Seasonal Variation in Contact Hypersensitivity to Parthenium in Patients of Parthenium Dermatitis.

BACKGROUND: Titer of contact hypersensitivity (TCH) is a measure of contact hypersensitivity to an allergen in an individual. Clinical severity of Parthenium dermatitis varies with season. However, the effect of seasonal variation on the TCH as determined by patch test to Parthenium has not been studied.
OBJECTIVE: To study the effect of seasonal variation on TCH to Parthenium hysterophorus in patients with Parthenium dermatitis.
MATERIALS AND METHODS: It was a prospective investigational study on clinically and patch test confirmed patients with airborne contact dermatitis to P. hysterophorus. The TCH values at baseline and after 6 months were recorded. The patients who were recruited in summers (April to September) and whose repeat patch test and TCH were determined in winters (October to March) were identified as Group I and those who were recruited in reverse order were identified as Group II.
RESULTS: The study had 47 patients, of which 23 were in Group I and 24 in Group II. Mean TCH in Group, I (summer to winter) in period I (summer) was 0.11 ± 0.28 whereas that in period II (winter), was 0.76± 0.41. Similarly, mean TCH in Group II (winter to summer) in period I (winter) and period II (summer) were 0.34± 0.44 and 0.166± 0.32, respectively. The difference in TCH values (95% confidence interval) in the two groups with a change of season was -0.41 (-0.58, -0.24) (P < 0.0001).
CONCLUSIONS: TCH values in Parthenium dermatitis are lower in the summer season, indicating increased sensitivity to Parthenium allergen in summer.

What was known?

Titer of contact hypersensitivity (TCH) is a reliable method of measuring the degree of contact hypersensitivity to Parthenium plant

Severity of dermatitis caused by Parthenium hysterophorus varies with season

Effect of seasonal change on patch test and TCH has not been studied.

Introduction

Allergic contact dermatitis to weed Parthenium, known as Parthenium dermatitis, has become a major dermatological problem in India. It is the most common cause of airborne contact dermatitis (ABCD) in our country, which primarily affects farmers and other outdoor workers.[1] In a recent study from South India on patients presenting with plant dermatitis, maximum patch positivity was found with Parthenium hysterophorus (52%), and it was statistically significant.[2] Dermatitis primarily involves exposed parts of the body and has varied clinical presentations. There is seasonal variation in the severity of dermatitis. The disease is more severe during the summer season which is considered to be one of the important points in making a clinical diagnosis of the disease. However, the diagnosis is confirmed by patch test, which is considered a gold standard investigation for the same. Titer of contact hypersensitivity (TCH) is used to determine the degree of contact hypersensitivity in an individual to an allergen which is determined by doing the serial dilutions of the standard extract of the allergen and the highest dilution which elicits a clear positive patch test reaction is the TCH in that individual. It has been used as a reliable method to measure the degree of contact hypersensitivity to Parthenium in patients with ABCD to Parthenium.[34] Since the severity of dermatitis caused by P. hysterophorus varies with season, the patch test, and TCH may also vary in these patients. However, the effect of seasonal change on patch test and TCH has not been studied. Therefore, we studied the effect of seasonal variation on TCH in patients with Parthenium dermatitis.

Materials and Methods

Study design

This data came out of a prospective investigational study on patients with ABCD, due to P. hysterophorus (Parthenium dermatitis).[5] The study subjects were recruited from the outpatient department, and allergy clinic of the Department of Dermatology of our center and the study was approved by the Institutional Ethics Board.

Patients

Clinically, diagnosed and patch test confirmed patients of Parthenium dermatitis were recruited. Since these patients were to be treated with azathioprine, pregnant and lactating females, children <15 years of age and patients with active liver, kidney, or hematological disorder were excluded.

Allocation

The patients who were recruited in summers (April to September) and whose repeat patch test and TCH were determined in winters (October to March) were identified as Group I and those who were recruited in winters (October to March) and whose repeat patch test and TCH were done in summers (April to September) were identified as Group II.

