Day #59 - Sclerdoderma Renal Crisis

Today we discussed a case of a patient with diffuse scleroderma who presented with a hypertensive crisis with acute renal failure and microangiopathic hemolytic anemia. The key in this case is recognizing the clinical presentation and aggressive management of the hypertension with supportive care for the hemolytic anemia.

We discussed the differential diagnosis of Raynaud's:

• Primary (younger age of onset, symmetrical, tend to be female, no ulcers/pitting, predictable and frequent attacks)
• Secondary
  
  • Trauma (i.e. jack hammer operators)
  • Collagen Vascular Associated - Scleroderma, SLE, MTCD (Scleroderma + SLE + myositis overlap), less likely in Sjogren's and RA
  • Secondary to vascultitis (i.e. Berger's disease)
  • Paraneoplastic (ovarian cancer, angioblastic lymphoma)
    
  • Vascular - peripheral vascular disease
  • Drugs (b-blockers, ergotamine, interferons, PVCs)
  • Hyperviscosity (Waldenstroms, cryoglobulinemia (HepC), cryofibrinogenemia, cold agglutinins, polycythemia)
  • Endocrine (carcinoid, pheo, hypothyroidism)

Treatment of Primary:

• Avoid precipitants (keep warm, pre-warm hands before going outside, avoid drugs that worsen)
• Calcium Channel Blockers (i.e. verapamil, amlodipine) or ARBs (losartan)
  
• Topical nitrates

Treatment of Ischemic Digit from Raynaud's:

• As above
• Analgesia
  
• Topical/Intravenous nitrates
• Limited evidence for prostaglandin, NO, sildenafil, epoprostinol

We also discussed limited scleroderma and distinguised it from diffuse disease by the absence of skin thickening above the elbow, or on the trunk and legs. We talked about the CREST syndrome (now referred to as limited scleroderma)

C = calcinosis of digits from infarcts
R = raynaud's
E = esophogeal reflux
S = sclerodactaly
T = telangectasia

10-15% of people with limited scleroderma will unfortunately develop pulmonary hypertension, which is the complication that is likely to cause significant morbidity and mortality. These patients should be screened yearly with PFT (with DLCO) and 2D echo and pulmonary hypertension should be treated.

Patients with diffuse disease tend to get other end organ complications including pulmonary fibrosis (and secondary pulmonary hypertension) which, once established cannot really be treated. We quickly touched upon the treatment of early pulmonary fibrosis with cyclophosphamide.

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 #52 - Multiple possibilities...

Today we heard a very complicated case of a patient with known hematologic malignancy and a previous bone marrow transplant who presented with acute dyspnea, fever, and hypoxemia. The clinical exam was suspicious for congestive heart failure, in particular with RV overload/dysfunction.

We cast an appropriately wide net, thinking about a differential diagnosis that was most consistent with one/multiple of:

• Pulmonary Embolism
• Congestive Heart Failure
• Pneumonia

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".

Another important point is that while inelligant, in significantly ill patients who are awaiting a diagnosis empiric therapy for multiple conditions may be considered. In this case emperic broad-spectrum antibiotics (for example ceftriaxone + quinolone), treatment of CHF (lasix, nitrates as tolerated, ideally IV) , and empiric treatment for PE (based on our clinical suspicion, the high likelihood that a secondary event would be fatal, and the delay in being able to get a diagnostic test) were all appropriate. In this case, with unclear renal function, IV heparin is probably safer.

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I alluded to the fact that the date of the allogeneic bone marrow transplant may be relevant to the differential diagnosis. The following figure from uptodate illustrates this point.

Early infections (pre-engraftment of the donor marrow) tend to occur with usual bacterial pathogens (gram positive and negative including pseudomonas), invasive candidiasis and aspergillosis, and herpes simplex and respiratory viruses.

Once the donor marrow has engrafted, the risk of non-encapsulated bacterial infections and decreases. However, the risk of encapsulated organisms and aspergillosis persists and the risk of more unusual opportunistic infections increases. These include CMV and other herpes viruses, toxoplasmosis, and PCP.

Later on, while the risk of VZV and EBV increases as well.

