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1.
J Clin Immunol ; 39(7): 702-712, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31401750

RESUMO

PURPOSE: Patients with primary immunodeficiency (PID) are at risk of serious complications. However, data on the incidence and causes of emergency hospital admissions are scarce. The primary objective of the present study was to describe emergency hospital admissions among patients with PID, with a view to identifying "at-risk" patient profiles. METHODS: We performed a prospective observational 12-month multicenter study in France via the CEREDIH network of regional PID reference centers from November 2010 to October 2011. All patients with PIDs requiring emergency hospital admission were included. RESULTS: A total of 200 admissions concerned 137 patients (73 adults and 64 children, 53% of whom had antibody deficiencies). Thirty admissions were reported for 16 hematopoietic stem cell transplantation recipients. When considering the 170 admissions of non-transplant patients, 149 (85%) were related to acute infections (respiratory tract infections and gastrointestinal tract infections in 72 (36%) and 34 (17%) of cases, respectively). Seventy-seven percent of the admissions occurred during winter or spring (December to May). The in-hospital mortality rate was 8.8% (12 patients); death was related to a severe infection in 11 cases (8%) and Epstein-Barr virus-induced lymphoma in 1 case. Patients with a central venous catheter (n = 19, 13.9%) were significantly more hospitalized for an infection (94.7%) than for a non-infectious reason (5.3%) (p = 0.04). CONCLUSION: Our data showed that the annual incidence of emergency hospital admission among patients with PID is 3.4%. The leading cause of emergency hospital admission was an acute infection, and having a central venous catheter was associated with a significantly greater risk of admission for an infectious episode.

2.
Transpl Infect Dis ; 21(3): e13060, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30753747

RESUMO

We studied cytokine profiles in BAL of LTRs with Aspergillus spp colonization who did not progress to IPA in the absence of antifungal prophylaxis. This was a retrospective, single center case-control study. BAL samples were analyzed for cytokines. Patients with Aspergillus spp in BAL who did not receive prophylaxis and did not develop IPA were compared to LTRs with Aspergillus spp that received prophylaxis, LTRs with IPA and controls. Twenty-one patients with Aspergillus colonization who did not develop IPA, seven patients with suspected IPA who received prophylaxis, 4 IPA and 19 controls were included. IPA group had significantly higher levels (median [IQR]) of MIP-1 beta compared to the Suspected IPA group (5 vs 5 P: 0.03). The Suspected IPA group had significantly higher levels of IL-12 (11.38 vs 1 P: 0.0001), IL-1 RA (86.11 vs 23.98 P: 0.0118), IP-10 (22.47 vs 0.86 P: 0.0151), HGF (40.92 vs 16.82 P: 0.0055), and MIG (169.62 vs 5 P: 0.0005) than Colonization group. We have identified a unique cytokine signature in patients with Aspergillus colonization that do not develop IPA. Our study forms basis for a larger study to use these cytokines profile to identify patients at a lower risk of developing IPA.


Assuntos
Citocinas/imunologia , Aspergilose Pulmonar Invasiva/imunologia , Transplante de Pulmão/efeitos adversos , Transplantados , Antifúngicos/uso terapêutico , Aspergillus , Lavagem Broncoalveolar , Citocinas/genética , Feminino , Humanos , Aspergilose Pulmonar Invasiva/tratamento farmacológico , Pulmão/imunologia , Pulmão/microbiologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Transcriptoma
3.
J Clin Immunol ; 39(1): 55-64, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30552536

