it is usually due to an underlying disease or
anatomical abnormality.” Id. at 1430.
56
Etanercept is “a soluble tumor necrosis factor receptor that inactivates tumor necrosis factor, used in the treatment
of rheumatoid arthritis and juvenile idiopathic arthritis. . . .” Dorland’s at 650.
57
Dr. Tsai initially wrote petitioner received flu vaccine in 2009, but corrected this to 1999 in an addendum dated
June 26, 2015. Med. recs. Ex. 108, at 27. He made this change at the request of petitioner. Med. recs. Ex. 13, at
212. Petitioner’s medical records show that she had left supraspinatus tendinitis after the flu vaccine she received
in her left arm on October 7, 1999. Med. recs. Ex. 69 at 1, 2, 4. She did not however have a reaction to the flu
vaccine she received in her left arm on October 14, 2009. Med. recs. Ex. 14, at 35.
18
avoid all flu vaccinations. Id. at 110. He noted she did not have any history to suggest
immunodeficiency. Id. Dr. Tsai wrote petitioner’s symptoms were delayed and not
characteristic of an IgE-mediated drug reaction. Id.

On July 12, 2013, petitioner saw MA Carmen Santana with swelling in her knuckles. Id.
at 112.

On August 7, 2014, petitioner’s ESR and CRP were normal. Id. at 119. Her C4
complement and C3 complement were normal. Id. at 120-21.

On August 19, 2013, petitioner saw Dr. Lin. Since she started etanercept, her joint
symptoms were better. She complained of hair loss. On physical examination, petitioner had
tender finger joints and knees, swelling in one PIP joint, synovitis in the left third PIP joint, and
skin thickening of her fingers. Dr. Lin told petitioner to stop taking MTX due to hair loss, start
Leflunomide58 (anti-rheumatic drug), and use Voltaren59 cream (anti-inflammatory). Id. at 125-
28. Dr. Lin noted petitioner did not have Raynaud’s phenomenon.60 Id. at 125.

On October 31, 2013, petitioner’s ESR and CRP were normal. Id. at 130-31. Her C4
complement and C3 complement were also normal. Id. at 132,

On November 25, 2013, petitioner saw Dr. Anna Graziella Barbara because of snoring.
Id. at 141. Petitioner said she was often tired during the day and had to take a nap. Id. Dr.
Barbara suggested petitioner take a sleep study to rule out obstructive sleep apnea. Id. at 143.

On January 6, 2014, petitioner saw Dr. Lin. Her joint tenderness continued but not the
swelling since she started etanercept. She had ulnar deviation which was noted before since
October 31, 2012. Dr. Lin had petitioner taper her steroids, and considered switching DMARD
(disease-modifying antirheumatic drug) treatment to abatacept61 or tocilizumab.62 Id. at 141-55.
Dr. Lin was not seeing any synovitis.63 Id. at 149. Petitioner wanted Dr. Lin to sign a statement

58
Leflunomide is “an immunomodulator that inhibits pyrimidine synthesis, used as a disease-modifying
antirheumatic drug in treatment of rheumatoid arthritis. . . .” Dorland’s at 1017.
59
Voltaren is “trademark for preparations of diclofenac sodium.” Dorland’s at 2070. Diclofenac is “a nonsteroidal
anti-inflammatory drug derived from phenylacetic acid.” Id. at 513. Diclofenac sodium is “the sodium salt of
diclofenac . . . in the treatment of rheumatoid arthritis, osteoarthritis, and ankylosing spondylitis and also for a
variety of nonrheumatic inflammatory conditions.” Id.
60
Raynaud phenomenon is “intermittent bilateral ischemia of the fingers, toes, and sometimes ears and nose, with
severe pallor and often paresthesias and pain, usually brought on by cold or emotional stimuli and relieved by heat;
it is usually due to an underlying disease or anatomical abnormality. When it is idiopathic or primary it is called
Raynaud disease.” Dorland’s at 1430; see also 542.
61
Abatacept is “a synthetic fusion protein produced by recombinant technology, comprising the extracellular
domain of human cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) linked to a portion of human
immunoglobulin G1 (IgG1), which acts as an inhibitor of T-cell activation; used in the treatment of moderate to
severe rheumatoid arthritis unresponsive to other medications, administered intravenously.” Dorland’s at 1.
62
Tocilizumab is trademark for Actemra. https://www.actemra.com/ra/consider-actemra/actemra-works-
differently.html (last visited October 19, 2018). It blocks the action of a protein called interleukin-6 (IL-6). Id.
63
Synovitis is “inflammation of a synovium; it is usually painful, particularly on motion, and is characterized by a
19
for petitioner to extend her disability which Dr. Lin did. Id. Petitioner was on modified work
from February 1, 2014 to December 31, 2014. Id. at 150. On January 6, 2014, petitioner’s ESR
and CSP were normal. Id. at 151-52. Her C4 complement and C3 complement were normal. Id.
at 153.

On March 27, 2014, petitioner’s ESR and CRP were normal. Id. at 158. Her C4
complement and C3 complement were also normal. Id. at 160.

On March 28, 2014, petitioner saw Dr. Lin to extend her disability. Id. at 162-63.
Petitioner’s joints were tender but not swollen. Dr. Lin noted again her ulnar deviation and
sclerodactyly. Petitioner did not have Raynaud’s phenomenon. Dr. Lin told petitioner to stop
taking etanercept and switch to abatacept because she was concerned petitioner had a lupus
component to MCTD. Id. at 163-66.

On April 8, 2014, petitioner had x-rays to rule out interstitial disease. Id. at 176. The
results were normal. Id.

On June 12, 2014, Dr. Lin switched petitioner to leflunomide. Id. at 180-82. On June 12,
2014, petitioner’s ESR and CRP were normal. Id. at 180.

On September 25, 2014, petitioner’s ESR and CRP were normal. Id. at 184. Her C4
complement and C3 complement were also normal. Id. at 186.

On November 19, 2014, petitioner saw Dr. Lin who started her on tocilizumab. Id. at
190-94. In the range of systems, Dr. Lin noted petitioner did not have sclerodactyly or
Raynaud’s phenomenon. Id. at 192. Yet in her assessment and plan, Dr. Lin wrote petitioner
had arthritis and Raynaud’s phenomenon currently. Id. at 194.

On December 8, 2014, petitioner saw Dr. Golara Honari, a dermatologist, for
telangiectasia64 and subtle erythema on her cheeks and nose, sparing the bridge of her nose, with
keratotic65 papules on the sides of her face. Dr. Honari diagnosed petitioner with rosacea66 and
keratosis pilaris67 rubra faceii. Med. recs. Ex. 13, at 409-11.

