Cutaneous granulomas with predominantly CD8(+) lymphocytic infiltrate in a child with severe combined immunodeficiency

BACKGROUND: Combined immunodeficiency disorders comprise a heterogeneous group of diseases characterized by both humoral and cell-mediated immunodeficiency. Cutaneous granulomas manifestations in children with combined immunodeficiency are rare. OBJECTIVE: We report the case of a 6-year-old boy who presented with disseminated cutaneous granulomas and a history of multiple infections. METHODS AND RESULTS: Laboratory evaluation revealed severe combined immunodeficiency, and deoxyribonucleic acid (DNA) analysis confirmed mutations on a gene of chromosome 19 that encodes an enzyme called Janus kinase 3 (Jak-3). Immunohistochemistry revealed expression of CD8(+) in the perivascular lymphocytic infiltrate CONCLUSION: Disseminated granulomatous lesions in children with a history of frequent infections should prompt the clinician to initiate detailed immunocompetence evaluation as they might prove to be the first manifestation of immunologic impairment.     

Jessner's lymphocytic infiltration of the skin: a CD8+ polyclonal reactive skin condition

BACKGROUND: Jessner's lymphocytic infiltration of the skin (JLIS) is a clinically and histologically distinct disease entity. Conflicting results have been reported concerning its differentiation from cutaneous lupus erythematosus and polymorphous light eruption, its relationship to palpable migratory arciform erythema and its classification as a B-cell or a CD4+ T-cell lymphoproliferative disease. OBJECTIVE: Our study was performed in order to re-evaluate JLIS clinically and by immunohistochemical and molecular analyses. METHODS: Stringent inclusion/exclusion criteria were used to collect a cohort of 34 patients with JLIS that did not overlap with lupus erythematosus or polymorphous light eruption. Clinical data were analysed, and immunohistochemical and molecular studies were performed including TCR-gamma PCR GeneScan software analysis of tissue and peripheral blood samples. RESULTS: In the majority of the patients, the lesions consisted only of papules and plaques while in 12% annular lesions were also seen. The lesions were found on the face (38%), on the trunk and arms (50%) or at both sites (12%). Immunohistochemical analyses revealed a clear predominance of T cells in all patients, and of CD8+ T cells in 77% of the patients. As judged by TCR-gamma PCR GeneScan analysis, 98 and 79% of the tissue and peripheral blood samples, respectively, showed a polyclonal T-cell population; identical T-cell clones were not detected concomitantly in both the skin and the peripheral blood of the same patient. CONCLUSIONS: JLIS occurs at 2 major predilection sites, that is the face and trunk. Therefore introduction of palpable migratory arciform erythema as a separate entity is not justified. The lymphoid infiltrates are dominated immunohistochemically by CD8+ T cells that do not show clonality on molecular analysis. Thus, JLIS represents a characteristic CD8+ polyclonal reactive skin condition.     

Prevalence and clinical spectrum of skin disease in patients infected with human immunodeficiency virus

We examined 100 serial patients who were receiving care in a county outpatient immunodeficiency clinic and whose serum was positive by Western blot test for the human immunodeficiency virus (HIV). Skin disorders were found in 92% of these HIV-infected patients, with little difference in prevalence or severity in three clinical categories: patients with the acquired immunodeficiency syndrome, patients with acquired immunodeficiency syndrome-related complex, and those who were asymptomatic. Patients positive for HIV antibodies had significantly more skin disease, with the exception of dermatophytosis, than did a historical control population. A strong association was observed between the use of zidovudine and the absence of infection with Candida albicans. We conclude that there is a high prevalence of skin disease in HIV-positive patients who seek medical care, and that specialists in skin disease should be included in these patients' initial evaluation and continuing care.     

