Russell v. Secretary of Health and Human Services

Opinion

In the United States Court of Federal Claims OFFICE OF SPECIAL MASTERS No. 18-457V Filed: September 10, 2019 UNPUBLISHED

LAURA RUSSELL,

Petitioner, Special Processing Unit (SPU); v. Findings of Fact; Onset and Site of Vaccination; Influenza (Flu) Vaccine; SECRETARY OF HEALTH AND Shoulder Injury Related to Vaccine HUMAN SERVICES, Administration (SIRVA)

Respondent.

Amy A. Senerth, Muller Brazil, LLP, Dresher, PA, for petitioner. Traci R. Patton, U.S. Department of Justice, Washington, DC, for respondent.

FINDINGS OF FACT1

Dorsey, Chief Special Master:

On March 28, 2018, petitioner filed a petition for compensation under the National Vaccine Injury Compensation Program, 42 U.S.C. §300aa-10, et seq.,2 (the “Vaccine Act”). Petitioner alleges that she suffered “right shoulder injuries” as a result of an influenza (“flu”) vaccine administered on December 31, 2016. Petition at 1. The case was assigned to the Special Processing Unit of the Office of Special Masters.

For the reasons discussed below, the undersigned finds that petitioner was administered a flu vaccine on December 31, 2016 in her right arm and that the onset of 1The undersigned intends to post this ruling on the United States Court of Federal Claims' website. This means the ruling will be available to anyone with access to the internet. In accordance with Vaccine Rule 18(b), petitioner has 14 days to identify and move to redact medical or other information, the disclosure of which would constitute an unwarranted invasion of privacy. If, upon review, the undersigned agrees that the identified material fits within this definition, the undersigned will redact such material from public access. Because this unpublished ruling contains a reasoned explanation for the action in this case, undersigned is required to post it on the United States Court of Federal Claims' website in accordance with the E-Government Act of 2002. 44 U.S.C. § 3501 note (2012) (Federal Management and Promotion of Electronic Government Services).

2National Childhood Vaccine Injury Act of 1986, Pub. L. No. 99-660, 100 Stat. 3755. Hereinafter, for ease of citation, all “§” references to the Vaccine Act will be to the pertinent subparagraph of 42 U.S.C. § 300aa (2012). her shoulder symptoms occurred within 48 hours of vaccination. Specifically, petitioner suffered shoulder pain within 48 hours of vaccination.

I. Relevant Procedural History

Following the initial status conference held on May 11, 2018, respondent was ordered to file a status report indicating how he intends to proceed in this case. ECF No. 8. On February 11, 2019, respondent filed a status report confirming that he intends to defend this case and requesting a deadline for the filing of his Rule 4(c) Report. ECF No. 19.

Respondent filed his Rule 4(c) Report (“Res. Report”) on March 22, 2019. ECF No. 21. In his report, respondent argued that, although petitioner alleged that she received the December 31, 2016 flu vaccination in her injured right arm, her medical records indicate the flu vaccination was administered in her left arm. Res. Report at 5. Respondent further asserted that petitioner has not established all of the elements necessary for a shoulder injury related to vaccine administration (“SIRVA”) Table Injury, including onset of the shoulder injury within 48 hours of the vaccination. Id. at 5-7.

Thereafter, a scheduling order was issued ordering petitioner to file a motion for subpoena authority to obtain additional vaccination records from Rite Aid. ECF No. 22. Petitioner filed vaccination records collected pursuant to subpoena on May 17, 2019. ECF No. 25.

On May 31, 2019, a scheduling order was issued noting that the undersigned had reviewed respondent’s Rule 4(c) Report and the evidence filed to date in this case. ECF No. 27. The undersigned stated that briefing and a hearing were not necessary to make findings of fact regarding the site of petitioner’s flu vaccination and the onset of her alleged injury. Id. The undersigned set a deadline for the parties to file any additional relevant evidence they wished to have considered regarding these issues. Id. No additional evidence was filed. This matter is now ripe for adjudication.

II. Issues

There are two issues in this case: (1) whether petitioner was administered a flu vaccine on December 31, 2016 in her injured right arm, and (2) whether petitioner’s first symptom or manifestation of onset after vaccine administration was within 48 hours as set forth in the Vaccine Injury Table. 42 C.F.R. § 100.3(a) XIV.B. (2017) (influenza vaccination). Additionally, the Qualifications and aids to interpretation (“QAI”) for a Table SIRVA also require that a petitioner’s pain occurs within 48 hours. 42 C.F.R. § 100.3(c)(10).

