Sex: F
Vaccine: FLUX
Symptoms: Fungal test negative, HLA-B*27 assay, Hyperplasia, Immunology test, Incorrect route of product administration
Clinical narrative: Likely had the shot administered very deeply, causing mechanical and chemical irritation of the posterior humeral head; Placed relatively high on her left upper arm; Lytic lesion in the proximal humerus; SIRVA; Adhesive capsulitis; This literature case was received on 24-Nov-2020 and concerned an adult, female patient. The patient was 51-year-old at 10-month presentation post vaccination.   The patient's concurrent condition included prolapsing mitral valve. The patient's concomitant medications were not reported. The patient had no history of shoulder issues and was able to work out and play recreational level sports before the flu shot. The patient was a healthy, fit woman with no significant medial or surgical history.   On an unknown date in Sep-2016, the patient was vaccinated with influenza virus vaccine polyvalent (brand not specified, anatomical location: left posterior deltoid, distal and slightly anterior to the posterolateral border of the acromion, also reported high on her left upper arm, dose, route of administration: not reported) for influenza vaccination. The batch number was not reported. The patient likely had the shot administered very deeply, causing mechanical and chemical irritation of the posterior humeral head (explicitly coded as 'Vaccine administered at inappropriate site' and 'Inappropriate route of vaccination').   On an unknown date in 2016, one day after receiving influenza virus vaccine polyvalent, the patient developed left shoulder symptoms. The patient later experienced unremitting left shoulder pain and loss of motion.   On 13-Oct-2016, two weeks after receiving flu shot, the patient presented to a primary care sports medicine (PCSM) specialist. On presentation, anteroposterior radiograph of the left shoulder was unremarkable showing no evidence of a lesion in the posterior proximal humerus.   On 08-Nov-2016, two months after the flu shot, magnetic resonance imaging (MRI) demonstrated a partial-thickness rotator cuff tear with a small hyperintense area on the posterior aspect of the rotator cuff footprint.   The differential diagnosis included infection, traumatic injury, or immunologic reactive inflammation. Her shoulder pain was managed conservatively, with a course of anti-inflammatory medications and physical therapy.  On an unspecified date in 2016, approximately three months after the flu shot, during the conservative treatment course of anti-inflammatory medications and physical therapy, the patient developed adhesive capsulitis. An ultrasound guided joint aspiration was performed and the sample was evaluated for the presence of aerobic and anaerobic bacteria, fungi, and mycobacteria. Ten aerobic bacterial cultures demonstrated no growth after five days of incubation. Ten anaerobic cultures had no growth after 14 days of incubation. Nine fungal cultures had no growth after four weeks of incubation, and seven cultures for mycobacteria had no growth after eight weeks of incubation. This was treated with two ultrasound-guided intraarticular cortisone steroid injections. Because of the presence of a prolapsing mitral valve, two blood cultures were obtained, which showed no growth. In addition, serologic studies for Lyme disease were negative (both immunoglobulin G and immunoglobulin M Enzyme Immunoassay (EIA)). Studies for rheumatologic disease, including antinuclear antibodies, rheumatoid factor, and human leukocyte antigen-B27, were also negative.  On an unspecified date in 2017, ten months after the flu shot, the patient's presenting symptoms included anterior and lateral shoulder pain, pain with shoulder flexion and abduction, and night pain. She denied paresthesias, fevers, chills, and night sweats. On presentation to physician's office, she had tenderness to palpation over the anterior fibers of the supraspinatus, with no evidence of muscle wasting. She had normal shoulder range of motion (ROM), with the exception of diminished active abduction (100 degrees on left vs. 170 degrees on right) and internal rotation (5 spinal levels less than the right side). Her strength examination was normal, with the exception of infraspinatus weakness (4/5).  On 12-Jul-2017, ten months after the flu shot and eight months after the initial MRI, a repeat MRI was obtained which demonstrated a significant increase in the signal within the humeral head with bony erosion. Given the change in MRI appearance, she was referred to an infectious disease specialist who recommended rheumatologic blood work (inflammatory markers, metabolic panels) and a computed tomography (CT) scan. The lab, including an erythrocyte sedimentation rate and C-reactive protein, were normal.   On 28-Aug-2017, the CT scan demonstrated a large lytic lesion in the posterior proximal humerus. A CT-guided needle biopsy of the bone and soft tissue performed at that time (11 months from the flu shot) was inconclusive.  