Pseudoxanthoma elasticum Q82.8

Author: Prof. Dr. med. Peter Altmeyer

Co-Autor: Johannes Heck

All authors of this article

Last updated on: 29.10.2020

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Synonym(s)

angioid streaks; Darier-Groenblad-Strandberg syndrome; Elastorrhexis systematic; elastorrhexis systematisata; Grönblad-Strandberg Syndrome; OMIM 264800; Pseudoxanthoma elasticum with angioid strips; PXE; Systematic Elastorrhexis

History
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Darier, 1896; Grönblad, 1929; Strandberg, 1929

Definition
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Rare, metabolic, autosomal inherited systemic disease(OMIM 264800) with consecutive mineralization disorder of the elastic connective tissue, manifesting on skin, eyes and cardiovascular system. Very few cases have also been reported of acquired Pseudoxanthoma elasticum.

Classification
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Classification according to Plomp et al (2010)

  • Main criteria
    • Skin: Irregular, scar-like skin relief due to flatly elevated, symptomless yellow papules/plaques laterally on the neck and/or in the large joint flexures (especially axillary); histopathologically fragmentation, agglutination and calcification of elastic fibres.
    • Eye: Peau d'orange (retina); "angioid streaks".
    • Genetics: Bi-allelic ABCC6 mutations; a 1st degree relative which meets the diagnostic criteria of PXE.
  • Secondary criteria
    • Eye: Retinal comets and/or "wing signs
    • Genetics: Heterozygote ABCC6 mutation

Occurrence/Epidemiology
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Incidence: Approx. 0.5-1.0/100,000 inhabitants/year. Prevalence is currently given as 1.0:25,000/100,000.

Etiopathogenesis
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The inheritance is mostly autosomal recessive (90% of cases), rarely autosomal dominant.

It is caused by mutations in the ABCC6 gene (syn.: MRP6 gene = multidrug resistance protein 6), which is mapped on chromosome 16p13.1. The ABCC6 gene encodes the transmembrane protein MRP6, which is responsible for a number of physiologically important processes. MRP6 belongs to the family of so-called "multidrug resistance-associated proteins (MRP)". MRPs are also involved in drug resistance, especially in combination with chemotherapy. The result is the production of non-functional MRP6, (S.u. ABC transporter). MRP6 proteins are preferentially expressed in the liver and kidney. They are responsible, among other things, for the transport of bilirubimetabolites from hepatocytes. So far, 32 PXE mutations have been detected.

In PXE, this dysfunction can no longer prevent calcification, fragmentation and degeneration of the elastic fibres. Ultimately, the exact mechanism has not been elucidated.

The cause of the few cases of acquired PXE that have become known worldwide is still unknown.

A significant number of patients with beta thalassemia develop clinical signs of PXE. Occasionally, a pseudoxanthoma-elasticum-like clinical picture has been described under therapy with penicillamine.

Manifestation
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Usually occurring before the age of 30.

Localization
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Especially the lateral neck and neck area, axillae, joint flexion, lateral trunk areas and navel are affected. Involvement of the oral mucosa and the mucosa of the nose, larynx, stomach, rectum, bladder and vagina is possible.

Clinical features
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Skin: Regionally limited, round or oval, symmetrically arranged, striped, spotted or hearth-shaped, slightly raised, soft, possibly confluent papules. Colour: Primarily violet, later white to yellowish, "ivory". At the "mature" stage of development, yellowish papules and plaques appear with a granular surface relief reminiscent of a plucked chicken skin (also cobbled).

An increased formation of wrinkles on the chin is regarded as a characteristic feature (goodbye sign).

Oral mucosa: analogous lesions are rarely found in the oral mucosa.

Eyes: visual defects in the 3rd to 4th decade of life, papillary "angioid streaks" of the ocular fundus. Calcification of elastic fibres causes tears in the choroidal lamina vitrea and the pigment epithelium(angioid streaks) and macular degeneration. There is a risk of retinal bleeding and loss of central vision.

