Friday, August 28, 2015

Acute Hepatitis with Enzymes > 1000

Today's case involved a middle-aged man with not much past medical history besides hypertension.  He presented secondary to abnormal laboratory values including a bilirubin of nearly 400, and elevated transaminases into the 1000’s.  He had ascites and imaging evidence of chronic cirrhosis, as well as a portal vein thrombus.  He did, however, have normal liver enzymes only a few weeks prior to his presentation suggesting this to be an acute process.

There were multiple valuable learning points today:

-Acute transaminase elevation into the range of thousands has a limited differential diagnosis which is worth remembering.  This includes viral hepatitis, autoimmune hepatitis, acute cholangitis/gallstone obstruction, acute fatty liver of pregnancy, drug-induced heptatitis (acetaminophen, not alcohol), portal vein thrombosis, and ischemic hepatitis (shock liver as it is so lovingly called).

-We spoke briefly about the physical examination for ascites.  It is worth remembering that ankle edema has a 93% sensitivity for ascites, meaning that ascites presence is extremely unlikely if there is no ankle edema.  That said, if there is ankle edema, you need a specific test to rule in ascites.  The combination of flank dullness, a positive shifting dullness, and a positive fluid wave can be helpful in this case.  Most of your patients will receive abdominal ultrasounds anyways.

-We briefly discussed hemolysis (the other cause of hyperbilirubinemia).  The hemolytic workup includes a CBC, blood film, LDH, haptoglobin, and bilirubin.  To this I sometimes add a DAT or Coomb’s test for autoimmune hemolytic anemia, and sometimes a fibrinogen level and/or D-Dimer for consumptive coagulopathies like disseminated intravascular coagulation.

-We talked about liver function which is frequently and erroneously misinterpreted as transaminase levels.  The two are completely different and occasionally unrelated.  The liver’s function is to produce albumin, coagulation factors (check INR/PTT), eliminate nitrogenous waste (asterixis/encephalopathy), clear portal blood of toxins/nutrients (ascites and thrombocytopenia from portal hypertension), and produce glucose in states of starvation (hypoglycemia is a feature of advanced liver failure).  Transaminase elevation can occur without impairing these functions, and these functions can be quite impaired with mild or no transaminase elevation.

For further reading, I’m including a review of an approach to abnormal liver enzymes, and a review and approach to thrombotic microangiopathy, as well as the JAMA Rational Clinical Exam series article about ascites.

Further Reading:

Kaplowitz, N. (2004). Drug-induced liver injury. Clinical Infectious Diseases, 38(Supplement 2), S44-S48.

Moake, J. L. (2002). Thrombotic microangiopathies. New England Journal of Medicine, 347(8), 589-600.

Limdi, J. K., & Hyde, G. M. (2003). Evaluation of abnormal liver function tests. Postgraduate medical journal, 79(932), 307-312.


Williams, J. W., & Simel, D. L. (1992). Does This Patient Have Ascites?: How to Divine Fluid in the Abdomen. Jama, 267(19), 2645-2648.

Thursday, August 27, 2015

Secondary Hypertension and Hypertensive Emergency

Today's case involved a hypothetical young woman who presented with headache and hypertension (BP 220/120mmHg).  She had a history of poorly-controlled hypertension, albeit with some medication non-adherence.  There was no evidence of end-organ dysfunction.  There were no intoxicants on history.  On her examination, there were cafĂ©-au-lait spots and neurofibromas.  She had a mild tremor and no renal bruits.  There was no papilledema, but some A-V nicking in her fundoscopy.  She was treated with intravenous labetalol, with fairly minimal effect on her hypertension.  Her age and hypertension resistance, coupled with her spontaneous hypokalemia, prompted workup for secondary hypertension.  Her urine metanephrines were significantly elevated, and she was diagnosed with pheochromocytoma.

There were multiple learning points:

-The CHEP guidelines can be found at and they detail the indications for investigation of secondary hypertension.

-Common causes include (but are not limited to): endocrine hypertension (pheochromocytoma, hyperaldosteronism or Conn’s syndrome), renal artery stenosis, sleep apnea, alcohol withdrawal, hypercarbia and drug intoxication.

-It can be dangerous to use pure beta-blockade in a patient with catecholamine excess.  The reason for this is that some beta adrenergic receptors cause systemic vasodilatation.  When you block beta receptors selectively, you block that vasodilatation and allow unopposed alpha adrenergic stimulation to paradoxically increase the blood pressure.

-Signs of end-organ damage indicate a hypertensive emergency rather than a hypertensive urgency.  The main distinguishing point is the need for intravenous antihypertensives, which preclude ward management and mandate ICU admission.  Take end-organ damage from head to toe: cerebral hemorrhage/stroke, hypertensive encephalopathy/PRES, aortic dissection, congestive heart failure, pulmonary edema, ruptured AAA, renal damage, etc.  If it’s there, generally an intravenous agent such as labetalol or nitroprusside is useful.  The goal is to reduce the mean arterial pressure by around 25% within the first 24 hours, not to reduce them to normotension.  This is because the cerebral vasculature autoregulates and becomes accustomed to high pressures – a normal pressure to such a hypertensive patient may cause cerebral hypoperfusion and stroke.

