Primary immunodeficiency diseases: a clinicopathological analysis of 3 cases

目的 探讨原发性免疫缺陷性疾病(primary immunodeficiency diseases,PID)的临床表现与病理学特征.方法 回顾分析3例PID的临床与病理资料,结合临床表现、实验室检查资料和免疫组化染色与组织化学染色明确诊断.结果 3例PID包括慢性肉芽肿病、高IgE综合征和T细胞缺乏合并弓形虫感染,患者均经历反复性、难治性感染,病理诊断及鉴别诊断中详细结合临床资料和实验室检查后才最终确诊.结论 PID是一类发病率低、与遗传相关的免疫缺陷性疾病,容易被临床和病理医师忽视,早期确诊此类疾病有助于患者获得正确治疗.     

原发性免疫缺陷病的实验室诊断

原发性免疫缺陷病(PIDs)是一类罕见的疾病,主要表现为发育、成熟及免疫功能细胞方面的异常.受累个体对反复性感染、变态反应、自身免疫性疾病和恶性肿瘤易感.目前,已鉴定出至少95种免疫缺陷病[1].反复感染仅是诊断PID的重要线索,确诊有赖于实验室检查.本文就PID实验室检查的一般原则及各种类型PID的实验室表现作一介绍.     

原发性免疫缺陷病的实验室诊断

原发性免疫缺陷病（PIDs）是一类罕见的疾病，主要表现为发育、成熟及免疫功能细胞方面的异常。受累个体对反复性感染、变态反应、自身免疫性疾病和恶性肿瘤易感。目前，已鉴定出至少95种免疫缺陷病。反复感染仅是诊断PID的重要线索，确诊有赖于实验室检查。本文就PID实验室检查的一般原则及各种类型PID的实验室表现作一介绍。     

易误诊为周围型肺癌的肺真菌病影像和病理学分析

目的分析术前误诊为周围型肺癌的肺部真菌病患者临床表现、影像学检查和病理组织学检查特征,探讨误诊原因,提高深部真菌病的诊治水平。方法回顾性分析24例肺部真菌肿块误诊为周围型肺癌患者的临床、影像和病理资料。结果 24例肺部周围型真菌性肿块患者术前均未发现糖尿病、自身免疫性疾病、免疫缺陷性疾病和其它器官恶性肿瘤,临床及影像均诊断为周围型肺癌或高度疑似为周围型肺癌,行肺段切除或肺叶切除术,术后病理诊断为肺曲霉菌病8例、肺隐球菌病14例、组织胞浆菌病1例和孢子丝菌病1例。结论无其它基础性疾病且免疫功能正常者出现的周围型肺部肿块,不能过分依赖或单凭影像学表现诊断为肺癌,肺隐球菌病和曲霉菌病是周围型肺肿块常见的肺部真菌病,术前穿刺活检可避免误诊。     

肝移植术后淋巴组织增生性疾病的临床病理分析

目的探讨肝移植术后淋巴组织增生性疾病（PTLD）的临床病理特征。方法对3例肝移植术后PTLD行HE、免疫组织化学染色及TCR、IgH基因重排检测,同时复习其临床资料并随访。结果3例中,2例位于肝门部,1例位于肝动脉旁淋巴结。临床表现为发热和梗阻性黄疸。病理诊断例1为单形性T细胞PTLD的周围T细胞淋巴瘤,例2、例3为单形性B细胞PTLD的淋巴浆细胞样淋巴瘤和弥漫大B细胞淋巴瘤。基因重排检测例1 TCR阳性,例2、例3 IgH阳性。3例EBV免疫组化染色均阳性。行再次移植降低免疫抑制剂用量并配合抗病毒、抗CD20单抗和化疗等治疗,例1、例3分别于术后6个月和4个月死于淋巴瘤复发和肺感染,例2随访11个月无瘤生存。结论PTLD是肝移植术后严重的并发症之一,具有独特的形态和临床特征。病因可能与EB病毒感染和免疫抑制有关,需经病理组织学检查确诊。     

人类免疫缺陷病毒感染患者临床特点分析

目的 探讨人类免疫缺陷病毒(HIV)感染后对人体的影响,为研究该病的临床特征提供和积累经验.方法 回顾性分析2013年3月至2014年3月曲靖市第一人民医院确诊HIV感染50例患者的临床表现和相关实验室检查指标.结果 50例HIV感染患者均合并其他感染,以结核感染最为常见,除有T淋巴细胞异常外,所有患者均出现血液学异常,其中贫血、白细胞异常、血小板降低常见;HIV感染患者可合并出现自身免疫症状和全身症状.结论 HIV感染患者临床表现复杂多样可合并出现多种感染和自身免疫情况异常、血液学及免疫学异常均较常见.     