RESUMO

PURPOSE: Progressive multifocal leukoencephalopathy (PML) is a rare but severe demyelinating disease caused by the polyomavirus JC (JCV) in immunocompromised patients. We report a series of patients with primary immune deficiencies (PIDs) who developed PML. METHODS: Retrospective observational study including PID patients with PML. Clinical, immunological, imaging features, and outcome are provided for each patient. RESULTS: Eleven unrelated patients with PIDs developed PML. PIDs were characterized by a wide range of syndromic or genetically defined defects, mostly with combined B and T cell impairment. Genetic diagnosis was made in 7 patients. Before the development of PML, 10 patients had recurrent infections, 7 had autoimmune and/or inflammatory manifestations, and 3 had a history of malignancies. Immunologic investigations showed CD4+ lymphopenia (median 265, range 50-344) in all cases. Six patients received immunosuppressive therapy in the year before PML onset, including prolonged steroid therapy in 3 cases, rituximab in 5 cases, anti-TNF-α therapy, and azathioprine in 1 case each. Despite various treatments, all but 1 patient died after a median of 8 months following PML diagnosis. CONCLUSION: PML is a rare but fatal complication of PIDs. Many cases are secondary to immunosuppressive therapy warranting careful evaluation before initiation subsequent immunosuppression during PIDs.


Assuntos
Síndromes de Imunodeficiência/complicações , Síndromes de Imunodeficiência/imunologia , Leucoencefalopatia Multifocal Progressiva/etiologia , Leucoencefalopatia Multifocal Progressiva/imunologia , Adolescente , Adulto , Azatioprina/uso terapêutico , Linfócitos B/imunologia , Feminino , Humanos , Imunoterapia/métodos , Vírus JC/imunologia , Leucoencefalopatia Multifocal Progressiva/terapia , Linfopenia/imunologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Rituximab/uso terapêutico , Linfócitos T/imunologia , Fator de Necrose Tumoral alfa/imunologia , Adulto Jovem
5.
J Heart Lung Transplant ; 37(10): 1226-1234, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30139546

RESUMO

BACKGROUND: Invasive aspergillosis (IA) is a frequent complication in lung transplant recipients (LTRs). Clinical risk factors for IA have not been fully characterized, especially in the era of extensive anti-fungal prophylaxis. The primary objective of this study was to evaluate the clinical risk factors associated with IA in LTRs. The secondary objective was to assess the mortality in LTRs who had at least 1 episode of IA compared with LTRs who never had experienced IA. METHODS: We conducted an international, multicenter, retrospective cohort study of 900 consecutive adults who received lung transplants between 2005 and 2008 with 4years of follow-up. Risk factors associated with IA were identified using univariate and multiple regression Cox proportional hazards models. RESULTS: Anti-fungal prophylaxis was administered to 61.7% (555 of 900) of patients, and 79 patients developed 115 episodes of IA. The rate to development of the first episode was 29.6 per 1,000 person-years. Aspergillus fumigatus was the most common species isolated (63% [72 of 115 episodes]). Through multivariate analysis, significant risk factors identified for IA development were single lung transplant (hazard ratio, 1.84; 95% confidence interval, 1.09-3.10; p = 0.02,) and colonization with Aspergillus at 1 year post-transplantation (hazard ratio, 2.11; 95% confidence interval, 1.28-3.49; p = 0.003,). Cystic fibrosis, pre-transplant colonization with Aspergillus spp, and use of anti-fungal prophylaxis were not significantly associated with the development of IA. Time-dependent analysis showed IA was associated with higher mortality rates. CONCLUSION: Incidence of IA remains high in LTRs. Single-lung transplant and airway colonization with Aspergillus spp. within 1 year post-transplant were significantly associated with IA.

