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The "three-body" problem of lupus and infection, strive to master the balance between immunity, infection and drug treatment~
Recently, the 9th International Forum on Pediatric Rheumatology Immunization and the 15th National Study Class on Pediatric Rheumatic Immune Diseases were held online
.
At the meeting, Professor Ye Shuang, Director of the Department of Rheumatology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, discussed "lupus and infection"
.
Systemic lupus erythematosus (SLE) and infection is an extremely complex trisomy problem that has puzzled many clinicians, covering etiology, host immunity, and pharmacologic therapies
that affect the immune system.
This article sorts out the content of the conference and shares the academic feast
with you.
What are the characteristics of infection in patients with SLE? Studies have shown that the incidence of serious infections and infection-related mortality in newly diagnosed SLE patients increased by 82% and 61%,
respectively, compared with the control non-SLE population.
So, what is the link between new-onset SLE and infection? What is the risk of infection in these patients? To address these issues, Prof.
Ye Shuang's team established an observational cohort of nascent SLE that included 494 patients diagnosed with SLE in the rheumatology department of Renji Hospital, with a duration of less than three months and admitted to the hospital [1].
The study found that in the first year of follow-up, 67 (14%) patients had 69 major infectious events, and these infections occurred almost within four months
of enrollment.
The most common infection was pneumonia (67%), followed by bacteremia (26%), skin and soft tissue infections (10%), and the main microorganisms that cause infection events are bacteria (58%), fungi (20%), and viruses (15%)
.
Multiple regression analysis after adjustment of glucocorticoid and immunosuppressant exposure showed that disease activity, hypolymphocytemia, and organ injury were high-risk factors for major infections in the first four months [1].
Professor Ye Shuang shared: "For new-onset active SLE, immune disorders cause susceptibility to infectious factors, and some specific indicators, such as hypolymphocytic and organ damage, are relatively independent risk factors
.
In clinical work, we can use this to carry out targeted infection prevention and control measures
for such patients.
So for patients with acute and severe SLE, what characteristics do they have and what kind of prognosis will they have? Professor Ye Shuang's team included 130 patients
with SLE with invasive infection admitted to the emergency department.
Statistically, age, hypolymphocytemia, blood urea nitrogen, and hormones (> 60 mg/day) were independent predictors of all-cause mortality, and the use of hydroxychloroquine was its protective factor [2].
Professor Ye Shuang pointed out that based on the above characteristics, patients with different risk factors can be reasonably triaged to achieve more efficient and accurate follow-up diagnosis and treatment, so as to improve the final prognosis
of patients.
Virus, disease activity and immunity - since the complex trisomy problem mentions infection, everyone must also think of the new crown
that has lasted for more than two years.
In April 2022, when the epidemic broke out in Shanghai, the south campus of Renji Hospital was recruited as a designated hospital for new crown patients, and Professor Ye Shuang led the team to supervise a critical ward, including patients
with SLE and new crown.
Professor Ye Shuang used a newly approved small molecule drug Paxlovid and found that immunocompromised patients had a much
longer virus elimination time than non-immunocompromised patients.
Moreover, the antiviral effect of Paxlovid has a linear relationship with time, that is, the early drive virus clearance, the shorter the time required for virus clearance [3].
How does infection with other viruses affect SLE patients? Professor Ye Shuang found that in the outpatient setting, two-thirds of shingles infections occur in patients with SLE in a state
of low disease activity.
SLE activity may be exacerbated by shingles infection, leading to an increased
risk of SLE recurrence.
The complex trisomy problem of SLE and infection covers both the susceptibility of SLE patients to infection in a high-mobility state and the fact that specific infections may in turn induce increased
SLE mobility.
In addition, immunotherapy may impair the body's ability to fight infection, which can worsen infection in patients [4].
Here, Professor Ye Shuang shared the optimization strategies for the prevention and treatment of SLE infection:
1.
Avoid "pan-immunosuppression" (reducing hormones), and precise targeted therapy is the general direction;
2.
Focus on the establishment of SLE immune homeostasis: "additional benefit" of reducing the risk of infection;
3.
Rebuilding immune defense, mainly including "correction" and prevention
.
Metformin reduces the risk of infection in SLE patients, how to prevent SLE infection in all aspects? In this context, how to develop a diagnosis and treatment plan for SLE? In clinical work, Professor Ye Shuang found that metformin, as a metabolic modulator, can be used as a secondary prevention means to reduce the possibility
of subsequent SLE recurrence in SLE patients at risk of recurrence.
