BACKGROUND:Evans' syndrome is an uncommon condition defined by the combination (either simultaneously or sequentially) of immune thrombocytopenia purpura and autoimmune hemolytic anemia with a positive direct antiglobulin test in the absence of known underlying etiology.

OBJECTIVES:We present a case of Evans' syndrome following influenza vaccination.

CASE REPORT:A 50-year-old man with no prior medical history developed Evans' syndrome 4 days after receiving influenza immunization. The patient improved following treatment with oral prednisone and intravenous immunoglobulin.

CONCLUSION:Influenza vaccine is one of the most commonly used vaccines worldwide, with millions of people being vaccinated annually. Despite its wide use, only sparse information has been published concerning any hematological effects of this vaccine. The rarity of such effects supports the safety of using this vaccine.

Adverse reactions following BCG vaccination are uncommon, with an estimated prevalance of 0.4 per 1000 vaccines [Lotte A, Wasz-Hockert O, Poisson N, et al. Second IUATLD study on complications induced by intradermal BCG vaccination. Bull Int Union Tuber 1988;63:47-59]. Complications include erythema, blistering, abscess formation, regional lymphadenitis and keloid formation. The onset of cutaneous tuberculosis (TB) has also been reported. We describe the case of 12-year-old girl who developed extensive primary ulceration involving most of her left upper arm at the site of a BCG vaccination. A skin graft to the arm failed to take at the periphery and the ulcerated area increased to involve most of the upper lateral arm. Over a period of 18 months, secondary lesions developed on her forehead prompting further investigation of a systemic disease process. Following extensive immunological and microbiological examination, a diagnosis of vaccine-induced granulomatous vasculitis was made and the patient responded to a combination of antituberculous therapy and steroids. Once the disease process was under control, skin grafting of the ulcerated area was successful in achieving wound closure. Non-healing ulceration may be referred to the plastic surgeon and a diagnosis of vasculitis should be considered in difficult cases. A multidisciplinary team approach involving immunologists, dermatologists and plastic surgeons provides the best opportunity for a successful long-term outcome in terms of disease control as well as immediate skin cover.

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Japanese encephalitis (JE) virus is estimated to result in 3500-50,000 clinical cases every year, with mortality rates of up to 20-50% and a high percentage of neurological sequelae in survivors. Vaccination is the single most important measure in preventing this disease. Inactivated Vero cell culture-derived JE vaccines have not been linked to any fatalities, and few serious adverse events after vaccination have been reported. Here, we report a case of sudden death in which a 10-year-old boy experienced cardiopulmonary arrest 5 min after receiving a Japanese encephalitis vaccination. He had been receiving psychotropic drugs for the treatment of pervasive developmental disorders. Postmortem examinations were nonspecific, and no signs of dermatologic or mucosal lesions or an elevation of the serum tryptase level, which are characteristic of anaphylaxis, were observed. A toxicological examination revealed that the blood concentrations of the orally administered psychotropic drugs were within the therapeutic ranges. The patient was considered to have died of an arrhythmia that was not directly associated with the vaccination.

Although Kawasaki disease (KD) is a self-limiting disease, it may cause sudden cardiac death. Diagnosis of KD is principally based on clinical signs; however, some infant cases do not meet the criteria. Such cases are identified as incomplete KD. The sudden death risk in incomplete KD cases is similar to conventional KD. In our 5-month-old case, he had been admitted to a hospital for a fever and suppuration at the site of Bacille de Calmette et Guerin (BCG) vaccination. However, after discharge from the hospital, his C-reactive protein (CRP) levels declined, he got indisposed and died suddenly. A medico-legal autopsy revealed myocarditis, coronaritis, platelet-aggregated emboli in coronary arteries, and myocardial degeneration, suggesting that the fatal myocardial infarction was due to thrombus emboli in the coronary arteries. Forensic pathologists therefore should pay attention to the cardiac pathology originated from incomplete KD as a potential cause in cases of sudden infant death.

A 15-year-old young woman received the Human papillomavirus (HPV) vaccines. Following the second HPV vaccination, intermittent fever, myalgia, arthritis and malar rash developed, and she was admitted to our hospital. Laboratory studies showed positive results for antinuclear antibody, anti-dsDNA antibody and anti-Sm antibody. Systemic lupus erythematosus (SLE) was diagnosed according to the Systemic Lupus International Collaborative Clinics 2012. Magnetic resonance imaging showed abnormal hyperintense areas in the fascia, and en bloc biopsy showed fasciitis. Treatment with prednisolone resulted in an amelioration of the symptoms. Reportedly, SLE developed after HPV vaccinations in some patients. Most such patients have a past or family history of autoimmune disease and presented SLE symptoms after the second vaccination. We describe herein a patient in whom SLE developed in association with HPV vaccination.

