Tools
Darier Disease
Introduction
Darier disease, previously known as keratosis follicularis, is a genodermatosis inherited in an autosomal dominant fashion.[1] This rare disease classically features multiple red or brown papules with hyperkeratosis, nail abnormalities (eg, longitudinal erythronychia), and mucosal changes that present initially around puberty and are exacerbated throughout the lifespan, usually with external exposures, such as sunlight.[2] The condition is found worldwide and classified with other acantholytic disorders, such as Hailey-Hailey disease and Grover disease.[3][1]
Etiology
Register For Free And Read The Full Article
Search engine and full access to all medical articles- 10 free questions in your specialty
- Free CME/CE Activities
- Free daily question in your email
- Save favorite articles to your dashboard
- Emails offering discounts
Learn more about a Subscription to StatPearls Point-of-Care
Etiology
Darier disease is caused by mutations in the ATP2A2 gene, which encodes a calcium pump in the endoplasmic reticulum.[1][4] The lack of a functional calcium ATPase pump ultimately leads to desmosomal breakdown, causing the classic acantholytic process.[5] Another hypothesis is that aggregates of the dysfunctional ATPase that are not degraded build up at toxic levels, leading to dyskeratotic acantholysis by causing stress to the endoplasmic reticulum.[6]
The condition has a high penetrance but has variable expressivity, indicating that everyone who inherits the genotype will have some manifestation of the disease but that its severity and features will not be the same across all affected persons. Accordingly, patients with the disease cannot always recall a family history. Thus, it is important not to exclude Darier disease based solely on a negative family history of the disease. Sunlight, heat, pyogenic infections, and friction or mechanical trauma can exacerbate the condition.[1][7]
Epidemiology
Darier disease is rare, with a prevalence of 1 case per 100,000 people, and affects men more frequently than women.[1] Likely due to dysregulation of calcium in the endoplasmic reticulum, patients with Darier disease have been shown to have an increased association with heart failure, though not with myocardial infarction.[8] They have also been shown to have an association with increased pancreatic beta-cell dysfunction, which may indicate a higher frequency or association of Darier disease in patients with diabetes.[9] In one Swedish study, Darier disease was also associated with intellectual disability. Another study showed that Darier disease may be associated with bipolar disorder.[10][11]
Pathophysiology
A mutation in the ATP2A2 gene causes Darier disease. This gene encodes a calcium pump in the endoplasmic reticulum called sarcoendoplasmic reticulum calcium ATPase (SERCA2).[4] This pump transports calcium from the cytosol to the inside of the endoplasmic reticulum, maintaining a high calcium concentration in the endoplasmic reticulum, where it is needed to process junctional proteins such as desmoplakins and desmogleins.[4] Impaired SERCA2 function leads to aberrant junctional protein processing and poor cohesion between keratinocytes. This impairment is believed to cause acantholysis, or loss of connection between keratinocytes, as seen in pathology.[4]
In addition to aberrant junctional protein processing, a decrease in calcium stores in the endoplasmic reticulum activates a cellular stress response.[12][4] The cellular stress response may explain 2 critical features of the disease: dyskeratosis seen in pathology and disease triggers.[6] On histology, Darier disease is characterized by corps ronds, which are rounded keratinocytes.[13] These keratinocytes likely represent dyskeratotic or apoptotic cells. This dyskeratosis/apoptosis is thought to result from the cellular stress response induced by depleted calcium stores in the endoplasmic reticulum.[4] This stress response could worsen due to triggers such as UV radiation and heat, leading to exacerbations of the disease.[14]
There are 2 segmentally distributed clinical variants in Darier disease since autosomal dominant disorders display 2 types of mosaicism.[15] A postzygotic mutation causes type 1 mosaicism, meaning that some cells have the change and others do not.[16] In dermatology, type 1 mosaicism presents with areas of diseased skin intermixed with areas of healthy skin, reflecting the cells with and without the mutation, respectively. The affected skin often follows lines of Blaschko, reflecting an embryonic migration of skin cells.