On June 7, 2015, petitioner wrote to Kaiser Permanente San Jose Medical Center
requesting a correction of her records. Petitioner did not file this request, but did file the
response from Kareem Olateju, Compliance Consultant, Corporate Compliance Department,
Kaiser Permanente San Jose Medical Center, dated June 29, 2015. Med. recs. Ex. 10, at 1. This

fluctuating swelling due to effusion within a synovial sac.” Dorland’s at 1856.
64
Telangiectasia is “permanent dilation of preexisting small blood vessels (Capillaries, arterioles, venules) to form
focal, discolored lesions, usually in the skin or mucous membranes.” Dorland’s at 1878.
65
Keratosis is “any horny growth. . . .” Dorland’s at 982.
66
Rosacea is “a chronic skin disease, usually involving the middle third of the face, characterized by persistent
erythema and often by telangiectasia with acute episodes of edema, papules, and pustules. . . .” Dorland’s at 1654.
67
Keratosis pilaris is “a common, benign condition in which hyperkeratosis occurs around hair follicles, usually on
the extensor surfaces of the thighs and arms, but sometimes elsewhere. . . .” Dorland’s at 982.
20
was after petitioner filed her petition pro se on March 13, 2015, but before she retained counsel
on August 11, 2015. The letter from Kareem Olateju in response to petitioner states as follows:

AMENDMENT REQUEST:

That Dr. Yuhjung J. Tsai should amend your medical record to
state that the Mixed Connective Tissue Disease you developed was
a result of the flu shot you received and also to amend the date of a
flu shot that you received from 10/7/2009 to 10/7/1999. You also
requested from Dr. Jan J. Lin to correct her statement in your
medical record regarding the duration of a condition you
experienced to “several weeks.”

RESPONSE: Dr. Tsai reviewed your request including your
medical record and denied your request regarding the cause of
the Mixed Connective Tissue Disease but agreed to change the
date you had a flu shot as requested. Dr. Lin also reviewed your
request including your medical record and agreed with your
request to change the duration of your condition to “several
weeks.” [emphasis added.]

On June 10, 2015, petitioner saw Dr. Xu, complaining of foot numbness for two months.
Dr. Xu diagnosed peripheral neuropathy. Id. at 587-91.

On June 19, 2015, Dr. Lin “corrected” her records as to onset of petitioner’s developing
symmetric joint pains of bilateral hands, knees, and toes, associated with prolonged morning
stiffness for two months since August 2012. Med. recs. Ex. 108, at 11. (In the original record
of Dr. Lin dated October 31, 2012, five weeks after flu vaccination, she wrote the onset of
petitioner’s symmetric joint pains of bilateral hands, knees, and toes, associated with prolonged
morning stiffness was many months. Med. recs. Ex. 8, at 48.)

On January 5, 2016, Dr. Lin again “corrected” her records as to onset of petitioner’s
developing symmetric joint pains of bilateral hands, knees, and toes, associated with prolonged
morning stiffness for four weeks since the end of September 2012. Med. recs. Ex. 108, at 11.

Also on January 5, 2016, petitioner saw Dr. Lin for a medical visit. Med. recs. Ex. 10, at
1. Petitioner still had a lot of pain in the PIPs associated with tightness of her fingers and a lot of
stiffness in her fingers and knees. Id. Petitioner did not have Raynaud’s phenomenon. Id. Dr.
Lin diagnosed petitioner with MCTD, and decided to raise her Actemra dose. Id. at 5. (These
records are also filed as Exhibit 86, at 9-14.)

In a letter dated January 19, 2016 to Kaiser Permanente, petitioner’s subject was
“Corrections to Errors in My Medical Records.” Med. recs. Ex. 112, at 1. She writes:

21
As a result of research that I have done to support my vaccine
compensation program claim (National Vaccine Injury
Compensation Program Claim No. 15-260V) I have become aware
of several errors in my medical records. It is important that that
[sic] these errors are corrected, not only for the purpose of the
claim but also to set the record straight regarding my past and
current health status.

1. On page 48 of my medical records (Exhibit 3 of the vaccine
claim) it is stated: Sandra E. Horvath is a 57 Y female with
family h/o Hashimoto’s, sister has Sjogren’s, taking mTX [sic],
developed symmetric joint pains of b hands, knees and toes,
associated with prolonged morning stiffness for many months.

The words “many months” are not correct [.] [T]hey do not
accurately describe the onset of my symptoms, and they are
misleading with regard to my medical condition at that time.
The symptoms pertaining to joint pain in my hands and knees
along with fatigue came to my attention in the later September,
2012 timeframe. This is why I made the appointment with my
primary care physician, Dr. Jing Qing Xu on October 3, 2012.

2. On page 51 of my medical records it states:
Note: she has Sjogren’s and could [sic] lupus, RA; but on page
41 the lab test for “Sjogren’s –A AB Ser” is noted to be a
negative value. Because of that the statement on page 51 that I
have Sjogren’s [sic] incorrect [.]

3. On page 107 of my medical records it states that I received a
flu shot on August 7, 2012 and my symptoms began in October
of 2012. This statement is not correct [.] I did receive a flu
shot on September 20, 2012 and I have produced the consent
form stating that to my doctors on several occasions. The
symptoms began in late September as stated in #1 above.

Please make these corrections as soon as possible, and please
ensure that they are [sic] accurately reflect what is written above.

On July 28, 2016, petitioner saw Dr. Lin. Med. recs. Ex. 86, at 173. Dr. Lin diagnosed
petitioner with MCTD and said that her right hand was very suspicious for early presentation of
scleroderma.68 Id. at 177. She also had sicca. Id.

Scleroderma is “chronic hardening and thickening of the skin, a finding in various different diseases. . . .”
68

Dorland’s at 1679.
22
On August 3, 2016, petitioner saw Dr. Richard A. Lau, a rheumatologist, for a second
opinion. Id. at 196. Dr. Lau was at Kaiser Permanente Medical Group at Santa Clara, CA. Id.
Petitioner reported that her symptoms began in 2012 possibly after a flu vaccination with
arthralgia/myalgia diffusely throughout her body. Id. at 197. Dr. Lau’s impression was
“possible overlap syndrome, even MCTD as her RNP was positive (though no titer)” or could be
“possible” undifferentiated connective tissue disease (“UCTD”) as petitioner did not quite meet
criteria for any specific CTD such as SSc or SLE with the exception of RA. Id. at 198. He wrote
that petitioner had several concrete signs and symptoms suggestive of rheumatologic illness
including arthralgia/myalgia (with synovitis on examination), Raynaud’s phenomenon,
heartburn, and scattered telangiectasia. She also had some other signs and symptoms that were
more speculative such as tightening of the skin of her fingers with edematous changes which
could be early signs of sclerodactyly and the recurrent oral ulcerations when she stopped taking
MTX. Id.

On July 13, 2017, petitioner saw Dr. Lin. Med. recs. Ex. 91, at 1. Petitioner had been
taking Mobic69 for joint pains. Id. at 2. She writes under “allergies” that petitioner is allergic to
flu vaccine. Id. at 3. She continues to diagnose her with MCTD and notes that petitioner had an
abnormal nailfold capillary exam, a finding consistent in patients with Raynaud’s phenomenon
or scleroderma. Petitioner did not have significant synovitis. Id. at 6.

