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SHORT COMMUNICATION
Year : 2022  |  Volume : 67  |  Issue : 5  |  Page : 543-546
Sex differences in alopecia areata treated with steroid pulse therapy: A retrospective study and review of literature


Department of Dermatology, Shiga University of Medical Science, Setatsukinowa, Otsu, Shiga, Japan

Date of Web Publication29-Dec-2022

Correspondence Address:
Hiraku Kokubu
Department of Dermatology, Shiga University of Medical Science, Setatsukinowa, Otsu, Shiga - 520-2192
Japan
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijd.ijd_418_21

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   Abstract 


Context: Few reports focused on the sex differences in alopecia areata (AA) treated with steroid pulse therapy. Aims: This study aimed to investigate the association between the clinical outcomes and distinction of gender in AA patients treated with steroid pulse therapy. Settings and Design: This study retrospectively investigated 32 cases (15 males and 17 females) treated with steroid pulse therapy at the Department of Dermatology at the Shiga University of Medical Science between September 2010 and March 2017. Methods and Material: The administration of corticosteroid was 500 mg methylprednisolone intravenous infusion for 3 consecutive days. Patients were followed up approximately once a month until March 2017. Statistical Analysis Used: The respective data were analyzed by examining and comparing males and females. Statistical analysis was performed using t-test and χ2 test. Results: There were no significant differences in periods from the onset of AA to the administration of steroid pulse therapy (P = 0.2), the degree of severity (P = 0.37) and improved rate (P = 0.0772) between males and females. In contrast, the remission rate was 20% (3 of 15 males) and 71% (12 of 17 females), which was statistically significant (P = 0.0042). Previous reports have also shown a significant difference in the remission rate between males and females (males: 32 of 114; females: 51 of 117; P = 0.014). Conclusions: Despite the limitations of a small sample size including the previous reports (n = 261), female patients with AA would have better outcomes than male patients after steroid pulse therapy.


Keywords: Alopecia areata, remission, response, sex differences, steroid pulse therapy


How to cite this article:
Kokubu H, Kato T, Fujimoto S, Tanaka T, Fujimoto N. Sex differences in alopecia areata treated with steroid pulse therapy: A retrospective study and review of literature. Indian J Dermatol 2022;67:543-6

How to cite this URL:
Kokubu H, Kato T, Fujimoto S, Tanaka T, Fujimoto N. Sex differences in alopecia areata treated with steroid pulse therapy: A retrospective study and review of literature. Indian J Dermatol [serial online] 2022 [cited 2023 Feb 8];67:543-6. Available from: https://www.e-ijd.org/text.asp?2022/67/5/543/366129





   Introduction Top


Alopecia areata (AA) deteriorates the quality of life of the patient. More effective therapies in the early stage are expected even now. Steroid pulse therapy is considered effective in the early stage of severe cases and is recommended for rapidly progressive cases.[1] However, steroid pulse therapy is not always effective in all cases, and the side effects of the treatment cannot be ignored. It is necessary to determine the factors that may influence the efficacy of the treatment. Thus, the outcomes of the progress of AA cases treated with steroid pulse therapy at our institution were retrospectively examined.


   Subjects and Methods Top


A retrospective review of 32 patients suffering from AA was conducted. Patients were treated with steroid pulse therapy at the Department of Dermatology at the Shiga University of Medical Science between September 2010 and March 2017. It was confirmed by blood examinations that all cases enrolled in this study had no diseases concerning hair loss, such as hypothyroidism, collagen diseases, iron deficiency anemia, and syphilis. The diagnosis of AA was confirmed by scalp biopsy with transverse and vertical sections in all cases. The indication and method of steroid pulse therapy were performed in accordance with the Japanese guideline based on the previous report.[1] The administration of corticosteroid was 500 mg methylprednisolone intravenous infusion for 3 consecutive days. After steroid pulse therapy, patients continued therapy, such as topical steroids and diphenylcyclopropenone. Patients were followed up approximately once a month until March 2017. Dropout patients were evaluated at the last visit. To evaluate the severity of each patient, the subgrouping score of the areas of scalp hair loss was used as a severity score.[2] The severity score at the time of administration and follow-up of each patient was examined. Complete response was defined as the disappearance of AA lesions, and partial response was defined as hair regrowth in some AA areas. This study was approved by the Shiga University of Medical Science Research Ethics Committee on March 23th, 2017 (reference no. 29-032). The respective data were analyzed by examining and comparing males and females. Statistical analysis was performed using t-test and χ2 test.


