ATP6V0A2‐related cutis laxa in 10 novel patients: Focus on clinical variability and expansion of the phenotype

In ATP6V0A2‐related cutis laxa, the skin phenotype varies from a wrinkly skin to prominent cutis laxa and typically associates with skeletal and neurological manifestations. The phenotype remains incompletely characterized, especially in adult patients. Glycosylation defects and reduced acidification of secretory vesicles contribute to the pathogenesis, but the consequences at the clinical level remain to be determined. Moreover, the morphology of the elastic fibres has not been studied in ATP6V0A2‐related cutis laxa, nor its relation with potential clinical risks. We report on the extreme variability in ATP6V0A2‐related cutis laxa in 10 novel patients, expand the phenotype with emphysema and von Willebrand disease and hypothesize on the pathogenesis that might link both with deficiency of glycosylation and with elastic fibre anomalies. Our data will affect clinical management of patients with ATP6V0A2‐related cutis laxa.     

Acquired Cutis Laxa: Case Report and Review of Disorders of Elastolysis

A 10-year-old boy developed cutis laxa while receiving isoniazid therapy; no systemic manifestations occurred. There are several well-documented cases of acquired cutis laxa. We propose a classification of the elastolysis syndromes, including inherited, neonatal, and acquired forms of cutis laxa.     

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.     

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.     

Acquired localized elastolysis associated with varicose veins

Localized elastolysis refers to a group of heterogeneous conditions which includes cutis laxa. We report a form of localized and non-inflammatory elastolysis evocative of cutis laxa, localized to the anteromedial aspect of the left thigh and knee, acquired at the age of 8 years and associated with unilateral adjacent venous dilatations appearing at the ape of 39 years. Our case is clinically and ultrastructurally compatible with cutis laxa. Localized forms of cutis laxa not preceded by inflammation are exceptional; localization on the leg has never been described. This clinical form of elastolysis calls into question the classification of acquired elastolysis. The adjacent varicose veins also raise the question of the risk of subcutaneous damage in this condition.     

Acquired Cutis Laxa Type II (Marshall Syndrome) in an 18-Month-Old Child: A Case Report

Abstract:  Cutis laxa is a rare disorder resulting from degradation and clumping of elastic fibers in dermis. Type II acquired cutis laxa, shows only cutaneous changes without any systemic involvement. We describe an infant with acquired cutis laxa type II following a generalized inflammatory dermatitis.     

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.     

Generalized Cutis Laxa Associated with Heavy Chain Deposition Disease

BACKGROUND: Cutis laxa is a heterogeneous group of inherited and acquired disorders characterized clinically by loose skin and histologically by altered elastic tissue. Heavy chain deposition disease is a very rare monoclonal immunoglobulin disorder, distinct from multiple myeloma, in which there is production and deposition of defective immunoglobulin heavy chains without light chain deposition. OBJECTIVE: We describe a case of acquired cutis laxa associated with heavy chain deposition disease. RESULTS: A 50-year-old male presented with acute renal failure, IgG4 heavy chain deposition in the kidneys, and no evidence of multiple myeloma. Four years later, he developed generalized acquired cutis laxa, emphysema, and a peripheral polyneuropathy. On pathology, there was destruction of elastic fibers within the dermis. CONCLUSION: This case describes a previously unreported association between acquired cutis laxa and heavy chain deposition disease.     

Acral localized acquired cutis laxa

We report the first case of acral localized acquired cutis laxa. The skin laxity was preceded by swelling of the fingers and toes and by the appearance of papular urticaria. Dapsone therapy was effective in controlling the swelling. Examination of skin biopsy specimens showed fragmentation and almost total loss of elastic fibers in the areas of cutis laxa. Electron microscopy showed no abnormalities in elastic structure and function in unaffected skin. In addition, electron microscopic examination of an urticarial lesion showed a neutrophilic dermatosis with polymorphonuclear leukocytes attached to the surface of either normal elastic fibers or fibers showing early degenerative changes. These findings suggest that there is no primary defect in the elastic fibers and that the polymorphonuclear leukocytes play a significant role in the destruction of the elastic fibers and the subsequent development of cutis laxa in this case.     

Cutis laxa type II and wrinkly skin syndrome: distinct phenotypes

Cutis laxa is a heterogeneous group of disorders with variable phenotypes and inheritance patterns. Type II cutis laxa has features overlapping with wrinkly skin syndrome, as a result of which they are regarded as one disorder with a variable spectrum of severity by some authors. To overcome this existing confusion, we present three patients with cutis laxa type II and review the literature to highlight the important differentiating features between cutis laxa type II and wrinkly skin syndrome.     