On August 3, 2017, petitioner saw Dr. Neelakshi Patel for a second opinion at Dr. Lin’s
request. (Actually, this was petitioner’s third rheumatology evaluation since she saw Dr. Lau at
Kaiser for a second rheumatology opinion). Med. recs. Ex. 102, at 2. The exhibit cover page
and the medical record do not identify Dr. Patel as working at a hospital. The undersigned
looked Dr. Patel up on the internet and found she is in private practice in San Jose and Los
Gatos, CA.70

Petitioner gave Dr. Patel a history that she was in her usual state of health when she
received a vaccine in 2012. Id. Two weeks later, she could not walk for two weeks. She started
to have pain and stiffness in symmetrical joints of her hands, knees, and toes. Sometimes, her
fingers were swollen. She found it hard to close her hand into a tight fist and had significant
morning stiffness. She is on IV Actemra monthly. At present, she feels that one week prior to
infusion, her symptoms return. Physicians at UCSF reviewed her file but did not see her. They
thought she does not have MCTD. She wondered about her diagnosis and presented to Dr. Patel.
Petitioner has dry eyes and mouth and occasional oral ulcers. She has ongoing fatigue which is
worse the week before infusion. She was off work from 2002-2005 because of a back injury. Id.
On physical examination, petitioner had unremarkable bilateral upper and lower extremities with

69
Mobic is “trademark for a preparation of meloxicam.” Dorland’s at 1171. Meloxicam is “a nonsteroidal anti-
inflammatory drug used in the treatment of osteoarthritis. . . .” Id. at 1126.
70
Dr. Patel received her medical degree from Netaji Subhas Chandra Bose Medical College, Jabalpur, India, had an
internship in internal medicine at the University of Massachusetts, had a fellowship in rheumatology at the
University of California, Irvine, CA, and had a residency in internal medicine at Kaiser Permanente Medical Group.
She is board-certified in rheumatology. She is affiliated with O’Connor Hospital, El Camino Hospital, and Good
Samaritan Hospital, all in San Jose, CA. US NEWS & WORLD REPORT, https://health.usnews.com/doctors/neelakshi-
patel-854330 (last visited September 24, 2018).
23
full range of motion and no deformities, synovitis, or pain with range of motion except for tender
and mildly prominent PIP joints. Id. at 4. All of petitioner’s fingers had mild, diffuse puffiness
and slightly thickened skin, but still had elasticity. Petitioner had mild erythema on her checks
and the bridge of her nose. She had a positive ANA of 1:320 in a homogeneous pattern and a
positive RNP. Dr. Patel reviewed petitioner’s capillaroscopy71 photos which showed dilated
capillary loops and tortuous loops. Dr. Patel noted that unfortunately she did not have access to
all of petitioner’s records. Id. Dr. Patel diagnosed petitioner with CTD, stating she certainly has
Raynaud’s phenomenon, mild early sclerodactyly, heart burn, malar erythema, and a positive
ANA. Dr. Patel did not see active synovitis, but she also noted that petitioner was taking the
drugs meloxicam, hydroxychloroquine, and Actemra, which likely were controlling her
symptoms. Id. In addition, she might have a component of seronegative RA, such as
inflammatory arthropathy. Id. at 4-5. Dr. Patel wrote that the only way to determine if
petitioner has RA was for her to stop taking Actemra and see if she has an inflammatory flare.
Id. at 5.

On November 15, 2017, petitioner returned to Dr. Lin. Med. recs. Ex. 113, at 5.
Petitioner came to Dr. Lin to have nailfold capillary pictures taken. Id. at 6. She saw the
rheumatologists Dr. Lau and Dr. Patel who concurred with the connective tissue disease
diagnosis. But she needed the capillary pictures to show the UCSF rheumatologist who had
never seen or examined her, but denied she has a connective tissue disease condition. Id. Dr.
Lin diagnosed petitioner with MCTD and scheduled petitioner for a pulmonary function test and
labs in three months. Id. at 9. If her arthritis symptoms became worse, she would consider doing
hand x-rays to rule out erosions. Petitioner was to continue on Plaquenil and Actemra.
Petitioner’s friend took photos of her nailfolds and petitioner was going to mail them to Dr. Lin
to put in her file. Id.

Other Material

On May 30 2013, petitioner’s Dr. Tsai filled out a VAERS Report, stating petitioner
received flu vaccine on August 17, 2012 (this is an incorrect date; the correct date is September
20, 2012), developed weakness several weeks later, and was diagnosed with MCTD several
months later. Ex. 68, at 1.

Affidavits

On August 28, 2015, petitioner filed her first affidavit. Ex. 7. She said onset of pain and
stiffness in her knees, hands, and lower back occurred within two weeks of her September 20,
2012 flu vaccination. Id. at ¶¶ 3 and 4. A few weeks later, she had extreme exhaustion. Id. at ¶¶
5, 6. She retired on July 1, 2014 because of her symptoms. Id. at ¶ 22.

On August 28, 2015, petitioner filed her husband’s affidavit, which was consistent with
the information in his wife’s affidavit. Ex. 8.

71
Capillaroscopy is “diagnostic examination of the capillaries with the microscope.” Dorland’s at 283.
24
On July 21, 2017, petitioner filed her supplemental affidavit, discussing her course of
disease and her nailfold capillary microscopy. Ex. 92.

On July 21, 2017, petitioner filed her husband’s supplemental affidavit. Ex. 93.

On January 26, 2018, petitioner filed an affidavit concerning nailfold capillaroscopy
images she provided to Dr. Lin. Ex. 114.

Medical Experts’ CVs

Dr. S. Sohail Ahmed

Petitioner filed an updated CV for Dr. Ahmed on August 1, 2017. Ex. 95. Dr. Ahmed
was an MD Anderson Cancer Center Research Fellow in immunology, researching the role of
NK cells in murine melanoma in 1992. Id. at 4. He attended The University of Texas Medical
School, Houston, TX, in 1993, receiving an M.D. in 1998. Id. at 5. During his time in medical
school, he had an Alpha Omega Alpha research scholarship in 1996 to do HLA genotyping in
rheumatoid arthritis. Id. at 4. That same year, he was a Sarnoff Cardiovascular Fellow to study
the role of cellular actin and myosin in ventricular hypertrophy induced by aortic banding. Id.

Dr. Ahmed did an internal medicine residency at The University of Texas Medical
School, from 1998-2000. Id. at 5. He was a Sarnoff Cardiovascular Scholar to study vascular
disease development in scleroderma in 2000. Id. at 4. He was a Sarnoff Cardiovascular Scholar
at The University of Texas Medical School, from 2000-2002. Id. at 5. During that time, he was
a Wyeth–Ayers Rheumatology Fellow in 2001. Id. at 4. He also won a clinical investigator
fellowship award from the Merck/American College of Rheumatology in 2002 and a Fellow
Award from the Merck/American College of Rheumatology in 2002. Id. He was a clinical
investigator at The University of Texas Medical School from 1998-2004. Id. at 5. During this
time period, he was first author of a medical article relating that a certain subgroup of patients
with RA had an increase in rheumatoid nodulosis that the drug MTX they were taking for RA
had induced.72 Dr. Ahmed was a rheumatology fellow at The University of Texas Medical
School from 2002-2003. Id. at 4. In 2003, he was a top finalist in the Amgen Rheumatology
Young Investigator proceeding. Id.

