Introduction
In 2021, humanity is faced with a new threat in the form of COVID-19.
The entire medical community has mobilized to fight the pandemic. The accumulated knowledge and experience have allowed us to stabilize the situation in terms of morbidity and mortality. While the world's population is waiting for the next wave of COVID-19, doctors are eliminating the consequences of the pandemic - those complications that have arisen in patients with previous (symptomatic or asymptomatic) coronavirus infection. The issues of post-Covid syndrome are currently being actively debated in the scientific world [1]. During the height of the pandemic, our outpatient practice began to encounter patients with arthritis of different localizations and varying degrees of severity of clinical manifestations, resistant to traditional therapy with nonsteroidal anti-inflammatory drugs (NSAIDs). What united such patients was a previous coronavirus infection. Often, the patients in question initially turned to specialists of a different profile and received symptomatic treatment for osteochondrosis, coxarthrosis, tendovaginitis, etc. Infectious etiology, as a rule, was not considered as a trigger for the occurrence of inflammation in the joints. If there was no therapeutic effect, a new NSAID was often recommended. To date, a large number of reviews of the practical application and effectiveness of drugs for the treatment of coronavirus infection have been published [2]. During the pandemic, as experience was gained, algorithms for providing care to patients with COVID-19 changed. However, neither in the domestic nor in the foreign literature the issues of diagnosis and treatment of arthritis against the backdrop of a coronavirus infection have been covered, which means that treatment algorithms for such complications have not been developed. In the absence of clinical recommendations for the treatment of complications from the musculoskeletal system against the background of a coronavirus infection and the resistance of arthritis to NSAIDs (according to our observations), we began to use glucocorticosteroids (GCS) to relieve clinical manifestations of inflammation. This group of drugs is also recommended for the treatment of coronavirus infection [3]. It is well known that GCS block the synthesis of a wide range of pro-inflammatory mediators, an increase in the concentration of which as part of a “cytokine storm” is associated with an unfavorable prognosis in COVID-19 [4]. It should be noted that in the pathogenesis of reactive arthritis, an important role is played by the imbalance of pro-inflammatory cytokines [5], the high content of which (in particular, interleukins) is found in the plasma of patients with coronavirus infection [6], which can be considered as an unrealized “cytokine storm”. We consider previous infection caused by SARS-CoV-2 as a trigger for joint syndrome. In this regard, we began to identify arthritis in patients with a significant history of coronavirus infection as “post-Covid arthritis.”
We present our own experience in treating patients with previous coronavirus infection and manifestations of reactive arthritis, in the treatment of which systemic corticosteroids were successfully used.
Own experience
Under our supervision at the Center for Traumatology and Radiography in Tver there are 916 adult patients who contacted an orthopedic traumatologist with clinical manifestations of arthritis against the background of a previously suffered (symptomatic or asymptomatic) confirmed infection caused by SARS-CoV-2 (M13.9 according to the ICD -10). The average age of the patients was 47.1±11.3 years. The majority of patients are women—773 (84.4%) people.
All patients, without exception, at their initial visit to an orthopedist-traumatologist complained of joint pain at rest and during exercise. Of note was the acute onset of the disease in the majority (92%) of patients (Table 1). Patients often experienced muscle pain and stiffness in the affected segments, worsening in the evening and at night (78.5%), and therefore many patients initially turned to neurologists. More than half of the patients with a positive epidemiological history of COVID-19, who applied for an outpatient orthopedic appointment with joint pain of varying nature and intensity, had typical clinical manifestations of inflammation: effusion (determined by palpation, in some cases confirmed by ultrasound and MRI), swelling and local hyperthermia in the area of the affected segment. However, in a third of patients, visual and palpatory changes were not detected at all. Rarely, those observed had low-grade fever (19.7%) and functional disorders in the form of lameness and restrictions of movement in the affected joint (37.8%).
The most common location of arthritis in the observed patients was the knee joint - 48.2% of cases. Patients were significantly less likely to present with pain in other segments (Table 2). The difference between the number of patients (n=916) and the number of localizations (n=1163) is due to the fact that in 54 (5.9%) cases there was simultaneous damage to several joints. Based on this, we can conclude that in the vast majority of cases the disease occurred in the form of monoarthritis (94.1%).
Pain syndrome in the majority, 628 (68.6%), patients was assessed as moderate - 4-6 points on VAS, 167 (18.2%) patients noted mild pain - 1-3 points on VAS, 121 (13.2%) ) the patient complained of severe pain - over 6 points on VAS.
Seven hundred fifty-one (82%) patients had a history of injury or degenerative disease (osteoarthritis, enthesopathies, hypermobility, dysplastic changes, etc.) of the arthritic joint, but in all cases a different type of pain was noted.
