Background: Over the last three decades, the oral retinoids etretinate and acitretin have revolutionized the treatment of disorders of keratinization (DOK). Many patients with DOK require life-long treatment with oral...Background: Over the last three decades, the oral retinoids etretinate and acitretin have revolutionized the treatment of disorders of keratinization (DOK). Many patients with DOK require life-long treatment with oral retinoids. However, the longest follow-up data of patients with DOK on oral retinoid therapy is 10 years for adults and up to 11 years for children. Objectives: The aim of our study was to collect long-term retrospective data including disease response, side-effects and pregnancy outcome in a cohort of patients with DOK who were among the first in the world to commence oral retinoids 25 years ago. Methods: Between 1979 and 1981, 30 patients with DOK were commenced on oral etretinate in our department. Case notes of these patients were reviewed retrospectively, and patients interviewed where possible to obtain the following information: diagnosis, age when treatment commenced, duration of treatment, reason for discontinuation of therapy, side-effects, abnormal investigation results and pregnancy outcomes. Results: Case notes of 23 of the 30 patients were available for review; of these, two patients were deceased and 14 were interviewed. In the 23 patients, the mean age of commencing treatment was 33.5 years (range 4.2-61) and the mean duration of etretinate therapy was 5.2 years (range 1 month to 14 years). Reasons for discontinuing treatment were an overall improvement in the skin disease (six of 23), no benefit ±side effects (11 of 23) and noncompliance (one of 23). Two patients died of causes unrelated to their skin disease or treatment, 12 and 4 years after stopping etretinate. Five patients (one female, four males) subsequently changed to acitretin and are currently continuing therapy. The mean total duration of retinoid therapy (etretinate and acitretin) for the four males was 23.7 years (range 20.6-25.1). The female patient continued intermittent courses (due to planned pregnancies) of oral retinoids for a total of 10.1 years over the last 25 years. Abnormal investigation results included elevated serum triglycerides and cholesterol (two of 23), isolated high triglycerides (three of 23), isolated high cholesterol (three of 23), worsening of liver enzymes in a patient with alcohol dependence, and elevated serum alkaline phosphatase (ALP) in healthy adults (three of 23). In two children, the elevated pretreatment ALP levels increased further after commencing etretinate but returned to normal in adulthood while treatment continued. One patient developed diffuse idiopathic skeletal hyperostosis after 21 years of retinoid therapy. One female patient had two early spontaneous abortions 2.75 and 3.2 years after discontinuing etretinate; she subsequently had two normal children. Two other females had normal children 1, 3 and 5 years after stopping etretinate. Two male patients fathered a total of three healthy children while on etretinate. Conclusions: This study provides the longest available follow-up data of children and adults with DOK on oral retinoid therapy. Such information is essential for clinicians and their patients with DOK embarking on life long treatment with retinoids.展开更多
Background: Dyskeratosis follicularis (Darier’ s disease) is rare autosomal dominant disease characterized by the loss of adhesion between epidermal cells and by abnormal keratinization. Methods: We performed a retro...Background: Dyskeratosis follicularis (Darier’ s disease) is rare autosomal dominant disease characterized by the loss of adhesion between epidermal cells and by abnormal keratinization. Methods: We performed a retrospective study of all the patients diagnosed with Darier’ s disease at the Department of Dermatology of Charles Nicolle Hospital of Tunis, between 1971 and 2002. Results: During the observation period, we identified 12 patients with Darier’ s disease; five males and seven females with a mean age of 17.36 years. No family history was found in eight patients. Skin lesions in the form of keratotic papules were noted in seborrhoeic areas, essentially the face (nine patients), chest and scalp. Seven patients had nail lesions. UV light exposure exacerbated the disease symptoms in seven cases. The patients were treated with topical and systemic retinoids (six cases). Conclusion: Although Darier’ s disease has a chronic course, most patients manage to lead a relatively normal life. Treatment is usually unsatisfactory despite much progress in understanding of the underlying abnormalities in Darier’ s disease.展开更多