7.
F1000Res ; 72018.
Artigo em Inglês | MEDLINE | ID: mdl-29899970

RESUMO

Background: Undergoing solid organ transplantation (SOT) exposes the recipient to various infectious risks, including possible transmission of pathogen by the transplanted organ, post-surgical infections, reactivation of latent pathogens, or novel infections. Recent advances: In the last few years, the emergence of Zika virus has raised concerns in the transplant community. Few cases have been described in SOT patients, and these were associated mainly with moderate disease and favorable outcome; the notable exception is a recent case of fatal meningo-encephalopathy in a heart transplant recipient. Because of the advances in treating hepatitis C, several teams recently started to use organs from hepatitis C-positive donors. The worldwide increasing incidence of multidrug-resistant pathogens, as well as the increasing incidence of Clostridioidesdifficile infection, is of particular concern in SOT patients. In the field of mycology, the main recent therapeutic advance is the availability of isavuconazole for the treatment of invasive aspergillosis and mucormycosis. This drug has the advantage of minimal interaction with calcineurin inhibitors. Regarding the viral reactivations occurring after transplant, cytomegalovirus (CMV) infection is still a significant issue in SOT patients. The management of resistant CMV remains particularly difficult. The approval of letermovir, albeit in bone marrow transplantation, and the therapeutic trial of maribavir bring a ray of hope. Another advancement in management of post-transplant infections is the development of in vitro tests evaluating pathogen-specific immune response, such as immunodiagnostics for CMV and, more recently, tests for monitoring immunity against BK virus. Conclusion: The increasing number of organ transplantations, the use of newer immunosuppressive drugs, and high-risk donors continue to define the landscape of transplant infectious diseases in the current era.

8.
Emerg Infect Dis ; 24(2): 193-200, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29350138

RESUMO

We describe the frequency, demographic and clinical features, and visual outcomes of ocular syphilis infections observed during 2012-2015 at a tertiary reference center in Paris, France. Twenty-one cases (29 eyes) were identified. The occurrence of ocular syphilis increased from 1 case in 2012 to 5 cases in 2013, 6 cases in 2014, and 9 cases in 2015 (2.22-25.21/1,000 individual patients/year for the period). Among case-patients, an annual 20%-33% were co-infected with HIV. Seventy-six percent of ocular syphilis infections occurred in men who have sex with men. Seventy-five percent of case-patients had a good final visual outcome (best-corrected visual acuity >0.3 logMAR score). Visual outcome was worse for HIV-positive patients than for HIV-negative patients (p = 0.0139). At follow-up, the best visual outcomes were observed in patients whose mean time from first ocular symptom to consultation was 15 days (SD +19 days).

10.
Mycopathologia ; 181(7-8): 575-81, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27038797

RESUMO

Aspergillus terreus, a saprophytic fungus, is recognized as an emerging pathogen responsible for various infections in human beings. However, bone and joint involvement is uncommon. We report a rare case of A. terreus spondylodiscitis in a 20-year-old male with a past history of recurrent, incompletely treated pulmonary tuberculosis. Clinical signs at the time of admission included cough, low-grade fever, general weakness and left-sided back pain. Histological examination of spinal biopsy samples revealed lesions of necrosis, granulomatous inflammation and septate hyphae with acute-angle branching. A. terreus was recovered from culture. The patient received antifungal therapy with voriconazole plus caspofungin and underwent surgical debridement. Further investigations revealed no cause of primary immunodeficiency such as chronic granulomatous disease, severe combined immunodeficiency syndrome or disorders of the IL-12/IFNγ signaling pathway. Moreover, HIV serological tests resulted negative and the patient was not under immunosuppressive therapy. Unfortunately, owing to precarity and medication non-adherence, vertebral sequelae occurred. This new report emphasizes the need to consider a fungal infection in patients with spondylodiscitis, regardless of the immune status.


Assuntos
Aspergilose/diagnóstico , Aspergilose/patologia , Aspergillus/isolamento & purificação , Discite/etiologia , Discite/patologia , Antifúngicos/uso terapêutico , Aspergilose/tratamento farmacológico , Aspergilose/microbiologia , Aspergillus/classificação , Biópsia , Caspofungina , Discite/tratamento farmacológico , Discite/microbiologia , Equinocandinas/uso terapêutico , Histocitoquímica , Humanos , Lipopeptídeos/uso terapêutico , Imagem por Ressonância Magnética , Masculino , Técnicas Microbiológicas , Microscopia , Coluna Vertebral/diagnóstico por imagem , Coluna Vertebral/microbiologia , Coluna Vertebral/patologia , Tuberculose Pulmonar/complicações , Voriconazol/uso terapêutico , Adulto Jovem
11.
Semin Respir Crit Care Med ; 36(5): 692-705, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26398536