From 2003-2004, Dr. Ahmed was an Assistant Professor of Medicine in the Division of
Rheumatology at The University of Texas Medical School. Id. From 2004-2006, he was an
attending physician at the Veterans Administration Hospital in West Roxbury, MA, and at
Boston University Medical Center. Id. at 3. From July 2004 to September 2006, he was
Assistant Professor of Medicine at the Department of Medicine section of rheumatology at
Boston University School of Medicine, becoming Clinical Assistant Professor of Medicine there
from September 2006 – May 2007. Id. From 2006-2007, he received a grant from the

72
S. Sohail Ahmed et al., The HLA-DRB1*0401 Allele and the Development of Methotrexate-Induced Accelerated
Rheumatoid Nodulosis: A Follow-Up Study of 79 Caucasian Patients with Rheumatoid Arthritis, 80 MEDICINE
4:271-78 (2001). Listed on Dr. Ahmed’s updated CV. Ex. 95 at 6.
25
Scleroderma Foundation to be principal investigator of vascular disease and fibrosis in patients
with systemic sclerosis. Id. at 4. From August 2007 to June 2008, Dr. Ahmed was a clinical
associate in the Division of Rheumatology, Allergy, and Immunology at Harvard Medical
School/Massachusetts General Hospital. Id. at 3.

From September 2006 to March 2008, Dr. Ahmed was a translational medicine expert at
Novartis Pharma, Cambridge, MA. Id. He led the clinical development of novel compounds
from Discovery (e.g., next generation follow-up to Gilenya) and mature compounds (e.g.,
Glivec) targeted for clinical profiling related to autoimmunity and inflammation. Dr. Ahmed
managed a matrix-based team involving representatives from drug metabolism and
pharmacokinetics, drug chemistry, research, toxicology, marketing, and clinical development to
support design and implementation of proof-of-concept (“PoC”) studies. He developed an
approach incorporating modeling and simulations for the design of studies targeting
immunosuppression and fibrotic pathways. He leveraged parallel collaborations with the
Genomics Institute of the Novartis Research Foundation for the identification of human
therapeutics (e.g., biologics) and their application to various autoimmune diseases. He was a
clinical expert for in-licensing opportunities. Id.

From March 2008 to January 2011, Dr. Ahmed was head of the Clinical Science Unit,
Translational Medicine, at Novartis Vaccines, Siena, Italy. Id. He directed an adjuvant safety
initiative to enable an approach that was rational for preclinical studies using novel adjuvants
such as toll-like receptor agonists to lessen safety risks in subsequent clinical trials. Id. Dr.
Ahmed managed a team that was responsible for designing and implementing an exploratory
trial of cell-mediated immunity from flu vaccination. He provided cross-functional support to
the clinical development personnel in response to regulatory authorities on safety topics of
autoimmune diseases associated with vaccination. He also led the design of clinical studies to
reach PoC rapidly for Group A streptococcus and respiratory syncytial virus vaccines. Id.

From January 2011 to March 2015, Dr. Ahmed was Global Head of Clinical Sciences, at
Novartis Vaccines, Siena, Italy. Id. at 2. He was Executive Manager. He was also chairman of
a steering committee to develop antibody repertoire signatures that would predict natural, rapid
recovery to guide future vaccine antigen discovery efforts or the design of clinical trials with
patient groups most likely to respond to vaccine candidates in clinical development. He also led
cross-functional teams working on staphylococcus aureus, influenza, or candida infections to
ensure “seamless” application of this next-generation approach to vaccine development. Id. Dr.
Ahmed managed the recruitment of applicants for World Health Organization-TDR Clinical and
Development Fellowships to develop human resources promoting high-quality clinical research
and development and enhancing capacity on diagnostics, drugs, and vaccines for infectious
diseases that disproportionately affect poor and marginalized populations. Id. at 2-3. He led a
cross-functional team to prioritize populations to be targeted with vaccines containing novel
adjuvants such as TLR-agonists and pushed efforts to mitigate potential safety risks with a novel
vaccine delivery platform of lipid nanoparticle self-amplifying RNA, e.g., anti-RNA antibodies
and autoimmune disease risk. Id. at 3. Dr. Ahmed guided project leaders in principles of
medicine and human infectious diseases to ensure preclinical studies aligned with subsequent

26
human target populations in vaccine clinical trials concerning clostridium difficile, nontypeable
haemophilus influenza, and Escherichia coli. Id. He led the design of clinical trials and
implemented exploratory studies to generate quick no/no go decisions that upper management
made concerning subsequent product development with staphylococcus aureus and candida
albicans. He managed a diverse matrix-based team involving clinical development, toxicology,
technical development, vaccine chemistry, research/clinical serology, and regulation. Id.

From May to December 2015, he was global head of clinical sciences at GSK
(GlaxoSmithKline) Vaccines, which acquired Novartis Vaccines in May 2015. Id. at 2. He was
Executive Manager. He had the same responsibilities he had at Novartis Vaccines plus he
managed an internal approach capitalizing on information technologies, e.g., health map which
Harvard Medical School developed, in order to provide rapid surveillance for Neisseria
meningitides disease activity and transmission in patients. Id. He led a two-tear global
collaboration with 21 scientists and physicians from Novartis Vaccines, Novartis Pharma AG,
Novartis Institutes of Biomedical Research, Atreca Inc., VisMederi Sri, Stanford University,
Harvard Medical School, Dalhousie University, University of Siena, and the National Institute of
Health and Welfare in Finland to: (1) reinforce the safety of emulsion adjuvants, e.g., MF59 and
AS03; and (2) dissect the molecular pathway responsible for narcolepsy associated with the
AS03-adjuvanted A (H1N1) pdm09 influenza vaccine. Id. Dr. Ahmed supervised a post-
graduate course entitled “From Bench to Bedside: Principles of Vaccine Research &
Development,” covering principles of pre-clinical design and assessment of antigens, adjuvants,
and formulation testing through the different phases of clinical evaluation, and elements of
management and licensure. Id. He managed an internal cross-matrix team and external
collaboration with a U.S. academic medical center to: (1) identify a correlate of protection for
staphylococcus aureus by applying proteomic analysis to clinical sera from healthy subjects that
are colonized compared to patients with infection; and (2) identify differences in antibody
profiles from patients with various types of staphylococcus aureus infections, e.g., soft-tissue,
joint, pulmonary, or blood infections, to enable selection of a patient subgroup most likely to
support vaccine efficacy in clinical development trials. Id.

From April 2016 to the present, Dr. Ahmed has been at Translational Medicine, Roche
Pharma AG, Basel, Switzerland, involved in immunology, inflammation, and infectious diseases,
and leading cross-functional global teams to bring effective therapies for autoimmune diseases
from the discovery phase to phase III clinical studies. Id.

Dr. Ahmed received an MBA at IE Business School, Madrid, Spain, in 2017. Id. at 5.
He is licensed to practice medicine in Italy and the US. Id. at 1. He is board certified in internal
medicine with a subspecialty in rheumatology. Id.

Dr. Ahmed belongs to the American Medical Association, the Stanley J. Sarnoff
Cardiovascular Research Foundation, the American College of Physicians, the American College
of Rheumatology, the Infectious Diseases Society of America, and the Beta Gamma Sigma
Honor Society for Business. Id. at 4.

