Keywords
bursitis - impingement, shoulder - shoulder pain - influenza vaccines
Introduction
Shoulder pain is a common finding in the primary care setting, and the prevalence
in United States has been reported from 6.7% to 26%.[1]
[2] After the establishment of the Vaccine Adverse Event Reporting System in 1990, accounts
of prolonged shoulder symptoms after vaccinations have been documented.[3]
[4] The Injection-Related Work Group of the U.S. Department of Health and Human Services
Health Resources and Services Administration Centers for Disease Control published
the 2011 Institute of Medicine Report, which generated “Proposals for Updates to the
Vaccine Injury Table.” This report suggests Shoulder Injury Related to Vaccination
Administration (SIRVA) applies when the vaccine recipient had a shoulder without prior
pain or dysfunction, and subsequently within 48 hours of vaccination had shoulder
pain with limited range of motion.[5]
SIRVA represents a complex series of reported injuries, onset of symptoms, treatments
and outcomes, and SIRVA was added to the Vaccine Injury Compensation Table published
by the Health Resources and Services Administration.[6] The structures reportedly involved have included the rotator cuff, labrum, capsule,
bursa, deltoid muscle, and this included diagnoses of bursitis, rotator cuff tears,
adhesive capsulitis, chondral injury, nerve injury and infection.[7]
[8]
[9]
[10]
[11]
[12]
[13]
[14]
[15]
[16]
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[22]
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[25]
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[31]
[32]
[33] The most common mechanism proposed is overpenetration of the deltoid muscle leading
to injury either from a mechanical injury and/or from an immune response to the vaccine
and/or adjuvants, and these events have frequently been correlated with an incorrect
injection technique.[7]
[8]
[9]
[10]
[11]
[12]
[13]
[14]
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[16]
[17]
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[21]
[22]
[23]
[24]
[25]
[26]
[27]
[28]
[29]
[30]
[31]
[32]
[33] Thus, the primary outcome of this review was to identify unique features of SIRVA
and the clinical results. The secondary outcome was to evaluated the etiology of the
proposed injury mechanism with regard to the most commonly suggested reasons for a
SIRVA (needle length, vaccination technique and autoimmune response).[7]
[8]
[9]
[10]
[11]
[12]
[13]
[14]
[15]
[16]
[17]
[18]
[19]
[20]
[21]
[22]
[23]
[24]
[25]
[26]
[27]
[28]
[29]
[30]
[31]
[32]
[33] We hypothesize that unique diagnostic findings will be identified and generalizable
clinical results will be demonstrated, and we further hypothesize that a critical
analysis of the factors associated with the proposed mechanism will provide guidance
for avoiding additional shoulder injuries.
Methods
A systematic review of PubMed and Ovid MEDLINE was performed on February 1, 2020.
The search terms “shoulder” and “vaccination” in were utilized in combination. Search
results were completed according to the Preferred Reporting Items for Systematic Reviews
and Meta-Analyses guidelines[34] (PRISMA), and a PRISMA checklist was employed for analysis of the search results.
In addition, a search of all citations present in the articles was performed. Level
I to V studies published in English were considered under the inclusion criteria,[35] and any clinical outcomes including but not limited to pain, reduced range of motion,
infection, tendon injury and chondral injury diagnoses. Exclusion criteria included
biomechanical studies, non-human related publications, non-English publications, review
articles without new cases reported or tumor events following vaccination.[36]
Results
Seventy-five unique studies were identified ([Fig. 1]). After selecting for studies that included shoulder vaccination in humans, forty-four
remained. Excluding papers that were not written in English left thirty-nine. Selecting
out cadaveric, biomechanical, incomplete, or studies without clinical data excluded
an additional twelve publications. The remaining twenty-seven studies were closely
examined and reviewed.
Fig. 1 Demonstration of Systematic Review Progression.
