RESUMO
OBJECTIVE: To determine the sensitivity and specificity of a commercial whole blood real-time PCR assay (RT-PCR) for the diagnosis of histoplasmosis when compared to direct organism identification and/or urine antigen quantification by enzyme immunoassay (UA-EIA). A secondary objective was to compare the sensitivity and specificity of RT-PCR to anti-Histoplasma immunoglobulin G antibody detection by enzyme immunoassay (IgG-EIA) and IgG-EIA to UA-EIA. ANIMALS: Cats presented to the Kansas State University Veterinary Health Center from February through September of 2023 in which histoplasmosis was diagnosed or suspected. METHODS: From February through September of 2023, cats were tested by RT-PCR, IgG-EIA, and UA-EIA if histoplasmosis was diagnosed cytologically or was a differential diagnosis for the presenting clinical signs. Cats were excluded if all 3 tests were not submitted or if the diagnosis of histoplasmosis could not be excluded despite a negative UA-EIA result. Cats with cytologically or histologically confirmed histoplasmosis were designated as proven histoplasmosis cases, and cats with a positive UA-EIA result without cytological or histological confirmation were designated as probable histoplasmosis cases. RESULTS: 10 cats were diagnosed with either proven (n = 6) or probable (4) histoplasmosis, and 10 cats were considered true negatives. Whole blood RT-PCR results were negative in all 20 cats (sensitivity, 0%; 95% CI, 0% to 30.85%). The IgG-EIA was 90% sensitive (95% CI, 55.50% to 99.75%) and 70% specific (95% CI, 34.75% to 93.33%). The UA-EIA results were positive in all cats with proven histoplasmosis. CLINICAL RELEVANCE: This commercial RT-PCR is insensitive when used on whole blood collected in EDTA and should not be used to diagnose feline histoplasmosis. Further studies are required to determine whether alternate RT-PCR protocols for EDTA-collected whole blood could be useful for diagnosing histoplasmosis in cats.
Assuntos
Doenças do Gato , Histoplasmose , Reação em Cadeia da Polimerase em Tempo Real , Animais , Gatos , Antígenos de Fungos/sangue , Antígenos de Fungos/urina , Doenças do Gato/diagnóstico , Doenças do Gato/sangue , Doenças do Gato/microbiologia , Histoplasma/isolamento & purificação , Histoplasmose/veterinária , Histoplasmose/diagnóstico , Histoplasmose/sangue , Técnicas Imunoenzimáticas/veterinária , Imunoglobulina G/sangue , Reação em Cadeia da Polimerase em Tempo Real/veterinária , Sensibilidade e EspecificidadeAssuntos
Antígenos de Fungos , Histoplasma , Histoplasmose , Humanos , Histoplasmose/urina , Histoplasmose/sangue , Histoplasmose/diagnóstico , Histoplasmose/imunologia , Histoplasma/imunologia , Antígenos de Fungos/urina , Antígenos de Fungos/sangue , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Hidratação/métodos , IdosoRESUMO
BACKGROUND: The advent of tumor necrosis factor-α (TNF-α) inhibitor therapy has transformed inflammatory bowel disease management; however, these medications carry a boxed warning for risk of serious infections, including invasive fungal infections. AIMS: We aimed to study the clinical features, severity, and outcomes of histoplasmosis in patients on TNF-α inhibitors for IBD. METHODS: We performed a retrospective review of IBD patients receiving TNF-α inhibitors who developed histoplasmosis from January 1, 2001, to May 31, 2018. Patients with drug indications other than ulcerative colitis or Crohn's disease were excluded. IBD was diagnosed histologically, radiographically, or endoscopically. RESULTS: We identified 49 patients (median age 44 years; range 19-76) with histoplasmosis on TNF-α inhibitors. Patients with disseminated disease had a median urine antigen of 10.76 ng/mL compared with pulmonary disease alone 0.375 ng/mL (p < 0.001). Charlson Comorbidity Index and urine antigen levels showed a trend toward predicting disease severity (p > 0.05). Median length of stay was 9.5 days. Itraconazole was used for maintenance in all patients. Median follow-up was 4.7 years. Total treatment duration ranged from 3 to 15 months. TNF-α inhibitor therapy was continued in nine and resumed in ten patients after completing antifungals. Three deaths occurred (6%). CONCLUSIONS: Histoplasmosis outcomes were mostly favorable. Many patients were young with few comorbidities; however, those with more comorbidities experienced more severe histoplasmosis. Compared to prior studies, many of these patients resumed or continued biologic therapy. There were no histoplasmosis recurrences after resuming TNF-α inhibitor therapy. Vigilance for disseminated fungal infections in this patient population is essential.