Keratosis lichenoides chronica (KLC) is a rare chronic disorder of keratinizat ion, characterized by the progressive development of erythematosquamous plaques and violaceous lichenoid hyperkeratotic papules, nodules a...Keratosis lichenoides chronica (KLC) is a rare chronic disorder of keratinizat ion, characterized by the progressive development of erythematosquamous plaques and violaceous lichenoid hyperkeratotic papules, nodules and ridges. These lesio ns are most commonly found in a symmetrical distribution on the trunk and extrem ities and display a unique linear and/or reticulate pattern. The etiology of KLC remains unknown and the eruptions tend to be refractory to treatment. We descri be a case of keratosis lichenoides chronica that improved with systemic retinoid s.展开更多
Background: T-cell infiltration in plaque psoriasis has recently been an important subject of investigation. Interestingly, comparative analyses of the disease-specific composition of the lesional T-cell infiltrate in...Background: T-cell infiltration in plaque psoriasis has recently been an important subject of investigation. Interestingly, comparative analyses of the disease-specific composition of the lesional T-cell infiltrate in plaque psoriasis and other inflammatory dermatoses have only sparsely been performed. Objectives: To compare plaque psoriasis vs. atopic dermatitis and lichen ruber planuswith respect to T-cell subsets, epidermal proliferation and keratinization. Patients and methods: Biopsies were taken from untreated lesional skin of patients, six with psoriasis, six with atopic dermatitis and six with lichen planus. T-cell subsets (CD4+, CD8+, CD45RO+, CD45RA+, CD2+, CD25+), an epidermal proliferation (Ki-67) and a keratinization marker (K10) were stained immunohistochemically and quantified using image analysis. Results: The high number of CD8+T cells (52±13 cells mm-1) found in the psoriatic epidermis was not found in the epidermis of atopic dermatitis (9±4), nor in the epidermis of lichen planus (34±10). The other T-cell subsets in the epidermis and dermis showed no statistically significant differences between psoriasis and atopic dermatitis. In contrast to the limited presence of CD4+, CD8+and CD2+in the psoriatic dermis (110±19, 27±9, 127±41, cells mm-1, respectively), more impressive numbers of these cells were observed in the dermis of lichen planus (300±53, 144±38, 272±48, respectively). CD45RO+memory effector T-cell counts were significantly higher in the epidermis of lichen planus (39±10) than in psoriasis (19±5). Psoriatic epidermis proved to have major keratinocyte hyperproliferation (247±26 cells mm-1 lamina basalis), as compared with atopic dermatitis (134±15) and lichen planus (128±20). Furthermore, a marked decreased expression of keratin 10 was observed in psoriasis (41%of epidermal area) contrary to atopic dermatitis (70%). Conclusions: Psoriatic epidermis exhibits a pronounced CD8+epidermotropism with accompanying epidermal hyperproliferation and abnormal keratinization, which changes are only minimally expressed in atopic dermatitis and lichen planus. In plaque psoriasis, substantially fewer activated CD4+and CD8+T cells in the dermis and less CD45RO+T cells in the epidermis are present in comparison with lichen ruber planus.展开更多
Ectodermal dysplasia/skin fragility syndrome (EDSFS)- (MIM604536) is a newly described autosomal recessive disorder characterized by skin fragility and blistering, palmoplantar keratoderma, abnormal hair growth, nail ...Ectodermal dysplasia/skin fragility syndrome (EDSFS)- (MIM604536) is a newly described autosomal recessive disorder characterized by skin fragility and blistering, palmoplantar keratoderma, abnormal hair growth, nail dystrophy, and occasionally defective sweating. It results from mutations in the PKP1 gene encoding plakophilin 1 (PKP1), which is an important component of stratifying epithelial desmosomes and a nuclear component of many cell types. Our study was performed to further characterize the histopathology of EDSFS in different cutaneous sites with a special emphasis on the hypotrichosis and keratoderma. A total of 4 biopsies were obtained from 2 EDSFS female patients, aged 9 days to 4 years. The biopsies were taken from the blistering skin of the leg and trunk, the hyperkeratotic skin of the sole, and the hypotrichotic scalp. The observed histopathologic features included: widened intercellular spaces, suprabasal intraepidermal clefts and blisters with acantholytic keratinocytes, detachments of the upper epidermal layers due to disadhesion, varying degrees of dyskeratosis thatweremuchmore pronounced in the plantar hyperkeratotic skin, and increased number of catagen- telogen hair follicles. The electron- microscopic observations attributed the disadhesion and acantholysis to reduced numbers of small hypoplastic desmosomes, and the dyskeratosis to the detachment of intracellular keratin filaments from the desmosomes with perinuclear condensation, which might also underlie the plantar keratoderma. The hair follicle findings suggest disturbance in the hair cycle, which might be attributed to disturbed nuclear PKP1 function or result from aberrant desmosomal signaling.展开更多
