Eczema Vaccinatum (smallpox vaccine)
- Vaccinia virus (smallpox vaccine)
- Eczema vaccinatum (EV) pathophysiology: autoinoculation from host vaccination site or from close contact w/ implantation in eczema site or healed lesion.
- Work in the murine model suggests that NK cells are present in lower numbers; inhibition of IL-17 allowed the development of severe skin lesions.
- The source in half of the cases in the 1960s was a household contact.
- It can be either localized or systemic spread of the vaccinia virus.
- Most common sites: face, flexor surfaces.
- Lesions look like vaccination site but confluent + systemic illness +/- bacterial superinfection.
- Ddx: smallpox, generalized vaccinia (no eczema), chickenpox, herpes viruses, Kaposi varicelliform eruption (due to HSV, enteroviruses in those with preexisting dermatosis), erythema multiforme.
- DX: multiple vaccinia skin lesions outside vaccination site + exposure to vaccinia + current eczema or hx of eczema.
- Eczema vaccinatum appears like the vaccination site, but confluent and with systemic illness.
- Eczema and atopic dermatitis are interchangeable terms.
- Relevance: most common contraindication to smallpox vaccination.
- Risk applies to vaccine candidates AND any household contacts with active eczema or eczema hx.
- Eczema pathophysiology: T cell immune defect + atopy with high IgE (85%).
- Prevalence: 6-22% of the general population has eczema or prior hx; many more misdiagnosed.
- Eczema dx in this context: clinical (history and exam) rather than lab-based diagnosis. Skin biopsies rarely pursued. High IgE levels or eosinophilia may be seen.
- Pruritis (dominant symptom)
- Dermatitis - flexor surfaces
- Dermatitis is chronic or recurrent
- Family hx atopy
- Onset by age 7
- Skin changes:
- Children: pruritic, red patches + scaling; face, scalp, extremities, trunk may be involved.
- Adults: lichenification of flexor surfaces.
- Recommended screening test questions (ACIP recommendation):
- Have you or family member
- Ever had eczema/atopic dermatitis dx?
- An itchy, red, scaly rash lasting over 2 wks?
- Have you or family member
Also, see CDC site for medical management of adverse reactions to vaccinia vaccination.
- Contact Emergency Operations Center/CDC: T 770-448-7100, for consultation.
- [Health care providers at military medical facilities (or civilian providers treating a U.S. Department of Defense healthcare beneficiary) should call the Defense Health Agency’s 24/7 Immunization Healthcare Support Center at 877-GETVACC (877-438-8222), and select option #1].
- Vaccinia immune globulin (VIG): licensed by FDA for treatment complications of vaccinia immunization.
- EV is a VIG CDCclear indication for urgent use. Early treatment may be life-saving.
- Dose: 0.6-1.0 mL/kg IM = 40ml IM
- Severe/extensive lesions: up to 5-10 mL/kg in divided doses over several days has been used.
- Currently only available as IM. Intravenous preparation may be available in the future.
- Cidofovir: effective against smallpox in vitro.
- Tecovirimat is FDA approved for the treatment of smallpox.
- Bacterial superinfections: common and should be treated to cover anticipated pathogens such as streptococci, staphylococci or Gram-negatives.
- Septic shock may complicate. Usual supportive care recommended.
- Eczema is the most common contraindication to the vaccine, and EV was the most common cause of vaccine mortality in the 1960s.
- The best prevention of EV: careful history to assess for current or prior hx of eczema/atopic dermatitis.
- VIG is brutal due to large IM volume; IV form is in production
- GREATEST RISKS: age < 1yr, active eczema, primary vaccination.
Pathogen Specific Therapy
1st Line Agent
2nd Line Agent
Basis for recommendation
- Torres T, Ferreira EO, Gonçalo M, et al. Update on Atopic Dermatitis. Acta Med Port. 2019;32(9):606-613. [PMID:31493365]
Comment: Given rising incidence, instructive to be fully up to date on diagnosing atopic dermatitis/eczema if administering smallpox vaccine.
- CDC. Smallpox vaccines. https://www.cdc.gov/smallpox/clinicians/vaccines.html (accessed 7/21/20)
Comment: Helpful images and directions regarding immunization with vaccinia (currently ACAM2000) regarding indications, exclusions, diagnosis of vaccina complications and management of adverse reactions.
- von Sonnenburg F, Perona P, Darsow U, et al. Safety and immunogenicity of modified vaccinia Ankara as a smallpox vaccine in people with atopic dermatitis. Vaccine. 2014;32(43):5696-702. [PMID:25149431]
Comment: This investigational vaccine did not appear to cause EV when administered to patients (n = 45) with either allergic rhinitis or atopic dermatitis. The MVA is not thought to significantly replicate within the skin.
- Said MA, Haile C, Palabindala V, et al. Transmission of vaccinia virus, possibly through sexual contact, to a woman at high risk for adverse complications. Mil Med. 2013;178(12):e1375-8. [PMID:24306023]
Comment: Report of EV in a non-vaccinee who had atopic dermatitis and likely acquired from a sexual encounter with a recently immunized military person.
- Kawakami Y, Tomimori Y, Yumoto K, et al. Inhibition of NK cell activity by IL-17 allows vaccinia virus to induce severe skin lesions in a mouse model of eczema vaccinatum. J Exp Med. 2009;206(6):1219-25. [PMID:19468065]
Comment: In this murine model, blocking IL-17 appeared to replicate severe skin lesions which these authors say implicates a role for NK cells in the pathogenesis potentially in humans with atopy, etc.