CD30 expression on CD1a+ and CD8+ cells in atopic dermatitis and correlation with disease severity

Atopic dermatitis (AD) is a chronic inflammatory skin disease associated with cutaneous hyperreactivity to environmental stimuli, resulting in increased infiltration of inflammatory cells, IgE production and enhanced expression of costimulatory molecules, cytokines and chemokines. CD30, a TNF receptor superfamily member, is a costimulatory molecule expressed on activated T and B cells. A positive correlation between soluble CD30 (sCD30) levels in patient serum and AD disease severity has been described previously. However, the relative frequencies and identities of cells expressing CD30 in AD patients and the relationship between the frequency of CD30 positive cells and serum sCD30 levels with disease severity remained unknown. To address these questions, immunofluorescence analysis of AD skin lesions representing different disease stages, was conducted. In addition to the CD4+ T cells, CD1a+ Langerhans cells and CD8+ T cells were found to express CD30 in AD lesions and the cell numbers correlated with disease severity. FACS analysis of AD patient blood samples revealed expression of CD30 on memory T-cells and a correlation with disease severity was identified. Finally, serum analysis of soluble mediators revealed positive correlations between sCD30, IgE, MDC, TARC and PARC levels with disease severity. Combined, our data provide correlative evidence that CD30+ cells, including Langerhans cells and CD8+ T-cells, may contribute to AD disease severity and that therapeutic strategies targeting CD30+ cells may provide benefit to AD patients.     

Different patterns of dermatological presentations in patients co-infected with human immunodeficiency virus and hepatitis C virus (HCV), and those infected with HCV alone

Background. Hepatitis C virus (HCV) and human immunodeficiency virus (HIV) share the same transmission routes. About 30% of HIV‐positive patients are co‐infected with HCV. Of the various HCV‐related extrahepatic events, those involving the skin may be the first sign of infection. Aim. To specify the skin presentations in patients co‐infected with HIV and HCV (co‐infected patients; CP) and compare them with those found in patients with HCV mono‐infection (mono‐infected patients; MP). Methods. This was a cross‐sectional study, in which the studied population consisted of MP and CP from a tertiary hospital in the South of Brazil, who underwent complete skin examination and laboratory tests. Results. In total, 201 patients were assessed, of whom 108 were CP, and 93 were MP. Pruritus tended to be more common in MP. MP also had significantly more dermatological conditions (mean of 5.2) than CP (mean of 4.5). In total, 104 different skin diseases were identified. There was a higher prevalence of infectious diseases and pigmentation disorders, such as verruca vulgaris and facial melasma, in CP, whereas trunk and facial telangiectasias, palmar erythema, and varicose veins were more common in MP. Conclusion. We found a high prevalence of skin conditions both in MP and in CP; however, the patterns of the dermatological conditions were different. CP were found to have significantly fewer skin lesions than MP, but had a higher prevalence of infectious and pigmentation disorders. By contrast, vascular conditions were more common in MP.     

寻常型银屑病患者外周血CD4~+CD25~+及CD8~+CD25~+细胞的检测

目的研究进展期寻常型银屑病患者外周血CD4+CD25+和CD8+CD25+调节性T细胞的数量变化及其在银屑病免疫病理学发病机制中的作用。方法应用流式细胞术对进展期寻常型银屑病患者外周血CD4+CD25+和CD8+CD25+调节性T细胞进行检测。结果进展期寻常型银屑病外周血CD4+CD25+细胞及CD8+CD25+调节性T细胞数量与正常对照组相比,均显著降低(P<0.05,P<0.005),而CD4+CD25+/CD8+CD25+比值无显著性差异(P>0.05)。结论寻常型银屑病的发病与CD4+CD25+和CD8+CD25+调节性T细胞的同步降低有关,与二者的比值无关。     

Effects of solar-simulated radiation dose fractionation on CD1a+ Langerhans cells and CD11b+ macrophages in human skin

BACKGROUND: There are few human studies investigating the immunosuppressive effects of exposure to solar-simulated radiation (SSR) and its relationship with sunburn/erythema, and few comparative data on the importance of SSR exposure regimens. OBJECTIVES: To evaluate whether SSR-induced erythema is a reliable end-point for assessing damage to antigen-presenting cells (APCs) in human skin. METHODS: We compared the relationship between SSR-induced erythema and alterations in epidermal CD1a+ Langerhans cells (LCs) and CD11b+ macrophages in human volunteers after single exposures to 0, 0.5, 1, 2 or 3 minimal erythema doses (MED). We also investigated whether SSR exposure leads to an accumulation or accommodation of the same end-points by comparing the effects of a relatively low cumulative SSR dose (3 MED) given in varying daily dose fractions (4 x 0.75 MED, 2 x 1.5 MED and 1 x 3 MED). RESULTS: Single SSR exposures induced a dose-dependent increase in erythema. CD1a+ LCs remaining in the irradiated epidermis showed a dose-dependent increase in cell size and altered morphology. Significant depletion of CD1a+ LCs and presence of CD11b+ macrophages only occurred in sites irradiated with 2 MED and 3 MED. Dose fractionation had no effect on the final erythemal response but the 4 x 0.75 MED and 1 x 3 MED protocols were better tolerated than 2 x 1.5 MED for alterations in CD1a+ LC and CD11b+ cell numbers. In contrast, dose fractionation protected against alterations in CD1a+ LC morphology or cell size. CONCLUSIONS: We found that erythema is a poor indicator of alterations in epidermal APCs and that dose fractionation is an important parameter in the immunological effects of ultraviolet radiation.     

