- Email: [email protected]
The surgical treatment of hypertrophic intertriginous Darier's disease
Journal of Plastic, Reconstructive & Aesthetic Surgery (2009) 62, e442ee446
CASE REPORT
The surgical treatment of hypertrophic intertriginous Darier’s disease U. Ahcan, M. Dolenc-Voljc, K. Zivec*, P. Zorman, V. Jurcic University Medical Centre Ljubljana, Zaloska 7, SI-1525 Ljubljana, Slovenia Received 5 January 2008; accepted 13 June 2008
KEYWORDS Darier’s disease; Intertriginous manifestation; Surgical treatment; Tissue expanders
Summary Darier’s disease is a rare autosomal-dominant genodermatosis characterised by persistent hyperkeratotic papules and plaques in seborrhoeic areas. The flexural areas of the body are especially difficult to treat, and they are often resistant to current topical and systemic treatment strategies. To our knowledge, this article provides the first description of a successful surgical treatment of a severely debilitating, hypertrophic Darier’s disease of intergluteal area, resistant to oral retionids. A 25-year-old male patient was successfully treated with the use of tissue expanders and diseased skin excision. There are no signs of recurrence of the disease in the perianal region 6 months postoperatively, and there is a good result in functional as well as cosmetic terms. The formation of new skin on the excision site was observed, and there were no evident signs of infection. These encouraging results suggest that a patient who responds poorly to conventional treatment in a specific area should be presented to the plastic surgeon at an earlier point in time. Therefore, unnecessary hospitalisations, antibiotic treatments, dose-related adverse effects of oral retionids can be avoided, and eventually a long-term result can be achieved. ª 2008 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.
Darier’s disease (dyskeratosis follicularis) is a rare autosomal-dominant skin disease, characterised by persistent hyperkeratotic papules and plaques in seborrhoeic areas. It is caused by mutations in the ATP2A2 gene at chromosome 12q, which encodes the sarco/endoplasmic reticulum Ca2þ * Corresponding author. University Medical Centre Ljubljana, Department of plastic, reconstructive, aesthetic surgery and burns, Zaloska 7, SI-1000 Ljubljana, Slovenia. Tel.:+386 522 32 84; fax: þ386 1 522 2239. E-mail address: [email protected] (K. Zivec).
ATPase type 2. Defects in calcium concentration in the endoplasmic reticulum result in impaired processing of desmosomal proteins, abnormal intercellular adhesion and altered keratinisation.1 The prevalence of Darier’s disease is estimated to be between 1 and 3.3 per 100 000 populations.2 Skin signs usually develop in adolescent period. Severity of disease varies and is unpredictable. External irritation and infection often aggravate the disease. In majority of the patients, the keratotic papules are distributed only at predilection seborrhoeic areas. In some patients, greasy hyperkeratotic plaques can arise in flexures and may form
1748-6815/$ - see front matter ª 2008 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.bjps.2008.06.060
The surgical treatment of hypertrophic intertriginous Darier’s disease warty or papillomatous, vegetating and malodorous masses. Flexural involvement with hypertrophic plaques is found in 6% of the patients with Darier’s disease.3 Treatment is based upon the extent of clinical manifestations. In mild forms, emollients, topical retinoids or corticosteroids are sufficient. For more severe forms, oral retinoids are required. Vegetating flexural plaques are resistant to conventional treatment, and additional therapeutic approaches are often necessary.3e5
Case report A 25-year-old male patient with Darier’s disease has been treated at the Department of Dermatovenereology for several years. The family history was positive. Skin manifestations with characteristic keratotic papules on seborrhoeic areas of the trunk, face, neck, ears and scalp appeared at the age of 12. Additionally, oral mucosa was involved, and the nails showed longitudinal ridging and splitting. The diagnosis was confirmed on histopathological examination. Topical corticosteroids and retinoids were the first choice of treatment for the affected areas. Later, skin manifestations on the trunk, arm, leg flexures, neck and face had worsened by the formation of severe keratotic papules and plaques. Severe hyperkeratotic malodorous papillomatous masses developed in the perineal and perianal region (Figure 1). A treatment with oral acitretin was introduced with a daily dose of 0.5 mg per kg of body weight. After 2 years of systemic treatment, moderate improvement of skin manifestations on the trunk, face and scalp was achieved; however, there was no improvement of plaques in the perianal region. Severe inflammatory exacerbations often occurred, and Staphylococci, Streptococci, Proteus mirabilis, Pseudomonas aeruginosa and difteroids were isolated. Topical antiseptics and antibiotics, sometimes in addition to systemic broad-spectrum antibiotics, were the choice of treatment. Due to persistent pain and irritation, normal daily needs and activities were impaired.