Procedure

Patch test was done with antigen impregnated discs prepared using an aqueous extract of the plant material (leaves) as per method described by Pasricha and Singh and standardized in our laboratory.[6] Mature, healthy looking leaves of P. hysterophorus were cleaned, air dried at room temperature over 7–10 days and powdered in a blender. Fifty grams of the dried leaf powder was thoroughly mixed with 300 ml of water and filtered through Whatman No. 1 filter paper to obtain a clear filtrate which was standard plant extract. To determine the TCH, 10-fold dilutions varying from 1:10 to 1:105 were prepared by diluting the standard plant extract with distilled water and antigen impregnated discs were prepared from each of these dilutions. The patients were patch tested with each of these dilutions in addition to the undiluted standard extract, using the standard technique. The maximum dilution which produced a definite dermatitic reaction in the patient was taken as the TCH.[3]

As per the study protocol, each patient was first patch tested at baseline (Period I) and again after 6 months (Period II) to determine the TCH on both occasions.

Data collection

Demographic details of all patients such as age, gender, and duration of disease were noted. The TCH values at baseline and after 6 months were recorded.

Statistical analysis

Data were presented as number and percentage or mean ± standard deviation or median and range as appropriate. TCH was compared between the two sequences of Group I (summer → winter) and Group II (winter → summer) using analysis of variance. In the usual crossover study, we study the treatment effect (drug vs. placebo), period effect (the order in which each patient received the two treatments) and finally, interaction of treatment and period is studied. In this study, the seasonal variation of TCH was called season effect and the order in which each patient's TCH value was measured between the two seasons (summer to winter/winter to summer) was called period effect. Hence, in order to study, the interaction between season and period, we analyzed this study as a 2 × 2 cross over model. Statistical analysis was carried out using STATA 11.0 (Statacorp, College station, Texas, USA). The results were reported as treatment effect (95% confidence interval [CI]). The P <0.05 was considered statistically significant.

Results

The study had 47 patients, 33 males and 14 females, between 30 and 72 years of age. There were 23 patients in Group I and 24 patients in Group II. The baseline demographic profile of the patients in two groups is summarized in Table 1.

Table 1

Demographic profile

The TCH values varied from undiluted to 1:1000 in these patients. The seasonal variation of TCH in the two groups is shown in Table 2. The mean TCH values for summer to winter group (Group I) in period I and in period II was 0.11 ± 0.28 and 0.76 ± 0.41, respectively, and the difference between the two periods was −0.66 ± 0.54. Similarly, the mean TCH values for winter to summer group (Group II) in period I and period II was 0.34 ± 0.44 and 0.17 ± 0.32, respectively, and the difference between the two periods was 0.17 ± 0.61. Therefore, the difference in TCH values with a change of season shown as season effect (95% CI), was −0.41 (−0.58, −0.24), and it was statistically significant (P < 0.0001). This shows that TCH values were significantly lower in summer as compared to winter in both groups, suggesting that increased sensitivity to Parthenium in summer is reflected in patch tests as well. In keeping with the above observation, TCH values increased in 19 patients and became negative (undetectable) in 2 patients in Group I from summer to winter and decreased in 13 patients in Group II from winter to summer. However, an opposite trend was seen in a subset of patients-TCH decreased in 1 patient (by 1:10 dilution) in Group I and increased in 6 (by 1:10–100 dilution) in Group II. There was no change in TCH in 1 patient in Group I and 5 patients in Group II.

Table 2

Periodic variation in TCH in two groups

The order in which the TCH values were measured was called period effect. The magnitude of period effect (95% CI) was −0.49 (−0.82, −0.15) and the difference between the means of TCH was significant (P = 0.006) showing a systematic period effect. Hence, the period effect reassures that the TCH is lower in summers as compared to winters. This reiterates an increased sensitivity to Parthenium in summer as compared to winter.

The sequence effect was also found to be statistically significant (P = 0.009) meaning that there is a season period interaction (season × period effect). Overall, the mean TCH values were higher in winters in both groups. However, the difference in seasonal variation of TCH was higher when the readings were done in summer to winter, than in winter to summer [Figure 1].

