The influenza vaccine is increasingly available to the general public and mandated by many employers in the United States. The prevalence of post-vaccination complications is likely on the rise. Complications are well known to general clinicians, but are under-reported in the imaging literature. We present four cases of post-vaccination shoulder pain with magnetic resonance imaging (MRI) findings. An intrasubstance fluid-like signal in deep muscular and/or tendinous structures was the most common finding on MRI of these four cases. Focal bone marrow signal within the humeral head and inflammatory changes in the subacromial/subdeltoid bursa were also observed. The most likely reason for a humeral intraosseous edema-like signal was presumed injection of vaccine substance directly into osseous structures that might lead to focal osteitis. In the published literature, there is little emphasis on the imaging of local injection site complications accompanying influenza vaccination. We intended to increase familiarity of MRI findings in the setting of prolonged or severe clinical symptoms following influenza vaccination through the imaging findings of these four cases.
Widespread availability of the influenza vaccination to the general public and increasing employer mandates have increased the number of people receiving the flu vaccine. Complications such as prolonged and severe shoulder pain are rare but are likely to become more prevalent. Requests for advanced imaging of potential vaccination-related complications are also likely to increase. Since most complications of influenza vaccination are self-limited and do not require imaging, radiologists may be less likely to consider the relationship between local vaccination and abnormalities on MR imaging. Recognizing and correctly interpreting the imaging findings related to post-vaccination complications by radiologists are essential to efficient clinical management and care of the patient.
This paper presents advanced imaging results of four cases with shoulder complaints after flu vaccine injection. Following IRB approval, the Picture Archival System and electronic medical records were reviewed for pertinent radiographic and MR imaging data, clinical presentation and outcome, and laboratory summary. The following information was retrieved:
A 66-year-old female with no past medical history was evaluated for left arm pain exacerbated by motion that began immediately after receiving the flu vaccination. Symptoms included cool, numb, heavy sensation in her left hand, with radiation down the arm, neck, and scapular region. Despite intense clinical presentation, physical examination was normal.
ESR was mildly increased at 43 mm/hr (range of normal, 0-30 mm/hr). BMI was recorded as 25.7 kg/m2 (range of normal, 18.5 and 24.9 kg/m2) and CBC was normal.
Nine days after presentation, left upper extremity venous duplex ultrasound and MRI cervical spine excluded venous thrombosis and radiculopathy. Degenerative changes were noted on cervical spine MR images.
Figure 1 demonstrates fluid within subacromial/subdeltoid bursa and physiologic glenohumeral joint fluid. Bone marrow signal on MRI was normal. Incidentally noted were low-grade undersurface tears in the posterior margin supraspinatus and anterior margin infraspinatus tendons. The measurement of subcutaneous fat thickness was noted to be 6.6 mm on oblique coronal T1-weighted MR images.
No medical or surgical intervention was initiated. A follow-up exam revealed a normal musculoskeletal exam. The patient had another normal musculoskeletal exam 2.5 years after the event.
A 59-year-old female was examined for complaints of worsening left upper arm and neck pain 1 week following influenza vaccination. On physical examination, there was tenderness and a palpable 3 cm × 3-cm non-fluctuant soft tissue mass at the injection site within the left upper extremity. Otherwise, the musculoskeletal exam was non-contributory. CBC and ESR were normal on laboratory assessment. BMI was recorded as 37.2 kg/m2. MRI of the shoulder was performed 20 days after vaccine injection.
Figure 2 demonstrates minimal increased T2-weighted signal in left deltoid muscle and subcutaneous fat tissue, which might suggest focal inflammatory changes. There was no evidence of a dominant mass or abscess/hematoma on MR images. Neither bone marrow signal changes nor bursitis were found. The subcutaneous fat thickness was 2.1 cm measured on the oblique coronal T1-weighted MR images.
The patient was treated conservatively with non-steroidal anti-inflammatory drugs and demonstrated complete resolution of symptoms at 33 days post-vaccination.
A 39-year-old male presented with prolonged, increasing left shoulder pain for 2 months following flu vaccination. Physical examination was normal. On laboratory assessment, leukopenia was noted on CBC (3–4,700 on serial tests for 4 months with normal range 4–10,000 per microliter) without defined source, although counts were otherwise normal. ESR was normal. BMI was recorded as 25.7 kg/m2.
