Close
New

Medscape is available in 5 Language Editions – Choose your Edition here.

 

Keratosis Follicularis (Darier Disease) Differential Diagnoses

  • Author: Pui-Yan Kwok, MD, PhD; Chief Editor: Dirk M Elston, MD  more...
 
Updated: Jun 03, 2016
 
 

Diagnostic Considerations

Also consider acantholytic dermatosis of the vulva.[38]

Differential Diagnoses

 
 
Contributor Information and Disclosures
Author

Pui-Yan Kwok, MD, PhD Henry Bachrach Distinguished Professor, Department of Dermatology and Cardiovascular Research Institute, University of California, San Francisco, School of Medicine

Pui-Yan Kwok, MD, PhD is a member of the following medical societies: American Academy of Dermatology, American Association for the Advancement of Science, American Society of Human Genetics, Dermatology Foundation, Society for Investigative Dermatology

Disclosure: Nothing to disclose.

Coauthor(s)

Wilson Liao, MD Associate Professor, Department of Dermatology, University of California, San Francisco, School of Medicine

Wilson Liao, MD is a member of the following medical societies: American Academy of Dermatology, Society for Investigative Dermatology, National Psoriasis Foundation

Disclosure: Nothing to disclose.

Tina Bhutani, MD Clinical Research Fellow, Department of Dermatology, University of California School of Medicine, San Francisco

Tina Bhutani, MD is a member of the following medical societies: American Medical Association, American Medical Womens Association, American Association of Physicians of Indian Origin, National Psoriasis Foundation, Indian Medical Association

Disclosure: Nothing to disclose.

Jillian Wong Millsop, MD, MS Resident Physician, Department of Dermatology, University of California, Davis, School of Medicine

Jillian Wong Millsop, MD, MS is a member of the following medical societies: American College of Physicians, American Medical Association, American Medical Womens Association

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Steven R Feldman, MD, PhD Professor, Departments of Dermatology, Pathology and Public Health Sciences, and Molecular Medicine and Translational Science, Wake Forest Baptist Health; Director, Center for Dermatology Research, Director of Industry Relations, Department of Dermatology, Wake Forest University School of Medicine

Steven R Feldman, MD, PhD is a member of the following medical societies: American Academy of Dermatology, American Society of Dermatopathology, North Carolina Medical Society, Society for Investigative Dermatology

Disclosure: Received honoraria from Amgen for consulting; Received honoraria from Abbvie for consulting; Received honoraria from Galderma for speaking and teaching; Received consulting fee from Lilly for consulting; Received ownership interest from www.DrScore.com for management position; Received ownership interest from Causa Reseasrch for management position; Received grant/research funds from Janssen for consulting; Received honoraria from Pfizer for speaking and teaching; Received consulting fee from No.

Chief Editor

Dirk M Elston, MD Professor and Chairman, Department of Dermatology and Dermatologic Surgery, Medical University of South Carolina College of Medicine

Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Nothing to disclose.

Additional Contributors

Arash Taheri, MD Research Fellow, Center for Dermatology Research, Department of Dermatology, Wake Forest University School of Medicine

Disclosure: Nothing to disclose.

Acknowledgements

The authors and editors of Medscape Reference gratefully acknowledge the contributions of previous authors, Sarah Fitzmaurice, MD, Jillian Wong Millsop, MD, MS, Tina Bhutani, MD, and Wilson Liao, MD, to the development and writing of this article.

References
  1. Sakuntabhai A, Ruiz-Perez V, Carter S, et al. Mutations in ATP2A2, encoding a Ca2+ pump, cause Darier disease. Nat Genet. 1999 Mar. 21(3):271-7. [Medline].

  2. Onozuka T, Sawamura D, Yokota K, Shimizu H. Mutational analysis of the ATP2A2 gene in two Darier disease families with intrafamilial variability. Br J Dermatol. 2004 Apr. 150(4):652-7. [Medline].

  3. Bchetnia M, Charfeddine C, Kassar S, Zribi H, Guettiti HT, Ellouze F. Clinical and mutational heterogeneity of Darier disease in Tunisian families. Arch Dermatol. 2009 Jun. 145(6):654-6. [Medline].

  4. Shi HJ, Li M, Zhang GL, et al. Novel splice-site and frameshift ATP2A2 mutations in Chinese patients with Darier disease. Clin Exp Dermatol. 2012. [Medline].