e443
The patient was presented to the Department of Plastic Surgery. The involvement of sacral, gluteal and anal region was extensive; this region measured approximately 15 cm 10 cm surrounding the anal aperture. The irritation, itching, pain and odour (as a consequence of secondary infections) were impairing patient’s normal daily activities (personal hygiene, defecating, sitting, walking, dressing, etc.) and had also been a cause of psychological distress. Since we could not achieve satisfactory improvement of skin manifestations in this region, a surgical approach under general anaesthesia using tissue expanders followed by wide excision and primary closure was considered. The bilateral endoscopical insertion of two expanders (TRC 300 Nagor Ltd., British Isles) under healthy skin in close proximity to the border of the lesion (Figure 2) was accomplished. The filling with saline started immediately, approximately 30e40 ml every 3e4 days, and depended on the patient’s pain tolerance. After 7 days, the left expander deflated, and a new expander of the similar shape and size was inserted successfully. A wide excision of all diseased skin was performed on day 20 (Figure 3). The expanders were removed and the defect was sutured in layers. The haemostasis was controlled with cautery. The specimen was sent for histopathological analysis. The histopathological picture was consistent with the Mb. Darier (‘corp ronds’, follicular keratosis, papilomatosis, suprabasal acantolysis with lacunae formation, narrow longitudinal retitformous epithelial extensions and chronic inflammatory infiltrate in dermis) (Figure 4). During the first few postoperative days, the wound healed in an uneventful manner. Later, due to inflammation, the wound became dehiscent on the right side. The dead tissue was removed, and the subcutaneous spaces were irrigated with peroxide and saline. Three drains were inserted, and the defect was again sutured in layers. While the patient was hospitalised, the following bacteria were isolated from the gluteal area: Pseudomonas aeruginosa, Enterococcus faecalis, Corynebacterium striatum and
Figure 1 A presentation of Darier’s disease in sacral, gluteal and anal region in a patient. The typical reddish papules forming confluent plaques and a warty texture.
e444
U. Ahcan et al.
Figure 2
Endoscopically inserted tissue expanders (TRC 300 Nagor Ltd., British Isles).
Bacteroides fragilis. The patient was treated with antibiotics on the basis of an antibiogram. After discharge, following a 46-day hospitalisation, the patient was advised to wear compression pants and to rinse the operated area with camomile solution and to apply chlorhexidine dichloride and dexpanthenol cream and gently massage the area. In addition, care for hygiene during normal daily activities (e.g., defecation) was stressed upon. Despite the delicate region, and therefore potential complications (e.g., inflammation), there are no signs of recurrence in the perianal region 6 months postoperatively, and has also resulted in favourable functional and cosmetic results. Therefore, the patient’s expectations were fulfilled.. A formation of new skin on the excision site is observed, and there are no evident signs of infection (Figure 5). All daily activities are possible from postoperative 6 months onwards.. Based upon these results, 6 months follow-up visits were scheduled. However, the patient is also being followed-up at the Department of Dermatovenereology since the disease is still manifest on the other parts of the body.
Figure 3
A wide excision of all diseased tissue.