Assuntos
Produtos Biológicos/uso terapêutico , Histoplasmose/diagnóstico por imagem , Histoplasmose/tratamento farmacológico , Doenças Inflamatórias Intestinais/diagnóstico por imagem , Doenças Inflamatórias Intestinais/tratamento farmacológico , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Adalimumab/farmacologia , Adalimumab/uso terapêutico , Adulto , Idoso , Produtos Biológicos/farmacologia , Estudos de Coortes , Feminino , Seguimentos , Histoplasmose/sangue , Humanos , Doenças Inflamatórias Intestinais/sangue , Infliximab/farmacologia , Infliximab/uso terapêutico , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto JovemRESUMO
Histoplasmosis is an opportunistic systemic infection caused by inhaling spores of a thermal dimorphic fungus Histoplasma capsulatum. Disseminated histoplasmosis is the most common form associated with acquired immune deficiency syndrome (AIDS). However, only a few cases of disseminated histoplasmosis are reported in immuno-competent hosts. Most infections in the immunocompetent hosts are asymptomatic or result in mild pulmonary disease. However the presence of Disseminated Histoplasmosis in immunocompetent host probably results due to prolonged exposure and delayed presentation We report two cases of progressive disseminated histoplasmosis in two immunocompetent patients from non-endemic region in Western Rajasthan, India. Also in both the cases, the first diagnosis was suggested by a peripheral blood smear, which is not a classical biological diagnostic method for fungal infection. Careful examination of Peripheral blood smear along with correct clinical history can aid in early diagnosis of disseminated histoplasmosis even in immunocompetent patients.
Assuntos
Histoplasmose/sangue , Histoplasmose/diagnóstico , Imunocompetência , Infecções Fúngicas Invasivas/diagnóstico , Antifúngicos/uso terapêutico , Coleta de Amostras Sanguíneas , Evolução Fatal , Histoplasma/patogenicidade , Histoplasmose/tratamento farmacológico , Humanos , Índia , Infecções Fúngicas Invasivas/microbiologia , Masculino , Pessoa de Meia-Idade , Centros de Atenção TerciáriaRESUMO
BACKGROUND: Hemophagocytic lymphohistiocytosis syndrome (HLS) is an immune-mediated life-threatening disease considered as a medical emergency, with a potentially fatal multisystem inflammatory outcome. We present a patient that developed HLS and was able to be diagnosed efficiently with the help of an academic research institute of immunology. CASE PRESENTATION: A 21 years old male Mexican with human immunodeficiency virus (HIV), late presenter; who developed cytomegalovirus (CMV) infection and a disseminated histoplasmosis-related HLS, as part of an immune reconstitution inflammatory syndrome (IRIS). The patient required a long course of corticotherapy, intravenous immunoglobulin and massive transfusions (more than 10 units in 24 h, and a total of 83 units), besides amphotericin-B and ganciclovir treatment. An academic research institute of immunology aided in the accurate diagnosis of HLS with the implementation of tests not available within the hospital, thus improving the care provided to the patient. The patient recovered, was discharged, and continue to improve. CONCLUSION: The objective of this report is to highlight the importance of having multidisciplinary support, including basic medical sciences groups providing specific tests that are sometimes very difficult to get, which provides a benefit to patients in the well-aimed diagnosis as part of applied translational medicine.
Assuntos
Infecções por Citomegalovirus/diagnóstico , Histoplasmose/sangue , Linfo-Histiocitose Hemofagocítica/diagnóstico , Antivirais/uso terapêutico , Infecções por HIV/complicações , Infecções por HIV/virologia , Histoplasmose/complicações , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Linfo-Histiocitose Hemofagocítica/etiologia , Linfo-Histiocitose Hemofagocítica/terapia , Masculino , Resultado do Tratamento , Adulto JovemRESUMO
A 50-year-old woman with a history of kidney transplant presented with 2 days of abdominal pain after 6 months of recurrent streptococcal pharyngitis, fevers, weight loss and a new rash on her chest and back. Her examination was notable for a unilateral tonsillar exudate and 2-3 mm pink papules with a fine scale over her chest and back. CT of the abdomen and chest demonstrated several large lymph nodes, and laboratory investigation revealed new cytopenias and elevated transaminases. Urine antigen testing for Histoplasma capsulatum was negative, but a fungal complement fixation panel was reactive for Histoplasma antibodies. Skin biopsy revealed intracellular organisms consistent with H. capsulatum She underwent treatment with liposomal amphotericin B but due to nephrotoxicity, drug interactions and worsening transaminitis, therapy was changed to itraconazole. The diagnosis and management of disseminated histoplasmosis presents multiple challenges, which are of particular importance in patients with a history of renal transplantation.
