Chapman, Gavin B

Dhaun, Neeraj

Lahiri , Rashmi

Leitch, Andrew E

Reid, Peter

English

PubMed

Edinburgh Research Explorer

     Edinburgh Research Explorer                                      Strawberry carina as a presentation of ANCA-associatedvasculitisCitation for published version:Chapman, GB, Leitch, AE, Lahiri , R, Reid, P & Dhaun, N 2021, 'Strawberry carina as a presentation ofANCA-associated vasculitis', Rheumatology. https://doi.org/10.1093/rheumatology/keab783Digital Object Identifier (DOI):10.1093/rheumatology/keab783Link:Link to publication record in Edinburgh Research ExplorerDocument Version:Version created as part of publication process; publisher's layout; not normally made publicly availablePublished In:RheumatologyGeneral rightsCopyright for the publications made accessible via the Edinburgh Research Explorer is retained by the author(s)and / or other copyright owners and it is a condition of accessing these publications that users recognise andabide by the legal requirements associated with these rights.Take down policyThe University of Edinburgh has made every reasonable effort to ensure that Edinburgh Research Explorercontent complies with UK legislation. If you believe that the public display of this file breaches copyright pleasecontact openaccess@ed.ac.uk providing details, and we will remove access to the work immediately andinvestigate your claim.Download date: 22. Dec. 2021Letter to the Editor (Case report)Rheumatology 2021;00:1–3https://doi.org/10.1093/rheumatology/keab783Advance access publication 20 October 2021Strawberry carina as a presentation of anti-neutrophil cytoplasm antibody–associatedvasculitisDEAR EDITOR, A 51-year-old man presented with a7-week history of dry cough, shortness of breath andankle swelling. There was no past medical history andthe patient took no regular medications. He had neversmoked and drank 20 units of alcohol per week. Hehad worked as a stonemason for 20 years.On examination, there was bilateral ankle oedemabut no other clinical findings of note. Blood testsshowed a systemic inflammatory response with an-aemia [115 g/l (normal range 130–180)], thrombocytosis[418 109/l (normal range 150–400), elevated CRP[85 mg/l (normal range 0–5 mg/l)] and hypolbuminaemia[29 g/l (normal range 36–47)]. Kidney excretory functionwas normal [serum creatinine 61 mmol/l (normal range64–111)] and there was no haematuria or proteinuria[urine protein:creatinine ratio 9 mg/mmol (normal range0–30)]. A chest X-ray showed prominent hila bilaterallywith some calcification (Fig. 1A). A CT scan of thechest, abdomen and pelvis with contrast demonstratedbilateral hilar and mediastinal lymphadenopathy withcoarse calcification (Fig. 1B). There was bronchial wallthickening and ground-glass changes evident in the leftupper lobe.The patient was reviewed in the general respiratoryclinic 10 days later. He had ongoing cough andbreathlessness and now complained of right foot painand drenching night sweats. The CT chest findingswere in keeping with chronic silica exposure, althoughthe differential included mycobacterial infection, sar-coidosis and lymphoma. Given the patient’s systemicsymptoms, an endobronchial ultrasound bronchos-copy was performed to obtain a tissue diagnosis. Ondirect visualization, the airways were grossly abnor-mal, and the patient went on to have a flexible bron-choscopy that showed discrete haemorrhagic plaquestraddling the main carina with small, yellow pusislands (reminiscent of a strawberry; Fig. 1C). Therewere further similarly discrete areas of haemorrhagicplaque in the left and right main bronchus. The inter-vening bronchial mucosa was normal. Bronchoalveolarlavage showed a minor excess of inflammatory cells.Biopsies of the bronchial wall showed only a minor ex-cess of chronic inflammatory cells within the sub-mucosa. There was no evidence of bacteria, acid-fastbacilli or malignant cells.Given the unusual airway appearances, further inves-tigations were requested. The patient had a circulatingANCA against MPO titre (6.9 IU/ml, upper limit of nor-mal 3.4 IU/ml). Complement levels were normal andthere were no antibodies against anti-nuclear or anti-cyclic citrullinated peptides or extractable nuclear anti-gens. The patient was reviewed in the Vasculitis Clinicwith ongoing right foot pain and tingling in both feetand weakness. Urinalysis now showed haematuria andmild proteinuria (urine protein:creatinine ratio 35 mg/mmol), however, kidney excretory function continued tobe normal. A kidney biopsy showed a pauci-immunefocal and necrotizing glomerulonephritis with cellularcrescents and no scarring (Fig. 1D). He was treatedwith immunosuppression. His respiratory symptomsresolved