Re-emergence of chikungunya as a public health problem in North India: A dermatologist’s perspective on the mucocutaneous manifestations — An observational cross-sectional study

INTRODUCTION

Chikungunya, a neglected tropical disease transmitted by the alphavirus genus in the Togaviridae family, has gained importance globally due to frequent outbreaks. Being a vector-borne disease (Aedes spp. Mosquitoes), it predominantly affects the musculoskeletal system in the form of joint pains and dermatological rash.

The first outbreak of chikungunya (CHIK) was documented in Tanzania in 1952, and India recorded its first outbreak in 1963. This was followed by cyclic and regular epidemics in Tamil Nadu, Maharashtra, and Andhra Pradesh till 1973. After the quiescent period of almost 3 decades, India saw a re-emergence of CHIK virus infection in 2006. Since then, regular outbreaks have been recorded in North and South India.^[1]

Muco-cutaneous involvement is prominent and a significant finding that may help in distinguishing this viral infection from other viral febrile exanthems. Generalized maculopapular rash has been the most common manifestation in 30–50% of the cases.^[1] The febrile episodes and maculopapular rash may be a coincidental feature during recurrent bouts of viremia. Systemic involvement has also been described.^[1,2]

Diagnosis of CHIKV (Chikungunya virus) infection is mainly clinical, as there are no pathognomonic findings. However, there are three specific tests for the detection of CHIKV infection: virus isolation, reverse transcriptase polymerase chain reaction (RT-PCR), and serological tests for identifying CHIKV-specific antibodies (Immunoglobulin M antibody capture (MAC-Ig) enzyme-linked immunosorbent assay [ELISA]).^[3] Viral isolation remains the gold standard to confirm the diagnosis.^[4] However, a definitive diagnosis can be established earlier in the acute phase of infection by RTPCR in less than 5 days of infection and by Immunoglobulin M (IgM) antibody detection in the sera using ELISA in more than 5 days.^[3] Serological diagnosis is made by demonstrating a fourfold rise of CHIKV IgG titer in acute and convalescent sera, as these CHIKV-specific IgM antibodies persist for several 3-months of infection.^[3] RT-PCR test has been developed using primer pairs amplifying specific components of the gene regions: capsid C, envelope E-2, and part of E-1 of CHIKV.^[4,5]

Communicable and neglected diseases pose a challenge to the healthcare sector. The impact on productivity, quality of life, and physical and mental well-being can be substantial.^[6] The present study is being conducted to establish the role of dermatologists in public health problems in viral epidemics on the basis of mucocutaneous manifestations.

MATERIAL AND METHODS

An observational, descriptive, hospital-based study was conducted in a tertiary care institute from North India through its fever clinic during the outbreak of Chikungunya from July 2023 to December 2023 after obtaining approval from the Institutional Ethics Committee. (IEC/RTR/23/34027) Patients who attended the outpatient department in dermatology were prospectively enrolled according to the case definition of the “suspect cases” of Chikungunya infection^[7,8] [Figure 1].

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Figure 1:

The protocol of the study conducted.

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The criteria for a suspected new case were sudden onset of fever associated with skin rash, myalgia, headache, and swelling of the joints^[7] [Table 1].^[7,9] Detailed history, clinical examination, and relevant investigations were conducted after obtaining written informed consent from each patient. Diagnosis was made clinically, and serological confirmation was performed using IgM ELISA.

Patients who refused to participate in the study, those having concomitant co-infection with dengue, having a seroreactivity to other viral illnesses, those suspected to have an autoimmune disease or suspected to have drug reaction, human immunodeficiency virus seroreactivity or immunocompromised status, with pre-existing dermatosis, pregnancy, lactation, and having seroreactivity to chikungunya before enrollment, were all excluded from the study.

Data were collected by authors (MM and TK) on a day-today basis for study variables, and then they were entered into a predesigned pro forma. Mean and standard deviation were used for descriptive statistics, and proportion/percentage for categorical variables. Pearson correlation was used for leukocyte, platelet, and C-reactive protein (CRP). Analysis of data was done using the Statistical Package for the Social Sciences version 23.

