Association between Alopecia Areata and Comorbid Allergies: Implications for Its Clinical Course.

Dear Editor:

Few studies have reported that history of allergy and comorbid atopic dermatitis (AD) were associated with increased risk of alopecia areata (AA) and also with severe types of AA (i.e., alopecia totalis and alopecia universalis)12. Although there were no strong evidences in these studies with a small number of patients, AD has been clinically suspected as a poor prognostic factor of AA3. However, the influence of comorbid allergies in clinical outcomes of AA has not been reported previously. Thus, we attempted to find out a correlation between comorbid allergies and clinical course of AA. The protocol for the study was approved by the institutional review board of the Kyungpook National University Hospital (KNUH 2019-03-009).

Among total of 954 patients diagnosed with AA from 2011 to 2017 in Kyungpook National University Hospital, 664 patients who did not measure serum total immunoglobulin E (IgE), those with follow-up periods fewer than 6 months, and those with insufficient medical records were excluded. Finally, 290 patients included in this study. History of comorbid allergies (AD, allergic rhinitis, asthma) and disease progression were reviewed by medical records and photographs. Clinical courses compared between the patient's first and latest visit were evaluated into three grades, aggravation or no hair regrowth, partial hair regrowth, and complete hair regrowth. Mean treatment duration was 42.1 months. Main therapeutic modalities were topicals and intralesional steroid injection (n=96), excimer laser and phototherapy (n=36), systemic immunosuppressants (n=43), diphenylcyclopropenone immunotherapy (n=28) combined and/or intercurrent (n=77), and others (n=10). Statistical analysis used one-way ANOVA and chi-square test. There were 136 males and 154 females and mean duration of AA was 70.4 months. The mean age was 35.3±16.3 years among total 290 patients, 77 (26.6%) had comorbid allergies, 28 (9.7%) with AD only, 26 (9.0%) with allergic rhinitis only, 3 (1.0%) for asthma only, and 20 (6.9%) with more than two allergies (AD and allergic rhinitis, n=13; AD and asthma, n=5; allergic rhinitis and asthma, n=2). There was no statistical difference in the rate of patients with comorbid allergies according to the initial severity of AA (Fig. 1A). Then, we compared clinical courses of AA between with or without comorbid allergies, but it showed no statistical difference (Fig. 1B). In addition, there was no statistical difference of IgE levels according to the initial severity of AA (Fig. 1C). We divided four groups according to their IgE levels and compared the clinical courses, but there was also no significant difference (Fig. 1D). Table 1 summarized the complete hair regrowth rate in demographic and clinical characteristics. There were no statistically significant factors except for disease duration. However, 5 patients who had both comorbid allergies and very high IgE levels (≥1,000 IU/ml), showed only aggravation or no hair regrowth. This presented the possibility of comorbid allergies and high IgE levels as poor prognostic factors of AA.

Fig. 1

The associations of the rate of patients with comorbid allergies and initial severity of AA (A), clinical courses of AA and comorbid allergies (B), mean serum total immunoglobulin E (IgE) levels and initial severity of AA (C), clinical courses of AA and serum total IgE levels (D) were investigated respectively, but none of them had statistically significant results. AA: alopecia areata, S0: no hair loss, S1: <25% hair loss, S2: 25%~49% hair loss, S3: 50%~74% hair loss, S4: 75%~99% hair loss, AT: alopecia totalis, AU: alopecia universalis.

Table 1

Multivariable analyses of the effects of demographic and clinical characteristics on complete hair regrowth in patients with alopecia areata

Characteristic	Number	Complete hair regrowth	p-value
Sex			0.7823
Male	136	21 (15.4)
Female	154	22 (14.3)
Age (yr)			0.1063
1~9	30	3 (10.0)
10~19	57	11 (19.3)
20~29	45	11 (24.4)
30~39	60	6 (10.0)
40~49	56	4 (7.1)
≥50	42	8 (19.0)
Duration of AA (yr)			0.0001
<2	85	25 (29.4)
2≤yr<5	99	10 (10.1)
5≤yr<10	61	4 (6.6)
≥10	45	4 (8.9)
Initial severity of AA			0.3152
S1	40	9 (22.5)
S2	62	10 (16.1)
S3	74	10 (13.5)
S4	51	9 (17.6)
AT/AU	63	5 (7.9)
Comorbid allergies			0.8759
Known allergies	77	11 (14.3)
No allergies	213	32 (15.0)
Serum total IgE levels (IU/ml)			0.4649
<100	161	26 (16.1)
100~499	101	15 (14.9)
≥500	28	2 (7.1)
Allergies×IgE levels (IU/ml)
No allergies
<100	121	20 (16.5)	0.5130
100~499	75	11 (14.7)
≥500	17	1 (5.9)
Known allergies
<100	40	6 (15.0)	1.000
100~499	26	4 (15.4)
≥500	11	1 (9.1)
Total	290	43 (14.8)

Values are presented as number (%). S0: no hair loss, S1: <25% hair loss, S2: 25%~49% hair loss, S3: 50%~74% hair loss, S4: 75%~99% hair loss, AT: alopecia totalis, AU: alopecia universalis, IgE: immunoglobulin E.

The immune response of AA has been traditionally explained to Th1 category. Although AD was known as Th2 category condition, it is now considered having complex heterogeneous immunopathogenesis involving Th1 and Th17 immune axis4. So, both entities might have overlapping immunologic pathway theoretically. Unlike previous studies, this study investigated whether comorbid allergic diseases could affect the courses of AA. The main limitations of this study include its retrospective design, single-center site and a small number of patients showed complete hair regrowth which also resulted limitation of statistical analysis. In conclusion, there was no significant difference in the clinical courses of AA according to both comorbid allergic diseases and the level of serum total IgE.