Vaccine

Complications of Vaccination

General Information on Complications (19:17)

More severe complications are rare but occur more than 10 times more often among revaccinees and are more frequent among primary vaccines than among revaccinees and are more frequent among infants than among older children and adults.

Fever is common after administration of the smallpox vaccine. 70% of children experience 1 or more days of temperature 100 F or higher for 4-14 days after primary vaccination.15-20% of children experience higher than 102¾ F. After revaccination, 35% of children experience temperature of 100¾ F or higher and 5% experience temperatures of 102¾ F or higher. Fever is less common among adults after vaccination or revaccination.

The most common symptoms experienced by vaccinees in a recent vaccine trial were: (22:V6:69) Fatigue in 50%, Headache in 40%, Muscle aches and chills or nausea in 20% and Fever in 10%.

Successful vaccination produces a lesion at the vaccination site. If the lesion is touched, virus can be transferred to another part of the body – this is called autoinoculation.

Death resulting from smallpox vaccination is rare, with approximately 1 death per million primary vaccinations and 1 death per 4 million revaccinations. (19:17) Death is most often the result of postvaccinial encephalitis or progressive vaccinia.

“ Around twenty percent of the population can’t be vaccinated. They’re immune compromised, or they have eczema, or they’re pregnant women, or they’re very young children. That’s a large number of people who will have no protection if smallpox comes back.” (15:158)

Autoinoculation (19:17) (major complication)

Autoinoculation or inadvertent inoculation is considered a major complication. This is the most frequent complication of smallpox vaccination. It is caused when live vaccinia virus is transferred from the inoculation site to another part of the body. Lesions of inadvertent inoculation could occur anywhere on the body, but the most common sites involved were the face, eyelid, nose, mouth, genitalia and rectum.

When it occurs at the time of vaccination, it can produce coprimary lesions. When it occurs at the time when the primary lesion is well developed, small or attenuated lesions may be produced.

Most lesions healed without incident, although VIG was useful in some cases of periocular implanation. (9:9) Inoculation of the virus in the eye can result in several clinical manifestations including blepharitis or infection of the eyelid, conjunctivitis, keratitis or iritis, or a combination of these conditions. (22:V1:44) Periocular and ocular implantation, otherwise referred to as ocular vaccinial disease, account for the majority of inadvertent inoculations and were often noted within 7-10 days of vaccination in first-time vaccinees. Because ocular vaccinia disease may occur in several forms, when evaluating a patient with new onset of a red eye or periocular vesicles, vaccinia infection should be considered. The patient should be asked about recent vaccinia exposures including a smallpox vaccination or close contact with a vaccine recipient.

Erythematous or Urticarial Rashes (minor complication)

This type of complication is considered a minor complication, as they usually resolve quickly. A variety of these types of rashes occur approximately 10 days after primary vaccination. (19:17) These rashes are referred to as erythema multiforme, roseola vaccinia, toxic erythema, ad postvaccinial uticaria.

These types of rashes are flat, erythematous, macular or uticarial lesions, usually with microscopic vasculitis. The pathophysiology of these rashes not well understood. Urticarial rashes usually don’t become vesicular, and don’t appear to involove viral multiplication. The rash resolves spontaneously within 2 to 4 days.

Patients with erythematous uticarial rashes associated with vaccinia are generally not severely ill and are usually afebrile despite extensive skin involvement (except upon the rare occasions when Stevens-Johnson syndrome, or bullous erythema multiforme develops.)

