Lymphocyte subtypes and adhesion molecules in actinic prurigo: observations with cyclosporin A

BACKGROUND: Actinic prurigo is a photodermatitis in which UV light is implicated by an unknown mechanism. METHODS: Skin biopsies of 19 patients with actinic prurigo and 11 controls were analyzed by immunohistochemistry. RESULTS: In actinic prurigo patients, there was a significant increase in the number of CD3, CD4, CD8, CD45RA, CD45RO, and CD45RB lymphocytes and Langerhans cells, as well as in the level of human leukocyte antigen-DR (HLA-DR) expression and cell adhesion molecules lymphocyte functional antigen-1 (LFA-1), intercellular adhesion molecule-1 (ICAM-1), and endothelial leukocyte adhesion molecule-1 (ELAM-1). Actinic prurigo patients were treated with cyclosporin A (CsA), and a final skin biopsy was taken after 6 months of treatment. All the cell populations and markers studied, except for the CD4 lymphocytes, Langerhans cells, and HLA-DR expression, returned to normal levels. CONCLUSIONS: CsA was found to be effective in relieving the clinical symptoms of actinic prurigo.     

Thalidomide: An option for the pediatric patient with actinic prurigo

Actinic prurigo (AP) is an immune-mediated photodermatosis that usually starts in childhood and is predominant among American indigenous and mestizo communities. In adults with AP, thalidomide is the treatment of choice; however, there is little information on its use in pediatric patients. We report the case of a 10-year-old girl with AP treated successfully with thalidomide.     

Dendritic cells and pattern of cytokines in paracoccidioidomycosis skin lesions

We demonstrated and quantified by immunohistochemistry epidermal Langerhans cells, CD34+ dermal dendrocytes (DDs), and cells expressing TNFalpha, interferon-gamma (IFNgamma), IL-5, and IL-10 in skin lesions of paracoccidioidomycosis (PCM). Sixty-one biopsies were classified in three groups according to the pattern of tissue response: Group 1, well-organized granuloma; Group 2, poorly organized granuloma; and Group 3, both kinds of granuloma. Langerhans cells had short and irregular dendrites in all groups and were decreased in number in Groups 1 and 2. CD34+ DDs did not differ in number from the control group. Group 1 was characterized by many cells expressing IFNgamma. Groups 2 and 3 exhibited large numbers of cells expressing IL-5 and IL-10. The data obtained suggest that well-organized granulomas reflect a better cellular immune response, and the large number of cells expressing IL-5 and IL-10 in Group 2 indicate an ineffective response in PCM skin lesions. Both kinds of granuloma in the same cutaneous lesion probably represent an intermediate response between the anergic and hyperergic poles. Group 3 also showed higher numbers of cells expressing TNFalpha when compared with the control group. Some cells expressing TNFalpha were dendritic and localized around the granuloma similar to the factor XIIIa+ DD localization that we previously described.     

Immunoregulatory effector cells in drug-induced toxic epidermal necrolysis

Toxic epidermal necrolysis (TEN) is a rare drug-induced disease for which the pathomechanism remains poorly understood. The effector cells of epidermal injury in TEN were studied by taking skin biopsies of early lesions in 23 TEN patients and by performing immunohistochemical tests using antibodies to factor XIIIa (type I dendrocytes), L1-protein (mainly Mac 387+ monocytes and macrophages), UCLHI (mainly CD45R0+ T-memory lymphocytes), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNFalpha). Computerized image analysis was used to evaluate the cell density relative to each immunolabeling. A statistical analysis of cellular counts revealed a numeric relation between the cell types in skin with TEN. Factor XIIIa+ dendrocytes were abundant and plump in the dermis, although Mac 387+ macrophages were the most numerous inflammatory cells in the epidermis. Their numbers greatly exceeded those of CD45R0+ T lymphocytes and cells showing immunoreactivity for either IL-6 or TNFalpha. In the epidermis, IL-6+ cells were significantly less numerous than TNFalpha+ cells. No quantitative difference was found between IL-6+ and CD45R0+ cell populations. Correlations were observed between either the numbers of TNFalpha+ cells or Mac 387+ macrophages and CD45R0+ lymphocytes. In the dermis, a significant correlation was also present between the numbers of Mac 387+ and factor XIIIa+ cells. These findings highlight the complex interactions between the inflammatory cells that mediate epidermal damage in skin with TEN. The high density of factor XIIIa+ dendrocytes and Mac 387+ macrophages in lesional skin assigns these cellular populations a prominent role in the pathomechanism of TEN. Despite a lower cell density, CD45RO+ T-memory lymphocytes likely participate in TNFalpha- and IL-6-regulated processes in the epidermis of TEN. TNFalpha seems to be a major cytokine involved in TEN, although a less prominent role can be ascribed to IL-6.     

