A study of cytokeratin profiles in localized cutaneous amyloids

The major component of localized cutaneous amyloids may be derived from cytokeratin (CK). However, the CK profiles of primary cutaneous amyloidosis (PCA) and secondary cutaneous amyloidosis (SCA) remain obscure. Paraffin-embedded sections of skin tissue from 64 patients with PCA, 111 with SCA and 3 with systemic amyloidosis were analyzed immunohistochemically using 12 different polyclonal or monoclonal anti-CK antibodies (34βE12, MNF116, LP34, AE1/AE3, anti-CK1, CK5, CK6, CK7, CK10, CK14, CK16 and CK17). In addition, frozen skin tissues from 12 patients with PCA were analyzed for comparison with the paraffin-embedded tissue. In all 64 PCA paraffin sections, the amyloid deposits were immunopositive for anti-CK5 antibody and 34βE12. In all 12 frozen sections of PCA, the amyloid deposits were immunopositive for anti-CK5 antibody, 34βE12, MNF116 and LP34, and seven (58.3%), three (25%) and one (8.3%) were immunopositive for anti-CK1, CK14, and CK10 antibodies, respectively. In all SCA sections, the amyloid deposits were immunopositive for CK5 and 34βE12. In addition, MNF116 immunolabeled amyloids of all sections from patients with basal cell carcinoma and trichoepithelioma, and MNF116 and LP34 immunolabeled amyloids of sections from patients with porokeratosis. Our results indicate that CK5 is the major CK present in the amyloid deposits of PCA and SCA, and “amyloid-K” is mainly derived from basal keratinocytes.     

Nodular localized primary cutaneous amyloidosis: a long-term follow-up study

We present long-term follow-up data on patients with nodular localized primary cutaneous amyloidosis (NLPCA) seen at the St John's Institute of Dermatology between 1968 and 1999. This is the largest clinical follow-up study of this type of amyloid to date. Based on these cases we estimate the rate of progression of NLPCA to systemic amyloidosis to be only 7%, much lower than the 50% rate currently quoted in the literature.     

Primary cutaneous amyloidosis of the external ear: a clinicopathological and immunohistochemical study of 17 cases

Primary cutaneous amyloidosis includes several forms of localized amyloidosis characterized by superficial amyloid deposits occurring at or near the dermal–epidermal junction in the absence of systemic involvement. Primary cutaneous amyloidosis of the auricular concha and external ear represents a rarely described variant. There have been 27 cases reported in the English language literature, and herein we report 17 additional cases. This article demonstrates that the amyloid observed in this context is generally positive for Congo red, crystal violet and thioflavin T. It also expresses cytokeratin 34ßE12 via immunohistochemistry. Our immunohistochemical results and review of the literature suggest that the amyloid in amyloidosis of the external ear is the result of basal keratinocyte degeneration and does not signify deposition from a systemic or generalized process. Wenson SF, Jessup CJ, Johnson MM, Cohen LM, Mahmoodi M. Primary cutaneous amyloidosis of the external ear: a clinicopathological and immunohistochemical study of 17 cases.     

A monoclonal anti-keratin antibody reactive with amyloid deposit of primary cutaneous amyloidosis

Specimens from cutaneous amyloidoses (lichen amyloidosis and macular amyloidosis) were stained immunohistochemically with monoclonal anti-keratin antibodies. One monoclonal antibody raised against hair keratin (HKN-6) reacted with the amyloids of both primary amyloidoses. Another monoclonal antibody, HKN-2, did not decorate the amyloid deposit. HKN-6 did not stain the interfollicular epidermis, but HKN-2 did. The possible explanations of these findings are 1) amyloid deposits contain keratin protein modulated to react with HKN-6; 2) amyloid deposits contain a protein unrelated to keratin protein, but reactive to HKN-6.     