27
He has patents in sphingosine 1 phosphate receptor modulators and their use to treat
muscle inflammation (WO2010010127A1), diagnostic and therapeutic methods for rheumatic
heart disease based upon group A streptococcus markers (WO2011048561A1), and avoiding the
risk of narcolepsy with influenza vaccines (WO2014180999A1). Id. at 5.

Dr. Ahmed’s CV lists 11 articles, only two of which deal with rheumatic diseases and
neither of those discusses clinical diagnosis. Id. at 5-6. His CV lists 18 reviews, letters,
chapters, and editorials, only two of which deal with rheumatic diseases and neither of those
discusses clinical diagnosis. Id. at 6-7.

During the last 12 years, Dr. Ahmed has been doing research and working for vaccine
manufacturers. His clinical practice (as a clinical associate) ended in June 2008, 10 years ago.

Dr. Mehrdad Matloubian

Respondent filed the CV of Dr. Matloubian on June 23, 2016. Ex. B. Dr. Matloubian
received his M.D. in 1996 from the University of California, Los Angeles. He also has a Ph.D.
in virology. Id. at 1. He did an internship and residency in medicine at the University of
California, San Francisco (“UCSF”),73 from 1996-1998, and was a fellow in rheumatology at the
same institution from 1998-2001, followed by a post-doctoral fellowship at the same institution
from 1999-2004. Id. He has a medical license in California and is board certified in internal
medicine with a subspecialty in rheumatology. Id. at 2. He has been at UCSF since 2001,
holding positions as assistant adjunct professor, assistant professor in residence, associate
professor in resident, and currently associate adjunct professor. Id. In 2001, he was awarded a
Pfizer Postdoctoral Fellowship in Rheumatology/Immunology. In the same year, he received the
American College of Rheumatology Distinguished Fellows Award. In 2003, he was awarded the
Ephraim P. Engleman Award for Research in Rheumatology. Id. He states in his CV that, since
July 2014, he has had a full-day clinic once a week and continues to attend one month on the
inpatient rheumatology consult service. Id.

Dr. Matloubian is a member of the American College of Rheumatology, the Northern
California chapter of the Arthritis Foundation, the American Association of Immunologists, and
the American Society for Clinical Investigation. Id. at 2-3. He has written 33 articles, all of
them on the immune response.

Medical Expert Reports filed before the hearing

On February 6, 2016, petitioner filed the expert report of Dr. Ahmed. Ex. 67, at 2.

Dr. Ahmed states in his expert report “the development of an autoantibody-mediated
disease is the result of a complex interaction between genetic and environmental factors.” Ex.

73
UCSF is ranked in 2018-2019 as the seventh best hospital for adult rheumatology in the United States. Best
Hospitals. Best Hospitals for Rheumatology, US NEWS & WORLD REPORT, https://health.usnews.com/best-
hospitals/rankings/rheumatology (last visited September 24, 2018).
28
67, at 4. The most common skin involvement in MCTD is Raynaud’s phenomenon. Id. Joint
involvement and muscle pain are common in MCTD. A major cause of death in MCTD is
pulmonary arterial hypertension (“PAH”). In answer to whether petitioner had signs and
symptoms of MCTD before her September 20, 2012 flu vaccination, Dr. Ahmed says no. Id. at
5-6. She had pre-vaccination shoulder tendinitis in 2000 with x-ray showing calcifications of the
supraspinatus muscle of the shoulder. Id. at 5. She had low back pain and right leg hypesthesia
in 2001 related to a work injury when transferring a patient from a slideboard. Petitioner had
asymmetric aching in the fingers and thumb of the right hand, a negative RF, a normal ESR,
none of which suggests RA, but are more consistent with osteoarthritis. Id. Dr. Ahmed views
the 2008 detection of ANA of 1:160 in a homogeneous pattern nonspecific which 20% of the
normal population has. He thinks that her normal CPK muscle enzymes in August 9, 2000 and
the nature of her musculoskeletal complaints make her having a myositis component of MCTD
unlikely prior to her flu vaccination in 2012. Id. Her 2000 complaint of erythema in the face
while having nausea and headaches was consistent with a vascular response, such as migraine.
In 2014, petitioner was diagnosed with rosacea. Thus, Dr. Ahmed says the erythema of
petitioner’s face was not consistent with a malar rash, and she does not have the SLE of MCTD
before flu vaccination in 2012. Id.

Dr. Ahmed says petitioner likely has high genetic susceptibility to MCTD because her
mother has Hashimoto’s74 thyroid disease and her sister has Sjögren’s syndrome (“SS”) for
which she takes methotrexate. Id. at 6. He states that since petitioner’s immediate family
members most likely carry genes that increased their susceptibility to autoimmune diseases
associated with antibodies to the thyroid (Hashimoto’s) or to glandular tissues (Sjögren’s),
petitioner’s family history of autoimmune disease was a risk factor for her to develop
autoimmune disease. Dr. Ahmed posits a sequence of events leading a genetically susceptible
host presented with an antigen/peptid stimulus which her regulatory mechanisms failed to
control, resulting in autoimmune disease, e.g., disease-specific autoantibodies such as anti-RNP.
Id.

To answer the question whether petitioner developed MCTD after receiving flu vaccine
in 2012, Dr. Ahmed comments that definitively diagnosing MCTD is often complicated since
overlapping features of SLE, SSc, and inflammatory myopathy often occur associated with high
titers of anti-RNP antibodies. He states a key feature to suspect MCTD is unexplained
Raynaud’s phenomenon. Diagnosing MCTD often takes years because of typical overlap
features. After petitioner received flu vaccine on September 20, 2012, she saw Dr. Xu on
October 3, 2012 with swelling in her hands for the first time. Blood tests showed antibodies to
RNP with an index at 1.2 (Ex. 3, at 37-41), positive ANA tier of 1:320 (Ex. 3, at 45-46), which
was greater than the prior titer of 1:160 four years earlier. From then on, petitioner’s swelling
and joint pain resembled RA (Ex. 3, at 98-101). Doctors put her on various disease-modifying
anti-rheumatic drugs, including methotrexate, hydroxychloroquine, etanercept, abatacept, and

74
Hashimoto disease is “a progressive type of autoimmune thyroiditis with lymphocytic infiltration of the gland and
circulating antithyroid antibodies; patients have goiter and gradually develop hypothyroidism. It has a familial
predisposition, usually affects women, and sometimes precedes the onset of Graves disease or is manifested after the
major symptoms subside.” Dorland’s at 535. Graves disease can manifest as hyperthyroidism. Id. at 534.
29
tocilzumab. On May 13, 2013, she had elevated CRP and elevated complement levels, evidence
for systemic inflammation, consistent with an evolving autoimmune disease (Ex. 3, at 86-89).
On May 15, 2013, petitioner was noted to have skin thickening over her fingers (sclerodactyly), a
feature of SS, which is another autoimmune disease (Ex. 3, at 98-101). Id.

