Fragmentation Of Elastic Fibers Research Articles

Persistent Truncus Arteriosus with Dissecting Aneurysm and Subsequent Cardiac Tamponade in a Lamb

The present case report describes the necropsy and histopathology findings of a 3-week-old lamb with persistent truncus arteriosus (PTA). This rare cardiac malformation was characterized by the presence of a common arterial trunk arising from the right ventricle and overriding a ventricular septal defect. The pulmonary arteries originated from a short common trunk from this PTA, which subsequently continued as the thoracic aorta. The death of the lamb was attributed to a rupture of the PTA with subsequent cardiac tamponade. Histologically, a dissecting aneurysm with elastic fiber fragmentation in the wall of the PTA was identified as the underlying pathologic condition. Altered hemodynamic forces with subsequent secondary vasculopathy, as well as congenital primary vasculopathies, should be considered as an underlying pathogenetic mechanism.

Pseudoxanthoma Elasticum: Genetics, Clinical Manifestations and Therapeutic Approaches

Pseudoxanthoma elasticum (PXE) is an inherited disorder that is associated with accumulation of mineralized and fragmented elastic fibers in the skin, vascular walls, and Bruch's membrane in the eye. Clinically, patients exhibit characteristic lesions of the posterior segment of the eye including peau d'orange, angioid streaks, and choroidal neovascularisations, of the skin including soft, ivory-colored papules in a reticular pattern that predominantly affect the neck and large flexor surfaces, and of the cardiovascular system with peripheral and coronary arterial occlusive disease as well as gastrointestinal bleedings. There is yet no definitive therapy. Recent studies suggest that PXE is inherited almost exclusively as an autosomal recessive trait. Its prevalence has been estimated to be 1:25,000–100,000. Very recently, the ABCC6 gene on chromosome 16p13.1 was found to be associated with the disease. Mutations within ABCC6 cause reduced or absent transmembraneous transport that leads to accumulation of extracellular material. Presumably, this mechanism causes calcification of elastic fibers. Despite the characteristic clinical features, the variability in phenotypic expressions, and the low prevalence may be responsible for the disease being underdiagnosed. This review compiles and summarizes current knowledge of PXE pathogenesis and clinical findings. Furthermore, different therapeutic strategies to treat retinal manifestations are discussed, including thermal laser coagulation, photodynamic therapy, and intravitreal injections of drugs inhibiting vascular endothelial growth factor.

Syndromic and non‐syndromic aneurysms of the human ascending aorta share activation of the Smad2 pathway

Common features such as elastic fibre destruction, mucoid accumulation, and smooth muscle cell apoptosis are co-localized in aneurysms of the ascending aorta of various aetiologies. Recent experimental studies reported an activation of TGF-beta in aneurysms related to Marfan (and Loeys-Dietz) syndrome. Here we investigate TGF-beta signalling in normal and pathological human ascending aortic wall in syndromic and non-syndromic aneurysmal disease. Aneurysmal ascending aortic specimens, classified according to aetiology: syndromic MFS (n = 15, including two mutations in TGFBR2), associated with BAV (n = 15) or degenerative forms (n = 19), were examined. We show that the amounts of TGF-beta1 protein retained within and released by aneurysmal tissue were greater than for control aortic tissue, whatever the aetiology, contrasting with an unchanged TGF-beta1 mRNA level. The increase in stored TGF-beta1 was associated with enhanced LTBP-1 protein and mRNA levels. These dysregulations of the extracellular ligand are associated with higher phosphorylated Smad2 and Smad2 mRNA levels in the ascending aortic wall from all types of aneurysm. This activation correlated with the degree of elastic fibre fragmentation. Surprisingly, there was no consistent association between the nuclear location of pSmad2 and extracellular TGF-beta1 and LTBP-1 staining and between their respective mRNA expressions. In parallel, decorin was focally increased in aneurysmal media, whereas biglycan was globally decreased in aneurysmal aortas. In conclusion, this study highlights independent dysregulations of TGF-beta retention and Smad2 signalling in syndromic and non-syndromic aneurysms of the ascending aorta.

