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Australasian Journal of Dermatology (2014) 55, 90–93
doi: 10.1111/ajd.12131
LETTERS TO THE EDITOR Dear Editor, Dermatitis Artefacta Presenting as a Recurrent Skin Eruption in a Patient with 1p36 Deletion Syndrome We would like to highlight the case of a young woman with 1p36 deletion syndrome presenting with dermatitis artefacta (DA) as a recurrent skin eruption. Self-harm may be a feature of complex genetic syndromes. We show here that the recognition of DA in a gene deletion syndrome may expedite optimal management of recurrent skin lesions. A 22-year-old woman was referred for a recurrent skin eruption. Known to have a 1p36 deletion syndrome and type 2 diabetes, she had an 11-year history of intermittent skin eruption. The lesions were reported to either begin in a mosquito bite or to appear spontaneously. Multiple courses of systemic antibiotics had been unhelpful. Although she had a childhood history of self-harm, she denied picking these lesions. On specific questioning, she said she had never had a lesion in any area that she could not reach with her fingers. On examination, the patient had a 1-cm papular lesion on the dorsum of her left forearm. On her left leg a second lesion, 2 cm in diameter, had superficial ulceration with surrounding erythema. She had numerous scars on her arms, legs and trunk from past similar lesions. A punch biopsy was taken from the lesion on her forearm. Histology showed an epidermis with relatively well-demarcated and mainly superficial necrosis with focal extension into the sub-adjacent dermis. Occasional thrombosed capillaries were seen. The dermis additionally showed oedema and a light, mixed inflammatory infiltrate that was likely to be secondary to epidermal changes. The features were consistent with our clinical diagnosis of DA. The 1p36 deletion syndrome was recognized in 1997 as a contiguous gene deletion syndrome.1 It is now acknowledged to be relatively common, occurring in between 1 in 5000 and 1 in 10 000 live births. Twice as many females have been recorded as males and it is thought to cause 0.5 to 1.2% of idiopathic mental retardation.2 Individuals with the 1p36 deletion syndrome have typical craniofacial features along with brachydactyly and camptodactyly. All affected individuals have an intellectual disability that varies from mild to profound. Seizures, congenital heart defects, hearing loss and visual impairment are among the many reported physical features. Behavioural problems occur frequently: one large study found behavioural problems in 47% of affected individuals, with biting of the hands and wrists reported in 30%.2 DA, also known as factitial dermatitis, is a condition where skin lesions are self-inflicted. It is a complicated dermatological manifestation of other underlying patholo-
gies. The method and mechanics of self-injury influence the appearance of the lesion: lesions may mimic recognizable geometric patterns or take bizarre shapes, and are usually well demarcated. A consistent feature of DA is that the lesions are usually on parts of the body that are easy to access – hands, arms, legs and face – and rarely found on inaccessible body parts.3 In genetic syndromes where self-harm is a recognised feature, a consideration of DA is prudent. Prompt diagnosis will avoid the need for unnecessary investigations and systemic treatments and allow for more effective management. Ingrid Winship and Anna Braue Royal Melbourne Hospital, Parkville, Melbourne, Victoria, Australia
REFERENCES 1.
Shapira SK, McCaskill C, Northrup H et al. Chromosome 1p36 deletions: the clinical phenotype and molecular characterization of a common newly delineated syndrome. Am. J. Hum. Genet. 1997; 61: 642–50. Battaglia A, Hoyme HE, Dallapiccola B et al. Further delineation of deletion 1p36 syndrome in 60 patients: a recognizable phenotype and common cause of developmental delay and mental retardation. Pediatrics 2008; 121: 404–10. Gattu S, Rashid RM, Khachemoune A. Self-induced skin lesions: a review of dermatitis artefacta. Cutis 2009; 84: 247–51.
2.
3.
Abbreviation: DA
Dear Editor, Chemical Leucoderma Induced by Homemade Lemon Toner A 61-year-old woman presented with multiple hypopigmented macules and patches on her face and neck 1 month after applying lemon toner (Fig. 1). The lemon toner, consisting of lemons, alcohol and glycerine, had been prepared at home and applied for 3 months in an attempt to eliminate freckles and aging spots. There was no history of any preexisting skin lesion on her face and neck. The patient had a
Conflict of interest: none
Abbreviations: KOH MART-1
Conflict of interest: none © 2014 The Australasian College of Dermatologists
dermatitis artefacta
potassium hydroxide melanoma antigen recognized by T-cells
Letters to the Editor
91
Figure 1 Multiple, non-scaly, welldemarcated hypopigmented macules and patches on (a) the face (b), neck; (c) and a close-up view of hypopigmented patch on the right hand mandible.
