Penicillamine induced pseudoxanthoma elasticum with elastosis perforans serpiginosa

Long term D-penicillamine therapy, especially when used to treat Wilson's disease has been shown to cause elastosis perforans serpiginosa, pseudoxanthoma elasticum perforans and other degenerative dermatoses. We report a 23-year-old male patient who presented with multiple firm papules, nodules over the neck, axillae, front of elbows for five years. He was a known case of Wilson's disease on long-term treatment with penicillamine for the past 12 years. The papulonodular lesions were non-tender and some were discrete while others were arranged in a circinate pattern. There was central scarring of the skin within the circinate lesions. In addition, there were several small yellowish papules on both sides of the neck which eventually became confluent to form plaques. Histopathology confirmed the diagnosis of elastosis perforans serpiginosa and pseudoxanthoma elasticum. He was treated with cryotherapy (using liquid nitrogen through cryojet) for former lesions. The lesions showed remarkable improvement after five sittings. Now the patient is under trientine hydrochloride (750 mg twice daily) for Wilson's disease.     

Elastosis perforans serpiginosa and pseudoxanthoma elasticum-like skin change due to D-penicillamine

High dose D-penicillamine is used in the therapy of Wilson's disease and cystinuria. Elastosis perforans serpiginosa (Guilaine, Benhamou & Molas, 1972), penicillamine dermopathy (Sternleib & Scheinberg, 1964; Katz, 1967; Beer & Cooke, 1967), cutis hyperelastica (Charlebois, Cadotte & Barbeau, 1972), excessive skin wrinkling (Greer, Askew & Richardson, 1976) and pseudoxanthoma elasticum-like skin change (Meyrick Thomas et al., 1984) have all been documented as developing in consequence of such therapy. We report a patient in whom mild pseudoxanthoma elasticum-like skin change and elastosis perforans serpiginosa developed, following high dose D-penicillamine treatment for cystinuria.     

Autosomal recessive type 2 pseudoxanthoma elasticum presenting with generalized skin laxity

Herein, we describe a sporadic case of recessive type 2 pseudoxanthoma elasticum. A 26-year-old woman without family history presented with cutis laxa-like marked wrinkling involving the whole-body and a serpiginous streak on the upper left arm. She denied any other systemic problems related to difficulty with visual acuity or vascular disease. A skin biopsy specimen from the loose skin showed the accumulation of calcified degenerated elastic fibers and foci of ossification in the dermis. Histopathological study from a serpiginous streak revealed mineralized debris that was eliminated through the epidermis, the finding consistent with elastosis perforans serpiginosa. Recessive type 2 pseudoxanthoma elasticum is very rare and the presenting case is interesting in that this patient presented with lesions of secondary ossification and elastosis perforans serpiginosa in association with pseudoxanthoma elasticum.     

What is Standard of Care in the Evaluation of Elastosis Perforans Serpiginosa? A Survey of Pediatric Dermatologists

Elastosis perforans serpiginosa is a rare chronic dermatosis characterized by extrusion of altered elastic fibers through the epidermis. It often occurs in association with a variety of connective tissue disorders, and may develop following penicillamine therapy; however, it may also present without comorbidities. There are currently no well-established protocols for the investigation of possible associated disorders in patients who present with elastosis perforans serpiginosa. We describe three patients with idiopathic elastosis perforans serpiginosa seen at our clinic and review the standard of care among 31 pediatric dermatologists surveyed who have cared for such a patient within the last 2 years. Based upon the results of our survey, we conclude that most pediatric dermatologists limit their evaluation of such patients to a thorough patient history and physical examination. This limited approach may be a sufficient evaluation in affected patients who are otherwise healthy.     

"Lumpy-Bumpy" Elastic Fibers in the Skin and Lungs of a Patient with a Penicillamine-Induced Elastosis Perforans Serpiginosa

Penicillamine-induced cutaneous elastosis perforans serpiginosa associated with a large air-cyst in the right lung is described in a 29-year-old female patient with Wilson disease. Identical light and electron-microscopic changes were present in both dermal and pulmonary elastic tissue, suggesting a disseminated drug-induced cutaneo-visceral elastosis. Lung cysts have not been previously reported in association with long term penicillamine treatment. The electron-microscopic morphology of the elastic fibers was found to be "specific" enough to allow separation of penicillamine-induced elastosis perforans serpiginosa from other forms of this disease.     

