Differentials
Smallpox
SIGNS / SYMPTOMS
Has more prominent fever and more noticeable constitutional symptoms than varicella.
Greatest number of lesions are on face and extremities (centrifugal distribution), and lesions present at the same stage in development.[63]
Review history of recent smallpox vaccine or other possible exposures. Since natural transmission has been eradicated, new cases would more likely occur through laboratory exposure or as an act of bioterrorism. If smallpox is considered a possible diagnosis, immediate consultation should be sought and the patient should be placed in immediate isolation (standard, contact, and airborne). The patient should not be permitted to leave isolation until smallpox has been excluded as a diagnostic possibility. Consultation with local health departments is also highly recommended.
INVESTIGATIONS
Polymerase chain reaction (PCR) test for smallpox will be positive.
PCR test for varicella-zoster virus will be negative.
Herpes zoster infection (shingles)
SIGNS / SYMPTOMS
Commonly presents in adulthood, particularly after the age of 60.
Rash typically follows a dermatomal distribution of a cranial nerve or dorsal root ganglion.
INVESTIGATIONS
Varicella zoster is a clinical diagnosis based on examination of the rash and history of exposure. Differentiating tests are not usually indicated.
Herpes simplex virus (HSV) infection
SIGNS / SYMPTOMS
Usually affects the mucous membranes of the oral or genital region, but skin infections, usually localized, can also be observed.
INVESTIGATIONS
Laboratory tests positive for HSV 1 or HSV 2.
Stevens-Johnson syndrome/toxic epidermal necrolysis
SIGNS / SYMPTOMS
Lesions can look like targets initially but eventually become flaccid blisters.
A large proportion of patients also present with diffuse erythema (erythroderma), and a significant number of patients complain of pain in involved areas.
Blisters can become confluent and are associated with a positive Nikolsky sign (epidermal layer easily sloughs off when pressure is applied to the affected area).[64]
Patients often have a history of exposure to an agent (medication) associated with the condition.
INVESTIGATIONS
Skin biopsy can be helpful; however, most often the diagnosis is made on clinical presentation.[65]
Mpox (Monkeypox)
SIGNS / SYMPTOMS
Recent travel to Africa or recent close contact (including sexual contact) with someone who has Mpox is likely to be present.[66]
Lesions present in similar stages (monomorphic) but are found on the palms and the soles of the feet.
Also associated with lymphadenopathy, which is rarely found in varicella.[67]
INVESTIGATIONS
PCR test for monkeypox will be positive.
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