Assuntos
Anticorpos Antifúngicos/sangue , Histoplasma , Histoplasmose , Itraconazol/administração & dosagem , Transplante de Rim , Linfadenopatia , Tomografia Computadorizada por Raios X/métodos , Antifúngicos/administração & dosagem , Antígenos de Fungos , Diagnóstico Diferencial , Feminino , Histoplasma/imunologia , Histoplasma/isolamento & purificação , Histoplasmose/sangue , Histoplasmose/diagnóstico , Histoplasmose/fisiopatologia , Histoplasmose/terapia , Humanos , Hospedeiro Imunocomprometido , Transplante de Rim/efeitos adversos , Transplante de Rim/métodos , Linfadenopatia/diagnóstico por imagem , Linfadenopatia/etiologia , Transtornos Linfoproliferativos/diagnóstico , Pessoa de Meia-Idade , Complicações Pós-Operatórias/diagnóstico , Radiografia Abdominal/métodos , Radiografia Torácica/métodos , Resultado do TratamentoRESUMO
Histoplasma capsulatum is an opportunistic dimorphic fungus caused by inhalation of spores present in the soil. It is extremely rare in the northern Himalayan region of India and is usually asymptomatic. It may rarely progress to disseminated histoplasmosis which is usually observed in immunocompromised patients associated with malignancy, acquired immunodeficiency syndrome or diabetes. The present case is being reported because of unusual cutaneous presentation of disseminated histoplasmosis in an immunocompetent patient of non-endemic region. The case also highlights the importance of fine needle aspiration cytology for its precise early diagnosis and avoiding of further complications.
Assuntos
Histoplasmose/diagnóstico , Linfo-Histiocitose Hemofagocítica/diagnóstico , Fagocitose , Pele/patologia , Adulto , Biópsia por Agulha Fina , Técnicas Citológicas , Diagnóstico Precoce , Histoplasma/patogenicidade , Histoplasmose/sangue , Histoplasmose/complicações , Humanos , Imunocompetência , Linfo-Histiocitose Hemofagocítica/patologia , Masculino , Pele/microbiologiaRESUMO
BACKGROUND: Histoplasmosis is a rare cause of 1, 25-dihydroxy vitamin-D-mediated hypercalcemia. In this study, we report 2 cases of hypercalcemia secondary to histoplasmosis seen at Mayo Clinic, Rochester and a review of cases reported in the literature. METHODS: We conducted a PubMed search using the keywords "hypercalcemia" and "histoplasmosis." Fourteen cases of hypercalcemia secondary to histoplasmosis were reported between 1977 and 2020. We identified an additional 2 patients from our institution. RESULTS: We reviewed a total of 16 cases. The median age at presentation was 58.5 years (interquartile range, 41.5-68.75 years), and 13 of 16 patients (81.2%) were men. Serum parathyroid hormone level was available in 13 of 16 (81.25%) patients, of whom 11 patients (84.6%) had a low level, 1 patient (7.6%) had a normal level, and 1 patient (7.6%) had an elevated level. 1, 25-dihydroxy vitamin D level was reported in 9 of 16 (56.25%) patients. Of these, 5 patients (55.5%) had levels within normal limits, and 4 patients (44.4%) had levels above normal. Serum angiotensin-converting enzyme level was evaluated in 4 of 16 patients (25%), and it was elevated in all 4 (100%) cases. Four patients received corticosteroids before a diagnosis of histoplasmosis was made, which resulted in rapidly progressive disease and death in 2 patients. CONCLUSIONS: In patients with granulomatous disorder and hypercalcemia, it is crucial to rule out infectious etiologies before initiating steroids. Histoplasmosis can cause nonparathyroid hormone-mediated hypercalcemia and, if not suspected, may have catastrophic implications.
