Keratosis Follicularis (Darier Disease) Clinical Presentation

  • Author: Pui-Yan Kwok, MD, PhD; Chief Editor: Dirk M Elston, MD   more...
 
Updated: May 14, 2010
 

History

Most patients with keratosis follicularis (Darier disease) have a family history of the disease. The pattern of inheritance is autosomal dominant. However, some patients, up to 47% in one series, have no clear family history. These cases may represent sporadic mutations, or these patients may have family members with mild disease that was not recognized.

  • The first skin lesions typically occur in the teenage years and are frequently associated with pruritus.
  • Heat, sweat, humidity, sunlight, UVB exposure,[13] lithium, oral corticosteroids, and mechanical trauma have been reported to exacerbate keratosis follicularis (Darier disease). Some females report flares around menstruation.
  • Even though the severity of keratosis follicularis (Darier disease) fluctuates over time, keratosis follicularis (Darier disease) is a chronic, unremitting condition. In one study, one third of patients noted improvement of the condition with age; however, another one third of patients showed worsening of the disease with age.
  • Although neuropsychiatric abnormalities such as epilepsy, mental impairment, and mood disorders have been associated with keratosis follicularis (Darier disease), no evidence indicates that mutations in ATP2A2 are associated with these disorders.[14] One study suggests that a susceptibility locus for bipolar disorder co-segregates with the keratosis follicularis (Darier disease) region, but it is distinct from the keratosis follicularis (Darier disease)–causing mutation.[15]
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Physical

The lesions may first appear as skin-colored or yellow-brown papules with a greasy, warty texture. These lesions are especially common in seborrheic areas such as the forehead, scalp, margin of the scalp, nasolabial folds, ears, chest, and back (see the image below). Approximately 80% of patients have mild flexural involvement with scattered papules in the groin, axillae, or, in women, submammary skin. In less than 10% of patients, flexural disease predominates, with large, warty, vegetative plaques in the axillae, groin, or perineum. These large flexural lesions are especially bothersome to patients because of their malodor.

Typical distribution of keratotic papules in the sTypical distribution of keratotic papules in the seborrheic regions. Courtesy of Susan Mallory, MD, Director of Pediatric Dermatology, Washington University School of Medicine.
  • Involvement of the hands is very common (approximately 95%). Lesions on the palms include punctate keratoses (80%), palmar pits (80%), and hemorrhagic macules (< 10%). Acrokeratosis verruciformis–like lesions (warty flat-topped papules on the dorsal hands) are present in approximately half the patients. Interestingly, several patients with acrokeratosis verruciformis of Hopf (who have dorsal hand lesions only) have been found to harbor mutations in ATP2A2, suggesting this condition may actually be a localized form of keratosis follicularis (Darier disease).
  • Nail changes in keratosis follicularis (Darier disease) provide important diagnostic clues (see the image below). White and red longitudinal bands, longitudinal nail ridges, longitudinal splitting, and subungual hyperkeratosis are frequently found. A sandwich of red and white longitudinal bands, often with a V-shaped nick at the free margin of the nail, is the most pathognomonic nail finding in persons with keratosis follicularis (Darier disease). These changes on the hands can also occur on the feet, albeit less commonly. Longitudinal ridges, red and white lines, and V-shLongitudinal ridges, red and white lines, and V-shaped nicks. Courtesy of Susan Mallory, MD, Director of Pediatric Dermatology, Washington University School of Medicine.
  • Mucosal lesions are detected in approximately 15% of patients, and they appear as white papules with a central depression. These cobblestone lesions are most commonly found in the mouth, but they also may occur on the anogenital mucosa. At times, oral lesions may affect the salivary glands and cause obstruction.[16]
  • Clinical variants of keratosis follicularis (Darier disease) include hypertrophic and vesicobullous types. Linear or segmental keratosis follicularis (Darier disease) has been shown in some cases to result from genetic mosaicism of ATP2A2.
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Causes

See Pathophysiology.

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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

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

Disclosure: Nothing to disclose.

Coauthor(s)

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 Association of Physicians of Indian Origin, American Medical Association, American Medical Women's Association, Indian Medical Association, and National Psoriasis Foundation

Disclosure: Nothing to disclose.

Wilson Liao, MD  Assistant Professor, Department of Dermatology, University of California at San Francisco

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

Disclosure: Nothing to disclose.

