Kaposi sarcoma-induced immune reconstitution syndrome: a case report.

Introduction and importance: Kaposi sarcoma (KS) is an angioproliferative disease, that mostly affects HIV-infected patients with a high viral load and a low CD4 count. In rare cases, the paradoxical worsening of a pre-existing or previously unrecognized opportunistic infection occurs in a phenomenon known as immune reconstitution inflammatory response (IRIS). Case presentation: The authors presented a male patient in his 30s with HIV, who developed a series of complications caused by KS following the initiation of antiretroviral therapy. Despite ongoing antiretroviral therapy (ART), chemotherapy, and supportive measures, the patient developed KS-related IRIS, characterized by rapid clinical deterioration, multiorgan failure, and ultimately succumbed to the disease. Clinical discussion: To the best of our knowledge, very rare cases have been reported with KS-IRIS after the initiation of ART. Many predictors of KS-IRIS development have been identified. Patients must meet the known diagnostic criteria to be diagnosed with IRIS. The treatment of KS-IRIS depends on the stage of KS. ART alone is usually adequate in mild cutaneous KS. Chemotherapy and ART are recommended for patients with severe cutaneous and visceral KS. Conclusion: HIV patients with KS undergoing ART initiation or modification should be closely monitored, particularly during the early stages and in those with extensive disease. Treating opportunistic infections before ART initiation may reduce the risk of KS-IRIS. The increasing prevalence of KS in ART-treated patients with HIV warrants further attention and highlights the need for better management strategies in this population.

Paradoxical and Unmasking HIV Immune Reconstitution Inflammation Syndrome in Antiretroviral-Naïve Pregnant Women: A Prospective Cohort Study.

BACKGROUND AND AIMS: Following antiretroviral therapy (ART) initiation, HIV-associated immune reconstitution inflammatory syndrome (IRIS), indicated by an array of opportunistic infections, may occur, presenting as either paradoxical, a worsening of a previously treated infection, or unmasking, a flare-up of an underlying, previously undiagnosed infection. The impact of ART as the backbone of HIV treatment and prevention has prolonged the survival of people living with HIV. In pregnancy, benefits have been shown by slowing HIV progression and preventing perinatal transmission; however, there have been risks of adverse reactions with ART, including immune responses to both the fetus and mother. This study sought to estimate the incidence of HIV-IRIS cumulatively and by type either paradoxical or unmasking IRIS, determine the baseline maternal and HIV clinical markers as predictors of, and analyze the log-rank test for survival time to IRIS outcome assessed by relying on an increase in CD4 count and/or a rapid decrease in viral load. METHODS: An active records study was conducted between June 2019 and March 2020 among ART-naïve pregnant women attending the antenatal care units (ANCu) at the Kenyatta National and Mbagathi Hospitals, Nairobi, Kenya. Participants were aged between 20 and 49 years and had a confirmed HIV-positive test. To ascertain a true case of IRIS, the diagnosis was adjudicated for accuracy and consistency by an independent review committee. Plasma HIV viral load, CD4 counts, and routine laboratory evaluations (hemoglobin, white blood cell count (WBC)) were performed by each hospital's clinical laboratory. The IRIS incidence was assessed using the International Network for Studies Against HIV-Associated IRIS (INSHI) during the first three months after ART initiation. Multivariate Cox regression with IRIS as the outcome, using the SPSSSurvival package, examined the relationship between baseline maternal characteristics and HIV clinical markers before ART initiation and IRIS, and finally, decision-tree analysis for predicting IRIS was performed. RESULTS: From a pool of 532 ART-naïve pregnant women, 133 (25%) developed IRIS, and 97 (72.9%) were in the unmasking category. The accumulated risk of experiencing IRIS symptoms increased from week two (hazard ratio (HR)=0.0287) to week 12 (HR=3.6158). Participants with a maternal BMI (MBMI) of 25-29.9 kg/m2 at baseline were at a higher risk of unmasking IRIS (HR=2.478; P=0.010). The WHO-HIV clinical stages 1 and 2 skewed towards paradoxical IRIS (regression coefficients =-0.111 and -0.276 (P<0.05)), while stage 4 skewed towards unmasking IRIS (regression coefficient=0.047, HR=1.048, P=0.941). A CD4 count > 500 cells/mm^3 skewed towards unmasking IRIS (regression coefficient=0.192, HR=1.211, P=0.416), while RNA-HIV viral loads >50 copies/ml towards paradoxical IRIS (regression coefficient=-0.199, HR=0.820, P=0.360. On decision tree analysis, 85% (P=0.001) of ART-naïve pregnant women with a baseline CD4 count below 500 copies/mm^3 presented with unmasking IRIS. CONCLUSION: For ART-naïve pregnant women, unmasking IRIS is the most common type, and an MBMI of 25-29.9 kg/m2, advanced HIV infection, a CD4 count <500 cells/mm^3, and a higher parity at baseline may be clinically useful predictors. The higher proportion of ART-naïve pregnant women experiencing unmasking as compared to paradoxical IRIS supports the need for earlier assessment based on potential predictors.