文摘Background: Over the last three decades, the oral retinoids etretinate and acitretin have revolutionized the treatment of disorders of keratinization (DOK). Many patients with DOK require life-long treatment with oral retinoids. However, the longest follow-up data of patients with DOK on oral retinoid therapy is 10 years for adults and up to 11 years for children. Objectives: The aim of our study was to collect long-term retrospective data including disease response, side-effects and pregnancy outcome in a cohort of patients with DOK who were among the first in the world to commence oral retinoids 25 years ago. Methods: Between 1979 and 1981, 30 patients with DOK were commenced on oral etretinate in our department. Case notes of these patients were reviewed retrospectively, and patients interviewed where possible to obtain the following information: diagnosis, age when treatment commenced, duration of treatment, reason for discontinuation of therapy, side-effects, abnormal investigation results and pregnancy outcomes. Results: Case notes of 23 of the 30 patients were available for review; of these, two patients were deceased and 14 were interviewed. In the 23 patients, the mean age of commencing treatment was 33.5 years (range 4.2-61) and the mean duration of etretinate therapy was 5.2 years (range 1 month to 14 years). Reasons for discontinuing treatment were an overall improvement in the skin disease (six of 23), no benefit ±side effects (11 of 23) and noncompliance (one of 23). Two patients died of causes unrelated to their skin disease or treatment, 12 and 4 years after stopping etretinate. Five patients (one female, four males) subsequently changed to acitretin and are currently continuing therapy. The mean total duration of retinoid therapy (etretinate and acitretin) for the four males was 23.7 years (range 20.6-25.1). The female patient continued intermittent courses (due to planned pregnancies) of oral retinoids for a total of 10.1 years over the last 25 years. Abnormal investigation results included elevated serum triglycerides and cholesterol (two of 23), isolated high triglycerides (three of 23), isolated high cholesterol (three of 23), worsening of liver enzymes in a patient with alcohol dependence, and elevated serum alkaline phosphatase (ALP) in healthy adults (three of 23). In two children, the elevated pretreatment ALP levels increased further after commencing etretinate but returned to normal in adulthood while treatment continued. One patient developed diffuse idiopathic skeletal hyperostosis after 21 years of retinoid therapy. One female patient had two early spontaneous abortions 2.75 and 3.2 years after discontinuing etretinate; she subsequently had two normal children. Two other females had normal children 1, 3 and 5 years after stopping etretinate. Two male patients fathered a total of three healthy children while on etretinate. Conclusions: This study provides the longest available follow-up data of children and adults with DOK on oral retinoid therapy. Such information is essential for clinicians and their patients with DOK embarking on life long treatment with retinoids.
文摘Background: Dyskeratosis follicularis (Darier’ s disease) is rare autosomal dominant disease characterized by the loss of adhesion between epidermal cells and by abnormal keratinization. Methods: We performed a retrospective study of all the patients diagnosed with Darier’ s disease at the Department of Dermatology of Charles Nicolle Hospital of Tunis, between 1971 and 2002. Results: During the observation period, we identified 12 patients with Darier’ s disease; five males and seven females with a mean age of 17.36 years. No family history was found in eight patients. Skin lesions in the form of keratotic papules were noted in seborrhoeic areas, essentially the face (nine patients), chest and scalp. Seven patients had nail lesions. UV light exposure exacerbated the disease symptoms in seven cases. The patients were treated with topical and systemic retinoids (six cases). Conclusion: Although Darier’ s disease has a chronic course, most patients manage to lead a relatively normal life. Treatment is usually unsatisfactory despite much progress in understanding of the underlying abnormalities in Darier’ s disease.