Figure 3 demonstrates findings on MRI of the shoulder, performed at 3 months following vaccination. Focal subcortical bone marrow edema-like signal within the greater tuberosity was observed, without associated obvious cortical destruction. There were periosseous soft tissue inflammatory changes and small subacromial/subdeltoid bursal fluid. The subcutaneous fat thickness was measured to be 4.7 mm on oblique coronal T1-weighted sequences.
The patient was treated conservatively with non-steroidal anti-inflammatory agents for 2 weeks and had complete resolution of symptoms after 5.5 months of observation.
A 36-year-old male presented with complaints of severe pain localized to the injection site following flu vaccination. There was a subjective decrease in range of motion due to pain. Physical examination was otherwise normal. A normal CBC with ESR was noted. BMI was recorded as 22 kg/m2.
Findings on the shoulder MR exam completed 1 week after vaccination are shown in Fig. 4. Subcortical bone marrow edema involving the greater tuberosity (without associated cortical destruction), periosseous inflammatory changes, and small fluid within the subdeltoid bursa are present. No dominant mass lesion, hematoma, or abscess was present. Subcutaneous fat thickness at the proposed site of injection was measured to be 4.2 mm on oblique coronal T1-weighted sequence.
Conservative treatment with short-term non-steroidal anti-inflammatory agents was initiated with complete resolution of symptoms within 2 months, and normal clinical exam at 2-year follow-up.
The MR findings of all four patients are shown in Table 1. Small fluid within subacromial/subdeltoid bursa was found in three of the four patients. Intrasubstance edema-like signal in deltoid muscle was also a common finding on MR images. Two of the four patients demonstrated focal bone marrow edema-like signal changes within the humeral head. Important clinical data obtained by the electronic charts are summarized in Table 2, including BMI, onset of pain, and physical exam findings. Table 3 shows clinical management and time to clinical resolution. Similarities between presentations of the four patients in Tables 2 and 3 include a non-contributory past medical history, no systemic symptoms or inflammatory changes on physical exam. BMI was low in three of the four cases presentations. Laboratory testing did not support any infectious etiology. None of the four patients were actively anti-coagulated.
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” . According to this report, “Shoulder injury related to vaccination administration” is applied if the recipient had shoulder pain with limited range of motion within 48 h after vaccine and had no prior history of pain, inflammation, or dysfunction of the affected shoulder prior to vaccine administration. A causal relationship between vaccine administration and deltoid bursitis has been formally established. It has been reported that unintentional injection of vaccine antigen into subacromial/subdeltoid bursa can trigger an inflammatory reaction. “Shoulder injury related to vaccination administration” has been detailed in Atanasoff et al.’s paper recounting persistent and severe shoulder pain in a series of 13 patients, which is the only series related to shoulder injury following vaccination in medical literature . As mentioned in the 2011 Institute of Medicine Report, Atanasoff et al. implied that “shoulder injury related to vaccination administration” may not only relate to deltoid bursitis but also may include tendonitis, rotator cuff tear, frozen shoulder, impingement syndrome, adhesive capsulitis, and shoulder bursitis. Localized intra-substance edema-like signal in deltoid muscle is the most common finding observed in Atanasoff et al.’s study.
There is little literature detailing imaging findings of complications following vaccination in general. It is not unexpected that there is no available information to determine if there is a difference between flu vaccination and other types of vaccination. For the purposes of this report, post-vaccination imaging findings will be considered similar, regardless of entity.
Considering bone marrow changes, focal T2-weighted edema-like signal changes in the humeral head with probable periosteal reaction following flu vaccine injection have been previously described in some reports [3, 4]. Two of our patients demonstrated humeral subcortical bone marrow abnormal signal at the probable injection site as well as periosteal hyperintense T2 signal changes. Osteonecrosis has been proposed as a possible source of the bone marrow edema following vaccination by some authors [5, 6]. Kuether et al. reported a case where incapacitating-prolonged shoulder dysfunction after vaccination was correlated with MRI findings of focal bone marrow edema and incongruity of the humeral head indicating atraumatic humeral head osteonecrosis . They hypothesized that the osteonecrosis might have been triggered by a focal vasculitis, which may have led to bone destruction and emphasized that mild forms of osteonecrosis following flu vaccine injection may have been under reported and they described “focal osteonecrosis” to be a possible side effect of adjuvant vaccines. Similar to Kuether’s report, Messerschmitt et al. presented a progressive osteolysis and surface chondrolysis case following influenza vaccine injection . In these two reports, a casual relationship between vaccine injection and osteonecrosis has been theorized, based on focal inflammatory reactions. In cases 3 and 4 presented here, outcomes and management do not support osteonecrosis or chondrolysis as the source of bone marrow edema-like signal.
