Table 3.

Key clinical information of patients

Connective tissue disease diagnosis	Presenting symptoms / Autoimmune serology	Evidence for diagnosis*	Pleural fluid glucose (mmol/L)	Pleural fluid LDH (IU/L)	Pleural fluid protein (g/L)	Pleural micro	Pleural fluid appearance	Pleural fluid cytology	Histology	CT chest findings	Outcome
Rheumatoid arthritis	Pleuritic chest pain, dyspnoea, polyarthralgia, fatigue anti-CCP + ve	Clinical assessment, autoimmune serology	3.4	794	55	Fluid MCS/AFB neg Biopsy AFB neg	Turbid yellow fluid	2/3/16 Neutrophils, lymphocytes, macrophages, prominent eosinophils. Few reactive mesothelial cells. 23/3/16 Mixed lymphoid cell population; plasma cells and eosinophils. Occasional mesothelial cells.	Pleural biopsy: moderate acute and mild chronic inflammation, surface mesothelial denudation, macrophages and fibrin.	Bilateral hilar lymphadenopathy. Left-sided pleural effusion and bibasal groundglass change with intralobular septal thickening demonstrated.	Resolution of pleural effusions on CXR by week 7 on weaning prednisolone (after pulsed methylprednisolone)
Rheumatoid arthritis	Fever, cough, fatigue, pleuritic chest pain, dyspnoea anti-CCP and RhF + ve	Previous CTD diagnosis, clinical assessment, autoimmune serology	None	None	None	n/a	n/a	None	None	Pericardial hyperattenuation, either in keeping with thickening and low-grade enhancement or a complex pericardial effusion. Shallow left pleural effusion.	Resolution of pleural effusions 5 months after pleural review (one prior week of prednisolone)
Rheumatoid arthritis	Cough, fever anti-CCP and RhF + ve	Previous CTD diagnosis, clinical assessment, pleural fluid glucose, pleural biopsy	0	5947	55	Fluid MCS/AFB neg Biopsy AFB neg	Turbid yellow fluid	Lymphocytes and macrophages and scattered histiocytic multi-nucleate giant cells	Pleural biopsy: fibrous tissue with a dense lymphoplasmacytic infiltrate. Suggestion of histiocyte palisading; possibility of rheumatoid nodule, but insufficient for definitive diagnosis.	Moderate right pleural effusion. A calcified granuloma is noted in the right lower lobe. Minor right subpleural nodularity is seen. Emphysema.	Pleural effusion stable 1 year after discharge from pleural clinic (during which 5 mg prednisolone daily started for joint pains)
IgG4-related disease	Dyspnoea, cough, oedema IgG4 2.71 (0.23–1.11 g/L) IgG1 11.3 (4.8–9.5 g/L)	Pericardiectomy histology, autoimmune serology	None	None	None	Fluid MCS/AFB neg Biopsy AFB/MCS neg	Bloodstained fluid	A few benign mesothelial cells (Pleural biopsy: mildly inflamed pleural tissue. Single non-necrotising granuloma.)	Pericardial biopsy: dense keloid-like fibrosis. Foci of chronic inflammation and in these IgG4 plasma cells comprise a high population of IgG+ plasma cells.	Right pleural effusion and ascites. Cervical and mediastinal lymphadenopathy. Pericardial calcification and thickening suggest previous pericardial effusion/pericarditis.	Pleural effusion improved over 2 months (prednisolone started then weaned off onto methotrexate)
IgG4-related disease	Dyspnoea, dizziness IgG4 1.53 (0.23–1.11 g/L) IgG1 12.4 (4.8–9.5 g/L)	Pericardiectomy histology, clinical assessment, autoimmune serology	None	27	6	Fluid Scanty growth Staphylococcus aureus, AFB neg	Slightly cloudy yellow fluid	Mesothelial cells and mixed inflammatory cells (predominantly neutrophil polymorphs).	Pericardial biopsy: Diffuse moderate to severe fibrosis associated with focal calcification and mild chronic inflammatory cell infiltrate. IgA shows non-specific patchy mild staining.	Small bilateral pleural effusions. No pericardial effusion although some pericardial calcification is noted. Likely reactive mediastinal nodes.	Left pleural effusion resolved and small right pleural effusion 1 year after pleural review (started on furosemide)
