Bone erosion and subacromial bursitis caused by diphtheria–tetanus–poliomyelitis vaccine

doi:10.1016/j.vaccine.2015.09.090

Vaccine

Volume 33, Issue 46, 17 November 2015, Pages 6152-6155

https://doi.org/10.1016/j.vaccine.2015.09.090 Get rights and content

Abstract

Revaxis^® is a vaccine against diphtheria, tetanus and poliomyelitis (dT-IPV). This vaccine should not be administered by the intradermal or intravenous route. Poor injection techniques and related consequences are rare.

We report a case of bursitis associated with reactive glenohumeral effusion complicated by bone erosion occurring after injection of the dT-IPV vaccine. A 26 year old patient was admitted for painful left shoulder causing functional impairment. Control magnetic resonance imaging showed bone oedema on the upper outer part of the humeral head, with a slight cortical irregularity, indicating that the vaccine was injected in contact with the bone at this location, causing erosion. Outcome was favourable after intra-articular corticosteroids.

Reports of articular or periarticular injury after vaccination are extremely rare, in view of the substantial number of vaccines administered every year. The potential complications of vaccination are well known to general practitioners but under-reported in the literature.

Introduction

Revaxis^® is a vaccine against diphtheria, tetanus and poliomyelitis (dT-IPV). This inert vaccine contains purified diphtheria toxoid, purified tetanus toxoid, inactivated poliomyelitis virus and aluminium hydroxide as adsorbant [1]. The excipients are phenoxyethanol, formaldehyde, acetic acid or sodium hydroxide to adjust the pH level, and Medium 199 containing in particular amino acids, mineral salts, vitamins and water for injections [1]. The safety of this vaccine is well established [1], [2], [3], [4]. Reactions such as pain and redness at the injection site in the vaccinated limb are mostly predictable and are usually benign and of short duration [2], [3], [4]. Among the possible local and systemic reactions, musculo-skeletal disorders are rare. According the Summary of Product Characteristics for the vaccine, the main side effects are myalgia (uncommon) and arthralgia (rare) [1], [3], [4]. Undesirable effects such as oedema, inflammation, numbness, paraesthesia and involuntary contractions occur in <1% of subjects [1], [3], [4].

The recommended mode of administration of the Revaxis vaccine is by intramuscular or deep subcutaneous injection [1], and it must not be administered by the intradermal or intravenous route. The recommended injection site is the deltoid region. Cases of poor injection technique and associated consequences are extremely rare. We report a case of bone erosion and bursitis associated with reactive glenohumeral effusion occurring after injection of the dT-IPV vaccine.

Section snippets

Case report

A 26-year old female patient consulted the rheumatology department in an emergency for a painful left shoulder causing functional impairment. She had no medical history. The pain had started 48 h before admission after receiving Revaxis^® vaccine in the upper third of the left deltoid during a work-related medical check-up. During the administration, the patient had felt a slight discomfort and the physician had noted some resistance to the injection (0.6 × 25 mm needle, 23 G). On clinical

Discussion

To the best of our knowledge, this is the first reported case of bone erosion and subacromial bursitis associated with reactive effusion occurring after injection of the Revaxis^® vaccine. According to the method coined by Begaud et al., the link between the vaccine and the shoulder injury is assessed on the basis of the intrinsic causal relationship (based on chronology and semiology, and absence of differential diagnosis), and unconfirmed extrinsic bibliographic evidence of causality [5]. In

Conclusion

This is the second documented case of bone erosion that occurs after a vaccine; the first after Revaxis^®. Reports of articular or periarticular injury after vaccination are extremely rare, in view of the substantial number of vaccines administered every year. The potential complications of vaccination are well known to general practitioners but under-reported in the literature. Apart from simple oversights, the fact that there are few, if any, clinical or functional consequences to

Funding

None.

Patient consent

Obtained.