Figure 1

Mean of titer of contact hypersensitivity values in two seasons and periods (the solid black line represents summer to winter, that is, Group I; the dashed line represents winter to summer, that is, Group II; and whiskers represent the standard error)

Discussion

Parthenium dermatitis has become a major problem in India, and about 40% patients attending a contact dermatitis clinic of tertiary care center in North India were reported to have Parthenium dermatitis.[7] The disease has variable clinical presentations and can mimic other eczematous and photosensitive eruptions.[89]

TCH is a method for assessing the degree of sensitivity to the allergen in patients affected with Parthenium dermatitis. The reproducibility of TCH in Parthenium dermatitis has been studied, and it has been found to be a reproducible and reliable test.[4] A subsequent study evaluated the correlation among TCH, clinical severity and therapeutic response in Parthenium dermatitis which demonstrated complete clearance to significant reduction in clinical severity following therapy but did not show a corresponding change in TCH values (P = 0.15).[10] Hence, it was concluded that TCH neither correlates with clinical severity of disease nor with the response to therapy.

Seasonal variation in the severity of dermatitis is well-known in Parthenium dermatitis. The disease is much more severe in summer than in winter, and some patients have a complete remission in winter, but the disease relapses in summer. However, there are no studies done to determine the effect of this seasonal variation on patch test outcomes in these patients. The present study is the first attempt to investigate the effect of seasonal variation on the degree of contact hypersensitivity as determined by TCH in Parthenium dermatitis. Our study patients had increased sensitivity to Parthenium allergen in summer as compared to winter. The exact reason for this increased sensitivity in summer is unknown, but it may be due to several reasons such as excess growth and drying up of leaves of the weed during summers which get suspended in the air making large amount of allergen available in the atmosphere, increased sweating as well as less clothing during summer etc. Hence, under hot and humid conditions in tropical countries like India, increased sweating may increase plant allergen penetration and accordingly increasing the chances of patch test positivity.

On the contrary, the studies looking at the effect of meteorological conditions on patch testing found increased incidence of irritant reactions under cold/arid conditions with some known allergens such as formaldehyde, paraben and fragrance mix, nickel, thiomersal and para phenylene diamine.[11121314] It was hypothesized that this probably occurred secondary to impairment of epidermal barrier function. Some studies suggested that patch positivity decreases in summers, which may be due to increased sweating leading to poor occlusion and ultraviolet induced cutaneous immunosuppression.[1415] On the other hand, Katsarou et al. showed no influence of seasonal variation on patch testing.[16]

Our study revealed that the order in which repeat patch testing is done in patients with Parthenium dermatitis also affects the results. When patch test sequence was summer to winter, the mean TCH values increased almost 7-fold. However, when patch test sequence was winter to summer, the TCH values reduced only 2-fold. On the whole, it means that the same patient may show different sensitivity toward P. hysterophorus when observed over same seasons of different calendar years. The exact reasons for this effect are unknown, but it may have occurred since several patients dependent and environment dependent factors may alter a patient's sensitivity toward the plant. This factor may be a consideration when comparative, prospective clinical trials involving Parthenium dermatitis patients recruited over different time frames are planned and analyzed.

Conclusions

More robust conclusions could be drawn regarding the effect of seasonal change on patch test results in our series if we could have followed up our study group into 1 more calendar year and repeated their patch tests. This was a possible limitation of our study. Variation in patch test positivity in a given patient, if recorded over the same seasons of different calendar years, would provide better understanding of the environmental and patient factors that influence the clinical manifestations of Parthenium dermatitis as well as the patch test results. Another research implication of our study would be to evaluate the effect of seasonal variations on results of patch testing in other dermatoses known to be affected by weather such as hand dermatitis and atopic dermatitis.

Our analysis indicates that the patients of Parthenium dermatitis have increased sensitivity to an allergen in summer season which can be picked up by even higher dilutions of the antigen extract (lower TCH values) on patch test. On the other hand, the patch test may be negative in winters due to lowered antigen sensitivity which may result in a negative patch test. Hence, we recommend that in a clinically suspected patient of Parthenium dermatitis, patch test should be repeated in the summer season if it is negative or doubtful positive in winters. However, further studies are needed to confirm our results.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

What is new?

Difference in titer of contact hypersensitivity (TCH) values with change of season was statistically significant, having lower TCH values in summers and reflecting increased sensitivity to Parthenium in summers

Patch test to Parthenium should be repeated in the summer season if it is negative or doubtful positive in winters.