III. Authority

Pursuant to Vaccine Act § 13(a)(1)(A), a petitioner must prove, by a preponderance of the evidence, the matters required in the petition by Vaccine Act

2 § 11(c)(1). A special master may find that the first symptom or manifestation of onset of an injury occurred “within the time period described in the Vaccine Injury Table even though the occurrence of such symptom or manifestation was not recorded or was incorrectly recorded as having occurred outside such period.” Vaccine Act § 13(b)(2). “Such a finding may be made only upon demonstration by a preponderance of the evidence that the onset [of the injury] . . . did in fact occur within the time period described in the Vaccine Injury Table.” Id. A special master must consider, but is not bound by, any diagnosis, conclusion, judgment, test result, report, or summary concerning the nature, causation, and aggravation of petitioner’s injury or illness that is contained in a medical record. Vaccine Act § 13(b)(1). “Medical records, in general, warrant consideration as trustworthy evidence. The records contain information supplied to or by health professionals to facilitate diagnosis and treatment of medical conditions. With proper treatment hanging in the balance, accuracy has an extra premium. These records are also generally contemporaneous to the medical events.” Curcuras v. Sec’y of Health & Human Servs., 993 F.2d 1525, 1528 (Fed. Cir. 1993). Additionally, when determining the impact of the evidence presented, the special master should consider factors such as the reliability and consistency of the evidence. See Burns v. Sec'y of Health & Human Servs., 3 F.3d 415, 416 (Fed. Cir. 1993). “Written records which are, themselves, inconsistent, should be accorded less deference than those which are internally consistent. If a record was prepared by a disinterested person who later acknowledged that the entry was incorrect in some respect, the later correction must be taken into account.” Murphy v. Sec’y of Health & Human Servs., No. 90-882V, 1991 WL 74931, at *4 (Fed. Cl. Spec. Mstr. Apr. 25, 1991), mot. for rev. denied, 23 Cl. Ct. 726 (1991), aff'd per curium, 968 F.2d 1226 (Fed. Cir. 1992).

IV. Findings of Fact

a. Site of Vaccination

The undersigned finds that the record in this case establishes that petitioner was administered a flu vaccination in her right arm on December 31, 2016. The undersigned makes the aforementioned finding after a complete review of the record, including all medical records, petitioner’s affidavit, and respondent’s Rule 4(c) Report.

Specifically, the undersigned bases the finding on the following evidence:

• The “Corp Pharmacy: Prescription Inquiry” and “Corp Pharmacy: Service Details” forms from Rite Aid document that a flu vaccine was administered intramuscularly in petitioner’s left upper arm on December 31, 2016. Petitioner’s Exhibits (“Pet. Exs.”) 1 at 2; 9 at 2. A “Screening Questionnaire and Consent Form” from Rite Aid reflects an entry of “LA,” or left arm, under the site of administration section for the December 31, 2016 flu vaccination. Pet. Ex. 9 at 4.

3 • On March 6, 2017, petitioner presented to Fusion Healthcare for a medical appointment following an emergency room admission on January 22, 2017.3 Pet. Ex. 2 at 17. Petitioner reported that she had suffered a “reaction” to a flu vaccine administered on December 31, 2016 and had experienced right arm soreness since that time. Id. Petitioner specified that the flu vaccine was administered in her right arm. Id.

• A March 27, 2017 MRI of petitioner’s right shoulder revealed, in pertinent part, mild supraspinatus and infraspinatus tendinopathy; trace amount of joint fluid; and minimal degenerative changes of the acromioclavicular joint. Pet. Ex. 3 at 3. These imaging findings are suggestive of a SIRVA. See Court Exhibit I, attached (S. Atanasoff, et al., Shoulder injury related to vaccine administration (SIRVA), 28 Vaccine 8049, 8051-52 (2010) (noting that shoulder MRI findings such as fluid collection, localized tendon inflammation, and bursitis may be consistent with over-penetration of the vaccine needle into the synovial space of the shoulder.)).

• On May 18, 2017, petitioner presented to Anderson Physical Therapy for an initial evaluation. Pet. Ex. 3 at 40. Petitioner noted that in “December 2016” she had received a flu vaccine in her “right side” and had experienced shoulder pain since that time. Id.

