Skip to main content
SpringerLink
Log in

Treatments for Non-Syndromic Inherited Ichthyosis, Including Emergent Pathogenesis-Related Therapy

  • Review Article
  • Published:
American Journal of Clinical Dermatology Aims and scope Submit manuscript

Abstract

The term ‘inherited ichthyosis’ refers to a heterogeneous group of mendelian disorders of cornification that involve the integument with varying degrees of scaling. The management of ichthyosis poses a challenge for most physicians. Treatment options proposed in the literature include moisturizers, topical keratolytics, topical and systemic vitamin D analogues, and topical and systemic retinoids; however, some of these modalities are less reliable than others. Despite the therapeutic impasse imposed by the options above, the emergence of pathogenesis-based treatments along with novel gene therapies appear promising and hold the potential to halt or even revert disorders that arise from single genetic mutations, although research is still quite lacking in this domain. Hence, this review aims to highlight the various treatment modalities available for the management of the cutaneous manifestations of non-syndromic inherited ichthyosis, with an added emphasis on pathogenesis-targeted therapies.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Oji VMD, Tadini GMD, Akiyama MMDP, Blanchet Bardon CMD, Bodemer CMDP, Bourrat EMD, et al. Revised nomenclature and classification of inherited ichthyoses: results of the First Ichthyosis Consensus Conference in Sorèze 2009. J Am Acad Dermatol. 2010;63(4):607–41. https://doi.org/10.1016/j.jaad.2009.11.020.

    Article  PubMed  Google Scholar 

  2. Mazereeuw-Hautier J, Vahlquist A, Traupe H, Bygum A, Amaro C, Aldwin M, et al. Management of congenital ichthyoses: European guidelines of care, part one. Br J Dermatol. 2019;180(2):272–81. https://doi.org/10.1111/bjd.17203.

    Article  CAS  PubMed  Google Scholar 

  3. Dreyfus I, Pauwels C, Bourrat E, Bursztejn A-C, Maruani A, Chiaverini C, et al. Burden of inherited ichthyosis: a French national survey. Acta Derm Venereol. 2015;95(3):326–8.

    Article  Google Scholar 

  4. Mazereeuw-Hautier J, Hernández-Martín A, O’Toole EA, Bygum A, Amaro C, Aldwin M, et al. Management of congenital ichthyoses: European guidelines of care, part two. Br J Dermatol. 2019;180(3):484–95. https://doi.org/10.1111/bjd.16882.

    Article  CAS  PubMed  Google Scholar 

  5. Malhotra R, Hernández-Martın A, Oji V. Ocular manifestations, complications and management of congenital ichthyoses: a new look. Br J Ophthalmol. 2018;102(5):586. https://doi.org/10.1136/bjophthalmol-2017-310615.

    Article  PubMed  Google Scholar 

  6. Elshtewi M, Archer DB. Congenital ichthyosis in a Libyan child with ophthalmic manifestations. Int Ophthalmol. 1991;15(5):343–5. https://doi.org/10.1007/BF00128954.

    Article  CAS  PubMed  Google Scholar 

  7. Litwin AS, Kalantzis G, Drimtzias E, Hamada S, Chang B, Malhotra R. Nonsurgical treatment of congenital ichthyosis cicatricial ectropion and eyelid retraction using Restylane hyaluronic acid. Br J Dermatol. 2015;173(2):601–3. https://doi.org/10.1111/bjd.13710.

    Article  CAS  PubMed  Google Scholar 

  8. Oestreicher JH, Nelson CC. Lamellar ichthyosis and congenital ectropion. Arch Ophthalmol. 1990;108(12):1772–3. https://doi.org/10.1001/archopht.1990.01070140126044.

    Article  CAS  PubMed  Google Scholar 

  9. Menke TB, Moschner S, Joachimmeyer E, Ahrens P, Geerling G. Congenital ectropion in ichthyosis congenita mitis and gravis. Der Ophthalmol. 2006;103(5):410.

    Article  CAS  Google Scholar 

  10. Bassotti A, Moreno S, Criado E. Successful treatment with topical N-acetylcysteine in urea in five children with congenital lamellar ichthyosis. Pediatr Dermatol. 2011;28(4):451–5. https://doi.org/10.1111/j.1525-1470.2011.01375.x.

