http://informahealthcare.com/cot ISSN: 1556-9527 (print), 1556-9535 (electronic) Cutan Ocul Toxicol, Early Online: 1–3 ! 2014 Informa Healthcare USA, Inc. DOI: 10.3109/15569527.2014.948684
CASE REPORT
Acitretin-induced alopecia areata: a case report Emin Ozlu, Ayse Serap Karadag, Necmettin Akdeniz, and Tugba Kevser Uzuncakmak Cutaneous and Ocular Toxicology Downloaded from informahealthcare.com by UMEA University Library on 04/01/15 For personal use only.
Department of Dermatology, Faculty of Medicine, Goztepe Research and Training Hospital, Istanbul Medeniyet University, Istanbul, Turkey
Abstract
Keywords
Alopecia areata is a common form of non-scarring hair disorder. The development of alopecia areata during anti-psoriatic treatment has been reported with the systemic therapies such as infliximab, etanercept, adalimumab, alefacept and efalizumab. Retinoid-induced alopecia areata on the eyelash and eyebrow has not been reported in the literature. We report a female patient who presented with alopecia areata of the eyebrow and eyelash one month after the initiation of acitretin therapy for psoriasis.
Acitretin, alopecia areata, drug reaction
Introduction Alopecia areata is a common form of non-scarring hair disorder of unclear etiology. The exact etiology is not known, but the possible responsible factors may be autoimmunity, genetic constitution, emotional stress, numerous psychological factors and drugs1. The development of alopecia areata during anti-psoriatic treatment has been reported with the systemic therapies such as infliximab, etanercept, adalimumab, alefacept and efalizumab2. Retinoid-induced alopecia areata on the eyelash and eyebrow has not been reported in the literature. Acitretin is the synthetic retinoid analogue used in various dermatological disorders, especially in psoriasis. Adverse effects of acitretin are similar to other systemic retinoids and usually dose dependent. Increased hair loss may occur during acitretin treatment but alopecia areata was not reported in the literature3. We report a female patient who presented with alopecia areata of the eyebrow and eyelash one month after the initiation of acitretin therapy for psoriasis.
Case report A 43-year-old female patient presented with loss of hair in the eyelashes and eyebrows. The patient’s past medical history was remarkable for psoriasis, for which she was on follow-up for the last 10 years and received a total of 40 sessions of dbUVB phototherapy within the last two years (20 sessions, one year apart). The patient was placed on systemic acitretin therapy (20 mg/day) two months prior, due to lack of Address for correspondence: Dr. Ayse Serap Karadag, Department of Dermatology, Faculty of Medicine, Goztepe Research and Training Hospital, Istanbul Medeniyet University, Istanbul, Turkey. E-mail: [email protected]
History Received 27 May 2014 Revised 14 July 2014 Accepted 22 July 2014 Published online 29 August 2014
improvement in the lesions after phototherapy. One month after the initiation of this therapy, the patient presented with hair loss on the eyelashes and eyebrows on both sides. The patient did not receive any other medication during this period. The patient has no stress or autoimmune disease history. The patient’s past and family history was not remarkable. The dermatological examination revealed total loss of both eyebrows and near total loss of eyelashes, without involvement of the scalp (Figure 1). Psychiatric examination of the patient was unremarkable. The laboratory tests including complete blood count, biochemistry, lipid profile, thyroid functions, vitamin B12 and folic acid levels were all in normal ranges and also thyroid autoantibodies and antiparietal antibodies were negative. In dermoscopic examination; yellow dots within the hair follicule ostia, black dots, cadaverized hairs, exclamation mark and/or dystrophic hairs were seen. Based on these findings, the patient was diagnosed with acitretin-induced alopecia areata, and acitretin therapy was discontinued. Topical clobetasol propionate 0.05% therapy was initiated for plaque psoriasis lesions. Three cycles of intralesional triamcinolone acetonide 10 mg/ml injection were performed to both eyebrows with 4-week intervals. Near total hair regrowth was observed on the eyelashes and eyebrows three months after the initiation of the therapy (Figure 2).
