Quantitative enzyme-histochemical analysis of tryptase- and chymase-containing mast cells in psoriatic skin

Summary Tryptase-containing mast cells have recently been found to be increased in the upper dermis of psoriatic lesions. In the present study, the distribution of chymaseand tryptase-containing mast cells was morphometrically analysed at different dermal levels of lesional and non-lesional psoriatic skin (12 patients) as well as normal human skin. Mast cell tryptase was identified enzyme-histochemically, using Z-Gly-Pro-Arg-MNA as the substrate. For demonstrating mast cell chymase, a simple and specific enzyme-histochemical staining method was developed, using Suc-Val-Pro-Phe-MNA as the substrate. All mast cells positive for chymase were also positive for tryptase and Giemsa stain. Although the number of tryptase-positive mast cells was slightly increased throughout the dermis of lesional psoriatic skin, this increase was most pronounced in the upper dermis immediately beneath, and in close contact with, the epidermis. In contrast, the number of chymase-positive mast cells was clearly decreased in the upper dermis of psoriatic lesions, but not in the deeper dermis, as compared with non-lesional psoriatic skin. In addition, all chymase-positive mast cells observed in the upper dermis were very weakly stained when compared with those in the deeper dermis. No differences were found between non-lesional psoriatic skin and normal skin in which the number of mast cells containing chymase was 72–73% of the number containing tryptase. The present results suggest that T mast cells particularly, containing tryptase but no chymase, proliferate in psoriatic lesions, and that the increase in tryptase activity and the decrease in chymase activitiy in the upper dermis may lead to an imbalance in the biochemical regulatory systems.     

Immunohistochemical evaluation of psoriatic plaques following selective photothermolysis of the superficial capillaries

BACKGROUND: Elongated and tortuous capillary loops are distinctive features of psoriasis. The significance of these microvascular changes in the pathogenesis of plaques, however, remains unclear. OBJECTIVES: To determine what part the expanded superficial capillary bed plays in the pathogenesis of clinical lesions by selectively thermolysing psoriatic capillaries with a pulsed dye laser (PDL). METHODS: Cutaneous lesions were biopsied before and after treatment and sections assessed by standard immunohistochemical techniques for changes in known indicators of angiogenesis, including endothelial surface area, endothelial cell proliferation and endothelial cell expression of adhesion molecules. We also measured lymphocytic infiltration and epidermal thickness, and quantified the presence of a marker of keratinocyte proliferation before and after treatment. RESULTS: The effect of the PDL was limited to the superficial capillary bed, with no changes in the microvessels (including venules and arterioles) of the upper reticular dermis. Although there was significant clinical improvement in plaques after treatment (P = 0.02), complete clearance of lesions was not achieved. Thermolysis of psoriatic capillaries caused a reduction in both endothelial surface area (P < 0.01) and endothelial cell proliferation in the superficial dermis (P = 0.04). Endothelial expression of surface adhesion molecules (integrins and E-selectin) important in angiogenesis was not, however, altered by treatment. The CD4+ and CD8+ T-cell infiltrate was significantly reduced in the superficial papillary dermis (P = 0.02 and P = 0.04, respectively), but not in the epidermis or upper reticular dermis. Laser treatment significantly reduced epidermal thickness (P = 0.001), but did not alter epidermal keratinocyte proliferation (P = 0.2). CONCLUSIONS: The results demonstrate that dermal capillary changes alone are unlikely to be causal in psoriasis. They indicate that the expanded psoriatic capillaries may be important in facilitating the access of activated T cells to the skin and in maintaining the psoriatic plaque. These results do not refute the consensus view that plaque formation may be mediated by the release of growth factors/cytokines from activated epidermal T cells/keratinocytes.     

Systemic amyloidosis manifestation in a patient with psoriatic arthritis

Systemic amyloidosis secondary to psoriatic arthritis is rare, and published data are based mainly on case reports and are associated with increased mortality. This is the report of a patient with long-term psoriatic arthritis and chronic sialadenitis, who showed an inadequate response to therapy. The diagnosis of secondary amyloidosis was attained through biopsies of genital skin lesions. Although very rare, it is important that dermatologists and general practitioners consider the possibility of amyloidosis in patients with chronic inflammatory diseases, since an early intervention can be implemented, and thus, the prognosis of this condition can be improved.     