文摘Keratosis lichenoides chronica (KLC) is a rare chronic disorder of keratinizat ion, characterized by the progressive development of erythematosquamous plaques and violaceous lichenoid hyperkeratotic papules, nodules and ridges. These lesio ns are most commonly found in a symmetrical distribution on the trunk and extrem ities and display a unique linear and/or reticulate pattern. The etiology of KLC remains unknown and the eruptions tend to be refractory to treatment. We descri be a case of keratosis lichenoides chronica that improved with systemic retinoid s.
文摘Background: T-cell infiltration in plaque psoriasis has recently been an important subject of investigation. Interestingly, comparative analyses of the disease-specific composition of the lesional T-cell infiltrate in plaque psoriasis and other inflammatory dermatoses have only sparsely been performed. Objectives: To compare plaque psoriasis vs. atopic dermatitis and lichen ruber planuswith respect to T-cell subsets, epidermal proliferation and keratinization. Patients and methods: Biopsies were taken from untreated lesional skin of patients, six with psoriasis, six with atopic dermatitis and six with lichen planus. T-cell subsets (CD4+, CD8+, CD45RO+, CD45RA+, CD2+, CD25+), an epidermal proliferation (Ki-67) and a keratinization marker (K10) were stained immunohistochemically and quantified using image analysis. Results: The high number of CD8+T cells (52±13 cells mm-1) found in the psoriatic epidermis was not found in the epidermis of atopic dermatitis (9±4), nor in the epidermis of lichen planus (34±10). The other T-cell subsets in the epidermis and dermis showed no statistically significant differences between psoriasis and atopic dermatitis. In contrast to the limited presence of CD4+, CD8+and CD2+in the psoriatic dermis (110±19, 27±9, 127±41, cells mm-1, respectively), more impressive numbers of these cells were observed in the dermis of lichen planus (300±53, 144±38, 272±48, respectively). CD45RO+memory effector T-cell counts were significantly higher in the epidermis of lichen planus (39±10) than in psoriasis (19±5). Psoriatic epidermis proved to have major keratinocyte hyperproliferation (247±26 cells mm-1 lamina basalis), as compared with atopic dermatitis (134±15) and lichen planus (128±20). Furthermore, a marked decreased expression of keratin 10 was observed in psoriasis (41%of epidermal area) contrary to atopic dermatitis (70%). Conclusions: Psoriatic epidermis exhibits a pronounced CD8+epidermotropism with accompanying epidermal hyperproliferation and abnormal keratinization, which changes are only minimally expressed in atopic dermatitis and lichen planus. In plaque psoriasis, substantially fewer activated CD4+and CD8+T cells in the dermis and less CD45RO+T cells in the epidermis are present in comparison with lichen ruber planus.
文摘Ectodermal dysplasia/skin fragility syndrome (EDSFS)- (MIM604536) is a newly described autosomal recessive disorder characterized by skin fragility and blistering, palmoplantar keratoderma, abnormal hair growth, nail dystrophy, and occasionally defective sweating. It results from mutations in the PKP1 gene encoding plakophilin 1 (PKP1), which is an important component of stratifying epithelial desmosomes and a nuclear component of many cell types. Our study was performed to further characterize the histopathology of EDSFS in different cutaneous sites with a special emphasis on the hypotrichosis and keratoderma. A total of 4 biopsies were obtained from 2 EDSFS female patients, aged 9 days to 4 years. The biopsies were taken from the blistering skin of the leg and trunk, the hyperkeratotic skin of the sole, and the hypotrichotic scalp. The observed histopathologic features included: widened intercellular spaces, suprabasal intraepidermal clefts and blisters with acantholytic keratinocytes, detachments of the upper epidermal layers due to disadhesion, varying degrees of dyskeratosis thatweremuchmore pronounced in the plantar hyperkeratotic skin, and increased number of catagen- telogen hair follicles. The electron- microscopic observations attributed the disadhesion and acantholysis to reduced numbers of small hypoplastic desmosomes, and the dyskeratosis to the detachment of intracellular keratin filaments from the desmosomes with perinuclear condensation, which might also underlie the plantar keratoderma. The hair follicle findings suggest disturbance in the hair cycle, which might be attributed to disturbed nuclear PKP1 function or result from aberrant desmosomal signaling.
