Introduction
Opportunistic and chronic infections, which occur more frequently or with greater severity in immunocompromised individuals, are commonly encountered in patients with autoimmune inflammatory rheumatic diseases (AIIRD) and are often associated with the immunosuppressive and immunomodulatory therapies used to treat these conditions. Although the importance of appropriate screening and prophylactic measures is well recognised, clinical practice remains heterogeneous, and relevant recommendations are often lacking or dispersed across the literature.1 In 2022, EULAR developed recommendations for screening and prophylaxis of chronic and opportunistic infections in adults with AIIRD, produced by an international Task Force of 22 members from 15 countries and informed by a systematic literature review (SLR).¹,² Complementary guidance has been produced regionally, including recommendations from the Spanish Society of Rheumatology (SER) on infection prevention in systemic autoimmune rheumatic diseases (SARD)³ and an Emirati Delphi consensus addressing both adult and pediatric AIIRD populations.⁴ More recently, the evolving treatment landscape, particularly the introduction of Janus kinase (JAK) inhibitors and other targeted therapies, has prompted renewed attention to opportunistic infection risk, including herpes zoster (HZ).⁵
Overarching principles and framework
EULAR’s recommendations comprise four overarching principles and eight recommendations, developed by Task Force consensus.¹ The principles state that the risk of chronic and opportunistic infections should be considered and discussed with all patients with AIIRD prior to treatment with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), targeted synthetic (ts)DMARDs, biological (b)DMARDs, immunosuppressants and/or glucocorticoids, and reassessed periodically.¹ Collaboration between rheumatologists and other specialists, including infectious disease (ID) physicians, gastroenterologists, hepatologists and pulmonologists, is considered important, and individual risk factors as well as national guidelines and region-specific factors relating to endemic infections should inform decisions.¹ Antirheumatic drugs were categorised into four groups for this purpose: bDMARDs/tsDMARDs (except apremilast); csDMARDs (methotrexate and leflunomide, with sulfasalazine and hydroxychloroquine excluded owing to their mild immunomodulatory effect); other immunosuppressants (cyclophosphamide, mycophenolate mofetil, azathioprine, ciclosporin and tacrolimus); and glucocorticoids.¹ The Emirati consensus also emphasises the importance of infection screening and vaccination in AIIRD, with its overarching statement receiving 94% agreement among the expert panel.⁴
The EULAR recommendations were informed by an SLR spanning inception to December 2021, searching PubMed, Embase and Cochrane Library, and excluding studies on postoperative infections, paediatric AIIRD, COVID-19, vaccination and non-English literature; of 5,641 studies retrieved, 568 full-text articles were assessed, and 194 were included.² SER has separately produced recommendations for infection prevention in SARD,³ and the Emirati Delphi consensus, developed by a UAE task force and adapted in part from EULAR and American College of Rheumatology guidance, structures its statements into nine areas of infection screening (23 sub-statements) and seven vaccination statements.⁴
Tuberculosis Screening
EULAR recommends screening for latent tuberculosis (TB) prior to starting bDMARDs or tsDMARDs, and considers screening in patients at increased risk of latent TB before starting csDMARDs, immunosuppressants and/or glucocorticoids, according to dose and duration.¹ EULAR’s recommendations further state that screening should follow national and/or international guidelines and would typically include a chest X-ray and interferon-gamma release assay (IGRA), with IGRA preferred over tuberculin skin test (TST) where available.¹ Choice and timing of latent TB therapy should likewise be guided by national and/or international guidelines, with attention to interactions with drugs commonly used to treat AIIRD.¹ The SLR underpinning these recommendations found that IGRA performs better than TST, is less affected by glucocorticoid or csDMARD treatment or by prior BCG vaccination, and that agreement between TST and IGRA is moderate to low.²
