Yellow-nail syndrome: report of three cases.

The yellow nail syndrome, a combination of yellow discolouration of and dystrophic changes in the nails, pleural effusions and lymphedema, is thought to be relatively rare; to date 44 cases have been reported. Of a further three patients with this syndrome, one had all three features, one had the yellow nails alone and the other had pleural effusions and lymphedema without classic nail changes. Each had recurrent lower respiratory tract infections; and of all 47, chronic pulmonary infections occurred in approximately one quarter and were frequently associated with chronic sinus infections. The underlying abnormality is presumed to be a congenital defect of the lymphatics, but so far this has not been demonstrated to be the cause of the nail changes, the pathogenesis of which remains obscure.     

Relevancia de la anfotericina B liposomal en el tratamiento de las infecciones fúngicas invasoras en pacientes oncohematológicos

Liposomal amphotericin B (L-AmB) has been a key cornerstone for the management of invasive fungal infections (IFI) caused by a wide array of molds and yeasts during the last three decades. Multiple studies performed over this period have generated a large body of evidence on its efficacy and safety, becoming the main antifungal agent in the management of IFI in patients with hematologic malignancies in several not mutually exclusive clinical settings. First, L-AmB is the most commonly used antifungal agent in patients undergoing intensive chemotherapy for acute leukemia and high-risk myelodysplastic syndrome, as well as in hematopoietic stem cell transplant recipients. Additionally, due to the administration of newer targeted therapies (such as monoclonal antibodies or small molecule inhibitors), opportunistic mold infections are increasingly being reported in patients with hematologic malignancies usually considered low-risk for IFI. These agents usually have a high drug-drug interaction potential, being triazoles, commonly used for antifungal prophylaxis, included. Finally, patients developing breakthrough IFI because of either subtherapeutic concentrations of antifungal prophylactic drugs in blood or selection of resistant strains, require broad spectrum antifungal therapy, usually with an antifungal of a different class. In both situations, L-AmB remains as the best option for early antifungal therapy.     

AIDS: acquired immunodeficiency syndrome.

Acquired immunodeficiency syndrome, or AIDS, is a new illness that occurs in previously healthy individuals. It is characterized by immunodeficiency, opportunistic infections and unusual malignant diseases. Life-threatening single or multiple infections with viruses, mycobacteria, fungi or protozoa are common. A rare neoplasm, Kaposi''s sarcoma, has developed in approximately one third of patients with AIDS. More than 800 cases of AIDS have been reported in North America, over 24 of them in Canada. The majority of patients are male homosexuals, although AIDS has also developed in abusers of intravenously administered drugs, Haitian immigrants, individuals with hemophilia, recipients of blood transfusions, prostitutes, and infants, spouses and partners of patients with AIDS. The cause of AIDS is unknown, but the features are consistent with an infectious process. Early diagnosis can be difficult owing to the nonspecific symptoms and signs of the infections and malignant diseases. Therefore, vigilance by physicians is of utmost importance.     

Idiopathic CD4 lymphocytopenia: a case of missing, wandering or ineffective T cells

Idiopathic CD4 lymphocytopenia (ICL) is a presumed heterogenous syndrome with key element low CD4 T-cell counts (below 300/mm³) without evidence of HIV infection or other known immunodeficiency. The etiology, pathogenesis, and management of ICL remain poorly understood and inadequately defined. The clinical presentation can range from serious opportunistic infections to incidentally diagnosed asymptomatic individuals. Cryptococcal and non-tuberculous mycobacterial infections and progressive multifocal leukoencephalopathy are the most significant presenting infections, although the spectrum of opportunistic diseases can be similar to that in patients with lymphopenia and HIV infection. Malignancy is common and related to opportunistic pathogens with an oncogenic potential. Autoimmune diseases are also seen in ICL with an increased incidence. The etiology of ICL is unknown. Mechanisms implicated in CD4 reduction may include decreased production, increased destruction, and tissue sequestration. New distinct genetic defects have been identified in certain patients with ICL, supporting the hypothesis of the lack of a common etiology in this syndrome. The management of ICL is focused on the treatment of opportunistic infections, appropriate prophylactic antibiotics, and close monitoring. In selected patients with life-threatening infections or profound immunodeficiency, strategies to increase T-cell counts or enhance immune function could be considered and have included interleukin-2, interferon-gamma, interleukin-7, and hematopoietic stem cell transplantation. The prognosis is influenced by the accompanying opportunistic infections and may be affected by publication bias of severe cases with unfavorable outcomes. As newer laboratory investigation techniques are being developed and targeted experimental treatments become available, our comprehension and prognosis of this rare syndrome could be significantly improved.Idiopathic CD4 lymphocytopenia (ICL) was described in 1992 as an immunodeficiency syndrome characterized by opportunistic infections and low CD4 T-cell counts in the absence of HIV infection. Despite the 20 years that have elapsed, the clinical spectrum, pathogenesis, and possible treatment for ICL remain obscure. Here, we attempt to summarize the salient features of this condition on the basis of the available literature to date.     

