Elastosis perforans serpiginosa Associated with Pseudo-Pseudoxanthoma elasticum during Treatment of Wilson’s Disease with Penicillamine

Abstract

Background: Elastosis perforans serpiginosa (EPS) is a reactive perforating dermatosis characterized by the elimination of abnormal elastic fibers from the upper dermis through the epidermis. In a few cases, it occurs as a side effect of treatment by D-penicillamine (DPA). The first case of EPS induced by DPA was described in 1972 in a patient treated for Wilson’s disease. Subsequently, cutaneous changes resembling pseudoxanthoma elasticum (PXE) were observed in patients treated with DPA and were reported as pseudo-PXE. Case Report: We report herein the clinical, pathological and ultrastructural study of 2 new cases of DPA-induced EPS and pseudo-PXE. These patients had been treated for Wilson’s disease since 14 and 16 years, respectively. Characteristic abnormal elastic fibers were found on histopathological examination of both EPS and pseudo-PXE skin and confirmed by an ultrastructural study. There was no ABCC6 mutation. Discussion: Penicillamine is able to induce widespread, cutaneous and systemic, elastic fiber damage. Our patients present typical features of DPA-induced elastosis, presenting as EPS and pseudo-PXE. ABCC6 mutation is associated with PXE and, as expected, it was absent in our cases of pseudo-PXE. This elastopathy has been related to morphologic changes in elastic fibers secondary to prolonged therapy in most cases. DPA may interfere with elastin cross-linking through inhibition of the enzyme lysyl oxidase, or by formation of complexes with the cross-linked precursors, impairing a normal maturation of elastic fibers. However, no fatal complication of DPA-induced elastopathy has been reported so far. An improvement of the cutaneous lesions is expected after the drug discontinuation.

Penicillamine-induced Elastosis Perforans Serpiginosa and Cutis Laxa in a Patient with Wilson's Disease

“…Furthermore, discontinuation of penicillamine therapy does not guarantee the prevention of further development of the dermatosis. Multiple case reports have described the abrupt onset or recurrence of EPS months to years after stopping penicillamine therapy 9,14,16 . This is likely related to the cumulative dose and the slow clearance of the drug with the remaining effects on the elastic tissue 9 .…”

Appearances in dermatopathology: The diagnostic and the deceptive

“…Similar appearance of elastic fibers can also be seen in D-penicillamine-induced PXE and periumbilical PXE. [51] …”

Pseudoxanthoma elasticum: the paradigm of ectopic mineralization disorders – diagnosis and treatment

“…These cutaneous findings are occasionally associated with angioid streaks. It should be noted that a histopathologically distinct disorder, elastosis perforans serpiginosa, which often accompanies d-penicillamine therapy [14,15], can also be encountered in patients with PXE.…”