Key messages

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We report the first case of bursitis associated with reactive glenohumeral effusion complicated by bone erosion occurring after injection of the diphtheria, tetanus and poliomyelitis (Revaxis^®) vaccine.
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Outcome was favourable after treatment by NSAIDs and and intra-articular corticosteroids.

Conflicts of interest statement

No author has any conflict of interest to report.

Acknowledgements

We thank Marie Hannetel and Centre régional de pharmacovigilance de Champagne-Ardenne, France.

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Cited by (19)

Chronic inflammation and extracellular matrix-specific autoimmunity following inadvertent periarticular influenza vaccination
2021, Journal of Autoimmunity
Viral infections may trigger autoimmunity in genetically predisposed individuals. Immunizations mimic viral infections immunologically, but only in rare instances vaccinations coincide with the onset of autoimmunity. Inadvertent vaccine injection into periarticular shoulder tissue can cause inflammatory tissue damage (‘shoulder injury related to vaccine administration, SIRVA). Thus, this accident provides a model to study if vaccine-induced pathogen-specific immunity accompanied by a robust inflammatory insult may trigger autoimmunity in specific genetic backgrounds.
We studied 16 otherwise healthy adults with suspected SIRVA occurring following a single work-related influenza immunization campaign in 2017. We performed ultrasound, immunophenotypic analyses, HLA typing, and influenza- and self-reactivity functional immunoassays. Vaccine-related bone toxicity and T cell/osteoclast interactions were assessed in vitro.
Twelve of the 16 subjects had evidence of inflammatory tissue damage on imaging, including bone erosions in six. Tissue damage was associated with a robust peripheral blood T and B cell activation signature and extracellular matrix-reactive autoantibodies. All subjects with erosions were HLA-DRB1*04 positive and showed extracellular matrix-reactive HLA-DRB1*04 restricted T cell responses targeting heparan sulfate proteoglycan (HSPG). Antigen-specific T cells potently activated osteoclasts via RANK/RANK-L, and the osteoclast activation marker Trap5b was high in sera of patients with an erosive shoulder injury. In vitro, the vaccine component alpha-tocopheryl succinate recapitulated bone toxicity and stimulated osteoclasts. Auto-reactivity was transient, with no evidence of progression to rheumatoid arthritis or overt autoimmune disease.
Vaccine misapplication, potentially a genetic predisposition, and vaccine components contribute to SIRVA. The association with autoimmunity risk allele HLA-DRB1*04 needs to be further investigated. Despite transient autoimmunity, SIRVA was not associated with progression to autoimmune disease during two years of follow-up.
Arthroscopic surgical management of shoulder secondary to shoulder injury related to vaccine administration (SIRVA): a case report
2021, Journal of Shoulder and Elbow Surgery
Although transient pain secondary to vaccine administration is common, persistent shoulder pain and dysfunction is rare. In this case report we describe a patient that presented with significant shoulder pain 3 months after vaccine administration despite conservative treatment. MRI showed rotator cuff bursitis and bursal foreign body reaction, and she was treated with arthroscopic débridement of inflamed tissue and bone. Shoulder injury related to vaccine administration (SIRVA) is a rare complication that presents similarly to other common etiologies of shoulder dysfunction. Proper recognition and management, discussed in this paper, is important to prevent delay in treatment and return of function.
Teres minor injury related to vaccine administration
2020, Radiology Case Reports
Shoulder injury related to vaccine administration is a relatively rare disorder, which occurs as a result of vaccine being inadvertently injected into the subdeltoid/subacromial bursa, rotator cuff, and or underlying bone. We present 2 cases of shoulder injury related to vaccine administration in 2 women of ages 38 and 42 with injury to the teres minor tendon insertions on magnetic resonance imaging, a location not previously described. When faced with a patient with chronic shoulder pain following a vaccination, the possibility of vaccine deposition or injury to the teres minor tendon insertion should be considered.