RESUMO

Mucormycosis is a rare, though increasingly prevalent, life-threatening fungal disease caused by Mucorales. The incidence has increased over the last decade and its mortality remains high at around 50%. Mucormycosis occurs mostly in patients with diabetes mellitus and/or in the context of immunosuppression resulting from chemotherapy for hematological malignancy, hematopoietic stem cell transplantation, or solid-organ transplantation. In this situation, lung and rhino-orbito-cerebral infections are the most frequent localizations of the disease. Prompt initiation of an effective treatment is essential to decrease mortality. However, mucormycosis and aspergillosis share close clinical and radiological features. Invasive procedures such as bronchial endoscopy and/or lung biopsy are necessary to confirm diagnosis, as no indirect tests are yet validated. Therefore, the challenge is to minimize the delay in diagnosis. When present, the reversed halo sign on CT scan is suggestive of mucormycosis. Quantitative polymerase chain reaction is a new promising approach to detect Mucorales DNA in serum and new molecular tools are available to detect Mucorales in tissues as well as to specify species. Recommendations from ECIL and ECMM/ESCMID have recently been published on management of mucormycosis. The recommended treatment is an amphotericin B lipid formulation in combination with surgery and modification of risk factors. High-dose (10 mg/kg) of liposomal amphotericin B is recommended in case of neurological involvement and posaconazole for maintenance therapy. Place of isavuconazole as well as posaconazole new formulations (tablets and intravenous) in first line treatment have to be defined. Improved radiologic descriptions of mucormycosis and new molecular tools may be key elements to help with rapid diagnosis in the future. Clinical trials are warranted to improve therapeutic success and hopefully survival.


Assuntos
Anfotericina B/uso terapêutico , Antifúngicos/uso terapêutico , Pneumopatias Fúngicas/diagnóstico , Mucorales/genética , Mucormicose/diagnóstico , Mucormicose/terapia , Terapia Combinada , Desbridamento/métodos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Pneumopatias Fúngicas/terapia , Nitrilos/uso terapêutico , Piridinas/uso terapêutico , Triazóis/uso terapêutico
12.
J Clin Immunol ; 35(4): 331-8, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25737324

RESUMO

X-linked inhibitor of apoptosis (XIAP) deficiency (also known as X-linked lymphoproliferative syndrome type 2, XLP-2) is a rare primary immunodeficiency. Since the disease was first described in 2006, more than 70 patients suffering from XIAP-deficiency have been reported, thus extending the clinical presentations of the disease. The main clinical features of XLP-2 are (i) elevated susceptibility to hemophagocytic lymphohistiocytosis (HLH, frequently in response to infection with Epstein-Barr virus (EBV)), (ii) recurrent splenomegaly and (iii) inflammatory bowel disease (IBD) with the characteristics of Crohn's disease. XIAP deficiency is now considered to be one of the genetic causes of IBD in infancy. Although XIAP is an anti-apoptotic molecule, it is also involved in many other pathways, including the regulation of innate immunity and inflammation. XIAP is required for signaling through the Nod-like receptors NOD1 and 2, which are intracellular sensors of bacterial infection. XIAP-deficient T cells (including innate natural killer T cells and mucosal-associated invariant T cells) are overly sensitive to apoptosis. NOD2 function is impaired in XIAP-deficient monocytes. However, the physiopathological mechanisms underlying the clinical phenotypes in XIAP deficiency, notably the HLH and the EBV susceptibility, are not well understood. Here, we review the clinical aspects, molecular etiology and physiopathology of XIAP deficiency.


