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Mid-dermal elastolysis is a rare acquired elastic tissue disorder with about 100 cases reported in the literature. It is characterized by localized patches of finely wrinkled skin on the shoulder and upper extremities and a band-like loss of elastic tissue in the mid-dermal layer on biopsy. Some patients may have symptoms of discomfort, erythema, and/or pruritis. Mid-dermal elastolysis is predominantly seen in young to middle-aged Caucasian females and extensive skin involvement may lead to cosmetic concerns. Furthermore, it is important to rule out other disorders of elastic fiber that are associated with systemic involvement. We present a case of MDE, discuss the differential diagnosis, and describe characteristic clinical features and histology findings of each condition.

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., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Introduction: Impairment of dermal elastic tissue occurs in different entities associated with immunoglobulins or immunoglobulin-derived protein-secreting clonal plasma cell proliferations, such as amyloid elastosis, anetodermic nodular amyloidosis or monoclonal gammopathy-associated cutis laxa. We report a case of cutaneous immunoglobulinemic amyloidosis revealed by a unique chalazodermic presentation and we review elastic tissue impairment in patients with monoclonal gammopathies., Observation: A 67-year-old woman consulted for non-infiltrated anetodermic lesions on the upper left quadrant of her abdomen present for ten years. She also had a chalazodermic plaque with abnormal skin wrinkling and laxity in her right axilla. Biopsies revealed deep dermal and subcutaneous amyloid deposits. Immunohistochemistry with lambda light chain was positive. Orcein staining and electron microscopy showed extensive elastolysis. The patient presented no signs of systemic involvement, but a very small amount of monoclonal IgGλ gammopathy was detected during follow-up., Discussion: This is a unique chalazodermic presentation of immunoglobulinemic amyloidosis that does not fit into a clearly-defined nosological setting. It highlights the complex interactions between immunoglobulin-derived proteins, including light and heavy chains, and elastic tissue components, leading to different types of impairment of the latter. We therefore suggest the unifying concept of immunoglobulinemic elastopathy, underscoring the need to screen for monoclonal gammopathy in patients presenting elastic tissue impairments., (Copyright © 2018. Published by Elsevier Masson SAS.)

Purpose: To assess changes in lymphatic vessels, collagen, and elastic fiber structure in excised tissues with dermatochalasis (DC)., Methods: In this prospective histopathological study, 70 upper eyelid skins of 35 patients operated on for dermatochalasis were compared with 10 eyelid skins of 10 patients operated on for other diagnoses. In histopathological examination, the two groups of patients were compared with respect to number of lymphatic vessels, largest lymphatic vessel diameter, number of elastic fibers, number of macrophages, edema between collagen fibers, and depth of stromal collagen bed., Results: As compared to the control group, the study group had a significantly greater number of dilated lymphatic vessels (p = 0.0001), largest lymphatic vessel diameter (p = 0.02), depth of stromal collagen bed (p = 0.0001), edema space between collagen fibers (p = 0.0001), elastic fiber density (p = 0.0001), and number of macrophages (p = 0.001)., Conclusion: According to the results of the present study, in addition to an increase in the diameter and number of lymphatic vessels, a reduction in elastic fibers that are essential for the structure and function of lymphatic system, disarrangement in collagen fibers, stromal edema, and increased number of macrophages play a role in the development of dermatochalasis.

Fibulin-4 is an extracellular matrix protein essential for elastic fiber formation. Frameshift and missense mutations in the fibulin-4 gene (EFEMP2/FBLN4) cause autosomal recessive cutis laxa (ARCL) 1B, characterized by loose skin, aortic aneurysm, arterial tortuosity, lung emphysema, and skeletal abnormalities. Homozygous missense mutations in FBLN4 are a prevalent cause of ARCL 1B. Here we generated a knock-in mouse strain bearing a recurrent fibulin-4 E57K homozygous missense mutation. The mutant mice survived into adulthood and displayed abnormalities in multiple organ systems, including loose skin, bent forelimb, aortic aneurysm, tortuous artery, and pulmonary emphysema. Biochemical studies of dermal fibroblasts showed that fibulin-4 E57K mutant protein was produced but was prone to dimer formation and inefficiently secreted, thereby triggering an endoplasmic reticulum stress response. Immunohistochemistry detected a low level of fibulin-4 E57K protein in the knock-in skin along with altered expression of selected elastic fiber components. Processing of a precursor to mature lysyl oxidase, an enzyme involved in cross-linking of elastin and collagen, was compromised. The knock-in skin had a reduced level of desmosine, an elastin-specific cross-link compound, and ultrastructurally abnormal elastic fibers. Surprisingly, structurally aberrant collagen fibrils and altered organization into fibers were characteristics of the knock-in dermis and forelimb tendons. Type I collagen extracted from the knock-in skin had decreased amounts of covalent intermolecular cross-links, which could contribute to the collagen fibril abnormalities. Our studies provide the first evidence that fibulin-4 plays a role in regulating collagen fibril assembly and offer a preclinical platform for developing treatments for ARCL 1B., (© 2015 by The American Society for Biochemistry and Molecular Biology, Inc.)

