Microanatomy of the dermis in relation to relaxed skin tension lines and Langer's lines

The microanatomy of the dermis was studied by optical and scanning electron microscopy in order to visualize the relationship between orientation of fibers and skin tension lines. In the reticular dermis of the normal adult human, skin tension lines have an anatomical counterpart consisting of a preferential parallel orientation and a straightening of thin collagen bundles and elastic fibers. This was observed only when mechanical tensions normally present in the skin were preserved during the processing of the samples, but was not observed in those that had retracted during biopsy. A comparative study of the fetal skin of calves, where relaxed skin tension lines were absent, offered further evidence that the presence of tension lines in the skin depends on the interrelationship between elastic fibers and collagen fibers, as well as on the anchorage of collagen bundles one upon another.     

Evolution of granuloma annulare to mid‐dermal elastolysis: report of a case and review of the literature

A 55‐year‐old healthy Caucasian female, on no medication, was seen by a dermatologist because of a patchy, slightly indurated and violaceous eruption involving her neck and trunk. The clinical impression was of granuloma annulare (GA). Over a period of several months the violaceous lesions became atrophic with loss of colour and eventual wrinkling of lesional skin. Sequential skin biopsies were obtained, which revealed a spectrum of changes. Those from early violaceous lesional zones displayed perivascular lymphocytic infiltrates and interstitial granulomatous inflammation, characteristic of interstitial GA. Samples from atrophic lesional areas appeared normal on routine sections but an Orcein–Giemsa (OG) stain, prompted by the clinical history of atrophy, revealed absence of elastic fibers in the mid‐reticular dermis. The combined clinicopathologic findings pointed to development of mid‐dermal elastolysis (MDE) at involutional sites of GA. Owing to consideration of a cutaneous T‐cell lymphoma in the differential diagnosis, genotyping in search of T‐cell monoclonality was performed and yielded a negative result. Our case supports the existing but scant evidence in the literature that the rare, enigmatic condition termed MDE is an end‐result of inflammatory destruction of dermal elastic fibers. GA is one form of dermatitis capable of culminating in this entity, but others have also been implicated.     

Nevus anelasticus: how should such lesions be classified?

Nevus anelasticus represents a rare entity that is most commonly classified as a connective tissue nevus. It typically presents before 20 years of age with asymmetrically distributed white‐to‐skin‐toned or pink‐to‐red papules or plaques on the trunk and upper extremities. The lesion is defined histopathologically by the absence or degeneration of elastic fibers in the dermis. We report the case of a healthy 17‐year‐old female who presented with an asymptomatic slowly progressive plaque on the right inferior areola. Histopathologic examination showed the absence of elastic fibers in the papillary and upper reticular dermis and fragmented elastic tissue fibers in the deep reticular dermis. Although there is ongoing controversy regarding the nosology of this uncommon disorder, we propose that it is a distinct entity based on its histopathologic and clinical features.     

Anetoderma: Biochemical and ultrastructural demonstration of an elastin defect in the skin of three patients

Three patients with localized cutaneous lesions characteristic of anetoderma were studied. Clinically, the onset of the disease was between the ages of 17 and 25, and numerous flaccid, saclike skin lesions developed over several subsequent years. Histologically, the lesions were characterized by paucity and fragmentation of the elastic fibers. Electron microscopy demonstrated that the elastic fibers, both in papillary and deep reticular dermis in the lesional skin, were fragmented and irregular in appearance. The concentration of elastin, determined by a radioimmunoassay of desmosine, an elastin-specific cross-link compound, was markedly reduced in the lesions, as compared with unaffected skin from the same patients or with normal skin from unrelated control subjects. In contrast, the concentrations of hydroxy pro line, an index of collagen, or deoxyribonucleic acid (DNA), a measure of cellularity, were not changed in the lesions. Thus, the results indicate that in the three patients studied, the elastic fibers are defective and reduced in quantity. These observations suggest that the deficiency of elastin in the dermis may lead to development of the cutaneous lesions of anetoderma.     

