Copyright © 2017 John Libbey Eurotext. Téléchargé par BIBLIOTHEQUE DIVISION DES ACQUISITIONS UNIVERSITE LAVAL le 09/06/2017.
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B
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D
Figure 1. A) Clinical feature of actinic cheilitis before MALPDT, B) Despite 5 sessions of MAL-PDT, the lesion of actinic cheilitis remains. C) Histological confirmation was made as actinic cheilitis before MAL-PDT, D) Keratinocytic atypia was observed even after MAL-PDT. (C, D : H&E, ×200).
observed in 84% and 62% of patients, respectively [3, 4]. There may be several explanations for the low therapeutic efficacy of PDT in the treatment of AC. Inadequate uptake of the photosensitizer owing to dilution by saliva and rapid regeneration of mucosal epithelium compared with the skin may result in a lower efficacy of the treatment. PDT was also shown to have low efficacy against Fordyce’s spots on the lip [5]. Therefore, intralesional injection of the photosensitizer may enhance the cure rate of PDT in the treatment of AC. Inappropriate light absorption owing to the curved surface of the lip may also contribute to the low therapeutic efficacy. Although 1-2 sessions of PDT are sufficient to achieve CR of actinic keratosis, AC lesions did not completely disappear despite multiple treatments in this study. To improve the therapeutic efficacy of AC with PDT, combination therapy with imiquimod cream has been introduced [6]. Through the PDT, reactive oxygen species are produced, resulting in local tissue destruction. On the other hand, imiquimod cream increases topical cellular immunity and tumor apoptosis. The lower lip is a high-risk area for change into squamous cell carcinoma (SCC) and its subsequent metastasis. Moreover, SCC may be diagnosed as AC depending on the site of biopsy. Considering the importance of therapeutic efficacy, we suggest that topical PDT may not be suitable as the first-line monotherapy for AC, even with repeated sessions. Combination therapy such as PDT with imiquimod cream could be considered for AC rather than PDT alone. Disclosure. Financial support: none. Conflict of interest: none. Department of Dermatology, Ajou University School of Medicine, 5 Wonchon-Dong, Yeongtong-Gu Suwon 443- Suwon Republic of Korea
Sue Kyung KIM Hyo Sang SONG You Chan KIM
1. Fai D, Romano I, Cassano N, Vena GA. Methyl-aminolevulinate photodynamic therapy for the treatment of actinic cheilitis: a retrospective evaluation of 29 patients. G Ital Dermatol Venereol 2012; 147: 99-101.
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2. Hauschild A, Lischner S, Lange-Asschenfeldt B, Egberts F. Treatment of actinic cheilitis using photodynamic therapy with methyl aminolevulinate: report of three cases. Dermatol Surg 2005; 31: 1344-7. 3. Ribeiro CF, Souza FH, Jordao JM, et al. Photodynamic therapy in actinic cheilitis: clinical and anatomopathological evaluation of 19 patients. An Bras Dermatol 2012; 87: 418-23. 4. Berking C, Herzinger T, Flaig MJ, Brenner M, Borelli C, Degitz K. The efficacy of photodynamic therapy in actinic cheilitis of the lower lip: a prospective study of 15 patients. Dermatol Surg 2007; 33: 825-30. 5. Kim YJ, Kang HY, Lee ES, Kim YC. Treatment of Fordyce spots with 5-aminolaevulinic acid-photodynamic therapy. Br J Dermatol 2007; 156: 399-400. 6. Sotiriou E, Lallas A, Goussi C, et al. Sequential use of photodynamic therapy and imiquimod 5% cream for the treatment of actinic cheilitis: a 12-month follow-up study. Br J Dermatol 2011; 165: 888-92. doi:10.1684/ejd.2013.2199
Persistent generalized lichen nitidus successfully treated with 0.03% tacrolimus ointment Generalized lichen nitidus (LN) is characterized by multiple, shiny, skin-colored papules covering the whole body. The clinical course is unpredictable and chronic, as opposed to the classic localized type [1]. Although there are numerous therapeutic options for treating generalized LN, the effect of tacrolimus has not been reported to date. We describe a case of persistent generalized LN in which the patient had impressive improvement with tacrolimus ointment after 5 years of various unsuccessful therapeutic modalities. A 9-year-old boy was referred to our department with a pruritic, generalized eruption of 5 years duration that first appeared on the trunk and gradually spread to the extremities. The child had been treated with topical and systemic corticosteroids, antihistamines and UV therapy but none of these efforts