Actinic prurigo: a retrospective analysis of 21 cases referred to an Australian photobiology clinic

Actinic prurigo (AP) is a rare acquired idiopathic photodermatosis, reported most often in American Indians, but also in Caucasian and Asian populations. The skin lesions in AP predominantly affect exposed sites but may involve covered areas, and often result in postinflammatory scarring. The diagnosis of AP can be difficult and relies on a combination of history, clinical experience and investigations including phototesting and human leucocyte antigen typing. Twenty-one patients (17 women, four men) diagnosed with AP at the photobiology clinic at St Vincent's Hospital Melbourne were reviewed in this retrospective study. The mean age of patients at presentation to the clinic was 25 years, with the mean age of onset being 14 years. Phototesting was undertaken in 20 patients, with 12 (60%) having reduced and eight (40%) normal minimal erythema doses. Human leucocyte antigen typing indicated 18 patients (85.7%) were DR4 positive, with further subtyping of the DR4 allele establishing that 15 patients (71.4%) were DRB1*0407 positive and that two (9.5%) were DRB1*0401 positive. This condition is often recalcitrant, with treatment options including photoprotection, topical and oral corticosteroids, antimalarials, phototherapy and thalidomide.     

Effectors of inflammation in actinic prurigo

BACKGROUND: Actinic prurigo is a specific familial photodermatosis of uncertain pathogenesis. OBJECTIVE: Our purpose was to investigate the immunohistologic presentation of actinic prurigo to explore the involved pathomechanisms. METHODS: The present immunohistochemical study was performed on biopsy specimens from 20 Mexican patients presenting with a severe and perennial form of the disease. RESULTS: The dense inflammatory infiltrate was composed predominantly of helper T type 1 lymphocytes admixed with scattered B-cell lymphoid follicles and numerous dermal dendrocytes. Keratinocytes contained abundant tumor necrosis factor-alpha and calprotectin. CONCLUSION: In subjects genetically predisposed to actinic prurigo, ultraviolet light may trigger excessive tumor necrosis factor-alpha production by keratinocytes whose sustained release in turn exerts its proinflammatory activity and deleterious epidermal effects. Such a cascade of events is in line with the therapeutic benefit already reported when thalidomide is used to treat actinic prurigo.     

A case of severe actinic prurigo successfully treated with thalidomide

Actinic prurigo is an uncommon and usually persistent idiopathic photodermatosis with typical human leukocyte antigen (HLA) associations (HLA-DR4, particularly subtypes DRB1*0407 and DRB1*0401). Although its mechanism of action is not clearly understood, thalidomide has been shown to be particularly efficacious in treating actinic prurigo, among other conditions. A 31-year-old Australian woman who had suffered actinic prurigo for most of her life was treated with two courses of thalidomide (50-100 mg nocte) over consecutive summers. Remission was observed after cessation of the second course of thalidomide and had continued 4 years later. Abnormalities in the cutaneous response to ultraviolet radiation at the time of diagnosis, detected by monochromator phototesting, reverted to normal following treatment.     

Pentoxifylline in the treatment of actinic prurigo. A preliminary report of 10 patients

BACKGROUND: Actinic prurigo (AP) is a chronic familial photodermatosis usually seen in Latin-American Mestizo and Indian populations. It frequently begins in childhood and is more prevalent in females. The pathogenesis of AP has not been clearly elucidated, but previous studies have suggested an immune-mediated condition. Many drugs have been employed to treat AP patients with variable success. OBJECTIVE: To assess the clinical efficacy of pentoxifylline (PTX) in the treatment of AP patients by measuring its effects on lesions and pruritus. METHODS: 10 patients with severe AP were included to receive PTX in a 6-month open-label uncontrolled study. RESULTS: Clinical improvement of lesions was evident in all patients. Relief in pruritus was evident after 1 month of treatment and was maintained while receiving PTX. Five patients were followed up for 2 years, 2 obtained complete remission, and 3 had an important reduction in the use of corticosteroids. CONCLUSION: PTX was useful in the treatment of our actinic prurigo patients. It may induce a complete or partial remission of lesions and allow a decrease in the use of topical corticosteroids.     