A total of 56 reported accounts of shoulder pain, injury or infection were identified
following a reported vaccination event. Data demonstrating vaccination type, time
to onset of symptoms, time to presentation, and age are demonstrated in [Table 1]. The age range was 21 months to 90 years old. The most common type of vaccination
reported was Influenza representing 61% of the cases (34/56). The second most common
vaccination reported was the Pneumococcal Polyvalent Vaccination (PPV) representing
14% (8/56). The exact onset of symptoms was not reported in five cases, but 3 of those
cases presented within two weeks of vaccination. In the remaining 51 accounts, the
onset of pain was reported to have occurred in two days (48 hours) or less in 84%
of the cases (43/51). Time to clinical presentation was not reported in 38% (21/56)
of cases. In papers including clinical presentation time, time at clinical presentation
was three weeks or less for 63% (22/35). Clinical findings, treatments and reported
outcomes are demonstrated in [Table 2]. Clinical treatment methods were reported in all but two accounts. The two most
common treatment modalities were physical therapy 41% (22/54) and CSI 33% (18/54).
12 cases (22%) were treated with surgery. Follow up clinical results were not available
in 12 accounts (21%). In accounts reporting clinical outcomes, 30% (13/44) were reported
to have persistent symptoms beyond the follow up period. Nine of the 12 were part
of one case series in which the presentation time for treatment was not reported.[7] The remaining 70% (31/44) of reports were noted to have improved functions and/or
symptoms.
Table 1
AUTHOR
|
Onset Time
|
Presentation Time
|
N
|
Vaccination
|
Age
|
Barnes et al.
|
< 24 hours
|
3 weeks
|
1
|
Influenza
|
22
|
Shaikh et al.
|
< 1 week
|
1 month
|
1
|
Influenza
|
46
|
Messerschmitt et al.
|
< 24 hours
|
3 weeks
|
1
|
Influenza
|
46
|
Floyd et al.
|
< 24 hours
|
3 days
|
1
|
PPV
|
59
|
Kuether et al.
|
< 24 hours
|
4 weeks
|
1
|
Influenza
|
48
|
Terreri et al.
|
Unknown
|
1 week
|
1
|
BCG
|
21 months
|
Bodor et al.
|
2 days
|
5 months
2 months
|
2
|
PPV and Influenza
|
71 and 89
|
Cross et al.
|
< 24 hours
|
3 days
|
2
|
PPV and dTpa
|
82 and 23
|
Saleh et al.
|
< 24 hours
|
6 weeks
3 months
2 years
|
3
|
PPV and 2 Influenza
|
67, 30, 69
|
Hexter et al.
|
< 24 hours
|
Immediate
|
1
|
Influenza
|
50
|
Salmon et al.
|
< 24 hours
|
2 days
|
1
|
Revaxis®
|
26
|
Okur et al.
|
< 24 hours: 1/4
Unknown: 3/4
|
1-2 week: 3/4
2 months: 1/4
|
4
|
All Influenza
|
66, 59, 39, 36
|
Cook et al.
|
< 24 hours
|
3 days
|
1
|
Influenza
|
76
|
Arias et al.
|
< 24 hours: 3/8
< 1 week: 3/8
1-2 months: 2/8
|
Unknown
|
8
|
6/8 Influenza
1/8 PPV
1/8 Diptheria, Tetanus toxoid
|
22–89
|
Anasoff et al.
|
< 24 hours: 12/13
4 days: 1/13
|
Unknown
|
13
|
8 Influenza, 2 Td, 2 Tdap, 1 HPV
|
22–83
|
Degreef I and Debeer P
|
< 24 hours: 2/3
< 1 week: 1/3
|
2 months 2/3
6 months 1/3
|
3
|
Hep A, Influenza, Tetatus
|
36, 54, 73
|
McColgan BP and Borschke FA
|
< 24 hours
|
< 24 hours
|
1
|
PPV
|
73
|
Bathia NA and Stitik T
|
< 24 hours
|
3 weeks
|
1
|
Influenza
|
34
|
Shafer B and Burroughs K
|
< 24 hours
|
3 weeks
|
1
|
Influenza
|
25
|
Uchida et al.
