Addressing DRESS

DRESS syndrome - Drug Reaction with Eosinophilia and Systemic Symptoms, also known as drug hypersensitivity reactions.

These commonly present 2 weeks after initiating a new medication with:

• Fever
• Rash: papular, macular, bullous
• Lymphadenopathy
• Arthralgias
• Hepatitis
• Eosinophilia

Medications which are commonly associated with DRESS syndrome include "aromatic" anticonvulsants (phenytoin, carbamazepine, and phenobarbitol) - but can occur with other anticonvulsants as well. Other classic DRESS syndromes occur with NSAIDs, abacavir, and allopurinol. Treatment revolves around discontinuing the culprit agent, supportive care, and perhaps steroid therapy.

In the case of abacavir, hypersensitivity reactions are known to occur more frequently in those who are HLA B5701-positive, and screening programs are now widely used to prevent this adverse reaction.

Community-Acquired Pneumonia

(the Stanly Cup, pictured left)

Community-acquired pneumonia is extremely common. When patients present with this condition, we are often faced with a situation in the ER where we either admit pateints to hospital, or decide to treat in an out-patient setting. How do we decide? There are two major ways to do this.....

• "Gestalt": take a careful history and physical exam, look at the bloodwork and chest x-ray, think about the patients' social situation and the time of day (or night), and put all the information into context and make a decision.

• Clinical Prediction Rules: There are a few of these, however the Pneumonia Severity Index (derived from PORT score) and CURB65 score are most widely used.

Pneumonia Severity Index: Here is a link to the original article from NEJM. Points are given for various clinical/historical feaures and patients are categorized into one of 5 classes. Class I, II, have very low all-cause mortality rates at 30 days and can usually be treated as outpatients. Class IV, and V have higher rates of morbidity and 30-day all cause mortality - these patients should be admitted to hospital.

CURB65: This is a much simpler scale requiring only 5 pieces of information. Here is a link to the original article in Thorax. Each feature is worth 1 point...then just add them up.

• C: confusion- disorientation to person, place, time
• U: urea >7 mmol/L
• R: respiration rate >30 breaths per minute
• B: Blood pressure- systolic <90 or diastolic <60 mmHg
  
• 65: age >65 years

30-day mortality rates are 0.6% with a score of 0, and 1.7% with a score of 1. Scores of 4 have roughly 15% 30-day mortality rates - oy vey (come find me if you don't know what that means). Patients with scores of 0 or 1 can most likely be treated as outpatients. 3 points or more should be brought into hospital, and 4 or more points should likely be evaluated by the ICU.

Remember, these scales are helpful tools meant to assist you - they are not substitutions for good clinical judgment.

Gonococcal Infection: a few syndromes

Pictured: Image from NEJM, a case of disseminated GC infection. Click here for the link. Note the tenosynovitis and 'countable' pustules.

Gonococcal Infection - syndromes:

• Localised inflammation of involved mucous membrane: urethritis, vaginitis, pharyngitis, etc.
• Pelvic inflammatory disease
• Fitz-Hugh and Curtis syndrome: inflammation of the liver capsule, from direct extension of the organism in a patient with pelvic inflammatory disease.
• Arthritis dermatitis syndrome: migratory arthralgia, tenosynovitis (Achilles, wrist,etc.), pustular lesions - usually not very many...they are "countable". Fever is common here.
  
• Septic arthritis
• Other very rare: meningitis, endocarditis

Link: updated treatment guidelines can be found here

Arthridites Associated with Inflammatory Bowel Disease

(above: monoarthritis in a patient with IBD)

Spondylitis and Sacroiliitis

• HLA B27 in 50-75% with axial arthritis
• Prolonged morning stiffness which improves with exercise
• Unrelated to GI disease...'disease discordant'
  
• Sacroiliitis may be asymptomatic
• Treatment: Back exercises, NSAIDs, maybe methotrexate
  

Peripheral arthritis

• Type 1
• Acute and pauciarticular peripheral arthritis
  
• Associated with flares of bowel disease....'disease concordant'
  
• Self limited with no joint deformity
• Knee most common site affected

• Type 2
• Polyarticular damage especially at MCPs
• Migratory
• Persist for months
• Can have exacerbations and remissions
• Treatment: NSAID/COX-2, sulfasalazine, methotrexate
  

HIV+ with Shortness of Breath

(a complex parapneumonic effusion pictured left)

Today we discussed the diagnosis and management of Parapneumonic Effusions. Check out some details here.

We also discussed an approach to patients with HIV who present with shortness of breath.

A few things to consider...