The Jugular Venous Pressure (JVP)

Draping and Positioning:

• Patient lying at 30-45 degrees
• Neck gently extended and rotated ~ 45 degrees to the left
• Tangential lighting

Locate the JVP and differentiate from carotid

• Look for the JVP along the line coursing between the two heads of the sternocleidomastoid towards the earlobe
• JVP usually has double waveform
• JVP varies with respiration (should decrease with inspiration, if increases this is called Kussmaul's sign seen in constrictive pericarditis, restrictive cardiomyopathy, RV failure/overload)
• JVP can be occluded and is non palpable
  
• JVP varies with position of the bed
  
• JVP will change position with abdominal pressure

Estimate the height of the JVP by measuring the height of the top of the wave above the sternal angle (in centimetres)

• Low <0>
• "Normal" 0-5cm
  
• High >5cm

There is a high degree of intra-observer variability in the JVP.

In general, a "low JVP" has a LR+ for low CVP of ~ 3.4 and a LR- for a high CVP of 0.2
A "high JVP" has a LR+ of 4.1 for a high CVP.

Comment on any abnormalities of the waveforms

Some notable abnormalities (there is a long list, these are but some):

• Large a waves seen in tricuspid stenosis, pulmonary hypertension, RA/RV masses
  
• Absent a waves (or flutter waves) seen in atrial fibrillation or flutter
• Canon a waves seen in AV dissociation
• large v waves (or c-v waves) seen in RV failure, severe TR, ASD

Abdominojugular reflux:

• With a semi-inflated BP cuff apply 20-30mmHg pressure to the central abdomen for 15-30 seconds while observing the JVP. An increase of more than 4cm which does not return to normal within 10 seconds in "positive".
• Indicated inability of right heart to accommodate increased venous return seen in constrictive pericarditis, restrictive cardiomyopathy, RV failure.

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From the JVP alone you can learn many things that will make the remainder of your exam more fruitful. For example if you go in knowing to listen specifically for the murmur of TR or perhaps a loud P2 or S3/S4 you may be more successful in hearing them.

Also, note that there is some evidence that the external jugular vein is also useful for estimating CVP and may, in fact be easier.

Day #51 - SVC Obstruction

Today we discussed a case of SVC obstruction.

The discussant demonstrated the iterative clinical reasoning that experienced clinicians use when they approach a case.

We use the chief complaint to initially generate a list of conditions that we think are most common or that we don't want to miss.

We then use the history of presenting illness in combination with the past medical history to generate diagnostic hypotheses. We test these hypotheses by asking questions that raise or lower the probability of these diagnoses

We then use the physical exam to look for evidence confirming or denying our hypotheses and arrive at several provisional diagnoses. At this point up to 90% of the time a diagnosis is strongly suspected.

At this point the laboratory, radiology and special tests are used to further refine the differential.

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SVC obstruction (Review from NEJM)

Causes

• 65% Malignancy (lung - NSCLC and SCLC ~75%, lymphoma ~ 10%, mets ~ 10%)
  
• 35% other
  
  • Infections - TB, syphilitic aortitis
  • Thrombosis - catheter/pacemaker related, other
  • Aortic aneurysm

Symptoms

• Facial and/or arm edema
• Distended neck and/or chest veins
• Facial phethora
• Dyspnea or cough
• Hoarse voice or stridor
• Headache
• Dizziness, confusion, obtundation

Pemberton's Sign:

Development of facial plethora, distended neck veins, stridor, and elevated JVP when elevating arms above head. This is a sign of SVC obstruction from a mediastinal mass or a thoracic inlet obstruction from a retrosternal goitre or mass.

Diagnosis

Best modality is CT with contrast to evaluate the SVC itself, the lung and mediastinum and the aorta.

Management

• Treat the underlying malignancy or condition (thrombosis, infection)
• Steroids are commonly used in malignancies; however there is little evidence of benefit
• Radiotherapy to radio-sensitive tumors
• Chemotherapy for sensitive tumors in patients who will tolerate
• Angioplasty and stenting of the SVC can be employed in non-chemo/non-radiotherapy cases or when rapid treatment is required
• Venous bypass surgery when above are not an option (mortality of surgery ~5%)

Day #50 - Pulmonary Embolism

Today we presented a case of a patient that developed a large, ultimately fatal, pulmonary embolism in hospital. This occurred despite adequate DVT prophylaxis.

Pulmonary embolism is a serious condition that is important to diagnose and treat effectively. The mortality of pulmonary embolism left untreated is approximately 33%.

Diagnosis of Pulmonary Embolism

In the past two-three years there have been two large studies on the diagnosis of PE that have been published. The Christopher study and PIOPED II (with associated editorial).