Dr. Ahmed opines that the two-week interval between petitioner’s 2012 flu vaccination,
detection of disease-specific autoantibodies for MCTD, and increasing ANA titer fall within a
plausible window for linking flu vaccine to the dysregulation of petitioner’s immune response.
Id. at 7. Petitioner’s gradual progression of clinical symptoms (eight months after vaccination,
systemic inflammation detected in lab tests and thickening of skin of her fingers; 18 months
later, Raynaud’s phenomenon diagnosed) is typical for MCTD. Dr. Ahmed concludes that the
presence of autoantibodies to RNP and Raynaud’s phenomenon occurring after flu vaccination
on September 20, 2012 suggests a causal relationship. Id. In the alternative, the flu vaccination
of September 20, 2012 may have caused significant aggravation of an underlying autoimmune
process that was asymptomatic, transforming it into a clinically apparent disease. Petitioner’s
initial positive ANA detected on March 5, 2008 may have been due to her October 7, 1999 flu
vaccination priming her (Ex. 14, at 20; Ex. 16, at 1). Priming involves generating immune
memory in a vaccinee. Thus, petitioner’s initial immune response to flu vaccination on October
7, 1999 started the process of asymptomatic autoimmunity and the next flu vaccination
administered October 14, 2009 further boosted it. The flu vaccination she received on
September 20, 2012 could have also boosted the immune response, transforming the underlying
autoimmunity into an autoimmune disease, i.e., MCTD. Ex. 67, at 7.

Dr. Ahmed says that vaccines can cause autoimmune diseases even if epidemiologic
studies do not confirm that because of the small number of cases, unlike the considerable number
of cases of GBS (500) among 45 million people who received swine flu vaccine in 1976. Id. at
8. He says “rare adverse events still occur in genetically susceptible subjects….” Id. Dr.
Ahmed states that molecular mimicry has been demonstrated specifically for MCTD in reaction
to various viruses: HIV, Epstein-Barr virus, and human influenza B virus dealing with systemic
sclerosis. Id. at 9.

On June 23, 2016, respondent filed the expert report of Dr. Mehrdad Matloubian. Ex. A.
Dr. Matloubian doubts that petitioner has MCTD and suspects that her musculoskeletal pain is
related to her chronic pain syndrome and osteoarthritis, and therefore unrelated to her flu
vaccinations. Id. at 5-6. He says MCTD is considered an overlap syndrome because it has
features of other better-defined autoimmune diseases, such as SLE, SS, and polymyositis. Id. at
6. The symptoms may occur over time, thus making diagnosis at the outset of the disease
challenging. He states a major characteristic of patients whom doctors eventually diagnose with
MCTD is the presence of Raynaud’s phenomenon in association with high-titer speckled ANA
with fine specificity for U1 RNP. The remaining criteria are clinical signs showing
inflammatory disease, e.g., myositis, acrosclerosis, synovitis, and swollen hands. Id.

Dr. Matloubian states that when Dr. Lin diagnosed petitioner with MCTD on October 31,
2012, she based her diagnosis on petitioner’s non-specific joint complaints without any clinical

30
sign of synovitis and primarily because petitioner had a positive anti-RNP. Dr. Matloubian
regards petitioner’s positive anti-RNP as a false positive result which does not support a
diagnosis of MCTD. On October 15, 2012, petitioner’s serologic tests showed a low to moderate
ANA titer of 1:320 with a homogeneous pattern (Ex. 3, at 45-46). This result is consistent with
petitioner’s previous ANA test done in 2008, which was positive at 1:160 with a homogeneous
pattern (Ex. 14, at 20). A homogeneous pattern as petitioner had corresponds to anti-dsDNA,
nucleosomes, and histones, usually seen in SLE, drug-induced lupus, and autoimmune thyroid
disease. Ex. A, at 6. In contrast, when someone has antibodies to U1-RNP, such as someone
with MCTD, the staining pattern is speckled, not homogeneous. Id. at 7. Dr. Matloubian’s
opinion is that petitioner’s homogeneous ANA result on two separate tests performed at two
different laboratories suggests the anti-RNP result was most likely a false positive. Id.

Dr. Matloubian has other issues with this positive anti-RNP test result. Firstly, the assay
showed a low positive anti-RNP at 1.2 with the cutoff for this assay being less than 1 and the
highest value being 8. Dr. Matloubian does not know how the tech person reached a value of 1.2
and how this relates to an ANA titer of 1:320, but in light of the moderate ANA titer and the
homogeneous pattern, petitioner’s 1.2 value does not seem to qualify for the high titer ANA
(>1:10,000) with speckled pattern that is a mandatory diagnostic criterion for MCTD. Secondly,
in addition to testing for anti-RNP, petitioner was tested for anti-Sm+RNP, and the result was
negative (Ex. 3, at 41). Since the same antigens are used to test for RNP as for Sm+RNP, Dr.
Matloubian expected both test results to be positive. Bio-Rad Laboratories, which manufactures
this assay, has a statement that if someone has a positive RNP test, but a negative SmRNP and
Sm test, this decreased the probability of connective tissue disease. Ex. 7, at 7. Bio-Rad
Laboratories’ Interpretation Guide also indicates that this result can be seen in 2.3% of normal
blood donors.75 Id.

Dr. Matloubian concludes that if petitioner had a truly positive anti-RNP associated with
MCTD, she should have had high-titer speckled ANA, positive anti-RNP (AI >8) and three
positive autoantibodies; all of the MCTD patients were positive for RNP and SM+RNP. Dr.
Matloubian ascribes petitioner’s false positive anti-RNP result to the type of bead-based
multiplex assay that Bio-Rad Laboratories used to determine autoantibodies. Id. He states many
experts have raised concerns about the sensitivity and specificity of such assays. False positives
are not uncommon and Dr. Matloubian thinks petitioner is an example of a false positive. She
initially tested low positive for anti-cardiolipin IgM and IgG antibodies, but testing several
months later resulted in normal results (Ex. 3, at 63, 82). He strongly believes based on his own
experience with patients whose lab results are contradictory that petitioner’s anti-RNP test result
was a false positive. Id.

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On August 1, 2017, respondent filed as exhibit E the Bio-Rad Laboratories BioPlex 2200 Interpretation Guide:
SmRNP vs Sm & RNP. If someone tests negative for Sm, positive for RNP, and negative for SmRNP, the
interpretation guide states: “If low titer without other associated antibodies, decreased probability of connective
tissue disease; retest patient every 6-12 months to monitor titer. Potential predictive antibody for early stage SLE.”
The prevalence of this test result of negative Sm, positive RNP, and negative SmRNP is 2.3% in normal blood
donors, and 4.1% in rheumatology patients. Id.

