A cluster of non-tuberculosis mycobacterial infections in patients with connective tissue diseases

Fernández-Codina, Andreu; Silverman, Michael; Pope, Janet E.
doi:10.1016/j.medcle.2019.04.046
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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Non-tuberculous mycobacteria &#40;NTM&#41; can be found in multiple reservoirs and cause infections in immunocompetent and immunocompromised patients&#46; The isolation of NTM in pulmonary samples increased in Ontario from 1998 to 2010&#44; but the isolation in extrapulmonary samples was stable &#40;4&#37;&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">1</span></a> Skin&#47;soft tissue NTM infections &#40;representing the second most common extra-pulmonary location&#41; decreased&#46; We report a cluster of NTM soft-tissue and bone infections in patients with connective tissue diseases &#40;CTD&#41; from a single Rheumatology practice in London&#44; Ontario &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0010" class="elsevierStylePara elsevierViewall">Case 1&#46; A 66-year-old woman with longstanding dermatomyositis in remission in February 2018&#46; She reported an ongoing left calf necrotic ulcer &#40;diameter 4<span class="elsevierStyleHsp" style=""></span>cm&#41; since December 2017&#44; a small ulcerative plaque in the proximal third of her left arm and a lump in the proximal third of her left elbow&#46; She also had some mechanical pain in her left scapula&#46; The elbow lump resulted in an abscess&#44; which was drained and sent for culture&#44; resulting positive for <span class="elsevierStyleItalic">Mycobacterium avium complex</span> &#40;MAC&#41;&#46; A bone scan showed an abscess posterior to the left scapula and a focus of osteomyelitis in the right ankle&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">Case 2&#46; An 87-year-old woman with longstanding systemic lupus erythematosus &#40;SLE&#41; in remission&#46; Since March 2017&#44; she had an ongoing dactylitis in the 2<span class="elsevierStyleSup">nd</span> finger left hand that progressed to a tenosynovitis of the left dorsal wrist in October 2017&#46; Given the functional impairment of the hand&#44; she had the tenosynovitis injected with 40<span class="elsevierStyleHsp" style=""></span>mg of triamcinolone and 0&#46;5<span class="elsevierStyleHsp" style=""></span>mL of a 1&#37; lidocaine solution with a clean technique in early January and February 2018&#46; In the later date&#44; a synovial fluid sample was sent for analysis and culture&#46; Ten days after&#44; the laboratory notified the growth of <span class="elsevierStyleItalic">Mycobacterium chelonae</span>&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">Case 3&#46; A 58 year-old woman with a longstanding overlap of dermatomyositis and limited cutaneous systemic sclerosis&#44; with interstitial lung disease&#44; presented with a flexor tenosynovitis of the 3<span class="elsevierStyleSup">rd</span> finger of her left hand in December 2017&#46; One month before she had been admitted due to a <span class="elsevierStyleItalic">Clostridium difficile</span> colitis&#44; after receiving 2 courses of antibiotics for an episode of sinusitis&#46; She had the finger injected with triamcinolone and lidocaine&#44; and prednisone was increased to 10<span class="elsevierStyleHsp" style=""></span>mg&#47;day&#46; In the following months&#44; the tenosynovitis had progressive worsening and she was injected on 2 more occasions&#46; In August 2018&#44; she had erythema&#44; swelling and pain in between the 3<span class="elsevierStyleSup">rd</span> metacarpophalangeal joint and the proximal interphalangeal joint&#46; There was some fluid collection and a sample was obtained&#44; resulting in a positive acid fast staining&#46; The culture was positive for <span class="elsevierStyleItalic">Mycobacterium marseillense</span>&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">All patients were evaluated by an Infectious Diseases specialist&#46; No patient had extra-risk factors &#40;trauma&#44; drug abuse&#44; previous injections or surgeries&#44; exposures&#41;&#44; testing for human immunodeficiency virus was negative&#44; none had symptoms of pulmonary involvement and all had normal chest X-rays&#46; Lidocaine and triamcinolone vials from the Rheumatology clinic tested negative for any contamination&#46; They all started specific anti-mycobacterial treatment &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#44; for 6 months in patient 2 &#40;elder and localized disease&#41; and 12 months in patients 1 &#40;multiple abscesses&#41; and 2 &#40;slow improvement and resistance to moxifloxacin and linezolid&#41;&#46; Corticoid sparing agents were held and glucocorticoids were reduced to the minimum effective dose&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">Recent American studies show an increase in the incidence of NTM cutaneous infections&#44; from 0&#46;7&#47;100&#44;000 person-years &#40;period 1980&#8211;1999&#41; to 2&#47;100&#44;000 person-years &#40;2000&#8211;2009&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">2</span></a> All series show a predominance of MAC among the overall isolates for NTM&#44; and also for the skin&#47;soft tissue infections&#46;<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">1&#44;2</span></a> Skin infections caused by rapid growing mycobacteria like <span class="elsevierStyleItalic">M&#46; marinum</span> or <span class="elsevierStyleItalic">M&#46; chelonae</span> have become more frequent recently&#46;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">2</span></a> Opportunistic infections by tuberculous and NTM were commonly associated with immunosuppression in inflammatory myopathy&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">3</span></a> A review of SLE patients with NTM skin infection reported cases of infections with or without ongoing immunosupressive treatment&#46;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">4</span></a> NTM infections are well known to be associated to the use of biologic therapies&#46; No solid association between CTD and NTM infections has been reported&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">Diagnosis of NTM skin&#47;soft tissue or bone infections can be challenging&#46; A retrospective study regarding upper extremity NTM infections&#44;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">5</span></a> showed a median diagnostic delay of 4 months due to the paucity of the symptoms&#46; Hands were the most commonly involved location&#46; Half of the patients presented with erythema&#44; joint pain and swelling&#46; These clinical signs might be mimicked by CTD or inflammatory arthritis&#46; Local steroid injections might contribute to worsen the infection and to mask it&#46; Nevertheless&#44; patients with autoimmune diseases&#44; when treated&#44; are immunosuppressed and injections might inoculate mycobacteria that could already be colonizing patients or the injectate&#46; Reducing immunosupressants to the minimally effective doses seems reasonable at the beginning of the anti-tuberculous treatment&#44; but disease flares may require dose increases&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">Physicians should be aware of NTM infections in patients with CTD&#46; Clinical suspicion and sending samples for specific mycobacteria smears and cultures are vital&#46;</p></span>"