Cutis laxa is characterized by dramatic wrinkling of skin that is lacking in elasticity due to inherent defects in dermal elastic fibers. Cutis laxa can be caused by genetic and metabolic disorders. It can also be acquired, possibly resulting from inflammatory processes with destruction of elastic fibers. This report describes a 26-year old woman who developed acquired cutis laxa and cutaneous mastocytosis leading to premature aging. She represents a unique co-occurrence of these two separate disease entities. To our knowledge, there has been only one published case report of acquired cutis laxa occurring in association with urticaria pigmentosa in a 4-year old girl. Our case would be a second case that exhibits the coexistence of these two disorders in an adult female.

Importance: Acquired cutis laxa is a rare cutaneous manifestation of hematologic malignancy. We report a case of γ heavy chain deposition disease (HCDD) associated with acquired cutis laxa, renal involvement, and hypocomplementemia and propose a mechanism of elastic fiber degradation in the skin of this patient with HCDD., Observations: To determine the localization of immunoglobulin heavy chains and complement activation in the skin of a patient with HCDD, we examined her skin biopsy specimens under light and electron microscopy. Analysis demonstrated the deposition of γ heavy chain and complement components C1q and C3 on the surfaces of dermal elastic fibers, indicating complement fixation by the deposited heavy chains. Electron microscopy revealed finely granular electron-dense deposits coating the surfaces of frayed dermal elastic fibers., Conclusions and Relevance: The pathogenesis of cutis laxa in this condition is poorly understood. We hypothesize a mechanism of elastic tissue destruction by complement fixation with resultant activation of the complement cascade ultimately causing elastolysis. Based on our findings and those of other reports, we propose that skin heavy chain deposition can serve as a marker of plasma cell secretory activity in HCDD, although further studies are needed.

Acquired cutis laxa (ACL) is a rare connective tissue disorder that affects the skin elastic fibers, resulting in the loss of elasticity. In 50% of cases, this condition is associated with other diseases, particularly plasma-cell dyscrasias. This report describes a case of ACL with unusual clinical and histopathological characteristics. A 29-year-old man presented with diffuse erythematous plaques that had first appeared 5 months previously. Examination revealed multiple flaccid erythematous plaques on his trunk, neck, and skinfolds. Immunophenotyping of bone marrow aspirate revealed 7% of monoclonal plasma cells with lambda light chain expression. Skin biopsy histology revealed foci of interstitial granulomatous reaction. Weigert stain showed a loss of elastic fibers in the dermis, areas with thickened fibers and elastophagocytosis. Immunohistochemistry was positive for CD68. The cutaneous findings enabled an early diagnosis of IgG lambda monoclonal gammopathy to be made. Microscopic examination revealed an interstitial granulomatous reaction and severe alterations in the elastic fibers that varied in intensity in the different biopsies. Curiously, little has been mentioned in the literature regarding the presence of an interstitial granulomatous reaction in ACL. It is our belief that this reaction is secondary to the degenerative process of the elastic fibers.

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., (© 2012 John Wiley & Sons A/S.)

Mycosis fungoides is the most common form of primary cutaneous T-cell lymphoma. Several clinical and clinicopathological variants of mycosis fungoides have been reported. A 75-year-old woman presenting with multiple ill-defined areas of marked cutaneous wrinkling on the trunk and extremities is reported. Histopathological examination showed characteristic features of mycosis fungoides along with an interstitial dermal infiltrate composed predominantly of atypical lymphocytes with histiocytes intermingled within the collagen bundles. A focal reduction and fragmentation of elastic fibers was demonstrated. This observation illustrates a peculiar and previously unreported clinicopathological presentation of mycosis fungoides: cutis laxa-like mycosis fungoides, expanding the spectrum of mycosis fungoides variants associated with abnormalities of the dermal elastic fibers., (© 2012 Japanese Dermatological Association.)

