Keratosis Follicularis (Darier Disease) Treatment & Management

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

Medical Care

Basic measures for keratosis follicularis (Darier disease) are as follows:

  • Sunscreen, cool cotton clothing, and avoidance of hot environments can help prevent flares, especially during the summer.
  • Moisturizers with urea or lactic acid can reduce scaling and hyperkeratosis.
  • A low- or mid-potency topical steroid is sometimes useful for inflammation.
  • When bacterial overgrowth is suspected or crusting is prominent, application of antiseptics such as triclosan or soaks in astringents such as Burrow or Domeboro solution can be helpful.

Topical medications for keratosis follicularis (Darier disease) are as follows:

  • Case reports have shown that topical retinoids (adapalene,[17] tazarotene gel 0.01%,[18, 19] tretinoin[20] ) can reduce hyperkeratosis in 3 months. However, irritation is a limiting factor.
  • Emollients and topical corticosteroids can be used in combination with topical retinoids to reduce irritation.
  • Topical 5-fluorouracil (5-FU) has been used effectively in some patients.[21, 22]

Injectables: Injection of botulinum toxin type A was reported in one case to significantly relieve the discomforting symptoms associated with keratosis follicularis (Darier disease) located in the submammary areas.[23]

Systemic medications for keratosis follicularis (Darier disease) are as follows:

  • Oral retinoids (eg, acitretin, isotretinoin,[20] etretinate) have been the most effective medical treatment for keratosis follicularis (Darier disease) , achieving some reduction of symptoms in 90% of patients. They reduce hyperkeratosis, smoothen papules, and reduce odor. In a study of 11 patients, 5 with keratosis follicularis (Darier disease) and 6 with pityriasis rubra pilaris, significant improvement occurred with isotretinoin therapy. All 11 patients received isotretinoin at 0.5 mg/kg/d, increasing to a maximum dose of 4 mg/kg/d, for a period of 16 weeks. Greater than 50% improvement occurred in all 5 patients with keratosis follicularis (Darier disease) and in 5 of 6 patients with pityriasis rubra pilaris. One patient showed no clinical improvement. Upon discontinuation of therapy, relapse occurred in all but 1 patient with pityriasis rubra pilaris.[24]
  • Acitretin is effective at 0.6 mg/kg/d. The starting dose is 10-25 mg/d, which is gradually increased as tolerated.
  • Isotretinoin at 0.5-1 mg/kg/d is especially useful in females of childbearing age because pregnancy need only be avoided for 1 month after stopping treatment. Unfortunately, prolonged remissions, such as those noted with isotretinoin for severe acne, are not seen in keratosis follicularis (Darier disease).
  • Etretinate has been reported useful if acitretin fails.[25]
  • Prolonged use of oral retinoids is limited by their significant adverse effects, including mucosal dryness, photosensitivity, hyperlipidemia, transaminitis, and skeletal hyperostosis. Oral retinoids are teratogenic, and appropriate counseling and contraception must be given.
  • Oral antibiotics are often necessary to clear secondary bacterial superinfection. They may also be used as prophylaxis to prevent infection.
  • Oral acyclovir may be used to treat or suppress herpes simplex virus infection.
  • Oral contraceptives have been reported to help with perimenstrual keratosis follicularis (Darier disease) flares.
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Surgical Care

Surgical treatments to be considered for keratosis follicularis (Darier disease) are as follows:

  • Dermabrasion has been used to smooth the hyperkeratotic lesions of keratosis follicularis (Darier disease), with acceptable results.[26]
  • Electrosurgery[27] and Mohs micrographic surgery have been used to treat localized keratosis follicularis (Darier disease) areas, with good results.
  • Amongst newer modalities, laser ablation of recalcitrant plaques has been reported in 7 keratosis follicularis (Darier disease) patients. Of these, 3 patients were treated with carbon dioxide lasers,[28, 29, 30] 2 with Er:YAG lasers,[31] and 2 with pulsed-dye lasers.[32] In all of these cases, treatment was successful, with only one patient developing disease recurrence in her axilla 7 months after treatment. Another report describes resolution of disease using 1550-nm erbium-doped fractional fiber laser.[33]
  • Carbon dioxide laser ablation with adjunctive dermabrasion, curettage, and shave excision in various combinations have also been reported to cause disease remission for 8 months to 2 years.[34]
  • Photodynamic therapy with 5-aminolevulinic acid was used to treat keratosis follicularis (Darier disease) lesions in 6 patients, with 4 patients showing sustained improvement or clearance for a follow-up period of 6 months to 3 years.[35, 36]
  • Surgical excision of hypertrophic intertriginous keratosis follicularis has been described in one case report.[37]
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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].

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  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].

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  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].

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

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  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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