Histopathologic Findings in Ascending Aortas From Individuals With Loeys-Dietz Syndrome (LDS)

Loeys-Dietz syndrome (LDS) is an autosomal dominant connective tissue disorder resulting from genetic mutations in the transforming growth factor beta receptors 1 and 2 (TGFBR1 and TGFBR2). The syndrome is characterized phenotypically by hypertelorism, bifid uvula, and/or cleft palate, and arterial tortuosity with aneurysms and dissections. LDS has a much more rapid clinical course than Marfan syndrome (MFS) and thus those diagnosed with LDS are currently being recommended for prophylactic aortic root replacement at younger ages and with smaller aortic dimensions. Aortic root tissue obtained at surgery was compared between 15 patients carrying a diagnosis of LDS, 11 patients with MFS and 11 control aortas to evaluate the range of histopathologic changes in LDS. Standard hematoxylin and eosin and Movat pentachrome stains were performed. LDS samples had increased medial collagen and a subtle but diffuse form of elastic fiber fragmentation and extracellular matrix deposition, referred to as diffuse medial degeneration. LDS samples had significantly more diffuse medial degeneration compared with MFS and control samples (P<0.05), significantly less medial degeneration of the "cystic" variety compared with MFS (P<0.01) and significantly more collagen deposition than control samples (P<0.01). Additionally, an immunohistochemical stain for pSmad2, a marker of TGFbeta activity, was significantly increased in LDS patients compared with controls (P<0.001). Overall, the histologic findings of LDS are best appreciated with special stains to evaluate fibrosis and elastic fiber fragmentation. The changes described, although not entirely specific for LDS, help differentiate this entity from other vascular diseases in the appropriate clinicopathologic setting.

The Expression of Matrix Metalloproteinase according to Hydrostatic Pressure in Varicose Veins

Purpose: The expression of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinase (TIMPs) caused by hydrostatic pressure stress is important in the development of varicose veins (VVs). This study was performed to analyse the expression of various MMPs and TIMPs according to the hydrostatic stress and the anatomical level of human great saphenous vein (GSV). Methods: Forty-nine vein samples were obtained from 10 patients with VVs (control group), and 34 samples from 7 VV patients after 1-hour hydrostatic stress just before surgery (stress group) at each anatomical site (proximal, Hunter, Dodd, and Boyd perforators) of GSV. Light microscopic examination and immunohistochemistry for MMP-1, -2, -9, -13 and TIMP-1, -2 were performed. Results: Intimal hyperplasia, fragmentation and loss of elastic fibers, infiltration of collagen fibers, and disorganization of medial muscle layers were evident in most vein samples. The degree of vein wall degeneration was not different between the 2 groups, and the anatomical sites of GSV. By immunohistochemistry, the expression of MMPs and TIMPs was not significantly different according to the group and the site. The expression of MMP-9 was more intense than that of other MMPs and TIMPs in all samples. MMP-9 was well localized to endothelial cells, medial muscle layers, and adventitial vasa vasorum. Conclusion: There are no distinct differences in the varicose vein samples after short-term postural blood stasis compared to the resting group. MMP-9 may be the key enzyme of the venous wall remodeling.

Abstract 424: Vascular Smooth Muscle Cell Expression of S100a12 in Vivo Induces Enhanced Oxidative Stress &amp; Vascular Remodeling

