All posts by vmcimchiefs

AST/ALT in thousands… Acute Hepatitis A! 3/12/2019

March 12, 2019 vmcimchiefs Leave a comment

Thanks to Kevin and Brayden for presenting a 36yo F with no medical history presenting with acute abdominal pain, nausea, and anorexia. Her AST/ALTs were in the thousands and she was ultimately diagnosed with acute hepatitis A! Incidentally her HB Core Ab came back “borderline…”

AST ALT Elevation

If AST/ALTs are in the thousands, there are only a few entities that can cause this:
- Ischemia (shock liver)
- Toxins (Tylenol is most common), Amanita aka magic mushrooms, herbal supplements (we don’t know what they put in these!)
- Acute viral hepatitis (HAV, HBV, HCV, HEV, HSV, CMV, VZV, parvovirus)
Less common:
- Autoimmune hepatitis
- Acute Budd Chiari
- Reactivation HBV, HDV
- HLH (we seem to see this a lot in this hospital for some reason?)
- Malignant infiltration
- HELLP
- Wilsonian Crisis (severe hemolysis and impending acute liver failure in setting of Wilson’s)
For acute viral hepatitis, ALT is typically higher than AST.

Hepatitis A

Epidemiology

Global, 1.4 mil cases per year, can be sporadic or epidemic form
Fecal oral route, either person-to-person contact or ingestion of contaminated food or water.
Other risk factors: Sexual transmission (anal/oral sex), day care, consumption of raw or undercooked shellfish, veggies, or eating food prepared by an infected food handler.

Presentation

Incubation period: 15-50 days, average of 28 days.
Acute onset N/V, fever, anorexia, abd pain are typical.
Bilirubinuria, pale stools can also be seen within a few days.
Jaundice + pruritus. Jaundice peaks within 2 weeks.
Exam: Jaundice, hepatomegaly, RUQ pain.
Serum aminotransferases often > 1000 IU/dL, bili typically < 10, alk phos can be nrl to mildly elevated. ALT is commonly higher than AST.
Kids: Can be asymptomatic.

Diagnosis

Serum Anti-HAV IgM is diagnostic, detectable at time of symptom onset, remain detectable for 3-6 months after infection.
Anti-HAV IgG: remain detectable for decades, protective vs future infections. Detection of anti-HAV IgM and IgG reflects past infection or vaccination.

Management

Primarily supportive, but transfer to a transplant center might be indicated if pt goes into fulminant liver failure (severe acute liver injury with encephalopathy and impaired synthetic function i.e. INR >5 in patients without pre-existing liver disease)
Report to public health! Fax a confidential morbidity report over to Santa Clara County Department of Public Health
- https://www.sccgov.org/sites/phd-p/report/Documents/morb-110a.pdf

Vaccination

Single Antigen inactivated virus: 2 IM doses 6-18 months apart
Combo HAV and HBV inactivated virus vaccine: Adults only, 0, 1, 6 mo (3 doses total)

Prognosis

Generally pretty good, less than 1% go into fulminant hepatic failure.
Risk factors for severe complications: > 50, underlying liver dz
Other Complications
- Relapsing hepatitis: Up to to 10% of pts experience a relapse of sx 6 months after the acute episode for ~ < 3 weeks. Multiple relapses can occur. These patients usually make a complete recovery
- Autoimmune hepatitis: HAV can trigger development of autoimmune hepatitis.
- Cholestatic hepatitis: Prolonged period of jaundice > 3 months, typically self-resolving

Hepatitis B serologies made ridiculously simple

Capture

Morning Report

Shingles and Complications 3/11/2019

March 11, 2019 vmcimchiefs Leave a comment

Thanks Elan for presenting a case of a 91 year old F presenting with a progressively painful and erythematous rash, 2 weeks after she was treated with presumed Shingles by her PCP. It turned out that she had superimposed cellulitis over her healing Shingles lesions and possibly elements of post-herpetic neuralgia, requiring a Dilaudid PCA for pain control.

Lame joke of the day: Shingles + Cellulitis = Shinglelitis, get it?