The Emirati consensus independently reaches the same position: latent TB screening is recommended before bDMARDs/tsDMARDs (100% agreement) and considered before csDMARDs based on clinical assessment and individual risk factors (100% agreement).⁴ For glucocorticoids, screening should be considered particularly for patients likely to receive at least 20 mg/day prednisolone (or equivalent) for more than 2–4 weeks (86% agreement), with decisions for lower doses (7.5–20 mg/day for under three months) left to physician judgement (89% agreement); physicians are advised not to start treatment before screening results are available (83% agreement).⁴ The consensus also specifies chest X-ray plus IGRA as the typical screening approach (100% agreement), with IGRA preferred over TST (100% agreement).⁴ On the question of how often screening should be repeated, the consensus explicitly states that no consensus or robust data exist on optimal re-screening frequency, a position that itself received 89% agreement; testing should instead be individualised according to clinical judgement and any change in the patient’s condition.⁴ It also notes recognised age-related limitations of IGRA testing in children below 3–5 years, warranting ID referral (78% agreement).⁴ When latent TB infection is diagnosed following evaluation of a positive IGRA result, referral to an ID specialist or pulmonologist is advised, and biological treatment may be initiated four weeks after starting TB therapy.⁴
Hepatitis B
EULAR recommends that all patients being considered for csDMARDs, bDMARDs, tsDMARDs, immunosuppressants and glucocorticoids should be screened for hepatitis B virus (HBV), with HBV antiviral treatment guided by HBV status defined prior to starting antirheumatic drugs.¹ The SLR found that the risk of reactivation is increased in patients positive for hepatitis B surface antigen (HBsAg); such patients should be referred for antiviral treatment, most commonly lamivudine, entecavir or tenofovir, particularly when bDMARDs are used.² Patients positive for antibody against HBV core antigen (anti-HBcore) are considered at low risk of reactivation, though not free of risk, and should be monitored periodically with liver function tests (LFTs) and/or HBV-DNA viral load, with prophylaxis irrespective of these results possibly considered in patients treated with rituximab; high titres of anti-HBs appear protective against reactivation. ²
The Emirati consensus specifies that all patients considered for bDMARDs, tsDMARDs, immunosuppressants and glucocorticoids (≥20 mg/day prednisolone equivalent for more than 2–4 weeks) should be screened for HBV (85% agreement), with the risk of reactivation before csDMARDs assessed case-by-case.⁴ Typical screening comprises HBsAg, anti-HBcore and anti-HBs, from which HBV status is classified as unexposed, vaccinated, carrier (HBsAg-positive) or resolved (anti-HBcore-positive/HBsAg-negative), established before initiating AIIRD treatment.⁴ Where antiviral therapy is indicated, the consensus states it should ideally begin before, or at least simultaneously with, AIIRD treatment and continue for at least 6–12 months after discontinuation of antirheumatic treatment.⁴ Data on the optimal frequency of periodic re-screening for reactivation in adults are lacking, so testing should be individualised according to risk factors and cost, with hepatology referral also recommended; in children, periodic re-testing after baseline screening is not generally repeated unless clinically indicated (e.g., after blood transfusion, abnormal liver enzymes, or
SER recommends that patients with chronic HBV infection undergoing immunosuppressive or biological therapy, especially anti-CD20 agent or glucocorticoids (prednisone equivalent ≥20 mg/day for four weeks) receive concomitant antiviral treatment, preferably entecavir 0.5 mg/day, given the high rate of resistance to lamivudine.³ SER also addresses HBV vaccination: three doses of recombinant vaccine (20 µg purified HBsAg) is recommended for patients with SLE or Behçet’s disease during the inactive/low-activity phase without concurrent immunosuppression, extrapolated to other SARD in the absence of direct evidence.³ In immunosuppressed SARD patients, schedules using four doses and/or a higher antigen load (40 µg) should be considered, with vaccination response verified one month after completing the schedule via anti-HBs antibody levels.³ These vaccination strategies are SER-specific and should not be read as universal recommendations across all AIIRD populations.