Type 2 mosaicism arises from a postzygotic mutation in patients with a prezygotic mutation. In this case, the disease originates with 1 mutation, or disease allele, in all cells. Then, another mutation happens farther into the cell division process that only some of the cells will have. These cells will have 2 mutations or 2 dominant alleles for the disease.[17] Patients with type 2 mosaicism have 2 types of cells: those with 1 mutation or dominant allele and those with 2.
Although only 1 dominant allele is needed for the disease phenotype, 2 dominant alleles will lead to a more severe presentation in those cells. Clinically, these patients will have linear segments of increased disease severity in a background of already diseased skin. The areas of increased severity often follow the lines of Blaschko.[17] This condition is also called a loss of heterozygosity because patients were initially heterozygous for an autosomal dominant mutation and later had another mutation, making some cells homozygous for the autosomal dominant mutation. Darier disease has demonstrated both type 1 and type 2 mosaicism, giving rise to segmental type 1 and segmental type 2 variants of Darier disease, respectively.[1]
Histopathology
Dyskeratosis and acantholysis on histopathology characterize Darier disease.[18] Dyskeratosis is the premature keratinization of keratinocytes and is related to apoptosis. In Darier disease, this is seen as corps ronds.[1][7][1] Corps ronds are round keratinocytes with basophilic nuclei.[13] Acantholysis means a loss of adhesion between cells. This loss can be seen as lacunae in the keratinocytes above the basal layer. In addition to these findings, the epidermis shows hyperkeratosis.[1]
History and Physical
The skin manifestations of Darier disease consist of red or brown hyperkeratotic papules and plaques.[19] These lesions develop in seborrheic and intertriginous areas.[1] The condition commonly starts on the upper trunk or neck.[20] The plaques can appear papillomatous or verrucous and can manifest painful fissures. It is common for these lesions to develop a secondary infection.[1] Wounds in the intertriginous areas can become malodorous, which can be very distressing for the patient. Sun exposure, friction, heat, and sweat can exacerbate the disease.[1]
Nail findings include red and white lines oriented longitudinally over the nail. Patients can also have V-shaped notches at the distal end of the nail plate, along with nail fragility. The oral mucosa is involved in 50% of patients with Darier disease.[1] The oral lesions consist of white or red firm papules. The papules may form crusts or ulcerations but are usually asymptomatic.[1] Neurologic abnormalities such as epilepsy and intellectual disability have been described in association with Darier disease.[21] Patients with Darier disease exhibit higher rates of depression and mood disorders.[22] Ocular findings can include blepharitis and dry eyes.[23]
Multiple variants of Darier disease can be distinguished by clinical features. The first variant is segmental, in which linear skin lesions may be present due to mosaicism of the ATP2A2 gene.[15] The acral hemorrhagic variant is uncommon and is thought to be related to trauma.[24][25] The acrokeratosis verruciformis of Hopf is thought to be a variant due to a slightly different missense mutation on the same gene; thus, this allelic variant is thought to include nail changes and palmoplantar pits, often in younger patients.[18][26]
Evaluation
Clinical and histopathologic correlation are used to diagnose Darier disease.[18] Family history may be helpful in the diagnosis; however, due to its variable expressivity, affected patients cannot always recall a family history of the illness.[27] Patients should be evaluated for any coexisting staphylococcal or herpetic lesions, as these lesions may complicate the presentation and may lead to significant morbidity or mortality.[28][29][30]
Treatment / Management