More likely, the bone marrow changes in our cases are related to injection technique combined with body habitus. Reference markers for shoulder anatomy have been previously described for a proper vaccination technique in relevant literature [7, 8]. Due to variable body habitus and muscle size, the optimum point for vaccine injection may vary among individuals. An improper angle of approach of the needle or increased needle length may result in bursal or cortical penetration, particularly in those with low BMI. Several articles suggested that an ideal needle length may be determined depending on gender, BMI, and deltoid subcutaneous fat thickness to specifically avoid these events [9, 10]. In order to give an inactivated influenza vaccine intramuscularly to adults, a 1- to 1.5-inch needle should be used, while some experts recommend a 5/8-inch needle for adults who weigh less than 60 kg. For vaccination with the intradermal vaccine, the specifically designed microinjector has a 3/50-inch needle (Centers for Disease Control and Prevention). Two cases presented showed bone marrow edema-like signal and also had a low BMI and shallow subcutaneous deltoid fat. Assuming the standard institutional 1.5” needle was employed for these patients, improper technique may easily have resulted in cortical penetration.
Additional soft tissue changes in the cases presented may also be partly related to technique, with accidental access to marginal spaces such as the bursa. Bodor et al. presented two cases of shoulder dysfunction following influenza and pneumococcal vaccine injections. Ultrasound evaluation in those cases suggested improper vaccination leading to direct injection of the bursa causing bursitis, tendinitis, and adhesive capsulitis . The inflammatory responses may be triggered by the antigenic or non-antigenic components of the vaccine and are not only specific to flu-vaccine. Three of our four cases had increased bursal fluid supporting improper needle length and orientation. Although coincidental bursal inflammation is possible, none had prior shoulder symptoms, diagnosis of bursal or rotator cuff pathology, or trauma.
Additionally, chemical inflammation/reaction should be considered as etiologies for soft tissue changes. A search up to November 2013 of Vaccine Adverse Event Reporting System data, a national vaccine safety surveillance program co-sponsored by the Centers for Disease Control and Prevention and the Food and Drug Administration, specifically for “injection site injury” (joint discomfort, injection site joint effusion, injection site joint inflammation, injection site joint movement impairment, injection site joint pain)” following influenza vaccination revealed 72 entries in the U.S. and its territories. There was no entry with “bursal fluid accumulation” but 172 entries with “bursitis”, four entries with “osteonecrosis”, and 98 entries with “shoulder musculoskeletal discomfort” [database accessed at http://wonder.cdc.gov/vaers.html on Jan 12, 2014]. Injection-site complications may be accepted to be relatively small numbers comparing with all 84,368 entries related to influenza vaccination. According to The Food and Drug Administration (FDA), different pharmaceutical companies in the U.S sell 16 different influenza vaccine products in intramuscular, intradermal, and nasal spray forms. These vaccine products contain different chemical substances called “adjuvants” (to enhance the immune response), “preservatives”, and “tissue fixatives” (to preserve and fixate the biological parts of the vaccine from any chemical reactions and decomposition in the multi-vial forms). The adjuvants are highly diverse compounds that could presumably cause adverse immunologic effects . These diverse, heterogeneous compounds may be an explanation for prolonged focal inflammatory reactions following vaccination, especially when injected into alternative sites. These processes may account for the bursal (cases 1, 3, and 4) and soft tissue signal changes (cases 2, 3, and 4), as there were no other definitive explanations such as evolving contusion, hematoma, or abscess.
It is clear that there is a lack of relevant literature reporting MR imaging findings of vaccination complication. In this report, we presented four cases with abnormal soft tissue and bone findings on MR related to recent influenza vaccination. Although most complications from influenza vaccination are self-limited and do not warrant imaging, severe signs or symptoms, local or systemic, may necessitate imaging. As a retrospective review without patient or vaccination standardization, the bone and soft tissue changes are presumed to be the consequence of technique (needle length and orientation) and/or inflammation due to chemical constituents. With an increasing percentage of the population undergoing influenza vaccination, secondary imaging may also become more frequent to assess unexpected outcome, warranting this review for imagers.
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Okur, G., Chaney, K.A. & Lomasney, L.M. Magnetic resonance imaging of abnormal shoulder pain following influenza vaccination. Skeletal Radiol 43, 1325–1331 (2014). https://doi.org/10.1007/s00256-014-1875-9
- Influenza vaccination
- Shoulder MRI
- Bone marrow edema