- Email: [email protected]
Aphthous ulcers and imiquimod
360 Letters
J AM ACAD DERMATOL AUGUST 2005
Fig 1. IVS6-1 G [ C mutation (arrow).
patient and both daughters, suggesting a possible mutation in heterozygosity. The sequencing analysis confirmed the existence of a point mutation in the 39 splice site of intron 6 (IVS6-1 G [ C) for all three patients (Fig 1). The majority of the germline mutations occurring in PTEN result from either truncation, abnormal RNA splicing, or gross deletion of the gene.4 A disruption of the 39 splice site in the PTEN gene presumably results in an adjacent exon skipping and a truncated protein, such as that described by Marsh et al.5 They described a family with the same mutation but with some differences in the phenotype. Two of our patients had a papillomatosis of the oral cavity, while none of the members of the previous reported family had it. Moreover, contrary to the family described by Marsh et al (which has members affected by both CD and Bannayan-Riley-Ruvalcaba syndrome), we only identified CD-affected relatives in the family. Nevertheless, both families have members affected by thyroid involvement and breast fibroadenomas. Interestingly, Marsh et al identified a statistically significant correlation between truncating PTEN mutations and the presence of cancer or breast fibroadenoma. All the members of the reported family had breast fibroadenomas, supporting the association previously identified. Cristina Mangas, MD Josep Maria Hilari, BS Miquel Ribera, MD, PhD Mercedes Robledo, PhD Miguel Urioste, PhD Javier Benı´tez, PhD Maria Jose Fuente, MD, PhD Carlos Ferra´ndiz, MD, PhD Department of Dermatology Hospital Universitari Germans Trias i Pujol Crta Canyet Barcelona, Spain E-mail: [email protected]
REFERENCES 1. Eng C. Cowden syndrome. J Genet Counsel 1997;6:181-91. 2. Nelen MR, Padberg GW, Peeters EA, Lin AY, van den Helm B, Frants RR, et al. Localization of the gene for Cowden disease to chromosome 10q22-q23. Nat Genet 1996;13:114-6. 3. Bonneau D, Longy M. Mutations of the human PTEN gene. Hum Mutat 2000;16:109-22. 4. Bussaglia E, Pujol RM, Gil MJ, Martı´ RM, Tuneu A, Febrer MI, et al. PTEN mutations in eight spanish families and one brazilian family with Cowden Syndrome. J Invest Dermatol 2002; 118:639-44. 5. Marsh DJ, Kum JB, Lunetta KL, Bennett MJ, Gorlin RJ, Ahmed SF, et al. PTEN mutation spectrum and genotype-phenotype correlations in Bannayan-Riley-Ruvalcaba syndrome cs suggest a single entity with Cowden sdrome. Hum Mol Genet 1999; 8:1461-72. doi:10.1016/j.jaad.2005.03.044
Aphthous ulcers and imiquimod To the Editor: We read with great interest the paper by Chakrabarty et al1 in the February 2005 case reports supplement. In this paper, the authors reported 3 patients who developed aphtous ulcers on the lower lip during treatment of actinic cheilitis with imiquimod. The authors speculated that the occurrence of aphtous ulcers during the treatment with imiquimod may represent more than a coincidence, because the immunomodulatory action of imiquimod induces the expression of proinflammatory cytokines, which also play an important role in the pathogenesis of aphtous ulcers. Although imiquimod might cause local reactions, such as burning, itching, and even erosion and ulceration at the application site, the authors underlined the development of the aphtous ulcers merely in the vicinity of the treated skin, and not at the application site. We recently observed a similar case and like to add our findings to the work by Chakrabarty et al.1 A 21-year-old, otherwise healthy woman presented with multiple facial plane warts located on the cheek, forehead, and chin. Based on a previous report,2 we initiated a treatment with 5% imiquimod cream to be applied once daily. After 1 week of treatment, the patient presented again for the occurrence of multiple painful, partially confluent, aphtous-like ulcers on her lower lip (Fig 1, A). She had no history of previous facial herpes simplex or aphtous ulcers and denied conceivably the possibility of an unaware application of imiquimod on her lips, since she used to wash her hands immediately after applying the cream on the warts. In addition, at the application site a marked inflammation of the plane warts was visible (Fig 1, A). Because of the ulcers on her lip,
Letters 361
J AM ACAD DERMATOL VOLUME 53, NUMBER 2
REFERENCES 1. Chakrabarty AK, Mraz S, Geisse JK, Anderson NJ. Aphthous ulcers associated with imiquimod and the treatment of actinic cheilitis. J Am Acad Dermatol 2005;52(suppl):S35-7. 2. Khan Durani B, Jappe U. Successful treatment of facial plane warts with imiquimod. Br J Dermatol 2002;147:1018.
