EDITORIAL - Vaccinate your immunocompromised patients!

[Guest guest]

Rheumatology 2006 45(1):9-10; doi:10.1093/rheumatology/kei237

© The Author 2006. Published by Oxford University Press on behalf of the

British Society for Rheumatology. All rights reserved. For Permissions,

please email: journals.permissions@...

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EDITORIAL

Vaccinate your immunocompromised patients!

T. Glück

Klinikum der Universität Regensburg, Franz-f-Strauss-Allee, 93042

Regensburg, Germany

Correspondence to: thomas.glueck@...

Patients with rheumatoid arthritis and other chronic rheumatic diseases are

at approximately doubled risk of infection compared with the normal

population [1]. This may be in part due to still ill-defined

immunoregulatory abnormalities associated with rheumatic diseases, but is

certainly in large part secondary to the immunosuppressive therapy

administered to these patients in the best interest of their joints, with

proven efficacy in delaying joint destruction. The effect of

disease-modifying therapies on the immune system, however, may be quite

dramatic, especially if aggressive protocols such as Fauci's are

administered, and they may lead to opportunistic infections otherwise only

seen in patients with advanced HIV infection [2]. Inhibition of lymphocyte

proliferation by DMARDs leading to lymphocytopenia is one of the key

underlying mechanism of this phenomenon, and lymphocyte counts less than

500/µl or CD4 counts less than 250/µl-quite comparable to patients with

HIV-infection-have been found associated with an increased risk of infection

[1, 3]. The respiratory tract is the organ system most commonly affected in

patients with rheumatic diseases under chronic immunosuppressive

disease-modifying therapy, similar to patients with other immunocompromising

conditions or therapies [1, 3]. Fortunately, typical opportunistic pathogens

such as Pneumocystis jiroveci (carinii) are rare in our patients, and

classic bacterial infections of the respiratory tract are far more common

[1, 3].

What can be done to overcome these problems? Antibiotic prophylaxis is a

theoretical option and has been tried, but is complicated by many

side-effects and may not be an effective long-term approach in the light of

increasing bacterial resistance worldwide (while possibly contributing to

it). There is certainly broad agreement that patients with rheumatic

diseases fulfil each of the criteria of patients with a chronic condition,

and for such patients pneumococcal and influenza vaccinations are advocated

in most national immunization guidelines, e.g. the Centers for Disease

Control and Prevention's recommended adult immunization schedule [4], or the

German STIKO recommendations [5].

Two questions arise in the context of these thoughts. (i) May the same

mechanism as that which puts our patients at increased risk of infection

also reduce their response to vaccines? (ii) Does the activation of the

immune system, when responding to the immunizing antigen, induce a flare of

the underlying rheumatic disease, e.g. due to proinflammatory cytokines?

Unfortunately, for both vaccinations no large-scale trials addressing these

questions have so far been performed in patients with rheumatic diseases.

In this issue of Rheumatology, Kapetanovic et al. present their results of

monitoring the immune response of patients with rheumatoid arthritis to

pneumococcal immunization with the standard 23-valent polysaccharide vaccine

[6]. They were able to show that the immune responses to pneumococcal

antigens were impaired by methotrexate (MTX) treatment but not by anti-TNF

agents. This may be explained by the different modes of action of these two

DMARDs: MTX inhibits cell proliferation unselectively, while anti-TNF agents

block TNF specifically, and TNF does not play a very important role in the

induction of an antibody immune response. The findings of Kapetanovic et al.

are in line with those of Mease et al., who investigated the response to the

23-valent pneumococcal vaccine in patients with psoriatic arthritis under

treatment with etanercept and/or MTX and found lower titres against the

vaccine antigens only in association with MTX treatment [7]. However, it

needs to be stressed that a substantial proportion of the patients receiving

MTX in both investigations have shown sufficient induction of antibodies.

Response to pneumococcal vaccination has also been studied in other

immunocompromised patient groups, such as patients on chronic corticosteroid

therapy for chronic obstructive pulmonary disease [8], among whom the

antibody responses were not found to be compromised by corticosteroid

therapy; cancer patients [9], who showed a weaker response compared with

healthy controls; patients on chronic stress [10], who did show impaired

responses; and in heart transplant recipients under a cyclosporin-based

regimen, who showed responses comparable to those of healthy adults [11]. Of

note, antibody titres tend to decline more rapidly in immunocompromised

patients, who may require booster vaccinations more frequently [12].

Whether immunization actually prevents disease is much more difficult to

prove than whether there is an immune response to vaccine antigens. In this

context no specific data for patients with rheumatic diseases exist.

Meta-analyses have suggested that pneumococcal vaccination is uniformly

effective in preventing infections, and is also cost-effective overall [13,

14]. More recently, a large study has questioned the preventive effects in

elderly persons, except for bacteraemia [15].

