The skin: an immunoreactive target organ during interleukin-2 administration?

Six patients with metastatic malignant melanoma were treated systemically with dacarbazine and interleukin-2 (IL-2). During IL-2 administration all patients developed a macular erythematous rash followed by scaling which began 24-48 h after IL-2 infusion. The dermatological changes were associated with elevated interferon-gamma and tumor necrosis factor alpha serum levels (immunoradiometric assay). Histology revealed nonspecific spongiotic foci in the epidermis and a perivascular mononuclear infiltrate in the dermis. Immunohistochemistry characterized this infiltrate mainly as activated T helper lymphocytes and revealed the expression of intercellular adhesion molecule 1 by endothelial cells and keratinocytes that might have been induced by interferon-gamma. The skin reactions associated with systemic IL-2 administration, show that the skin actually participates as a target organ. They should be differentiated from drug eruptions.     

Lichen sclerosus vulvae

Vulvar lichen sclerosus (LS) is a chronic progressive skin disease of unclear etiology. It is often overlooked in early stages, but progresses to destructive atrophy and is associated with an increased risk of vulvar squamous cell carcinoma. The classical symptoms are pruritus and pain, but they are often not distinctive, so that unclear vulvar problems often lead to a biopsy. The histological picture of early LS is quite different from that of late LS with an atrophic epidermis, markedly sclerotic dermis and stiff dilated vessels. The epidermis in early LS is usually normal with only minor irregularities in the rete pattern. The basement membrane is normal or focally widened, while the edematous dermis has only scattered ectatic vessels. The often dense lichenoid and intraepidermal infiltrate explains the spongiosis and vacuolization of the basal layer keratinocytes. Very early cases may only have a sparse lymphocytic infiltrate and hyper-/parakeratosis of the follicular ostia. Early topical therapy can dampen the progression to atrophic, irreversible LS.     

Immunohistochemical localization of lipocortins in normal and psoriatic human skin

The distribution of lipocortin I, a steroid-induced inhibitory protein of phospholipase A₂, was examined in normal and psoriatic human skin. Using immunoblotting analysis with specific antibody against human lipocortin I purified from human placenta, lipocortin I was detected as a 37 kDa protein in cultured epidermal cells, whole skin and epidermis. In the dermis and stratum corneum, lipocortin I was only weakly detectable by Western blotting. In contrast to normal skin, much less lipocortin I was detected by Western blotting analysis in psoriatic skin. Using immunoperoxidase immunohistochemical analysis, lipocortin I was demonstrated in the cytoplasm of keratinocytes in the upper and middle layers of the epidermis and in some infiltrating cells in the dermis in normal skin. In involved psoriatic skin, by contrast, lipocortin I was almost undetectable in the epidermis, although it was demonstrated in some infiltrating cells in the dermis. No immunostaining of lipocortin I was observed in the stratum corneum of normal or psoriatic skin. These results, together with the finding that phospholipase A₂ activity is higher in psoriatic epidermis than in normal epidermis, suggest that lipocortin I plays an important role in the regulation of differentiation and proliferation of epidermal keratinocytes.     

Histologic characteristics of lichen planus transplanted onto nude mice and cultured in vitro

Summary Typical confluent lesions of lichen planus were transplanted onto nude mice and cultured in organ culture. The characteristic histologic appearance of lichen planus disappeared after grafting and became similar to normal skin within 6 weeks on nude mice: the dense lymphocyte infiltrate in dermis disappeared, the basal cell layer normalized, and the colloid bodies disappeared from epidermis, although some of them were found in dermis. The granular layer also normalized, but the stratum corneum remained hyperkeratotic 6 weeks after transplantation. In organ culture, characteristic histologic features of lichen planus disappeared in 3–5 days via a rapid necrosis of the upper part of the epidermis and formation of a new, normal-looking basal epidermis. These results suggest that lesions of lichen planus are primarily dependent on the influence of the host to maintain their typical histologic appearance.     