    Article  PubMed  Google Scholar 

  11. Gicquel JJ, Vabres P, Dighiero P. Use of topical cutaneous N-acetylcysteine in the treatment of major bilateral ectropion in an infant with lamellar ichthyosis. J F Ophtalmol. 2005;28(4):412–5.

    Article  Google Scholar 

  12. Hanson B, Becker L, Hook K, Polcari I, Areaux RG Jr, Maguiness S. Ectropion improvement with topical tazarotene in children with lamellar ichthyosis. Pediatr Dermatol. 2017;34(5):584–9. https://doi.org/10.1111/pde.13240.

    Article  PubMed  Google Scholar 

  13. Craiglow BG, Choate KA, Milstone LM. Topical tazarotene for the treatment of ectropion in ichthyosis. JAMA Dermatol. 2013;149(5):598–600. https://doi.org/10.1001/jamadermatol.2013.239.

    Article  PubMed  Google Scholar 

  14. Singh M, Kaur M, Kaur R, Singh S. Severe ectropion in lamellar ichthyosis managed medically with oral acitretin. Pediatr Dermatol. 2018;35(2):e117–20. https://doi.org/10.1111/pde.13410.

    Article  PubMed  Google Scholar 

  15. Sethuraman G, Marwaha RK, Challa A, Yenamandra VK, Ramakrishnan L, Thulkar S, et al. Vitamin D: a new promising therapy for congenital ichthyosis. Pediatrics. 2016;137(1): e20151313. https://doi.org/10.1542/peds.2015-1313.

    Article  Google Scholar 

  16. Sigurdsson H, Baldursson BT. Inverting sutures with systemic retinoids and lubrication can correct ectropion in ichthyosis. Ophthalmic Plast Reconstr Surg. 2016;32(5):e112–3.

    Article  Google Scholar 

  17. Abboud J-PJ, Whittington A, Ahmed M, Himebaugh JT, Wiley LA, Haffar A, et al. Apremilast use in a case of cicatricial ectropion secondary to severe lamellar ichthyosis. Ophthalmic Plastic Reconstr Surg. 2018;34(3): e76.

    Article  Google Scholar 

  18. Taban M, Mancini R, Nakra T, Velez FG, Ela-Dalman N, Tsirbas A, et al. Nonsurgical management of congenital eyelid malpositions using hyaluronic acid gel. Ophthalmic Plast Reconstr Surg. 2009;25(4):259–63. https://doi.org/10.1097/IOP.0b013e3181ac984b.

    Article  PubMed  Google Scholar 

  19. Zachara MG, Drozdowski PH, Łątkowski IT. Surgical management of ichtyosis-related ectropion. Description of four cases and a literature review. J Plastic Surg Hand Surg. 2014;48(3):179–82. https://doi.org/10.3109/2000656X.2013.842923.

    Article  Google Scholar 

  20. Das S, Honavar SG, Dhepe N, Naik MN. Maternal skin allograft for cicatricial ectropion in congenital icthyosis. Ophthalmic Plast Reconstr Surg. 2010;26(1):42–3.

    Article  Google Scholar 

  21. Culican SM, Custer PL. Repair of cicatricial ectropion in an infant with harlequin ichthyosis using engineered human skin. Am J Ophthalmol. 2002;134(3):442–3. https://doi.org/10.1016/S0002-9394(02)01567-2.

    Article  PubMed  Google Scholar 

  22. Cicinelli MV, Dave TV, Madhuri BK, Tiple S, Naik MN. Non-surgical management of congenital ichthyosis using hyaluronic acid gel injection. Eur J Ophthalmol. 2020;30(1):NP7–10. https://doi.org/10.1177/1120672118805622.

    Article  PubMed  Google Scholar 

  23. Ozgur OR, Akcay L, Tutas N, Ozkurt Y. Cicatricial upper and lower eyelid ectropion in an ichthyosis patient. Surgical correction. J Dermatol Case Rep. 2011;5(2):27–9. https://doi.org/10.3315/jdcr.2011.1068.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Alkatan HM, Aljebreen MA, Alsuhaibani AH. Long term follow up of mucous membrane grafting for cicatricial ectropion in Ichthyosis: a case report. Int J Surg Case Rep. 2017;33:21–3. https://doi.org/10.1016/j.ijscr.2017.02.008.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Nayak S, Rath S, Kar BR. Mucous membrane graft for cicatricial ectropion in lamellar ichthyosis: An approach revisited. Ophthalmic Plast Reconstr Surg. 2011;27(6):e155–6. https://doi.org/10.1097/IOP.0b013e3182082f4e.

