eMedicine Specialties > Dermatology > Papulosquamous Diseases

Keratosis Follicularis (Darier Disease): Treatment & Medication

Author: Pui-Yan Kwok, MD, PhD, Henry Bachrach Distinguished Professor, Department of Dermatology and Cardiovascular Research Institute, University of California, San Francisco
Coauthor(s): Sarah Fitzmaurice, BS, MS, University of California Davis School of Medicine; Wilson Liao, MD, Assistant Professor, Department of Dermatology, University of California at San Francisco
Contributor Information and Disclosures

Updated: Feb 25, 2009

Treatment

Medical Care

  • Basic measures
    • 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
    • Case reports have shown that topical retinoids (adapalene, tazarotene gel 0.01%,12,13 tretinoin14 ) 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.15,16
  • 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.17
  • Systemic medications
    • Oral retinoids (eg, acitretin, isotretinoin,14 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.18
    • 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.19
    • 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.

Surgical Care

  • Dermabrasion has been used to smooth the hyperkeratotic lesions of keratosis follicularis (Darier disease), with acceptable results.20
  • Electrosurgery21 and Mohs micrographic surgery have been used to treat localized keratosis follicularis (Darier disease) areas, with good results.
  • Amongst newer modalities, carbon dioxide laser ablation of recalcitrant plaques has been reported in 2 keratosis follicularis (Darier disease) patients, and the Er:YAG laser (which has a decreased risk of thermal injury) has been used in another 2 patients. In these cases, remission of the treated lesions and alleviation of pruritus lasted at least 11 and 20 months.22 Another report described resolution of disease lasting more than 15 months following treatment with a flashlamp-pumped pulsed-dye laser.23
  • Carbon dioxide laser ablation with adjunctive dermabrasion, curettage, and shave excision in various combination has also been reported to cause disease remission for 8 months to 2 years.24
  • 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.25

Medication

The goals of pharmacotherapy are to reduce morbidity and prevent complications.

Retinoids

These agents decrease cohesiveness of abnormal hyperproliferative keratinocytes and may reduce potential for malignant degeneration. They also modulate keratinocyte differentiation.


Adapalene (Differin)

Modulates cellular differentiation, inflammation, and keratinization. May be tolerated by individuals who cannot tolerate tretinoin creams. Available as 0.1% gel or solution.

Adult

Apply hs; some patients may tolerate bid dosing

Pediatric

Not established

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Avoid contact with mucous membranes, eyes, mouth, and nostrils; avoid exposure to sunlight and sunlamps; dryness of skin, scaling, erythema, burning, and pruritus may occur


Tazarotene (Avage, Tazorac)

Retinoid prodrug whose active metabolite modulates differentiation and proliferation of epithelial tissue; may also have anti-inflammatory and immunomodulatory properties.

Adult

Apply thin film (ie, 2 mg/cm2) hs to clean, dry skin where lesions appear

Pediatric

Children: Not established
Adolescents: Administer as in adults

Do not use concomitantly with dermatologic drugs or cosmetics that have a strong drying effect on the skin (eg, salicylic acid, benzoyl peroxide, astringents)

Pregnancy

X - Contraindicated; benefit does not outweigh risk

Precautions

May cause burning or stinging sensations; discontinue if excessive irritation occurs; rinse thoroughly if contact with eyes, eyelids, or mouth; may cause severe irritation in eczematous skin; photosensitivity may occur


Tretinoin (Avita, Altinac, Renova, Retin-A)

Inhibits microcomedo formation and eliminates lesions present. Makes keratinocytes in sebaceous follicles less adherent and easier to remove. Available as 0.025, 0.05, and 0.1% creams or 0.01 and 0.025% gels.

Adult

Begin with lowest concentration of tretinoin formulation and increase as tolerated; apply hs or qod; lower frequency of application if irritation develops

Pediatric

<12 years: Not established
>12 years: Administer as in adults

Other skin irritants (ie, astringents, benzoyl peroxide, salicylic acid, resorcinol, topical sulfur, other keratolytics, abrasives, astringents, spices, lime) may exacerbate irritation; coadministration with other drugs causing photosensitivity (eg, tetracycline, sulfonamides) may increase risk of sunburn

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Photosensitivity may occur with excessive sunlight exposure; burning, stinging, peeling, pruritus, or erythema has been reported at site of application; caution with eczema (may cause severe irritation); avoid contact with mucous membranes, mouth, and angles of nose


Acitretin (Soriatane)

Metabolite of etretinate and related to both retinoic acid and retinol (vitamin A). Mechanism of action unknown.

Adult

0.5-0.75 mg/kg/d PO; alternatively, 10-25 mg/d PO gradually increased to 35 mg/d as tolerated

Pediatric

1 mg/kg/d PO; quickly reduce to minimal effective dose

Increases toxicity of methotrexate (avoid concomitant use); interferes with effects of microdose progestin minipill; coadministration with alcohol may result in formation of etretinate, which has much longer half-life than acitretin (>120 d); may increase toxicity of phenytoin; toxicity may occur with vitamin A coadministration

Documented hypersensitivity; intention of pregnancy during or within 3 y of therapy; severely impaired liver/kidney function; chronic abnormal elevated lipid levels; concomitant use of methotrexate; concomitant use of tetracyclines; ingestion of alcohol (in females of reproductive potential)