|
< 24 hours
|
3 weeks
|
1
|
HPV
|
45
|
DeRogatis et al.
|
< 24 hours
|
1 week
|
1
|
PPV
|
90
|
Jotwani et al.
|
< 24 hours
|
2 weeks
|
1
|
Influenza
|
61
|
Imran et al.
|
< 24 hours
|
Unknown
|
1
|
Influenza
|
73
|
Meirelles et al.
|
< 24 hours
|
1 day
|
1
|
Influenza, Diphtheria, Tetanus
|
67
|
Erickson et al.
|
Unknown
|
2 weeks
|
1
|
Influenza
|
51
|
Shahbaz et al.
|
< 24 hours
|
1 hour
|
1
|
Influenza
|
34
|
Macomb et al.
|
< 24 hours
|
< 24 hours
4 days
|
2
|
PPV, Zoster
|
69, 84
|
Table 2
AUTHOR
|
Findings
|
Treatment
|
Outcome
|
Barnes et al.
|
Shoulder pain, loss of ROM
|
PT
|
Improvement in pain at 11 weeks
Resolution of symptoms 16 months
|
Shaikh et al.
|
EMG – axonal denervation of deltoid and supraspinatus
|
Oral Prednisolone
|
Resolved pain but persistent “mild” weakness 8 months
|
Messerschmitt et al.
|
Shoulder Pain, loss of ROM, cartilage lesion
|
Surgery - hemiarthroplasty
|
Resolution of pain and symptoms at 3 years
|
Floyd et al.
|
Shoulder Pain, loss of ROM
|
Surgery – arthroscopic debridement
|
Resolution of pain and symptoms at 12 weeks
|
Kuether et al.
|
Shoulder Pain, osteonecrosis of humeral head
|
PT, Oral NSAIDs
|
Resolution of pain and symptoms at 6 months
|
Terreri et al.
|
Shoulder Pain, fever, osteitis
|
Antibiotics
|
Improved symptoms at 19 days after antibiotics
|
Bodor et al.
|
Shoulder Pain, loss of ROM, tendinitis
|
PT and CSI
|
Resolution of pain and symptoms at 5 and 6 months
|
Cross et al.
|
Shoulder Pain both, infection markers for one patient
|
1) Surgery – Debridement 2) PT and CSI
|
Resolution of pain and symptoms 1 month after surgery and 3 months after PT and CSI
|
Saleh et al.
|
All 3 Shoulder Pain and loss of ROM
|
PT 3/3
CSI 2/3
|
Resolution of pain and symptoms 50 days for one patient, unknown for second, no results
for 3rd patient
|
Hexter et al.
|
Shoulder Pain
|
Surgical Debridement
|
Resolution of pain and symptoms
|
Salmon et al.
|
Shoulder Pain and effusion
|
NSAIDs and CSI
|
Resolution of pain and symptoms at 5 months
|
Okur et al.
|
Shoulder Pain
|
NSAIDs 3/4
No treatment 1/4
|
Resolution of pain and symptoms at 5 months 33 days, 5.5 months, 2 years and 2.5 years
|
Cook et al.
|
Shoulder Pain
|
CSI
|
Resolution of pain and symptoms at 1 months
|
Arias et al.
|
Shoulder Pain
|
Unknown
|
Unknown
|
Anasoff et al.
|
Shoulder Pain: 13/13
Loss of ROM: 11/13
Weakness: 4/13
|
NSAIDS: 8/13
CSI: 8/13
PT: 6/13
Surgery: 4/13
|
Full Recovery 4/13
Residual Symptoms: 9/13
Symptoms for at least 6 months 13/13
|
Degreef I and Debeer P
|
All 3 Shoulder Pain and loss of ROM
|
CSI: 1/3
PT: 3/3
|
Resolution of pain and symptoms at 1 month 6 weeks and 3 months
|
McColgan BP and Borschke FA
|
Shoulder Pain and Swelling
|
c
|
Improvement at 2 weeks postop
|
Bathia NA and Stitik T
|
Shoulder pain
|
Unknown
|
Unknown
|
Shafer B and Burroughs K
|
Shoulder Pain and loss of ROM
|
Unknown
|
Unknown
|
Uchida et al.