• On June 18, 2018, petitioner filed a detailed affidavit providing additional information regarding her December 31, 2016 flu vaccination. Pet. Ex. 8. At the time of the vaccination, petitioner recalled that she was sitting in a private room and had turned sideways to the left-facing wall while her right arm faced the vaccine administrator. Id. at ¶ 7. Petitioner confirmed that she was administered the flu vaccination in her right arm. Id.

b. Onset

Based upon the record as a whole, and specifically the evidence cited below, the undersigned finds that the onset of petitioner’s right shoulder pain occurred within 48 hours after the administration of the December 31, 2016 flu vaccine. • As established above, petitioner received a flu vaccine in her right arm on December 31, 2016.

• On March 6, 2017, petitioner presented to Fusion Healthcare with complaints of “right shoulder/arm pain” following a December 31, 2016 flu vaccination. Pet. Ex. 2 at 17. Petitioner stated that she had been

3Petitioner presented to the emergency room on January 22, 2017 with complaints of sore throat and difficulty breathing. Pet. Ex. 4 at 5. Petitioner was discharged the same day in stable condition with diagnoses of acute pharyngitis and acute anxiety. Id. at 6-7.

4 experiencing soreness since receiving the flu vaccination and denied any previous injury or trauma. Id. On examination, petitioner presented with right shoulder tenderness to palpation, “very guarded” range of motion, inability to move her arm behind her back, and positive scarf and empty can testing. Id. at 18.

• On May 18, 2017, petitioner presented to Anderson Physical Therapy for an initial evaluation. Pet. Ex. 3 at 40. Petitioner noted that in “December 2016” she had received a flu vaccine in her “right side” and had experienced shoulder pain since that time. Id. A contemporaneous “Physical Therapy Evaluation and Treatment Plan” form linked the onset of petitioner’s shoulder condition to the flu vaccination and noted that her arm “never got better.” Id. at 47. On examination, petitioner presented with tightness, right shoulder tenderness to palpation, reduced range of motion, and reduced strength. Id. at 40.

• On June 18, 2018, petitioner filed a detailed affidavit providing additional information regarding her December 31, 2016 flu vaccination. Pet. Ex. 8. Petitioner noted that her right shoulder symptoms, including pain, began “immediately” following vaccination. Id. at ¶¶ 7, 9. Petitioner averred that her symptoms did not subside but instead grew worse over time. Id. at ¶¶ 8-9. Petitioner indicated that her injury limited her ability to perform activities of daily living. Id. at ¶¶ 9, 12. Petitioner averred that, although her symptoms have improved, she continues to suffer from right shoulder pain. Id. at ¶ 13.

V. Conclusion

In light of all of the above and in view of the record as a whole, the undersigned finds that (1) petitioner was administered an influenza vaccine in her right arm on December 31, 2016, and (2) the onset of petitioner’s right shoulder symptoms, including pain, occurred within 48 hours of vaccination. The parties are encouraged to consider an informal resolution of this claim. Petitioner shall file a joint status report by no later than Friday, October 11, 2019, updating the court on the status of the parties’ settlement discussions.

IT IS SO ORDERED.

s/Nora Beth Dorsey Nora Beth Dorsey Chief Special Master

5 Vaccine 28 (2010) 8049-8052

Contents lists available at ScienceDirect

Vaccine ELSEVIER jo u rnal homep a ge : www.e lsevier.com/l ocate/vacc ine

Short communication

Shoulder injury related to vaccine administration (SIRVA)* S. AtanasofP ·· , T. Ryan a, R. Lightfoot b, R.Johann-Liang a •US.Department of Health and Human Services. Health Resources and Services Administration. National Vaccine Injury Compensation Program, United States bThe Division of Rheumatology and Women's Health, University of Kentucky School of Medicine, United States

ART I C L E I N FO ABSTRACT

Article history: Shoulder pain is a common transient side-effect of vaccination. Infrequently, patients can develop pro- Received 30 July 2010 longed shoulder pain and dysfunction following vaccination. A series of 13 cases are described in which Received in revised form 1 October 2010 persistent shoulder dysfunction and pain developed following immunization. Common clinical char- Accepted 3 October 2010 acteristics include absence of a history of prior shoulder dysfunction, previous exposure to vaccine Available online 16 October 2010 administered, rapid onset of pain, and limited range of motion. The proposed mechanism of injury is the unintentional injection of antigenic material into synovial tissues resulting in an immune-mediated Keywords: Vaccination inflammatory reaction. Careful consideration should be given to appropriate injection techn ique when Shoulder pain administering intramuscular vaccinations to reduce the risk of shoulder injury. Immune-mediated inflammatory reaction Published by Elsevier Ltd. Bursitis Tendonitis