Discussion Alopecia areata is an autoimmune inflammatory disorder characterized by non-scarring hair loss, affecting the skin sites with hair follicles. It is estimated that alopecia areata has a prevalence rate around 0.1% throughout the world. Both genders, all age groups, and all races are affected equally. The exact etiology and pathogenesis of the disease is
Cutaneous and Ocular Toxicology Downloaded from informahealthcare.com by UMEA University Library on 04/01/15 For personal use only.
2
E. Ozlu et al.
Figure 1. Total loss of both eyebrows and near total loss of eyelashes are seen.
Figure 2. Posttreatment appearence.
unknown. Alopecia areata may present in a clinical spectrum from patchy hair loss to alopecia totalis or alopecia universalis, the latter being characterized by the loss of all body hair. AA is considered to be an organ-specific autoimmune disorder, and it can coexist with thyroid disorders, vitiligo, or other autoimmune disorders such as systemic lupus erythematosus. The histopathological findings include inflammatory lymphocytic infiltration in the peribulbar area and increased proportion of catagen and telogen follicles. The corticosteroids are the most commonly used agent in its treatment4. Acitretin is a metabolite of an aromatic retinoid etretinate, and it has been used successfully in the treatment of psoriasis since 1980s. In addition to its utility in classic plaque psoriasis, acitretin can also be used alone or in combination with other therapies in the treatment of pustular, erythrodermic and palmoplantar psoriasis. Acitretin is a derivative of vitamin A, and it has been demonstrated to non-selectively activate all three types of nuclear retinoic acid receptors (RARalpha, RARbeta and RARgamma). Acitretin exerts regulator effects on the proliferation, differentiation and cornification of the epidermal cells. In addition, it is thought to have immunomodulator effects on neutrophil migration and dermal microvascular endothelial cells3,5,6.
Cutan Ocul Toxicol, Early Online: 1–3
Side effects, such as cheilitis, desquamation, pruritus, alopecia, rhinitis, xerophthalmia and xerosis are common with acitretin therapy and are generally dose dependent. Hepatotoxicity, changes in the serum lipid profile and pancreatitis are less commonly observed side effects. Acitretin is a potent teratogen agent and its use during pregnancy can cause severe side effects in the fetus. Common side effects associated with the use of acitretin, such as cheilitis and hair loss, are dose dependent and may necessitate dose reduction or discontinuation of the therapy in some patients7. Hair loss can be observed in up to 75% of the patients receiving acitretin therapy; however, alopecia areata less commonly occurs6. There is no report in the literature on cases with alopecia areata on the eyelashes and eyebrows in association with acitretin therapy. Similarly, hair shaft abnormalities can occur in patients receiving acitretin therapy, and there is one case in the literature reported to have hair kinking6. The present case did not have hair shaft abnormality. Cases of developing alopecia areata during treatment with immunosuppressive anti-psoriatic biological drugs, who received adalimumab, infliximab, etanercept, alefacept, efalizumab and ustekinumab were previously described. A phase 2, placebo controlled trial of efalizumab treatment showed no statistically effect on hair regrowth, quality of life in patients with alopecia areata2,8. It has been previously reported that systemic medications used in the treatment of psoriasis might have a role in the development of alopecia areata4. However, controversy exists regarding whether the development of alopecia areata in patients with psoriasis should be regarded as a co-existence or a side effect induced by the administered anti-psoriatic therapy. It was suggested that the immune system can prevent the development of alopecia areata in patients with severe psoriasis. On the other hand, the same study also suggested that immunomodulator agents used in the treatment of psoriasis can facilitate the development of alopecia areata8. It has not been fully understood through which mechanisms retinoids produce changes in the hair abnormalities6. One study suggested that retinoids shortened anagen phase and prematurely moved hair follicles into telogen phase9. Systemic acitretin-induced autoimmune disease has not been reported in the literature before. Retinoids have multiple effects, and it has been previously reported that retinoids might play a role in the development of alopecia areata. Using microarray transcriptional profiling of alopecia areata lesions in the C3H/Hej Mouse model, Duncan et al. showed that the genes that play a role in retinoid metabolism are up-regulated when compared to the control group, and these findings were further supported by histochemical analyses performed in human, mouse and rat tissues10. In the same study, a vitamin A deficient diet was associated with lymphocytic infiltration, epidermal hyperplasia, and dystrophic follicles, and conversely, a vitamin A rich diet partially protected against alopecia. The same study reported increased hair loss in mice fed with a diet containing vitamin A seven times higher than normal, and vitamin A deficient diet was also associated with alopecia. The authors in this study suggested that vitamin A played a role both in hair cycle and
DOI: 10.3109/15569527.2014.948684
regulation of immune responses to the progression of alopecia areata10. In conclusion, further studies are warranted in order to gain insight into the effects of retinoids on hair cycle and hair structure. Further studies will allow the physicians to provide their patients with more information regarding the side effects of retinoids.
