Vaccines and autoimmune disease

[Guest guest]

Go to the website for better viewing of the graph - but wanted to include

the info in case it disappears from the net.

Sheri

http://www.rheuma21st.com/archives/cutting_aronmaor_shoenfeld_vaccination_re

visited.html

VACCINATION AND ARTHRITIS REVISITED

Reported by Anabel Aron-Maor, Yehuda Shoenfeld

Department of Internal Medicine B, Sheba Medical Center Tel Hashomer and

Center for Autoimmune Diseases, Sackler School of Medicine, Tel Aviv

University

published 11. September 2000

Vaccination and the possible autoimmune side effects have been discussed

recently in several articles (1-4). Not omitting for one moment the

immeasurable benefits of vaccination, the question of whether this practice

may be one of the factors implicated in the onset of autoimmune illness has

arisen (3).

Based on existing case reports, there seems to be at least a temporal

connection between several vaccines and autoimmune phenomena; however, no

causal relation has been proven yet. In this cutting-edge article, we wish

to focus our attention specifically on the combination of immunization and

arthritis.

The occurrence of arthritis has been described after various types of

vaccines (Table 1) have been given and can be divided into isolated or

reactive arthritis (poly or monoarticular) and arthritis as part of a

systemic autoimmune disease (such as systemic lupus erythematosus [sLE] or

rheumatoid arthritis [RA]). Some vaccines have been implicated more often

than others. We will review the existing reports, within the last 10 years,

on arthritis following vaccination.

Arthritis and Hepatitis B Vaccine

In the last 10 years, at least 32 cases of arthritis following immunization

against hepatitis B have been described. Some cases have been isolated

inflammation of the joints and others were part of frank RA (Table 1).

In 1990, two cases of arthritis were reported (5,6). One patient developed

erythema nodosum and polyarthritis and the other reactive arthritis shortly

after receiving an HBV vaccination. More reports were published during the

following years (7-13). Some of the patients described had high titers of

rheumatoid factor in the serum, even though they did not fulfill other

criteria for frank RA (8). Others were carriers of genetic markers

predisposing to autoimmune diseases (13). A 1998 report (13) described 11

patients who developed arthritis after receiving HBV recombinant vaccine.

Ten of the 11 patients reviewed fulfilled the revised ARC criteria for RA.

Nine of those required disease modifying drugs. Five subjects were HLA-DR4

positive. Nine of eleven patients genotyped for HLA-DR and DQ expressed the

RA shared motif in their HLA class II genes. Findings raised the

possibility that HBV recombinant vaccine may trigger RA in genetically

prone individuals. An additional case reported in 1996 (10) supports, to a

certain extent, the hypothesis that people genetically prone to develop

autoimmune disease will more readily develop arthritis after vaccination

(of any kind). In this case, a 44-year old man who had had myasthenia

gravis 20 years earlier developed arthritis, hypercalcemia, and lytic bone

lesions shortly after administration of HBV recombinant vaccine. It is

noteworthy that a definite connection between the arthritis and the vaccine

itself has not been established (serologically) in any of the cases

mentioned so far. Additional cases of frank RA where the HBV vaccine was

the trigger for the onset of the disease, at least temporally, have been

reported (9,11).

An autoimmune disease that is often connected with the HBV vaccine is

systemic lupus erythematosus (SLE). Numerous cases of SLE manifesting for

the first time after immunization against HBV have been described (14-18);

some cases have occurred in members of the same family (15). The disease

developed in patients of both sexes and all ages (15,18). In many cases,

manifestations of the disease included mono- or polyarthritis (14,16).

The possible connection between arthritis (reactive or as part of systemic

autoimmune illness) and the recombinant HBV vaccine is important and worthy

of further research, because the disease itself is a potentially lethal

one, and vaccination against it has become mass practice. We think that

special emphasis should be put on possible autoimmune side effects in

infants and children, as well as prospective studies in individuals that

have been vaccinated against HBV as newborns. Are they more or less prone

to develop autoimmune side effects as their system is exposed to these

foreign antigens at a very early stage?

Arthritis and Rubella Vaccine

The rubella vaccine has been mentioned often in connection with the onset

of reactive arthritis. The wild virus itself has been reported to trigger

arthritis in a large number of patients. Similarly, arthritis has also been

described in temporal proximity to the administration of the vaccine.

