Pseudoxanthoma elasticum: a review of the literature with a clinical case

Cover Page

Cite item

Full Text

Open Access Open Access
Restricted Access Access granted
Restricted Access Subscription Access

Abstract

Pseudoxanthoma elasticum (Grönblad–Strandberg syndrome) is an inherited disease of an autosomal recessive type associated with a mutation in the ABCC6 gene, which causes a violation of the elastogenesis process. The disease is characterized by defects in the tissues of the skin, eyes and blood vessels. Skin lesions of Pseudoxanthoma elasticum represent small xanthomatous papules with tendency to be confluent; most frequently, they are located on the occipital skin, in axillary creases, on the lateral surfaces of the neck, and in skin deflection areas. The ocular involvement manifests as retinal angioid streaks on the fundus, representing the breaks in Bruch’s membrane, which often complicate by development of choroidal neovascularization. Timely diagnosis and early treatment of patients with active choroidal neovascularization caused by angioid streaks makes possible to stabilize the process and preserve visual functions.

About the authors

Ekaterina K. Gladysheva

Academician I.P. Pavlov First St. Petersburg State Medical University

Email: Woodstoree@ya.ru
ORCID iD: 0000-0001-9186-0994
Russian Federation, 6-8 L’va Tolstogo st., Saint Petersburg, 197022

Tatyana R. Parasunko

Academician I.P. Pavlov First St. Petersburg State Medical University

Email: exclamation@bk.ru
ORCID iD: 0000-0003-4533-7590
SPIN-code: 4362-6730
Russian Federation, Saint Petersburg

Kristina K. Gladysheva

Privolzhsky Research Medical University

Email: Gladysheva.Kristyna@yandex.ru
ORCID iD: 0000-0003-1261-3376
Russian Federation, Nizhniy Novgorod

Darya R. Parasunko

South Federal University

Author for correspondence.
Email: dariaparasunko@gmail.com
ORCID iD: 0000-0002-0559-7163
Russian Federation, Rostov-on-Don

Gassan B. Shaar

Academician I.P. Pavlov First St. Petersburg State Medical University

Email: ghassan_shaar@mail.ru
SPIN-code: 2956-4480

MD, Cand. Sci. (Medicine)

Russian Federation, Saint Petersburg

Svetlana G. Belekhova

Academician I.P. Pavlov First St. Petersburg State Medical University

Email: beleksv@yandex.ru
ORCID iD: 0000-0003-0293-4811
SPIN-code: 3637-7441

MD, Cand. Sci. (Medicine)

