Sex: F
Vaccine: HEPA, HPV4, MNQ, TDAP
Symptoms: Erythema, Injection site erythema, Injection site swelling, Peripheral swelling, Type III immune complex mediated reaction
Clinical narrative: Arthus reaction; swelling of the right upper arm down to the elbow; redness of the right upper arm down to the elbow; This case was reported in a literature article and described the occurrence of arthus reaction in a 11-year-old female patient who received Hepatitis A vaccine for prophylaxis.   Co-suspect products included GARDASIL for prophylaxis, MENACTRA (batch number U3518AA, expiry date unknown) for prophylaxis and DIPHTHERIA TOXOID + PERTUSSIS TOXOID + TETANUS TOXOID (ADACEL) (batch number C3489AA, expiry date unknown) for prophylaxis.   The subject's past medical history included asthma, eczema, environmental allergy and peanut allergy. Previously administered products included MMR with an associated reaction of adverse event, inactivated polio vaccine with an associated reaction of adverse event, ADVAIR, Albuterol, FLONASE, CLARITIN, EPIPEN and DTaP vaccine.   On 8th February 2011, the patient received Hepatitis A vaccine, GARDASIL, the 1st dose of MENACTRA (intramuscular) and the 1st dose of ADACEL (intramuscular). On 8th February 2011, less than a day after receiving Hepatitis A vaccine, the patient experienced arthus reaction (serious criteria GSK medically significant), swelling arm and erythema of extremities. On an unknown date, the outcome of the arthus reaction, swelling arm and erythema of extremities were unknown.   It was unknown if the reporter considered the arthus reaction, swelling arm and erythema of extremities to be related to Hepatitis A vaccine.  Additional details were provided as follows: This case was reported in a literature article and described the occurrence of arthus reaction of swelling and redness of the right upper arm down to the elbow in a 11-year-old female patient, who was vaccinated with unspecified hepatitis A vaccine (Hep A) (manufacturer unknown) for prophylaxis. This case corresponds to supplementary table 1 (Table S1) reported in this literature article. The VAERS ID was 451776. Initial report was received from a health care professional on 10 February 2011. The patient was a part of the study that aimed to describe trends in spontaneously reported Arthus reactions following tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccines (Tdap) and to assess the risk of this phenomenon in persons receiving Tdap repeatedly. The goal of this literature review was to identify published studies of Tdap vaccines administered in adolescents and adults who received a tetanus toxoid-containing vaccine less than or equal to 5 years previously. [It was reviewed Arthus reports in the Vaccine Adverse Events Reporting System (VAERS), 1990-2018. A systematic literature review was conducted in database for any Arthus cases reported in Tdap clinical trials and observational studies published between 2000 and 2019. Of the total of 619,479 reports in VAERS, it was identified 192 records coded with the "Type III immune complex mediated reaction" MedDRA term. All but one had vaccination dates between 2000 and 2018. The reports mentioned 35 different vaccines administered alone or coadministered in various combinations. The most frequently reported vaccine types, i.e., mentioned in more than 10 reports, were inactivated influenza vaccine (n = 39), pneumococcal polysaccharide vaccine (n = 39), Tdap (n = 36), measles mumps rubella (n = 20), inactivated polio vaccine (n = 17), Td (n = 16), hepatitis A vaccine (n = 14), meningococcal conjugate vaccine (n = 14), and varicella vaccine (n = 14). 36 (thirty-six) reports mentioning Tdap were received between 2006 and 2018. The Vaccine Adverse Events Reporting System (VAERS) received spontaneous reports of adverse events after vaccination from healthcare providers, patients, parents, vaccine manufacturers, and others. It was searched for the preferred MedDRA term "Type III immune complex mediated reaction" in reports submitted to VAERS between 11 June 1990 (the start of VAERS system database) and 14 December 2018]. The patient's previous vaccination included Measles + Mumps + Rubella vaccine (no brand name) (Adverse event NOS); Polio Virus vaccine, Inact. (Ipol) (Adverse event NOS). The patient's other medications included ADVAIR; Albuterol; FLONASE; CLARITIN; EPIPEN. Preexisting conditions/medical history included the patient had a history of asthma, eczema, environmental allergies and an allergy to peanuts. The patient had no illness at the time of vaccination. The patient also had to be revaccinated after having a DTaP vaccine when the patient was five year old because it was thought that the vaccine had been "unstable" from being too cold. No information on patient's family history was provided. On 08 February 2011, the patient received unspecified hepatitis A vaccine (Hep A) (Site: UN/ Route: UN; dosage unknown; Lot: not provided); GARDASIL vaccine (HPV4/ MERCK & CO. INC) (Site: UN/ Route: UN; dosage unknown; Lot: not provided); 1st dose of MENACTRA vaccine (MNQ: meningococcal conjugate/ SANOFI PASTEUR) (Site: right deltoid injection/ Route: IM; Lot: U3518AA); 1st dose of ADACEL vaccine (TDAP/ SANOFI PASTEUR) (Site: right deltoid injection/ Route: IM; Lot: C3489AA). [Tetanus toxoid-containing vaccines included pediatric diphtheria and tetanus toxoids vaccine (DT), tetanus toxoid vaccine (Ttox), adult tetanus toxoid reduced diphtheria