Generalized Vaccinia (major complication)

Generalized vesicular skin lesions occurring in the absence of eczema or other preexisting skin diseases characterize generalized vaccinia, a major complication. (22:V6:84) It is believed to be the result of a vaccinia viremia with implantations in the skin in a person with underlying illnesses. (19:17)

A secondary eruption almost always following primary vaccination, generalized vaccinia resulted from blood-borne dissemination of virus. (9:9) Lesions emerged between 6 and 9 days after vaccination andwere either few in number or generalized. (9:9) It consists of vesicles or pustules appearing on normal skin at a distance from the vaccination site. (19:17)

This complication was usually self-limited. Fever and systemic signs vary widely, but are generally mild. (22:V6:84) Most rashes labeled as generalized vaccinia produces only minor illness with little residual damage. (19:17) In severe cases, VIG was indicated. (9:9)

The differential diagnosis for this vaccine complication includes other non-specific immune rashes that can also occur following vaccination, eczema vaccinatum, metastatic lesions of early progressive vaccinia, or non-vaccinia related conditions, such as disseminated herpes or severe varicella. (22:V6:86)

Eczema Vaccinatum (major complication)

Eczema vaccinatum is the generalized spread of vaccinia on the skin of patients with eczema, atopic dermatitis or a those with a history of these conditions even when the condition is not active. (22:V1:47) It is considered a major complication. Some of the most severe cases of eczema vaccinatum have occurred in people with eczema or atopic dermatitis who were contacts to recently vaccinated individuals.

It occurs once per 25,000 primary vaccinations. (19:17) Is generally mild and self-limited, but can be severe. (19:17) Extensive skin involvement may result from inoculation of vaccinia virus in skin sites with compromised dermal integrity due to eczema or other skin conditions or may be the result of hematogenous spread following initial infection with the virus. Eczema vacciniatum could involve either blood dissemination of vaccinia virus or by direct skin inoculation of vaccinia on affected skin. Lesions of eczema vaccinatum can result in skin discoloration or scarring following resolution. (22:V6:88)

The rash of eczema vaccinatum can occur anywhere on the body but has a predilection for areas effected by atopic dermatitis or eczema. (22:V6:88) The rash can be quite extensive and even become confluent with popular, vesicular, or pustular lesions. Patients with significant skin involvement can become severely ill. (22:V6:88)

A less severe form of eczema vaccinatum can also occur in people with other skin disorders, like psoriasis or burns, that are currently active and effecting the integrity of the skin. (22:V1:45)

Vaccinia immune globulin was found therapeutic in treating this complication. (9:9)

Progressive Vaccinia (major complication)

Progressive vaccinia, also known as Vaccinia Necrosum or Vaccinia Gangrenosa, is a potential major complication of smallpox vaccination. A severe potentially fatal illness characterized by progressive necrosis in the area of vaccination, often with metastatic lesions. (19:17)

It occurs almost exclusively among persons with cellular immunodeficiency, but can occur in persons with humoral immunodeficiency. (19:17) Cases of progressive vaccinia occurred both among primary vaccines and revaccinees. (9:9) It occurs approximately once per 600,000 primary vaccinations. (19:17) It may be more common now, with HIV and post transplant immunosuppression widely present.

People with progressive vaccinia usually present with a non-healing, expanding vaccination site. The site often ulcerates and central necrosis, or necrosis of the surrounding skin can occur. There is generally little or no inflammation at the site initially, because of the poor local immune response to the infection that is induced by vaccination. This lack of adequate local immune response presumably allows the virus to spread locally and systemically. Medical conditions or medications that suppress the immune system would put a person at risk for this complication. It is currently unknown exactly what level of immune suppression would put a person at risk for this complication. (22:V1:46)

VIG, vaccine immunoglobulin, is the suggested treatment for this complication. It was almost always fatal before the introduction of VIG and antiviral agents. The vaccinial lesion failed to heal and progressed to involve adjacent skin with necrosis of tissue, spreading to other parts of the skin, to bones, and to viscera. (9:9)

Postvaccinial Encephalitis (major complication)

Postvaccinial encephalitis is a major unavoidable complication, which occurs once in about 80,000 primary vaccinations. (19:17) [1 case per 300,000 vaccinations] (9:9)

It has only observed in primary vaccines. (9:9) Approximately, 15-25% of affected vaccines with this complication die. (19:17) Of those who experience this complication, 25% develop permanent neurological sequelae. (19:17) It was frequently seen in vaccinated infants less than 1 year old or in older adolescents or adults receiving their first vaccination. (22:V6:91) Most cases are believed to result from autoimmune or allergic reactions, similar to other postviral CNSsyndromes rather than direct viral invasion of the nervous system. (19:17)

