Day #278 - Cavitary Lung Lesion

Today we heard the case of a young man with a history of constitutional symptoms (sweats, weight loss) in association with a non-productive cough and a cavitary right upper lobe infiltrate.

I have previously blogged about the differential of cavitary lung lesions

Based on the presentation I favor an infectious etiology, most likely tuberculosis. The absence of AFB on the bronchoscopy does *not* mean this isn't tuberculosis.

This study of 230 cases of culture positive pulmonary tuberculosis showed that the BAL AFB stain was only positive in 48/95 patients without spontaneous sputum production. In this study, the sensitivity of BAL AFB stain was better, but still only 70%.

The take home message is that a negative smear does not exclude TB in a compatible case. Repeat samples are sometimes indicated and awaiting the final culture is also required. In this case I would add induced sputum daily in the AM for three days to maximize my chances of making the diagnosis.

This article reviews the various radiographic manifestations of pulmonary tuberculosis.

Treatment of Pulmonary TB (see Canadian Tuberculosis Standards):
Initial:

• Isoniazid (INH) +/- Vitamin B6
  
• Rifampin (RIF)
  
• Pyrazinamide (PZA)
  
• Ethambutol (ETH)
  

If demonstrated susceptible to INH/RIF/PZA:

• Can stop ETH immediately
  
• Continue INH/RIF/PZA until 2 months then stop PZA
• Continue INF/RIF 4 months to complete 6 total months
  

Day #111 - TB Pleuritis

Today we talked about a great case.

There is a *great* free resource called the Canadian Tuberculosis Standards available here.

First we talked about the diagnosis and treatment of latent tuberculosis infection.

Diagnosis:

• Positive mantoux test
  
  • Interpret in context of patient's history
    
    • less than 5mm - negative (or false negative in immunosuppressed or very ill patient)
    • 5mm-10mm - HIV, close contact with known case, chest xray evidence of old TB as fibronodular disease, children, immunosuppression (chemo, TNF alpha, high dose steroids)
    • Greater than 10 - positive for all others
    • Increase in 6 from previous known positive.
      
  • BCG -- only consider BCG as the cause of a TST if it was given after 12 months of age to a patient from a low risk country and does not have radiographic evidence of old TB
• Can consider inferferon based assay, though this is not the standard
  
• Evidence of prior tuberculosis on imaging
• No evidence of active disease

Treatment:

• Tend to treat people who are at the highest risk of re-activating or those with the lowest risk of drug side-effects
  
  • High risk includes: HIV, organ transplant, TNF alpha inhibitors and other immunosuppression
  • Risk in health normal person is ~ 5% in first 2 years and 10% over the lifetime
  • Immigration and reactivation risk
    
• INH 300mg PO OD x 9 months with Vitamin B6 25mg po OD
• Alternative (not as good): RIFAMPIN 600mg po OD x 4 months

We then talked about diagnosis and treatment of TB pleuritis

Diagnosis:

Acute to subacute illness (2/3 present less than 1 month) with fever, pleuritic chest pain, minimally productive cough. Unilateral effusion.

• Exudative effusion
• pH usually ~ 7.4
• Glucose usually normal
  
• Lymphocytic pleocytosis (though can be neutrophils early)
  
• Usually less than 5% mesothelial cells
• AFB stain less than 10%
• Culture ~ 30% (yield may improve by inoculating into special culture media)
  
• PCR positive in 90-100% of culture positive but only 30-60% of culture negative
• Sputum positive in ~ 50%
• Pleural biopsy shows either granulomas or AFB or is culture positive in up to 95%
  

• Measurement of Adenosine Deaminase
• The future: Other novel tests

Treatment:

• INH, RIF, ETH (add PZA if sputum positive, sick, bilateral effusions, other extrapulmonary disease) x 2 months then if INF/RIF sensitive INF/RIF to complete 6 months
• Adjuvant steroids are not clearly indicated
  
• Effusion may take up to 6 months post treatment to resolve.
  

Day # 202 - Presumed TB Meningitis

This was a case of a man from an endemic country with an encephalopathy of several weeks duration and a lumbar puncture with a lymphocytic pleocytosis, elevated protein, low glucose and no organisms on the LP. Viral PCR was also negative as were fungal studies. The presumed diagnosis on clinical grounds was TB meningitis.

A modern era review article including a discussion on the role of nuclear antigen testing is here.

The role of adjunctive dexamethasone in TB meningitis is described in an article from NEJM here.

There is a *great* free resource called the Canadian Tuberculosis Standards available here. This reference text provides a plethora of useful information on tuberculosis and would be a worthy addition to anyone's collection.