1. Introduction findings in patients with shoulder pain related to vaccine adminis- tration and offers considerations for reducing the risk of shoulder The Vaccine Injury Compensation Program (VICP) was created injury related to vaccine administration. in 1988 to ensure an adequate supply of vaccines, stabilize vaccine costs, and establish and maintain an accessible and efficient forum 2. Materials and methods for individuals found to be injured by certain vaccines. The VICP is a no-fau lt a lternative to the traditional tort system for resolving The Vaccine Injury Compensation Program houses an adminis- vaccine injury claims and provides compensation to people found trative database containing information on recent claims submitted to be injured by specific covered vaccines [ 1). At its inception, the to the Program. A query of t he database was conducted to identify vast majority ofVICP cases involved evaluation of possible vaccine- potentially relevant cases based on a claimed injury of "shoul- related injuries in children. In recent years. however, the program's der pain," "arm pain", "shoulder dysfunction", "frozen shoulder". demographics have shifted d ramatically with more than 50% of "adhesive capsulitis", or "shoulder bursitis". "Brachia I neuritis" was submitted cases now involving adults (2). a lso included since this injury is frequently claimed when the arm Thousands of vaccinations are administered to child ren, adoles- is involved rega rdless of the actual diagnosis. Case histories of all cents and adults every day in the United States with transient pain submitted medical records were reviewed in detail to ve rify vacci- at the vaccine injection site recognized as one of the more com- nation date, symptom onset and clinical course. monly seen side-effects of vaccination [3 ). The experience at VICP Cases consistent with a diagnosis ofbrachial neuritis or complex suggests that vaccination may infrequently cause more severe, per- regional pain syndrome were excluded, as were cases of superficial sistent shoulder pain with prolonged restriction of function. This localized soft tissue swelling with pain and/or superficial scarring. report summarizes a series of cases in which persistent shoulder Two cases claiming arm pain were excluded because the onset of pain following vaccination was felt to be related to administra- a rm pai n was reported many months following vaccination and tion of the vaccine, proposes a mechanism by which such injuries records lacked sufficient documentation to ve rify any association may occur, identifies common historical and physical examination between the onset of symptoms and vaccination. Following the review, 13 potential cases submitted between 2006 and 2010 we re identified for inclusion in this report. * Several of the authors are employees of the United States Department of Health A literature search was conducted using PubMed and search and Human Services. The positions expressed and recommendations made in this paper do not necessarily represent those of the United States Government ter ms of "vaccination," with "shoulder," "shoulder dysfunction," * Corresponding author. Tel.: +1 301 443 2377; fax: +1 301 443 5443. "arm pain," "needle length," and "BMI." The literature search was E-mail addresses: satanasoff@hrsa.gov. tryan@hrsa.gov (S. Atanasoff). limited to publications in English.

0264-41 OX/$ - see front matter. Published by Elsevier Ltd. doi: 10.1016/j.vaccine2010.10.005

Court Exhibit I, p.1 8050 S. Atanasoff et al. / Vaccine 28 (2010) 8049–8052

Table 1 Clinical Characteristics of n = 13 patients with shoulder injury related to vaccination.

Demographics: gender 11 Female (85%) 2 Male (15%) Demographics: age Mean age: 50 years Age range: 26–83 Body habitus BMI mean: 27.2 BMI range: 19.4–41.3 Overweight/Obese 8 (62%) Vaccine 8 Influenza (62%) 2 Td (15%) 2 Tdap (15%) 1 HPV (8%) Repeat or sequential vaccination Confirmed: 11 (85%) Unconfirmed: 2 (15%) Onset of pain Immediate: 7 (54%) Within 24 h: 5 (39%) Within 4 days: 1 (8%) Comment in records Vaccine injection “too high”: 6 (46%) Signs and symptoms Shoulder pain (100%) Limited ROM 11 (85%) Altered sensation 4 (31%) Weakness 4 (31%) Local injection site reactions (0%) reduced deep tendon reflexes (0%) Diagnostic tests MRI MRI performed 9 (69%) Fluid collections in deep deltoid/overlying tendons, fluid in bursa, tendonitis, tears X-ray X-ray performed 7 (54%) No diagnostic benefit EMG/NCV EMG/NCV 5 (39%) No indication of neurological disorder such as brachial neuritis Surgical exploration Surgical exploration 1 (8%): path of vaccine administration replicated by inserting a needle into the deltoid, area contained an inflamed and scarred bursa/thickened tissue around a damaged tendon. Treatment NSAIDs: 8 (62%) Steroid injection: 8 (62%) Physical therapy: 6 (46%) Surgery: 4 (31%) Clinical course Full recovery: 4 (31%) Residual symptoms 9 (69%)