Russian Federation, Saint Petersburg

References

  1. Gronblad E. Angioid streaks — pseudoxanthoma elasticum. Acta Ophthal. 1929;7:329.
  2. Strandberg J. Pseudoxanthoma elasticum. Z Haut Geschlechtskr. 1929;31:689.
  3. Bartstra JW, Risseeuw S, de Jong PA, et al. Genotype-phenotype correlation in pseudoxanthoma elasticum. Atherosclerosis. 2021;324:18–26. doi: 10.1016/j.atherosclerosis.2021.03.012
  4. Jansen RS, Küçükosmanoglu A, de Haas M, et al. ABCC6 prevents ectopic mineralization seen in pseudoxanthoma elasticum by inducing cellular nucleotide release. PNAS USA. 2013;110(50): 20206–20211. doi: 10.1073/pnas.1319582110
  5. Uitto J, Li Q, van de Wetering K, et al. Insights into pathomechanisms and treatment development in heritable ectopic mineralization disorders: summary of the PXE international biennial research symposium-2016. J Invest Dermatol. 2017;137(4):790–795. doi: 10.1016/j.jid.2016.12.014
  6. Jansen RS, Duijst S, Mahakena S, et al. ABCC6-mediated ATP secretion by the liver is the main source of the mineralization inhibitor inorganic pyrophosphate in the systemic circulation-brief report. Arterioscler Thromb Vasc Biol. 2014;34(9):1985–1989. doi: 10.1161/ATVBAHA.114.304017
  7. Li Q, Kingman J, van de Wetering K, et al. Abcc6 knockout rat model highlights the role of liver in PPi homeostasis in pseudoxanthoma elasticum. J Invest Dermatol. 2017;137(5):1025–1032. doi: 10.1016/j.jid.2016.11.042
  8. Dedinszki D, Szeri F, Kozák E, et al. Oral administration of pyrophosphate inhibits connective tissue calcification. EMBO Mol Med. 2017;9(11):1463–1470. doi: 10.15252/emmm.201707532
  9. Kuzaj P, Kuhn J, Michalek RD, et al. Large-scaled metabolic profiling of human dermal fibroblasts derived from pseudoxanthoma elasticum patients and healthy controls. PLoS One. 2014;9(9): e108336. doi: 10.1371/journal.pone.0108336
  10. Hosen MJ, Lamoen A, De Paepe A, Vanakker OM. Histopathology of pseudoxanthoma elasticum and related disorders: histological hallmarks and diagnostic clues. Scientifica (Cairo). 2012;2012:598262. doi: 10.6064/2012/598262
  11. Plomp AS, Toonstra J, Bergen AAB, et al. Proposal for updating the pseudoxanthoma elasticum classification system and a review of the clinical findings. Am J Med Genet A. 2010;152A(4):1049–1058. doi: 10.1002/ajmg.a.33329
  12. Jensen OA. Bruch’s membrane in pseudoxanthoma elasticum. Histochemical, ultrastructural and x-ray microanalytical study of the membrane and angioid streak areas. Albrecht Von Graefes Arch Klin Exp Ophthalmol. 1977;203:311–320. doi: 10.1007/BF00409836
  13. Gheduzzi D, Sammarco R, Quaglino D, et al. Extracutaneous ultrastructural alterations in pseudoxanthoma elasticum. Ultrastruct Pathol. 2003;27(6):375–384. doi: 10.1080/01913120390248584
  14. Lebwohl M, Neldner K, Pope FM, et al. Classification of pseudoxanthoma elasticum: report of a consensus conference. J Am Acad Dermatol. 1994;30(1):103–107. doi: 10.1016/s0190-9622(08)81894-4
  15. Christen-Zach S, Huber M, Struk B, et al. Pseudoxanthoma elasticum: evaluation of diagnostic criteria based on molecular data. Br J Dermatol. 2006;155(1):89–93. doi: 10.1111/j.1365-2133.2006.07278.x
  16. Marconi B, Bobyr I, Campanati A, et al. Pseudoxanthoma elasticum and skin: Clinical manifestations, histopathology, pathomechanism, perspectives of treatment. Intractable Rare Dis Res. 2015;4(3):113–122. doi: 10.5582/irdr.2015.01014
  17. Laube S, Moss C. Pseudoxanthoma elasticum. Arch Dis Childhood. 2005;90(7):754–756. doi: 10.1136/adc.2004.062075
  18. Maronese CA, Spigariolo CB, Boggio FL, et al. Clinical, genetic, and ultrasonographic features of periumbilical perforating pseudoxanthoma elasticum. Skin Res Technol. 2021;27(4):646–647. doi: 10.1111/srt.13014
  19. Lewis KG, Bercovitch L, Dill SW, Robinson-Bostom L. Acquired disorders of elastic tissue: part I. Increased elastic tissue and solar elastotic syndromes. J Am Acad Dermatol. 2004;51(1):1–21. doi: 10.1016/j.jaad.2004.03.013
