Clinico-etiological profile of atopic dermatitis in Northeast India

INTRODUCTION

Atopic dermatitis (AD) is an itchy, chronically relapsing inflammatory skin condition that often starts in early childhood presenting with erythema, itchy papules or vesicles, which may become excoriated and lichenified and typically has a flexural distribution.^[1] Although it is considered a predominantly pediatric disease, it affects a significant number of adults. Its clinical presentation can vary based on age, ethnicity, and underlying pathological mechanism.^[2-5] Various studies conducted in India in different age groups from 2002 to 2020 have reported prevalence ranging from 0.55% to 29.9%.^[6] A two- to three-fold increase in disease prevalence has been observed in the last few decades, which has been attributed to changing environmental conditions and urbanization.^[7]

Pathogenesis of AD is an extensively explored area, and multiple factors have been postulated such as dysfunctional skin barrier, genetic, immunological, environmental, and microbiological factors. Increased serum IgE is a common finding in AD with some studies suggesting a correlation between the levels of IgE and severity of the disease.^[8] The tribal ethnicity and peculiar environmental conditions of the area including higher altitude, prolonged winters, and low temperature make the population of Meghalaya a unique study group. Moreover, there is no data available on AD in this population. With the above considerations, the aim of our study was to assess the unexplored clinical spectrum and exacerbating and precipitating factors associated with AD in Meghalaya, India.

MATERIAL AND METHODS

The present study was undertaken in the Department of Dermatology, North Eastern Indira Gandhi Regional Institute of Health and Medical Sciences (NEIGRIHMS), Shillong, India. Ethical approval was obtained from the Institution Ethics Committee (IEC), NEIGRIHMS on 14^th May 2020 (NEIGR/IEC/M10/T6/2020).

All patients attending the Dermatology outpatient department were clinically screened for AD and diagnosed on the basis of Hanifin and Rajka criteria and included in the study.^[1,8] Written consent was obtained from patients/guardians after explaining about the nature and purpose of the study. A detailed history was obtained from patients including present age, age at onset, residence, personal and family history of atopy, history of pruritus, seasonal variation, and history of allergy and associated diseases. A thorough clinical examination was done, and types of lesions were noted along with the distribution of eczema and predominant sites of involvement (face, flexor, extensor limbs). All findings were recorded in the pro forma. Serum IgE levels were tested for every patient using electrochemiluminescence immunoassay (ECLIA).

Descriptive statistics were used for data analysis. The distribution of frequencies in the demographic data of the patients in the study has been presented. The continuous variables are presented as mean ± standard deviation or median (range) if the data is skewed. Categorical variables are presented as absolute numbers and percentages.

RESULTS

A total number of 50 patients with AD were included in the study, and the prevalence was found to be 2.85%.

Clinical findings

Clinical findings including features in Hanifin and Rajka criteria and other atypical features are presented in Tables 1-4 and Figures 1-8.

Table 1: Distribution of features of major criteria in study population (n=50).

Major criteria	Present	Absent	Total
Pruritus	50	0	50
Typical morphology and distribution	44	6	50
Chronic or relapsing dermatitis	42	8	50
Personal or family history of atopy	39	11	50

Table 2: Distribution of features of minor criteria in study population (n=50).

Minor criteria	Present	Absent	Total
Xerosis	49	1	50
Ichthyosis, palmar hyperlinearity, or keratosis pilaris	39	11	50
Immediate (type 1) skin-test reactivity	-	-	-
Raised serum IgE	29	21	50
Early age of onset	35	15	50
Tendency toward cutaneous infections	21	29	50
Tendency toward non-specific hand or foot dermatitis	18	32	50
Nipple eczema	1	49	50
Cheilitis	18	32	50
Recurrent conjunctivitis	9	41	50
Dennie-Morgan infraorbital fold	23	27	50
Keratoconus	1	49	50
Anterior subcapsular cataracts	1	49	50
Orbital darkening	10	40	50
Facial pallor or facial erythema	38	12	50
Pityriasis alba	22	28	50
Anterior neck folds	31	19	50
Itch when sweating	31	19	50
Intolerance to wool and lipid solvents	24	26	50
Perifollicular accentuation	6	44	50
Food intolerance	11	39	50
Course influenced by environmental or emotional factors	35	15	50
White dermographism or delayed blanch	15	35	50

IgE: Immunoglobulin E

Table 3: Distribution of atypical features in study pop``ulation (n=50).

