Das entzündliche Immunrekonstitutionssyndrom

Overwhelming immune reaction resulting in granulomatous inflammation after infection with opportunistic pathogens has been termed immune reconstitution inflammatory syndrome (IRIS). IRIS has mainly been described in patients with human immunodeficiency virus (HIV). However, IRIS is not restricted to HIV-patients and may occur in other infections and immunodeficiencies. In our clinic, we experienced a Whipple's disease patient with IRIS. IRIS occurs mainly after initiation of the highly active anti-retroviral therapy (HAART). Soon after HAART initiation, a marked inflammatory reaction can occur, triggered by restoration of pathogen-specific immunity. IRIS may be targeted by various infective antigens, dead or dying infective antigens, host antigens, tumor antigens and other antigens, giving rise to a heterogenous range of clinical manifestations. Treatment should be optimized for the associated condition and initiated immediately. Glucocorticoids should be used in patients who are severely affected by IRIS.     

Cryptococcal immune reconstitution inflammatory syndrome: report of four cases in three patients and review of the literature

Immune reconstitution inflammatory syndromes (IRIS) in patients with AIDS are characterized by atypical manifestations of opportunistic pathogens in patients experiencing improvement in CD4 cell counts following receipt of highly active anti-retroviral therapy (HAART). We report four cases of IRIS due to Cryptococcus neoformans in three patients and review the literature of cryptococcal IRIS in AIDS (an additional 21 episodes). The IRIS presentation was lymphadenitis in all three patients; one patient also had meningeal IRIS. Combining our patients with the literature review revealed the following IRIS presentations: lymphadenitis (n=14), central nervous system (CNS) IRIS (n=10): meningitis in six and mass lesions in four, and pulmonary cavities (n=1). The median CD4 count of cases at the time of initial cryptococcal diagnosis and prior to the start of HAART was 25 cells/μl and the median HIV viral load was 439 053 copies/ml. At time of presentation of the IRIS, the median CD4 count had increased by 197 cells/μl. The median time from initial cryptococcal diagnosis and the start of HAART to the IRIS was 11 months (range 7 weeks to 3 years) and 7 months (range <2 weeks to 22 months), respectively. Patients with CNS IRIS tended to have shorter intervals from initiation of HAART to presentation compared to patients with lymphadenitis: median 3.5 months compared to 7 months. In 24 of 25 cases, the clinical manifestations of the IRIS resolved (range: days to months). Only four patients were given anti-inflammatory medications: corticosteroids in two and non-steroidal anti-inflammatory drugs in two, thus precluding assessment of efficacy. Patients with cryptococcal disease who initiate HAART are at risk for cryptococcal IRIS.     

Immune reconstitution inflammatory syndrome in the first year after HAART: influence on long-term clinical outcome

Little is known about the effect of immune reconstitution inflammatory syndrome (IRIS) on the long-term clinical outcome. Of 52 opportunistic infections (OI) occurring within one year after the start of HAART in 387 HIV patients, 33 (63%) were classified as having IRIS. The patients with IRIS showed no significant difference in the AIDS event-free survival curve compared with the matched control group without OI and in contrast to non-IRIS OI.     

Pulmonary complications of immune reconstitution inflammatory syndromes in HIV-infected patients

Immune reconstitution inflammatory syndrome (IRIS) describes a paradoxical worsening of clinical status related to recovery of the immune system, as can occur after the initiation of highly active antiretroviral therapy (HAART) in HIV-infected patients. Most commonly, IRIS results from opportunistic infections that can unmask or develop paradoxical worsening following HAART. Cancers, autoimmune conditions and sarcoidosis have also been associated with IRIS. Pulmonary complications may be frequently encountered. This article reviews the types and clinical presentation of IRIS, with a focus on the pulmonary manifestations. Management and outcome of IRIS are considered.     