During the last 10 years more than 100 cases of rubella vaccine related

arthropathies have been reported (19,20). In 1991, the Institute of

Medicine released a report in JAMA examining 18 adverse effects of

diphtheria-pertussis-tetanus (DPT) vaccine and four adverse effects of

rubella vaccine strain 27/3. The report concluded that the evidence

suggests a causal relation between rubella vaccine and acute arthritis in

adult women (21,22). No animal studies were available to support (or

disprove) this conclusion.

In 1997, a study published in JAMA (21) evaluated the risk of persistent

joint and neurological symptoms in rubella seronegative women, subsequently

vaccinated with rubella vaccine strain RA 27/3. The study was retrospective

and included 900 to 1000 women, 15 to 59 years old. No significantly

increased risk was associated with receipt of rubella vaccine for any

condition, except for carpal tunnel syndrome for vaccinated women at least

30 years old compared to seropositive non-vaccinated women. Six of the

seronegative immunized women had onset of symptoms during the 1-year

follow-up period. Four of these had transient arthritis or arthralgias (of

less than 6 weeks duration), one had arthralgia of indeterminate

chronicity, and one had carpal tunnel syndrome (20). The conclusion of this

large retrospective study was that no clear-cut evidence indicates

increased chronic arthropathies (or neurological symptoms) in women

receiving rubella RA 27/3 vaccine. The data supported the continued

vaccination of rubella-susceptible women to reduce the risk of congenital

rubella syndrome. Postpartum women were less likely to develop non

traumatic arthropathies following rubella vaccination.

As with HBV vaccine, a genetic predisposition to develop autoimmune disease

may play a role in the appearance of acute reactive arthritis in proximity

to the administration of rubella vaccine. In 1998 (23), a group of

scientists examined the frequency of HLA class II (HLA-DR) in relation to

the incidence of acute arthralgia or arthritis in 283 white women who had

received RA 27/3 rubella vaccine (n=146) or placebo (n=137) postpartum.

Leukocyte DNA was molecularly typed for HLA-DRB1 gene expression. After

statistical analysis of the results, which included adjustment for

variables such as age, treatment, time postpartum, the conclusion was that

the risk of developing arthropathy was 1.9 times greater after rubella

vaccination than after placebo. The risk for arthropathy was also

influenced by DR interactions. Odds were 8 times greater in individuals

with both DR1 and DR4 and 7.1 times greater with both DR4 and DR6 present,

suggesting that coexpression of these specificities may predispose to

postpartum arthropathies (23).

Apart from the genetic predisposition discussed above, an additional

possible risk factor to post-vaccine arthropathy was examined. et

al (24) described the results of a study that examined whether

pre-vaccination rubella virus specific IgG levels have any correlation with

the development of acute or chronic (persistent or recurrent) joint

manifestations. Specific IgG levels were determined by whole enzyme

immunoassay (EIA), neutralization domain peptide, and neutralization

bioassay in prevaccine samples of seronegative women. Of rubella vaccinated

women tested for prevaccine antibodies, 21.7% were positive (by EIA) ,

17.6% were positive by neutralization domain peptide, and 12.7% had

neutralization titers of at least 1:8. Seropositivity tests were

significanlty lower in women who developed joint symptoms after

immunization compared with those of asymptomatic women. The authors`

conclusion was that the risk for arthropathy following RA 27/3 rubella

vaccination may be higher in women who have very low prevaccine levels of

rubella antibodies, particularly in assays measuring functional

(neutralizing) antibodies (24).

Arthritis and Other Vaccines

Fewer reports have appeared on arthritis following other types of vaccines.

Mumps and measles (25), influenza (26), DPT (27), and typhoid (28) are each

connected with some cases described during the last 10 years. In the first

case, the mumps component of the vaccine was deemed to be responsible for

the development of acute monoarthritis (25). In the case of influenza

vaccination, the arthritic manifestations were accompanied by neurologic

symptoms and signs, namely orbital myosistis and posterior scleritis (26).

Indeed, the influenza vaccine has been more often connected to neurologic

manifestations (1) than to joint involvement.