Skin disorders in Korean patients infected with human immunodeficiency virus and their association with a CD4 lymphocyte count: a preliminary study

Background Dermatological disorders are quite common in human immunodeficiency virus (HIV)‐infected patients. However, cutaneous findings in Korean HIV‐infected patients have not been properly investigated. Objective To investigate the spectrum of dermatological disorders in Korean HIV‐infected individuals according to a CD4 lymphocyte count. Methods A retrospective clinical study was carried out from June 2002 to January 2008. We comprehensively collected information regarding HIV‐associated skin problems, laboratory data and the history of highly active antiretroviral therapy (HAART). Results Ninety‐nine HIV‐seropositive patients (mean age: 39.6 ± 11.3 years, males: 94.9%) were included in this study. Of them, 55 patients (55.6%) presented with at least one skin problem. The four most common dermatological disorders were eosinophilic pustular folliculitis (18.6%), symptomatic syphilis (comprising of primary and secondary syphilis) (17.1%), seborrhoeic dermatitis (17.1%) and condyloma acuminatum (12.8%). The group with a CD4 lymphocyte count < 200 × 10⁶ cells/L showed a significantly higher prevalence of Kaposi sarcoma compared with the group with a CD4 lymphocyte count > 200 × 10⁶ cells/L (P = 0.014). Condyloma was more prevalent in the group with a CD4 count > 200 × 10⁶ cells/L (P = 0.022). The patients treated with HAART had a lower prevalence of neurosyphilis compared with the non‐treated group (P = 0.018). Conclusions Diverse dermatological conditions were demonstrated in Korean HIV‐infected patients. Kaposi sarcoma was associated with a low CD4 lymphocyte count, but condyloma was associated with a high CD4 lymphocyte count. The prevalence of syphilis in our study was higher than that of Western countries. HAART seemed to be associated with the low prevalence of neurosyphilis.     

梅毒患者外周血CD4~+、CD8~+调节性T细胞表达的临床意义

目的:监测梅毒患者外周血CD4~+、CD8~+调节性T细胞的表达水平,考察其在临床的参考价值。方法:将2014年12月至2015年9月,我院收治并确诊的32例梅毒患者作为研究对象。其中,Ⅰ期、Ⅱ期、潜伏期梅毒患者分别有11例、15例和6例。采用细胞免疫芯片检测(淋巴细胞CD4~+、CD8~+绝对数检测)技术检测并计算患者外周血中的调节性T细胞CD4~+、CD8~+表达水平及CD4~+、CD8~+的比值。并与同期就诊我科的30例非梅毒患者的相应指标数据进行比较。结果:与非梅毒患者比较,梅毒患者外周血中CD4~+、CD8~+细胞绝对值计数均显著下降(P0.05);CD4~+、CD8~+比值显著低于非梅毒患者组(P0.05)。在Ⅰ期、Ⅱ期、潜伏期梅毒患者间CD4~+、CD8~+绝对值计数均值水平的差异有统计学意义(P0.05)。结论:在梅毒患者外周血中CD4~+、CD8~+表达水平及CD4~+、CD8~+比值均显著降低,而在梅毒感染的不同疾病发展时期CD4~+、CD8~+表达水平也有着显著的差异。     

CD4+ CD8+ (thymocyte-like) T lymphocytes present in blood and skin from patients with atopic dermatitis suggest immune dysregulation