Discussion The conventional treatment of severe forms of Darier’s disease is usually unsatisfactory. Oral retinoids are still the most effective treatment for severe disease.4,5 They can improve skin lesions by reducing the hyperkeratosis, but a long-term therapy is often limited because of the adverse effects. The treatment of hypertrophic flexural disease is particularly difficult and resistant to oral retinoids.3,5 For recalcitrant hypertrophic growths, surgical treatment is often necessary. Different techniques have been advocated: partial-thickness removal of skin,6 dermabrasion,7 partial-thickness resection and deep dermabrasion,8 surgical excision and closure by primary suture,9 electrosurgical excision10 and sharp debridement.11 The advantage of treatment of etretinate-resistant Darier’s disease with deep, split-thickness skin excision with electrosurgery over dermabrasion, dermatome shaving and free-hand, scalpel-shave excision is the ease of obtaining haemostasis and, thus, surgical visibility.10 In this case, such a procedure could cause an extensive defect that needed to be covered with a skin graft. In addition, the extensive bacterial contamination of this area could prevent the graft take. Laser treatment (e.g., Er: YAG laser) could also be considered as a treatment option. However, in this patient, the diseased lesion was too extensive for laser therapy. The vascularity of the diseased region seemed augmented, and therefore complete haemostasis would not have been possible. The healing process would have been prolonged, and also the scars that might have evolved could have caused additional functional disabilities. It is suggested that surgical intervention must be sufficiently deep, up to the papillary dermis, to provide longterm remission.7 There is a theoretical possibility that surgery itself could precipitate new lesions, because of the isomorphic phenomenon seen in response to trauma, but this does not seem to be a problem with sufficiently deep surgery.4 With the use of tissue expanders, the excision can be wide and deep enough in order to remove all of the
The surgical treatment of hypertrophic intertriginous Darier’s disease
e445
Figure 4 Darier’s disease. (A) characteristic ‘‘corps ronds’’ (original magnification: 400); (B) follicular keratosis, narrow longitudinal retiformous epithelial extensions and focal suprabasal acantholysis (original magnification: 100).
diseased tissue and to gain enough tissue for the reconstruction of the defect. Changes in the histology of the expanded skin are prominent, and they might contribute to the final outcome; for example, epidermis becomes thicker, reticular dermis is thinned, collagen bundles are thickened, elastic fibres may rupture and undergo fibrotic changes, vascularity is increased, dermal appendages show degenerative changes and the skin generally becomes drier. The endoscopic tissue expander placement needs smaller incision, which might prevent expander extrusion, and allows for starting with early aggressive expansion. Despite potential complications, such as infection or cellulitis, exposure, rupture and skin loss, a decision was made in favour of this approach. The hospitalisation period was 46 days, mainly due to infectious complications. This is consistent with common secondary infections seen in these patients and the need for focussed antibiotic treatment following consultation
Figure 5
with the infectious disease specialist. Since the quality of life in some patients is very deprived and psychological consequences might also be evident, a psychologist and a genetic counsellor could be also considered as members of a multidisciplinary team. In summary, the patient with a severely debilitating hypertrophic Darier’s disease of intergluteal area, resistant to oral retionids in this intertriginous area, was successfully treated with the use of tissues expanders and diseased-skin excision. The encouraging results obtained thus suggest that a patient who responds poorly to a conventional treatment in a specific area should be presented to a plastic surgeon at an earlier point in time. An appropriate surgical approach for every individual patient and intensive preoperative planning is the rule. In this sense, we may avoid unnecessary hospitalisations, antibiotic treatments, doserelated adverse effects of oral retionids and, eventually, a long-term result can be achieved successfully.
Six months after surgery. The patient is asymptomatic and free of disease. A formation of a new mucosa is seen.
e446
References 1. Sakuntabhai A, Ruiz-Perez V, Carter S, et al. Mutations in ATP2A2, encoding a Ca2þ pump, cause Darier disease. Nat Genet 1999;21:271e7. 2. Munro CS. The phenotype of Darier’s disease: penetrance and expressivity in adults and children. Br J Dermatol 1992;127: 126e30. 3. Burge SM, Wilkinson JD. DariereWhite disease: a review of the clinical features in 163 patients. J Am Acad Dermatol 1992;27: 40e50. 4. Cooper SM, Burge SM. Darier’s disease: epidemiology, pathophysiology and management. Am J Clin Dermatol 2003;4:97e105. 5. Burge S. Management of Darier’s disease. Clin Exp Dermatol 1999;24:53e6.
U. Ahcan et al. 6. Dellon AL, Chretien PB, Peck GL. Successful treatment of Darier’s disease by partial-thickness removal of skin. Plast Reconstr Surg 1977;59:823e30. 7. Zachariae H. Dermabrasion in Darier’s disease. Acta Derm Venereol 1979;59:184e6. 8. Mandel MA. Cornifying Darier’s disease. Plast Reconstr Surg 1979;63:167e72. 9. McFadden JP, Mayou BJ, Griffiths WAD. Darier’s disease of the groin treated by surgery. Br J Dermatol 1991;125(Suppl.):52. 10. Toombs EL, Peck GL. Electrosurgical treatment of etretinateresistant Darier’s disease. J Dermatol Surg Oncol 1989;15: 1277e80. 11. Wheeland RG, Gilmore WA. The surgical treatment of hypertrophic Darier’s disease. J Dermatol Surg Oncol 1985; 11:420e3.