Assuntos
Transtornos Linfoproliferativos/diagnóstico , Transtornos Linfoproliferativos/terapia , Humanos , Transtornos Linfoproliferativos/etiologia , Prognóstico , Proteínas Inibidoras de Apoptose Ligadas ao Cromossomo X/genética , Proteínas Inibidoras de Apoptose Ligadas ao Cromossomo X/metabolismo
13.
Semin Cell Dev Biol ; 39: 115-23, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25666262

RESUMO

The X-linked inhibitor of apoptosis (XIAP) deficiency, also known as the X-linked lymphoproliferative syndrome type 2 (XLP-2), is a rare primary immunodeficiency. XIAP deficiency is characterized by a key triad of clinical manisfestations, which consist of a high susceptibility to develop hemophagocytic lymphohistiocytosis (HLH) frequently triggered by Epstein-Barr virus (EBV) infection, recurrent splenomegaly and inflammatory bowel disease (IBD) with the features of a Crohn's disease. XIAP deficiency can be considered as one of the genetic causes for inherited IBD. XIAP is an anti-apoptotic molecule, but it is also involved in many other pathways. Recent findings demonstrate the role of XIAP in innate immunity and in the negative regulation of inflammation. In this review, we focus on the clinical aspects, the molecular etiology and the immunopathogenesis of XIAP deficiency. We also discuss recent progress in the understanding of XIAP function in relation to the pathophysiology of XLP-2.


Assuntos
Doenças Genéticas Ligadas ao Cromossomo X/imunologia , Doenças Genéticas Ligadas ao Cromossomo X/patologia , Transtornos Linfoproliferativos/imunologia , Transtornos Linfoproliferativos/patologia , Proteínas Inibidoras de Apoptose Ligadas ao Cromossomo X/genética , Animais , Humanos , Imunidade Inata , Inflamação/imunologia
14.
Clin Infect Dis ; 59(10): 1462-70, 2014 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-25124061

RESUMO

Because infectious diseases are a major source of morbidity and mortality in the majority of patients with primary immunodeficiencies (PIDs), the application of a prophylactic regimen is often necessary. However, because of the variety of PIDs and pathogens involved, and because evidence is scarce, practices are heterogeneous. To homogenize practices among centers, the French National Reference Center for PIDs aimed at elaborating recommendations for anti-infectious prophylaxis for the most common PIDs. We performed a literature review of infectious complications and prophylactic regimens associated with the most frequent PIDs. Then, a working group including different specialists systematically debated about chemoprophylaxis, immunotherapy, immunization, and recommendations for patients. Grading of prophylaxis was done using strength of recommendations (decreasing from A to D) and evidence level (decreasing from I to III). These might help infectious diseases specialists in the management of PIDs and improving the outcome of patients with PIDs.


Assuntos
Controle de Doenças Transmissíveis , Doenças Transmissíveis/etiologia , Síndromes de Imunodeficiência/complicações , Controle de Infecções , Infecção/etiologia , Humanos , Síndromes de Imunodeficiência/diagnóstico , Profilaxia Pré-Exposição
15.
J Allergy Clin Immunol ; 134(5): 1131-41.e9, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24942515