RESULTS

Of 164 patients screened from the fever clinic for new cases of suspected chikungunya, 157 were found eligible for enrollment. Of these, 66 were male, and 91 were female. The mean age was 37.27 ± 17.3 years with a range of 36.2–38.1 ± 16.1–19 years. The male-to-female ratio was 1:1.37. The most common age group affected was 20–40 years. The mean duration of the fever with rash was 3 days ± 2 days. Clinicodemographic profile and comorbid conditions are summarized in Table 2. Mucocutaneous lesions observed during the 1^st week of the disease presentation are summarized in Table 3. These manifestations were further divided into the following groups:

1. The most common cutaneous manifestation was erythematous maculopapular rash with pruritus in 43.9% (n = 69) of the patients [Figure 2a].

2. The second common mucocutaneous manifestation in our study was pigmentary changes seen in 23.4% (n = 37) [Figure 2b-d].

3. Oral ulceration and desquamation of palms and soles [Figure 2e and f] were observed in 5.0% (n = 8) each, while genital ulceration [Figure 3a] was present in 3.1% (n = 5) over the scrotum and groin in the acute phase.

4. Palmar erythema and urticaria [Figure 3b] were present in 3.8% and 3.1% of the cases, respectively.

5. Scrotal dermatitis and edema of the hands and feet occurred in 2.5% (n = 4) of the cases each. [Figure 3c].

6. Miscellaneous: Vesico-bullous lesions 2.5% (n = 4) [Figure 3d], Milan’s sign of erysipelas in 1.9% (n = 3), purpuric lesions in 1.8% (n = 2), [Figure 3e and f] conjunctivitis exacerbation of the pre-existing dermatosis in 0.6% (n = 1) of the cases, respectively.

CRP is significantly negatively corelated with leukocytes (r = −0.255) and platelets (r = −5.40) at P = 0.001 [Figure 4a-c].

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Figure 2:

(a) Maculopapular rash involving the trunk during the acute phase. (b) Melasma-like pigmentation on face; (c) Melasma-like pigmentation on face (Lateral view); (d) Centro-facial region hyperpigmentation (Post chikungunya); (e) Desquamation of hands in acute phase; (f) Desquamation of feet during post-febrile phase.

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Figure 3:

(a) Punched out scrotal ulceration during the acute phase; (b) Urticarial lesions over the forearm during the acute phase; (c) Edema of hands during the acute phase; (d) Multiple vesicular eruptions seen over the thigh in an adult patient during the acute phase, (e) Purpuric lesions over the forearm; (f) Pinpoint hemorrhagic lesions over the anterior aspect of the legs during the acute phase.

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Figure 4:

(a) Correlation between C-reactive protein (CRP), Leukopenia, and thrombocytopenia; (b) Scatter plot diagram (Leukopenia and CRP); (c) Scatter plot diagram (Thrombocytopenia and CRP).

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DISCUSSION

After a gap of 29 years, an urban epidemic of CHIKV was reported in the Democratic Republic of Congo. Similar outbreaks were reported in India during 2005– 2006 after a period of 32 years. These outbreaks are usually associated with multiple risk factors such as heavy rainfalls, absence of herd immunity, poor vector control, globalization, viral mutations, and increased international travel.^[9] CHIKV infection can present with varied mucocutaneous manifestations. Recognizing and understanding a plethora of these mucocutaneous manifestations is, therefore, essential for early diagnosis and timely intervention.

The present study is in accordance with that of Mohan^[9] where females outnumbered males, but was in contrast to previous studies of Riyaz et al.^[10] and Inamadar et al.^[1] where males outnumbered females.

Generalized maculopapular rash (43%, n = 69) was the most common observation of our study; presenting on day 3–5 with fever and resolved by day 4. The rash showed preference for the trunk, face, and extremities along with pruritus. These findings were consistent with earlier studies of Inamadar et al.,^[1] Gulanikar and Abrol.^[11] Other researchers like Rueda et al. and Kumari et al.^[12,13] observed them in 40–50% of the cases. While Bhat et al.,^[14] Chatterjee et al.^[15] and Kumar et al.^[16] observed them in 53.5–80% of their patients. This may be due to the cytopathic and immunological factors directly leading to endothelial capillary injury.

