The severity of atopic dermatitis and the relation to the level of total IgE, onset of atopic dermatitis and family history about atopy

ABSTRACT

The aim of this study is the evaluation, if the level of total IgE, onset of atopic dermatitis (AD) and the family history are in the significant dependence to the severity of AD. The statistical evaluation of the dependence between the severity of AD and the the level of total IgE, family history and onset of AD was performed. 296 patients were examined. The level of total IgE above 200 IU/ml is recorded in 93 % of patients suffering from severe form and the positive data about atopy in family history are recorded in 66 % of patients with severe form of AD. The significant dependence was recorded between the severity of AD and parameters such as the level of total IgE, and family history about atopy. No dependence was recorded between the severity of AD and the onset of AD.

KEYWORDS:

• Atopic dermatitis
• severity of atopic dermatitis
• SCORAD index
• total IgE
• onset of atopic dermatitis
• family history

Introduction

Atopic dermatitis (AD) is a chronic relapsing genetically predisposed inflammatory skin disease characterized by intense pruritus and by scaly, dry eczematous lesions; it is often associated with other atopic disorders, such as allergic rhinitis and asthma. Generally, atopic diseases can be divided into two distinct variants: the extrinsic, allergic variant, which occurs in the context of sensitization toward environmental allergens and is accompanied by elevated serum IgE levels, and the intrinsic, nonallergic variant, with no detectable sensitization and with low serum IgE levels (Wüthrich, 1989). The pathogenesis of AD involves interactions among multiple factors including susceptibility genes, environmental factors, skin barrier defects and immunologic factors (Boguniewicz & Leung, 2010; Leung & Bieber, 2003). Skin barrier dysfunction is one of the major manifestations of AD and a key contributor to its pathogenesis resulting from genetic defects (Howell et al., 2007; van den Oord & Sheikh, 2009; Palmer et al., 2006; Weidinger et al., 2006). Regarding the onset of AD, early-onset AD is a particular phenotype that may convey a risk of developing multiple sensitizations to allergens (Just et al., 2014). Many patients with AD (80–90%) have high serum levels of IgE (Demis, 1992). It is determined in recent times that IgE causes IL-1, IL-3, IL-4, IL-5, IL-6, GM-CSF and TNF-α to be synthesized and released by binding to basophils and mast cells. These cytokines play an important role in the late phase of allergic response (Galli, Gordon, & Wershil, 1991). The normal serum IgE level does not mean that atopy does not exist. On the other hand, very high serum IgE level can be accepted as one of the important data showing allergy existence if there is no parasitic infestation (Galli et al., 1991). Although IgE has a role on the formation of allergic rhinitis and some forms of allergic asthma, there are few publications in the literature that IgE has a major role on the pathogenesis of AD. According to the literature, the risk of developing AD is much higher in those whose family members are affected. For example, the concordance rate of AD in monozygotic twins is around 75%, meaning that the risk of the disease in the twin sibling is 75% if the cotwin is affected (Thomsen et al., 2007). There are few studies dealing with the question if the serum IgE levels, onset of AD and the genetical predisposition correlate with AD severity in adolescents and adults suffering from AD (Worm & Henz, 1997).

The severity of AD is usually evaluated with SCORAD index. This index has been developed on consensus by the European Task Force on Atopic Dermatitis (ETFAD) in 1993. The acronym SCORAD was proposed by Arnold Oranje, and stands for SCORing AD (European Task Force on Atopic Dermatitis, 1993). By using this instrument, different studies are more comparable in routine practice, as well as in observational or double-blind randomized clinical trials (Gelmetti & Colonna, 2004).

Aim: The question of our study is if the parameters, such as the level of total IgE, onset of AD and family history about atopy, are in significant dependence to the severity of AD evaluated with SCORAD index.

Method

In the period 2008–13, 296 patients suffering from AD at the age of 14 years and older were examined at the Department of Dermatology – Faculty Hospital in Hradec Králové, Charles University of Prague. The diagnosis of AD was made with the Hanifin–Rajka criteria (Hanifin & Rajka, 1980). Complete dermatological and allergological examination was performed. The following parameters were examined: severity of AD was evaluated with SCORAD index, total IgE, onset of AD and family history about atopy. We asked if there was a significant relationship between the patients with the level of total IgE under/above 200 IU/ml and the occurrence of mild, moderate and severe form of AD, onset of AD and family history. This study was approved by Ethics Committee of Faculty Hospital Hradec Králové, Charles University of Prague, Czech republic.