Penicillamine-induced pseudo-pseudoxanthoma elasticum in a patient with rheumatoid arthritis

Penicillamine is a heavy metal chelator which is used in the treatment of Wilson's disease, cystinuria, rheumatoid arthritis and scleroderma. The cutaneous side-effects of prolonged, high dose (1–2 g/day) treatment include skin fragility, elastosis perforans serpiginosa (EPS), cutis laxa and rarely pseudoxanthoma elasticum-like changes.^1,2 We describe the clinical and post-mortem findings in a patient who developed pseudo-pseudoxanthoma elasticum and multi-system penicillamine-induced elastosis while taking D-penicillamine (750 mg/day). There are no previous reports of penicillamine-induced elastic tissue damage in a patient with rheumatoid arthritis.     

Elastosis perforans serpiginosa in a patient with pseudoxanthoma elasticum

A 34-year-old female previously diagnosed of pseudoxanthoma elasticum developed an annular plaque with serpiginous borders of 42 by 30 mm in diameter on the inner left arm. A similar lesion later appeared on the inner right arm. Histopathological examination of a papule showed short, fragmented, granular, basophilic and calcified elastic fibers in the mid-reticular dermis. The epidermis showed hyperplasia surrounding degenerated and normal elastic fibers. Transepidermal elimination channels of these elastic fibers were also observed. These findings were consistent with the diagnosis of elastosis perforans serpiginosa. Abundant multinucleated giant cells were observed surrounding the area of epidermal hyperplasia and in the reticular dermis. The patient was treated with tazarotene, and the plaques disappeared in 9 months.     

Heterogeneity of clinical features of pseudoxanthoma elasticum: analysis of thirteen cases in Oita Prefecture from a population of 1,240,000

Thirteen cases among 16,260 patients seen at our department during the nine years from 1981 were diagnosed as pseudoxanthoma elasticum (PXE). The sex and age distributions were similar to those so far reported in the literature. There were two cases of the autosomal dominant type. One patient had skin lesions typical of PXE in association with Ehlers-Danlos syndrome. In two of three patients with cutis laxa-like lesions, eruptions of elastosis perforans serpiginosa were present. In three cases, we failed to detect deposition of calcium in typical skin lesions in either an early or a late stage by histochemical staining, in spite of the presence of slightly degenerated elastic fibers.     

Penicillamine-Induced Degenerative Dermatoses: Report of a Case and Brief Review of Such Dermatoses

We describe a case of elastosis perforans serpiginosa with additional findings of degenerative skin changes. A 20-year-old man with hepatolenticular degeneration, under prolonged treatment with D-penicillamine, presented with a circular or serpiginous arrangement of nuchal papules. Histopathologically, transepidermal channels were accompanied by granulomatous reactions, with several giant cells engulfing elastic fibers. In addition to these findings of a typical elastosis perforans serpiginosa, we observed scar-like skin changes inside the circular arrangement of the papules. At the scar-like tissue, we found electron-microscopical evidence of randomly aggregated thin collagen fibers with no tendency toward systemic combined bundle formation, which is a characteristic feature of normal collagen fiber formation. Pseudoxanthoma-elasticum-like changes were observed on his neck. On his axillae and groin, slight skin thickening and wrinkling were detected. The diagnosis of elastosis perforans serpiginosa does not represent all of the manifestations or the pathological background described above. The skin manifestations described here represent not only an elastosis but also a total degenerative dermatosis with over-healed collagenosis. Thus, those dermatoses should be summarized as one entity, penicillamine-induced degenerative dermatosis. After considering the pathogenic background and clinical similarities, we further propose to simplify the penicillamine-induced skin manifestations to three categories: acute sensitivity reactions, bullous dermatoses, and degenerative dermatoses.     

Penicillamine-induced elastosis perforans serpiginosa. Tip of the iceberg?

