Clinical manifestations
Monkeypox evolves through 2 stages: a pre-eruptive stage and an eruptive stage. Prodromal symptoms include malaise, severe headache, myalgias, fever, drenching sweats, backache, fatigue, sore throat, dyspnea, and cough. Within 2-3 days, the characteristic skin eruption develops. The lesions usually begin on the face and then spread in a centrifugal manner to the trunk and extremities, including the palms of the hands and soles of the feet. The lesions typically progress from macules to papules to vesicles to pustules. They then crust and scab over. An interesting additional finding is the presence of prominent lymphadenopathy behind the ear, beneath the mandible, in the neck, and in the groin.1
Several different illnesses must be considered in the differential diagnosis of monkeypox infection. They include measles, scabies, secondary syphilis, and medication-associated allergic reactions. However, the 2 conditions most likely to be confused with monkeypox are chickenpox (varicella) and smallpox. Lymphadenopathy is much more prominent in monkeypox compared with chickenpox. Moreover, with monkeypox, all lesions tend to be at the same stage of evolution as opposed to appearing in crops as they do in chickenpox. Smallpox would be extremely unlikely in the absence of a recognized laboratory accident or a bioterrorism incident.7
Diagnosis
The presumptive diagnosis of monkeypox infection is made primarily based on clinical examination. However, laboratory testing is indicated to definitively differentiate monkeypox from other orthopoxvirus infections such as varicella and smallpox.
In specialized laboratories that employ highly trained personnel and maintain strict safety precautions, the virus can be isolated in mammalian cell cultures. Electron microscopy is a valuable tool for identifying the characteristic brick-shaped poxvirus virions. Routine histologic examination of a lesion will show ballooning degeneration of keratinocytes, prominent spongiosis, dermal edema, and acute inflammation, although these findings are not unique to monkeypox.1
The Centers for Disease Control and Prevention (CDC) has developed serologic tests that detect immunoglobulin (Ig) M- and IgG-specific antibody. However, the most useful and practical diagnostic test is assessment of a skin scraping by polymerase chain reaction (PCR). This test is more sensitive than assessment of serum PCR.1
When the diagnosis of monkeypox is being considered, the clinician should coordinate testing through the local and state public health departments and through the CDC. Effective communication with all agencies will ensure that laboratory specimens are processed in a timely and efficient manner. The CDC website presents information on specimen collection.8
How do we manage monkeypox?
Prevention
The first step in prevention of infection is to isolate infected individuals until all lesions have dried and crusted over. Susceptible people should avoid close contact with skin lesions, respiratory and genital secretions, and bedding of patients who are infected.
The ultimate preventive measure, however, is vaccination of susceptible people either immediately before exposure (eg, military personnel, first responders, infection control investigators, health care workers) or immediately after exposure (general population). Older individuals who received the original smallpox vaccine likely have immunity to monkeypox infection. Unfortunately, very few women who currently are of reproductive age received this vaccine because its use was discontinued in the United States in the early 1970s. Therefore, the vast majority of our patients are uniquely susceptible to this infection and should be vaccinated if there is an outbreak of monkeypox in their locality.7,9
The current preferred vaccine for prevention of both smallpox and monkeypox is the Jynneos (Bavarian Nordic A/S) vaccine.10 This agent incorporates a replication-deficient live virus and does not pose the same risk for adverse events as the original versions of the smallpox vaccine. Jynneos is administered subcutaneously rather than by scarification. Two 0.5-mL doses, delivered 28 days apart, are required for optimal effect. The vaccine must be obtained from local and state health departments, in consultation with the CDC.7,9
There is very little published information on the safety of the Jynneos vaccine in pregnant or lactating women, although animal data are reassuring. Moreover, the dangers of monkeypox infection are significant, and in the event of an outbreak, vaccination of susceptible individuals, including pregnant women, is indicated.
Key points at a glance
- Monkeypox is a member of the orthopoxvirus genus and is closely related to the smallpox virus. It is a large, double-stranded, enveloped DNA virus.
- The virus is transmitted primarily by close contact with infected animals or other humans or by consumption of contaminated bushmeat.
- The infection evolves in 2 phases. The pre-eruptive phase is characterized by severe flu-like symptoms and signs. The eruptive phase is distinguished by a diffuse papular-vesicular rash.
- The most valuable test for confirming the diagnosis is a polymerase chain reaction test of a fresh skin lesion.
- In women who are pregnant, monkeypox has been associated with spontaneous abortion and fetal death.
- Three antiviral agents may be of value in treating infected patients: cidofovir, brincidofovir, and tecovirimat. Only the latter has an acceptable safety profile for women who are pregnant or lactating.
- The new nonreplicating smallpox vaccine Jynneos (Bavarian Nordic A/S) is of great value for pre- and post-exposure prophylaxis.
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