    Article  PubMed  Google Scholar 

  26. Soparkar CNS, Patrinely JR, Hunt MG, Shenaq SM. Transforming mucous membrane grafts into skin grafts. Ophthalmology. 2001;108(11):1933–4. https://doi.org/10.1016/S0161-6420(01)00785-0.

    Article  CAS  PubMed  Google Scholar 

  27. Vahlquist A, Gånemo A, Virtanen M. Congenital ichthyosis: an overview of current and emerging therapies. Acta Derm Venereol. 2008;88(1):4–14. https://doi.org/10.2340/00015555-0415.

    Article  PubMed  Google Scholar 

  28. Nguyen V, Cunningham BB, Eichenfield LF, Alio AB, Buka RL. Treatment of ichthyosiform diseases with topically applied tazarotene: risk of systemic absorption. J Am Acad Dermatol. 2007;57(5 Suppl):S123–5.

    Article  Google Scholar 

  29. Cortés H, Del Prado-Audelo ML, Urbán-Morlán Z, Alcalá-Alcalá S, González-Torres M, Reyes-Hernández OD, et al. Pharmacological treatments for cutaneous manifestations of inherited ichthyoses. Arch Dermatol Res. 2019. https://doi.org/10.1007/s00403-019-01994-x.

    Article  PubMed  Google Scholar 

  30. Ogawa M, Akiyama M. Successful topical adapalene treatment for the facial lesions of an adolescent case of epidermolytic ichthyosis. J Am Acad Dermatol. 2014;71(3):e103–5. https://doi.org/10.1016/j.jaad.2014.04.010.

    Article  PubMed  Google Scholar 

  31. Cotellessa C, Cuevas-Covarrubias SA, Valeri P, Fargnoli MC, Peris K. Topical tazarotene 0.05% versus glycolic acid 70% treatment in X-linked ichthyosis due to extensive deletion of the STS gene. Acta Dermato-Venereol. 2005;85(4):346–8.

    Google Scholar 

  32. Hofmann S, Ruzicka L. Effect of topical tazarotene in the treatment of congenital ichthyoses. Br J Dermatol. 1999;141(4):642–6. https://doi.org/10.1046/j.1365-2133.1999.03101.x.

    Article  CAS  PubMed  Google Scholar 

  33. Kundu RV, Garg A, Worobec SM. Lamellar ichthyosis treated with tazarotene 0.1% gel. J Am Acad Dermatol. 2006;55(5, Supplement):S94–5. https://doi.org/10.1016/j.jaad.2005.09.018.

    Article  PubMed  Google Scholar 

  34. Hohl D, Williams M. Mendelian disorders of cornification (MEDOC): the ichthyoses. Oxford: Wiley-Blackwell; 2011. p. 121–70.

    Google Scholar 

  35. Rajiv S, Rakhesh SV. Ichthyosis bullosa of Siemens: response to topical tazarotene. Indian J Dermatol Venereol Leprol. 2006;72(1):43.

    Article  CAS  Google Scholar 

  36. Behera B, Chandrashekar L, Singh N, Thappa DM, Gochhait D. Lamellar ichthyosis associated bilateral pseudoainhum of fingers and toes successfully treated with tazarotene. Dermatol Ther. 2017;30(5): e12516. https://doi.org/10.1111/dth.12516.

    Article  Google Scholar 

  37. Liu RH, Becker B, Gunkel J, Teng J. Rapid improvement in digital ischemia and acral contracture in a collodion baby treated with topical tazarotene. J Drugs Dermatol. 2010;9(6):713–6.

    PubMed  Google Scholar 

  38. Lucker GPH, Verfaille CJ, Heremans AMC, Vanhoutte FP, Boegheim JPJ, Steijlen PPM. Topical liarozole in ichthyosis: a double-blind, left–right comparative study followed by a long-term open maintenance study. Br J Dermatol. 2005;152(3):566–9. https://doi.org/10.1111/j.1365-2133.2005.06399.x.

    Article  CAS  PubMed  Google Scholar 

  39. Veit JGS, De Glas V, Balau B, Liu H, Bourlond F, Paller AS, et al. Characterization of CYP26B1-selective inhibitor, DX314, as a potential therapeutic for keratinization disorders. J Invest Dermatol. 2021;141(1):72–83. https://doi.org/10.1016/j.jid.2020.05.090.