had resulted in any benefit. Physical examination revealed numerous 1-2 mm, skin-colored, flat-topped, shiny papules on the face, upper extremities, back and buttocks (figure 1A). He had no history of atopic dermatitis or any other atopic manifestations. Routine laboratory studies were within normal ranges. Histopathological examination revealed a well-circumscribed lymphohistiocytic infiltration with widened dermal papilla and elongated rete ridges embracing the infiltrate, producing a ‘clawclutching-a-ball’ pattern. Hydropic degeneration within the basal epidermal layer was also seen (figure 1B). Based on the clinicopathological findings, a diagnosis of generalized LN was made and treated with topical 0.03% tacrolimus ointment (Protopic® ) twice daily (about 2.5 g in every application). After two weeks, the skin lesions were dramatically improved (figure 1C). A total of 70 g of ointment was used during the first two weeks. From that time onwards, we gradually reduced the frequency of ointment application to twice weekly, based on the maintenance regimen approved in Europe. After nine weeks, the skin eruption had nearly resolved. There was no recurrence and no significant cutaneous or systemic side effect during the 22-month follow-up. EJD, vol. 23, n◦ 6, November-December 2013
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Copyright © 2017 John Libbey Eurotext. Téléchargé par BIBLIOTHEQUE DIVISION DES ACQUISITIONS UNIVERSITE LAVAL le 09/06/2017.
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Figure 1. A) Numerous 1-2 mm flesh-colored, flat-topped, shiny papules on the child’s back, buttock and upper face. B) Histopathological examination revealed well-circumscribed lymphohistiocytic infiltration with widened dermal papilla and elongated rete ridges embracing the infiltrate, producing a ‘claw-clutching-a-ball’ pattern. Hydropic degeneration within the basal epidermal layer was also seen (H&E stain, ×200).C) Clinical improvement after two weeks of treatment with tacrolimus 0.03% cream.
Generalized LN tends to be more chronic than localized, although the localized form of LN spontaneously resolves without any sequelae after many months. Treatment is necessary when the disease is considered to be cosmetically undesirable or when accompanied by symptoms such as pruritus. Various therapeutic options, including potent topical steroids, H1-antagonists such as astemizole [2], antituberculous agents [3], narrow-band UVB phototherapy [4], acitretin [5] and low-dose cyclosporine [6] have been reported for the treatment of generalized LN. In our patient, various therapeutic approaches had been used without any effect on the skin lesions over the 5 years prior to the initiation of treatment with tacrolimus ointment. Topical tacrolimus, a calcineurin inhibitor, is an antiinflammatory agent that might replace steroids in the topical treatment of many pediatric inflammatory skin diseases, such as atopic dermatitis and contact dermatitis, without having atrophogenic potential or risking other steroidspecific side effects. Although the exact mechanism by which tacrolimus acts in the treatment of LN is unknown, it is proposed to have an effect on various cells of the cutaneous immune system, specifically on T cells, through inhibition of the phosphatase calcineurin and prevention of the transcription of proinflammatory cytokines. The cell-mediated response caused by antigen-presenting cells and the immune response influenced by specific cytokines produced by the inflammatory cells are considered important in LN, suggesting that the anti-inflammatory and immunomodulatory effects of tacrolimus may be effective [7]. Pimecrolimus, another topical calcineurin inhibitor and
EJD, vol. 23, n◦ 6, November-December 2013
immunomodulator, has also proven beneficial in generalized LN [8]. Successful treatment of localized LN with tacrolimus ointment has been reported in two cases [9, 10], however, its effect in generalized LN has not been reported to date. In the present case, we felt that topical tacrolimus treatment of patients with generalized LN might be a promising option, based on previous reports of successful treatment of localized LN. Consequently, we prescribed the application of tacrolimus ointment and observed rapid improvement and full remission of the skin lesions. We used 0.03% tacrolimus ointment opposed to 0.1% because only 0.03% ointment is indicated for children aged two to 15 years. To our knowledge, this is the first case of successful treatment of generalized LN with topical 0.03% tacrolimus therapy. We believe topical tacrolimus might be a more potent and safe immunomodulator than steroids, especially for the treatment of persisting generalized LN. Disclosure. Financial support: none. Conflict of interest: none. 1