Assuntos
Histoplasmose/complicações , Hipercalcemia/etiologia , Adulto , Idoso , Antifúngicos/uso terapêutico , Conservadores da Densidade Óssea/uso terapêutico , Calcitonina/uso terapêutico , Calcitriol/sangue , Difosfonatos/uso terapêutico , Feminino , Hidratação , Histoplasmose/sangue , Histoplasmose/tratamento farmacológico , Humanos , Hipercalcemia/sangue , Hipercalcemia/terapia , Lactente , Masculino , Pessoa de Meia-Idade , Hormônio Paratireóideo/sangue , Proteína Relacionada ao Hormônio Paratireóideo/sangue , Peptidil Dipeptidase A/sangue , Fósforo/sangue , Vitamina D/análogos & derivados , Vitamina D/sangue , Adulto JovemRESUMO
BACKGROUND: Pneumonia caused by opportunistic fungi is a serious complication in immunocompromised patients. Hypercalcemia has been described in renal transplantation associated with Pneumocystis jirovecii (PJP) or Histoplasma capsulatum (HCP) pneumonia. METHODS: We describe 5 patients who underwent kidney transplant between 2014 and 2019 and developed hypercalcemia before the diagnosis of pulmonary fungal infection: 4 patients with PJP and 1 with HCP. We assessed calcium metabolism and kidney function by total and ionized calcium, phosphorus, intact parathormone (iPTH), 25-OH vitamin D, 1,25(OH)2 vitamin D, and serum creatinine levels. RESULTS: Mean albumin-corrected calcium and ionized calcium were 12.56 mg/dL (range, 10.8-13.8 mg/dL) and 1.57 mmol/L (range, 1.43-1.69 mmol/L). Patients were normocalcemic, at 10.12 mg/dL (range, 9.6-10.5 mg/dL), before diagnosis and resolved hypercalcemia after antifungal treatment, at 8.86 mg/dL (range, 8.0-9.5 mg/dL). All patients had low or normal iPTH values, at 29.1 pg/mL (range, <3-44 pg/mL), with higher PTH levels 3 months before diagnosis and after treatment, at 147.3 pg/mL (range, 28.1-479 pg/mL) and 117.5 pg/mL (range, 18.2-245 pg/mL), respectively. The mean value for 25-OH vitamin D was 30.8 ng/mL (range, 14.6-62.8 ng/mL). This supports a PTH-independent mechanism, and we postulated an extrarenal production of 1,25(OH)2 vitamin D. CONCLUSION: In kidney transplant patients, hypercalcemia independent of PTH and refractory to treatment should alert for the possibility of opportunistic fungal pneumonia.
Assuntos
Hipercalcemia/etiologia , Hospedeiro Imunocomprometido , Transplante de Rim , Micoses/imunologia , Infecções Oportunistas/complicações , Pneumonia/imunologia , Adulto , Feminino , Histoplasmose/sangue , Histoplasmose/imunologia , Humanos , Hipercalcemia/sangue , Hipercalcemia/imunologia , Masculino , Pessoa de Meia-Idade , Micoses/sangue , Micoses/complicações , Infecções Oportunistas/imunologia , Infecções Oportunistas/microbiologia , Pneumonia/complicações , Pneumonia/microbiologia , Pneumonia por Pneumocystis/complicações , Pneumonia por Pneumocystis/imunologia , Adulto JovemRESUMO
Histoplasmosis is a rare disease in nonendemic areas. We report a case of a 23-year-old male patient who presented with fever of unknown origin, cytopenias, organomegaly, and allograft dysfunction 4 months after renal transplant with father as donor. Bone marrow examination showed intracellular budding yeast cells, which was confirmed as histoplasmosis by culture of bone marrow biopsy sample. The patient was treated with intravenous liposomal amphotericin and responded well.
