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Spiny keratoderma in association with autosomal dominant polycystic kidney disease with liver cysts
Spiny keratoderma in association with autosomal dominant polycystic kidney disease with liver cysts Dina Anderson, MD, David E. Cohen, MD, MPH, H y u n Soo I.e~, MD, and Cheryl Thellman, MD New York, New York Spiny keratoderma of the palms and soles has been rarely reported. Debate exists regarding the proper nosologic classification of this disorder. We describe a patient and her mother with concurrent autosomal dominant polycystic kidney disease with liver cysts. (J AM ACADDERMATOL 1996;34:935-6.) Spiny keratoderma is rare and has not been assod a t e d with an underlying genetic disease. CASE REPORT
A 46-year-old white woman had a 2-year history of asymptomatic multiple spiny papules on her palms and soles (Fig.l). She had no history of hyperhidrosis or hypohidrosis and was unaware of any exposure to arsenic. Medical history included autosomal dominant polycystic kidney disease (ADPKD) with liver cysts. Her mother had similar spiny papules of her palms and ADPKD. Examination revealed numerous, farm, flesh-colored 0.5 to 2 mm keratotic spiny papules on the palms and soles. Each papule was firmly attached at its base. A biopsy specimen revealed a narrow dell of epidermis with a diminished granular layer surmounted by a distinct column of parakeratosis with slight epidermal hyperplasia at the periphery of the column (Fig. 2). The patient returned 3 years later. Tretinoin gel 0.05% was applied twice daily to her left hand and an ointment base (Aquaphor) to her right hand. She reported no significant improvement. A trial of 5% 5-fluorouracil cream to both palms produced no response. A combination of 0.05% tretinoin cream and ammonium lactate 12% lotion twice daily has produced some improvement.
Fig. 1. Keratotic spiny lesions on plantar surfaces of toes.
DISCUSSION Since 1971 there have been nine case reports 1-9 of " s p i n y " keratotic lesions located exclusively on volar surfaces. Considerable confusion exists as to From the Ronald O. Perelman Department of Dermatology, New York University School of Medicine, Charles C. Harris Skin and Cancer Pavilion, and the Dermatopathology Section, New York University Medical Center. Reprint requests: David E. Cohen, MD, MPH, Department of Dermatology H-100, New York University Medical Center, 530 First Avenue, New York, NY 10016. Copyright © 1996 by the American Academy of Dermatology, Inc. 0190-9622/96 $5.00 + 0 16/4/69650
Fig. 2. Focal hypogranulosis surmounted by column of parakeratosis.
whether this is a punctate keratoderma or a porokeratosis variant. Terms for this disorder include punctate keratoderma, 1 punctate porokeratotic keratoderma,2, 6, 8 punctate porokeratosis, 3 porokeratosis punctata palmaris et plantaris 5' 7 and, most recently,
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spiny keratoderma. 9 Clinically and histopathologically, spiny keratoderma is a single distinct entity and should not be confused with porokeratosis and punctate keratodermas because these have been linked to cutaneous 1° and internal malignancy, 11, 12 respectively. Analysis of keratotic plugs of spiny keratoderma have identified keratin 6 and 16, which are typically present in hyperproliferative epidermal cells, s The cases reported to date do not consistently show a link to any other associated disease. Both our patient and her mother had spiny keratoderma and polycystic kidney disease with liver cysts. The mode of inheritance of the liver and kidney disease is distinctly autosomal dominant. The transmission mode of the cutaneous findings is less clear because a large pedigree could not be constructed for this family. However, the similarity between the mother' s and daughter's presentations makes an autosomal dominant inheritance pattern likely. The expression of differentiation antigens and growth-related genes in ADPKD show some additional relationships to spiny keratoderma. Klingel et al. 13 identified an epithelial development antigen Exo- 1 (polar neutral glycolipid) expressed in 50% to 80% of cyst-lining epithelia in polycystic kidney tissue and not in normal kidney cell controls. The expression of this antigen is associated with hyperproliferation in epithelial tissue composed of cells that have not reached their terminal differentiation state. J3 Whether this is related to an epidermal hyperproliferative process in the same patient is unclear. In addition, increased expression of epidermal growth factor receptor and its ligand, transforming growth factor (TGF-o0, was present in the epithelium of ADPKD tissue as compared with normal kidney cells. 13Transforming growth factor [3 (TGF-[3) is an inhibitory component of this autocrine system. Wilson 14 showed that inhibition of renal tubule epithelium proliferation by TGF-[3 was reduced to 41% of normal in ADPKD epithelium. These findings of altered regulation contribute to the hypothesis that hyperproliferation is an underlying mechanism in ADPKD. 13