doi:10.1016/j.jaad.2005.03.040
Acquired acrodermatitis enteropathica caused by anorexia nervosa
Fig 1. A, Multiple aphtous-like ulcers on the lower lip occurring during the treatment of facial plane warts with imiquimod 5% cream. In addition, an intense inflammation of the warts located on the chin is visible. B, Complete remission of the ulceration after 2 weeks.
To the Editor: Patients with anorexia nervosa have a markedly depressed body mass index, are malnourished, and are recalcitrant to pharmacologic or cognitive therapy. Acrodermatitis enteropathica, a disorder of zinc deficiency, can present in patients with anorexia.1 Treatment involves oral supplementation of zinc. A 36-year-old white female was referred to the dermatology department for a 1-year history of erythematous erosive patches involving her thighs, intergluteal folds, and palmoplantar surfaces (Figs 1, A and B,
treatment with imiquimod was discontinued and a topical steroid cream (clobetasol propionate) was prescribed twice daily for 2 weeks resulting in a complete healing of the labial ulcers (Fig 1, B). Remarkably, during the follow-up consultation there was no further clinical evidence of the plane warts. As plausibly speculated by Chakrabarty et al,1 our case might provide further evidence for the possibility that the occurrence of aphthous ulcers during imiquimod treatment may result from direct induction of proinflammatory cytokines near, but not necessarily at, the site of its application. Iris Zalaudek, MD Gianluca Petrillo, MD Giuseppe Argenziano, MD Department of Dermatology Second University of Naples Naples, Italy Correspondence to: Giuseppe Argenziano, MD Department of Dermatology Second University of Naples Via S. Pansini, 5 I-80131 Naples, Italy E-mail: [email protected]
Fig 1. Initial presentation of acrodermatitis enteropathica. A, Intergluteal and acral distribution of plaques. B, Erosions and ruptured bullae on the digits.
J AM ACAD DERMATOL AUGUST 2005
Fig 1. IVS6-1 G [ C mutation (arrow).
patient and both daughters, suggesting a possible mutation in heterozygosity. The sequencing analysis confirmed the existence of a point mutation in the 39 splice site of intron 6 (IVS6-1 G [ C) for all three patients (Fig 1). The majority of the germline mutations occurring in PTEN result from either truncation, abnormal RNA splicing, or gross deletion of the gene.4 A disruption of the 39 splice site in the PTEN gene presumably results in an adjacent exon skipping and a truncated protein, such as that described by Marsh et al.5 They described a family with the same mutation but with some differences in the phenotype. Two of our patients had a papillomatosis of the oral cavity, while none of the members of the previous reported family had it. Moreover, contrary to the family described by Marsh et al (which has members affected by both CD and Bannayan-Riley-Ruvalcaba syndrome), we only identified CD-affected relatives in the family. Nevertheless, both families have members affected by thyroid involvement and breast fibroadenomas. Interestingly, Marsh et al identified a statistically significant correlation between truncating PTEN mutations and the presence of cancer or breast fibroadenoma. All the members of the reported family had breast fibroadenomas, supporting the association previously identified. Cristina Mangas, MD Josep Maria Hilari, BS Miquel Ribera, MD, PhD Mercedes Robledo, PhD Miguel Urioste, PhD Javier Benı´tez, PhD Maria Jose Fuente, MD, PhD Carlos Ferra´ndiz, MD, PhD Department of Dermatology Hospital Universitari Germans Trias i Pujol Crta Canyet Barcelona, Spain E-mail: [email protected]
REFERENCES 1. Eng C. Cowden syndrome. J Genet Counsel 1997;6:181-91. 2. Nelen MR, Padberg GW, Peeters EA, Lin AY, van den Helm B, Frants RR, et al. Localization of the gene for Cowden disease to chromosome 10q22-q23. Nat Genet 1996;13:114-6. 3. Bonneau D, Longy M. Mutations of the human PTEN gene. Hum Mutat 2000;16:109-22. 4. Bussaglia E, Pujol RM, Gil MJ, Martı´ RM, Tuneu A, Febrer MI, et al. PTEN mutations in eight spanish families and one brazilian family with Cowden Syndrome. J Invest Dermatol 2002; 118:639-44. 5. Marsh DJ, Kum JB, Lunetta KL, Bennett MJ, Gorlin RJ, Ahmed SF, et al. PTEN mutation spectrum and genotype-phenotype correlations in Bannayan-Riley-Ruvalcaba syndrome cs suggest a single entity with Cowden sdrome. Hum Mol Genet 1999; 8:1461-72. doi:10.1016/j.jaad.2005.03.044
