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because they share similar characteristics&#44; and moreover&#44; both entities can coexist in the same patient&#46;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">4</span></a> The definitions of vasculitis and its different forms are well established&#46;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">5</span></a> We report the case of a patient that who presented simultaneous TB and microscopic polyangitis &#40;MPA&#41;&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">This was a 68-year-old man with a history of TB&#44; who attended the emergency room with a 1-month history of fever&#44; bloody sputum&#44; asthenia&#44; weight loss&#44; and dyspnea&#46; His temperature was 38&#46;4<span class="elsevierStyleHsp" style=""></span>&#176;C&#44; with no other significant findings&#46; Blood tests were normal&#44; and chest X-ray revealed scarring in the upper right lobe and a solid&#44; spiculated parenchymal lesion&#46; Chest computed tomography &#40;CT&#41; showed no changes in the middle and lower fields &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>A&#41;&#46; No upper respiratory tract involvement was observed&#46; Polymerase chain reaction was positive for <span class="elsevierStyleItalic">Mycobacterium tuberculosis</span> in bronchial aspirate and bronchoalveolar lavage&#46; Core needle biopsy of the spiculated lesion revealed necrotizing granulomatous inflammation with multinucleated Langhans giant cells &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>B&#41;&#44; and positive Ziehl&#8211;Neelsen staining and polymerase chain reaction for <span class="elsevierStyleItalic">M&#46; tuberculosis</span>&#46; The patient developed sudden onset hemoptysis with anemia &#40;hemoglobin&#62;6&#46;8<span class="elsevierStyleHsp" style=""></span>g&#47;dL&#44; hematocrit 20&#46;8&#37;&#41;&#44; acute renal failure &#40;urea 123<span class="elsevierStyleHsp" style=""></span>mg&#47;dL&#44; creatinine 8&#46;3<span class="elsevierStyleHsp" style=""></span>mg&#47;dL&#41;&#44; oligoanuria and elevated transaminases &#40;values 5 times the upper limit of normal&#41;&#46; Intubation&#44; mechanical ventilation&#44; and hemodialysis were required&#46; In view of the patient&#39;s hepatic and renal insufficiency&#44; antituberculosis treatment began with ethambutol&#44; levofloxacin&#44; and streptomycin&#46; Chest CT showed diffusely increased pulmonary radiodensity&#44; mainly ground glass opacities and areas of consolidation in the peribroncovascular region&#44; with moderate left loculated pleural effusion&#44; with a fissural component&#44; that was interpreted as diffuse alveolar hemorrhage &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>C&#41;&#46; Renal biopsy revealed vasculitis with fibrinoid necrosis of the small arteries associated with focal and segmental necrotizing glomerulonephritis with an absence of immunoglobulin&#44; complement and light chain deposits&#44; suggestive of MPA &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>D and E&#41;&#46; Pleural fluid was a lymphocytic exudate&#59; ADA 45<span class="elsevierStyleHsp" style=""></span>U&#47;L&#44; with no other significant changes&#46; Anti-neutrophil cytoplasmic antibodies &#40;ANCA&#41; &#40;dilution 1&#47;320&#59; p-ANCA pattern&#41; with anti-myeloperoxidase antibodies&#62;300<span class="elsevierStyleHsp" style=""></span>IU&#47;mL were detected&#46; Anti-glomerular basement membrane antibodies were negative&#46; Treatment was administered with corticosteroids &#40;3 initial boluses of methylprednisolone 500<span class="elsevierStyleHsp" style=""></span>mg&#47;day&#44; tapered to 15<span class="elsevierStyleHsp" style=""></span>mg&#47;day of prednisone&#41;&#44; plasmapheresis &#40;7 sessions&#41;&#44; and rituximab &#40;700<span class="elsevierStyleHsp" style=""></span>mg&#47;week for 4 weeks&#41;&#46; Rifampicin and isoniazid could subsequently be reintroduced&#46; Progress was slow but favorable&#44; with stabilization of respiratory symptoms and radiological improvement &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>F&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0020" class="elsevierStylePara elsevierViewall">The association between TB and vasculitis has been described&#44; but generally always in association with granulomatosis with polyangitis&#46;<a class="elsevierStyleCrossRefs" href="#bib0080"><span class="elsevierStyleSup">4&#44;6&#44;7</span></a> As far as we know&#44; this is the second case in which TB has been associated with MPA&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">7</span></a> Both diagnoses appear to be confirmed&#58; positive polymerase chain reaction in 2 