Systematic Infection of Chlamydia Pneumoniae.

BACKGROUND: Chlamydia pneumoniae (Cpn) is one of the most common respiratory pathogens in children and adults. It is characterized as an obligate intracellular parasite. Peripheral blood monocytes (PBMC), lymphocytes, and macrophages are involved in spreading chlamydia infection to extrapulmonary organs indicating that Cpn infection can cause systematic symptoms in vivo via blood transmission. METHODS: This review summarizes the mechanisms of Cpn infection in host cells, the immune response of the body, and the relationship between Cpn infection and some chronic diseases. RESULTS: Cpn participation in extrapulmonary chronic diseases has been proven owing to the presence of Cpn DNA in AS plaque, nerve tissues, and synovium tissues of the joints. CONCLUSIONS: Cpn infection is related to the development of chronic diseases such as atherosclerosis, Alzheimer's Disease (AD), and reactive arthritis through in vivo and in vitro experiments.

Chlamydia pneumoniae-associated pleuropericarditis: a case report and systematic review of the literature.

BACKGROUND: Chlamydia pneumoniae is a common cause of atypical community acquired pneumonia (CAP). The diagnostic approach of chlamydial infections remains a challenge. Diagnosis of delayed chlamydial-associated complications, involving complex autoimmune pathophysiological mechanisms, is still more challenging. C. pneumoniae-related cardiac complications have been rarely reported, including cases of endocarditis, myocarditis and pericarditis. CASE PRESENTATION: A 40-year old female was hospitalized for pleuropericarditis following lower respiratory tract infection. The patient had been hospitalized for CAP (fever, dyspnea, chest X-ray positive for consolidation on the left upper lobe) 5 weeks ago and had received ceftriaxone and moxifloxacin. Four weeks after her discharge, the patient presented with fever, shortness of breath and pleuritic chest pain and was readmitted because of pericardial and bilateral pleural effusions (mainly left). The patient did not improve on antibiotics and sequential introduction of colchicine and methylprednisolone was performed. The patient presented impressive clinical and laboratory response. Several laboratory and clinical assessments failed to demonstrate any etiological factor for serositis. Chlamydial IgM and IgG antibodies were positive and serial measurements showed increasing kinetics for IgG. Gold standard polymerase chain reaction of respiratory tract samples was not feasible but possibly would not have provided any additional information since CAP occurred 5 weeks ago. The patient was discharged under colchicine and tapered methylprednisolone course. During regular clinic visits, she remained in good clinical condition without pericardial and pleural effusions relapse. CONCLUSIONS: C. pneumoniae should be considered as possible pathogen in case of pleuritis and/or pericarditis during or after a lower respiratory tract infection. In a systematic review of the literature only five cases of C. pneumoniae associated pericarditis were identified. Exact mechanisms of cardiovascular damage have not yet been defined, yet autoimmune pathways might be implicated.

Chronic infection with Chlamydia pneumoniae in asthma: a type-2 low infection related phenotype.

BACKGROUND: Chlamydia pneumoniae and Mycoplasma pneumoniae have been implicated in the pathogenesis of asthma and are responsible for chronic inflammation when host immune system fails to eradicate the bacteria. METHOD: We performed a prospective study on 410 patients who underwent a visit at the asthma clinic of CHU of Liege between June 2016 and June 2018 with serology testing for C. pneumoniae and M. pneumoniae. RESULTS: 65% of our asthmatic population had serum IgA and/or IgG towards C. pneumoniae, while only 12.6% had IgM and/or IgG against M. pneumoniae. Compared to seronegative asthmatics, asthmatics with IgA+ and IgG+ against C. pneumoniae were more often male and older with a higher proportion of patients with smoking history. They received higher doses of inhaled corticosteroids (ICS) and displayed lower FEV1/FVC ratio, higher RV/TLC ratio and lower conductance. They had higher levels of fibrinogen, though in the normal range and had lower sputum eosinophil counts. Patients with IgA- and IgG+ against C. pneumoniae were older and had higher blood monocyte counts and alpha-1-antitrypsin levels as compared to seronegative patients. Patients with IgM and/or IgG towards M. pneumoniae were more often males than seronegative asthmatics. In a subpopulation of 14 neutrophilic asthmatics with Chlamydia pneumoniae IgA + /IgG + treated with macrolides, we found a significant decrease in blood neutrophils and normalization of sputum neutrophil count but no effect on asthma quality of life and exacerbations. CONCLUSION: Positive Chlamydia serologic test is more common than positive Mycoplasma serology. Asthmatics with IgA and IgG against C. pneumoniae have more severe disease with increased airway obstruction, higher doses of ICS, more signs of air trapping and less type-2 inflammation.