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., (Copyright © 2011 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.)

A patient is presented with severe cutis laxa of the abdomen. Molecular investigations, including sequencing of the fibulin-5 and elastin gene, failed to endorse the diagnosis of inherited cutis laxa. Ultrasonographical discovery of renal calcifications during his general work-up suggested a possible diagnosis of pseudo-xanthoma elasticum (PXE). A discrete yellowish reticular pattern in the anterior neck region was detected upon careful clinical examination. Clinically, the patient presented characteristics of both classic PXE (retinopathy, renal calcifications) and the PXE-like syndrome (cutis laxa beyond the flexural areas). Skin biopsy and ophthalmological examination confirmed the diagnosis of PXE. In addition, ultrastructural evaluation revealed calcium deposits in the periphery of elastic fibers, a typical observation in the PXE-like syndrome. Immunohistochemical experiments and ELISA tests for various inhibitors of calcification displayed results which were partly reminiscent of both PXE and the PXE-like syndrome. Molecular analysis revealed not only two ABCC6 mutations (related to PXE), but also a gain of function SNP in the GGCX gene, in which loss-of-function mutations cause the PXE-like syndrome. We conclude that the patients phenotype and--to a further extent--the PXE-like syndrome, are part of a spectrum of ectopic calcification disorders which are clinically and/or pathogenetically related to PXE. The molecular findings in this patient are however insufficient to explain the entire phenotype and suggest a role for multiple genetic factors in soft tissue mineralization., (Copyright © 2011 Wiley Periodicals, Inc.)

Elastolysis mediodermalis is a rare disorder typically observed in middle-aged women. Sites of predilection are the trunk and upper arms. The clinical picture varies and may appear as cigarette paper-like wrinkling, perifollicular protrusions or reticular erythema. In contrast to the different clinical morphology, there is a consistent histology, i. e. localized, band-shaped, and rarely focal loss of elastic fibers in the middle dermis. The etiology of elastolysis mediodermalis is unclear. UV radiation or immunological mechanisms may increase the release of matrix metalloproteinases, leading to a degradation of elastic fibers. There is no effective treatment for this condition., (© The Authors • Journal compilation © Blackwell Verlag GmbH, Berlin.)

Objective: To determine the presence, degree, and extent of lymphatic, elastic, and collagen fiber alterations in dermatochalasis (DC) specimens., Design: Case control study of patients with DC compared with age-, gender-, and site-matched controls., Participants: A total of 25 eyelid specimens were studied; 15 of these were blepharoplasty specimens (experimental) and 10 were entropion/ectropion specimens of patients without DC (controls)., Methods: The number and maximal dilation of lymphangiectasia was measured by light microscopy, immunohistochemistry with lymphatic marker D2-40, and elastic tissue content by Verhoeff-van Gieson histochemistry. The number of macrophages was compared between patients with DC and controls in CD68 immunostained specimens., Main Outcome Measures: Lymphatic density, edema, and inflammation., Results: Dermatochalasis eyelid specimens showed increased lymphangiectasia density (5.6 vs. 2.4 lymphatics/high power field; P<0.05), maximal lymphatic dilation (127 vs. 51.5 μm; P<0.05), loss of elastic fibers (2.2 vs. 8.9 fibers/high power field; P<0.05), and greater disruption of collagen networks and edema compared with controls (increased stromal collagen bed of 752 vs. 269 μm; P<0.05; increased intercollagen space of 32.5 vs. 11.8 μm; P<0.05). Macrophages were present in greater quantities in DC specimens (28.6 vs. 11.9 macrophages/high power field; P<0.05)., Conclusions: Patients with DC show an increase in number and maximal dilation of lymphatic vessels in conjunction with widely spaced collagen bundles. This finding coexists with loss of elastic fibers, components known to be essential to the structure and function of the lymphatic system. Governed by macrophages, the pathogenesis of DC may begin with subclinical inflammation leading to elastolysis and secondary lymphostasis., Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article., (Copyright © 2011 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Autosomal dominant cutis laxa (ADCL) is characterized by a typical facial appearance and generalized loose skin folds, occasionally associated with aortic root dilatation and emphysema. We sequenced exons 28-34 of the ELN gene in five probands with ADCL features and found five de novo heterozygous mutations: c.2296&#95;2299dupGCAG (CL-1), c.2333delC (CL-2), c.2137delG (CL-3), c.2262delA (monozygotic twin CL-4 and CL-5), and c.2124del25 (CL-6). Four probands (CL-1,-2,-3,-6) presented with progressive aortic root dilatation. CL-2 and CL-3 also had bicuspid aortic valves. CL-2 presented with severe emphysema. Electron microscopy revealed elastic fiber fragmentation and diminished dermal elastin deposition. RT-PCR studies showed stable mutant mRNA in all patients. Exon 32 skipping explains a milder phenotype in patients with exon 32 mutations. Mutant protein expression in fibroblast cultures impaired deposition of tropoelastin onto microfibril-containing fibers, and enhanced tropoelastin coacervation and globule formation leading to lower amounts of mature, insoluble elastin. Mutation-specific effects also included endoplasmic reticulum stress and increased apoptosis. Increased pSMAD2 staining in ADCL fibroblasts indicated enhanced transforming growth factor beta (TGF-β) signaling. We conclude that ADCL is a systemic disease with cardiovascular and pulmonary complications, associated with increased TGF-β signaling and mutation-specific differences in endoplasmic reticulum stress and apoptosis., (© 2011 Wiley-Liss, Inc.)