Nodular amyloidosis at the sites of insulin injections

Amyloid is characterized by its fibrillary ultrastructure, and more than 20 proteins have been described to date as possible precursors. Among them, insulin and enfuvirtide represent the only medications described as amyloidogenic substances. We describe two diabetic patients, who were undergoing long‐standing subcutaneous insulin treatment, who developed subcutaneous nodules at the sites of insulin injections. Histopathologic examination showed the presence of eosinophilic and amorphous masses in deep dermis, which stained positive with Congo red, amyloid P substance and anti‐human insulin antibody. Whether the type of injected insulin played a role or not in the pathogenesis of the process is still uncertain, because all described patients used both fast‐acting and slow‐acting insulins at the same injection sites. Our second case showed nodular insulin‐derived amyloid tumors only at the sites where exclusively fast‐acting insulin was injected, which supports the notion that fast‐acting insulin may also be the cause of this disorder. Insulin‐derived nodular amyloidosis is probably underdiagnosed because of the small body of literature in comparison with the prevalence of insulin dependent diabetic patients. This underdiagnosis probably is because of its clinical similarity with the lesions of lipohypertrophy at the sites of insulin injections, which is rarely biopsied.     

细胞角蛋白和波形蛋白在皮肤淀粉样变淀粉样蛋白中表达的研究

目的:探讨皮肤淀粉样变淀粉样蛋白的生物学来源.方法:应用免疫组化染色技术检测4种角蛋白(cytokeratins,CKs)及波形蛋白在20例斑状或苔藓样型皮肤淀粉样变淀粉样蛋白中的表达情况.结果:①CK3413E12和CK5/6在20例标本的淀粉样蛋白团块中均呈阳性表达:而AE1/AE3、CK10/13和波形蛋白在淀粉样蛋白团块中均呈阴性表达;②淀粉样蛋白团块中波形蛋白表达阳性的成纤维细胞明显增生.结论:淀粉样蛋白主要来源于凋亡的表皮基底细胞而非真皮组织.     

Suggestive linkage of familial primary cutaneous amyloidosis to a locus on chromosome 1q23

BACKGROUND: Large or deteriorated skin defects are sometimes life threatening. There is increasing evidence that adult stem cells are useful for tissue regeneration. Human mesenchymal stem cells (hMSCs) are self-renewing and are potent in differentiating into multiple cells and tissues. OBJECTIVES: To investigate the effects of hMSCs in cutaneous wound healing. METHODS: Wound healing was studied in an hMSC-populated porcine skin substitute, using a nude rat model to minimize immune reactions. Full-thickness skin and soft tissue defects of 1.5 x 1.5 cm in size, including the panniculus carnosus, were excised and covered with hMSCs and basic fibroblast growth factor (bFGF)-soaked skin substitutes and an evaluation was made of wound size, histology and protein expression at 3, 7 and 42 days after injury. RESULTS: The wound size was significantly smaller in the hMSC-treated groups (P < 0.01) and any dose of bFGF (1, 10, 100 microg) enhanced the healing (P < 0.01). The re-epithelialization markers integrin alpha3 and skin-derived antileucoproteinase were remarkably increased with the presence of bFGF in a dose-dependent manner, while the mesenchymal cell surface markers CD29 and CD44 were downregulated in a time-dependent manner. Human pancytokeratin, which does not cross-react with rat antigens, was observed by Western blotting at 38 kDa and 42 kDa from the hMSC-treated tissues on day 7. The expression levels were elevated by 10 microg bFGF (P < 0.01). The immunohistochemical expression of human pancytokeratin was only observed in the hMSC-treated groups. CONCLUSIONS: These data suggest that hMSCs together with bFGF in a skin defect model accelerate cutaneous wound healing as the hMSCs transdifferentiate into the epithelium.     

Anosacral cutaneous amyloidosis: a study of 10 Chinese cases

BACKGROUND: Primary cutaneous amyloidoses are rare in Western countries, but are relatively common in Taiwan. Anosacral cutaneous amyloidosis is a rare type of primary cutaneous amyloidoses, first reported in Japanese patients. PATIENTS/METHODS: In the present study, we investigated the age of onset, sites of involvement, associated systemic diseases, and histopathological findings in 10 cases of anosacral cutaneous amyloidosis seen during the past 27 years. RESULTS: In previous reports the aetiology of anosacral cutaneous amyloidosis was thought to be a senile change, but half of our patients developed the disease before the age of 60 years. Based on our histopathological findings, apoptosis may be the initial event causing amyloid deposition, although the precise mechanism causing apoptosis needs further investigation. Three patients were found to have diabetes mellitus, but any relationship to anosacral cutaneous amyloidosis is unclear. CONCLUSIONS: No cases of this cutaneous disorder have been reported in the Western literature; there seems to be a racial difference accounting for the disease, although the precise factor is not clarified yet. The disease could easily be misdiagnosed as lichen simplex chronicus, postinflammatory hyperpigmentation or tinea cruris; therefore, a thorough history, a careful physical examination and a skin biopsy is needed to establish a firm diagnosis.     