Alterations of Clinically Normal Skin in Early Eruptive Guttate Psoriasis

In clinically normal skin of early eruptive guttate psoriasis, in patients with psoriasis for the first time, the epidermal changes were restricted to small tissue areas showing a slight hyperplasia and a condensed stratum corneum but no parakeratosis. The center (zone 1) of the small tissue areas was characterized by (1) exoserosis with spongiotic dilatation of the intercellular space in the non-cornified epidermis, (2) derangement of keratinocytes with respect to shape, orientation, and number of desmosomes and fibrils, (3) dyskeratotic keratinocytes of two types, A and B, (4) agranulosis restricted to the dyskeratotic keratinocytes of type A, (5) exocytosis of mononuclear cells and Langerhans' cells into the entire non-cornified epidermis, (6) large gaps in the basement membrane between the dermis and epidermis. No polymorphonuclear leukocytes were seen. The periphery (zones 2) of the small tissue areas showed slight changes. The alterations of the upper dermis were slight: besides a very mild general inflammatory reaction with capillary dilatation and perivascular cell infiltrate there was also a focal accumulation of inflammatory cells immediately beneath the epidermis, with cells seemingly infiltrating the stratum basale. It is postulated that the epidermal and dermal changes as shown here represent primary psoriatic changes.     

Lichenoid tissue reaction

Lichenoid tissue reaction (LTR) is characterised by epidermal basal cell damage which takes the form of liquefaction degeneration or cell death either apoptosis or necrosis with an associated cascade of histologic events in epidermis and dermis. LTR is found in clinical conditions with lichenoid poikilodermatous and pigmentary dermatoses. A selected group of fifty lichenoid and pigmentary dermatoses such as Lichen planus (LP) Discoid lupus erythematosus (DLE) Lichenoid melanodermatitis (LM) and Lichen nitidus (LN) were studied. In LP basal cell liquefaction degeneration was extensive in comparison to other disease with large number of Civatte bodies and colloid bodies. There were significant vasodilatation in upper dermis inside the massive band like infiltrate. PAS positive basement membrane was disrupted in reaction area. Hypergranulosis was conspicuous. Chronic DLE showed spotty lichenoid reaction in the form of basal cell liquefaction degeneration. Civatte bodies and colloid bodies were infrequent. Infiltrate was more focal but could be band like. Epidermal atrophy and thickening of PAS positive basement membrane were important differentiating features, LM or Melanodermatitis toxica revealed focal mild to moderate liquefaction degeneration of basal cells with atrophy of the epidermis. The infiltrate although band like was less dense with marked pigmentary incontinence in clumps and giant melanophages. Civatte bodies, colloid bodies were not found and vascular changes were less prominent. LN showed localised basal cell damage with claw like rete ridges clutching a dense infiltrate. The dermal infiltrate often showed multinucleated giant cell. Civatte bodies and colloid bodies were not present. In some cases of the overlap syndrome LP/LE a careful study of lichenoid tissue reaction could distinguish these two diseases.(ABSTRACT TRUNCATED AT 250 WORDS)     

Relationship between tissue reactions and morphological changes of the fungi in chromoblastomycosis: morphometry and electron microscopy

Summary To investigate the histological distribution and the morphology of the fungi and the tissue reactions in chromoblastomycosis, especially in the process of trans-epidermal elimination, cutaneous lesions of two patients with this disease were studied morphometrically and ultrastructurally. In the dermis, most of the fungal elements appeared as sclerotic cells and their cell wall showed an irregular, worm-eaten leaf-like appearance; they seemed to be continuously attacked by polymorphonuclear neutrophils. The epidermis eliminated 10–20% of all the organisms in the skin lesions, and the hypha-forming activity tended to be higher in the epidermis than in the dermis. Ultrastructurally, basal keratinocytes facing the dermal abscess containing fungal elements frequently appeared as dark cells, suggesting an increased proliferation activity. Spinous keratinocytes facing intraepidermal microabscesses containing fungal elements showed an abnormal accumulation of tonofilaments and further early keratinization in the spinous cell layer. All of the morphological changes of the dermis and epidermis are regarded as defence reactions against the fungi existing in the skin lesions. There is a close relationship between tissue reactions and morphological changes of fungi in chromoblastomycosis.     

