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Generalized Vaccinia After Smallpox Vaccination with Concomitant Primary Epstein Barr Virus Infection

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Generalized Vaccinia After Smallpox Vaccination with Concomitant Primary Epstein Barr Virus Infection Case in Point Generalized Vaccinia After Smallpox Vaccination With Concomitant Primary Epstein Barr Virus Infection Jeremy Mandia, MD; and Kathryn Buikema, DO A patient presents with a spreading rash 9 days following inoculation with the smallpox vaccine. eneralized vaccinia (GV) is atopic dermatitis, or other rashes a rare, self-limiting complica- and reported no systemic symptoms. Figure 1. Satellite Lesions Seen tion of the smallpox vacci- His vitals also were within normal on Postvaccination Day 1 Gnation that is caused by the limits. A clinical diagnosis of inad- systemic spread of the virus from vertent inoculation (also termed ac- the inoculation site. The incidence cidental infection) with satellite of GV became rare after routine vac- lesions was made, and he was dis- cination was discontinued in the U.S. charged with counseling on wound in 1971 and globally in the 1980s care and close follow-up. Two days after the disease was eradicated.1,2 later, on postvaccination day 11, he However in 2002, heightened con- presented with new symptoms of a cerns for the deliberate release of the headache, fever, chills, diffuse my- smallpox virus as a bioweapon led algia, sore throat, and spreading er- the U.S. military to restart its small- ythematous macules, papules, and pox vaccination program for soldiers vesicles on his arms, chest, abdo- and public health workers.3,4 Here, men, back, legs, and face (Figures the authors describe a patient with 2A-2D). His vital signs were remark- concomitant GV and mononucleosis. able for tachycardia with heart rate of 100 bpm and a fever of 103º F (39.4º stabilized with conservative treat- CASE REPORT C). He was sent to the emergency ment without the need for vaccine A 19-year-old active-duty marine department with a presumed GV immune globulin (VIG). He conva- presented to his battalion aid station diagnosis. lesced for 72 hours and was referred with concern for a spreading vesicu- A complete blood count, liver to dermatology on the following day. lar rash 9 days after a primary inocu- function tests, and basic metabolic Quarantining him in a single occu- lation with the smallpox vaccine. The panel were unremarkable. Given his pancy barracks room until all lesions rash was limited to the inoculation symptom of pharyngitis, a rapid strep crusted over addressed the concern site on his left shoulder (Figure 1). test was performed. The test was for spread of the virus to nonimmu- He had no medical history of eczema, negative, and a throat culture showed nized marines or family members. no growth. A mononucleosis screen On postvaccination day 12, the Dr. Mandia is the general medical officer at also was performed and was posi- patient continued to be clinically Combat Logistics Battalion 3 in Kaneohe Bay, tive. The patient was diagnosed with well, and he remained afebrile. The Hawaii. Dr. Buikema is the general medical offi- cer at Fort Belvoir Community Hospital Dermatol- mononucleosis and GV. His condi- dermatologist obtained a skin bi- ogy Clinic in Virginia. tion improved, and his vital signs opsy from a lesion on the patient’s 34 • FEDERAL PRACTITIONER • MARCH 2017 www.fedprac.com Figures 2A-2D. Postvaccination day 11 A B C D Figures 3A-3D. Postvaccination day 22 A B C D right shin. The biopsy demonstrated may be due to a subtle immunologic value given the large number of tests marked epidermal necrosis with defect, specifically in the B-cell line.6,7 needed to prevent a single case of GV. peripheral keratinocytes showing Epstein-Barr virus affects the B-cell Generalized vaccinia is a rare ballooning degeneration and viral line, and concurrent infection may complication after smallpox vaccina- cytopathic changes consistent with depress humoral immunity and allow tion. Despite its dire appearance, GV GV. Antibody titers showing high lev- for systemic spread of the virus.8,9 typically resolves spontaneously with els of Epstein-Barr virus (EBV) cap- This case illustrates the poten- limited adverse effects (AEs).14 The sid IgM and IgG present confirmed tial for a severe reaction after small- pre-eradication reported incidence mononucleosis infection within the pox vaccination in a patient with a was 17.7 per 1,000,000 recipients in past 6 months. The patient remained concomitant EBV infection. Service a national survey.15 Posteradication clinically well and was released from members primarily receive the small- the incidence of GV was 3 times as quarantine on postvaccination day pox vaccination early in their career high with 2 reported cases in 2003 22 when all lesions crusted over (Fig- when the risk of mononucleosis is at after administration of 38,440 vacci- ures 3A-3D). its highest incidence among young nations.16 Inflammatory reactions can adults, 11 to 48 per 