Assuntos
Febre de Causa Desconhecida/microbiologia , Histoplasma/isolamento & purificação , Histoplasmose/microbiologia , Transplante de Rim/efeitos adversos , L-Lactato Desidrogenase/sangue , Administração Intravenosa , Anfotericina B/administração & dosagem , Antifúngicos/administração & dosagem , Biomarcadores/sangue , Febre de Causa Desconhecida/sangue , Febre de Causa Desconhecida/diagnóstico , Histoplasma/efeitos dos fármacos , Histoplasmose/sangue , Histoplasmose/diagnóstico , Histoplasmose/tratamento farmacológico , Humanos , Masculino , Valor Preditivo dos Testes , Resultado do Tratamento , Adulto JovemRESUMO
We report a case of disseminated histoplasmosis in a renal transplant recipient who presented with a nodular pulmonary lesion and elevated serum and bronchoalveolar lavage (BAL) Aspergillus galatomannan. This almost led to an erroneous diagnosis of invasive aspergillosis since the donor respiratory tract was known to be colonized with Aspergillus terreus. However, distinctive intracelluar Histoplasma yeasts on peripheral blood smear led to early diagnosis and appropriate treatment. The cross-reactivity between Aspergillus galactomannan and Histoplasma antigen is discussed further.
Assuntos
Histoplasmose/sangue , Histoplasmose/diagnóstico , Transplante de Rim/efeitos adversos , Mananas/sangue , Transplantados , Antifúngicos/uso terapêutico , Aspergilose/sangue , Aspergillus/imunologia , Corantes Azur , Sangue/microbiologia , Líquido da Lavagem Broncoalveolar/microbiologia , Feminino , Galactose/análogos & derivados , Histoplasma/imunologia , Histoplasma/isolamento & purificação , Histoplasmose/tratamento farmacológico , Humanos , Pessoa de Meia-IdadeAssuntos
Dor Abdominal/etiologia , Diarreia/etiologia , Febre/etiologia , Histoplasmose/diagnóstico , Idoso , Anfotericina B/administração & dosagem , Antifúngicos/administração & dosagem , Diagnóstico Diferencial , Feminino , Histoplasma/isolamento & purificação , Histoplasmose/sangue , Histoplasmose/tratamento farmacológico , HumanosAssuntos
Febre de Causa Desconhecida/imunologia , Imunossupressores/efeitos adversos , Transplante de Rim/efeitos adversos , Linfo-Histiocitose Hemofagocítica/diagnóstico , Adolescente , Anfotericina B/administração & dosagem , Antígenos de Fungos/sangue , Antígenos de Fungos/imunologia , Antivirais/administração & dosagem , Biópsia , Medula Óssea/patologia , Citomegalovirus/imunologia , Citomegalovirus/isolamento & purificação , Infecções por Citomegalovirus/sangue , Infecções por Citomegalovirus/diagnóstico , Infecções por Citomegalovirus/tratamento farmacológico , Infecções por Citomegalovirus/imunologia , Feminino , Febre de Causa Desconhecida/sangue , Febre de Causa Desconhecida/tratamento farmacológico , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/prevenção & controle , Histoplasma/imunologia , Histoplasma/isolamento & purificação , Histoplasmose/sangue , Histoplasmose/diagnóstico , Histoplasmose/tratamento farmacológico , Histoplasmose/imunologia , Humanos , Imunossupressores/administração & dosagem , Falência Renal Crônica/terapia , Linfo-Histiocitose Hemofagocítica/complicações , Linfo-Histiocitose Hemofagocítica/tratamento farmacológico , Linfo-Histiocitose Hemofagocítica/imunologia , Ácido Micofenólico/administração & dosagem , Ácido Micofenólico/efeitos adversos , Diálise Renal , Resultado do Tratamento , Carga ViralRESUMO
BACKGROUND: Granulomas caused by infectious lung diseases present as indeterminate pulmonary nodules (IPNs) on radiography. Newly available serum enzyme immunoassay (EIA) for histoplasmosis has not been studied for the evaluation of IPNs. We investigated serum biomarkers of histoplasmosis antibodies as an indication of benign disease in IPNs from a highly endemic region. METHODS: A total of 152 serum samples from patients presenting with pulmonary nodules ≤30 mm in maximum diameter were analyzed for histoplasmosis antibodies by immunodiffusion and EIA IgG and IgM tests. Serology and FDG-PET/CT scan diagnostic test characteristics were estimated and compared. RESULTS: Cancer prevalence was 55% (n = 83). Thirty-nine (26%) individuals were positive for IgG histoplasmosis antibodies. Twelve samples were IgM antibody positive. Immunodiffusion serology was similar to IgM antibody results with 13 positive tests. Diagnostic likelihood ratios for benign disease were 0.62, 0.33, and 0.28 for FDG-PET/CT, IgG, and IgM antibodies, respectively. When both IgG and IgM were positive (n = 8), no nodules were cancerous and six were FDG-PET/CT avid. CONCLUSIONS: A positive EIA test for both IgM and IgG strongly suggested histoplasmosis etiology and benign granuloma for 12% of benign nodules arising from a highly endemic region. Presence of either IgG or IgM histoplasma antibodies was associated with benign disease. The EIA test was more sensitive in assessing histoplasma exposure than immunodiffusion serology. IMPACT: A new CLIA-certified histoplasmosis antibody EIA test measures histoplasmosis exposure, offers a possible alternative clinical diagnosis for benign IPNs, and may improve IPN evaluation while avoiding harmful invasive biopsies.