3. Results rotator cuff tendon was noted. Sixty-three percent of the MRIs per- formed in our case series were conducted within three months of In the course of reviewing claims submitted from 2006 through the date of symptom onset and half were performed within six 2010, the VICP identified 13 claims in which it appeared that weeks of symptom onset. Routine X-rays of the shoulder were vaccine administration led to significant shoulder pain and dys- performed less frequently and did not provide helpful diagnostic function. The demographic and clinical characteristics of these 13 information among patients in this series. cases are shown in Table 1. All individuals in this case series were adults, 85% were women, and, with one exception, all received 3.3. Clinical course either influenza vaccine or a tetanus-containing vaccine prior to the onset of symptoms. The mean body mass index (BMI) of patients in The severity and duration of shoulder dysfunction varied among the case series was 27.2 (range 19.4–41.3). patients in this case series. More than half of the patients required A history of prior immunization with the same vaccine was at least one injection of a corticosteroid over time. Surgical inter- confirmed in 85% of the cases. Among patients in whom a his- vention was performed in 31% of cases with half of those cases tory of previous vaccination was confirmed, the interval between requiring a second surgical intervention. Review of the available vaccinations was no less than 10 years for those receiving tetanus- records showed that shoulder symptoms persisted among our cases containing vaccines and no less than 11 months for influenza from six months to many years. All patients had symptoms for vaccine. One patient developed shoulder symptoms following at least six months. Less than one third of patients had complete administration of the third of a three dose series of human papil- recovery while the majority of patients in this series had continu- lomavirus (HPV) vaccine which was administered three months ing symptoms including persistent pain, limited range of motion, following the second HPV vaccination. and pain on range of motion at last follow-up.

3.1. History and physical examination 4. Discussion

Shoulder pain was present in all patients. Onset of pain was Bodor and Montalvo [4] reported two cases of shoulder pain, reported as occurring less than 24 h after vaccination in 93% and weakness, and reduced range of motion following vaccination with occurred immediately following injection in 54% of our cases. the onset of symptoms in both cases occurring two days after vacci- Forty-six percent of the patients voiced concerns regarding vaccine nation. Both patients had shoulder dysfunction and pain involving administration, specifically that the vaccination had been admin- multiple structures of the shoulder with reduced range of shoulder istered “too high” in the deltoid. The most common findings on motion. One patient developed adhesive capsulitis. Both required examination were limited and painful range of motion. Skin and multiple steroid injections in locations including the subacromial local injection site reactions were not reported and sensory symp- bursa, bicipital tendon sheath and glenohumeral joint to reach com- toms such as tingling and numbness in the affected extremity were plete resolution of pain. Using ultrasound the authors investigated uncommon. Weakness was not a common finding in any of the the location and depth of the subdeltoid bursa in their two patients cases during the initial examination and when found was attributed and in 21 healthy controls. They found that the bursa extended to pain. Deep tendon reflexes, when tested, were noted to be nor- from 3.0 to 6.0 cm (1.18–2.36 in.) beyond the lateral border of the mal. acromion and that it lay anywhere from 0.8 to 1.6 cm (0.31–0.62 in.) below the skin surface; depths easily reached by the 1 in. needle 3.2. Diagnostic evaluation used in both patients. The authors hypothesized that the vaccine was injected into the subdeltoid bursa in both of their patients caus- Among the 39% of patients who underwent electrodiagnostic ing a robust local inflammatory and immune response. They further studies, none had findings suggestive of a neurological disorder hypothesized that since the subdeltoid1 bursa is contiguous with such as brachial neuritis. When performed, MRI findings varied but the subacromial bursa, this led to bursitis, tendonitis, and inflam- included fluid collections in the deep deltoid or overlying the rota- mation of the shoulder capsule. We found no other case reports tor cuff tendons (39%), bursitis, fluid “greater than typically seen” within the bursa, tendonitis, rotator cuff tears, and, in one patient, subchondral changes in the humerus with overlying severe ten- 1 For consistency and to reduce confusion, we will use the term “subacromial donitis and fluid accumulation. A complete rotator cuff tear was bursa” to refer to both the subdeltoid bursa and subacromial bursa in the remainder found in 15% of cases and, in one case, associated atrophy of the of the paper.