    Article  CAS  PubMed  Google Scholar 

  40. Cosio T, Di Prete M, Gaziano R, Lanna C, Orlandi A, Di Francesco P, et al. Trifarotene: a current review and perspectives in dermatology. Biomedicines. 2021;9(3):237. https://doi.org/10.3390/biomedicines9030237.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Pharmaceuticals T. Timber Pharmaceuticals Receives FDA Breakthrough Therapy Designation for TMB-001 for the Treatment of Congenital Ichthyosis 2022. 2022. https://www-timberpharma-com.filesusr.com/html/e02db4_e15c6b0a9f8074ab103c2ddcbe952e41.html?qmodStoryID=7129573901766610.

  42. Rubeiz N, Kibbi A-G. Management of ichthyosis in infants and children. Clin Dermatol. 2003;21(4):325–8. https://doi.org/10.1016/s0738-081x(03)00051-8.

    Article  PubMed  Google Scholar 

  43. Kragballe K, Steijlen PM, Ibsen H, et al. Efficacy, tolerability, and safety of calcipotriol ointment in disorders of keratinization: results of a randomized, double-blind, vehicle-controlled, right/left comparative study. Arch Dermatol. 1995;131(5):556–60. https://doi.org/10.1001/archderm.1995.01690170058008.

    Article  CAS  PubMed  Google Scholar 

  44. Lucker GPH, Van de Kerkhof PCM, Van Dijk MR, Steijlen PM. Effect of topical calcipotriol on congenital ichthyoses. Br J Dermatol. 1994;131(4):546–50.

    Article  CAS  Google Scholar 

  45. Mizuno Y, Suga Y, Hasegawa T, Haruna K, Kohroh K, Ogawa H, et al. A case of peeling skin syndrome successfully treated with topical calcipotriol. J Dermatol. 2006;33(6):430–2. https://doi.org/10.1111/j.1346-8138.2006.00102.x.

    Article  PubMed  Google Scholar 

  46. Garg K, Singh D, Mishra D. Peeling skin syndrome: current status. Dermatol Online J. 2010;16(3):10.

    Article  Google Scholar 

  47. Bogenrieder T, Landthaler M, Stolz W. Bullous congenital ichthyosiform erythroderma: safe and effective topical treatment with calcipotriol ointment in a child. Acta Derm Venereol. 2003;83(1):52–4.

    Article  CAS  Google Scholar 

  48. Umekoji A, Fukai K, Ishii M. A case of mosaic-type bullous congenital ichthyosiform erythroderma successfully treated with topical maxacalcitol, a vitamin D3 analogue. Clin Exp Dermatol (Print). 2008;33(4):501–2.

    Article  CAS  Google Scholar 

  49. Vahlquist A, Fischer J, Törmä H. Inherited nonsyndromic ichthyoses: an update on pathophysiology, diagnosis and treatment. Am J Clin Dermatol. 2018;19(1):51–66. https://doi.org/10.1007/s40257-017-0313-x.

    Article  PubMed  Google Scholar 

  50. Kaplan L, Castelo-Soccio L. Topical N-acetylcysteine in ichthyosis: experience in 18 patients. Pediatr Dermatol. 2018;35(4):528–30. https://doi.org/10.1111/pde.13489.

    Article  PubMed  Google Scholar 

  51. Davila-Seijo P, Flórez A, Davila-Pousa C, No N, Ferreira C, De la Torre C. Topical N-acetylcysteine for the treatment of lamellar ichthyosis: an improved formula. Pediatr Dermatol. 2014;31(3):395–7. https://doi.org/10.1111/pde.12305.

    Article  PubMed  Google Scholar 

  52. Sarýcý SÜ, Þahin M, Yurdakök M. Topical N-acetylcysteine treatment in neonatal ichthyosis. Turk J Pediatr. 2003;45:245–7.

    Google Scholar 

  53. Batalla A, Dávila-Pousa C, Feal C, Flórez Á. Topical carbocysteine: a new option for the treatment of ichthyosis. Pediatr Dermatol. 2018;35(6):e357–9. https://doi.org/10.1111/pde.13638.