Assuntos
Granuloma/diagnóstico por imagem , Histoplasmose/imunologia , Técnicas Imunoenzimáticas , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Pneumopatias Fúngicas/imunologia , Idoso , Feminino , Histoplasma , Histoplasmose/sangue , Histoplasmose/complicações , Histoplasmose/diagnóstico por imagem , Humanos , Pneumopatias Fúngicas/sangue , Pneumopatias Fúngicas/complicações , Pneumopatias Fúngicas/diagnóstico por imagem , Neoplasias Pulmonares/complicações , Masculino , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons , Sensibilidade e EspecificidadeRESUMO
Histoplasmosis is the most common endemic mycosis in the Americas. Currently, there is no laboratory test capable to detect subclinical or latent infections by Histoplasma capsulatum (Hc), which might develop as severe infections in immunocompromised individuals. For the first time to our knowledge, we explore the suitability of an interferon gamma release assay (IGRA) to detect latent Hc infection in asymptomatic individuals. A cohort of 126 volunteers was enrolled in the study, 13 of which underwent a Hc infection in the past, and 93 of them showing risk factors for this infection. The remaining 20 participants did not refer any risk factors of Hc infection, but eight of them showed evidences of infection with Mycobacterium tuberculosis. All participants were recruited in Medellin, Colombia, between January 2014 and December 2017. Whole blood samples were cultured with four different Hc crude antigens and phytohemaglutinin as positive control. The interferon (IFN)-γ released by T lymphocytes upon antigen stimulation was quantified by ELISA. A defined cutoff value of 20 pg/ml for the IFN-γ concentration allowed us to distinguish between the group with documented past infections and the group of noninfected individuals with high sensitivity (70-92%) and specificity (85-95%), for the four tested antigens. Positive 82-95% and negative 77-92% predictive values were also very high, comparable to those reported for commercially available IGRAs. The new test constitutes a promising screening method to detect individuals with latent Hc infection, even decades after the primary infection, as evidenced in this study.
Assuntos
Infecções Assintomáticas , Histoplasmose/diagnóstico , Testes de Liberação de Interferon-gama , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos de Fungos/imunologia , Criança , Estudos de Coortes , Colômbia , Feminino , Histoplasma/isolamento & purificação , Histoplasmose/sangue , Histoplasmose/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudo de Prova de Conceito , Fatores de Risco , Sensibilidade e Especificidade , Linfócitos T/imunologia , Adulto JovemRESUMO
Biologic agents are effective treatments for rheumatoid arthritis but are associated with important risks, including severe infections. Tumor Necrosis Factor (TNF) α inhibitors are known to increase the risk of systemic fungal infections such as disseminated histoplasmosis. Abatacept is a biologic agent with a mechanism different from that of TNFα inhibitors: It suppresses cellular immunity by competing for the costimulatory signal on antigen-presenting cells. The risk of disseminated histoplasmosis for patients on abatacept is not known. We report a case of abatacept-associated disseminated histoplasmosis and review the known infectious complications of abatacept. While the safety of resuming biologic agents following treatment for disseminated histoplasmosis is also not known, abatacept is recommended over TNFα inhibitors for rheumatoid arthritis patients with a prior serious infection. We discuss the evidence supporting this recommendation and discuss alternative treatments for rheumatoid arthritis patients with a history of a serious infection.