Ús de la PCR de bacteris atípics en el maneig ambulatori de pacients amb pneumònia adquirida a la comunitat que acudeixen a urgències / Uso de la PCR de bacterias atípicas en el manejo ambulatorio de pacientes con neumonía adquirida en la comunidad que acuden a urgencias / Use of PCR for atypical bacteria in the ambulatory management of patients with community-acquired pneumonia seen in the emergency departament

FONAMENT: Mycoplasma pneumoniae I Chlamydophila pneu-moniae són agents causals freqüents de la pneumònia adquirida a la comunitat (PAC) en pediatria, I les tècniques com la reacció en cadena de la polimerasa (PCR) poden facilitar-ne el diagnòstic etiològic precoç, adequant l'antibioteràpia emprada. OBJECTIU: Descriure l'ús d'aquesta tècnica en el maneig ambulatori dels pacients pediàtrics amb PAC que acudeixen a urgències. MÈTODE: Estudi observacional, retrospectiu I descriptiu de pacients pediàtrics diagnosticats de PAC a urgències amb maneig ambulatori. RESULTATS: De 67 pacients, el 32,8% va obtenir un resultat positiu per a bacteris atípics. El percentatge de resultats positius en <4 anys va ser del 10,0% I en ≥4 anys del 42,6% (p = 0,021). Van rebre antibiòtic empíric a l'alta 49 pacients dels 67 (73,1%): 31 macròlids, 12 betalactàmics I 6 ambdós. Amb el resultat de la PCR, per resultat negatiu es van retirar els macròlids a 25 dels 37 als quals se'ls havia pautat (67,6%) I es va pautar a 10 dels 22 casos positius que no els estaven rebent (45,5%). CONCLUSIONS: La PCR de bacteris atípics facilita el diagnòstic microbiològic ràpid I l'adequació de l'antibioteràpia, i, sobretot, evita l'excés de tractament amb macròlids a les urgències pediàtriques

FUNDAMENTO: Mycoplasma pneumoniae y Chlamydophila pneumoniae son agentes causales frecuentes de la neumonía adquirida en la comunidad (NAC) en pediatría, y las técnicas como la reacción en cadena de la polimerasa (PCR) pueden facilitar su diagnóstico etiológico precoz, adecuando la antibioterapia utilizada. OBJETIVO: Describir el uso de esta técnica en el manejo ambulatorio de los pacientes pediátricos con NAC que acuden a urgencias. MÉTODO: Estudio observacional, retrospectivo y descriptivo de pacientes pediátricos diagnosticados de NAC en urgencias manejados ambulatoriamente. RESULTADOS: De 67 pacientes, el 32,8% obtuvo resultado positivo para bacterias atípicas. El porcentaje de resultados positivos en <4 años fue del 10,0% y en ≥4 años de 42,6% (p = 0,021). Recibieron antibiótico empírico 49 pacientes de los 67 (73,1%): 31 macrólidos, 12 betalactámicos y 6 ambos. Con el resultado de la PCR, por resultado negativo se retiraron los macrólidos a 25 de los 37 a los que se les había pautado (67,6%) y se pautó a 10 de los 22 casos positivos que no los estaban recibiendo (45,5%). CONCLUSIONES: La PCR de bacterias atípicas facilita el diagnóstico microbiológico rápido y la adecuación de la antibioterapia, evitando sobre todo el exceso de tratamiento con macrólidos en urgencias