RESUMO

BACKGROUND: Crohn disease is an inflammatory bowel disease (IBD) with a complex mode of inheritance. Although nucleotide binding and oligomerization domain containing 2 (NOD2) is the strongest risk factor, the cause of Crohn disease remains unknown in the majority of the cases. X-linked inhibitor of apoptosis (XIAP) deficiency causes X-linked lymphoproliferative syndrome type 2. IBD has been reported in some XIAP-deficient patients. OBJECTIVE: We characterize the IBD affecting a large cohort of patients with mutations in XIAP and examine the possible pathophysiologic mechanisms. METHODS: We performed a phenotypical and histologic analysis of the IBD affecting 17 patients with hemizygous mutations in XIAP, including 3 patients identified by screening 83 patients with pediatric-onset IBD. The X chromosome inactivation was analyzed in female carriers of heterozygous XIAP mutations, including 2 adults with IBD. The functional consequences of XIAP deficiency were analyzed. RESULTS: Clinical presentation and histology of IBD in patients with XIAP deficiency overlapped with those of patients with Crohn disease. The age at onset was variable (from 3 months to 41 years), and IBD was severe and difficult to treat. In 2 patients hematopoietic stem cell transplantation fully restored intestinal homeostasis. Monocytes of patients had impaired NOD2-mediated IL-8 and monocyte chemoattractant protein 1 (MCP-1) production, as well as IL-10, in response to NOD2 and Toll-like receptor 2/4 costimulation. Nucleotide binding and oligomerization domain containing 1 (NOD1)-mediated IL-6 and IL-8 production was defective in fibroblasts from XIAP-deficient patients. The 2 heterozygous female carriers of XIAP mutations with IBD displayed abnormal expression of the XIAP mutated allele, resulting in impaired activation of the NOD2 pathway. CONCLUSION: IBD in patients with XIAP deficiency is similar to Crohn disease and is associated with defective NOD2 function in monocytes. Importantly, we report that it is not restricted to male patients because we identified 2 symptomatic female heterozygous carriers of XIAP mutations.


Assuntos
Cromossomos Humanos X , Doença de Crohn , Doenças Genéticas Ligadas ao Cromossomo X , Hemizigoto , Heterozigoto , Transtornos Linfoproliferativos , Proteínas Inibidoras de Apoptose Ligadas ao Cromossomo X/genética , Adolescente , Adulto , Idade de Início , Criança , Pré-Escolar , Cromossomos Humanos X/genética , Cromossomos Humanos X/metabolismo , Estudos de Coortes , Doença de Crohn/sangue , Doença de Crohn/genética , Doença de Crohn/patologia , Citocinas/sangue , Citocinas/genética , Feminino , Doenças Genéticas Ligadas ao Cromossomo X/sangue , Doenças Genéticas Ligadas ao Cromossomo X/genética , Doenças Genéticas Ligadas ao Cromossomo X/patologia , Humanos , Lactente , Transtornos Linfoproliferativos/sangue , Transtornos Linfoproliferativos/genética , Transtornos Linfoproliferativos/patologia , Masculino , Proteína Adaptadora de Sinalização NOD2/genética , Proteína Adaptadora de Sinalização NOD2/metabolismo
17.
Blood ; 121(4): 614-23, 2013 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-23223428

RESUMO

Invariant natural killer (iNKT) T cells and mucosal-associated invariant T (MAIT) cells represent peculiar T-lymphocyte subpopulations with innate-like properties that differ from conventional T cells. iNKT are reduced in the primary immunodeficiency caused by mutations in the X-linked inhibitor of apoptosis (XIAP). By studying the mechanism of this depletion, we herein report that iNKT cells exhibit a high susceptibility to apoptosis that is not observed with conventional T cells. Elevated expression of caspases 3 and 7 accounts for the proapoptotic phenotype of iNKT cells, which is inhibited by XIAP although it exerts a moderate effect in conventional T cells. Similarly, MAIT cells exhibit a proapoptotic propensity with elevated expression of activated caspases and are decreased in XIAP-deficient individuals. Knockdown of the transcription factor PLZF/ZBTB-16, which is involved in the effector program of iNKT cells, diminishes their proapoptotic phenotype. Conversely, overexpression of PLZF/ZBTB-16 in conventional T cells leads to a proapoptotic phenotype. Our findings identify a previously unknown pathway of regulation of innate-like T-cell homeostasis depending on XIAP and PLZF. The proapoptotic feature of iNKT cells also gives a reliable explanation of their exhaustion observed in different human conditions including the XIAP immunodeficiency.