Fibulin-4 is a member of the fibulin family, a group of extracellular matrix proteins prominently expressed in medial layers of large veins and arteries. Involvement of the FBLN4 gene in cardiovascular pathology was shown in a murine model and in three patients affected with cutis laxa in association with systemic involvement. To elucidate the contribution of FBLN4 in human disease, we investigated two cohorts of patients. Direct sequencing of 17 patients with cutis laxa revealed no FBLN4 mutations. In a second group of 22 patients presenting with arterial tortuosity, stenosis and aneurysms, FBLN4 mutations were identified in three patients, two homozygous missense mutations (p.Glu126Lys and p.Ala397Thr) and compound heterozygosity for missense mutation p.Glu126Val and frameshift mutation c.577delC. Immunoblotting analysis showed a decreased amount of fibulin-4 protein in the fibroblast culture media of two patients, a finding sustained by diminished fibulin-4 in the extracellular matrix of the aortic wall on immunohistochemistry. pSmad2 and CTGF immunostaining of aortic and lung tissue revealed an increase in transforming growth factor (TGF)beta signaling. This was confirmed by pSmad2 immunoblotting of fibroblast cultures. In conclusion, patients with recessive FBLN4 mutations are predominantly characterized by aortic aneurysms, arterial tortuosity and stenosis. This confirms the important role of fibulin-4 in vascular elastic fiber assembly. Furthermore, we provide the first evidence for the involvement of altered TGFbeta signaling in the pathogenesis of FBLN4 mutations in humans.

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.

Anetoderma, is characterized by herniated atrophic macules clinically and by decreased to absent dermal elastic fibers histopathologically. Atrophoderma is characterized by depressed, atrophic, pigmented patches clinically and by thickened and homogenized dermal collagen bundles with absence of elastolysis histopathologically. Atrophoderma elastolyticum discretum describes lesions that are reminiscent of atrophoderma clinically but they are compatible with anetoderma histopathologically. A 34-year-old female patient presented with diffuse, hypopigmented, atrophic, shiny macules on the upper limbs and upper trunk. Histopathological examination revealed an atrophic epidermis with disorganized, hyalinized and coarse collagen bundles in the middle and lower dermis. Elastic fiber loss and fragmentation were detected in the upper dermis. The other patient was a 42-year-old female patient. She applied with diffuse, hypopigmented, shiny, atrophic macules on the upper limbs and upper trunk. Histopathological examination revealed findings that were similar to those of the first case but there was near complete loss of elastic fibers throughout the whole thickness of dermis. Our cases did not show depressed or herniated atrophic macules clinically but the macules were at the same level with the surrounding healthy skin. Histopathological findings in these cases showed the histopathological features of both atrophoderma and anetoderma. These two cases are interesting because they may represent a clinicopathological entity which has not been described before.