Hepatitis C
EULAR states that screening for chronic hepatitis C should be considered prior to starting csDMARDs, bDMARDs, tsDMARDs, immunosuppressants and glucocorticoids, according to dose and duration, and that screening is recommended for patients with elevated alanine aminotransferase or known risk factors.¹ All patients positive for hepatitis-C-RNA should be referred for antiviral treatment.¹ According to the SLR, the risk of hepatitis C virus (HCV) reactivation exists but is low in patients treated with bDMARDs, and appears less common overall than HBV reactivation.² The treatment landscape for HCV has changed substantially with the development of direct-acting antivirals, although most existing reactivation studies in AIIRD predate their wide availability; treatment with bDMARDs appears relatively safe in HCV-RNA-positive patients, with only a small proportion showing increases in viral load or transaminases, while evidence for other drug categories remains more limited.²
The Emirati consensus mirrors the EULAR wording closely at the level of its overarching statement: screening should be considered before initiating csDMARDs, bDMARDs, tsDMARDs, immunosuppressants and glucocorticoids according to dose, duration and individual risk factors, and is recommended for patients with elevated alanine aminotransferase or known risk factors.⁴ Within this overarching statement, however, one sub-statement goes further and specifies that screening is mandatory before starting bDMARDs and tsDMARDs.⁴ Screening should also be done before prednisolone doses of at least 20 mg/day for more than 2–4 weeks, and on a case-by-case basis before csDMARDs.⁴ Screening comprises anti-HCV antibodies, with positive patients referred to a hepatologist or ID specialist for further testing and treatment.⁴
HIV
EULAR recommends HIV screening prior to treatment with bDMARDs, and considers screening prior to treatment with csDMARDs, tsDMARDs, immunosuppressants and glucocorticoids, according to dose and duration.¹ The Emirati consensus takes a more conservative, risk-based position overall, stating that HIV screening is considered, rather than routinely recommended, based on high-risk situations assessed by the treating physician.⁴ Within this, one-time screening via HIV-Ag (1+2) before treatment with bDMARDs and tsDMARDs is a conditional recommendation, with positive results referred to an ID specialist; no screening is recommended for paediatric populations.⁴
Varicella zoster virus
EULAR recommends that all patients starting csDMARDs, bDMARDs, tsDMARDs, immunosuppressants and/or glucocorticoids who are non-immune to varicella zoster virus (VZV) be informed about the availability of postexposure prophylaxis should they have contact with the virus.¹ The Emirati consensus reaches the same position (94% agreement) but adds that no serological screening for VZV immunity is recommended before starting these treatments.⁴ Instead, vaccination should be offered to all patients before starting tsDMARDs and bDMARDs, using the non-live recombinant subunit adjuvant zoster vaccine, and can be recommended and administered by any physician, including rheumatologists or ID specialists.⁴
The evolving treatment landscape has heightened attention to HZ risk more broadly. Newer therapies, including JAK inhibitors and the type 1 interferon receptor inhibitor anifrolumab, have been associated with an increased risk of HZ compared with other existing immunosuppressive agents used in rheumatology, adding to an already high baseline risk.⁵ The adjuvanted, non-live zoster vaccine has enabled safer immunisation in immunocompromised rheumatology patients, although recent population-based studies suggest reduced effectiveness compared with immunocompetent individuals.⁵ Glucocorticoid use remains substantial and continues to contribute to opportunistic infection risk despite advances in immunosuppressive therapy, and infection risk assessment overall requires stratification by host, disease and treatment-related factors.⁵
Pneumocystis jirovecii pneumonia prophylaxis
EULAR’s formal recommendation states that prophylaxis against Pneumocystis jirovecii pneumonia (PCP) should be considered in patients with AIIRD in whom high doses of glucocorticoids are used, especially in combination with immunosuppressants, depending on the risk–benefit ratio.¹ Both the EULAR and SLR abstracts further note that prophylaxis appears beneficial in patients treated with daily doses of more than 15–30 mg prednisolone (or equivalent) for more than 2–4 weeks.¹,² The SLR discussion adds that glucocorticoid treatment, although the exact dose/duration threshold is not well defined,appears to be a significant risk factor for PCP, and that evidence regarding prophylaxis needs for other, more geographically endemic pathogens remains insufficient.²
The Emirati consensus specifies a threshold of at least 20 mg/day prednisolone (or equivalent) for more than 2-4 weeks, particularly in combination with immunosuppressants, with the decision made according to risk–benefit ratio and physician judgement, ideally through shared discussion between rheumatologist and ID specialist.⁴ The recommended regimen is trimethoprim-sulfamethoxazole (TMP-SMX) 480 mg/day (single strength) or 960 mg three times weekly, with other alternative regimens of comparable efficacy and fewer adverse effects also available.⁴ For allergy or side effects to TMP-SMX, dapsone is the first suggested alternative, followed by atovaquone and nebulised pentamidine.⁴ The Emirati consensus identifies atovaquone as a preferred alternative to TMP-SMX in selected patients with SLE at higher risk of allergic reactions or lupus flares, and in Caucasian patients, those with lymphopenia, and those positive for anti-SSA antibodies, who face a higher risk of mixed reactions with TMP-SMX.⁴
SER separately recommends TMP-SMX prophylaxis for SARD patients treated continuously with glucocorticoids at doses ≥20 mg/day, noting that no minimum duration of glucocorticoid treatment beyond which prophylaxis is indicated has been established.³ TMP-SMX prophylaxis is also recommended, irrespective of immunosuppressive therapy, in any patient with sustained CD4+ T-cell counts below 200/mm³.³ SER recommends a TMP-SMX dose of 400/80 mg/day as the best-documented regimen for safety and efficacy, with folic acid supplementation recommended for treatment lasting longer than one month.³ The Emirati and SER dosing regimens should be read as distinct, source-specific recommendations rather than competing universal standards.
