2013 May - Petite Fours
Drs. P S CHEUNG and C M CHU
Division of Respiratory Medicine, Department of Medicine & Geriatrics, United Christian Hospital
Case 1 - A patient with unresolved pneumonia
The patient is a seventy-five years old man and is a non-smoker and non-drinker. For the past medical history, patient was admitted for acute abdomen with laparotomy done when he was 19 years old but he could not recall the details of the operation. Patient has history of minor stroke several years ago and also history of lung shadow which required annual follow-up at the chest clinic. Three years ago he was admitted to the hospital for per rectal bleeding and pleural effusion. Colonoscopy showed diverticulosis at the ascending colon and caecum and hemorrhoids. Ultrasound of the chest just showed a small right pleural effusion so he was referred back to the chest clinic for subsequent management.
For the index admission, the patient was initially presented with fever and cough with sputum for 2 days. Physical examination found decrease air-entry in the right lower chest; heart sounds were normal; the abdomen was soft with a surgical scar in the right frank. CXR showed opacity in right lower zone (picture 1),but the diagnostic chest tap did not yield any fluid. He was managed as a case of chest infection and was started on Augmentin. Blood test showed a normochromic normocytic anaemia (9.7), the CEA (Carcinoembryonic antigen) was markedly elevated (84). Sputum grew E.coli. His fever subsided and he was then discharged home with CT scan of thorax and colonoscopy arranged. The patient was admitted six weeks later for one day history of fresh mouthful haemoptysis. He also complained of persistent cough and on-going weight loss since last admission. Sputum grew ESBL E.coli. He was given Cravit only in view of stable clinical condition. On the day after completion of antibiotic, the patient was admitted again for fever and purulent sputum. CXR did not show any significant interval change. This time sputum grew commensals only, but in view of the persistent symptoms and recent positive sputum culture, he was put on Ertapenem. However, 2 weeks later, he was admitted again for haemoptysis. Respiratory team was consulted for the unresolved pneumonia.
Picture 1
The team assessed the patient and reviewed all his medical history. This patient had repeated positive growth of ESBL E.coli from the respiratory tract which is uncommon cause of community acquired pneumonia. Moreover, the unresolved pneumonia might be related to the history of intra-abdominal operation which resulted in damage of the thoracic-abdominal barrier. The history of lung shadow also suggested a long existing lung problem. Therefore, we advanced the appointment of the CT scan of thorax and abdomen. (Picture 2) CT showed empyema necessitates in the right lower thorax with extension through the diaphragm and involvement of the abdominal wall. Finding was suggestive of long standing infection with disruption of the thoracic-abdominal barrier due to previous surgery. Barium follow-through showed mucosal irregularity in the hepatic flexure without definite communication to the right pleural cavity.
Picture 2
The patient was referred to the cardiothoracic surgeon. Surgical exploration with decortication and/or right lower lobe lobectomy and diaphragmatic repair was suggested, however, patient refused invasive surgery in view of advance age and high operative risk.
Bring home message – when encountering an unusual cause of a vanishing condition (empyema necessitates), we should have relentless pursuit of the underlying mechanism.
Case 2 Sleeping with the enemy
The patient is a housewife who is a non-smoker with good exercise tolerance. She enjoyed good past health except history of chest infection that was followed up in the Chest clinic.
One year ago, patient was admitted for fever and productive cough for four days. First CXR showed left middle zone infiltrate. She was treated as chest infection and given a course of Rocephin. The sputum culture and AFB smear were negative. Six weeks later, follow-up CXR revealed persistent left middle and right middle zone shadows, which was confirmed in the subsequent CT scan of thorax. Clinically, the patient was asymptomatic and follow-up blood tests were unrevealing. A bronchoscopy was arranged. There was no endobronchial lesion and the BAL (bronchoalveolar lavage) for bacteria, AFB smear, MTB PCR, cytology and fungus were all negative. Four months after the admission, CXR showed significant resolution of the lung shadow so the patient was referred back to chest clinic.