The average time for the onset of arthritis was approximately 6 weeks. from a confirmed case of coronavirus infection (45.0±7.1 days). These figures differ from the average time to contact a specialized specialist - 62.2±12.8 days. Such delayed clinical manifestations, in our opinion, are the main reason for the misinterpretation of articular syndrome. We observed many patients who, before visiting an orthopedist, were examined by doctors of related specialties and underwent expensive examinations that did not facilitate the diagnostic search. At the time of their visit to the clinic, 709 (77.4%) patients used traditional NSAIDs (prescribed by a doctor or used on their own initiative) orally, parenterally or locally as initial therapy for arthritis. This group of patients was asked to answer the question about the effectiveness of using NSAIDs for pain relief. Of the 709 patients surveyed, 560 (79%) reported no improvement in the affected joints while taking NSAIDs. 16% of patients (112 people) experienced short-term improvement, and after stopping the course of NSAID treatment, pain returned. Only 35 (5%) of respondents received the desired effect - a decrease in the severity of pain compared to the initial level. The survey results indicate that arthritis is resistant to NSAIDs. In this regard, we decided to prescribe GCS to patients with clinical manifestations of post-Covid arthritis. As a basic treatment for arthritis against the background of a coronavirus infection, the drug betamethasone (Diprospan®) was used in a dosage of 1 ml, which was administered intramuscularly, taking into account the comorbid background and possible allergic reactions, which in 93 cases served as a contraindication to the administration of the drug. Diprospan® has a pronounced anti-inflammatory effect. The drug is a combination of soluble and poorly soluble betamethasone esters for intramuscular, intraarticular, periarticular, intrasynovial and intradermal administration, as well as for administration directly into the lesion. Betamethasone sodium phosphate is a highly soluble component that is rapidly absorbed from the injection site, which ensures a rapid onset of therapeutic action. Betamethasone dipropionate is a poorly soluble component that is slowly absorbed from the depot created at the injection site and provides a long-lasting effect of the drug.
Control examinations were carried out on the 7th, 14th and 28th days of observation. The effectiveness of treatment was assessed subjectively (severity of pain on the VAS scale) and objectively (dynamics of inflammatory changes).
In total, the drug was prescribed to 823 (89.8%) patients. For 570 (69.3%) people, a single dose of the drug was sufficient. They showed positive dynamics in the form of relief of pain and inflammatory changes in the affected joints. In 112 (13.6%) cases, due to pain remaining at the initial level, repeated administration of the drug at the same dosage was required after 2 weeks. after the first injection. The third injection (2 weeks after the second) was given to 44 patients with insufficient effect from the first two. 97 patients did not return to the clinic after the first injection, which cannot be regarded as a positive result after a single use of betamethasone dipropionate due to the lack of feedback.
In general, there was a persistent decrease in pain in the entire observation group, starting from the 7th day of observation (Fig. 1).
12/04/2021 Events
About vaccination against COVID-19 in immunoinflammatory rheumatic diseases
Information for specialists
Dear Colleagues!
During the coronavirus disease 2021 (COVID-19) pandemic, we all have great hopes for the introduction into clinical practice of vaccines against the SARS-CoV-2 virus (Severe acute respiratory syndrome-related coronavirus 2)
Currently, the following vaccines against COVID-19 are registered in the Russian Federation: combined vector - Gam-COVID-Vac (Sputnik-V), as well as its lyophilized form - Gam-COVID-Vac-Lio (FSBI N.N. F. Gamaleya" of the Ministry of Health of Russia), peptide - "EpiVacCorona" (SSC VB "Vector") and whole virion - "CoviVac" (Federal State Budgetary Institution "FNTsIRIP named after M.P. Chumakov RAS"). All of these vaccines are being intensively studied in post-registration clinical trials.
However, the use of vaccines in patients with immunoinflammatory rheumatic diseases (IRIRD) raises a number of questions related to the effectiveness and safety of vaccination, especially in patients receiving treatment with immunosuppressive drugs. Currently, it remains unclear how long protective immunity lasts after infection and vaccination against SARS-CoV-2.
As with all vaccines that have undergone strictly controlled trials and licensing processes, the benefit of immunization against COVID-19 (preventing or reducing the severity of infection) is expected to significantly outweigh any risk associated with vaccination. Please note that there is currently no data obtained from large clinical studies examining the effectiveness, immunogenicity and safety of vaccines against SARS-CoV-2 in patients with IVRD, both in Russia and around the world.
In accordance with the recommendations of the Association of Rheumatologists of Russia*, we currently consider it necessary to adhere to the following principles:
- During the COVID-19 pandemic, in the absence of contraindications, all patients with IRD and family members should be recommended to be vaccinated against influenza and pneumococcal infection in accordance with the national preventive vaccination calendar and the vaccination calendar for epidemic indications.
- After vaccination against SARS-CoV-2, patients with IRD and their families should continue to follow all recommendations regarding the prevention of COVID-19 (social distancing, wearing masks, hand hygiene, etc.).
