Adhesive Capsulitis After COVID-19 Vaccination

Abstract

Of the many bizarre complications of administration of the COVID 19 vaccine, adhesive capsulitis is almost unheard of, although shoulder injury related to vaccine administration, which by definition has symptom onset within 48 hrs and is caused by faulty injection technique, has been rarely reported. Nine cases of adhesive capsulitis, five males and four females with a mean age of 48.7 ± 12.7 yrs, presenting within 1 mo of intramuscular Covishield vaccine on the ipsilateral deltoid and fulfilling the standard UK FROST Multicenter Study diagnostic criteria are reported. The mean time interval from vaccination until symptom onset was 12.3 ± 3.1 days, and mean symptom duration was 9.4 ± 2.4 wks. Conventional treatment with nonsteroidal anti-inflammatory drugs, followed by intra-articular steroid injection coupled with suprascapular nerve steroid block, improved the pain score and range of movement in 8 wks. The exact pathogenesis remains an enigma, although mechanisms such as local spread via deltoid muscle microvasculature, nerves, or shoulder injury related to vaccine administration causing secondary adhesive capsulitis have been hypothesized. While adhesive capsulitis is a very common diagnosis in the physiatric outpatient setting, the possible association with Covishield vaccination, the Indian version of the Oxford AstraZeneca recombinant ChAdOx1 nCoV-19 vaccine, is almost absent in existing literature and hence likely to be missed by clinicians, which necessitates this report.

Jayson Villagomez

SIRVA (shoulder injury related to vaccine administration) is an elusive condition that does not have much explanation in the existing literature. It has been observed after vaccines against influenza, pneumococcus, and tetanus.¹ A recent review article using data from the VAERS (Vaccine Adverse Effects Reporting System) database has pointed out the occurrence of SIRVA after COVID 19 vaccination.² However, it is well established that SIRVA occurs within 48 hrs of injection when an intramuscular deltoid injection is administered into the shoulder joint.³ Proper landmarking should be done and a needle of appropriate length for body habitus and body weight has to be chosen to avoid this particular complication.⁴ Idiopathic periarthritis (PA) of the shoulder, known as adhesive capsulitis or frozen shoulder in common parlance, is a chronic, painful self-limiting condition that usually takes approximately 6 mos to develop significant pain symptoms and takes more than a year to recover with the correct treatment, even after which 30%–40% of patients can have persistent mild to moderate symptoms at 2–3 yrs of follow-up.⁵ Sporadic instances of adhesive capsulitis shoulder have been reported after vaccination with other vaccines⁶; however, thorough search in MEDLINE, Google Scholar, and Cochrane database shows only one case series involving 10 patients who report PA shoulder after COVID 19 vaccination⁷ and 3 case reports that have reported shoulder pain secondary to rotator cuff pathology or subacromial-subdeltoid bursitis after COVID-19 vaccination till date.^8–10 This study presents a series of nine cases of post–COVID vaccination adhesive capsulitis of the shoulder presenting in the outpatient clinic of an apex rehabilitation center with the complaint of pain and restriction in shoulder range of motion within 1 mo of administration of the Covishield vaccine, which is the Indian version of the Oxford AstraZeneca recombinant ChAdOx1 nCoV-19 vaccine.

CASE SERIES

Nine consecutive patients, five males and four females with mean age 48.7 ± 12.7 yrs who presented between November 2021 and July 2022 in the outpatient clinic of the Department of Physical Medicine and Rehabilitation, All India Institute of Medical Sciences, Patna, India, with complaints of pain and restriction in range of motion (ROM) of shoulder upon receiving intramuscular Covishield vaccine in their ipsilateral deltoid within the past 1 mo are reported.

Patients were diagnosed as having adhesive capsulitis of the shoulder if (1) active and passive ROM were restricted in at least two directions and external rotation (with the adducted arm) was restricted to 50% compared with opposite normal extremity (as per the FROST multicenter study diagnostic criteria),¹¹ (2) a normal shoulder anteroposterior and lateral radiograph, (3) pain and stiffness persisting for at least 1 mo, and (4) absence of any apparent trauma or a secondary cause. After detailed history taking and examinations performed by a single qualified senior physiatrist, routine investigations that included complete blood count, erythrocyte sedimentation ratio, C reactive protein, fasting blood glucose, oral glucose tolerance test, hemoglobin A1c, serum urea, serum creatinine, T3, T4, thyroid stimulating hormone, and serum uric acid were done. Those who had significant shoulder pain and stiffness before the first dose of the COVID-19 vaccine and those with known comorbid conditions that predispose them to develop adhesive capsulitis of the shoulder-like history of previous shoulder trauma, structural pathology of the shoulder like rotator cuff lesions, diabetes, prediabetic state, thyroid disorders, autoimmune disease, coronary artery disease, and cerebrovascular accident were excluded based on history, clinical examination, and laboratory findings.