For this index admission, patient was referred to our respiratory clinic due to cough with whitish sputum and shortness of breath on exertion for the past one month. There was no an associated symptom nor constitutional upset. She was started on Rocephin. The sputum culture, AFB smear and the paired atypical pneumonia titer were negative. Autoimmune markers including RF, ANA and ANCA were normal. The patient underwent another bronchoscopy which did not show any endobronchial lesion, the BAL was again negative for bacteria, AFB smear, MTB PCR, cytology and fungus. The transbronchial biopsy showed the lung parenchyma was focally infiltrated by mononuclear and lymphocytic cells. The alveolar space contained occasional foamy histiocytes. There was no granuloma or fungus and no evidence of malignancy. CT scan showed multiple small consolidations bilaterally. At that juncture, the differential diagnoses for this patient were infection including tuberculosis or fungus, interstitial lung disease (ILD) especially organizing pneumonia(BOOP), eosinophilic pneumonia (EP) or hypersensitivity pneumonitis(HP), pulmonary vasculitis such as Wegener’s granulomatous(WG) or Churg-strauss syndrome(CSS) and pulmonary infiltrate due to drug or toxic. Among them, the most likely cause would be ILD which rely on histological proof. Therefore, the patient was then underwent a video assisted (VAT) lung biopsy by cardiothoracic surgeon.
In the VAT lung specimen, microscopically there were well formed granulomas, multinucleated giant cells with calcification and chronic bronchiolocentric inflammatory infiltrates and fibrosis. The Gram stain, ZN and Grocott stains were negative. The histological findings were not compatible with infection or vasculitis. BOOP and EP were also unlikely in view of the absence of classical histological features. The most likely diagnosis would be HP supported by the well-formed granuloma and the bronchiolocentric distribution. T-spot test was negative. Serum precipitant showed markedly elevated serum precipitants to Aspergillus Fumigatus and Aureobasidium.
In order to find the allergen, our team had arranged a home visit for her. Apparently the overall home environment was clean. A thorough search in the patient’s bedroom found that patient’s pillow core underneath a “clean” pillow case was filled with mold spots. The patient was asked to discard the pillow and was given systemic prednisolone. Initially she responded well to steroid treatment with most of the symptoms subsided one month later. However, her symptoms recurred soon after the cessation of steroid treatment. Upon questioning, patient admitted that she had not discarded that expensive pillow, she used the pillow again after sending it to washing and streaming. Patient finally threw away the pillow and then she was free from recurrent attack of hypersensitivity pneumonitis.
Bring home message –
Pattern recognition of episodic lung infiltrate.
We should go to any length to uncover the etiology
Case 3 In the wrong place
A man with known history of Crohn’s disease in remission, end stage renal failure on peritoneal dialysis was incidentally found to have diffuse parenchymal infiltrate in the CXR. High resolution CT showed diffuse ground glass opacities (picture 3).
Picture 3
The physical examination was normal with oxygen saturation 97 percent in room air. Our respiratory team was consulted for tissue biopsy via bronchoscopy. The differential diagnosis list for this patient was extensive (chart).
Differential Diagnosis
1. APO/fluid retention
2. Autoimmune diseases: WG, CSS, Goodpasture’s, polyangiitis, APL
3. Infection: Hantavirus, CMV, leptospira, sepsis
4. TTP, HUS
5. Renal vein thrombosis with PE
6. Immunosuppressed (transplant) with opportunistic pneumonia
7. Metastatic calcification (Discordant HRCT vs. clinical severity)
As a result of that, the patient might need to go through a long list of investigations. After assessing this patient and reviewed the CT images; we found that there was significant discordant between the alarming CT features and the totally asymptomatic clinical status. This discordance made metastatic calcification the most likely diagnosis. Bone scan was then arranged(picture 4) which showed intense uptakes in patient’s both lungs that almost equal to the uptake of bone.
