Case summary: Thanks to Vaibhav for presenting this case of a 74M with DMT2, HLD presenting with mild transaminitis and imaging findings of fatty infiltration, possible early cirrhosis and lesions concerning for HCC.
See these prior morning report pearls from our favorite Anna Parks that reviewed causes of liver masses in a non-cirrhotic liver and cancers that do not need biopsy.
The big take away points are:
- Cancers you can diagnose without biopsy:
- HCC- CT quad phase or MRI based on “LI-RADS”
- Testicular cancer- orchiectomy
- RCC- nephrectomy
- Diseases that can lead to HCC without cirrhosis: think about HBV, NASH, alpha-1-anti-trypsin, and transformation of a hepatic adenoma.
How do we diagnose cirrhosis?
- Liver biopsy is the gold standard but often not necessary if clinical findings, laboratory results and imaging findings are consistent with cirrhosis
- See this excellent NEJM review article of the role of liver biopsy in the diagnosis of cirrhosis.
- Ways of measuring fibrosis besides a biopsy
- Indirect serologic markers
- Using AST/ALT and platelets to give a risk score for fibrosis
- In chronic liver disease AST/ALT is often elevated due to decreased clearance of AST and decreased production of ALT
- Based on evidence that in cirrhosis the AST/ALT ratio is important
- Thrombocytopenia is the earliest routine laboratory indicator of cirrhosis due to decreased thrombopoetin production by the liver and splenic sequestration from portal hypertension
- Examples: NAFLD Fibrosis Score, APRI, FIB-4
- Direct Serologic markers
- Direct measures of fibrosis assess circulating evidence of fibrogenesis, fibrinolysis, or both.
- Proprietary algorithms for these assays are commercially available:
- FibroTest (BioPredictive) (known as FibroSure [LabCorp] in the United States), FibroMeter (Echosens), HepaScore (Quest Diagnostics), FIBROSpect (Prometheus Laboratories), and the Enhanced Liver Fibrosis Score (Siemens Healthcare Diagnostics)
- More expensive and less available than indirect markers
- Variety of ways: vibration-controlled transient elastography, magnetic resonance elastography, acoustic radiation force–based elastography, and shear wave elastography
- Wave is introduced into liver via probe and then the wave propagation is measured by a receiver probe
- Waves velocity is converted into a measure of liver stiffness
- Consider liver biopsy in a patient with intermediate fibrosis score or discordant results between tests and imaging if a biopsy would change management
- Other ways non-invasive measures of liver fibrosis are helpful
- Risk stratify patients
- Example: Numerous patietns have NAFLD but not all will need to see a liver specialist
- Guide treatment decisions
- Example in a patient with chronic HBV to determine if they need treatment
- Predict adverse outcomes
- Predict which patients are at risk of disease related complications and death
Case summary: Thanks to Adam Tabbaa (double-double) for presenting a case of a 70M with PMH obesity presenting with LLE edema and dyspnea and found to have a PE that made our nerd-hearts sing!
- Anti-coag clinic pearl: for patients with a positive LE ultrasound OR CTPE, getting that second confirmatory imaging study (e.g. either CTPE or LE ultrasound) can seem like overkill. However, for providers who follow patients longitudinally, this additional imaging is useful (e.g. for serial imaging comparison, to monitor clot burden when considering whether to come off of anticoagulation)
- The most recent CHEST VTE guidelines recommend DOACs (e.g. apixaban) as FIRST LINE for DVT/PE over vitamin K antagonists except patients with cancer-associated thrombosis (though clinical trials are underway to test DOACs in cancer).
- Per a recent NEJM study, there is little benefit to screening for malignancy in unprovoked PE.
Why get an ultrasound in addition to a CTPE? Can be helpful for providers who follow patients longitudinally!