Autoimmune Liver Disease in Human Immunodeficiency Virus-Infected Patients: 3 Case Series.

We present 3 cases of autoimmune liver disease in human immunodeficiency virus (HIV)-infected patients and describe the different diagnostic and therapeutic approaches used in each case. The first patient was diagnosed with primary biliary cholangitis (PBC) with features of autoimmune hepatitis (AIH), requiring second-line therapy due to incomplete response to ursodeoxycholic acid. The second patient was diagnosed with AIH with features of PBC and had the particular challenges of presenting with advanced liver fibrosis and having a past history of disseminated cytomegalovirus infection. The last case concerns an AIH with acute liver injury, successfully treated with corticosteroids and azathioprine. Recently, the number of patients on antiretroviral therapy (ART) for HIV disease has increased significantly. Therefore, more patients with this chronic infection have been diagnosed with autoimmune diseases, leading to concerns regarding immunosuppressive therapies in this population. With these cases, we alert for these increasingly incident diseases and support the safety of immunosuppressive therapies, provided that HIV is suppressed with ART.

Apresentamos três casos distintos de doença hepática autoimune em doentes com infeção pelo vírus da imunodeficiência humana (VIH), descrevendo as diferentes abordagens diagnósticas e terapêuticas. O primeiro doente foi diagnosticado com colangite biliar primária (CBP) com caraterísticas de hepatite autoimune (HAI), necessitando de terapêutica de segunda linha por resposta incompleta ao ácido ursodesoxicólico (AUDC). O segundo doente foi diagnosticado com HAI com caraterísticas de CBP, com as particularidades de se apresentar com fibrose hepática avançada e de ter tido uma infeção disseminada pelo citomegalovírus. O terceiro caso apresentou-se como uma hepatite aguda grave, tratada com corticoterapia e azatioprina. Recentemente, o número de doentes sob terapêutica antirretroviral (TARV) para a infeção pelo VIH tem aumentado significativamente. Consequentemente, mais doentes com esta infeção crónica têm sido diagnosticados com doenças autoimunes, levando a receios na administração de terapêuticas imunossupressoras. Com esta série de casos pretendemos alertar para esta incidência crescente e para a segurança dos imunossupressores, desde que os doentes apresentem a sua infeção pelo VIH controlada com a TARV.

When the Cure Becomes the Problem: A Case Report of Immune Reconstitution Inflammatory Syndrome Associated With Varicella Encephalitis.