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">87&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">58&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Baseline disease&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Dermatomyositis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Systemic lupus erythematosus&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Dermatomyositis and scleroderma overlap&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Relevant infections&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">None&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">None&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">C&#46; difficile</span> November 2017&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Immunosuppression&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">AZA 100<span class="elsevierStyleHsp" style=""></span>mg&#47;day Prednisone 5<span class="elsevierStyleHsp" style=""></span>mg&#47;dayMTX 20<span class="elsevierStyleHsp" style=""></span>mg po weeklyHCQ 400<span class="elsevierStyleHsp" style=""></span>mg&#47;day&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Prednisone 5<span class="elsevierStyleHsp" style=""></span>mg&#47;day when needed&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">MTX 25<span class="elsevierStyleHsp" style=""></span>mg po weeklyPrednisone 7&#46;5<span class="elsevierStyleHsp" style=""></span>mg daily&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Intra-articular injections&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">January 2018&#44; February 2018&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">December 2017&#44; March 2018&#44; April 2018&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Onset date&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">December 2017&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">March 2017&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">November 2017&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Diagnosis date&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">February 2018&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">February 2018&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">August 2018&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Initial manifestation&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Skin ulcer and subcutaneous abscess&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Dactylitis and finger-wrist extensor tenosynovitis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Finger flexor tenosynovitis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Acid fast smear&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4 bacilli per field&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2 bacilli per field&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1 bacillus per field&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">PCR or culture&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">M&#46; avium</span> complex &#40;PCR&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">M&#46; chelonae</span> &#40;culture&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">M&#46; marseillense</span> &#40;culture&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Extension study&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Left periscapular abscess&#44; right lateral malleolus osteomyelitis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Negative&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Negative&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Treatment&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Hold MTX and AZAStart erythromycin &#40;diarrhea&#41;&#44; rifabutin &#40;liver toxicity&#41;&#44; ethambutol&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Hold prednisoneStart imipenem&#44; clarithromycin &#40;confusion interacting with amitriptyline&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Hold MTXStart azithromycin&#44; ethambutol and rifampicin&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Treatment adjustment&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Switched to azithromycin&#44; ethambutol and moxifloxacin&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">None&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Clarithromycin&#44; rifampicin and ethambutol&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Evolution at 6 months&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Improvement&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Improvement&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Initial lack of improvement&#44; after changes slow improvement&#46; Myositis flare restarting MTX&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab2307170.png"
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        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Characteristics of the CTD patients with NTM infections&#46;</p>"
        ]
      ]
    ]
    "bibliografia" => array:2 [
      "titulo" => "References"
      "seccion" => array:1 [
        0 => array:2 [
          "identificador" => "bibs0015"
          "bibliografiaReferencia" => array:5 [
            0 => array:3 [
              "identificador" => "bib0030"
              "etiqueta" => "1"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Pulmonary versus nonpulmonary nontuberculous mycobacteria&#44; Ontario&#44; Canada"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "S&#46;K&#46; Brode"
                            1 => "A&#46; Marchand-Austin"
                            2 => "F&#46;B&#46; Jamieson"
                            3 => "T&#46;K&#46; Marras"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.3201/eid2311.170959"
                      "Revista" => array:6 [
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                        "fecha" => "2017"
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                            "web" => "Medline"
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                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            1 => array:3 [
              "identificador" => "bib0035"
              "etiqueta" => "2"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Increased incidence of cutaneous nontuberculous mycobacterial infection&#44; 1980 to 2009&#58; a population-based study"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "A&#46;B&#46; Wentworth"
                            1 => "L&#46;A&#46; Drage"
                            2 => "N&#46;L&#46; Wengenack"
                            3 => "J&#46;W&#46; Wilson"
                            4 => "C&#46;M&#46; Lohse"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.mayocp.2012.06.029"
                      "Revista" => array:6 [
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                        "fecha" => "2013"
                        "volumen" => "88"
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                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23218797"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            2 => array:3 [
              "identificador" => "bib0040"
              "etiqueta" => "3"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Opportunistic infections in patients with idiopathic inflammatory myopathies"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "A&#46; Redondo-Benito"
                            1 => "A&#46; Curran"
                            2 => "A&#46; Villar-Gomez"
                            3 => "E&#46; Trallero-Araguas"
                            4 => "A&#46; Fern&#225;ndez-Codina"
                            5 => "I&#46; Pinal-Fernandez"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/1756-185X.13255"
                      "Revista" => array:6 [
                        "tituloSerie" => "Int J Rheum Dis"
                        "fecha" => "2018"
                        "volumen" => "21"
                        "paginaInicial" => "487"
                        "paginaFinal" => "496"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/29314762"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            3 => array:3 [
              "identificador" => "bib0045"
              "etiqueta" => "4"
              "referencia" => array:1 [
                0 => array:2 [
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