Adult Still’s disease	Fever, cough, dyspnoea, chest pain, myalgia, sore throat, rash	Clinical assessment, raised ferritin	10.3	894	33	Fluid MCS/AFB neg	Straw coloured fluid	Acute inflmmatory cells. A few reactive mesothelial cells, histiocytes and lymphocytes.	None	Small bilateral pleural effusions with bibasal collapse/consolidation. Moderate pericardial effusion.	Pleural effusions resolved after 1 month (weaning prednisolone and colchicine)
Adult Still’s disease	Pleuritic chest pain, dyspnoea, fever, sore throat, arthralgia	Clinical assessment	None	None	34	Fluid MCS/AFB neg	Cloudy yellow fluid	Numerous neutrophils (95%) with occasional macrophages and mesothelial cells.	None	Small bilateral pleural effusions and a trace of pericardial fluid.	Pleural effusions resolved after 2 months (weaning prednisolone and colchicine)
Vasculitis	Dyspnoea, weight loss, appetite loss P-ANCA, Anti-MPO 222 (0-10 U/ml)	Clinical assessment, autoimmune serology, CT showing adrenal infarcts	6.9	279	48	Fluid MCS/AFB neg	Bloodstained fluid	Mixed lymphoid cell population along with neutrophil polymorphs, histiocytes and very occasional mesothelial cell.	none	Bilateral calcified pleural plaques. Right pleural thickening and effusion. Emphysema. Multiple solid subpleural and peri-fissural bilateral nodules	Pleural effusion resolved after 5 months (4 month course of weaning prednisolone)
SLE	Pleuritic chest pain, dyspnoea Anti ds-DNA 415 (0-10 IU/ml), anti-Smith +ve	Previous CTD diagnosis, clinical assessment	5.2	304	59	Fluid MCS/AFB neg	Cloudy light brown fluid	Mesothelial cells, macrophages, neutrophils and lymphocytes.	none	None	Pleural effusion resolved after 7 months (prednisolone weaned to maintenance)
Drug-induced lupus (cabamazepine)	Dyspnoea, rash, ulceration of hands and feet ANA +ve, ENA RNP + ve, ENA SSA (Ro) + ve, ENA Sm + ve ANCA neg	Clinical assessment, autoimmune serology	6.5	228	47	Fluid MCS/AFB neg Biopsy AFB/MCS neg	Turbid orange fluid	16/11/12 Reactive mesothelial cells, polymorphs, lymphocytes and histiocytes. 5/12/12 Numerous mesothelial cells, macrophages and a mixed population of lymphocytes. 11/12/12 Histiocytes, a few lymphocytes and reactive mesothelial cells. 18/12/12 Reactive mesothelial cells, lymphocytes and histiocytes. 27/12/12 Histiocytes, lymphocytes, reactive mesothelial cells, neutrophils, plasma cells. 13/1/13 Blood only.	16/11/12 pleural biopsy: Single focus of large cells at the edge of one fragment, most likely reactive mesothelial cells. Nuclei are pleomorphic, irregular nuclear membranes and nuclear chromatin clearing. 13/1/13 pleural biopsy: Pleura markedly oedematous; granulation tissue at the surface, scattered foci of chronic inflammatory cells.	Left pleural effusion with minimal nodularity and mild volume loss in the left hemithorax. Shallow pericardial effusion. Widespread mild lymphadenopathy.	Pleural effusion resolved after 9 months (prednisolone weaned to maintenance)
Behcet’s	Chest tightness	Clinical assessment	4.8	380	44	Fluid MCS/AFB neg	Turbid bloodstained fluid	Numerous lymphocytes, histiocytes and blood.	none	Large right main pulmonary artery thrombus. Multiple left sided pulmonary emboli. Bilateral pleural effusions with consolidaton/atelectasis. 2 small round pulmonary foci and a band of consolidation in the right upper lobe. Wedge-shaped consolidation in the middle and right lower lobes.	Pleural effusions resolved after 1 year (cyclophosphamide and weaning prednisolone)

*These were the key factors used by the mutldisciplinary team in securing a diagnosis