Hyperelasticity syndromes

A review of hyperelasticity syndromes is included. Ehlers-Danlos syndrome, pseudoxanthoma elasticum, cutis laxa and Marfan's syndrome are discussed.     

Connective tissue diseases: pseudoxanthoma elasticum, anetoderma, and Ehlers-Danlos syndrome in pregnancy

The relationship between pregnancy and diseases of the elastic fibers, such as pseudoxanthoma elasticum, cutis laxa, and anetoderma, is discussed in this article. Dermatologists and other physicians must be aware that these problems may be present in pregnant women and must also know how to counsel those who suffer from these diseases because they can have severe manifestations and consequences during or after this period for both the pregnant mother and her offspring.     

Morphometric analysis of elastic skin fibres from patients with: cutis laxa, anetoderma, pseudoxanthoma elasticum, and Buschke–Ollendorff and Williams–Beuren syndromes

Computed morphometric analysis of elastic skin fibres in patients with cutis laxa, anetoderma, Williams-Beuren syndrome, pseudoxanthoma elasticum (PXE), and Buschke-Ollendorff syndrome, all clinically ascertained, was performed and compared with data obtained from healthy individuals of the same age. The diameters, area fractions (AA%) and volume fractions (VV%) occupied by pre-elastic fibres and dermal elastic fibres were determined. Irrespective of age the diameter of dermal elastic fibres followed a Gaussian distribution for all groups studied. These diameters were taken into consideration for VV% determinations. Compared with data from skin of healthy subjects of similar age range, VV% of pre-elastic fibres was significantly decreased in patients with cutis laxa, anetoderma, Williams-Beuren syndrome, and PXE and undetectable in Buschke-Ollendorff patients. VV% of dermal elastic fibres was four- to fivefold increased in Buschke-Ollendorff syndrome, two- to threefold increased in PXE skin, four- to fivefold decreased in cutis laxa and anetoderma skin and about twofold decreased in Williams-Beuren skin. The diameter of oxytalan fibres was decreased in anetoderma and Williams-Beuren syndrome while oxytalan fibre diameter was unchanged in PXE and cutis laxa. The diameter of dermal elastic fibres was increased in PXE and Buschke-Ollendorff syndrome, but was decreased in anetoderma and Williams-Beuren syndrome and unchanged in cutis laxa. We demonstrated that cutis laxa, anetoderma, Williams-Beuren syndrome, PXE, and Buschke-Ollendorff syndrome could be easily differentiated by morphometric analysis of elastic skin fibres. Thus we propose that morphometric analyses together with skin biopsies are a valuable tool for distinguishing between inherited and/or acquired skin diseases known to display alterations of elastic fibres.     

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.     

A Case of Cutis Pleonasmus

In 2005, Kreidstein first proposed the term "Cutis pleonasmus," a Greek term meaning "redundancy," which refers to the excessive skin that remains after massive weight loss. Cutis pleonasmus is clearly distinguishable from other diseases showing increased laxity of the skin, such as pseudoxanthoma elasticum, congenital and acquired generalized cutis laxa. Although individuals who are severely overweight are few and bariatric surgeries are less common in Korea than in the West, the number of these patients is increasing due to changes to Western life styles. We report a case for a 24-year-old man who presented with generalized lax and loose skin after massive weight loss. He was diagnosed with cutis pleonasmus based on the history of great weight loss, characteristic clinical features and normal histological findings. To the best of our knowledge, this is the first report of cutis pleonasmus in Korea.     

Reactions to Penicillamine: A Case of Cutis Laxa,Elastosis Perforans Serpiginosa and “Pseudo” Pseudoxanthoma

This patient was a 61‐year‐old white female who received several years of penicillamine therapy for the treatment of cystinuria. She subsequently developed penicillamine induced cutis laxa, elastosis perforans serpiginosa, and pseudoxanthoma elasticum like skin lesions. In addition, she suffered from numerous chronic bilateral lower extremity skin ulcerations. Her past medical history was also significant for end stage renal disease requiring hemodialysis and pulmonary fibrosis. She presented to the University of Miami Wound Care Center in 1/04 for treatment of her chronic ulcerations. On physical examination, the patient had multiple large hyperpigmented plaques with central ulcerations on her lower extremities. Some of the ulcers had overlying crust and others were covered with yellow fibrinous tissue. She also had generalized thickened, lax skin with multiple folds. On her neck, thighs, back and arms were violaceous, atrophic, serpiginous plaques with peripheral crusted erosions. A biopsy taken from the patients left thigh revealed dermal elastosis and the features of pseudo‐pseudoxanthoma. Two additional biopsies taken from the left thigh demonstrated elastosis perforans serpiginosa. This case highlights multiple skin manifestations of penicillamine therapy.     