BACKGROUND: Mycoplasma pneumoniae and Chlamydophila pneu-moniae are frequent causative agents of community-acquired pneumonia (CAP) in children. Techniques such as the polymerase chain reaction (PCR) can facilitate early diagnosis and adequacy of antibiotic therapy. OBJECTIVE: To describe the use of this test in the ambulatory management of children with CAP seen in the emergency room. METHOD: Observational, retrospective and descriptive study of children diagnosed with CAP in the emergency room and managed as outpatients. RESULTS: Sixty-seven patients were recruited and 22 (32.8%) had a positive PCR for atypical bacteria. The percentage of positive results in children <4 years was 10.0% and it was 42.6% in children ≥4 years (p = 0.021). Forty-nine (73.1%) patients received antibiotic treatment: 31 received macrolides, 12 beta-lactams and 6 both. The results of the PCR test resulted in discontinuation of macrolide treatment in 25 of 37 patients (67.6%) after a negative PCR test and in its prescription to 10 of the 22 (45.5%) positive cases that were not receiving it. CONCLUSIONS: The use of PCR for atypical bacteria in the emergency department facilitates rapid microbiological diagnosis and the adequacy of antibiotic therapy, avoiding over-treatment with macrolides

Diagnostic utility of serology and polymerase chain reaction for detection of Mycoplasma pneumoniae and Chlamydophila pneumoniae in paediatric community-acquired lower respiratory tract infections.

Purpose: Mycoplasma pneumoniae (M. pneumoniae) and Chlamydophila pneumoniae (C. pneumoniae) play a significant role in children of all ages with lower respiratory tract infections (LRTIs). This study was conducted to detect M. pneumoniae and C. pneumoniae in children with community-acquired LRTIs employing serology, polymerase chain reaction (PCR) and nested PCR analysis. Material and Methods: This study included 75 children with acute LRTIs for detection of M. pneumoniae and C. pneumoniae. Blood was obtained for M. pneumoniae and C. pneumoniae antibodies and nasopharyngeal aspirates for M. pneumoniae PCR and C. pneumoniae nested PCR. Results: M. pneumoniae infection was positive in 9 (64.21%) children aged 2-6 months and in 5 (35.79%) aged 7 months-12 years, and this difference was statistically significant (P = 0.002). C. pneumoniae infection was comparable within the age group and statistically insignificant (P = 0.43). Clinical and radiological profiles of M. pneumoniae- and C. pneumoniae-positive and negative patients were numerically comparable. Serology and PCR together detected M. pneumoniae infection in 14 (18.6%) children. The sensitivity, specificity and positive and negative predictive values of serology were 77.78%, 92.42%, 58.33% and 96.83%, respectively. C. pneumoniae infection was positive in 11 (14.6%) children by serology and nested PCR with 50% sensitivity, 87.67% specificity, 10% positive predictive value and 98.46% negative predictive value. Conclusions: Our study confirms that M. pneumoniae and C. pneumoniae play a significant role in community-acquired LRTIs and a combination of serology and nested PCR is useful for its diagnosis.

Diagnosis and Treatment of Adults with Community-acquired Pneumonia. An Official Clinical Practice Guideline of the American Thoracic Society and Infectious Diseases Society of America.

Background: This document provides evidence-based clinical practice guidelines on the management of adult patients with community-acquired pneumonia.Methods: A multidisciplinary panel conducted pragmatic systematic reviews of the relevant research and applied Grading of Recommendations, Assessment, Development, and Evaluation methodology for clinical recommendations.Results: The panel addressed 16 specific areas for recommendations spanning questions of diagnostic testing, determination of site of care, selection of initial empiric antibiotic therapy, and subsequent management decisions. Although some recommendations remain unchanged from the 2007 guideline, the availability of results from new therapeutic trials and epidemiological investigations led to revised recommendations for empiric treatment strategies and additional management decisions.Conclusions: The panel formulated and provided the rationale for recommendations on selected diagnostic and treatment strategies for adult patients with community-acquired pneumonia.

Clinical study of chlamydia pneumoniae infection in patients with coronary heart disease.