Journal of the American Academy of Dermatology May 1996
The cases of spiny keratoderma reported to date do not consistently show a link to any other disease. There is one report of three generations of males that were affected whereas all female family members were spared. This report adds to the previous five of nine cases of autosomal dominant transmission but is the fu'st associated with a concomitant genetic disease. REFERENCES
1. Brown FC. Punctate keratoderma. Arch Dermatol 1971; 104:682-3. 2. Herman PS. Punctate porokeratotic keratoderma. Dermatologica 1975;147:206-19. 3. Himmelstein R, Lynfield YL. Punctate porokeratosis. Arch Dermatol 1984;120:243-4. 4. Schiff BL, Hughes D. Palmoplantar keratoses acuminata with facial sebaceous hyperplasia. Arch Dermatol 1974; 109:86-9. 5. Sakas EL, Gentry RH. Porokeratosis punctata palmaris et plantaris (punctate porokeratosis). J AM ACADDERMATOL 1985;139908-12. 6. Friedman SJ, Herman PS, Pittelkow MR, et al. Punctate porokeratotic keratoderma. Arch Dennatol 1988; 124:167882. 7. Lestringant GG, Berge T. Pomkeratosis punctata palmaris et plantaris: A new entity? Arch Dermatol 1989; 125:816-9. 8. Kondo D, Shimoura T, Hozini Y, et al. Punctate porokeratotic keratoderma: some pathogenic analyses of hyperproliferation and porokeratosis. Acta Derm Venereol (Stockh) 1990;70:478-82. 9. Osman Y, Daly TJ, Don PC. Spiny keratoderma of the palms and soles. J AM ACAD DERMATOL 1992;26: 879-81. 10. Wolff-Scheiner EC. Porokeratosis. In: Fitzpatrick TB, Eisen AZ, Wolff K, et al., eds. Dermatology in general medicine. New York:McGraw-Hill, 1987:534-40. 11. Bennion SD, Patterson JW. Keratosis punctate palmaris et plantaris and adenocarcinoma of the colon. J AM ACAD DERMATOL 1984;10:587-91. 12. Fegueux S, Bilet S, Crickx B. Hyperkeratose palmo-plantare filiforme et cancer rectosigmoidien. Ann Dermatol 1988;115:1145-6. 13. Klingel R, Dippold W, Storkel S, et al. Expression of differentiation antigens and growth-related genes in normal kidney, autosomal dominant polycystic kidney disease, and renal cell carcinoma. Am J Kidney Dis 1992;19: 22-30. 14. Wilson PD. Aberrant epithelial cell growth in autosomal dominant polycystic kidney disease. Am J Kidney Dis 1991;17:634-7.
A 46-year-old white woman had a 2-year history of asymptomatic multiple spiny papules on her palms and soles (Fig.l). She had no history of hyperhidrosis or hypohidrosis and was unaware of any exposure to arsenic. Medical history included autosomal dominant polycystic kidney disease (ADPKD) with liver cysts. Her mother had similar spiny papules of her palms and ADPKD. Examination revealed numerous, farm, flesh-colored 0.5 to 2 mm keratotic spiny papules on the palms and soles. Each papule was firmly attached at its base. A biopsy specimen revealed a narrow dell of epidermis with a diminished granular layer surmounted by a distinct column of parakeratosis with slight epidermal hyperplasia at the periphery of the column (Fig. 2). The patient returned 3 years later. Tretinoin gel 0.05% was applied twice daily to her left hand and an ointment base (Aquaphor) to her right hand. She reported no significant improvement. A trial of 5% 5-fluorouracil cream to both palms produced no response. A combination of 0.05% tretinoin cream and ammonium lactate 12% lotion twice daily has produced some improvement.
Fig. 1. Keratotic spiny lesions on plantar surfaces of toes.
DISCUSSION Since 1971 there have been nine case reports 1-9 of " s p i n y " keratotic lesions located exclusively on volar surfaces. Considerable confusion exists as to From the Ronald O. Perelman Department of Dermatology, New York University School of Medicine, Charles C. Harris Skin and Cancer Pavilion, and the Dermatopathology Section, New York University Medical Center. Reprint requests: David E. Cohen, MD, MPH, Department of Dermatology H-100, New York University Medical Center, 530 First Avenue, New York, NY 10016. Copyright © 1996 by the American Academy of Dermatology, Inc. 0190-9622/96 $5.00 + 0 16/4/69650
Fig. 2. Focal hypogranulosis surmounted by column of parakeratosis.