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

Elastosis perforans serpiginosa (EPS) is a rare reactive perforating dermatosis that is characterized by the transepidermal elimination of abnormal elastic fibers. Penicillamine, which is one of the clear triggers for EPS, is a heavy metal chelator that is primarily used for disorders such as cystinuria and Wilson''s disease. It may cause alterations in the dermal elastic tissue such as pseudo-pseudoxanthoma elasticum, acquired cutis laxa, EPS and anetoderma. Herein we present a case of cutis laxa and EPS in a 34-year-old man who was previously on a long-term, high-dose of penicillamine for Wilson''s disease. The combination of EPS and cutis laxa induced by penicillamine has rarely been reported and we report the first such case in Korea.     

Case of dystrophic calcinosis cutis in epidermal cyst arising from verrucous epidermal nevus

Dystrophic calcinosis cutis is diagnosed when calcium is deposited into previously damaged tissue by connective tissue disease, panniculitis, pseudoxanthoma elasticum or trauma. We report a case of dystrophic calcinosis cutis arising from the lesion of an epidermal cyst on the verrucous epidermal nevus. A 20‐year‐old woman presented with a polypoid pinkish tumor on a brownish, verrucous plaque. Histopathological findings of the pinkish tumor showed calcium deposits as amorphous, basophilic material lining the true epidermis in the upper dermis, which were compatible with dystrophic calcinosis cutis and the plaque was diagnosed as a verrucous epidermal nevus.     

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.     

An unusual case of calcinosis cutis

A case of calcinosis cutis is presented in a patient with hypercalcemia of unknown etiology. The axillae and inguinal areas were involved and the clinical and histologic picture is compared with pseudoxanthoma elasticum. We propose that the similarities between the two diseases stem from a common origin in damaged elastic fibers.     

Clinical and molecular abnormalities in lipoid proteinosis

Lipoid proteinosis (hyalinosis cutis et mucosae) is a rare, autosomal recessive disease. The main clinicopathological features comprise skin and mucous membrane infiltration and scarring with deposition of hyaline material. In this report, we describe a 6-year-old boy in whom a diagnosis of lipoid proteinosis was first suspected when he presented with blisters and erosions at 4 years, a history of life-long dysphonia and a previous epileptic convulsion. The diagnosis was confirmed by histology and identification of a homozygous frameshift mutation, 501insC, in exon 6 of the gene encoding extracellular matrix protein 1, ECM1. Lipoid proteinosis may show protean clinical features and be difficult to diagnose on clinical grounds alone. This case report illustrates that lipoid proteinosis may show protean clinical features and yet remain undiagnosed for many years. Although the gold standard for definite diagnosis remains histology, molecular characterisation of the gene mutation will add to our understanding of genotype-phenotype correlation and perhaps to the development of a rationale for future therapeutics.     

Postinflammatory elastolysis and cutis laxa. A case report

One of the rarest forms of cutis laxa is postinflammatory elastolysis and cutis laxa, a disease previously reported only in children in Africa and South America. This disease is characterized by an urticarial or papular eruption followed by acute destruction of elastic tissue that results in atrophy and severe disfigurement. It is distinguished from anetoderma and acquired cutis laxa by its clinical features, its occurrence in young children, and its relatively benign course. This article describes the first case of postinflammatory elastolysis and cutis laxa reported in a white child from North America.     

Hyalinosis cutis et mucosae (Urbach-Wiethe disease)--ultrastructural and immunological characteristics

In this report on a young female patient with hyalinosis cutis et mucosae (Urbach-Wiethe disease, lipoid proteinosis), we present the clinical, immunological and ultrastructural features of this inherited disorder and discuss the differential diagnosis against other interstitial connective tissue depositions. Immunologically, the most important result was the increased amount of collagen type IV at the junction zones of epidermis, dermal vessels and appendages. This was in accordance with the ultrastructural deposition of hyalin material, mainly consisting of multiplied basal laminae at the respective junction zones. The pathogenesis (gene defect or defective gene regulation?) and therapy are discussed.     

Cutis laxa: a review

Cutis laxa is a rare disorder of elastic tissue resulting in loose, redundant, hypoelastic skin. Both acquired and inherited forms exist, some of which have significant systemic manifestations. Here, we review the various forms of cutis laxa, with focus on the inherited forms. Recent molecular studies have provided many new insights into the causes of cutis laxa and revealed greater genetic heterogeneity than previously appreciated.     

