Risk of relapse of Guillain-Barré syndrome or chronic inflammatory demyelinating polyradiculoneuropathy following immunisation
- Department of Neuroimmunology, Guy's, King's & St Thomas' School of Medicine, Hodgkin Building, Guy's Hospital, London SE1 1UL
- Correspondence to: Dr J Pritchard;
- Guillain-Barré syndrome
- chronic inflammatory demyelinating polyradiculoneuropathy
Reports of the rare occurrence of Guillain-Barré syndrome (GBS) or chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) following immunisation1 and recurrence of symptoms following subsequent immunisation2 have given rise to concern over the safety of vaccine administration in this patient group. Similar concerns have been addressed and dismissed in patients with multiple sclerosis,3 but no such information exists for inflammatory neuropathy. To provide more information about vaccine safety in GBS and CIDP we audited the recurrence of neurological symptoms following immunisation.
The Guillain-Barré Syndrome Support Group, a British patient organisation, posted 3000 questionnaires to its members, asking them to identify their illness, record all immunisations administered after their illness, and describe any symptoms within six weeks of immunisation suggestive of recurrence of GBS or worsening of CIDP.
All but one of the patients who reported neurological symptoms after immunisation were contacted by telephone to confirm their history and to grade their symptoms using the modified Rankin scale.4 For the patient who could not be contacted by telephone, the patient's consultant neurologist provided the information. Questionnaires were sent to the general practitioner for each patient who reported a “relapse” to confirm which vaccine had been administered.
A total of 1114 patients (37.1%) completed the questionnaires, of whom 927 had had GBS, 179 had CIDP, and eight were excluded because they had other diseases. Of the 927 patients with GBS, 311 had received immunisations since having GBS. Eleven (3.5%, 95% confidence limits (CL) 1.8%, 6.2%) reported symptoms including increased fatigue, weakness, numbness, and paraesthesiae, but these were usually mild and no patient required hospitalisation or treatment. In three cases symptoms came on within 24 hours of immunisation and all but one developed symptoms within one week of immunisation. One patient reported symptoms rendering him unable to walk unaided or drive for six weeks, which increased his modified Rankin scale score from grade 2 to 4.
Influenza, tetanus, and typhoid were the most common immunisations associated with a relapse after GBS but the number of patients who reported symptoms was small compared with the total numbers receiving each of these vaccines (table 1). Although the results suggest that some vaccines that are administered less frequently (such as diphtheria) may be associated with a higher relapse risk, the numbers were small and most of these vaccines were administered at the same time as other vaccines.
Of the 311 patients with GBS who had received vaccines after having GBS, 29 had also received a vaccine in the six weeks before the onset of their initial illness. Two of these patients (6.9%, 95% CL 0.85%, 22.8%) had a recurrence of symptoms after a second, different, vaccine was subsequently administered.
Of the 179 patients with CIDP, 65 had been immunised after disease onset. Five reported worsening of neurological symptoms following immunisation. In three the symptoms were similar to a typical relapse of their CIDP, but only one of these patients required treatment within two months of immunisation. The other two patients with CIDP were immunised when already experiencing mild neurological symptoms, which then worsened, so that their modified Rankin scale score increased from 1 to 4 and they became dependent on a walking stick and unable to drive.
Of the patients with CIDP who experienced a relapse after immunisation, two relapses occurred among 23 patients who received the tetanus vaccine, giving a risk of relapse of 8.7%. Two of 46 (4.3%) patients with CIDP had relapses after influenza vaccine, of whom one had simultaneous pneumococcus vaccine. Two of six (33%) patients, including the last mentioned, experienced relapses after pneumococcus vaccine. Fourteen patients with CIDP had no symptoms of relapse following immunisation with typhoid vaccine. Between one and seven patients with CIDP had no symptoms after yellow fever, diphtheria, meningococcus, oral polio, BCG, hepatitis A, hepatitis B, cholera, or rubella vaccine.
This audit of patients with GBS and CIDP who have received vaccines suggests that the risk of relapse following immunisation is low. The response rate to the questionnaire was small as a proportion of the membership of the GBS Support Group. This is partly because an unknown but large proportion of members are relatives or friends and not former GBS or CIDP patients.
Only 11 of 311 patients with GBS (3.5%, 95% CL 1.8%, 6.2%) who had been immunised after having the disease reported a recurrence of symptoms. All of the vaccines that were associated with neurological symptom recurrence had also been received by many more patients who remained well. Some of the patients who reported symptoms after receiving vaccines had also received the same or other vaccines on other occasions without experiencing any problems. Only one respondent experienced symptoms that increased their modified Rankin scale score. The risk of relapse severe enough to alter the modified Rankin scale score is 0.3% (95% CL 0.01%, 1.78%) while the risk of a relapse requiring treatment or hospitalisation is at most 1.18% (95% CL).
It is more difficult to draw conclusions about the risk of immunisation for relapse in CIDP because our sample size was smaller. Five (7.7%, 95% CL 2.5%, 17.0%) of 65 patients noted a return of symptoms following immunisation. The reports of minor symptoms or acceleration of deterioration following influenza and pneumococcus vaccines merit caution in recommending these immunisations in patients with CIDP, although the risk of infection in immunosuppressed patients may outweigh any potential risk. Of greatest concern is the risk of relapse following tetanus toxoid, which was 8.7% (95% CL 1.7%, 28.0%) in our patient sample. In view of these figures and previous reports of relapse of CIDP following tetanus toxoid2,5 patients may wish to avoid routine tetanus toxoid immunisation.
Finally, it is important to acknowledge the difficulties in drawing conclusions from a questionnaire in which the patients reported their diagnostic classification and relapses. It is intuitively likely that more patients who experienced symptoms following immunisation responded to the questionnaire, which would overestimate the frequency of relapses. Consequently the true risks of relapse following immunisations after GBS or in CIDP may be less than those discovered in this audit.
We thank Mr Roland Price and members of the GBS Support Group for facilitating this audit and Dr A V Swan for statistical advice.