Cutis laxa (CL) is an inherited or acquired connective tissue disorder characterized clinically by loosely hanging skin folds. There is often preceding cutaneous inflammatory eruption (ie, urticaria, eczema, erythema multiforme), and there is frequently internal organ involvement of the gastrointestinal, urogenital, pulmonary, and cardiovascular systems. Histologically, there are degenerative changes in the dermal elastic fibers. Of the few reports on this rare disorder, authors have speculated about an immune-mediated destruction of elastic fibers, and monoclonal gammopathies, such as multiple myeloma or heavy chain deposition disease, have a recognized association with CL. We report an unusual case of rapidly progressing acquired CL associated with leukocytoclastic vasculitis, IgA myeloma, and an immune complex-mediated glomerulonephritis. Light microscopy of the lax skin revealed complete absence of elastic fibers in areas of vasculitis.

Acquired cutis laxa (generalized acquired elastolysis) is a condition of unknown etiology characterized by a degeneration of elastic fibers in the skin, resulting in laxity with reduced elastic recoil. We describe a patient with acquired cutis laxa associated with an underlying heavy chain deposition disease. Direct immunofluorescence testing of lesional skin demonstrated immunoglobulin G deposition on elastic fibers, suggesting that in some cases, cutis laxa may have an immune-mediated etiopathogenesis.

A 49-year-old man presented with a 20-year history of an asymptomatic reticular eruption on his upper trunk. On examination, there were well-demarcated orange-red patches with reticular margins and irregular central atrophy on the lateral chest and proximal upper limbs. Skin biopsies showed histological evidence of elastophagocytosis with scant lymphocytic inflammation. Elastin stains demonstrated focal loss of elastic fibers in the reticular dermis, consistent with mid-dermal elastolysis. Mid-dermal elastolysis is a rare disorder characterized by focal loss of elastic tissue in the mid-dermis. The etiology remains obscure. Reticular presentations of mid-dermal elastolysis have rarely been described and extend the clinical spectrum of dermal elastolytic disorders.

Mutations involving elastic tissue proteins result in a broad spectrum of phenotypes affecting skin, skeleton, ocular and vascular structures, including tortuous blood vessels and cutis laxa. Here we report on a female newborn with apparently long fingers, aortic aneurysm, tortuous pulmonary arteries and mild generalized lax skin. She died at 27 days of age due to severe respiratory distress and inoperable systemic vascular abnormalities. Skin biopsy showed marked paucity and fragmentation of elastic fibers and autopsy revealed occlusion of the pulmonary artery. DNA analysis identified compound heterozygous mutations ((c.835C > T (p.R279C)/c.1070&#95;1073dupCCGC) in fibulin-4, a recently recognized elastic fiber associated protein. Analyses of dermal fibroblasts from the patient indicated that fibulin-4 mRNAs with the 4-bp duplication transcribed from one allele are probably subject to nonsense-mediated decay, whereas synthesis and secretion of the missense R279C fibulin-4 protein from the other allele is severely impaired. Immunostaining demonstrated a total absence of fibulin-4 fibers in the extracellular matrix deposited by the patient's fibroblasts. Our studies provide evidence that deficiency in fibulin-4 leads to a perinatal lethal condition associated with elastic tissue abnormalities., ((c) 2007 Wiley-Liss, Inc.)

Cutis laxa (CL) is a condition characterized by redundant, pendulous, and inelastic skin. Acquired CL has been reported in patients with inflammatory diseases. The goal of this study was to investigate whether genetic lesions predispose patients to the development of acquired CL. We report a patient who developed CL following a Toxocara canis parasitism. He later had an aortic root aneurysm that required surgical correction. Histological evaluation showed inflammation followed by destruction of elastic fibers in both the skin and the aorta. Mutational analysis showed that the patient was heterozygous for an inherited fibulin-5 (FBLN5) allele G202R and compound heterozygous for elastin (ELN) alleles A55V and G773D. Western blotting indicated abnormal proteolytic processing of tropoelastin (TE) in patient fibroblasts. The FBLN5 202R allele on the other hand led to increased interaction of FBLN5 and TE and increased deposition of insoluble ELN partially rescuing the deficiency conferred by ELN mutation G773D. We demonstrated that the interaction of ELN and FBLN5 alleles results in elastic fibers susceptible to inflammatory destruction. These results suggest that the pathogenesis of acquired CL involves an underlying genetic susceptibility and highlight the importance of molecular genetic analysis in patients with idiopathic connective tissue disorders.

