A comparison of expression of surface-bound immunoglobulin E on antigen-presenting cells in cutaneous tissue between patients with allergic, irritant and atopic dermatitis

The expression of surface-bound immunoglobulin E by dendritic cells within cutaneous tissue has been compared in atopic and contact dermatitis. 45 patients were recruited into 4 groups using clinical criteria and patch testing to a standard series of allergens: atopic (12 cases), allergic contact dermatitis (14 cases), irritant contact dermatitis (10 cases) and the control group (9 cases); using clinical criteria and patch testing to a standard series of allergens. Skin biopsies from each patient were analysed by the indirect immunofluorescence technique. This differentiated 3 patterns of cutaneous IgE distribution: (i) no detectable cutaneous IgE; (ii) detection of IgE solely within the dermis; (iii) detection of IgE within both epidermis and dermis. Detection of IgE within the epidermis was always associated with the presence of IgE within the dermis. In each case, IgE was surface-bound by dendritic cells. Immunoglobulin E was detected within both epidermis and dermis in skin biopsies from 8 (66.7%) atopic patients and 2 (20%) patients with irritant contact dermatitis. No other cases demonstrated IgE deposition within both the epidermis and dermis. Atopic patients were significantly more likely to have detectable IgE deposition, within both epidermis and dermis, than patients with contact dermatitis (allergic and irritant groups combined, p = 0.0011) or controls (p = 0.0049). This finding suggests that the demonstration of IgE within both epidermis and dermis supports a diagnosis of atopic dermatitis. It would therefore be of value in differentiating between atopic and contact dermatitis, where clinical diagnosis is in doubt.     

钙通道阻滞剂对小鼠接触性皮炎的影响

为了探讨钙通道阻滞剂对小鼠接触性皮炎的作用及其作用机理,我们首先用钙通道阻滞剂(硝苯地平、地尔硫、维拉帕米和盐酸氟桂利嗪)对二硝基氯苯和巴豆油引起的小鼠变应性和刺激性接触性皮炎进行了研究,发现它们可显著减少二硝基氯苯引起的小鼠耳肿胀(P<0.01和P<0.05)及真皮单一核细胞浸润(P<0.01);而对巴豆油引起的小鼠耳肿胀及真皮单一核细胞浸润无明显减少或增加(P均>0.05)。其次,采用MTT比色分析法,用硝苯地平、地尔硫、维拉帕米对小鼠体外和盐酸氟桂利嗪对小鼠体内淋巴细胞转化及白介素2产生进行研究,发现无论在体外还是在体内,它们皆可抑制小鼠淋巴细胞转化及白介素2产生。提示钙通道阻滞剂可抑制小鼠变应性接触性皮炎,而对小鼠刺激性接触性皮炎无明显作用。钙通道阻滞剂直接抑制淋巴细胞转化及白介素2产生,并通过抑制白介素2而间接地进一步影响淋巴细胞增殖,可能是其免疫抑制的重要机制。     

Changes in Lymphocyte and Langerhans Cell Populations in Allergic and Irritant Contact Dermatitis

We observed in situ changes in lymphocyte subpopulations and Langerhans cells during allergic and irritant contact dermatitis using immunohistochemical staining methods with monoclonal antibodies to cell surface antigens. In both types of contact dermatitis, there was a perivascular infiltrate of T lymphocytes, with helper/inducer T cells predominating. B cells were absent, and natural killer cells were absent or sparse. During the course of allergic contact dermatitis, Langerhans cells showed a striking sequential change in location, with the cells first in the epidermis, then perivascularly in the dermis (days 1-14), and returning to the epidermis (days 14-21). In irritant contact dermatitis, the Langerhans cells were initially identified in the epidermis and then appeared diffusely in the dermis (days 1-2). The numbers in the dermis then decreased abruptly (day 4). They were again identified in normal numbers in the epidermis (day 21). The response of Langerhans cells appears to be different between allergic and irritant contact dermatitis.     

Keratinocyte expression of MHC class II antigens in allergic sensitization and challenge reactions and in irritant contact dermatitis

Keratinocytes expressed major histocompatibility complex class II antigens during the development of irritant contact dermatitis, and during the induction of contact hypersensitivity, as well as in established allergic contact dermatitis. A battery of anti-class II monoclonal antibodies, some of which are specific for class II subregion products (DP, DQ, DR), was used in an immunohistochemical study of the sequential changes in the allergic challenge reactions to dinitrochlorobenzene (DNCB) and nickel, the irritant response to anthralin, and the induction of sensitization to DNCB. The induction of keratinocyte class II expression paralleled the influx of Leu-3a+ T cells into the skin and had occurred by 24 or 48 h in each type of reaction. Differential expression of class II subregion products on keratinocytes was noted: DR was the most frequently expressed molecule, followed by DP and DQ, although in the irritant response, DP expression was not observed. The importance of these observations can be decided only by functional studies.     