Atypical Features	Present	Absent	Total
Infra-auricular fissure	14	36	50
Retroauricular fissure	11	39	50
Infranasal fissure	3	47	50
Eyelid eczema	10	40	50
Genital dermatitis	4	46	50
Posterior thigh eczema	18	32	50
Juvenile plantar dermatoses	4	46	50
Follicular variant	2	48	50
Others	10	40	50

Table 4: Pattern of distribution of lesions in study population.

Sites of involvement	Total (n=50)		Pediatric (n=37)		Adult (n=13)
	Present	Absent	Present	Absent	Present	Absent
Flexures	37	13	25	12	12	1
Extensors	34	16	26	11	8	5
Face	39	11	34	3	5	8

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Figure 1:

A child with prominent facial eczema and pityriasis alba.

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Figure 2:

Palmer hyperlinearity in child with atopic dermatitis.

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Figure 3:

Prominent anterior neck folds seen in a child with atopic dermatitis.

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Figure 4:

Cheilitis and perioral dermatitis.

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Figure 5:

Atopic child with posterior and infra-auricular fissures.

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Figure 6:

Flexure involvement in atopic dermatitis.

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Figure 7:

Extensor involvement in atopic dermatitis.

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Figure 8:

Facial involvement in atopic dermatitis.

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DISCUSSION

Atopic dermatitis is a common, chronic inflammatory skin disease with a relapsing course that primarily affects young children and is often associated with raised serum IgE.^[8] Some recent studies suggest a delayed onset of the disease, calling the same as “adult-onset AD.”^[9,10]

The prevalence of AD in our study was found to be 2.85%, which was higher when compared to reports in previously conducted studies by Pandya and Agrawal,^[7] Dhar et al.,^[11] Swamy et al.,^[12] and Sehgal et al.^[13] who reported the prevalence of 1.9%, 0.55%, 0.58%, and 0.98%, respectively. This variation in findings can be possibly attributed to differences in geographical factors, environmental factors, and food habits. Meghalaya with a cooler climate experiences a prolonged winter and low humidity from October to March, especially in the Shillong plateau. Cold and dry weather conditions are known to increase the risk of flares in AD by decreasing skin barrier function and increasing susceptibility towards mechanical stress. Skin becomes more reactive towards irritants and allergens as pro-inflammatory cytokines, and cortisol are released by keratinocytes, and the number of dermal mast cells increases.^[14]

The median age of onset in our study population was found to be 21.5 months (1.8 years) with minimum and maximum being 2 months and 728 months (61 years), respectively. Another study conducted in the Indian subcontinent reported a mean age-of-onset of 3.63± 1.42, with a minimum of one year to a maximum of six years.^[13]

In infants, a mean age of onset of 11.4 months and a mean duration of disease of 3.1 months were found in our study. Dhar and Kanwar^[15]and Sarkar and Kanwar^[16] reported a mean age of onset of 4.2 months and 4.5 months, respectively, and a mean duration of disease of 3.3 months and 3 months, respectively, in infants.

In children, a mean age of onset of 3.75 years and a mean duration of disease of 4 years were found in our study, which is similar to previous studies.^[15,16]

The male-to-female ratio found in our study was 1:1.17 suggesting slight female preponderance, though not statistically significant (P = 0.57), which was also seen in studies conducted by Upendra et al.^[17] and Kumar et al.^[18] who reported male-to-female ratio of 1:1.73 and 1:1.3, respectively. A male preponderance was reported by Dhar and Kanwar^[15] with a ratio of 2.13:1, Sarkar and Kanwar^[16] with a ratio of 2.25:1 and Pandya and Agrawal^[7] with a ratio 2:1. This difference in findings signifies the difference in the sex ratio in parts of the country and better healthcare seeking behavior of women in Meghalaya.