Influenza vaccination is also recommended for immunocompromised patients, as

influenza can take a more severe course in such patients. In contrast to the

pneumococcal vaccine, influenza vaccination must be given every year. As the

antigens in the two vaccines are different (polysaccharides in the

pneumococcal vaccine and viral proteins in the influenza vaccine), the

immune responses may also differ. Two studies in patients with rheumatoid

arthritis found antibody responses following influenza immunization to be

similar to those in normal controls [16, 17], but responses in patients

after heart transplantation were somewhat impaired [11]. Despite these

limitations, there is profound evidence that influenza vaccination is highly

effective in preventing morbidity and mortality in elderly people and in

patients with chronic conditions [18]. It may even be cost-effective for

normal working adults [19].

Occasional case reports described an exacerbation or precipitation of

rheumatic disease in close time association with immunizations. A detailed

review is beyond the scope of this editorial; however, in controlled trials

such concerns could not be confirmed [12].

Thus, it can be concluded that the standard 23-valent pneumococcal and the

yearly influenza vaccines should be safe and sufficiently antigenic to

induce an antibody response in patients with rheumatic diseases, even if

some patients will not respond to all antigens in the vaccine preparations

and the titres may be somewhat lower and less persistent than in healthy

adults. More research needs to be done to optimize immunization protocols

for immunosuppressed patients, e.g. by giving booster doses more frequently.

It has to be mentioned, though, that even healthy persons do show

substantial interindividual variation in titre and the number of antibody

responses to vaccines [20].

So, vaccinate your immunosuppressed patients! Especially now, in the winter

season, this take-home message must be regarded as most appropriate.

Currently, vaccination rates are 20-35% at best. It is up to us doctors to

motivate our patients to receive adequate immunization. We have to make

immunization part of the treatment plans for our patients, otherwise these

vaccination rates will not increase and our patients will be left

unprotected [21].

The author has declared no conflicts of interest.

http://rheumatology.oxfordjournals.org/cgi/content/full/45/1/9

Not an MD

I'll tell you where to go!

Mayo Clinic in Rochester

http://www.mayoclinic.org/rochester

s Hopkins Medicine

http://www.hopkinsmedicine.org

[Guest guest]

Thank you ,

immunisation is something that I'd thought of , but I somehow had the crazy idea

that my " overactive " immune system wouldn't need any help. Your posts are

definetly worth reading.

Pennie

[ ] EDITORIAL - Vaccinate your immunocompromised patients!

Rheumatology 2006 45(1):9-10; doi:10.1093/ rheumatology/ kei237

© The Author 2006. Published by Oxford University Press on behalf of the

British Society for Rheumatology. All rights reserved. For Permissions,

please email: journals.permission s@oxfordjournals .org

------------ --------- --------- --------- --------- --------- -

EDITORIAL

Vaccinate your immunocompromised patients!

T. Glück

Klinikum der Universität Regensburg, Franz-f- Strauss-Allee, 93042

Regensburg, Germany

Correspondence to: thomas.glueck@ klinik.uni- regensburg. de

Patients with rheumatoid arthritis and other chronic rheumatic diseases are

at approximately doubled risk of infection compared with the normal

population [1]. This may be in part due to still ill-defined

immunoregulatory abnormalities associated with rheumatic diseases, but is

certainly in large part secondary to the immunosuppressive therapy

administered to these patients in the best interest of their joints, with

proven efficacy in delaying joint destruction. The effect of

disease-modifying therapies on the immune system, however, may be quite

dramatic, especially if aggressive protocols such as Fauci's are

administered, and they may lead to opportunistic infections otherwise only

seen in patients with advanced HIV infection [2]. Inhibition of lymphocyte

proliferation by DMARDs leading to lymphocytopenia is one of the key

underlying mechanism of this phenomenon, and lymphocyte counts less than

500/µl or CD4 counts less than 250/µl-quite comparable to patients with

HIV-infection- have been found associated with an increased risk of infection

[1, 3]. The respiratory tract is the organ system most commonly affected in

patients with rheumatic diseases under chronic immunosuppressive

disease-modifying therapy, similar to patients with other immunocompromising

conditions or therapies [1, 3]. Fortunately, typical opportunistic pathogens

such as Pneumocystis jiroveci (carinii) are rare in our patients, and

classic bacterial infections of the respiratory tract are far more common

[1, 3].

What can be done to overcome these problems? Antibiotic prophylaxis is a

theoretical option and has been tried, but is complicated by many

side-effects and may not be an effective long-term approach in the light of

increasing bacterial resistance worldwide (while possibly contributing to

it). There is certainly broad agreement that patients with rheumatic

diseases fulfil each of the criteria of patients with a chronic condition,

and for such patients pneumococcal and influenza vaccinations are advocated

in most national immunization guidelines, e.g. the Centers for Disease

Control and Prevention's recommended adult immunization schedule [4], or the

German STIKO recommendations [5].

Two questions arise in the context of these thoughts. (i) May the same

mechanism as that which puts our patients at increased risk of infection

also reduce their response to vaccines? (ii) Does the activation of the

immune system, when responding to the immunizing antigen, induce a flare of

the underlying rheumatic disease, e.g. due to proinflammatory cytokines?