Reports of atypical shoulder pain and dysfunction following inactivated influenza vaccine, Vaccine Adverse Event Reporting System (VAERS), 2010–2017
2020, Vaccine
Citation Excerpt :
The National Academy of Medicine relied heavily on a case series review of 13 petitioner claims from 2006 through 2010 to the National Vaccine Injury Compensation Program (VICP) of severe persistent shoulder pain with limited range of motion following vaccination [3]. Other case reports in the medical literature describe similar findings [4–12]. The Health Resources and Services Administration in the U.S. Department of Health and Human Services manages the VICP [13].
Vaccines administered into or too close to underlying joint structures have the potential to cause shoulder injuries. Limited data exist on the epidemiology of such events.
To describe case reports of atypical shoulder pain and dysfunction following injection of inactivated influenza vaccine (IIV).
We searched the Vaccine Adverse Event Reporting System (VAERS) database from July 2010 to June 2017 for reports of atypical shoulder pain and dysfunction following IIV. When identifying reports, we made no assumptions about true incident injury or causality with respect to vaccination. Pain had to begin <48 h after vaccination and signs and symptoms had to continue for >7 days to differentiate from self-limited local reactions. We conducted descriptive analysis.
We identified 1220 reports that met our case definition (2.0% of all IIV reports, range 1.5%-2.5% across influenza seasons). Median age was 52 years (range 16–94) and most patients (82.6%) were female. Shoulder pain (44.1%), injected limb mobility decreased (40.8%), joint range of motion decreased (21.2%), rotator cuff syndrome (9.2%), and bursitis (9.0%) were frequently reported. In 86.6% of reports, signs and symptoms had not resolved by the time of report submission. In reports that included descriptions suggesting contributing factors (n = 266), vaccination given “too high” on the arm was cited in 81.2%. Nearly half (n = 605, 49.6%) of reports described a healthcare provider evaluation. Treatments included non-narcotic analgesics, physical therapy, and corticosteroid injection. Vaccinations were most commonly administered in a pharmacy or retail store (41.0%) or doctor’s office or hospital (31.6%).
Reports of atypical shoulder pain and dysfunction following IIV were uncommon, considering the amount of IIV use, and stable across influenza seasons. While specific etiology of cases is unknown, improperly administered vaccine, which is preventable, might be a factor. Prevention strategies include education, training, and adherence to best practices for vaccine administration.
Shoulder Injury Related to Vaccine Administration (SIRVA): Petitioner claims to the National Vaccine Injury Compensation Program, 2010–2016
2020, Vaccine
Citation Excerpt :
SIRVA is thought to occur when vaccine is injected above or through the deltoid into underlying non-muscular tissues, such as the bursae, ligaments, and tendons [3]. Specific impairments include bursitis [4–8], bone erosion [8], and damage to the rotator cuff and bicipital tendons [4,6]. The authors, including a rheumatologist, hypothesized that an inflammatory response to vaccine contents in tissues other than the muscle may be causative [4,5,8].
Since 2010, petitioner claims of shoulder injury related to vaccine administration (SIRVA) to the National Vaccine Injury Compensation Program (VICP) have been increasing.
To conduct a scientific review of clinical characteristics of SIRVA petitions to the VICP.
We queried the VICP’s Injury Compensation System database for medical reports of alleged SIRVA and SIRVA-like injuries. Medical reports are summaries of petitioner claims and supporting documentation along with a VICP clinician reviewer diagnosis and assessment of criteria for concession. We conducted a descriptive analysis of SIRVA petitioner claims recommended by the VICP for concession as SIRVA injuries.