Assuntos
Abatacepte/efeitos adversos , Antirreumáticos/efeitos adversos , Artrite Reumatoide/tratamento farmacológico , Histoplasmose/induzido quimicamente , Abatacepte/administração & dosagem , Antirreumáticos/administração & dosagem , Feminino , Histoplasma/citologia , Histoplasma/isolamento & purificação , Histoplasmose/sangue , Histoplasmose/diagnóstico , Humanos , Pessoa de Meia-IdadeRESUMO
Histoplasmosis is a fungal infection caused by a dimorphic fungus, Histoplasma capsulatum. We report a first case of disseminated histoplasmosis in a 34-year-old woman, infected with human immunodeficiency virus (HIV), originating from Ivory Coast and living in Tunisia for 4 years. She was complaining from fever, chronic diarrhoea and pancytopenia. The Histoplasma capsulatum var. capsulatum was identified by direct microscopic examination of the bone marrow. She was treated by Amphotericin B, relayed by itraconazole. Even though a regression of symptoms and normalization of blood cell count (BCC), the patient died in a respiratory distress related to CMV hypoxemic pneumonia.
Assuntos
Medula Óssea/microbiologia , Infecções por HIV/microbiologia , Histoplasma/isolamento & purificação , Histoplasmose/sangue , Histoplasmose/diagnóstico , Infecções Oportunistas Relacionadas com a AIDS/complicações , Infecções Oportunistas Relacionadas com a AIDS/epidemiologia , Infecções Oportunistas Relacionadas com a AIDS/microbiologia , Infecções Oportunistas Relacionadas com a AIDS/virologia , Adulto , Anfotericina B/uso terapêutico , Antifúngicos/uso terapêutico , Doenças Transmissíveis Importadas/epidemiologia , Doenças Transmissíveis Importadas/microbiologia , Côte d'Ivoire/epidemiologia , Evolução Fatal , Feminino , Infecções por HIV/complicações , Infecções por HIV/epidemiologia , Histoplasma/ultraestrutura , Histoplasmose/epidemiologia , Histoplasmose/microbiologia , Humanos , Itraconazol/uso terapêutico , Microscopia , Síndrome do Desconforto Respiratório/epidemiologia , Síndrome do Desconforto Respiratório/microbiologia , Tunísia/epidemiologiaRESUMO
OBJECTIVES: Serum and urine antigen (SAg, UAg) detection are common tests for Histoplasma capsulatum. UAg detection is more widely used and reportedly has a higher sensitivity. We investigated whether SAg detection contributes meaningfully to the initial evaluation of patients with suspected histoplasmosis. METHODS: We reviewed 20,285 UAg and 1,426 SAg tests ordered from 1997 to 2016 and analyzed paired UAg and SAg tests completed on the same patient within 1 week. We determined the positivity rate for each test. RESULTS: Of 601 paired specimens, 542 were concurrent negatives and 48 were concurrent positives (98% agreement). Medical records were available for eight of 11 pairs with discrepant results. UAg was falsely positive in six instances, truly positive once, and falsely negative once. CONCLUSIONS: These findings support using a single antigen detection test, rather than both UAg and SAg, as an initial screen for suspected histoplasmosis. This aligns with the current practice of most physicians.
Assuntos
Antígenos de Fungos/urina , Histoplasma/imunologia , Histoplasmose/diagnóstico , Adulto , Idoso , Antígenos de Fungos/sangue , Biomarcadores/sangue , Biomarcadores/urina , Reações Falso-Negativas , Reações Falso-Positivas , Feminino , Histoplasma/isolamento & purificação , Histoplasmose/sangue , Histoplasmose/urina , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Sensibilidade e EspecificidadeRESUMO
ABSTRACT Fluconazole is extensively used for the treatment of candidiasis and cryptococcosis. Among other factors, successful treatment is related to appropriate fluconazole levels in blood and cerebrospinal fluid. In the present study, fluconazole levels were determined in 15 patients, 14 of whom had AIDS and 13 had neurocryptococcosis. The only selection criterion was treatment with fluconazole, which was performed with a generic or similar form of the drug. Fluconazole level was determined by high performance liquid chromatography and the susceptibility profile of Cryptococcus spp. isolated from the patients was assessed by broth microdilution. Blood and cerebrospinal fluid fluconazole levels were found to be related to the fluconazole daily dose, and exceeded the minimum inhibitory concentration of this antifungal for the Cryptococcus spp. isolates. A good correlation was observed between serum and cerebrospinal fluid drug concentration. In conclusion, treatment with non-original fluconazole under usual medical practice conditions results in appropriate blood and cerebrospinal fluid levels of the drug for inhibiting Cryptococcus spp. susceptible to this antifungal drug. The relatively common failures of neurocryptococcosis treatment appear not to be due to insufficient fluconazole levels in the cerebrospinal fluid, especially with the use of daily doses of 400-800 mg.