Immune reconstitution inflammatory syndrome (IRIS) describes a constellation of inflammatory symptoms that develop following the initiation of antiretroviral therapy (ART) in patients with advanced human immunodeficiency virus (HIV). Here, we present a case of a 39-year-old male-to-female transgender patient with advanced HIV who was started on ART during a hospitalization for acute encephalopathy due to a combination of methicillin-resistant Staphylococcus aureus (MRSA) meningitis and varicella encephalitis. After adequate treatment of these infections and five weeks after initiation of ART, she developed inflammatory symptoms of malaise, fever, and tachycardia, as well as laboratory findings of leukocytosis consistent with an inflammatory process. Infectious workup did not reveal any evidence of a new infection, and no other undiagnosed inflammatory processes were discovered to explain these symptoms. A diagnosis of IRIS was suspected, possibly induced by a prior varicella infection. Diagnosis of IRIS can be difficult due to heterogeneous symptoms, differing etiologies, variable patient presentations, and the lack of universal diagnostic criteria. As instances of IRIS are not uncommon in patients with a low CD4 count who start on ART, there should be a high index of suspicion when patients present with inflammatory symptoms after initiation of ART. With increased recognition of the disease and improved standardization of diagnostic criteria, more could be understood about the underlying disease process which may allow for better targeted therapies and individualized treatments for patients who develop the immune reconstitution inflammatory syndrome.

Morbidity and mortality in tuberculosis associated immune reconstitution inflammatory syndrome in children living with HIV: A narrative review.

Tuberculosis-associated immune reconstitution syndrome (TB-IRIS) is an increasingly recognized complication of children living with HIV who are receiving treatment for active tuberculosis (TB). The purpose of the study was to appraise available evidence of morbidity and mortality related to TB IRIS among the paediatric population. A non-systematic review of the literature was conducted by retrieving records from Scopus, PubMed and Google Scholar). Four specific research questions assessing the risk factors (age, undernutrition, extrapulmonary TB and degree of immunosuppression) for TB-IRIS were discussed. The search yielded 370 articles, subsequently screened for eligibility according to the inclusion criteria. The majority of the articles were adult studies. Six studies were identified: Three retrospective and three prospective studies. The majority of the studies were conducted in TB/HIV-endemic countries. Only one study addressed mortality due to TB-IRIS as an outcome. A total of 6 mortalities related to TB-IRIS were reported. Advanced immunosuppression is universally agreed as an established risk factor for mortality in TB-IRIS in children. The severe presentation was more common in children with extrapulmonary tuberculosis. There is a paucity of data available on mortality in HIV-infected children with TB-IRIS. Future research is needed to assess the predictive factors of morbidity and mortality in HIV-infected children with TB-IRIS especially in low resource and high endemic countries.

Invasive aspergillosis in liver transplant recipients.

BACKGROUND: Liver transplantation is increasing worldwide with underlying pathologies dominated by metabolic and alcoholic diseases in developed countries. METHODS: We provide a narrative review of invasive aspergillosis (IA) in liver transplant (LT) recipients. We searched PubMed and Google Scholar for references without language and time restrictions. RESULTS: The incidence of IA in LT recipients is low (1.8%), while mortality is high (∼50%). It occurs mainly early (<3 months) after LT. Some risk factors have been identified before (corticosteroid, renal, and liver failure), during (massive transfusion and duration of surgical procedure), and after transplantation (intensive care unit stay, re-transplantation, re-operation). Diagnosis can be difficult and therefore requires full radiological and clinicobiological collaboration. Accurate identification of Aspergillus species is recommended due to the cryptic species, and susceptibility testing is crucial given the increasing resistance of Aspergillus fumigatus to azoles. It is recommended to reduce the dose of tacrolimus (50%) and to closely monitor the trough level when introducing voriconazole, isavuconazole, and posaconazole. Surgery should be discussed on a case-by-case basis. Antifungal prophylaxis is recommended in high-risk patients. Environmental preventative measures should be implemented to prevent outbreaks of nosocomial aspergillosis in LT recipient units. CONCLUSION: IA remains a very serious disease in LT patients and should be promptly sought and, if possible, prevented by clinicians when risk factors are identified.

The IRIS paradox: Imaging findings in a case of PJP-IRIS.

