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Year : 2020  |  Volume : 11  |  Issue : 1  |  Page : 72-78  

Darier's disease - response to oral Vitamin A: report of a case and brief review

Department of Dermatology, Venereology and Leprosy, Dr. R.P. Govt. Medical College, Kangra (Tanda), Himachal Pradesh, India

Date of Web Publication13-Jan-2020

Correspondence Address:
Vikram K Mahajan
Department of Dermatology, Venereology and Leprosy, Dr. R.P. Govt. Medical College, Kangra (Tanda) - 176 001, Himachal Pradesh
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/idoj.IDOJ_85_19

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Darier's disease is an uncommon chronic dermatosis of autosomal dominant inheritance with significant psychosocial morbidity and shows unsatisfactory response to several topical and systemic therapies or various resurfacing or surgical procedure. A 24-year-old woman having characteristic asymptomatic and progressive, hyperkeratotic papular lesions involving the scalp, face, upper trunk, and dorsal hands and feet was diagnosed clinicopathologically as Darier's disease. She was treated successfully with oral Vitamin A 25000 IU given twice daily. The response was apparent within 4 weeks and most lesions cleared in 2 months without any adverse effects. Oral Vitamin A provides an effective and safe low-cost therapeutic alternative in Darier's disease, especially when systemic retinoids, the only effective treatment, remain contraindicated or is not tolerated and for maintenance therapy in the long-term.

Keywords: Darier-white disease, keratosis follicularis, retinoids, Vitamin A

How to cite this article:
Sondhi M, Vashist S, Mahajan VK. Darier's disease - response to oral Vitamin A: report of a case and brief review. Indian Dermatol Online J 2020;11:72-8

How to cite this URL:
Sondhi M, Vashist S, Mahajan VK. Darier's disease - response to oral Vitamin A: report of a case and brief review. Indian Dermatol Online J [serial online] 2020 [cited 2020 Aug 8];11:72-8. Available from: http://www.idoj.in/text.asp?2020/11/1/72/275686

   Introduction Top

Darier's disease (synonyms: Keratosis follicularis, Darier-White disease) is an uncommon chronic dermatosis of autosomal dominant inheritance. It's response to a plethora of therapeutic modalities such as topical keratolytics, steroids, 5-fluorouracil, pimecrolimus or retinoid creams, systemic retinoids or antibiotics, Er:Yag, pulse-dye or CO2 laser and other fractional resurfacing devices, electron beam therapy, photodynamic therapy, dermabrasion, electrosurgery, and surgical excision vary from inconsistent to complete failure.[1],[2] We describe a patient with Darier's disease who showed complete clearance of skin lesions two months after treatment with oral Vitamin A and also briefly review cases described in English literature.

   Case Report Top

A 24-year-old woman, born to otherwise healthy non-consanguineous parents after an uneventful pregnancy, presented with numerous asymptomatic hyperkeratotic papular lesions over scalp, forehead and face [Figure 1]a and [Figure 1]b, neck, and chest predominantly involving seborrheic areas for more than 2 years with infrequent remissions and relapses. They were progressively increasing in number and had also appeared over dorsal hands [Figure 1]c and feet during last few months. The examination also showed fine punctate pitting over palms [Figure 2]a and soles, and white longitudinal streaks over fingernails and “V” shaped nicks at their free end [Figure 2]b. Hair and mucosae showed no abnormality. Her 21-year-old maternal sister also had similar lesions while her 18-month-old daughter, two younger siblings, and parents were reportedly healthy. Her other medical and obstetric history and systemic examination were unremarkable. Biopsy from the lesion showed features consistent with Darier's disease [Figure 3]. Laboratory investigations including complete hemogram, blood sugar, lipidogram, thyroid, liver and renal function tests, and urinalysis revealed no abnormalities. Treatment with ketoconazole (2%) shampoo for alternate day scalp washing, topical clobetasol propionate 0.05% + salicylic acid 3% lotion for once daily scalp application, and bland emollient for face and body application for two months did not benefit. Oral treatment with water-miscible Vitamin A palmitate 25000 IU twice daily (Aquasol A®, USV Pvt Ltd, Mumbai) and bland emollients for face/skin was initiated as she was breastfeeding. Her lesions started improving 4 weeks after treatment and her scalp, face [Figure 4]a and [Figure 4]b and dorsal hands [Figure 4]c and body lesions cleared almost completely 2 months after this treatment. At a recent visit, she was highly satisfied with near total clearance of her skin lesions. She did not show any evidence of hepatotoxicity, blurred vision, drowsiness, mild frontal headache, and dryness of lips or nose associated usually with very high cumulated doses of vitamin A. The dose of Vitamin A was reduced to 25000 IU once daily for maintenance, and she was asked to follow-up regularly.
Figure 1: (a and b) Numerous keratotic and comedo-like lesions over forehead, mid face, nasolabial folds, and temple at the hairline. (c) Multiple keratotic papules over dorsal hand. Similar lesions were present over dorsal feet