- Vora S, Damon I, Fulginiti V, et al. Severe eczema vaccinatum in a household contact of a smallpox vaccinee. Clin Infect Dis. 2008;46(10):1555-61. [PMID:18419490]
Comment: Severe case of eczema vaccinatum in a child of vaccinated Iraq soldier on leave after smallpox vaccination. The child had eczema and was critically but survived with vaccinia IG, cidofovir, ST-246 and skin grafts.
- Reif DM, McKinney BA, Motsinger AA, et al. Genetic basis for adverse events after smallpox vaccination. J Infect Dis. 2008;198(1):16-22. [PMID:18454680]
Comment: Genotyping of patients with severe reactions to smallpox vaccination showed single nucleotide polymorphisms in the interferon regulatory factor-1 gene in those with severe reactions.
- Greenberg RN, Kennedy JS. ACAM2000: a newly licensed cell culture-based live vaccinia smallpox vaccine. Expert Opin Investig Drugs. 2008;17(4):555-64. [PMID:18363519]
Comment: Review of ACAM 2000 which was FDA approved as a suitable replacement for Dryvax in the event of bioterrorism in 2007.
- Centers for Disease Control and Prevention (CDC). Secondary and tertiary transfer of vaccinia virus among U.S. military personnel--United States and worldwide, 2002-2004. MMWR Morb Mortal Wkly Rep. 2004;53(5):103-5. [PMID:14961003]
Comment: Among 407,923 there were 30 reported cases of contact vaccinia. Most were "bed partners" - 12 spouses and 8 adult friends. There were no transmissions to health care workers or pts. The rate with primary vaccinees was 7.4/100,000 and for secondary vaccines, it was 5.2/100,000 (this may be underreported, but the data may be better in the military population and the paucity of children compared to prior experience is striking).
- Naleway AL, Belongia EA, Greenlee RT, et al. Eczematous skin disease and recall of past diagnoses: implications for smallpox vaccination. Ann Intern Med. 2003;139(1):1-7. [PMID:12834312]
Comment: The frequency of atopic dermatitis is 0.8% involving 2.3% of households. History will miss 30-40%.
- Neff JM, Lane JM, Fulginiti VA, et al. Contact vaccinia--transmission of vaccinia from smallpox vaccination. JAMA. 2002;288(15):1901-5. [PMID:12377090]
Comment: Review of contact vaccinia, which is the transmission of this virus to others. Risk is close contact nearly always household contact, occasionally in hospitals. Frequency from the 1960’s was 20-60/mil vaccinees. Disease in recipient depends on host-the the greatest risks are vaccinia necrosum in persons w/T cell, cell defects & eczema. Vaccination in persons w/eczema was a major risk. This accounted for most vaccine-associated deaths and most uses of VIG. The greatest risks were young age & primary vaccination. The risk of EV is thought to be substantially increased due to an increased rate of atopic dermatitis.
- De Clercq E. Cidofovir in the treatment of poxvirus infections. Antiviral Res. 2002;55(1):1-13. [PMID:12076747]
Comment: Cidofovir is active in vitro vs. vaccinia and all other poxviruses. Clinical data are limited to case reports of treatment of molluscum contagiosum and orf.
- Breman JG, Henderson DA. Diagnosis and management of smallpox. N Engl J Med. 2002;346(17):1300-8. [PMID:11923491]
Comment: Review of the disease. The last case was 1977; last in the U.S. was 1949. SP vaccination stopped in the US in 1971 so few (< 30yrs have been vaccinated). The vaccine is highly effective for 5-10yrs. Disease is acquired by inhalation. Contagious primarily at the rash stage or about 3wks.
- Smee DF, Bailey KW, Sidwell RW. Treatment of lethal vaccinia virus respiratory infections in mice with cidofovir. Antivir Chem Chemother. 2001;12(1):71-6. [PMID:11437324]
Comment: Mice were challenged with cowpox and treated with cidofovir that was 100% effective at 30mg/kg/d.
- Laughter D, Istvan JA, Tofte SJ, et al. The prevalence of atopic dermatitis in Oregon schoolchildren. J Am Acad Dermatol. 2000;43(4):649-55. [PMID:11004621]
Comment: This study showed a prevalence of atopic dermatitis to be 7-17%.
- Nettleton PF, Gilray JA, Reid HW, et al. Parapoxviruses are strongly inhibited in vitro by cidofovir. Antiviral Res. 2000;48(3):205-8. [PMID:11164507]
Comment: The MIC50 for cidofovir vs. vaccinia was 1.32 mcg/ml.
- Cooper KD, Kazmierowski JA, Wuepper KD, et al. Immunoregulation in atopic dermatitis: functional analysis of T-B cell interactions and the enumeration of Fc receptor-bearing T cells. J Invest Dermatol. 1983;80(3):139-45. [PMID:6219166]
Comment: Atopic dermatitis is associated with reduced CMI, defective antibody-dependent cellular cytotoxicity, reduced immunoregulatory T cells, elevated IgE, and high incidence of IgE mediated responses to skin tests to common inhaled antigens.
- Shirasawa K, Akai K, Kawaguchi Y, et al. Widespread eczema vaccinatum acquired by contacts. A report of an autopsy case. Acta Pathol Jpn. 1979;29(3):435-55. [PMID:377910]
Comment: A case report of lethal EV in a 4-month-old with "allergic dermatitis". Skin lesions showed vaccinia was cytoplasm of cells at the stratum malpighii of the dermis + neutrophils and macrophages. The virus was also cultivated.
Typical rash of EZ.