    Article  PubMed  Google Scholar 

  54. Virtanen M, Gedde-Dahl T, Mork N-J, Leigh I, Bowden PE, Vahlquist A. Phenotypic/genotypic correlations in patients with epidermolytic hyperkeratosis and the effects of retinoid therapy on keratin expression. Acta Derm Venereol. 2001;81(3):163–70. https://doi.org/10.1080/000155501750376221.

    Article  CAS  PubMed  Google Scholar 

  55. DiGiovanna JJ, Mauro T, Milstone LM, Schmuth M, Toro JR. Systemic retinoids in the management of ichthyoses and related skin types. Dermatol Ther. 2013;26(1):26–38. https://doi.org/10.1111/j.1529-8019.2012.01527.x.

    Article  PubMed  Google Scholar 

  56. Katugampola RP, Finlay AY. Oral retinoid therapy for disorders of keratinization: single-centre retrospective 25 years’ experience on 23 patients. Br J Dermatol. 2006;154(2):267–76. https://doi.org/10.1111/j.1365-2133.2005.06906.x.

    Article  CAS  PubMed  Google Scholar 

  57. Nassif PW, Nakandakari S, Fogagnolo L, Contin LA, Alves C. Epidermolytic hyperkeratosis: a follow-up of 23 years of use of systemic retinoids. An Bras Dermatol. 2011;86(4 Suppl 1):S72–5.

    Article  Google Scholar 

  58. Macbeth AE, Johnston GA. Twenty-one years of oral retinoid therapy in siblings with nonbullous ichthyosiform erythroderma. Clin Exp Dermatol Clin Dermatol. 2008;33(2):190–1.

    Article  CAS  Google Scholar 

  59. Verfaille C, Vanhoutte F, Blanchet-Bardon C, Van Steensel M, Steijlen P. Oral liarozole vs. acitretin in the treatment of ichthyosis: a phase II/III multicentre, double-blind, randomized, active-controlled study. Br J Dermatol. 2007;156(5):965–73.

    Article  CAS  Google Scholar 

  60. Vahlquist A, Blockhuys S, Steijlen P, van Rossem K, Didona B, Blanco D, et al. Oral liarozole in the treatment of patients with moderate/severe lamellar ichthyosis: results of a randomized, double-blind, multinational, placebo-controlled phase II/III trial. Br J Dermatol. 2014;170(1):173–81. https://doi.org/10.1111/bjd.12626.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Verfaille CJ, Borgers M, van Steensel MA. Retinoic acid metabolism blocking agents (RAMBAs): a new paradigm in the treatment of hyperkeratotic disorders. J German Soc Dermatol. 2008;6(5):355–64. https://doi.org/10.1111/j.1610-0387.2007.06541.x.

    Article  Google Scholar 

  62. Singh S, Bhura M, Maheshwari A, Kumar A, Singh CP, Pandey SS. Successful treatment of harlequin ichthyosis with acitretin. Int J Dermatol. 2001;40(7):472–3. https://doi.org/10.1046/j.1365-4362.2001.01173.x.

    Article  CAS  PubMed  Google Scholar 

  63. Rajpopat S, Moss C, Mellerio J, Vahlquist A, Gånemo A, Hellstrom-Pigg M, et al. Harlequin ichthyosis: a review of clinical and molecular findings in 45 cases. Arch Dermatol. 2011;147(6):681–6. https://doi.org/10.1001/archdermatol.2011.9.

    Article  PubMed  Google Scholar 

  64. Neema S, Mukherjee S, Vasudevan B, Verma R, Moorchung N, Chatterjee M. Vitamin D deficiency after oral retinoid therapy for ichthyosis. Pediatr Dermatol. 2015;32(4):e151–5. https://doi.org/10.1111/pde.12614.

    Article  PubMed  Google Scholar 

  65. ten Katharina F, Hans-Wilhelm K, Proelss J, Tüting T, Bieber T, Wenzel J. Successful treatment of bullous congenital ichthyosiform erythroderma with erythromycin. Dermatology. 2007;215(1):81–3.

    Article  Google Scholar 

  66. Paller AS, Renert-Yuval Y, Suprun M, Esaki H, Oliva M, Huynh TN, et al. An IL-17-dominant immune profile is shared across the major orphan forms of ichthyosis. J Allergy Clin Immunol. 2016;139(1):152–65. https://doi.org/10.1016/j.jaci.2016.07.019.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Malik K, He H, Huynh TN, Tran G, Mueller K, Doytcheva K, et al. Ichthyosis molecular fingerprinting shows profound TH17 skewing and a unique barrier genomic signature. J Allergy Clin Immunol. 2019;143(2):604–18. https://doi.org/10.1016/j.jaci.2018.03.021.