Risk factors for immune reconstitution inflammatory syndrome under combination antiretroviral therapy can be aetiology-specific

In order to discriminate general from aetiology-specific risk factors for immune reconstitution inflammatory syndrome (IRIS), we followed up, during six months, 99 patients with advanced HIV infection commencing antiretroviral therapy (ART) without active opportunistic infections or evident inflammation. IRIS predictors were determined by univariate analysis using clinical data from 76 ART-responding patients either completing follow-up or developing IRIS, and by multivariate analysis of inflammation, disease progression and nutrition status variables. We identified 23 primary IRIS events (30.3%). Univariate predictors for all IRIS events were higher platelet counts and lower CD4/CD8 ratio, whereas subclinical inflammation was the multivariate predictor. Platelets, alkaline phosphatase levels and %CD8 T-cells in univariate analysis also predicted mycobacteria-associated IRIS independently, remaining elevated during follow-up. Herpesvirus IRIS was predicted by platelets and inflammation. Indicators of advanced HIV disease and subclinical inflammation jointly predict IRIS, and some are specific of the underlying microbial aetiology, possibly explaining previous reports.     

Soft tissue abscess and lymphadenitis due to Mycobacterium avium complex as an expression of immune reconstitution inflammatory syndrome after a second scheme of highly active antiretroviral therapy

Immune reconstitution inflammatory syndrome (IRIS) is an atypical and unexpected reaction related to highly active antiretroviral therapy (HAART) in human immunodeficiency virus (HIV) infected patients. IRIS includes an atypical response to an opportunistic pathogen (generally Mycobacterium tuberculosis, Mycobacterium avium complex, cytomegalovirus and herpes varicella-zoster), in patients responding to HAART with a reduction of plasma viral load and evidence of immune restoration based on increase of CD4+ T-cell count. We reported a case of a patient with AIDS which, after a first failure of HAART, developed a subcutaneous abscess and supraclavicular lymphadenitis as an expression of IRIS due to Mycobacterium avium complex after starting a second scheme of HAART.     

The Immune Reconstitution Inflammatory Syndrome: A Clinical Update

The immune reconstitution inflammatory syndrome (IRIS) is a well-described phenomenon in HIV-infected patients following initiation of antiretroviral therapy and can lead to significant morbidity and mortality in some patients. Risk for IRIS is enhanced in those with low CD4 counts and preexisting opportunistic infections. The development of pathogen-specific definitions of IRIS has aided classification of patients and has facilitated research. Newer data on optimal timing of ART initiation, with additional data in the setting of tuberculosis and cryptococcal meningitis, will help guide strategies to decrease the risk of IRIS but must balance the risks of HIV disease progression. Managing patients with IRIS can be challenging. Treatment options include pathogen-specific therapy, antiinflammatory therapies, and other novel approaches.     

Incidence and risk factors of immune reconstitution inflammatory syndrome complicating HIV-associated cryptococcosis in France

BACKGROUND: Immune reconstitution inflammatory syndrome (IRIS) in association with cryptococcosis has been anecdotically reported following administration of highly active antiretroviral therapy (HAART). OBJECTIVE: To analyse the incidence and risk factors for IRIS-associated cryptococcosis among HIV-infected patients. DESIGN: Retrospective multicentre study between 1996 and 2000 through the French Cryptococcosis Database. METHODS: Subsequent occurrence of IRIS examined in 120 HIV-infected adult patients treated with HAART and experiencing a first episode of culture-confirmed cryptococcosis. RESULTS: Ten patients developed IRIS during the study period, giving an incidence of 10/239, or 4.2/100 person-years [95% confidence interval (CI), 2.2-7.8]. IRIS consisted of acute symptoms consistent with inflammation occurring within a median of 8 months (range, 2-37) after the diagnosis of cryptococcosis in the context of negative cultures and immunological and/or virological response to HAART. Radiology and histopathology detected features compatible with inflammation. Symptom severity required transfer into intensive care units for three patients and use of anti-inflammatory drugs for four. Three patients with evolutive IRIS died. Compared with patients without IRIS for whom complete clinical and microbiological information were available at baseline, previously unknown HIV infection [odds ratio (OR), 4.8; 95% CI, 1.0-21.7], CD4 cell count < 7 x 10 cells/l (OR, 4.0; 95% CI, 0.9-17.2), fungaemia (OR, 6.1; 95% CI, 1.1-35.2) and HAART initiation within 2 months of cryptococcosis diagnosis (OR, 5.50; 95% CI, 1.0-29.6) were independently associated with the risk of subsequent IRIS. CONCLUSIONS: IRIS-related cryptococcosis was observed more frequently in severely immunocompromised patients with disseminated infection and HAART initiation soon after the diagnosis.     