CASE REPORT
The surgical treatment of hypertrophic intertriginous Darier’s disease U. Ahcan, M. Dolenc-Voljc, K. Zivec*, P. Zorman, V. Jurcic University Medical Centre Ljubljana, Zaloska 7, SI-1525 Ljubljana, Slovenia Received 5 January 2008; accepted 13 June 2008
KEYWORDS Darier’s disease; Intertriginous manifestation; Surgical treatment; Tissue expanders
Summary Darier’s disease is a rare autosomal-dominant genodermatosis characterised by persistent hyperkeratotic papules and plaques in seborrhoeic areas. The flexural areas of the body are especially difficult to treat, and they are often resistant to current topical and systemic treatment strategies. To our knowledge, this article provides the first description of a successful surgical treatment of a severely debilitating, hypertrophic Darier’s disease of intergluteal area, resistant to oral retionids. A 25-year-old male patient was successfully treated with the use of tissue expanders and diseased skin excision. There are no signs of recurrence of the disease in the perianal region 6 months postoperatively, and there is a good result in functional as well as cosmetic terms. The formation of new skin on the excision site was observed, and there were no evident signs of infection. These encouraging results suggest that a patient who responds poorly to conventional treatment in a specific area should be presented to the plastic surgeon at an earlier point in time. Therefore, unnecessary hospitalisations, antibiotic treatments, dose-related adverse effects of oral retionids can be avoided, and eventually a long-term result can be achieved. ª 2008 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.
Darier’s disease (dyskeratosis follicularis) is a rare autosomal-dominant skin disease, characterised by persistent hyperkeratotic papules and plaques in seborrhoeic areas. It is caused by mutations in the ATP2A2 gene at chromosome 12q, which encodes the sarco/endoplasmic reticulum Ca2þ * Corresponding author. University Medical Centre Ljubljana, Department of plastic, reconstructive, aesthetic surgery and burns, Zaloska 7, SI-1000 Ljubljana, Slovenia. Tel.:+386 522 32 84; fax: þ386 1 522 2239. E-mail address: [email protected] (K. Zivec).
ATPase type 2. Defects in calcium concentration in the endoplasmic reticulum result in impaired processing of desmosomal proteins, abnormal intercellular adhesion and altered keratinisation.1 The prevalence of Darier’s disease is estimated to be between 1 and 3.3 per 100 000 populations.2 Skin signs usually develop in adolescent period. Severity of disease varies and is unpredictable. External irritation and infection often aggravate the disease. In majority of the patients, the keratotic papules are distributed only at predilection seborrhoeic areas. In some patients, greasy hyperkeratotic plaques can arise in flexures and may form
1748-6815/$ - see front matter ª 2008 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.bjps.2008.06.060
The surgical treatment of hypertrophic intertriginous Darier’s disease warty or papillomatous, vegetating and malodorous masses. Flexural involvement with hypertrophic plaques is found in 6% of the patients with Darier’s disease.3 Treatment is based upon the extent of clinical manifestations. In mild forms, emollients, topical retinoids or corticosteroids are sufficient. For more severe forms, oral retinoids are required. Vegetating flexural plaques are resistant to conventional treatment, and additional therapeutic approaches are often necessary.3e5
Case report A 25-year-old male patient with Darier’s disease has been treated at the Department of Dermatovenereology for several years. The family history was positive. Skin manifestations with characteristic keratotic papules on seborrhoeic areas of the trunk, face, neck, ears and scalp appeared at the age of 12. Additionally, oral mucosa was involved, and the nails showed longitudinal ridging and splitting. The diagnosis was confirmed on histopathological examination. Topical corticosteroids and retinoids were the first choice of treatment for the affected areas. Later, skin manifestations on the trunk, arm, leg flexures, neck and face had worsened by the formation of severe keratotic papules and plaques. Severe hyperkeratotic malodorous papillomatous masses developed in the perineal and perianal region (Figure 1). A treatment with oral acitretin was introduced with a daily dose of 0.5 mg per kg of body weight. After 2 years of systemic treatment, moderate improvement of skin manifestations on the trunk, face and scalp was achieved; however, there was no improvement of plaques in the perianal region. Severe inflammatory exacerbations often occurred, and Staphylococci, Streptococci, Proteus mirabilis, Pseudomonas aeruginosa and difteroids were isolated. Topical antiseptics and antibiotics, sometimes in addition to systemic broad-spectrum antibiotics, were the choice of treatment. Due to persistent pain and irritation, normal daily needs and activities were impaired.
