1. Rheumatoid associated interstitial lung disease (RA-ILD). RA-ILD is the most common mani festation of rheumatoid lung disease. Radiologically, clinically and histologically, RA-ILD is similar to the idiopathic interstitial pneumonias, with usual interstitial pneumoni- ti s (UIP), non-specific interstitial pneumonitis (NSIP) and cryp- togenic organizing pneumoni a (COP) the most common seen in rheumatoid. In this case, the bilateral volume loss and zon al distribu- tion is in favor of UIP, whereas the relatively short history and aggressive p rogress is against this. UIP does not explain the right basal consolidation, whereas COP co uld cause this. However, COP is typi- cally associated with bilateral infiltrates (as oppos ed to reticulation as seen here) and preserved lung volumes on CXR. 2. Drug induced lung disease. Pulmonary effects can result from a host of medication for the treatment of RA. Agents to consider are: Methotrexate. Although infective complications are reported in patients treated with methot rexate (including PCP and fungal pneumonias), the most common pulmonary manifestation is ac ute pneumonitis (0.3 and 11.6% of patients). It is more common in those with underlying lun g disease (including RA-ILD). It usually occurs within 2 years of starting therapy, but may occur after ces- sation of treatment. Diabetes, increased age and low albumin are all risk factors for acute pneumonitis. The clinical presentation is CASE 41 353 typically acute or subacute (weeks), and radiologically bilateral interstitial infiltrates or a combination of interstitial infiltrates and consolidation (as seen here) may occur. Corticosteroids. RA patients taking steroids are at greater risk of pneumonia requiring hos pitalization. Taking prednisolone at \211 10mg per day for a month is a small but signific ant risk factor for PCP. Anti-TNFa therapy. All anti-TNFa and other biologic therapies for RA (e.g. B cell depletors , anti-IL1 therapy) have been associated with increased risk of pulmonary infections. The c ommonest is an asso- ciation with bacterial pneumonia. There is also a well-known risk of t he development of active pulmonary tuberculosis after initiation of anti-TNFa therapies, an d screening is recommended prior to begin- ning such therapy (see British Thoracic Society website in Further reading). More recently, the use of anti-TNFa therapy has been associate d with exacerbations and an increased risk of mortality (see Ostor et al), although further evidence is needed. In this case, the clinical history and radiographic appearances make TB or other pulmonary infection alone unlikely. The time course of disease is very fast for RA-ILD alone. However , we are not given information on the patient \200\231s prior respiratory status (and she i s quite likely to have been limited by joint disease therefore a history of exercise tolera nce may be uninformative of her respiratory reserve) or exactly which drugs are being taken (i.e. is she still on methotrexate?). The two most likely pos- sibilities are methotrexate induced pnuemonitis or undiagnosed and asymptomatic RA-ILD (most likely UIP) with intercur rent infection. 41d) Describe two key initial investigations and their rationale. Important investigations include: \227\206 Pulmonary function tests \200\224these may aid in the diagnosis of RA-ILD (restri ctive PFTs, small lung volumes, decreased TLCO) or suggest COP (preserved volumes on CXR, d ecreased KCO). However, this patient may be too compromised to perform anything except simp le spirometry \227\206 HRCT chest \200\224this would enable assessment of the zonal predominance of the infiltrates (basal and subpleural implying UIP), the relative pres- ence of ground glass an d reticulation (NSIP or methotrexate pneumo- nitis versus UIP), consolidation (COP, intercu rrent infection, PCP) and lobar involvement (pneumonia) CASE HISTORIES IN RESPIRATORY MEDICINE 354 \227\206 Bronchoscopy, +/ \200\223 lavage, +/ \200\223 transbronchial biopsy. Exclusion of infection (lavage) before consideration of the other diagnoses is key, especially if the H RCT is not definitively RA-ILD and, as in this case, the history is short. Transbronchial b iopsy may be useful in the diagnosis of COP, and provides a modest increase in diagnostic y ield for PCP (around 10%) \200\224however, it is unlikely that this patient would tolerate a pneumothorax. \227\206 Consideration should be given to open lung biopsy if there is real diagnostic uncertainty after the above tests. Progress The patient was commenced on broad-spectrum antibiotic therapy, oxygen and thrombo-embolism prophylaxis and HRCT was performed ( Fig. 41.2 ). Fig. 41.2 HRCT chest. CASE 41 355 Questions 41e) Describe the HRCT findings. 