Acute peritonitis as presentations of tuberculosis-associated immune reconstitution inflammatory syndrome in an HIV-infected man

Immune reconstitution inflammatory syndrome (IRIS) is particularly observed after the start of therapy for pathogenic antigens in patients infected with human immunodeficiency virus (HIV) and receiving highly active antiretroviral therapy (HAART). Although tuberculosis (TB)-associated IRIS is the most common form, its presentation as a primary feature of acute peritonitis is extraordinarily rare. We report a 43-year-old man diagnosed with acquired immunodeficiency syndrome and pulmonary TB coinfection. His symptoms, sputum quantity, and chest radiologic appearance improved markedly after 3 weeks of antituberculous therapy, and HAART was initiated on the fourth week. However, acute abdomen with peritoneal signs resulting from the established tuberculous peritonitis developed on the seventh day of HAART. His clinical symptoms resolved after maintenance of HAART and antituberculous regimens. Tuberculous peritonitis must be considered in the differential diagnosis of acute abdomen in HIV-infected patients on antiviral therapy, especially in patients with known underlying TB. Early recognition of IRIS is important when managing HIV-infected patients with opportunistic infections.     

126例HIV/结核分枝杆菌合并感染临床观察

目的 观察治疗HIV/结核分枝杆菌(Mycobacterium tuberculosis, MTB)合并感染的临床疗效. 方法 分析126例HIV/MTB合并感染者的临床疗效,统计高效抗反转录病毒治疗(highly active antiretroviral therapy, HAART)后1年内免疫重建炎症反应综合征(immune reconstitution inflammatory syndrome, IRIS)发病率及CD4+T淋巴细胞上升水平. 结果 126例均完成了抗结核治疗,HAART 1年内无死亡及复发结核病例. HAART后CD4+T淋巴细胞计数逐渐升高,以12周时上升幅度最大.治疗过程中37 例(29.37%)出现IRIS.CD4+ T 淋巴细胞计数＜200 个/mm3组IRIS 发病率高于≥200 个/mm3组（χ2=6.206,P=0.013）,且在HAART 后12 周及48 周CD4+ T 淋巴细胞上升幅度低于≥200 个/mm3组（P＜0.05）.结论HIV/MTB 合并感染者在CD4+ T 淋巴细胞≥200 个/mm3时接受HAART,IRIS 发病率低,免疫重建良好.     

艾滋病抗病毒治疗后机会感染的变化和分布状况

目的探讨艾滋病(AIDS)抗病毒治疗后机会感染疾病谱的变化及分布状况。方法采用回顾性分析的方法,对2006年9月-2008年12月期间,在郑州市第六人民医院接受门诊及住院治疗的128例HIV/AIDS病人,抗病毒治疗前后机会感染发生情况进行总结分析。结果 (1)128例HIV/AIDS病人中,高效抗反转录病毒疗法(HAART)治疗3-12月期间共发生100例次机会感染,主要为呼吸系统(46.09%)和消化系统(11.72%)感染,其中前4位机会感染是细菌性肺炎(29.69%)、肺结核(9.38%)、口腔念珠菌感染(7.81%)、带状疱疹(3.91%);与HAART治疗前相比,治疗后机会感染中细菌性肺炎、肺结核占绝大多数(86.46%),存在一定比例的口腔念珠菌感染和带状疱疹,AIDS晚期常见的机会感染如肺孢子菌肺炎、感染性腹泻及消耗综合征、中枢神经系统病变发病明显减少。(2)128例HIV/AIDS病人HAART治疗前机会感染发病率为80.47%,治疗后3-6月时下降至28.13%,治疗6-12月时为25.89%,3组相比差异有统计学意义(P<0.05)。HAART治疗后同时合并多种机会感染的病例减少。结论 HAART治疗后的机会感染发病率明显下降,机会感染疾病谱较治疗前有所不同,同时合并多种机会感染的几率减少。     

Reactive hemophagocytosis associated with the initiation of highly active antiretroviral therapy (HAART) in a patient with AIDS

Reactive hemophagocytosis has been associated with neoplasia, bacteria, parasitic, and viral infections including human immunodeficiency virus (HIV). Here we present a case of reactive hemophagocytosis associated with the initiation of highly active antiretroviral therapy (HAART), probably representing a syndrome termed the immune reconstitution inflammatory syndrome (IRIS) or immune reconstitution syndrome.     

