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.     

Quantitative analysis of tryptase- and chymase-containing mast cells in atopic dermatitis and nummular eczema

The distribution of mast cells (MCs) containing tryptase (T) and chymase (C) was studied in the non-lesional and lesional skin of 26 patients with atopic dertnatitis (AD) and 23 patients with non-atopic nummular eczema (NE). and in the skin of eight healthy controls. T and C activities were demonstrated enzymehistochemically using 2-Gly-Pro-Arg-MNA and Suc-Val-Pro-Phe-MNA as substrates, respectively. The T- and C-containing MCs were counted separately in the epidermis, in contact with the basement membrane. In the papillary dermis and in different dermal levels (0·2 mm each). Also, the C protein was determined immunohistochemically. T-positive MCs were similarly distributed in non-lesional and lesional skin of both AD and NE. The MC number was relatively high in the upper dermis (papillary dermis and levels I and I!) of non-lesional and lesional skin of AD. In the upper dermis of non-lesional AD and NE skin and in normal skin, about 50% of T-positive MCs displayed C activity, whereas the percentage in lesional AD and NE skin was only about 30%. hi this respect, the non-lesional and lesional samples differed significantly froLu each other in both dennatoses (in AD p = 0%005, in NEP = 0·002. Students' t-test). In all samples the MC number decreased in the deeper dermal levels, although numerous T-containing MCs were still counted in the deeper dermis (dermal levels IV-VII) of lesional AD and NE skiti. differing significantly from the MC number in normal skin (In ADp = 0·005. in NE p=0·041). In the deeper dermis. the percentage of MCs containing active C was about 70% in non-lesional and lesional AD and NE. and about 90% in normal healthy skin. However, in the upper dermis of non-lesional and lesional skin of both AD and NE. about H()% of all MCs contained the C protein, which differed significantly from the value of 100% in normal skin (p<0·5). In conclusion, the increased number of T-positive MCs in the upper dermis of non-lesional and lesional AD contributes to promoting inflammation. C apparently loses its activity in the upper dermis of lesional AD and especially in NE. Thus. Ihe enzyme partially lacks its capability to suppress inflammation, such as degradation of neuropeptides and proteins. The dysregulation of these proteinases exists already in non-lesional skin of AD and NE.     

Functional studies of skin mast cells in lichen planus

In order to identify possible functional differences between mast cells obtained from the skin of lichen planus (LP) patients and healthy donors, biopsies from lesional skin of 11 lichen planus patients and from normal skin of 7 healthy donors were sampled. Mast cells were obtained from the skin using an enzymatic dispersion technique. The cells were challenged in vitro with substance P (SP), tumor necrosis factor α (TNF-α) and anti-IgE. Their reactivity was estimated on the basis of histamine release. LP skin mast cells and healthy skin mast cells showed similar sensitivity to stimulation with TNF-α at a concentration of 10 ^–7 M (15.2% histamine release, as a proportion of total cellular content vs 15.9%) and to stimulation with anti-IgE at a dilution of 1:100) (38.8% vs 37.0%). Spontaneous histamine release was also very similar in both the populations of mast cells (10.2% vs 12.7%, respectively). However, LP skin mast cells showed significantly higher ( P < 0.01) sensitivity towards stimulation with SP at a concentration of 10 ^–4 M than healthy skin mast cells (15.9% histamine release vs 7.0%). This finding could suggest that neurogenic inflammatory mechanisms contribute to the pathogenesis of LP. Received: 3 July 1996     

Intraepithelial mast cells in gingival lichen planus: an ultrastructural study.

Intraepithelial mast cells, identified by ultrastructural criteria, were seen in lesions of gingival lichen planus. The mast cells were found either singly, interspersed among keratinocytes, or in combination with other mononuclear cell types, especially lymphocytes. The mast cells were seen in regions with relatively normal intercellular spaces, as well as in regions of more severely disrupted keratinocytes. They had cytologic features indicative of active synthesis and release of granules. Moreover, the finding of centrioles in several intraepithelial mast cells, in combination with certain other cytologic features, suggested that these cells might be in an early stage of differentiation. It is speculated that intraepithelial mast cells have a role in the pathogenesis of gingival lichen planus.     

Coexisting lichen planus and subacute cutaneous lupus erythematosus

We report a patient who presented with annular erythematous skin lesions and generalized lichenoid papules. The clinical picture as well as histopathology, immunofluorescence and laboratory findings indicated coexistence of subacute cutaneous lupus erythematosus (SCLE) and extensive generalized lichen planus (LP). Clinically and historically, SCLE-like lesions appeared to progress into LP-like lesions, supporting the concept of a common autoimmune pathophysiology in these disorders. Treatment with cyclosporin A (2.5 mg/kg body weight) resulted in a significant remission of the inflammatory skin lesions.     