- Vaccination is recommended against the background of low activity or remission of IVRD, optimally 4 weeks before the start of treatment with drugs with expected immunosuppressive activity and the mandatory obtaining of the patient's informed voluntary consent.
- Patients with a history of drug allergies or suffering from diseases in which there is a high risk of drug allergies or idiosyncrasies (systemic lupus erythematosus, etc.) should be observed for at least 150 minutes after vaccination.
- Given the lack of reliable data on the relationship between the effectiveness of vaccination and anti-SARS-CoV-2 titers, the determination of antibodies over time is not mandatory, although in the future it may be important for assessing the severity of herd immunity.
- In patients with IVRD receiving glucocorticoids, it is recommended to reduce their dose to <10 mg/day if possible.
- In patients with IVRD receiving immunosuppressive therapy, it is recommended to adhere to the following principles regarding therapeutic tactics:
- methotrexate: discontinue the drug for 2 weeks after each vaccination procedure;
- targeted synthetic disease-modifying anti-inflammatory drugs (Janus kinase inhibitors), mycophenolate mofetil, cyclophosphamide: skip the drug for 1 week after each dose of the vaccine;
- abatacept for subcutaneous administration: skip the drug for 1 week before and 1 week after the first dose of the vaccine, 2nd dose - unchanged;
- abatacept for intravenous administration: skip the drug for 4 weeks before and 1 week after the first dose of the vaccine, 2nd dose - unchanged;
- rituximab: start vaccination 12 weeks (minimum) – 6 months (optimally) from the last drug administration and 4 weeks before the upcoming infusion.
The issue of temporary withdrawal of immunosuppressive therapy in connection with vaccination is strongly recommended to be discussed in advance in each specific case!11
8. In patients receiving intravenous pulse therapy with cyclophosphamide and glucocorticoids, vaccination should be performed before infusions or no earlier than 1 month after the planned infusion.
* Nasonov EL, Lila AM, Mazurov VI, Belov BS, Karateev AE, Dubinina TV, Nikitinskaya OA, Baranov AA, Abdulganieva DI, Moiseev SV, Zagrebneva AI, on behalf of the presidium of the All-Russian public organization “Association of Rheumatologists of Russia”. Coronavirus disease 2021 (COVID-19) and immunoinflammatory rheumatic diseases. Recommendations of the All-Russian public organization “Association of Rheumatologists of Russia”. Scientific and practical rheumatology. 2021;59(3):239–254.
| #information for doctors #vaccination #covid-19 |
Discussion
Based on the data presented in our work, a number of preliminary conclusions can be made:
some patients with a history of coronavirus infection may experience inflammatory changes in the joints;
post-Covid joint lesions most often occur in patients who have had a mild or asymptomatic coronavirus infection (presumably this is the effect of an unrealized “cytokine storm”); due to the fact that patients with post-Covid arthritis had a history of injuries or diseases of the affected joints, persons suffering from osteoarthritis, rheumatic diseases, as well as trauma patients may be included in the risk group for the development of this complication of coronavirus infection;
no clear relationship between the occurrence of post-Covid arthritis and age has been identified, and the predominance of female patients corresponds to the daily statistics of visits to the orthopedic office;
Post-Covid arthritis in the vast majority of cases is inert to traditional NSAID therapy;
preliminary data indicate that laboratory and instrumental diagnostics do not improve the prognosis of post-Covid arthritis and do not affect the effectiveness of treatment;
An effective initial treatment for post-Covid inflammatory joint lesions is the administration of betamethasone in a dose of 1 ml intramuscularly once;
the indication for prescribing betamethasone intramuscularly as the main starting drug for the relief of arthritis should be considered a coronavirus infection suffered by the patient, so doctors need to carefully collect anamnesis;
It is advisable to treat post-Covid arthritis in several stages. After relief of the main symptoms of inflammation, an individual selection of a course of treatment is necessary, including symptom-modifying and symptomatic drugs, as well as rehabilitation measures. Similar measures were carried out for all our patients (the results of their use were not the subject of this publication).
In general, our experience allows us to talk about the presence of post-Covid complications in the joints, despite the fact that this issue has not yet been properly reflected in the literature and there is no clear understanding of the cause-and-effect relationships. Trigger coronavirus infection and inflammatory changes in the joints can be considered as “major” diagnostic criteria for reactive arthritis [7, 8], because, according to the definition, reactive arthritis is an immunoinflammatory lesion of the joints against the background of an infectious process [9], which is based on the development of hyperimmune response to an agent located intra- or extra-articularly [10]. It is necessary to study the correlation between the occurrence of post-Covid arthritis and the severity of coronavirus infection, since in our observations, patients often suffered from it asymptomatically or in a mild form. This may be due to the fact that patients with a more severe course of coronavirus infection already received GCS as part of complex treatment.