Immune reconstitution inflammatory syndrome (IRIS) in patients with human immunodeficiency virus (HIV) and Pneumocystis jirovecii pneumonia infection reflects an exaggerated inflammatory response of the host immune system to an antigen, which is temporally related to recovery of the immune system. Clinical manifestations include fever, cough, dyspnoea and hypoxia following the commencement of antiretroviral therapy. Diagnosis is made on clinical and radiological criteria with exclusion of other infective and non-infective causes. Unrecognized, IRIS may be associated with significant morbidity and mortality. Treatment with corticosteroids often results in prompt recovery. There is limited literature on radiological findings of Pneumocystis jirovecii pneumonia-associated IRIS. Here we describe cross-sectional imaging findings of PJP-IRIS in a patient following commencement of antiretroviral therapy.

Alemtuzumab-Induced Autoimmune Thyroid Dysfunction.

Alemtuzumab, a humanized monoclonal antibody used as a disease-modifying treatment in relapsing-remitting multiple sclerosis (RRMS), frequently causes autoimmunity as its principal adverse effect. We describe a typical case of a young man treated with two courses of alemtuzumab presenting 18 months later with initial hyperthyroidism due to Graves' disease (GD) followed by persistent hypothyroidism. We discuss the pathophysiological role of stimulating and blocking thyrotropin receptor antibodies in the development of alemtuzumab-induced autoimmune thyroid dysfunction and clinical challenges posed by spontaneous, bidirectional switching between hyperthyroidism and hypothyroidism. Guidelines recommend monitoring thyroid function pre-treatment and every three months for four years following alemtuzumab treatment. Patient education is crucial for maintaining adherence to monitoring programs.

Serious and Atypical Presentations of Bartonella henselae Infection in Kidney Transplant Recipients.

This article describes 5 cases of bartonellosis with fever and atypical clinical presentations in kidney transplant recipients: thrombotic microangiopathies, recurrent hemophagocytosis, and immune reconstitution syndrome after treatment. The diagnosis, the pathological lesions, and treatments are described. Bartonellosis must be researched in solid organ transplant recipients with fever of undetermined origin.

Hypercalcemia Secondary to Immune Reconstitution Inflammatory Syndrome in an HIV-Infected Individual With Mycobacterium avium Complex.

Immune reconstitution inflammatory syndrome (IRIS) is an uncommon cause of hypercalcemia in HIV-infected patients recently started on highly active antiretroviral therapy (HAART). It is hypothesized that increased granulomatous formation due to IRIS leads to an overproduction of calcitriol. High levels of calcitriol, then, can lead to significant hypercalcemia. We present the case of a 63-year-old male with HIV off HAART presented to the emergency room for confusion, frequent falls, and cough. His CD-4 count was noted to be below 35 cells/µL (255-2,496). Over the course of the hospitalization, the patient was found to have disseminated Mycobacterium avium complex (MAC) infection and was initiated on HAART. Initiation of HAART was followed by an increase in calcium up to 14.1 mg/dL. The hypercalcemia did not respond to either Calcitonin or Pamidronate. Consideration was then given to IRIS in the setting of MAC infection leading to increased granulomatous formation. Calcium levels normalized within three days of therapy after initiation of prednisone for the treatment of IRIS.  It is thought that an increase in CD-4 counts leads to the recovery of an immune response. This can lead to granulomatous inflammation. An increase in granuloma formation can cause hypercalcemia due to overproduction of calcitriol via increased 1𝛼-hydroxylase activity from macrophages. Our case report describes IRIS-mediated hypercalcemia in an HIV-infected individual with MAC infection. This unusual cause of severe hypercalcemia should be considered in differential diagnoses for immunocompromised patients in the appropriate setting. Prompt treatment of IRIS with glucocorticoids can lead to the resolution of hypercalcemia.

Outcome of Hematopoietic Stem Cell Transplantation in patients with Mendelian Susceptibility to Mycobacterial Diseases.