Shingles

Epidemiology

Risk inc with age, esp for pts > 50, but it can develop at any age
Fortunately, most people will only have one outbreak in their life time, < 4% recurrence

Pathophysiology

Reactivation of the varicella zoster virus in sensory ganglia after a long latency period following primary infection from varicella (chicken pox). When the virus activates, the virus travels down the nerve fibers to the skin, hence a dermatomal distribution.
Weakening of the immune system is associated with outbreaks, i.e. AIDS, lymphoma, immune-suppressives.

Presentation

2-3 days prior to rash: pt might develop a tingling sensation, hypersensitivity, or itching over a particular dermatome. Later on vesicles on an erythematous base develop. Painful and very sensitive.
Blisters form over 3-5 days, then dry and crust over the next 5 days
Blisters are CONTAGIOUS until the vesicles scab over.
- Keep affected area dry and clean!
Expanding rash or blisters that persist for > 2 weeks indicate immune-compromised status

Complications

Most common is post-herpetic neuralgia
- 10% of patients, inc with age
- Pain can be very debilitating, some patients need to be admitted for pain control.
Zoster ophthalmicus
- Involves the eye, seen in 10-25% of cases when shingles hit V1
- Antiviral should be administered ASAP, preferably within 72 hours of onset of sx.
- Valacyclovir is recommended, 7-day course, 1000mg PO TID
- Alternative: Acyclovir 800mg PO 5 times daily x 7-10 days, Famciclovir 500mg PO TID.
- If e/o keratitis or uveitis, topical steroids can be used.
- Can lead to vision loss, especially with corneal scarring. Some patients would require corneal transplant.
- Post-herpetic neuralgia occurs in 36.6% of pts over 60, and 47.5% over age 70.
Disseminated zoster
- If > 3 contiguous dermatomes or 2 separated dermatomes are affected.
Bacterial infection of the skin:
- Risks inc with scratching
- Inc risk of scarring
Ramsey Hunt Syndrome:
- Reactivation of VZV at the geniculate ganglion.
- Triad of Ipsilateral facial paralysis, ear pain, vesicles on face/ear or IN THE EAR. Can lead to deafness, tinnitis or vertigo due to vestibulocochlear nerve involvement.
- Mgx: Anti-viral within 72 hours, steroids. Hearing loss is likely permanent so treat ASAP.

Diagnosis

Primarily clinical
Swabbing ulcer/vesicular fluid for HSV PCR has high sensitivity, quick turn around time.

Management

Acute management
- Anti-viral: Valacyclovir, famiciclovir, acyclovir. Start ASAP and preferably even before blisters occur. Effectiveness is greatest if antiviral is started within 72 hours of onset of symptoms (even before vesicles appear if clinical suspicion is high enough!)
- IV antiviral recommended for disseminated disease
- Options: Acyclovir (5 times a day dosing), Valacyclovir (TID dosing), famiciclovir (TID as well).
- Help shorten duration and complications
- Pain control:
  - Lidocaine, capsaicin, gabapentin, Lyrica.
  - Use opioids if and only if necessary.
  - Antidepressants i.e. Cymbalta and Effexor have variable benefits for post-herpetic neuralgia.
- Keep area dry and clean, DO NOT SCRATCH.
Infection Control:
- Localized herpes zoster: Standard precautions, contact
- Disseminated: airborne + contact
- Immunocompromised patient: airborne + contact regardless
Post-exposure:
- Previously received 2 doses of varicella vaccine: Monitor for 8-21 days for sx
- Previously only received 1 dose of varicella vaccine: Should get the 2^nd dose ASAP (minimum of 4 weeks apart from 1^st dose). Monitor for sx.
- No prior vaccination: Potentially contagious from days 8-21 post exposure, should be removed from patient care duties. Post-exposure vaccination should be provided ASAP. If varicella vaccination is contraindicated (i.e. pregnant), varicella-zoster immune globulin is recommended.
Vaccination/Prevention
- Vaccinate children
- Vaccinate adults > 50 regardless of whether they have had chicken pox or shingles and regardless of whether they had the older vaccine
  - Older: Weakened live virus, Zostavax
  - Newer: Recombinant Herpes Zoster vaccine, Shingrix, 2 doses IM, 2-6 months apart, at least 2 months after the older vaccine. Contains inactivated parts of the virus, not a live vaccine.
    - Effectiveness: 97% effective in preventing shingles for pts > 50, vs Zostavax which is 50-64% effective.
    - Reduces post-herpetic neuralgia if you get it shingles