Bring home message – recognition of clinic-radiological discordance
Picture 4
Case 4 TB or not TB? That is the question
A forty years old Pakistan man, who came to Hong Kong 17 years ago, is a nonsmoker and non-drinker. He enjoyed good past health. The patient was initially presented with diabetic ketoacidosis with acute abdominal pain and diagnosed to have acute pancreatitis. CT scan of the abdomen showed acute pancreatitis with pseudocyst formation. There were small mesenteric lymph nodes. A formal CT Thorax was then arranged and he was referred to respiratory clinic for further assessment. Patient did not have any respiratory symptoms, physical examination was normal, blood test including CBP, and bone profile was normal. CT scan of the thorax showed enlarged bilateral hilar LN, with no lung parenchymal lesion. He was referred to another hospital for consideration of mediastinoscopy or EBUS (endobronchial ultra-sound). The patient underwent EBUS of the subcarinal LN. Histology showed granulomatous inflammation. Microscopically there were well formed granulomas consisting of aggregates of epithelioid histiocytes surrounded by lymphocytes. No sclerosis or necrosis was seen. There were no frank cytological atypia. The ZN and Grott stain were negative. The AFB smear of the LN was negative. The patient was started on empirical anti-tuberculosis drug. However, he did not want to take the drug and also requested to stop treatment. When we saw him again in the respiratory clinic, we reviewed all the clinical features and investigation results. The most likely cause for granuloma of LN in our locality would be tuberculosis, however, for this patient who came from Pakistan, Sarcoidosis was also possible. Therefore, T-spot test, PET scan and slit lamp examination were arranged.
The probability for TB on this patient can be estimated by the modified Bayes theorem. Mathematically, Bayes' theorem gives the relationship between the
probabilities of A and B, P(A) and P(B), and the
conditional probabilities of A given B and B given A, P(A|B) and P(B|A). In its most common form, it is:
In Pakistan patient who presented with bilateral hilar lymph node (BHL), the pre-test probability for Sarcoidosis would be 71.1%, tuberculosis 17.1%, lymphoma (2.6%) and miscellaneous (8.5%) respectively1. Since the T-spot test for our patient was negative, the calculated post-test probability of TB was only 2.5%. The estimated therapeutic threshold of anti-TB treatment for this patient will be
1/ (Benefit / Risk + 1)
With overall 20% mortality for untreated TB in non-HIV patient, mortality for treated TB will be 3.71%, and then benefit equals to
(20% - 3.71%) = 16.29%
Assuming the anti-TB (isoniazid, INAH) induced hepatitis is 8% in Pakistan, mortality of INAH induced hepatitis is 10% in Pakistan, then risk will be 8% times 10% i.e. 0.8%
So therapeutic threshold will be
1/[ 16.29% / 0.8% + 1]
= 1/ (21.36 + 1)
= 4.68 %
Using this mathematical model, with a negative T-spot test, TB will be very unlikely (only 2.5%), and sarcoidosis will be more likely (97.5%). Therefore, empirical TB treatment would be unwarranted as 2.5% is well below the therapeutic index of 4.68%.
This diagnostic problem can be viewed from another way – since the probability of TB in patient with BHL and a negative T-spot test would be 2.5%, therefore, a cohort of 10,000 similar men would include 250 patients with TB and 9,750 patients with sarcoid. For patients with TB (n=250), the overall mortality for untreated TB in non-HIV patient will be 20%. If we give all patients anti-TB drug,
250 x (1-0.2) = 200 patients survive
250-200 = 50 patients die of untreated TB
On the other hand, the overall mortality for treated TB will be 3.71%, therefore, if we withhold anti-TB drug from all these patients,
250 x (100-3.71%) = 241 patients survive and 9 patients die
250 x 8% = 20 patients have hepatitis and 2 patients (2%) die
For patients with sarcoid (n=9,750), if we give empirical ant-TB drug,
78 (9750 x 8% x 10%) patients will die of hepatotoxicity.
As a result, if all these 10,000 patients were given TB treatment, 89 patients (9+2+78) will die of TB or hepatotoxicity whereas 50 patients will die from untreated TB if we withhold anti-TB drug from all patients.
Obviously, more patients will die from TB drug related hepatotoxicity than untreated TB.
For our patient, we did not resume the empirical TB treatment. His PET scan (picture 5) demonstrated active uptake in BHL and also the classical Panda sign compatible with sarcoidosis
Picture 5
Bring home message – clinical reasoning using Bayes’ Theorem and Therapeutic threshold
Reference
- The pretest probability of bilateral, symmetrical, hilar lymphadenopathy on chest x-ray in asymptomatic patients in a high TB prevalence area. Khan et al. P717 ERS annual congress 2007
