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Variola (Smallpox) and its Mimics

Variola (Smallpox) and its Mimics Table

Variola (Smallpox)

Smallpox in a man: Notice the diffuse and extensive distribution of lesions.

Used with Permission from the Centers for Disease
Control and Prevention

Smallpox in a child: Notice that all lesions are in the same stage of development.

Used with Permission from the Centers for Disease
Control and Prevention

Smallpox close-up: Notice that all lesions are in the same stage of development and that they are umbilicated.

Used with Permission from the Centers for Disease
Control and Prevention

Smallpox is an acute exanthematous disease caused by infection with the poxvirus variola. The significant clinical features include a three-day prodromal illness characterized by fever, headache, backache, and vomiting. A generalized vesicular or pustular eruption in the absence of a severe febrile prodrome is unlikely to be smallpox. The generalized centrifugal rash (it spreads from the face, hands, and forearms to the trunk and legs) that follows is a rapid succession of papules, vesicles, pustules, umbilication, and crusting over a 14-day period. The smallpox eruption is concentration on the face and distal extremities, with fewer lesions on the face, abdomen, and back.

Prior vaccination may alter the clinical presentation of smallpox. The following description applies to the classic presentation in unvaccinated individuals.

A macular red rash may precede the appearance of the papules, which are tense to palpation. Papules soon vesiculate, forming a circumscribed, elevated lesion that contains clear fluid. The rash at this point can be very sparse, although individual vesicles can coalesce to form large patches. As the vesicles mature, they turn into pustules.

Central umbilication of the pustule is characteristic of smallpox. Eventually, the pustule crusts over and heals with scar formation. A second important distinguishing characteristic of smallpox is that on any one part of the body, all of the lesions at a given time are in the same stage of development. That is, at any one point in time the lesions are all papules or vesicles or pustules. Bacterial infection of the lesions can occur, producing localized abscesses and cellulitis.

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Varicella (Chickenpox)

Chickenpox vesicle behind the ear. Notice the translucent quality of the vesicle on the skin, the classic "dew drop on a rose petal" appearance.

Chickenpox on the palate. Notice the glistening, water-drop characteristic of the chickenpox vesicle on the palate.

Chickenpox on the hand. Notice the simultaneous occurrence of lesions in different stages of development: macules, papules, vesicles, pustules, and crusts.

Chickenpox in an infant. Notice the rose-colored macules, papules, vesicles, pustules, necrotic pustules, and crusted lesions occurring simultaneously.

Varicella (chickenpox) and herpes zoster (shingles) are distinct clinical entities cause by the varicella-zoster virus (VZV). In young children, prodromal symptoms of chickenpox are uncommon, but in older children and adults, the manifestation of the rash may be preceded by two or three days of fever and chills, malaise, headache, backache, sore throat, and dry cough. A generalized vesicular or pustular eruption in the absence of a significant febrile prodrome is unlikely to be chickenpox.

The rash begins on the face and scalp and spreads rapidly to the trunk, with relative sparing of the extremities. New lesions arise in crops, usually appearing centrally. Chickenpox lesions are most concentrated in the center of the body (trunk more than extremities) or are equally distributed. Each crop proceeds through the developmental phase described below, so that at any given time, a patient can have macules, papules, vesicles, pustules, and crusts. In smallpox, by contrast, at any given time, all lesions on the patient's body are in the same phase of development.

The first sign of chickenpox is rose-colored macules that rapidly progress to papules then to vesicles, then to pustules, and finally to scabbing over with crusts. The typical wall of the vesicle is so thin that it often resembles a drop of water on the reddened surface of the skin (the "dew drop on a rose petal" appearance). As the lesion dries and changes from a vesicle to a pustule, it umbilicates and then crusts over. The crusts fall off in one to two weeks. Scarring is rare unless the lesions become secondarily infected vesicles can occur on the mucous membranes, most commonly on the palate; they can also occur in the nose, pharynx, larynx, trachea, gastrointestinal tract, conjunctiva, and vagina.

Differential Diagnosis: Chickenpox can be distinguished from smallpox in the following manner.

Chickenpox Smallpox
* Begins on the face and scalp, spreads to the trunk
* Lesions in various stages of development can simultaneously be present on the patient's skin
* Begins centrally, then spreads outward to face and extremities
* All lesions are always in a single stage of development

Variola (Smallpox) and its Mimics Table

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Herpes Zoster (Shingles)

Herpes (varicella) zoster on the arm. Notice the characteristic grouping of vesicles

Varicella zoster on the face. Notice the dermatomal distribution of the papules, vesicles, and pustules.

Herpes zoster is a localized disease caused by the varicella-zoster virus (VZV). It is characterized by unilateral radicular pain and a vesicular eruption that is typically limited to one or two dermatomes innervated by a spinal or cranial nerve.

The most distinctive characteristics of herpes zoster are its localization and it distribution, which is almost always unilateral. The individual lesions of varicella (chickenpox) and of zoster are identical, but the lesions of zoster evolve more slowly and are characterized by grouped vesicles. The lesions of varicella, by contrast, are more widely distributed. As in varicella, zoster vesicles evolve into pustules, then dry and crust.

Differential Diagnosis: Zoster can be distinguished from smallpox in the following manner.

Herpes (varicella) zoster Smallpox
* Lesions are unilaterally distributed along a dermatome
* Lesions at any given time are in different stages of development (vesicles, pustules, and crusts are in evidence at one time)
* Lesions are widely distributed
* Lesions at any given time are all at the same stage of development
* Associated with severe constitutional symptoms

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Molluscum Contagiosum

Molluscum contagiosum is a common, benign viral infection of the skin and mucous membranes caused by the molluscum contagiosum virus. It typically affects children, but can be transmitted sexually in adults. The mature lesion is an umbilicated papule.

Lesions begin as small (3 to 6 mm) papules that are smooth, flesh-colored domes with a central dimple. Inside the papule is a white, curd-like core that can be easily expressed. Lesions can occur anywhere on the skin and mucous membranes, but are usually grouped in one or two areas. Occasionally, they may be widely disseminated. Typically fewer than 20 lesions are present, but some individuals may have hundreds. The head, eyelids, trunk, and genitalia are most commonly affected, the genitalia being the predominant site in adults.

The lesions are characteristically asymptomatic, but a few patients may complain of itching or may develop an eczematous reaction around the lesions.

Differential Diagnosis: Molluscum contagiosum can be distinguished from smallpox (and chickenpox) in the following manner.

Molluscum contagiosum Smallpox
* Lesions usually grouped in one or two areas
* Not associated with clinical symptoms
* Lesions are papules only
* Lesions are widespread
* Associated with severe clinical symptoms * Lesions progress from macules to vesicles to papules to crusts (progression occurs all at the same time in smallpox but at different times in chickenpox)

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