Assuntos
Fatores de Transcrição Kruppel-Like/genética , Células T Matadoras Naturais/metabolismo , Subpopulações de Linfócitos T/metabolismo , Proteínas Inibidoras de Apoptose Ligadas ao Cromossomo X/genética , Apoptose/genética , Apoptose/imunologia , Proteínas Reguladoras de Apoptose/genética , Proteínas Reguladoras de Apoptose/imunologia , Regulação da Expressão Gênica , Humanos , Fatores de Transcrição Kruppel-Like/imunologia , Contagem de Linfócitos , Células T Matadoras Naturais/imunologia , Fenótipo , Proteína com Dedos de Zinco da Leucemia Promielocítica , Receptores de Antígenos de Linfócitos T alfa-beta/genética , Receptores de Antígenos de Linfócitos T alfa-beta/metabolismo , Subpopulações de Linfócitos T/imunologia , Proteínas Inibidoras de Apoptose Ligadas ao Cromossomo X/imunologia
18.
Med Mycol ; 50(5): 518-21, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22142219

RESUMO

Cutaneous Alternaria spp. infections occur mainly in immunosuppressed patients and itraconazole is considered as the drug of choice. We report the case of a 64-year-old heart transplanted female patient with multiple cutaneous lesions caused by Alternaria infectoria. Treatment with posaconazole resulted in complete recovery. Due to lower minimal inhibitory concentrations, better distribution and less drug interactions than with itraconazole, posaconazole may become the antifungal drug to consider in the management of cutaneous infections caused by Alternaria spp. in solid organ transplant recipients.


Assuntos
Alternaria/efeitos dos fármacos , Alternariose/tratamento farmacológico , Antifúngicos/uso terapêutico , Transplante de Coração/efeitos adversos , Triazóis/uso terapêutico , Alternaria/classificação , Alternariose/microbiologia , Feminino , Humanos , Pessoa de Meia-Idade , Resultado do Tratamento
20.
Am J Clin Pathol ; 135(2): 278-90, 2011 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21228369

RESUMO

A retrospective analysis of 173 skin biopsy specimens of myeloid leukemia cutis (MLC) was performed to determine histologic and immunophenotypic criteria that could distinguish the varied myeloid disorders from one another. For the study, 11 relevant histologic items were scored and 12 antigens were studied (CD68 [KP1], CD163, CD14, CD4, myeloperoxidase [MPO], CD33, CD117, CD34, CD56, MIB-1, CD303, and CD123). Underlying myeloid disorders were essentially acute myeloid leukemias (65.3%), chronic myelomonocytic leukemias (11.0%), and refractory anemia (10.4%). Skin lesions were de novo in 7.5%, concurrent in 26.6%, and subsequent in 60.7%. Several morphologic characteristics (density, size of tumor cells, inflammatory background) were statistically useful in distinguishing between varied myeloid disorders. De novo MLCs displayed a specific morphologic profile. Association of CD68, CD33, and MPO could diagnose 100% of the cases of MLC. However, the immunohistochemical panel could not distinguish between the varied underlying myeloid disorders, with the exception that CD123 was particularly powerful in recognizing chronic myelomonocytic leukemia and also permitted reclassification of 4 cases as blastic plasmacytoid dendritic cell neoplasm.


Assuntos
Antígenos CD/análise , Biomarcadores Tumorais/análise , Leucemia Mieloide Aguda/patologia , Leucemia Mieloide/patologia , Leucemia Mielomonocítica Crônica/patologia , Neoplasias Cutâneas/patologia , Idoso , Idoso de 80 Anos ou mais , Anemia Refratária/patologia , Antígenos de Diferenciação Mielomonocítica/análise , Feminino , Humanos , Imunofenotipagem , Recém-Nascido , Leucemia Mieloide/genética , Leucemia Mieloide Aguda/congênito , Masculino , Pessoa de Meia-Idade , Peroxidase/análise , Estudos Retrospectivos , Lectina 3 Semelhante a Ig de Ligação ao Ácido Siálico
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