|
Shoulder pain
|
Surgery – arthroscopic debridement
|
Resolution of pain and symptoms at 1 year postop
|
DeRogatis et al.
|
Shoulder pain and infection
|
Surgical Debridement
|
Improvement at 2 weeks postop
|
Jotwani et al.
|
Shoulder pain
|
CSI
|
Improvement but no time frame noted
|
Imran et al.
|
Shoulder pain and weakness
|
PT
|
ROM limitations at 6 weeks follow up
|
Meirelles et al
|
Shoulder pain and weakness
|
PT
|
Significant recovery at 1 year, return of sensation and function at 31 months
|
Erickson et al
|
Shoulder pain
|
PT and CSI
Surgical Debridement
|
Resolution of pain and symptoms at 1 year
|
Shahbaz et al.
|
Shoulder Pain and loss of ROM
|
PT and NSAIDs
|
8 month improvement with continued pain
|
Macomb et al.
|
Shoulder Pain and loss of ROM
|
NSAIDs, PT, CSI
|
Resolution of pain and symptoms at 1 month
|
Discussion
The collection of data regarding vaccine-related shoulder dysfunction is relatively
new with only 56 published reports. According to the Vaccine Injury Table,[6] the onset of symptoms needs to occur within 48 hours of the vaccination. This review
demonstrated that 84% of the published accounts, with time to onset reported, actually
met the 48 hours or less criteria, and this suggests a portion of the published literature
would not fall under the Vaccine Injury table description of a SIRVA. In addition,
the onset reporting symptoms was variable. Several of the presentations were reported
greater than three months from the vaccination event, with the longest reported presentation
event occurring 2 years later.[14]
[16]
[21]
[22]
[29] Multiple studies also referenced pathologies such as rotator cuff tears, and many
of the accounts were in people over the age of 60. Several studies have demonstrated
MRI findings such as rotator cuff tears may be found in asymptomatic individuals with
rates of 50% progression to symptomatic tears in an average of 2.8 years.[7]
[37]
[38]
[39] Thus delays in initial presentation compounded with the potential for other underlying
conditions does not allow for trend to be demonstrated, but the majority of studies
did conform to the less than 48 hour definition.
The most common physical exam findings were consistent with impingement and loss of
range of motion. Despite this, there was not one unique physical examination finding
for SIRVA. There was also no clear correlation between a type of vaccine and severity
of symptom presentation or duration. There was variability in the time before treatment
was initiated. These treatments included physical therapy, corticosteroid injections,
anti-inflammatory medications and/or surgical interventions, and patients who began
a physician directed treatment pathways within three weeks of pain demonstrated a
trend towards good to excellent outcomes. This was with the exception of patients
who sustained a nerve injury or patients who ultimately required surgery. In the nerve
injury patients, persistent symptoms were noted, and the surgical cases had a more
prolonged course. Though many of the cases treated surgically were also noted to make
an excellent recovery. Overall this demonstrates that there was not one particular
physical exam findings unique to SIRVA patients, but in patients who do not sustain
an neurologic injury, near or full recovery is the most common outcome. In addition,
patients who begin treatment within three weeks of symptoms onset had overall good
reported outcomes.
Imaging analysis with MRI did demonstrate a trend.[8]
[10]
[12]
[13]
[21]
[24]
[26]
[32] Salmon et al.[8] describes a MRI performed two days after the vaccination demonstrating a glenohumeral
effusion, subacromial bursitis, subdeltoid bursitis and subscapular bursitis. A subsequent
MRI 5 months later demonstrated regression of the joint effusion and decreased bursitis.
Kuether et al.[13] illustrated an initial MRI with minor effusions in the subacromial and subdeltoid
bursa. Subsequent MRIs at 4 months and 12 months demonstrated decreasing bursitis.