Figure 2 Decreased or absent melanin pigmentation in the basal layer at (a,c,) lesional epidermis compared with (b,d) normal skin. No (e,f ) decrease in the number of melanocytes in the basal layer of lesions compared with normal skin. (g,h) No difference of the number of melanocytes between lesion and normal basal layer was evident. Magnifications were: (a) (H&E) 200×; (b) H&E 200×; (c) Fontana–Masson 200×; (d) Fontana– Masson 200×; (e) S-100 protein 200×; (f) S-100 protein 200×; (g) melanoma antigen recognized by T-cells (MART)-1 200×; h, MART-1 200×. © 2014 The Australasian College of Dermatologists
92
Letters to the Editor
history of hypertension, epilepsy and asthma. There was no personal and familial history of vitiligo or autoimmune diseases. Hypopigmentation was clearly evident under the Wood’s light examination. The histopathological examination and immunohistochemical stains showed decreased melanin pigmentation in the basal layer at the depigmented lesion compared with adjacent normal skin. The number of melanocytes was normal (Fig. 2). The patient was diagnosed with chemical leucoderma by a history of repeated exposure to lemon toner, the whitish macules localized at the exposure site, and the histopathological findings. She was advised to stop using the lemon toner, receive UVB therapy and apply topical tacrolimus ointment. However, she refused and continued using the homemade lemon toner for a whitening effect. Chemical compounds with depigmenting activity have been used in dermatology and cosmetics for a long time. A huge number of phenolic compounds have been tested as inhibitors of melanin synthesis and as photoprotectors. Naturally occurring herbal extracts, active compounds such as phenols, flavonoids and coumarins, and other derivatives have been identified as putative hypopigmenting agents.1 Lemon juice is a depigmenting agent that may cause contact leucoderma and phytophotodermatitis.2,3 The patient used a lemon toner containing niacin (vitamin B3) and ascorbic acid (vitamin C). These compounds can cause depigmentation by suppressing melanosome transfer and reducing the production of melanin and reactive oxygen species.4 These depigmenting components may have been the basis of the chemical leucoderma in our patient. It is important to diagnose chemical leucoderma differentially from vitiligo, as chemical leucoderma has a better outcome than vitiligo and the management of chemical leucoderma involves a strict avoidance of the offending chemicals. Although it is difficult to differentiate between chemical leucoderma and idiopathic vitiligo, our patient showed histopathologically decreased epidermal pigmentation with no decrease in the number of melanocytes. In addition, there were small hypopigmented lesions (‘confetti macules’) and the lesions were located on the skin that had been repeatedly exposed to the lemon toner. The possibilities of fungal infection, melasma and congenital hypomelanosis were ruled-out by negative skin scraping (KOH test), fluorescence testing by Wood’s lamp, histopathological findings and the fact that it was an acquired hypopigmented lesion.5 A recent trend has been the exuberant use of homemade cosmetics containing various kinds of natural ingredients. In this case, the patient presented with chemical leucoderma occurred after using homemade lemon toner. This is an example of the uncontrolled and detrimental consequences of homemade cosmetics made of natural ingredients. Jiwon Gye, Chan H Nam, Ji S Kim, Jee Y Kim, Seung P Hong, Byung C Park and MyungHwa Kim Department of Dermatology, College of Medicine, Dankook University, Cheonan, Korea © 2014 The Australasian College of Dermatologists
REFERENCES 1.
Solano F, Briganti S, Picardo M et al. Hypopigmenting agents: an updated review on biological, chemical and clinical aspects. Pigment Cell Res. 2006; 19: 550–71. Ghosh SK, Bandyopadhyay D. Chemical leukoderma induced by colored strings. J. Am. Acad. Dermatol. 2009; 61: 909–10. Goskowicz MO, Friedlander SF, Eichenfield LF. Endemic ‘lime’ disease: phytophotodermatitis in San Diego County. Pediatrics 1994; 93: 828–30. Briganti S, Camera E, Picardo M. Chemical and instrumental approaches to treat hyperpigmentation. Pigment Cell Res. 2003; 16: 101–10. Ghosh S, Mukhopadhyay S. Chemical leukoderma: a clinicoaetiological study of 864 cases in the perspective of a developing country. Br. J. Dermatol. 2009; 160: 40–7.