GARDASIL (Merck&Co., Inc., Whitehouse Station, NJ, USA) is a quadrivalent human papillomavirus (HPV4) vaccine. An epidemiological study was undertaken to evaluate concerns about the potential for HPV4 vaccination to induce serious autoimmune adverse events (SAAEs). The vaccine adverse event reporting system (VAERS) database was examined for adverse event reports associated with vaccines administered from January 2006 through December 2012 to recipients between 18 and 39 years old with a listed residence in the USA and a specified female gender. It was observed that cases with the SAAE outcomes of gastroenteritis (odds ratio (OR) = 4.6, 95% confidence interval (CI) = 1.3-18.5), arthritis (OR = 2.5, 95% CI = 1.4-4.3), systemic lupus erythematosus (OR = 5.3, 95% CI = 1.5-20.5), vasculitis (OR = 4, 95% CI = 1.01-16.4), alopecia (OR = 8.3, 95% CI = 4.5-15.9), or CNS conditions (OR = 1.8, 95% CI = 1.04-2.9) were significantly more likely than controls to have received HPV4 vaccine (median onset of SAAE symptoms from 6 to 55 days post-HPV4 vaccination). Cases with the outcomes of Guillain-Barre syndrome (OR = 0.75, 95% CI = 0.42-1.3) or thrombocytopenia (OR = 1.3,95% CI = 0.48-3.5) were no more likely than controls to have received HPV4 vaccine. Cases with the general health outcomes of infection (OR = 0.72, 95% CI = 0.27-1.7), conjunctivitis (OR = 0.88, 95% CI = 0.29-2.7), or diarrhea (OR = 1.01, 95% CI = 0.83-1.22) were no morelikely than controls to have received HPV4 vaccine. Previous case series of SAAEs and biological plausibility support the observed results. Additional studies should be conducted to further evaluate the potential biological mechanisms involved in HPV4 vaccine-associated SAAEs in animal model systems, and to examine the potential epidemiological relationship between HPV4 vaccine-associated SAAEs in other databases and populations.

BACKGROUND:Thimerosal is a preservative commonly used in ophthalmic solutions, otic drops, and vaccines because of its bactericidal property.

OBJECTIVE:To report a case of a generalized reaction to thimerosal in a patient who received an influenza vaccine.

METHODS:We describe a patient who developed a generalized maculopapular eruption after receiving a thimerosal-containing influenza vaccine. Patch testing was performed to determine if there was an allergy to thimerosal.

RESULTS:Patch testing confirmed a T-cell-mediated sensitivity to thimerosal.

CONCLUSIONS:Physicians need to be aware that thimerosal is found in many products, including vaccinations. Clinicians should also be aware that allergic reactions occur with exposure to thimerosal even in vaccines. To our knowledge, this is the first case report in the literature of a generalized reaction to thimerosalfrom an influenza vaccine.

PURPOSE OF REVIEW:The cause of primary ovarian insufficiency (POI) is multifactorial. Known causes include external factors such as chemotherapy, radiotherapy, exposure to endocrine-disrupting chemicals, infections that lead to a permanent insult to the ovary, autoimmune conditions, and genetic causes. An association between the quadrivalent antihuman papilloma vaccine (HPV4) and POI was recently suggested.

RECENT FINDINGS:An increasing number of cases of POI post-HPV4 are being reported. Possible mechanisms for the suspected effect of HPV on female reproductive function are a toxic effect or an autoimmune response. The trigger could be the vaccine immunogen contents or the adjuvants, the latter are used to increase the immune reaction. The adjuvant in HPV4 contains aluminum. Animal models have shown aluminum exposure to inhibit expression of female reproductive hormones and to induce histologic changes in the ovaries. Specific genetic compositions may be more susceptible to developing an autoinflammatory syndrome after exposure to an environmental factor.

SUMMARY:The mechanisms responsible for POI are not yet fully understood. Although case reports cannot establish causation, awareness of a possible link between HPV4 and POI will help to identify and manage future cases that may arise.