  5. Folster-Holst R, Nellen RG, Jensen JM, et al. Molecular genetic support for the rule of dichotomy in type 2 segmental Darier disease. Br J Dermatol. Feb 2012. 166:464-6. [Medline].

  6. Wang Y, Bruce AT, Tu C, et al. Protein aggregation of SERCA2 mutants associated with Darier disease elicits ER stress and apoptosis in keratinocytes. J Cell Sci. Nov 2011. 124:3568-80. [Medline].

  7. Harboe TL, Willems P, Jespersgaard C, et al. Mosaicism in segmental Darier disease: an in-depth molecular analysis quantifying proportions of mutated alleles in various tissues. Dermatology. Jul 2011. 222:292-6. [Medline].

  8. Pedace L, Barboni L, Pozzetto E, Amantea A, Zambruno G, Preziosi N, et al. Molecular characterization of 11 Italian patients with Darier disease. Eur J Dermatol. May-Jun 2011. 21:334-8. [Medline].

  9. Klausegger A, Nischler E, Wagner RN, Pletschacher F, Hintner H, Bauer JW. Seven novel mutations in the ATP2A2 gene of Austrian patients with Darier's disease. Arch Dermatol Res. 2011 Jul. 303(5):371-4. [Medline].

  10. Godic A, Strazisar M, Zupan A, Korosec B, Kansky A, Glavac D. Darier disease in Slovenia: spectrum of ATP2A2 mutations and relation to patients' phenotypes. Eur J Dermatol. 2010 May-Jun. 20(3):271-5. [Medline].

  11. Li CR, Cui PG, Jia H, et al. Identification of a novel mutation in a Chinese patient with mild Darier’s disease. Int J Dermatol. Nov 2010. 49:1286-8. [Medline].

  12. Huo J, Liu Y, Ma J, Xiao S. A novel splice-site mutation of ATP2A2 gene in a Chinese family with Darier disease. Arch Dermatol Res. Dec 2010. 302:769-72. [Medline].

  13. Lu FY, Xu L, Yin XG, Wan P, Zhang XD, Chen WW, et al. Identification of mutation c.632G>A (p.G211D) in the ATP2A2 gene and genotype-phenotype correlation in a large Chinese family with Darier's disease. Int J Dermatol. 2011 Nov. 50(11):1366-70. [Medline].

  14. Shi HJ, Li M, Zhang GL, Xu SX, Shao MH, Gu Y, et al. Novel splice-site and frameshift ATP2A2 mutations in Chinese patients with Darier disease. Clin Exp Dermatol. 2012 Aug. 37(6):677-9. [Medline].

  15. Shi BJ, Xue M, Zhong GS, Jiang Y, Chen DY, Feng J, et al. The ATP2A2 gene in patients with Darier's disease: one novel splicing mutation. Int J Dermatol. 2012 Sep. 51(9):1074-7. [Medline].

  16. Ueo D, Hamada T, Hashimoto T, Hatano Y, Okamoto O, Fujiwara S. Late-onset Darier's disease due to a novel missense mutation in the ATP2A2 gene: a different missense mutation affecting the same codon has been previously reported in acrokeratosis verruciformis. J Dermatol. 2013 Apr. 40(4):280-1. [Medline].

  17. Green EK, Gordon-Smith K, Burge SM, Grozeva D, Munro CS, Tavadia S, et al. Novel ATP2A2 mutations in a large sample of individuals with Darier disease. J Dermatol. 2013 Apr. 40(4):259-66. [Medline].

  18. Pengjun Z, Jianwen R, Biao Y. A novel missense mutation of ATP2A2 gene in a Chinese family with Darier disease. Int J Dermatol. 2014 Mar. 53(3):e204-5. [Medline].

  19. Miyabe C, Mitsuhashi Y, Saito M, Tsuboi R. Novel mutation in the ATP2A2 gene in a Japanese Darier's disease patient with extremely hyperkeratotic lesions. J Dermatol. 2012 Apr. 39(4):401-3. [Medline].

  20. Shi BJ, Xue M, Zhu YJ, Wang SP, Du Y, Chen DY, et al. Exon 12 of the ATP2A2 gene in patients with Darier disease: one novel mutation and one previously described. J Eur Acad Dermatol Venereol. 2014 Feb 19. [Medline].