Predisposition to mycobacterial infection is a key presenting feature of several rare inborn errors of intrinsic and innate immunity. Hematopoietic stem cell transplantation (HSCT) can be curative for such conditions, but published reports are few. We present a retrospective survey of the outcome of 11 affected patients (7 males, 4 females) who underwent HSCT between 2007 and 2019. Eight patients had disseminated mycobacterial infection prior to transplant. Median age at first transplant was 48 months (9 -192); three patients were successfully re-transplanted due to secondary graft failure. Donors were matched family (1), matched unrelated (3), and mismatched unrelated and haploidentical family (5 each). Stem cell source was peripheral blood (9), bone marrow (4), and cord blood (1). TCRαß/CD19 + depletion was performed in 6. Conditioning regimens were treosulfan, fludarabine (4), with additional thiotepa (in 8), and fludarabine, melphalan (2); all had serotherapy with alemtuzumab (8) or anti T-lymphocyte globulin (6). Median hospital stay was 113 days (36-330). Three patients developed acute grade I-II skin and one grade IV skin graft versus host disease. Four patients had immune-reconstitution syndrome. Two reactivated cytomegalovirus (CMV), 1 Epstein-Barr virus, and 3 adenovirus post HSCT. Nine are alive, 1 died early post-transplant from CMV, and the other was a late death from pneumococcal sepsis. Patients with active mycobacterial infection at HSCT continued anti-mycobacterial therapy for almost 12 months. In conclusion, HSCT is a successful treatment for patients with mycobacterial susceptibility even with disseminated mycobacterial infection and in the absence of an HLA matched donor.

Acute Liver Failure and Fever of Unknown Origin.

We describe a case of acute liver failure in a woman in whom a diagnosis was initially unable to be established. The patient rapidly deteriorated, requiring admission to the intensive care unit, and was placed under consideration for liver transplantation. On consultation with the infectious disease service, thorough history taking was performed that uncovered salient epidemiologic information pointing toward the eventual diagnosis of disseminated histoplasmosis. We discuss aspects of diagnosis and management, including the management of immune reconstitution syndrome which complicated treatment.

Co-infection of HIV in patients with Buruli ulcer disease in Central Ghana.

BACKGROUND: Previous studies have reported that presence and severity of Buruli ulcer (BU) may reflect the underlying immunosuppression in HIV infected individuals by causing increased incidence of multiple, larger and ulcerated lesions. We report cases of BU-HIV coinfection and the accompanying programmatic challenges encountered in central Ghana. METHODS: Patients with PCR confirmed BU in central Ghana who were HIV positive were identified and their BU01 forms were retrieved and reviewed in further detail. A combined 16S rRNA reverse transcriptase / IS2404 qPCR assay was used to assess the Mycobacterium ulcerans load. The characteristics of coinfected patients (BU+HIV+) were compared with a group of matched controls. RESULTS: The prevalence of HIV in this BU cohort was 2.4% (compared to national HIV prevalence of 1.7%). Eight of 9 BU+HIV+ patients had a single lesion and ulcers were the most common lesion type. The lesions presented were predominantly category II (5/9) followed by category I lesions. The median (IQR) time to healing was 14 (8-28) weeks in the BU+HIV+ compared to 28 (12-33) weeks in the control BU+HIV- group (p = 0.360). Only one BU+HIV+ developed a paradoxical reaction at week 16 but the lesion healed completely at week 20. The median bacterial load (16SrRNA) of BU+HIV+ patients was 750 copies /ml (95% CI 0-398,000) versus 500 copies/ml (95% CI 0-126,855,500) in BU+HIV- group. Similarly, the median count using the IS2404 assay was 500 copies/ml (95% CI 0-500) for BU+HIV+ patients versus 500 copies/ml (95% CI 500-31,000) for BU+HIV- patients. BU+HIV- patients mounted a significantly higher interferon-γ response compared to the BU+HIV+ co-infected patients with respective median (range) responses of [1687(81.11-4399) pg/ml] versus [137.5(4.436-1406) pg/ml, p = 0.03]. There were challenges with the integration of HIV and BU care in this cohort. CONCLUSION: The prevalence of HIV in the BU+ infected population was not significantly increased when compared to the prevalence of HIV in the general population. There was no clear relationship between BU lesion severity and HIV viral load or CD4 counts. Efforts should be made to encourage the integration of care of patients with BU-HIV coinfection.