Day #295 - Tuberculosis and Immune Reconstitiution

We discussed a case of pulmonary and extrapulmonary tuberculosis which presented on TNF-alpha antagonist therapy.

Addendum: TB Immune Reconstitution Reviewed Recently here.

We also discussed paradoxical worsening of TB post-discontinuation of immunosuppression. The case report I was talking about is available here.

Day #94 - Hemoptysis

The discussant today gave an excellent approach to hemoptysis, which has a broad differential. We highlighted the importance of distinguising hemoptysis from hematemesis and epistaxis. I wanted to discuss "massive" hemoptysis in more detail.

Severe/Massive hemoptysis can be defined as blood volume >100-600cc and may be associated with hemodynamic instability and respiratory comprimise. Massive hemoptysis makes up ~5% of all hemoptysis and has a mortality quoted as up to 80%.

There are many potential causes. The most common in case series are:

• Bronchiectasis
• Tuberculosis
• Bronchogenic carcinoma
• Pneumonia
• Aspergilloma
• "Bronchitis"
• Coagulopathy
• Other -- Includes pulmonary renal syndrome, diffuse alveolar hemmorhage

Key issues in management:

1. Protect the airway. Includes positioning the patient with bleeding lung down, intubating patient with selective bronical intubation of "good lung" if possible and blockage of the "bad lung"
   
   • In cases related to the left lung, you may, at the bedside be able to advance the ETT into the right mainstem bronchus once the patient is intubated because of the anatomy
2. Supportive measures:
   
   • IV access, fluids, pressors, blood
   • Fix coagulopathies
3. Investigate/Treat:
   
   • Fiberoptic bronchscopy to visualize. If inadequate, rigid bronchoscopy. Certain therapies can be performed with the rigid bronch
     
   • If continues to bleed, and/or source can't be found angiography, usually bronical artery to localize and embolize bleeding source
   • High res CT scan if patient stable enough to move there and diagnostic uncertainty.
     

Day #306 - TB Pleuritis

We discussed a great case of tuberculosis causing pleural effusion today. I have previously blogged about this before.

Previous blogs on pleural effusion here and here (including discussion of Light's Criteria and parapneumonic effusions/empyema).

Modified Light's Criteria (see review here):

• Change LDH pleural fluid 0.45 ULN (increases sensitivity but reduces specificity)

Alternative tests:

• LDH (0.45ULN), cholesterol (45mg/dl) and protein (29g/L) of pleural fluid, done in combination have similar performance characteristics to Light's criteria and don't require paired serum samples.

TGH "Case of the Week" July 14-18, 2008

30F with known HIV (CD4 unknown, not on treatment) presents with acute onset fever, chills, rigors, and cough with sputum. On exam she is febrile, tachycardic, hypotensive, hypoxemic on room air requiring hi-flow oxygen to maintain saturations >90% and in moderate respiratory distress.

The chest x-ray is taken and appears below:



Questions:

1) What is the most likely microbiological diagnosis?
2) What is the differential diagnosis?
3) What tests would you order to make your diagnosis?
4) What empiric treatment would you initiate in the ED?

BONUS: What "management strategy" would you employ in the ED and what journal was the study published in?

Thank you to the people who submitted answers. The "contest" is closed for this week. The winner will be notified in person.

"Answers"

1) The most likely etiologic agent to cause a lobar pneumonia in a patient with HIV is still streptococcus pneumoniae. In fact, patients with HIV are at an increased risk of getting pneumococcal infections and should all be vaccinated with the polysaccharide vaccine.

2) The differential diagnosis includes lobar pneumonia with the other organisms of community acquired pneumonia including haemophilus influenzae, moraxella cattharalis, and Staphylococcus aureus. Of particular concern in a patient who is rapidly deteriorating is community acquired MRSA necrotizing pneumonia.

Other causes would include Legionella pneumophillia and if risk factors such as underlying structural lung disease enteric gram negative organisms.

Upper lobe pneumonia should prompt concern for tuberculosis, although in this case the acquity and sepsis-syndrome argue more strongly in favor of bacterial pneumonia.

PCP tends not to be lobar and consolidative and the classic x-ray appearance looks more like bilateral peri-hilar interstitial infiltrates.

Fungal pneumonias like cryptococcal pneumonia, blastomycosis, invasive aspergillosis are unlikely and would not generally have this radiographic appearance and acute presentation.

3) Blood cultures should be sent ASAP (ideally before antibiotics) as they may be positive in up to 25% of cases of pneumococcal pneumonia. Sputum cultures should also be sent for conventional culture, legionella culture and TB culture. I would not recommend sputum for PCP in this case.