No apparent cure exists for Darier disease; however, there are ways to address symptoms and prevent triggers to prevent flares. The avoidance of triggers is paramount in preventing exacerbations of Darier disease. Triggers can include sunlight, heat, occlusive clothing, and friction.[1] Patients should avoid sun exposure, wear loose clothing, use sunscreen, and employ proper hygiene practices. As Darier disease is inherited in an autosomal dominant fashion, patients should be offered genetic counseling.[31] In addition to keeping the skin cool, topical therapies may be helpful, particularly in addressing possible infections and hyperkeratosis.[32](B3)
Keratolytic moisturizers containing lactic acid or urea can treat hyperkeratosis and scaling.[1] Topical corticosteroids may be used, as they are often used in many skin diseases, to help reduce the inflammation and irritation associated with the dyskeratotic areas. Topical corticosteroids may also aid in pruritus, although this observation is based mostly on clinical experience.[33] Topical retinoids can also improve hyperkeratosis by causing keratinocyte turnover, much like in other skin diseases.[34][24] Cleaning with antiseptic solutions can prevent infections.[35] Case reports describe topical 5-fluorouracil as an effective treatment.[1] (B3)
Oral retinoids, such as acitretin, isotretinoin, and alitretinoin, also represent appropriate treatment options.[1][32][1][36] A new glucosylceramide synthase inhibitor, miglustat, which has been used to treat Gaucher disease and Niemann-Pick disease, has been developed and has been found to increase the adhesion strength of desmosomes in keratinocytes in patients with Darier disease, thus providing promise for a future treatment for this disease.[4][12][37] Other treatments can include topical calcineurin inhibitors, vitamin D analogues, naltrexone, laser treatment, and surgical excision of lesions.[34][38][39][40][41](A1)
Differential Diagnosis
The differential diagnosis of Darier disease includes acanthosis nigricans, confluent and reticulated papillomatosis, seborrheic dermatitis, and acrokeratosis verruciformis of Hopf.[1] Acrokeratosis verruciformis of Hopf presents with flesh-colored flat papules on the distal extremities. The disease shares the same mutation as Darier disease.[42] This histological differential diagnosis includes Hailey-Hailey disease, pemphigus vulgaris, and Grover disease.[1]
On histology, Darier disease and Hailey-Hailey disease both have some level of dyskeratosis, apoptosis, and acantholysis, although Darier disease usually shows more dyskeratosis. Hailey-Hailey disease is caused by a mutation in the ATP2C1 gene, which encodes a calcium pump in the Golgi apparatus.[43] Mutations in this gene lead to calcium depletion in the Golgi apparatus. This deficiency is thought to impair the processing of proteins essential to cell-cell adhesion.[43] However, calcium depletion in the Golgi apparatus does not seem to elicit the same cellular stress response as that of calcium depletion in the endoplasmic reticulum, as seen in Darier disease. This difference could account for the fact that although both Darier disease and Hailey-Hailey disease feature acantholysis and dyskeratosis, the dyskeratosis is more pronounced in Darier disease.
Prognosis
Darier disease persists for life in a relapsing-remitting manner. Avoiding triggers and using the appropriate treatments can allow for at least partial disease control.
Complications
One serious complication for patients with Darier disease is susceptibility to serious bacterial and viral cutaneous infections, including human papillomavirus, herpes simplex virus, and poxvirus infections.
Deterrence and Patient Education
Environmental factors influence the appearance of plaques and papules in Darier disease. When exposed to heat and humidity, most patients experience increased lesions during summer. Exposure to ultraviolet light, friction (eg, tight-fitting clothing), minor injury or friction such as rubbing or scratching, and ingesting certain medications can also increase the appearance of lesions. Therefore, patients should receive counsel on these precipitating factors to practice appropriate preventative measures.
