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.

Day #46 - Jaundice

Today we discussed a patient with jaundice and the approach to a patient with jaundice. One can think of the causes of jaundice by looking anatomically:

Obstructive causes:

• Pancreatic mass -- i.e. cancer of the head of the pancreas
• Mass at the porta hepatis -- i.e. lymph nodes
• Obstructing stone in the biliary tree
• Biliary duct pathology -- primary biliary cirrhosis, primary sclerosis cholangitis, cholangiocarcinoma, HIV cholangiopathy
• Parasitic -- Clonorchis sinensis, Fasciola hepatica, Schistosomiasis
  

Intrahepatic causes

• Viral hepatitis
• ETOH/toxin hepatitis
• Non-alcoholic steatohepatitis
  
• Paraneoplastic (Stauffer's syndrome -- RCC)
• Infiltration by tumor -- HCC, mets, lymphoma
  
• Infiltrating Infection -- E.g. TB
• Drugs -- e.g. beta-lactams, ethinyl estradiol, jamaican bush tea
• Sepsis
• Cirrhosis
• Cholestasis of Pregnancy
  

Non-obstructive causes:

• Hemolysis
• Resorption of a large hematoma
  
• Drug effects on conjugation -- e.g. atazanavir
• Genetic deficiencies of bilirubin metabolism -- Gilbert's syndrome, Crigler-Najjar syndrome

Day #45 - Fever of Unknown Origin Redux

Today we discussed a very complicated (perhaps too complicated) case of a patient with fever of unknown origin, pancytopenia with granulomas in the bone marrow, probable disseminated intravascular coagulation, altered mental status and abnormal liver function.

The consultant, an infectious diseases specialist, went through a very broad differential diagnosis which I will attempt to re-create for you.

Non-infectious:

• Hematologic malignancy
• Non-hematologic malignancy (i.e. renal cell carcinoma)
• Venous thromboembolism
• Inflammatory:
  
  • Vasculitis -- i.e. temporal arteritis
  • Collagen Vascular Disease -- i.e. SLE
    
• Endocrine -- i.e. hyperthyroidism
• Periodic Fever Syndromes
• Factitious fever

Infectious:

• Viral:
  
  • HIV, EBV, CMV, influenza, measles/mumps, other.
• Bacterial:
  
  • Endocarditis, occult abscess, osteomyelitis from various pathogens
  • Unusual bacterial causes (see below)
    
• Fungal:
  
  • Endemic fungi such as:
    
    • Histoplasmosis (Ohio river valley, St. Laurence River Valley, Montreal in 1960s, Caves w/bats)
    • Blastomycosis (Northwestern Ontario)
    • Coccidiomycosis (Southwestern US)
• Mycobacterial
• Parasitic -- i.e. malaria (usually non-falciparum), babesiosis

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Unusual bacterial causes

Some of these were discussed today:

• Rat-bite fever
• Meilodosis (travel to Australia, Southeast Asia)
• Plague
• Brucellosis (travel, exposure to sheep, cattle, goats, unpasturized cheese)
  
• Bartonella Henselae (Cat Scratch Disease)
• Q-Fever (Sheep, Pregnant Cats, high rates in Nova Scotia)

The key is the travel and exposure history and an open mind.

Day #44 - HIV

Today's case was a patient with HIV who presented with fever, confusion, headache, anorexia and malaise. His CD4 count was less than 100.

We discussed, based on the clinical features that the patient probably had a CNS infection of a indolent nature. The differential included toxoplasmosis, cryptococcosis, TB meningitis, syphilis, viral encephalitis or non-infectious causes like primary CNS lymphoma. The normal CT scan left cryptococcosus, TB meningitis, syphilis or viral encephalitis. The CSF studies confirmed cryptococcal meningitis, of which this was a fairly classic case.

The IDSA has guidelines for the management of cryptococcal meningitis, and this RCT in NEJM is probably the landmark study.

