Day #113 - Fever of Unknown Origin (FUO)

Today we talked about a case of true FUO. The discussant is published on the issue and I have linked to that article in previous blogs.

FUO blog #1
FUO blog #2

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 #101 - Eosinophilia

Today we discussed a case of hypereosinophilia.

We discussed the differential diagnosis of eosinophilia including:

• Idiopathic Hypereosinophilic Syndrome (HES)
  
• Eosinophilic malignancies
• Systemic mastocytosis
  
• Associated with lymphoma (IL5 production)
  
• Infections
  
  • Parasitic (during tissue invasion): strongyloidiasis, ascariasis, hook worm, angiostronyliasis, liver flukes (fasciolysis, chlonorcis), trichenosis, filariases, paragonamiasis.
    
  • Viral: HIV
  • Fungal: Aspergillosis (especially ABPA), coccidiomycosis
    
• Allergy including asthma
  
• Medications
  
  • NSAIDS, allopurinol, phenytoid, semisynthetic penicillins, ASA
    
• Autoimmune disease
  
  • Churg-Strauss
    
• Addison's disease (usually low level)
  
• Cholesterol embolism
  

NB: from up to date: "Strongyloides can persist for decades without causing major symptoms. The infection elicits varying degrees of eosinophilia ranging from minimal to such high magnitude that it is mistaken for idiopathic hypereosinophilic syndrome."

Day #100 - Pleural Effusion/Empyema

Today we talked about the approach to pleural effusions:

1) How to do a thoracentesis

Pleural fluid can be mainly water (transudate) or exudative: blood (hemothorax), pus (empyema/complicated parapneumonic effusion), inflammatory, or chyle (chlothorax)

2) Light's Criteria for transudate vs. exudate

One of:

• Protein in pleural fluid >0.5 plasma
• LDH in pleural fluid >0.6 plasma
• LDH in pleural fluid >2/3 upper limit of normal in serum

False positive rate ~25%. Can measure SAPG (like SAAG) which if >12 suggests transudate. Do this if you had a low pre-test probablity of exudate.

This article discusses liklihood ratios for each value of these measurements and can be really helpful.

3) Management of complicated pleural effusion/empyema (great article here)

• • "The Sun Should Never Set of An Undrainded [Unsampled] Parapneumonic Effusion"
    
  • Sample the fluid at least
  • If >50% of lung has effusion, loculated, air-fluid levels, pleural thickening or pleural enhancement on CT highly suggestive that you will need drainage
  • Aspiration of frank pus, anaerobic smell, positive gram stain/culture, pH below 7.2, LDH >1000 imply you will need drainage
  • Drainage options include:
    
    • repeated thoracentesis
    • pig tail catheter (probably safer than surgical chest tube, less morbidity, but more likely to become clogged if frank pus. can also be inserted by seldinger technique with initial thoracentesis)
      
    • surgical chest tube (probably required for very thick, poorly flowing purulent material. higher morbidity than pig-tail)
      
    • VATS drainage: for failure of above, for patients with chronic empyema, ongoing sepsis, if need for decortication of "trapped lung"

Shameless self plug: here is my talk on the epidemiology of pneumococcal empyema.

Day #99 - PCP Pneumonia

Today we talked about a classic case of PCP pneumonia as a presenting illness for HIV.

Classically PCP presents with progressive dyspnea, usually initially with exertion then at rest, with dry hacking cough and fever. Classically the respiratory exam is relatively normal (sometimes there is a pleural rub) despite often remarkably abnormal chest x-ray. The classic x-ray, shown here, is of bilateral perihilar infiltrates.

LDH is usually elevated but can be normal in up to 10%. LDH can also be elvated in a number of other infections and malignancies.

Exercise induced desaturation is classic and one can do walking oximetry on their patients to see this effect.

The diagnosis is confirmed by direct calciflor stain or silver stain for organisms in the sputum, induced sputum, or BAL fluid.

There is some evidence that high resolution CT can be helpful in excluding the diagnosis and perhaps saving a bronchoscopy.

Treatment is ideally TMP/SMX (dosed 15mg/kg TMP component divided TID/QID) either IV or PO depending on status. Adjunctive steroids should be considered in patients who are hypoxemic on presentation (PaO2 <70,>35), who are in severe respiratory distress, or who have poor cardiopulmonary reserve. Ironically, this Toronto study showed that steroids did not influence outcome but did reduce septra intolerance. However, a cochrane metanalysis showed a NNT of 9 to prevent one death.

The use of HAART in acute PCP remains contraversial. You shouldn't stop someone's HAART if they are on it already (unless it is clearly failing); however, initiation of new HAART is unclear. Some studies show survival benefit, others mortality.

