Dr. Borja De Miguel
MADRID, ESP. “We must not forget that the main cause of mortality in patients with systemic autoimmune diseases is infections, ahead of the disease activity itself,” he commented to Medscape in Spanish Dr. Borja De Miguel Campo, specialist in internal medicine at the Autoimmune and Systemic Diseases Unit of the 12 de Octubre University Hospital in Madrid, who participated in the 44th National Congress of Internal Medicine of the Spanish Society of Internal Medicine.[1]
The clinician added that it is necessary to improve vaccine coverage for patients with autoimmune diseases with more proactive prescription.
Specifically, common bacterial infections comprise the main cause of morbidity and mortality in these patients, as confirmed, among other studies, by the large Birmingham SLE cohort with a follow-up of 21 years, 382 patients and a follow-up of 2,958 patients/year where there were 37 deaths (9.7%) and 37.8% of the causes of mortality were due to infections, followed by cardiovascular diseases (27%) and 13.5% were due to malignant diseases.
Another study presented by Dr. De Miguel on 848 participants from 17 European countries exposed the long-term episodes and survival prognostic factors that patients with antineutrophil cytoplasmic antibodies associated with vasculitis have, in which they have a high mortality compared to the general population and the therapy of complications or organ damage are the main causes of limited survival, with infection as the most important cause of mortality (26%). Furthermore, the most frequent cause of death during the first year was also by far infection (36 patients).
Infections: the worst enemy of systemic autoimmune diseases
Likewise, the expert illustrated his presentation with another Latin American study that shows poor flu and pneumococcus vaccination coverage in 1,130 patients with systemic lupus erythematosus treated with immunosuppressants. There is a low vaccination rate; As for the causes, 64% are due to lack of medical prescription, almost 13% to reactions by patients and another 11.3% to vaccine non-availability or cost. Dr. De Miguel compared it with another European study where vaccination rates for these two infectious agents were between 7% and 11% higher, although the reasons for non-vaccination are practically superimposable.
The specialist pointed out that the main factor that explains the poor vaccination coverage in these patients “is the absence of vaccine prescription by the doctors responsible for these patients.” Therefore, to improve these figures “we must carry out active training about the vaccine indications for these patients to the different professionals involved.” Likewise, it is useful to establish protocols for the implementation of vaccination both in the hospital (through the Preventive Medicine Services) and in health centers, “being the ideal moment for the diagnosis of the disease and in episodes of remission of the same”.
Proactivity to improve vaccination
Therefore, “vaccination rates for systemic autoimmune diseases can clearly be improved and we must be active in the indication of vaccines including influenza, pneumococcus, herpes zoster, hepatitis B virus and human papillomavirus.” In addition, the immunological windows must be “optimized to improve vaccine effectiveness without delaying treatment in moderate to severe cases,” added the expert.
On the other hand, the specialist reviewed the EULAR 2019 recommendations for vaccinating adults with inflammatory rheumatic autoimmune diseases, highlighting the items with the greatest consensus:[2] “They should be set annually by the rheumatologist, administered before immunosuppression; non-live vaccines can be administered to these patients, even those treated with systemic corticosteroids, and vaccinate them preferably in a non-active situation of the disease.”
Vaccinate with knowledge
Dr. De Miguel highlighted various important aspects of each of the vaccines, where for pneumococcus he highlighted the differences between the 23-valent vaccine versus the 13- and 20-serotype vaccines. “The first activates B cells without an immune response mediated by T cells, does not induce immune memory, offers a hyporesponse in revaccination and has a limited impact on nasopharyngeal colonization.” Compared to the other two that “generate a dependent T response, they do not offer hyporesponses in revaccination and reduce the nasopharyngeal carrier state.”
Regarding the human papillomavirus vaccine, another study highlights that 80% of women with systemic lupus erythematosus have infection with this virus compared to the control group (35%), therefore, “patients with this rheumatic disease should receive the human papillomavirus vaccine according to the same guidelines as the general population,” the expert added.