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Remember in HIV there is a marked increase in the risk of certain infections:

• Any CD4 count: TB, pneumococcus, herpes simplex, varicella zoster
  
• CD4 less than 200 Pneumocystis Carini
• CD4 less than 100 Toxoplasmosis, Cryptococcus
  
• CD4 less than 50: CMV, Mycobacterium Avium Complex
  

We also talked about HIV treatment using the viral life cycle as a guide. In general, we initiate treatment if:

• The patient is ready to take the medication
• AIDS defining event OR
• CD4 >350 with rapidly decreasing CD4 and very high viral load
• CD4 less than 350 stongly consider starting
  
• CD4 less than 200 start
  

Using the viral life cycle, we talked about the various medications that are available:

• Viral fusion inhibitors (T20)
• Chemokine inhibitors CCR5 (miraviroc)
• Reverse transcriptase inhibitors (NRTI -- eg tenofovir, ermtrictabine/lamivudine, abacavir) and (NNRTI -- effavirenz)
• Protease inhibitors (lopinavir/ritonavir, atazanavir/ritonavir)
• Integrase inhibitors (raltegravir)

General rule: 2NRTI + PI or NNRTI in treatment naive, in experienced patients who are failing goal is to develop regimen which has 3 active drugs in multiple classes.

We discussed the "AIDS" defining criteria (CD4 less than 200 or specific conditions - see list). Guidelines for the management of HIV and opportunistic infections are available here.

Day #43 - Endocarditis

Today we discussed a great case of subacute bacterial endocarditis which presented as renal failure, uremia, and life threatening hyperkalemia. We discussed the approaches to altered level of consciousness and hyperkalemia. We also briefly discussed the approach to renal failure.

I wanted to touch upon the diagnosis of endocarditis. Endocarditis is a clinical and microbiological diagnosis which is established using epidemiologic criteria. The criteria are called the Modified Duke Criteria. They include:

Major Criteria

Microbiologic:
Positive blood cultures (>=2) with an organism that classically causes endocarditis (viridans group streptococci, staphylococcus aureus, enterococcus, HACEK organisms)
OR
Persistantly positive (>=3 or >=2 12h apart) for another organism

Echocardiologic:
Vegetation on valve not otherwise explainable or dehiscence of mechanical valve or abscess

OR

Clinical: *NEW* (not worsening) regurgitant murmur

Minor Criteria

• Predisposition -- known pre-existing valvular disease or IVDU
• Fever
• Evidence of vascular phenomenon -- septic emboli, mycotic aneurysm, Janeway lesions,
• Immunologic: glomerulonephritis (like this case), positive RF, roth spots, Osler nodes,
• Microbiologic: Blood culture not meeting major
• Echocardiographic not meeting major

Diagnosis: 2 Major, or 1 major 3 minor, or 5 minor

The ACC has updated guidelines on the management of valvular heart disease including endocarditis and endocarditis prophylaxis. These address the diagnostic algorithm and treatment in more detail.

Day #42 - Herpes Zoster (Shingles)

This morning we discussed a case of dermatomal vessiculobullous lesions in an immunosuppressed patient.

Differential diagnosis of vessiculobullous lesions::

• Herpes zoster
• Herpes simplex
• Bullous impetigo (staph/strep)
• Ecthyma gangenosum (gram neg esp pseudomonas)
• Hemorhagic bullous cellulitis (nec fasc, clostridial myonecrosis, vibrio
• vulnificus)

• Dermatitis herpeteformis
• Bullous skin diseases (eg bullous pemphigoid)

Treatment of herpes zoster (shingles):

Should be given to:

• Immunocomprimised patients
  
• V1 Zoster (Zoster Opthalmicus)
• Ramsey hunt syndrome
• Pregnant patients
• Age over 50 (decreases incidence of zoster associated pain)
  

Should be offered to all patients within 72h of lesions

Treatment options:

Disseminated Zoster (multiple non-contiguous dermatomes) or visceral/end organ involvement should probably be initially treated with IV.

Acyclovir 10mg/kg iv q8h (needs to be renal dosed, is nephrotoxic - need to keep extremely
well hydrated to prevent acyclovir crystals causing ATN)

Acyclovir 800mg po FIVE TIMES DAILY
Famciclovir 500mg po TID
Valacyclovir 1000mg po TID

Duration depends on clinical context. Non-immunosuppressed uncomplicated zoster - 7 days

The article on the zoster vaccine is here.

Day #39 - Anemia

Today we talked about a case of hemolytic anemia in a patient with rheumatoid arthritis on immunosuppressive medications including methotrexate, azathioprine and etanercept, as well as significant alcohol use and poor nutrition.

