Skin related manifestations of Japanese encephalitis-Observations from an outbreak in Assam (India)

Dear Editor,

Japanese encephalitis (JE) is a mosquito-borne zoonotic viral disease caused by a flavivirus(JE virus), which is endemic to the Asian subcontinent. As per WHO, the global disease burden is around 68,000 clinical cases per year with around 2,500 cases being reported from India alone. Most of the JE infections are asymptomatic, with <1 % developing clinical disease. The most dreaded clinical manifestation of this infection is acute encephalitis, with a case fatality ratio varying from 20-30%. There is a 30-50% chance of significant neurologic, cognitive, or psychiatric sequelae among survivors.^1,2 There is a paucity of data on the skin related manifestation of this disease. These could act as a marker of early disease diagnosis and serve as an important tool for epidemiological surveillance.

Six patients of JE were admitted to a tertiary care centre in Guwahati, Assam during the epidemic outbreak of July 2024. The diagnosis was based on criteria laid down by the National Vector Borne Diseases Control Programme (NVBCDP), India. All patients had fever, altered sensorium, joint pain, headache, and myalgia, along with skin lesions and serological evidence of JE virus infection. Routine biochemical and haematological investigations were performed along with CSF-PCR analysis for IgM Ab specific to JE.

Three of six (50%) patients had palpable purpura over the dependent parts of the body. Other findings were vesiculopustular rash (4/6, 33.3%), urticaria (4/6, 33.3%), petechiae (4/6, 33.3%), and skin necrosis at the site of lumbar puncture (33.3%), respectively [Table 1]. All patients tested positive for CSF IgM antibody.

JE is a mosquito-borne encephalitis endemic to the northeastern states of India, particularly Assam.³The virus is transmitted through the bite of Culex mosquitoes, particularly the Culex vishnui group, Culex tritaeniorhychus, and Culex pseudovishnui.⁴ Transmission occurs most commonly due to the waterlogging of paddy fields by flooding of the Brahmaputra river in Assam and the breeding of pigs around these areas. The majority of the cases are asymptomatic, initially spreading from the site of the bite to the nearby lymph nodes and resolving thereafter.⁵ The subclinical cases result from viremia with clearance of the virus before it enters the central nervous system. Rarely, the virus evades the central nervous system(∼1% cases) and causes encephalitis with high fever, headache, disorientation, coma, tremors, and mental status changes.⁶ The case fatality may range from 20-30% in these cases. JE poses a major public health problem, causing around 50,000 cases and 10,000 deaths each year. A total of 434 cases were recorded between July 1 and September 23, 2022, in 17 separate districts of Assam. In July 2024, we saw a sudden surge of cases, with six progressing to encephalitis and requiring critical care.⁷

The prodromal phase is characterised by fever, malaise, vomiting, and headache. Skin lesions in the prodromal stage were characterised by the development of a generalised vesiculopustular rash [Figure 1a] and urticarial plaques [Figure 1b]. The vesiculopustular rash was predominantly follicular in distribution, precipitated by extreme sweating during the prodromal and acute encephalitic stages. The urticarial plaques were evanescent and mostly resolving in 2-3 hours without treatment. Trauma to the epithelial cells due to high opening pressure during lumbar puncture could be attributed to the localised skin necrosis at the site of puncture during the acute encephalitis phase [Figure 1c]. Apart from these, purpura was seen at pressure sites [Figure 1d] and petechiae were observed at dependent sites [Figure 1e]. Patients also showed bruising at sites of attachment of electrocardiogram leads [Figure 1f] and blood pressure cuffs. No abnormalities in clotting factors were found and platelet counts were normal. The macular, papular and vesicular rashes in the prodromal stage could be a response to viraemia causing cytopathic effects, leading to epidermal, dermal and capillary endothelial injury [Figure 2]. The haemorrhagic manifestations, such as petechiae and purpura that are generally seen in haemorrhagic fevers such as dengue and chikungunya,are associated with platelet/clotting abnormalities. However, our patients had no derangement of clotting factors/platelets, indicating altered vascular permeability in these cases. Skin necrosis at sites of lumbar puncture may be due to apoptotic pathway stimulation by the virus particles in CSF coming in contact with skin causing damage to its cells.

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Figure 1:

(a) Multiple pinpoint vesiculopustular rashes all over the body (black arrow) in the prodromal stage, (b) Multiple erythematous evanescent urticarial plaques over the body (black arrow), (c) Localised skin necrosis at the site of lumbar puncture (black arrow), (d) Solitary purpura located at sites of pressure (black arrow), (e) Petechiae at dependent sites (black arrow) following minor trauma, (f) Easy bruising at sites of attachment of ECG leads (black arrow).

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Figure 2:

Perivascular infiltrate predominantly comprising of neutrophils (red arrow) along with nuclear dust and extravasation of erythrocytes (black arrow). Vessels with plump endothelial cells are also noted (Haematoxylin & eosin, 400x).

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There is a paucity of literature on the skin related manifestations of JE due to the under-reporting of cases. However, we feel that JE cases have at least one cutaneous manifestation, which may be ignored in the initial prodromal phase. We would also like to draw attention to the fact that in presence of primary symptoms like fever, headache /altered sensorium with no platelet abnormalities (like in dengue haemorrhagic fever), the presence of purpura/petechiae at sites of friction in an area endemic for JE should raise high index of suspicion for JE.