Clinical Challenge: Cutaneous Textural Changes on the Neck of a Middle-Aged Woman

Discussion: Pseudoxanthoma Elasticum

Pseudoxanthoma elasticum (PXE) is an autosomal-recessive connective tissue disorder caused primarily by mutations in the ABCC6 gene.^1-3 The manifestations of PXE occur in the skin, eyes, and cardiovascular system.^1-3 The physical findings are attributed to the progressive calcification of elastic fibers in the mid and deep reticular dermis, the internal elastic lamina of medium-sized blood vessels, and the Bruch membrane of the retina.⁴ Subsequent morbidity in patients with PXE is often attributed to resulting cardiovascular pathology, which can include hypertension, angina pectoris, and intermittent claudication.⁴ The ophthalmologic manifestations of PXE can lead to loss of central vision.³

PXE occurs in all races but appears to affect women disproportionately, although this finding may be the result of gender differences in symptom reporting.⁵ Frequency in the general population is estimated to be approximately 1:50,000 persons, yet a precise incidence is unknown because many patients have a mild phenotype that may go clinically unrecognized.^5,6 Cutaneous changes tend to be the first sign, and these may be followed by extracutaneous disease in the ocular, cardiovascular, and gastrointestinal systems.

Cutaneous manifestations usually develop during adolescence and into the second or third decade of life.^1,6 The classic findings are yellowish papules on the lateral aspect of the neck. Lesions are often described as resembling “plucked chicken skin” or “Moroccan leather” and having a “cobblestone” appearance.⁷ Mental creases commonly occur in people with PXE.⁸ Neck involvement can be followed by similar lesions affecting the axilla and flexural surfaces, and less commonly the periumbilical region.⁶ As PXE progresses, the skin can lose its elasticity prematurely and become lax, resulting in redundant skin folds and prominent skin creases of the chin, forehead, and corners of the mouth.

The differential diagnosis of PXE based on cutaneous lesions is broad and depends on presentation. Papular lesions may mimic acquired PXE (related to hemoglobinopathy), actinic elastosis related to skin aging, papillary dermal elastolysis, dermatofibrosis lenticularis (of Buschke-Ollendorff syndrome), elastosis perforans serpiginosa, and pseudo-PXE related to D-penicillamine. An accurate diagnosis may not be made until ocular or cardiovascular complications develop in the third or fourth decade of life.⁶

The gold standard for diagnosis is clinical presentation with biopsy showing calcification of elastic fibers, confirmed by a calcium stain such as hematoxylin and eosin, von Kossa, or Verhoeff-van Gieson.⁷ Following diagnosis, skin, cardiac, and fundoscopic examinations are recommended for both the patient and all first-degree relatives. Genetic counseling is recommended for all patients with a personal or family history, even in cases of minimal phenotypical expression. If a definitive diagnosis of PXE is in question, a mutation analysis for ABCC6 is warranted.⁴

There are no known specific or effective treatments for the systemic manifestations of PXE, and symptom-directed therapy continues to be the mainstay of treatment.^5,6 Progress has been made in treating the ocular complications of PXE with the intravitreal injection of vascular endothelial growth factor antagonists to prevent neovascularization.⁹ Lifestyle modification, including smoking cessation, weight loss, and moderate physical exercise, are recommended to reduce cardiovascular risk factors.¹

People with PXE should be treated by a multidisciplinary team, including a dermatologist, primary care physician, ophthalmologist, cardiologist, and genetics professional.

Case Conclusion

The patient was informed of the diagnosis and had a negative in-office stool guaiac test. She was referred for cardiology and ophthalmology consultations, but shortly thereafter moved out of state and was lost to follow up. 

References

1. Germain DP. Pseudoxanthoma elasticum. Orphanet J Rare Dis. 2017;12:85.
2. Li Q, Jiang Q, Pfendner E, Váradi A, Uitto J. Pseudoxanthoma elasticum: Clinical phenotypes, molecular genetics and putative pathomechanisms. Exp Dermatol. 2009;18:1-11.
3. Moitra K, Garcia S, Jaldin M, et al. ABCC6 and pseudoxanthoma elasticum: the face of a rare disease from genetics to advocacy. Int J Mol Sci. 2017;18:1488.
4. Uitto J, Li Q, Jiang Q. Pseudoxanthoma elasticum: molecular genetics and putative pathomechanisms. J Invest Dermatol. 2010;130:661-670.
5. Uitto J, Váradi A, Bercovitch L, Terry PF, Terry SF. Pseudoxanthoma elasticum: progress in research toward treatment: summary of the 2012 PXE International Research Meeting. J Invest Dermatol. 2013;133:1444-1449.
6. Marconi B, Bobyr I, Campanati A, et al. Pseudoxanthoma elasticum and skin: Clinical manifestations, histopathology, pathomechanism, perspectives of treatment. Intractable Rare Dis Res. 2015;4:113-122.
7. Plomp AS, Toonstra J, Bergen AB, van Dijk MR, de Jong P. Proposal for updating the pseudoxanthoma elasticum classification system and a review of the clinical findings. Am J Med Genet. 2010;152A:1049-1058.
8. Lebwohl M, Lebwohl E, Bercovitch L. Prominent mental (chin) crease: a new sign of pseudoxanthoma elasticum. J Am Acad Dermatol. 2003;48:620-622.
9. Finger RP, Charbel Issa P, Schmitz-Valckenberg S, Holz FG, Scholl HN. Long term-effectiveness of intravitreal bevacizumab for choroidal neovascularization secondary to angioid streaks in pseudoxanthoma elasticum. Retina. 2011;31:1268-1278.