A 57-year-old Caucasian woman suffered from dyspnea on exertion. One year following a supposed pulmonary embolism event, a chronic thromboembolic vasculopathy was diagnosed and a pulmonary thromboendarterectomy was performed. However, a granulomatous pulmonary arterial vasculitis was identified upon examination. DNA of Mycobacterium goodii was detected as the most likely causative agent. Anti-inflammatory and anti-mycobacterial therapy was initiated for more than 12 months. Regular PET-CT scans revealed improvement under therapy. The last PET-CT did not show any tracer uptake following 10 months of therapy

Bley, Thorsten

Bohle, Rainer M.

Buck, Andreas

Held, Matthias

Heyckendorf, Jan

Langen, Heinz-Jakob

Pfeuffer-Jovic, Elena

Reischl, Udo

Schäfers, Hans-Joachim

Wilkens, Heinrike

International Journal of Infectious Diseases

English

Acronym

International Journal of Infectious Diseases 104 (2021) 178–180Pulmonary vasculitis due to infection with Mycobacterium goodii:A case reportElena Pfeuffer-Jovica,*, Jan Heyckendorfb,c, Udo Reischld, Rainer M. Bohlee,Thorsten Bleyf, Andreas Buckg, Heinrike Wilkensh, Hans-Joachim Schäfersi,Heinz-Jakob Langenj, Matthias HeldaaDepartment of Internal Medicine, Respiratory Medicine and Ventilatory Support, Medical Mission Hospital, Central Clinic Würzburg, Academic TeachingHospital of the Julius Maximilian University of Würzburg, Würzburg, GermanybGerman Center for Infection Research (DZIF), Borstel, GermanycUniversity of Lübeck, Lübeck, Germanyd Institute of Medical Microbiology and Hygiene, University Hospital of Regensburg, Regensburg, GermanyeDepartment of Pathology, Saarland University, Homburg Saar, Germanyf Clinic for Radiology, Julius Maximilian University of Würzburg, Würzburg, GermanygClinic for Nuclear Medicine, Julius Maximilian University of Würzburg, Würzburg, GermanyhDepartment of Internal Medicine V, Pulmonology, Allergology, Respiratory Intensive Care Medicine, Saarland University, Homburg Saar, GermanyiDepartment of Thoracic and Cardiovascular Surgery, Saarland University, Homburg Saar, GermanyjDepartment of Radiology, Medical Mission Hospital, Central Clinic Würzburg, Academic Teaching Hospital of the Julius Maximilian University of Würzburg,Würzburg, GermanyA R T I C L E I N F OArticle history:Received 22 October 2020Received in revised form 22 December 2020Accepted 24 December 2020Keywords:Nontuberculous MycobacteriaMycobacterium goodiiArteritisVasculitisA B S T R A C TA 57-year-old Caucasian woman suffered from dyspnea on exertion. One year following a supposedpulmonary embolism event, a chronic thromboembolic vasculopathy was diagnosed and a pulmonarythromboendarterectomy was performed. However, a granulomatous pulmonary arterial vasculitis wasidentified upon examination. DNA of Mycobacterium goodii was detected as the most likely causativeagent. Anti-inflammatory and anti-mycobacterial therapy was initiated for more than 12 months. RegularPET-CT scans revealed improvement under therapy. The last PET-CT did not show any tracer uptakefollowing 10 months of therapy.© 2020 The Author(s). Published by Elsevier Ltd on behalf of International Society for Infectious Diseases.This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).IntroductionMycobacterium goodii (M. goodii) is a rare, rapidly growing andnontuberculous mycobacterium (Brown et al. 1999) and can befound in soil, dust and drinking water (Griffith et al. 2007; Mohajeriet al. 2017). It causes nosocomial infections such as secondarywound infections (Ferguson et al. 2004; Salas and Klein 2017).Nontuberculous mycobacteria (NTM) causing any form of vasculi-tis are uncommon in literature. There are case reports of small-vessel vasculitis due to NTM infection (Asano et al. 2016; Lee et al.2016), but an induced large vessel disease has not yet beenreported.Case presentationA 57-year-old woman with Caucasian ethnicity reporteddyspnea and chest pain since June 2016. She had been cleaningup a flooded basement a few weeks earlier. On CT scan inSeptember 2016, pulmonary embolism (PE) was diagnosed andtherapy with rivaroxaban was initiated. The only comorbidity atthat time was previous hypothyroidism, which had been suffi-ciently treated for