   Results Top


[Table 1] shows the characteristics of patients enrolled in this study and the outcomes. There were 15 males and 17 females. Their ages ranged from 17 to 59 years, with a mean of 36.4 ± 10.0 years (males: 36.7 ± 12.1 years; females: 36.1 ± 7.6 years; P = 0.45). The mean area of scalp hair loss and severity score were 50.3 ± 23.8% (males: 51 ± 22%; females: 50 ± 25%; P = 0.47) and 2.6 ± 1.0 (males: 2.67 ± 0.94; females: 2.53 ± 1.09; P = 0.37), respectively. The periods from the onset of AA to the administration of steroid pulse therapy ranged from 1 to 146 months. Considering the data of these periods, one outlier was excluded based on the Smirnov–Grubbs test. The mean was 3.1 ± 1.8 months after excluding the outlier (males: 3.4 ± 1.6 months; females: 2.9 ± 1.8 months; P = 0.2). Six males (partial response: 2; non-response: 4) and 2 females (partial response: 1, non-response: 1) stopped visiting our hospital before March 2017. The observation period was 12.1 ± 16.3 months (males: 6.2 ± 7.1 months; females: 17 ± 19.8 months; P = 0.07; dropout patients: 11.1 ± 10.7 months; non-dropout patients: 12 ± 17.6 months; P = 0.90). Representative clinical images of pre-treatment and post-treatment and histopathological figures are shown in [Figure 1]a, [Figure 1]b, [Figure 1]c, [Figure 1]d, [Figure 1]e, [Figure 1]f, [Figure 1]h. There were no significant differences in the ratio of partial response between males and females (males: 8 of 15; females: 14 of 17; P = 0.078); however, there was a significant difference in the ratio of complete response (males: 3 of 15; females: 12 of 17; P = 0.004).
Table 1: Patient characteristics and outcomes

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Figure 1: (a) A woman in her 30s suffered from diffuse hair loss for a month. (b) She had a complete response 19 months after steroid pulse therapy. There is no relapse even now. (c, d) Histopathological examination of a biopsy specimen from her head showed an increase in the number of telogen follicles and peribulbar infiltration of lymphocytes surrounding anagen follicles [hematoxylin-eosin (H and E) staining; original magnification, ×40 (c), ×200 (d)]. (e) A man in his 30s suffered from hair loss on the parietal for 3 weeks. (f) He did not have a complete response 5 years after steroid pulse therapy. (g, h) Histopathological examination of a biopsy specimen from his head showed an increase in the number of telogen follicles and peribulbar infiltration of lymphocytes [hematoxylin-eosin (H and E) staining; original magnification, ×40 (g), ×200 (h)]

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   Discussion Top


The use of steroid pulse therapy was introduced for severe types of AA in 1975 to minimize the side effects associated with prolonged systemic corticosteroid therapy.[3] Some studies have shown the efficacy of steroid pulse therapy for patients with AA.[4],[5],[6],[7],[8],[9] However, this is the first study that showed more significant effectiveness in females compared to males.

There are only six studies in which the results of the efficacy in each gender were described.[4],[5],[6],[7],[8],[9] Almost all studies did not pay close attention to sex differences, except for one.[9] The efficacy of the treatment from these results was evaluated [Table 2]. In [Table 2], the outcomes of partial response in females were superior to males in five studies, including this study.[4],[5],[6],[7] However, in seven studies, there was no significant difference in partial response between males and females (males: 74 of 124; females: 90 of 137; P = 0.315). For complete response, females were superior to males in four studies, including this study. In seven studies, there was a significant difference in complete response between males and females (males: 32 of 114; females: 51 of 117; P = 0.014). Although the reason why each study has different results is not clear, it is deducible from the described facts. One reason is that the periods from the onset of AA to the administration of steroid pulse therapy were not matched at all in each study. The periods from the development of alopecia to the administration of steroid pulse therapy are less than 12 months,[4] 0.5–36 months,[5] 1–12 months[7] and 0–103 months.[8] Nakajima et al.[1] reported that the recent-onset group (duration of AA <6 months) are good responders. Likewise, the early administration of steroid pulse therapy enables the efficient suppression of active inflammation and maximizes the effectiveness.[10] As various periods coexist in these studies, the efficacy of the treatment might be controversial.
Table 2: Outcomes of steroid pulse therapy in AA: review of the literature

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We consider about the reason why there was a significant gender difference in this study. Females probably have more serious AA than males from the same collapse of the immune privilege because of the presence of estrogen. Cytokine secretion from lymphocytes is generally enhanced in-vitro in the presence of estrogen, and it is observed most prominently with interferon-γ (IFN-γ), interleukin (IL)-1 and IL-10. Besides, IFN-γ, IL-4 and IL-5 secretion was decreased in the presence of androgens.[11] Furthermore, a more increased percentage of IL-2-producing lymphocytes was observed in females than males.[12] Meanwhile, it was considered that IFN-γ develops AA.[13] Likewise, a role for IL-2 in the pathogenesis of AA has been established, and IL-2 is also considered an aggravating cytokine of AA.[14] Therefore, female patients with AA tend to have a more severe inflammatory condition than male patients. Although anagen hair follicle is normally an immune-privileged site, this is disrupted in AA.[13] It occurs due to the increase of major histocompatibility complex I and II molecules along with adhesion molecules, which correlate with increased leukocytes trafficking into the dermis.[15] These changes enhance the presentation of antigens by hair follicle cells and the migration of T cells to hair follicles in AA lesions. That is to say, females have a less severe collapse of immune privilege than males in the same degree of AA.