S100A12 is a small calcium binding protein that is a signal transduction ligand of the receptor for advance glycation endproducts (RAGE). S100A12, like RAGE, is expressed in the vessel wall of atherosclerotic vasculature, particularly in smooth muscle cells (SMC). While RAGE has been extensively implicated in inflammatory states such as atherosclerosis, the role of S100A12 is less clear. We tested the hypothesis that expression of human S100A12 directly exacerbates vascular inflammation. Several lines of Bl6/J transgenic mice (tg) expressing human S100A12 in SMC under control of the SM22a promoter were generated. Primary aortic SMC from tg and wild type (wt) littermates were isolated and analyzed for (i) proliferation using MTS/Formazan Assay and BrdU incorporation, (ii) oxidative stress using using flow cytometry with MitoSOX antibody, oxidative DNA damage using immunofluorescence microscopy with anti-8-oxo-dG antibody, and NF-kB activation measured by EMSA and (iii) cytokine expression measured by IL-6 ELISA. Furthermore, the aortas from tg and wt mice were examined. Results: Tg but not wt SMC expressed S100A12 protein. Tg SMC had a significant 1.9 to 2.7 fold increase in conversion of MTS into Formazan at 24–96 hours likely reflective of increased metabolic activity since BrdU incorporation into DNA was less in tg compared to wt SMC (4% vs 21% positive BrdU nuclei, p &lt;0.05). Tg SMC showed significantly higher levels of mitochondrial generated ROS, nuclear staining for oxidative DNA damage which was not detected in the nuclei of wt SMC’s, and a 2.5 fold increase in NFkB activity. IL-6 production at baseline was higher in tg SMC’s (615 vs 213 pg/ml, p&lt; 0.05) and increased dramatically after LPS treatment (10 ng/ml) in tg SMC’s (2130 vs 415 pg/ml). Histologic examination of the thoracic aorta at 10 weeks of age revealed increased collagen deposition in the aortic media with fragmentation and disarray of elastic fibers. In vivo ultrasound revealed a progressive dilation of the aortic arch from age 10 weeks to 16 weeks of age (1.27 to 1.60 mm, p&lt;0.05) in tg but not in wt littermate mice (1.30 to 1.33 mm, p=0.1). These data reveal the novel finding that targeted expression of human S100A12 in SMC modulates oxidative stress, inflammation and vascular remodeling.

Abstract 2607: TGF-beta 1 as a Diagnostic Biomarker for Acute Aortic Dissection Type A in a Mouse Model of Marfan Syndrome

Objectives: Acute aortic dissection type A is the main cause of mortality in patients with Marfan Syndrome (MFS). The aim of this study was to develop a procedure to surgically induce an acute aortic dissection type A in a mouse model of MFS, and to discover a diagnostic biomarker of the aortic lesion. Methods: Ten fibrillin-1 deficient (Fbn1C1039G/+) and ten wild-type (WT) mice at 8 months of age were intubated, ventilated and the aorta exposed via hemisternotomy. We hypothesized that an aortic dissection type A could be induced by performing an aortic clamp injury. Serum samples were collected before and after induction (30 min) of the aortic lesion from the right femoral vein. Total (acid activated) TGF-beta 1 concentrations were measured by ELISA. Echo measurements of the aortic root were obtained from a parasternal long axis view in all mice. Results: Transthoracic echocardiography of the aortic root performed prior to surgery showed significantly larger diameters in Fbn1C1039G/+ mice compared to WT (p&lt;0.0001). Aortic clamp injury led in Fbn1C1039G/+ and WT mice to a reproducible aortic wall hematoma, and intimal tears. Hematoxylin-eosin stained histological sections revealed aortic dissection of the medial layer in Fbn1C1039G/+ mice but not in WT (p&lt;0.001). Elastin-stained sections revealed a significantly higher elastic fiber fragmentation and disarray in Fbn1C1039G/+ aortas compared to WT (p&lt;0.001). Aortic dissection in Fbn1C1039G/+ mice was limited to the ascending aorta. Mean TGF-beta 1 serum concentrations significantly increased after inducing the aortic lesion in Fbn1C1039G/+ mice (p=0.01; 130 ng/ml vs 412.9 ng/ml) but not in WT mice (p=0.2). Sham operated Fbn1C1039G/+ and WT mice showed no difference in TGF-beta 1 serum concentrations before and after surgery (p=0.7; n=4). Conclusions: We present a reproducible and in the short-term non-lethal mouse model of a surgically induced acute aortic dissection type A in MFS. TGF-beta 1 serum concentrations after inducing the aortic lesion significantly increased in Fbn1C1039G/+ mice but not in WT and Sham operated mice. TGF-beta 1 is a promising diagnostic biomarker for an acute aortic dissection type A in MFS.