Department of Dermatology, Research Institute of Clinical Medicine, 3 Plastic and Reconstructive Surgery, Chonbuk National University Medical School, 20, Geonji-ro (Geumam-dong), Deokjin-gu, Jeonju, 561-712, South Korea 2
Jin PARK1,2 Joo-Ik KIM1 Dae-Woo KIM1 Su-Ran HWANG1 Si-Gyun ROH2,3 Han-Uk KIM1,2 Seok-Kweon YUN1,2
1. Al-Mutairi N, Hassanein A, Nour-Eldin O, Arun J. Generalized lichen nitidus. Pediatr Dermatol 2005; 22: 158-60. 2. Kim SW, Lee UH, Park HS, Jang SJ. A clinical study of generalized lichen nitidus. Korean J Dermatol 2008; 46: 1201-7. 3. Kubota Y, Kiryu H, Nakayama J. Generalized lichen nitidus successfully treated with an antituberculous agent. Br J Dermatol 2002; 146: 1081-3. 4. Nakamizo S, Kabashima K, Matsuyoshi N, Takahashi K, Miyachi Y. Generalized lichen nitidus successfully treated with narrowband UVB phototherapy. Eur J Dermatol 2010; 20: 816. 5. Lucker G, Koopman R, Steijlen P, Valk P. Treatment of palmoplantar lichen nitidus with acitretin. Br J Dermatol 1994; 130: 791-3. 6. Rallis E, Verros C, Moussatou V, Sambaziotis D, Papadakis P. Generalized purpuric lichen nitidus. Report of a case and review of the literature. Dermatol Online J 2007; 13: 5. 7. Daoud MS, Pittelkow MR. Lichen nitidus, In: Goldsmith LA, Katz SI, Gilchrest BA, Paller AS, Leffell DJ, Wolff K, editors. Fitzpatrick’s dermatology in general medicine. 8th ed. New York: McGraw-Hill, 2012: 312. 8. Farshi S, Mansouri P. Generalized lichen nitidus successfully treated with pimecrolimus 1 percent cream. Dermatol Online J 2011; 17: 11. 9. Son YM, Na SY, Lee HY, et al. A Case of Lichen Nitidus That Was Improved with Topical Tacrolimus. Korean J Dermatol 2009; 47: 74951. 10. Dobbs CR, Murphy SJ. Lichen nitidus treated with topical tacrolimus. J Drugs Dermatol 2004; 3: 683-4. doi:10.1684/ejd.2013.2200
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A
B
C
D
Figure 1. A) Clinical feature of actinic cheilitis before MALPDT, B) Despite 5 sessions of MAL-PDT, the lesion of actinic cheilitis remains. C) Histological confirmation was made as actinic cheilitis before MAL-PDT, D) Keratinocytic atypia was observed even after MAL-PDT. (C, D : H&E, ×200).
observed in 84% and 62% of patients, respectively [3, 4]. There may be several explanations for the low therapeutic efficacy of PDT in the treatment of AC. Inadequate uptake of the photosensitizer owing to dilution by saliva and rapid regeneration of mucosal epithelium compared with the skin may result in a lower efficacy of the treatment. PDT was also shown to have low efficacy against Fordyce’s spots on the lip [5]. Therefore, intralesional injection of the photosensitizer may enhance the cure rate of PDT in the treatment of AC. Inappropriate light absorption owing to the curved surface of the lip may also contribute to the low therapeutic efficacy. Although 1-2 sessions of PDT are sufficient to achieve CR of actinic keratosis, AC lesions did not completely disappear despite multiple treatments in this study. To improve the therapeutic efficacy of AC with PDT, combination therapy with imiquimod cream has been introduced [6]. Through the PDT, reactive oxygen species are produced, resulting in local tissue destruction. On the other hand, imiquimod cream increases topical cellular immunity and tumor apoptosis. The lower lip is a high-risk area for change into squamous cell carcinoma (SCC) and its subsequent metastasis. Moreover, SCC may be diagnosed as AC depending on the site of biopsy. Considering the importance of therapeutic efficacy, we suggest that topical PDT may not be suitable as the first-line monotherapy for AC, even with repeated sessions. Combination therapy such as PDT with imiquimod cream could be considered for AC rather than PDT alone. Disclosure. Financial support: none. Conflict of interest: none. Department of Dermatology, Ajou University School of Medicine, 5 Wonchon-Dong, Yeongtong-Gu Suwon 443- Suwon Republic of Korea
Sue Kyung KIM Hyo Sang SONG You Chan KIM
1. Fai D, Romano I, Cassano N, Vena GA. Methyl-aminolevulinate photodynamic therapy for the treatment of actinic cheilitis: a retrospective evaluation of 29 patients. G Ital Dermatol Venereol 2012; 147: 99-101.
