Systemic lupus erythematosus associated with HIV infection: a retrospective case-control study.

OBJECTIVES: The association of systemic lupus erythematosus (SLE) and human immunodeficiency virus (HIV) remains scarcely described in the literature. Our objectives were to describe the characteristics of SLE in patients living with HIV (SLE-PLHIV) and compare it with SLE characteristics in patients without HIV infection. METHODS: We performed a retrospective study of 13 patients with SLE-PLHIV diagnosed between 1975 and 2020 in four different French hospitals. These patients were compared in a case-control study with a 1:5 ratio to age-, sex- and year of diagnosis- matched patients with SLE without HIV infection. RESULTS: Median (IQR) age at SLE diagnosis for patients with SLE and HIV infection was 43 years (36-53). There were 77% women. Main clinical manifestations were polyarthrtitis (84%), cutaneous lupus (69%), kidney disease (54%), serositis (15%) and autoimmune cytopenias (auto-immune haemolytic anaemia and/or immune thrombocytopenia) (31%). There were no neuropsychiatric manifestations. All patients had positive antinuclear antibody test with a titre ≥1:160. Anti-dsDNA antibodies were present in 75% of patients, and anti-Sm antibodies in 33%. SLE-PLHIV had more frequently renal manifestations (54 vs. 16%, p=0.006) and autoimmune cytopenia (31 vs 8%, p=0.04) than patients without HIV infection. CONCLUSIONS: SLE and HIV infection appear to be a rare association. Patients with SLE-PLHIV seem to have more renal manifestations and autoimmune cytopenias than patients with SLE without HIV infection.

A Prospective Comparative Study of Health Inequalities and the Epidemiology of Stroke in French Guiana and Dijon, France.

Background: In French Guiana poverty is widespread and specialized care is lacking. We aimed to compare strokes between precarious and non-precarious patients within French Guiana and to compare the epidemiology of ischemic strokes and their outcomes between French Guiana and mainland France. Methods: A multicenter prospective cohort examined the influence of social inequalities on stroke characteristics. Consecutive patients aged > 18 years admitted for an acute ischemic stroke, confirmed by neuroimaging were eligible. Exclusion criteria were a history of symptomatic stroke, presence of other short-term life-threatening diseases and inability to contact patients by telephone during follow-up. Social deprivation was measured using the EPICES score, which is based on a multidimensional questionnaire. Results: Overall, 652 patients with ischemic stroke were included. The patients in French Guiana were 7 years younger, were more frequently male, of sub-Saharan ancestry, they had a low level of education, and were more often precarious (67.7%) than the patients included in Dijon (39.2%). The origin of the ischemic stroke was predominantly lacunar for patients included in French Guiana and cardioembolic for patients included in Dijon, with greater severity for patients included in Dijon. The proportion of patients with known pre-stroke hypertension, diabetes, or a history of Transient Ischemic Accident was greater in French Guiana than in Dijon. In contrast, hypercholesterolemia, atrial fibrillation, and history of Myocardial Infarction were more frequently found in patients included in Dijon than in patients included in French Guiana. Fibrinolysis was less frequent in French Guiana than in Dijon, 24% of patients arriving early enough receiving thrombolysis in French Guiana vs. 45% in Dijon, P < 0.0001. However, after adjustment for patient characteristics, the effect of the center on the use of fibrinolysis disappeared. When comparing precarious and non-precarious patients within French Guiana, the main difference was the younger age and the lower mortality of precarious patients-notably immigrants. Conclusion: Precariousness was widespread in French Guiana. Within French Guiana, despite a younger age among foreigners than French patients, the risk factors, mechanisms, and outcomes were homogenous across socioeconomic strata. The observed differences between the two contrasted French territories suggested that, beyond health inequalities, the epidemiology of cardiovascular risk factors may differ between French Guiana and mainland France.

Review of diagnostic methods and results for HIV-associated disseminated histoplasmosis: Pathologists are not sufficiently involved.