Declaration of interest
Cutaneous and Ocular Toxicology Downloaded from informahealthcare.com by UMEA University Library on 04/01/15 For personal use only.
The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.
References 1. Seetharam KA. Alopecia areata: an update. Indian J Dermatol Venereol Leprol 2013;79:563–575.
Acitretin-induced alopecia areata
3
2. Kos L, Conlon J. An update on alopecia areata. Curr Opin Pediatr 2009;21:475–480. 3. Sarkar R, Chugh S, Garg VK. Acitretin in dermatology. Indian J Dermatol Venereol Leprol 2013;79:759–771. 4. Wasserman D, Guzman-Sanchez DA, Scott K, McMichael A. Alopecia areata. Int J Dermatol 2007;46:121–131. 5. Clarke JT, Price H, Clarke S, et al. Acquired kinking of the hair caused by acitretin. J Drugs Dermatol 2007;6:937–938. 6. Jeaneen AC, Melinda BC, Katherine M, et al. Acitretin-induced poliosis with concurrent alopecia. J Drugs Dermatol 2012;11: 247–249. 7. Katz HI, Waalen J, Leach EE. Acitretin in psoriasis: an overview of adverse effects. J Am Acad Dermatol 1999;41:7–12. 8. Slowinska M, Kardynal A, Warszawik O, et al. Alopecia areata developing parallel to improvement of psoriasis during ustekinumab therapy. J Dermatol Case Rep 2010;4:15–17. 9. Berth-Jones C, Graham-Brown R. A study of etretinate alopecia. Br J Dermatol 1993;129:356–363. 10. Duncan F, Silva K, Johnson, et al. Endogenous retinoids in the pathogenesis of alopecia areata. J Invest Dermatol 2012;133:325–333.
CASE REPORT
Acitretin-induced alopecia areata: a case report Emin Ozlu, Ayse Serap Karadag, Necmettin Akdeniz, and Tugba Kevser Uzuncakmak Cutaneous and Ocular Toxicology Downloaded from informahealthcare.com by UMEA University Library on 04/01/15 For personal use only.
Department of Dermatology, Faculty of Medicine, Goztepe Research and Training Hospital, Istanbul Medeniyet University, Istanbul, Turkey
Abstract
Keywords
Alopecia areata is a common form of non-scarring hair disorder. The development of alopecia areata during anti-psoriatic treatment has been reported with the systemic therapies such as infliximab, etanercept, adalimumab, alefacept and efalizumab. Retinoid-induced alopecia areata on the eyelash and eyebrow has not been reported in the literature. We report a female patient who presented with alopecia areata of the eyebrow and eyelash one month after the initiation of acitretin therapy for psoriasis.
Acitretin, alopecia areata, drug reaction
Introduction Alopecia areata is a common form of non-scarring hair disorder of unclear etiology. The exact etiology is not known, but the possible responsible factors may be autoimmunity, genetic constitution, emotional stress, numerous psychological factors and drugs1. The development of alopecia areata during anti-psoriatic treatment has been reported with the systemic therapies such as infliximab, etanercept, adalimumab, alefacept and efalizumab2. Retinoid-induced alopecia areata on the eyelash and eyebrow has not been reported in the literature. Acitretin is the synthetic retinoid analogue used in various dermatological disorders, especially in psoriasis. Adverse effects of acitretin are similar to other systemic retinoids and usually dose dependent. Increased hair loss may occur during acitretin treatment but alopecia areata was not reported in the literature3. We report a female patient who presented with alopecia areata of the eyebrow and eyelash one month after the initiation of acitretin therapy for psoriasis.