The first step in diagnosis is to establish what you believe the clinical probability of PE is. For this, I use the Wells Criteria for PE:

• PE is the most likely diagnosis (Score 3 Points)
• Clinical DVT on history and exam (Score 3 Points)
• Heart rate >100 (Score 1.5 Points)
• Immobility >3 days or surgery in last 4 weeks (Score 1.5 Points)
• PMH of PE or DVT (Score 1.5 Points)
• Haemoptysis (Score 1 Point)
• Malignancy within 6 months or palliative (Score 1 Point)

The total score is proportionate to the risk group:

less than 2 = "Low" (1.3% of PE in original study)
2-6 =" Medium" (~17% chance of PE in original study)
>6 = High risk (37.5% Chance of PE in original study)

If the patient is low risk, I will perform a D-dimer assay and if negative I feel it is safe to say, based on the Christoper and other studies, that PE is excluded.

If the patient is medium or high risk, the D-dimer will not help you. They need some other form of investigation. I then think about which investigations are available, how well they perform, how long until I can get them and what contraindications the patient has.

V/Q Scan:

• Requires: Relatively normal chest x-ray and no significant COPD
• Difficult to get after hours (or even during normal hours)
• If positive PE is confirmed
• If negative PE is excluded
• Problem: "Low probability V/Q" is not normal, and not low enough to exclude PE and you will need a follow up test

Doppler Ultrasound of Legs:

• No radiation, no contrast, relatively easy to get (except after hours at some hospitals)
• Good at detecting symptomatic DVT, but relatively insensitive for asymptomatic DVT or pelvic DVT
• Will miss upper extremity sources
• I use this in a patient where V/Q isn't an option and I don't want to subject the patient to a CT angiogram if at all possible (i.e. contrast allergy).
  
• I also use doppler in patients for whom the V/Q is intermediate, or in whom the CT scan is negative/equivocal in whom there is still a significant post-test probability of PE (see CT scan, below)

CT Pulmonary Angiogram

• Rapidly becoming the most common test that we use and is readily available
• Contrast is used, so contrast allergy, contrast induced nephropathy are a concern
• Radiation exposure

• From PIOPED II (figure above) you can see that the performance characteristics of CT angiography are very dependent on the clinical probability and you should interpret them as such before making serious clinical decisions.
  
• High clinical probability -- Positive test rules in PE, negative test does not exclude (sensitivity 60%)
  NB in the Christopher study <1.5>
• Medium clinical probability -- Positive test essential rules in PE (PPV 92%), negative test performs well but could miss up to 10% (NPV 90%).
  
• Low clinical probability -- Negative study rules out PE, positive test positive predictive value only 60% so unless there is another compelling reason to anticoagulate perhaps other tests would be required.

Basics of Treatment:

• Supportive care
• Heparin -- either IV Heparin infusion, or low molecular weight heparin injection (I favor LMWH in most cases except for renal failure or high risk of bleeding)
  
• Long term anti-coagulation with coumadin or LMWH (duration depends on risk factors)
• Consider IVC filter -- UPDATE -- READ THIS and consider
  
  • Can't anticoagulate (e.g. bleeding, other contraindication)
    
  • Recurrent PE on appropriate therapy
  • Unstable patient with large DVT
    

Advanced Management:

"Massive PE" with hemodynamic instability -- there is little good evidence

Options include:

• Thrombolysis (either IV or IA) with TPA
• Clot fragmentation and aspiration (interventional radiology)
• Surgical thrombectomy

Day #49 - Cryptococcus and HIV Redux

2 cases of cryptococcal meningitis admitted in 1 week. This is somewhat unusual.

We have previously discussed HIV+Cryptococcus here.

We talked again about the management including:

(a) effective anti-fungal therapy (amphotericin B 0.7mg/kg) induction (14d +/- flucytosine) followed by consolidation with fluconazole 400mg x 10 weeks followed by maintenance with fluconazole 200mg until CD4 >200 x 6 months and

(b) effective management of increased ICP.

If OP >320mmH20 -- they should have aggressive management of ICP (serial LP to <200) or VP shunt

If OP >180 and symptomatic -- they should also have aggressive management

The OP should also be measured at the end of the 14d induction therapy.

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FYI -- The US HIV guidelines are available here and here.

For the CC4s we will be discussing HIV again in seminar later this month.