27例重症肌无力患者的记忆功能测评

随机选择27例重症肌无力(MG)患者作为病例组(其诊断主要依据临床表现及实验室检查,用常规病理方法检查确诊).     

中、晚期肾结核40例临床分析

目的探讨中晚期肾结核的临床表现特征及其有效治疗方法。方法对40例中晚期肾结核患者的临床资料进行回顾性分析。对所有患者进行尿常规、红细胞沉降率、尿抗酸杆菌、尿结核杆菌-PCR（Tb—PCR）、B超、静脉尿路造影（IVU）、CT等检查，8例患者行药物治疗，32例患者行手术治疗。结果临床表现为腰痛18例（45％），膀胱刺激症24例（60％），血尿28例（70％）。尿常规检查异常38例（95％），红细胞沉降率异常升高36例（90％），尿抗酸杆菌阳性11例（27．5％），尿结核杆菌-PCR（Tb—PCR）阳性18例（45％）。B超检查肾积水、肾结石或／和肾结构异常40例（100％）；静脉尿路造影（IVU）确诊肾结核23例（57．5％），患肾不显影17例（42．5％）；CT确诊肾结核31例（77．5％）。肾结核合并膀胱结核16例，肺结核5例，附睾结核8例。8例患者药物治疗治愈，32例患者手术后经病理确诊为肾结核。结论中晚期肾结核的临床表现多不典型，其诊断应在结合临床表现的前提下以实验室检查与影像学诊断为主。尿沉渣染色查抗酸杆菌仍重要，尿Tb-PCR检查是术前确诊肾结核的主要手段．IVU和B超可作为泌尿系结核诊断首选的影像学检查，治疗仍以手术切除肾脏为主，应尽可能切除患侧全程输尿管。     

单中心174例原发性免疫缺陷病临床预警症状的初步探讨

目的分析并总结原发性免疫缺陷病（PID）患儿的临床感染特征和预警症状,了解预警症状对PID早期识别的应用价值。方法参考2011年免疫学会国际联合会（IUIS）PID分类委员会公布的方案、泛美免疫缺陷病组（PAGID）和欧洲免疫缺陷病协会（ESlD）提出的PID诊断和分类标准,在首都医科大学附属北京儿童医院2000年10月至2011年11月病例检索系统检索出院诊断中含有上述PID分类疾病的病历,对于诊断低丙种球蛋白血症和联合免疫缺陷的患儿除外继发性免疫缺陷病,逐份查阅病历重新诊断,并做出明确、可以和可能诊断,以明确、可以诊断的病例进行预警症状的分析。结果①174例PII）患儿进入分析,男女比例为4．4：1,其中抗体缺陷为主的免疫缺陷101例（58．0％）,严重联合免疫缺陷病（SCID）34例（19．5％）,吞噬细胞功能缺陷19例（10．9％）,定义明确的免疫缺陷综合征10例（5．7％）,免疫失调性疾病10例（5．7％）。渤5例（43．1％）存在反复呼吸道感染,以抗体缺陷为主的免疫缺陷最为常见,与SCID间差异有统计学意义;卡介苗接种后异常反应在慢性肉芽肿病（CGD）中最多见,与抗体缺陷为主的免疫缺陷和SCID比较差异有统计学意义;腹泻病在定义明确的免疫缺陷综合征中较常见,败血症在SCID和CGD患儿中较常见,但PID各类型间比较差异无统计学意义。③72例（41．4％）患儿存在营养发育落后,PID各类型间差异无统计学意义;淋巴结、肝和脾肿大以CGD和免疫失调性疾病最为常见;鹅口疮在SCID中常见,与抗体缺陷为主的免疫缺陷差异有统计学意义;肛周脓肿以CGD多见,与其他PID类型比较差异有统计学意义。107例（61．5％）有明确微生物学证据。④PID患儿共电话随访到85例（48．8％）,其中死亡28例（32．9％）。⑤124例为明确和可以诊断PID,其中106例（85．5％）具备〉12条预警症状。静脉应用抗生素清除病灶（96．0％）、体重不增或生长发育极度迟缓（41．1％）、反复呼吸道感染（41．9％）和P1D家族史（22．6％）在不同类型PID中均占有较高的比例。结论预警症状对PID有着很好的提示作用,需要静脉应用抗生素清除病灶、体重不增或生长发育极度迟缓和PID家族史对PID有预警意义,中耳炎、中枢神经系统感染和反复呼吸道感染在抗体缺陷为主的免疫缺陷中较为多见,深部脓肿、卡介苗接种后异常反应对CGD有预警意义。慢性反复发作性腹泻对PID预警作用值得进一步关注。     