Aphthous ulcers and imiquimod To the Editor: We read with great interest the paper by Chakrabarty et al1 in the February 2005 case reports supplement. In this paper, the authors reported 3 patients who developed aphtous ulcers on the lower lip during treatment of actinic cheilitis with imiquimod. The authors speculated that the occurrence of aphtous ulcers during the treatment with imiquimod may represent more than a coincidence, because the immunomodulatory action of imiquimod induces the expression of proinflammatory cytokines, which also play an important role in the pathogenesis of aphtous ulcers. Although imiquimod might cause local reactions, such as burning, itching, and even erosion and ulceration at the application site, the authors underlined the development of the aphtous ulcers merely in the vicinity of the treated skin, and not at the application site. We recently observed a similar case and like to add our findings to the work by Chakrabarty et al.1 A 21-year-old, otherwise healthy woman presented with multiple facial plane warts located on the cheek, forehead, and chin. Based on a previous report,2 we initiated a treatment with 5% imiquimod cream to be applied once daily. After 1 week of treatment, the patient presented again for the occurrence of multiple painful, partially confluent, aphtous-like ulcers on her lower lip (Fig 1, A). She had no history of previous facial herpes simplex or aphtous ulcers and denied conceivably the possibility of an unaware application of imiquimod on her lips, since she used to wash her hands immediately after applying the cream on the warts. In addition, at the application site a marked inflammation of the plane warts was visible (Fig 1, A). Because of the ulcers on her lip,
Letters 361
J AM ACAD DERMATOL VOLUME 53, NUMBER 2
REFERENCES 1. Chakrabarty AK, Mraz S, Geisse JK, Anderson NJ. Aphthous ulcers associated with imiquimod and the treatment of actinic cheilitis. J Am Acad Dermatol 2005;52(suppl):S35-7. 2. Khan Durani B, Jappe U. Successful treatment of facial plane warts with imiquimod. Br J Dermatol 2002;147:1018.
doi:10.1016/j.jaad.2005.03.040
Acquired acrodermatitis enteropathica caused by anorexia nervosa
Fig 1. A, Multiple aphtous-like ulcers on the lower lip occurring during the treatment of facial plane warts with imiquimod 5% cream. In addition, an intense inflammation of the warts located on the chin is visible. B, Complete remission of the ulceration after 2 weeks.
To the Editor: Patients with anorexia nervosa have a markedly depressed body mass index, are malnourished, and are recalcitrant to pharmacologic or cognitive therapy. Acrodermatitis enteropathica, a disorder of zinc deficiency, can present in patients with anorexia.1 Treatment involves oral supplementation of zinc. A 36-year-old white female was referred to the dermatology department for a 1-year history of erythematous erosive patches involving her thighs, intergluteal folds, and palmoplantar surfaces (Figs 1, A and B,
treatment with imiquimod was discontinued and a topical steroid cream (clobetasol propionate) was prescribed twice daily for 2 weeks resulting in a complete healing of the labial ulcers (Fig 1, B). Remarkably, during the follow-up consultation there was no further clinical evidence of the plane warts. As plausibly speculated by Chakrabarty et al,1 our case might provide further evidence for the possibility that the occurrence of aphthous ulcers during imiquimod treatment may result from direct induction of proinflammatory cytokines near, but not necessarily at, the site of its application. Iris Zalaudek, MD Gianluca Petrillo, MD Giuseppe Argenziano, MD Department of Dermatology Second University of Naples Naples, Italy Correspondence to: Giuseppe Argenziano, MD Department of Dermatology Second University of Naples Via S. Pansini, 5 I-80131 Naples, Italy E-mail: [email protected]
Fig 1. Initial presentation of acrodermatitis enteropathica. A, Intergluteal and acral distribution of plaques. B, Erosions and ruptured bullae on the digits.