BACKGROUND: This study aims to investigate the chlamydia pneumoniae infection (PC) in patients with coronary heart disease. METHODS: A total of 92 patients with coronary heart disease, who were treated with percutaneous coronary intervention (PCI), were selected as the case group. In addition, 50 healthy people were enrolled as the control group. The incidences of CP infection and serum Chlamydia pneumoniae IgA antibody (CP-IgA), high sensitive C-reactive protein (hs-CRP), and interleukin-6 (IL-6) were compared in these two groups. The classification of coronary artery lesion, the incidence of perioperative cardiovascular events, and adverse prognosis events within six months after procedure were compared. RESULTS: The incidence of CP infection in the case group was higher (42.4% vs. 0%, P < 0.05). Furthermore, 17 patients were at grade I, 39 patients were at grade II, and 36 patients were at grade III. The incidences for these three kinds of patients were 17.6, 30.8, and 66.7%. The incidence of CP infection at grade III was higher than that of grade I or II (P < 0.05). Serum CP-IgA, hs-CRP and IL-6 levels increased with the severity of the coronary artery disease (P < 0.05), and the serum hs-CRP and IL-6 levels of patients with perioperative cardiovascular events were higher (P < 0.05). Moreover, the serum CP-IgA levels of the patients with adverse prognosis events were also higher (P < 0.05). CONCLUSIONS: Patients with coronary heart disease have a high CP infection rate. The degree of infection is relevant to the severity of the coronary artery lesions and postoperative prognosis of patients, suggesting that CP infection may be an important factor affecting the incidence and prognosis of coronary heart disease.

Atypical and Typical Bacteria in Children with Community Acquired Pneumonia.

This study seeks to determine the pathogens in respiratory specimens and blood serum obtained from children who present with community acquired pneumonia (CAP) diagnosed on the basis of clinical and radiological evidence. The study group consisted of 46 hospitalized children aged 1-11 years. The material for research consisted of pharyngeal swabs and samples of blood serum. One hundred and thirty eight pharyngeal swabs were examined for the presence of C. pneumoniae antigen, C. pneumoniae DNA, and for typical pathogens. C. pneumoniae DNA was detected in pharyngeal swabs with nested PCR. Classical microbiological culture was used for detection of typical bacteria. ELISA test were used for detection anti-C. pneumoniae and anti-M. pneumoniae antibodies in the serum. C. pneumoniae DNA was identified in 10.9% of children. Positive culture for typical pathogens was observed in 8.7% of children. Specific anti-C. pneumoniae IgM antibodies were found in 8.7% of children, and IgG and IgA antibodies in 1 child each. Specific anti-M. pneumoniae IgG antibodies were found in 13.1% of children and IgM antibodies in 1 child. We conclude that the underlying bacterial etiology of CAP is rather rarely conclusively confirmed in children. Nonetheless, determining the etiology of CAP is essential for the choice of treatment to optimize the use and effectiveness of antimicrobials and to avoid adverse effect. Due to considerable variations in the power of detection of the type of atypical bacteria causing CAP, the search for the optimum diagnostic methods continues.

A retrospective seroepidemiologic survey of Chlamydia pneumoniae infection in patients in Beijing between 2008 and 2017.

BACKGROUND: Chlamydia pneumoniae (C. pneumoniae) is an obligate intracellular bacterium and a human pathogen that causes respiratory infectious diseases. More than 50% of the adult population worldwide was once infected with C. pneumoniae, but investigations into this topic are insufficient in mainland China. METHODS: Anti-C. pneumoniae IgG and IgM antibodies were detected using micro-immunofluorescence test in serum samples of patients visiting Peking Union Medical College Hospital between 2008 and 2017 for routine medical purposes, and the aim of this retrospective study was to analyze the test results. RESULTS: Among 12,050 serum specimens tested for anti-C. pneumoniae IgG and IgM antibodies, the overall prevalence of anti-C. pneumoniae IgG antibodies was 86.6%, 87.2% for men and 86.0% for women. Adult men (>20 years) were found to have a significantly higher prevalence of anti-C. pneumoniae IgG than women (χ2 = 30.32, P = 0.000). 3 to 5 years old patients were observed to have the lowest prevalence of anti-C. pneumoniae IgG, 42.8%, then increased with age, reaching the highest level of 98.6% in patients over 70 years of age. In the 10,434 specimens with C. pneumoniae IgG antibodies, the total geometric mean titer (GMT) for C. pneumoniae IgG was 45.71. Although GMTs were found to be significantly higher among all men than among all women (t = 5.916, P = 0.000), sex difference actually began in patients over 40 years of age and increased in the elderly. In the total 12,050 specimens, 1.2% had anti-C. pneumoniae IgM, 3.3% had anti-C. pneumoniae IgG with titers equal to or greater than 1:512; 0.39% had ≥4-fold increasing titers of antibodies in acute and convalescent phase paired samples, and 4.4% were finally confirmed to have acute antibodies against C. pneumoniae. 6 to 10 years old patients were found to have the highest rate of both IgM antibodies (3.9%) and acute antibodies (6.2%) against C. pneumoniae. Acute antibodies against C. pneumoniae were found to be more frequent in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD, 14.0%, χ2 = 20.43, P = 0.000), patients with pneumonia (7.8%, χ2 = 51.87, P = 0.000) and patients with acute respiratory tract infection (12.3%, χ2 = 60.91, P = 0.000) than among all patients (4.4%). Both anti-C. pneumoniae IgG and IgM antibodies should be tested for acute antibodies against C. pneumoniae as testing for either alone will underestimate by a maximum of two-thirds the incidence of acute antibodies against C. pneumoniae. CONCLUSIONS: More than 86% of Chinese patients on an average were once infected with C. pneumoniae. Adult men had both a higher prevalence and higher levels of antibodies than women. 6 to10 year old patients were found to have the most frequent acute infection of C. pneumoniae. C. pneumoniae is associated with AECOPD, pneumonia and acute respiratory tract infection. Anti-C. pneumoniae IgG and IgM should be tested simultaneously to avoid underestimation of acute antibodies against C. pneumoniae.