Further Reading:

Dasgupta, K., Quinn, R. R., Zarnke, K. B., Rabi, D. M., Ravani, P., Daskalopoulou, S. S., ... & Tremblay, G. (2014). The 2014 Canadian Hypertension Education Program recommendations for blood pressure measurement, diagnosis, assessment of risk, prevention, and treatment of hypertension. Canadian Journal of Cardiology, 30(5), 485-501.

Tuesday, August 25, 2015

Asymmetric Polyarthritis in a Young Woman

Today's case was interesting and was predominantly related to diagnostic reasoning.  The patient is a young woman who presented with a year-long history of migratory arthritis with effervescent skin lesions in the area of the arthritis.   The affected joints were asymmetric, and currently involved the ankle and wrist.  She denied constitutional symptoms, alopecia, oral ulcers, photosensitivity, malar or discoid rash, hematuria, family history of connective tissue disease, or recurrent thrombosis/miscarriages.  There was no travel, and no recent infectious symptoms.   There were no other antecedent new medications, besides hydroxychloriquine having been started a short time prior to presentation.  There was no morning stiffness.

Her bloodwork revealed a microcytic anemia, leukocytosis, and normal platelet count.  Her creatinine was normal, but her urinalysis showed red cells and protein (microscopic to be performed).  Her ANA was positive at 1:320, and her anti-double stranded DNA was also positive at an outside lab (albeit not here).  Her c-ANCA was also positive.  The rest of the extractable nuclear antigens were negative.  The effused joints have not been sampled by arthrocentesis yet, and a skin biopsy is underway for the skin lesions which appear vasculitic.

There were multiple learning points from this case, and I want to stress that a seemingly complex case can be broken down into a group of syndromes such as “polyarthritis” in this case, and worked on from there:

-A polyarthritis involves a differential diagnosis which includes seropositive and seronegative entities. From the seropositive standpoint, the common things are systemic lupus erythematosus, rheumatoid arthritis, mixed connective tissue disease, and systemic sclerosis.

-There are several large groups of seronegative arthropathies, which are more likely to involve large joints in an asymmetric fashion.  These include inflammatory bowel disease-associated arthritides (usually flare concurrently with the IBD), ankylosing spondylitis, psoriatic arthritis, and reactive arthritis.  Finally, adult-onset Still’s disease would also be considered.  Typical findings would include fever, constitutional symptoms, lymphadenopathy, sore throat, a ‘salmon pink’ effervescent rash, an elevate ferritin, and leukocytosis.

-Psoriatic arthritis has five potential distributions of joint involvement: distal (DIP-predominant) arthritis, asymmetric oligoarthritis, symmetric polyarthritis (indistinguishable from rheumatoid arthritis), arthritis mutilans (destructive and deforming arthritis), and spondyloarthritis.  We discussed that the diagnostic/classification criteria for psoriatic arthritis do not mandate the presence of psoriatic skin plaques, and that they may only be discovered on a thorough skin examination after the incident presentation of the arthritis.

-We discussed reactive arthritis, which really encompasses three different syndromes.  The disease can occur following a dysenteric (bloody diarrheal) illness, following a genitourinary infection typically with Chlamydia or following a Group A streptococcal infection either through Acute Rheumatic Fever or an immune complex-mediated process.  Seeking these infectious syndromes is paramount in the diagnostic workup.

-We discussed a number of viruses that may cause joint symptoms.  While arthralgia (painful joints) are common in a number of viral infections (think of the last time you had a URTI!) only a few viruses can cause an arthritis (effused joints, or joints with pain on stress).  These include hepatitis viruses (particularly hepatitis B during immune complex clearance), acute HIV seroconversion illness, rubella, parvovirus B19 (associated with erythema infectiosum in children), mumps virus, dengue virus, enterovirus infections, and chikungunya virus.

-Other infectious etiologies included bacterial infections such as those occurring with infective endocarditis.  This can manifest either with multiple septic arthritis events as as embolic phenomena, or with an immune complex-mediated disease (remember that rheumatoid factor is often positive in bacterial endocarditis due to immune complexes).  Lyme disease could also be considered in this differential.  Both viral and bacterial causes are less likely to produce a year-long syndrome, making an inflammatory etiology more likely.

-Always consider systemic lupus in a woman of this age group.  The lupus classification crtieria include serositis (pericarditis/pleuritic), oral ulcers, photosensitivity, arthritis, blood abnormalities (cytopenias), renal disease (six types ranging from nephritic to nephrotic presentaitons), ANA, other immunological markers such as anti-Smith and anti-DS-DNA, neurologic disease, and the characteristic rashes.

Further reading:

Dhir, V., & Aggarwal, A. (2013). Psoriatic arthritis: a critical review. Clinical reviews in allergy & immunology, 44(2), 141-148.

Edwards, J., Paskins, Z., & Hassell, A. (2012). The approach to the patient presenting with multiple joint pain. Age, 15, 49.

Zochling, J., & Smith, E. U. (2010). Seronegative spondyloarthritis. Best Practice & Research Clinical Rheumatology, 24(6), 747-756.

Ytterberg, S. R. (1999). Viral arthritis. Current opinion in rheumatology, 11(4), 275-280.