Élastorrhexie papuleuse : deux cas

Papular elastorrhexis is a rare dermatosis characterized by asymptomatic papules on the trunk and the upper extremities. Histological examination shows loss and fragmentation of elastic fibres as well as thickening of collagen bundles. Case 1: a 46-year-old man was examined with asymptomatic papular lesions for 20 years. Firm and clearly delineated papules ranging from few millimetres to 2cm in diameter became wrinkled at their surface. They were located on the back and symmetrically on the upper limbs. The oldest of them were 15cm wide. Histological examination showed thickened collagen bundles with almost complete loss of dermal elastic fibres, fragmentation of elastic fibres around the lesion and mucin deposits. Standard laboratory tests and bone X-rays were normal. Case 2: a 34-year-old man consulted for clearly delineated asymptomatic papules on the back present for four years. Histological examination was similar to the previous patient and the laboratory tests were normal. He developed Hodgkin's lymphoma. We report these two cases because of their particularities as well as the rarity of papular elastorrhexix. The first exhibited large lesions and mucin deposits while the second was associated with Hodgkin's disease. Differential diagnosis of papular elastorrhexis includes Buschke-Ollendorff syndrome, eruptive collagenoma and elastic tissue disorders: macular anetoderma, mid-dermal elastolysis, nevus anelasticus, acne scars and pseudoxanthoma elasticum. The aetiology is unknown. There are no extracutaneous signs.

Interstitial granulomatous drug reaction to anakinra

Interstitial granulomatous drug reactions are an uncommon entity presenting as asymptomatic, annular, erythematous to violaceous plaques. The incidence of such reactions has been increasing with the use of biologic agents. We report, to the best of our knowledge, the first such reaction to the interleukin (IL)-1 inhibitor anakinra. Our patient presented with pink dermal plaques and nodules in the periaxillary region which resolved with discontinuation of anakinra and recurred upon restarting anakinra. Biopsy revealed a diffuse dermal infiltrate of lymphocytes and histiocytes with interspersed neutrophils and eosinophils. Fragmentation and degeneration of collagen and elastic fibers was also present. Withdrawal of anakinra led to complete resolution of the lesions. Interstitial granulomatous drug reactions are increasing in frequency and we add anakinra to the list of causative agents.

Pseudoxanthoma elasticum in a patient with sickle cell disease: case report

An 18 year female sickler (HbSS) presented with repeated history of epistaxis and bleeding gums. Features consistent with pseudoxanthoma elasticum were observed, such as hyper-extensile redundant skin folds in the neck, axilla, inguinal areas and abdomen. The skin biopsy showed swollen, clumped and fragmented elastic fibres and calcium deposits in the deep and mid reticular dermis, consistent with pseudoxanthoma elasticum. This is a well recognised complication of sickle cell disease which has not been described in Kenya.

Highly variable cutis laxa resulting from a dominant splicing mutation of the elastin gene

Autosomal dominant congenital cutis laxa (ADCL) is genetically heterogeneous and shows clinical variability. Only seven ADCL families with mutations in the elastin gene (ELN) have been described previously. We present morphological and molecular genetic studies in a cutis laxa kindred with a previously undescribed highly variable phenotype caused by a novel ELN mutation c.1621 C > T. The proband presented with severe cutis laxa, severe congenital lung disease previously undescribed in ADCL and pulmonary artery disease, which is often seen in ARCL but rare in ADCL. He also developed infantile spasms (OMIM 308350; West syndrome), which we consider a coincidental association although recessive cutis laxa or even digenic inheritance cannot be excluded. Electron microscopy of the proband's dermis revealed only mild rarefication of elastic fibers (in contrast to most recessive cutis laxa types). Apart from mild elastic fiber fragmentation, dermal morphology of the proband's father was within normal range. Molecular analysis of the ELN gene using genomic DNA from blood and RNA from cultured skin fibroblasts indicated a novel splice site mutation in the proband and his clinically healthy father. Analysis of ELN expression in fibroblasts provided evidence for a dominant-negative effect in the child, while due to an unknown mechanism, the father showed haploinsufficiency which might explain the significant clinical variability.