Differential hypermelanosis induced by allergic contact dermatitis

In moderately colored guinea-pig skin, UVB, PUVA (psoralen plus UVA), and allergic contact dermatitis were shown to induce visibly well-defined hyperpigmentation that resembled the pigmentary changes observed in Mongoloid human skin. To clarify mechanisms of allergen-induced hyperpigmentation, we compared the effects of allergic contact dermatitis on pigmentation by using 6 different allergens: dinitrochlorobenzene (DNCB), 1-phenylazo-2-naphthol (PAN), benzyl salicylate (BS), jasmine oil (JO), hydroxycitronella (HC), and ylang ylang oil (YYO). The PAN-, JO-, HC-, and YYO-induced allergic reactions caused a definite visible hyperpigmentation that began to appear within 14 days, reaching maximum intensity about 40 days after the induction of the allergic reaction. These hyperpigmentations were accompanied by a significant increase in the population of dopa-positive melanocytes on day 24 following allergic reactions. In contrast, BS- and DNCB-induced allergic reactions did not give rise to visibly distinct hyperpigmentation in spite of the intensive allergic reactions following their challenge application. In a nonsensitized group, primary irritant reactions were induced by the application of 100% JO, but no distinctive hyperpigmentation was found 40 days after the last application. Quantitative analysis of the number of melanophages in the dermis showed that there was a marked increase in the number of melanophages in PAN, YYO, and HC allergy-induced hyperpigmented areas, with PAN showing a significant increase compared with those in non-treated areas of the same animals, whereas JO was associated with no such increase in hyperpigmented area, despite the stimulated pigmentation. In the case of the lack of induced hyperpigmentation, as seen in BS and DNCB allergy and JO irritation, there was also no substantial increase in the number of melanophages. Our findings indicate that allergic contact dermatitis is a unique melanogenic stimulant different from UV irradiation.     

Cytochemical and Ultrastructural Studies of the Langerhans'' cells

In the guinea pig, experimental allergic contact dermatitis (ACD) and primary irritant contact dermatitis (PICD) were induced with different concentrations of dinitrochlorobenzene (DNCB). The epidermal Langerhans' cells (LCs) were observed sequentially by both adenosine triphosphatase (ATPase) and electron microscopy. Light microscopically, in ACD, the density and dendritic processes of LC decreased markedly within 12 h after antigen challenge. Almost no recognization LCs could be seen within 2 to 5 days. Later, LCs began to repopulate in the epidermis. Within 14 days, the density and shape of the LCs returned to normal. On the contrary, LCs changed more rapidly in PICD. The dendritic processes of LC decreased within 2 h and cell density decreased dramatically within 6 h after DNCB application. LCs also repopulated more rapidly in the epidermis. Electron microscopically, in ACD, we observed that lymphocyte-like cells apposed to LCs; LCs were activated and damaged; however, in PICD, we found neither the apposition of lymphocyte-like cells to LCs, nor the activation of LCs. LCs play an important role in the convalescence phase as well as in the early and later phases of contact allergic reaction.     

Cytochemical and Ultrastructural Studies of the Langerhans' Cells

Abstract: In the guinea pig, experimental allergic contact dermatitis (ACD) And primary irritant contact dermatitis (PICD) were induced with different concentrations of dinitrochlorobenzene (DNCB). The epidermal Langerhans' cells (LCs) were observed sequentially by both adenosine triphosphatase (ATPase) and electron microscopy. Light microscopically, in ACD, the density and dendritic processes of LC decreased markedly within 12 h after antigen challenge. Almost no recognization LCs could be seen within 2 to 5 days. Later, LCs began to repopulale in the epidermis. Within 14 days, the density and shape of the LCs returned to normal. On the contrary, LCs changed more rapidly in PICD. The dendritic processes of LC decreased within 2 h and cell density decreased dramatically within 6 h after DNCB application. LCs also repopulated more rapidly in the epidermis. Electron microscopically, in ACD, we observed that lymphocyte-like cells apposed to LCs; LCs were activated and damaged; however, in PICD, we found neither the apposition of lymphocyte-like cells to LCs, nor the activation of LCs. LCs play an important role in the convalescence phase as well as in the early and later phases of contact allergic reaction.     