918
2. Hauschild A, Lischner S, Lange-Asschenfeldt B, Egberts F. Treatment of actinic cheilitis using photodynamic therapy with methyl aminolevulinate: report of three cases. Dermatol Surg 2005; 31: 1344-7. 3. Ribeiro CF, Souza FH, Jordao JM, et al. Photodynamic therapy in actinic cheilitis: clinical and anatomopathological evaluation of 19 patients. An Bras Dermatol 2012; 87: 418-23. 4. Berking C, Herzinger T, Flaig MJ, Brenner M, Borelli C, Degitz K. The efficacy of photodynamic therapy in actinic cheilitis of the lower lip: a prospective study of 15 patients. Dermatol Surg 2007; 33: 825-30. 5. Kim YJ, Kang HY, Lee ES, Kim YC. Treatment of Fordyce spots with 5-aminolaevulinic acid-photodynamic therapy. Br J Dermatol 2007; 156: 399-400. 6. Sotiriou E, Lallas A, Goussi C, et al. Sequential use of photodynamic therapy and imiquimod 5% cream for the treatment of actinic cheilitis: a 12-month follow-up study. Br J Dermatol 2011; 165: 888-92. doi:10.1684/ejd.2013.2199
Persistent generalized lichen nitidus successfully treated with 0.03% tacrolimus ointment Generalized lichen nitidus (LN) is characterized by multiple, shiny, skin-colored papules covering the whole body. The clinical course is unpredictable and chronic, as opposed to the classic localized type [1]. Although there are numerous therapeutic options for treating generalized LN, the effect of tacrolimus has not been reported to date. We describe a case of persistent generalized LN in which the patient had impressive improvement with tacrolimus ointment after 5 years of various unsuccessful therapeutic modalities. A 9-year-old boy was referred to our department with a pruritic, generalized eruption of 5 years duration that first appeared on the trunk and gradually spread to the extremities. The child had been treated with topical and systemic corticosteroids, antihistamines and UV therapy but none of these efforts had resulted in any benefit. Physical examination revealed numerous 1-2 mm, skin-colored, flat-topped, shiny papules on the face, upper extremities, back and buttocks (figure 1A). He had no history of atopic dermatitis or any other atopic manifestations. Routine laboratory studies were within normal ranges. Histopathological examination revealed a well-circumscribed lymphohistiocytic infiltration with widened dermal papilla and elongated rete ridges embracing the infiltrate, producing a ‘clawclutching-a-ball’ pattern. Hydropic degeneration within the basal epidermal layer was also seen (figure 1B). Based on the clinicopathological findings, a diagnosis of generalized LN was made and treated with topical 0.03% tacrolimus ointment (Protopic® ) twice daily (about 2.5 g in every application). After two weeks, the skin lesions were dramatically improved (figure 1C). A total of 70 g of ointment was used during the first two weeks. From that time onwards, we gradually reduced the frequency of ointment application to twice weekly, based on the maintenance regimen approved in Europe. After nine weeks, the skin eruption had nearly resolved. There was no recurrence and no significant cutaneous or systemic side effect during the 22-month follow-up. EJD, vol. 23, n◦ 6, November-December 2013
A
C
Copyright © 2017 John Libbey Eurotext. Téléchargé par BIBLIOTHEQUE DIVISION DES ACQUISITIONS UNIVERSITE LAVAL le 09/06/2017.
B
Figure 1. A) Numerous 1-2 mm flesh-colored, flat-topped, shiny papules on the child’s back, buttock and upper face. B) Histopathological examination revealed well-circumscribed lymphohistiocytic infiltration with widened dermal papilla and elongated rete ridges embracing the infiltrate, producing a ‘claw-clutching-a-ball’ pattern. Hydropic degeneration within the basal epidermal layer was also seen (H&E stain, ×200).C) Clinical improvement after two weeks of treatment with tacrolimus 0.03% cream.