different samples in the case of TB&#59; and for MPA&#44; granulomatous inflammation with necrosis and multinucleated giant cells in lung tissue with positive Ziehl&#8211;Neelsen staining&#44; and confirmed diagnostic criteria with rapidly progressing diffuse alveolar hemorrhage and necrotizing glomerulonephritis&#46;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">5</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">The question here is&#44; is this association incidental or does one disease &#40;TB&#41; lead to another &#40;MPA&#41;&#63; The inverse association is possible&#44; and the administration of an immunosuppressive treatment for a diagnosis of vasculitis as a trigger for TB has been documented&#44;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">8</span></a> but this could be ruled out in our patient by the order of events&#46; Flores-Su&#225;rez et al&#46; observed high odds ratios for positive p-ANCA by indirect immunofluorescence in TB patients&#44; compared with asthma patients &#40;odds ratio 2&#46;96 &#91;1&#46;19&#8211;7&#46;38&#93;&#59; <span class="elsevierStyleItalic">P</span>&#60;0&#46;027&#41; and healthy subjects &#40;odds ratio 18 &#91;3&#46;88&#8211;83&#46;4&#93;&#59; <span class="elsevierStyleItalic">P</span>&#60;0&#46;0001&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">9</span></a> It is difficult to establish an association between TB and MPA&#44; although the coexistence of TB and positive ANCA may be a causative factor&#46; Some drugs&#44; especially isoniazid and rifampicin&#44; can be transformed into active metabolites that develop cytotoxic products that destroy the neutrophils with subsequent synthesis of ANCA&#44; a phenomenon which might explain the presence of anti-myeloperoxidase antibodies in patients receiving these drugs&#46;<a class="elsevierStyleCrossRefs" href="#bib0110"><span class="elsevierStyleSup">10&#44;11</span></a> However&#44; this is unlikely in our patient&#44; because he had not yet received these products when the diffuse alveolar hemorrhage and necrotizing glomerulonephritis occurred&#46; On the other hand&#44; <span class="elsevierStyleItalic">M&#46; tuberculosis</span> can stimulate the release of oxygen metabolites from the neutrophils&#46; When these cells are activated in the initial stages of mycobacterial infection&#44; lysosomal enzymes are released that could lead to the development of autoantibodies &#40;ANCA&#41; against the granular components of these cells&#46;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">9</span></a> These IgG antibodies that act against neutrophilic and monocytic cytoplasmic antigens &#40;proteinase-3 and myeloperoxidase&#41; induce neutrophil migration and degranulation in the vessel wall&#44; and release proteases and other toxic metabolites that cause vascular damage&#44;<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">12</span></a> which could give rise to this or any other vasculitis&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">In summary&#44; TB is more common in our setting than vasculitis&#44; so diagnosis must be established promptly and treatment must be initiated in case of objective evidence&#46; The characteristics of vasculitis and TB can overlap&#44; and vasculitis should be considered in the differential diagnosis&#44; particularly if azotemia is observed&#46; Sometimes the possibility of a simultaneous presentation must be considered&#44; and while no association between the 2 entities has been demonstrated&#44; the mechanisms we describe may provide a physiopathological explanation&#46; A high index of suspicion and clinical experience in the management of this presentation is necessary&#44; since diagnostic errors and delays in treatments can lead to life-threatening situations&#46;</p></span>"
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        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as&#58; Riveiro V&#44; Ricoy J&#44; Toubes ME&#44; Vald&#233;s L&#46; Tuberculosis y poliangitis microsc&#243;pica&#46; Una asociaci&#243;n muy poco frecuentex&#46; Arch Bronconeumol&#46; 2018&#59;54&#58;635&#8211;637&#46;</p>"
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Scientific Letter
Tuberculosis and Microscopic Polyangiitis. A Rare Combination
Tuberculosis y poliangitis microscópica. Una asociación muy poco frecuente
Vanessa Riveiroa,
Corresponding author
, Jorge Ricoya, María E. Toubesa, Luis Valdésa,b
a Servicio de Neumología, Complejo Hospitalario Universitario de Santiago, Santiago de Compostela, La Coruña, Spain
b Grupo Interdisciplinar de Investigación en Neumología, Instituto de Investigaciones Sanitarias de Santiago (IDIS), Santiago de Compostela, La Coruña, Spain