Background: Hereditary gelsolin amyloidosis (AGel amyloidosis) is an age-associated systemic disease with global distribution, caused by a G654A or G654T gelsolin gene mutation. Cutis laxa is a principal clinical manifestation of this disease. However, only few data on the dermatological involvement are available, and the pathogenesis of this amyloidosis-associated form of cutis laxa has remained unknown., Objectives: To elucidate the pathomechanism of this less well-known genodermatosis., Methods: We performed systematic clinical, histological, immunohistochemical and ultrastructural skin biopsy studies in 12 patients with a G654A gelsolin gene mutation. For comparison, skin specimens from 10 control subjects were analysed., Results: All patients had clinically characteristic cutis laxa, and frequently other signs of symptomatic skin disease such as increased fragility and risk for intracutaneous bleeding. All patients showed cutaneous deposition of gelsolin amyloid (AGel), mainly attached to basement membranes or basal laminae of various cutaneous structures, dermal nerves and blood vessel walls, and elastic fibres, particularly in the lower reticular dermis. AGel often encircled the elastic fibres, and colocalized with amyloid P component (AP), an elastic fibre microfibrillar sheath-associated protein. Fragmentation and loss of elastic fibres, epidermal atrophy, and reduction of dermal appendages were also common. Antibodies to wild-type gelsolin bound to S-100-positive epidermal dendritic cells, a previously unrecognized immunoreaction. Patients had fewer gelsolin-positive dendritic cells than controls., Conclusions: Widespread skin involvement with AGel deposition and elastic fibre involvement are essential pathological features in AGel amyloidosis, and contribute to the characteristic cutis laxa, dramatic in old age. Codistribution of AGel and AP, with demonstrated specific binding affinity for amyloid fibrils, suggests that elastic fibre-associated AP acts as a matrix for cutaneous amyloid deposition in AGel amyloidosis.

Background: Cutis laxa is an uncommon entity characterized by laxity of the skin, which hangs in loose folds, producing the appearance of premature aging. It can be subdivided into congenital and acquired. This latter variant is rare and the skin involvement varies from generalized to localized. We report a case of a localized acquired cutis laxa confined to the face, without preceding inflammatory lesions or systemic compromise. Four similar cases have been reported to date. The etiology remains unknown and there is no definitive treatment., Methods: A 27-year-old White woman came to our hospital with a wrinkled face, pendulous earlobes and drop eyelids. Changes began 5 years prior, and she appeared much older than her age., Results: Histological analysis and ultrastructural examination of skin biopsy revealed reduction and fragmentation of elastic fibers, confirming the diagnosis of cutis laxa. No systemic involvement was diagnosed. The patient was submitted to plastic surgery for repair, with satisfactory results to date., Conclusions: Acquired localized cutis laxa confined to the face without preceding inflammatory lesions is extremely rare. The etiology remains unknown. Clinical features and histopathologic findings confirm the diagnosis. Surgical repair seems to be the only therapeutic choice, but the results are variable and temporary.

A 36-year-old male patient presented with unilateral periocular skin atrophy. The blepharochalasis developed without any obvious inflammation of the eyelids over the past 10 years. Interestingly, elongated blood vessels and microaneurysmatic vessel changes were found in the tarsal conjunctiva. A punch biopsy revealed a nearly complete loss of elastic fibres in the papillary and superficial reticular dermis. The contralateral side was histopathologically normal. On immunohistology IgA-deposits could be observed especially on perifollicular elastic fibres. Immunoelectronmicroscopy confirmed the diagnosis and suggested fibulin and fibronectin as potential binding sites for the autoantibodies. This further report of elastolysis in association with IgA-autoantibodies defines the autoantibody binding site in more detail and suggests that the immune mechanisms may also play a role in vessel changes of the conjunctiva.