  21. Miyauchi Y, Daiho T, Yamasaki K, Takahashi H, Ishida-Yamamoto A, Danko S. Comprehensive analysis of expression and function of 51 sarco(endo)plasmic reticulum Ca2+-ATPase mutants associated with Darier disease. J Biol Chem. 2006 Aug 11. 281(32):22882-95. [Medline].

  22. Müller EJ, Caldelari R, Kolly C, Williamson L, Baumann D, Richard G, et al. Consequences of depleted SERCA2-gated calcium stores in the skin. J Invest Dermatol. 2006 Apr. 126(4):721-31. [Medline].

  23. Kassar S, Tounsi-Kettiti H, Charfeddine C, Zribi H, Bchetnia M, Jerbi E, et al. Histological characterization of Darier's disease in Tunisian families. J Eur Acad Dermatol Venereol. 2009 Oct. 23(10):1178-83. [Medline].

  24. Dhitavat J, Fairclough RJ, Hovnanian A, Burge SM. Calcium pumps and keratinocytes: lessons from Darier's disease and Hailey-Hailey disease. Br J Dermatol. 2004 May. 150(5):821-8. [Medline].

  25. Dhitavat J, Cobbold C, Leslie N, Burge S, Hovnanian A. Impaired trafficking of the desmoplakins in cultured Darier's disease keratinocytes. J Invest Dermatol. 2003 Dec. 121(6):1349-55. [Medline].

  26. Leinonen PT, Hägg PM, Peltonen S, Jouhilahti EM, Melkko J, Korkiamäki T, et al. Reevaluation of the normal epidermal calcium gradient, and analysis of calcium levels and ATP receptors in Hailey-Hailey and Darier epidermis. J Invest Dermatol. 2009 Jun. 129(6):1379-87. [Medline].

  27. Celli A, Mackenzie DS, Zhai Y, Tu CL, Bikle DD, Holleran WM, et al. SERCA2-controlled Ca²+-dependent keratinocyte adhesion and differentiation is mediated via the sphingolipid pathway: a therapeutic target for Darier's disease. J Invest Dermatol. 2012 Apr. 132(4):1188-95. [Medline]. [Full Text].

  28. Savignac M, Simon M, Edir A, Guibbal L, Hovnanian A. SERCA2 Dysfunction in Darier Disease Causes Endoplasmic Reticulum Stress and Impaired Cell-to-Cell Adhesion Strength: Rescue by Miglustat. J Invest Dermatol. 2014 Jul. 134(7):1961-70. [Medline].

  29. Fong G, Capaldi L, Sweeney SM, Wiss K, Mahalingam M. Congenital Darier disease. J Am Acad Dermatol. 2008 Aug. 59(2 Suppl 1):S50-1. [Medline].

  30. Okada E, Nagai Y, Motegi S, Tamura A, Ishikawa O. Fatal case of Darier's disease with recurrent severe infections. Acta Derm Venereol. 2009. 89(4):408-9. [Medline].

  31. Woo SM, Won CH, Cho S. Darier's disease: variable clinical presentation and a fatal outcome. Clin Exp Dermatol. 2009 Jul. 34(5):628-9. [Medline].

  32. Tang C, Chan M, Lee J, Hariram J. Darier's disease and schizophrenia. East Asian Arch Psychiatry. 2010 Dec. 20(4):190-2. [Medline].

  33. Dodiuk-Gad RP, Cohen-Barak E, Khayat M, Milo H, Amariglio-Diskin L, Danial-Faran N, et al. Darier disease in Israel: combined evaluation of genetic and neuropsychiatric aspects. Br J Dermatol. 2016 Mar. 174 (3):562-8. [Medline].

  34. Cederlöf M, Bergen SE, Långström N, Larsson H, Boman M, Craddock N, et al. The association between Darier disease, bipolar disorder, and schizophrenia revisited: a population-based family study. Bipolar Disord. 2015 May. 17 (3):340-4. [Medline].

  35. Cederlöf M, Karlsson R, Larsson H, Almqvist C, Magnusson PK, Nordlind K, et al. Intellectual disability and cognitive ability in Darier disease: Swedish nation-wide study. Br J Dermatol. 2015 Jul. 173 (1):155-8. [Medline].

  36. Otley CC, Momtaz K. Induction of Darier-White disease with UVB radiation in a clinically photo-insensitive patient. J Am Acad Dermatol. 1996 May. 34(5 Pt 2):931-4. [Medline].