    Article  CAS  PubMed  Google Scholar 

  68. Czarnowicki T, He H, Leonard A, Malik K, Magidi S, Rangel S, et al. The major orphan forms of ichthyosis are characterized by systemic T-cell activation and Th-17/Tc-17/Th-22/Tc-22 polarization in blood. J Investig Dermatol. 2018;138(10):2157–67. https://doi.org/10.1016/j.jid.2018.03.1523.

    Article  CAS  PubMed  Google Scholar 

  69. Akiyama M. Understanding immune profiles in ichthyosis may lead to novel therapeutic targets. J Allergy Clin Immunol. 2022;149(4):1210–2. https://doi.org/10.1016/j.jaci.2022.02.010.

    Article  CAS  PubMed  Google Scholar 

  70. Paller AS. Pathogenesis-based therapy with repurposed biologics for monogenic inflammatory skin disorders. JAMA Dermatol. 2020. https://doi.org/10.1001/jamadermatol.2020.1018.

    Article  PubMed  PubMed Central  Google Scholar 

  71. Haiges D, Fischer J, Hörer S, Has C, Schempp CM. Biologic therapy targeting IL-17 ameliorates a case of congenital ichthyosiform cornification disorder. JDDG Journal der Deutschen Dermatologischen Gesellschaft. 2019;17(1):70–2. https://doi.org/10.1111/ddg.13716.

    Article  PubMed  Google Scholar 

  72. Poulton C, Gration D, Murray K, Baynam G, Halbert A. Autosomal recessive congenital ichthyosis due to homozygous variants in NIPAL4 with a dramatic response to ustekinumab. Pediatr Dermatol. 2019;36(6):1002–3. https://doi.org/10.1111/pde.13995.

    Article  PubMed  Google Scholar 

  73. Lefferdink R, Rangel SM, Chima M, Ibler E, Pavel AB, Kim H, et al. Secukinumab responses vary across the spectrum of congenital ichthyosis in adults. Arch Dermatol Res. 2022:1–11.

  74. Cottle DL, Ursino GMA, Ip SCI, Jones LK, Ditommaso T, Hacking DF, et al. Fetal inhibition of inflammation improves disease phenotypes in harlequin ichthyosis. Hum Mol Genet. 2015;24(2):436–49. https://doi.org/10.1093/hmg/ddu459.

    Article  CAS  PubMed  Google Scholar 

  75. O’Shaughnessy RFL, Choudhary I, Harper JI. Interleukin-1 alpha blockade prevents hyperkeratosis in an in vitro model of lamellar ichthyosis. Hum Mol Genet. 2010;19(13):2594–605. https://doi.org/10.1093/hmg/ddq145.

    Article  CAS  PubMed  Google Scholar 

  76. Paller AS, van Steensel MA, Rodriguez-Martin M, Sorrell J, Heath C, Crumrine D, et al. Pathogenesis-based therapy reverses cutaneous abnormalities in an inherited disorder of distal cholesterol metabolism. J Invest Dermatol. 2011;131(11):2242–8. https://doi.org/10.1038/jid.2011.189.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Bergqvist C, Abdallah B, Hasbani DJ, Abbas O, Kibbi AG, Hamie L, et al. CHILD syndrome: a modified pathogenesis-targeted therapeutic approach. Am J Med Genet A. 2018;176(3):733–8. https://doi.org/10.1002/ajmg.a.38619.

    Article  CAS  PubMed  Google Scholar 

  78. Lai-Cheong JE, Elias PM, Paller AS. Pathogenesis-based therapies in ichthyoses. Dermatol Ther. 2013;26(1):46–54. https://doi.org/10.1111/j.1529-8019.2012.01528.x.

    Article  PubMed  PubMed Central  Google Scholar 

  79. Jensen TG, Jensen UB, Jensen PKA, Ibsen HH, Brandrup F, Ballabio A, et al. Correction of steroid sulfatase deficiency by gene transfer into basal cells of tissue-cultured epidermis from patients with recessive X-linked ichthyosis. Exp Cell Res. 1993;209(2):392–7. https://doi.org/10.1006/excr.1993.1326.