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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Tuberculosis &#40;TB&#41; is one of the most common causes worldwide of morbidity and mortality due to infection&#44; with a recorded incidence in Spain in 2015 of 21&#46;5 cases&#47;100<span class="elsevierStyleHsp" style=""></span>000 inhabitants&#46;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">1</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Vasculitis is a general term for a heterogeneous group of diseases characterized by inflammation and destruction of blood vessel walls&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">2</span></a> Most cases are primary&#44; but vasculitis can also be secondary to other diseases&#44; including infections&#46;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">3</span></a> At times the difference between TB and vasculitis can be difficult to determine&#44; because they share similar characteristics&#44; and moreover&#44; both entities can coexist in the same patient&#46;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">4</span></a> The definitions of vasculitis and its different forms are well established&#46;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">5</span></a> We report the case of a patient that who presented simultaneous TB and microscopic polyangitis &#40;MPA&#41;&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">This was a 68-year-old man with a history of TB&#44; who attended the emergency room with a 1-month history of fever&#44; bloody sputum&#44; asthenia&#44; weight loss&#44; and dyspnea&#46; His temperature was 38&#46;4<span class="elsevierStyleHsp" style=""></span>&#176;C&#44; with no other significant findings&#46; Blood tests were normal&#44; and chest X-ray revealed scarring in the upper right lobe and a solid&#44; spiculated parenchymal lesion&#46; Chest computed tomography &#40;CT&#41; showed no changes in the middle and lower fields &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>A&#41;&#46; No upper respiratory tract involvement was observed&#46; Polymerase chain reaction was positive for <span class="elsevierStyleItalic">Mycobacterium tuberculosis</span> in bronchial aspirate and bronchoalveolar lavage&#46; Core needle biopsy of the spiculated lesion revealed necrotizing granulomatous inflammation with multinucleated Langhans giant cells &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>B&#41;&#44; and positive Ziehl&#8211;Neelsen staining and polymerase chain reaction for <span class="elsevierStyleItalic">M&#46; tuberculosis</span>&#46; The patient developed sudden onset hemoptysis with anemia &#40;hemoglobin&#62;6&#46;8<span class="elsevierStyleHsp" style=""></span>g&#47;dL&#44; hematocrit 20&#46;8&#37;&#41;&#44; acute renal failure &#40;urea 123<span class="elsevierStyleHsp" style=""></span>mg&#47;dL&#44; creatinine 8&#46;3<span class="elsevierStyleHsp" style=""></span>mg&#47;dL&#41;&#44; oligoanuria and elevated transaminases &#40;values 5 times the upper limit of normal&#41;&#46; Intubation&#44; mechanical ventilation&#44; and hemodialysis were required&#46; In view of the patient&#39;s hepatic and renal insufficiency&#44; antituberculosis treatment began with ethambutol&#44; levofloxacin&#44; and streptomycin&#46; Chest CT showed diffusely increased pulmonary radiodensity&#44; mainly ground glass opacities and areas of consolidation in the peribroncovascular region&#44; with moderate left loculated pleural effusion&#44; with a fissural component&#44; that was interpreted as diffuse alveolar hemorrhage &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>C&#41;&#46; Renal biopsy revealed vasculitis with fibrinoid necrosis of the small arteries associated with focal and segmental necrotizing glomerulonephritis with an absence of immunoglobulin&#44; complement and light chain deposits&#44; suggestive of MPA &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>D and E&#41;&#46; Pleural fluid was a lymphocytic exudate&#59; ADA 45<span class="elsevierStyleHsp" style=""></span>U&#47;L&#44; with no other significant changes&#46; Anti-neutrophil cytoplasmic antibodies &#40;ANCA&#41; &#40;dilution 1&#47;320&#59; p-ANCA pattern&#41; with anti-myeloperoxidase antibodies&#62;300<span class="elsevierStyleHsp" style=""></span>IU&#47;mL were detected&#46; Anti-glomerular basement membrane antibodies were negative&#46; Treatment was administered with corticosteroids &#40;3 initial boluses of methylprednisolone 500<span class="elsevierStyleHsp" style=""></span>mg&#47;day&#44; tapered to 15<span class="elsevierStyleHsp" style=""></span>mg&#47;day of prednisone&#41;&#44; plasmapheresis &#40;7 sessions&#41;&#44; and rituximab &#40;700<span