Regarding the hepatitis B vaccine, he showed data from a study on its efficacy and safety in patients with seronegative autoimmune rheumatic disease who receive disease-modifying drugs or biological therapies, where it can be seen that almost 70% of the former respond with antibodies against the virus (greater than 10 mIU/ml) and up to half (50%) of patients treated with biologicals.
High expectations with tolerogenic vaccines
Finally, Dr. De Miguel addressed the issue of tolerogenic (reverse) vaccines that may represent a therapeutic weapon in the near future for systemic autoimmune diseases. In a simplified way, he explained that these vaccines consist of administering to the patient nanoparticles with antigens of pathophysiological interest in the autoimmune entity that is desired to be treated. These nanoparticles will be recognized by the antigen-presenting cells, generating immunological tolerance in the regulatory CD4+ T cells, thereby “reducing both the autoimmune attack of the autoreactive cells against the aforementioned antigen and the phenomenon of epitope dissemination ( which under normal conditions entails an amplification of the immune response, both for that antigen and for other related ones)”.
Coronavirus: trigger of autoimmune diseases
Dr. Iván Cusacovich, from the Valladolid University Clinical Hospital, addressed the topic of autoimmune diseases in relation to COVID-19.[3] “SARS-CoV-2 infection can activate the immune system, acting as a trigger for autoimmune diseases.” The viral infection itself produces a systemic inflammatory reaction in which the release of cytokines and, above all, endothelial damage predominates, which explains microthrombosis.
A review of Frontiers in immunology details various rheumatic and autoimmune manifestations associated with COVID-19 in adults, including: organ vasculitis, reactive arthritis, flares of previous antiphospholipid antibody syndrome, Kawashaki disease, myocarditis, reactivation of rheumatoid arthritis, Schonlein-Henoch, cases of systemic lupus erythematosus, myositis, spondylitis, etc.
Another review shows that the vaccine against SARS-CoV-2 also “contains molecular mimicry, with its own inflammatory reaction and the consequent production of antibodies, as well as an effect of the adjuvants themselves, which through the inflammasome can trigger autoimmune phenomena,” he added.[4]
Dr. Cusacovich also exposed a series of new autoimmune phenomena that can occur after vaccination, such as: immune thrombocytopenic purpura; Guillain-Barré syndrome, immunoglobulin A nephropathy, autoimmune liver diseases and arthritis, among others.[5]
Differential diagnosis with persistent COVID-19
Regarding thrombotic thrombocytopenia associated with the vaccine, Dr. Cusacovich pointed out that “it can occur exceptionally and is mediated by antiplatelet factor 4 antibodies and appears in the month after vaccination.” It causes thrombosis in unusual territories, such as the cerebral vein, the splanchnic vein, and pulmonary thromboembolism with pulmonary microthrombosis, without forgetting that “this condition has a high mortality and is treated with corticosteroids and intravenous immunoglobulin.”
He also commented on the differential diagnosis between persistent COVID-19 and systemic autoimmune diseases, where he explained that “the former begins after infection and lasts weeks or months; on the contrary, systemic autoimmune diseases maintain chronic symptoms for years, have specific immunological markers and respond to a specific specific treatment.
Dr. Cusacovich highlighted some similarities between the chikungunya and COVID-19: “Both have an acute infection and another subacute/chronic phase in a biphasic manner, in both there are joint and neurological symptoms that are defined as mental fog.”
Regarding COVID-19 and treatment with rituximab indicated that this drug prevents the formation of antibodies against SARS-CoV-2 and memory B cells.
The cellular response is good but insufficient and causes a low humoral response to the vaccine. “In short, mortality from the infection increases, which must be treated with a mixture of antivirals, monoclonal antibodies, and immunosuppressants that stop the inflammatory response caused by the virus,” concluded the specialist.
Doctors De Miguel and Cusacovich have declared that they have no relevant financial conflicts of interest.
2023-12-26 18:28:15
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