Enhancing Healthcare Team Outcomes
Darier disease is a rare genetic skin disorder without a cure. The disorder is treated symptomatically. The avoidance of triggers is paramount in preventing exacerbations of Darier disease. The primary care clinician, internist, dermatologist, nursing staff, genetic counselor, and pharmacist should function as an interprofessional team to educate the patient on avoiding triggers like sunlight, heat, occlusive clothing, and friction.[1] Patients should avoid sun exposure, wear loose clothing, use sunscreen, and employ proper hygiene practices. As Darier disease is inherited in an autosomal dominant fashion, patients should receive an offer for genetic counseling. Because the disorder has a profound effect on cosmesis, a mental health consult may be necessary to manage depression and anxiety.[44]
References
Suryawanshi H, Dhobley A, Sharma A, Kumar P. Darier disease: A rare genodermatosis. Journal of oral and maxillofacial pathology : JOMFP. 2017 May-Aug:21(2):321. doi: 10.4103/jomfp.JOMFP_170_16. Epub [PubMed PMID: 28932054]
Redondo Mateo J. On Darier Disease: A Case Series of 20 Patients and Review of the Literature. Actas dermo-sifiliograficas. 2022 Apr:113(4):442. doi: 10.1016/j.ad.2021.10.008. Epub 2021 Dec 17 [PubMed PMID: 35623738]
Level 2 (mid-level) evidenceStanisz H, Mitteldorf C, Janning H, Bennemann A, Schön MP, Frank J. Subcellular compartmentalization of STIM1 for the distinction of Darier disease from Hailey-Hailey disease. Journal der Deutschen Dermatologischen Gesellschaft = Journal of the German Society of Dermatology : JDDG. 2022 Dec:20(12):1613-1619. doi: 10.1111/ddg.14912. Epub 2022 Nov 28 [PubMed PMID: 36442136]
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. The Journal of investigative dermatology. 2014 Jul:134(7):1961-1970. doi: 10.1038/jid.2014.8. Epub 2014 Jan 3 [PubMed PMID: 24390139]
Ashok Kumar P, Paulraj S, Dutta S. Debilitating Darier's Disease and Its Impact on the Quality of Life. Cureus. 2020 May 15:12(5):e8133. doi: 10.7759/cureus.8133. Epub 2020 May 15 [PubMed PMID: 32550053]
Wang Y, Bruce AT, Tu C, Ma K, Zeng L, Zheng P, Liu Y, Liu Y. Protein aggregation of SERCA2 mutants associated with Darier disease elicits ER stress and apoptosis in keratinocytes. Journal of cell science. 2011 Nov 1:124(Pt 21):3568-80. doi: 10.1242/jcs.084053. Epub 2011 Nov 1 [PubMed PMID: 22045735]
Level 3 (low-level) evidenceEngin B, Kutlubay Z, Erkan E, Tüzün Y. Darier disease: A fold (intertriginous) dermatosis. Clinics in dermatology. 2015 Jul-Aug:33(4):448-51. doi: 10.1016/j.clindermatol.2015.04.009. Epub 2015 Apr 9 [PubMed PMID: 26051059]
Bachar-Wikstrom E, Curman P, Ahanian T, Leong IUS, Larsson H, Cederlöf M, Wikstrom JD. Darier disease is associated with heart failure: a cross-sectional case-control and population based study. Scientific reports. 2020 Apr 23:10(1):6886. doi: 10.1038/s41598-020-63832-9. Epub 2020 Apr 23 [PubMed PMID: 32327688]
Level 2 (mid-level) evidenceAhanian T, Curman P, Leong IUS, Brismar K, Bachar-Wikstrom E, Cederlöf M, Wikstrom JD. Metabolic phenotype in Darier disease: a cross-sectional clinical study. Diabetology & metabolic syndrome. 2020:12():12. doi: 10.1186/s13098-020-0520-0. Epub 2020 Feb 5 [PubMed PMID: 32042314]