Clearing of psoriatic erythroderma following heliotherapy in the Dead Sea area

We report herein a patient suffering from psoriatic erythroderma and psoriatic arthritis treated successfully in the Dead Sea area. Sun exposure (heliotherapy) and emollients, without any additional topical or systemic treatments, resulted in clearing of the erythroderma within 4 weeks of treatment. Additional regimens of climatotherapy and balneotherapy, given for another 2 weeks, led to marked alleviation of his arthritic complaints. The remission of skin disease persisted for 5 months without further therapy.     

In situ localization of CD83-positive dendritic cells in psoriatic lesions

BACKGROUND: Dendritic cells (DC) are considered to be the most potent antigen-presenting cells, and CD83 is expressed at a high level on immune-competent, activated and mature DC. Although changes in the number or localization of mature and activated CD83+ DC could be expected in psoriasis, there is little information on such changes. AIM: Morphological identification of CD83+ DC in psoriatic skin lesions. MATERIALS AND METHODS: Immunohistochemical staining was performed in 5 specimens of psoriasis vulgaris and 6 specimens of pustular psoriasis. Formalin-fixed, paraffin-embedded sections were used for examination in this study. The skin sections were pretreated with 0.1% trypsin for 60 min at 37 degrees C prior to immunostaining for CD83. RESULTS: A small but significant subpopulation of CD83+ DC was found in the upper dermis. In addition, CD83+ DC were occasionally scattered in the epidermis. The most common distribution pattern of CD83+ DC was as clusters with mononuclear lymphoid cells in the upper dermis. CD83+ DC were in close contact with lymphocytes. High-intensity staining of CD83 antigens was detected not only on the surface, but also in the cytoplasm of DC. CONCLUSION: These results indicate that activated and mature CD83+ DC may play a role in the immune response in psoriasis and provide in vivo support for the concept that CD83+ DC provide signals for direct intralesional T cell activation.     

Immunohistochemical demonstration of myoepithelial cells in sweat gland carcinomas

Although myoepithelial cells are detectable in many benign sweat gland tumours, little is known about their role in sweat gland carcinomas. To specifically demonstrate myoepithelial cells, paraffin sections from 46 sweat gland carcinomas were stained, using a standard avidin-biotin-peroxidase complex method, with the monoclonal α-smooth muscle actin antibody 1A4. Myoepithelial cells were not found in adenoid cystic eccrine carcinoma (n=2), malignant nodular hidradenoma (n=2), porocarcinoma (n=4), extramammary Paget's disease (n= 12), sclerosing sweat duct carcinoma (n=4) or in adenosquamous mucoepidermoid carcinoma (n=l). In contrast, myoepithelial cells were demonstrated in two of eight apocrine adenocarcinomas, one of six mucinous eccrine carcinomas and two of seven eccrine adenocarcinomas. In all these tumours myoepithelial differentiation was found in peripheral cells of solid tumour islands, or in basal cells of tubular structures. However, in most areas of the tumours, myoepithelial layers were discontinuous. Cells in the centre of solid tumour nodules, and luminal cells of tubular structures, were negative for α-smooth muscle actin. In analogy to breast tumours, in which malignancy and invasiveness correlate with scattered or absent myoepithelial cells, we suggest that disrupted myoepithelial layers in sweat gland carcinomas may be interpreted as a loss of the invasion barrier.     