years.In October 2016, the patient presented to the specializedoutpatient clinic for pulmonary hypertension at the MedicalMission Hospital (Würzburg, Germany). Transthoracic echocardi-ography and lung function testing did not show any abnormalresults. Signs of gas exchange disturbance and massive hyperven-tilation were noticed during cardiopulmonary exercise testing,* Corresponding author at: Department of Internal Medicine, RespiratoryMedicine and Ventilatory Support, Medical Mission Hospital, Central ClinicContents lists available at ScienceDirectInternational Journal of Infectious Diseasesjournal home page: www.elsevier .com/ locat e/ i j idWürzburg, Academic Teaching Hospital of the Julius Maximilian University ofWürzburg, Medical Mission Hospital, Salvatorstrasse 7, 97074 Würzburg, Germany.E-mail address: elena.pfeuffer-jovic@kwm-klinikum.de (E. Pfeuffer-Jovic).https://doi.org/10.1016/j.ijid.2020.12.0741201-9712/© 2020 The Author(s). Published by Elsevier Ltd on behalf of International license (http://creativecommons.org/licenses/by-nc-nd/4.0/).which were interpreted as part of the recently diagnosed PE. Due topersistent dyspnea, a lung-scintigraphy was performed in April2017, revealing a ventilation-perfusion mismatch. PulmonarySociety for Infectious Diseases. This is an open access article under the CC BY-NC-NDaadptduiaSnTgmaucQfD(ciaPtvogTbifi2bS2pCtucFpE. Pfeuffer-Jovic et al. International Journal of Infectious Diseases 104 (2021) 178–180ngiography showed several obstructions of the right pulmonaryrtery. Chronic thromboembolic pulmonary hypertension wasiagnosed by right heart catheter, with a pulmonary arteryressure of 22 mmHg, and the patient was admitted for pulmonaryhromboendarterectomy (PEA) in September 2017.The surgical dissection of the right artery during PEA wasifficult. The resected tissue appeared atypical compared withsual thrombus material. Histology revealed lymphocellularnflammation of the intima and media of the right pulmonaryrtery with epithelioid granuloma (Figure 1). Gram and Warthin-tarry stain of the samples did not detect bacteria. The patient hado symptoms of any systemic infection, with negative tests for HIV,reponema pallidum, Mycobacterium tuberculosis or other patho-ens on serological and microbiological screening of differentaterials, including blood cultures out of the right pulmonaryrtery. The laboratory results including auto-antibodies werenspecific (Supplementary Table 1).Molecular methods were applied for bacterial species identifi-ation. DNA was extracted from the tissue samples by using theiaAmp DNA Mini Kit (Qiagen, Hilden, Germany), and a 510-bpragment of the ribosomal 16S rDNA was amplified and sequenced.ata were analyzed with the Integrated Database Network SystemSmartGene Services, Lausanne, Switzerland; www.smartgene.om). The resulting sequence was assigned to M. goodii. Sequencedentity to GenBank accession no. Y12872.1 was complete withoutny mismatches in the sequenced segment of 448 bp. An 18F-FDG-ET-CT in December 2017 showed high tracer activity rates in thehoracic aorta and right pulmonary artery, indicating a localizedasculitis. Due to the DNA detection of M. goodii and the exclusionf other differential diagnoses, a pulmonary vasculitis due to M.oodii was concluded.reatment and follow-upCombination therapy consisting of prednisolone (0.5 mg/kgody weight), amikacin, doxycycline and moxifloxacin wasnitiated in July 2018. Due to a moderate deterioration in renalunction, amikacin was replaced by cotrimoxazole. Dyspneamproved very slowly during the first months. In December018, a PET-CT depicted an unchanged accumulation of the tracerut revealed a decrease in the pulmonary artery wall thickness.ince then, prednisolone therapy was reduced stepwise. In May019, another PET-CT did not show any tracer activity in theulmonary artery (Supplementary Figure 1 for CT sequences).DiscussionMycobacterium goodii is still an uncommon pathogen (Griffith etal. 2007). This is the first published case of a large vessel vasculitiscaused by M. goodii. M. goodii was only proven by PCR. However,the reference standard for mycobacterial infections is stillmycobacterial culture (Griffith et al. 2007), which could not betested