Level 2 (mid-level) evidenceCederlöf M, Karlsson R, Larsson H, Almqvist C, Magnusson PK, Nordlind K, Landén M, Lichtenstein P. Intellectual disability and cognitive ability in Darier disease: Swedish nation-wide study. The British journal of dermatology. 2015 Jul:173(1):155-8. doi: 10.1111/bjd.13740. Epub 2015 May 29 [PubMed PMID: 25704118]
Cederlöf M, Bergen SE, Långström N, Larsson H, Boman M, Craddock N, Östberg P, Lundström S, Sjölander A, Nordlind K, Landén M, Lichtenstein P. The association between Darier disease, bipolar disorder, and schizophrenia revisited: a population-based family study. Bipolar disorders. 2015 May:17(3):340-4. doi: 10.1111/bdi.12257. Epub 2014 Sep 12 [PubMed PMID: 25213221]
Level 2 (mid-level) evidenceMauro T. Endoplasmic reticulum calcium, stress, and cell-to-cell adhesion. The Journal of investigative dermatology. 2014 Jul:134(7):1800-1801. doi: 10.1038/jid.2014.97. Epub [PubMed PMID: 24924761]
Kositkuljorn C, Suchonwanit P. Darier's Disease: Report of a Case with Facial Involvement. Case reports in dermatology. 2019 Sep-Dec:11(3):327-333. doi: 10.1159/000504925. Epub 2019 Dec 10 [PubMed PMID: 31911771]
Park K, Lee SE, Shin KO, Uchida Y. Insights into the role of endoplasmic reticulum stress in skin function and associated diseases. The FEBS journal. 2019 Jan:286(2):413-425. doi: 10.1111/febs.14739. Epub [PubMed PMID: 30586218]
Šujica A, Pagon A, Bartenjev I. A case of segmental form of type 1 mosaic Darier's disease. Acta dermatovenerologica Alpina, Pannonica, et Adriatica. 2022 Mar:31(Suppl):S33-S35 [PubMed PMID: 35339142]
Level 3 (low-level) evidencePhillips D, Gumparthy K, Farrar CW, Karumanchery R, Tan BB. Localized Darier disease: three cases of Type 1 segmental mosaicism. Clinical and experimental dermatology. 2022 Jan:47(1):167-169. doi: 10.1111/ced.14866. Epub 2021 Sep 1 [PubMed PMID: 34347305]
Level 3 (low-level) evidenceItin PH, Büchner SA, Happle R. Segmental manifestation of Darier disease. What is the genetic background in type 1 and type 2 mosaic phenotypes? Dermatology (Basel, Switzerland). 2000:200(3):254-7 [PubMed PMID: 10828637]
Level 3 (low-level) evidencePaudel V, Pradhan MB, Shrestha B, Paudel S. Clinical and Histopathological Findings in a Patient of Darier-White Disease with Acrokertasosis Verruciformis of Hopf. Case reports in dermatological medicine. 2022:2022():5233837. doi: 10.1155/2022/5233837. Epub 2022 Jul 4 [PubMed PMID: 35837260]
Level 3 (low-level) evidenceDhanaraj M, Danny GC, Srinivasan S, Nagaraju S. Late onset Darier's disease in a genetically predisposed individual: a case report. The Pan African medical journal. 2022:42():208. doi: 10.11604/pamj.2022.42.208.32696. Epub 2022 Jul 15 [PubMed PMID: 36284569]
Burge SM, Wilkinson JD. Darier-White disease: a review of the clinical features in 163 patients. Journal of the American Academy of Dermatology. 1992 Jul:27(1):40-50 [PubMed PMID: 1619075]
Level 2 (mid-level) evidenceCurman P, Bern J, Sand L, Cederlöf M, Bachar-Wikström E, Wikström JD. Patients with Darier Disease Exhibit Cognitive Impairment while Patients with Hailey-Hailey Disease Do Not: An Experimental, Matched Case-control Study. Acta dermato-venereologica. 2021 Jun 22:101(6):adv00476. doi: 10.2340/00015555-3818. Epub 2021 Jun 22 [PubMed PMID: 33928397]