2. 3.
4.
5.
Dear Editor, Mutation Analysis of the ADAR1 Gene in a Chinese Family with Dyschromatosis Symmetrica Hereditaria Dyschromatosis symmetrica hereditaria (DSH) is a rare autosomal dominant cutaneous disorder characterized by a mixture of hyperpigmented and hypopigmented macules of various sizes, which appear in infancy or early childhood, on the dorsal aspect of the hands and feet. Mutations in the ADAR1 gene on chromosome 1q11-q21 have been identified as the cause of DSH.1,2 We performed a mutation analysis of the ADAR1 gene in a four-generation Chinese family with DSH (Fig. 1a) and identified a novel heterozygous mutation. The patients, in whom the age of onset of DSH varied from 2–9 years, were diagnosed based on the hyperpigmented and hypopigmented macules on the dorsa of the extremities (Fig. 1b). After the participants’ informed consent was obtained, genomic DNA was extracted from the peripheral blood of family members and 100 healthy controls. All exons of the ADAR1 gene, including intron–exon boundaries, were amplified by polymerase chain reaction. The product was directly sequenced on an ABI Prism 377 sequencer (Applied Biosystems ABI, Foster, CA, USA). We identified a novel nonsense mutation c.2857 A > T (p.K953X) in exon 10 of ADAR1 gene (Fig. 1c). The ADAR1 encoded protein possesses one tRNA-specific and dsRNA adenosine deaminase catalytic domain that is located in exons 9–15.3 The mutation resulted in a premature stop signal at codon 953, leading to the truncated protein with no adenosine deaminase catalytic domain, which conceivably underlies the pathogenesis of DSH.
Xiaoyan Zhao and Qin Mei contributed equally to this study. Conflict of interest: none.
Abbreviation: DSH
dyschromatosis symmetrica hereditaria
Australasian Journal of Dermatology (2014) 55, 90–93
doi: 10.1111/ajd.12131
LETTERS TO THE EDITOR Dear Editor, Dermatitis Artefacta Presenting as a Recurrent Skin Eruption in a Patient with 1p36 Deletion Syndrome We would like to highlight the case of a young woman with 1p36 deletion syndrome presenting with dermatitis artefacta (DA) as a recurrent skin eruption. Self-harm may be a feature of complex genetic syndromes. We show here that the recognition of DA in a gene deletion syndrome may expedite optimal management of recurrent skin lesions. A 22-year-old woman was referred for a recurrent skin eruption. Known to have a 1p36 deletion syndrome and type 2 diabetes, she had an 11-year history of intermittent skin eruption. The lesions were reported to either begin in a mosquito bite or to appear spontaneously. Multiple courses of systemic antibiotics had been unhelpful. Although she had a childhood history of self-harm, she denied picking these lesions. On specific questioning, she said she had never had a lesion in any area that she could not reach with her fingers. On examination, the patient had a 1-cm papular lesion on the dorsum of her left forearm. On her left leg a second lesion, 2 cm in diameter, had superficial ulceration with surrounding erythema. She had numerous scars on her arms, legs and trunk from past similar lesions. A punch biopsy was taken from the lesion on her forearm. Histology showed an epidermis with relatively well-demarcated and mainly superficial necrosis with focal extension into the sub-adjacent dermis. Occasional thrombosed capillaries were seen. The dermis additionally showed oedema and a light, mixed inflammatory infiltrate that was likely to be secondary to epidermal changes. The features were consistent with our clinical diagnosis of DA. The 1p36 deletion syndrome was recognized in 1997 as a contiguous gene deletion syndrome.1 It is now acknowledged to be relatively common, occurring in between 1 in 5000 and 1 in 10 000 live births. Twice as many females have been recorded as males and it is thought to cause 0.5 to 1.2% of idiopathic mental retardation.2 Individuals with the 1p36 deletion syndrome have typical craniofacial features along with brachydactyly and camptodactyly. All affected individuals have an intellectual disability that varies from mild to profound. Seizures, congenital heart defects, hearing loss and visual impairment are among the many reported physical features. Behavioural problems occur frequently: one large study found behavioural problems in 47% of affected individuals, with biting of the hands and wrists reported in 30%.2 DA, also known as factitial dermatitis, is a condition where skin lesions are self-inflicted. It is a complicated dermatological manifestation of other underlying patholo-
gies. The method and mechanics of self-injury influence the appearance of the lesion: lesions may mimic recognizable geometric patterns or take bizarre shapes, and are usually well demarcated. A consistent feature of DA is that the lesions are usually on parts of the body that are easy to access – hands, arms, legs and face – and rarely found on inaccessible body parts.3 In genetic syndromes where self-harm is a recognised feature, a consideration of DA is prudent. Prompt diagnosis will avoid the need for unnecessary investigations and systemic treatments and allow for more effective management. Ingrid Winship and Anna Braue Royal Melbourne Hospital, Parkville, Melbourne, Victoria, Australia
REFERENCES 1.