Barnes et al.[10] demonstrated an MRI 8 weeks after a vaccination with an effusion in the subacromial
bursa. Uchida et al.[26] also demonstrated an MRI with subacromial bursitis after a vaccination. Atanasoff
reviewed 13 cases when MRI findings were available, and 69% of MRIs demonstrated fluid
collections in the bursa or rotator cuff tendinitis. Thus, early MRI findings after
a SIRVA event correlated with inflammatory changes such as increased fluid, bursitis
and tendinitis, but MRIs taken months later may not be an accurate method of assessment.
As a secondary outcome of this review, the mechanism associated with SIRVA was evaluated.
This is suggested to involve an overpenetration of the deltoid muscle allowing for
a mechanical injury from the needle and/or an immune response from the injected material.
One possible cause is utilization of a long needle. The Centers for Disease Control
and Prevention guidelines recommend a 1-inch needle for patients in all but two categories.[40] The first is for females over 200 pounds and males over 260 pounds. In those settings,
a 1.5 inch needle is recommended. The second exception is for newborns, where 5/8th inch needle is recommended.[38] Poland et al.[41] evaluated deltoid fat pad thickness with ultrasound and suggested a 1 inch needle
for men but stratified the recommendation for women for 5/8ths inch needle for less
than 60 kg, a 1 inch needle for 60-90 kg and a 1.5 inch needle for over 90 kg. A similar
study was performed by Lippert et al.[42] using 250 imaging series but focused on overpenetration. This study suggested needle
overpenetration would have been experienced by 11% of patients with a 5/8th inch needle, 55% of patients with a 7/8th inch needle and 61% of patients with a 1 inch needle. They suggested a weight-based
scale that could possibly eliminate overpenetration rates with a 10% risk of under
penetration. Cook et al.[43] discussed the importance of understanding body mass index (BMI) demonstrating that
in all males and females with a BMI less than 35 a 25 mm long needle could be safely
utilized, but in females with a BMI greater than 35, a 32 mm needle would be required
for adequate penetration. Atanasoffa et al.[7] examined thirteen patients with persistent shoulder pain without a history of shoulder
injury and supported the possible correlation of a SIRVA event and needle size. Overall
these studies have demonstrated that a one size fits all approach is not appropriate,
and this has been supported by other authors analyzes.[44] Thus, it is conceivable that overpenetration is possible with lower weight, lower
BMI, longer needles or a combination of needle length and lower body weight/BMI, but
an appropriate needle length should significantly decrease the risk of overpenetration.
Vaccination technique is also commonly discussed with many of SIRVA cases reporting
the vaccination was placed “Too High” (less than 3 cm from the lateral edge of the
acromion).[7]
[8]
[12]
[14]
[15]
[19]
[20]
[26] One account attempted to measure the bursa of two patients demonstrating it to extend
3.5 cm from the acromion in a female patient and 4 cm in a male patient.[14] Beals et al.[45] examined the bursa of 17 cadaveric shoulders. They noted the average distance from
the anterolateral corner of the acromion to the posterior bursal curtain was 2.8 cm
and that the bursa margins were always 2 cm or more from the from the anterolateral
corner of the bursal acromial surface. Avoidance of the bursa can potentially be obtained
by a more distal placement of the injection. The national injection technique recommendations
suggest the injection should be placed 2-3 finger breadths (2 inches) below the acromion
and recommends “to avoid causing an injury, do not inject too high (near the acromion
process) or too low”,[46] but increasingly distal placement increases risk to the axillary nerve. Meirelles
et al.[30] in fact illustrated a case of a 67 year old male who underwent a vaccination and
experienced immediate pain and dysfunction. A nerve conduction study revealed axillary
nerve compromise and return of function was not until 31 months. Imran et al.[29] described a case of a 73 year old male with acute pain following a vaccination.