1,000.10-13 Al- be common; however, these reactions DISCUSSION though the potential for disseminated are not due to systemic viral spread.5 The CDC current definition for GV vaccinia following vaccination is rare, When dealing with a vaccinia-spe- is “the spread of lesions to other clinicians need to remain cognizant cific AE, it is important to distinguish parts of the body that are benign in of the risk, which may be enhanced the benign inadvertent inoculations appearance and occur as a result of by recent or subsequent infection and GV from the more serious reac- viremia.”5 Although the exact mecha- with EBV. However, regular screen- tions of eczema vaccinatum (EV) or nisms of viral spread are unknown, it ing for EBV would be of questionable progressive vaccinia (PV). 5 www.fedprac.com MARCH 2017 • FEDERAL PRACTITIONER • 35 GENERALIZED VACCINIA Inadvertent inoculations and GV challenges with the smallpox vaccine (HICPAC). MMWR Recomm Rep. 2003;52(RR- 7):1-16. are usually benign and self-limited— allows for better patient selection that 5. Cono J, Casey CG, Bell DM. Smallpox vaccination requiring only prevention of second- eliminates those with conditions that and adverse reactions. https://www.cdc.gov/mmwr /preview/mmwrhtml/rr5204a1.htm. Updated Febru- ary transmission and nosocomial impair their immune system and im- ary 10, 2003. Accessed February 2, 2017. infection. Eczema vaccinatum occurs proves patient education. 6. Chahroudi A, Chavan R, Kozyr N, Waller EK, Sil- vestri G, Feinberg MB. Vaccinia virus tropism for among persons with atopic dermatitis primary hematolymphoid cells is determined by or eczema.5 The rash that is indica- Author disclosures restricted expression of a unique virus receptor. J Virol. 2005;79(16):10397-10407. tive of EV has similar characteristics The authors report no actual or poten- 7. Sánchez-Puig J, Sánchez L, Roy G, Blasco R. to GV, it can occur anywhere but tial conflicts of interest with regard to Susceptibility of different leukocyte cell types to Vaccinia virus infection. Virol J. favors areas of previous atopic der- this article. 2004;1(1):10. matitis lesions. Unlike patients expe- 8. Küppers R. B cells under influence: transformation of B cells by Epstein-Barr virus. Nat Rev Immunol. riencing GV, patients with EV often Disclaimer 2003;3(10):801-812. are systemically ill and usually re- The opinions expressed herein are 9. Nemerow G, Cooper N. Infection of B lympho- 5,17 cytes by a human herpesvirus, Epstein-Barr virus, is quire VIG treatment. A progres- those of the authors and do not nec- blocked by calmodulin antagonists. Proc Natl Acad sive enlarging necrosis at the primary essarily reflect those of Federal Sci U S A. 1984;81(15):4955-4959. 10. Hallee TJ, Evans AS, Niederman JC, Brooks CM, vaccination site characterizes PV, also Practitioner, Frontline Medical Com- Voegtly JH. Infectious Mononucleosis at the United known as vaccinia necrosum and vac- munications Inc., the U.S. Govern- States Military Academy. A prospective study of a single class over four years. Yale J Biol Med. cinia gangrenosa; unlike GV there are ment, or any of its agencies. This 1974;47(3):182-195. no viral metastases to distant sites.5,18 article may discuss unlabeled or in- 11. Evans AS, Robinton ED. An epidemiological study of infectious mononucleosis. N Engl J Med. Progressive vaccinia is confined to vestigational use of certain drugs. 1950;242:492-496. immune-compromised individuals Please review the complete prescribing 12. Niederman JC, Evans AS, Subrahmanyan L, Mc- 18,19 Collum RW. Prevalence, incidence and persistence with defective cellular immunity. information for specific drugs or drug of EB virus antibody in young adults. N Engl J Med. Due to high mortality rates associ- combinations—including indications, 1970;282(7):361-365. 13. Sawyer RN, Evans AS, Niederman JC, McCollum ated with PV, the CDC advocates ag- contraindications, warnings, and ad- RW. Prospective studies of a group of Yale Univer- gressive therapy with VIG, intensive verse effects—before administering sity freshmen. I. Occurrence of infectious mono- nucleosis. J Infect Dis. 1971;123(3):263-270. monitoring, and tertiary-level sup- pharmacologic therapy to patients. 14. Henderson DA, Borio LL, Lane MJ. Smallpox and portive care.5 vaccinia. In: Plotkin SA, Orenstein WA, Offit PA, eds. Vaccines. 4th ed. Philadelphia, PA: Elsevier; REFERENCES 2004:123-153. CONCLUSION 1. Centers for Disease Control and prevention. Public 15. Lane JM, Ruben FL, Neff JM, Millar JD. Compli- Health Service recommendation on smallpox vac- cations of smallpox vaccination, 1968—national The smallpox vaccination is unique cination. MMWR Recomm Rep. 1971;20:339 surveillance in the United States. N Engl J Med. among vaccinations. It is the only 2. The global eradication of smallpox. World Health 1969;281(22):1201-1208. Organization Web site. http://apps.who.int/iris 16. Vellozzi C, Lane JM, Averhoff F, et al. Generalized vaccine that is administered via in- /bitstream/10665/39253/1/a41438.pdf.
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