  37. Bernabé DG, Kawata LT, Beneti IM, Crivelini MM, Biasoli ER. Multiple white papules in the palate: oral manifestation of Darier's disease. Clin Exp Dermatol. 2009 Oct. 34(7):e270-1. [Medline].

  38. Mansura A, Maly A, Ramot Y, Zlotogorski A. Acantholytic dermatosis of the vulva. Dermatol Online J. 2015 May 18. 21 (5):[Medline].

  39. Casals M, Campoy A, Aspiolea F, Carrasco MA, Camps A. Successful treatment of linear Darier's disease with topical adapalene. J Eur Acad Dermatol Venereol. 2009 Feb. 23(2):237-8. [Medline].

  40. Abe M, Inoue C, Yokoyama Y, Ishikawa O. Successful treatment of Darier's disease with adapalene gel. Pediatr Dermatol. 2011 Mar-Apr. 28(2):197-8. [Medline].

  41. Burkhart CG, Burkhart CN. Tazarotene gel for Darier's disease. J Am Acad Dermatol. 1998 Jun. 38(6 Pt 1):1001-2. [Medline].

  42. Oster-Schmidt C. The treatment of Darier's disease with topical tazarotene. Br J Dermatol. 1999 Sep. 141(3):603-4. [Medline].

  43. Dicken CH, Bauer EA, Hazen PG, Krueger GG, Marks JG Jr, McGuire JS, et al. Isotretinoin treatment of Darier's disease. J Am Acad Dermatol. 1982 Apr. 6(4 Pt 2 Suppl):721-6. [Medline].

  44. Schmidt H, Ochsendorf FR, Wolter M, Geisslinger G, Ludwig RJ, Kaufmann R. Topical 5-fluorouracil in Darier disease. Br J Dermatol. 2008 Jun. 158(6):1393-6. [Medline].

  45. Yoon TY, Kim JW, Kim MK. Successful treatment of Darier disease with topical 5-fluorouracil. Br J Dermatol. 2006 Jun. 154(6):1210-2. [Medline].

  46. Abe M, Yasuda M, Yokoyama Y, Ishikawa O. Successful treatment of combination therapy with tacalcitol lotion associated with sunscreen for localized Darier's disease. J Dermatol. 2010 Aug. 37(8):718-21. [Medline].

  47. Pérez-Carmona L, Fleta-Asín B, Moreno-García-Del-Real C, Jaén-Olasolo P. Successful treatment of Darier's disease with topical pimecrolimus. Eur J Dermatol. 2011 Mar-Apr. 21(2):301-2. [Medline].

  48. Millán-Parrilla F, Rodrigo-Nicolás B, Molés-Poveda P, Armengot-Carbó M, Quecedo-Estébanez E, Gimeno-Carpio E. Improvement of Darier disease with diclofenac sodium 3% gel. J Am Acad Dermatol. 2014 Apr. 70(4):e89-90. [Medline].

  49. Kontochristopoulos G, Katsavou AN, Kalogirou O, Agelidis S, Zakopoulou N. Letter: Botulinum toxin type A: an alternative symptomatic management of Darier's disease. Dermatol Surg. 2007 Jul. 33(7):882-3. [Medline].

  50. Letulé V, Herzinger T, Ruzicka T, Molin S. Treatment of Darier disease with oral alitretinoin. Clin Exp Dermatol. 2013 Jul. 38(5):523-5. [Medline].

  51. Zamiri M, Munro CS. Successful treatment with oral alitretinoin in women of childbearing potential with Darier's disease. Br J Dermatol. 2013 Sep. 169(3):709-10. [Medline].

  52. Farb RM, Lazarus GS, Chiaramonti A, Goldsmith LA, Gilgor RS, Balakrishnan CV. The effect of 13-cis retinoic acid on epidermal lysosomal hydrolase activity in Darier's disease and pityriasis rubra pilaris. J Invest Dermatol. 1980 Aug. 75(2):133-5. [Medline].

  53. Suzuki K, Aoki M, Kawana S. Localized Darier's disease of the scalp: successful treatment with oral etretinate. Dermatology. 2004. 208(1):83-4. [Medline].

  54. Kamijo M, Nishiyama C, Takagi A, Nakano N, Hara M, Ikeda S, et al. Cyclooxygenase-2 inhibition restores ultraviolet B-induced downregulation of ATP2A2/SERCA2 in keratinocytes: possible therapeutic approach of cyclooxygenase-2 inhibition for treatment of Darier disease. Br J Dermatol. 2012 May. 166(5):1017-22. [Medline].

