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located on the cranial vertex&#44; had appeared over the previous few weeks &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46; The patient had no family or personal history of AA and reported no events involving infection&#44; vaccination&#44; or stress prior to the loss of hair&#46; AA was diagnosed&#44; adalimumab treatment was stopped&#44; and a daily application of clobetasol propionate 0&#46;05&#37; cream was prescribed&#46; After 6 months the diameter of both alopecia plaques had not changed despite the withdrawal of adalimumab&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0015" class="elsevierStylePara elsevierViewall">Adalimumab is a recombinant and fully humanized monoclonal antibody that works against tumor necrosis factor &#945; &#40;TNF-&#945;&#41; and has been approved for the treatment of rheumatoid arthritis&#44; ankylosing spondylitis&#44; Crohn disease&#44; psoriasis&#44; and psoriatic arthritis&#46; TNF-&#945; is a proinflammatory cytokine in the body&#39;s immune system&#44; but when it is neutralized by anti-TNF-&#945; antibodies like adalimumab&#44; autoimmune disorders such as systematic sclerosis and systemic lupus erythematosus have been known to develop&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> The role of TNF-&#945; in the physiopathology of these processes is complex&#44; but the cytokine has been shown to originate in the mononuclear cells that surround the hair follicle in AA<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> and inhibit hair follicle growth during in vitro testing&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> TNF-&#945; is thus linked to hair loss&#46; Accordingly&#44; anti-TNF-&#945; medications and other biologic therapies have been used to treat AA&#44; but with poor results&#59; in some sporadic cases satisfactory responses have been reported&#44; but no large study has demonstrated any significant therapeutic effects of etanercept&#44;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> alefacept&#44;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> or efalizumab&#46;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">At the same time&#44; new cases of AA have become more frequent in patients undergoing treatment with anti-TNF-&#945; and other biologic therapies&#46; Cases of AA induced by etanercept&#44; infliximab&#44; and adalimumab are being reported&#46; Garc&#237;a Bartels et al<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> were the first to describe adalimumab-induced AA&#59; the patient was a 23-year-old woman who developed AA universalis 2 months after starting treatment&#46; Seven patients have since been described&#59; only 2 had a past history of AA and 3 developed the universalis form&#46;<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#44;6&#8211;10</span></a> The amount of time from starting treatment with anti-TNF-&#945; to the appearance of AA ranged between 2 months and 2 years&#46; In cases in which adalimumab was withdrawn&#44; no new hair growth occurred in any of the patients studied&#46; Similarly&#44; hair did not regrow on our patient&#39;s plaques&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">The mechanism by which TNF-&#945; inhibition induces AA is unknown&#46; In 2005&#44; De Bandt et al<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> hypothesized&#44; on the basis of 22 cases of anti-TNF-&#945;-induced systemic lupus erythematosus in France&#44; that TNF-&#945; initiates the spread of suppressed CD4<span class="elsevierStyleSup">&#43;</span> regulatory T lymphocytes that are responsible for maintaining immunological tolerance and preventing autoimmunity&#46; Thus&#44; both AA and other autoimmune processes induced by anti-TNF-&#945; may develop through the inhibition of regulatory T cells&#46; However&#44; whereas all patients with lupus went into remission after the withdrawal of anti-TNF-&#945;&#44; patients with AA do not usually respond&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">In this new case of AA associated with adalimumab treatment&#44; the possibility of coincidence cannot be ruled out&#59; however&#44; earlier reports of AA in patients treated with adalimumab and the implication of anti-TNF-&#945; 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Case and research letters
Alopecia Areata After Biologic Therapy: Report of a Case Related to Adalimumab
Alopecia areata y terapias biológicas. Presentación de un caso asociado a adalimumab
J. Neila
Autor para correspondencia
drneils@hotmail.com

Corresponding author.
, A. Carrizosa, C. Ceballos, F.M. Camacho
Departamento de Dermatología Médico Quirúrgica, Hospital Universitario Virgen Macarena, Sevilla, Spain
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located on the cranial vertex&#44; had appeared over the previous few weeks &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46; The patient had no family or personal history of AA and reported no events involving infection&#44; vaccination&#44; or stress prior to the loss of hair&#46; AA was diagnosed&#44; adalimumab treatment was stopped&#44; and a daily application of clobetasol propionate 0&#46;05&#37; cream was prescribed&#46; After 6 months the diameter of both alopecia plaques had not changed despite the withdrawal of adalimumab&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0015" class="elsevierStylePara elsevierViewall">Adalimumab is a recombinant and fully humanized monoclonal antibody that works against tumor necrosis factor &#945; &#40;TNF-&#945;&#41; and has been approved for the treatment of rheumatoid arthritis&#44; ankylosing spondylitis&#44; Crohn disease&#44; psoriasis&#44; and psoriatic arthritis&#46; TNF-&#945; is a proinflammatory cytokine in the body&#39;s immune system&#44; but when it is neutralized by anti-TNF-&#945; antibodies like adalimumab&#44; autoimmune disorders such as systematic sclerosis and systemic lupus erythematosus have been known to develop&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> The role of TNF-&#945; in the physiopathology of these processes is complex&#44; but the cytokine has been shown to originate in the mononuclear cells that surround the hair follicle in AA<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> and inhibit hair follicle growth during in vitro testing&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> TNF-&#945; is thus linked to hair loss&#46; Accordingly&#44; anti-TNF-&#945; medications and other biologic therapies have been used to treat AA&#44; but with poor results&#59; in some sporadic cases satisfactory responses have been reported&#44; but no large study has demonstrated any significant therapeutic effects of etanercept&#44;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> alefacept&#44;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> or efalizumab&#46;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">At the same time&#44; new cases of AA have become more frequent in patients undergoing treatment with anti-TNF-&#945; and other biologic therapies&#46; Cases of AA induced by etanercept&#44; infliximab&#44; and adalimumab are being reported&#46; Garc&#237;a Bartels et al<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> were the first to describe adalimumab-induced AA&#59; the patient was a 23-year-old woman who developed AA universalis 2 months after starting treatment&#46; Seven patients have since been described&#59; only 2 had a past history of AA and 3 developed the universalis form&#46;<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#44;6&#8211;10</span></a> The amount of time from starting treatment with anti-TNF-&#945; to the appearance of AA ranged between 2 months and 2 years&#46; In cases in which adalimumab was withdrawn&#44; no new hair growth occurred in any of the patients studied&#46; Similarly&#44; hair did not regrow on our patient&#39;s plaques&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">The mechanism by which TNF-&#945; inhibition induces AA is unknown&#46; In 2005&#44; De Bandt et al<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> hypothesized&#44; on the basis of 22 cases of anti-TNF-&#945;-induced systemic lupus erythematosus in France&#44; that TNF-&#945; initiates the spread of suppressed CD4<span class="elsevierStyleSup">&#43;</span> regulatory T lymphocytes that are responsible for maintaining immunological tolerance and preventing autoimmunity&#46; Thus&#44; both AA and other autoimmune processes induced by anti-TNF-&#945; may develop through the inhibition of regulatory T cells&#46; However&#44; whereas all patients with lupus went into remission after the withdrawal of anti-TNF-&#945;&#44; patients with AA do not usually respond&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">In this new case of AA associated with adalimumab treatment&#44; the possibility of coincidence cannot be ruled out&#59; however&#44; earlier reports of AA in patients treated with adalimumab and the implication of anti-TNF-&#945; 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