Severity of atopic dermatitis

Severity of AD was scored in agreement with SCORAD (Čelakovská & Bukač, 2013; European Task Force on Atopic Dermatitis, 1993) with the assessment of topography items (affected skin area), intensity criteria and subjective parameters. This examination was performed during one year every three months and the average SCORAD index was recorded. The severity of AD was evaluated with SCORAD as a mild form to 25 points, as moderate over 25–50 points and as a severe form over 50 points.

The serum level of total IgE has been measured with the method of FEIA (Pharmacia CAP system, Uppsala, Sweden). The level of total IgE higher than 200 IU/ml was assessed as positive.

The onset of AD: It was evaluated according to the patient history (the onset of AD under five years of age or later).

The family history: The atopy history was evaluated according to the patient information (the occurrence of allergy, AD, asthma bronchiale, rhinoconjunctivitis in parents, brothers, sisters and children).

Statistical analysis

We analysed the data to determine whether the occurrence of mild, moderate and severe form of AD is in relation to the level of total IgE, onset of AD and family history about atopy.

Pairs of these categories were entered in the contingency tables and the chi-square test for independence of these variables was performed with the level of significance set to 5%.

Results

Patients and tested parameters

Two hundred and ninety-six patients were examined – 95 men and 201 women with the average age 26.7 years (s.d. 9.5 years) and with the average SCORAD 32.9 (s.d. 14.1) points.

The occurrence of monitored parameters in percent in 296 patients with AD is shown in Table 1. The mild form of AD was recorded in 96 patients (31%), the moderate form in 173 patients (60%) and the severe form in 27 patients (9%). Positive IgE above 200 IU/ml was recorded in 196 patients (66%) and negative IgE under 200 IU/ml was recorded in 100 patients (34%). Positive data about atopy in family history were recorded in 172 patients (46%), onset of AD under 5 years of age in 228 patients (77%).

Table 1. The occurrence of monitored parameters in percents in 296 patients with AD.

Monitored parameter	Number of patients from 296 (100%)
Total IgE	Under 200 IU/ml 100 (34%)	Above 200 IU/ml 196 (66%)
Onset of AD	Under 5 years of age 228 (77%)	Above 5 years of age 68 (23%)
Family history about atopy	Positive 172 (58%)	Negative 124 (42%)
Mild form of AD	96 (32%)
Moderate form of AD	173 (59%)
Severe form of AD	27 (9%)

The number of patients with total IgE under and above 200 IU/ml and the severity of AD according to SCORAD are shown in Table 2. In group of patients with positive IgE above 200 IU/ml, the mild form of AD was recorded in 48 patients (16%), moderate form in 123 patients (42%) and severe form in 25 patients (8%). In group of patients with negative IgE under 200 IU/ml, the mild form of AD was recorded in 48 patients (16%), moderate form in 50 patients (17%) and severe form in 2 patients (0.6%). The relationship between the severity of AD and the level of total IgE is significant, p-value = 0.000. The significant rising occurrence of positive total IgE in mild, moderate and severe form is shown in complement to Table 2.

Table 2. The number of patients with total IgE under and above 200 IU/ml and the severity of AD according to SCORAD.

Total IgE	Mild form	Moderate form	Severe form	Total number of patients
No. of patients total IgE under 200 IU/ml	48 (16%)	50 (17%)	2 (0.6%)	100 (34%)
No. of patients total IgE above 200 IU/ml	48 (16%)	123 (42%)	25 (8%)	196 (66%)
Total number of patients	96 (32%)	173 (59%)	27 (9%)	296 (100%)
p-Value	.000

The number of patients with positive and negative data about atopy in family history and the severity of AD according to SCORAD are shown in Table 3. Positive data about family history were recorded in 172 patients (58%), negative data about family history were recorded in 124 patients (42%). In group of patients with positive family history, the mild form of AD was recorded in 42 patients (14%), moderate form in 112 patients (38%) and severe form in 18 patients (6%). In group of patients with negative family history, the mild form of AD was recorded in 54 patients (18%), moderate form in 61 patients (21%) and severe form in 9 patients (3%). The relationship between the severity of AD and the data about atopy in family history is significant, p-value = 0.002. The significant rising occurrence of positive data about atopy in family history in mild, moderate and severe form is shown in complement to Table 3.