- Serial imaging comparison
- Helps when trying to get patients OFF anticoagulation (can follow serial U/S)
- Helps if patient has subsegmental PE on CTPE (if have a DVT, this supports anticoagulation)
No benefit to screening for malignancy with CT abdomen/pelvis in unprovoked PE
- 854 patients randomized to limited cancer screening (basic blood testing, chest radiography, and screening for breast, cervical, and prostate cancer) versus limited + CT A/P. There was no significant difference between the two study groups in the mean time to a cancer diagnosis (4.2 months in the limited-screening group and 4.0 months in the limited-screening-plus-CT group, P=0.88) or in cancer-related mortality (1.4% and 0.9%, P=0.75).
DOACs are FIRST LINE for DVT/PE!
- In AT10, the first-line recommended anticoagulant therapy includes dabigatran, rivaroxaban, apixaban, or edoxaban over vitamin K antagonists (VKA) or low molecular weight heparin (LMWH).
- The one exception is in patients with cancer-associated thrombosis. In this subset, AT10 recommends LMWH over VKA or DOACs with extended therapy.
PE Risk stratification
- Rely on vital signs, biochemical markers, TTE and imaging to risk stratify VTE patients.
- Note that degree of clot burden does not factor into risk stratification (as long as PE is segmental).
- Here is a nifty risk stratification algorithm.
Management of PE: An Update. J Am Coll Cardiol 2016;67;976-990.
Thank you to Kendra Wulczyn and Cynthia, our Sub-I, for presenting a very interesting case of a patient with 4 months of weight loss, confusion who presented initially with hypotension and tachycardia, ultimately found to have a new diagnosis of HIV and HIV-Encephalopathy which is now responding well to ART. Special thanks to Susa Coffey, our HIV expert for dropping lots of knowledge!
- Indolent HIV-associated infections causing AMS to consider: TB, CNS lymphoma, endemic fungal infections, PML (related to JC virus)
- HIV-encephalopathy is part of a broader category of HIV-associated neurocognitive disorders that can range from asymptomatic changes is neurocognitive function to dementia
- HIV-Encephalopathy should be considered when infectious and malignancy-associated diagnoses have been ruled out and there are characteristic MRI findings (discussed below).
HIV-Associated Neurocognitive disorders include a broad-spectrum of disease
- Asymptomatic neurocognitive impairment
- Mild neurocognitive impairment
- HIV dementia
- HIV is neuroinvasive – HIV invades mononuclear cells in the CNS
- Infected cells -> microglial activation -> diffuse myelin loss -> neuronal death -> astroglial proliferation
- ARVs can have low penetrance through the blood-brain barrier
- Remember that the pathophysiology of HIV-related neurocognitive disorders coincides with normal aging and now there are many more older people with HIV
The clinical syndrome of HAD comprises of a combination of cognitive, behavioral and motor dysfunction like gait disturbance and tremors . While there is some individual variation, frequent manifestations include: inattention and reduced concentration, apathy and dulling of personality, psychomotor slowing, marked motor slowing and ataxia.
Often presents after years of untreated HIV and with low CD4 counts.
- Rule out infectious etiologies and PML (JC virus)
- Brain parenchymal loss – increased CSF fluid, decrease in striatal gray matter volume, decrease in cerebral white matter volume
- Patchy areas of high signal intensity on T2-weighted and fluid-attenuated inversion recovery sequences with relative sparing of the subcortical white matter and posterior fossa structures.
-HAART treatment – although variable in the degree to which this reverses the cognitive impairment
- Mateen FJ & Mills EJ. (2012). Aging and HIV-related cognitive loss. JAMA 308(4):349-350.
- Silva MTT, Wagner S, Grinsztejn B. (2009). Human immunodeficiency virus encephalopathy: Cognitive and radiographic improvement after antiretroviral therapy. Arch Neurol. 66(8):1040-1041.