  20. Ibanez-Samaniego L, Ochoa-Palominos A, Catalina-Rodriguez MV, et al. Penicillamine induced pseudopseudoxanthoma elasticum in a patient with Wilson’s disease, which role plays the hepatologist? Rev Esp Enferm Dig. 2015;107(3):190–191.
  21. Kazakis AM, Parish WR. Periumbilical perforating pseudoxanthoma elasticum. J Am Acad Dermatol. 1988;19(2):384–388. doi: 10.1016/s0190-9622(88)70183-8
  22. Wang AR, Fonder MA, Telang GH, et al. Late-onset focal dermal elastosis: an uncommon mimicker of pseudoxanthoma elasticum. J Cutan Pathol. 2012;39(10):957–961. doi: 10.4081/dr.2022.9337
  23. Finger RP, Charbel Issa P, Ladewig M, et al. Fundus autofluorescence in Pseudoxanthoma elasticum. Retina. 2009;29(10):1496–1505. doi: 10.1097/IAE.0b013e3181aade47
  24. Miksch S, Lumsden A, Guenther UP, et al. Molecular genetics of pseudoxanthoma elasticum: type and frequency of mutations in ABCC6. Hum Mutat. 2005;26(3):235–248. doi: 10.1002/humu.20206
  25. Germain DP. Pseudoxanthoma elasticum. Orphanet Journal of Rare Disease. 2017;12:85. doi: 10.1186/s13023-017-0639-8
  26. Leftheriotis G, Omarjee L, Le Saux O, et al. The vascular phenotype in Pseudoxanthoma elasticum and related disorders: contribution of a genetic disease to the understanding of vascular calcification. Front Genet. 2013;4:4. doi: 10.3389/fgene.2013.00004
  27. Vanakker OM, Leroy BP, Coucke P, et al. Novel clinico-molecular insights in pseudoxanthoma elasticum provide an efficient molecular screening method and a comprehensive diagnostic flowchart. Hum Mutat. 2008;29(1):205. doi: 10.1002/humu.9514
  28. Struk B, Cai L, Zach S, et al. Mutations of the gene encoding the transmembrane transporter protein ABC-C6 cause pseudoxanthoma elasticum. J Mol Med (Berl). 2000;78:282–286. doi: 10.1007/s001090000114
  29. Letavernier E, Kauffenstein G, Huguet L, et al. ABCC6 deficiency promotes development of randall plaque. J Am Soc Nephrol. 2018;29(9):2337–2347. doi: 10.1681/ASN.2017101148
  30. Rosina C, Romano M, Cigada M, et al. Intravitreal bevacizumab for choroidal neovascularization secondary to angioid streaks: A long-term follow-up study. Eur J Ophthalmol. 2015;25(1):47–50. doi: 10.5301/ejo.5000505
  31. Zimmo L, Rudarakanchana N, Thompson M, et al. Renal artery aneurysm formation secondary to pseudoxanthoma elasticum. J Vasc Surg. 2013;57(3):842–844. doi: 10.1016/j.jvs.2012.09.016
  32. Van den Berg JS, Hennekam RCM, Cruysberg JRM, et al. Prevalence of symptomatic intracranial aneurysm and ischaemic stroke in pseudoxanthoma elasticum. Cerebrovasc Dis. 2000;10(4):315–319. doi: 10.1159/000016076
  33. Germain DP, Boutouyrie P, Laloux B, Laurent S. Arterial remodeling and stiffness in patients with pseudoxanthoma elasticum. Arterioscler Thromb Vasc Biol. 2003;23(5):836–841. doi: 10.1161/01.ATV.0000067428.19031.28
  34. Goral V, Demir D, Tuzun Y, et al. Pseudoxantoma elasticum, as a repetitive upper gastrointestinal hemorrhage cause in a pregnant woman. World J Gastroenterol. 2007;13(28):3897–3899. doi: 10.3748/wjg.v13.i28.3897
  35. Viljoen DL, Bloch C, Beighton P. Plastic surgery in pseudoxanthoma elasticum experience in nine patients. Plast Reconstr Surg. 1990;85(2):233–238. doi: 10.1097/00006534-199002000-00011
  36. Ng ABY, O’Sullivan ST, Sharpe DT. Plastic surgery and pseudoxanthoma elasticum. Br J Plast Surg. 1999;52:594–596. doi: 10.1054/bjps.1999.3139
  37. Stumpf MJ, Schahab N, Nickeing G, et al. Therapy of pseudoxanthoma elasticum: current knowledge and future perspectives. Biomedicines. 1895;9(12):1895. doi: 10.3390/biomedicines9121895
  38. Fuisting B, Richard G. Transpupillary thermotherapy (TTT) — Review of the clinical indication spectrum. Med Laser Appl. 2010;25(4):214–222. doi: 10.1016/j.mla.2010.07.002
  39. Ozdek S, Bozan E, Gürelik G, Hasanreisoglu B. Transpupillary thermotherapy for the treatment of choroidal neovascularization secondary to angioid streaks. Can J Ophthalmol. 2007;42(1):95–100. doi: 10.3129/can.j.ophthalmol.06-089
  40. Shaikh S, Ruby AJ, Williams GA. Photodynamic therapy using verteporfin for choroidal neovascularization in angioid streaks. Am J Ophthalmol. 2003;135(1):1–6. doi: 10.3341/kjo.2007.21.3.142