Level 2 (mid-level) evidenceGordon-Smith K, Jones LA, Burge SM, Munro CS, Tavadia S, Craddock N. The neuropsychiatric phenotype in Darier disease. The British journal of dermatology. 2010 Sep:163(3):515-22. doi: 10.1111/j.1365-2133.2010.09834.x. Epub 2010 Apr 29 [PubMed PMID: 20456342]
Hammad H, Adler E, Yeshurun A, Abayev L, Vered S, Briscoe D, Ziv M, Dodiuk-Gad RP. Ophthalmic Assessment in Patients With Darier Disease. American journal of ophthalmology. 2021 Jul:227():139-142. doi: 10.1016/j.ajo.2021.03.011. Epub 2021 Mar 15 [PubMed PMID: 33737033]
Flores-Terry MÁ, García-Arpa M, Llamas-Velasco M, Mendoza-Chaparro C, Ramos-Rodríguez C. Acral Hemorrhagic Darier Disease. Actas dermo-sifiliograficas. 2017 Sep:108(7):e49-e52. doi: 10.1016/j.ad.2017.02.012. Epub 2017 Apr 10 [PubMed PMID: 28407871]
Vender R, Vender R. Acral Hemorrhagic Darier's Disease: A Case Report. Journal of cutaneous medicine and surgery. 2016 Sep:20(5):478-80. doi: 10.1177/1203475416640993. Epub 2016 Mar 18 [PubMed PMID: 26992421]
Genedy R, Taha A. Acrokeratosis verruciformis of Hopf: dermoscopic and histopathological study of two siblings. Clinical and experimental dermatology. 2021 Oct:46(7):1313-1314. doi: 10.1111/ced.14691. Epub 2021 May 10 [PubMed PMID: 33866599]
Beiu C, Giurcaneanu C, Mihai M, Popa L, Hage R. Darier Disease - A Clinical Illustration of Its High Variable Expressivity. Cureus. 2019 Dec 4:11(12):e6292. doi: 10.7759/cureus.6292. Epub 2019 Dec 4 [PubMed PMID: 31938586]
Westerdahl JS, Grant J, Sontheimer R, Zussman J. Darier disease, radiation therapy, and herpesvirus -- an unfortunate triad. Dermatology online journal. 2021 Aug 15:27(8):. doi: 10.5070/D327854698. Epub 2021 Aug 15 [PubMed PMID: 34755961]
Dodiuk-Gad R, Cohen-Barak E, Ziv M, Shani-Adir A, Shalev S, Chazan B, Raz R, Colodner R, Amichai B, Zlotogorski A, Keness Y, Rozenman D. Bacteriological aspects of Darier's disease. Journal of the European Academy of Dermatology and Venereology : JEADV. 2013 Nov:27(11):1405-9. doi: 10.1111/jdv.12025. Epub 2012 Oct 19 [PubMed PMID: 23078077]
Milavec-Puretić V, Lipozencić J, Sustić N, Pećina-Slaus N. Sepsis as an unusual event in dyskeratosis follicularis. Croatian medical journal. 2001 Feb:42(1):64-6 [PubMed PMID: 11172658]
Level 3 (low-level) evidenceHarboe TL, Willems P, Jespersgaard C, Mølgaard Poulsen ML, Sørensen FB, Bisgaard ML. Mosaicism in segmental Darier disease: an in-depth molecular analysis quantifying proportions of mutated alleles in various tissues. Dermatology (Basel, Switzerland). 2011:222(4):292-6. doi: 10.1159/000328404. Epub 2011 Jul 1 [PubMed PMID: 21720150]
Level 3 (low-level) evidenceHaber RN, Dib NG. Management of Darier disease: A review of the literature and update. Indian journal of dermatology, venereology and leprology. 2021 Jan-Feb:87(1):14-21. doi: 10.25259/IJDVL_963_19. Epub [PubMed PMID: 33580925]
Hagino T, Nakano H, Saeki H, Kanda N. A Case of Darier's Disease with a Novel Missense Mutation in ATP2A2 Successfully Treated with Calcipotriol/Betamethasone Dipropionate Two-Compound Ointment. Clinical, cosmetic and investigational dermatology. 2022:15():367-372. doi: 10.2147/CCID.S354694. Epub 2022 Mar 5 [PubMed PMID: 35283639]