Physical examination and manual muscle testing demonstrated poor deltoid function,
and the authors suggested a direct injury to the axillary nerve as the cause. This
patient had follow up of 6 weeks demonstrating improvements in shoulder function but
continued range of motion deficits. Thus shoulder vaccinations with overpenetration
risks injury to the bursa with a superior location and risks injury to the axillary
nerve with an inferior location.
Finally, penetration of the vaccination needle past the deltoid muscle also risks
injection of the vaccine contents into the shoulder tissues. The capacity for an immune
response from the injection material has been proposed by several authors.[7]
[8]
[12]
[13] Dumonde and Glynn[47] demonstrated the capacity to cause an intraarticular reaction using an animal model.[48]
[49] Jasin[50] also utilized a rabbit model to examine the mechanism of trapping of immune complexes
in collagen tissues of joints and found the trapping depended on the presence of antibody
in the extra-vascular space and the diffusion of antigen or soluble complexes into
this space. Trollmo et al.[51] evaluated peripheral blood of six healthy adults before and 14 days after antigen
exposure. They demonstrated the influenza virus antigen induces a strong systemic
antibody response, but no significant systemic level difference was detected between
subjects injected in the intra-articular space when compared with a subcutaneous injection.
Several accounts of suspected inflammatory reaction have been reported in the literature.
Anasoff et al.[7] suggested that an injection into the subacromial space would have the potential
to cause a reaction. Salmon et al.[8] report on an event following a vaccination where an MRI demonstrated a bony reaction.
Kuether et al.[13] reported on a 48 year old woman who had demonstrated signs of osteonecrosis in the
humeral head in MRI scan immediately, at 4 months and at 12 months after a vaccination.
They state that a direct causal relationship cannot be confirmed but propose an immune
response to the injection as a possible cause of the osteonecrosis. Messerschmitt
et al.[12] discussed a 46 year old male with immediate shoulder pain following a vaccination.
The patient was ultimately taken for surgery, and the biopsies obtained demonstrated
inflammatory cells and granulation tissue.
Although the capacity to cause an immune response has been supported by animal data,
a definitive clinical study demonstrating a quantitative link between a vaccine antigen
and/or vaccine adjuvant and an immune mediate shoulder inflammation causing prolonged
clinical symptomatology is still lacking. This is supported by the statements at the
end of several of the SIRVA accounts. Kuether et al.[13] stated multiple times that a causal link could not be drawn. Messerschmitt et al.[12] suggested that they were uncertain if the chondrolytic changes predated the event.
Uchida et at.[26] go further and stated that the consequences of improper injection technique are
not currently known and the biopsy samples they obtained seven months after the vaccination
cannot provide conclusive evidence. Furthermore, the diagnoses, duration and treatment
following the cases reported in this review are heterogenous as were the types of
vaccines which were reported. Thus, quantitative support for an immune response was
not found in reported cases.
Conclusion
Overall this review demonstrated that in patients who do not sustain an neurologic
injury, near or full recovery is the most common outcome. No unique physical exam
feature was identified, but early MRI utilization may assist by demonstrating an increased
fluid signal and bursitis. Because of the heterogenous treatments utilized, treatments
such as physical therapy, CSIs, NSAIDs or surgery cannot be recommended cannot be
individually recommended. Instead, a recommendation for treating the resulting pathology
based on evidence based guidelines for the appropriate diagnoses would be appropriate.
As patients who presented for treatment within three weeks of symptoms onset had overall
good reported outcomes, a recommendation can be made that all patients who experience
shoulder pain for greater than 14 days after a vaccination injection should seek immediate
medical evaluation. In regards to needle length, a weight/BMI based scale should be
utilized, and vaccination techniques must balance the need to avoid superior locations
while minimizing axillary nerve risk. Finally it is still unclear as to whether or
not shoulder injury related to vaccine administration “SIRVA” is a unique event. It
would seem for SIRVA to remain a descriptive term these events would have to be unique
to vaccinations and not simply an event that could happen with any over penetrated
injected material. Thus more data is needed to separate out a mechanical injury from
an immune response.