- HIV Encephalopathy: https://www.evernote.com/shard/s509/sh/ac41a753-0706-4fe7-899f-45e4160734b3/de194e1409950b0c41954c964057e749
Cardiology Report Pearls 9/19/17 – Syncope & Aortic Stenosis
Thank you, Kelly, for presenting a case of an older male who presented with exertional syncope found to have severe, progressive aortic stenosis.
- Aortic stenosis with a tricuspid aortic valve is generally a disease of octogenarians. If presenting earlier, consider monocuspid (20-30s) or bicuspid valves (40s-60s).
- Remember that bicuspid aortic valves are also associated with aortic root dilatation – which increases the risk of both aortic insufficiency and aortic dissection.
- Severity of aortic stenosis is determined by valve area (< 1.1 cm), peak velocity (> across the valve, and gradient across the valve. These metrics have some caveats (e.g low EF and cirrhosis c/b portal HTN) and are very operator dependent.
Approach to Sudden Collapse:
- Abnormal structural
- HCM (35%) -> also remember ARVC or LV non-compaction
- Anomalous origin of a coronary artery (17%)
- Myocarditis (6%)
- Valvular – mitral valve prolapse or aortic stenosis (~2%)
- Structural normal
- Long QtC
- Channel defects such as Brugada syndrome
- Catecholaminergic polymorphic VT
- Electrolytes – Potassium, Magnesium, Calcium
- Trauma – commotio cordis
- Heat Stroke
- Seizure or neurological – bleeds
- Toxicology – supplements in athletes
Flashback to this previous post on syncope.
Schematic of the Continuity Equation to Calculate Velocity:
Survival in Aortic Stenosis
Remember the big 3 symptoms that portend significantly increased mortality in aortic stenosis: syncope, angina, and heart failure. Mortality remains low while patients are asymptomatic. After angina, syncope, or dyspnea related to heart failure develops, the prognosis worsens dramatically if severe aortic stenosis is left untreated. The epidemiology of untreated and treated aortic stenosis was first described in the 1960s by Ross and Braunwald.
Simplified Approach to Management of Aortic Stenosis:
Case summary: We chatted about an 83M with PMH mod-severe aortic stenosis (AS) and myelodysplastic syndrome (MDS) who presented with fatigue and was found to have new heart failure from his AS and slowly downtrending hemoglobin. Gerald Hsu made a guest appearance and taught us a ton about MDS!
- Myelodysplastic syndrome (MDS)- a clonal stem cell disorder of ineffective hematopoesis– encompasses a spectrum of phenotypes ranging from asymptomatic patients with macrocytic anemia to transformation to acute myeloid leukemia.
- The severity of MDS is based on the magnitude of cytopenias, bone marrow blast percentage, and cytogenetic abnormalities. These are combined into a scoring system called the revised International Prognostic Scoring System (IPSS-R) that divides patients into high- and low-risk categories.
- Higher-risk patients are at increased risk of progression to AML and short survival, which directs treatment toward altering the natural history of the disease. For lower-risk patients, the priority is treatment of cytopenias to improve quality of life.
Myelodysplastic syndrome crash course
- MDS is the most common myeloid neoplasm in the US, with 15,000 new diagnoses annually
- Blood smear:
- Red and white blood cells are most commonly dysplastic
- Red cells- macrocytosis, ovalomacrocytosis most common but can see elliptocytes, teardrops, acanthocytes (spur cells), basophilic stippling, Howell-Jolly bodies and nucleated reds
- White blood cells- pseudo-pelter-Huet, which are WBCs with reduced segmentation and granulation
- You can consider MDS as a spectrum disorder similar to colon cancer
- Some patients have small hyperplastic polyps that rarely progress to cancer
- Others have large tubular adenomas that commonly undergo malignant transformation
- Use the International Prognostic Scoring System (IPSS-R) to stratify MDS patients into low-risk and high-risk categories and direct treatment
- high-risk patients have a median survival of <1 year
- survival in high-risk MDS is worse than stage IV non-small cell lung cancer!
