Clinically, the condition is characterized by a combination of exanthems and enanthems. Reports from Asia-pacific region indicated occurrence of epidemics in 1997 (Sarawak) [3], 1998 (Taiwan) [4], 1999 (Perth) [5] and 2000 (Singapore, Korea, Malaysia and Taiwan) [6]. The first epidemic from India was reported from Kerala in 2003 [7]. The others were reported from Nagpur in 2005-06 [8] and West Bengal in 2007 [9]. HFMD was reported for the first time from state of Orissa (presently Odisha) in 2009 [10]. The clinical presentation and demography of the affected population in the above outbreak are described herein.

The first suspected case was identified in the Dermatology outpatient department of IMS&SH, Bhubaneswar on 7 September, 2009. After clinical diagnosis of the case as HFMD, pediatricians and dermatologists serving in clinics and hospitals of Bhubaneswar were sensitized and requested to refer all the suspected cases to the Department for clinical evaluation. Sensitization was done through presentations about the case and importance of investigation in seminars and meetings organized by the local physician associations.

Besides case enrollment in the above hospitals, a community survey was undertaken by an epidemic investigation team from Regional Medical Research Centre, Bhubaneswar by visiting the households in an affected urban location. Cases were examined and extent of involvement was recorded. Detailed history was collected from the suspected patients that included contact history in the family or neighbours. Symptoms and signs were recorded in a structured format, after clinical examination. Stool, urine and blood samples (3-4 mL) were collected from subjects for investigation.

The first clinically suspected case was a 15-month-old female child from Rasulgarh area of Bhubaneswar. A total of 78 cases were recorded till November 6, 2009 and out of them 46 were followed up till recovery. The patients belonged to four urban locations, namely Rasulgarh (16 cases), Nayapalli (22 cases), Sahid Nagar (15 cases) and Dumduma (25 cases) under Bhubaneswar municipal corporation. One affected urban area (Nayapalli) was investigated by household visits, and survey was undertaken in 48 households covering 250 individuals, and recorded 9 cases of suspected HFMD. A typical index case in the area was not identified. However, household spread was evidenced by two cases from one family.

Age of the subjects ranged from 4 months to 31 years (Mean (SD) 5.13 (4.94) years (Table I). Fever (74.3%) with rash (100%) were the most common presenting symptom along with associated features like anorexia, irritability etc. The disease started as small (1-3mm) erythematous maculopapular rash that rapidly enlarged and progressed to papulovescicular lesions with a prominent erythematous halo. Most of the lesions turned to gray vesicles in 2-3 days time.

TABLE I Age and Sex Distribution of HFMD Cases

The lesions had a characteristic distribution with involvement of buttocks (Fig. I), knees, hands and feet. Buttocks were the most severely and commonly affected sites in majority (83.3 %) of patients followed by the knees (77.5 %). In very few cases, wrist, ankle area and trunk were involved. In the hands, vesicles were more pronounced over the dorsal aspect (Fig.2) but papulovesicluar lesions were more on the palmar side. Lesions were localised to margins of fingers, hands, thenar and hypothenar eminences and dorsal surfaces than the volar aspect. Full blown vesicles were more common on the dorsal aspect.

Fig 1. Papulovesicular lesions on the buttocks.

Fig 2. Papulovesicular lesions on the dorsum of hand with involvement of margins of fingers.

Secondary infection and impetigenization of the lesions were observed in 11 cases. The lesions were associated with itching in 24 cases which was more pronounced during the healing phase. In the 46 cases having complete follow-up, average healing time was 8.6 days (SD 1.6 days). Healing was uneventful except post inflammatory hypo and hyper-pigmentation. Three patients had shedding of nails 4-5 weeks after recovery from the acute symptoms.

Oral lesions were found in 61 (78.2%) cases. Sites involved were inner aspect of the lips, gums, buccal mucosa, tongue and the hard palate. Small aphthous like lesions measuring 1 to 3 mm were the usual mucosal presentation. Most common systemic symptoms (Table II) were fever and anorexia. History of mild fever either preceding to or simultaneously with the eruption was present in 58 (74.3%) cases. Fever appeared on the same day in 70% cases and 1 day before onset of rash in 30% cases. Fever persisted for 1 to 2 days following onset. Sore throat was a symptom during the prodrome or on the first day in 38 (48.7%) patients. Malaise was also a dominant complain amongst 41 (52.5%) cases. Nine patients (11.5%) had a typical viral prodrome comprising of fever, sorethroat and malaise.