class="elsevierStyleHsp" style=""></span>mg&#47;week for 4 weeks&#41;&#46; Rifampicin and isoniazid could subsequently be reintroduced&#46; Progress was slow but favorable&#44; with stabilization of respiratory symptoms and radiological improvement &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>F&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0020" class="elsevierStylePara elsevierViewall">The association between TB and vasculitis has been described&#44; but generally always in association with granulomatosis with polyangitis&#46;<a class="elsevierStyleCrossRefs" href="#bib0080"><span class="elsevierStyleSup">4&#44;6&#44;7</span></a> As far as we know&#44; this is the second case in which TB has been associated with MPA&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">7</span></a> Both diagnoses appear to be confirmed&#58; positive polymerase chain reaction in 2 different samples in the case of TB&#59; and for MPA&#44; granulomatous inflammation with necrosis and multinucleated giant cells in lung tissue with positive Ziehl&#8211;Neelsen staining&#44; and confirmed diagnostic criteria with rapidly progressing diffuse alveolar hemorrhage and necrotizing glomerulonephritis&#46;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">5</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">The question here is&#44; is this association incidental or does one disease &#40;TB&#41; lead to another &#40;MPA&#41;&#63; The inverse association is possible&#44; and the administration of an immunosuppressive treatment for a diagnosis of vasculitis as a trigger for TB has been documented&#44;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">8</span></a> but this could be ruled out in our patient by the order of events&#46; Flores-Su&#225;rez et al&#46; observed high odds ratios for positive p-ANCA by indirect immunofluorescence in TB patients&#44; compared with asthma patients &#40;odds ratio 2&#46;96 &#91;1&#46;19&#8211;7&#46;38&#93;&#59; <span class="elsevierStyleItalic">P</span>&#60;0&#46;027&#41; and healthy subjects &#40;odds ratio 18 &#91;3&#46;88&#8211;83&#46;4&#93;&#59; <span class="elsevierStyleItalic">P</span>&#60;0&#46;0001&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">9</span></a> It is difficult to establish an association between TB and MPA&#44; although the coexistence of TB and positive ANCA may be a causative factor&#46; Some drugs&#44; especially isoniazid and rifampicin&#44; can be transformed into active metabolites that develop cytotoxic products that destroy the neutrophils with subsequent synthesis of ANCA&#44; a phenomenon which might explain the presence of anti-myeloperoxidase antibodies in patients receiving these drugs&#46;<a class="elsevierStyleCrossRefs" href="#bib0110"><span class="elsevierStyleSup">10&#44;11</span></a> However&#44; this is unlikely in our patient&#44; because he had not yet received these products when the diffuse alveolar hemorrhage and necrotizing glomerulonephritis occurred&#46; On the other hand&#44; <span class="elsevierStyleItalic">M&#46; tuberculosis</span> can stimulate the release of oxygen metabolites from the neutrophils&#46; When these cells are activated in the initial stages of mycobacterial infection&#44; lysosomal enzymes are released that could lead to the development of autoantibodies &#40;ANCA&#41; against the granular components of these cells&#46;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">9</span></a> These IgG antibodies that act against neutrophilic and monocytic cytoplasmic antigens &#40;proteinase-3 and myeloperoxidase&#41; induce neutrophil migration and degranulation in the vessel wall&#44; and release proteases and other toxic metabolites that cause vascular damage&#44;<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">12</span></a> which could give rise to this or any other vasculitis&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">In summary&#44; TB is more common in our setting than vasculitis&#44; so diagnosis must be established promptly and treatment must be initiated in case of objective evidence&#46; The characteristics of vasculitis and TB can overlap&#44; and vasculitis should be considered in the differential diagnosis&#44; particularly if azotemia is observed&#46; Sometimes the possibility of a simultaneous presentation must be considered&#44; and while no association between the 2 entities has been demonstrated&#44; the mechanisms we describe may provide a physiopathological explanation&#46; A high index of suspicion and clinical experience in the management of this presentation is necessary&#44; since diagnostic errors and delays in treatments can lead to life-threatening situations&#46;</p></span>"
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