• Is this an HIV or non-HIV related condition?
• What is this patient's immune status (last CD4+ count and Viral Load)
• Is this patient on Antiretroviral therapy?
• Is this patient taking the appropriate prophylactic therapy (eg. Septra for PJP)
  
• Are there other Tuberculosis risk factors?
• Can the past medical history help me here?

HIV-related causes of shortness of breath:

1. Infectious

• Community acquired pneumonia: >10x more likely in HIV + patients with CD4+ counts less than 200. Watch out for parapneumonic effusions and empyema. S. pneumoniae is common.
  
• Pneumocystis Carinii Pneumonia or Pneumocystis Jirovecii Pneumonia or PCP or PJP... whatever you want to call it, this is still the most common AIDS-defining opportunistic infection. You can read more on this here.
• Viral: Influenza, CMV
• Tuberculosis must be considered, but also think about non-tuberculous mycobacteria as well, like MAC (usually disseminated rather than pulmonary)
  
• Fungal: Cryptococcus, Histoplasma, Coccidioides. Also think about Aspergillus - though more common in neutropenia.

2. Malignant:

• Lymphoma: non-Hodgkins > Hodgkins
  
• Kaposi's sarcoma and associated Castleman's Disease
• Metastatic disease
  

3. Other:

• Cardiovascular: think about cardiomyopathy or other cardiac risk factors associated with HIV as a cause for shortness of breath
• Pulmonary Hypertension
• Drug toxicity
  
• Inflammatory conditions

A Good Link:

• Here is a great case and approach to shortness of breath in HIV+ individuals.
  

Lemierre's Syndrome

(pictured left: image from NEJM...arrow pointing to a thrombosed jugular vein)

Lemierre's Syndrome

What is it? a septic thrombus of the jugular vein.

Which bacteria are implicated? usually oral flora, and typically Fusobacterium species.

How does one get it? typically after acute pharyngitis, there may be a small abscess or erosion of the mucosa. Bacteria can then invade the peri-pharyngeal space which houses the carotid sheath (encasing the jugular vein), and neck musculature.

How do patients present? more common in younger patients with a prodrome of a sore throat. They commonly have a fever, and possibly tenderness over the thrombosed vein. Septic emboli frequently spread to the lungs so an element of respiratory distress may be seen.

Treatment? use a beta-lactamase resistant beta-lactam. Surgical exploration may be required. The role of anticoagulation is controversial.

A great reference: check out this case

The Solitary Pulmonary Nodule

An Approach to the solitary pulmonary nodule.....

Differential Diagnosis:

• Malignant: can be primary (adenoCa, squamous, large cell, or small cell), or metastatic
• Infectious: Granuloma from TB or fungal infection (eg. histoplasmosis, coccidiomycosis), abscess, aspergilloma
• Vascular: arteriovenous malformation, infarction
• Inflammatory: Wegener's granulomatosis, rheumatoid nodule
• Benign neoplasm: hamartoma, lipoma

Risk Factors for Malignancy:

• Size greater than 3 centimeters
• spiculated border
• "eccentric" calcification pattern (see above image; calcium deposition is off-centre)
• doubling time of the nodule is between 20 and 400 days
• Clinical clues: constitutional symptoms, smoking history

As always:

• Take a good history and physical exam
  
• Get an old Chest X-ray
• If you susptect malignancy: Get a tissue sample with Bronchoscopy vs Video-Assisted Thorascopic Surgery vs Open Thorascopy

A good link:

• approach to the solitary pulmonary nodule from NEJM.

Pancreatitis

We have previously discussed our physical exam and diagnostic approach to Ascites here.

The mainstays of treating pancreatitis includes identifying an underlying cause and correcting it (eg. gallstone, hypertriglyceridemia, hypercalcemia, etc.), pain control and fluid resuscitation. Other issues that should be considered are feeding status and preventing infection.

1. Infection: patients are prone to infection by translocation of gut organisms if pancreatic necrosis is present. There is debate in the literature whether prophylactic antibiotics are indicated, and this uncertainty is reflected in guidelines from gastroenterology societies - one recommends it, one does not. Take a look at this Cochrane review and decide for yourself: http://www.cochrane.org/reviews/en/ab002941.html

2. Feeding: The classic teaching was that we do not feed our patients with acute pancreatitis. Newer evidence suggests that early oral feeding is alright if the patient can tolerate it. Here is a good meta analysis from the BMJ.

