Severe Inflammation Following Vaccination Against Streptococcus Pneumoniae in Patients with Cryopyrin-Associated Periodic Syndromes

Ulrich A. Walker^1,2, Philip N. Hawkins³, Rene Williams⁴, Hal M. Hoffman⁵ and Jasmin B. Kuemmerle-Deschner⁶, ¹Rheumatology, Unispital Basel, Basel, Switzerland, ²Rheumatology, University Hospital, Basel, Basel, Switzerland, ³University College London Medical School, London, United Kingdom, ⁴University College, London, England, ⁵University of California at San Diego, San Diego, CA, ⁶Universitätsklinikum Tübingen, Klinik fuer Kinder- und Jugendmedizin, Tübingen, Germany

Meeting: 2015 ACR/ARHP Annual Meeting

Date of first publication: September 29, 2015

Keywords: inflammasome activation, innate immunity and vaccines, Muckle-Wells syndrome

Session Information

Date: Sunday, November 8, 2015

Title: Miscellaneous Rheumatic and Inflammatory Diseases Poster I

Session Type: ACR Poster Session A

Session Time: 9:00AM-11:00AM

Background/Purpose: Pneumococcal vaccination is recommended for patients requiring treatment with immunosuppressive drugs. The aim of this report is to describe unusually severe adverse reactions to pneumococcal vaccination in each of seven consecutive patients with cryopyrin associated periodic syndromes (CAPS).

Methods: Seven consecutive patients with CAPS were vaccinated with pneumococcal polysaccharide or conjugate vaccines according to current guidelines. Clinical information was collected retrospectively.

Results: Within a few hours after the vaccination, all seven patients developed severe local reactions at the injection site (Table). Two patients had to be hospitalized for systemic reactions including fever. One patient had developed a severe headache associated with neck stiffness and photophobia. A florid red rash was covering much of the arm where the vaccine had been administered. The patient was admitted to her local hospital that evening with a diagnosis of presumed viral meningitis. Lumbar puncture revealed elevated white cells (96 per cubic millimetre, neutrophils 84%), normal glucose 2.3 mmol/L and elevated protein at 0.79 g/L In all patients, the symptoms resolved in a period of 3 to 17 days. The reaction occurred with pneumococcal vaccines from three different manufacturers and in patients with different CAPS phenotypes. Four vaccination reactions occurred in temporal association with concomitant co-injections of canakinumab, two other vaccination reactions were separated by 15 days from last canakinumab dose. In one case, an event was also observed prior to any canakinumab therapy. Some patients had been vaccinated with a variety of other vaccines without complications.

Table.Clinical characteristics of CAPS patients who developed severe inflammation after pneumococcal vaccination

Case Nr. Age, gender	Clinical presen-tation	NLRP3 Mutation	CAPS duration	CAPS treatment	Vaccine/ manufacturer	Days since last canakinumab	Days until onset	Local symptoms	Systemic reaction	Days until resolution	Previous uneventful vaccines
Case 1 43 years, female	MWS	T348M	43 years	Canakinumab 150 mg every 8 weeks	Pneumovax II / Sanofi Pasteur	New canakinumab dose given on day of vaccination (63 days since previous dose)	0	Swelling, rubor, dolor, calor	Fever, nausea, headache, stiff neck	17	Nil
Case 2 20 years, female	NOMID	L632F	20 years	Canakinumab 300 mg every 8 weeks	Pneumovax II/ Sanofi Pasteur	New canakinumab dose given on day of vaccination (56 days since previous dose)	0	Swelling, rubor, dolor, calor	Fever	12	Influenza
Case 3 26 years, female	NOMID	A352T	26 years	Canakinumab 300 mg every 8 weeks	Pneumovax II/ Sanofi Pasteur	New canakinumab dose given on day of vaccination (49 days since previous dose)	0	Swelling, rubor, dolor, calor	Not known	14	Nil
Case 4 43 years, male	MWS	T348M	43 years	Canakinumab 150 mg every 8 weeks	Pneumovax II/ Sanofi Pasteur	New canakinumab dose given on day of vaccination (63 days since previous dose)	0	dolor	None	4	Influenza
Case 5 24 years, female	MWS	E311K	10 years	Canakinumab 150 mg every 8 weeks	Pneumovax 23/ Merck	Canakinumab was given 15 days prior to vaccination	0	Swelling, rubor, dolor, calor	None	3	Influenza, HiB
Case 6 52 years, female	MWS	E 311K	51 years	Canakinumab 300 mg every 8 weeks	Pneumovax 23/ Merck	Canakinumab was given 15 days prior to vaccination	0	Swelling, rubor, dolor, calor	None	10	Influenza
Case 7 7 years, female	FCAS	No known mutation	7 years	None	Prevenar 13/ Wyeth	No prior or concomitant canakinumab	0	Swelling, rubor, dolor, calor	None	4	Diphtheria Polio Tetanus

Conclusion: Pneumococcal vaccines can trigger a severe local and systemic inflammatory reaction in patients with CAPS and possibly patients with other autoinflammatory diseases. TLR triggering by pneumococcal vaccine components with subsequent inflammasome hyperactivation in CAPS patients with NLRP-3 mutations may explain the high incidence rate of this event, its rapid onset, severity, and systemic nature.

Careful consideration is warranted when implicating current EULAR immunization guidelines in this patient population.

Disclosure: U. A. Walker, Novartis Pharmaceutical Corporation, 5; P. N. Hawkins, Novartis Pharmaceutical Corporation, 5; R. Williams, None; H. M. Hoffman, Novartis Pharmaceutical Corporation, 8,Novartis and Sobi, 5; J. B. Kuemmerle-Deschner, Novartis Pharmaceutical Corporation, 8,Novartis and Sobi, 5.

To cite this abstract in AMA style:

Walker UA, Hawkins PN, Williams R, Hoffman HM, Kuemmerle-Deschner JB. Severe Inflammation Following Vaccination Against Streptococcus Pneumoniae in Patients with Cryopyrin-Associated Periodic Syndromes [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/severe-inflammation-following-vaccination-against-streptococcus-pneumoniae-in-patients-with-cryopyrin-associated-periodic-syndromes/. Accessed .

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