Morning Report

Cardiorenal Syndrome 3/5/2019

March 5, 2019 vmcimchiefs Leave a comment

Thanks Elan for presenting a case of a 63yo M with HIV HFrEF (25%), EtOH cirrhosis (CP Class A, MELD 8), HTN, HLD, and ongoing alcohol use with dietary nonadherence presenting with shortness of breath and anasarca. His JVD was elevated on presentation, and CT PE/AP in the ED revealed dilated IVC and e/o pulmonary edema.

He underwent diuresis and initially improved, but 48 hours into his hospitalization, he developed oliguric AKI, hepatic encephalopathy, and relative hypotension.

Urine studies were consistent with activation of RAAS and ADH (kidneys seeing low perfusion, and echo was concerning for biventricular failure with EF < 20%. A trial of Lasix managed to produce a UOP of 800cc in 24 hours, so a decision was made to transfer pt to the Stepdown for dobutamine assisted diuresis for suspected Cardiorenal Syndrome. Pt ultimately diuresed 18L of fluid (his weight also went down 10+kg, that’s around 22lbs!) and his renal function quickly returned to baseline after aggressive diuresis.

Cardiorenal Syndrome

The diagnosis dilemma for this case was the etiology of pt’s AKI. He was exposed to contrast, hence 48 hours later contract-induced nephropathy can be expected. He also has liver cirrhosis with acute decompensation, hence hepatorenal syndrome (HRS) is something that we cannot miss. Given his poor cardiac function, cardiorenal syndrome (CRS) is also high on the differential!

Keep in mind that there are 5 types of Cardiorenal Syndrome:

Type 1: Acute heart failure -> AKI, decreased renal arterial flow due to acutely decompensated HF
Type 2: Chronic HF leading to chronic renal hypoperfusion leading to CKD
Type 3: AKI leading to adverse cardiac events
Type 4: CKD leading to adverse cardiac events
Type 5: Multifactorial, systemic insult leads to both cardiac and renal failure

Regardless, the general principle is to restore renal perfusion. Given his biventricular failure, volume status, and initial presentation, Cardiorenal is suspected as more likely, hence pt received inotropic support (improves forward flow) and diuresis (Get pt back on the right side of the Frank Starling curve, also improves forward flow). Overall management of CRS is not much different compared to acute decompensated heart failure.

There is some evidence that more aggressive diuresis is associated with better outcomes (ESCAPE trial).

Morning Report

Stanford Type B Dissection in a Young Patient! 3/4/2019

March 4, 2019 vmcimchiefs Leave a comment

A 41 (below 45 is young in my book) man with infrequent medical care, but otherwise no medical history other than obesity, presenting with acute onset chest pressure when he was showering. He initially tried to walk it off, but the pressure became sharp, and it started to radiate from the anterior chest to his shoulder blades. At the same time, he started feeling short of breath, dizzy, and diaphoretic. CTA revealed a Stanford Type B aortic dissection extending all the way to the R renal artery!

Chest pain: This is a topic we deal with almost every single day. In general, I like to classify chest pain in two categories:

Can’t Miss!

ACS & associated complications
Pulmonary emboli
Pneumothorax
Aortic dissection
Tamponade
Esophageal rupture

Everything Else!

Infection (abscess, pneumonia, etc), arguably also belongs in the Can’t Miss category
Peri/myocarditis
Pleuritis
Mass
Effusion
MSK
Trauma
etc

When it comes to dissection, there are two classification systems that describes the nature of the dissection (source: Grepmed). The Stanford classification is used more commonly.

classification-dissection-diagnosis-stanford-typeiii-original

Epidemiology

Men > women
Age 60-80 most common, mean age 63, 65% men
Younger < 40: 34% with HTN, 8.5% with h/o Marfan