Specialty Editor Board

James W Patterson, MD  Professor of Pathology and Dermatology, Director of Dermatopathology, University of Virginia Medical Center

James W Patterson, MD is a member of the following medical societies: American Academy of Dermatology, American College of Physicians, American Society of Dermatopathology, Royal Society of Medicine, Society for Investigative Dermatology, and United States and Canadian Academy of Pathology

Disclosure: Nothing to disclose.

Michael J Wells, MD  Associate Professor, Department of Dermatology, Texas Tech University Health Sciences Center

Michael J Wells, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Medical Association, and Texas Medical Association

Disclosure: Nothing to disclose.

Rosalie Elenitsas, MD  Herman Beerman Associate Professor of Dermatology, University of Pennsylvania School of Medicine; Director, Penn Cutaneous Pathology Services, Department of Dermatology, University of Pennsylvania Health System

Rosalie Elenitsas, MD is a member of the following medical societies: American Academy of Dermatology and American Society of Dermatopathology

Disclosure: Lippincott Williams Wilkins Royalty Textbook editor; DLA Piper Consulting fee Consulting

Joel M Gelfand, MD, MSCE  Medical Director, Clinical Studies Unit, Assistant Professor, Department of Dermatology, Associate Scholar, Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania

Joel M Gelfand, MD, MSCE is a member of the following medical societies: Society for Investigative Dermatology

Disclosure: AMGEN Consulting fee Consulting; AMGEN Grant/research funds Investigator; Genentech Grant/research funds investigator; Centocor Consulting fee Consulting; Abbott Grant/research funds investigator; Abbott Consulting fee Consulting; Novartis investigator; Pfizer Grant/research funds investigator; Celgene Consulting fee DMC Chair; NIAMS and NHLBI Grant/research funds investigator

Chief Editor

Dirk M Elston, MD  Director, Department of Dermatology, Geisinger Medical Center

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

Disclosure: Nothing to disclose.

References

  1. Sakuntabhai A, Ruiz-Perez V, Carter S, et al. Mutations in ATP2A2, encoding a Ca2+ pump, cause Darier disease. Nat Genet. Mar 1999;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. Apr 2004;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. Jun 2009;145(6):654-6. [Medline].

  4. Miyauchi Y, Daiho T, Yamasaki K, et al. Comprehensive analysis of expression and function of 51 sarco(endo)plasmic reticulum Ca2+-ATPase mutants associated with Darier disease. J Biol Chem. Aug 11 2006;281(32):22882-95. [Medline].

  5. Muller EJ, Caldelari R, Kolly C, et al. Consequences of depleted SERCA2-gated calcium stores in the skin. J Invest Dermatol. Apr 2006;126(4):721-31. [Medline].

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

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

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

  9. Leinonen PT, Hagg PM, Peltonen S, 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. Dec 4 2008;[Medline].

  10. 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].

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

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

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

  14. Jacobsen NJ, Lyons I, Hoogendoorn B, et al. ATP2A2 mutations in Darier's disease and their relationship to neuropsychiatric phenotypes. Hum Mol Genet. Sep 1999;8(9):1631-6. [Medline].

  15. Jones I, Jacobsen N, Green EK, Elvidge GP, Owen MJ, Craddock N. Evidence for familial cosegregation of major affective disorder and genetic markers flanking the gene for Darier's disease. Mol Psychiatry. 2002;7(4):424-7. [Medline].

  16. Bernabe DG, Kawata LT, Beneti IM, Crivelini MM, Biasoli ER. Multiple white papules in the palate: oral manifestation of Darier's disease. Clinical and Experimental Dermatology. 2009;34:e270-e271.

  17. 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. Feb 2009;23(2):237-8. [Medline].

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

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

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

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

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

  23. 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. Jul 2007;33(7):882-3. [Medline].

  24. 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. Aug 1980;75(2):133-5. [Medline].

  25. 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].

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

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

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

  29. 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. Nov 1990;23(5 Pt 1):893-7. [Medline].

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

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

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

  33. Katz TM, Firoz BF, Goldberg LH, Friedman PM. Treatment of Darier's disease using a 1550nm erbium doped fiber laser. Dermatol Surg. 2010;36:142-146.

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

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

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

  37. 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. Nov 2009;62(11):e442-6. [Medline].

 
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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).
 
 
 
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