OBJECTIVES: Disseminated histoplasmosis is a major killer of HIV-infected persons in Latin America. Antigen detection, fungal culture and Polymerase Chain Reaction are often not available, but cytology and histology are present in most hospitals and may offer a diagnostic alternative. In this study, we review 34 years of clinical experience to describe the roles of cytology and histology in diagnosing disseminated histoplasmosis. METHODS: Retrospective multicentric study of 349 patients between 1 January 1981 and 1 October 2014 with confirmed disseminated histoplasmosis. RESULTS: Around 32/214 (14.9%) of samples were screened using cytopathology, as were 10/101 (9.9%) bronchoalveolar lavage samples and 5/61 (8.2%) of spinal fluid samples. The samples most commonly sent to pathology were liver biopsies, lower digestive tract and lymphnode biopsies; the greatest proportion of positive results were found in lower digestive tract (43/59 (72.9%) positives), lymph node (39/63 (66.1%)), and liver (38/75 (50.7%)) samples. Overall, 97.2% of bone marrow and 97% of bronchoalveolar lavage samples were directly examined by a mycologist. Positive direct examination was independently associated with death (aHR = 1.5 (95%CI = 1-2.2)). CONCLUSIONS: Opportunities for a rapid diagnosis were regularly missed, notably for bone marrow samples, which could have been examined using staining methods complementary to those of the mycologist.

HIV-Associated Disseminated Histoplasmosis and Rare Adrenal Involvement: Evidence of Absence or Absence of Evidence.

Adrenal histoplasmosis and primary adrenal insufficiency are mostly described in immunocompetent patients. This particular tropism is attributed to the presence of cortisol within the adrenal gland, a privileged niche for Histoplasma growth. In French Guiana, disseminated histoplasmosis is the main opportunistic infection in HIV patients. Our objective was to search in our HIV-histoplasmosis cohorts to determine how frequent adrenal insufficiency was among these patients. Between January 1, 1981 and October 1, 2014, a multicentric retrospective, observational study of histoplasmosis was conducted. Patients co-infected by HIV and histoplasmosis were enrolled in French Guiana's histoplasmosis and HIV database. Among 349 cases of disseminated histoplasmosis between 1981 and 2014, only 3 had adrenal insufficiency (0.85%). Their respective CD4 counts were 10, 14 and 43 per mm3. All patients had regular electrolyte measurements and 234/349 (67%) had abdominal ultrasonography and 98/349 (28%) had abdominopelvic CT scans. None of these explorations reported adrenal enlargement. Overall, these numbers are far from the 10% reports among living patients and 80-90% among histoplasmosis autopsy series. This suggests 2 conflicting hypotheses: First, apart from acute adrenal failure with high potassium and low sodium, less advanced functional deficiencies, which require specific explorations, may have remained undiagnosed. The second hypothesis is that immunosuppression leads to different tissular responses that are less likely to incapacitate the adrenal function. Furthermore, given the general immunosuppression, the adrenal glands no longer represent a particular niche for Histoplasma proliferation.

Gastrointestinal disseminated histoplasmosis in HIV-infected patients: A descriptive and comparative study.

Disseminated histoplasmosis is one the main AIDS-defining opportunistic infections in HIV-infected patients, notably in Latin America. The non-specific and proteiform clinical presentation leads to diagnostic delays that may lead to fatal outcomes. This retrospective multicentric study aimed to describe the frequency and manifestations of gastrointestinal histoplasmosis in French Guiana, and to compare patients with disseminated histoplasmosis with or without gastrointestinal involvement. Between January 1, 1981 and October 1, 2014 co-infections with HIV and histoplasmosis were enrolled. Inclusion criteria were: age >18 years, confirmed HIV infection; first proven episode of histoplasmosis. Among 349 cases of disseminated histoplasmosis, 245 (70%) had a gastrointestinal presentation. Half of patients with gastrointestinal signs had abdominal pain or diarrhea, mostly watery. Half of patients with abdominal pain had diarrhea (63/124) and half of those with diarrhea (63/123) had abdominal pain. A significant proportion of patients also had hepatomegaly and, to a lesser degree, splenomegaly. After adjusting for potential confounding, the presence of lymphadenopathies >2cm (AOR = 0.2, IC95 = 0.04-0.7, P = 0.01), Haitian origin (AOR = 0.04, IC95 = 0.004-0.4, P = 0.006) were associated with a lower prevalence of gastrointestinal signs and positive gastrointestinal presence of H. capsulatum. Persons with a gastrointestinal H. capsulatum were more likely to have a decreased prothrombin time, lower ferritin, lower liver enzymes, and lower concentrations of LDH than those without gastrointestinal signs and symptoms. They also had a shorter interval between symptoms onset and diagnosis. Patients with a positive gastrointestinal identification of H. capsulatum were less likely to die at 1 month than those without a gastrointestinal presentation (respectively, 4.6% vs 18.5%, P = 0.01). Subacute or chronic gastrointestinal presentations are very frequent during disseminated histoplasmosis, they seem less severe, and should lead to suspect the diagnosis in endemic areas. There were populational or geographic differences in the frequency of gastrointestinal manifestations that could not be explained.