- it’s therefore imperative to start therapy (taking performance status, competing comorbidities, etc. into account)
- options include: stem cell transplant, hypomethylating agents (e.g. azacitadine) or chemotherapy
- low-risk patients have a median survival >8 years
- over half of low risk MDS patients die from something else before succumbing to MDS and/or AML
- the predominant cytopenia is anemia, which is managed with transfusions and erythropoiesis stimulating agents (e.g. Epo)
- if patients fail these therapies, hypomethylating agents and lenalidomide can be effective in a minority of patients
- See these two great articles for more details: low-risk & high-risk
Thank you to Mike Incze for presenting a SUPER interesting case of a patient with a history of Parkinson’s Disease who presented with fever, ridigity, tremor. CSF showed an elevated protein. In looking into this presentation, I learned about a clinical entity called Parkinsonism-Hyperpyrexia Syndrome (aka Akinetic Crisis). See below for more details
CSF Fluid Analysis:
Purulent meningitis (bacterial) community-acquired
Granulomatous meningitis (mycobacterial, fungal)
100-1000, mostly lymphocytes
100-1000, mostly lymphocytes
Moderately high (<50)
Normal to slightly elevated
Aseptic meningitis, viral or meningoencephalitis
25-2000, mostly lymphocytes
Normal or low
Neighborhood reaction – infection near CNS that spills cells, protein into CNS
Normal or high
Isolated Elevated Protein in CSF Fluid:
- Immunoglobulins typically excluded by blood-brain barrier
- Can occur either if disruption of blood-brain barrier or intrathecal production of IgG (multiple sclerosis)
- Infections (Lyme disease)
- Lymphoproliferative disease
- Multiple sclerosis
- Autoimmune diseases
- Brain tumors
- TB meningitis
- Subarachnoid hemorrhage
- Leptomeningial disease
Case reports exist for patients who develop a clinical entity similar in nature to neuroleptic malignant syndrome (NMS) in the context of sudden withdrawal of medications or dose reductions of levodopa or dopamine agonists OR administration of typical and some atypical neuroleptics.
Pathophysiology (Similar to NMS):
-Blockage of dopamine receptors (or acute withdrawal of dopamine agonists) is the primary driver and effects correlate to different locations of dopamine receptors
- Hypothalamus = Hyperthermia
- Nigrostriatal pathways = Rigidity and Tremor
-Alternative hypothesis, rigidity and muscle damage effects the peripheral muscle system due to direct changes on the muscle mitochondrial function.
Clinical Presentation of Akinetic Crisis:
- Altered mental status
- Total Akinesia with dysphagia
- Elevation of muscle enzymes
-Replace the anti-Parkinson medications at the dose that was used prior to the onset of symptoms
-Note: You can give meds orally via NG tube OR IV, there are also transdermal, IV and infusion agents
-Recommended to admit to the ICU for monitoring especially if significant hyperthermia and rigidity
-If not getting better after giving anti-Parkinson meds, consider dantrolene, bromocriptine, and/or amantadine (although there is not an evidence basis for these medications!)
- Onorfj M et al. (2009). Emergencies in parkinsonism: akinetic crisis, life-threatening dyskinesias and polyneuropathy during L-Dopa gel treatment. Parkinsonism and Related Disorders. 15S3: S233-S236
- Thomas A et al. (2003). Acute akinesia or akinetic crisis in Parksinson’s Disease. Neurol Sci. 24:219-220.
- CSF Fluid Analysis: https://www.evernote.com/shard/s509/sh/30cbf910-2a2e-4581-8a31-a23343e6fdf5/db7a8e1506919c51a0e35f517f0d9eb2
- Parkinson’s Disease Overview: https://www.evernote.com/shard/s509/sh/a417cadc-e2df-480c-a4ca-aabfff701d6e/28fe44a36757ab53454d58a8656d3340
- Parkinsonism-Hyperpyrexia Syndrome: https://www.evernote.com/shard/s509/sh/6e482206-fa77-4597-8d5a-0fcf43efb64c/b9f7eda61ac857337f3e6aae73d5e7bc
Thank you to Rabih for presenting this interested case of a young man presenting to clinic with fatigue, weight gain, hypopigmented skin lesions found to have pernicious anemia, hashimoto’s and possible vitiligo.