Court Exhibit I, p.2 S. Atanasoff et al. / Vaccine 28 (2010) 8049–8052 8051

ACROMION exist between vaccine administration and shoulder dysfunction in some cases [12]. The clinical details of the patients in this series SUBACROM IAL together with the published research literature on this subject meet BURSA SPACE many of Hill’s suggested criteria for a causal relationship including specificity, temporal association, biological plausibility, coherence, DELTOID MUSCLE and experimental evidence. Of the patients in our series, none had a history of symptomatic shoulder problems prior to vacci- nation. They all received a vaccine to which they had previously been exposed. They all experienced the rapid onset of shoulder pain (range: immediate to four days) following vaccination. They all developed shoulder symptoms limited to the vaccinated shoul- der. They all had symptoms and physical findings consistent with a local immune-mediated inflammatory musculoskeletal shoulder ~SCAPULA injury. One of our cases provided additional evidence to support vac- (SHOULDER BLADE) cine administration as a causal element in this type of injury. In this case, surgeons replicated the path of vaccine administration SHOULDER JOINT SPACE by inserting a needle into the deltoid area at the location identified by the patient as the injection site during reparative arthroscopic BICEPS TENDON shoulder surgery. The path of the needle led through an area con- GROOVE taining an inflamed and scarred bursa and thickened tissue around Fig. 1. Anatomy of the shoulder girdle. The relationships of the subdel- a damaged tendon. Beneath the tendon the needle came into con- toid/subacromial bursa and shoulder joint space to the supraspinatus tendon and tact with abnormally friable bone on the greater tuberosity of the to the greater tuberosity on which it inserts. humerus that gave way with pressure from the needle. We believe it is likely that this patient as well as the other patients in our series or epidemiologic studies regarding shoulder dysfunction resulting developed shoulder pain and dysfunction through the mechanism from vaccination. proposed by Bodor and demonstrated experimentally by Dumonde. There have been several larger studies which utilized body Although shoulder dysfunction due to mechanical or overuse weight, gender, and/or body mass index (BMI) together with ultra- injury is always a diagnostic consideration, the rapid onset of pain sound evaluation of deltoid fat pad and skin fold thickness to with limited range of motion following vaccination in our series determine the appropriate needle length for intramuscular injec- of patients is consistent with a robust and prolonged immune tion in different patient groups [5–7]. In one of the few studies response within already-sensitized shoulder structures following addressing the risk of injecting into shoulder tissues underlying injection of antigenic substance into the subacromial bursa or the the deltoid muscle, Lippert and Wall [8] assessed the risk of over- area around the rotator cuff tendon. We believe that this type of penetration through the deltoid muscle in children ages 3–18 using phenomenon is not due to a specific vaccine but results from injec- the needle lengths recommended by the Centers for Disease Con- tion of a vaccine antigen to which a person has previously been trol. They reported a risk of over-penetration ranging from 11 to 61% sensitized as a result of previous naturally occurring infection or when using the needle lengths recommended for each age group. past vaccination. This concept is consistent with the vaccines which We found no publications regarding the risk of over-penetration were given in this case series, namely influenza and tetanus vac- due to needle length in an adult population. However, considering cines which are given repeatedly over time and HPV vaccine which the ultrasound measurement findings by Bodor and Montalvo, it is is given as a series of injections. We confirmed that almost all of conceivable that a needle length of one inch or greater could reach our cases had received at least one dose of the same vaccine in the bursa or other tissues in some patients, particularly adults with the past. The two cases for which prior vaccination could not be a lower BMI (Fig. 1). confirmed by the medical records included one case of influenza The act of inserting a needle or injecting a non-antigenic sub- vaccine administration and one case involving administration of a stance into the deltoid muscle would not be expected to cause tetanus-containing vaccine. It is likely that an adult patient would an immune-mediated inflammatory response. Even when an indi- have received a prior tetanus-containing vaccination at some point vidual is vaccinated in the deltoid muscle with a previously in their lifetime. Although it is possible that an adult may receive a administered vaccine any local injection site reaction caused by first-time influenza vaccine, it is unlikely that an adult would not vaccine antigen–antibody interaction is expected to be relatively have had exposure to influenza virus or an influenza infection in the brief and resolve as the antigen is cleared from the soft tissues past. The immune response to both vaccines and infections wanes over a period of several days. If, however, a vaccine is inadver- over time and may explain some of the variation in severity and tently injected into the synovial space of the shoulder (bursa or duration of symptoms in our case series. joint), pre-existing antibody in the synovial tissues, present as a In general, chronic shoulder pain with or without reduced shoul- result of earlier naturally occurring infection or vaccination, may der joint function can be caused by a number of common conditions lead to a more prolonged inflammatory response [9,10]. A study including impingement syndrome, rotator cuff tear, biceps ten- by Dumonde using rabbits demonstrated that antigen injected into donitis, osteoarthritis and adhesive capsulitis [13]. In many cases, the synovial space was bound to existing antibody in the connec- these conditions may cause no symptoms until provoked by trauma tive tissues of the joint leading to formation of antigen–antibody or other events. Reilly et al. [14] reviewed a series of shoulder complexes and acute inflammation which lasted for six weeks [11]. ultrasound and MRI studies obtained in asymptomatic persons past We took these publications into consideration as we ana- middle age and found partial or complete rotator cuff tears in 39% of lyzed our case series to determine whether the injuries could be those individuals. Therefore, some of the MRI findings in our case caused by vaccine administration. Since it is usually not possi- series, such as rotator cuff tears, may have been present prior to ble to attribute causation from a case series, we took Sir Austin vaccination and became symptomatic as a result of vaccination- Bradford Hill’s proposed set of nine criteria or “viewpoints” into associated synovial inflammation. Other findings such as fluid consideration in determining whether a causal relationship might collections, localized tendon inflammation, and bursitis are more