AIDS: acquired immunodeficiency syndrome

Acquired immunodeficiency syndrome, or AIDS, is a new illness that occurs in previously healthy individuals. It is characterized by immunodeficiency, opportunistic infections and unusual malignant diseases. Life-threatening single or multiple infections with viruses, mycobacteria, fungi or protozoa are common. A rare neoplasm, Kaposi''s sarcoma, has developed in approximately one third of patients with AIDS. More than 800 cases of AIDS have been reported in North America, over 24 of them in Canada. The majority of patients are male homosexuals, although AIDS has also developed in abusers of intravenously administered drugs, Haitian immigrants, individuals with hemophilia, recipients of blood transfusions, prostitutes, and infants, spouses and partners of patients with AIDS. The cause of AIDS is unknown, but the features are consistent with an infectious process. Early diagnosis can be difficult owing to the nonspecific symptoms and signs of the infections and malignant diseases. Therefore, vigilance by physicians is of the utmost importance.     

Leishmania, Trypanosoma and monoxenous trypanosomatids as emerging opportunistic agents

Immunosuppression is associated with the occurrence of a large variety of infections, several of them due to opportunistic protozoa. The parasitic protozoa of the family Trypanosomatidae vary greatly in their importance as potential opportunistic pathogens. African trypanosomiasis is no more common nor severe during AIDS. The situation with Chagas' disease, however, is much different. Although the process is not clearly understood, there appears to be a reactivation of Trypanosoma cruzi infection, which can lead to severe meningoencephalitis. In persons with AIDS, leishmaniasis is often exacerbated, particularly Leishmania infantum, which causes visceral leishmaniasis in southern Europe. Since 1990, 1,616 cases of visceral leishmaniasis/HIV co-infection have been reported, mainly from southern Europe, and particularly from Spain, southern France, and Italy. The co-infected patients are primarily young adults and belong to the risk group of intravenous drug users. Isoenzymatic identification of 272 isolates showed 18 different L. infantum zymodemes, of which 10 represent new zymodemes hitherto found only during HIV co-infection. New foci of co-infection are emerging in various parts of the world, including Brazil and East Africa. Moreover, since 1995, non-human monoxenous trypanosomatids have been found in AIDS patients, causing both diffuse cutaneous lesions and visceral infections. In countries where visceral leishmaniasis is endemic, particularly in southern Europe, immunosuppressive treatments for organ transplants or malignant diseases often result either in reactivation of asymptomatic visceral leishmaniasis or in facilitation of new infections.     

Severe acquired immunodeficiency in European homosexual men.

Four previously healthy Danish homosexual men developed Kaposi''s sarcoma or opportunistic infections with fever of unknown origin and lymphadenopathy. One patient died of a Pneumocystis carinii pneumonia. Three patients had defective cell-mediated immunity with absent leucocyte interferon production and decreased proliferative response to mitogens and antigens. T lymphocyte helper subsets and natural killer cell activity were reduced. Unstimulated mononuclear cells produced leucocyte migration inhibitor factor. Two patients were sexual partners and three had never been to the USA, where cases of severe acquired immunodeficiency have been reported. Thus, the syndrome must also be suspected in European homosexual men who present with fever of unknown origin, opportunistic infections, or Kaposi''s sarcoma.     