I suspect that the anemia in this case is multifactorial. The discussant took us through an approach to anemia. I like to approach anemia in two ways:

The first is based on the size of the RBC:

1. Microcytic -- iron deficiency, hemoglobinopathy, sideroblastic anemia (lead, ETOH)
2. Normocytic -- anemia of chronic disease, mixed microcytic/normocytic cause, hypothyoidism, renal failure, acute blood loss, early iron deficiency, sometimes bone marrow suppression
3. Macrocytic -- ETOH, drugs (methotrexate, AZT), B12/folate deficiency, myelodysplasia, hereditary spherocytosis, haemolysis, cirrhosis

The second is similar to the approach to thrombocytopenia

1. Decreased production -- EPO or substrate deficiencies, bone marrow problem (infiltrative process -- mets, infection, myelodysplasia/leukemia/stage IV lymphoma, toxins like ETOH or lead, hypothryoidism)
2. Blood loss -- if big drop and no obvious external bleeding, consider retroperitoneal bleed in the appropriate context
   
3. Destruction -- haemolytic anemia (intravascular and extravascular causes)

I integrate these two approaches to formulate a focussed differential diagnosis.

In all cases of anemia a thorough blood film review can be helpful. In cases where multiple lineages are involved (such as our case today where there was a leukopenia) a concomittent bone marrow cause should be considered.

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Approach to haemolytic anemia

Extravascular

• Hemoglobinopathies, Red Cell morphology defects (spherocytosis), G6PD/PDK deficiencies
• Hyperspenism, Infections (malaria), Toxins/drugs, Microangiopathic haemolytic anemia (MAHA -- eg TTP/HUS, malignant hypertension, scleroderma renal crisis, DIC)

Intravascular

• Prosthetic valves (low grade haemolysis)
• Transfusion reacton (incompatability)
• Hypotonic infusions (i.e. IV D5W too rapidly infused)
• Infection (i.e. severe malaria, Clostridial sepsis, paroxysmal nocturnal hemoglobinuria)
• Autoimmune Haemolytic Anemia
  

"Initial Haemolytic Workup"

• CBC with blood film: may see fragments (TTP/HUS), intracellular parasites (malaria), spherocytes (autoimmune) or clues to other causes (megaloblastic in B12, etc)
  
• Reticulocyte count: should be high if bone marrow is working properly. Inadequate reticulocyte response suggests some problem with production (including substrate deficiency)
  • Reticulocyte production index (RPI) = (Retic% * Hematocrit/0.45 )/RMT where RMT = 1 if HCT ~ 0.45, 1.5 if 0.35, 2 if 0.25, 2.5 if 0.15)
  • Normal RPI is 1; the RPI should be >2 in anemia
    
• Coombs test -- looks for antibody
• LDH: should be high
• Bilirubin (indirect) should be elevated
• Haptoglobin: should be low in
• D-Dimer, PT/INR elevated in DIC
• Fibrinogen decreased in DIC
• Urine haemosiderin elevated in intravascular haemolysis

From uptodate.com: "The combination of an increased LDH and reduced haptoglobin is 90 percent specific for diagnosing hemolysis, while the combination of a normal LDH and a serum haptoglobin greater than 25 mg/dL is 92 percent sensitive for ruling out hemolysis"

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This figure from uptodate is helpful:

Day #38 - Invasive Pulmonary Aspergillosis

Today we talked about a case of a patient with acute myelogenous leukemia on chemotherapy who is presenting with febrile neutropenia.

In this case, the patient had a CT scan which had numerous pulmonary nodules with the so-called CT Halo sign (which is a nodule with ground glass haziness surrounding it). This led to the suspicion for an invasive fungal infection, the most commonly encountered in this population is invasive pulmonary aspergillosis.

If you are interested, you can email me and I will send you a copy of a talk I have given on IPA diagnosis and management.

The key to successful treatment is appropriate antifungal therapy and, if possible, recovery of the neutrophil count and reduction of immunosuppression. Treatment is "usually" for ~12 weeks or complete resolution of the clinical syndrome/lesions, whichever is longer.

Day #37 - Thyroid Cancer

Today we discussed a case of metastatic thyroid cancer complicated by complete collapse of the left lung from compression of the main-stem bronchus.

One important concept we discussed was the concept of West's zones of lung and ventillation/perfusion (V/Q) matching. The central tenant is that blood flow is proportional to gravity and therefore the best perfusion occurs at the bases in an upright pair of lungs. In a patient with complete collapse of the left lung, oxygenation can be improved by improving V/Q mismatch. This is done by "directing" perfusion to the ventillated lung by placing the good lung down. Sometimes you can even observe this effect at the bedside!