IgE-positive epidermal Langerhans cells in allergic contact dermatitis lesions provoked in patients with atopic dermatitis

Summary To see whether or not IgE-bearing epidermal Langerhans cells are specific to skin lesions of atopic dermatitis (AD), we performed immunohistochemical and immunoelectron microscopic examinations of dinitrochlorobenzene (DNCB) contact dermatitis lesions provoked in uninvolved skin of eight patients with AD. In all of the eight examined, IgE-positive epidermal Langerhans cells were observed in the DNCB dermatitis lesions. Typical staining of anti-IgE was absent in the epidermis of normal-appearing skin of five patients with AD. Thus, it is likely that IgE positive epidermal Langerhans cells non-specifically occur in different eczematous diseases provoked in patients with AD.     

Tissue fibrinolytic activity of allergic contact dermatitis

One of our co-workers was sensitized with a 1% DNCB solution in acetone. Biopsies were obtained from skin lesions 1, 2, 4, 8, 12, 24, 30, 36 and 48 hours after a challenge with 0.1% DNCB solution. In the upper dermis, a rapid decrease of tissue fibrinolytic activity was found which disappeared after 30 hours. In the lower dermis, biphasic changes were observed. Tissue fibrinolytic activity increased one hour and 12-36 hours after challenge, whereas at 48 hours, when erythema was most intensive, it decreased in comparison to the normal activity. Erythema and histological changes of the epidermis and the dermis appeared after approximately 12 hours. As for lymphocytes, T-cells were seen at first. Furthermore, B-cells were noted after approximately 30 hours when marked infiltration began to appear.     

Inhibition of irritation and contact hypersensitivity by phenoxyacetic acid methyl ester in mice

New anti-irritant treatments are required to prevent irritation and sensitization reactions to consumer medicines and dermatological drugs. We report here that phenoxyacetic acid methyl ester (PAME) is an effective agent to prevent and treat irritant and allergic contact dermatitis. Balb/c mice skin-treated with 1% PAME do not lose weight relative to vehicle-treated mice, nor is it irritating to mouse skin. Topical PAME prevents skin irritation to a wide variety of irritants including: arachidonic acid, capsaicin, sodium lauryl sulfate (SLS), disodium laureth sulfosuccinate and tetradecanoylphorbol-13-acetate. Histological studies showed that 1% PAME greatly diminished dermal neutrophilic infiltration and dermal capillary vessel dilation, and prevented epidermal hyperproliferation and hyperkeratosis that accompanies detergent (SLS)-induced skin irritation. Topical PAME inhibited ear swelling following ear challenge during the elicitation phase of contact hypersensitivity in mice sensitized with 1-chloro-2, 4-dinitrochlorobenzene (DNCB), oxazolone and the hair coloring dye rho-phenylenediamine (PPD). Finally, topical administration of 1% PAME prior to PPD or DNCB sensitization prevented the induction phase of contact hypersensitivity. These results indicate that PAME represents a potential new category of potent topical anti-inflammatory agents.     

Iatrogenic benign lymphoplasia induced by allergic contact dermatitis from squaric acid dibutylester: immunohistologic study of cellular infiltrates

We report of a 62-year-old male patient with a dull red itchy nodule on the induction area of allergic contact dermatitis to squaric acid dibutylester. Which had been used for the therapy of alopecia universalis. The excised biopsy specimen showed dense infiltration of lymphoid cells in the dermis and subcutaneous tissue, associated with the formation of lymphoid follicles, Immunohistologic analysis of the infiltrates indicated mixed proliferation of T- and B-cells. A biopsy specimen from the challenge area showed spongiosis in the epidermis and lymphoid cell infiltration in the upper dermis, while the infiltrates consisted mainly of T-cells. The following points are discussed: (i) the lesion had an iatrogenic origin and the causative agent was quite evident: (ii) the route of allergen application was only through the epidermis and not directly in the dermis; (iii) lymphoid cell infiltrates of the induction and challenge areas were different.     