All patients were screened on the first day by a single physiatrist once with musculoskeletal ultrasound on an outpatient basis, to rule out rotator cuff pathology/SIRVA. A second opinion from the Department of Radiology was also taken with high-resolution ultrasound imaging. However, magnetic resonance imaging was not done because of cost issues and also because no evidence indicates that magnetic resonance imaging confirmation of PA shoulder modifies treatment protocol. Standard goniometric measurements of shoulder ROM were taken. All nine patients were of lower socioeconomic backgrounds, lived in rural areas, and received vaccination from rural vaccine centers. The four women were homemakers while the men worked menial jobs involving manual labor.

The mean time between vaccine administration and the patient being aware of his shoulder joint ROM restriction and glenohumeral joint pain, that is, symptom onset, was 12.3 ± 3.1 days, the highest being 17 days (median, 12 days; interquartile range, 6 days), while mean symptom duration was 9.4 ± 2.4 wks (median, 9 wks; interquartile range, 4 wks). All the patients gave a similar history of pain in the deltoid region around the site of injection, which subsided within a day but “later reappeared in the joint.” Oral medications prescribed by local general physicians did not improve the symptoms after which they presented in our outpatient clinic (OPD).

These patients were given 10 days of conservative treatment with oral nonsteroidal anti-inflammatory drugs and individualized home-based shoulder mobilization exercises as per existing guidelines. The patients were advised to begin with short-duration ROM exercises, were asked to gradually increase the repetitions and the total duration of exercises, along with cold pack application, and were advised to not push their limits beyond the tolerated ROM.^12–14

None of them reported any improvement in pain, for which all patients (except case 3 and case 7) were given ultrasonography-guided suprascapular nerve block along with an intra-articular steroid. Patients were asked to continue exercises and take nonsteroidal anti-inflammatory drugs as and when required. Patients were followed up after 8 wks. Cases 3 and 7 did not consent to injection procedures and failed to return to our OPD after 8 wks and were lost to follow-up. Adherence of patients to the home-based exercise regimen was checked depending on feedback from patient during the follow-up visits.

All cases showed improvement in the patient-reported numerical pain rating scale and Oxford Shoulder scores, as well as improvements in ROM, especially external rotation and abduction (Table 1). This study conforms to all Case Report guidelines and reports the required information accordingly (see Supplementary Checklist, Supplemental Digital Content 1, http://links.lww.com/PHM/B964).

TABLE 1.

Showing the patient characteristics and response to treatment after 8 wks

Case	Sex	Age, yr	Laterality	Onset, d	Duration, wk	External Rotation ROM (CL)	External Rotation ROM (IL)		Internal Rotation ROM (IL)		Flexion ROM (IL)		Abduction ROM (IL)		Oxford Shoulder Score		NPRS
							B	A	B	A	B	A	B	A	B	A	B	A
1	F	38	L	10	7	79	9	40	35	43	150	150	85	90	34	7	8	2
2	F	55	L	6	13	84	17	54	44	68	135	155	146	150	40	10	8	4
3	M	34	L	14	5	90	13	—	39	—	127	—	35	—	31	—	6	—
4	M	42	L	7	5	90	26	30	60	60	67	160	70	175	25	11	7	3
5	M	42	R	5	9	70	5	34	57	60	92	160	93	124	42	12	8	3
6	F	50	L	17	6	90	15	15	35	85	55	165	115	165	36	6	7	1
7	F	77	R	11	14	85	27	—	12	—	68	—	85	—	24	—	5	—
8	M	60	L	4	4	87	20	28	70	76	95	145	75	120	27	22	6	4
9	M	40	L	13	7	84	28	60	52	62	90	150	90	160	36	19	7	3

Contralateral shoulder ROM has been measured in order to compare with the affected side as per FROST criteria.

A, after 8 wks; B, before; CL, contralateral; Duration, number of weeks since symptom onset till first OPD visit; F, female; IL, ipsilateral; Laterality, whether involvement is of the left or right shoulder; M, male; NPRS, Numerical Pain Rating Scale; Onset, number of days from vaccination till the start of symptoms.

DISCUSSION

The occurrence of well-defined adhesive capsulitis of shoulder within a few weeks of COVID-19 vaccination with symptoms lasting more than a month is almost unheard of in existing literature, although a single case series with Indian patients implicated the same Covishield vaccine that every subject of our study had also received. However, eight of nine of those subjects receiving Covishield had known comorbidities, unlike our patients.⁷ A big problem facing us is the lack of a clear understanding of the pathophysiology of the development of adhesive capsulitis after intramuscular injection in the deltoid. One probable cause could be SIRVA after an accidental injection into the joint space. However, each one of our subjects could specifically pinpoint with a finger the exact location on the deltoid where the jab was given.