   Conclusions Top


Despite the limitations of a small sample size including the previous reports (n = 261), the results indicated that female patients with AA would have better outcomes than male patients after steroid pulse therapy. Although further investigations are needed to evaluate the differences in therapeutic values of steroid pulse therapy for AA between males and females, steroid pulse therapy might be suited for an early-onset stage of AA in females.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
   References Top

1.
Nakajima T, Inui S, Itami S. Pulse corticosteroid therapy for alopecia areata: Study of 139 patients. Dermatology 2007;215:320-4.  Back to cited text no. 1
    
2.
Olsen E, Hordinsky M, McDonald-Hull S, Price V, Roberts J, Shapiro J, et al. Alopecia areata investigational assessment guidelines. National alopecia areata foundation. J Am Acad Dermatol 1999;40:242-6.  Back to cited text no. 2
    
3.
Burton JL, Shuster S. Large doses of glucocorticoid in the treatment of alopecia areata. Acta Derm Venereol 1975;55:493-6.  Back to cited text no. 3
    
4.
Friedli A, Labarthe MP, Engelhardt E, Feldmann R, Salomon D, Saurat JH. Pulse methylprednisolone therapy for severe alopecia areata: An open prospective study of 45 patients. J Am Acad Dermatol 1998;39:597-602.  Back to cited text no. 4
    
5.
Seiter S, Ugurel S, Tilgen W, Reinhold U. High-dose pulse corticosteroid therapy in the treatment of severe alopecia areata. Dermatology 2001;202:230-4.  Back to cited text no. 5
    
6.
Im M, Lee SS, Lee Y, Kim CD, Seo YJ, Lee JH, et al. Prognostic factors in methylprednisolone pulse therapy for alopecia areata. J Dermatol 2011;38:767-72.  Back to cited text no. 6
    
7.
Staumont-Sallé D, Vonarx M, Lengrand F, Segard M, Delaporte E. Pulse corticosteroid therapy for alopecia areata: Long-term outcome after 10 years. Dermatology 2012;225:81-7.  Back to cited text no. 7
    
8.
Friedland R, Tal R, Lapidoth M, Zvulunov A, Ben Amitai D. Pulse corticosteroid therapy for alopecia areata in children: A retrospective study. Dermatology 2013;227:37-44.  Back to cited text no. 8
    
9.
Sato Y, Kinoshita-Ise M, Fukuyama M, Yamazaki Y, Ohyama M. Development of a scoring system to predict outcomes of i.v. corticosteroid pulse therapy in rapidly progressive alopecia areata adopting digital image analysis of hair recovery. J Dermatol 2021;48:301-9.  Back to cited text no. 9
    
10.
Sato M, Amagai M, Ohyama M. Detailed clinicopathological characterization of progressive alopecia areata patients treated with i.v. corticosteroid pulse therapy toward optimization of inclusion criteria. J Dermatol 2014;41:957-63.  Back to cited text no. 10
    
11.
Whitacre CC. Sex differences in autoimmune disease. Nat Immunol 2001;2:777-80.  Back to cited text no. 11
    
12.
Bouman A, Schipper M, Heineman MJ, Faas MM. Gender difference in the non-specific and specific immune response in humans. Am J Reprod Immunol 2004;52:19-26.  Back to cited text no. 12
    
13.
Strazzulla LC, Wang EH, Avila L, Lo Sicco K, Brinster N, Christiano AM, et al. Alopecia areata: Disease characteristics, clinical evaluation, and new perspectives on pathogenesis. J Am Acad Dermatol 2018;78:1-12.  Back to cited text no. 13
    
14.
Freyschmidt-Paul P, McElwee KJ, Hoffmann R, Sundberg JP, Kissling S, Hummel S, et al. Reduced expression of interleukin-2 decreases the frequency of alopecia areata onset in C3H/HeJ mice. J Invest Dermatol 2005;125:945-51.  Back to cited text no. 14
    
15.
Ghersetich I, Campanile G, Lotti T. Alopecia areata: Immunohistochemistry and ultrastructure of infiltrate and identification of adhesion molecule receptors. Int J Dermatol 1996;35:28-33.  Back to cited text no. 15
    


    Figures

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    Tables

  [Table 1], [Table 2]



 

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