TARC and RANTES, but not CTACK, are induced in two models of allergic contact dermatitis. Effects of cilomilast and diflorasone diacetate on T-cell-attracting chemokines

BACKGROUND: Skin-infiltrating T cells play a predominant role in allergic and inflammatory skin diseases such as atopic dermatitis and allergic contact dermatitis. These T cells are attracted by chemotactic factors, e.g. RANTES (regulation on activation, normal T cell expressed and secreted; CCL5), TARC (thymus and activation regulated chemokine; CCL17) and CTACK (cutaneous T-cell attracting chemokine; CCL27). OBJECTIVES: To investigate which T-cell-attracting chemokines are involved in allergic contact dermatitis in mice. METHODS: Allergic contact dermatitis was induced by application of dinitrochlorobenzene (DNCB) or toluene-2,4-diisocyanate (TDI), and chemokine concentrations were determined by enzyme-linked immunosorbent assay. The effects on chemokine concentrations of the highly selective phosphodiesterase 4 inhibitor cilomilast and the glucocorticoid diflorasone diacetate were studied in mouse ears. RESULTS: RANTES and TARC were elevated in both models of allergic contact dermatitis 24 h after challenge, whereas CTACK remained unchanged. The increase in RANTES was diminished in mouse ears pretreated with cilomilast or diflorasone diacetate. TARC was reduced by diflorasone diacetate in the DNCB model but was highly induced in the TDI model; in contrast, TARC was not influenced by cilomilast. CONCLUSIONS: TARC and RANTES, but not CTACK, are involved in these two models of allergic contact dermatitis.     

Immunohistochemical comparison of actinic reticuloid with allergic contact dermatitis.

Biopsy specimens of chronic lesions and ultraviolet-induced lesions from actinic reticuloid patients were examined by immunoperoxidase techniques and compared with those of allergic contact dermatitis skin, one of the delayed-type hypersensitivity conditions. Each lesion of actinic reticuloid showed a clear predominance of suppressor/cytotoxic T cells to helper/inducer T cells and an increase of Langerhans cells in the epidermis and the dermis. These findings are generally similar to those in the late phase (on day 7 and 11) but not in the early phase (on day 2) of allergic contact dermatitis and suggest that delayed-type hypersensitivity might be involved in some parts of the pathogenesis of actinic reticuloid. CD36+DR+ epidermal cells were also observed in ultraviolet-induced lesions from actinic reticuloid patients, suggesting a possible role in the modulation of the mechanism.     

Alterations of epidermal lectin binding sites in acute contact dermatitis

We investigated alterations of epidermal lectin binding sites, as well as of pemphigus and bullous pemphigoid antigens, in 28 human patch test reactions, both allergic (nickel, formaldehyde, N,N'-1,3-dimethylbutyl-N'-phenylenediamine) and irritant (sodium lauryl sulfate). The epidermal reactivity to a panel of lectins and human antisera to pemphigus vulgaris and bullous pemphigoid antigens was compared with samples obtained from normal skin and from skin under tape occlusion. We observed selective perturbations of lectin and antibody binding in acute contact dermatitis, whether allergic or irritant. The main findings were a loss of terminal sialic acids and longer bi- and triantennary mannosyl residues as well as a loss of pemphigus vulgaris antigen. The only difference between allergic and irritant patch test reactions was in topography of loss of WGA binding sites: in the former, it was most pronounced in the lower and middle epidermis, whereas in the latter it was seen in the uppermost subcorneal layers. Our findings support a common pathway of cell membrane alterations of keratinocytes in acute contact dermatitis.     

Electron microscopic observations of dyskeratosis, apoptosis, colloid bodies and fibrillar degeneration after skin irritation with dithranol

Dying cells undergo coagulative necrosis or apoptosis. In the skin, apoptosis is known to occur in graft-versus-host reactions, in lichen planus, during regression of plane warts and neoplasms, and after physical injury caused by ultraviolet light resulting in sunburn cells. The present study shows that primary skin irritation also causes apoptosis. Mild, or moderate-to-considerable, dithranol irritation of healthy uninvolved human skin caused focally coagulative necrosis of keratinocytes and also apoptosis of scattered keratinocytes, i.e. condensation of chromatin and cytosol, clumping of tonofilaments and budding of membrane-bound cell fragments. These apoptotic cell fragments were engulfed in the epidermis by macrophages. Colloid bodies were detected in the upper dermis and apparently represented nonphagocytosed apoptotic cell fragments that had dropped down from the epidermis. Dithranol also caused fibrillar degeneration of melanocytes and in some cases of Langerhans' cells, indicating that colloid bodies in the upper dermis could partly derive from these cell types. The significance of apoptosis in irritant contact dermatitis could be to maintain homeostasis of epidermis and counteract the hyperplastic response caused by irritant stimuli. Another possibility is that apoptosis was the response to an injury less severe than that causing necrosis.     