Case report A 43-year-old female patient presented with loss of hair in the eyelashes and eyebrows. The patient’s past medical history was remarkable for psoriasis, for which she was on follow-up for the last 10 years and received a total of 40 sessions of dbUVB phototherapy within the last two years (20 sessions, one year apart). The patient was placed on systemic acitretin therapy (20 mg/day) two months prior, due to lack of Address for correspondence: Dr. Ayse Serap Karadag, Department of Dermatology, Faculty of Medicine, Goztepe Research and Training Hospital, Istanbul Medeniyet University, Istanbul, Turkey. E-mail: [email protected]
History Received 27 May 2014 Revised 14 July 2014 Accepted 22 July 2014 Published online 29 August 2014
improvement in the lesions after phototherapy. One month after the initiation of this therapy, the patient presented with hair loss on the eyelashes and eyebrows on both sides. The patient did not receive any other medication during this period. The patient has no stress or autoimmune disease history. The patient’s past and family history was not remarkable. The dermatological examination revealed total loss of both eyebrows and near total loss of eyelashes, without involvement of the scalp (Figure 1). Psychiatric examination of the patient was unremarkable. The laboratory tests including complete blood count, biochemistry, lipid profile, thyroid functions, vitamin B12 and folic acid levels were all in normal ranges and also thyroid autoantibodies and antiparietal antibodies were negative. In dermoscopic examination; yellow dots within the hair follicule ostia, black dots, cadaverized hairs, exclamation mark and/or dystrophic hairs were seen. Based on these findings, the patient was diagnosed with acitretin-induced alopecia areata, and acitretin therapy was discontinued. Topical clobetasol propionate 0.05% therapy was initiated for plaque psoriasis lesions. Three cycles of intralesional triamcinolone acetonide 10 mg/ml injection were performed to both eyebrows with 4-week intervals. Near total hair regrowth was observed on the eyelashes and eyebrows three months after the initiation of the therapy (Figure 2).
Discussion Alopecia areata is an autoimmune inflammatory disorder characterized by non-scarring hair loss, affecting the skin sites with hair follicles. It is estimated that alopecia areata has a prevalence rate around 0.1% throughout the world. Both genders, all age groups, and all races are affected equally. The exact etiology and pathogenesis of the disease is
Cutaneous and Ocular Toxicology Downloaded from informahealthcare.com by UMEA University Library on 04/01/15 For personal use only.
2
E. Ozlu et al.
Figure 1. Total loss of both eyebrows and near total loss of eyelashes are seen.
Figure 2. Posttreatment appearence.
unknown. Alopecia areata may present in a clinical spectrum from patchy hair loss to alopecia totalis or alopecia universalis, the latter being characterized by the loss of all body hair. AA is considered to be an organ-specific autoimmune disorder, and it can coexist with thyroid disorders, vitiligo, or other autoimmune disorders such as systemic lupus erythematosus. The histopathological findings include inflammatory lymphocytic infiltration in the peribulbar area and increased proportion of catagen and telogen follicles. The corticosteroids are the most commonly used agent in its treatment4. Acitretin is a metabolite of an aromatic retinoid etretinate, and it has been used successfully in the treatment of psoriasis since 1980s. In addition to its utility in classic plaque psoriasis, acitretin can also be used alone or in combination with other therapies in the treatment of pustular, erythrodermic and palmoplantar psoriasis. Acitretin is a derivative of vitamin A, and it has been demonstrated to non-selectively activate all three types of nuclear retinoic acid receptors (RARalpha, RARbeta and RARgamma). Acitretin exerts regulator effects on the proliferation, differentiation and cornification of the epidermal cells. In addition, it is thought to have immunomodulator effects on neutrophil migration and dermal microvascular endothelial cells3,5,6.