41f) What is the most likely diagnosis and what treatment would you consider? CASE HISTORIES IN RESPIRATORY MEDICINE 356 Answers 41e) Describe the HRCT findings. There is widespread ground glass opacification, with a peripheral, subp- leural predominanc e ( Fig. 41.3 ). On the basal cuts, there is coarse reticu- lation with areas of traction b ronchiectasis (see Fig. 41.3 ). Fig. 41.3 Expanded HRCT chest. 41f) What is the most likely diagnosis and what treatment would you consider? The HRCT is suggestive of RA-ILD with coarse reticulation and traction dilatation of airway s (or \200\230bronchiectasis \200\231; implying a chronic fibrotic process, e.g. UIP). The ground glass opacity may represent an additional pathology (e.g. drug-induced lung disease , infection, inflammation such as NSIP) or established fibrosis, which is beyond the resolu tion of the CT scanner. Given the acute deterioration in the patient, the putative diag- no sis of RA-ILD (UIP) in association with methotrexate induced pneu- monitis was made. Treatment of methotrexate induced pneumonitis: \227\206 Immediate cessation of methotrexate \227\206 Patients will usually respond to this alone, but high-dose oral steroids are reco mmended to speed recovery if patients are acutely unwell (as here) CASE 41 357 \227\206 In general, methotrexate should be avoided in the future (although if no other th erapeutic options exist, slow re-introduction and careful monitoring of pulmonary function and CXR may be considered). Treatment of RA-ILD (UIP): \227\206 There are no large studies addressing the management of patients with RA-ILD and treatment is based on the associated idiopathic interstitial pneumonia (i.e. UIP). \227\206 NSIP and COP are, therefore, treated with oral steroids, as per the treatment of non-RA entities. \227\206 The treatment of RA-UIP is more controversial. There are many case reports of suc cessful treatment with a variety of anti-RA drugs, but all of these are associated with pos sible significant pulmonary toxicity. \227\206 One study has suggested that anti-TNF the rapy may slow progression of RA-ILD, but another has reported severe respiratory failure wi th this treatment. Further reading Gauhar UA , Gaffo AL , Alarc n GS ( 2007 ). Pulmonary manifestations of rheumatoid arthritis . Semin Respir Crit Care Med ; 28 ( 4 ): 430 \200\223 440. Kim DS ( 2006 ). Interstitial lung disease in rheumatoid arthritis: recent advances . Curr Opin Pulm Med ; 12 ( 5 ): 346 \200\223 353. Nannini C , Ryu JH , Matteson EL ( 2008 ). Lung disease in rheumatoid arthritis . Curr Opin Rheumatol ; 20 ( 3 ): 340 \200\223 346 . Ostor AJ, Crisp Aj, Somerville MF, Scott DG (2004). Fatal exacerbation of rheumatoid athrit is assoicated fibrosing alveolitis in patients given infliximab. BMJ ; 329 :1266. British T horacic Society Standards of Care Committee (2005). BTS recommendations for assessing risk and for managing Mycobacterium tuberculosis infection and disease in patients due to anti-T NF- treatment. Thorax ; 60 : 800 \200\2235. Case 42 A 47-year-old man presented with progressive increasing breathlessness over 2 years, with a n exercise tolerance of 100 meters, in association with a cough occasionally productive of mucopurulent sputum. His GP had tried increasing doses of budesonide and formoterol, sever al courses of antibiotics and short steroid courses with no benefit. He had stopped smoking 20 years previously. On examination he had a BMI of 46.4, no finger clubbing or cyanosis. Resting oxygen saturation on air was 94%. Respiratory examination revealed fine left basal crackles, and otherwise examination was normal. Investigations \227\206 Hb 15.5g/dL, WCC 8.01 \227 10 9 /L (eosinophils 0.4 \227 10 9 /L), platelets 267 \227 10 9 /L, ESR 8mm/h \227\206 U&E, LFTs normal, ACE 57U/L (18 \200\22355), rheumatoid factor and ANA negative \227\206 Pulmonary function (Table 42.1) . Table 42.1 Pulmonary function tests Measured (% Predicted) FEV1(L) 1.3 40 FVC(L) 1.5 38 Patient unable to manage static lung volumes or gas transfer measurement CASE 42 359 Fig. 42.1 CXR. Questions 42a) Interpret the CXR ( Fig. 42.1 ). 42b) What is the next investigation? CASE HISTORIES IN RESPIRATORY MEDICINE 360 Answers 42a) Interpret the CXR ( Fig. 42.1 ). The CXR shows reduced lung volumes. There are reticular opacities in both lower zones, more marked on the left. There is loss of definition of the left and right heart borders and th e left hemi-diaphragm. The heart size is borderline but the lack of septal lines or pleural effusions makes heart failure unlikely. Overall the appearances are suggestive of an inter - stitial process but no firm diagnosis can be made at this point. 42b) What is the next investigation? The next investigation of choice is a high-resolution CT thorax ( Fig. 42.2 ). Questions 42c) Interpret the HRCT images ( Fig. 42.2 ). 