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. 44e) What further serological tests should be performed? Serological tests that should be performed are: 1. Mycoplasma pneumoniae antibody titres. Peak levels are reached approximately 2 weeks aft er the onset of symptoms and decrease as symptoms resolve. Enzyme immunoassay (EIA) detecti on of acute and convalescent phase specific IgG and IgM antibodies are more sensitive for d etecting acute infection than culture. A four-fold rise in titre is suggestive of acute inf ection. IgM antibodies against CASE 44 383 Mycoplasma pneumoniae may not be produced during re-infection in patients over 40 years wit h pre-existing IgG antibodies. 2. A confirmatory cold agglutinin titre could be requested. Causes of cold agglutinin disorders may be classified as: \227\206 Primary (idiopathic cold agglutinin disease) when the titre is very high (often > 100,000 \200\2231,000,000 and associated with monoclonal auto-antibodies) \227\206 Secondary: Associated with monoclonal auto-antibodies, usually chronic, and related to B-cell lymphopr oliferative conditions or non- hematological neoplasia Associated with polyclonal auto-antibodies, usually acute and transient, often precipitated by infection, as in this case Related to collagen vascular disease. 3. Complement levels (C3 and C4) are usually normal. 4. Direct Coomb \200\231s Test (DCT). Cold agglutininaemia arises as the result of specific immunoglobulin M (IgM) production (or less commonly IgA or IgG) to the \200\230I \200\231 antigen on erythrocyte membranes, whi ch induces haemagglutination mainly at 4 C and not at 37 C. This commonly arises 1 \200 \2232 weeks after the acute infection (as in this case) and is more common in childhood inf ection, decreasing with age. The titre gradually falls with treatment and becomes negative by 4 months. Cold agglutinin related haemolytic anemia due to complement mediated red blood cell destruction may also arise. However, this is relatively uncommon given the inefficien cy of the process in the absence of continued cold exposure, and is rarely clinically signi ficant. The DCT reaction is usually negative with anti- IgG, but positive with anti-complem ent 3 in cold agglutinin disease. 5. Antinuclear antibodies, anti-DNA antibodies, anticardiolipin anti- bodies, cryoglobulins and rheumatoid factor. 6. Urinary Legionella antigen. CASE HISTORIES IN RESPIRATORY MEDICINE 384 Investigations \227\206 Elevated cold agglutinin titre 1:1280 at 4 C (upper limit of normal 1:40) \227\206 DCT was negative for presence of bound IgG \227\206 Antinuclear antibodies, anti-DNA antibodies, anticardiolipin antibod- ies, cryogl obulins and rheumatoid factor (<10IU/mL): all negative \227\206 Normal C3 and C4 \227\206 Legionella urinary antigen negative. CASE 44 385 Question 44f) What treatment should be initiated? CASE HISTORIES IN RESPIRATORY MEDICINE 386 Answer 44f) What treatment should be initiated? Empirical macrolide antibiotic therapy: macrolides remain the first-line therapy for atypic al pneumonia, despite the recent emergence of resist- ant organisms in Japan. Doxycycline o r fluoroquinolones are alternative agents. The most effective treatment for cold agglutinin-induced acrocyanosis (and haemolysis) is a voidance of the cold. Calcium-channel blockers or -receptor antagonists may be added and relieve symptoms in most cases. Corticosteroids may have a role in reducing the severity of haemolytic anemia due to cold h aemagglutination, and cytotoxic drugs, such as cyclophosphamide, azathioprine and ciclospor ine, have been success- fully used, but are rarely required in acute infection-related dise ase. Plasmapheresis can be used as an adjuvant, temporizing, treatment to remove the IgM antibod y, if symptoms associated with acute infection related cold agglutinaemia are severe. Progress The patient was treated with clarithromycin and nifedipine, and advised to keep warm. His c ough and acrocyanosis improved. At 6 weeks, finger oximetry showed good arterial pulsation giving a valid reading, and his CXR had returned to normal. A repeat cold agglutinin titre was 1:32 at 4 C. CASE 44 387 List of cases by etiology Allergic/inflammatory Anatomical Congenital Degenerative Genetic Infectious disease Inflamm atory disease Malignancy Physiological syncope Psychological Toxic/inflammatory Trauma/infl ammatory Vascular Vascular/genetic 1 21, 25 7 14 9, 11, 16 4, 13, 20, 24, 31, 36, 44 3, 5, 8, 10, 17, 18, 26, 30, 33, 35, 38, 39, 42 6, 19, 22 15 12, 29 23, 37, 41 27 2, 28, 32, 34, 40, 43 34 CASE HISTORIES IN RESPIRATORY MEDICINE 388 List of cases by diagnosis 1 2 Hepatopulmonary syndrome 3 4 5 6 Malignant pleural disease presenting as ? TB 7 Pulmona ry sequestration 8 Hypersensitivity pneumonitis Lymphangioleiomyomatosis 9 Bronchiolitis ob literans/Chronic graft versus host disease 10 11 Cystic fibrosis 12 Hyperventilation syndro me 13 14 15 16 17 18 19 Hypothalamic lesion 20 Mycobacterium bovis infection 21 22 Mesothel ioma 23 24 25 26 Wegener \200\231s granulomatosis 27 28 29 30 31 32 33 34 Masssive haemopty sis in CF 35 36 37 38 Allergic bronchopulmonary aspergillosis Diffuse cutaneous systemic sclerosis Chronic Haemophilus influenzae, panbronchiolitis Asthm a Oesophageal perforation and empyema secondary to TB lymph nodes Shy-Drager syndrome Cough s yncope/chronic cough Alpha-1 antitrypsin deficiency & COPD Sarcoidosis and pulmonary hypert ension Chronic eosinophilic pneumonia OSA Nitrofurantoin pulmonary toxicity/UIP Post polio syndrome Primary spontaneous pneumothorax Pseudochylothorax/Chylothorax Pulmonary emboli Exercise induced vocal cord dysfunction Chur g Strauss syndrome Pulmonary TB Chronic thromboembolic disease Cryptogenic organizing pneum onia Lymphoid interstitial pnuemonitis Non-tuberculous mycobacterial infection Severe COPD and s urgical treatments Upper airway obstruction secondary to Wegener \200\231s granulomatosis CASE 44 389 39 40 Sarcoidosis Pulmonary arterio-venous malformation/Hereditary Haemorrhagic Telangiectasia 41 Methotrexate induced pneumonitis/RhA associated fibrosis NSIP 42 43 Intrapleural bleed 4 4 Mycoplasma pneumonia