There have been many studies looking at prognostication. Obviously more severe disease at presentation is related to more adverse outcomes. This study found that age, previous history of PCP, treatment other than TMP/SMX, CMV PCR+ in the BAL, and previous use of PCP prophylaxis when diagnosed were all highly associated with mortality.

This simple prognostic score seemed to identify survivors from those who died.

I have previously written about HIV and cryptococcal meningitis here and here. These blogs link to the HIV treatment guidelines as well as the guidelines for the management of opportunistic infections.

Day #98 - Pneumonia

Today we talked about a case of pneumonia. I previously presented a case of pneumonia in "case of the week" back in July.

We stressed the management which includes:

Stabilize the patient:

• IV fluids, pressors if required, oxygen, mechanical ventilation if required. Early goal directed therapy.

Obtain microbiological specimens:

• sputum, blood culture, legionella urinary antigen if appropriate, other special tests as appropriatge
• pathogens most likely: streptococcus pneumoniae, haemophilus influenza, moraxella catarrhalis, staphylococcus aureus (including MRSA if risk factors), legionella, mycoplasma pneumoniae, chlamydia pneumoniae

Empiric antibiotic therapy (within 4h)

• Cover the most likely pathogens
• IDSA/ATS joint guidelines (are being revised to make more use of beta-lactams -- my suggestions include these guidelines and some new evidence)
• Healthy young person: macrolide (like azithromycin 500mg po x1 then 250mg po OD x 4d), beta-lactam like amoxicillin (1g po TID)
• Older, more ill:
• respiratory fluoroquinolone (like levofloxacin -- 750mg po Q24h x 5days)
• beta-lactam (ceftriaxone 1g IV q24, amoxicillin - high dose) plus macrolide
• MRSA: vancomycin (1g IV q12, renal dosed)
• Pseudomonas or other hospital acquired: Piperacillin-Tazobactam (4.5g IV q8h infuse over 4 hours) or Meropenem (1g IV q8h infuse over 4 hours)

Decision re: admission

• Prognostic score like PORT or SMART-COP.

Decision re: sending home

• Eating, drinking, mobilizing
• Off oxygen
• Ideally afebrile
• tolerating PO antibiotics
• Reliable follow up

Day #93 - Staphylococcus Aureus Bacteremia

Today we talked about a patient who presented with a febrile gastrointestinal illness who happened to have two diagnoses. First, a probable viral gastroenteritis acquired from his daycare aged son. Second, a concomitant staphylococcus aureus bacteremia.

I wanted to talk about the management of Staphylococcus Aureus Bacteremia. There is a good article here on the management of MRSA bacteremia.

• Never treat staphylococcus aureus in the blood as a contaminant. Like fungus in the blood, this always needs to be treated!
• The *minimum* treatment duration is 14 days (intravenous). This is for uncomplicated infections only.
  
  • Risk factors for complication:
    
    • Longer duration of illness
    • Community acquired infection
    • Persistent fever at 72h (OR 2)
      
    • Persistent positive blood culture at 96h (OR 5)
      
    • Hemodialysis patients
    • Indwelling lines or other prosthetic material
    • MRSA
    • No identifiable source for the bacteremia (i.e. no skin or line focus)
    • Blood cultures positive within 14 hours of drawing them
      
• You need to exclude bacterial endocarditis. Present in 10-13% of cases...
  
  • TEE is much more sensitive than TTE for making this diagnosis (103 patients with SA -- TEE dx endocarditis in 25%, TTE only found 7%). In patients for whom you are planning 14d therapy (particularly those who have risk factors for complication) you should probably not rely on a TTE to exclude IE.
• Can also cause pacemaker and AICD infections
• Vertebral osteomyelitis
• Septic arthritis
• Splenic abscess (persistant fever, LUQ pain)
  
• Septic thrombophlebitis (particularly with lines)
• Septic pulmonary emboli
  
• Brain abscess/meningitis/mycotic aneurysms
• Skin/soft tissue abscesses

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Treatment:

• Ideal treatment for MSSA is with a beta-lactam like cloxacillin or cefazolin. These are superior head to head with vancomycin for the treatment of MSSA.
• Removable foci should be removed if feasible and practical to do so
• Duration depends on complications. IE 4-6 weeks. Osteo ~6 weeks.
  

Risk of Death

• 20 to 40%!
• Age
  
• MRSA (OR 9.3)
• Blood cultures positive less than 12 hours (OR 7)
• Complication (OR 9)
  

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In medicine we often attempt to find one unifying diagnosis that explains all symptoms -- in satisfying what is known as Occam's Razor.

The important teaching point in a complicated case like this is that the patient may have multiple diagnoses and that we must keep an open mind. In response to Occam's Razor, Hickam's Dictum states that "[the patient] can have as many diseases as the damn well please".