in the paraffin-embedded resectate. A contamination of theparaffin-embedded resectate could have been possible but seemsunlikely as paraffin was tested negative by DNA sequencing formycobacteria species. A reoperation to gain native material forcultivation was not performed due to procedural risk, but detectionof M. goodii by PCR was confirmed by Germany’s NationalReference Center for mycobacteria (Borstel). Due to the exclusionof other differential diagnoses, it is believed that M. goodii mighthave caused this vasculitis. The underlying pathomechanism ofthis vasculitis is still unclear. Case reports describing vasculitis inpatients with Mycobacterium tuberculosis infections can be foundin the literature (Walters et al. 2013; Reshkova et al. 2016). A cross-reactivity between mycobacteria and a human heat shock protein(HSP) has been suggested (Aggarwal et al. 1996). A mycobacterialHSP-induced immune response may cross-react with human HSP,which leads to autoimmune reactions and inflammation (Kumaret al. 2004). A similar mechanism may have induced the vasculitisin the current case.The adequate therapeutic procedure of how to treat a vasculitisassociated with mycobacterial infection is unclear. Anti-inflam-matory therapy may result in an aggravation of an activemycobacteriosis. In a case report of Takayasu arteritis accompaniedby tuberculosis, the exclusive immunosuppressive therapy withsteroids did not lead to an improvement in the disease (Duzovaet al. 2000). A solely antimycobacterial therapy in a vasculitis witha high inflammatory activity, as in this case, seemed to beinsufficient. It was decided to treat the patient with both anti-inflammatory and antimycobacterial drugs.There are no guidelines for the treatment of NTM associatedwith vasculitis. However, therapeutic strategies in this casewere based on ATS recommendations for NTM lung disease.Combination therapy with amikacin, doxycycline and trimeth-oprim-sulfamethoxazole is recommended for M. goodii (Griffithet al. 2007). The few reported pulmonary infections due to M.goodii have recommended therapy with at least two drugs for >12months (Martinez-Gonzalez et al. 2011; Waldron et al. 2019).M. goodii could not be cultivated and a molecular resistance testwas not available; therefore, empiric therapy was induced. Thenecessary treatment duration was unclear. Therapyresponse measured by culture conversion, as recommended bythe guidelines, was not possible in this case (Griffith et al. 2007);therefore, the treatment response was evaluated by 18F-FDG-PET.Tracer uptake in the right pulmonary artery in the first 18F-FDG-PET in December 2017 could have been affected by the PEA, whichwas performed 3 months before imaging. Nevertheless, the 18F-FDG-PET in June 2018 remained unchanged, so it seems unlikelythat the tracer uptake was caused by the previous surgicalintervention.This is the first published case of large vessel disease caused byM. goodii. The combination therapy of antimycobacterial and anti-inflammatory drugs was able to induce remission of theinflammatory alterations of the affected pulmonary arteries.18F-FDG-PET served as the main disease monitoring tool. Theigure 1. Resectate showing lymphocellular inflammation of the media of the rightulmonary artery with epithelioid granuloma (hematoxylin and eosin stain).orticosteroids were tapered down and finally stopped. At thatime, the patient was on prednisolone for 10 months andnchanged therapy with cotrimoxazole, moxifloxacin and doxy-ycline, which was continued for the following 11 months.17antimycobacterial therapy has been continued for more than 18months. The systemic steroid therapy was gradually reducedduring this time. Currently, the patient seems to be in a stablesituation without any inflammatory activity.9E. Pfeuffer-Jovic et al. International Journal of Infectious Diseases 104 (2021) 178–180Conflict of interestDr. Pfeuffer-Jovic reports fees for travel/accommodation fromActelion, Boehringer Ingelheim, Novartis and OMT, outside thesubmitted work. PD Dr. Heyckendorf reports honoraria forindependent lectures at symposia sponsored by Chiesi and AstraZeneca. Prof. Dr. Reischl has nothing to declare. Prof. Dr. Bohle hasnothing to declare. Prof. Dr. Bley