Table 3. The number of patients with positive and negative data about atopy in family history and the severity of AD according to SCORAD.

Family history	Mild form	Moderate form	Severe form	Total number of patients
No. of patients positive family history	42 (14%)	112 (38%)	18 (6%)	172 (58%)
No. of patients negative family history	54 (18%)	61 (21%)	9 (3%)	124 (42%)
Total number of patients	96 (32%)	173 (59%)	27 (9%)	296 (100%)
p-Value	.002

The number of patients with onset of AD under and above 5 years of age and the severity of AD according to SCORAD is shown in Table 4.

Table 4. The number of patients with onset of AD under and above 5 years of age and the severity of AD according to SCORAD.

Onset of AD	Mild form	Moderate form	Severe form	Total number of patients
No. of patients onset under 5 years of age	68 (23%)	139 (47%)	21 (7%)	228 (77%)
No. of patients onset above 5 years of age	28 (9%)	34 (11%)	6 (2%)	68 (23%)
Total number of patients	96 (32%)	173 (59%)	27 (9%)	296 (100%)
p-Value	.205

The onset of AD under 5 years of age was recorded in 228 patients (77%) and the onset above 5 years of age was recorded in 68 patients (23%). In group of patients with the onset under 5 years of age, the mild form of AD was recorded in 68 patients (23%), moderate form in 139 patients (47%) and severe form in 21 patients (7%). In group of patients with the onset above 5 years of age, the mild form of AD was recorded in 28 patients (9%), moderate form in 34 patients (11%) and severe form in 6 patients (2%). The relationship between the severity of AD and the onset of AD is not significant, p-value = 0.205.

Discussion

According to the database in Medline, Pubmed and Web of science, there are few studies dealing with the question if the parameters, such as the level of total IgE, onset of AD and family history about atopy, are in significant dependence to the severity of AD. According to our results, the level of total IgE above 200 IU/ml and the positive family history about atopy are significantly more frequent in patients suffering from moderate and severe form of AD in comparison to patients suffering from mild form of AD. The level of total IgE above 200 IU/ml is recorded in 50% of patients suffering from mild form of AD, in 71% of patients with moderate form and in 93% of patients with severe form. Although there is a significant rising occurrence of positive level of IgE in mild, moderate and severe form of AD, our results show that in 29 % of patients suffering from moderate form and in 7% of patients with severe form, there is the level of total IgE under 200 IU/ml. Other non-immunologic factors may contribute to the developing of AD at these patients. The positive data about atopy in family are recorded in 43% of patients with mild form, in 64% of patients with moderate form and in 66% of patients suffering from severe form of AD. Although our study confirmed the significant dependence between the genetical predisposition and the severity of AD, we recorded in nine patients (34% of all patients with severe form) no genetical predisposition to atopy. As well, in 54 patients with mild form (57% of all patients with mild form), there are no data about positive family history – it means that more than a one half of patients suffering from mild form have no genetical predisposition; according to our results we suspect that besides genetical predisposition other factors are important in the onset of AD, such as the environmental factors (food and inhalant allergens), skin barrier defects and immunologic factors. In the previous studies, the problem of the severity of AD and the occurrence of food allergy, food hypersensitivity reactions had been dealt, as well as the occurrence of concomitant allergic diseases and parameters, such as the family history about atopy and the onset of AD (Čelakovská, 2015; Čelakovská & Bukač, 2011, 2015a, 2015b; Čelakovská, Bukač, & Ettler, 2015; Čelakovská & Ettlerová, 2009; Čelakovská, Ettlerová, Ettler, & Bukač, 2015; Čelakovská, Ettlerová, Ettler, & Krčmová, 2010; Čelakovská, Ettlerová, Ettler, Vaněčková, & Bukač, 2015a, 2015b, 2015c; Čelakovská, Ettlerová, Vaněčková, & Ettler, 2011; Čelakovská, Ettlerová, Vaněčková, Ettler, & Bukač, 2011). According to these results, the onset of AD (under or above 5 years of age) is in the significant dependence to the level of total IgE, to the occurrence of food allergy and to the occurrence of sensitization to bird feather (Čelakovská & Bukač, 2015a; Čelakovská, Ettlerová, et al., 2015; Čelakovská et al., 2015c). As well, the occurrence of positive family history about atopy is in the significant dependence to the level of total IgE, the occurrence of food allergy and to the occurrence of sensitization to mites, dust and animal dander (Čelakovská & Bukač, 2015a; Čelakovská, Ettlerová, et al., 2015; Čelakovská et al., 2015c). In patients with total IgE above 200 IU/ml, the onset of AD under 5 years of age and the occurrence of positive family history are significantly more frequent. Patients with confirmed food allergy have positive data about atopy in their family history more often; peanuts, soy and wheat are of great importance (Čelakovská & Bukač, 2015a). As well, AD patients with sensitization to mites, dust and animal dander have significantly more often the positive data about atopy in their family history (Čelakovská et al., 2015c). Regarding the severity of AD evaluated with SCORAD index, the significant dependence between the severity of AD and the occurrence of food hypersensitivity reactions was confirmed; 96% of patients with severe form of AD suffer from food reactions. In evaluating the single foods, the significant dependence was found between the severity of AD and the reactions to nuts, apples and fishes (Čelakovská & Bukač, 2015b; Čelakovská, Bukac, et al., 2015). Interestingly, the occurrence of food hypersensitivity reactions is not in significant dependence to the onset of AD and to the occurrence of positive family history (Čelakovská, Bukac, et al., 2015).