TABLE II Systemic Symptoms Observed in Patients (N=78)

Anorexia was a presenting feature in 35 (44.1%) patients. The presence of oral ulcers might have contributed towards the manifestation of anorexia. Irritability was a predominant clinical presentation in 21(26.9%) patients. Mostly infants and young children presented with irritability.

Personal history of atopy was present in 22 (28.2%) patients and family history of atopy was recorded in 35(44.8%) patients, while 18 (12.8%) patients had both. Patients with personal history of atopy were more significantly associated with sorethroat compared to non-atopics (P=0.01). Average lesion healing time in patients with both personal and family history of atopy vs non-atopics was 10.13 (SD 1.25) vs. 7.27 (SD 0.65) days.

Blood counts were within normal range in most cases except, three cases showing eosinophilia and two cases with neutrophilia. Routine and microscopic examination of stool and urine samples did not reveal any abnormality. CA16 virus was identified as the causative agent for the outbreak [10].

Most patients were managed conservatively with topical antibiotics, oral antihistamines and antipyretics. Oral antibiotics were rarely required, i.e. only in two patients because of secondary impetigenization. All the subjects recovered with the above treatment.

EV71 and CA16 viruses belong to picornaviridae family of genus Enterovirus. They have single positive -strand genomic RNA with high mutation rate. Due to presence of multiple genotypes and sub genotypes of the two viruses, repeated epidemics of HFMD have occurred and others are expected in future. An outbreak is usually followed by a quiescent phase of few years. Like all other enteroviruses, children are the most significant target as well as reservoirs. Feco-oral route is the principal mode of transmission.

Diagnosis in most cases can be made from clinical presentation with certainty; if the clinician has a strong suspicion. Differentials include papular urticaria, chickenpox, mosquito bite etc. Rarity of cases and lack of suspicion as well as uneventful recovery are the most important causes of missing a case clinically. Though laboratory confirmation depends on direct isolation of virus in cell cultures, Indirect fluorescent assays (IFA), RT-PCR or serum neutralization techniques are also useful. Clinical presentation is quite characteristic to raise the suspicion of the condition and remains the sole diagnostic modality in resource constrained areas. Previous outbreaks in Kerala and West Bengal also showed predominant affliction of children [7,9] during the outbreak, there were two adults affected with the disease during the outbreak. The disease in these two adults was similar to the affected children. There was no statistically significant gender difference in disease. We found a significant association between the severity as well as healing time of the disease with either personal or family history of atopic diseases. Though the incidence of EV71 isolation from HFMD outbreaks is on the higher side in various reports [2-6], CA 16 was confirmed to be the viral agent in this outbreak. Follow up after healing of the lesions had revealed shedding of nail in three patients, which is a rare observation.

The report is important, as the large rural, especially tribal population, base with lack of general hygiene and water sanitation practices in Odisha can facilitate the spread of the disease [10]. The randomness of the epidemic and unequal time gap between epidemics also suggest possibilities of multiple such events in the coming years. The present report is expected to increase the awareness amongst the practitioners regarding the clinical presentation and benign and self-limiting nature of the presented HFMD cases. This will be helpful for early clinical diagnosis and case management, thereby supporting public health measures, during future episodes if any.

Acknowledgments: Dr V Gopalkrishna and Dr Shoba Chitambar of the National Institute of Virology, Pune for providing laboratory support and help in investigating the disease. Dr A Mohapatra, Dr B Mishra, Dr D Das, Dr A Jena and Dr A Patra for referring cases to the hospital.

Contributors: BRK: Enrollment of cases in hospital, clinical examination and recording, data interpretation and manuscript preparation; BD: Field investigation, Clinical examination and recording, data interpretation, study design and manuscript preparation; SKK: study design, supervision and coordination, data interpretation and manuscript preparation.

Funding: Indian Council of Medical Research, Dept. of Health Research, Ministry of Health and Family Welfare, Govt. of India; Competing interests: None stated.