Anetoderma is circumscribed atrophy of the skin due to a localized deficiency in elastic tissue. It can follow inflammatory skin diseases of several types, and occasionally is present in the skin around neoplasms. There are a few reports of anetoderma in the lesional skin of cutaneous lymphoma. We report on two patients who presented with multiple lesions of anetoderma and who later proved to have low-grade cutaneous B-cell lymphomas. One patient (Patient 1) is a 39-year-old man and the other patient is a 26-year-old woman who is a renal transplant recipient (Patient 2). Some biopsy specimens from the anetodermic skin of Patient 1 appeared to show an urticarial reaction, although plasma cells were present. A large nodule showed lymphoid follicles surrounded by plasmacytoid lymphocytes, with loss of elastic tissue in the adjacent dermis. The plasmacytoid cells stained overwhelmingly for lambda light chain, and staining of the urticarial lesions from this patient also showed a marked majority of lambda positive cells. Immunoglobulin heavy chain gene (IgH) rearrangements showed a dominant clonal pattern in the nodular lesion. We classified the disease in Patient 1 as marginal zone lymphoma and the disease in Patient 2 as a post-transplant lymphoproliferative disorder. Because of the intimate association of anetoderma and cutaneous B-cell lymphoproliferative disorders in these two patients, it seems possible that anetoderma could result from either a local effect of the neoplastic cells or associated inflammatory cells, especially neutrophils as in Case 1. The infiltrates of Case 1 had many interstitial neutrophils and only a few clonal plasmacytoid lymphocytes, indicating that this presentation of B-cell lymphoma can be a diagnostic pitfall. Given these two cases and similar ones in the literature, biopsy of lesional skin in anetoderma should be performed to ensure that lymphomatous infiltrates are not present. Even if plasma cells are sparse, studies to detect clonality are appropriate. Cutaneous B-cell lymphoma can be added to the list of associations of elastolysis and cutaneous lymphoma, which includes granulomatous slack skin (T-cell lymphoma) and cutis laxa (myeloma).

Despite lupus erythematosus (LE) being considered a "connective tissue disease," little has been written about the elastic fiber changes in the skin of affected patients. We report our histologic findings in two patients with unusual cutaneous lesions. Elastic fiber loss was noted, and scattered giant cells with elastic fiber phagocytosis were prominent in one patient. The findings are similar to those described for middermal elastolysis. Other authors have reported patients with LE and elastic fiber loss resembling anetoderma. We believe that a spectrum of elastic fiber changes can occur in patients with LE and may be induced by infiltrating lymphocytes and/or circulating antibodies.

Background: Mid-dermal elastolysis is an acquired disorder of elastic tissue clinically characterized by diffuse fine wrinkling, most often of the trunk and arms. Histologically, a clear band of elastolysis is present in the mid-dermis., Objective: Although examples of diffuse elastolysis are well known, only a small number of patients with mid-dermal elastolysis have been reported to date. We present two patients with clinical and histological evidence of mid-dermal elastolysis, review the literature, and summarize the salient features of some common disorders of elastic tissue., Methods: The first patient presented with fine wrinkles and papules over the upper arms, upper chest, and axillae, and demonstrated increased laxity of the eyelids. The second patient had striking wrinkles extending in a band-like pattern on her arms, upper chest, back, and abdomen. Neither one of our patients had a previous history of skin inflammation, urticaria, or any other underlying diseases related to their skin changes. Skin biopsies were taken from lesional and perilesional skin of both patients, and were stained with hematoxylin and eosin, and with elastic tissue stain. In addition, a tissue sample from Patient 1 was fixed for electron-microscopy., Results: Hematoxylin and eosin stains did not demonstrate specific changes or diagnostic patterns. However, elastic tissue stains revealed a band-like loss of elastic tissue in the mid-dermis. Elastic tissue in the remaining superficial and deep dermis stained normally. Electron-microscopy was consistent with these findings and revealed significant loss of elastic tissue limited to the mid-dermis., Conclusion: We have presented two cases of mid-dermal elastolysis and reviewed the literature. To date, the pathophysiology of mid-dermal elastolysis had not been elucidated and no definitive therapy exists.