reports fees from Chugai, GSK,Roche and Novartis and grants from German Research Foundation(DFG) and from Siemens Healthineers, outside the submittedwork. Prof. Dr. Buck has nothing to declare. Prof. Dr. Wilkens hasreceived personal fees for lectures and/or advisory board activitiesfrom Actelion, Janssen, Bayer Healthcare, Boehringer Ingelheim,GSK, MSD, Pfizer and Roche. Prof. Dr. Schäfer has nothing todeclare. Prof. Dr. Langen has nothing to declare. PD Dr. Held reportsgrants from Actelion, honoraria for lectures from Actelion, BayerHealthCare, Berlin Chemie, Boehringer Ingelheim, GSK, Novartis,Pfizer, honoraria for advisory board activities from Actelion, BayerHealthCare, GSK, MSD, and participation in clinical trials ofActelion, Bayer HealthCare, GSK, Pfizer, United Therapeutics,outside the submitted work.FundingThere was no funding.Ethical approvalAll procedures performed in studies involving human partic-ipants were in accordance with the ethical standards of theinstitutional and/or national research committee and with the1964 Declaration of Helsinki and its later amendments orcomparable ethical standards.AcknowledgementsContribution: Writing - original draft: Elena Pfeuffer-Jovic,Matthias Held. Writing - review and editing: Elena Pfeuffer-Jovic,Matthias Held, Jan Heyckendorf, Udo Reischl, Heinrike Wilkens,Heinz-Jakob Langen, Rainer M. Bohle, Thorsten Bley, Andreas Buck,Hans-Joachim Schäfers. All authors were actively contributing tointerpretation of the results and discussion of the findings. They allapproved the final version of the manuscript.Appendix A. Supplementary dataSupplementary data associated with this article can be found, inthe online version, at https://doi.org/10.1016/j.ijid.2020.12.074.ReferencesAggarwal A, Chag M, Sinha N, Naik S. Takayasu’s arteritis: role of Mycobacteriumtuberculosis and its 65 kDa heat shock protein. Int J Cardiol 1996;55:49–55, doi:http://dx.doi.org/10.1016/0167-5273(96)02660-5.Asano S, Mizuno S, Okachi S, Aso H, Wakahara K, Hashimoto N, et al. Antineutrophilcytoplasmic antibody-associated vasculitis superimposed on infection-relatedglomerulonephritis secondary to pulmonary mycobacterium avium complexinfection. Intern Med 2016;55:2439–45, doi:http://dx.doi.org/10.2169/internal-medicine.55.6588.Brown BA, Springer B, Steingrube VA, Wilson RW, Pfyffer GE, Garcia MJ, et al.Mycobacterium wolinskyi sp. nov. and Mycobacterium goodii sp. nov., two newrapidly growing species related to Mycobacterium smegmatis and associatedwith human wound infections: a cooperative study from the InternationalWorking Group on Mycobacterial Taxonomy. Int J Syst Bacteriol 1999;49:1493–511, doi:http://dx.doi.org/10.1099/00207713-49-4-1493.Duzova A, Turkmen O, Cinar A, Cekirge S, Saatci U, Ozen S. Takayasu’s arteritis andtuberculosis: a case report. Clin Rheumatol 2000;19:486–9, doi:http://dx.doi.org/10.1007/s100670070013.Ferguson DD, Gershman K, Jensen B, Arduino MJ, Yakrus MA, Cooksey RC, et al.Mycobacterium goodii infections associated with surgical implants at Coloradohospital. Emerg Infect Dis 2004;10:1868–71, doi:http://dx.doi.org/10.3201/eid1010.040402.Griffith DE, Aksamit T, Brown-Elliott BA, Catanzaro A, Daley C, Gordin F, et al. Anofficial ATS/IDSA statement: diagnosis, treatment, and prevention of non-tuberculous mycobacterial diseases. Am J Respir Crit Care Med 2007;175:367–416, doi:http://dx.doi.org/10.1164/rccm.200604-571ST.Kumar Chauhan S, Kumar Tripathy N, Sinha N, Singh M, Nityanand S. Cellular andhumoral immune responses to mycobacterial heat shock protein-65 and itshuman homologue in Takayasu’s arteritis. Clin Exp Immunol 2004;138:547–53,doi:http://dx.doi.org/10.1111/j.1365-2249.2004.02644.x.Lee TL, Agrawal R, Tan JY, Ong KH, Wong CS, Ho SL. Disseminated nontuberculousmycobacterial infection with multifocal retinitis and vasculitis in an immuno-compromised patient with anti-IFN- autoantibodies. 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Pulmonary vasculitis due to infection with Mycobacterium goodii : A case report

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Pulmonary vasculitis due to infection with Mycobacterium goodii : A case report

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