Court Exhibit I, p.3 8052 S. Atanasoff et al. / Vaccine 28 (2010) 8049–8052

consistent with the vaccine needle over-penetration mechanism toid muscle due to inappropriate needle length and/or injection proposed here. technique [4–8]. The research literature supports the potential for The fact that six patients in our case series reported vaccine inducing a prolonged immune-mediated inflammatory reaction if administration “too high” in the shoulder indicates that in some of a vaccine antigen is injected into synovial tissue structures under- our cases the injury may have been the result of improper injection lying the deltoid muscle [9–11]. technique. Given that 62% of our cases were overweight or obese Our clinical case series provides additional evidence supporting based upon BMI and that no case was considered underweight, the report by Bodor and Montalvo [4] that vaccine administra- needle length alone may not have been the cause of injection into tion in the upper third of the deltoid area can have long-lasting tissues other than the deltoid. Bodor’s ultrasound findings revealed consequences unrelated to the specific vaccine administered. Com- that the subacromial bursa can extend over 2.36 in. laterally from monalities of history and physical examination among patients in the acromion in some cases. Therefore, we agree with Bodor that our case series may be helpful in identifying patients who may have avoiding the top third of the deltoid would help to reduce the risk of developed shoulder pain and dysfunction as a result of inadver- penetrating the bursa. In addition, while patients are often seated tent vaccination into the bursa or other tissues beneath the deltoid for vaccinations, the standing position of the provider adminis- muscle. tering the injection may also contribute to injecting inadvertently Soft tissue atrophy including tendon atrophy or rupture is a rec- high into the deltoid. A seated patient may help to reduce the risk ognized side effect of corticosteroid injection. In situations where of injury during a syncopal episode, but an awareness of proper recent vaccination is suspected as a possible cause of shoulder injection technique on the part of the vaccine administrator should pain we suggest consideration of non-invasive imaging such as also be emphasized. Thus, concurrent seating positions for both the MRI or high resolution musculoskeletal ultrasonography, prior to administrator and the receiver may minimize the risk of the injec- steroid injection to define any pre-existing anatomic abnormal- tion being “too high”. Additional considerations for possible future ities. Non-invasive imaging might assume greater importance if study would include the benefit of abducting the arm a few degrees symptoms persist and additional steroid injections are being con- laterally so that the bulk of the bursa is protected by the acromion sidered. process and possibly exploring alternate injection sites in patients The risk of vaccine administration-related shoulder injury may with little shoulder muscle mass. be reduced by giving careful consideration to appropriate needle There is a notable absence of children in our case series despite length based on individual patient characteristics such as gender the fact that they have exposure to a broad range of vaccine antigens and body mass index. Care should be taken to insure that the in the first decade of life. A number of factors may explain their lack needle is not inserted into the upper third of the deltoid mus- of representation in this case series. The thigh is the preferred site cle. of vaccination in toddlers and infants thus eliminating the risk of shoulder injury in this group. In older children and adolescents, the References subacromial bursa may not be as developed or as extensive as those in adults. Vaccine administration in older children may more com- [1] For more