rapidly and there was normalization of thesystemic inflammatory response (Fig. 1E). Renal excre-tory function remained normal throughout. The neuro-logical symptoms improved more gradually.There are several pulmonary manifestations of systemicvasculitis, including interstitial lung disease, alveolarhaemorrhage, tracheobronchial stenosis and pulmonarynodules (with or without cavitation). The pulmonary ab-normality here was focussed on the airways, but therewas no excess of tracheobronchial airway mucosal tissueand no evidence of stenosis. Interstitial lung disease maybe part of a systemic autoimmune disease and a positiveMPO ANCA is often found. However, many of thesepatients do not have other symptoms or signs consistentwith a systemic vasculitis at initial diagnosis. Interestingly,a recent retrospective study demonstrated that MPOANCA positivity in patients with idiopathic interstitialpneumonia is associated with future development ofANCA-associated vasculitis (AAV) [1]. Therefore it is im-portant to comprehensively assess these patients at initialpresentation and during follow-up for features of smallvessel inflammation in other organs.In this case, the combination of abnormal CT chestfindings, positive ANCA serology, active urinary sedi-ment and neurological symptoms was most in keepingwith AAV affecting the airways and lung parenchyma,kidneys and nerves. This was confirmed by typical hist-ology on kidney biopsy. The MPO ANCA was only mod-estly elevated; the ANCA titre correlates poorly withdisease activity in AAV and having positive serology perse is more significant clinically than the titre itself.Conversely, in patients with a suggestive clinical presen-tation and/or compatible histology, the diagnosis can bemade in the absence of positive ANCA testing [2]. Inpatients with active AAV, strawberry-like inflammationRheumatology key message. Strawberry-like inflammation of the airways may be adisease feature in patients with AAV.LETTERVC The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Rheumatology.This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, andreproduction in any medium, provided the original work is properly cited.RheumatologyDownloaded from https://academic.oup.com/rheumatology/advance-article/doi/10.1093/rheumatology/keab783/6404617 by University of Edinburgh user on 04 November 2021has been described in the gingiva [3]. This is the firsttime, to our knowledge, it has been described within theairways. Disease induction treatment here comprisedtwo doses of intravenous cyclophosphamide and rituxi-mab. This novel approach allowed a rapid glucocorticoidtaper. A number of studies have investigated remission-induction regimens that allow a significant reduction inor complete avoidance of glucocorticoid exposure, oftenby using combinations of non-glucocorticoid immuno-suppressive agents [4, 5].FIG. 1 Radiological, pathological and biochemical results(A) Chest X-ray on admission showing enlarged, calcified hilar lymph nodes. (B) Axial view of CT of the chest demon-strating enlarged calcified hilar and subcarinal lymph nodes with minor left upper lobe interstitial and nodular change.(C) Bronchoscopic image demonstrating normal airway in foreground with discrete, haemorrhagic plaque (yellow cir-cle) straddling the main carina with small, yellow pus islands (yellow line) reminiscent of a strawberry. (D) Kidney bi-opsy demonstrating glomerulus with necrotizing lesion (red line) and cellular crescent (yellow line) secondary to AAV.(E) Haematological and biochemical results from presentation. Vertical dashed line at 10 weeks representing whentreatment commenced. PCR: protein:creatinine ratio.Letter to the Editor2 https://academic.oup.com/rheumatologyDownloaded from https://academic.oup.com/rheumatology/advance-article/doi/10.1093/rheumatology/keab783/6404617 by University of Edinburgh user on 04 November 2021Stonemasonry, particularly when working withstones such as granite ,which have a high quartz con-tent, is known to increase the risk of developing sili-cosis. In this case, the lung parenchymal change wassubtle, with the most striking abnormality being thepresence of enlarged and calcified hilar and medias-tinal lymph nodes. This highlights the role of the al-veolar macrophage in clearing any silica deposited inthe alveoli to the lymphatic system. The resulting in-flammatory and fibrotic reaction results in enlargedglands that finally calcify. Once sufficient silica isinhaled to overwhelm and impair lung clearance, thesame inflammatory and fibrotic processes occur in theparenchyma of the lung, leading to the developmentof silicosis. The typical changes of silicosis include bi-lateral upper lobe