Red-brown macules on the abdomen

Conflict of interest: none declared. A healthy 63‐year‐old man presented with progressive impairment of vision. Fundoscopy examination revealed angioid streaks and neovascularization of the retina in the right eye. No visible skin lesions in the neck, axillae, groin and oral mucosa were found. The patient had a 30‐year history of a red‐brown rash on the upper abdomen, which consisted of small round red‐brown macules in a weak reticular arrangement (Fig. 1). There was no history of cardiovascular disease. ... Skin from a macule showed a band of eosinophilic granular material mainly at the border of the mid and lower dermis (Fig. 2a). Elastic van Gieson stain showed fragmentation and clumping of elastic fibres in the mid and lower dermis (Fig. 2b), where calcification of the degenerated fibrous components was revealed by von Kossa stain. There was some surrounding inflammation in the form of a few foreign‐body giant cells scattered in the dermis. Anti‐elastin antibody stain confirmed the degenerated matrix components contained elastic fibres. A skin biopsy from the neck did not show any abnormalities.

Anetoderma Associated with Lyme Disease: A Case Report

Anetoderma is a rare skin disease characterized by circum-scribed areas of wrinkled, atrophic or slack skin due to the loss of elastic tissue in the dermis (1). Histologically, it is characterized by a decreased amount of dermal elastic tissue and variable levels of inflammatory infiltrate. Currently, anetoderma is classified as either a pri-mary or secondary form. The aetiopathogenesis of anetoderma is unknown. The frequent association of anetoderma with immune-mediated diseases and finding immunoglobulin at the anetodermic lesions suggests a possible immunological mechanism in the fragmenta-tion and/or loss of elastic fibres (2). CASE REPORT

Pseudoxanthoma elasticum and nephrolithiasis: a rare association.

Pseudoxanthoma elasticum (PXE) is a multi-systemic, genetic disorder of connective tissue characterized by progressive calcification and fragmentation of elastic fibers in skin, retina and cardiovascular system. A young patient reported to urologist in emergency with azotemia secondary to acute bilateral obstructive uropathy. Upon successful management, he was found to have full-blown skin and eye manifestations and was evaluated thoroughly regarding extent and potential systemic complications of Pseudoxanthoma elasticum.

Pathologic Aneurysmal Dilation of the Ascending Aorta and Dilation of the Main Pulmonary Artery in Patients with Kabuki Syndrome: Valve-sparing Aortic Root Replacement

We report the aneurysmal dilation of the ascending aorta and the main pulmonary artery in 2 children with Kabuki syndrome. In 1 patient, there was progressive aneurysmal dilation of the ascending aorta necessitating aortoplasty. Histologic examination of the resected aorta revealed disrupted and fragmented elastic fibers in the medial layer, along with mucinous degeneration of the aortic wall. This is the first recognition and report of these findings as part of the Kabuki syndrome.

Compound heterozygous mutations in fibulin‐4 causing neonatal lethal pulmonary artery occlusion, aortic aneurysm, arachnodactyly, and mild cutis laxa

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_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.

Pseudoxanthoma elasticum: genetic variations in antioxidant genes are risk factors for early disease onset.

Pseudoxanthoma elasticum (PXE) is a rare hereditary disorder characterized by progressive calcification and fragmentation of elastic fibers in connective tissues. PXE is caused by mutations in the ABCC6 gene, which encodes the membrane transporter multidrug resistance-associated protein 6. Chronic oxidative stress was recently suggested to play a crucial role in the pathogenesis of the disease. Our aim was to investigate the association of PXE with genetic variation in genes coding for antioxidant enzymes. We used restriction fragment length polymorphism and allele-specific PCR analyses to evaluate the distribution of single-nucleotide polymorphisms in the genes encoding catalase (CAT), superoxide dismutase 2 (SOD2), and glutathione peroxidase 1 (GPX1) in DNA samples from 117 German PXE patients and 117 healthy age- and sex-matched control individuals. The investigated genetic variants had previously been shown to affect the activities of these antioxidant enzymes. We found a correlation between genotype and age of disease onset for polymorphisms in CAT (c.-262C>T), SOD2 (c.47C>T), and GPX1 (c.593C>T). Furthermore, the age of disease onset was inversely correlated with the number of mutated alleles, indicating a cumulative effect on the time of disease onset [mean (SD) age of 40.9 (13.6) years, 32.4 (16.3) years, and 25.7 (15.9) years for carriers of 0, 1-2, and >2 mutated alleles, respectively; P = 0.03]. Our findings demonstrate that increased oxidative stress due to activity-affecting polymorphisms in genes encoding antioxidant enzymes leads to earlier PXE onset.