information on the VICP go to http://www.hrsa.gov/ Vaccinecompensation/. monly include techniques such as “bunching” of the subcutaneous [2] Johann-Liang R. Institute of medicine project review of adverse events, and deltoid tissue prior to vaccination thus increasing the distance http://www.hrsa.gov/vaccinecompensation/Docs/Transcript -ACCV-6-5- between the skin and subacromial bursa. Children, as a group, have 09.pdf, p. 82–94 [accessed 07.12.10]. [3] Possible side-effects from vaccines, http://www.cdc.gov/vaccines/vac-gen/ a much lower likelihood of pre-existing asymptomatic shoulder side-effects.htm [accessed 7.12.10]. injuries which might be aggravated as a result of an inflammatory [4] Bodor M, Montalvo E. Vaccination-related shoulder dysfunction. Vaccine reaction related to vaccination. Finally, annual influenza vaccina- 2006;25(4):585–7. [5] Poland GA, Borrud A, Jacobson RM, McDermott K. Determination of deltoid fat tion, the most common vaccine associated with shoulder injury pad thickness: implications for needle length in adult immunizations. JAMA in this series, may have been more selectively encouraged for chil- 1997;277(21):1709–11. dren at higher risk for influenza-related complications in past years [6] Cook IF, Williamson M, Pond D. Definition of needle length required for intra- thus reducing the possibility of vaccine-related shoulder injury in muscular deltoid injection in elderly adults: an ultrasonographic study. Vaccine 2006;24(7):937–40. children by chance alone. [7] Koster MP, Stellato N, Kohn N, Rubin LG. Needle length for immu- Our study is limited by the absence of a control group to allow nization of early adolescents as determined by ultrasound. Pediatrics comparison of outcomes. Additionally, patients submitting peti- 2009;124(2):667–72. [8] Lippert WC, Wall EJ. Optimal intramuscular needle-penetration depth. Pedi- tions to the Vaccine Injury Compensation Program may not be atrics 2008;122(30):e556–563. representative of the general public, leading to the possibility of [9] Cooke TD, Jasin HE. The pathogenesis of chronic inflammation in experimental a reporting bias similar to that which might be seen with the Vac- antigen-induced arthritis. I. The role of antigen on the local immune response. Arthritis Rheum 1972;15(4):327. cine Adverse Event Reporting System (VAERS) [15]. The strength [10] Cooke TD, Hurd ER, Ziff M, Jasin HE. The pathogenesis of chronic inflamma- of our case series is that the medical records in VICP petitions are tion in experimental antigen-induced arthritis. II. Preferential localization of typically voluminous and comprehensive, allowing detailed analy- antigen-antibody complexes to collagenous tissues. J Exp Med 1972;135(2): 323. sis of each case. Thus, although there is no specific diagnostic test [11] Dumonde DC, Glynn LE. The production of arthritis in rabbits by an immuno- for shoulder dysfunction due to vaccine needle over-penetration, logical reaction to fibrin. Brit J Exp Pathol 1962;43:373. we are able to describe clinical qualifications and aids to diagnosis [12] Hill AB. The environment and disease: association or causation? Proc R Soc Med 1965;58:295–300. for this entity allowing identification of possible cases of shoulder [13] Woodward T, Best T. The painful shoulder. Part II. Acute and chronic disorders. injury related to vaccine administration (SIRVA). Am Fam Physician 2000;61:3000–291. [14] Reilly P, Macleod I, Macfarlane R, Windley J, Emery RJ. Dead men and radiolo- gists don’t lie: a review of cadaveric and radiological studies of rotator cuff tear 5. Conclusions prevalence. Ann R Coll Surg Engl 2006;88(2):116–21. [15] The Main Limitations of VAERS Data. About the VAERS Program, http://vaers. The medical literature supports the possibility that a vaccine hhs.gov/about/index [accessed 7.12.10]. can be unintentionally injected into structures underlying the del-

Court Exhibit I, p.4