Level 3 (low-level) evidenceHanna N, Lam M, Fleming P, Lynde CW. Therapeutic Options for the Treatment of Darier's Disease: A Comprehensive Review of the Literature. Journal of cutaneous medicine and surgery. 2022 May-Jun:26(3):280-290. doi: 10.1177/12034754211058405. Epub 2021 Nov 28 [PubMed PMID: 34841914]
Rogner DF, Lammer J, Zink A, Hamm H. Darier and Hailey-Hailey disease: update 2021. Journal der Deutschen Dermatologischen Gesellschaft = Journal of the German Society of Dermatology : JDDG. 2021 Oct:19(10):1478-1501. doi: 10.1111/ddg.14619. Epub [PubMed PMID: 34661345]
Silva-Hirschberg C, Cabrera R, Rollán MP, Castro A. Darier disease: the use of dermoscopy in monitoring acitretin treatment. Anais brasileiros de dermatologia. 2022 Sep-Oct:97(5):644-647. doi: 10.1016/j.abd.2021.05.021. Epub 2022 Jul 16 [PubMed PMID: 35853773]
Leonart LP, Fachi MM, Böger B, Silva MRD, Szpak R, Lombardi NF, Pedroso MLA, Pontarolo R. A Systematic Review and Meta-analyses of Longitudinal Studies on Drug Treatments for Gaucher Disease. The Annals of pharmacotherapy. 2023 Mar:57(3):267-282. doi: 10.1177/10600280221108443. Epub 2022 Jul 11 [PubMed PMID: 35815393]
Level 1 (high-level) evidenceJfri A, Litvinov IV, Netchiporouk E. Naltrexone for the Treatment of Darier and Hailey-Hailey Diseases. Journal of cutaneous medicine and surgery. 2019 Jul/Aug:23(4):453-454. doi: 10.1177/1203475419843122. Epub [PubMed PMID: 31337235]
Flores-Terry MA, Zamberk Majlis P, Franco-Muñoz M, Vera-Iglesias E, García-Arpa M, Martín-Dávila F. Dermatosis papular acantolítica de la vulva con buena respuesta a tacrólimus tópico. Dermatology online journal. 2017 Apr 15:23(4):. pii: 13030/qt13x8t8fm. Epub 2017 Apr 15 [PubMed PMID: 28541878]
Pérez-Carmona L, Fleta-Asín B, Moreno-García-Del-Real C, Jaén-Olasolo P. Successful treatment of Darier's disease with topical pimecrolimus. European journal of dermatology : EJD. 2011 Mar-Apr:21(2):301-2. doi: 10.1684/ejd.2011.1309. Epub [PubMed PMID: 21489907]
Level 3 (low-level) evidenceDunnigan AV, Salence B, McPherson T, Walker NPJ. A case of severe refractory Darier's disease of the feet in which management with carbon dioxide (CO(2)) laser therapy demonstrated superior outcomes to surgical excision. Journal of cosmetic and laser therapy : official publication of the European Society for Laser Dermatology. 2020 Jul 3:22(4-5):174-176. doi: 10.1080/14764172.2020.1783453. Epub 2020 Jul 13 [PubMed PMID: 32654543]
Level 3 (low-level) evidenceDhitavat J, Macfarlane S, Dode L, Leslie N, Sakuntabhai A, MacSween R, Saihan E, Hovnanian A. Acrokeratosis verruciformis of Hopf is caused by mutation in ATP2A2: evidence that it is allelic to Darier's disease. The Journal of investigative dermatology. 2003 Feb:120(2):229-32 [PubMed PMID: 12542527]
Level 3 (low-level) evidenceRaiko L, Siljamäki E, Mahoney MG, Putaala H, Suominen E, Peltonen J, Peltonen S. Hailey-Hailey disease and tight junctions: Claudins 1 and 4 are regulated by ATP2C1 gene encoding Ca(2+) /Mn(2+) ATPase SPCA1 in cultured keratinocytes. Experimental dermatology. 2012 Aug:21(8):586-91. doi: 10.1111/j.1600-0625.2012.01520.x. Epub 2012 May 29 [PubMed PMID: 22639968]
Newman AJ, Mullens D, Manway M, Barr J. Red, white and blues: Darier disease and mood disorder. BMJ case reports. 2018 Aug 27:2018():. pii: bcr-2018-227004. doi: 10.1136/bcr-2018-227004. Epub 2018 Aug 27 [PubMed PMID: 30150355]
Level 3 (low-level) evidence