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Table. 5 
Cases of Alopecia Areata and Narcolepsy
Cases of Alopecia Areata and Narcolepsy
1.
Domíinguez Ortega  L Narcolepsy and alopecia areata: a new association? [in Spanish]. An Med Interna 1992;9 (5) 234- 236
PubMed
2.
Pelin  ZGuilleminault  CRisch  NGrumet  FCMignot  EUS Modafinil in Narcolepsy Multicenter Study Group, HLA-DQB1*0602 homozygosity increases relative risk for narcolepsy but not disease severity in two ethnic groups. Tissue Antigens 1998;51 (1) 96- 100
PubMedArticle
3.
Mignot  ELin  LRisch  N  et al.  Identification of a novel HLA narcolepsy susceptibility subtype, HLA DQB1*0301. Sleep 1999;22 ((suppl 1)) 121- 122
4.
Hallmayer  JFaraco  JLin  L  et al.  Narcolepsy is strongly associated with the T cell receptor alpha locus. Nat Genet 2009;41 (6) 708- 711
PubMedArticle
5.
Rosenblum  MDOlasz  EBYancey  KB  et al.  Expression of CD200 on epithelial cells of the murine hair follicle: a role in tissue-specific immune tolerance? J Invest Dermatol 2004;123 (5) 880- 887
PubMedArticle
Research Letter
June 2010

A Potential Association Between Alopecia Areata and Narcolepsy

Author Affiliations

Author Affiliations: Vanderbilt Dermatology Clinic, Vanderbilt University Medical Center, Nashville, Tennessee (Drs King, Curcio, and Schmidt); and University of Tennessee Health Science Center, Memphis (Ms Eastham).

Arch Dermatol. 2010;146(6):677-679. doi:10.1001/archdermatol.2010.108

To our knowledge, narcolepsy was first associated with alopecia areata (AA) in the Spanish-language literature in 1992.1 The author described 2 patients with alopecia universalis and 1 with AA who subsequently developed symptoms suggestive of narcolepsy. In all 3 cases, the diagnosis of narcolepsy was made with the multiple sleep latency test (MSLT), which is considered 1 of 2 confirmatory tests for narcolepsy, the other being polysomnography (PSG). To our knowledge, this association has not since been described.

We report herein 2 additional cases of AA in connection with narcolepsy seen in the Vanderbilt Dermatology Alopecia Clinic. These cases were observed by chance, and our report is meant only to add to the literature so that a possible association between the 2 likely autoimmune disorders is not overlooked.

Report of Cases
Case 1

A 19-year-old African American woman developed AA 3 years after a diagnostic MSLT revealed pathologic sleepiness. However, baseline PSG and MSLT had shown no evidence of clinically significant sleep apnea, diminished stage II or REM sleep, or clinically significant oxygen desaturation. She also had asthma, allergic rhinitis, and cyclic vomiting syndrome. The patient was started on modafinil treatment in November 2005 and continued that therapy at last follow-up, but she developed occasional sleep paralysis 18 months after modafinil treatment was begun.

Case 2

A 20-year-old Asian American woman with a 2-year history of chronically active AA involving the scalp and lateral eyebrows developed narcolepsylike symptoms of daytime somnolence: nodding off while driving, difficulty concentrating, fatigue, irritability, and decreased athletic and academic performance. The MSLT findings were consistent with narcolepsy, and the patient was started on modafinil therapy.

Comment

Narcolepsy is a sleep-wake disorder characterized by excessive daytime sleepiness, hypnagogic hallucinations, sleep paralysis and cataplexy, and/or sudden muscle weakness that results from a loss of hypothalamic neurons producing the neuropeptides orexin A and orexin B (hypocretin 1 and 2). An immunogenetic mechanism with a tight link with HLA allele DQB1*0602 across ethnic groups has been established.2 In patients heterozygous for DQB1*0602, an increased risk is conferred with DQB1*0301, especially in African Americans.3 An autoimmune hypothesis for narcolepsy gained support with the recent discovery of a genetic link between narcolepsy and a gene encoding T-cell receptor alpha that interacts with HLA proteins to generate an immune response.4

Similar to other autoimmune diseases, AA is associated with particular major histocompatibility complex class II haplotypes that confer an increased risk, including DQB1*03, DRB1*1104, DRB1*0401, and DQB1*0301. The overlap in the DQB1 regions in narcolepsy and AA suggests a concordance in patients with AA and narcolepsy that may link the 2 presumed autoimmune diseases in susceptible patients. In addition, CD200, which is expressed predominantly in outer root sheath follicular keratinocytes and may prevent undesired activation of autoreactive T cells,5 was originally designated orexin 2. Orexins 1 and 2 are G protein–coupled receptors to which orexins A and B bind. The data from the 2 cases reported herein and the 3 taken from the literature1 (Table) suggest, but do not prove, that there may be more than a random association of AA and narcolepsy occurring in some patients.

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Article Information

Correspondence: Dr Schmidt, Vanderbilt Dermatology Clinic, Vanderbilt Health–One Hundred Oaks, 719 Thompson Ln, Ste 26300, Nashville, TN 37204 (adriana.schmidt99@gmail.com).

Accepted for Publication: January 4, 2010.

Author Contributions: Drs King and Schmidt had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: King and Schmidt. Acquisition of data: King, Eastham, and Curcio. Analysis and interpretation of data: King and Schmidt. Drafting of the manuscript: King, Eastham, and Schmidt. Critical revision of the manuscript for important intellectual content: King and Curcio. Obtained funding: King. Administrative, technical, and material support: King. Study supervision: King and Schmidt. Translation of cited article from Spanish: Curcio.

Financial Disclosure: None reported.

References
1.
Domíinguez Ortega  L Narcolepsy and alopecia areata: a new association? [in Spanish]. An Med Interna 1992;9 (5) 234- 236
PubMed
2.
Pelin  ZGuilleminault  CRisch  NGrumet  FCMignot  EUS Modafinil in Narcolepsy Multicenter Study Group, HLA-DQB1*0602 homozygosity increases relative risk for narcolepsy but not disease severity in two ethnic groups. Tissue Antigens 1998;51 (1) 96- 100
PubMedArticle
3.
Mignot  ELin  LRisch  N  et al.  Identification of a novel HLA narcolepsy susceptibility subtype, HLA DQB1*0301. Sleep 1999;22 ((suppl 1)) 121- 122
4.
Hallmayer  JFaraco  JLin  L  et al.  Narcolepsy is strongly associated with the T cell receptor alpha locus. Nat Genet 2009;41 (6) 708- 711
PubMedArticle
5.
Rosenblum  MDOlasz  EBYancey  KB  et al.  Expression of CD200 on epithelial cells of the murine hair follicle: a role in tissue-specific immune tolerance? J Invest Dermatol 2004;123 (5) 880- 887
PubMedArticle
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