e443
The patient was presented to the Department of Plastic Surgery. The involvement of sacral, gluteal and anal region was extensive; this region measured approximately 15 cm 10 cm surrounding the anal aperture. The irritation, itching, pain and odour (as a consequence of secondary infections) were impairing patient’s normal daily activities (personal hygiene, defecating, sitting, walking, dressing, etc.) and had also been a cause of psychological distress. Since we could not achieve satisfactory improvement of skin manifestations in this region, a surgical approach under general anaesthesia using tissue expanders followed by wide excision and primary closure was considered. The bilateral endoscopical insertion of two expanders (TRC 300 Nagor Ltd., British Isles) under healthy skin in close proximity to the border of the lesion (Figure 2) was accomplished. The filling with saline started immediately, approximately 30e40 ml every 3e4 days, and depended on the patient’s pain tolerance. After 7 days, the left expander deflated, and a new expander of the similar shape and size was inserted successfully. A wide excision of all diseased skin was performed on day 20 (Figure 3). The expanders were removed and the defect was sutured in layers. The haemostasis was controlled with cautery. The specimen was sent for histopathological analysis. The histopathological picture was consistent with the Mb. Darier (‘corp ronds’, follicular keratosis, papilomatosis, suprabasal acantolysis with lacunae formation, narrow longitudinal retitformous epithelial extensions and chronic inflammatory infiltrate in dermis) (Figure 4). During the first few postoperative days, the wound healed in an uneventful manner. Later, due to inflammation, the wound became dehiscent on the right side. The dead tissue was removed, and the subcutaneous spaces were irrigated with peroxide and saline. Three drains were inserted, and the defect was again sutured in layers. While the patient was hospitalised, the following bacteria were isolated from the gluteal area: Pseudomonas aeruginosa, Enterococcus faecalis, Corynebacterium striatum and
Figure 1 A presentation of Darier’s disease in sacral, gluteal and anal region in a patient. The typical reddish papules forming confluent plaques and a warty texture.
e444
U. Ahcan et al.
Figure 2
Endoscopically inserted tissue expanders (TRC 300 Nagor Ltd., British Isles).
Bacteroides fragilis. The patient was treated with antibiotics on the basis of an antibiogram. After discharge, following a 46-day hospitalisation, the patient was advised to wear compression pants and to rinse the operated area with camomile solution and to apply chlorhexidine dichloride and dexpanthenol cream and gently massage the area. In addition, care for hygiene during normal daily activities (e.g., defecation) was stressed upon. Despite the delicate region, and therefore potential complications (e.g., inflammation), there are no signs of recurrence in the perianal region 6 months postoperatively, and has also resulted in favourable functional and cosmetic results. Therefore, the patient’s expectations were fulfilled.. A formation of new skin on the excision site is observed, and there are no evident signs of infection (Figure 5). All daily activities are possible from postoperative 6 months onwards.. Based upon these results, 6 months follow-up visits were scheduled. However, the patient is also being followed-up at the Department of Dermatovenereology since the disease is still manifest on the other parts of the body.
Figure 3
A wide excision of all diseased tissue.
Discussion The conventional treatment of severe forms of Darier’s disease is usually unsatisfactory. Oral retinoids are still the most effective treatment for severe disease.4,5 They can improve skin lesions by reducing the hyperkeratosis, but a long-term therapy is often limited because of the adverse effects. The treatment of hypertrophic flexural disease is particularly difficult and resistant to oral retinoids.3,5 For recalcitrant hypertrophic growths, surgical treatment is often necessary. Different techniques have been advocated: partial-thickness removal of skin,6 dermabrasion,7 partial-thickness resection and deep dermabrasion,8 surgical excision and closure by primary suture,9 electrosurgical excision10 and sharp debridement.11 The advantage of treatment of etretinate-resistant Darier’s disease with deep, split-thickness skin excision with electrosurgery over dermabrasion, dermatome shaving and free-hand, scalpel-shave excision is the ease of obtaining haemostasis and, thus, surgical visibility.10 In this case, such a procedure could cause an extensive defect that needed to be covered with a skin graft. In addition, the extensive bacterial contamination of this area could prevent the graft take. Laser treatment (e.g., Er: YAG laser) could also be considered as a treatment option. However, in this patient, the diseased lesion was too extensive for laser therapy. The vascularity of the diseased region seemed augmented, and therefore complete haemostasis would not have been possible. The healing process would have been prolonged, and also the scars that might have evolved could have caused additional functional disabilities. It is suggested that surgical intervention must be sufficiently deep, up to the papillary dermis, to provide longterm remission.7 There is a theoretical possibility that surgery itself could precipitate new lesions, because of the isomorphic phenomenon seen in response to trauma, but this does not seem to be a problem with sufficiently deep surgery.4 With the use of tissue expanders, the excision can be wide and deep enough in order to remove all of the
The surgical treatment of hypertrophic intertriginous Darier’s disease
e445
Figure 4 Darier’s disease. (A) characteristic ‘‘corps ronds’’ (original magnification: 400); (B) follicular keratosis, narrow longitudinal retiformous epithelial extensions and focal suprabasal acantholysis (original magnification: 100).