Elastosis perforans serpiginosa (EPS) is now a well-recognized potential complication of long-term penicillamine therapy. By itself, EPS appears to be a relatively innocuous cutaneous side effect of penicillamine. However, suspicion has been raised in recent literature that EPS may represent only a superficial manifestation of more serious penicillamine-induced systemic elastic tissue damage, particularly involving blood vessels. This is a report of a patient with Wilson's disease who was treated with penicillamine for 14 years. She developed EPS, and histologic examination of the skin revealed the characteristic penicillamine-induced "lumpy-bumpy" elastic fibers in the dermis. More important, nonlesional skin showed the same elastic fiber changes. Of greatest significance was the finding of identical elastic fiber alterations in an artery.     

Acrokeratoelastoidosis

A 45-year-old white woman presented with several years' history of firm, shiny papules on the lateral hands with slight extension to the dorsal fingers. The lesions first appeared between the index fingers and thumbs on both hands. They gradually increased in number, coalescing into plaques and affecting the junction between the palmar and dorsal skin. The patient did not have involvement of her feet. She had been diagnosed previously with chronic eczema that had failed to respond to multiple topical medications. In addition, the patient's sister had similar lesions on both hands. The patient denied any symptoms of hyperhidrosis, excessive sun exposure, or trauma. The plaques were asymptomatic, but were cosmetically unappealing to the patient. On physical examination, small, firm, skin-colored, hyperkeratotic papules, coalescing into plaques, were located on the junction between the palmar and dorsal skin on both lateral margins of the thumb and on the radial side of the index finger (Fig. 1). There were no lesions on the feet. A biopsy taken from a papule on the patient's left hand was consistent histologically with acrokeratoelastoidosis. The biopsy showed marked degeneration of collagen in the dermis with solar elastosis and some smudging of the papillary dermal collagen (Fig. 2). She was treated with clobetasone cream to the affected areas on the hands. After 6 weeks of treatment, she reported no significant improvement.     

Penicillamine-induced elastosis perforans serpiginosa with abnormal "lumpy-bumpy" elastic fibers in lesional and non-lesional skin

Four types of elastosis perforans serpiginosa (EPS) have been described in literature: 1) idiopathic EPS, 2) reactive perforating elastosis associated with connective tissue disorders, 3) in some instances of pseudoxanthoma elasticum (PXE), disease-specific calcified elastic tissue is extruded, producing a clinical picture indistinguishable from other types, may also be seen in patients undergoing hemodialysis and 4) EPS induced by long-term treatment with D-penicillamine is observed in patients suffering from Wilson's disease. Long term D-penicillamine therapy causes an alteration in the dermal elastic tissue. D-penicillamine induced EPS has a distinctive histopathologic feature - serrated appearance of elastic fibers due to perpendicular budding from their surface giving a "lumpy-bumpy" look. D-penicillamine induced elastic fiber alteration may not always manifest clinically as EPS. We report a case of D-penicillamine induced widespread alteration in skin elastic tissue with distinct histopathologic features.     

Elastosis perforans serpiginosa with widespread arterial lesions: a case report.

A case is presented of elastosis perforans serpiginosa (EPS) with unilateral dermal lesions, widespread arterial lesions with aortic rupture, and elastosis of the endocardium and bronchiolar walls. Other chronic skin disorders with lesions resembling EPS are discussed; and the arterial lesions compared with some arterial diseases. The findings support a concept of the disease as a focal affection of elastic tissue, not only in the skin, but also in arteries and other organs.     

Elastic fibre damage induced by low-dose D-penicillamine

We have studied 23 patients receiving penicillamine for the treatment of rheumatoid arthritis to determine the prevalence of penicillamine-induced elastosis. One female patient had pseudoxanthoma elasticum-like skin changes and bramble-bush elastosis without calcification in the involved skin. Penicillamine elastosis was present in the joint capsule in 62% of eight patients or 64% of II joints examined and was detected in joint capsules after as little as I year of treatment.     

A case of elastosis perforans serpiginosa

A 17-year-old white boy with no underlying connective tissue disorders presented with flat-topped annular plaques, with slight central atrophy on the bilateral neck. Results from histopathology revealed changes consistent with elastosis perforans serpiginosa (EPS). The idiopathic form of EPS occurs rarely in children. We report a patient with this rare pediatric diagnosis and review the literature.     