以结节性痒疹为首发表现的艾滋病3例及文献复习

结节性痒疹是艾滋病患者较为常见的皮肤表现,是多因素导致的疾病,其皮损与非艾滋病患者相似。本文3例均为男性,临床表现为全身散在丘疹、结节、表皮剥脱、结痂伴剧烈瘙痒,淋巴细胞分类计数示CD4、CD4/CD8比值降低。HIV血清抗体初筛实验及确证实验均(+)。皮损组织病理符合结节性痒疹。2例予抗组胺药物和外用糖皮质激素软膏后症状减轻,1例放弃治疗。沙利度胺是治疗艾滋病相关性结节性痒疹最有效的药物。     

Prurigo pigmentosa: role of ICAM-1 in the localization of the eruption

Immunohistochemical studies were carried out on the skin lesions of two cases of prurigo pigmentosa. There was a predominance of CD4+ cells in the dermal infiltrate, whereas those lymphocytes in the epidermis were mainly CD8+ cells. The majority of dermal and epidermotropic lymphocytes showed an intense expression of lymphocyte function-associated antigen 1 (LFA-1). The number of CD1+ cells was increased in the epidermis. There was intense expression of ICAM-1 by keratinocytes in the erythematous papules. Focal expression of ICAM-1 was still observed in the residual pigmented areas and could explain the recurrence of the lesions at these sites.     

Infiltrating cells, related cytokines and chemokine receptors in lesional skin of patients with dermatomyositis

BACKGROUND: There have been only two reports on immunophenotypic characterization in the cutaneous lesions of dermatomyositis (DM) that emphasize the importance of the infiltrating CD4+ T lymphocytes. OBJECTIVES: To characterize the immunophenotype of the cells that infiltrate the lesional skin of DM and to evaluate the possible T-helper (Th) polarization Th1/Th2 through detection of specific cytokines, chemokine receptors and markers of cellular activation. METHODS: Skin biopsy specimens derived from pathognomonic lesions (Gottron's papules and Gottron's sign) of eight patients with DM were immunostained with a large panel of monoclonal antibodies to CD3, CD4, CD8, myeloperoxidase (MPO), eosinophil cationic protein, tryptase, CD40, CD40 ligand (CD40L), HLA-DR, interleukin (IL)-2, IL-4, IL-5, IL-13, interferon-gamma, tumour necrosis factor-alpha, receptor 3 for CXC chemokines (CXCR3) and receptor 3 for CC chemokines, using the alkaline phosphatase-antialkaline phosphatase method. Control specimens were obtained from five healthy subjects and from six patients with discoid lupus erythematosus. RESULTS: Activated CD4+ Th lymphocytes (HLA-DR+ CD40L+) were the principal infiltrating cells in the lesional skin of DM; the CD4/CD8 ratio was approximately 2.5. A mixed Th1/Th2 profile and higher Th1 cytokine production together with significant staining for CXCR3 were detected. Neutrophil granulocytes were the second most abundant population; eosinophil granulocytes were very poorly represented. CONCLUSIONS: Activated CD4+ T cells presumably mediate the main pathogenetic mechanisms in pathognomonic skin lesions. The interaction between CD40 and CD40L could be an important mechanism of cellular activation in cutaneous immune-mediated inflammation by induction of secretion of proinflammatory cytokines and chemokines. Neither Th1 nor Th2 clear polarization was found, although there was a slight Th1 prevalence. There was a significant quantity of MPO+ cells (neutrophil granulocytes) in the inflamed tissue, and they might have a role in sustaining the chronic inflammation.     