Low-fluence carbon dioxide laser irradiation of lentigines

Low-fluence carbon dioxide (CO2) laser irradiation of skin has previously been shown to induce damage limited primarily to the epidermis. To evaluate whether this technique was therapeutically effective for pigmented epidermal lesions, ten lentigines caused by methoxsalen and ultraviolet light therapy were treated in one patient using the CO2 laser at fluences ranging from 3.0 to 7.7 J/cm2 for 0.1-s exposures with 4.5-mm spot size. Based on substantial clearing in seven of ten lesions treated, 146 solar lentigines were treated in five patients at fluences of 3.0, 3.7, or 4.4 J/cm2. Biopsies were performed on a total of 30 lesions immediately and 24 hours, seven days, and six weeks after irradiation. Of 125 lesions followed up clinically for six weeks, 12 cleared completely, 81 lightened substantially, and 28 remained unchanged. Only two demonstrated atrophic change. Hyperpigmentation or hypopigmentation did not occur. All lesions that improved had been treated at 3.7 or 4.4 J/cm2. Immediate histologic injury consisted of vacuolar and spindly change and subsequent vesiculation limited to the basilar epidermis. Twenty-four hours later there was epidermal necrosis with regeneration, 0.1 mm of dermal basophilia and stromal condensation, and a mild inflammatory infiltrate. These alterations were dose-dependent, with near complete epidermal necrosis and superficial dermal involvement at the highest fluence, and only focal epidermal necrosis at the lowest. At seven days, epidermal regeneration was complete with traces of melanin remaining in keratinocytes. Melanophages first appeared at seven days and persisted at six weeks, by which time the inflammatory infiltrate had cleared. No lentiginous proliferation was evident and epidermal pigmentation had become normal. Low-fluence CO2 laser irradiation is an effective means of damaging the epidermis with only minimal dermal change. This mode of therapy is an effective way to lighten the pigmentation of lentigines without substantial scarring.     

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.     

The keratotic tumors of Cowden''s disease: an electronmicroscopic study

Cowden's disease is characterized by multiple hamartomas of the skin, breast, thyroid, and gastrointestinal tract. In the past, a viral hypothesis for the keratotic lesions of the skin has led to much controversy. The present study describes the results of a detailed fine structural analysis of 10 hyperkeratotic extremity lesions and 2 keratotic lesions from the face of a patient with Cowden's disease. Increases in the keratinocyte population were primarily confined to the basal and suprabasal regions. Differentiation products characteristic of keratinization were normal in both quantity and appearance. Nuclear remnants and numerous lipid droplets, markers of abnormal keratinization, were noted within horny cells. However, viral particles and/or virus-like particles were not observed in keratinocytes. Melanocytes and Langerhans cells were numerous. The latter contained membrane-bound pigment vacuoles in addition to the characteristic Birbeck granules. These unusual Langerhans cells were observed in the dermis as well as the epidermis. A large number of fully granulated "resting" mast cells was uniformly distributed throughout the dermis, associated with a prominent cellular infiltrate. Our observations do not support the concept of a viral etiology for these tumors.     

Lymphocyte subsets and Langerhans cells/indeterminate cells in erythema multiforme

A peroxidase-antiperoxidase study using monoclonal antibodies directed against T and B lymphocytes and Langerhans cells/indeterminate cells (LC/IC) was undertaken in order to understand more clearly the changes observed in erythema multiforme. At the various stages of development, from normal skin to target lesions, the quantity of inflammatory cells differed, but in each case the number of T8+ (cytotoxic/suppressor) cells was greater than the number of T4+ (helper/inducer) cells in the epidermis, whereas the latter exceeded the former in the dermis. Concomitant with the initial epidermis changes, there was an increase in the number of T6+ (LC/IC) cells in the upper and lower epidermis. With slight to moderate basal unit destruction, the number of LC/IC in the upper epidermis exceeded those in the lower epidermis. With severe basal unit destruction, there was a loss of LC/IC in the lower epidermis as detected by T6 reactivity. In fully formed blisters, the LC/IC in the upper half of the epidermis were decreased in parallel with the degree of epidermal necrosis. The character of the lymphocytic inflammatory infiltrate and redistribution in LC/IC are similar to those findings described in allergic contact dermatitis. The clinical, histologic, and immunopathologic changes in erythema multiforme appear to be due in part to cellular immune mechanisms with the lymphocyte as the predominant effector cell, and our data suggest a possible role for LC/IC in this disorder.     