42d) What is the differential diagnosis? CASE 42 361 Fig. 42.2 HRCT thorax. CASE HISTORIES IN RESPIRATORY MEDICINE 362 Answers 42c) Interpret the HRCT images ( Fig. 42.2 ). The predominant feature on the CT (Fig. 42.3) is bilateral multifocal ground glass opacity throughout the lungs. In addition, there is superim- posed interlobar septal thickening, an d areas of reticulation. There is no convincing traction bronchial dilatation (or traction bronchiectasis). There is pericardial fat, which explains the borderline cardiothoracic rat io on the CXR. Reticulation Interlobar septal thickening Ground glass opacification Pericardial fat Fig. 42.3 Enlarged portions of HRCT. The appearances are in keeping with interstitial lung disease, with reticu- lation and volu me loss on the left suggesting an element of fibrosis. The lack of honeycombing and tractio n bronchial dilatation would go against a usual interstitial pneumonia (UIP) pattern. Media stinal settings (not shown) demonstrated a 1.5cm lymph node just lateral to the pulmonary t runk in the mediastinum and further lymphadenopathy in both hila. 42d) What is the differential diagnosis? The differential diagnosis would include an atypical appearance of UIP (with idiopathic pul monary fibrosis (IPF) as the clinical diagnosis), non- specific interstitial pneumonia (NSI P), drug reactions, sub-acute on chronic hypersensitivity pneumonitis and (far less likely) sarcoidosis. CASE 42 363 Questions 42e) Which of the following would be the optimum management strategy? A. Treatment with high dose steroids (40mg prednisolone/day) for 4 \200\2236 weeks followed by tapering, according to response to lower maintenance dose B. Transbronchial biopsy (TBB) + lavage followed by high dose ster- oids as above if infection excluded C. TBLB followed by surgical lung biopsy if non-diagnostic D. Surgical lung biopsy CASE HISTORIES IN RESPIRATORY MEDICINE 364 Answer 42e) Which of the following would be the optimum management strategy? A. Treatment with high dose steroids (40mg prednisolone/day) for 4 \200\2236 weeks followed by tapering, according to response to lower maintenance dose B. Transbronchial biopsy (TBB) + lavage followed by high dose ster- oids as above if infection excluded C. TBLB followed by surgical lung biopsy if non-diagnostic D. Surgical lung biops y There is no right answer to this question. Purists would say C or D, and pragmatists A. How ever, most would argue that the management strat- egy at this point should be to establish an accurate diagnosis. The clinical diagnosis of IPF can only confidently be made in the co ntext of charac- teristic clinical, physiological and radiological features (Wells et al . 2008). The absence of marked honeycombing in particular goes against UIP as the likely unde rlying pathology, as does the absence of other radiological features to suggest established fibrosis, such as traction bronchial dilata- tion. In cases of doubt, such as this, biopsy confirmation is required. Initiating steroid treatment at this point would not be appropri ate as this could make subsequent biopsy difficult to interpret. Choice of biopsy route is best guided by the most likely diagnosis. Transbronchial lung bio psy (TBLB) has a high sensitivity for diagnosis of sarcoidosis and cryptogenic organizing p neumonia, but a surgical lung biopsy is best to identify the other idiopathic interstitial pneumonias. In this case TBLB was performed initially given the radiological suspi- cion (albeit perhap s not high) of sarcoidosis. Culture of BAL fluid was negative and cytology showed no predom inant cellular population. Histology showed two fragments of alveolar tissue within which t here was some interstitial fibrosis, type 2 pneumocyte hyperplasia and macro- phages within the air spaces. Patchy mild interstitial infiltration was present, but no well-formed gran ulomas were seen. Overall the appear- ances were not specific, and therefore a surgical lun g biopsy was performed. This showed much of the lung parenchyma to be essentially normal, a part from two foci of interstitial fibrosis with some smooth muscle hyperplasia and focal c hronic inflammation. No granulomas nor birefringent material were seen, and only occasional eosinophils were present. The apparent temporal homogeneity in the fibrosis was felt to be consistent with NSIP. CASE 42 365 Question 42f) What is the most appropriate management strategy? A. High dose steroids for 4 \200\2236 weeks (40mg prednisolone/day) followed by tapering ac cording to response to lower maintenance dose B. High-dose steroids and tapering as above plus azathioprine C. IV cyclophosphamide followed by maintenance prednisolone D. IV cyclophosphamide followed by maintenance oral cyclophos- phamide and low dose steroids E. High dose steroids (0.5mg/kg/day) tapering to low-dose mainte- nance (0.125mg/kg/day) pl us azathioprine and N-acetylcysteine (NAC). CASE HISTORIES IN RESPIRATORY MEDICINE 366 Answer 42f) What is the most appropriate management strategy? A. High dose steroids for 4 \200\2236 weeks (40mg prednisolone/day) followed by tapering according to response to lower maintenance dose B. High-dose steroids and tapering as above