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Figure 2: (a) Characteristic multiple palmar pits. (b) Alternating longitudinal white and red streaks over nail plate with V-shape nicking (inset) of free edge of nail plate (arrow)

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Figure 3: Extensive hyperkeratosis (HK), papillomatosus (P), corp ronds and grains (arrows) in the stratum granulosum, suprabasal acantholytic clefting (C) with villus-like dermal papillae (P) projecting into it, no acantholytic cells, and minimal dermal infiltrate are notable features (stain, H and E, ×40, inset ×10)

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Figure 4: (a and b) Substantial clearance of all facial lesions at 2 months after oral Vitamin A therapy. (c) Substantial clearance of all lesions over dorsal hands at 2 months after oral Vitamin A therapy

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   Discussion Top

Treatment of Darier's disease mostly remains unsatisfactory, and it tends to persist for life with partial remissions. Exacerbations are frequent from heat, sweat, humidity, and secondary bacterial infections. Although systemic antibiotics help to control flare-ups from bacterial infections, oral retinoids (acitretin, isotretinoin, and alitretinoin) remain the mainstay of treatment as they decrease hyperkeratosis and smoothen keratotic papules in Darier's disease.[1],[3] However, significant adverse effects (mucocutaneous dryness, hyperlipidemia, skeletal hyperostosis, transaminits, and pseudotumor cerebri) in general and teratogenicity concerns, in particular, limit their use in practice.[4],[5] Moreover, long-term remissions cannot be maintained after stopping retinoids. Oral Vitamin A had been used to treat Darier's disease prior to retinoids became widely acceptable treatment option. A PubMed search for use of oral Vitamin A in Darier's disease on Mar 29, 2019 showed 8 reports comprising 28 cases published in English literature between 1941 and 1987 [Table 1].[6],[7],[8],[9],[10],[11],[12],[13] Their review shows that oral Vitamin A had been used safely in doses between 18000 and 240,000 IU/day with significant efficacy in them without obvious hypovitaminosis A. The overall outcome was graded as complete clearance in 4, considerable, great or much improvement in 6, 80% improvement in one, 50% improvement in 2, and some or slight improvement in 7 patients, respectively. Three patients who did not benefit with Vitamin A alone improved significantly even at reduced dose after addition of Vitamin E (1200 IU/day) given for 7 months to 2 years. Overall, 5 patients did not benefit at all. Porter et al.[8] had used a cumulative dose as high as 21,000,000 IU to 30,000,000 IU of Vitamin A in their six patients given over a period of 3 to 30 months with results varying from none to great improvement. They also reviewed 11 additional cases treated successfully with oral Vitamin A between 1941 and 1942 (original reports could not be retrieved). We also observed highly encouraging results in our patient just one month after initiating treatment and substantial clearance of all lesions two months after oral Vitamin A, whereas response to topical therapies for 2 months remained unsatisfactory.
Table 1: Clinical studies using oral Vitamin A in the treatment of Darier's disease

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Vitamin A is important for retinal photoreceptor function, epithelial proliferation, and keratinization. However, any attempt to delineate the mechanism of therapeutic efficacy of Vitamin A in Darier's disease will be speculative. Darier's disease results from a mutation in ATP2A2 gene encoding sarcoplasmic/endoplasmic reticulum Ca2+-ATP isoform 2 protein (SERCA2) mapped to chromosome 12q23-24.1 that affects cell adhesion. The defect manifests clinically with characteristic skin lesions, and pathognomic features of suprabasal acantholysis, corps ronds, and grains (dyskeratosis cells) in the stratum corneum as in our patient. The two clinically important and active metabolites of Vitamin A are retinal, a key component of rhodopsin generation in retina, and retinoic acid that regulates keratinization, cell differentiation, and immune competence.[14],[15] Retinoic acid acts on transcriptional regulation of hundreds of genes involved in many processes such as embryogenesis, growth, cell multiplication and differentiation, apoptosis, immunity, hematopoiesis, spermatogenesis, and bone/tissue homeostasis.[14],[15],[16] Retinoids, natural or synthetic derivatives of retinol (Vitamin-A alcohol) with activity and a toxicity profile similar to Vitamin A, too have a profound effect on epithelial cell growth, differentiation, cellular tonofilaments-desmosomes adhesiveness, and keratinocyte apoptosis in various hyperproliferative, keratinizing, inflammatory, and malignant dermatoses through diverse biological activity.[17],[18] We hypothesize that Vitamin A perhaps exerts its retinoid-like therapeutic effect in Darier's disease by virtue of its retinoic acid metabolite. Because low blood level of Vitamin A is not in itself indicative of deficiency and its high levels have no permanent influence on clinical condition in each case, it has been suggested that a subset of patients respond slowly and might be considered non-responders if treatment is discontinued early.[7],[8],[9] This warrants continuation of treatment until maximum benefit is achieved or at least for two months when the dose can be reduced to maintain remission.[8] However, the use of Vitamin A within the recommended dietary intake (1300 μg retinol per day) for lactating women is usually considered safe.