Key Learning Points
- For skin hypopigmentation try to determine if there is complete depigmentation vs. hypopigmentation to narrow your differential
- Decision to treat subclinical hypothyroidism is based on level of TSH elevation, age, CV risk factors, and symptoms
- Consider pernicious anemia as a cause of B12 deficiency especially in patients with other autoimmune diseases
Hypopigmentation of the skin
- First try to determine if it is complete depigmentation or hypopigmentation. This can be difficult especially in lighter skin individuals.
- Vitiligo – most frequent cause of depigmentation
- Loss of epidermal melanocytes
- Etiology not known, but associated with autoimmune diseases
- No racial or ethnic propensity but often causing more impact on darker skin individuals due to is being more disfiguring
- Consider exposures to chemicals (such as those found in hair dyes, insecticides, adhesives) or meds (topical steroids, imatinib, pegylated interferon)
- Commonly seen after an inflammatory skin process
- Infections – pityriasis versicolor, leprosy, syphilis, non-syphilis treponema, onchocerciasis
- Atopic – pityriasis alba
- Rheumatologic causes – scleroderma, discoid lupus
- idiopathic guttate hypomelanosis – seen with aging
- progressive macular hypomelanosis – unknown cause, possibly related to infection, typically seen in young adults, more common in darker skin individuals
- Nutritional deficiencies – B12, copper, iron, kwashiorkor
- Endocrinopathies – hypopituitarism, Cushing syndrome,
- Definition: Elevated TSH with Normal T4
- Always recheck after 2-3 months given these are numbers are dynamic to confirm subclinical hypothyroidism
- When should we treat subclinical hypothyroidism? Based on TSH level, age, symptoms, TPO antibody status, and CV risk factors
- TSH >10
- Treat all patients <70
- For patients >70 only treat if symptoms are present or have +TPO antibody
- TSH 7-10
- If symptoms are present
- If patient is <70 and has cardiac risk factors or has +TPO
- Patients who are younger and have +TPO antibodies are more likely to progress to overt hypothyroidism
- TSH 4-7 AND
- Symptoms of hypothyroidism: consider 6 month trial of treatment but stop therapy is symptoms do not improve with treatment
- See this discussion in NEJM for more review of subclinical hypothyroidism
- Recent study in NEJM showed no benefit to treating subclinical hypothyroidism in adult s> 65 years
Pernicious Anemia Fun Facts
- What is pernicious anemia? Anemia due to autoimmune atrophic gastritis.
- Autoanitbodies to intrinsic factor and parietal cells –> Loss of parietal cell mass –> hypochlorhydria and inadequate production of intrinsic factor –> B12 malabsorption –> anemia
- It is called pernicious anemia because when it was described patients symptoms would progress gradually over time without available treatment
- Macrocytic anemia, low B12
- Autoantibodies to parietal cells and intrinsic factor
- Antibodies to IF are specific but not sensitive
- Antibodies to parietal cells have better sensitivity, but only ~80%
- If high enough concern and negative antibodies, may need EGD with biopsy demonstrating atrophic gastritis in the gastric body
- Can also check serum gastrin which will be elevated
- 40% of patients will have autoimmune thyroid disease
- There is a theory that H. pylori infection may trigger the autoimmune destruction of parietal cells. However patients with pernicious anemia are less likely than age matched controls to have h. pylori. Associated with H. pylori infection thought possibly due to active infection gradually replaced by an autoimmune process
- Increased risk of gastric neuroendocrine tumors and adenocarcinoma