In our study, 66% of patients were urban residents whereas 34% were rural residents, which were in concordance with the findings of a previous Indian study conducted by Sehgal et al.^[13] (70% urban and 30% rural). Other Indian studies also reported urban predominance including Sarkar and Kanwar^[16] (76.9% urban and 23.1% rural) and Swamy et al.^[12] (76% urban and 24% rural). These findings are depicting that urbanization, modified lifestyle, changed food habits, and reduced exposure to antigens are playing a role in increasing disease prevalence.

The majority of our patients (90%) belonged to the upper middle class (socioeconomic class II) while 2% of patients belonged to the lower middle class (class III) and 6% to the upper lower class (class IV) according to modified Kuppuswamy scale. Swamy et al.^[12] also reported middle socio economic class as most commonly affected (52%). This is possibly due to awareness and better healthcare seeking behavior in the upper middle class as compared to people from low socioeconomic strata.

We found that 70% of patients had winter exacerbation of symptoms while summer exacerbation was seen only in 10% of patients. Similar findings were noted by Dhar and Kanwar^[15] where 67.14% of patients had aggravation during winters, and 23.36% had a summer exacerbation. Exacerbation in winter is attributed to dry climate and low humidity whereas increased sweating leading to itching and secondary infections cause exacerbation of symptoms in summer.

Family history of respiratory or cutaneous atopy was noted in 70% of patients, which was the same as reported by Hanifin and Rajka.^[1] A family history of atopy was reported by Dhar et al.^[11] in 65%, Kumar et al.^[18] in 68.9%, and Singh and Yadav^[19] in 32.9% of the patients.

Allergic rhinitis was found to be coexisting with AD in 8% of patients whereas a prior diagnosis of asthma was found in only 2% of patient in our study. Ellis et al.^[20] have reported parallel findings with allergic rhinitis in 7% of patients with AD and asthma in 5% of patients with AD. Rystedt^[21] reported that 32% of patients of AD with bronchial asthma and 60% with allergic rhinitis.

Pruritus was the most consistent symptom and was present in all patients in our study, which was consistent with the findings of studies by Swamy et al.^[12] and Nadeem et al.,^[22] where they noted pruritus in all patients. Pruritus has been reported as the most common symptoms in other studies conducted in India and internationally.^{[13,16,23,24]}

Among our study population, 74% of patients had flexures involved [Figure 6], 68% of patients had extensors involved [Figure 7], and facial involvement [Figure 8] was seen in 78% of patients. Among adult patients (≥18 years) in our study, 92.3% patients had flexures involved, 61.5% patients had extensors involved, and 38.4% had facial involvement whereas among pediatric patients, 67.6% had flexures involved, 70.3% had extensors involved, and 91.9% had facial involvement. In a study conducted by Dhar and Kanwar,^[15] 42% of patients with flexural involvement, 52.3% with extensor involvement, and 79% with facial involvement were reported in the infantile group, and in the childhood group, corresponding figures were 35.5%, 56.32%, and 74.5%, respectively. Sarkar and Kanwar^[16] have noted flexures, extensors, and face involvement in 15.4%, 26.9%, and 80.8% of infants and 45.4%, 37.4%, and 66.7% of children. In another Indian study, 39%, 38%, and 20% of patients had flexor, extensor, and face involvement, respectively.^[11]

Among the minor criteria of Hanifin and Rajka, the most common feature present in our study population was xerosis, which was noted in 98% of patients that was similar to the findings in studies conducted by Nadeem et al.^[22]and Swamy et al.,^[12] who reported xerosis in 100% and 99% of patients, respectively. Xerosis was also the most common feature reported by Barbarot et al.^[24]

A second most common feature among minor criteria noted in our study was presence of ichthyosis, palmar hyperlinearity [Figure 2] or keratosis pilaris, which were seen in 78% patients in contrast to 51% patients in study conducted by Swamy et al.,^[12] 50% patients in study conducted by Sehgal et al.,^[13] and 34.9% patients in study conducted by Kumar et al.^[18] Facial pallor or facial erythema was noted in 76% of patients in our study whereas it was reported in only 6% of patients by Swamy et al.^[12]