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We also discussed thyroid cancer. Evaluation of the thyroid nodule is a relatively common referral to general internists and endocrinologist. A proposed algorithm for the evaluation of solitary thryoid nodules is presented in the figure.



Thyroid malignancies include:

1. Differentiated thyroid cancers: Papillary and follicular
2. Undifferentiated thyroid cancers: Anaplastic
3. Medullary thyroid cancer (neuroendocrine tumor of the C-cells)
   
4. Thyroid lymphoma

Medullary cancers, like in this case, can occur sporatically or as part of the MEN2 syndromes (autosomal dominant):

• MEN2A -- MTC, pheochromocytoma, primary hyperparathyroidism
• MEN2B -- MTC (aggressive, high risk of death), pheochromocytoma, marfanoid habitus, mucosal neuromas
  
• Familary Medulary Thyroid Cancer -- like 2A but no pheo/PTH
  

Inherritable MTC tends to present in the 30's. Measuring serum calcitonin in response to IV calcium can serve as screening in 1st degree relatives. One can also look at the RET oncogene for mutations. Prophylactic thyroidectomy in positives.

Non-syndromic patients tend to present in their 40/50's with a palpable nodule. Often there is metastasis at presentation (primarily to locoregional lymph nodes, occasionally systemic).

Five and ten year survival varies with age. Age <40 have 95% 5 year and 75% 10y survival all-comers.

Day #36 - Acute Confusion

Today we talked about a case of an elderly woman with an acute confusion. In approaching this problem, the history is important to exclude dementia which was sub-clinical for a long period but subsequently becomes obvious to the family.

We looked at a differential for an acute change in level of consciousness and the following general framework is helpful:

1. Drugs/Iatrogenic
2. Infection
   
   • Meningitis (bacterial, viral, TB, other -- e.g. cryptococcal, neurosyphilis)
   • Encephalitis (HSV1/2, HIV, CMV, WNV, Eastern Equine encephalitis, other)
   • Non-CNS infection with delerium
     
3. Metabolic
   
   • Electrolytes (hyper Ca, hypo/hyper Na, hypoglycemia)
   • hypothyroidism. B12/folate not usually acute.
     
4. Structural
   
   • Tumour
   • Bleed (SDH, SAH, ICH)
   • Other mass lesion
   • Epileptogenic focus (post ictal)
   • Stroke syndrome
   • Vasculitis
5. End-organ Failure
   
   • Cirrhosis (encephalopathy)
   • CHF
   • Respiratory -- Hypoxemia/Hypercarbia
   • Renal - Uremia
     

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We then talked a bit about aphasias because the patient had anomia with a non-fluent aphasia and inability to understand.

Aphasias
1-naming-if normal - no aphasia
2-command-

DON'T UNDERSTAND
non fluent, no repeat - global aphasia
non fl - can repeat mixed transcortical
fluent - no repeating - wernikes
- can repeat - trans cortical sensory aphasia
UNDERSTAND
non fl--no repeat - brocas
non fl - can repeat - transcortical motor
fl - no repeat - conductive
fl - repeat - no name - nominal

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We then entertained the possibility of neurosyphilis or a paraneoplastic syndrome such as paraneoplastic limbic encephalitis.

Neurosyphilis can present with a variable presentation.

"Early" <>

• asymptomatic
• meningitis (with cranial nerve palsies)
• meningovascular -- clinical picture of strokes, recurrent. Part of the differential for stroke in the young.
• otic syphilis -- tinnitus, vertigo, hearing loss
• occular syphilis -- uveitis, retinitis, vitritis
  

"Late" >10 years

• General paresis (of the insane):
  P - personality changes
  A - affect changes
  R - reflexes (hyper-reflexia)
  E - Eye (argyll-robertson pupils)
  S - Sensorium - delusions, hallucinations
  I - Intellect
  S - Speech (abnormal)
  
• Tabes dorsalis: sensory loss (dorsal columns), ataxia, bladder dysfunction, "lightning" pains in legs
  

Patients should have a positive RPR (though can be negative) and positive confirmatory test like the TPPA.

CSF should:

1. Have a positive VDRL (specific, but not sensitive)
2. OR Have a lymphocytic pleocytosis (WBC >20) and/or protein >500mg and positive peripheral serologies
   
3. Be suspected in positive CSF FT-ABs is positive