Although we make no recommendations, we feel that oral Vitamin A particularly water-miscible formulation is safe and provides an economical and effective alternative to retinoids for treating Darier's disease, especially in patients who are intolerant or have a contraindication to oral retinoids, or need long-term maintenance therapy as relapses remain a major concern. However, our viewpoints are open to debate.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

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Conflicts of interest

There are no conflicts of interest.

   References Top

Sehgal VN, Srivastava G. Darier's (Darier-White) disease/keratosis follicularis. Int J Dermatol 2005;44:184-92.  Back to cited text no. 1
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;21:301-2.  Back to cited text no. 2
Zeglaoui F, Zaraa I, Fazaa B, Houimli S, El Fekih N, Ezzine N, et al. Dyskeratosis follicularis disease: Case reports and review of the literature. J Eur Acad Dermatol Venereol 2005;19:114-7.  Back to cited text no. 3
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;75:133-5.  Back to cited text no. 4
Liang J, Chen P, Chen H, Tian X, Wu Z, Zhang S, et al. Long-term safety and efficacy of continuous acitretin monotherapy for three children with different severe hyperkeratotic disorders in China. J Dermatol 2018;45:1003-8.  Back to cited text no. 5
Peck SM, Chargin L, Sobotka H. Keratosis follicularis (Darier's disease): Vitamin A deficiency disease. Arch Dermatol Syphilol 1941;43:223-9.  Back to cited text no. 6
Carleton A, Steven D. Keratosis follicularis. A study of four cases. Arch Dermatol Syphilol 1943;48:143-50.  Back to cited text no. 7
Porter AD, Godding EW, Brunauer SR. Vitamin A in Darier's disease. Arch Dermatol Syphilol (Chicago) 1947;56:306-16.  Back to cited text no. 8
Leitner ZA, Moore T. Vitamin A in Darier's disease. Br J Dermatol 1948;60:41-50.  Back to cited text no. 9
Fulton JE Jr, Gross PR, Cornelius CE 3rd, Kligman AM. Derier's disease. Treatment with topical vitamin A acid. Arch Dermatol 1968;98:396-9.  Back to cited text no. 10
Ayers S, Mihan R. Keratosis follicularis (Darier's disease). Response to simultaneous adminsteration of vitamin A and E. Arch Dermatol 1972;106:909-10.  Back to cited text no. 11
Thomas JR 3rd, Cooke JP, Winkelmann RK. High-dose vitamin A therapy for Darier's disease. Arch Dermatol 1982;118:891-4.  Back to cited text no. 12
Mohamed KN. Darier's disease: Response to combination of vitamin A and E. Singapore Med J 1987;28:80-2.  Back to cited text no. 13
Goss GD, Mc Burney MW. Physiological and clinical aspects of vitamin A and its metabolites. Crit Rev Clin Lab Sci 1992;29:185-215.  Back to cited text no. 14
O'Byrne SM, Blaner WS. Retinol and retinyl esters: Biochemistry and physiology. J Lipid Res 2013;54:1731-43.  Back to cited text no. 15
Al Tanoury Z, Piskunov A, Rochette-Egly C. Vitamin A and retinoid signaling: Genomic and non-genomic effects. J Lipid Res 2013;54:1761-75.  Back to cited text no. 16
Patton TJ, Zirwas MJ, Wolverton SE. Systemic retinoids: Mechanism of action. In: Wolverton SE, editor. Comprehensive Dermatologic Drug Therapy. 2nd ed. Philadelphia: Saunders Elsevier; 2007. p. 280-1.  Back to cited text no. 17
Breathnach SM, Smith CH, Chalmers RJG, Hay RJ. Systemic therapy: Retinoids. In: Burns T, Breathnach S, Cox N, Griffiths C, editors. Rook's Textbook of Dermatology. 8th ed. Oxford: Blackwell Publishing; 2010. p. 74.33-7.  Back to cited text no. 18


  [Figure 1], [Figure 2], [Figure 3], [Figure 4]

  [Table 1]


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