Shapira SK, McCaskill C, Northrup H et al. Chromosome 1p36 deletions: the clinical phenotype and molecular characterization of a common newly delineated syndrome. Am. J. Hum. Genet. 1997; 61: 642–50. Battaglia A, Hoyme HE, Dallapiccola B et al. Further delineation of deletion 1p36 syndrome in 60 patients: a recognizable phenotype and common cause of developmental delay and mental retardation. Pediatrics 2008; 121: 404–10. Gattu S, Rashid RM, Khachemoune A. Self-induced skin lesions: a review of dermatitis artefacta. Cutis 2009; 84: 247–51.
2.
3.
Abbreviation: DA
Dear Editor, Chemical Leucoderma Induced by Homemade Lemon Toner A 61-year-old woman presented with multiple hypopigmented macules and patches on her face and neck 1 month after applying lemon toner (Fig. 1). The lemon toner, consisting of lemons, alcohol and glycerine, had been prepared at home and applied for 3 months in an attempt to eliminate freckles and aging spots. There was no history of any preexisting skin lesion on her face and neck. The patient had a
Conflict of interest: none
Abbreviations: KOH MART-1
Conflict of interest: none © 2014 The Australasian College of Dermatologists
dermatitis artefacta
potassium hydroxide melanoma antigen recognized by T-cells
Letters to the Editor
91
Figure 1 Multiple, non-scaly, welldemarcated hypopigmented macules and patches on (a) the face (b), neck; (c) and a close-up view of hypopigmented patch on the right hand mandible.
Figure 2 Decreased or absent melanin pigmentation in the basal layer at (a,c,) lesional epidermis compared with (b,d) normal skin. No (e,f ) decrease in the number of melanocytes in the basal layer of lesions compared with normal skin. (g,h) No difference of the number of melanocytes between lesion and normal basal layer was evident. Magnifications were: (a) (H&E) 200×; (b) H&E 200×; (c) Fontana–Masson 200×; (d) Fontana– Masson 200×; (e) S-100 protein 200×; (f) S-100 protein 200×; (g) melanoma antigen recognized by T-cells (MART)-1 200×; h, MART-1 200×. © 2014 The Australasian College of Dermatologists
92
Letters to the Editor
history of hypertension, epilepsy and asthma. There was no personal and familial history of vitiligo or autoimmune diseases. Hypopigmentation was clearly evident under the Wood’s light examination. The histopathological examination and immunohistochemical stains showed decreased melanin pigmentation in the basal layer at the depigmented lesion compared with adjacent normal skin. The number of melanocytes was normal (Fig. 2). The patient was diagnosed with chemical leucoderma by a history of repeated exposure to lemon toner, the whitish macules localized at the exposure site, and the histopathological findings. She was advised to stop using the lemon toner, receive UVB therapy and apply topical tacrolimus ointment. However, she refused and continued using the homemade lemon toner for a whitening effect. Chemical compounds with depigmenting activity have been used in dermatology and cosmetics for a long time. A huge number of phenolic compounds have been tested as inhibitors of melanin synthesis and as photoprotectors. Naturally occurring herbal extracts, active compounds such as phenols, flavonoids and coumarins, and other derivatives have been identified as putative hypopigmenting agents.1 Lemon juice is a depigmenting agent that may cause contact leucoderma and phytophotodermatitis.2,3 The patient used a lemon toner containing niacin (vitamin B3) and ascorbic acid (vitamin C). These compounds can cause depigmentation by suppressing melanosome transfer and reducing the production of melanin and reactive oxygen species.4 These depigmenting components may have been the basis of the chemical leucoderma in our patient. It is important to diagnose chemical leucoderma differentially from vitiligo, as chemical