Background: Acquired cutis laxa is a rare disease characterized by sagging skin, premature wrinkling and reduced skin elasticity., Observation: We report a 21-year-old woman, who presented with acquired cutis laxa on the face and the ear lobes. Urticarial papules had preceded for 6 years. There was no systemic involvement. Skin specimens were obtained from lax skin and urticarial papules, and from healthy controls. Histology showed only few perivascular lymphocytes in lax ear skin and a dense inflammatory infiltrate in urticarial skin. In both biopsies elastic fibres were decreased as demonstrated by computerized morphometric analyses. Elastase activities of fibroblasts in culture were evaluated. There was a 2- to 3-fold increase in elastase activity in urticarial skin fibroblasts, contrasting with a normal elastase activity in lax ear skin., Conclusion: Our findings suggest that the inflammatory cells could play a significant role in the destruction of elastic fibres.

First described by Shelley and Wood in 1977, mid-dermal elastolysis (MDE) is a rare acquired disorder in which there is a bandlike absence of elastic tissue limited to the mid-dermis. In their patient, MDE developed in an area previously involved with recurrent episodes of urticaria. We describe a 15-year-old white girl with well-circumscribed, minimally palpable yellow-white plaques and wrinkling diagnosed histologically as MDE in areas clinically diagnosed 5 years previously as granuloma annulare. As in the first described patient, five years elapsed between clearance of the original skin lesions and the clinical appearance of MDE. To our knowledge, we report the first adolescent case of MDE localized to previous sites of lesions clinically consistent with granuloma annulare and propose that MDE represents an abnormal end-stage reaction to multiple processes.

A 49-year-old patient developed acquired generalized cutis laxa, manifest as involvement of the elastic fibres of the dermis and the internal organs, leading to pulmonary emphysema, bilateral inguinal hernia and two oesophageal diverticula. The patient's serum levels of IgG lambda paraprotein were elevated. Direct immunofluorescence examination revealed intensive linear deposits of IgG lambda light chains, an early component of complement C1q and discrete C3 deposits. The deposits were found along the preserved elastic fibres in the dermis, especially in the papillary dermis, at the dermoepidermal junction around the sweat and sebaceous glands and in the walls of small vessels. Dermal alterations of this kind have not been described previously.

Congenital cutis laxa (CCL) is a rare, genetically heterogeneous connective tissue disorder, manifested by loose, hanging skin, giving the appearance of premature aging. We report a 6-year-old female child with autosomal recessive CCL type III, to assess possible correlations between clinical, ultrastructural, cellular and biochemical features. Morphological aberrations of the elastic and collagen tissue, increased collagen I mRNA expression associated with increased protein synthesis and increased collagenase gene expression of the cutis laxa fibroblasts could be established. Our results suggest that CCL is not only a disease of the elastic fibers of the connective tissue but also of the collagen fibers, with a central role of the fibroblast.

Cutis laxa is grouped with the other hyperelastic skin conditions, but it shows almost total lack of skin elasticity. Numerous other medical and surgical conditions may coexist with the skin problem, since it is a generalized affliction of the supporting connective tissues. Our patient had cutis laxa proved by skin biopsy. All surgical procedures were done without any wound complications. He had many associated medical conditions and so served as an excellent opportunity to review the condition of cutis laxa.

Idiopathic middermal elastolysis (IMDE) is a rare disorder with two different clinical presentations: type I lesions, with tiny wrinkles along skin cleavage lines in large confluent areas, and type II lesions, with small perifollicular papular protrusions. The histopathological picture is characteristic. IMDE is mainly seen in healthy young or middle-aged women. We describe a 60-year-old male patient with this disorder. The special interest of this case report is that there was no photosensitivity and no exacerbation with PUV therapy. IMDE is probably a special sort of elastolytic disorder, for which immunologic mechanisms seem possible.

Background: Degeneration of elastic tissue in acquired cutis laxa has been previously described, but microfibrils have not been adequately studied., Objective: We determined whether the microfibrillar component of elastic tissue is affected in skin of a patient with acquired cutis laxa., Methods: Lesional skin was examined with indirect immunofluorescence and immunoelectron microscopy with antibodies to fibrillin., Results: Indirect immunofluorescence showed a reduction in the distribution of fibrillin in the papillary dermis, where there was loss of the usual pattern of microfibrils perpendicular to the epidermis. Immunoelectron microscopy showed a typical distribution of elastic microfibrils around elastin of normal skin. In skin affected by cutis laxa microfibrils appeared morphologically normal but appeared less frequently in selected sites., Conclusion: The microfibrillar component of elastic fibers was reduced in the papillary dermis of this patient with acquired cutis laxa.