We identified 476 petitioner claims recommended for concession. Claims per year increased from two in 2011, the first full year in the analytic period, to 227 in 2016. Median age was 51 years, 82.8% were women, and median body mass index was 25.1 (range 17.0–48.9). Four hundred cases (84.0%) involved influenza vaccine. Pharmacy or store (n = 168; 35.3%) was the most common place of vaccination followed by doctor’s office (n = 147; 30.9%). Fewer than half of cases reported a suspected administration error; 172 (36.1%) reported ‘injection too high’ on the arm. Shoulder pain, rotator cuff problems, and bursitis were common initial diagnoses. Most (80.0%) cases received physical or occupational therapy, 60.1% had at least one steroid injection, and 32.6% had surgery. Most (71.9%) healthcare providers who gave opinions on causality considered the injury was caused by vaccination. A minority (24.3%) of cases indicated that symptoms had resolved by the last visit available in medical records.
Most conceded claims for SIRVA were in women and involved influenza vaccines. Injection too high on the arm could be a factor due to the risk of injecting into underlying non-muscular tissues. Healthcare providers should be aware of proper injection technique and anatomical landmarks when administering vaccines.
Risk of bursitis and other injuries and dysfunctions of the shoulder following vaccinations
2017, Vaccine
Citation Excerpt :
This can induce an intense immune and inflammatory response in the shoulder capsule [34–37]. This, in turn, would cause injuries and dysfunctions, like edema, erosion, and even necrosis of the humeral head [8,10,17,19,38]. In our study, we noted that shoulder injuries and dysfunctions following vaccination were most frequent with the influenza vaccine compared with the rest of vaccines, probably because the former is given to the highest number of patients.
While vaccination injection site adverse reactions are usually mild and transient in nature, several cases of bursitis and other shoulder injuries have been reported in the medical literature. However, these lesions are not included in vaccine label inserts.
To identify the characteristics of post-vaccination shoulder injuries and those of patients and involved vaccines, as well as their potential causes, a systematic review of the cases of vaccination-related bursitis and other shoulder injuries reported in the literature and notified to the Spanish Pharmacovigilance System database (FEDRA) have been conducted.
We found 45 cases of bursitis and other shoulder injuries that appeared following the vaccine intramuscular injection given into the deltoid muscle (37 from the systematic review of the literature, and 8 from the scrutiny in the Spanish Pharmacovigilance System database, FEDRA). All the patients were adult, 71.1% females, with a mean and median age of 53.6 years (range: 22–89). The most frequently involved vaccines were influenza and pneumococcal vaccines, respectively; followed by diphtheria-tetanus-pertussis, diphtheria-tetanus toxoid, human papillomavirus, and hepatitis A vaccines. The most frequent shoulder lesion was bursitis. Most of patients required medical care due to severe local pain and arm mobility restriction. In a majority of cases, symptoms started 48 h post vaccination.
Subdeltoid or subacromial bursitis and other shoulder lesions may be more common than suspected. Such lesions predominantly affect women. The cause may be related to antigens or adjuvants contained in the vaccines that would trigger an immune or inflammatory response. However, they are more likely to be the consequence of a poor injection technique (site, angle, needle size, and failure to take into account patient’s characteristics, i. e., sex, body weight, and physical constitution). Therefore, vaccination-related shoulder injuries would be amenable to prevention.

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Short communicationBone erosion and subacromial bursitis caused by diphtheria–tetanus–poliomyelitis vaccine

Abstract

Introduction

Section snippets

Case report

Discussion

Conclusion

Funding

Patient consent

Key messages

Conflicts of interest statement

Acknowledgements

Rev Rhum Monogr

Vaccine

Vaccine

Vaccine

Vaccine

Vaccine

Am J Emerg Med

Appl Nurs Res: ANR

The immunogenicity and safety of a new combined diphtheria, tetanus and poliomyelitis booster vaccine (Td-eIPV)

Infection

REVAXIS—CT-9853-revaxis_-_ct_-_9853.pdf [Internet]

Summary of product characteristics (SPC)—(eMC) [Internet]

Short communication
Bone erosion and subacromial bursitis caused by diphtheria–tetanus–poliomyelitis vaccine