Pivotal Pathogenic and Biomarker Role of Chlamydia Pneumoniae in Neurovascular Diseases.

Chlamydia Pneumoniae (C. Pn) is an obligatory intracellular bacterium that is associated with respiratory tract infections like pneumonia, pharyngitis and bronchitis. It has also been implicated in cerebrovascular (stroke) as well as cardiovascular diseases. The most possible pathway via which C. Pn elicits its pathogenesis could be via activation of Human Vascular Smooth Muscle Cells (VSMCs) proliferation resulting in the stimulation of Toll-Like Receptor-4 (TLR-4) and/or phospho-44/42(p44/p42) Mitogen-Activated Protein Kinases (MAPK). It is also established that tyrosine phosphorylation of IQ domain GTPase-activating protein 1 (IQGAP1) also contributed to C. Pn infection-triggered Vascular Endothelial Cell (VEC) movements via the SRC tyrosine kinase inhibitor PP2 (4-amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine) resulting in angiogenesis. It is also proven that restricted inflammatory cell infiltrates as well as apoptosis have been linked to C. Pn or C. Pn-specific proteins in atherosclerotic plaques of patients with stroke. It is further an evidence that C. Pn enters the cerebral vasculature during the initial infection and worsen atherosclerosis either directly or indirectly. Chronic, persistent C. Pn infection is also capable of triggering the secretion of Chlamydial Heat Shock Protein 60 (cHSP60) in the vessel wall resulting in augmentation of inflammation. C. Pn also aids in the activation of explicit cell-intermediated immunity within plaques. Macrophages in the carotid plaques co-exist with CD4+ lymphocytes which are capable of triggering the release of pro-inflammatory cytokines resulting in the augmentation of atherogenic development during C. Pn infection. C. Pn actively participated in the modification of both histones H3 and H4 during chromatin analysis via the interleukin 8(IL-8) gene facilitator as well as conscription of nuclear factor kappa-B(NF-κB) or NF- κB/p65 complex and polymerase II (Pol II). This review, therefore, focuses on the crucial involvement of C. Pn in the pathogenesis of cerebrovascular events.

Development of a multiplex TaqMan real-time PCR assay for the detection of Chlamydia psittaci and Chlamydia pneumoniae in human clinical specimens.

Diagnosis of Chlamydia psittaci and Chlamydia pneumoniae infections has traditionally relied on serological assays. We developed a multiplex real-time PCR assay for detection of C. psittaci, C. pneumoniae and an internal control. Results of this assay demonstrated 100% concordance compared to results of previously tested human clinical specimens.

Presence of atopy increases the risk of asthma relapse.