BACKGROUND: Atopic dermatitis (AD) is a chronic inflammatory skin disease expressed early in life. Disease development is primarily determined by as yet unknown genetic factors, leading to the accumulation of activated T lymphocytes in the skin. OBJECTIVES: To investigate the nature of these T cells. METHODS: T-cell lines could be established from AD skin biopsies, but not from normal skin or AD peripheral blood, when placed in RPMI 1640 medium with 10% human AB serum, antibiotics, and the T-lymphocyte growth factors interleukins 2 and 4. The cell lines were subjected to phenotypic analysis using a fluorescence-activated cell sorter and compared with lymphocytes from AD and normal control peripheral blood. RESULTS: T-cell lines from 22 of 24 consecutive skin biopsies taken from 24 adult patients with AD were established. All cells were T lymphocytes expressing several activation markers. A significant proportion of the lymphocytes had stable expression of a CD4+ CD8+ phenotype (26% +/- 6%; mean +/- SEM). Such double-positive T lymphocytes are normally only seen in the thymus and not in the peripheral immune system. CD4+ CD8+ cells in peripheral blood of the patients (12.5% +/- 3.3%) were also detected. CONCLUSIONS: We suggest that a basic pathophysiological change in AD may be a faulty maturation of the T-lymphocyte system, leading to skin inflammation with CD4+ CD8+ T lymphocytes resembling immature T cells. This is likely to lead to skewing of many immune reactions in the patients.     

火针联合卤米松乳膏治疗稳定期白癜风患者的疗效观察及对CD4+、CD8+、CD4+/CD8+水平的影响

 目的 观察火针联合卤米松乳膏治疗稳定期白癜风的临床疗效,检测对患者CD4⁺、CD8⁺及CD4⁺/CD8⁺水平的影响。方法 选择我院皮肤科及中医科门诊自2018年1月—2019年12月诊治的60例稳定期白癜风患者作为研究对象,随机分成对照组 (30例) 和试验组(30例),对照组采用卤米松乳膏治疗,试验组予以火针联合卤米松乳膏治疗,比较两组患者治疗前后的白癜风面积评分指数(VASI),观察总有效率以及不良反应发生率。同时检测患者治疗前后CD4⁺、CD8⁺及 CD4⁺/CD8⁺的表达水平。结果两 组患者治疗前的VASI对比无显著差异(P＞0.05)。治疗后,试验组VASI明显低于对照组(9.73±0.56比10.79±1.13,t=4.60,P＜0.05）,总有效率明显高于对照组(86.67%比63.33%,X²=4.36,P=0.037）。两组治疗后CD3⁺、CD4⁺、CD4⁺/CD8⁺均高于治疗前,试验组治疗后CD3+为(69.23±5.27)%,CD4⁺ 为(44.03±3.94)%,CD4⁺/CD8⁺比值为 (2.54±0.99),对照组治疗后CD3⁺为(66.60±7.56)%,CD4⁺为(38.13±6.51)%, CD4⁺/CD8⁺比值为(1.91±0.87),试验组各指标均高于对照组（均P＜0.05）;治疗后试验组CD8⁺为(19.30±5.55)%,低于对照组的(23.20±8.36)%,差异有统计学意义（P＜0.05）。结论 火针联合卤米松乳膏治疗不仅能有效促进稳定期白癜风患者皮肤恢复正常肤色,提高有效率,且能调节患者T淋巴细胞亚群,提高患者细胞免疫功能。因此火针是一种安全、高效的治疗方法,值得临床推广。     

Poikilodermatous mycosis fungoides with a CD8+ CD56+ immunophenotype: a case report and literature review

Mycosis fungoides (MF) represents the most common type of cutaneous lymphoma. MF shows varieties in both its clinical presentation and immunophenotype. We herein report one case of poikilodermatous MF with a CD8+ CD56+ immunophenotype and present a literature review. A 20‐year‐old Japanese woman presented with a 10‐year history of multiple poikilodermatous and reddish or brownish patches with mild pruritus on the chest, abdomen, back, buttock and thighs. Histopathologically, small‐ to medium‐sized atypical lymphocytes infiltrated into the epidermis, indicating epidermotropism, along the basal layer, and distributed in band‐like appearance in the papillary dermis. Immunohistochemically, atypical lymphocytes expressed CD3, CD8, CD56, T‐cell intracellular antigen (TIA)‐1, granzyme B and beta F1 but lacked expression of CD4, CD20, CD30 and Epstein‐Barr virus (EBV) latent membrane protein 1. An EBV‐encoded small non‐polyadenylated RNA‐1 (EBER‐1) signal was not detected. On the basis of these findings, the diagnosis of CD8+ CD56+ MF was established. Poikilodermatous MF with a CD8+ CD56+ immunophenotype, as presented herein, is extremely rare. Although further investigation is needed to fully clarify the nature of this aberrant phenotype of MF, we stress that it is important to recognize this rare immunophenotype of MF to distinguish it from aggressive cytotoxic cutaneous lymphomas.     