肺隐球菌病25例临床病理分析

目的探讨肺隐球菌病(PC)的临床和病理特征及其鉴别诊断。方法对25例PC手术标本进行常规HE染色及淀粉酶消化后过碘酸雪夫(D-PAS)、黏液卡红(MC)和Gorcott六胺银(GMS)特殊染色,观察PC在组织中的形态特点,并结合相关文献进行讨论。结果25例中,男16例,女9例,年龄18～52岁,平均36岁。人类免疫缺陷病毒抗体(HIV-Ab)阳性3例。胸部影像学检查:18例表现为单发或多发肺部结节,7例表现为片状实变影。25例均经胸腔镜活检手术切除,病理检查确诊。HE染色:多核巨细胞内外见大量淡蓝色圆形或卵圆形隐球菌菌体,具有折光性强的胶样荚膜;D-PAS、MC及GMS特殊染色:隐球菌菌体呈紫红色、鲜红色和黑色,更清晰。结论PC多由新型隐球菌引起,其临床及影像学表现缺乏特异性,易误诊和漏诊;组织病理学检查及特殊染色,PC具有典型的形态结构,是确诊本病的重要手段。     

Autoimmune and Inflammatory Manifestations in 247 Patients with Primary Immunodeficiency—a Report from the Slovenian National Registry

An abnormal regulation of immune responses leads to autoimmune and inflammatory manifestations in patients with primary immunodeficiencies (PIDs). The objective of our study was to evaluate the frequency of non-infectious and non-malignant manifestations in a large cohort of patients included in the Slovenian national PID registry and to assess the time of manifestation onset with respect to the time of PID diagnosis. Medical records of registered patients were reviewed. Data on autoimmunity, lymphoproliferation, autoinflammation, allergies, PID diagnosis, and underlying genetic defects were collected and analyzed. The time of each manifestation onset was determined and compared with the time of PID diagnosis. As of May 2015, 247 patients with 50 different PIDs were registered in the Slovenian national PID registry (147 males, 100 females; mean age 20 years). Mean disease duration was 14 years; 78 % of patients were younger than 18 years; and 22 % of patients were adults. Diagnosis of PID was genetically confirmed in 51 % of patients. Non-infectious and non-malignant manifestations were present in 69/235 (29 %) patients, including autoimmune manifestations in 52/235 (22 %), lymphoproliferative/granulomatous in 28/235 (12 %), autoinflammatory in 12/247 (5 %), and allergic manifestations in 10/235 (4 %) of all registered patients. Autoimmune manifestations were present in all patients whose PIDs were classified as diseases of immune dysregulation, 47 % of patients with chronic granulomatous disease, and 38 % of patients with predominantly antibody immune deficiencies. A high prevalence of non-infectious and non-malignant manifestations among patients in the Slovenian national PID registry suggests common genetic factors of autoimmunity, inflammation, and immunodeficiency. Patients with PID should be routinely screened for autoimmune and inflammatory manifestations at the time of PID diagnosis and during the long-term follow up.     

Distribution and Clinical Features of Primary Immunodeficiency Diseases in Chinese Children (2004–2009)

Two hundred and one patients have been diagnosed with primary immunodeficiency diseases (PIDs) in our center from January 2004 to December 2009. The male-to-female ratio was 5.29:1. Spectrums of PIDs were as follows: predominantly antibody deficiency disease was the most common category (94 patients, 48.2%), followed by other well-defined immunodeficiency syndromes (40 patients, 20.5%), combined T and B cell immunodeficiencies (33 patients, 16.9%), congenital defects of phagocyte number and/or function (21 patients, 10.8%), and diseases of immune dysregulation (six patients, 3.1%). Agammaglobulinemia was the most frequent disease type. The median of diagnosis lag was 18.0 months. Pneumonia was the most common manifestation of PID patients. Some manifestations were prone to concentrate in certain diseases. As for therapy, 99 patients (50.8%) received intravenous immunoglobulin replacement therapy; 13 patients received hematopoietic stem cell transplantation and nine of them were still alive. In this study, we sought to describe and analyze the distribution, clinical features, and therapy methods of PIDs among children diagnosed in our country and to compare with reports from other countries and regions.     