They then conducted a randomized controlled trial of SLE patients who had had at least one recurrence of SLE within 12 months, divided into metformin and control
.
In the metformin group, there was a significant decrease in infection events, with a statistically significant reduction in the risk of infection by approximately 40 percent over 12 months [5].
Professor Ye Shuang pointed out that this result suggests that if the condition of SLE patients is more stable, the risk of co-infection of SLE patients may also be reduced
.
Clinically, a full range of preventive measures should be achieved in response to infection: 1.
Preventive treatment for high-risk patients:
high-risk patients with prophylactic antibiotics (such as SMZ-CO), and the dose of
immunosuppressive drugs should be adjusted in time during treatment.
In severe infection, immunosuppressive drugs
should be discontinued.
2.
Patient education: environmental cleaning and disinfection; Shortening the length of hospital stay; Improve the hospital sense system; hygienic and aseptic operation; nutritional support; Skin and oral care
.
3.
Get vaccinated
.
EULAR recommends vaccination for patients with SLE and strongly recommends influenza and streptococcal vaccines (PCV13 and PPSV23), with particular emphasis on stable disease
.
In addition, attention should also be paid to improving the vaccination
of shingles vaccine and new crown vaccine.
Summary:
1.
SLE and infection are a very complex trisomy problem, and the three interact
.
SLE activity may be a concomitant susceptibility state, and specific infections may exacerbate SLE activity, which is related
to age, host, disease status, involvement of specific organs, and drug exposure.
2.
In terms of prevention and control, it is necessary to avoid generalized immune support and advocate precise targeting
.
Stabilisers of disease may have additional benefit
in terms of infection.
3.
In addition, promote the immune systemCorrection and active immunity support the patient's normal immune defense system
from patient education, vaccination, preventive treatment, etc.
Expert profile
Professor Ye Shuang Renji
Hospital affiliated to Shanghai Jiao Tong University School of Medicine
Director of the Department of Rheumatology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, M.
D.
, Chief PhysicianMember of the Chinese Society of Rheumatology and the Rheumatology Branch of the Chinese Medical Doctor Association
Member of the Standing Committee of the Rheumatology and Immunology Branch of the Chinese Association for the Promotion of Medical Care
Member of the Standing Committee of the ILD Multidisciplinary Committee of the Chinese Association of Research Hospitals
Vice Chairman of the Rheumatology and Immunology Branch of the Chinese Geriatric Health Care Research Association
Vice President of the Internal Medicine Branch of Shanghai Medical Doctor Association
Head of Shanghai Shenkang Municipal Hospital Rheumatology Specialist Alliance
Member of
Internal Medicine Branch and Rheumatology Branch of Shanghai Medical Association.He has published more than 70 SCI papers including NEJM, Lancet ID, Lancet Rheumatology, ARD, A&R, and won the title of
Shanghai Medical Artisan.
References:
[1] Wang H,Zhou Y,Yu L,et al.
Major infections in newly diagnosed systemic lupus erythematosus:an inception cohort study[J].
Lupus Sci Med,2022,9(1).
DOI:10.
1136/lupus-2022-000725.
[2] Wu W,Ma J,Zhou Y,et al.
Mortality risk prediction in lupus patients complicated with invasive infection in the emergency department:LUPHAS score[J].
Ther Adv Musculoskelet Dis,2019,11:1759720X-19885559X.
DOI:10.
1177/1759720X19885559.
[3] Sun F,Lin Y,Wang X,et al.
Paxlovid in patients who are immunocompromised and hospitalised with SARS-CoV-2 infection[J].
Lancet Infect Dis,2022,22(9):1279.
DOI:10.
1016/S1473-3099(22)00430-3.
[4] Sun F,Chen Y,Wu W,et al.
Varicella zoster virus infections increase the risk of disease flares in patients with SLE:a matched cohort study[J].
Lupus Sci Med,2019,6(1):e339.
DOI:10.
1136/lupus-2019-000339.
[5] Sun F,Geng S,Wang H,et al.
Effects of metformin on disease flares in patients with systemic lupus erythematosus:post hoc analyses from two randomised trials[J].
Lupus Sci Med,2020,7(1).
DOI:10.
1136/lupus-2020-000429.
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