Cutan Ocul Toxicol, Early Online: 1–3
Side effects, such as cheilitis, desquamation, pruritus, alopecia, rhinitis, xerophthalmia and xerosis are common with acitretin therapy and are generally dose dependent. Hepatotoxicity, changes in the serum lipid profile and pancreatitis are less commonly observed side effects. Acitretin is a potent teratogen agent and its use during pregnancy can cause severe side effects in the fetus. Common side effects associated with the use of acitretin, such as cheilitis and hair loss, are dose dependent and may necessitate dose reduction or discontinuation of the therapy in some patients7. Hair loss can be observed in up to 75% of the patients receiving acitretin therapy; however, alopecia areata less commonly occurs6. There is no report in the literature on cases with alopecia areata on the eyelashes and eyebrows in association with acitretin therapy. Similarly, hair shaft abnormalities can occur in patients receiving acitretin therapy, and there is one case in the literature reported to have hair kinking6. The present case did not have hair shaft abnormality. Cases of developing alopecia areata during treatment with immunosuppressive anti-psoriatic biological drugs, who received adalimumab, infliximab, etanercept, alefacept, efalizumab and ustekinumab were previously described. A phase 2, placebo controlled trial of efalizumab treatment showed no statistically effect on hair regrowth, quality of life in patients with alopecia areata2,8. It has been previously reported that systemic medications used in the treatment of psoriasis might have a role in the development of alopecia areata4. However, controversy exists regarding whether the development of alopecia areata in patients with psoriasis should be regarded as a co-existence or a side effect induced by the administered anti-psoriatic therapy. It was suggested that the immune system can prevent the development of alopecia areata in patients with severe psoriasis. On the other hand, the same study also suggested that immunomodulator agents used in the treatment of psoriasis can facilitate the development of alopecia areata8. It has not been fully understood through which mechanisms retinoids produce changes in the hair abnormalities6. One study suggested that retinoids shortened anagen phase and prematurely moved hair follicles into telogen phase9. Systemic acitretin-induced autoimmune disease has not been reported in the literature before. Retinoids have multiple effects, and it has been previously reported that retinoids might play a role in the development of alopecia areata. Using microarray transcriptional profiling of alopecia areata lesions in the C3H/Hej Mouse model, Duncan et al. showed that the genes that play a role in retinoid metabolism are up-regulated when compared to the control group, and these findings were further supported by histochemical analyses performed in human, mouse and rat tissues10. In the same study, a vitamin A deficient diet was associated with lymphocytic infiltration, epidermal hyperplasia, and dystrophic follicles, and conversely, a vitamin A rich diet partially protected against alopecia. The same study reported increased hair loss in mice fed with a diet containing vitamin A seven times higher than normal, and vitamin A deficient diet was also associated with alopecia. The authors in this study suggested that vitamin A played a role both in hair cycle and
DOI: 10.3109/15569527.2014.948684
regulation of immune responses to the progression of alopecia areata10. In conclusion, further studies are warranted in order to gain insight into the effects of retinoids on hair cycle and hair structure. Further studies will allow the physicians to provide their patients with more information regarding the side effects of retinoids.
Declaration of interest
Cutaneous and Ocular Toxicology Downloaded from informahealthcare.com by UMEA University Library on 04/01/15 For personal use only.
The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.
References 1. Seetharam KA. Alopecia areata: an update. Indian J Dermatol Venereol Leprol 2013;79:563–575.
Acitretin-induced alopecia areata
3
2. Kos L, Conlon J. An update on alopecia areata. Curr Opin Pediatr 2009;21:475–480. 3. Sarkar R, Chugh S, Garg VK. Acitretin in dermatology. Indian J Dermatol Venereol Leprol 2013;79:759–771. 4. Wasserman D, Guzman-Sanchez DA, Scott K, McMichael A. Alopecia areata. Int J Dermatol 2007;46:121–131. 5. Clarke JT, Price H, Clarke S, et al. Acquired kinking of the hair caused by acitretin. J Drugs Dermatol 2007;6:937–938. 6. Jeaneen AC, Melinda BC, Katherine M, et al. Acitretin-induced poliosis with concurrent alopecia. J Drugs Dermatol 2012;11: 247–249. 7. Katz HI, Waalen J, Leach EE. Acitretin in psoriasis: an overview of adverse effects. J Am Acad Dermatol 1999;41:7–12. 8. Slowinska M, Kardynal A, Warszawik O, et al. Alopecia areata developing parallel to improvement of psoriasis during ustekinumab therapy. J Dermatol Case Rep 2010;4:15–17. 9. Berth-Jones C, Graham-Brown R. A study of etretinate alopecia. Br J Dermatol 1993;129:356–363. 10. Duncan F, Silva K, Johnson, et al. Endogenous retinoids in the pathogenesis of alopecia areata. J Invest Dermatol 2012;133:325–333.