Successful thalidomide therapy for actinic prurigo in a European woman

Actinic prurigo is a rare, often difficult‐to‐treat, idiopathic photodermatosis. Actinic prurigo is divided into a hereditary form appearing in the Native American population and a sporadic form occurring in non‐Native Americans. We present a 28‐year‐old Caucasian woman who developed typical clinical signs and symptoms of actinic prurigo, just as had her mother and grandmother. The patient and her mother were HLA‐A24 and HLA‐DR 4 with the subtype HLA‐DRB1*0408. Based on clinical symptoms and the HLA pattern, the diagnosis of actinic prurigo was made. Treatment with thalidomide led to resolution of the disease. This case report of a Caucasian woman suffering from a hereditary form of actinic prurigo questions the established classification of actinic prurigo into a hereditary Native American form and a sporadic form occurring in the non‐Native American population.     

Diagnosis and treatment of actinic prurigo

Actinic prurigo (AP) is an idiopathic photodermatosis that affects mainly the mestizo population in Latin America. It has an early onset, a slight predominance in women, and affects the sun-exposed areas of the skin, causing erythematous papules and lichenified plaques secondary to intense and chronic pruritus. Lesions can be induced by both ultraviolet A (UVA) and ultraviolet B (UVB). An association with several human leukocyte antigen (HLA) alleles has been reported. AP is unique among all photodermatoses in its remarkable response to thalidomide. In the past the microscopic features of AP have been considered as nonspecific; however, the constant finding of dense lymphocytic inflammatory infiltrates and the immunogenetic features of AP support the existence of an immunologic mechanism in its pathogenesis.     

特应性皮炎患者外周血T淋巴细胞Rho激酶活性变化及其意义

目的 观察特应性皮炎（AD）患者外周血T淋巴细胞中Rho激酶活化情况,分析其临床意义。方法 收集60例AD患者和60例健康儿童外周肝素抗凝血8 ml,分离提取T细胞和血清。分别用AD血清和健康对照血清培养AD患者T细胞或健康对照T细胞,分为患者T细胞 + 自身血清组、患者T细胞 + 健康对照血清组、健康对照T细胞 + 自身血清组、健康对照T细胞 + AD血清组。此外,分别用Rho激酶特异性抑制剂Y27632（Y27632组）、CD3/CD28单抗（CD3/CD28单抗组）、Y27632 + CD3/CD28单抗（Y27632 + CD3/CD28单抗组）处理AD患者T细胞,自身血清培养AD患者T细胞为患者T细胞组。采用Western印迹法检测各组Rho激酶活性,四甲基偶氮唑蓝比色法（MTT）检测T细胞增殖活性,ELISA检测白细胞介素（IL）6、IL-10水平。 结果 新鲜分离的AD患者外周血T细胞Rho激酶活性（2.47% ± 0.89%）显著高于健康对照组（0.65% ± 0.35%,t = 2.729,P < 0.05）。AD患者T细胞在体外经10%胎牛血清培养24 h后Rho激酶活性（0.70% ± 0.38%）较培养前显著降低（t = 2.658,P < 0.05）,但与培养24 h后健康对照T细胞（0.63% ± 0.32%）相比,差异无统计学意义（t = 1.010,P > 0.05）。与健康对照血清培养T细胞相比,AD血清培养T细胞会增加Rho激酶活性（F = 8.22,P < 0.001）,患者T细胞 + 自身血清培养24 h后Rho激酶活性（2.41% ± 0.87%）明显高于患者T细胞 + 健康对照血清组（0.76% ± 0.41%）,健康对照T细胞 + AD血清组（2.17% ± 0.85%）显著高于健康对照T细胞 + 自身血清组（0.64% ± 0.33%）,差异均有统计学意义（P < 0.05）。Y27632可显著抑制AD患者T细胞的增殖和IL-6的分泌（F = 18.68、22.95,P < 0.001）,Y27632组T细胞增殖率、IL-6的表达均显著低于患者T细胞组（均P < 0.05）,且Y27632 + CD3/CD28单抗组也显著低于CD3/CD28单抗组（均P < 0.05）,而Y27632对AD患者T细胞IL-10分泌无显著影响。 结论 AD患者T淋巴细胞存在Rho激酶信号活化异常,提示Rho激酶信号异常在AD发病过程中可能发挥着一定的作用。