Acquired cutis laxa secondary to Sweet syndrome in a child (Marshall syndrome): A rare case report

Sweet syndrome is rare in the pediatric population and usually responds well to treatment, resolving without sequelae. Marshall syndrome is a rare pediatric skin disease characterized by loss of elastic tissue (cutis laxa) secondary to acquired, localized neutrophilic dermatitis without any internal organ involvement. Only few cases of Marshall syndrome (acquired cutis laxa type II) have been reported. Systemic steroids and dapsone show excellent results in Sweet syndrome. Although there is no satisfactory treatment for cutis laxa, dapsone can be used in the acute phase for control of swelling.     

Bilateral Congenital Entropion with Cutis Laxa

Cutis laxa is a rare connective tissue disorder characterized by redundant and pendulous skin due to a defect in the elastic fiber network. Two cases of entropion associated with cutis laxa have been reported, although entropion was due to elongation of the anterior lamella or horizontal lid laxity. Thorough systemic and ophthalmic evaluations were performed, as well as chart review for the perinatal period. Surgical correction of entropion through posterior tarsotomy was done. An infant boy with dysmorphic features and furrowing of the skin of the entire body without hyperelasticity, which is typical for cutis laxa, presented with bilateral congenital entropion. We report here for the first time a different etiology of congenital entropion with cutis laxa: the eyelashes were abnormally directed due to the unusual location of their roots, which were embedded within the tarsus. Moreover, this is the only case of cutis laxa with congenital entropion involving both upper and lower eyelids. Congenital entropion can be associated with cutis laxa. Although elongation of the anterior lamella and horizontal lid laxity predispose to such an entropion, abnormal location of the roots of the eyelashes might be encountered and marginal eyelid rotation surgery is indicated.     

Cutis laxa for diagnosis of γ1‐heavy‐chain deposition disease: Report of four cases

Heavy‐chain deposition disease (HCDD) is characterized by tissue deposits of a truncated monoclonal immunoglobulin heavy‐chain (HC) on basement membranes. Diagnosis is usually made on kidney biopsy, showing nodular glomerulosclerosis with HC deposits which can be missed, resulting in delay in diagnosis. We report four γ1‐HCDD patients presenting with cutis laxa, hypocomplementemia and hypoalbuminemia. In two patients, unsuspected HCDD was revealed by cutis laxa and diagnosis was made on skin biopsy. In all patients, serum albumin and complement represented surrogate markers for disease monitoring. In γ‐HCDD, extrarenal manifestations such as cutis laxa may precede renal injury and are precious tools for an early diagnosis, which is crucial to avoid progression of irreversible renal and elastic tissue damage.     

Mineralization of collagen and elastic fibers in superficial dystrophic cutaneous calcification: an ultrastructural study

The ultrastructural morphology of localized skin calcifications without associated diseases and with normal serum calcium and phosphate ion values is still unknown. In a case of superficial dystrophic calcinosis cutis (DCC), the role of collagen, elastin and ground substance in the process of calcification and the organization of the apatite crystals could be studied by light and electron microscopy despite technical difficulties in sectioning the hard tissue. Ultrastructural investigation revealed the nucleation of calcification being related to collagen and elastic fibers. No intracellular calcification was found. A flower-like arrangement of pleomorphic crystals was found around single collagen fibrils resembling the calcification of collagen seen in bone tissue. The elastic fibers showed a different pattern of calcification compared with other diseases (e.g. pseudoxanthoma elasticum) with known calcification of the elastic fibers. The process of mineralization was initially linked to the microfibrils of the elastic fiber.     

The molecular basis of lipoid proteinosis: mutations in extracellular matrix protein 1

Lipoid proteinosis (OMIM 247100), also known as Urbach-Wiethe disease or hyalinosis cutis et mucosae, is a rare autosomal recessive disorder characterized by generalized thickening and scarring of the skin and mucosae. In 2002, the disorder was mapped to a locus on chromosome 1q21 and pathogenic mutations were identified in the ECM1 gene, which encodes for the glycoprotein extracellular matrix protein 1 (ECM1). ECM1 has since been shown to have several important biological functions. It has a role in the structural organization of the dermis (binding to perlecan, matrix metalloproteinase-9 and fibulin) as well as being targeted as an autoantigen in the acquired disease lichen sclerosus. ECM1 also shows over-expression in certain malignancies and is abnormally expressed in chronologically aged and photo-aged skin. Thus far, 26 different inherited mutations in ECM1 have been reported in lipoid proteinosis. In this article, we provide an update on the molecular pathology of lipoid proteinosis, including the addition of 15 new mutations in ECM1 to the mutation database, and review the biological functions of the ECM1 protein in health and disease.