Maillefert et al describe two patients who developed monoarthritis after

DPT immunization. One patient developed monoarthritis of the knee that

resolved only after synovectomy and recurred 5 years later after a booster

vaccine injection (27), and the second patient developed monoarthritis of

the ankle that persisted for 3 days and resolved spontaneously. These cases

suggest that DPT vaccine may cause arthritis, however additional evidence

is needed in order to confirm this possibility. An additional vaccine

mentioned in connection with arthritis is typhoid. Two cases, both of which

were HLA-B27 negative, are reported (28). Reactive arthritis occurred in

two travelers who received oral Ty21a typhoid vaccine.

In a previous article (1), we raised the question whether administration of

polyvaccines might be more inductive of autoimmune side effects than

monovaccines. A series of patients (all of them previously healthy army

personnel) have been reported (29) who developed SLE after receiving a

number of vaccines among them typhoid, tetanus toxoid, hepatitis B,

influenza, and meningococcal vaccine. All patients met the ARC criteria for

SLE; all manifested mono- or polyarthritis.

Possible Mechanisms for Post-vaccination Reactive Arthritis

As we mentioned in previous reviews of this subject (1-4), possible

mechanisms to explain this phenomenon have been suggested. One of the

popular explanations is the " molecular mimicry " mechanism. Certainly in

live vaccines, but also in attenuated preparations, antigens of the

infective organism remain intact and immunologically potent. Structural

similarity between these bacterial or viral antigens and host antigens may

enable the triggering of an autoimmune response. In a recent article (30),

the author suggests an immunologically based explanation for reactive

arthritis (along the lines of molecular mimicry as mentioned above) and

possible therapy. He proposes an anti-idiotypic model for the disease.

Based on this hypothesis (in support of which evidence is presented in the

article) a bacterial lipopolysaccharide (LPS) epitope is recognized by

idiotypic (Id) T-cell receptors and antibody Fab immune recognition

surfaces (IRS), which have the immunologic appearance of an antigen on the

synovial surface. These Id immune effectors utilize an HLA-B27 molecule to

present their IRS on their surface, which results in an anti-idiotypic

immune response that can also target the synovial antigen. The

anti-idiotypic IRS have the immunlogic appearance of LPS and their

detection in the arthritic joints falsely suggests the presence of

bacterial LPS. The synovial antigen is attacked by the anti-idiotypic

response against the bacterial LPS. Therapeutic vaccination is supported by

this hypothesis (30).

Additional data supporting the molecular mimcry mechanism are found in a

recent study performed on dogs, which, to the best of our knowledge, is the

only one of its kind, so far (31). In this study, newborn puppies were

immunized with a number of mandatory vaccines (rabies and multivalent

vaccine). Based on interpretation of the results, the authors concluded

that vaccination did not cause immunosuppression, but it did induce

autoantibodies and antibodies to heterologous antigens. None of the dogs

developed autoimmune illness, even though the study was discontinued at 22

weeks of age, a time well before any clinical signs of collagen disease

usually become apparent. The authors mention similar findings in a

follow-up study in dogs that were immunized with the rabies vaccine only

and with the multivalent vaccine only.

Summary

We have reviewed the existing data on the incidence of acute and chronic

arthritis following various immunizations. The vaccines most often

connected with the occurrence of reactive arthritis (either isolated or as

part of systemic RA) are HBV recombinant vaccine and rubella vaccine.

Individuals genetically prone to develop autoimmune illness (namely

carriers of HLA-DR1, DR4, DR6, or HLA-B27) are more likely to contract

post-immunization arthritis. The serological immune status of rubella

seronegative women prior to vaccination also influences the likelihood of

acute or chronic arthritis after immunization with rubella vaccine. Immune

mechanisms are suggested to explain this phenomenon. A clear causal

relation was not proved in any of the cases, however a temporal one

apparently exists. There are no means as yet to anticipate which

individuals will develop post-vaccination arthritis (other than the genetic

tendency detailed above). Vaccination against HBV and rubella, as well as

other infectious diseases, no doubt continues - as it should. However, we

should be aware of the possibility of autoimmune side effects (in this case

specifically joint involvement) to vaccination and perhaps abstain from

less than necessary vaccination of patients at known risk for autoimmune

illness. These would include people with previously diagnosed disease, with

family members suffering from autoimmune disease, or known carriers of

genetic risk factors (as detailed above).

Table I. Vaccines associated with post-vaccination reactive arthritis and RA .

Disease Vaccine No. of cases Additional symptoms Ref.