plus azathioprine C. IV cyclophosphamide followed by maintenance prednisolone D. IV cyclophosphamide followed by maintenance oral cyclophos- phamide and low dose steroids E. High dose steroids (0.5mg/kg/day) tapering to low-dose mainte- nance (0.125mg/kg/day) pl us azathioprine and N-acetylcysteine (NAC). There are no randomized controlled trials of treatment in patients with NSIP. In the absenc e of any evidence to make firm recommendations, recently published BTS guidelines suggest a pragmatic approach basing treatment on the clinicoradiological profile of disease (i.e. mo st closely resembling IPF, organizing pneumonia or, more rarely, hypersensitivity pneumonit is). In our patient, whose distribution of disease on CT is similar to that seen in IPF, th e new guidelines would recommend option E for treatment, although many physicians would ado pt strategy B. This is based on the IFEGENIA study (Demedts et al . 2005), which demon- str ated attenuation in the fall of lung function in IPF patients treated with steroids/azathio prine/NAC, versus steroids and azathioprine alone. A trial of high-dose steroid as monother apy is not recommended in the new BTS guidelines, nor is steroid and azathioprine without N AC. Small observational studies have examined other agents, such as cyclophospha- mide and colchicine, but their use is not recommended. As with IPF, in appropriate cases with unresp onsive, progressive disease, lung transplan- tation should be considered. CASE 42 367 Question 42g) What are the principle ways NSIP differs from IPF in terms of pathology, radiological appearance and prognosis? CASE HISTORIES IN RESPIRATORY MEDICINE 368 Answer 42g) What are the principle ways NSIP differs from IPF in terms of pathology, radiological appearance and prognosis? \227\206 Pathology. NSIP is characterized by spatially and temporally homoge- neous lung f ibrosis or inflammation with further subgrouping accord- ing to predominance of cellularity or fibrosis. IPF on the other hand, with UIP as the underlying pathology, displays spatial and temporal hetero geneity (different areas of fibrotic lung at different stages of evolu tion from normal to severe fibrosis). Dense fibrosis and honey- combing are present in UIP and a further pathological hallmark is the finding of fibroblastic foci in UIP. Formal diag nosis of NSIP and IPF must not, however, be based solely on the pathology, but on an inte- grated clinic-radiological-pathological approach (Travis et al . 2008). \227\206 Radiology. Given this homogeneity with NSIP, the predominant fea- ture on HRCT is ground glass attenuation with a basal predominance and subpleural and/or peribronchovascul ar distribution. Signs of fibrosis (volume loss, reticulation, traction bronchiectasis) can be present but should not predominate. Although honeycombing was previously said to be rar e (Lynch et al . 2005), a radiological review of 50 cases of biopsy proven NSIP found this in 15 (30%), and bilateral in 13 cases (Hartman et al . 2000). Traction bronchiectasis was found in 18/50 (36%) and in association with honeycombing in 9. More recently, in an ATS re port (Travis et al . 2008), with perhaps a stricter multidisciplinary concensus on diagnosi s, traction bronchiectasis was relatively common (50/61 patients with evaluable radiology, 82%) but honeycombing unusual (3/61, 5%). Even in experienced radiological hands, there can be differences of opinion. In a study examining inter- rater reliability of 11 thoracic ra diologists in the diagnosis of 131 patients with diffuse parenchymal lung disease (Aziz et al . 2004), NSIP was a frequent source of variation and involved in 138 (55%) of discrepanc ies. Overall the co-efficient of agreement was higher in this study (kappa 0.50) for IPF th an NSIP (kappa 0.38). This emphasizes the general importance of seeking biopsy supporting e vidence in radi- ologically suspected NSIP. \227\206 Prognosis. When patients with NSIP are separated from those with UIP, in series o f patients presenting with \200\230cryptogenic fibrosing alveo- litis \200\231, several st udies have found patients with NSIP to have an improved prognosis in comparison to those wi th IPF/UIP, and there seems to be further improved survival in those with cellular NSIP CASE 42 369 compared to fibrotic NSIP. For example, in a UK series of 78 patients who had a prior clini cal diagnosis of CFA and had lung biopsies (Nicholson et al . 2000), median survival was be tter in fibrotic NSIP (n = 25, 52 months) than UIP ( n = 37, 27 months). Three had cellular NSIP and all were alive at follow up. In the recent ATS project report (Travis et al . 