  41. American Academy of Ophthalmology. Macular translocation. Ophthalmology. 2000;107(5):1015–1018. doi: 10.1016/S0161-6420(00)00082-8
  42. Ehlers JP, Maldonado R, Sarin N, Toth CA. Treatment of non-age-related macular degeneration submacular diseases with macular translocation surgery. Retina. 2011;31(7):1337–1346. doi: 10.1097/IAE.0b013e31820668cf
  43. Fujii GY, Humayun MS, Pieramici DJ, et al. Initial experience of inferior limited macular translocation for subfoveal choroidal neovascularization resulting from causes other than age-related macular degeneration. Am J Ophthalmol. 2001;131(1):90–100. doi: 10.1016/s0002-9394(00)00769-8
  44. Lomoriello DS, Parravano MC, Chiaravalloti A, Varano M. Choroidal neovascularization in angioid streaks and pseudoxanthoma elasticum: 1 year follow-up. Eur J Ophthalmol. 2009;19(1):151–153. doi: 10.3980/j.issn.2222-3959.2011.04.25
  45. Myung JS, Bhatnagar P, Spaide RF, et al. Long-term outcomes of intravitreal antivascular endothelial growth factor therapy for the management of choroidal neovascularization in pseudoxanthoma elasticum. Retina. 2010;30(5):748–755. doi: 10.1097/IAE.0b013e3181c596b1
  46. Ladas ID, Kotsolis A, Ladas DS, et al. Intravitreal ranibizumab treatment of macular choroidal neovascularization secondary to angioid streaks. Retina. 2010;30(8):1185–1189. doi: 10.1097/iae.0b013e3181d2f11d
  47. Zebardast N, Adelman RA. Intravitreal ranibizumab for treatment of choroidal neovascularization secondary to angioid streaks in pseudoxanthoma elasticum: Five-year follow-up. Semin Ophthalmol. 2012;27(3–4):61–64. doi: 10.3109/08820538.2012.680644
  48. Mimoun G, Ebran J-M, Grenet T, et al. Ranibizumab for choroidal neovascularization secondary to pseudoxanthoma elasticum: 4-year results from the PIXEL study in France. Graefe’s Arch Clin Exp Ophthalmol. 2017;255:1651–1660. doi: 10.1007/s00417-017-3685-y
  49. Huang J, Snook A, Uitto J, Li Q. Adenovirus-mediated ABCC6 gene therapy for heritable ectopic mineralization disorders. J Investig Dermatol. 2019;139(6):1254–1263. doi: 10.1016/j.jid.2018.12.017
  50. Lee CS, Bishop ES, Zhang R, et al. Adenovirus-mediated gene delivery: Potential applications for gene and cell-based therapies in the new era of personalized medicine. Genes Dis. 2017;4(2):43–63. doi: 10.1016/j.gendis.2017.04.001
  51. Aravalli RN, Steer CJ. Gene editing technology as an approach to the treatment of liver diseases. Expert Opin Biol Ther. 2016;16(5): 595–608. doi: 10.1517/14712598.2016.1158808
  52. Von Niessen AGO, Poleganov MA, Rechner C, et al. Improving mRNA-based therapeutic gene delivery by expression-augmenting 3' utrs identified by cellular library screening. Mol Ther. 2019; 27(4):824–836. doi: 10.1016/j.ymthe.2018.12.011
  53. Schibler D, Russell RG, Fleisch H. Inhibition by pyrophosphate and polyphosphate of aortic calcification induced by vitamin D3 in rats. Clin Sci. 1968;35(2):363–372.
  54. Pomozi V, Brampton C, Van De Wetering K, et al. Pyrophosphate supplementation prevents chronic and acute calcification in ABCC6-deficient mice. Am J Pathol. 2017;187(6):1258–1272. doi: 10.1016/j.ajpath.2017.02.009
  55. Pomozi V, Julian CB, Zoll J, et al. Dietary pyrophosphate modulates calcification in a mouse model of pseudoxanthoma elasticum: Implication for treatment of patients. J Investig Dermatol. 2019;139(5):1082–1088. doi: 10.1016/j.jid.2018.10.040
  56. Lee SJ, Lee I-K, Jeon J-H. Vascular calcification — new insights into its mechanism. Int J Mol Sci. 2020;21(8):2685. doi: 10.3390/ijms21082685
  57. Hilaire CS, Ziegler SG, Markello TC, et al. NT5E mutations and arterial calcifications. N Engl J Med. 2011;364:432–442. doi: 10.1056/NEJMoa0912923
  58. Ziegler SG, Ferreira CR, MacFarlane EG, et al. Ectopic calcification in pseudoxanthoma elasticum responds to inhibition of tissue-nonspecific alkaline phosphatase. Sci Transl Med. 2017;9(393):9. doi: 10.1126/scitranslmed.aal1669

