Review Rheumatological Patients Undergoing Immunosuppressive
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Review Rheumatological patients undergoing immunosuppressive treatments and parasitic diseases: a review of the literature of clinical cases and perspectives to screen and follow-up active and latent chronic infections S. Fabiani and F. Bruschi Department of Translational Research ABSTRACT Conclusions. Considering parasitic in- and New Technologies in Medicine and Objective. Nowadays, several po- fections as emerging and potentially se- Surgery, School of Infectious Diseases, tent immunosuppressive drugs are rious in their evolution, additional strat- Università di Pisa, Pisa, Italy available for patients with rheumato- egies for the prevention, careful screen- Silvia Fabiani, MD logic disorders. In general, these treat- ing and follow-up, with a high level of Fabrizio Bruschi, MD ments are acceptably well tolerated. suspicion, identification, and pre-emp- Please address correspondence to: Nevertheless, in patients with rheu- tive therapy are necessary in candidate Fabrizio Bruschi, matic diseases, who are taking immu- patients for biological agents. Scuola Medica, Via Roma 55, nosuppressive drugs, an increased risk 56126 Pisa, Italy. of bacterial, viral and fungal, as well Introduction E-mail: [email protected] as parasitic infections, exists. Rationale Received on October 14, 2013; accepted Methods. We have reviewed literature, Immunosuppressive drugs, other than in revised form on February 18, 2014. on PubMed library, on the topic “par- corticosteroids (CS), are used in the Clin Exp Rheumatol 2014; 32: 587-596. asitic infections in rheumatic disease treatment of various rheumatologic con- © Copyright CLINICAL AND patients treated with immunosuppres- ditions to induce or maintain a remis- EXPERIMENTAL RHEUMATOLOGY 2014. sive drugs, including biological thera- sion, to reduce the frequency of flare pies”. We used no language or time or relapse, and to guarantee disease Key words: rheumatic diseases, restrictions. Search was concluded on control. In particular, treatment options immunosuppressive therapies, January 15th 2014. We grouped all have been substantially improved in parasitic infections, parasitic screening parasitic events among rheumatologic, recent years thanks to the introduction flow-chart therapeutically immuosuppressed, pa- of disease-modifying anti-rheumatic tients to estimate the magnitude of this drugs (DMARDs), including drug-in- risk. Then we gave our viewpoint in the hibiting cytokines, such as, for example, perspective to screen and follow-up for TNF-alpha antagonists, and/or block- active and latent chronic parasitoses, ing cytokine receptors (i.e. tocilizumab developing an hypothetical flow-chart. (TCZ), a monoclonal antibody blocking Results. From data published in the the interleukin-6 receptor). In general, literature the real burden of parasi- these therapies seem to be acceptably toses, among patients with rheumatic well tolerated, however, taking into ac- diseases treated with immunosuppres- count the increased risk of infections, sive treatments, can not be estimated. the situation is less optimistic, especial- Nevertheless, a positive trend on pub- ly for patients treated with anti-TNF- lication number exists, probably due to alpha drugs (i.e. monoclonal antibodies, more than one reason: i) the increasing such as infliximab (IFX) and adalimum- number of patients treated, especially ab (ADA), soluble TNF-alpha recep- with more than one immunosuppres- tors, like etanercept (ETN), and others, sive treatment, including new biologi- certolizumab-pegol (CZP), golimumab cal agents; ii) the increasing number of (GLM), anakinra (ANA), and abatacept individuals who move from the north to (ABT) (1-14), probably because of the the south of the world (endemic areas inhibition of this crucial molecule that for parasitic infections) and viceversa, has a key role in the early phase of the due to globalisation, and iii) the fact host defense against bacterial, viral and that more attention is paid for notifica- parasitic infections (15-17). However, Competing interests: none declared. tion/publication of cases. even data obtained before the begin- 587 REVIEW Parasitic infection screening in immunosuppressed patients / S. Fabiani & F. Bruschi ning of the TNF-alpha blockers era, showed an incidence rate of infections in the rheumatoid arthritis (RA) popula- tion nearly twice as high as in matched non-RA controls. Indeed, the risk of infections in rheumatic diseases can be explained with a combination of actions defined by the disease itself, with its perturbations of immune functions and impairment of general health (18), and the use of older different kind of drugs, too, that in general interfere with im- mune system and that are yet