The pathogenesis of idiopathic adhesive capsulitis shoulder is still unclear for most parts although detailed molecular studies about the pathogenesis have indeed been conducted.¹⁵ To summarize, the pathophysiology includes both inflammation and fibrosis of the capsule mediated by cytokines including interleukin 1α (IL-1α), IL-1β, IL-6, IL-8, tumor necrosis factor α, cyclooxygenase 1, cyclooxygenase 2, growth factors, matrix metalloproteinases, and immune cells like B-lymphocytes, T lymphocytes, mast cells, and macrophages.¹⁶

One thing is evident from these cases: that these are definite cases of adhesive capsulitis, which have presented with shoulder ROM reduction and no concomitant pathology in the rotator cuff or other related structures, the reason why the authors are reluctant to label these cases as SIRVA. It is worthy to mention that adhesive capsulitis has indeed been included under the umbrella term SIRVA in the systemic review by Bass et al.²

First, SIRVA usually has symptom onset within 48 hrs of vaccination,^1,3 while our cases had a much longer mean of 12.3 ± 3.1 days before symptom onset with each case having a definite symptom-free interval, the highest being 17 days (median, 12 days; interquartile range, 6 days). The subjects in the article by Sahu et al.,⁷ on the other hand, had symptoms immediately after the vaccination in 6 patients (60%), at 48 hrs in 1 patient (10%), and at 10 days in 3 patients (30%), with a mean onset at 1.6 ± 3.1 days (median, immediate; interquartile range, 10 days). Second, all of our cases had radiologic evidence of structural capsular changes like thickened coracohumeral ligament or thickening of the inferior glenohumeral capsule on high-resolution ultrasound or other changes confirmed by a qualified radiologist, along with the absence of high-resolution ultrasound findings in the rotator cuff and related structures.^17,18 Third, all of our cases responded favorably in 2 mos when given the common treatment for adhesive capsulitis, namely, intra-articular steroid injected along with suprascapular nerve block for pain relief and a home-based shoulder mobilization exercise regime. Fourth, while 9 of 11 patients in the study by Sahu et al.⁷ had known risk factors, we had nine cases with no risk factor known to us except for a probable suspect: a Covishield jab at the ipsilateral deltoid. The observation of the longer than previously reported delay in onset of symptoms may be because our patients had no risk factors, or in other words, it may be hypothesized that the presence of risk factors may establish the conditions for a quicker onset. Moreover, all these patients took the vaccine from a government-run vaccination center where the jab was performed by trained healthcare professionals; hence, the possibility of SIRVA, which is an injury caused by inadvertent direct inoculation of the injection into the shoulder joint due to faulty landmarking technique, later giving rise to secondary adhesive capsulitis, is quite unlikely, though not impossible.³ A similar mechanism of injection of the antigen in the subacromial-subdeltoid bursa, thus leading to acute and prolonged hyperinflammatory reaction can also be hypothesized.³ Another vaguely explainable possibility is that of vaccine materials spreading to unintended locations through the vasculature of the deltoid muscle or nerves.^19,20 It may even be worthwhile to consider with the help of future larger studies whether an alternate route of vaccine administration (i.e., gluteal or even nasal vaccine where available) would be beneficial, especially for patients who already have shoulder pathology and/or medical comorbidities that predispose them to adhesive capsulitis.

The World Health Organization declared a public health emergency of international concern on January 30, 2020, shortly after the isolation and genomic sequencing of the etiological agent later called COVID-19. Vaccine development and clinical trials had to go simultaneously in this emergency as the virus was a novel one. To expedite the process, the World Health Organization included COVID-19 vaccine under emergency use listing while they were still under development to save lives. Therefore, all the adverse effects are not completely known to date, although the manufacturers are encouraging the recipients to report the experience of adverse effects to them. However, in the accessible documents of Covishield, no mention of adhesive capsulitis of the shoulder as an adverse effect has been found.²¹

While our study does not seek to undermine the usefulness of vaccines in preventing the ongoing COVID 19 pandemic, the authors feel that it is important to note peculiar adverse effects, though rare. In addition, the lack of proper documentation and maintenance of a national database of adverse effects of COVID 19 vaccines leads to the possibility of underreporting in a populous country like India. In addition, while Covishield is the Indian version of the Oxford AstraZeneca recombinant ChAdOx1 nCoV-19 vaccine, manufactured by Serum Institute of India Pvt, Ltd, because there are definite reports of postvaccination shoulder pathology coming out of India, it is important to be vigilant about similar complaints, if any, from subjects in countries that received some other version of the Oxford vaccine.

Our study suffers from a few limitations. A rather small patient population for a quite rare and bizarre complication, and a relatively long (usually more than 1 yr) follow-up required to fully rehabilitate adhesive capsulitis precludes a detailed understanding of the abovementioned problem or the consideration of probable risk factors.⁵

Notwithstanding these limitations, this study has selectively included subjects without any known risk factors for adhesive capsulitis, who were found to respond to conventional treatment for adhesive capsulitis, and had a longer than previously reported onset, which makes these cases noteworthy.

The authors feel that the medical community, especially physiatrists in their day-to-day practice, must be aware of this unusual phenomenon of adhesive capsulitis shoulder after COVID-19 vaccination to facilitate early suspicion, identification, and treatment of the same.