The dermatological evolution of the first case of monkeypox reported in India

Discussion

The monkeypox virus (genus: Orthopoxvirus, family: Poxviridae),¹ has two genetic clades, the West African and Central African.³ The current strain is now said to belong to a new clade 3, of the West African strain, which is milder and less fatal (<1%) as per Centre for Infectious Disease Research and Policy (CIDRAP News of Jun 24, 2022). There have been only about 10 fatalities since January 2022. Although first discovered in monkeys in a research facility in 1958 in Copenhagen, Denmark,⁴ which gave it its name, the largest animal reservoirs of the virus have been found in rodents, including squirrels and giant pouched rats, both of which are hunted for food.³ The first human case was documented in 1970 in an infant from The Democratic Republic of Congo,² while smallpox which is caused by a related virus, was declared eradicated by WHO in 1980 as a result of vaccinations. Smallpox vaccination confers 85% immunity against monkeypox too,⁵ but the waning herd immunity due to the discontinuation of smallpox vaccination 42 years ago, could be a reason for the resurgence of monkeypox.⁶ The virus spreads by close skin or mucosal contact with an infected person (touching, kissing, cuddling, sex), or through aerosols, contaminated fomites (beddings, towels, utensils) or by handling an infected animal or its meat. (CDC)

The incubation period of monkeypox is 5–21 days,⁷ (average 8.1 days), after which a prodrome of fever, headache, myalgia, chills, nasal congestion, cough and fatigue occur, along with lymphadenopathy, a feature which differentiates it from smallpox. Prodrome is followed by small oral mucosal papules or erosions and skin lesions over the face which extend centrifugally to the extremities. Over the next four weeks, the rashes evolve through macular, papular, vesicular and pustular phases in 1–2 day increments, being monomorphic at each stage. All lesional changes are synchronous and the pustular phase heals in 5–7 days with crusting. In most patients, the scabs fall off in 7–14 days and patients are considered to cease being infective at this point.⁸ Monkeypox can spread to others from the time of onset of symptoms till the crust has fallen off, the rash has fully healed and a new layer of skin has formed.⁹ Extracutaneous manifestations like secondary infection of skin and/or soft-tissue, pneumonitis, encephalitis, eye involvement and blindness, foetal transmission in infected pregnant women, etc., are possible complications.¹⁰ Atypical presentations without prodrome, onset of lesions in genitalia,¹¹ perianal lesions associated with proctitis,⁹ pleomorphism of skin lesions or even absence of skin lesions etc can also occur.¹² In the current outbreak, monkeypox has been found more in males having sex with males and had onset of lesions on genitalia.¹¹

The oral mucosal lesions of herpes simplex present as 1–2 mm blisters that rapidly break down and coalesce to form small painful shallow irregular ulcers covered by a yellowish-grey pseudomembrane and surrounded by an erythematous halo.¹³ The co-existence of herpes simplex infection could explain the extensive painful oral lesions in this patient.

Lab diagnosis is crucial to differentiate monkeypox from smallpox infection. Real-time PCR is the gold standard for diagnosis and this patient tested positive in all the samples sent, throughout the stages from maculopapular to crust and became negative from the stage when the crust fell off and re-epithelialisation occurred. This means that the patient has to be in the infective state for a diagnosis.¹⁴ Conventional tests such as viral isolation from a clinical specimen, electron microscopy, and immunohistochemistry are valid techniques but require advanced technical skills and training and a sophisticated laboratory.¹⁴

The current treatments for human monkeypox include oral tecovirimat, brincidofovir, cidofovir and vaccinia immune globulin-VIGIV.¹⁵ The vaccines available are JYNNEOS and ACAM2000, both live vaccines. JYNNEOS is administered subcutaneously, 0.5 mL, two doses four weeks apart, including as post-exposure prophylaxis.¹⁶ ACAM2000 is given as a single 0.0025 mL percutaneous dose.¹⁶

The extensive oral involvement seen in this patient is not a common feature in the ongoing monkeypox outbreak and could be due to the concurrent HSV infection. This patient is being reported as the first confirmed case of monkeypox in India and is unique with respect to the shorter duration and rapid clearance of lesions.