routinely used in these patients [i.e. methotrexate (MTX); cyclophosphamide (CTX); cy- closporine (CSA); azathioprine (AZA)] (18-20). The cumulative immunosup- pressive activity of rheumatologic treat- ments, both traditional and new drugs, Fig. 1. PRISMA flow chart: data collection and selection of studies. continues to represent one of the main factor predisposing for infections, es- exists, probably also due to the re- OR rheumatic patients AND immuno- pecially in concomitant use of CS (21), cent greater attention for notification / suppressive therapies OR biological with some variations related to the dose publication of cases, but mainly to the DMARDs OR anti-tumour necrosis and the duration of CS treatment (22). increasing number of patients treated, factor (TNF)-alpha. We used no lan- Thus, despite different mechanisms of especially with more than one immu- guage or time restrictions. The search action, and the lack of strict correlation nosuppressive treatment, including was concluded on January 15th 2014. between a specific drug and a particular new biological agents, and the advance type of infection, any immunosuppres- of the era of globalisation with more Results sive therapy can facilitate any type of and more people having contact with Study selection infection (23-27). In particular, many endemic areas for certain diseases, the We identified and screened 45 records. bacterial (28-44), viral (32, 45-49), and parasitic risk seems to be emerging in From these records we extrapolated 83 fungal (50-57) infections have been such a population. cases of interest assessed for eligibil- described among these patients. In ad- To limit the spread of this infective ity. Among these we excluded only six dition, the impact of the parasitic dis- complication in rheumatological pa- cases with concomitant manifestation eases among rheumatic disease patients tients candidate for immunosuppres- of systemic rheumatic disorders and during immunosuppressive treatments, sive agents, specific recommendations, parasitic diseases, in which no immu- including biologic therapies, is hard to based on a multidisciplinary contri- nosuppressive treatment was adminis- estimate since few reports exist in the bution and a systematic review of the tered (60, 61) (Fig. I). literature, however, recent observations literature, for screening and follow-up lead to consider parasitic infections as of active and latent chronic infections Description of results emerging in such a population (58). have to be elaborated as happened for We grouped on literature reported cas- those caused by viruses or bacteria. es of parasitic infections in rheumatic Objectives We want to give our viewpoint in the disease patients treated with immuno- With this literature review we want to perspective of a proposition to screen suppressive drugs, including biological deal with the parasitosis risk among and follow-up for parasites the patients therapies in Table I (see hereinafter). rheumatic disease patients treated with undergoing immunosuppressive treat- A positive trend, probably due to i) the immunosuppressive drugs, including ments (59). increasing number of patients treated, biological therapies. especially with more than one immu- For this purpose we analysed records Methods nosuppressive treatment, including on this topic, identified through Pub- To review case reports of parasitic in- new biological agents, ii) globalisa- Med database searching. fections on rheumatological patients tion, and finally iii) to higher attention We also grouped the clinical cases pre- in immunosuppressive treatment, and for notification/publication of cases, sented in literature to estimate if the risk analyse the magnitude of the data, we exists. First case reports of parasitoses of parasitoses among the patient catego- searched the literature on PubMed li- during anti TNF agents treatments ap- ry considered actually exists and if the brary combining the terms parasitic peared in 2003, more or less 5 years af- problem can be considered as emerging. diseases OR parasitic infections OR ter the introduction of these drugs into As a positive trend on publications parasitoses AND rheumatic diseases the clinical practice. 588 Parasitic infection screening in immunosuppressed patients / S. Fabiani & F. Bruschi REVIEW Table I. Published reported cases of parasitic infections in rheumatic disease patients treated with immunosuppressive drugs, including biologic therapies, found on PubMed (60-104). Parasitic diseases Country Pts (Age y/sex) Rheumatologic Immunosuppressive Treatment Reference of report Disease treatments (Agents) duration (mo) before onset of parasitic disease Chagas disease Brazil 43/F RA CS NA Cossermelli et al., 1978 (62) NA 1 case (y/sex NA) SLE NA NA Barousse et al., 1980 (61) NA 1 case (y/sex NA) SLE NA NA