Centro-facial hyperpigmentation was present in 13.3% (n = 21), Lichenoid rash in 4,4% (n = 7), while Chik sign [Figure 2ac] was observed in 5.7% (n = 9) of the patients in our study. Centro-facial pigmentation (30.3%) was the commonest finding present in the study of Inamadar et al.,^[1], and while it was seen in 27% in Raju et al.^[17] The most common site involved was the nose and cheek. This may be due to increased intraepidermal retention and dispersion of melanin triggered by bouts of viremia or post-inflammatory hyperpigmentation.^[1,18]

Desquamation of palms and soles was present in 15% of the patients. This was in contrast to Riyaz et al.^[10] who observed them in only 5% of the cases, which is attributed to subsiding inflammation in this area.

In our study, oral mucosal involvement was seen in 8.1% (n = 13) of the patients, while Riyaz et al.^[10] observed them in 13.6% (n = 22), and Rueda et al.^[12] in 2.6% (n = 14) of the cases. Penoscrotal ulceration was seen in the studies of Prashant et al.,^[19] Gulanikar and Abrol^[11] who observed them in 23.7% (n = 27) and 30% (n = 15) cases, respectively, while we observed them in 3.1% (n = 5). These ulcers were observed after 3–4 days of fever onset and healed without any sequelae in 2 weeks. All other relevant investigations pertaining to ulceration were negative (Herpes simplex virus (HSV) antibodies, viral markers, VDRL, Gram staining, and Tzanck smear).

Vesiculobullous lesions appeared on day 2 after fever and disappeared in 2 weeks. Similar lesions were reported by Gulanikar and Abrol^[11] and Kumari et al.^[13] in their study. These vesicular eruptions were due to viral replication leading to focal necrosis and ballooning degeneration.^[16]

Joint involvement was a prominent finding in our study, being present in 66% of the patients. This was in accordance with the studies by Simon et al.^[4] and Pialoux et al.^[3] Small joints of the hand, wrist, and ankles were involved in accordance with the study of Borgherini et al.^[20] and Mizuno et al.^[21]

Hematological abnormalities such as Leukopenia and thrombocytopenia were observed in 12.7% (n = 20) and 5.0% (n = 8) of the patients in our study, while Suryawanshi et al.^[22] observed thrombocytopenia in their study. These findings were variable in various studies, consisting of Leukopenia, thrombocytopenia, lymphocytosis, or lymphopenia.^[4]

Hemorrhagic manifestations like purpura were present in 1.8% in contrast to Kumar et al.^[23] who found them in 3.5% of the cases. This can be attributed to thrombocytopenia induced by the viral replication in capillary endothelium, leading to vascular damage. The immune mechanism is another possibility causing vascular damage by type-3 immune reaction.^[16]

Mucocutaneous manifestations of chikungunya provides an early clinical clue for their detection.^[24-26] Table 4 summarizes the characteristics of cutaneous manifestations of chikungunya in the literature.

Exacerbation of pre-existing diseases has been reported in the studies of Bhat et al.^[14] and Inamadar et al.^[1] which is in accordance with our study.

Systemic involvement was reported by Pialoux et al.^[3] in the form of central nervous system and hepatic involvement, while Rueda et al.^[12] found gastrointestinal findings to be an important finding in their cases.

All patients were managed symptomatically. Protective clothing was emphasized along with vector control measures. The quest for a leap forward for safe and effective vaccine is the demand of the present time.^[27-29]

Limitations: Being a single-center study, it included only those cases that reported to the tertiary care institute and hence represents the tip of the iceberg. Small sample size study, selection bias, lack of gene sequencing, and non-availability of RT-PCR were some limitations.

CONCLUSION

Dermatologists are playing a pivotal role in detecting neglected tropical diseases. Therefore, awareness regarding a plethora of these cutaneous manifestations by dermatologists not only becomes essential for their detection, rather they also help in halting the spread and re-emergence of viral infection. Further, the re-emergence of chikungunya has opened doors for ample opportunities in the field of viral replication, genomic coding, diagnostic, and field research.

There are currently two approved chikungunya vaccines: IXCHIQ (Valneva, Vienna, Austria; live-attenuated, single dose) and VIMKUNYA (Bavarian Nordic, Hellerup, Denmark; virus-like particle, single dose). VIMKUNYA is currently only licensed for those aged 12 years and older, and IXCHIQ for adults aged 18 years and older. However, these are not widely available and are licensed in few regions (European union, UK and U.S.A.) for travellers to high risk areas and should be given after careful consideration of the benefits and risks.