Reactive arthritis HBV 1 Erythema nodosum 5

1 Migratory arthritis, urticaria, oedema of the glottis 8

1 Hypercalcemia, lytic bone lesions 10

4 Myalgia 11

3 Vasculitis 11

1 Adult-onset Still`s disease 12

>10 Reactive arthritis alone 6-9,11,13

Rubella >100 14,16-19

Mumps and measles 1 20

Influenza 1 21

DPT 2 22

Typhoid 2 23

Rheumatoid arthritis HBV 15 Reviewd in 1,4

1 9

6 11

5 13

Tetanus 13 Reviewed in 1

SLE HBV 7 Cutaneous, renal, hematological 14-18

Polyvaccine: mumps, measles, tetanus, meningococcal, hepatitis A, polio

5 Cutaneous, renal, hematological 30

References:

1. Shoenfeld Y, Aron-Maor A. Vaccination and autoimmunity - " Vaccinosis: A

dangerous liaison? J Autoimun 2000;14:1-10.

2. Nossal GJV. Vaccination and autoimmunity. JAI 2000;14:15-22.

3. Shoenfeld Y, Aron-Maor A, Sherer Y. Vaccination as an additional player

in the mosaic of autoimmunity. Clin Exp Rheumatol 2000;18 4. Cohen AD,

Shoenfeld Y. Vaccine-induced autoimmunity, J Autoimmun 1996;9:699-703.

4. Cohen AD, Shoenfeld Y. Vaccine-induced autoimmunity, J Autoimmun

1996;9:699-703.

5.on SJ. Nye FJ. Hepatitis B vaccine associated with erythema nodosum

and polyarthritis. BMJ 1990;301:345.

6. Haschulla E, Houvenagel E, Mingui A, G, Laine A. Reactive

arthritis after hepatitis B vaccination. J Rheumatol 1990;17:1250-1251.

7.Biasi D, De Sandre G, Bambara LM, Carletto A, Caramaschi P, Zanoni G,

Tridente G. A new case of reactive arthritis after hepatitis B vaccination.

Clin Exp Rheumatol 1993;11:215.

8. Biasi D, Carletto A, Caramaschi P, Frigo A, Pacor ML, Bezzi D, Bambara

LM. Rheumatological manifestations following hepaatitis B vaccination. A

report of 2 clinical cases (article in Italian). Recenti Prog Med

1994;85:438-440.

9. Gross K. Combe C, Kruger K, Schattenkirschner M. Arthritis after

hepatitis B vaccination. Report of three cases. Scand J Rheumatol

1995;24:50-52.

10. Cathebras P, Cartry O, Lafage-Proust MH, Lauwers A, Acquart S,

T, Rousset H. Arthritis, hypercalcemia and lytic bone lesions after

hepatitis B vaccination. J Rheumatol 1996;23:558-560.

11. Maillefert JF, Sibilia J, Toussirot E, Vignon E, Eschard JP, Lorcerie

B, Juvin R, Parchin-Geneste N, Piroth C, wendling D, Kuntz JL, Tavernier C,

Gaudin P. Rheumatic disorders developed after hepatitis B vaccination.

Rheumatology (Oxford) 1999;38:978-983.

12. Grasland A, Le Maitre F, Pouchot J, Hazera P, Bazin C, Vinceneux P.

Adult-onset Still's disease after hepatitis A and B vaccination (article in

French). Rev Med Interne 1998;19:134-136.

13. Pope JE, s A, Howson W, Bell DA. The development of rheumatoid

arthritis after recombinant hepatitis B vaccination. J Reumatol

1998;25:1687-1693.

14. Tudela P, Marti S, Bonanl J. Systemic lupus erythematosus and

vaccination against hepatitis B. Nephron 1992;62:236.

15. Finielz P, Lam-Kam-Sang LF. Systemic lupus erythematosus and

thrombocytopenic purpura in two members of the same family. Nephrol Dial

Transplant 1998;13:2420-2421.

16. Guiseriz J. Systemic lupus erythematosus following hepatitis B vaccine.

Nephron 1996;74:441.

17. Mamoux V, Dumont C. Lupus erythemateux dissemine et vaccination contre

l'hepatite B. Arch Pediatr 1994;1:307-308.