leucoderma has a better outcome than vitiligo and the management of chemical leucoderma involves a strict avoidance of the offending chemicals. Although it is difficult to differentiate between chemical leucoderma and idiopathic vitiligo, our patient showed histopathologically decreased epidermal pigmentation with no decrease in the number of melanocytes. In addition, there were small hypopigmented lesions (‘confetti macules’) and the lesions were located on the skin that had been repeatedly exposed to the lemon toner. The possibilities of fungal infection, melasma and congenital hypomelanosis were ruled-out by negative skin scraping (KOH test), fluorescence testing by Wood’s lamp, histopathological findings and the fact that it was an acquired hypopigmented lesion.5 A recent trend has been the exuberant use of homemade cosmetics containing various kinds of natural ingredients. In this case, the patient presented with chemical leucoderma occurred after using homemade lemon toner. This is an example of the uncontrolled and detrimental consequences of homemade cosmetics made of natural ingredients. Jiwon Gye, Chan H Nam, Ji S Kim, Jee Y Kim, Seung P Hong, Byung C Park and MyungHwa Kim Department of Dermatology, College of Medicine, Dankook University, Cheonan, Korea © 2014 The Australasian College of Dermatologists
REFERENCES 1.
Solano F, Briganti S, Picardo M et al. Hypopigmenting agents: an updated review on biological, chemical and clinical aspects. Pigment Cell Res. 2006; 19: 550–71. Ghosh SK, Bandyopadhyay D. Chemical leukoderma induced by colored strings. J. Am. Acad. Dermatol. 2009; 61: 909–10. Goskowicz MO, Friedlander SF, Eichenfield LF. Endemic ‘lime’ disease: phytophotodermatitis in San Diego County. Pediatrics 1994; 93: 828–30. Briganti S, Camera E, Picardo M. Chemical and instrumental approaches to treat hyperpigmentation. Pigment Cell Res. 2003; 16: 101–10. Ghosh S, Mukhopadhyay S. Chemical leukoderma: a clinicoaetiological study of 864 cases in the perspective of a developing country. Br. J. Dermatol. 2009; 160: 40–7.
2. 3.
4.
5.
Dear Editor, Mutation Analysis of the ADAR1 Gene in a Chinese Family with Dyschromatosis Symmetrica Hereditaria Dyschromatosis symmetrica hereditaria (DSH) is a rare autosomal dominant cutaneous disorder characterized by a mixture of hyperpigmented and hypopigmented macules of various sizes, which appear in infancy or early childhood, on the dorsal aspect of the hands and feet. Mutations in the ADAR1 gene on chromosome 1q11-q21 have been identified as the cause of DSH.1,2 We performed a mutation analysis of the ADAR1 gene in a four-generation Chinese family with DSH (Fig. 1a) and identified a novel heterozygous mutation. The patients, in whom the age of onset of DSH varied from 2–9 years, were diagnosed based on the hyperpigmented and hypopigmented macules on the dorsa of the extremities (Fig. 1b). After the participants’ informed consent was obtained, genomic DNA was extracted from the peripheral blood of family members and 100 healthy controls. All exons of the ADAR1 gene, including intron–exon boundaries, were amplified by polymerase chain reaction. The product was directly sequenced on an ABI Prism 377 sequencer (Applied Biosystems ABI, Foster, CA, USA). We identified a novel nonsense mutation c.2857 A > T (p.K953X) in exon 10 of ADAR1 gene (Fig. 1c). The ADAR1 encoded protein possesses one tRNA-specific and dsRNA adenosine deaminase catalytic domain that is located in exons 9–15.3 The mutation resulted in a premature stop signal at codon 953, leading to the truncated protein with no adenosine deaminase catalytic domain, which conceivably underlies the pathogenesis of DSH.
Xiaoyan Zhao and Qin Mei contributed equally to this study. Conflict of interest: none.
Abbreviation: DSH
dyschromatosis symmetrica hereditaria