Distribution of CD1a-positive cells in psoriatic skin during the evolution of the lesions

Normal skin and psoriatic lesions from 35 patients were investigated immunohistochemically with regard to the CD1a+ cell population (Langerhans' cells and indeterminate cells) in the epidermis as well as in the dermal infiltrate. In the normal-appearing skin, we found the regularly typical pattern of CD1a+ dendritic cells in suprabasal position, but in lesional skin of chronic psoriasis the CD1a+ cells were scattered in the acanthotic epidermis. In initial lesions, CD1a+ cells represent up to 50-60% of the infiltrating cells of the dermal compartment, in several cases being preferentially localized in the upper part of the papillar dermis close up to the epidermal CD1a+ cells in basal position, whereas in chronic psoriasis they represent less than 10%. These results suggest that in psoriasis vulgaris, CD1a+ cells actively migrate between the epidermis and the dermal vessels.     

Monkeypox virus: histologic, immunohistochemical and electron-microscopic findings

BACKGROUND: Human monkeypox, an emerging viral zoonosis first recognized in Africa, has recently emerged in the mid-western US. Initially, it presents with skin eruptions and fevers with diaphoresis and rigors. Clinically, the skin lesions progress from papules to vesiculopustules to resolving eschars. METHODS: Three cutaneous biopsy specimens from two patients with polymerase chain reaction (PCR)-proven monkeypox were available for review. The histologic, immunohistochemical and electron-microscopic features were identified. RESULTS: The clinical progression of lesions is mirrored histologically with ballooning degeneration of basal keratinocytes and spongiosis of a mildly acanthotic epidermis progressing to full thickness necrosis of a markedly acanthotic epidermis containing few viable keratinocytes. A lichenoid-mixed inflammatory cell infiltrate is present, which exhibits progressive exocytosis with the keratinocyte necrosis. Inflammation of the superficial and deep vascular plexes, eccrine units and follicles is also present. Viral cytopathic effect is manifest by multinucleated syncytial keratinocytes. Immunohistochemically, viral antigen is detected within keratinocytes of the lesional epidermis, follicular and eccrine epithelium and few dermal mononuclear cells. Electron microscopy reveals virions at various stages of assembly within the keratinocyte cytoplasm. CONCLUSIONS: The histologic differential diagnosis includes herpes simplex virus, varicella and other pox viruses, such as smallpox. The first one may be differentiated histologically, immunohistochemically and electron microscopically. The last two may be differentiated using PCR assay for the monkeypox extracellular-envelope virus protein gene.     

Apoptosis in different cutaneous manifestations of lupus erythematosus

BACKGROUND: It has been shown that dysregulation of apoptosis may play an important part in the development of autoimmune diseases such as lupus erythematosus (LE). OBJECTIVES: The aim of the study was to investigate whether apoptosis may contribute to the pathogenesis of cutaneous changes in LE and whether certain apoptosis-related markers such as Fas antigen, Fas ligand (FasL), Bcl-2 and Bax proteins take part in this process. METHODS: Cryostat sections of lesional skin from 31 patients with LE-specific skin lesions [discoid (DLE) n = 17, subacute cutaneous (SCLE) n = 10 and acute cutaneous (ACLE) n = 4] and normal skin samples (n = 10) were stained with monoclonal antibodies against Fas antigen, FasL, Bcl-2 and Bax proteins. For the detection of apoptotic nuclei, terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labelling technique (TUNEL) was employed. RESULTS: The keratinocytes of the epidermis and mononuclear cells of the dermal infiltrate in LE showed a significant increase in Fas antigen expression as compared with normal skin. The anti-Bcl-2 staining intensity within the epidermis was markedly decreased, while the mononuclear infiltrate stained for this protein just like single lymphocytes scattered in normal skin. There was an increase of FasL and/or Bax-positive cells within the dermal infiltrate, but not in the epidermis or in the hair follicles. Accumulation of FasL-bearing cells around hair follicles was a hallmark of DLE. Numerous cells with pyknotic, TUNEL-positive nuclei were demonstrated in the epidermis, in hair follicles and among the cells of the dermal infiltrate. The extent of apoptosis in lesional skin was greater in acute and subacute cutaneous than in discoid forms of LE. CONCLUSIONS: The exact stimulus triggering apoptosis in cutaneous LE still remains unknown but the present study provides strong evidence that the reduction of Bcl-2 expression in the basal cells is associated with the overexpression of Fas antigen and correlates directly with the extent of apoptosis in the epidermis. Furthermore, the current study indicates that the extent of apoptosis in both the epidermis and dermal infiltrate may correlate with the chronological development of LE skin lesions.     