40 nm, but not 750 or 1,500 nm, nanoparticles enter epidermal CD1a+ cells after transcutaneous application on human skin

Although conventional vaccines have generated major successes in the control of infectious diseases, several obstacles remain in their development against chronic diseases (HIV, tuberculosis), against which no current candidate vaccines yet ensure protection. The transcutaneous route of vaccine administration appears to be a promising approach of targeting vaccines toward antigen-presenting cells (APCs) and thus improving immune responses. We investigated the suitability of nanoparticles in this approach. We found a high density of Langerhans cells (LCs) around hair follicles that, when sorted, readily internalized all size particles. However, flow cytometry after transcutaneous application of 40, 750, or 1,500 nm nanoparticles on human skin samples revealed that only 40 nm particles entered epidermal LC. Fluorescence and laser scan microscopies, which were carried out to identify the penetration pathway of transcutaneously applied nanoparticles, revealed that only 40 nm particles deeply penetrate into vellus hair openings and through the follicular epithelium. We conclude that 40 nm nanoparticles, but not 750 or 1,500 nm nanoparticles, may be efficiently used to transcutaneously deliver vaccine compounds via the hair follicle into cutaneous APCs.     

Plasmacytoid dendritic cells: an overview of their presence and distribution in different inflammatory skin diseases,with special emphasis on Jessner's lymphocytic infiltrate of the skin and cutaneous lupus erythematosus

Background: Plasmacytoid dendritic cells (PDC) play a pivotal role in the induction of autoimmune diseases and other skin diseases. The present study focuses on the distribution patterns of PDC in patients with cutaneous lupus erythematosus (LE) and Jessner's lymphocytic infiltrate (LI) of the skin and compares them with other skin diseases. The goal was to scrutinize the involvement of PDC in LI, and to show that PDC present a specific pattern of distribution in various cutaneous disorders. Methods: 353 skin biopsies of LE (various subtypes), LI, and other inflammatory skin diseases as well as two halo melanocytic nevi and 10 epithelial tumors were immunohistochemically investigated for the presence of PDC by employing antibodies against CD123 and CD2AP. Results: PDC were constantly detected as distinct perivascular and periadnexal clusters in LE and LI. In other forms of dermatitis, PDC could be found as single cells or scattered throughout the infiltrate or beneath the epidermis. Conclusions: Our data suggest that the distribution of PDC in tumid LE and LI is identical, and this observation suggests that both designations signify one disease. The distinct PDC arrangement in LE represents as useful diagnostic tool in the differential diagnosis with other forms of dermatitis. Tomasini D, Mentzel T, Hantschke M, Cerri A, Paredes B, Rütten A, Schärer L, Kutzner H. Plasmacytoid dendritic cells: an overview of their presence and distribution in different inflammatory skin diseases, with special emphasis on Jessner's lymphocytic infiltrate of the skin and cutaneous lupus erythematosus.     

早期隐性梅毒对慢性HIV感染者CD4+T及CD8+T淋巴细胞内Caspase-1/3水平的影响

目的：明确早期隐性梅毒感染对HIV感染者CD4+T及CD8+T细胞Caspase-1/3水平的影响。方法：流式细胞仪检测18例早期隐性梅毒合并慢性HIV感染者（合并组）以及18例单纯慢性HIV感染者（HIV组）CD4+T及CD8+T细胞内Caspase-1(细胞焦亡标志物)和Caspase-3(细胞凋亡标志物)含量。驱梅治疗6个月后再检测合并组CD4+T及CD8+T细胞内Caspase-1/3含量,与治疗前进行比较。结果：与单纯HIV感染组比较,合并组CD4+T及CD8+T细胞中Caspase-1升高（均P＜0.05）,Caspase-3含量无统计学差异（均P＞0.05）。与治疗前比较,合并组驱梅治疗6个月后,CD4+T及CD8+T细胞中Caspase-3明显下降（均P＜0.05）,Caspase-1含量治疗前后无统计学差异（均P＞0.05）。结论：合并梅毒螺旋体感染可能影响HIV感染者CD4+T和CD8+T淋巴细胞的焦亡和凋亡。