Primary Immune Deficiencies Presenting in Adults: Seven Years of Experience from Iran

Primary immunodeficiencies (PIDs) are not solely diseases of childhood. We describe the clinical presentation and outcome for 55 adult patients with previously unrecognized PIDs. This series provides unique data regarding PIDs presenting in adulthood, and serves as a timely reminder that physicians must consider the diagnosis of PIDs in their adult patients. Using the experience gained from these patients, we outline key “warning signs” suggestive of an underlying PID. Only through increased physician awareness will patients with PIDs receive timely diagnosis and optimal management.     

Analysis of scoring systems for primary immunodeficiency diagnosis in adult immunology clinics

Failure to spot the signs of primary immunodeficiency (PID) often results in delayed diagnosis. Scoring systems to identify PID exist, such as the immunodeficiency disease‐related (IDR) score. This research aims to analyse and improve the diagnostic sensitivity and specificity of the IDR scoring system in a small preselected group of adult patients referred to immunology with clinical suspicion of a PID. Records of all patients presenting for the first time to an adult immunology clinic in 2018 at Addenbrooke’s Hospital, Cambridge, were scored using the unmodified IDR score and modified versions of it. Included records were searched for a subsequent diagnosis of PID, and the diagnostic sensitivity and specificity of the scoring systems were analysed. Of 400 patients, 213 were excluded: 141 due to secondary immunodeficiency, 69 due to no clinical suspicion of a PID, and hence no investigation for PID, and three due to ongoing diagnostic investigations. Of 187 included patients, 71 were found to have a clinically significant PID. The unmodified IDR score was useful in discriminating between those with and without PID. Modification of the scoring system with seven additional criteria improved the sensitivity and specificity for PID diagnosis to the greatest extent. A modified IDR score with seven additional criteria validated in adults referred to immunology with suspicion of a PID could be used clinically to aid PID diagnosis, although further validation in different patient cohorts is required before it is used in other contexts.     

Importance of the confirmatory diagnosis in viral exanthematic diseases in Zulia State, Venezuela: a review of the problem

A great variety of viruses which cause exanthema share other clinical manifestations, making etiologic identification relying exclusively on clinical examination a very difficult task. The most common agents include the measles virus, rubella, dengue, varicella, cytomegalovirus, Epstein Barr, enteroviruses, human parvovirus B19 and type 6 human Herpes virus. The fact that most these diseases are self limited represents an important challenge to the development of clinical and epidemiological resources, identification of new infectious agents, monitor changes in their behavior, and to evaluate the impact of immunization on the modification of viral disease with cutaneous manifestations that are considered along whit classical exanthematic pathology, and specially the macullopapular type. In spite the fact that viral exanthematic diseases are common in Zulia state, several difficulties are encountered in order to determine a precise etiologic diagnosis. Even though some are fairly benign and self limited, some represent an important risk to certain age groups, gravid and immunocompromized patients, since they can progress to more serious processes. Therefore it is of great importance to ascertain the etiological diagnosis that might be implicated with viral exanthematic diseases in order to guarantee an adequate treatment and to establish the required measures for disease control.     

1型自身免疫性胰腺炎的流行病学及临床特点

目的总结自身免疫性胰腺炎(AIP)的流行病特征、临床表现和诊断经验,提高诊治水平。方法回顾性分析了北京协和医院自1998年1月至2016年12月所有确诊为AIP的临床资料。结果共纳入194例1型AIP。该病发病的男女比例为3.51/1,平均发病年龄为(57±15)岁。最常见的症状是黄疸和腹痛等。最常见的胰腺外受累疾病是硬化性胆管炎、涎腺炎和IgG4肾病。36.68%AIP患者合并糖尿病。IgG4、ANA、ESR、C反应蛋白和CA199均有助于疾病诊断和病情判断。病理、pet-CT和激素治疗反应均有助于AIP的诊断。结论作为一种系统性疾病的胰腺表现,1型AIP有特殊的临床特点和实验室检查特点。AIP的诊断可应用多种检测手段和方法。     

Ocular Involvement in Primary Immunodeficiency Diseases

Primary immunodeficiency diseases (PID) are a group of inherited disorders characterized by recurrent infections, and in many cases autoimmunity and malignancies. A number of PID patients suffer from a variety of ocular manifestations. Although these associated ocular features are not common, awareness combined with better understanding of the contributing mechanisms will allow prompt diagnosis and specific treatment, leading to reduction or prevention of serious visual morbidities.     

Comprehensive Report of Primary Immunodeficiency Disorders from a Tertiary Care Center in India

Objectives

There is paucity of data on Primary immunodeficiency disorders (PID) from India. Here we describe the frequency of different primary immunodeficiency disorders, their clinical features and disease complications of 159 patients with PID diagnosed in a tertiary care center from India over the last 3 years.

