# Presentation: 942741

## Dermatologic Manifestations of Hypersensitivity ReactionsErythema Multiforme

**Notes:**
Erythema multiforme (EM), sometimes called roseola vaccinia or toxic urticaria, may present as a variety of lesions, including macules, papules, urticaria, and typical bull’s-eye  (targetoid or iris) lesions (1,[i]). Since few clinical descriptions of vaccinia-associated erythema multiforme rashes are available, the following details are extrapolated from the common descriptions of EM occurring after herpes simples or mycoplasma infections.  The hallmark target lesion of EM associated with other infections usually presents with a central, dark papule or vesicle, surrounded by a pale zone and a halo of erythema, usually within 10 days following viral infection (35).  The limited clinical description of EM following smallpox vaccination appears to follow a similar time course (1).  The rash of EM may be extremely pruritic, lasting up to 4 weeks, and patients benefit from administration of oral antipruritics (35).  
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Reference:[i] Habif. Clinical Dermatology, 3rd ed.
Annotation:  Note the hallmark bull’s eye lesion of erythema multiforme above the ankle on day 8.
Source:  New England Journal of Medicine.  NEJM, Frey et al, 346(17), April 25, 2002.  Copyright©2002  Massachusetts Medical Society.  All rights reserved.

## Dermatologic Manifestations of Hypersensitivity ReactionsStevens-Johnson Syndrome

**Notes:**
Less commonly, erythema multiforme can progress to Stevens-Johnson syndrome (SJS), a more serious condition.  Stevens-Johnson syndrome typically includes systemic symptoms with involvement of 2 or more mucosal surfaces, or 10% of body surface area and requires hospitalization and supportive care.    

The role of systemic steroids for treatment of SJS is controversial; therefore the decision to administer systemic steroids to patients with post-vaccinial SJS, should be made with expert consultation (e.g., with a dermatologist, immunologist, or infectious disease specialist), according to the prevailing standard-of-care.  Vaccinia immune globulin is not used to treat non-specific rashes, EM or Stevens-Johnson syndrome, because these lesions are likely a manifestation of a hypersensitivity reaction and are not thought to contain vaccinia virus.  
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Reference:
[i] Hurwitz S. Clinical Pedatric Dermatology. Saunders; Philadelphia, 1993
Annotation:  Stevens-Johnson Syndrome approximately 2 weeks after vaccination of an 8 month old boy.  The lesions are raised, circinate and widespread.
Source:  J. Michael Lane, Teaching Slide set.  J.M. Lane, M.D.

## Vaccinia Specific Adverse EventsInadvertent Inoculation

**Notes:**
Inadvertent inoculation is a common but avoidable complication of smallpox vaccination.  Inadvertent inoculation occurs when vaccinia virus is transferred from a vaccination site to second location on the vaccinee or to a close contact.  The most common sites involved are the face, eyelid, nose, mouth, lips, genitalia, and anus.  In immunocompetent individuals, lesions follow the same course as the vaccination site.  

Clinicians of the smallpox eradication era observed that lesions from inadvertent inoculation mature at the same pace as the vaccination site.    In contrast, lesions from inadvertent inoculation which occurred greater than 5 days post vaccination appeared attenuated, which suggested that the developing immune response may limit the reaction.
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Annotation:  Six year old with multiple inadvertent inoculation sites on face which healed without scarring.
Source:  J. Michael Lane, Teaching Slide set.  J.M. Lane, M.D.

## Vaccinia Specific Adverse EventsInadvertent Inoculation

**Notes:**
A primary prevention strategy to avoid inadvertent inoculation is to instruct vaccinees and their close contacts to avoid touching or scratching the vaccination site from the time of vaccination until the scab separates.  In addition, vigilant hand washing with soap and warm water, or 60% based alcoholic hand rub solutions, after touching an unhealed vaccination site or changing a vaccination dressing is critical.  Lesions from an inadvertent inoculation contain live vaccinia virus and the same contact precautions necessary for a vaccination site are necessary for these secondary lesions.    Individuals at highest risk for inadvertent inoculation appears to be are the very young (e.g., ages 1-4 years) and those with disruption of the epidermis.
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Annotation:  Five year old girl with inadvertent inoculation to bilateral lower eyelids.  Typical vaccinia lesions are visible.
Source:  J. Michael Lane, Teaching Slide set.  J.M. Lane, M.D.

## Vaccinia Specific Adverse EventsPalebral Autoinoculation

**Notes:**
Periocular and ocular implantation (hereafter 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.  
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References:[i] Ruben F, Lane M: Ocular vaccinia: an epidemiologic analysis of 348 cases. Arch Ophthal 1970;84
[ii] Pavan-Langston, D.  Ocular Viral Diseases, In: Galasso G, Whitley R. and Merigan T, eds:  Antiviral Agents and Viral Diseases of Man. Lippincott-Raven Press, 1997.
[iii] Fulginiti V, Winograd L, Jackson M, Ellis P: Therapy of experimental vaccinal keratitis: effect of idoxuridine and VIG. Arch Ophthalmol 1965;74:539-44.
Annotation:  Palebral autoinoculation in contact of a vaccinee.  This and the next four slides demonstrate the progression and reside of severe palpebral vaccinia.
This 2-year-old boy acquired vaccinia from his mother who was vaccinated 12 days before his ocular vaccinia became apparent.  He was hospitalized for 9 days and treated with VIG.  (Photograph taken 4 days after onset of his vaccinia.)
Source:  J. Michael Lane, Teaching Slide set.  J.M. Lane, M.D.