Supplementary files

Supplementary Files
Action
1. JATS XML
Download
2. Fig. 1. The skin lesions of Pseudoxanthoma elasticum syndrome are confluent xanthomatous papules on the lateral surface of the neck

Download (164KB)
Indexing metadata
3. Fig. 2. The fundus photo of the right and left eyes. In the posterior pole of the right eye, there are dark red vascular-like lines (angioid streaks) with yellow areas of atrophy radially diverging from the optic disc to the periphery: a — hard exudates in the macular area, subretinal hemorrhage and fibrosis; b — dark red angioid streaks in the posterior pole of the left eye. In the macular area, angioid streaks are located in the parafoveal zone

Download (178KB)
Indexing metadata
4. Fig. 3. The OCT of the macular area of the retina of the right eye. Fibrovascular detachment of neuroepithelium, intraretinal fluid

Download (443KB)
Indexing metadata
5. Fig. 4. The OCT of the macular area of the retina of the left eye. The macular profile is preserved, in the peripapillary area there are a defect in the ellipsoid zone, a fibrovascular detachment of the pigment epithelium

Download (468KB)
Indexing metadata
6. Fig. 5. The fundus image of the right eye (a) and the left eye (b) in the short-wave autofluorescence mode, there are hypoautofluorescence loci in the peripapillary and papillomacular areas

Download (170KB)
Indexing metadata
7. Fig. 6. Fluorescein angiography of the right eye: leakage and accumulation of dye in the fibrosing choroidal neovascularization in the parafoveal area (a), the late phase (b)

Download (157KB)
Indexing metadata
8. Fig. 7. The fundus photo of the right eye (a) and the left eye (b) at the last visit

Download (225KB)
Indexing metadata

Copyright (c) 2024 Eco-Vector

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
 


This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies