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4 principles + 8 recommendations
Opportunistic and chronic infections, i.
e.
infections that are more common or more severe in immunocompromised people, are encountered in patients with autoimmune inflammatory rheumatism (AIIRD) and are often associated with
immunosuppression and immunomodulatory therapy.
Although it is recognized that screening procedures and precautions should be followed, clinical practice is largely heterogeneous
.
Recently, the European Union Against Rheumatism (EULAR) has developed the first guidelines for the screening and prevention of chronic and opportunistic infections in patients with AIIRD to serve as a reference
for routine clinical practice.
Figure 1: Screenshot of the guide
4 general principles
1.
Before using traditional synthetic disease-modifying antirheumatic drugs (csDMARDs), targeted synthetic DMARDs (tsDMARDs), biologic DMARDs (bDMARDs), immunosuppressants, and/or glucocorticoid therapy, the risk of chronic and opportunistic infections should be discussed with all patients with AIIRD and reassessed
regularly.
- Risks, including how to minimize them, should be explained and discussed with patients with AIIRD
. - The link between
disease activity and increased infection rates should be considered. - These patients should be educated on timely recognition of signs and symptoms of infection and on how to seek relevant medical care
.
2.
Cooperation between rheumatologists and other physicians is very important, including but not limited to infectious disease doctors, gastroenterologists, hepatologists and respiratory doctors
.
Given that tuberculosis and hepatitis are among the most common infections in people with AIIRD, it is important
to work as a team with respiratory doctors and hepatologists/gastroenterologists.
Others, including infectious diseases, radiologists, haematologists and microbiologists, also play a key role
in guiding the screening and prevention of chronic and opportunistic infections in patients with AIIRD.
3.
Individual risk factors should be considered in the screening and prevention of chronic and opportunistic infections, and reassessed
regularly.
Several factors are known to increase susceptibility to specific preventable infections, including age, comorbidities (e.
g.
, lung disease), combination therapy with other medications, and travel life history
in endemic areas.
Given the variability of these factors, the presence of
risk factors for chronic and opportunistic infection should be regularly reassessed.
4.
In addition to other national/regional factors related to endemic infectious diseases, national guidelines and recommendations
should also be considered.
The Working Group was of the view that the strategies adopted by different countries/regions varied considerably
.
TB is more prevalent in specific parts of the world, and drug resistance to Mycobacterium tuberculosis varies from country to country, reflecting the need for different regimens/strategies to prevent recurrence
of latent TB infection.
8 recommendations
1.
Before starting bDMARDs or tsDMARDs, it is recommended to screen patients for latent tuberculosis infection
.
Screening
should also be considered in patients at increased risk of latent TB infection before initiating csDMARDs, immunosuppressants, and/or glucocorticoids (depending on dose and duration).
- Patients with AIIRD who are receiving csDMARDs and/or glucocorticoids also increase the risk of
potential TB recurrence. - Particular consideration should be given to screening
patients receiving prednisone (or equivalent) >15 mg/day over a longer period of time (> 4 weeks). - Screening for latent TB infection in patients with TB risk factors, including alcoholism, smoking, living with a person with TB, and living in endemic countries and other regions
, should be considered before initiating treatment with bDMARDs, tsDMARDs, csDMARDs, and/or glucocorticoids.
2.
Screening for latent TB infection should follow national or/international guidelines and usually include chest x-ray and interferon γ release test, and if possible, tuberculin skin test
.
In diagnosing latent TB infection, γ interferon release test is better than tuberculin skin test, which is less
affected by glucocorticoids, DMARDs, or immunosuppressant therapy.
Therefore γ interferon release test is more suitable for tuberculosis screening
.
Chest x-ray screening for tuberculosis is feasible
if γ interferon release test or tuberculin skin test is negative and active or latent TB infection cannot be excluded.
3.
The selection and timing of treatment for latent TB infection should be guided
by national and/or international guidelines.
Particular attention should be paid to interactions
with drugs commonly used in the treatment of AIIRD.
- Given the recommendations for TB's burden and drug resistance by region/country, the guidelines recommend following relevant national guidelines
. - In patients treated with a combination of isoniazid and hepatotoxic drugs such as methotrexate and leflunomide, monitoring of liver function tests is necessary
. - Combined drug therapy with rifampicin may affect the pharmacokinetics
of JAK inhibitors and glucocorticoids.
4.
All patients considering treatment with csDMARDs, bDMARDs, tsDMARDs, immunosuppressants, and glucocorticoids (according to dose and duration) should be screened for HBV
.
- The risk of HBV reactivation depends on HBV status [unexposed, vaccinated, carrier (i.
e.
, HBsAg-positive)) and HBV recovery (anti-HBcore-positive and HBsAg-negative), which should be determined
before starting treatment for AIIRD.
HBV status can also help identify at-risk patients (e.
g.
, determining who should be vaccinated based on occupation).
Figure 2: Screening for HBsAg, anti-HBcore, and anti-HBs HBsAg-positive
patients (HBV carriers) may benefit from prophylaxis and referral to a hepatologist for antiviral prophylaxis
is recommended.
For patients who are anti-HBcore-positive and HBsAg-negative (hepatitis B rehabilitation), HBV-DNA and liver function tests are recommended at baseline, followed by regular monitoring
.
If hepatitis B virus reactivation is suspected, referral to a hepatologist for antiviral therapy
is recommended.
For high-risk patients (e.
g.
, starting anti-CD20 regimens), prophylactic therapy may be considered rather than monitoring HBV-DNA levels
.
- People living with HBV will benefit from prophylaxis and are therefore advised to refer to a hepatology unit for antiviral prophylaxis
. - Corticosteroids increase the risk of
HBV reactivation.
Patients receiving ≥ 10 mg/day prednisone or equivalent hormone therapy for 4 weeks are considered to be at high risk for
HBV reactivation. - For patients who have recovered from HBV (anti-HBcore-positive and HBsAg-negative), the risk of HBV reactivation is low
. - Baseline measurements of liver function and HBV-DNA levels are recommended, followed by periodic (eg, every 3 to 6 months) measurement of liver function and HBV-DNA levels, and comprehensive prophylaxis
. - In particular, patients receiving rituximab, regardless of HBV-DNA level, should be referred to a hepatology department for consideration of prophylactic therapy
.
5.
It is recommended that patients should be considered for chronic hepatitis C screening
before starting csDMARDs, bDMARDs, tsDMARDs, immunosuppressants, and glucocorticoids (depending on dose and duration).
Screening
is recommended in patients with elevated alanine aminotransferase (ALT) or known risk factors.
- Given cost-effectiveness and geographic variation, the threshold for screening should be lower, particularly ALT
, for patients with comorbid risk factors for hepatitis C (e.
g.
, intravenous medication) and/or abnormal liver function. - HCV screening involves anti-HCV antibodies and, if positive, measuring HCV-RNA levels
.
Antiviral therapy
should be considered in patients with detectable HCV-RNA.
6.
HIV screening is recommended prior to treatment with bDMARDs, and should be considered
before treatment with csDMARDs, tsDMARDs, immunosuppressants, and glucocorticoids (according to dose and duration).
7.
All patients starting csDMARDs, bDMARDs, tsDMARDs, immunosuppressants and glucocorticoids (according to dose and duration) who are not immune to varicella-zoster virus (VZV) should be informed of precautions
after exposure to VZV.
8.
In patients with AIIRD who use high-dose glucocorticoids, the prevention of Pneumocystis carinii pneumonia (PCP) should be considered, especially when
combined with immunosuppressants.
- Although the minimum dose and duration of glucocorticoid therapy currently recommended for prophylaxis are not defined, there is evidence that a daily dose > 15 to 30 mg of prednisone or equivalent hormone therapy > 2 to 4 weeks is beneficial
in preventing PCP. - The combination of immunosuppressants with glucocorticoids increases the risk of
PCP. - Advanced age and prior lung disease are also risk factors
for PCP. - The most commonly used prophylaxis for PCP is trimethoprim pyrimidine/combination sulfamethoxazole (TMP/SMZ) 480 mg/day (single dose) or 960 mg/tiw
.
small
knot
This is EULAR's first set of recommendations
for screening and prevention of chronic and opportunistic infections in AIIRD.
Based on treatment, geography and other differences, four overarching principles and eight recommendations
are proposed.
These recommendations provide guidance
for screening and prevention of chronic and opportunistic infections.
These recommendations are recommended in clinical practice to standardize and optimize care to reduce the burden
of infection in patients with AIIRD.
References:
[1] Fragoulis G E,Nikiphorou E,Dey M,et al.
2022 EULAR recommendations for screening and prophylaxis of chronic and opportunistic infections in adults with autoimmune inflammatory rheumatic diseases[J].
Ann Rheum Dis,2022.
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