On an unspecified date in Oct-2017, 13 months after the flu shot, the patient had left shoulder arthroscopy with bone and soft-tissue biopsy and debridement. At the time of arthroscopy, there was evidence of patchy synovitis in the joint with a focal synovitic area at the site of the lytic lesion and a bone defect in the posterior aspect of the humeral head, adjacent to the infraspinatus insertion. Tissue cultures were taken from throughout the anterior capsule, posterior capsule, and synovium. A spinal needle was then used to localize the defect, and an incision was made for insertion of a 7 mm core biopsy needle. The core biopsy was taken from this defect, with debridement of unhealthy-appearing tissue in and at the edges of the defect. Additionally, tissue samples were taken from various locations within the joint. All cultures came back negative. Each location shared inflammatory features of varying degrees. Tissue from the anterior capsule consisted of synovium that showed papillary hypertrophy with a moderate degree of hyperplasia of the synovial lining layer. There was a moderate degree of chronic lymphoplasmacytic inflammation that had a high proportion of plasma cells, some of which contained more than one nucleus. Tissue from the posterior capsule, adjacent to the bone erosion, also showed papillary hypertrophy with greater degrees of hyperplasia and chronic inflammation imparting a much higher degree of cellularity including lymphocytes, plasma cells, and stromal elements. Tissue from the defect in the posterior aspect of the humeral head showed inflammatory destruction of the articular cartilage and bone. The superficial cartilage showed inflammatory destruction of the cartilage with Weichselbaum lacunae and a small amount of pannus. The bony endplate was focally destroyed, and the bone while eroded was demonstrating remodelling activity. The marrow space showed replacement of the fat by dense and loose fibrous and fibromyxoid tissue associated with a variable dense inflammatory infiltrate that was composed of lymphocytes and plasma cells, some of which, as elsewhere, contained more than one nucleus.  Once the area of inflammatory tissue was removed and healthy bone/tissue was stimulated at the time of arthroscopy, the patient's body was able to mount a response to heal the injured area. Postoperatively, the patient was placed into a sling for immobilization for two weeks, followed by the initiation of shoulder ROM exercises. Once full ROM was obtained, a supervised shoulder strengthening program was begun.   On an unknown date in 2018, at 1-year follow-up, the patient recovered from all events. She had regained full passive and active ROM in all directions, and strength and functional capacity have returned to normal. No new imaging was obtained given her full functional status with no complaints.  The reporters assessed the events of 'osteolytic lesion', 'shoulder injury related to vaccine administration' and 'adhesive capsulitis' as related to influenza virus vaccine polyvalent. Based on a strong temporal relationship between the influenza vaccination, placed relatively high on her left upper arm, and the onset of patient's left shoulder symptoms the day after the injection, there was a concern that her symptoms were related to the injection.  The events of 'osteolytic lesion', 'shoulder injury related to vaccine administration' and 'adhesive capsulitis' were considered to be medically significant by a Physician within Seqirus' Pharmacovigilance and Risk Management Department.   Company comment: A 51-year-old female patient started experiencing symptoms, which will later be determined as osteolysis, shoulder injury (related to vaccine administration) and periarthritis, one day after administration of influenza virus vaccine polyvalent in the area described as: left posterior deltoid, distal and slightly anterior to the posterolateral border of the acromion, also reported as 'high on her left upper arm'. Reportedly, the patient likely had the shot administered very deeply, causing mechanical and chemical irritation of the posterior humeral head (explicitly coded as 'Vaccine administered at inappropriate site' and 'Inappropriate route of vaccination'). The patient's concurrent condition included prolapsing mitral valve, while concomitant medications were not reported. She had no history of shoulder issues and was able to work out and play recreational level sports before the flu shot. It was also reported that she was a healthy, fit woman with no significant medial or surgical history. Causality is assessed as possibly related for all 3 events (having in mind detailed and comprehensive diagnostics (both visual and laboratory - microbiological, inflammatory, metabolic) which excluded any other confounder) but also related to medication error. Incorrect route of product administration and product administered at inappropriate site are assessed as unrelated per company conventions.; Reporter's Comments: Based on a strong temporal relationship between the influenza vaccination, placed relatively high on her left upper arm, and the onset of patient's left shoulder symptoms the day after the injection, there was a concern that her symptoms were related to the injection.; Sender's Comments: A 51-year-old female patient started experiencing symptoms, which will later be determined as osteolysis, shoulder injury (related to vaccine administration) and periarthritis, one day after administration of influenza virus vaccine polyvalent in the area described as: left posterior deltoid, distal and slightly anterior to the posterolateral border of the acromion, also reported as 'high on her left upper arm'. Reportedly, the patient likely had the shot administered very deeply, causing mechanical and chemical irritation of the posterior humeral head (explicitly coded as 'Vaccine administered at inappropriate site' and 'Inappropriate route of vaccination'). The patient's concurrent condition included prolapsing mitral valve, while concomitant medications were not reported. She had no history of shoulder issues and was able to work out and play recreational level sports before the flu shot. It was also reported that she was a healthy, fit woman with no significant medial or surgical history. Causality is assessed as possibly related for all 3 events (having in mind detailed and comprehensive diagnostics (both visual and laboratory - microbiological, inflammatory, metabolic) which excluded any other confounder) but also related to medication error. Incorrect route of product administration and product administered at inappropriate site are assessed as unrelated per company conventions.