Oral manifestations after immune reconstitution in HIV patients on HAART

In order to verify possible association between immune reconstitution inflammatory syndrome (IRIS) and oral manifestations (OMs), we selected AIDS patients who had low CD4 count before the initiation of highly active antiretroviral therapy (HAART) and who returned three months later for therapy evaluation. The oral lesions observed three months after the initiation of HAART were evaluated and associated with the type of antiretroviral therapy (ART), CD4 count and HIV-RNA load levels (before and three months after HAART initiation). A total of 105 patients matched the selected criteria. Immune reconstitution (IR) was identified in 35.2%. Among these patients, the mean CD4 cell count rose from 105.97 to 330.29 and the mean viral load dropped from 168.005 (log 5.22) to 21.852 (log 4.33). There was no significant difference in age (P = 0.78), sex (P = 0.41) or previous history of ART (P = 0.55) between IR and non-IR patients. In the IR group, the most common OM was parotid enlargement (57.14%) (P = 0.019), whereas in the non-IR group candidiasis (46.15%) was the most common OM. The results of our study suggest that the parotid gland enlargement found in the studied population might be an IRIS event, as it was found in patients with IR three months after the initiation of HAART.     

Tegumentary leishmaniasis as a manifestation of immune reconstitution inflammatory syndrome in 2 patients with AIDS

Immune reconstitution inflammatory syndromes (IRISs) have been reported in patients with human immunodeficiency virus/acquired immunodeficiency syndrome (AIDS) since the introduction of highly active antiretroviral therapy (HAART). This syndrome is characterized by clinical manifestations of opportunistic infections when signs of immune reconstitution are observed during therapy. We report on leishmaniasis, suggestive of HAART-induced IRIS, in 2 patients with AIDS. After beginning HAART, 1 patient presented with disseminated, tegumentary lesions, whereas the other patient's preexisting lesions worsened and became more extensive; however, at the same time, their CD4(+) T cell counts were recovering and their virus loads were decreasing significantly. The lesions healed with anti-Leishmania therapy.     

Immune reconstitution inflammatory syndrome (IRIS) of the small bowel in an immunocompromised patient suffering from systemic lupus erythematosus and non-tuberculous mycobacteriosis

An overwhelming immune reaction resulting in granulomatous inflammation after infection with opportunistic pathogens is termed immune reconstitution inflammatory syndrome (IRIS). It has mainly been described in patients with human immunodeficiency virus (HIV) infection on highly active antiretroviral therapy (HAART) who show a significant increase of low CD4 T cells (initially <50/microl). IRIS may lead to organ damage and differential diagnosis is often difficult. We report the case of a 38-year-old female patient who developed a Mycobacteria genavense infection of the liver and the bowel after several immunosuppressive therapies for systemic lupus erythematosus. CD4 T cell counts as low as 17/microl were found and immunosuppressive therapy was stopped. Despite several courses of antibiotic treatment and rising CD4 T cell counts, severe malabsorption persisted. Upper endoscopy revealed a continuous inflammation with pseudopolyps of the small bowel and histologically, a granulomatous infiltrate was detected. After exclusion of a persisting infection by Mycobacteria genavense, IRIS of the small bowel was suspected and treatment with prednisolone was started. The clinical and histological picture improved significantly, the number of CD25(+)CD4(+) cells decreased in the lamina propria of the duodenum under treatment with prednisolone and Foxp3+ regulatory T cells (Treg) accumulated around granulomas. This case shows that IRIS is not restricted to HIV patients but may also occur in otherwise immunosuppressed patients. Due to different treatment strategies, distinguishing IRIS from infectious diseases is essential. The role of Treg in IRIS has to be elucidated.     

艾滋病免疫重建炎性综合征与基线CD4^＋T淋巴细胞计数的相关性及治疗分析

目的探讨艾滋病（AIDS）免疫重建炎性综合征（IRIS）与基线CD4^＋T淋巴细胞（简称CD4细胞）计数的相关性及治疗方法。方法将选取的艾滋病病毒（HIV）感染者／艾滋病（AIDS）病人（HIV／AIDS病人）,根据不同基线CD4细胞水平分为两组,观察这两组在高效抗反转录病毒治疗（HAART）后,发生IRIS的情况,以及糖皮质激素在治疗IRIS中的作用。结果共选取HIV／AIDS病人312例,A组157例,CD4细胞计数≤100个／μL：B组155例,CD4淋巴细胞计数〉100个／μL。A组IRIS发生率为40．1％（63／157）,死亡率为6．3％（4／63）;B组IRIS发生率为3．9％（6／155）,无死亡病例;两组IRIS发生率差异有统计学意义（P〈0．01）,死亡率虽有差异,但无统计学意义（P〉0．05）。两组IRIS最常见并发结核病,分别为71．4％（45／63）和33．3％（2／6）。糖皮质激素治疗重症病人症状的有效率为90．2％。结论基线CD4细胞低下是IRIS发生的重要因素,CD4细胞计数≤100个／μL的病人发生IRIS合并结核的较多见,糖皮质激素治疗有效。     