  55. Wheeland RG, Gilmore WA. The surgical treatment of hypertrophic Darier's disease. J Dermatol Surg Oncol. 1985 Apr. 11(4):420-3. [Medline].

  56. Toombs EL, Peck GL. Electrosurgical treatment of etretinate-resistant Darier's disease. J Dermatol Surg Oncol. 1989 Dec. 15(12):1277-80. [Medline].

  57. Brown VL, Kelly SE, Burge SM, Walker NP. Extensive recalcitrant Darier disease successfully treated with laser ablation. Br J Dermatol. 2010 Jan. 162(1):227-9. [Medline].

  58. McElroy JA, Mehregan DA, Roenigk RK. Carbon dioxide laser vaporization of recalcitrant symptomatic plaques of Hailey-Hailey disease and Darier's disease. J Am Acad Dermatol. 1990 Nov. 23(5 Pt 1):893-7. [Medline].

  59. Minsue Chen T, Wanitphakdeedecha R, Nguyen TH. Carbon dioxide laser ablation and adjunctive destruction for Darier-White disease (keratosis follicularis). Dermatol Surg. 2008 Oct. 34(10):1431-4. [Medline].

  60. Beier C, Kaufmann R. Efficacy of erbium:YAG laser ablation in Darier disease and Hailey-Hailey disease. Arch Dermatol. 1999 Apr. 135(4):423-7. [Medline].

  61. Roos S, Karsai S, Ockenfel HM, Raulin C. Successful treatment of Darier disease with the flashlamp-pumped pulsed-dye laser. Arch Dermatol. 2008 Aug. 144(8):1073-5. [Medline].

  62. Katz TM, Firoz BF, Goldberg LH, Friedman PM. Treatment of Darier's disease using a 1,550-nm erbium-doped fiber laser. Dermatol Surg. 2010. 36(1):142-6. [Medline].

  63. Krakowski AC, Nguyen TA, Eichenfield LF. Treatment of segmental keratosis follicularis (Darier disease) using ablative fractional laser resurfacing. Dermatol Surg. 2015 Apr. 41 (4):516-8. [Medline].

  64. Minsue Chen T, Wanitphakdeedecha R, Nguyen TH. Carbon dioxide laser ablation and adjunctive destruction for Darier-White disease (keratosis follicularis). Dermatol Surg. 2008 Oct. 34(10):1431-4. [Medline].

  65. Kittridge A, Wahlgren C, Fuhrer R, Zirwas M, Patton T. Treatment of recalcitrant Darier's disease with electron beam therapy. Dermatol Ther. 2010 May-Jun. 23(3):302-4. [Medline].

  66. Exadaktylou D, Kurwa HA, Calonje E, Barlow RJ. Treatment of Darier's disease with photodynamic therapy. Br J Dermatol. 2003 Sep. 149(3):606-10. [Medline].

  67. Avery HL, Hughes BR, Coley C, Cooper HL. Clinical improvement in Darier's disease with photodynamic therapy. Australas J Dermatol. 2010 Feb. 51(1):32-5. [Medline].

  68. Ahcan U, Dolenc-Voljc M, Zivec K, Zorman P, Jurcic V. The surgical treatment of hypertrophic intertriginous Darier's disease. J Plast Reconstr Aesthet Surg. 2009 Nov. 62(11):e442-6. [Medline].

  69. Jacobsen NJ, Lyons I, Hoogendoorn B, Burge S, Kwok PY, O'Donovan MC, et al. ATP2A2 mutations in Darier's disease and their relationship to neuropsychiatric phenotypes. Hum Mol Genet. 1999 Sep. 8(9):1631-6. [Medline].

Previous
Next
 
Typical distribution of keratotic papules in the seborrheic regions. Courtesy of Susan Mallory, MD, Director of Pediatric Dermatology, Washington University School of Medicine.
Longitudinal ridges, red and white lines, and V-shaped nicks. Courtesy of Susan Mallory, MD, Director of Pediatric Dermatology, Washington University School of Medicine.
Acantholysis and dyskeratosis (abnormal keratinization) are the 2 main features of Darier disease. Loss of epidermal adhesion with acantholysis frequently results in the formation of suprabasal clefts (lacunae).
 
 
 
All material on this website is protected by copyright, Copyright © 1994-2016 by WebMD LLC. This website also contains material copyrighted by 3rd parties.