nodularity often accompanied byperilymphatic beading similar to that reported in casesof sarcoidosis, but so far as the authors are aware,the endobronchial changes described here have notbeen reported and we believe may represent a localreaction to inhaled silica.In addition to silicosis, the inhalation of silica alsoincreases the risk of developing pulmonary mycobac-terial disease, lung cancer and chronic obstructivepulmonary disease and has been implicated in thepathogenesis of autoimmune conditions such as SSc,RA and SLE. This case highlights the potential role ofrespirable silica in the pathogenesis of AAV, whichhas been the subject of several case reports andcase–control and cohort studies [6]. A recent study inFrance demonstrated a clear geospatial associationbetween cases of granulomatosis with polyangiitis, aform of AAV, and the presence of quarries, a sourceof silica, which has been associated with the develop-ment of positive ANCA serology [7].The evidence for the role of silica in the developmentof AAV is strongest in patients with glomerulonephritisand is underpinned by experimental evidence demon-strating how silica may contribute to the development ofautoimmunity and chronic inflammation from which bio-logically plausible mechanisms may be postulated.However, while a few small studies have reported bothan increased prevalence of ANCA and AAV in silica-exposed populations, the rarity of these conditions inev-itably means that further large-scale studies with moreclearly defined exposures are required before greaterconfidence in causation may be inferred. Nonetheless,the unresolved but potential role of silica in these condi-tions highlights the importance of adherence to strictoccupational hygiene and the provision of personal pro-tective equipment to all workers exposed to respirablesilica.AcknowledgementsAll authors contributed to data acquisition and ana-lysis, as well as drafting and critically appraising themanuscript.Funding: This research received no specific grant fromany funding agency in the public, commercial or not-for-profit sectors.Disclosure statement: The authors have declared noconflicts of interest. Informed consent was obtained forthe publication of this article.Data availability statementAll relevant data are included in the article.Gavin B. Chapman1,2, Andrew E. Leitch3,Rashmi Lahiri4, Peter Reid3 andNeeraj Dhaun 1,21British Heart Foundation Centre of Research Excellence,Centre for Cardiovascular Science, Queen’s MedicalResearch Institute, University of Edinburgh, 2Department ofRenal Medicine, Royal Infirmary of Edinburgh, 3Department ofRespiratory Medicine, Western General Hospital and4Department of Pathology, Royal Infirmary of Edinburgh,Edinburgh, UKAccepted 12 October 2021Correspondence to: Neeraj Dhaun, Queen’s MedicalResearch Institute, 47 Little France Crescent, EdinburghEH16 4TJ, UK. E-mail: bean.dhaun@ed.ac.ukReferences1 Hozumi H, Oyama Y, Yasui H et al. Clinical significance ofmyeloperoxidase-anti-neutrophil cytoplasmic antibody inidiopathic interstitial pneumonias. PLoS One 2018;13:e0199659.2 Yates M, Watts RA, Bajema IM et al. EULAR/ERA-EDTA recommendations for the management ofANCA-associated vasculitis. Ann Rheum Dis 2016;75:1583–94.3 Dhalkari CD, Patil SC, Indurkar MS. Strawberry gingivitis –first sign of Wegener’s granulomatosis. J Oral MaxillofacPathol 2020;24:172–5.4 McAdoo SP, Medjeral-Thomas N, Gopaluni S et al. Long-term follow-up of a combined rituximab and cyclophos-phamide regimen in renal anti-neutrophil cytoplasmantibody-associated vasculitis. Nephrol Dial Transplant2019;34:63–73.5 Farrah TE, Prendecki M, Hunter RW et al. Glucocorticoid-free treatment of severe anti-neutrophil cytoplasmantibody-associated vasculitis. Nephrol Dial Transplant2021;36:739–42.6 Industrial Injuries Advisory Council. Occupationalexposure to silica or asbestos and antineutrophilcytoplasmic antibodies (ANCA)-associated vasculitis:position paper 46. London: Industrial Injuries AdvisoryCouncil, 2020.7 Giorgiutti S, Dieudonne Y, Hinschberger O et al.Prevalence of antineutrophil cytoplasmic antibody(ANCA)-associated vasculitis and spatial association withquarries in a French northeast region. Arthritis Rheumatol2021;doi: 10.1002/art.41767.Letter to the Editorhttps://academic.oup.com/rheumatology 3Downloaded from https://academic.oup.com/rheumatology/advance-article/doi/10.1093/rheumatology/keab783/6404617 by University of Edinburgh user on 04 November 2021

Strawberry carina as a presentation of ANCA-associated vasculitis

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Strawberry carina as a presentation of ANCA-associated vasculitis

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