HIV and tuberculosis in India

The global impact of the converging dual epidemics of tuberculosis (TB) and human immunodeficiency virus (HIV) is one of the major public health challenges of our time. The World Health Organization (WHO) reports 9.2 million new cases of TB in 2006 of whom 7.7% were HIV-infected. Tuberculosis is the most common opportunistic infection in HIV-infected patients as well as the leading cause of death. Further, there has been an increase in rates of drug resistant tuberculosis, including multi-drug (MDRTB) and extensively drug resistant TB (XDRTB), which are difficult to treat and contribute to increased mortality. The diagnosis of TB is based on sputum smear microscopy, a 100-year old technique and chest radiography, which has problems of specificity. Extra-pulmonary, disseminated and sputum smear negative manifestations are more common in patients with advanced immunosuppression. Newer diagnostic tests are urgently required that are not only sensitive and specific but easy to use in remote and resource-poor settings. Treatment of HIV-TB co-infection is complex and associated with high pill burden, overlapping drug toxicities, risk of immune reconstitution inflammatory syndrome (IRIS) and challenges related to adherence. From a programmatic point of view, screening of all HIV-infected persons for tuberculosis and vice-versa will help identify co-infected patients who require treatment for both infections. This requires good coordination and communication between the TB and AIDS control programs, in India.     

Abnormal expression of CD54 in mixed reactions of mononuclear cells from hyper-IgE syndrome patients

Hyper-IgE syndrome (HIES) is a rare multisystem disorder characterized by increased susceptibility to infections associated with heterogeneous immunologic and non-immunologic abnormalities. Most patients consistently exhibit defective antigen-induced-T cell activation, that could be partly due to altered costimulation involving accessory molecules; however, the expression of these molecules has never been documented in HIES. Therefore, we investigated the expression of CD11a, CD28, CD40, CD54, CD80, CD86, and CD154 in peripheral blood mononuclear cells from six patients and six healthy controls by flow cytometry after autologous and mixed allogeneic reactions. Only the allogeneic stimuli induced significant proliferative responses and interleukin 2 and interferon gamma production in both groups. Most accessory, molecules showed similar expression between patients and controls with the exception of CD54, being expressed at lower levels in HIES patients regardless of the type of stimulus used. Decreased expression of CD54 could partly explain the deficient T cell activation to specific recall antigens in HIES patients, and might be responsible for their higher susceptibility to infections with defined types of microorganisms.     

Microsporidia of mammals--widespread pathogens or opportunistic curiosities?

The microsporidia are primitive eukaryotic parasites - well known in some invertebrates and in fish, and increasingly recognized in mammals. One species, Encephalitozoon cuniculi is widespread in rodents, lagomorphs and carnivores and has been reported in human and non-human primates. But although clinical expressions of E. cuniculi infections are well substantiated in carnivores, evidence for its pathogeniciry in primates is less clear. Indeed, serological evidence suggests that latent infections may be quite common in man. Another species, Enterocytozoon bieneusi has now been reported several times from AIDS patients, associated with a severe, intractable diarrhoea. Other records of microsporidia in mammals have also been associated with an immunoprivileged site or immunocompromized host. In this article Elizabeth Canning and Wafaa Hollister discuss the recent findings, and consider the likelihood that microsporidial infections of man will be increasingly revealed following immunosuppressive therapy. But will they be opportunistic infections, or manifestations of common parasites that are otherwise held at sub-patent levels?     