200 8) overall 5-year survival (67 patients) was 82.3%, and 10-year survival 73.2%. Despite thi s, however, it may be that patients with fibrotic NSIP, and more significant functional imp air- ment at presentation, do not necessarily do much better than those with IPF/UIP. A rec ent study found that although overall fibrotic NSIP had improved survival in comparison to IPF/UIP after 3 years follow-up and longer, there was no difference in \200\230early morta lity \200\231 at 2 years and this seemed to be linked to significant functional impair- men t at presentation (Latsi et al . 2003). There was no difference in survival between NSIP an d UIP in those with a DLCO of <35 % at presentation suggesting, in this sub-group, biopsy c onfirmation is less clinically relevant (and usually impossible anyway). Further reading Aziz ZA , Wells AU , Hansell DM, Bain GA, Copley SJ, Desai SR et al . ( 2004 ). HRCT diagno - sis of diffuse parenchymal lung disease: inter-observer variation . Thorax ; 59 : 506 \200\223 511. Demedts M , Behr J , Buhl R, Costabel U, Dekhuijzen R, Jansen HM et al . ( 20 05 ). High-dose acetylcysteine in idiopathic pulmonary fibrosis . NEJM ; 353 : 2229 \200\223 2242. Hartman TE , Swensen SJ , Hansell DM, Colby TV, Myers JL, Tazelaar HD et al . ( 2000 ). Non specific interstitial pneumonia: variable appearance at high-resolution chest . Radiology ; 217 : 701 \200\223 705. Latsi PI , du Bois RM , Nicholson AG, Colby TV, Bisirtzoglou D, Nikolakopoulou A et al . ( 2003 ). Fibrotic idiopathic interstitial pneumonia: the prognostic value of longitudinal functional trends . Am J Resp Crit Care Med ; 168 : 531 \200\223 537. Lynch DA , Travis WD , M ller NL, Galvin JR, Hansell DM, Grenier PA et al . ( 2005 ). Idiopathic interstitial pneumonias: CT features . Radiology ; 236 : 10 \200\223 21. Nicholson AG , Colby TV , du Bois RM , Hansell DM , Wells AU et al . ( 2000 ). The prognost ic significance of the histologic pattern of interstitial pneumonia inpatients presenting w ith the clinical entity of cryptogenic fibrosing alveolitis . Am J Resp Crit Care Med ; 162 : 2213 \200\223 2217. Travis WD , Hunninghake G , King TE Jr, Lynch DA, Colby TV, Galvin JR et al . ( 2008 ). Idiopathic nonspecific interstitial pneumonia \200\224report of an American Thoracic Societ y project . Am J Resp Crit Care Med ; 177 : 1338 \200\223 1347. Wells AU , Hirani N ( 2008 ). Interstitial lung disease guideline . Thorax ; 63 ( Suppl 5 ) : V1 \200\22358. Case 43 An 89 \200\223year-old woman presented with increasing shortness of breath over a 4-week pe riod. This was associated with an irritable dry cough and lethargy, but no chest pain or co nstitutional symptoms. She had an extensive back- ground history including ischaemic heart disease, myocardial infarction 2 years previously, left ventricular failure, mild and well- controlled asthma, and treated hypertension. She also suffered with short-term memory loss, which had been worsening for the last 2 years, and had been diagnosed as vascular dementia . Her normal exercise tolerance had been limited for several years by a combi- nation of left ventricular failure and hip osteoarthritis, but this had signifi- cantly reduced from 100 meters to 30 meters in the last three weeks. She was on multiple cardiac medications, had never smoked, and had no known asbestos exposure. On examination, she was apyrexial, tachypnoeic (28/min), afebrile and had an SaO 2 at rest of 96%. Her venous pressure was visible at the jaw and there was pitting oedema to the calf bilaterally. The left chest was dull to percussion with absent breath sounds and decreased expansion, associated with rightward tracheal shift. Investigations Blood tests: \227\206 Hb: 14.3g/dL \227\206 WCC: 8.6 \227 10 9 /L (neutrophilia) \227\206 Platelets: 372 \227 10 9 /L \227\206 Urea and electrolytes normal \227\206 CRP = 2mg/L \227\206 Clotting screen normal. Pleural aspirate: \227\206 Blood stained, serous, no odor \227\206 Protein = 48g/dL \227\206 Glucose = 6.5mmol/L \227\206 LDH = 478IU/L (serum normal 150 \200\223220) \227\206 Cytology \200\224no malignant cells, 40% lymphocytes \227\206 Microbiology \200\224no bacteria, no mycobacteria on ZN stains \227\206 See also Fig. 43.1 . CASE 43 371 Fig. 43.1 CXR. Questions 43a) What are the three most likely causes of the effusion? 43b) How would you investigate this patient further? 43c) How would you manage this patient? CASE HISTORIES IN RESPIRATORY MEDICINE 372 Answers 43a) What are the three most likely causes of the effusion? Given this lady \200\231s history of ischaemic heart disease, left ventricular failure must be considered as a possible diagnosis. The fluid is a clearcut exudate on the basis of the protein and LDH levels (>50% serum normal), which makes heart failure less likely as a cau se, and the fluid is unilateral and bloodstained. However, up to 50% of heart failure effu- sions are unilateral (although only 33% are usually on the left side) and patients on diur etic therapy may have effusions which are classified as exudates on Light \200\231s criteri a (see case 61). However, given the size of the effusion (more than two-thirds of the hemithorax), and the a ge of the patient, malignant pleural