Frictional amyloidosis: a study of 10 cases

Ten patients with macular amyloidosis were studied with particular reference to the role of friction. All 10 patients had a history of prolonged rubbing over a period of 2-5 years with various objects, such as bath sponges, brushes, towels, plant sticks and leaves. The presence of amyloid was confirmed by histochemical stains in six cases and by electron microscopy in four cases. The study confirms the role of friction in the causation of macular amyloidosis and hence, the term 'frictional amyloidosis' aptly describes the condition. The study also emphasizes the need for electron microscopy in the diagnosis of frictional amyloidosis.     

Apoptosis in primary cutaneous amyloidosis

Amyloid deposits in primary cutaneous amyloidosis (PCA) may be initially derived from cytokeratin. possibly after keratinocyte death. However, the mechanism of keratinocyte death remains obscure. To investigate the potential role of apoptosis in the pathogenesis of PCA, a retrospective study was conducted on the skin tissues from 20 Chinese patients with PCA. We used a terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labelling (TUNEL) method for detecting the apoptotic cells. Immunohistochemical staining was performed to examine the expression of the B-cell leukemia/lymphoma-2 gene (bcl-2) and Fas. Apoptotic cells were shown in 11 of 20 cases (55%) by TUNEL. Histological sections showed that dyskeratotic cells and vacuolar alteration of the basal cells were more commonly observed in the TUNEL-positive group. In all cases of PCA, epidermal expression of bcl-2 was minimal, while expression of Fas was observed on keratinocytes in the basal to granular layers: however, these findings were not different from those in normal skin. Our results suggest that the keratinocyte destruction in PCA may occur as an initial result of apoptosis, which in turn leads to the amyloid formation.     

结节、斑疹双相型皮肤淀粉样变一例

患者女,40岁,腰、腹部结节14年,无自觉症状,进行性加重;上背部色素性斑疹,痒十余年,于1989年来我院首诊,给予手术切除并行病理检查,诊断为结节型皮肤淀粉样变.最近因腰、腹部出现新的结节、斑块,背部出现褐色斑疹,痒,再次来我院就诊.既往体健,家族中无类似病史.皮肤科检查:双肩胛间见片状褐色斑疹,轻度肥厚(图1);腰、腹、臀部数个大小不等的结节、斑块,黄豆粒至红枣大小,呈黄红色,具蜡样光泽,部分区域有萎缩、紫癜及色素沉着,质硬,无触痛(图2).     

原发性结节型皮肤淀粉样变性

报告1例原发性结节型皮肤淀粉样变性。患者男,41岁,双侧鼻孔缘下斑块、结节4年就诊,无自觉症状。组织病理检查:表皮基底细胞轻度液化变性,真皮浅、深层及皮下组织胶原纤维间可见嗜酸性物沉积,血管壁见类似改变。结晶紫和刚果红染色阳性,PAS染色弱阳性,偏振光显微镜下呈苹果绿双折光。诊断:原发性结节型皮肤淀粉样变性。     

Amyloidogenesis in a case of cutaneous amyloidosis: an electron microscopic study using the refixation-reembedding method

A case of the hyperkeratotic type of macular amyloidosis was electron microscopically examined using the refixation-reembedding method. All the cytoid bodies seen in the dermis were amyloid islets associated with malformed basal lamina-like material. The uppermost amyloid islets were in close apposition to the basal cells, which had neither hemidesmosomes nor intact basal lamina. Anchoring fibril-like filaments were seen between the amyloid islets and the basal lamina-like material. Many fibrillar bodies and clusters were present in the spinous layer, but not in the dermis. Masses of eosinophilic, PAS-positive ovoid bodies seen in the horny layer were tightly packed fibrillar bodies shifted from the spinous layer to the horny layer. These findings suggest that the disturbed basal cells produce an amyloid substance in the dermis, as well as malformed basal lamina. The colloid bodies formed by the degeneration of the basal cells seemed to shift up to the horny layer but not to contribute to the amyloidogenesis in this case.     