Immunrekonstitutionssyndrom des Dünndarms bei einer immunsupprimierten Patientin mit systemischem Lupus erythematodes und nichttuberkulöser Mykobakteriose

An overwhelming immune reaction resulting in granulomatous inflammation after infection with opportunistic pathogens is termed immune reconstitution inflammatory syndrome (IRIS). It has mainly been described in patients with human immunodeficiency virus (HIV) infection on highly active antiretroviral therapy (HAART) who show a significant increase of low CD4 T cells (initially <50/μl). IRIS may lead to organ damage and differential diagnosis is often difficult. We report the case of a 38-year-old female patient who developed a Mycobacteria genavense infection of the liver and the bowel after several immunosuppressive therapies for systemic lupus erythematosus. CD4 T cell counts as low as 17/μl were found and immunosuppressive therapy was stopped. Despite several courses of antibiotic treatment and rising CD4 T cell counts, severe malabsorption persisted. Upper endoscopy revealed a continuous inflammation with pseudopolyps of the small bowel and histologically, a granulomatous infiltrate was detected. After exclusion of a persisting infection by Mycobacteria genavense, IRIS of the small bowel was suspected and treatment with prednisolone was started. The clinical and histological picture improved significantly, the number of CD25⁺CD4⁺ cells decreased in the lamina propria of the duodenum under treatment with prednisolone and Foxp3+ regulatory T cells (Treg) accumulated around granulomas. This case shows that IRIS is not restricted to HIV patients but may also occur in otherwise immunosuppressed patients. Due to different treatment strategies, distinguishing IRIS from infectious diseases is essential. The role of Treg in IRIS has to be elucidated.     

Incidence and risk factors for immune reconstitution inflammatory syndrome during highly active antiretroviral therapy

BACKGROUND: There is little systematic information regarding the immune reconstitution inflammatory syndrome (IRIS). OBJECTIVE: To determine the incidence, risk factors, and long-term outcome of IRIS in HIV-infected patients receiving highly active antiretroviral therapy (HAART) who were coinfected with one of three common opportunistic pathogens. DESIGN: A retrospective cohort identified through a city-wide prospective surveillance program. METHODS: A retrospective chart review was performed for 180 HIV-infected patients who received HAART and were coinfected with Mycobacterium tuberculosis, Mycobacterium avium complex, or Cryptococcus neoformans between 1997 and 2000. Medical records were reviewed for baseline demographics, receipt and type of HAART, response to antiretroviral therapy, development of IRIS, and long-term outcome. RESULTS: In this cohort, 31.7% of patients who received HAART developed IRIS. Patients with IRIS were more likely to have initiated HAART nearer to the time of diagnosis of their opportunistic infection (P < 0.001), to have been antiretroviral naive at time of diagnosis of their opportunistic infection (P < 0.001), and to have a more rapid initial fall in HIV-1 RNA level in response to HAART (P < 0.001). CONCLUSIONS: IRIS is common among HIV-infected persons coinfected with M. tuberculosis, M. avium complex, or C. neoformans. Antiretroviral drug-naive patients who start HAART in close proximity to the diagnosis of an opportunistic infection and have a rapid decline in HIV-1 RNA level should be monitored for development of this disorder.     

Immune reconstitution inflammatory syndrome presenting as sinusitis with inflammatory pseudotumor in an HIV-infected patient: a case report and review of the literature

Immune reconstitution inflammatory syndrome (IRIS) encompasses a variety of conditions that occur among HIV-infected patients in a temporal relationship with increases in CD4 cell count as a result of highly active antiretroviral therapy (HAART). Most conditions associated with IRIS are infectious. Malignancies, such as Kaposi's sarcoma, have also been reported. We report a case of sinusitis with presumptive inflammatory pseudotumor as a manifestation of IRIS that occurred 20 weeks after the initiation of HAART.