Expression of extracellular matrix proteins in reticular variant of mid‐dermal elastolysis

Background Mid‐dermal elastolysis (MDE) is a rare disorder of the elastic tissue that is characterized histopathologically by selective loss of elastic fibres in the mid dermis. Objective We aimed to investigate the protein and mRNA expression of extracellular matrix‐related proteins and growth factors in the skin (lesional and non‐lesional) of a female patient with the reticular variant of MDE. Methods Real‐time RT‐PCR and immunohistochemistry was performed for matrix metalloproteinase‐1 (MMP‐1), tissue inhibitor of metalloproteinase‐1, decorin, biglycan, versican, fibronectin, elastin, extracellular matrix protein 1, cathepsin G, transforming growth factor ß1 and connective tissue growth factor. Results Although protein expression of decorin, biglycan and versican was reduced in the mid dermis of lesional skin, mRNA expression did not differ between lesional and non‐lesional skin. As expected, elastin expression was significantly diminished in the mid dermis of lesional skin, whereas mRNA expression levels of elastin were equal to non‐lesional skin. Immunoreactivity of MMP‐1 was increased in lesional upper and mid dermis. Accordingly, MMP‐1 mRNA was also significantly higher expressed in MDE when compared with non‐lesional skin. Conclusions The results of this study confirm data of the previous investigations indicating that increased MMP‐1 activity followed by elastin degradation seems to constitute the pathogenetic background of MDE.     

Oxytalan, elaunin, and elastic fibers in the human skin.

The elastic system of normal human skin was studied by light and electron microscopy. By light microscopy three different types of fibers were observed: oxytalan, elaunin, and elastic. The most superficial ones (oxytalan fibers) are very thin and directed perpendicularly to the dermoepidermal junction. They start from a plexus with the tinctorial characteristics of elaunin fibers which is connected with the thicker elastic fibers of the reticular dermis. At the electron microscopic level the oxytalan fibers are formed by bundles of tubular microfibrils 10 to 12 nm in diameter. In the deepest layers of the dermis an amorphous material is seen in the core of these bundles. In the elaunin fibers the amorphous material is sparse, while in the elastic fibers it is abundant and compact.     

弹性假黄瘤样真皮乳头层弹性纤维溶解症国内首例报告

报告国内首次发现的弹性假黄瘤样真皮乳头层弹性纤维溶解症1例。患者女,38岁。因多发性肌炎10月余,颈部起黄色斑丘疹2月就诊。双侧颈部、锁骨上方有数十个绿豆至黄豆大淡黄色柔软丘疹或斑块,呈鹅卵石样。临床及实验室检查符合多发性肌炎,无眼及心血管改变。组织病理检查以韦杰尔特染液染色,可见真皮乳头层弹力纤维完全消失,真皮网状层内弹性组织轻度减少,von-kossa染色未见钙化。透射电镜真皮乳头层内弹力纤维消失,在真皮网状层上部可见大量未成熟的弹力纤维,胶原纤维结构正常。     

Primary anetoderma: a case report and its modified classification

A fifty-nine-year-old healthy male presented with fifteen round pouches around his bilateral shoulders and proximal thighs, at which elasticity was lost on palpation. Histopathological examinations demonstrated that the lesional dermis was thinner than normal skin and there was loss of elastic fibers and mild inflammatory cell infiltration. Because there was no preceding inflammatory skin lesion or associated diseases, the patient was diagnosed with primary anetoderma. This is a rare case of primary anetoderma that showed loss of elastic fibers and the thinner dermis. In addition, a modified classification is proposed considering associated diseases with a review of literature.     

Familial anetoderma

A 31-year-old Caucasian male presented with a history of erythematous, saccular outpouchings of the skin on his back, shoulders, and upper extremities (Fig. 1). The patient reported that his mother and aunt had a similar skin disorder, which initially began with inflammation, but healed leaving lax skin in its wake. He did not recall the name of the skin condition. Physical examination revealed large confluent zones of sac-like protrusions of erythematous skin on the back and shoulders. Histopathologic examination of the excisional biopsy revealed a relatively unremarkable epidermis. Perivascular lymphocytes were present in small numbers in the papillary dermis. Adnexal structures and deep dermis remained intact. The acid-orcein-Giemsa stain highlighted the absence of elastic fibers within the mid and lower reticular dermis (Fig. 2a,b), consistent with anetoderma.     

Expression of 36-kDa microfibril-associated glycoprotein (MAGP-36) in human keratinocytes and its localization in skin

Microfibril-associated glycoprotein-36 (MAGP-36) is a recently isolated elastin-binding protein and considered to be a member of microfibril-associated glycoproteins (MAGPs). We studied the expression of MAGP-36 in cultured normal human keratinocytes and its localization in the skin. MAGP-36 was found to be expressed in cultured human keratinocytes by Western blot and RT-PCR assays. The levels of MAGP-36 (polypeptide and mRNA) and the number of MAGP-36-producing keratinocytes were greatly increased during Ca(2+)-induced differentiation of keratinocytes. Immunohistochemical studies demonstrated that MAGP-36 colocalized with elastic fibers and formed candelabra like-fibers in the superficial dermis of normal skin. In the elderly skin of sun-exposed region, immunoreactivity of MAGP-36 in the superficial dermis disappeared. In the lesional skin of pseudoxanthoma elasticum which is an elastin-related disorder, immunoreactivity of MAGP-36 was found in the accumulation of disintegrated elastic fibers. The results show that MAGP-36 is a component of elastic fibers in the dermis and co-operates with elastin in normal and diseased conditions.     