An autopsy case of pseudoxanthoma elasticum: histochemical characteristics

An autopsy case of pseudoxanthoma elasticum is reported. A Japanese female patient complained of yellow papules on the neck, precordium, and axilla, beginning at 54 years of age. When the patient was 58 years old, in response to her visual disturbance a funduscopic examination was performed, revealing angioid streaks, and skin biopsy identified a characteristic pseudoxanthoma elasticum (PXE) lesion. The patient developed congestive heart failure, and following mitral valve prolapse and regurgitation flow into the left atrium, mitral valve replacement with a prosthetic valve was performed when the patient was 65 years old. Soon afterward, the patient complained of gait disturbance, and she died of congestive heart failure at 68 years of age. Autopsy specimen revealed fragmented, granular, and calcified elastic fibers in the middle to deep dermis and in the thickened subendocardium, and small to medium-sized muscular arteries revealed fragmented, laminated, and calcified elastic lamina; vascular changes were seen in the heart, lung, kidney, gastrointestinal tract, and iliac artery. Disrupted elastic fibers were visualized using the Weigert resorcin fuchsin method and were stained positive by antielastin and antifibronectin antibodies. Calcification was confirmed by von Kossa staining. Affected areas were PAS-positive after diastase digestion, indicating the presence of glycoprotein. Affected areas were colloidal iron-positive, indicating the presence of proteoglycan matrix.

Correction of Clinical Manifestations of Canine Mucopolysaccharidosis I with Neonatal Retroviral Vector Gene Therapy

Mucopolysaccharidosis I (MPS I) (Hurler syndrome) is due to deficient alpha-L-iduronidase (IDUA) activity and is the most common of the MPS disorders. Neonatal MPS I dogs were injected intravenously (IV) with a gamma retroviral vector containing a complete long-terminal repeat (LTR) and an internal human alpha(1)-antitrypsin (hAAT) promoter upstream of the canine IDUA complementary DNA (cDNA). This resulted in stable serum IDUA activity of 366 +/- 344 units (U)/ml (28-fold normal) for up to 1.8 years, which likely derived primarily from secretion of IDUA by transduced liver cells. Retroviral vector (RV)-treated dogs had >18% of normal IDUA activity in organs and had decreased severity and/or incidence of hernias, chest deformities, joint disease, facial dysmorphia, corneal clouding, valvular heart disease, and aortic dilatation as compared with untreated MPS I dogs. The marked reduction that was observed in lysosomal storage in the brain of RV-treated dogs may have been due in part to expression from the LTR of the vector in cells in the brain. This possibility will be explored in future studies, because the potential for insertional mutagenesis has raised concerns about using vectors with an intact LTR. If proven safe, this gene therapy technique may be utilized in treating children with Hurler syndrome.

Pseudoxanthoma elasticum: biopsy of clinically normal skin in the investigation of patients with angioid streaks

Pseudoxanthoma elasticum (PXE) is a genetic disorder characterized by fragmentation and calcification of elastic fibres with resultant pathological changes in the dermis, Bruch's membrane and blood vessels. Defects in Bruch's membrane produce angioid streaks on the retina but this appearance is not pathognomonic of PXE. Biopsy of clinically normal skin or scar tissue in patients with angioid streaks may show the histological features of PXE. To test the hypothesis that biopsy of clinically normal skin is a useful investigation in patients with angioid streaks. This prospective study investigated 18 consecutive patients with angioid streaks. Each patient underwent a full dermatological examination and was investigated for diseases known to be associated with angioid streaks. Axillary skin biopsies were taken from 14 consenting patients. Typical PXE was found in 11 patients. No other diseases associated with angioid streaks were identified. Five patients had angioid streaks in the absence of systemic disease. Two patients had nondiagnostic dermatological features which were not clarified by histology. Two of the 11 patients with PXE showed histological evidence of PXE from clinically normal axillary skin. However, in both cases flexural skin elsewhere showed the typical clinical and histological features of PXE. This study demonstrates the association between angioid streaks and PXE. However, it does not support the hypothesis that biopsy of normal-looking skin is helpful in the investigation of adult patients with angioid streaks.