Two Japanese cases of lichen planus pigmentosus-inversus

Case 1 was a 51-year-old Japanese woman. She presented with an asymptomatic brown macule located on the right axilla of 2 months' duration. The smooth macule was 2 cm in diameter with a sharp demarcation (Fig. 1A). Case 2 was a 62-year-old Japanese man. He presented with asymptomatic, symmetric, gray-brown macules located on the groin, axillae, and popliteal region of 6 months' duration. The smooth macules were several millimeters to centimeters in diameter and sharply demarcated (Fig. 1B). Oral or nail lesions, previous inflammatory processes in affected areas, and internal malignancies were absent. A causal relationship with drugs, recent sun exposure, or trauma could not be identified. Findings for work-up, including blood cell count, fasting blood sugar levels, liver function, serum electrolyte levels, serum electrophoresis, urinalysis, antinuclear antibodies, and serological examinations for human hepatitis viruses and syphilis, were within normal limits or negative. The lesions gradually disappeared without medication within 6 months. Biopsy specimens showed a lymphocytic infiltrate with basal vacuolar changes and prominent melanin incontinence in the upper dermis (Fig. 2A). The band-like lymphocytic infiltrate was moderate in Case 1 and mild in Case 2. Immunohistochemistry showed infiltrative CD8(+) T lymphocytes with keratinocytic damage, indicating cytotoxic injury of the keratinocytes (Fig. 2B). Both the epidermis and the upper dermis contained CD1a(+) cells (Fig. 2C). The keratinocytes focally and weakly expressed HLA-DR (Fig. 2D). These findings were identical in samples from both patients.     

Wavelength and fluence effect on vascular damage with photodynamic therapy on skin

Normal skin phototoxicity is clinically predictable during photodynamic therapy with light at 690 and 458 nm wavelengths, in the first 5 h after intravenous bolus infusion of benzoporphyrin derivative mono-acid ring A. This study goal was to determine histologic milestones that lead to tissue necrosis with exposure to red (690 nm) and blue (458 nm) light. The threshold doses for skin necrosis on rabbits were equal at both wavelengths. Lower, equal to, and higher than threshold fluences were delivered in duplicates at hourly intervals, with 40% increments, at constant irradiance. Pathology specimens from irradiated and control sites, were collected at 0, 2, 7, 24, 48 h, and 2 wk after treatment and were paired to equivalent treated sites for clinical evaluation. Immediately after irradiation, at 690 and 458 nm thresholds, light microscopy showed stasis and inflammatory infiltrate in the papillary dermis, respectively; electron microscopy demonstrated pericyte and endothelial cell damage - greater at 690 than 458 nm. At day 1, vascular stasis in the dermis showed a steeper dose-response with red than blue light, and led to necrosis of skin appendages (day 1) and epidermis (days 1-2) at both wavelengths. Sub-threshold fluences induced similar, but significantly milder (p < 0.05) changes and epidermis recovered. Skin necrosis, at threshold fluences in photodynamic therapy with benzoporphyrin derivative mono-acid ring A, was primarily due to vascular compromise to a depth potentially reaching the subcutaneous muscle at 690 nm, whereas at 458 nm vascular damage was confined to upper dermis. This system facilitates selective destruction of skin vasculature, sparing normal epidermis.     

PIXE analysis in different stages of psoriatic skin

Elemental distribution in psoriatic skin varies with the functional state of the keratinocytes, e.g., electrolytes influence cell metabolism and cell proliferation, and trace elements play a crucial role in a great number of enzymes. Elemental distribution in pinpoint lesions, old plaques, and uninvolved skin of 5 psoriatic patients and 4 healthy controls was studied by means of PIXE (proton-induced x-ray emission) analysis. This technique allows the simultaneous detection of elements with an atomic number greater than or equal to 14 along the epidermis and dermis in freeze-dried skin biopsies. Trace elements such as Fe, Cu, and Zn were determined down to a level of 1 ppm. In comparison with uninvolved skin, concentrations of P and K were elevated in psoriatic epidermis. In addition, increased levels of K were correlated with the stage of the psoriatic lesion. Zinc concentrations were significantly elevated in pinpoint lesions. The Zn concentration profiles within the epidermis and upper dermis showed high correlation to the P concentration profiles. Iron levels were decreased in old psoriatic plaques, whereas Cu concentrations varied considerably. In comparison to the controls, Cl concentrations were markedly decreased in the dermis of involved and uninvolved psoriatic skin, whereas epidermal Cl levels were unaffected. As high K levels prevent the Ca-induced differentiation of keratinocytes, high K levels may be the cause of the high cell differentiation in psoriatic skin. Elevated DNA- and RNA-polymerases might be the cause of elevated Zn levels in pinpoint lesions.     