Urinary antigen detection for pneumococcal antigen is used in some centres (not here). Urinary antigen testing for legionella can help make this diagnosis.

CD4 testing in acute illness may not be helpful as the acute illness could cause a decrease in the counts; however, it would not be unreasonable as if the CD4 count was >200 rare causes are much more unlikely.

4) In a septic patient with community acquired pneumonia you need to cover broadly for the most likely pathogens. There are many ways to do this and in some cases what you choose will depend on recent antibiotic exposure.

In this case a combination of VANCOMYCIN 1gIV q12h and LEVOFLOXACIN 750mg IV/PO q24h would be appropriate. This would cover MRSA and quinolone resistant pneumococcus, the usual pathogens including the majority of pneumococcus, unusual pathogens like legionella, and many enteric gram negatives.

BONUS: The management strategy to be employed is "Early Goal Directed Therapy in Sepsis"

Day #24 - Colitis

Today we discussed a gay male with fever, abdominal cramping, tenesmus and bloody diarrhea. The discussant made a very important point -- the clinical context and history are very important in making the diagnosis in acute colitis.

Before making the diagnosis of IBD one should exclude infections by history and special tests. Infections can mimic IBD clinically, radiographically, and endoscopically.

I wanted to talk about the differential diagnosis of bloody diarrhea with fever.

Differential Diagnosis

Infectious

• Enteroinvasive infection: Salmonella, Shigella, Campylobacter, E. Coli 0157:H7 (associated with HUS, frequently afebrile), Clostridium difficile, Klebsiella oxytoca
  
• Associated with receptive anal intercourse: HSV proctitis, gonorrhea, chlamydia (L serovar - AKA LGV/lymphogranuloma venerium), syphilis
  
• Associated with oral-anal practices or colonic irrigation: intestinal amebiasis
• More chronic, associated with the terminal illeum: intestinal tuberculosis
• Immunosuppressed patients: CMV colitis
  

Inflammatory

• Ulcerative colitis/Crohn's disease
  

Ischemic Colitis

There is also a good case of a patient with fever and diarrhea in the NEJM available here.

Day #314 - Pulmonary Eosinophilia

Very complex case facilitated by an expert discussant. The key focus, other than on the case at hand was a demonstration of clinical reasoning and Bayes theorem.

We highlighted the importance of Occam's Razor -- but stressed the importance of recognizing Hickam's dictum.

I have previously blogged about pulmonary eosinophilia here (with references). In my mind, an important consideration in this patient (given travel to China) is to exclude disseminated strongyloidiasis because like infliximab related interstitial lung disease (NEJM article here) 'strongy' can appear to improve on steroids.

This is a recent review from the Lancet on TNF-alpha blockade and the interaction with tuberculosis.

NB: Review of radiographic manifestations of pulmonary TB.

Day #56 - Acute Monoarthritis Redux

We again approached this issue today.

The differential diagnosis of subacute-acute monoarthritis includes:

• Septic arthritis (gonococcal, non-gonnococcal bacterial, tuberculosis, fungal)
• Crystal (gout, pseudogout AKA CPPD, hydroxyapatate)
• Osteoarthritis flare

More rarely an acute monoarthritis can be a presentation of

• Seropositive and seronegative arthridities including reactive arthritis and post-streptococcal arthritis
• Hemarthrosis (in hemophilia and acquired hemophilia)

We use the history and physical to help us form an opinion on the etiology, but ultimately because septic arthritis is so damaging if missed, a synovial fluid analysis is required if there is suspicion of septic arthritis.

A previous blog discussed septic arthtiris and synovial fluid analysis.

Day #67 - Malignant Ascites

Previously I have talked about cirrhosis, ascites, and paracentesis.

The take home point from today's case was that you should be suspicious of a malignant cause of ascites when there is massive ascites without leg edema. The overwhelming majority of patients with ascites from portal hypertension will have leg edema. In this case the cause was an adenocarcinoma seen on cytology.

TB peritoneal disease can mimic a cancer. In fact, sometimes tumour markers such as CA-125 are elevated in TB peritoneal disease mimicking ovarian cancer. The diagnosis of TB peritonitis can be difficult.

The cell count is usually in the hundreds with a lymphocytic predominance.

The SAAG is usually <11.

Adenosine deaminase may be elevated -- if you can measure it.

Obviously the cytology for malignancy will be negative; however, the ascitic fluid rarely stains positive for AFB and the cultures are often negative. AMTD has a higher yield, but it is still disappointing.

Diagnosis usually requires a peritoneal biopsy sent for AFB stain as well as MTB culture.

There is a great nejm case of TB peritonitis here.

A huge (and awesome) free textbook on tuberculosis is available online here.