diseased tissue and to gain enough tissue for the reconstruction of the defect. Changes in the histology of the expanded skin are prominent, and they might contribute to the final outcome; for example, epidermis becomes thicker, reticular dermis is thinned, collagen bundles are thickened, elastic fibres may rupture and undergo fibrotic changes, vascularity is increased, dermal appendages show degenerative changes and the skin generally becomes drier. The endoscopic tissue expander placement needs smaller incision, which might prevent expander extrusion, and allows for starting with early aggressive expansion. Despite potential complications, such as infection or cellulitis, exposure, rupture and skin loss, a decision was made in favour of this approach. The hospitalisation period was 46 days, mainly due to infectious complications. This is consistent with common secondary infections seen in these patients and the need for focussed antibiotic treatment following consultation
Figure 5
with the infectious disease specialist. Since the quality of life in some patients is very deprived and psychological consequences might also be evident, a psychologist and a genetic counsellor could be also considered as members of a multidisciplinary team. In summary, the patient with a severely debilitating hypertrophic Darier’s disease of intergluteal area, resistant to oral retionids in this intertriginous area, was successfully treated with the use of tissues expanders and diseased-skin excision. The encouraging results obtained thus suggest that a patient who responds poorly to a conventional treatment in a specific area should be presented to a plastic surgeon at an earlier point in time. An appropriate surgical approach for every individual patient and intensive preoperative planning is the rule. In this sense, we may avoid unnecessary hospitalisations, antibiotic treatments, doserelated adverse effects of oral retionids and, eventually, a long-term result can be achieved successfully.
Six months after surgery. The patient is asymptomatic and free of disease. A formation of a new mucosa is seen.
e446
References 1. Sakuntabhai A, Ruiz-Perez V, Carter S, et al. Mutations in ATP2A2, encoding a Ca2þ pump, cause Darier disease. Nat Genet 1999;21:271e7. 2. Munro CS. The phenotype of Darier’s disease: penetrance and expressivity in adults and children. Br J Dermatol 1992;127: 126e30. 3. Burge SM, Wilkinson JD. DariereWhite disease: a review of the clinical features in 163 patients. J Am Acad Dermatol 1992;27: 40e50. 4. Cooper SM, Burge SM. Darier’s disease: epidemiology, pathophysiology and management. Am J Clin Dermatol 2003;4:97e105. 5. Burge S. Management of Darier’s disease. Clin Exp Dermatol 1999;24:53e6.
U. Ahcan et al. 6. Dellon AL, Chretien PB, Peck GL. Successful treatment of Darier’s disease by partial-thickness removal of skin. Plast Reconstr Surg 1977;59:823e30. 7. Zachariae H. Dermabrasion in Darier’s disease. Acta Derm Venereol 1979;59:184e6. 8. Mandel MA. Cornifying Darier’s disease. Plast Reconstr Surg 1979;63:167e72. 9. McFadden JP, Mayou BJ, Griffiths WAD. Darier’s disease of the groin treated by surgery. Br J Dermatol 1991;125(Suppl.):52. 10. Toombs EL, Peck GL. Electrosurgical treatment of etretinateresistant Darier’s disease. J Dermatol Surg Oncol 1989;15: 1277e80. 11. Wheeland RG, Gilmore WA. The surgical treatment of hypertrophic Darier’s disease. J Dermatol Surg Oncol 1985; 11:420e3.