Virus propagation, virus replication and virus elimination in the human skin in zoster]

The purpose of this study was to investigate the spreading, the replication and the elimination of Varicella-Zoster-Virus (ZV) in human skin. Typical skin lesions of thoracic zoster in different stages of development and of exanthematic vesicles in ophthalmic zoster were examined under the electron microscope. We found that ZV may be detected in fully developed vesicular skin lesions only, whereas in immature lesions and in the surrounding non involved skin axonal alterations may be seen, with no ZV present. The replication of the virus in the skin takes place almost exclusively in the malpighian keratinocytes of the involved epidermis. Blister formation in zoster is basically a result of the acantholysis of the infected epidermal cells. Mature ZV are then extruded into the intercellar space and become phagocytised by mononuclear cells which infiltrate the epidermis and eliminate the virus in large phagolysosomes. Only few virions were found in the dermis extracellularly or in dermal macrophages. In some of these cells stages of ZV-replication were also seen. Other cell types (i.e. Langerhans cells) were rarely infected. The application of the periodic acid-silver methenamine technique (PASM) in zoster revealed that a glycoprotein-rich coat surrounds each mature virion, obviously originating from the plasma membrane of the infected keratinocytes. This coat may be reason for the ability of the ZV to adhere on the cell surface and to infect the cell.     

Detection of nitric oxide and nitric oxide synthases in psoriasis

Biopsies from psoriasis lesions and clinically uninvolved skin of eight patients and five normal subjects were studied by immunocytochemistry with computerized image analysis for the presence of endothelial, neuronal and inducible isoforms of nitric oxide synthase. Endothelial nitric oxide synthase was expressed in the endothelium and weakly in some keratinoctyes. Its expression was not significantly different in psoriasis. Inducible nitric oxide synthase, however, was absent from normal skin but was significantly upregulated in psoriatic lesional skin, focally in keratinocytes but to the greatest extent in the papillary dermis and to a lesser extent in clinically uninvolved psoriatic skin. Inducible nitric oxide synthase staining was greatest in the more severe lesions and correlated with the inflammatory infiltrate (CD3-positive cells) and with keratinocyte proliferation (Ki-67-positive cells). In normal skin, neuronal nitric oxide synthase was expressed only in keratinocytes in the granular layer and eccrine sweat glands. However, in psoriasis and clinically uninvolved skin the neuronal form was present through all levels of the epidermis. Direct measurement of nitric oxide production from the skin surface revealed a tenfold increase in the lesions of 16 psoriatic patients compared with their nonlesional skin, and this nitric oxide production was inhibited by topical betamethasone. Received: 4 March 1996     

The role of perforin-mediated apoptosis in lichen planus lesions

Lichen planus is recognized as a T-cell-mediated disease. Histologically, it is characterized by the formation of colloid bodies representing apoptotic keratinocytes. The apoptotic process mediated by CD8⁺ cytotoxic T lymphocytes (CTLs) and NK cells mainly involves two distinct pathways: the perforin/granzyme pathway and the Fas/FasL pathway. So far, little is known regarding the role of perforin-mediated apoptosis in lichen planus. In the present study, the expression and distribution of perforin, T and NK cell subsets in the epidermis and dermis of lesional and nonlesional lichen planus skin were studied. Skin biopsy specimens from lesional and nonlesional skin of ten patients with lichen planus and eight healthy persons were analysed by immunohistochemistry. Significant accumulation of T cells, particularly of CD4⁺ and CD8⁺ subsets, was found in both epidermis and dermis of lichen planus lesions compared with nonlesional and healthy skin. There were no significant differences in the incidence of NK cells (CD16⁺ and CD56⁺) between lesional, nonlesional and healthy skin. Perforin expression was significantly upregulated in the epidermis of lichen planus lesions. In conclusion, accumulation of perforin⁺ cells in the epidermis of lichen planus lesions suggest a potential role of perforin in the apoptosis of basal keratinocytes.