Half-and-half cells in lichen planus

In the course of a study of wound healing in four patients with lichen planus, we found transformed keratinocytes with a hitherto undescribed ultrastructure in both wounded and undisturbed papules. We have called these epidermal cells half-and-half cells because they showed changes on the one hand of increased synthetic activity and, on the other hand, of fibrillar transformation closely resembling that seen in fully developed colloid bodies. We suggest that these half-and-half cells may provide a useful clue to the early changes occurring in colloid body formation.     

Systemic isotretinoin treatment of oral and cutaneous lichen planus

Lichen planus of the skin and mucous membranes may be disabling. Severe pruritus or bullous lesions may be incapacitating when they occur while erosive oral lesions may be extremely painful. Various treatment modalities have been attempted including corticosteroids (parenteral, intralesional, and topical) and photochemotherapy. Recent successful therapeutic trials of topical retinoic acid and oral etretinate have been completed. Two patients with cutaneous and severe erosive oral lichen planus unresponsive to conventional therapies responded to a trial of oral isotretinoin with prompt and successful remission of cutaneous and oral lesions. This suggests that systemic isotretinoin may have a unique position in the treatment of mucous membrane lichen planus that is refractory to conventional therapies.     

扁平苔藓皮损中肥大细胞数和P物质的表达及其意义

目的:探讨肥大细胞和P物质在扁平苔藓发病中的作用。方法:采用组织化学和免疫组化的染色方法,检测扁平苔藓皮损中未脱颗粒的肥大细胞数和P物质的表达情况。结果:甲苯胺蓝特殊染色发现,扁平苔藓皮损中未脱颗粒的肥大细胞数(3.56±1.52)明显低于正常对照组(5.22±1.28),其差异具有统计学意义(P<0.01);免疫组化染色发现,扁平苔藓皮损中P物质的表达强度明显高于正常对照组,其差异具有统计学意义(P<0.01);采用Spearman等级相关分析,二者呈一定的负相关(rs=-0.397,P<0.05)。结论:肥大细胞和P物质在扁平苔藓的发病中可能起一定的作用。     

Quantitative analysis of contact sites between mast cells and sensory nerves in cutaneous psoriasis and lichen planus based on a histochemical double staining technique

Summary The aim of the present study was to test further our previous hypothesis that the inflammatory reaction in psoriasis is neurogenic. For this purpose, contact sites between mast cells and sensory nerves were morphometrically analysed in the basement membrane zone, papillary dermis and three dermal zones of lesional/non-lesional psoriatic and lichen planus skin as well as in healthy control skin. The analyses were made on sections stained with a histochemical double stain developed for this study. With the double stain, active mast cell tryptase was stained blue enzyme histochemically, and the sensory nerves black using specific monoclonal anti-neurofilament antibodies with immunogold. In psoriatic lesions, both mast cells and mast cell — nerve contacts were markedly more frequent in the basement membrane zone and in the papillary dermis when compared with the corresponding areas in the other groups. Mast cell numbers were increased in both lesional and symptom-free skin in lichen planus, but no increase was found in the mast cell — nerve contacts. Increased contacts between mast cells and sensory nerves indicate that the elements exist for neurogenic inflammation in psoriatic lesions. These increased contacts are not due to the extensive inflammatory reaction only, because they were not observed in lichen planus lesions.     

Systemic treatment of cutaneous lichen planus: an update

Lichen planus (LP) is a chronic and remitting dermatosis that may be idiopathic or associated with underlying systemic diseases, such as hepatitis C virus. Although numerous cases of LP resolve spontaneously, many cases require systemic treatment. Several therapeutic advances have occurred in the last 10 years: acitretin (30 mg daily for 8 weeks) remains a first-line therapy (level B, controlled clinical trial >20 participants); systemic corticosteroids are second-line therapies (level C, clinical trial <20 participants, or larger trial without appropriate controls); and new data recommend against the use of tetracycline (level C). This article reviews the current status of systemic therapies for cutaneous LP.     

Bullous lichen planus and lichen planus pemphigoides-clinico-pathological comparisons

Two patients with lichen planus pemphigoides and two with bullous lichen planus were compared. Lichen planus pemphigoides was clinically distinguished by a more generalized lichen planus, more extensive blistering, the need for systemic corticosteroids and by a longer course. The blister of bullous lichen planus was a subepidermal bulla showing degeneration of the epidermal basal layer and other features of lichen planus, whereas in lichen planus pemphigoides the bulla was similar to that of bullous pemphigoid albeit with rather more neutrophils than are usually seen. Direct immunofluorescence was positive in lichen planus pemphigoides and negative in bullous lichen planus. Lichen planus pemphigoides and bullous lichen planus are separate entities: the former is an auto-immune disease precipitated by lichen planus and not related to bullous pemphigoid, the latter is probably not auto-immune but represents the extreme consequence of the lymphoid infiltrate at the dermo-epidermal junction.     

Immunohistochemistry in lichen planus.

An immunohistochemical study has been undertaken on 25 biopsy specmens taken from lichen planus lesions, using antisera against human fibrin, immunoglobulins IgG, IgA, IgM and C3 (B1C/B1A) complement component. The findings of the present research are discussed and evaluated in relation to the problem of the etiopathogenesis of the disease.