UKIVAS Meeting Edinburgh 7/6/18 Two cases of lung-limited GPA

1. UKIVAS Meeting Edinburgh 7/6/18Two cases of lung-limited GPA Philip W Ind, Luis Ribiero NHLI at Hammersmith Imperial College Healthcare Trust London

2. Case 1 presented in 2006 55 y old male, Caucasian, solicitor –LUL pneumonia cough with green sputum + minor haemoptysis, fever + rigors PMH COPD (35 pack-y smoking history) Rx salbutamol previous Right empyema rhinitis Treated with antibiotics but relapsed with haemoptysis + non-resolving CXR despite further antibiotics

3. Investigations CXR no resolution of LUL consolidation CT emphysema, LU Lobe solid opacity PET pos opacity (SUV 12 suggestive of malignancy) FEV1 2.1 (55%) VC 3.5 (72%) TLCO 59% pred kCO 69% needle Bxnon-diagnostic

4. 55 y old man presented with cough, sputum + SOBprev heavy smoker mild airflow obstruction FDG-PET scan CT scan

5. Left upper lobectomy histology no evidence of malignancy ‘small cavity, surrounding inflammatory granulation tissue, intra-alveolar fibrosis, organising pneumonia, lymphocytes, plasma cells, a few eosinophils, scattered giant cells. Obliteration of peri-bronchial vessels with damage to elastic lamina. Reactive changes only in lymph nodes (no granulomas).’ cultures negative for bacteria, fungi and TB

6. Referred to Hammersmith clinically well, only complaint -mild SOBOE Investigations normal FBC, ESR, U+E, liver + bone profile CRP, immunoglobulins negative ANCA, MPO, PR3 spirometry improved Management did not wish immunosuppression -careful monitoring inhaler therapy

7. 3-6 month follow up has remained well 12 years on OSA, presbycusis + tinnitus, loin pain + passed renal stone neg urine, US, CTKUB + MRI persistently negANCA normal bloods stable PFTs FEV1 1.75 (52%) VC 4.0.(100%) Progress 3/11/15 13/2/18

8. Case 2 presented in 2011 27 y old female, Caucasian, civil servant, never smoker CXR showed incidental opacity 6/12 right lat chest pain Rx physio PMH Turners syndrome hypothyroidism (neg antibodies)

9. Investigations CXR RUL consolidation CT RU Lobe solid opacity T7 vertebral fracture PET positive suggestive of malignancy FEV1 2.9 (128%) VC 3.35 (132%) bronchoscopy non-diagnostic

10. VATs Right Upper lobe wedge resection 29/2/12 frozen section no evidence of malignancy histology ‘necrotising granulomas, surrounding organising pneumonia and neutrophilicmicroabscesses. Luminal expansion and intimal obliteration of peri-bronchial vessels.‘ cultures negative for bacteria, fungi and TB

11. Referred to Hammersmith clinically well, no vasculitic symptoms short 141 cm, overweight 55.2 kg, euthyroid Investigations normal FBC, ESR, U+E, bone + liver profile (ALT 52) CRP, immunoglobulins, thyroid function negative RF, ANA, ANCA, MPO, PR3 abdo US mild hepatic steatosis only Management careful monitoring

12. chest X ray unchanged 27/11/12 post-op 11/7/17

13. Progress has remained gen well after 6 y follow up unchanged CXR, supra-normal lung function normal bloods inc CRP, ESR, neg ANCA re-referred with minor epistaxis 2-3x/month ENT follow up 12/12 ‘dilated vessels in Little’s area L>R’ RxNaseptin (cautery if worse)

15. GPA subclassification 2005 Limitedupper +/ lower resp tract Liebow 1966 Localisedlung NOT renal diseaseEUVAS 2001 Early any organ NOT renal systemicNO vital organ failure imminent Generalisedrenal +/ imminent organ failure LimitedNOT vital organ/ life-threatening WGET 2003 NO need for aggressive therapy ?granulomatous variants

16. Limited vs severe GPA n=180 WGET 2003 limited (n=52) severe (n=128) p age at onset 41 + 16 50 + 16 0.005 sex % female5833 0.002 % new diagnosis 33 49 0.043 months since onset 25 14 0.057 m since diagnosis 13 2.7 0.097 BVAS 4.5 7.9 <0.001 VDI score 1.5 1.3 0.214 ANCA+ (IF)% 78 91 0.028 cANCA (%+) 90 87 anti-PR3+ (EIA%) 59 78 0.028 Lung dis (nodules) 52 (39) 63 (28) 0.159 ENT disease 89 72 0.017 Renal 29 64 <0.001 Nervous system 0 14 0.017 Thyroid disease 0 19 0.013

17. GPA subclassification2009 Localised Early systemic Generalised Severe Refractory Limited = ‘non-renal, ‘indolent’ ‘early systemic’ ‘locoregional’ cf ‘generalised, classic generalised’

18. Localised GPA is rare initial description n=16 (inc 7 extrapulmonary lesions)Carrington et al, 1966 16 patients (3.2%) in French Vasculitis database Pagnoux C et al, 2011 iLiterature search 93 cases 68 no systemic involvement (limited FU) mainly solitary lesions great majority managed with Immunosup Rx

19. Prospective long-term follow up of localised WG 50/99 locWG from 1024 suspected WG Schleswig-Holstein 1989-2009 pos biopsy resp tract/orbit + FU >1y all had sino/nasal disease pulm masses in 13% at diagnosis, 20% by 4y mean age 43y, 72% women, 46% ANCA+ (PR3+ 20/23) symptoms present for median 12/12 pre2000 and 6.7/12 post 2000 median FU 48/12 all responded, 34% CR, 1-4 relapses in 46% (range 1-14.5 y) 5 (10%) systemic disease at median 6y 66% developed organ damage (nose/orbit) treatment T/S, MTX, cyclo in 47% (for lung nodules in 36%)Holle et al, 2010

20. Summary 2 cases presented to the same hospital with abnormal CXR, CT and FDG-PET scans histology at lobectomy was very suggestive of GPA with other diagnoses excluded neither received immunosuppressive treatment both have remained well at prolonged + careful follow up no evidence of active disease,neg inflammatory + vasculitic markers What is significance of limited/localised disease?

21. Acknowledgements Hammersmith joint vasculitis clinic renal Charles Pusey, Tom Cairns rheumatology Justin Mason ENT Guri Sandhu, RomanaKuchai ophthalmic SusanLightman histopathology Francesco Mauri, Roberto Dina