Acquired perforating dermatosis in diabetes mellitus: An unusual case

A case of elastosis perforans serpiginosa in a patient who presented with insulin-dependent diabetes mellitus secondary to pancreatic insufficiency in a background of common variable immunodeficiency and endocrinopathy, as evidenced by pernicious anaemia and growth hormone deficiency, is described. In acquired perforating dermatosis occurring in patients with diabetes or renal failure, there is a spectrum of changes that may show an overlap of histological features of the four classic perforating diseases. The biopsy changes of the patient described in the present study most closely resembled those of elastosis perforans serpiginosa.     

Penicillamine Revisited: Historic Overview and Review of the Clinical Uses and Cutaneous Adverse Effects

Penicillamine is a well-known heavy metal chelator, classically used in the treatment of Wilson disease, rheumatoid arthritis, and cystinuria. From a dermatologic standpoint, penicillamine was found to be useful in the treatment of systemic sclerosis. The successful therapeutic uses of penicillamine have been hindered by its numerous adverse effects, both cutaneous and extra-cutaneous. It is a unique drug since it provokes a diversity of dermatologic manifestations that include (1) acute hypersensitivity reactions, (2) dermopathies characterized by elastic fiber abnormalities including elastosis perforans serpiginosa and pseudo-pseudoxanthoma elasticum, (3) autoimmune disorders such as pemphigus and penicillamine-induced lupus erythematosus-like syndrome, and (4) miscellaneous dermatoses that result from undefined mechanisms. These cutaneous adverse effects may correlate with the dosage and duration of penicillamine therapy as well as the disease being treated.     

Acquired disorders of elastic tissue: part I. Increased elastic tissue and solar elastotic syndromes

Elastic fibers in the extracellular matrix are an integral component of dermal connective tissue. The resilience and elasticity required for normal structure and function of the skin may be attributed to the network of elastic tissue. Advances in our understanding of elastic tissue physiology provide a foundation for studying the pathogenesis of elastic tissue disorders. Many acquired disorders are nevertheless poorly understood due to the paucity of reported cases. Several acquired disorders in which accumulation or elastotic degeneration of dermal elastic fibers produces prominent clinical and histopathologic features have recently been described. They include elastoderma, linear focal elastosis, and late-onset focal dermal elastosis and must be differentiated from better-known disorders, among them acquired pseudoxanthoma elasticum, elastosis perforans serpiginosa, and Favré-Racouchot syndrome. Learning objective At the conclusion of this learning activity, participants should understand the similarities and differences between acquired disorders of elastic tissue that are characterized by an increase in elastic tissue, as well as the spectrum of solar elastotic dermatoses.     

Generalized elastosis perforans serpiginosa in Down''s syndrome

Elastosis perforans serpiginosa is a rare disorder of epidermal perforation characterized by the extrusion of dermal elastic tissue through the epidermis. Its aetiology is unknown, but there is histological and biochemical evidence of an abnormality of elastic tissue. Three forms of elastosis perforans serpiginosa exist. It may be either idiopathic, iatrogenic, or, in approximately one quarter of cases, associated with certain genetically determined disorders of connective tissue. Cutaneous lesions appear between the ages of 6 and 20 years, and persist for 6 months to 5 years. They may be confined to one anatomic area, or less frequently are disseminated. We review the case of a 28-year-old woman with recent onset of unusually extensive elastosis perforans serpiginosa with co-existing Down's syndrome and (secondary) sclerosing cholangitis.     

D-penicillamine elastosis perforans serpiginosa: description of two cases and review of the literature

Long term D-penicillamine (DPA) therapy to treat Wilson disease can induce elastosis perforans serpiginosa (EPS), a very rare degenerative skin disease characterized by a transepidermal elimination of elastic fiber aggregates. The iatrogenous disease depends on DPA capacity to chelate copper and cause its depletion. Lysyl-oxidase is a copper dependent enzyme crucial to the dermal elastic fiber cross-linking, which is strongly affected by DPA copper depletion. Direct binding of the drug to collagen precursors also affects elastic fiber assemblage and maturation. The abnormal elastin accumulates into the middle dermis and produces a characteristic bramble brush or "lumpy-bumpy" appearance. In this way it acts as a foreign body and is progressively extruded through the epidermis. Clinically, the disease presents with multiple firm keratotic papules and nodules arranged in annular plaques over the neck, axillae, antecubital fossae, and forearms. The rarity of the disease frequently causes misdiagnoses and the process continues unabated causing concerns about systemic elastopathy.