    Article  CAS  PubMed  Google Scholar 

  80. Freiberg RA, Choate KA, Deng H, Alperin ES, Shapiro LJ, Khavari PA. A model of corrective gene transfer in X-linked ichthyosis. Hum Mol Genet. 1997;6(6):927–33. https://doi.org/10.1093/hmg/6.6.927.

    Article  CAS  PubMed  Google Scholar 

  81. Aufenvenne K, Rice RH, Hausser I, Oji V, Hennies HC, Rio MD, et al. Long-term faithful recapitulation of transglutaminase 1-deficient lamellar ichthyosis in a skin-humanized mouse model, and insights from proteomic studies. J Investig Dermatol. 2012;132(7):1918–21. https://doi.org/10.1038/jid.2012.65.

    Article  CAS  PubMed  Google Scholar 

  82. Aufenvenne K, Larcher F, Hausser I, Duarte B, Oji V, Nikolenko H, et al. Topical enzyme-replacement therapy restores transglutaminase 1 activity and corrects architecture of transglutaminase-1-deficient skin grafts. Am J Hum Genet. 2013;93(4):620–30. https://doi.org/10.1016/j.ajhg.2013.08.003.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Plank R, Yealland G, Miceli E, Cunha DL, Graff P, Thomforde S, et al. Transglutaminase 1 replacement therapy successfully mitigates the autosomal recessive congenital ichthyosis phenotype in full-thickness skin disease equivalents. J Investig Dermatol. 2019;139(5):1191–5.

    Article  CAS  Google Scholar 

  84. Plank R, Obst K, Yealland G, Calderón M, Hedtrich S, Martina Eckl K, editors. Nanogel-mediated protein replacement therapy for autosomal recessive congenital ichthyosis (ARCI)2016.

  85. Freedman JC, Parry TJ, Zhang P, Majumdar A, Krishnan S, Regula LK, et al. Preclinical evaluation of a modified herpes simplex virus type 1 vector encoding human TGM1 for the treatment of autosomal recessive congenital ichthyosis. J Investig Dermatol. 2021;141(4):874-82.e6. https://doi.org/10.1016/j.jid.2020.07.035.

    Article  CAS  PubMed  Google Scholar 

  86. Zhang L, Ferreyros M, Feng W, Hupe M, Crumrine DA, Chen J, et al. Defects in stratum corneum desquamation are the predominant effect of impaired abca12 function in a novel mouse model of harlequin ichthyosis. PLoS ONE. 2016;11(8): e0161465-e. https://doi.org/10.1371/journal.pone.0161465.

    Article  Google Scholar 

  87. Grond S, Eichmann TO, Dubrac S, Kolb D, Schmuth M, Fischer J, et al. PNPLA1 deficiency in mice and humans leads to a defect in the synthesis of omega-O-acylceramides. J Investig Dermatol. 2017;137(2):394–402. https://doi.org/10.1016/j.jid.2016.08.036.

    Article  CAS  PubMed  Google Scholar 

  88. Khalil S, Bardawil T, Saade S, Chedraoui A, Ramadan N, Hasbani DJ, et al. Use of topical glycolic acid plus a lovastatin-cholesterol combination cream for the treatment of autosomal recessive congenital ichthyoses. JAMA Dermatol. 2018;154(11):1320–3. https://doi.org/10.1001/jamadermatol.2018.2904.

    Article  PubMed  PubMed Central  Google Scholar 

  89. Cottle DL, Ursino GMA, Jones LK, Tham MS, Zylberberg AK, Smyth IM. Topical aminosalicylic acid improves keratinocyte differentiation in an inducible mouse model of harlequin ichthyosis. (2666–3791 (Electronic)).

  90. Morgan JR, Choate KA, Medalie DA, Khavari PA. Corrective gene transfer in the human skin disorder lamellar ichthyosis. Nat Med. 1996;2(11):1263–7. https://doi.org/10.1038/nm1196-1263.

    Article  PubMed  Google Scholar 

  91. Gorell E, Nguyen N, Lane A, Siprashvili Z. Gene therapy for skin diseases. Cold Spring Harb Perspect Med. 2014;4(4): a015149.

    Article  Google Scholar 

  92. Richard G, Choate K, Milstone L, Bale S. Management of ichthyosis and related conditions gene-based diagnosis and emerging gene-based therapy. Dermatol Ther. 2013;26(1):55–68. https://doi.org/10.1111/j.1529-8019.2012.01553.x.