Generalized LN tends to be more chronic than localized, although the localized form of LN spontaneously resolves without any sequelae after many months. Treatment is necessary when the disease is considered to be cosmetically undesirable or when accompanied by symptoms such as pruritus. Various therapeutic options, including potent topical steroids, H1-antagonists such as astemizole [2], antituberculous agents [3], narrow-band UVB phototherapy [4], acitretin [5] and low-dose cyclosporine [6] have been reported for the treatment of generalized LN. In our patient, various therapeutic approaches had been used without any effect on the skin lesions over the 5 years prior to the initiation of treatment with tacrolimus ointment. Topical tacrolimus, a calcineurin inhibitor, is an antiinflammatory agent that might replace steroids in the topical treatment of many pediatric inflammatory skin diseases, such as atopic dermatitis and contact dermatitis, without having atrophogenic potential or risking other steroidspecific side effects. Although the exact mechanism by which tacrolimus acts in the treatment of LN is unknown, it is proposed to have an effect on various cells of the cutaneous immune system, specifically on T cells, through inhibition of the phosphatase calcineurin and prevention of the transcription of proinflammatory cytokines. The cell-mediated response caused by antigen-presenting cells and the immune response influenced by specific cytokines produced by the inflammatory cells are considered important in LN, suggesting that the anti-inflammatory and immunomodulatory effects of tacrolimus may be effective [7]. Pimecrolimus, another topical calcineurin inhibitor and
EJD, vol. 23, n◦ 6, November-December 2013
immunomodulator, has also proven beneficial in generalized LN [8]. Successful treatment of localized LN with tacrolimus ointment has been reported in two cases [9, 10], however, its effect in generalized LN has not been reported to date. In the present case, we felt that topical tacrolimus treatment of patients with generalized LN might be a promising option, based on previous reports of successful treatment of localized LN. Consequently, we prescribed the application of tacrolimus ointment and observed rapid improvement and full remission of the skin lesions. We used 0.03% tacrolimus ointment opposed to 0.1% because only 0.03% ointment is indicated for children aged two to 15 years. To our knowledge, this is the first case of successful treatment of generalized LN with topical 0.03% tacrolimus therapy. We believe topical tacrolimus might be a more potent and safe immunomodulator than steroids, especially for the treatment of persisting generalized LN. Disclosure. Financial support: none. Conflict of interest: none. 1
Department of Dermatology, Research Institute of Clinical Medicine, 3 Plastic and Reconstructive Surgery, Chonbuk National University Medical School, 20, Geonji-ro (Geumam-dong), Deokjin-gu, Jeonju, 561-712, South Korea 2
Jin PARK1,2 Joo-Ik KIM1 Dae-Woo KIM1 Su-Ran HWANG1 Si-Gyun ROH2,3 Han-Uk KIM1,2 Seok-Kweon YUN1,2
1. Al-Mutairi N, Hassanein A, Nour-Eldin O, Arun J. Generalized lichen nitidus. Pediatr Dermatol 2005; 22: 158-60. 2. Kim SW, Lee UH, Park HS, Jang SJ. A clinical study of generalized lichen nitidus. Korean J Dermatol 2008; 46: 1201-7. 3. Kubota Y, Kiryu H, Nakayama J. Generalized lichen nitidus successfully treated with an antituberculous agent. Br J Dermatol 2002; 146: 1081-3. 4. Nakamizo S, Kabashima K, Matsuyoshi N, Takahashi K, Miyachi Y. Generalized lichen nitidus successfully treated with narrowband UVB phototherapy. Eur J Dermatol 2010; 20: 816. 5. Lucker G, Koopman R, Steijlen P, Valk P. Treatment of palmoplantar lichen nitidus with acitretin. Br J Dermatol 1994; 130: 791-3. 6. Rallis E, Verros C, Moussatou V, Sambaziotis D, Papadakis P. Generalized purpuric lichen nitidus. Report of a case and review of the literature. Dermatol Online J 2007; 13: 5. 7. Daoud MS, Pittelkow MR. Lichen nitidus, In: Goldsmith LA, Katz SI, Gilchrest BA, Paller AS, Leffell DJ, Wolff K, editors. Fitzpatrick’s dermatology in general medicine. 8th ed. New York: McGraw-Hill, 2012: 312. 8. Farshi S, Mansouri P. Generalized lichen nitidus successfully treated with pimecrolimus 1 percent cream. Dermatol Online J 2011; 17: 11. 9. Son YM, Na SY, Lee HY, et al. A Case of Lichen Nitidus That Was Improved with Topical Tacrolimus. Korean J Dermatol 2009; 47: 74951. 10. Dobbs CR, Murphy SJ. Lichen nitidus treated with topical tacrolimus. J Drugs Dermatol 2004; 3: 683-4. doi:10.1684/ejd.2013.2200
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![[Generalized lichen nitidus].](/assets/img/hold.png)
