Arthus Reaction as an Adverse Event Following Tdap Vaccination

Repeat administration of tetanus toxoid-containing vaccines has rarely been associated with Arthus phenomenon, an immune-complex reaction. In the US, since 2013, tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccines (Tdap) have been recommended for administration during each pregnancy. Separately, in 2019, one Tdap was approved for repeat administration in adults in the US. We aimed to describe trends in spontaneously reported Arthus reactions following Tdap in the US and to assess the risk of this phenomenon in persons receiving Tdap repeatedly. We reviewed Arthus reports in the Vaccine Adverse Events Reporting System (VAERS), 1990–2018. Reporting rates were estimated using Tdap doses distributed data. A systematic literature review was conducted in MEDLINE for any Arthus cases reported in Tdap clinical trials and observational studies published between 2000 and 2019. We found 192 Arthus reports in VAERS after any vaccine, of which 36 occurred after Tdap and none were reported during pregnancy. The Arthus reporting rate was estimated at 0.1 per million doses distributed. We identified eight published studies of Tdap administration within five years after a previous dose of tetanus toxoid-containing vaccine; no Arthus cases were reported. We conclude that Arthus reaction following Tdap is extremely rare. Increasing frequency of repeat Tdap administration in adults in the US did not result in a detectable increase in reporting rates of this phenomenon, confirming the favorable safety profile of Tdap.

Comparative measurement of concentration of lithium, circulating immune complexes and complement activity in blood and lymph in experimental anaphylactic shock and Arthus phenomenon

Aim. Comparative measurement of concentration of lithium, circulating immune complexes and complement activity in animals’ blood and lymph in experimental anaphylactic shock and Arthus phenomenon. Methods. Experiments were conducted on 27 chinchilla rabbits in double series. The studied values of lithium, concentration of circulating immune complexes and complement activity in intact animals were used as controls. Results. On day 7 of sensibilisation before anaphylactic shock the titer of complement components in the blood decreased by 1.4 times (p <0.001) compared to parameters of intact animals, at the stage of anaphylactic shock sharp decrease of its concentration to undetermined values was observed (p <0.001). The blood concentration of circulating immune complexes increased by 4.4 times, and at the stage of anaphylactic shock (day 21) its increase by 7.1 times was observed (p <0.001). Lithium concentration decreased to 0.03 mmol/L at the stage of anaphylactic shock (p <0.001). In Arthus phenomenon at the stage of sensibilisation (day 5) the blood complement titer decreased by 1.1 times (p <0.001), during resolution period - by 10.1 times (p <0.001). The blood concentration of circulating immune complexes increased by 4.5 times (p <0.001) at the stage of sensibilisation (day 5), and at the stage of Arthus phenomenon - by 11.8 times compared to intact animals (p <0.001). Conclusion. The concentration of circulating immune complexes increases in anaphylactic and immunocomplex reactions, besides, more significantly in Arthus phenomenon (23 r.u. in anaphylactic shock versus 38.1 r.u. in Arthus phenomenon); lithium concentration in anaphylactic shock decreases by 5.2 times which is indicative of inhibitory action of this microelement in allergic reactions.

Determination of the concentration of circulating immune complexes, immunoglobulin E and G and histamine in the blood and lymph in experimental anaphylactic shock and Arthus phenomenon

Цель. Изучение изменения содержания концентрации циркулирующих иммунных комплексов, уровней иммуноглобулинов E и G и гистамина в крови и лимфе при экспериментальном анафилактическом шоке и феномене Артюса. Методы. Эксперименты проведены на 27 кроликах породы шиншилла в двух сериях. Контролем служили исследуемые показатели концентраций циркулирующих иммунных комплексов, гистамина и иммуноглобулинов E и G в крови и лимфе интактных животных. Результаты. Уровень гистамина при анафилактическом шоке повышается в 3,8 раза, тогда как уровень иммуноглобулинов E и G повышается соответственно в 14,7 и 3,5 раза в сравнении с интактными животными, а концентрация циркулирующих иммунных комплексов возрастает до 23 ммол/л за этот период. В условиях феномена Артюса уровень иммуноглобулина E в крови повышается в 1,3 раза, а иммуноглобулина G - в 4,3 раза. Концентрация циркулирующих иммунных комплексов возрастает в 11,8 раза, уровень гистамина повышается только в 3,5 раза в сравнении с интактными животными. Вывод. Концентрация циркулирующих иммунных комплексов повышается как при анафилактическом шоке, так и при феномене Артюса; уровни иммуноглобулинов изменяются по-разному: при анафилактическом шоке происходит увеличение уровня иммуноглобулина E и снижение иммуноглобулина G, а при феномене Артюса, наоборот, повышение уровня иммуноглобулина G и снижение иммуноглобулина E; уровень гистамина увеличивается как при анафилактическом шоке, так и при феномене Артюса, однако при анафилактическом шоке - более значимо; в повышении концентрации гистамина в обеих аллергических реакциях роль циркулирующих иммунных комплексов не исключена, но основная роль, по-видимому, принадлежит иммуноглобулину E.