effusion is the most likely diagnosis in this case. Up to 40% of malignant effusions will be cytology negative after a single pleural aspiration. Pleural infection is a possibility, but it would be unusual to develop such a large infecte d effusion in the absence of other symptoms and normal inflammatory markers. Pericardial di sease is a possibility, but likely to be associated with other signs and symptoms. TB effusions may sometimes be this large; however, the pleural fluid biochemistry is agains t this (one would expect a low normal or low glucose level), and lack of lymphocyte predomi nant fluid is also non-supportive. Effusion from pulmonary emboli should also be considered in an unexplained exudate (especia lly if blood stained), however again the large size is somewhat against this diagnosis. 43b) How would you investigate this patient further? The investigation of a unilateral cytology negative pleural exudate is covered elsewhere (c ase 13). Invasive tests are likely to be required to obtain pleural tissue. In this case, c onsidering the likely differential diagnosis: \227\206 Heart failure \200\224she is already on treatment for this and known to have a poorly functioning left ventricle \227\206 Malignancy \200\224in an elderly lady of poor performance status with short-term memory loss, establishing a diagnosis of malignancy is unlikely to alter management, and th e benefits of chemotherapy are slim in most metastatic pleural malignancies. There may be a n argu- ment for establishing the diagnosis of malignancy for prognostic information. CASE 43 373 \227\206 TB pleuritis is unlikely in this case given the pleural fluid characteristics \200\224 fluid was also sent for TB culture. \227\206 Pulmonary embolus \200\224a CTPA is a low risk procedure for this patient, and sh ould be considered. However, management of warfarin therapy in this lady with short-term me mory loss would require careful coordination. One should consider carefully the risk/benefit of invasive tests to solely achieve a diagno sis. 43c) How would you manage this patient? Given the above, a pragmatic approach to management is appropriate. Her heart failure treat ment should be reviewed. Regardless of etiology, she is currently symptomatic, and the effu sion is likely to increase in size. Therapeutic drainage is likely to be required in the ab sence of a clear diagnosis. In a few cases of resistant and recurrent unilateral heart fail ure- effusions, pleurodesis can be a useful therapeutic strategy. Progress The options were discussed with the patient and her family, and the joint deci- sion made n ot pursue a diagnosis. An elective therapeutic drainage procedure was planned, and given th e size of the effusion, and the wish to minimize repeated interventions, chest drain insert ion and drainage to dryness was pursued. A 12F catheter was inserted in to the intercostal space in the mid-axillary line using Seld inger technique, and connected to an underwater seal bottle. Insertion was uncomplicated an d pleural fluid drained freely. Two hours later the patient began to complain of tightness in the chest and breathlessness, and then lost consciousness. Oxygen saturations were 97% on 4L inspired oxygen, blood pres sure was 90/40mmHg and she was tachycardic (125bpm). Questions 43d) What are the likely causes of her deterioration? 43e) How would you investigate/manage her? CASE HISTORIES IN RESPIRATORY MEDICINE 374 Answers 43d) What are the likely causes of her deterioration? Possibilities to consider in the case of patient with such symptoms after chest drainage ar e: \227\206 Vasovagal episode \200\224insertion of chest drains, and the associated pain caus ed by irritation of the parietal pleura, may lead to vasovagal reactions which are characte rized by a transient drop in both blood pressure and heart rate, sometimes leading to brief loss of consciousness if the patient is upright. \227\206 Re-expansion pulmonary oedema should be considered. This entity is generally beli eved to occur after moderate volumes (>1000ml or so) of fluid are removed from a long-stand ing effusion. Re-expansion pulmonary oedema is a clinical diagnosis made on the basis of ty pical symptoms (chest tightness, pain, and cough) in association with a drainage procedure. The mechanism is unknown, but is speculated to be related to fluid shift and loss of compr ession of the large veins in the thorax, or related to reperfusion damage in the expanding lung associated with vascular leak. \227\206 Intrapleural bleed \200\224chest drainage is associated with a low (around 1 \200 \2233%) chance of intrapleural bleeding, usually due to laceration of an intercostal artery . Correct technique on insertion of the drain is the most important preventative measure (i .e. entry in the midaxillary line and just over the lower rib to avoid the neurovascular bu ndle which lies in the groove beneath each rib) in addition to ensuring there is no bleedin g diathesis. The intercostal artery is NOT shielded by the rib groove until the angle of th e rib \200\224therefore posterior entry sites (around 4 \200\2235cm from the spine) should be avoided. 