31
Dr. Matloubian describes petitioner’s treating rheumatologist Dr. Lin’s charting of
petitioner’s clinical symptoms of MCTD as “not ideal.” Id. at 8. He noted that Dr. Lin did not
correct her initial incorrect diagnoses in subsequent records and her records have many internal
inconsistencies. Id. Dr. Matloubian describes as “clear” was Dr. Lin’s not observing petitioner
having hand or joint swelling or clear synovitis when petitioner first came to her on October 31,
2012. During the next three years, Dr. Lin documented only one possible swelling in a PIP joint
(Ex. 3, at 124) which apparently resolved. He states Dr. Lin never documented diffuse hand
swelling in petitioner, even though diffuse hand swelling is often seen in early MCTD. Dr. Lin
thought petitioner might have sclerodactyly. Id. Being certain of the presence of synovitis is
more difficult in patients, such as petitioner, who are overweight. Id. Petitioner’s BMI on May
17, 2013 was 30 (Ex. 3, at 99). Dr. Matloubian would have used an MRI to determine if
petitioner had synovitis, but Dr. Lin did not perform any imaging studies of petitioner, such as x-
rays of her hand and knees or an MRI of her hands to detect inflammation or other causes of
joint pain, such as osteoarthritis. Id. Dr. Matloubian thinks Dr. Lin diagnosed MCTD solely
based on the results of the RNP test without any clinical findings to support the diagnosis and
then over time looked for signs and symptoms to justify her diagnosis. Dr. Matloubian noted
that 75 percent of patients with MCTD have lung involvement including pulmonary
hypertension, but Dr. Lin did not order a high-resolution CT or echocardiogram to screen
petitioner for this possibility. In addition, Dr. Lin did not note administering a PPD76 test, which
is a requirement before beginning a patient on anti-TNF therapy such as Enbrel. Id.

Dr. Matloubian says patients with MCTD generally have Raynaud’s disease as an early
symptom. Id. But the earliest notation Dr. Lin made of petitioner having Raynaud’s
phenomenon is November 19, 2014, a year after Dr. Lin diagnosed petitioner with MCTD. Id. at
9. Petitioner does not mention in her affidavit dated August 2015 that Raynaud’s phenomenon
was part of her symptoms. Dr. Lin again diagnosed petitioner with Raynaud’s phenomenon on
January 5, 2016 and prescribed topical medication (Ex. 20, at 1-5). Dr. Matloubian states that it
would be quite unusual for Raynaud’s phenomenon to be a late manifestation of MCTD. Dr.
Matloubian thinks that petitioner’s moderately positive ANA with a homogeneous pattern is
more consistent with autoimmune thyroid disease than MCTD. Id. That petitioner’s sister has
Sjögren’s disease, which is autoimmune, increases the likelihood that petitioner would have a
positive ANA. Id.

Dr. Matloubian thinks petitioner’s true diagnosis is chronic pain syndrome and
osteoarthritis, both of which predate her flu vaccination in September 2012. Id. at 10. As for Dr.
Ahmed’s opinion, Dr. Matloubian takes issue with Dr. Ahmed’s reliance on the theory of
molecular mimicry because the presence of linear sequence homology does not necessarily
translate to immunogenicity. Id. at 11. Proteins consist of linear sequences of amino acids, but
fold into complex three-dimensional structures. Dr. Ahmed’s diagram in Exhibit 25 is too
simplistic and does not convey that a similar linear sequence of amino acids in one protein may
be hidden within its three-dimensional structure and not accessible to antibodies. Id. Thus
sequence homology is insufficient evidence for molecular mimicry. Id. at 12. Concerning the

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PPD is “purified protein derivative (tuberculin). . . .” Dorland’s at 1506. Tuberculin is “used in skin tests for
tuberculosis” and is also “a commonly used antigen in laboratory immunology.” Id. at 1979.
32
theory that if a vaccine can cause a disease, so can the infection that the vaccine was created to
prevent cause the same disease, Dr. Matloubian did medical article research, but could not find
any medical articles linking flu virus infection with MCTD. Id. at 12-13. He concludes that
since the flu virus shares genetic similarity with components of flu vaccine but is not associated
with MCTD, it is highly unlikely that a mechanism such as molecular mimicry causes MCTD
due to flu vaccine. Id. at 13.

Dr. Matloubian is unimpressed with the two-fold change in ANA titer petitioner had from
1:160 in 2008 to 1:320 in 2012 because the change has unclear clinical significance. Id. He
takes issue with Dr. Ahmed’s opinion that petitioner’s 1999 and 2009 flu vaccinations primed
her ANA, which the 2012 flu vaccination then boosted so that petitioner developed autoimmune
disease. Id. at 14. Dr. Matloubian questions why, if the 1999 flu vaccination primed petitioner,
the 2009 flu vaccination did not boost her to have clinical autoimmune disease, instead of just
being another priming vaccination. To Dr. Matloubian, it seems as if Dr. Ahmed were
interpreting events to fit his thesis and not considering other interpretations. Id. Dr. Matloubian
does accept the prime and boost theory as applied to an acute infection or a vaccination when
someone’s immune system is exposed briefly to an antigen, but it does not make sense in the
context of an autoimmune response for which self-antigen persists. He gives an example of a
memory response proceeding to a reaction against poison ivy or poison oak. When someone is
exposed to poison ivy, he may have no symptoms but is immunized and generates memory T-
cells to the plant’s antigens. When the person has a subsequent exposure, he develops a severe
and rapid response within a couple of days due to expansion of poison ivy specific memory T-
cells and localization to exposed areas. This response also subsides because the antigen is not
persistent. Thus, the poison ivy specific memory T-cells are dormant and do not cause any
symptoms. Id.

Dr. Matloubian says a similar process occurs after flu immunization, i.e., generation of
memory T-cells to the vaccine component. These memory T-cells are inactive unless they
encounter their specific antigen through exposure to flu virus or re-immunization with the same
seasonal flu vaccine. If Dr. Ahmed’s opinion that prior flu vaccinations generate memory T-
cells that are cross-reactive for self-antigens is correct, Dr. Matloubian says he would not expect
these cells to be dormant and inactive waiting for another flu vaccination since their putative
self-antigens are always around and constantly stimulating them. In addition, they would not
need a boost from another flu vaccination since their antigen is a self-antigen and always present.
To Dr. Matloubian, Dr. Ahmed’s explanation does not make biologic sense. Id.

Dr. Matloubian further discounts Dr. Ahmed’s opinion that petitioner has a genetic
predisposition and thus was susceptible to developing an autoimmune disease because immediate
family members have autoimmune diseases. He states that multiple studies in medical literature
show that patients with autoimmune diseases receive vaccinations, including against flu, without
exacerbation of their disease or developing a new one. Id.

Dr. Matloubian concludes his report by stating petitioner’s tests do not support a
diagnosis of MCTD because MCTD necessitates a high-titer ANA with a speckled pattern. Id. at

33
15. Petitioner on two occasions had two different laboratories conclude she had a relatively low-
titer ANA with a homogeneous pattern, inconsistent with a diagnosis of MCTD. Moreover,
petitioner’s marginally positive anti-RNP was most likely a false positive. Dr. Matloubian
opines petitioner suffers from chronic pain syndrome and osteoarthritis, both of which pre-
existed her September 2012 flu vaccination. Id.

On June 28, 2016, petitioner filed Dr. Ahmed’s response to Dr. Matloubian. Ex. 70. Dr.
Ahmed states that a low-titer positive RNP suggests a decreased probability of connective tissue
disorder, but does not exclude the diagnosis of MCTD. Id. at 2. Guidelines for diagnosing
MCTD capture most, but not all, MCTD patients. Id. Dr. Ahmed states that natural flu infection
but not flu vaccine have been observed to exacerbate RA and SLE. Id. at 4. He explains this
discrepancy as due to degree, duration, and dispersion of inflammation in the context of a
systemic infection which is greater than the controlled immune stimulation involved in
vaccination. Id. Dr. Ahmed states, “In my opinion, it is possible that influenza vaccination
triggered MCTD” in petitioner. Id. at 5.