18. Grezard P, Chafi M, Philippot V, Perrot H, Faisant M. Cutaneoius lupus

erythematosus and buccal aphthosis after hepatitis B vaccination in a

6-year-old child. Ann Dermatol Venereol 1996;123:657-659.

19. Weibel RE, Bemor DE. Chronic arthropathy and musculoskeletal symptoms

associated with rubella vaccines. A review of 124 claims submitted to the

National Vaccine Injury Compensation Program. Arthritis Rheum

1996;39:1529-1534.

20. Ray P, Black S, Shinefield H, Dillon A, Schwalbe J, Holmes S, Hadler S,

Chen R, Cochi S, Wassilak S. Risk of chronic arthropathy among women after

rubella vaccination. Vaccine Safety Datalink Team. JAMA 1997;278:551-556.

21. Howson CP, Fineberg HV. Adverse events following pertussis and rubella

vaccines. Summary of a report of the Institute of Medicine. JAMA

1992;267;392-396.

22. Howson CP, Katz M, ston RB Jr, Fineberg HV. Chronic arthritis after

rubella vaccination. Clin Infect Dis 1992;15:307-312.

23. LA, Tingle AJ, Mac L, Horne C, Keown P, Gaur LK, Nepom

GT. HLA-DR class II associations with rubella vaccine-induced joint

manifestations. J Infect Dis 1998;177:5-12.

24. LA, Tingle AJ, Grace M, Middleton P, Chalmers AC. Rubella

virus vaccine associated arthropathy in postpartum immunized women:

influence of preimmunization serologic status on development of joint

manifestations. J Rheumatol 2000;27:418-423.

25. Nussinovitch M, Harel L, Varsano I. Arthritis after mumps and measles

vaccination. Arch Dis Child 1995;72:348-349.

26. Thurairajan G, Hope-Ross MW, Situnayake RD, Murray PI. Polyarthropathy,

orbital myositis and posterior scleritis: an unusual adverse reaction to

influenza vaccine. Br J Rheumatol 1997;36:120-123.

27. Maillefert JF, Tonolli-Serabian I, Cherasse A, Demoux AL, Tavernier C,

Piroth L. Arthritis following combined vaccine against diphtheria,

polyomyelitis and tetanus toxoid. Clin Exp Rheumatol 2000;18:255-256.

28. Adachi JA, D`Alessio FR, sson CD. Reactive arthritis associated

with typhoid vaccination in travelers: report of two cases with negative

HLA-B27. J Travel Med 2000;7:35-36.

29. Older SA, Battafarano DF, Enzenauer RJ, Krieg AM. Can immunization

precipitate connective tissue disease? Report of five cases of systemic

lupus erythematosus and review of the literature. Sem Arthritis Rheum

1999;29:131-139.

30. Kennedy JR. Reactive arthritis: the result of an anti-idiotypic immune

response to a bacterial lipopolysaccharide antigen where the idiotype has

the immunological appearance of a synovial antigen. Med Hypotheses

2000;54:723-725.

31. Hogenesch H, Azcona-Olivera J, -Montcrieff C, Snyder PW, Glickman

LT. Vaccine-induced autoimmunity in the dog. Adv Med Vet 1999;41:733-747.

Address for Correspondence: Prof. Yehuda Shoenfeld,

Department of Medicine B,

Tel Hashomer, Ramat Gan 52621, Israel

Tel: 972-3-5302652

Fax: 972-3-5352855 .

To top

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

Sheri Nakken, R.N., MA

Vaccination Information & Choice Network, Nevada City CA & UK

530-740-0561 Voicemail in US

http://www.nccn.net/~wwithin/vaccine.htm

" All that is necessary for the triumph of evil is that good men ( &

women) do nothing " ...Edmund Burke

ANY INFO OBTAINED HERE NOT TO BE CONSTRUED AS MEDICAL OR LEGAL ADVICE. THE

DECISION TO VACCINATE IS YOURS AND YOURS ALONE.

Well Within's Earth Mysteries & Sacred Site Tours

http://www.nccn.net/~wwithin

International Tours, Homestudy Courses, ANTHRAX & OTHER Vaccine Dangers

Education, Homeopathic Education

CEU's for nurses, Books & Multi-Pure Water Filters

----------

---

Outgoing mail is certified Virus Free.

Checked by AVG anti-virus system (http://www.grisoft.com).

Version: 6.0.273 / Virus Database: 143 - Release Date: 08/16/2001