This is a good review article from NEJM touching on most of these topics

Physical Exam for Pulmonary Hypertension

Physical Exam for Pulmonary Hypertension:

• JVP: may be elevated with prominent A waves (from right ventricular hypertrophy). CV waves are seen in tricuspid regurgitation. A positive Kussmaul's sign and Abdominal Jugular Reflux will be seen if there is right ventricular failure.
• Inspection of the precordium: look for an apical beat. This may be displaced when left ventricular failure is the cause of pulmonary hypertension. Also look for right ventricular heaves.
• Palpation: palpate for a right ventricular heave and sub-xyphoid impulsations (from RV hypertrophy). You may also find a palpable P2. There may be a pulsatile liver edge from tricuspid regurgitation.
• Auscultation: listen for a normal S1 and loud S2. There may also be a split S2. You may hear a right sided S3 in right ventricular failure, or a right sided S4 in right ventricular hypertrophy. Finally, listen for the murmur of tricuspid regurgitation - a systolic murmur best heard at the left lower sternal border that classically gets louder with inspiration (Carvallo's sign).
• Other: patients may have peripheral edema, and rarely ascites.

Links: here is a good review article on the causes of pulmonary hypertension.

Thyroid Cancers

(psammomma body in Papillary thyroid cancer)

There are many types of thyroid malignancies

• Papillary carcinoma: Very common, spreads via lymphatics, more common in woman (3:1) aged 30-50, very high cure rate. Psammomma bodies are seen on histology.
• Follicular carcinoma: The second most common thyroid cancer behind Papillary. This spreads hematogenously, so distant metastases are more common. It typically presents in the 40-60 year old age group with a cold thyroid nodule. It is difficult to distinguish between a follicular adenoma and carcinoma on cytology - so often a partial thyroidectomy is preferred over a fine needle aspiration for diagnosis.
  
• Medullary carcinoma: This originates from C-cells (involved in calictonin production). This commonly affects families and is associated with the Multiple Endocrine Neoplasia syndromes. We discussed these here.
• Anaplastic carcinoma: These are very undifferentiated tumors. Fortunately they are uncommon as the cure rate is low and life span is usually measured in months

A few other thyroid cancers to remember:

• Lymphoma
• Metastatic disease

Here is a good approach to the Thyroid Nodule.

Less is More...

The Syndrome of "Leser and Trelat" came up today in our discussion. It is certainly not that common, but one we should know about. This is a rapid eruption of seborrheic keratoses which can be pruritic and have an inflammatory base. It is a paraneoplastic condition commonly associated with intraabdominal malignancies - particularly gastrointestinal adenocarcinoma.

Here is a case from NEJM.

my mumps,......my mumps my mumps my mumps...check it out.

Please pardon the horrible Black Eyed Peas reference.

A great "Advanced Morning Report" today. We discussed a case that was likely Mumps.

More details can be found here.

HoPingKong-isms

(hyperthermia can cause rhabdomyolysis)

1. "....What are you lying on? This is a giant question...a maximus question....are you crushed by this?"..... this was in the context of patients found either unconscious or unable to get up for prolonged periods of time. He is referring to rhabdomyolysis. The 'maximus' comment must refer to the gluteus maximus, and the 'are you crushed?'....for sure that is for crush injuries. We discussed rhabdomyolysis here.

2. "...Let's think about cardiac causes of syncope...hey....Adam is here today...". Yep, this is a Stokes-Adams Attack, named after William Stokes and Robert Adams - two Irish physicians.

3. "...Sometimes you have overt alcoholics, then there are social drinkers...I'm thinking of the smallest room in the house..." So what's the smallest room in the house? The closet. He was referring to "closet alcoholics". We discussed alcohol related issues here, seizure disorders here, and toxic alcohol ingestions here.

4. "....Think about Captain Morgan!...". This was said in the context of him shaking his arms and head - convulsing. "Yes...this is a 'Rum Fit'". Also known as an alcohol withdrawal seizure. Remember your CAGE questionnaire to screen for alcohol-related problems:

• do you feel the need to Cut back your drinking?
• do you ever feel Annoyed at people critiquing your drinking?
• do you ever feel Guilty about your alcohol consumption?
• do you ever have an Eye opener? (Alcohol first thing in the morning)

• 1 point is given every time your patient answers "yes" to a question. ....then you just add up the points.
  

• Most patients with alcohol dependence will have a score of 2 or greater. About 80% of patients without alcoholism will score 0 points.
  

Here is a paper from JAMA written by local talent on the utility of alcohol screening tools.

There is the artist formerly known as Prince...