toxoid vaccine (Td), and Tdap. Tdap was administered alone in 22 of these cases. In 14 persons it was coadministered with other vaccines, such as inactivated influenza, hepatitis B, hepatitis A, human papilloma virus, meningococcal conjugate, measles-mumps-rubella, and pneumococcal polysaccharide vaccines]. On 08 February 2011, an unspecified amount of time later the same day, the patient experienced a arthus reaction of swelling and redness of the right upper arm down to the elbow. The patient was evaluated by a physician. Treatments were not reported. According to the reporter the patient had a "similar reaction" after the patient had received an IPOL and MMR vaccine. No further information was available at the time of the report. [MedDRA PT terms: Erythema, Injection site reaction, Oedema peripheral, Type III immune complex mediated reaction]. [Most reports provided very limited information on the clinical course and laboratory workup. There were no cases of severe sequelae, such as skin necrosis. One report represented a literature case of erythema nodosum in temporal association with Tdap vaccination (VAERS captures cases and case-series of adverse events published in the literature as spontaneous reports). Arthus reaction was mentioned in the manuscript as one of several differential diagnoses (the final diagnosis being vaccine-associated erythema nodosum). No reports mentioned the use of Tdap during pregnancy. Between 2011 and 2018, approximately 169,000,000 doses of Tdap vaccines were distributed. During the same time, 24 presumed Arthus reaction cases following Tdap were reported to VAERS, for an estimated reporting rate of 0.1 per million doses distributed]. The patient's outcome was unknown. The patient had ER visit. The author commented, "Since the 1980s, literature reports and reviews of Arthus reaction following tetanus-containing vaccines have become rare. This is probably due to a wider acceptance by vaccine providers of the general recommendation not to re-administer tetanus vaccines more frequently than every 10 years. Other factors are undoubtedly improvements in standardization and purity of modern tetanus toxoid-containing vaccines. In this review, we found that the risk of Arthus reactions following vaccines used in the past two decades is extremely low. Only 36 reports were found in the VAERS database following Tdap booster. Several studies identified in our literature review support the idea that Tdap vaccines do not noticeably increase the risk of injection site reactions, when administered following a recent dose of tetanus toxoid-containing vaccine. The safety of multiple doses of Tdap vaccine administered in pregnant women was evaluated in a retrospective large database study in the Cases were reported after a wide variety of pediatric and adult vaccines. Most reactions reported were mild and self-limiting without treatment. The review confirmed that overall incidence of Arthus reactions was very low. No information related to Tdap vaccine was presented in the review. The authors stressed the need for the standard definition and diagnostic criteria of the reaction. Arthus reaction following vaccination is difficult to study, because of its rarity. The prescribing information documents for all tetanus toxoid-containing vaccines used provide a warning about the use of these products in persons who have experienced an Arthus-type hypersensitivity following a prior dose of a tetanus toxoid-containing vaccine. They state that such persons usually have a high level of tetanus antitoxin and that they should not receive tetanus toxoid-containing vaccines unless at least 10 years have elapsed since the last dose. Providers who suspect an Arthus reaction in adult patients receiving a tetanus toxoid- containing vaccine, including Tdap, should consider serology testing for tetanus and diphtheria antibodies. Very high concentrations measured in the patient's blood within a few days after vaccination would support the diagnosis. Other conditions and reactions that may present similar symptoms and complaints (e.g., sterile abscess, cellulitis, SIRVA, etc.) may need to be ruled out. Accurate diagnosis and confirmation of Arthus reaction is important, and, ideally, it should be a histological diagnosis with demonstration of a vasculitis. Confusing an expected injection site reaction (not Type III hypersensitivity) for Arthus reaction with the subsequent recommendation to avoid tetanus or diphtheria toxoid-containing vaccines may have negative consequences for the individual. Limitations of our study include those inherent to passive surveillance systems, such as VAERS, including over- or underreporting, biased reporting, inconsistency in quality and completeness of reports, and, in general, inability to assess the causality." The author concluded, "In conclusion, the risk of Arthus reaction following Tdap vaccine administration appears to be extremely low. This should provide reassurance to vaccine providers considering the increasing use of Tdap vaccines in the adult population, including in pregnant women. Future research into Arthus reaction following immunization would benefit from the development of a standard case-definition." This article corresponding to this case is not available for regulatory submission due to copyright restriction. This is 1 of the 10 valid cases reported in the same literature article.; Sender's Comments:  US-GLAXOSMITHKLINE-US2020GSK143477:Same reporter