Birth rates in the United States have recently fallen. Birth rates per 1000 females aged 25-29 fell from 118 in 2007 to 105 in 2015. One factor may involve the vaccination against the human papillomavirus (HPV). Shortly after the vaccine was licensed, several reports of recipients experiencing primary ovarian failure emerged. This study analyzed information gathered in National Health and Nutrition Examination Survey, which represented 8 million 25-to-29-year-old women residing in the United States between 2007 and 2014. Approximately 60% of women who did not receive the HPV vaccine had been pregnant at least once, whereas only 35% of women who were exposed to the vaccine had conceived. For married women, 75% who did not receive the shot were found to conceive, while only 50% who received the vaccine had ever been pregnant. Using logistic regression to analyze the data, the probability of having been pregnant was estimated for females who received an HPV vaccine compared with females who did not receive the shot. Results suggest that females who received the HPV shot were less likely to have ever been pregnant than women in the same age group who did not receive the shot. If 100% of females in this study had received the HPV vaccine, data suggest the number of women having ever conceived would have fallen by 2 million. Further study into the influence of HPV vaccine on fertility is thus warranted.

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OBJECTIVES: This analysis examined the incidence rate of chronic arthritis adverse reactions reported following adult rubella and hepatitis B vaccinations. In this analysis, etiologic mechanisms for chronic arthritis following adult rubella and hepatitis B vaccines were also explored. METHODS: The Vaccine Adverse Events Reporting System (VAERS) database was analyzed for the incidence rate of reported cases of chronic arthritis in comparison to Tetanus-diphtheria (Td) and tetanus toxoid adult vaccine control groups. RESULTS: Chronic arthritis adverse reactions following adult rubella vaccination were primarily reported in females (female/male ratio = 3.0), at about 45 years-old, and at a mean onset time of 10-11 days following vaccination. Chronic arthritis adverse reactions following adult hepatitis B vaccination were also primarily reported in females(female/male ratio = 3.5), at about 33 years-old, and with a mean onset time of 16 days following vaccination. The incidence rates of chronic arthritis following adult rubella and adult hepatitis B vaccinations were statistically significantly increased, by chi 2 analysis, in comparison to the adult vaccine control groups. The attributable risk of chronic arthritis following adult rubella vaccine ranged from 32 to 53 and from 5.1 to 9.0 following adult hepatitis B vaccine in comparison to the adult vaccine control groups. CONCLUSION: This study revealed that adult rubella and adult hepatitis B vaccines were statistically associated with chronic arthritis which persisted for at least one year. The etiology for these adverse reactions may involve autoimmune mechanisms. Furthermore, potential biases in the reporting rates of adverse reactions to VAERS were not observed.

An 11-year-old female patient, whose systemic type juvenile idiopathic arthritis (JIA) had maintained in remission for the previous 4 years while taking only a small amounts of ibuprofen, showed an abrupt 2nd relapse with congestive heart failure five days after receiving a live-attenuated rubella vaccine, which was a primary immunization. Her serum levels of anti-rubella IgM and IgG antibodies increased, and her laboratory findings such as a leukocytosis, elevated serum levels of CRP, IL-6 and other inflammatory cytokine profiles were similar to the findings observed during her previous JIA active stage. After being administration of co-therapy with steroid pulse, ibuprofen, methotrexate and phosphodiesterase inhibitor gradually improved her clinical symptoms such as spiky fever, heart failure and arthralgia. Her intermittent fever and increased serum levels of CRP and IL-6, however, have been sustained for more than 2 years, and this prolonged active clinical course therefore differed from her previous JIA active stage.This abrupt relapse only five days after vaccination was suggested not to be directly related with rubella infection, but instead to be related with the molecular mimicry between rubella and JIA.

BACKGROUND:To counter the possibility of smallpox being used as a biological weapon, in 2002 the US government restarted a smallpox vaccination campaign. Myopericarditis is a possible cardiac complication of smallpox vaccination. We report 2 cases of vaccine-associated myopericarditis in military recruits who were treated at our facility. Chest pain, shortness of breath, and electrocardiographic changes of pericarditis, with a recent history of smallpox vaccination, were useful in making the diagnosis of probable post-vaccinial myopericarditis. Nonsteroidal, anti-inflammatory drugs (NSAIDs) were used to manage myopericarditis. Both patients had complete resolution of symptoms and electrocardiographic changes and subsequently returned to active duty.

CONCLUSION:Myopericarditis should be suspected when patients with recent history of smallpox vaccination present with chest pain or shortness of breath. Nonsteroidal anti-inflammatory drugs are useful in the management of post-vaccinial myopericarditis.

Hypersensitivity vasculitis (HV) or leukocytoclastic vasculitis is a rare small-vessel vasculitis that may occur as a manifestation of the body's extreme allergic reaction to a drug, infection, or other foreign substance. Characterized by the presence of inflammatory neutrophils in vessel walls, HV results in inflammation and damage to blood vessels, primarily in the skin. Histologically, when neutrophils undergo leukocytoclasia and release nuclear debris into the vasculature, vascular damage manifests as palpable purpura. The incidence of HV is unknown and its relationship and interaction with certain vaccinations is rare and poorly understood. Affected patients with HV generally have a good prognosis; however, fatality may occur if organs such as the central nervous system, heart, lungs, or kidneys are involved. We report a unique case of a 60-year-old man who presented with a serious case of HV after receiving the herpes zoster vaccine. A thorough literature review yielded only one similar case of vascular reaction to the varicella vaccine that was reported in the Annals of Internal Medicine in 1997; however, no other reported cases with regard to the herpes zoster vaccine have been found. Our case presents a rare glimpse into HV that may result from varicella vaccine administration.