Immunohistochemical analysis of S100-positive epidermal Langerhans cells in dermatofibroma

Dermatofibroma is a dermal fibrohistiocytic neoplasm. The Langerhans cells are the immunocompetent cells of the epidermis, and they represent the first defense barrier of the immune system towards the environment. The objective was to immunohistologically compare the densities of S100-positive Langerhans cells in the healthy peritumoral epidermis against those in the epidermis overlying dermatofibroma (20 cases), using antibodies against the S100 molecule (the immunophenotypic hallmark of Langerhans cells). The control group (normal, healthy skin) included ten healthy age and sex-matched individuals who underwent skin biopsies for benign skin lesions. A significantly high density of Langerhans cells was observed both in the epidermis of the healthy skin (6.00 ± 0.29) and the peritumoral epidermis (6.44 ± 0.41) vs. those in the epidermis overlying the tumor (1.44 ± 0.33, p < 0.05). The quantitative deficit of Langerhans cells in the epidermis overlying dermatofibroma may be a possible factor in its development.     

Immunohistochemical demonstration of D2-40 in basal cell carcinomas of the skin

Background: Recently, immunoreactivity to D2‐40, a monoclonal antibody to lymphatic endothelium, was shown in a subgroup of epidermal basal cells and the majority of squamous cell carcinomas, but the immunoreactivity to this antibody has not been examined in basal cell carcinomas (BCCs) of the skin. Methods: Expression of D2‐40 was analyzed together with that of cytokeratin (CK) 17, CK 19, CD34 and Ber‐EP4 by immunohistochemical methods in 10 non‐neoplastic skin tissue samples and 20 BCCs. Results: Immunoreactivity to D2‐40 was shown in the basal cells at the outer root sheath (ORS) of hair follicles, similar to the CK 19 expression pattern. CK 17 was strongly expressed in the suprabasal cells at the ORS. D2‐40 and CK 19 were focally expressed in 13/20 (65%) and 14/20 (70%) cases of BCCs, respectively, although the distributions of D2‐40 and CK 19 immunoreactivity were not always identical. However, BCC cells were constantly positive for CK 17 even tumor cells that were positive for D2‐40 and/or CK 19. Ber‐EP4 was diffusely expressed in all BCCs, and CD34 was focally expressed in 2/20 cases. Conclusion: Our results suggested that D2‐40 immunoreactivity in BCCs showed differentiation toward the ORS of hair follicles.     

Immunolabeling pattern of cytokeratin 19 expression may distinguish sebaceous tumors from basal cell carcinomas

Background:  Distinction between sebaceous tumors and basal cell carcinomas can often pose diagnostic problems. Recent work with the antibody to cytokeratin 19 (CK 19) has shown that this marker has high specificity for undifferentiated basaloid cells. Our aim was to evaluate the use of CK 19 staining patterns in differentiating between sebaceous tumors and basal cell carcinomas. The sebaceous tumors that were examined in this study included sebaceous adenomas, sebaceous epitheliomas (sebaceomas) and sebaceous carcinomas.
Methods:  Thirty-seven cases including 5 sebaceous adenomas, 16 sebaceous epitheliomas, 6 sebaceous carcinomas and 14 basal cell carcinomas (7 being of the morpheaform type and 7 nodular basal cell carcinomas) were tested with a monoclonal mouse antibody to human CK 19.
Results:  CK 19 was focally positive in 1/5 (20%) sebaceous adenomas, 8/16 (50%) of sebaceous epitheliomas and 1/6 (17%) of sebaceous carcinomas. Strongly positive expression of CK 19 was not seen in any of the sebaceous adenoma, sebaceous epithelioma or sebaceous carcinoma specimens. CK 19 was found to be strongly positive in 9/14 (64%) and focally positive in 2/14 (14%) of basal cell carcinomas.
Conclusion:  CK 19 expression can be helpful in differentiating sebaceous tumors (including sebaceous adenomas, sebaceous epitheliomas and sebaceous carcinomas) from basal cell carcinomas and may be a useful adjunct when these entities are included in the differential diagnosis.     