Cardiovascular and other symptoms: hypertension (25%), arteriosclerotic changes (calcification of the elastica of the vessels) with midline claudication (20%) and angina pectoris (20%). Rarer are:

  • myocarditis
  • Aortitis
  • cerebral insults
  • Bleeding of the gastrointestinal tract and the kidneys (here also calcifications).
  • Bleeding tendencies: spontaneous vascular ruptures are the most frequent cause of death.

Symptoms of the disease often appear only in the second decade of life; slow development.

Histology
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  • Partially swollen, broken, mineralised, elastic fibres rich in calcium salts and acidic proteoglycans.
  • Electron microscopy: enlargement, cavern formation and fragmentation of the elastic fibres. Enlargement of a variable proportion of collagen fibrils with a flower-like structure in cross-section. Granulo-filamentary material and small calibre collagen.

Differential diagnosis
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Therapy
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Symptomatic, possibly surgery for cosmetic indication.

Prevention of consequential damages due to nicotine withdrawal, avoidance of atherogenic lipid metabolism disorders.

Therapy attempts with vitamin E or chelating agents (EDTA) are described in the same way as low-calcium diets, but are without lasting success.

Interdisciplinary cooperation with internists and ophthalmologists.

Progression/forecast
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Slowly progressive course, no regression, danger of blindness. Quoad vitam dependent on cardiovascular involvement.

Note(s)
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The diagnosis is probably:

  • Existence of 2 main criteria from the category skin or eye
  • Presence of a main criterion and (at least) one secondary criterion that does not belong to the same category as the main criterion.

Practical tips
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A presentation in a specialised centre for the diagnosis and therapy of the ophthalmological aspect of the disease is highly recommended. A molecular biological confirmation of the diagnosis is necessary. Human genetic counselling should be offered. The connection of patients to a self-help group is recommended.

Literature
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  1. Darier J (1896) Pseudoxanthoma elasticum. Mh Practical Derm 23: 609-611
  2. Finger RP et al (2009) Pseudoxanthoma elasticum: genetics, clinical manifestations and therapeutic approaches. Surv ophthalmol 54: 272-285
  3. Frank J et al (2011) Hereditary metabolic diseases with cutaneous manifestation. Dermatologist 62: 98-106
  4. Gheduzzi D et al (2003) Extracutaneous ultrastructural alterations in pseudoxanthoma elasticum. Ultrastruct Pathol 27: 375-384
  5. Grönblad E (1929) Angioid streaks - pseudoxanthoma elasticum. Acta ophthalmol 7: 329
  6. Hamlin N et al (2003) Acquired pseudoxanthoma elasticum-like syndrome in beta-thalassaemia patients. Br J Haematol 122: 852-854
  7. Jacobi H et al (1997) Pseudoxanthoma elasticum. Skin changes as a marker of systemic illness. Dermatologist 48: 191-194
  8. Jiang Q et al (2009) Pseudoxanthoma elasticum is a metabolic disease. J Invest Dermatol 129: 348-354
  9. Farewell M et al (2003) Prominent mental (chin) crease: a new sign of pseudoxanthoma elasticum. J Am Acad Dermatol 48: 620-622
  10. Plomp AS et al (2010) Proposal for updating the pseudoxanthoma elasticum classification system and review of the clinical findings. Am J Med Genet A 152A: 1049-1058
  11. Sies K, Ruzicka T (2015) Dangerous hereditary disease: Pseudoxanthoma elasticum. dermatologist 66: 31-32
  12. Strandberg J (1929) Pseudoxanthoma elasticum. Meeting of the Dermatological Society in Stockholm. Zentralbl skin venereal disease 31: 689
  13. Taylor NE et al (2004) Tumefactive lipedema with pseudoxanthoma elasticum-like microscopic changes. J Cutan Pathol 31: 205-209
  14. Vogel A et al (1985) On the light and electron microscopy of Pseudoxanthoma elasticum. Dermatologist 36: 269-273

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Please ask your physician for a reliable diagnosis. This website is only meant as a reference.

Authors

Last updated on: 29.10.2020