Risk Factors for Mortality among HIV-Infected Patients with Disseminated Histoplasmosis.

Identifying prognostic factors is important in order to guide the choice of first-line therapy for disseminated histoplasmosis. Our objective was to identify factors associated with death among a cohort of 330 patients compiled over 34 years of clinical practice in French Guiana. Survival analysis was performed with death as the failure event and date of symptom onset as the origin event. Incidence rates were and Cox proportional hazards models were computed. Overall, 330 HIV-infected patients with disseminated histoplasmosis were included in the analysis, with 126 deaths occurring. One-quarter of all patients died within 6 months of the first symptoms. Patients with dyspnea, renal failure, arterial blood pressure < 90 mmHG, and a WHO performance score > 2 had a greater incidence of death. Bivariate analyses showed that patients with increased LDH, low hemoglobin, low serum protein, low CD4 counts, and low platelets tended to have a greater incidence of death. After adjusting for potential confounders, patients with dyspnea, a WHO performance score > 2, serum protein < 60 g/L, and hemoglobin < 8.9 g/dL had an increased risk of dying. The interaction terms showed that patients treated with liposomal amphotericin B had a marked reduction in death among patients with renal failure; among renal failure patients, the elevation of LDH was associated with a significant risk of death.

Heterogeneity of Clinical Presentations and Paraclinical Explorations to Diagnose Disseminated Histoplasmosis in Patients with Advanced HIV: 34 Years of Experience in French Guiana.

We aimed to describe the ways patients with disseminated histoplasmosis-a multifaceted and often lethal disease-present themselves and are explored. A retrospective, observational, multicentric study spanned the period between 1 January 1981 and 1 October 2014. Principal component analysis was performed for the sampling sites and for the clinical signs and symptoms. The factor loadings of the principal components were selected for eigenvalues > 1. The most frequent signs and symptoms were an alteration of the WHO general performance status, fever, digestive tract, respiratory signs and symptoms and lymphadenopathies. The most common sites sampled were bone marrow, respiratory tract, blood, lymph node and liver biopsies, with significant variations in the number of sites from which samples were taken to try to identify the pathogen. The principal component analysis clinical signs and symptoms leading to the diagnosis showed four main lines of variation. The factor loadings of the four main components were compatible with four broad types of clinical presentations and four types of exploration strategies. Extracting simple algorithms was difficult, emphasizing the importance of clinical expertise when diagnosis depends on obtaining a sample where Histoplasma can be seen or grown. Histoplasma antigen detection tests will help simplifying the algorithms.

Disseminated Histoplasmosis in HIV-Infected Patients: A Description of 34 Years of Clinical and Therapeutic Practice.

Disseminated histoplasmosis is the main AIDS-defining infection of French Guiana. We aim to describe our therapeutic experience for 349 patients with disseminated histoplasmosis between 1 January 1981 and 10 January 2014 in French Guiana. Survival, delays for treatment initiation, duration of induction therapy, and associated initial treatments are described. The death rate was 14.9 per 100 person-years, with an early drop in survival. Among those who died, >1/3 died within a year of HIV diagnosis, and ¾ of all patients with histoplasmosis had been diagnosed for HIV within a year. As induction treatment, 29% received liposomal amphotericin B, 12.9% received deoxycholate amphotericin B, 54% received itraconazole alone, and 21.8% received liposomal amphotericin B and itraconazole. The median delay between symptoms-onset and hospitalization was 19.5 days (IQR = 5-105). Liposomal amphotericin B or itraconazole was initiated shortly after admission. Treatment initiation was often presumptive for liposomal amphotericin B (27%) and itraconazole (20%). The median duration of liposomal amphotericin B treatment was 7 days (IQR = 5-11 days). The present study shows that ¾ of the patients were profoundly immunocompromised and had been diagnosed for HIV within the past year. Antifungal treatment was often initiated presumptively on admission. Over time there was a significant gradual decline in early death.