A 22-year-old woman with no significant medical history developed acute left shoulder pain and severe restrictions in range of motion after a seasonal influenza vaccine injection. Imaging by MRI, approximately 8 weeks after the injection, and by ultrasound, approximately 9.5 weeks after the injection demonstrated contusions on the humerus, injury of the supraspinatus, and effusion in the subacromial bursa. Her reaction was reported to the Vaccine Adverse Event Reporting System as a case of shoulder injury related to vaccine administration, likely due to injection of the influenza vaccine into the subacromial bursa. This case serves as a catalyst for discussion regarding vaccination technique and the potential to prevent complications arising from vaccine overpenetration.

OBJECTIVE: To determine the ability of Brucella abortus strain RB51 to induce placentitis and abortion in bison after SC vaccination. ANIMALS: 10 pregnant bison cows, 3 to 10 years old and at 3 to 8 months' gestation. PROCEDURE: Pregnant bison cows on a Montana ranch were vaccinated SC with 10(9) colony-forming units of B abortus strain RB51. Two cows, identified prior to the study, were euthanatized and examined 5 weeks after vaccination to obtain optimal histologic samples of placenta. Other cows were euthanatized and examined after abortion. After euthanasia, tissue specimens were collected for histologic and immunohistochemical evaluation. Tissue and fluid specimens for bacteriologic culture were also collected during necropsy. RESULTS: Of 8 cows, 2 aborted at 68 and 107 days after vaccination. Aborting cows had endometritis. Strain RB51 was isolated from reproductive tissues and supramammary lymph nodes. Fetal lesions were not seen; however, fetal bronchial lymph nodes and amniotic fluid contained strain RB51. Cows examined 5 weeks after vaccination had placentitis and endometritis, with numerous bacteria within trophoblastic epithelial cells that were immunoreactive for strain RB51 antigen. Strain RB51 was isolated from placentomes and numerous lymph nodes. Fetal lesions were not seen 5 weeks after vaccination; however, strain RB51 was isolated from numerous lymph nodes and lung, allantoic fluid, and rectal swab specimens. CONCLUSIONS: The vaccine candidate B abortus RB51 has tropism for the bison placenta, and can cause placentitis, which induces abortion in pregnant bison. The vaccine dose used was similar to that being tested in cattle, but may not be appropriate for pregnant bison.

We report one woman with acute cerebellar ataxia (ACA), a well-defined clinical syndrome, which occurred 10 days after the second vaccination with recombinant hepatitis B vaccine. The patient had no previous symptoms or signs of neurological disease and there was no evidence of neurologic disease in the family history. Within nine months the symptoms remitted completely according to other reports of ACA. As there was a close temporal connection and no noticeable other cause we assume a causal link between the vaccination and the disease. As far as we known this is the first case of ACA after hepatitis B vaccination.

Acute disseminated encephalomyelitis is an inflammatory demyelinating disease of the central nervous system that has been associated with influenza immunization, but only a few cases related to vaccination for influenza have been reported. Acute disseminated encephalomyelitis developed in a 42-year-old woman within 3 weeks of receiving the seasonal influenza vaccine. She had 80% recovery after 3 months of treatment with methylprednisolone. Although cases of acute disseminated encephalomyelitis after vaccination for influenza are rare, enough of them have occurred that critical care nurses should be aware of the possibility. Early treatment can prevent serious residual signs and symptoms; therefore, correct and quick diagnosis is important. Medical history obtained from patients with central nervous system problems should include history of recent vaccinations.

Although neurological complications have been described after tetanus vaccinations, they are rare. The authors report a case of acute disseminated encephalomyelitis (ADEM) in a 28-year-old pregnant woman at a gestational age of 10 weeks, admitted 15 days after a tetanus vaccination, with spastic tetraplegia and sphincter disturbances. Corticosteroid treatment led to partial recovery of the neurological deficit. Differential diagnosis of infectious and demyelinating diseases of the central nervous system is difficult in view of clinical and laboratory aspects of post-vaccination ADEM. Without any specific diagnostic markers, the clinical examination, magnetic resonance imaging and negative etiological findings were key to this diagnosis. Medical staff must bear in mind the possible complications of this vaccine.