Dr. George Han discusses clinical considerations for dermatologists during the monkeypox outbreak.

As case counts of monkeypox cases increase in Europe and other parts of the globe including the US, dermatologists may have an important role to play in terms of making differential diagnoses. George Han, MD a dermatologist at Lenox Hill Hospital in New York City, spoke to Practical Dermatology® magazine about the current monkeypox outbreak. “As we are all learning more about monkeypox of late, it is important to keep in mind the salient features of monkeypox for dermatologists,” he says.

Tell us about the monkeypox rash and its stages? 

George Han: “Monkeypox causes a cutaneous eruption over the course of about two to four weeks. The infection starts with an incubation period of a week or two on average. There is a prodromal phase of up to four days with fever, malaise, and lymphadenopathy, followed by the development of a rash. Importantly, the fever is often milder than that seen with smallpox and the lymphadenopathy (usually submandibular, cervical, or inguinal) also distinguishes it from smallpox, where this feature is usually absent. The rash tends to appear quickly, and lesions tend to be found in the same stage across all affected areas. Lesions can be numerous and range into the thousands; they tend to start on the face and central trunk and spread distally (centrifugal pattern). Mucous membrane and genital involvement are common features, while acral involvement is also more common than varicella. There is a distinct progression from erythematous macules to papules, then vesicles/pustules, and eventuates into umbilication, scab/eschar formation, and finally, desquamation. In this sense, the progression of lesions is quite similar to smallpox and cowpox exanthems. Patients should be isolated until all lesions have scabbed over and a throat swab (for PCR) is negative. “

What rashes might this be confused with?

Dr. Han: “The differential diagnosis of monkeypox includes, of course, the other orthopoxviruses, chiefly smallpox, and cowpox. It would be very unlikely to encounter smallpox without a known outbreak. Nonetheless, a few salient features are worth noting. First, a smallpox patient would likely appear much 'sicker,' with severe malaise and high fever. As noted above, lymphadenopathy would be relatively rare in smallpox; however, the skin lesions and the rash itself would not be any different. Indeed, the histology of a lesion, if a biopsy were to be done, would show nonspecific changes that would mimic other viral exanthems such as ballooning degeneration of keratinocytes, spongiosis, dermal edema, and a mixed inflammatory cell infiltrate. To that end, it wouldn't help distinguish this from other orthopoxviruses or even herpesviruses, for that matter, so a biopsy would not be indicated or very helpful in this case. Varicella is an entity we encounter commonly in inpatient dermatology, and the lesions can vary greatly depending on previous exposure and immune status. An important clue would be the heterogeneous lesions one would expect to see with varicella, in contrast with the monomorphic lesions of monkeypox. The prodrome of varicella also tends to be less severe. Coxsackievirus (hand-foot-mouth disease or HFMD) could be considered, but the ovoid lesions that are primarily acral and mucosal are less likely to progress to vesicular/pustular stages. However, atypical and severe forms of HFMD could be concerning as a mimic of monkeypox. The distribution is important here, as is the prodrome which tends to be mild. Syphilis is, of course, the great mimicker, but systemic complaints would be quite different and this wouldn't be as much of an acute illness. Finally, morbilliform rashes, such as those seen with measles, nonspecific viral exanthems, and drug hypersensitivity, could be considered, but the lesions themselves would be smaller and would not go through the evolution and progression described above. Hopefully, this outbreak will be self-contained with heightened vigilance, but we as dermatologists should be alerted to the possibility of encountering monkeypox in our clinical practices.”

What should dermatologists look out for?

Dr. Han: “As dermatologists, especially those of us with hospital inpatient consult responsibilities, we tend to be called for 'maculopapular' rashes of all kinds, it is conceivable that we may be on the front lines of diagnosing monkeypox, so it's good to keep salient features of this clinical entity in mind. There are certain features of monkeypox that are important to keep in mind. There is some disagreement about how easily transmissible this is from person to person, with earlier literature suggesting that person-to-person transmission is rare. However, this is likely related to the exact strain of monkeypox in question, as African endemic forms tend to be more virulent than imported zoonoses where African rodents (the likely reservoir for monkeypox) infect other animals that they come into contact with humans (such as an outbreak related to prairie dogs in the US Midwest in 2003). Overall, this is a less transmissible virus than varicella (and certainly less than influenza or coronavirus) that likely requires prolonged contact, especially sustained direct physical contact or contact with bodily fluids. But there is no doubt that the skin lesions themselves are reservoirs of infectious virus particles, so care must be taken when manipulating them.”