Deficiency of tenascin-X causes abnormalities in dermal elastic fiber morphology

Deficiency of the extracellular matrix protein tenascin-X (TNX) was recently described as the molecular basis of a new, recessive type of Ehlers-Danlos syndrome. Here we report gross abnormalities of the elastic fibers and microfibrils in the dermis of these patients, and reduced dermal collagen content, as determined by quantitative image analysis. The ascending, fine elastic fibers in the papillary dermis were absent or inconspicuous and had few branches. The coarse elastic fibers of the reticular dermis were fragmented and clumped. At the ultrastructural level, irregular and immature elastin fibers and fibers devoid of microfibrils were observed. In TNX-deficient patients the dermal collagen density was reduced, but no structural abnormalities in the collagen fibrils were found. These findings suggest that both elastic fiber abnormalities and reduced collagen content contribute to the observed phenotype in TNX-deficient patients.     

Morphea limited to the superficial reticular dermis: an underrecognized histologic phenomenon.

Morphea (localized scleroderma) is a disease of unknown etiology, presenting as circumscribed areas of indurated skin. Histologically, most cases of morphea feature thickened collagen bundles in the deep reticular dermis, sometimes also extending into the superficial dermis or into the subcutis. We present six cases of morphea in which typical histologic features were restricted to the superficial dermis and contrast these with 27 additional biopsies of conventional morphea seen during the same time period. Sections were stained for elastic fibers, and dermal dendritic cells were labeled with antibodies to CD34 and Factor XIIIa. All six cases showed thickened collagen bundles restricted to the superficial dermis, sparing the deep dermis and without associated evidence of lichen sclerosus et atrophicus (LSA). Dermal elastic fibers were not appreciably decreased in number. There was loss of CD34-positive dermal spindle cells in each of our six superficial examples of morphea, which was restricted to the area of altered collagen in four of the six cases. This report highlights the distinctly uncommon phenomenon of morphea presenting solely as alteration of the superficial reticular dermis, without features of LSA. The selective loss of CD34-labeled spindle cells may provide information regarding the role of these putative immune accessory cells in morphea. Recognition of this manifestation of morphea may be helpful diagnostically.     

Non‐invasive imaging of mid‐dermal elastolysis

Mid‐dermal elastolysis (MDE) is a rare disease that is characterized histopathologically by selective loss of elastic tissue in the mid dermis. We aimed to assess MDE using noninvasive skin imaging techniques in vivo. We examined both the lesional and adjacent healthy skin of a woman with the reticular variant of MDE, using confocal scanning laser microscopy, optical coherence tomography (OCT) and high‐frequency ultrasound (HFUS). The median diameter of blood vessels at the top of dermal papillae was significantly increased in erythematous lesional skin compared with healthy skin. The mid‐dermal signal intensity detected by OCT was higher in healthy skin than in lesional skin. With HFUS, mid‐dermal density values were significantly higher in healthy skin than in lesional skin. Our preliminary findings indicate that noninvasive skin imaging methods such as OCT and HFUS might be suitable techniques for the evaluation and monitoring of elastolytic skin disorders such as MDE.     

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.     

The -SH and SS positive components in dermal connective tissues: a study by N-(7-dimethylamino-4-methyl-3-coumarinyl) maleimide (DACM) stain

Summary Although -SH and SS positive components in dermal connective tissue have been observed by N-(7-dimethylamino-4-methyl-3-coumarinyl) maleimide (DACM) stain, their nature is as yet unknown. In our study, we stained several organs such as human skin, rabbit aorta, auricle, and trachea using DACM stain, and studied the distribution of -SH groups and SS linkages among the elastic fibers in those organs. In the dermis of human skin, a moderately strong fluorescence by both -SH and SS stain was present all over the layer, especially in the lower half among collagen fibers in a fine linear or wavy pattern, and a fluorescence ascending vertically from the lower papillary dermis toward the epidermis was also observed. In rabbit aorta, a strong fluorescence by both -SH and SS stain was observed on well-developed elastic fibers. In the matrix of rabbit elastic cartilage, a strong reticular fluorescence by both -SH and SS stain was present. On the other hand, in rabbit hyaline cartilage, no -SH fluorescence was present on any components of the cartilage. However, though a diffuse moderate fluorescence for SS linkages was observed in the matrix, there was no reticular fluorescence such as that seen in the elastic cartilage. These results suggest that the -SH and SS components observed in the dermis by DACM stain are in fact elastic fibers, more precisely, elastic tissue microfibrils.     

