Vitamin D Status in Distinct Types of Ichthyosis: Importance of Genetic Type and Severity of Scaling

Authors

  • Mi-Ran Kim
  • Vinzenz Oji
  • Frederic Valentin
  • Heiko Traupe
  • Jerzy-Roch Nofer
  • Ingrid Hausser
  • Hans Christian Hennies
  • Katja Eckl
  • Stefan A. Wudy
  • Alberto Sánchez-Guijo
  • Laura Kerschke
  • Judith Fischer
  • Kira Süßmuth Department of Dermatology, University Hospital Münster, DE-48149 Münster, Germany

DOI:

https://doi.org/10.2340/00015555-3887

Keywords:

ichthyosis, vitamin D deficiency, parathyroid hormone

Abstract

Data on vitamin D status of patients with inherited ichthyosis in Europe is scarce and unspecific concerning the genetic subtype. This study determined serum levels of 25-hydroxyvitamin D3 (25(OH)D3) in 87 patients with ichthyosis; 69 patients were additionally analysed for parathyroid hormone. Vitamin D deficiency was pronounced in keratinopathic ichthyosis (n = 17; median 25(OH)D3: 10.5 ng/ml), harlequin ichthyosis (n = 2;7.0 ng/ml) and rare syndromic subtypes (n = 3; 7.0 ng/ml). Vitamin D levels were reduced in TG1-proficient lamellar ichthyosis (n = 15; 8.9 ng/ml), TG1-deficient lamellar ichthyosis (n = 12; 11.7 ng/ml), congenital ichthyosiform erythroderma (n = 13; 12.4 ng/ml), Netherton syndrome (n = 7; 10.7 ng/ml) and X-linked ichthyosis (n = 8; 13.9 ng/ml). In ichthyosis vulgaris 25(OH)D3 levels were higher (n = 10; 19.7 ng/ml). Parathyroid hormone was elevated in 12 patients. Low 25(OH)D3 levels were associated with high severity of scaling (p = 0.03) implicating scaling as a risk factor for vitamin D deficiency. Thus, this study supports our recent guidelines for ichthyoses, which recommend screening and substituting for vitamin D deficiency.

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References

Oji V, Tadini G, Akiyama M, Blanchet Bardon C, Bodemer C, Bourrat E, 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: 607–641.

Hoppe T, Winge MC, Bradley M, Nordenskjöld M, Vahlquist A, Berne B, et al. X-linked recessive ichthyosis: an impaired barrier function evokes limited gene responses before and after moisturizing treatments. Br J Dermatol 2012; 167: 514–522.

Perusquía-Ortiz AM, Oji V, Sauerland MC, Tarinski T, Zaraeva I, Seller N, et al. Complete filaggrin deficiency in ichthyosis vulgaris is associated with only moderate changes in epidermal permeability barrier function profile. J Eur Acad Dermatol Venereol 2013; 27: 1552–1558.

Chouhan K, Sethuraman G, Gupta N, Sharma VK, Kabra M, Khaitan BK, et al. Vitamin D deficiency and rickets in children and adolescents with ichthyosiform erythroderma in type IV and V skin. Br J Dermatol 2012; 166: 608–615.

Reid IR. What diseases are causally linked to vitamin D deficiency? Arch Dis Child 2016; 101: 185–189.

Trochoutsou AI, Kloukina V, Samitas K, Xanthou G. Vitamin-D in the immune system: genomic and non-genomic actions. Mini Rev Med Chem 2015; 15: 953–963.

Wang TT, Nestel FP, Bourdeau V, Nagai Y, Wang Q, Liao J, et al. Cutting edge: 1,25-dihydroxyvitamin D3 is a direct inducer of antimicrobial peptide gene expression. J Immunol 2004; 173: 2909–2912.

Heilborn JD, Weber G, Grönberg A, Dieterich C, Ståhle M. Topical treatment with the vitamin D analogue calcipotriol enhances the upregulation of the antimicrobial protein hCAP18/LL-37 during wounding in human skin in vivo. Exp Dermatol 2010; 19: 332–338.

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: e151–e155.

Angmo D, Patil B, Agarwal R, Mohanty K, Singh A. A unique case of joag with lamellar ichthyosis with rickets: a case report and review of the literature. J Glaucoma 2016; 25: e280–e283.

Bhagat SB, Bhagat SS, Sharma HK, Naik M, Amin P, Pandit J. Severe bilateral rachitic genu valgum in patients with nonbullous congenital ichthyosiform erythroderma: a report of two cases and review of literature. J Pediatr Orthop B 2007; 16: 423–428.

Frascari F, Dreyfus I, Rodriguez L, Gennero I, Ezzedine K, Salles JP, et al. Prevalence and risk factors of vitamin D deficiency in inherited ichthyosis: a French prospective observational study performed in a reference center. Orphanet J Rare Dis 2014; 9: 127.