## Vaccinia Specific Adverse EventsPalebral Autoinoculation

**Notes:**
Note how quickly this patient’s lesions have resolved.  This photograph was taken 8 days after onset.
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Annotation:  Demonstrates considerable resolution and beginning of scarring of the eyelids.  (Photograph taken 8 days after onset.)
Source:  J. Michael Lane, Teaching Slide set.  J.M. Lane, M.D.

## Vaccinia Specific Adverse EventsPalebral Autoinoculation

**Notes:**
The affected eye had nearly complete loss of eyelashes and rolled-up lid margins by two weeks after onset.
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Annotation:  Note the essentially complete loss of eyelashes and the rolled-up lid margins.  (Photograph taken 2 weeks after onset.)
Source:  J. Michael Lane, Teaching Slide set.  J.M. Lane, M.D.

## Vaccinia Specific Adverse EventsPalebral Autoinoculation

**Notes:**
To compare, look at the child’s other eye.
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Annotation:  Same child’s normal contralateral eye with sharp lid margins and normal eyelashes.
Source:  J. Michael Lane, Teaching Slide set.  J.M. Lane, M.D.

## Vaccinia Specific Adverse EventsBlepharoconjunctivitis

**Notes:**
Ocular vaccinia disease may occur in several forms, including blepharitis (inflammation of the eyelid), conjunctivitis, keratitis (inflammation of the cornea, including epithelial and stromal forms), iritis, or combinations thereof. When evaluating a patient with the new onset of a red eye or periocular vesicles, vaccinia infection should be considered and history of recent vaccinia exposure (e.g. smallpox vaccination or close contact with a vaccine recipient) should be sought. The goal of therapy of ocular disease is to prevent complications, especially corneal scarring associated with keratitis, and the patient should be co-managed with an ophthalmologist. Untreated ocular vaccinial infection and the administration of VIG in rabbits have been reported to result in corneal scarring. The current ACIP recommendation states that VIG is contraindicated in a patient with vaccinial keratitis.  However, this recommendation has been re-evaluated by the Public Health Service.  VIG should not be withheld if there is a comorbid condition where the administration of VIG could be life-saving (e.g., eczema vaccinatum or progressive vaccinia) and may be considered to treat vision-threatening lid disease even if keratitis is present. 

Uncomplicated lesions are self-limited, resolving in about 3 weeks, and require no therapy.  If extensive body surface area is involved, or ocular vaccinia infection (without keratitis) or severe manifestation of inoculation has occurred, treatment with vaccinia immune globulin may speed recovery.
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Annotation:  Acute blepharoconjuncitvitis in 22 yo male (military).
Source:  American Journal of Ophthamology.  Pepose & Langston, “Ocular Complications of...” (submitted for publication), photographs.  Deborah Pavan-Langston, MD, FACS, Harvard Medical School, Massachusetts Eye and Ear Infirmary.

## Vaccinia Specific Adverse EventsBlepharoconjunctivitis

**Notes:**
This is the same patient as in the previous picture after 14 days and treatment with vaccinia immune globulin.
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Annotation:  Same patient in previous picture.  Healing blepharoconjunctivitis 14 days later.  Treated with vaccinia immune globulin x 2.
Source:  American Journal of Ophthamology.  Pepose & Langston, “Ocular Complications of...” (submitted for publication), photographs.  Deborah Pavan-Langston, MD, FACS, Harvard Medical School, Massachusetts Eye and Ear Infirmary.

## Vaccinia Specific Adverse EventsKeratitis

**Notes:**
The goal of therapy of ocular disease is to prevent complications, especially corneal scarring associated with keratitis, and the patient should be co-managed with an ophthalmologist. Untreated ocular vaccinial infection and the administration of VIG in rabbits have been reported to result in corneal scarring. The current ACIP recommendation states that VIG is contraindicated in a patient with vaccinial keratitis.  However, this recommendation has been re-evaluated by the Public Health Service.  VIG should not be withheld if there is a comorbid condition where the administration of VIG could be life-saving (e.g., eczema vaccinatum or progressive vaccinia) and may be considered to treat vision-threatening lid disease even if keratitis is present. 
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Annotation:  Acute vaccinial corneal ulcer (keratitis).
Source:  American Journal of Ophthamology.  Pepose & Langston, “Ocular Complications of...” (submitted for publication), photographs.  Deborah Pavan-Langston, MD, FACS, Harvard Medical School, Massachusetts Eye and Ear Infirmary.