Vaccination beyond hepatitis B
SER addresses vaccination against human papillomavirus (HPV), Streptococcus pneumoniae and influenza in SARD patients. General population HPV vaccination recommendations should be followed for all SARD patients. Universal vaccination is recommended for girls, ideally at 12 years of age. Specific consideration is also given to older patients with cervical excisional treatment or WHIM syndrome, as well as individuals younger than 26 years with HIV infection, a history of prostitution, or men who have sex with men.³ In other older SARD patients, particularly those with SLE who fall outside these groups, the decision to vaccinate should be individualised according to prior and future risk of HPV exposure, and vaccination is recommended before the onset of immunosuppression and during remission or low disease activity.³
Pneumococcal vaccination is recommended for all SARD patients under the SER recommendations, immunogenicity is slightly lower than in healthy individuals, particularly in SLE, but remains sufficiently effective and safe, ideally administered before immunosuppression onset, particularly before rituximab, following a sequential strategy of a conjugate vaccine followed by a polysaccharide (non-conjugate) dose at least two months later.³ For influenza, SLE patients are recommended to receive vaccination against AH1N1, AH3N2 and influenza B strains, preferably adjuvanted, with this recommendation extended to other SARD by extrapolation; a second booster dose 3–4 weeks after the first is suggested for patients on immunosuppressive drugs or those treated with rituximab within the preceding three months.³
The Emirati consensus separately addresses vaccination through general principles and disease-specific statements covering influenza, pneumococcal disease, HPV, VZV, tetanus and COVID-19, with strong Delphi consensus reported among its expert panel.⁴
Conclusion
EULAR, the SLR informing it, SER and the Emirati consensus together outline a largely convergent, though not identical, approach to infection screening and prevention in patients with AIIRD/SARD, spanning tuberculosis, hepatitis B, hepatitis C, HIV, VZV and PCP, alongside disease- and drug-specific vaccination strategies.1,2,3,4 Where recommendations differ, these differences may reflect variations in the scope, evidence base, population, regional context and consensus methodology of the respective documents, rather than a single unified standard of care. Screening and prophylaxis decisions should account for antirheumatic drug category, glucocorticoid dose and duration, individual patient risk factors, and national or regional guidelines, with close collaboration between rheumatologists and specialists in infectious diseases, hepatology, gastroenterology and pulmonology.1,3,4 As the therapeutic landscape continues to evolve, most notably with newer agents such as JAK inhibitors and anifrolumab being associated with HZ risk, ongoing reassessment of opportunistic infection risk and the effectiveness of preventative vaccines and prophylactic regimens remains an important component of caring for patients with AIIRD.⁵
Given the absence of clearly established India-specific recommendations, there is a need for nationally relevant guidance on infection screening and prevention in patients with AIIRD, potentially developed through the national rheumatology association.
Reference list
- Fragoulis GE, Nikiphorou E, Dey M, Zhao SS, Courvoisier DS, Arnaud L, et al. 2022 EULAR recommendations for screening and prophylaxis of chronic and opportunistic infections in adults with autoimmune inflammatory rheumatic diseases. Ann Rheum Dis. 2023 Jun;82(6):742–753.
- Fragoulis GE, Dey M, Zhao S, Schoones J, Courvoisier D, Galloway J, Hyrich KL, Nikiphorou E. Systematic literature review informing the 2022 EULAR recommendations for screening and prophylaxis of chronic and opportunistic infections in adults with autoimmune inflammatory rheumatic diseases. RMD Open. 2022 Nov;8(2):e002726.
- Rúa-Figueroa Fernández de Larrinoa Í, Carreira PE, Brito García N, Díaz Del Campo Fontecha P, Pego Reigosa JM, Gómez Puerta JA, et al. Recommendations for prevention of infection in systemic autoimmune rheumatic diseases. Reumatol Clin (Engl Ed). 2022 Jun–Jul;18(6):317–330.
- Almarzooqi A, Abdalla J, Elsadeg MS, Zamani N, Ginawi AAG, Alrawi Z, et al. Infection Screening and Vaccination of Adult and Pediatric Patients with Autoimmune Inflammatory Rheumatic Diseases: An Emirati Delphi Consensus. Curr Rheumatol Rev. 2025;21(5):545–561.
- Yeo AL, Winthrop KL. Risk of herpes zoster and opportunistic infections with treatments for autoimmune rheumatic disease. Curr Treat Options Rheumatol. 2025;11:15.