Cytokines and Chemokines Involved in Hepatitis B Surface Antigen Loss in Human Immunodeficiency Virus/Hepatitis B Virus Coinfected Patients.

It has been reported that hepatic flare (HF), attributable to the development of immune reconstitution inflammatory syndrome (IRIS) in human immunodeficiency virus (HIV)/hepatitis B virus (HBV) coinfected patients, occurs frequently after the start of anti-retroviral therapy (ART). We have observed several cases of hepatitis B surface antigen (HBsAg) loss after IRIS. However, the factors leading to HBsAg clearance remain unknown. We measured CD4+ and CD8+ T cells, cytokines and chemokines in 16 patients coinfected HIV-1 and HBV with IRIS, and analyzed the factors leading to HBsAg clearance after IRIS. There was no significant difference in the CD4+ and CD8+ T cell counts between the HBsAg clearance and non-clearance groups, while the serum concentrations of almost all cytokines and chemokines in the HBsAg clearance group were higher than in the HBsAg non-clearance group at any time of observation. In particular, IP-10 at the ALT peak, GM-CSF and IL-12 one month after the ALT peak and TNF-α and GM-CSF after the ALT concentrations fell to within normal limits, were significantly higher in the HBsAg clearance group. It seems that HBsAg loss after IRIS requires continued immune responses against HBV, involving Th1 cytokines.

Cytomegalovirus infection as an underestimated trigger for checkpoint inhibitor-related pneumonitis in lung cancer: a retrospective study

Objectives Checkpoint inhibitor-related pneumonitis (CIP) is a rare but potentially fatal complication of immune checkpoint inhibitors (ICIs). At present, the mechanism of CIP is not completely clear. Cytomegalovirus (CMV) infection is widespread in the population. Chemotherapy and radiotherapy can lead to the reactivation of CMV. We aimed to investigate the association between CMV infection and CIP. Materials and methods We retrospectively identified all lung cancer patients treated with ICIs at our institute from January 2016 to May 2020. The association between the development of CIP and CMV infection status was analyzed. Results Among 251 cases analyzed, 29 (11.6%) patients with CIP were identified, of whom 12 (4.78%) cases had grade 3–4 CIP. All 12 patients with grade 3–4 pneumonitis were CMV-IgG-positive, indicating a previous CMV infection. Except for one CMV-DNA-positive patient, the other patients were CMV-DNA-negative. All but one patient was CMV pp65 antigen-positive, indicating an early reactivation of the virus. The histological features of CMV pneumonia were not found in all available lung tissues, including lung transplantation pathology in one patient and lung biopsies in three patients. Except for one patient who received delayed antiviral therapy, the symptoms improved after glucocorticoid combined with antiviral therapy. Conclusions The use of ICIs can restore the immune function and cause an immune response to CMV antigen while the infection is still latent. Our study suggests that CIP may be an immune reconstitution syndrome associated with CMV infection. CMV infection may represent a potentially important trigger for CIP. Patients with severe CIP should be vigilant against CMV infection. The early use of glucocorticoid combined with antiviral therapy is pivotal to good prognosis (AU)

Cytomegalovirus infection as an underestimated trigger for checkpoint inhibitor-related pneumonitis in lung cancer: a retrospective study.