whether this is a punctate keratoderma or a porokeratosis variant. Terms for this disorder include punctate keratoderma, 1 punctate porokeratotic keratoderma,2, 6, 8 punctate porokeratosis, 3 porokeratosis punctata palmaris et plantaris 5' 7 and, most recently,
935
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Anderson et al.
spiny keratoderma. 9 Clinically and histopathologically, spiny keratoderma is a single distinct entity and should not be confused with porokeratosis and punctate keratodermas because these have been linked to cutaneous 1° and internal malignancy, 11, 12 respectively. Analysis of keratotic plugs of spiny keratoderma have identified keratin 6 and 16, which are typically present in hyperproliferative epidermal cells, s The cases reported to date do not consistently show a link to any other associated disease. Both our patient and her mother had spiny keratoderma and polycystic kidney disease with liver cysts. The mode of inheritance of the liver and kidney disease is distinctly autosomal dominant. The transmission mode of the cutaneous findings is less clear because a large pedigree could not be constructed for this family. However, the similarity between the mother' s and daughter's presentations makes an autosomal dominant inheritance pattern likely. The expression of differentiation antigens and growth-related genes in ADPKD show some additional relationships to spiny keratoderma. Klingel et al. 13 identified an epithelial development antigen Exo- 1 (polar neutral glycolipid) expressed in 50% to 80% of cyst-lining epithelia in polycystic kidney tissue and not in normal kidney cell controls. The expression of this antigen is associated with hyperproliferation in epithelial tissue composed of cells that have not reached their terminal differentiation state. J3 Whether this is related to an epidermal hyperproliferative process in the same patient is unclear. In addition, increased expression of epidermal growth factor receptor and its ligand, transforming growth factor (TGF-o0, was present in the epithelium of ADPKD tissue as compared with normal kidney cells. 13Transforming growth factor [3 (TGF-[3) is an inhibitory component of this autocrine system. Wilson 14 showed that inhibition of renal tubule epithelium proliferation by TGF-[3 was reduced to 41% of normal in ADPKD epithelium. These findings of altered regulation contribute to the hypothesis that hyperproliferation is an underlying mechanism in ADPKD. 13
Journal of the American Academy of Dermatology May 1996
The cases of spiny keratoderma reported to date do not consistently show a link to any other disease. There is one report of three generations of males that were affected whereas all female family members were spared. This report adds to the previous five of nine cases of autosomal dominant transmission but is the fu'st associated with a concomitant genetic disease. REFERENCES
1. Brown FC. Punctate keratoderma. Arch Dermatol 1971; 104:682-3. 2. Herman PS. Punctate porokeratotic keratoderma. Dermatologica 1975;147:206-19. 3. Himmelstein R, Lynfield YL. Punctate porokeratosis. Arch Dermatol 1984;120:243-4. 4. Schiff BL, Hughes D. Palmoplantar keratoses acuminata with facial sebaceous hyperplasia. Arch Dermatol 1974; 109:86-9. 5. Sakas EL, Gentry RH. Porokeratosis punctata palmaris et plantaris (punctate porokeratosis). J AM ACADDERMATOL 1985;139908-12. 6. Friedman SJ, Herman PS, Pittelkow MR, et al. Punctate porokeratotic keratoderma. Arch Dennatol 1988; 124:167882. 7. Lestringant GG, Berge T. Pomkeratosis punctata palmaris et plantaris: A new entity? Arch Dermatol 1989; 125:816-9. 8. Kondo D, Shimoura T, Hozini Y, et al. Punctate porokeratotic keratoderma: some pathogenic analyses of hyperproliferation and porokeratosis. Acta Derm Venereol (Stockh) 1990;70:478-82. 9. Osman Y, Daly TJ, Don PC. Spiny keratoderma of the palms and soles. J AM ACAD DERMATOL 1992;26: 879-81. 10. Wolff-Scheiner EC. Porokeratosis. In: Fitzpatrick TB, Eisen AZ, Wolff K, et al., eds. Dermatology in general medicine. New York:McGraw-Hill, 1987:534-40. 11. Bennion SD, Patterson JW. Keratosis punctate palmaris et plantaris and adenocarcinoma of the colon. J AM ACAD DERMATOL 1984;10:587-91. 12. Fegueux S, Bilet S, Crickx B. Hyperkeratose palmo-plantare filiforme et cancer rectosigmoidien. Ann Dermatol 1988;115:1145-6. 13. Klingel R, Dippold W, Storkel S, et al. Expression of differentiation antigens and growth-related genes in normal kidney, autosomal dominant polycystic kidney disease, and renal cell carcinoma. Am J Kidney Dis 1992;19: 22-30. 14. Wilson PD. Aberrant epithelial cell growth in autosomal dominant polycystic kidney disease. Am J Kidney Dis 1991;17:634-7.