Cutis laxa

Two sisters with inherited generalized cutis laxa and a young man with possible acquired cutis laxa are presented.     

The complexity of elastic fibre biogenesis in the skin – a perspective to the clinical heterogeneity of cutis laxa

Elastic fibres are critical connective tissue components providing elasticity and resilience to skin and other tissues. These fibres are composed of elastin and a number of elastin‐associated microfibrillar proteins that assemble in a complex fibre network in a multi‐step process. Multiple cellular processes, including mitochondrial function, specific molecules in the secretory pathways and temporally and spatially ordered production of elastic fibre components, are required for the biogenesis of functional elastic fibres. Abnormalities in these processes can lead to loss of functional elastic fibres manifesting phenotypically as a skin disease. The paradigm of elastic fibre diseases affecting the skin is cutis laxa, a clinically and genetically heterogeneous group of disorders characterized by loose and sagging skin, frequently associated with extracutaneous manifestations in the lungs and the arterial blood vessels. The complexity of cutis laxa is emphasized by the fact that as many as 10 distinct genes can harbour mutations in this and related disorders. Understanding of the pathomechanistic pathways involved in perturbed elastic fibre assembly in cutis laxa provides information potentially helpful for the development of molecular strategies towards treatment of these, currently intractable, diseases.     

A novel elastin gene mutation resulting in an autosomal dominant form of cutis laxa

BACKGROUND: Cutis laxa is an extremely rare disorder characterized by marked skin laxity. Few cases of cutis laxa have been described worldwide. Clinical presentation and mode of inheritance show considerable heterogeneity; autosomal dominant, autosomal recessive, and X-linked recessive forms have been reported. Only 3 mutations in the elastin gene have been described as the genetic cause of the autosomal dominant form of cutis laxa. OBSERVATIONS: A 45-year-old woman and her 19-year-old son presented with inelastic, loose-hanging, and wrinkled skin that appeared prematurely aged and were clinically diagnosed as having cutis laxa. Mutational analysis of the elastin gene evidenced a novel mutation (2292delC) that predicts a frameshift in the coding region and causes translation to proceed into the 3'-untranslated region. This would replace the C-terminal amino acid of the normal elastin protein with a novel sequence. CONCLUSION: This article is the fourth report of autosomal dominant cutis laxa to appear in the literature in which a mutation in the elastin gene has been correlated with the disease.     

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.     

Autosomal recessive cutis laxa in two siblings associated with blue sclera

Abstract:  Cutis laxa is a clinical entity found in a heterogeneous group of genetic and acquired disorders characterized by premature aging of the skin with normal wound healing. We report two siblings born of consanguineous parents who presented with growth retardation, delayed developmental milestones, and the classical phenotypic manifestations of type 2 recessive cutis laxa. They showed remarkable blue sclera, which to our knowledge has not been reported previously in cutis laxa.     

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.     

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.     

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.     

Acquired cutis laxa and myeloma: large vacuolated cells in the dermis

INTRODUCTION: Cutis laxa is a rare disorder characterized by loss of elastic tissue. Several organs are often involved such as the skin, lungs, heart, digestive system or genitourinary tract. It may be inherited or acquired, generalized or localized. Its pathogenesis is unclear. Association of acquired cutis laxa with myeloma or plasma cell dyscrasia is very rare. We report a case of acquired cutis laxa associated with a myeloma. CASE REPORT: A 59 year-old woman was admitted for skin hyperlaxity present for a number of years. Light microscopic examination of a skin sample revealed fragmented elastic fibers. Electron microscopic examination of the elastic network demonstrated numerous large vacuolated cells with the appearance of macrophages around abnormal elastic and collagen fibers of the reticular dermis. In addition, a stage-1 IgG lambda myeloma was detected. The patient was treated by thalidomide for one year. After this treatment, electron microscopy examination did not reveal any large vacuolated cells in the dermis, and elastic and collagen fibers were not modified and skin laxity seemed to be stabilized. DISCUSSION: Acquired cutis laxa may be associated with many systemic diseases or can appear after inflammatory skin diseases. Seven cases of generalized cutis laxa associated with myeloma and four cases associated with plasma cell dyscrasia have been reported in the literature. In our case, as in 2 previously described cases, large vacuolated cells resembling macrophages were seen in the dermis. They were thought to play a role in cutis laxa.