Increased elongated and stabilized microtubules in psoriatic keratinocytes

Summary Microtubules (MT) occur in the keratinocytes as 20 nm broad tubular structures with an electron-lucent core surrounded by an electron-dense wall. The number and the length of the MT increased to the upper epidermal layers.In the normal keratinocytes the MT were relatively short (maximal length 2.2 m) and slightly tortuous. Their outline was tenuous and irregular. Sometimes the MT were interrupted indicating a high fragility. In the upper layers of the psoriatic epidermis the MT reached a maximal length of 3.1 m, showing a greater elongation than in the normal epidermis. The MT were straight and distinctly limited, most likely resulting from a higher grade of stabilization or polymerisation.By their interaction with the tonofilaments the MT may contribute to the stability of the cell shape, delaying the flattening of the psoriatic keratinocytes in the upper epidermal layers. Nowhere did the MT make direct contact with the cell membrane. At some places they did gain access to the cell membrane by short microfilaments.Presented at the 5th European Meeting on Electron Microscopy Applied to Cutaneous Pathology, Copenhagen, May 12–13, 1978     

Immunohistochemical characterization of pleomorphic giant cells in basal cell carcinoma

Over 20 cases of basal cell carcinomas with pleomorphic giant cells of the mononuclear or multinucleate type have been described. The nature of these cellular and nuclear changes has not been elucidated. Some authors found that these cells have phagocytic properties and others reported an aneuploid DNA content. We have seen mitotic figures in some of these giant cells, and postulate that these cells are capable of proliferation. Twelve cases of basal cell carcinoma with pleomorphic giant cells were examined using monoclonal antibodies recognizing the proliferating cell nuclear antigen (PCNA), Ki-67, and bcl-2 antigens. Expression of proliferation associated antigens in the giant cell population was higher than in the small cell population. Over expression of bcl-2 was detected in both the small and giant cells in all cases. The results demonstrate that the giant tumor cells are cycling and express bcl-2 protein in a manner consistent with basal cell carcinoma. The changes are unlikely to represent a senescent change as seen occasionally in mesenchymal neoplasms.     

Increased production of transforming growth factor-alpha in psoriatic epidermis

To elucidate the involvement of transforming growth factor-alpha (TGF-alpha) in the pathogenesis of psoriasis, we measured TGF-alpha levels in the extracts from six normal epidermis and four psoriatic involved epidermis samples by enzyme-linked sorbent assay using monoclonal antibody specific for TGF-alpha. The amount of TGF-alpha in the extracts of normal epidermis was 1.45 +/- 1.06 ng/g of wet tissue, while the amount in psoriatic involved epidermis was 6.71 +/- 0.75 ng/g of wet tissue. The TGF-alpha level in psoriatic involved epidermis was thus 4.62 fold higher than that of normal epidermis (P less than 0.001). TGF-alpha binds to epidermal growth factor receptors and functions as an autocrine growth factor for epidermal keratinocytes. Therefore, the increased levels of TGF-alpha may be involved in the induction or the maintenance of hyperproliferation of psoriatic epidermal keratinocytes.     

新型冠状病毒肺炎疫情期间银屑病患者使用生物制剂的指导意见

【摘要】 新型冠状病毒肺炎疫情对银屑病患者使用生物制剂可能产生一定的影响,生物制剂的免疫抑制作用可能改变患者对病毒的易感性或造成感染者病情加重,甚至影响预后。参考国际银屑病学术组织和专家的建议,结合我国实际情况,分别针对正在进行生物制剂治疗和拟进行生物制剂治疗的银屑病患者、高风险和低风险患者以及合并或不合并新型冠状病毒感染的患者提出了使用生物制剂的指导性建议,供临床实践中参考。     

Immunohistochemical study of cytokeratin expression in nevus sebaceous

Background The histogenesis of nevus sebaceous (NS) is unclear. Methods To elucidate the histogenesis of NS, cytokeratin (CK) profiles were examined immunohistochemically using 10 anti‐keratin antibodies in the three stages of NS. Results In the first stage, stratified differentiated keratins (CK1 and 10) were reduced, and basal keratin (CK14) was increased in the epidermis and primitive follicular structure (PFS). In the second stage, in addition to reduced CK1 and CK10 expressions and increased CK14 expression, CK17 expression was strongly expressed in the sebaceous ducts in proportion to the development of sebaceous gland. In the third stage, CK14, CK17 and CK19 were expressed in secondary tumors. CK16 was not detected throughout all stages of NS. Conclusion These results suggest that NS is not hyperproliferative but involves hamartomatous differentiation with undifferentiated keratins.