OBJECTIVES: Checkpoint inhibitor-related pneumonitis (CIP) is a rare but potentially fatal complication of immune checkpoint inhibitors (ICIs). At present, the mechanism of CIP is not completely clear. Cytomegalovirus (CMV) infection is widespread in the population. Chemotherapy and radiotherapy can lead to the reactivation of CMV. We aimed to investigate the association between CMV infection and CIP. MATERIALS AND METHODS: We retrospectively identified all lung cancer patients treated with ICIs at our institute from January 2016 to May 2020. The association between the development of CIP and CMV infection status was analyzed. RESULTS: Among 251 cases analyzed, 29 (11.6%) patients with CIP were identified, of whom 12 (4.78%) cases had grade 3-4 CIP. All 12 patients with grade 3-4 pneumonitis were CMV-IgG-positive, indicating a previous CMV infection. Except for one CMV-DNA-positive patient, the other patients were CMV-DNA-negative. All but one patient was CMV pp65 antigen-positive, indicating an early reactivation of the virus. The histological features of CMV pneumonia were not found in all available lung tissues, including lung transplantation pathology in one patient and lung biopsies in three patients. Except for one patient who received delayed antiviral therapy, the symptoms improved after glucocorticoid combined with antiviral therapy. CONCLUSIONS: The use of ICIs can restore the immune function and cause an immune response to CMV antigen while the infection is still latent. Our study suggests that CIP may be an immune reconstitution syndrome associated with CMV infection. CMV infection may represent a potentially important trigger for CIP. Patients with severe CIP should be vigilant against CMV infection. The early use of glucocorticoid combined with antiviral therapy is pivotal to good prognosis.

Histoplasmosis diseminada asociada a síndrome de reconstitución inmune en un paciente con virus de la inmunodeficiencia humana / Disseminated histoplasmosis associated to immune reconstitution syndrome in a patient with human immunodeficiency virus

Introducción: La histoplasmosis es una micosis profunda o sistémica causada por un hongo dimórfico que se puede diseminar principalmente en pacientes con inmunosupresión, como los que tienen diagnóstico de virus de la inmunodeficiencia humana. El síndrome de reconstitución inmune consiste en un empeoramiento paradójico de una condición conocida o de nueva aparición después del inicio de la terapia antirretroviral. Objetivo: Describir un caso de histoplasmosis diseminada asociada a síndrome de reconstitución inmune en un paciente con infección por virus de la inmunodeficiencia humana. Caso clínico: Paciente masculino de 32 años con diagnóstico de infección por virus de la inmunodeficiencia humana, con cuadro clínico de tres semanas de evolución. Este cuadro inició posterior al comienzo de la terapia antirretroviral, que consistió en pápulo-nódulos umbilicados diseminados, con compromiso pulmonar; además, tenía histopatología y cultivo positivos para Histoplasma capsulatum sl. y prueba de antigenuria para histoplasma también positiva. Se consideró un diagnóstico de histoplasmosis diseminada con presentación cutánea, fue la expresión de un síndrome de reconstitución inmune por desenmascaramiento. Se inició manejo con anfotericina B liposomal y se mantuvo la terapia antirretroviral; posteriormente se continuó el tratamiento con itraconazol durante 12 meses con mejoría de las lesiones. Conclusiones: El diagnóstico clínico, histopatológico y microbiológico fue oportuno; el paciente presentó una adecuada respuesta al tratamiento. Esta es una micosis curable e incluso prevenible, si se diagnostica a tiempo, se inicia tratamiento precoz y se mantiene la terapia retroviral(AU)

Introduction: Histoplasmosis is a deep or systemic mycosis caused by a dimorphic fungus which may disseminate mainly in immunocompromised patients, such as those diagnosed with human immunodeficiency virus. Immune reconstitution syndrome is a paradoxical worsening of a known condition or a condition appearing after the start of antiretroviral therapy. Objective: Describe a case of disseminated histoplasmosis associated to immune reconstitution syndrome in a patient with human immunodeficiency virus infection. Case report: A case is presented of a male 32-year-old patient diagnosed with human immunodeficiency virus with a clinical status of three weeks' evolution. The current status developed after the start of antiretroviral therapy. It consisted in disseminated umbilicated papular nodules with pulmonary involvement, as well as positive Histoplasma capsulatum sl. histopathology and culture, and a positive histoplasma antigen test. A diagnosis of disseminated histoplasmosis with a cutaneous presentation was considered. It was the expression of immune reconstitution syndrome by unmasking. Treatment was started with liposomal amphotericin B, maintaining the antiretroviral therapy. Management was then continued with itraconazole for 12 months with improvement of the lesions. Conclusions: Timely clinical, histopathological and microbiological diagnosis was performed. The patient displayed an adequate response to treatment. This mycosis is curable and even preventable when a diagnosis is made in time, treatment is started early and the retroviral therapy is maintained(AU)