Rhodotorula infection. A systematic review of 128 cases from literature

Rhodotorula is an emerging opportunistic pathogen, particularly in immunocompromised patients. Many cases of fungemia associated with catheters, endocarditis, peritonitis, meningitis, and endophthalmitis are infections incited by this yeast. The main purpose of this study was to review all cases of Rhodotorula infection reported in the literature and to describe risk factors, underlying conditions and outcome. From 128 cases, 79% were fungemia (103 cases), 7% eye infections (nine cases) and 5% (six cases) peritonitis associated with continuous ambulatory peritoneal dialysis. Eighty seven percent of Rhodotorula infections are associated with underlying immunosuppression or cancer. The most common isolated risk factor associated with Rhodotorula infection was the use of a central venous catheter, which was found in 83.4% of Rhodotorula fungemia (86 cases). Rhodotorula mucilaginosa was the most common species of fungemia (74% of cases), followed by Rhodotorula glutinis with 7.7%. The species was not identified in 17% of the cases of fungemias. Amphotericin was the drug of choice in the treatment of fungemia and most of the eye infections were treated with topical amphotericin, although all patients lost their vision. All peritonitis cases associated with continous ambulatory peritoneal dialysis needed to have the Tenckoff catheter changed. The overall mortality of Rhodotorula infection was 12.6%.     

Immunogenetic Variability Associated with Different Susceptibility Patterns to Candida and Aspergillus Infections

Fungal infections remain a serious clinical problem with a high disease and financial burden, especially among immunocompromised and critically ill patients. Numerous efforts have not fully identified clinical and laboratory risk factors for increased susceptibility to fungal infections. The recent acquisition of knowledge about innate immune responses to fungi and genetic alterations in immunologic mechanisms has revealed additional genetic risk factors and has shed more light on the predisposition of individuals to fungal infections. The aim of this review is to address the findings of recent studies associating genetic factors with susceptibility to fungal infections, focusing on the most common opportunistic fungi, Candida and Aspergillus species.     

Recent developments in new and old viral infections

Until recently, concerns regarding viral infections and hematologic malignancies were primarily focused on the transplantation of an allogeneic graft. In the last years, the use of immunomodulatory agents such as monoclonal antibodies (e.g. anti CD20, anti CD52) directed against lymphocyte antigens in the treatment of hematopoietic malignancies (e.g. lymphoma, chronic lymphocytic leukemia) has added a great potential to impact on the incidence, severity and timing of viral infections. Patients may acquire viral infections through several mechanisms including transfusion, community exposure or via the donor origin in the case of stem cell transplant. Endogenous reactivation of latent viruses is also commonly observed. Viral replication may lead directly to viral diseases or induce indirect effects such as increased incidence of opportunistic infections and decreased patient survival. Traditionally, herpesviruses have been and are still today the most important viruses in patients with hematologic malignancies. Nowadays, several emerging viral infections have been highlighted as being of concern in this patients' population.     

Candida krusei : biotechnological potentials and concerns about its safety

Yeasts have a tradition in biotechnological applications, and Saccharomyces species are the most dominating representatives. Among the yeast species, Candida krusei has been isolated from different habitats, and in recent years, it has gained increased interest because of its diverse biotechnological role. It is found in many fermented food items and dairy products and has also been exploited for production of biochemicals and enzymes. However, because of its opportunistic pathogenic nature, it draws scientific attention regarding the safety of its industrial exploitation. Candida?krusei generally causes infections in immunocompromised patients, such as those suffering from Human immunodeficiency virus - acquired immune deficiency syndrome, and also in cancer patients. The recent increase in the use of immunosuppressive drugs has increased the chances of C.?krusei infections. Candida?krusei possesses an intrinsic resistance to many triazole antifungal drugs, especially fluconazole, which is a main drug used in antifungal therapy; therefore, there is serious concern regarding its safe industrial use.     

Opportunistic infections and acquired cellular immune deficiency among Haitian immigrants in Montreal.

Eight Haitian immigrants (five with acquired immune deficiency syndrome [AIDS] and three with the signs and symptoms of AIDS but without opportunistic infections or malignant diseases) are described. All had malaise, weight loss, fever and generalized lymphadenopathy. All five of those with opportunistic infections died from the infections, which were multiple in four cases. Septic shock due to Escherichia coli or Klebsiella pneumoniae developed in two patients. Evidence of immune deficiency in the AIDS patients included anergy, lymphocytopenia (in all but two), polyclonal hypergamma-globulinemia and abnormal sizes of the subsets of circulating T lymphocytes. Autopsies revealed no recognizable causes for immune deficiency; the lymph nodes showed follicular hyperplasia in four cases and lymphocyte depletion in one case. Except for the absence of opportunistic infections, the illness in the three patients not classed as having AIDS was indistinguishable from that in the other five, which suggests that this syndrome is AIDS-related, like the persistent generalized lymphadenopathy that occurs in homosexual men and patients with hemophilia.     