43e) How would you investigate/manage her? Immediate management of this patient includes basic resuscitation (lie flat, obtain blood p ressure, ensure intravenous access), which will not be covered in detail here. Vasovagal re actions will, in general, recover quickly and spontaneously on lying flat. Oxygen saturatio n should be measured, and the chest drain contents should be examined for evidence of blood or blood staining. In cases of doubt about blood stained effusion or frank haemothorax, a pleural fluid haematocrit is useful (and can be obtained on most blood gas analysers quickl y). A pleural fluid haematocrit of >50% of the blood haematocrit is diagnostic of haemothor ax. Thoracic ultrasound, if readily available, is a useful test to quickly diagnose CASE 43 375 intrapleural hemorrhage at the bedside. An urgent CT scan with contrast may be required in cases of doubt if the patient is clinically sufficiently stable. Progress Oxygen saturations were maintained, and after lying flat for a short period, the patient re gained consciousness, although she still complained of chest pain and increasing shortness of breath. Bloodstained fluid was seen in the chest tube bottle. Pleural fluid haematocrit was 0.32 (blood = 0.38), confirming haemothorax. The 12F catheter was not draining further fluid and appeared clotted at the skin entry site. Her blood pressure remained low (80/30mm Hg) and she was tachycardic (130bpm) despite fluid rescucitation. An urgent thoracic ultrasound is shown in Fig. 43.2 . Fig. 43.2 Thoracic ultrasound. Question 43f) How would you now manage this patient? CASE HISTORIES IN RESPIRATORY MEDICINE 376 Answer 43f) How would you now manage this patient? The diagnosis is a significant intrapleural bleed, likely secondary to iatro- genic interco stal artery laceration. Although care was taken during drain insertion to avoid the neurova scular bundle, the course of the intercostal artery in the elderly is variable (they may be more tortuous and lie in the middle of the intercostal space), and vessels are often ectat ic. Specific Management An arterial intrapleural bleed is potentially life-threatening and unlikely to settle spont aneously \200\224intercostal arteries may bleed briskly and tam- ponade of the bleeding poi nt will not take place until massive blood loss has occurred. Plans for definitive interven tion should be put in to place immediately: \227\206 External pressure in the intercostal space of the approximate bleeding point may help to slow the bleeding. \227\206 An urgent CT scan with contrast may be required, as above, if the diagnosis is in doubt. \227\206 Definitive management is dependant on local facilities. Intercostal angiography a nd embolization of the bleeding point is possible where the facilities exist, otherwise tho racic surgery is required. In many cases, urgent thoracotomy is the only realistic treatmen t option. \227\206 The small-bore drain is likely to block in the face of frank blood (as here). Ins ertion of a large-bore drain (at a different site) may be required, if the collecting haemo thorax causes respiratory distress. \227\206 Whether to remove the drain that has caused the bleed is a contentious issue \200 \224its presence may provide a degree of tamponade; however, it should be noted, as above, that a small-bore drain is unlikely to provide adequate drainage in the case of frank haemo thorax. Progress Firm pressure was applied to the drain insertion site, and the patient was immediately tran sferred to the angiography suite. In transit, she experienced increasing respiratory distre ss and on arrival a large-bore chest drain (24F) was inserted. 1.6L of frank blood was drai ned immediately, with relief of symp- toms. Angiography was commenced, during which she und erwent a three-unit blood transfusion. CASE 43 377 At angiography, the smaller chest drain was removed and the site of skin insertion marked w ith a small bead. The aorta was catheterized via the right femoral artery and the bleeding vessel located (see Fig. 43.3 ). Fig. 43.3 Angiography and embolization of intercostal artery. Images courtesy of Dr P Board man. Angiography revealed a small pseudoaneurysm with active bleeding at the left intercostal ar tery over the drain insertion site (B). This was successfully embolized with 4 \227 3mm Mi cro coils (C). Further reading Echevarria C , Twomey D , Dunning J , Chanda B ( 2008 ). Does re-expansion pulmonary oedema exist? Interact Cardiovasc Thorac Surg; 7 : 485 \200\2239. Case 44 Six weeks previously a 75-year-old retired farmer had developed \200\230bronchitis \200 \231 with a cough, fever and wheeze. Two courses of antibiotics (amoxicillin and doxycyclin e) provided little