On July 11, 2016, respondent filed Dr. Matloubian’s response to Dr. Ahmed. Ex. C. He
reiterates that he thinks Dr. Lin’s assessment of petitioner suffers from confirmation bias, i.e.,
her subsequent records presume her initial diagnosis of MCTD was correct without considering
other possible causes of petitioner’s symptoms. Id. at 2. He is suspicious of Dr. Lin’s physical
examinations of petitioner. Id. He states that Dr. Ahmed’s interpretation of petitioner’s
numbness in the bottom of her feet as indicative of Raynaud’s phenomenon is absolutely
incorrect. Id. at 3. Dr. Matloubian denies that petitioner was ever diagnosed with scleroderma
and did not have documented laboratory features of scleroderma which most commonly affects
the skin and lungs. Id. He reiterates that petitioner’s ANA was low specificity and can be seen
in autoimmune thyroid disease, with which petitioner was diagnosed. Id. at 6. He notes that the
ANA titer does not correlate with disease activity. Id. Dr. Matloubian also notes that the Bio-
Rad laboratory insert states that 2.3 percent of blood donors have borderline positive anti-RNP
and negative everything else. Id.

Dr. Matloubian asked his rheumatology colleagues at UCSF, including the Chief of the
UCSF Rheumatology Clinic and the director of the UCSF Scleroderma Center, how they would
interpret petitioner’s test results and they unanimously said that the anti-RNP was a false positive
and they would repeat the test with a different type of assay. Id. at 7. They also said petitioner
did not have MCTD and they had great doubt that she had any rheumatologic disease. He also
asked a rheumatology colleague who has practiced at Kaiser in the bay area about petitioner’s
serologies and he replied that the subserologies were done by automated testing and the so-called
BioPlex testing and unfortunately automated testing can give non-specific results. Id.

Dr. Matloubian agrees with Dr. Ahmed that natural infections, such as flu virus, lead to a
much stronger immune response that immunization with inactivated flu vaccine. Id. at 11. Thus,
it would be highly unlikely for a vaccine, which induces a much weaker immune response than a
natural infection, to lead to autoimmune disease when the natural infection with the flu virus
itself is not associated with that autoimmune disease. Id. Dr. Matloubian concludes with the

34
statement:
As a practicing rheumatologist at a major academic referral center,
neither I nor any of my colleagues would have diagnosed the
petitioner as having MCTD or any other rheumatologic
autoimmune disease based on the provided serological testing for
autoantibodies. Her anti-RNP test result, the sole basis of the
diagnosis of MCTD made by Dr. Lin, was most likely a false
positive since it was discordant with the remainder of her test
results. It is my strong opinion that the petitioner did not develop
MCTD or any other rheumatic autoimmune disease as the result of
receiving the influenza vaccine.

Id. at 12.

On August 19, 2016, petitioner filed Dr. Ahmed’s response to Dr. Matloubian. Ex. 87.
Dr. Ahmed states that patients with autoimmune disease do not always fulfill the standard
criteria. Id. at 6. Most of the standard criteria were designed for the purpose of following and
classifying patients in clinical studies. Moreover, the association of anti-RNP antibodies with
MCTD does not occur in up to 5 percent of patients with MCTD. Therefore, it is not always
present in MCTD. If petitioner did not have anti-RNP antibodies, that would not exclude her
from the diagnosis of MCTD in light of her clinical signs after flu vaccination. Id. Dr. Ahmed
explains petitioner’s ANA homogeneous pattern as due either to the 5 percent of MCTD patients
who do not have RNP antibodies, or the laboratory detecting the ANA pattern used a different
technology and thus reflected a different pattern at initial dilutions. Id. at 8. Dr. Ahmed states
that antibodies can fluctuate during a stage of a disease and a low positive does not mean a false
positive. He says the manufacturer Bio-Rad states that a low-titer positive RNP suggests a
decreased probability of connective disorder. This does not mean a low-titer positive RNP
excludes the diagnosis of MCTD since five percent of patients with MCTD do not have anti-
RNP antibodies. Id.

Dr. Ahmed states that molecular mimicry is not speculative and is proven for
streptococcus and rheumatic fever. Id. at 9. The theory is also accepted to explain GBS
following the 1976 swine flu vaccine campaign. Id.

On May 2, 2017, respondent filed the second supplemental report of Dr. Matloubian
responding to the additional medical records (Ex. 86) and Dr. Ahmed’s supplemental report (Ex.
87). Ex. D. He states that he highly doubts the diagnosis of MCTD and recommended petitioner
seek a second opinion from a doctor with an academic rheumatology practice, such as Stanford
or UCSF. Id. at 3. However, petitioner obtained a second opinion from Dr. Lau, who is another
rheumatologist at Kaiser Permanente, just as Dr. Lin is. Id. Dr. Lau “speculated” petitioner
could have MCTD or UCTD. Id.

Dr. Matloubian notes that petitioner had one positive anti-RNP result while another RNP
antigen test (anti-RNP/Smith) was negative. This is highly unusual. Id. at 3. That makes two

35
discrepancies in her autoantibody testing, which makes these tests results inconsistent with a
diagnosis of MCTD. Id. at 3-4. The consultant rheumatologist Dr. Lau appeared to be unaware
that petitioner had a history of rosacea when he diagnosed her with CTD. Id. at 4. What is more,
Dr. Lau attributed petitioner’s skin problem as telangiectasia due to connective tissue diseases.
Id. Petitioner’s GERD predates her flu vaccination on September 20, 2012. Id. Dr. Matloubian
disagrees that the pictures of petitioner’s fingers reflect active Raynaud’s phenomenon. Id. at 5.
Petitioner’s main complaints are musculoskeletal pain, but she does not have elevated muscle
enzymes, which rules out inflammatory myopathy (usually associated with MCTD and other
connective tissue diseases). Two of petitioner’s rheumatologists, Dr. Lau and Dr. Lin, performed
physical examinations of petitioner within one week and came to different conclusions as to what
they saw. Determining a diagnosis of joint inflammation in an overweight patient such as
petitioner makes the doctors’ conflicting diagnoses suspect. Id. This is why Dr. Matloubian
relies on objective studies as MRIs to detect joint inflammation. Dr. Lau appeared unaware that
petitioner’s oral ulcers when she was not taking MTX were due to herpes simplex virus and
treated with acyclovir. Id. Dr. Matloubian states that some of the therapies petitioner received,
e.g., Enbrel, Orencia, and Actemra, could have led to her developing further autoantibodies. Id.
at 6. He states if he were petitioner’s treating rheumatologist, he would repeat autoimmune tests
using an ELISA77 assay, discontinue her immunosuppressive medications, do MRI imaging of
her hands while she was off medications to evaluate her for joint inf

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Source: Frix Law Library, https://www.frixlaw.com/law-library/cases/4355839. Public record. Not legal advice.