Rare Ocular Involvement in a Newly Diagnosed AIDS Patient With Diffuse Kaposi's Sarcoma.

Kaposi's sarcoma (KS) is a cancer that often affects individuals with human immunodeficiency virus, acquired immunodeficiency syndrome (AIDS), those who have received an organ transplant, or others who are immunocompromised. KS is a vascular tumor that most often presents in cutaneous sites, including the lower extremities, oral mucosa, and genitalia. Literature regarding KS with ocular involvement is scarce. We present a rare case in which a patient diagnosed with AIDS-associated KS exhibited ocular and diffuse manifestations. The lesions of cutaneous KS are frequently mistaken for an alternative diagnoses; therefore, the clinician should have a high index of suspicion for this vascular tumor in AIDS patients.

Effects of time of initiation of antiretroviral therapy in the treatment of patients with HIV/TB co-infection: A systemic review and meta-analysis.

This systemic review and meta-analysis aimed to investigate the burden of tuberculosis immune reconstitution syndrome (TB-IRIS) and associated mortality to highlight the importance of future direction in preventing and treatment of TB-IRIS. Randomized clinical trials (RCTs) that compared early antiretroviral therapy (ART) versus late ART were included. PubMed, EMBASE, Science Direct and Cochrane Central Register of Controlled Trials electronic databases were searched. This meta-analysis included 8 RCTs with a total of 4, 425 participants. The result of analysis showed that early initiation of ART was associated with increase in TB-IRIS (RR = 1.83; 95% CI: 1.24-2.70, p = 0.002; I2 = 74%, p = 0.0007) and TB-IRIS associated mortality (RR = 6.05; 95% CI: 1.06-34.59, p = 0.04; I2 = 0%, p = 0.78). Early ART was associated with overall mortality compared with late ART initiation. Grade 3 or 4 adverse events, achieving lower viral load and development of new AIDS-defining illness were not associated with the time of ART initiation. Early ART in HIV/TB co-infected patients resulted conclusive evidence of increased TB-IRIS incidence and TB-IRIS associated mortality. Hence, the finding calls for clinical judgment as to the benefits of initiating ART earlier against the risk of TB-IRIS and associated mortality.

[Periorbital erythematous plaques and papules in an HIV-positive patient : A case report]. / Periorbitale erythematöse Plaques und Papeln bei einem HIV-positiven Patienten : Ein Fallbericht.

Prior to the introduction of antiretroviral therapy, the concomitant occurrence of sarcoidosis and human immunodeficiency virus (HIV) was extremely rare. Today, an increased prevalence of sarcoidosis as a result of immune reconstitution syndrome (IRIS) is observed in HIV patients. A 37-year-old male patient that was co-infected with HIV and hepatitis C had a 6­month history of gradually progressive asymptomatic periorbital erythematous plaques and papules. Routine clinical examinations were normal. Skin punch biopsy taken from the upper portion of the right cheek showed several non-caseating dermal granulomas with multinucleated giant cells, enabling unequivocal histological diagnosis. Based on the clinical picture and histological findings, the patient was diagnosed with cutaneous sarcoidosis. This case study underlines the change in possible rheumatological and dermatological comorbities in HIV-positive patients treated with highly active antiretroviral therapy. Therefore, physicians treating HIV infections should be familiar with the definition of IRIS.