In Kumar, Singh, and Patel’s (2014) study, clinical features, absolute eosinophil count and total immunoglobulin E level and their association with severity of AD were evaluated. This study identified that total IgE increased significantly in about 66% patient and directly correlated with the severity of the AD. According to Thijs et al. (2015), a large number of biomarkers have been found to correlate with the disease severity in AD. The most frequently reported serum biomarkers for disease severity in AD include eosinophilic cationic protein, total IgE, soluble interleukin-2 receptor (sIL-2R) and thymus and activation-regulated chemokine (TARC/CCL17), (Čelakovská & Bukač, 2015a). Laske and Niggemann performed a retrospective study on 345 child patients with AD and determined that SCORAD values were statistically significantly related with serum IgE levels (2004). According to Aral, a statistically significant relationship between SCORAD values and serum levels of total IgE was determined. These results show that serum levels of IL-18 can be a sensitive parameter that importantly correlates with clinical severity of AD, can play a role in the immunopathogenesis of AD and furthermore may be used in the diagnosis and follow-up of the disease in addition to other parameters (Aral et al., 2006).

Our results may be useful in prevention of severe form of AD in patients with positive family history because the significant dependence between the positive family history about atopy and the severity of AD was confirmed. Epidemiological evidence points to the protective effects of early day care, endotoxin exposure, consumption of unpasteurized milk and early exposure to dogs; there is currently no strong evidence of benefit for exclusive breastfeeding, hydrolyzed protein formulas, soy formulas, maternal antigen avoidance, omega-3 or omega-6 fatty-acid supplementation, or use of prebiotics or probiotics (Torley, Futamura, Williams, & Thomas, 2013).

Conclusion

The significant dependence was recorded between the severity of AD and parameters such as the level of total IgE, and family history about atopy. The level of total IgE above 200 IU/ml is recorded in 93% of patients suffering from severe form and the positive data about atopy in family are recorded in 66% of patients with severe form of AD. No relation was recorded between the severity of AD and the onset of AD.

Disclosure statement

No potential conflict of interest was reported by the authors.

Notes on contributor

Jaroslava Vaneckova works as the specialist for contact dermatitis in the Department of Dermatology and Venereology Faculty Hospital and Medical Faculty of Charles University, Hradec Králové, Czech Republic. At this department, she collaborates in the research of atopic dermatitis of some immunological parameters in patients suffering from this diseases and she collaborates in the elaboration of the methods for using atopy patch tests.