Pregnancy

X - Contraindicated; benefit does not outweigh risk

Precautions

Do not use in severe obesity; women of childbearing age must be capable of complying with effective contraceptive measures; recommended that contraception be continued for at least 3 y after stopping treatment; etretinate may form from acitretin, which takes approximately 2-3 y to clear from body; caution if impaired renal or liver function; perform AST, ALT, and LDH tests prior to initiation of therapy at 1- to 2-wk intervals until stable and thereafter at intervals as clinically indicated


Isotretinoin (Accutane, Amnesteem, Claravis, Sotret)

Oral agent that treats serious dermatologic conditions. Synthetic 13-cis isomer of the naturally occurring tretinoin (trans -retinoic acid). Both agents are structurally related to vitamin A. Decreases sebaceous gland size and sebum production. May inhibit sebaceous gland differentiation and abnormal keratinization.
A US Food and Drug Administration–mandated registry is now in place for all individuals prescribing, dispensing, or taking isotretinoin. For more information on this registry, see iPLEDGE. This registry aims to further decrease the risk of pregnancy and other unwanted and potentially dangerous adverse effects during a course of isotretinoin therapy.

Adult

Initial dose: 0.5 mg/kg/d
Maintenance dose: 1.8 mg/kg/d for 16 wk, followed by a rest period of at least 8 wk; drug treatment restarted if significant flare of disease

Pediatric

Not established

Toxicity may occur with vitamin A coadministration; pseudotumor cerebri or papilledema may occur when coadministered with tetracyclines; may reduce plasma levels of carbamazepine
Increases toxicity of methotrexate (avoid concomitant use); interferes with effects of microdose progestin minipill; coadministration with alcohol may result in formation of etretinate, which has much longer half-life than acitretin (>120 d); may increase toxicity of phenytoin

Pregnancy

X - Contraindicated; benefit does not outweigh risk

Precautions

May decrease night vision; inflammatory bowel disease may occur; may be associated with development of hepatitis and pancreatitis; diabetes patients may experience problems in controlling blood glucose while on isotretinoin; avoid exposure to UV light or sunlight until tolerance achieved; discontinue treatment if rectal bleeding, abdominal pain, or severe diarrhea occurs; mood swings or depression may occur; caution in history of depression


Etretinate (Tegison)

Not available in the United States. Retinoic acid analog. Mechanism of action unknown.

Adult

25-75 mg/d PO

Pediatric

Not established

Do not use in severe obesity; toxicity may occur with vitamin A coadministration; absorption increased with milk; increases toxicity of methotrexate (avoid concomitant use); interferes with effects of microdose progestin minipill

Documented hypersensitivity; severe obesity

Pregnancy

X - Contraindicated; benefit does not outweigh risk

Precautions

Women of childbearing age must be capable of using effective contraceptive measures; perform AST, ALT, and LDH tests prior to therapy at 1- to 2-wk intervals until levels stabilize and thereafter at intervals as clinically indicated

More on Keratosis Follicularis (Darier Disease)

Overview: Keratosis Follicularis (Darier Disease)
Differential Diagnoses & Workup: Keratosis Follicularis (Darier Disease)
Treatment & Medication: Keratosis Follicularis (Darier Disease)
Multimedia: Keratosis Follicularis (Darier Disease)
References
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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. 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].

  4. 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].

  5. 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].

  6. 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].

  7. 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].

  8. 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].

  9. 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].

  10. 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].

  11. 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].

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

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

  14. 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].

  15. 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].

  16. 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].

  17. 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].

  18. 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].

  19. 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].

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

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

  22. 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].

  23. 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].

  24. 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].

  25. 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].

  26. Burge S. Management of Darier's disease. Clin Exp Dermatol. Mar 1999;24(2):53-6. [Medline].

  27. Burge SM, Wilkinson JD. Darier-White disease: a review of the clinical features in 163 patients. J Am Acad Dermatol. Jul 1992;27(1):40-50. [Medline].

  28. Sehgal VN, Srivastava G. Darier's (Darier-White) disease/keratosis follicularis. Int J Dermatol. Mar 2005;44(3):184-92. [Medline].

  29. Szigeti R, Kellermayer R. Autosomal-dominant calcium ATPase disorders. J Invest Dermatol. Nov 2006;126(11):2370-6. [Medline].

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Further Reading

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Keywords

keratosis follicularis, Darier disease, Darier-White disease, DD, Darier's disease, warty plaques, malodorous plaques, hypertrophic DD, hypertrophic Darier disease, vesicobullous DD, vesiculobullous Darier disease, linear DD, linear Darier disease, segmental DD, segmental Darier disease

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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 Society of Human Genetics, and Society for Investigative Dermatology
Disclosure: Nothing to disclose.

Coauthor(s)

Sarah Fitzmaurice, BS, MS, University of California Davis School of Medicine
Sarah Fitzmaurice, BS, MS is a member of the following medical societies: American Medical Association and Student National Medical Association
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.

Medical Editor

James W Patterson, MD, Director of Dermatopathology, Professor of Pathology and Dermatology, Departments of Pathology and Dermatology, 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 Medical Association, American Society of Dermatopathology, Medical Society of Virginia, Royal Society of Medicine, Society for Investigative Dermatology, and United States and Canadian Academy of Pathology
Disclosure: Nothing to disclose.

Pharmacy Editor

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.

Managing Editor

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: Nothing to disclose.

CME Editor

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 None; Genentech Consulting fee Consulting; Centocor Consulting fee Consulting; Centocor Grant/research funds None; Covance Consulting fee Consulting; Shire  Consulting

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.

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