....and the pneumonia formerly known as Pneumocystis Carinii Pneumonia. Many people still refer to it as PCP , but you will also hear it called Pneumocystis Jirovecii Pneumonia (PJP). Either is fine. It is a common respiratory opportunistic infection in HIV+ individuals. Those with a CD4 count less than 200 are at the greatest risk. It is a protozoa, and is found ubiquitously in soil - we are all exposed, but this organism poses few problems to healthy immune systems.

The classic clinical presentation is dyspnea with subacute onset, and a dry cough. Patients may have a low-grade fever, tachycardia, and tachypnea. The chest exam is variable - you may hear crackles...you may have a normal exam (in up to 50% of cases). The Chest X-ray often reveals bilateral interstitial infiltrates, but virtually any abnormality may be seen.

Remember, we can make the diagnosis roughly 90% of the time with history and physical exam alone. Still, it is nice to confirm your diagnosis by isolating an organism. Methenamine silver or Immunofluorescent stains on induced sputum (or bronchoalveolar lavage) has a high sensitivity and specificity.

Treatment: TMP-SMX in high doses. This has some interesting complications associated with it (see below). If patients are allergic to sulfa drugs or have complications, other agents can be used, such as TMP-Dapsone, or Atovaquone.

Steroids? Yep. If the PaO2 is less than 70, this is very helpful. Of note, this was a major breakthrough in medicine and was discovered by local talent here in Toronto.

What else? Watch these patients closely. There is often a profound inflammatory reaction to the dying organisms, and patients often get worse on day 2-ish of treatment. That is why the steroids are added in severe disease.

Links:

• Treatment guidelines for HIV can be found here.
• Treatment guidelines for Opportunistic infections are here.
• A great review of PCP from NEJM here.
• Local talent publishing on an interesting complication from high dose trimethoprim-sulfamethoxazole.
  

Below: Methenamine silver (top) and Immunofluorescent (bottom) stains on induced sputum showing PCP.

Would you like fries with that?

Today we discussed Non-Alcoholic Fatty Liver Disease.

We have previously discussed the etiology of liver diseases here, and some complications of liver disease like ascites here, and spontaneous bacterial peritonitis here.

I don't know about you, but I'm dying for a burger right now.

Check out this review from CMAJ on Non-Alcoholic Fatty Liver Disease.

No Country for Old ________........

(Does this man have acromegaly?)











Multiple Endocrine Neoplasia (MEN) syndromes can often be a bit confusing. It should be considered in those with....uhhhh....endocrine neoplasia - at multiple sites.

MEN 1: An autosomal dominant disease with mutations in the MENIN gene.
Remember "the 3 P's":

• Pituitary tumors: particularly the anterior pituitary.
• Pancreas: islet cell tumors like Insulinomas, Glucagonomas, and VIPomas.
• Parathyroid hyperplasia, usually in all glands.

MEN 2: Also an autosomal dominant disease. The mutation is in the RET proto-onco gene.

• MEN 2A: aka Sipple Syndrome
  
• Medullary thyroid cancer; typically bilateral. In non-MEN disease this is mostly unilateral.
  
• Pheochromocytoma in about 50%. Also can be bilateral.
• Parathyroid hyperplasia

• Men 2B
• Medullary thyroid cancer: as above.
• Parathyroid hyperplasia: as above.
• Marfanoid habitus: high arched palate, pectus excivatum.
  

HoPingKong-isms

(Modigliani's Paul Guillaume Novo Pillota. In Paris' Musee d'Orangerie)

1. "....if you are anemic with your chronic renal failure, are you drinking the Tour de France drink?..." Okay...this one isn't too tough. He is referring to erythropoietin, a glycoprotein hormone produced by interstitial fibroblasts in the renal cortex, responsible for stimulating red blood cell production. Patients with chronic renal failure commonly have anemia secondary to low levels of this hormone. It is also a common performance enhancing drug which some famous athletes on the Tour de France were caught with recently.

2. "....is is hard to diagnose rheumatoid arthritis? No, they are usually deviant...". I liked this one. He is referring to ulnar deviation of the metacarpal bones in RA. Other common findings in the rheumatoid hand include swelling of the small joints - namely the MCPs and the PIPs, swan neck and boutonniere deformities in the fingers, median nerve entrapment, and trigger fingers (from nodules forming on tendon sheaths).

3. "...do you do math? Adding and subtracting? C'mon...this is a crisis!..." This was mentioned in the context of an elderly person on longstanding prednisone for a hemolytic anemia. "Adding"? "Crisis"? In a person on steroids? Yes, this is an Addisonian Crisis (adrenal crisis). Patients may present with clinical evidence of volume depletion, nausea, vomiting, shock, abdominal pain, and hyperkalemia with or without hyponatremia and hypoglycemia.