The pathophysiology of this complication is not well understood, but it is thought to be a result of a post vaccination immune response, similar to other post-infectious encephalitides. It has not been causally linked to the presence of vaccinia virus in the CNS. (22:V1:45) Between 8 and 15 days after vaccination, encephalitic symptoms developed – fever, headache, vomiting, drowsiness, and sometimes, spastic paralysis, meningitic signs, coma, and convulsions. It also can present with any variety of CNS signs, such as ataxia, confusion, paralysis, seizures, or coma. (19:17) Cerebrospinal fluid usually showed a pleocytosis.

Recovery was either complete or associated with residual paralysis and other central nervous system symptoms and, sometimes, death. (9:9) One case in a soldier with acquired immunodeficiency syndrome was successfully treated with VIG and ribavirin. These treatment strategies were off-label and would be considered experimental. (9:9)

Lymphangitis (minor complication)

Lymphangitis, or inflammation of the lymphatic vessels is a minor complication. This is usually due to a normal robust reaction at the site that peaks around days 8-10, but can be seen in secondary bacterial cellulitis. It can also be confused with allergic reactions to the dressing tape. (22:V1:38)

Robust Primary Reaction (minor complication)

Some individuals can have a robust primary reaction (minor complication) that presents with a large amount of erythema, swelling, pain, and warmth at the vaccine site. The redness and swelling can sometimes be greater than 3 inches or may even involve the entire upper arm. This large reaction is usually seen on days 8-10, corresponding to the same time when the peak vaccine inflammatory reaction usually occurs. In recent studies, this robust reaction, or take, occurred in 5%-15% of vaccine recipients. Both people getting vaccinated for the first time and people getting revaccinated after a long period since their last vaccination can have these robust takes. These robust reactions are expected variants of the evolution of the vaccination site and generally improve on their own within 24-72 hours. (22:V1:39)

However, sometimes these large vaccination reactions have been reported as adverse events and misinterpreted as a “bacterial cellulitis,” prompting antibiotic treatment. (22:V1:39)

Satellite Lesions (minor complication)

Satellite lesions can occur next to the primary lesion. These usually heal at the same rate as the primary vaccination site. They are considered a minor complication. (22:V1:40)

Tape Allergy (minor complication)

Local reactions due to a tape allergy (minor complication) can occur. This can usually be distinguished from lymphangitis by observing that the reaction only occurs in the distribution of the tape. Usually, individuals with reactions to tape have no other systemic symptoms. (22:V1:41)

Secondary Bacterial Infection (minor complication)

Secondary bacterial infections are categorized as a minor complication. Individuals suspected of having bacterial cellulitis at the site should be evaluated with gram stain and culture of the lesion, and blood cultures if systemic symptoms like high fever and malaise are present. (22:V6:76) An elevated peripheral white blood cell count may also be more indicative of a bacterial infection than a robust vaccine take. (22:V6:76)

The most common organisms causing secondary infections are Staphylococcus aureus and Group A streptococci. Some anaerobic or mixed infections can be seen, and may occur if occlusive dressings are used for prolonged periods that prevent aeration of the site and promote an anaerobic environment. (22:V6:76)

Fetal Vaccinia (minor complication)

Fetal vaccinia is a very rare complication that can occur following primary vaccination of a pregnant woman in the second or third trimester, from hematogenous spread of the virus to the amniotic fluid, or directly to the fetus. (22:V1:49) It is categorized as a minor complication.

Only about fifty cases of this complication have been reported in the literature. (22:V1:49) Studies are contradictory as to whether spontaneous abortions were increased in pregnant women vaccinated during the first trimester. (22:V1:49) There is no known reliable intrauterine diagnostic test to detect the presence of the vaccinia virus. (22:V1:49)

VIG may benefit live born infant. (22:V6:92) 

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