OBJECTIVES: To describe the point prevalence of respiratory viruses/atypical bacteria using PCR and evaluate the impact of respiratory viruses/atypical bacteria and atopy on acute severity and clinical recovery in children with hospitalised and non-hospitalised asthma exacerbations. DESIGN: This was a prospective study performed during 2009-2011. SETTING: The study was performed in the emergency departments of two hospitals. PATIENTS: 244 children aged 2-16 years presenting with acute asthma to the emergency departments were recruited. A nasopharyngeal aspirate and allergen skin prick test were performed. MAIN OUTCOME MEASURES: The outcomes were divided into (1) acute severity outcomes (Australian National Asthma Council assessment, hospitalisation, Functional Severity Scale, Acute Asthma Score, asthma quality of life questionnaires for parents (PACQLQ) on presentation, asthma diary scores (ADS) on presentation and length of hospitalisation) and (2) recovery outcomes (PACQLQ for 21 days, ADS for 14 days and representation for asthma for 21 days). RESULTS: PCR for viruses/atypical bacteria was positive in 81.7% of children (75.1% human rhinovirus, codetection in 14.2%). Mycoplasma pneumoniae and Chlamydophila pneumoniae were rarely detected. The presence of micro-organisms had little impact on acute asthma or recovery outcomes. Children with atopy were significantly more likely to relapse and represent for medical care by day 14 (OR 1.11, 95% CI 1.00 to 1.23). CONCLUSIONS: The presence of any viruses is associated with asthma exacerbations but does not appear to influence asthma recovery. In contrast, atopy is associated with asthma relapse. M. pneumoniae and C. pneumoniae are rare triggers of acute asthma in young children.

Investigation of Chlamydia pneumoniae infection in Moroccan patients suffering from cardiovascular diseases.

Chlamydia pneumoniae is an intracellular bacterium responsible for respiratory diseases and is highly involved in cardiovascular disease development, mainly atherosclerosis. The main objective of our study was to evaluate C. pneumoniae prevalence in Moroccan patients suffering from cardiovascular diseases. A total of 115 patients with cardiovascular diseases were enrolled, and their clinical and behavioral information was recorded. Blood was sampled from all patients as well as the atheroma plaques from 36 patients undergoing surgery. Nested PCR was performed for C. pneumoniae DNA detection in both peripheral blood mononuclear cells (PBMCs) and atheroma plaques. Statistical analysis was performed using EpiInfo software. Data analysis showed cardiovascular disease dominance in men, with a sex ratio M/F of 3.4, a majority of tobacco users (52.2%), and many diabetics (44.3%). A significant difference between genders was shown for tobacco use (p<0.05). Positive cases for PBMCs and atheroma plaques were 61% and 86%, respectively, and a significant difference between PBMCs and atheroma plaque infection was identified (p=0.02). Data analysis also showed that 12% of patients presented only C. pneumoniae infection as a risk factor. Therefore, the high prevalence of C. pneumoniae suggests its involvement in atherosclerosis, and further investigation is recommended for confirmation.

Mucositis Secondary to Chlamydia pneumoniae Infection: Expanding the Mycoplasma pneumoniae-Induced Rash and Mucositis Concept.

The term Mycoplasma pneumoniae-induced rash and mucositis (MIRM) was recently proposed to identify the mucocutaneous condition secondary to M. pneumoniae infection that had historically been regarded among the more confusing pathologies of erythema multiforme and Stevens-Johnson syndrome. Based on a number of previous reports, these syndromes require differentiation since they have different prognoses and specific treatment requirements. We report a case of oral and genital erosions that strongly resembled MIRM without rash but were found to be secondary to a Chlamydia pneumoniae infection. After a thorough review of the literature on this subject, we propose that C. pneumoniae should also be considered a potential causative agent of MIRM and that this term should be amended to include C. pneumoniae infection.

Ocular adnexal marginal zone lymphoma: Clinical presentation, pathogenesis, diagnosis, prognosis, and treatment.

Ocular adnexal marginal zone lymphoma (OAML) represents 1-2% of all non Hodgkin lymphomas. In the last few years many advances in understanding the pathogenesis and the molecular basis involved in its development have been done. Many potential risk factors have been proposed; a dysregulation of immune response in association with a chronic antigenic stimulation, have been hypothesized as possible pathogenic mechanism. In particular, Chlamydia psittaci infection has been related to OAML arising, and eradicating antibiotic therapy has been addressed as a safe and cost-effective approach. Management of OAML is still heterogeneous and matter of debate. There is no consensus about the best upfront treatment and therapeutic decision should take into account several patient-, lymphoma- and treatment-related factors. Novel agents and chemotherapy-free strategies are being investigated to reduce side effects and improve tumor control. This review is focused in recent knowledge improvements in this lymphoma.