Methods

We retrospectively reviewed the records of all the patients identified to have specific PID from 2008 to 2011. The diagnosed patients were classified according to guidelines of International Union of Immunological Society (IUIS) into eight different sub groups.

Results

The distribution pattern was as follows: diseases of immune dysregulation (29 %), phagocytic defects (29 %), predominant antibody deficiency (13 %), combined T and B cell deficiency (19 %) and other well defined diseases (10 %).

Conclusion

The distribution pattern of PID varied significantly from those reported by western studies. This study highlights the need for development of more advanced facilities for diagnosis and management of PID in India and also the need for establishing population and hospital based registries.     

Clinical Features,Non-Infectious Manifestations and Survival Analysis of 161 Children with Primary Immunodeficiency in Mexico: A Single Center Experience Over two Decades

Purpose

The hallmark of Primary immunodeficiencies (PID) is unusual infection, although other immunological non-infectious manifestations such as autoimmunity, allergy and cancer are often present. Most published reports focus on one disease or defect groups, so that a global prevalence of non-infectious manifestations of PID is hard to find. We aimed to describe the clinical features of our pediatric patients with PID, as well as the frequency and evolution of allergy, cancer and autoimmunity.

Methods

We reviewed all the available charts of patients being followed for PID from 1991 to the spring of 2012 at the National Institute of Pediatrics, Mexico City, to describe their demographic, clinical and laboratory features. Their diagnoses were established by pediatric immunologists in accordance to ESID criteria, including routine immunological workup and specialized diagnostic assays. We divided patients by decade of diagnosis to analyze their survival curves.

Results

There were 168 charts available, from which we excluded one duplicate and six equivocal diagnoses. We studied the charts of 161 PID patients (68 % male, 86 % alive), mostly from the center of the country, with a positive family history in 27 % and known consanguinity in 11 %. Eighty percent of the patients were diagnosed during the last decade. Current median age was 124 months; median age at onset of infections, 12 months; median age at diagnosis, 52 months; median age at death, 67.5 months. Severe infection and bleeding were the cause of 22 deaths. Eighty-six percent of all patients had at least one infection, while non-infectious manifestations had a global prevalence of 36 %, namely: autoimmunity 19 %, allergies 17 %, and cancer 2.4 %. Survival curves were not significantly different when compared by decade of diagnosis.

Conclusions

Compared to other registry reports, we found a lower prevalence of antibody defects, and of associated allergy and cancer. We could only locate two isolated IgA deficiencies and four cases of cancer among our PID patients. Although antibody defects are the most prevalent group (30 %), the distribution we found is similar to that reported in Iran, Kuwait, Egypt and Taiwan, with a close 27 % share for phagocyte defects, and 26 % for the formerly called “well-defined” syndromes. Of note, autoimmune and inflammatory complications are high among our patients with chronic granulomatous disease, as has been reported in both the United States and Japan, but not in Europe.

     

Primary Immunodeficiency Diseases in Australia and New Zealand

INTRODUCTION: Despite rapid developments in the science of primary immunodeficiency diseases (PID), population characteristics and the burden of disease are poorly characterized. Aggregated data on PID via patient registries are a key component of the public health response. The web-enabled Australasian Society of Clinical Immunology and Allergy PID Register was designed and implemented to address gaps in knowledge of PID. METHODS: The register provided a cumulative, cross-sectional survey of PID patients in Australia and New Zealand via an online, single time point, center-based, voluntarily recalled, and patient-consented questionnaire. RESULT: Eighty-eight centers reported 1,209 patients across 56 separate PID syndromes. The study prevalence (cases per 100,000 population) was 5.6 for Australia, 12.4 for the state of South Australia, and 4.9 for Australia and New Zealand combined. Predominately antibody deficiency syndromes accounted for 77% of patients. Common variable immunodeficiency was the most common diagnosis. Patients were geographically dispersed with 80% of centers reporting caseloads of less than 20 patients. Potentially preventable complications of disease were common. Immunoglobulin replacement therapy was used in 30 conditions with 26.5% of the total recipients having antibody deficiency disorders with normal serum IgG. CONCLUSION: PID in Australia and New Zealand are prevalent, clinically diverse, geographically dispersed, and are characterized by high rates of potentially preventable morbidity and resource utilization. A public health focus on PID is required, including strategies to correct disparities in access to care, improve molecular diagnostics and reduce preventable complications of disease. Further studies in antibody deficiency syndromes with normal serum IgG are required.