HIV/AIDS患者机会性感染与CD4+ T淋巴细胞间的关联性

目的 研究人免疫缺陷病毒（HIV）感染者及艾滋病（AIDS）患者发生机会性感染的概率与自身CD4+ T淋巴细胞之间的关系,为HIV患者机会性感染的防治提供参考。方法 以2016年6月至2017年6月我院400例HIV患者为研究对象,回顾性分析不同CD4+T淋巴细胞计数HIV患者发生机会性感染的情况。结果 400例HIV患者发生机会性感染178例,总感染率为44.5%。CD4+T淋巴细胞计数≤50个/μL的患者机会性感染发生率（86.67%）最高,与其他各组比较差异有统计学意义（P<0.05）。随着CD4+ T淋巴细胞计数的减少,HIV患者机会性感染率升高。178例机会性感染者中,单一感染82例,2部位感染52例,3部位感染28例,4部位以上感染16例。感染病原体检测显示,细菌感染84例（47.19%）,结核杆菌感染36例（20.22%）,病毒感染30例（16.85%,包括巨细胞病毒感染18例、单纯疱疹病毒感染12例）,真菌感染77例（43.25%,包括假丝酵母感染35例,肺孢子菌感染20例,马尔尼菲青霉菌感染12例,新型隐球菌感染10例）,未明确病原体性质34例（19.10%）,复合感染多见。结论 CD4+ T淋巴细胞水平与HIV患者继发机会性感染的概率关系密切。HIV患者CD4+ T淋巴细胞水平的监测对其继发机会性感染的防控具有重要临床意义。     

Microbiologic consequences of new approaches to managing hematologic malignancies

Opportunistic infections have always been pitfalls on the road of progress in the treatment of diseases that are accompanied by compromised host defences. Because of the severe morbidity and mortality associated with these infections, they have become substantial challenges for the clinicians who offer such patients care. With medical progress, the number of immunocompromised patients is still steadily climbing and it has become evident that deficiencies in host defences mechanisms are multiple as well as changing in harmony with alterations in treatment modalities for underlying diseases. Under normal circumstances, the intact epithelial surfaces of the gastrointestinal tract will prohibit invasion by micro-organisms and the mucociliary barrier of the respiratory tract prevents aspiration of fungal cells and spores, while, in contrast, dead or damaged tissue creates a nidus for infection. It is, however, questionable whether transmigration of organisms inevitably leads to infection. With the growing use of potent immunosuppressive purine analogues, fludarabine, pentostatin and cladibrine, and anti-T and anti-B cell antibodies, such as rituximab and campath, in the management of lymphoreticular malignancies, in combination with increasing emphasis on dose intensity, the number of patients at risk has almost reached levels encountered in recipients of allogenic stem cell grafts as a consequence of long-lasting deficiencies in the cellular immunity. The spectrum of opportunistic pathogens are shifting as anti-leukemic and anti-lymphoma therapy become more intensive and bone marrow transplant practices evolve. Recent studies demonstrate, that patients treated with nonmyeloablative allogeneic transplantation (or "minitransplants") to reduce transplant-related toxicity, are at high risk of contracting a serious infections. Initially bacterial infections were most problematic. However, as strategies to control bacterial infections improved, viruses demanded more attention from the clinicians but the associated morbidity declined due to advances in rapid diagnostics and the introduction of effective antivirals such as acyclovir and ganciclovir. Next to viruses, resistant bacteria, particularly Gram-positive organisms like enterococci and methicillin-resistant staphylococci urged to vigilance. It was obvious that enhanced use of antibacterials inevitably will be accompanied by selection and induction of resistant organisms. Today, opportunistic fungi have become the most frequent and dangerous pathogens. Since the 1980's the rate of nosocomial invasive fungal diseases has doubled without any sign of slowing at the turn of the millenium. During the past decades we have even observed an increased incidence of invasive fungal infections in patients who are not in an end stage of their underlying disease. Yeasts and moulds rank amongst the most frequently isolated pathogens. The relative incidence of the various fungal infections depends on geography as well as on medical practices and local conditions. Candida Aspergillus species remain the prominent fungal pathogens but more rare species are increasingly cultured.     