The Elastic Tissue of the Skin

In order to separate the changes of actinic damage from those of simple aging, we studied the elastic fibers in low and high sun-exposed skins of normal subjects at different ages. Low sun-exposed skin shows chronologic aging lesions only. These begin at age 30 with a disappearance of oxytalan fibers and with some abnormalities in the reticular and deep dermis; at age 40, aging changes are established: no oxytalan fibers, marked abnormalities, and lysis of elaunic and elastic fibers. In high sun-exposed skin, age-related lesions also occur but are associated with more or less precocious elastotic degeneration in reticular and deep dermis. Both types of aging fibers are revealed by the antielastin antibody HB 8, disappear with elastase, but resist collagenase. Actinic elastosis clearly originates from elastin. The two types of change differ in electron microscopic appearance: with spontaneous aging, elastic fibers are disintegrated (loose and porous fibers); in actinic damage, elastotic fibers are thicker and have accentuated microfibril dense masses. The age-associated lesions could be due to the activity of protease of fibroblastic origin whereas the elastotic degeneration is probably due to the actinic stimulation of fibroblasts.     

Collagen studies in congenital cutis laxa

Summary A case of congenital cutis laxa (CCL) of unclear mode of inheritance associated with multiple pulmonary artery branch stenosis was extensively investigated to assess possible correlations between clinical, ultrastructural, and biochemical features. Light microscopy revealed that elastic fibers were absent in the papillary dermis, while hypoplastic elsewhere. Transmission electron microscopy showed a poor elastin matrix content in some elastic fibers, variable diameters of collagen fibrils, and abundant glycogen granules in most dermal cells. Measurement of collagen fibril diameters, using an image analyzer, was carried out in the patient and two age- and site-matched controls. A biomodal distribution was found in the upper reticular dermis of the patient. In vitro analysis of collagen in skin fibroblast cultures of the patient showed increased collagen synthesis with a balanced production of type I and type III procollagens. Our study confirms that CCL represents a disorder both of collagen and elastic connective tissue.     

Immunoglobulin A (IgA) deposits in lesional skin of a patient with blepharochalasis

Summary We describe a 21-year-old male patient with blepharochalasis, a form of localized acquired cutis laxa. He had a 13-year history of recurrent swelling attacks of the eyelids of unknown origin leading to periocular localized cutis laxa. Histology of lesional skin confirmed almost complete loss of elastic fibres in the reticular and papillary dermis. Immunofluorescence and immunoelectron microscopy studies showed abundant immunoglobulin A (IgA) deposits around the remaining elastic fibres. Control skin of the forearm was negative. These findings support the hypothesis that immunopathogenetic mechanisms may contribute to the elastolytic process of blepharochalasis.     

Decay-accelerating factor in human skin is associated with elastic fibers

Recently a complement inhibitor, decay-accelerating factor (DAF), has been found in association with uncharacterized fibers in the extracellular matrix of human dermis. Here we show by immunohistochemistry and immunoelectronmicroscopy that DAF is on the periphery of elastic fibers, and that it appears to be associated with some microfibrillar elements that cover the fibers. That DAF is a component of these microfibrils is also suggested by studies of lesional skin from anetoderma, a disease characterized by destruction of elastic fibers. In two patients we found a network of residual fine fibers in the dermis that stain with antibodies against DAF and fibrillin (one of the proteins known to be present in the microfibrils of elastin), but do not stain with antibodies to elastin. Western blot analysis of dermal extracts with monoclonal antibodies to DAF identified a 67 kDa molecule, slightly smaller than membrane DAF, and similar in size to soluble DAF found in secretions. It is possible that together with vitronectin, an inhibitor of the membrane attack complex recently identified in association with elastin, DAF prevents damage of elastic fibers by complement.     

Multiple whitish papules on the posterior neck of an elderly woman

White fibrous papulosis of the neck is a rare entity, with fewer than 50 cases described. It is a benign pathology whose main interest lies in its broad differential diagnosis, especially with pseudoxanthoma elasticum. The authors report the case of a 77-year-old woman with multiple yellow-white monomorphic papules on the posterior cervical region, with years of evolution. Cutaneous biopsy revealed a nodular area in the superficial and middle reticular dermis, with slight thickening of the collagen fibers and focally enlarged elastic fibers, aspects highlighted in the Verhoeff staining that additionally showed absence of elastic fibers in the papillary dermis.