Unfortunately, for both vaccinations no large-scale trials addressing these

questions have so far been performed in patients with rheumatic diseases.

In this issue of Rheumatology, Kapetanovic et al. present their results of

monitoring the immune response of patients with rheumatoid arthritis to

pneumococcal immunization with the standard 23-valent polysaccharide vaccine

[6]. They were able to show that the immune responses to pneumococcal

antigens were impaired by methotrexate (MTX) treatment but not by anti-TNF

agents. This may be explained by the different modes of action of these two

DMARDs: MTX inhibits cell proliferation unselectively, while anti-TNF agents

block TNF specifically, and TNF does not play a very important role in the

induction of an antibody immune response. The findings of Kapetanovic et al.

are in line with those of Mease et al., who investigated the response to the

23-valent pneumococcal vaccine in patients with psoriatic arthritis under

treatment with etanercept and/or MTX and found lower titres against the

vaccine antigens only in association with MTX treatment [7]. However, it

needs to be stressed that a substantial proportion of the patients receiving

MTX in both investigations have shown sufficient induction of antibodies.

Response to pneumococcal vaccination has also been studied in other

immunocompromised patient groups, such as patients on chronic corticosteroid

therapy for chronic obstructive pulmonary disease [8], among whom the

antibody responses were not found to be compromised by corticosteroid

therapy; cancer patients [9], who showed a weaker response compared with

healthy controls; patients on chronic stress [10], who did show impaired

responses; and in heart transplant recipients under a cyclosporin- based

regimen, who showed responses comparable to those of healthy adults [11]. Of

note, antibody titres tend to decline more rapidly in immunocompromised

patients, who may require booster vaccinations more frequently [12].

Whether immunization actually prevents disease is much more difficult to

prove than whether there is an immune response to vaccine antigens. In this

context no specific data for patients with rheumatic diseases exist.

Meta-analyses have suggested that pneumococcal vaccination is uniformly

effective in preventing infections, and is also cost-effective overall [13,

14]. More recently, a large study has questioned the preventive effects in

elderly persons, except for bacteraemia [15].

Influenza vaccination is also recommended for immunocompromised patients, as

influenza can take a more severe course in such patients. In contrast to the

pneumococcal vaccine, influenza vaccination must be given every year. As the

antigens in the two vaccines are different (polysaccharides in the

pneumococcal vaccine and viral proteins in the influenza vaccine), the

immune responses may also differ. Two studies in patients with rheumatoid

arthritis found antibody responses following influenza immunization to be

similar to those in normal controls [16, 17], but responses in patients

after heart transplantation were somewhat impaired [11]. Despite these

limitations, there is profound evidence that influenza vaccination is highly

effective in preventing morbidity and mortality in elderly people and in

patients with chronic conditions [18]. It may even be cost-effective for

normal working adults [19].

Occasional case reports described an exacerbation or precipitation of

rheumatic disease in close time association with immunizations. A detailed

review is beyond the scope of this editorial; however, in controlled trials

such concerns could not be confirmed [12].

Thus, it can be concluded that the standard 23-valent pneumococcal and the

yearly influenza vaccines should be safe and sufficiently antigenic to

induce an antibody response in patients with rheumatic diseases, even if

some patients will not respond to all antigens in the vaccine preparations

and the titres may be somewhat lower and less persistent than in healthy

adults. More research needs to be done to optimize immunization protocols

for immunosuppressed patients, e.g. by giving booster doses more frequently.

It has to be mentioned, though, that even healthy persons do show

substantial interindividual variation in titre and the number of antibody

responses to vaccines [20].

So, vaccinate your immunosuppressed patients! Especially now, in the winter

season, this take-home message must be regarded as most appropriate.

Currently, vaccination rates are 20-35% at best. It is up to us doctors to

motivate our patients to receive adequate immunization. We have to make

immunization part of the treatment plans for our patients, otherwise these

vaccination rates will not increase and our patients will be left

unprotected [21].

The author has declared no conflicts of interest.

http://rheumatology .oxfordjournals. org/cgi/content/ full/45/1/ 9

Not an MD

I'll tell you where to go!

Mayo Clinic in Rochester

http://www.mayoclin ic.org/rochester

s Hopkins Medicine

http://www.hopkinsm edicine.org

Send instant messages to your online friends http://au.messenger.

[Guest guest]

Thank you, . I am sure I speak for many when I express to you my

profound appreciation for the tremendously helpful information you

provide to us on a daily basis.

[Guest guest]

You're welcome! Thanks very much for your kind words.

Not an MD

I'll tell you where to go!

Mayo Clinic in Rochester

http://www.mayoclinic.org/rochester

s Hopkins Medicine

http://www.hopkinsmedicine.org

[ ] Re: EDITORIAL - Vaccinate your immunocompromised

patients!

> Thank you, . I am sure I speak for many when I express to you my

> profound appreciation for the tremendously helpful information you

> provide to us on a daily basis.