Apolipoprotein E polymorphism and lipoprotein compositions in normolipidaemic xanthelasma patients

BACKGROUND: Apolipoprotein E (apoE) phenotypes and lipoprotein compositions in xanthelasma patients have been reported in different series. OBJECTIVE: To investigate the apoE polymorphism and lipoprotein compositions in xanthelasma patients by using rapid polymerase chain reaction, and searched for an association between apoE polymorphism and the lipoprotein levels in xanthelasma patients. DESIGN: ApoE polymorphism and the different types of serum lipoproteins were studied in 25 patients with xanthelasma and compared with 27 normal subjects. RESULTS: All of patients were found to be normolipidaemic. The patients had significantly higher concentrations of total cholesterol and apolipoprotein B, and lower concentrations of apolipoprotein A. There was no difference in serum triglyceride, low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol concentrations. The distribution of apoE genotypes and alleles was the same in both groups. CONCLUSIONS: The apoB, apoA and cholesterol levels did show statistically significant differences in the direction of an increased risk of atherosclerosis. Patients with xanthelasma demonstrated slight differentiations in the apoE polymorphism and metabolism of lipoproteins that require further clarifications.     

Relevance of vitamins C and E in cutaneous photoprotection

Ultraviolet (UV) radiation-induced oxidative stress may result in acute and chronic photodamage. Based on the endogenous antioxidant system, the administration of antioxidants for scavenging reactive oxygen species might be a promising strategy in the prevention of UV-induced skin reactions. The relevance of the most common antioxidants, vitamins E and C, is reviewed focusing on topical and systemic photoprotective effects in animals and humans. Topically applied vitamin C induced significant photoprotective effects at concentrations of at least 10% in animals and humans, whereas a photoprotective effect has not been demonstrated by oral administration even at high doses in humans. Topical vitamin E reduced erythema, sunburn cells, chronic UV-B-induced skin damage, and photocarcinogenesis in the majority of the published studies, whereas only high doses of oral vitamin E may affect the response to UV-B in humans. Combination of vitamins C and E, partly with other photoprotective compounds, did increase the photoprotective effects dramatically compared to monotherapies. This synergistic interplay of several antioxidants should be taken into consideration in future research on cutaneous photoprotection.     

Haptoglobin from psoriatic patients exhibits decreased activity in binding haemoglobin and inhibiting lecithin-cholesterol acyltransferase activity

Objective The aim of this work was to assess whether psoriasis is associated with phenotype prevalence and altered activity of haptoglobin (Hpt). Background Hpt is a plasma acute‐phase glycoprotein, displaying in humans three phenotypes. Phenotype prevalence or structure modification of Hpt was associated with several diseases. The Hpt main function is to bind and carry to the liver free haemoglobin for degradation and iron recycling. Hpt was recently found able to bind the apolipoprotein A‐I (ApoA‐I), thus impairing its stimulation on the activity of the enzyme lecithin‐cholesterol acyl‐transferase (LCAT). Study design Hpt was isolated from patients with psoriasis vulgaris, and its activity in haemoglobin or ApoA‐I binding and LCAT inhibition was compared with that of normal protein. Methods Two affinity chromatography steps, the first using resin‐coupled haemoglobin and the second anti‐Hpt antibodies, were used to purify Hpt. The protein phenotype was assessed by electrophoresis. Binding experiments were performed by Enzyme‐linked immunosorbent assay with stationary haemoglobin or ApoA‐I, Hpt in solution and anti‐Hpt antibodies for detection of bound Hpt. Standard LCAT assays were carried out in the presence of Hpt purified from patients or healthy subjects. Results Phenotype prevalence of Hpt in psoriasis was not found. After affinity chromatography by haemoglobin, albumin and ApoA‐I were routinely found heavily contaminating only Hpt from normal subjects. Isolated Hpt from patients had lower activity than normal protein in both haemoglobin binding and LCAT inhibition. Conclusions In psoriasis, Hpt displays some structure modification(s), which might be associated with the protein function in the disease.     

Case of primary localized cutaneous amyloidosis with protean clinical manifestations: lichen, poikiloderma-like, dyschromic and bullous variants

Primary localized cutaneous amyloidosis (PLCA) commonly presents as macular and lichen variants. We present a case of a 27-year-old Chinese woman with cutaneous features of the rarely reported poikiloderma-like, dyschromic and bullous forms of PLCA, and the commoner lichen variant. There were no syndromic associations or systemic involvement, and the various morphological subtypes occurred in isolation from one another. We review the clinical spectrum of PLCA, highlight its protean clinical manifestations in this patient, and discuss its postulated pathogenesis in relation to its histopathological features.