Sethuraman G, Sreenivas V, Yenamandra VK, Gupta N, Sharma VK, Marwaha RK, et al. Threshold levels of 25-hydroxyvitamin D and parathyroid hormone for impaired bone health in children with congenital ichthyosis and type IV and V skin. Br J Dermatol 2015; 172: 208–214.

Süßmuth K, Gruber R, Rodriguez E, Traupe H, Amler S, Sánchez-Guijo A, et al. Increased prevalence of filaggrin deficiency in 51 patients with recessive X-linked ichthyosis presenting for dermatological examination. J Invest Dermatol 2018; 138: 709–711.

Oji V, Seller N, Sandilands A, Gruber R, Gerss J, Hüffmeier U, et al. Ichthyosis vulgaris: novel FLG mutations in the German population and high presence of CD1a+ cells in the epidermis of the atopic subgroup. Br J Dermatol 2009; 160: 771–781.

Sánchez-Guijo A, Oji V, Hartmann MF, Schuppe HC, Traupe H, Wudy SA. High levels of oxysterol sulfates in serum of patients with steroid sulfatase deficiency. J Lipid Res 2015; 56: 403–412.

Oji V, Oji ME, Adamini N, Walker T, Aufenvenne K, Raghunath M, et al. Plasminogen activator inhibitor-2 is expressed in different types of congenital ichthyosis: in vivo evidence for its cross-linking into the cornified cell envelope by transglutaminase-1. Br J Dermatol 2006; 154: 860–867.

Hotz A, Kopp J, Bourrat E, Oji V, Komlosi K, Giehl K, et al. Meta-analysis of mutations in ALOX12B or ALOXE3 identified in a large cohort of 224 patients. Genes (Basel) 2021; 12: 80.

Arin MJ, Oji V, Emmert S, Hausser I, Traupe H, Krieg T, et al. Expanding the keratin mutation database: novel and recurrent mutations and genotype-phenotype correlations in 28 patients with epidermolytic ichthyosis. Br J Dermatol 2011; 164: 442–447.

Rodríguez-Manchón S, Pedrón-Giner C, Cañedo-Villarroya E, Muñoz-Codoceo RA, Hernández-Martín Á. Malnutrition in children with ichthyosis: recommendations for monitoring from a multidisciplinary clinic experience. J Am Acad Dermatol 2021; 85: 144–151.

Thyssen JP, Thuesen B, Huth C, Standl M, Carson CG, Heinrich J, et al. Skin barrier abnormality caused by filaggrin (FLG) mutations is associated with increased serum 25-hydroxyvitamin D concentrations. J Allergy Clin Immunol 2012; 130: 1204–1207.e2.

Milstone LM, Ellison AF, Insogna KL. Serum parathyroid hormone level is elevated in some patients with disorders of keratinization. Arch Dermatol 1992; 128: 926–930.

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. doi: 10.1542/peds.2015–1313.

Chung C, Silwal P, Kim I, Modlin RL, Jo EK. Vitamin D-cathelicidin axis: at the crossroads between protective immunity and pathological inflammation during infection. Immune Netw 2020; 20: e12.

Ebadi M, Montano-Loza AJ. Perspective: improving vitamin D status in the management of COVID-19. Eur J Clin Nutr 2020; 74: 856–859.

Amrein K, Papinutti A, Mathew E, Vila G, Parekh D. Vitamin D and critical illness: what endocrinology can learn from intensive care and vice versa. Endocr Connect 2018; 7: R304–R315.

Smolders J, van den Ouweland J, Geven C, Pickkers P, Kox M. Letter to the Editor: Vitamin D deficiency in COVID-19: Mixing up cause and consequence. Metabolism 2021; 115: 154434.

Panagiotou G, Tee SA, Ihsan Y, Athar W, Marchitelli G, Kelly D, et al. Low serum 25-hydroxyvitamin D (25[OH]D) levels in patients hospitalised with COVID-19 are associated with greater disease severity, Clin Endocrinol 2020; 93: 508–514.

Rabenberg M, Mensink GBM. Vitamin-D-status in Deutschland. J Health Monitoring 2016; 1: 36–42.

Sengler C, Zink J, Klotsche J, Niewerth M, Niewerth M, Liedmann I, et al. Vitamin D deficiency is associated with higher disease activity and the risk for uveitis in juvenile idiopathic arthritis – data from a German inception cohort. Arthritis Res Ther 2018; 20: 276.

Additional Files

Published

2021-09-15

How to Cite

Kim, M.-R., Oji, V., Valentin, F., Traupe, H., Nofer, J.-R., Hausser, I., … Süßmuth, K. (2021). Vitamin D Status in Distinct Types of Ichthyosis: Importance of Genetic Type and Severity of Scaling. Acta Dermato-Venereologica, 101(9), adv00546. https://doi.org/10.2340/00015555-3887