History of disease activity being influenced by environmental and emotional factors was present in 70% of patients in our study, which was in conformity to those reported by Sehgal et al.,^[13] whereas Swamy et al.^[12] reported a history of emotional and environmental influence in only 49% of patients. Anterior neck folds [Figure 3] and itching with sweating were seen in 62% of patients while it was seen in only 2% of patients in a study conducted by Swamy et al.^[12]

We found the history of intolerance to wool and lipid solvents in 48% of patients whereas Sehgal et al.^[13] has reported this feature in 68%, and Swamy et al.^[12] has reported the same feature in only 9% of patients.

Pityriasis alba [Figure 1] was seen in 44% of patients in our study population in contrast to previous studies where a 27% frequency of the same feature was reported by Swamy et al.^[12], and a frequency of 20% was reported by Sehgal et al.^[13]

In contrast to the study conducted by Sehgal et al.,^[13] where they found Dennie-Morgan infraorbital fold, hand and foot dermatitis, and white dermographism to be occurring very commonly; these were found in 46%, 36%, and 30% of patients, respectively, in our study.

In our study, an increased tendency towards cutaneous infections was noted in 42% of patients whereas Sehgal et al.^[13] has reported it in 62% of patients, and Swamy et al.^[12] has reported the same in 68% of patients in their study.

Cheilitis [Figure 4] was noted in 36% and orbital darkening in 20% of patients, in the current study, which was higher in comparison to findings of Swamy et al.^[12], who found cheilitis in 8% of patients and orbital findings in only 2% of patients whereas the frequency of both was found to be 58% of patients in a study conducted by Sehgal et al.^[13]

We found the history of food intolerance in 22% of patients in our study population. The most common items reported by patients included brinjal followed by egg and dry fish. Sehgal et al.,^[13] Swamy et al.,^[12] Sendrasoa et al.,^[25] and Upendra et al.^[17] have reported a history of food intolerance in 70%, 8%, 16.5%, and 2.2% patients, respectively.

Recurrent conjunctivitis was present in 18% of patients in our study, which was consistent with the findings of the previous studies.^[12,13]

Perifollicular accentuation was seen in 12% of patients in our study, which was higher than as seen by Swamy et al. (2%).^[12] Nipple eczema was seen in only 2% of patients in our study, which was the same as observed by Swamy et al.,^[12] but lower than as observed by Sehgal et al. (20%).^[13] Anterior subcapsular cataract and keratoconus were seen in 2% of patients each in our study while Swamy et al.^[12] noted anterior subcapsular cataract in 2% of patients and did not find any patient with keratoconus.

Serum IgE was found to be raised in 58% of patients in our study, which was in consonance with the findings of the meta-analysis done by Yew et al.^[23] Akdis et al.^[26] have reported an elevated serum IgE levels in about 80% of AD patients. Somani^[27] conducted a study on allergen specific IgE antibody in patients of AD and found IgE to be raised in 88% of patients.

Other than features mentioned in Hanifin and Rajka criteria for diagnosis of AD, we came across some other common features in patients as well including posterior thigh eczema, infra- and retroauricular fissures [Figure 5], eyelid eczema, genital dermatitis, juvenile plantar dermatoses, and infranasal fissures.

CONCLUSION

Atopic dermatitis of chronic type with slight female preponderance having predominant facial involvement in children and predominant flexural involvement in adults was common in our study. Pruritus and xerosis were the most frequent presenting features. Seasonal changes, urbanization, food items (egg, fish, and milk), and woolen cloths were principal causative and exacerbating factors; and allergic rhinitis, asthma, and family history of atopy were associated features found. Some atypical presentations included posterior thigh eczema, infra-auricular fissures, retroauricular fissures, eyelid eczema, genital dermatitis, juvenile plantar dermatoses, infranasal fissure, and follicular variant of the disease. The majority of patients were found to have raised serum IgE during exacerbation of the disease. These findings help us in better understanding of disease dynamics and preventive aspects of the disease; however, confirmation of any such correlation needs further study.