A case of pulmonary cestodiasis in a simian immunodeficiency virus-infected pigtailed macaque (Macaca nemestrina) in which virus-infected leukocytes are present within the lesion

Abstract: The larvae of Mesocestoides are rarely encountered in nonhuman primates, with most cases reported in baboons. Infection of macaques has been occasionally diagnosed, but Mesocestoides in the lung parenchyma is extremely rare. We have previously demonstrated that in macaques with terminal AIDS, simian immunodeficiency virus (SIV)-infected leukocytes are rarely found in cellular infiltrates associated with opportunistic infections or preexisting disease. Here we describe larvae (tetrathyridia) of the cestode Mesocestoides in the lung of an adult, pigtailed macaque (Macaca nemestrina) during acute SIV infection in which virus-positive cells are present within the cellular infiltrates. These results describe a rare parasitic disease in pigtailed macaques and demonstrate that lentivirus-infected leukocytes can be associated with inflammatory sites during acute infection.     

Deficiency of the CD3-TCR signal pathway in three patients with idiopathic CD4+ lymphocytopenia

Idiopathic CD4+ lymphocytopenia (ICL) is a rare syndrome affecting adults and defined by a stable loss of CD4+ T cells in the absence of any known cause of immune deficiency. Defective T-cell proliferations to mitogens and antigens have been described in some of such patients displaying clinical signs of immune deficiency such as opportunistic infections. We investigated here the hypothesis that T-cell depletion and dysfunction could be due to biochemical defects of the CD3-TCR pathway in CD4+ and/or CD8+ subsets from three patients with severe stable ICL (below 150 CD4+ T cells/microliter) and opportunistic infections. Patient 1 had a general T lymphocytopenia, whereas patients 2 and 3 displayed a selective loss of CD4+ T cells. We observed in all patients a major reduction of the proliferative response to CD3-TCR stimulation that affected only the depleted T-cell subpopulation. Moreover, in two cases, impaired early biochemical events of the CD3-TCR pathway were detected. In patient 1 and 3, we found a defect (of distinct intensity) of CD3-induced protein tyrosine phosphorylation in CD4+ cells compared to control cells, whereas this process was normally induced in CD4+ T cells from patient 2. Taken together, this study reveals that the heterogeneity of the ICL syndrome was situated at the cellular level, and involved in two cases abnormalities of transducing molecules of the CD3-TCR pathway.     

A new syndrome of long-term idiopathic, severe CD4+ lymphocytopenia: isolated paraparesis and conjunctival ischemic microangiopathy

An extraordinary case report of an adult patient followed-up for a decade with an extremely severe idiopathic CD4+ T-lymphocytopenia (as expressed by an absolute CD4+ count of 8-25 cells/microL), associated with an isolated paraparesis and a conjunctival ischemic microangiopathy is described, and discussed on the grounds of the available literature. Despite such a severe and prolonged immunodeficiency, no opportunistic disease occurred, in a observation period longer than ever reported to date. The neurological disorder was diagnosed concurrently with idiopathic CD4+ lymphocyte depletion, while the ocular complication occurred two years later, but remained stable thereafter. Both disorders remained stable during the subsequent eight years. Despite extensive and repeated instrumental and laboratory workout, only very limited immunological abnormalities were detected (besides the extremely low CD4+ lymphocyte count), and no apparent explaination was found for the disabling paraparesis syndrome. Idiopathic CD4+ lymphocytopenia, whose pathogenesis deserves careful investigation, has been associated with a very broad spectrum of signs and symptoms, ranging from negligible or no disturbances, to severe lymphoproliferative disorders, different opportunistic infections, and other focal diseases, including neurological pathologies. However, the association of a long-lasting profound peripheral CD4+ lymphocyte depletion in absence of any opportunistic infection or neoplasm, and isolated paraparesis and conjunctival microangiopathy, represents an absolutely unique finding, especially due to the apparently stable course of the above-mentioned syndrome.