Reduced Severity in Patients With HIV-Associated Disseminated Histoplasmosis With Deep Lymphadenopathies: A Trench War Remains Within the Lymph Nodes?

Background: Disseminated histoplasmosis is a major killer of patients with advanced HIV. It is proteiform and often hard to diagnose in the absence of diagnostic tests. We aimed to describe disseminated histoplasmosis with lymphadenopathies in French Guiana and to compare survival and severity of those patients to patients without lymphadenopathies. Methods: A retrospective cohort study was performed on data records collected between January 1, 1981 and October 1, 2014. Results: Among 349 cases of disseminated histoplasmosis 168 (48.3%) had superficial lymphadenopathies and 133(38.1%) had deep lymphadenopathies. The median LDH concentration, ferritin concentration, TGO concentration, and WHO performance status were lower among patients with deep lymphadenopathies than those without deep lymphadenopathies. There was a significant decrease in the risk of early death (<1 month) among those with deep lymphadenopathies relative to those without (OR=0.26 (95%CI=0.10-0.60), P=0.0006) and in the overall risk of death (OR=0.33 (95%CI=0.20-0.55), P<0.0001). These associations remained strongly significant after adjusting for time period, CD4 counts, age, delay between beginning of symptoms and hospital admission, antifungal and antiretroviral treatment. Conclusions: The present data show that in patients with advanced HIV and disseminated histoplasmosis, the presence of deep lymphadenopathies is associated with fewer markers of severity and a lower risk of death. To our knowledge it is the first study to show this. The presence of deep lymphadenopathies is hypothesized to reflect the patient's partially effective defense against H. capsulatum.

Population movements and the HIV cascade in recently diagnosed patients at the French Guiana -Suriname border.

Border areas are particular "hot spots" generating high levels of HIV vulnerability and facing great challenges to control epidemics. The objective of this study is to describe the sociodemographic, clinical and biological profiles of newly HIV diagnosed people at the French Guiana - Suriname border, to construct an HIV care cascade and compare it with the Surinamese one. HIV-patients aged over 15 years newly diagnosed in western French Guiana in 2011 and 2012 were included in a retrospective cohort study. Patients were identified using different sources (n = 121). The male-to-female ratio was 0.8, 85% of the patients were of foreign origin, 72% were undocumented migrants, 21% were living in Suriname and 48% had baseline CD4 cell counts <200 cells/mm3. After one year, 34% were lost to follow-up, 54% received treatment, 34% had controlled viremia and 6% died. We observed a disappointing HIV cascade, like that of Suriname, requiring to develop a coordinated healthcare offer on both sides of the border. Targeted efforts through a bi-national collaboration are needed to address the specific issues of cross-border patients to reach the 90*3 UNAIDS's diagnosis, link to care and treatment targets and better control the local epidemic.

Fever in hospitalized HIV-infected patients in Western French Guiana: first think histoplasmosis.

In Western French Guiana, there was a dramatic increase in HIV prevalence between 1990 and 2000. The present study describes the causes of fever among HIV patients hospitalized in the medical ward of the only hospital in the western part of French Guiana. A retrospective descriptive study was conducted between 1 January 2008 and 30 June 2010 in the department of medicine of Saint Laurent du Maroni Hospital. The main characteristics of 67 patients having presented with fever in the first 48 hours of hospitalization were described. Among patients with CD4 <200/mm(3)the main febrile opportunistic infection was disseminated histoplasmosis (41.1%). Among patients with CD4 counts <50/mm(3)and fever without focal points 85.7% had disseminated histoplasmosis. Three patients died and all had disseminated histoplasmosis. Disseminated histoplasmosis is the most common febrile opportunistic infection in western French Guiana. Primary prophylaxis with itraconazole among immunocompromised patients seems warranted.