symptomatic benefit. Two weeks prior to his appointment, in late-January , he noticed his fingers intermittently becoming \200\230purple and cold \200\231, but wit h no associated white or red skin finger discoloura- tion ( Fig. 44.1 ). This only occurred when helping his son on their pig farm early in the morning, and improved a little as the day progressed. He had never smoked and was on no regular medication. On examination, he had bibasal crackles on auscultation. Finger oximetry failed to register a peripheral arterial waveform or a valid oxygen saturation. Despite palpable symmetrical peripheral pulses, his distal phalanges were cyanosed ( Fig. 44.1 ). His toes appeared norm al. His CXR is shown in Fig. 44.2 . Fig. 44.1 CASE 44 379 Fig. 44.2 CXR. Questions 44a) What phenomenon is shown in Fig. 44.1 ? 44b) What does his CXR ( Fig. 44.2 ) show? CASE HISTORIES IN RESPIRATORY MEDICINE 380 Answers 44a) What phenomenon is shown in Fig. 44.1 ? Fig. 44.1 demonstrates distal digital cyanosis. Raynaud \200\231s phenomenon is unlikely du e to the absence of white and red skin discolouration, despite the fact that symptoms were precipitated by cold exposure. This kind of digital cyanosis is often called acrocyanosis ( \200\230acro \200\231-meaning extremity or tip). Acrocyanosis is related to reduced delivery of oxygenated blood to the extremities as a con sequence of local arteriolar spasm or occlusion. The pathophysiology of acrocyanosis is unc lear but is thought to relate to abnormally increased arteriolar tone, possibly as a conseq uence of elevated endothelin-1 levels, and increased whole blood viscosity. The persistent purple discolouration usually disappears on warming and there is little or no reactive hype raemia. Acrocyanosis should be differ- entiated from: \227\206 Peripheral cyanosis: associated with hypoxaemia, confirmed on arte- rial blood ga s analysis, and central cyanosis causing mucosal discol- ouration \227\206 Peripheral vascular disease: often determined from the patient \200\231s his- tor y, diminished distal pulses (e.g. pedal) and other signs of arterial insufficiency \227\206 Raynaud \200\231s phenomenon: characterized by a triphasic color change (white, b lue and red) with associated pain and/or paraesthesia due to resultant sensory nerve ischae mia \227\206 Erythromelalgia: a rare condition associated with erythema, warmth and burning pa in of the extremities precipitated by heat exposure, alcohol, or exertion. 44b) What does his CXR ( Fig. 44.2 ) show? His CXR shows patchy right-upper lobe consolidation . Investigations \227\206 Hb 14.5g/dL, MCV 88.2fL, WCC 7.8 \227 10 9 /L (normal differential), platelets 387 \22710 9 /L \227\206 Coagulation studies, U&E, LFT all normal, CRP 27mg/L, ESR 14mm/h \227\206 Fig. 44.3 shows the result of a diagnostic test performed on arrival. CASE 44 381 Fig. 44.3 Diagnostic test result. Questions 44c) What is this test and what does it show? 44d) Suggest a unifying diagnosis. 44e) What further serological tests should be performed? CASE HISTORIES IN RESPIRATORY MEDICINE 382 Answers 44c) What is this test and what does it show? The \200\230bedside cold agglutinins \200\231 test can be performed to rapidly assess for cold agglutininaemia, i.e. blood in a tube containing citrate (or other anticoagulant) is p laced in ice cold water or a freezer compartment for 5min and then assessed against a light for haemagglutination, compar- ing it to a warm control tube ( Fig. 44.3 ). Haemagglutinat ion is maximal between 0 and 5 C. Red cell agglutination can be seen in the cold vial, whi ch is consistent with a cold agglutininaemia and the patient \200\231s symptoms. Transient red cell agglutination precipitating acrocyanosis is particularly likely on peripheral regi ons where temperatures drop below 32 C. Gangrene as a consequence of transient cold haemag glutination is rare but a few cases have been reported in the literature. NB: A falsely low hemoglobin level and high MCV may arise as a result of red cell clumping in the sample, and in this situation examination of a peripheral blood smear is prudent. 44d) Suggest a unifying diagnosis. Mycoplasma pneumoniae pneumonia is the most likely diagnosis in this patient. Mycoplasma is responsible for approximately 20% of community acquired pneumonia and 5% of patients hospi talized with pneumonia. Mycoplasma infection is endemic, but punctuated by epidemics at 4 \200\2237-year intervals. It is about five times more common in smokers. Cold agglutinins are detected in about 60% of cases and other extra- pulmonary complication s develop in 15%, including neurological, renal, musculoskeletal, cardiovascular, gastroint estinal, skin and immunological manifestations. Other infective precipitants of cold agglut ination include Epstein-Barr virus (infectious mononucleosis) and, less commonly, cytome- g alovirus (CMV) , Legionella spp . , influenza, HIV, hepatitis and malaria.