Effect of sodium lauryl sulfate-induced skin irritation on in vivo percutaneous penetration of four drugs.

The influence of sodium lauryl sulfate-induced irritant contact dermatitis on in vivo percutaneous penetration was investigated for four 14C-labeled compounds with diverse physicochemical properties: hydrocortisone (HC), indomethacin (IM), ibuprofen (IB), and acitretin (AC). Hairless guinea pigs were pretreated for 24 h with either 0.5% sodium lauryl sulfate (SLS) to induce irritant contact dermatitis or with water (controls). Twenty-four hours after pretreatment, 450 microliters saturated solutions of HC, IM, IB, or AC in isopropylmyristate were applied to the pretreated skin for 24 h. Systemic absorption was determined by urinary and fecal excretion of compounds. Drug concentrations in stratum corneum (obtained by tape cellophane stripping after decontamination of the application site) and in epidermis/dermis (punch biopsy) were also investigated. Systemic absorption of topically applied drugs (as evaluated by urinary and fecal excretion) in SLS-irritated skin was significantly increased for HC (factor 2.6) followed by IB (1.9 times) and IM (1.6 times) but not increased for AC. However, drug concentrations in the viable epidermis and dermis were 70% lower in SLS-irritated than normal skin for HC, but not different for IB, IM, and AC. Thus, the influence of the state of the skin (irritant dermatitis versus healthy) on percutaneous penetration was different for diverse drugs. The general assumption that percutaneous penetration and drug tissue concentrations were higher in diseased versus healthy skin was not found to be true in our irritated-skin model.     

Results of evaluating health care workers with prick and patch testing.

BACKGROUND: Health care workers are exposed to many agents that can cause irritant or allergic contact dermatitis. Recently, much attention has been focused on latex sensitivity, which commonly causes contact urticaria. Most studies have examined the conditions of irritant or allergic contact dermatitis and contact urticaria independently. Therefore, we have little information about the possible occurrence of these conditions in the context of combined assessment including both prick and patch testing. OBJECTIVE: To determine the prevalence of irritant and allergic contact dermatitis and contact urticaria in a group of health care workers presenting with skin problems. METHODS: Retrospective review of health care workers assessed by both prick and patch testing in an occupational health clinic. RESULTS: The diagnoses included 61% with irritant contact dermatitis, 31% with allergic contact dermatitis, and 27% with contact urticaria to latex. Eleven percent had both allergic contact dermatitis related to thiuram and contact urticaria to latex. Ninety five percent were deemed to be work-related. CONCLUSION: Health care workers presenting with skin complaints should be assessed with both prick and patch testing.     

Histamine metabolism in delayed type hypersensitivity — Comparative analysis with cellular infiltrates

Summary We examined the dynamic changes of histamine metabolism and infiltrating cell populations in lesional sites of representative cutaneous delayed type hypersensitivity (DTH), including dinitrochlorobenzene (DNCB) allergic dermatitis, purified protein derivative of tuberculin (PPD) reaction, and keyhole limpet homocyanin (KLH)-induced cutaneous basophil hypersensitivity. The concentration of histamine increased with time in all DTH reactions examined, though the time course varied among these reactions. In DNCB allergic dermatitis, the maximum content of the amine at 3 days after the initiation was about three times that of the control baseline. In PPD reaction, the maximum content and the time course were almost similar to that in DNCB allergic dermatitis. However, in KLH-induced cutaneous basophil hypersensitivity the maximum content was about ten times that in DNCB allergic dermatitis or PPD reaction, and was observed earlier, on the 2nd day. There was no remarkable change in the activities of histamine-degrading enzymes in these reactions. There was little infiltration of mast cells, while time-dependent changes of the basophil infiltration were almost parallel those of the histamine concentration in all these reactions. Basophils in DNCB allergic dermatitis showed a piecemeal degranulation, while those in either the PPD reaction or KLH-induced cutaneous basophil hypersensitivity remained intact. These results clearly suggest that the increase of histamine concentration in cutaneous DTH depends on the number of basophils infiltrating the lesional sites, even if the regulatory mechanisms of the activation of the cells differ among the DTH reactions.