4. "...is it dangerous to take antibiotics? Is this a difficult hospital...?" Hmmm...'antibiotics'? 'Difficult'? Yep, this has got to be Clostridium difficile infection. A good review by local talent can be found here.

5. "...you look unflappable....is it frosty in here?...." I really liked this one. We were discussing a case of an elderly gentleman who presented with 1 week of malaise. He is referring to some signs of renal failure, including asterixis (unflappable - may also be seen in hepatic encephalopathy or hypercarbia), and the uremic frost. We don't really see uremic frost all that much - it's from severe uremia such that there are nitrogenous deposits on the skin Here's a case from NEJM with picture below.

Oh Schist!(....ocyte)

Microangiopathic Hemolytic Anemia (MAHA):

It is important to rule out the microangiopathic hemolytic anemia's when you see a CBC with anemia and thrombocytopenia. After a very detailed history and physical exam, a few additional tests must be done to clinch the diagnosis:

• Hemolyitic work up: LDH, unconjugated bilirubin, haptoglobin
• Coomb's test: to assess for autoimmune hemolytic anemia
• Blood film: looking for schistocytes
  

If there your patient has biochemical evidence of hemolysis and schistocytes on the blood film then this is likely MAHA. Note that a positive Coomb's test in autoimmune hemolysis will typically be associated with spherocytes on the blood film - this is not MAHA

What are some of the more important causes of MAHA?

1. Thrombotic Thrombocytopenia Purpura: presents with a classic pentad of fever, neurologic changes, renal failure, hemolytic anemia, and thrombocytopenia....although most patients have only 2-3 of these features. A great case-based approach to TTP can be found here.
   
2. Hemolytic Uremic Syndrome: on the same spectrum as TTP, more common in children, and as the name implies it has a renal failure phenotype. Here is a cool paper from JAMA looking at the risk of developing HUS after treating E. coli 0157:H7 strains.
   
3. Disseminated Intravascular Coagulation: check for coagulopathy with an INR, PTT, fibrinogen, and fibrin degradation products.
   
4. HELLP Syndrome: a variant of pre-eclampsia with hemolysis, elevated liver enzymes, and low platelets. Read more about this here.
   
5. Malignant Hypertension. More on this here.
   

Mitral Regurgitation

Mitral regurgitation is common. When you hear this murmur and are trying to determine the underlying cause, think about the individual components of the mitral valve, and particular disease states which may affect them. Let's start at the annulus, and work our way down:

1. Annulus: This may be dilated from cardiomyopathies, or calcified in diseases like rheumatic fever or chronic renal failure.
2. Leaflets: The mitral leaflets can fail in a number of disease states, including infectious endocarditis (acute or chronic), rheumatic fever, autoimmune conditions (SLE, scleroderma), myxomatous degeneration (MVP), connective tissue diseases (eg. Marfans), and congenital malformations.
3. Chordae: These can be damaged or rupture under ischemic, infected, or traumatic conditions and in rheumatic heart disease.
4. Papillary Muscle: These muscles can rupture after trauma or infarct. They become 'dysfunctional' under ischemic conditions, or when the LV becomes dilated (myopathy or aneurysm). Papillary muscle can also become infected, and rarely can have infiltration with amyloid deposits or granuloma (eg. sarcoid).

Here is a good review on the evaluation and management of mitral regurgitation from NEJM.

"Shot through the heart, and you're to blame.....You give love a bad name "......Bon Jovi, circa 1986

Pericarditis: an approach....

1. Idiopathic: many patients do not have an underlying etiology established. We assume that many of these patients have a 'viral' pericarditis.
2. Infectious:
   • Viral: classically Coxsackie, Echovirus, and Adenovirus, but certainly others.
   • Bacterial: think about Staph and Strep species, and never forget TB (mycobacterial)
   • Fungal: Histoplasmosis, Aspergillosis, Blastomycosis
   • Parasitic: Toxoplasomosis, Echinococcus
3. Malignant: usually metastatic disease like lung or breast cancers, or lymphoma.
4. Autoimmune: Think about lupus, rheumatoid arthritis, and mixed connective tissue diseases.
5. Metabolic: Uremic pericarditis is common, and hypothyroidism can cause a pericardial effusion.
6. Cardiac: a pericarditis can be seen early after an infarction, or sometimes within 3-4 weeks afterwards....the so called Dressler's Syndrome.
7. Drugs: can cause a drug-induced lupus. Common culprits include procainamide, INH, and hydralazine.
8. Other things: Radiation, Trauma.