    Article  PubMed  Google Scholar 

  93. Akiyama M, Sugiyama-Nakagiri Y, Sakai K, McMillan JR, Goto M, Arita K, et al. Mutations in lipid transporter ABCA12 in harlequin ichthyosis and functional recovery by corrective gene transfer. J Clin Investig. 2005;115(7):1777–84.

    Article  CAS  Google Scholar 

  94. Rout DP, Nair A, Gupta A, Kumar P. Epidermolytic hyperkeratosis: clinical update. Clin Cosmet Investig Dermatol. 2019;12:333.

    Article  CAS  Google Scholar 

  95. Steijlen PM, Van Doorkn-Greebe RJ, Happle R, Van de Kerkhof PCM. Ichthyosis bullosa of Siemens responds well to low-dosage oral retinoids. Br J Dermatol. 1991;125(5):469–71.

    Article  CAS  Google Scholar 

  96. Ramot Y, Oláh A, Paus R. Cover image: neuroendocrine treatment of inherited keratin disorders by cannabinoids? Br J Dermatol. 2018;178(6):1469.

    Article  CAS  Google Scholar 

  97. March OP, Lettner T, Klausegger A, Ablinger M, Kocher T, Hainzl S, et al. Gene editing-mediated disruption of epidermolytic ichthyosis-associated KRT10 alleles restores filament stability in keratinocytes. J Investig Dermatol. 2019;139(8):1699-710.e6. https://doi.org/10.1016/j.jid.2019.03.1146.

    Article  CAS  PubMed  Google Scholar 

  98. Valentin FA-O, Wiegmann HA-O, Tarinski T, Nikolenko H, Traupe HA-O, Liebau EA-O, et al. Development of a pathogenesis-based therapy for peeling skin syndrome type 1. (1365–2133 (Electronic)).

  99. Marulli GC, Campione E, Chimenti MS, Terrinoni A, Melino G, Bianchi L. Type I lamellar ichthyosis improved by tazarotene 0.1% gel. Clin Exp Dermatol. 2003;28(4):391–3. https://doi.org/10.1046/j.1365-2230.2003.01318.x.

    Article  CAS  PubMed  Google Scholar 

  100. Cambiaghi S, Ermacora E. Antibiotic therapy in a boy affected by generalized epidermolytic hyperkeratosis. Dermatology. 1992;184(3):226. https://doi.org/10.1159/000247549.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Dermatology, American University of Beirut Medical Center, Riad El Solh/Beirut 1107 2020, P.O. Box 11-0236, Beirut, Lebanon

    Divina Justina Hasbani M.D. , Edward Eid M.D., Ossama Abbas M.D. & Mazen Kurban M.D.

  2. Department of Dermatology, Division of Pediatric Dermatology, Medical College of Wisconsin, Milwaukee, WI, USA

    Lamiaa Hamie M.D., MSc.

  3. Department of Radiology, American University of Beirut, Beirut, Lebanon

    Christel Tamer M.D.

  4. Department of Biochemistry and Molecular Genetics, American University of Beirut, Beirut, Lebanon

    Mazen Kurban M.D.

  5. Division of Genomics and Translational Biomedicine, College of Health and Life Sciences, Hamad Bin Khalifa University, Doha, Qatar

    Mazen Kurban M.D.

Authors
  1. Divina Justina Hasbani M.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Lamiaa Hamie M.D., MSc.
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Edward Eid M.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Christel Tamer M.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ossama Abbas M.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Mazen Kurban M.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Mazen Kurban M.D..

Ethics declarations

Funding

No sources of funding were used to conduct this study or prepare this manuscript.

Conflict of interest

The authors have no conflicts of interest to disclose.

Ethics approval

Not applicable.

Consent to participate/publish

Not applicable.

Availability of data and material

Not applicable.

Code availability

Not applicable.

Author contributions

All authors contributed significantly to the concept and planning, drafting, and revision of the manuscript. All authors approved the final submitted version of the manuscript.

Rights and permissions

Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Hasbani, D.J., Hamie, L., Eid, E. et al. Treatments for Non-Syndromic Inherited Ichthyosis, Including Emergent Pathogenesis-Related Therapy. Am J Clin Dermatol 23, 853–867 (2022). https://doi.org/10.1007/s40257-022-00718-8

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40257-022-00718-8

Search

Navigation