Other Risk Factors

Trauma
Hypertension (most important predisposing factor of acute aortic dissection, up to 72% of pts will have underlying HTN. HTN is more common in those with type B vs type A.
Pheochromocytoma (very rare, case reports, thanks Alexa for pointing this out!)
Connective tissue disorders
Turner Syndrome
Vasculitis
Pregnancy
Crack cocaine, meth
Biscuspid aortic valve (9% of pts under age 40 have biscuspid AV)\
Pre-existing aortic aneurysm
Heavy lifting
Cardiac cath

Pathophysiology:

In a nut shell, due to a tear in the aortic intima, blood flow creates a false lumen separating the intima and the media. The higher the blood pressure, the higher the size of the false lumen due to shear force.
50-65% originate in the ascending aorta, while 20-30% originate near the left subclavian artery and extend distally.

Presentation

Typical Triad
- Acute chest or abdominal pain, can be sharp, tearing, or ripping
- Pulse/pressure deficit between extremities
- Mediastinal/aortic widening on CXR
Ascending aortic dissections are 2x as common as descending, 30% involves aortic arch
Acute onset chest pain that radiates to the back is the typical illness script. Pain can be the classic tearing or sharp.
- Type A: more likely to experience anterior chest pain
- Type B: more likely to experience back pain or abd pain > anterior chest pain
Propagation leads to acute AR, tamponade, stroke, shock, can propagate proximal or distally

Physical Exam Highlights

You might have heard of a term called pulse/pressure deficit when it comes to aortic dissections. In a nut shell, if there is a difference in SBP of greater > 20mmHg between right and left, then there is a deficit. This deficit is only found in 30% of cases of its presence can be very useful. High specific but poor sensitivity.
Findings Sensitivity Specificity LR if Present LR if Absent

Pulse Deficit 12-49% 82-99% 4.2 0.8
Presence of an aortic regurg murmur has a LR of 1.5
The presence of 3 findings increase likelihood of a Type A dissection:
- SBP < 100
- AR
- Pulse deficit
Presence of mediastinal or aortic widening on CXR increases probability of dissection somewhat, with LR 2.0

Diagnosis

CTA is fastest and easiest to get, 90+ % sensitivity and specificity
Can also do MRA or echo (TEE preferred) but might get longer to arrange in our hospital
EKG won’t have any specific signs but it can help you rule out other things.

Management/Prognosis

Stanford Type A
- Surgical emergency, CT Surgery should be consulted ASAP.
- High mortality, 2% per hour if left untreated.
- Surgical mortality: up to 30%
- Typically open repair, role of endovascular repair is not well studied.
Stanford Type B
- Uncomplicated:
  - Medical management, goal is to reduce BP < 120/80 and HR < 60
  - Medical management:
    - Beta blocker: Esmolol or labetalol or propranolol, first line
    - Vasodilator: Nicardipine or nitroprusside, can cause reflexive tachycardia, hence do NOT use alone and only add if BP remains elevated with beta blocker
      - Nitroprusside over time can lead to cyanide toxicity
    - CCB: Non-DHP i.e. verapamil or diltiazem if there is a contraindication to beta blockers
  - Complicated:
    - If impending aortic rupture, end organ damage, continuing pain and hypertension despite medical therapy, false lumen extension, or large area of involvement, Type B is now considered complicated.
    - Endovascular intervention with Vascular Surgery is recommended (INSTEAD-XL study)
Long term management
- Identify associated genetics factors
- HR, HTN control
- Serial imaging: 3, 6, and 12 months after event, and then annually after initial episode

Morning Report

Sarcoidosis

February 28, 2019 vmcimchiefs Leave a comment

Today, we talked about the fascinating case of a middle-aged man presenting with subacute cough, night sweats, and 15 pound weight loss, found to have bilateral hilar LAD on CXR and CT concerning for pulmonary sarcoidosis. While awaiting LN biopsy, he developed L sided Bell’s palsy with MRI showing inflammation of CN5 and CN7 as well as nodular dural thickening of the trigeminal cave concerning for neurosarcoidosis. LN biopsy showed non-caseating granulomas and he was subsequently started on high dose steroids for neurosarcoidosis.

Clinical Pearls

Sarcoidosis is a multisystem granulomatous disorder of unknown etiology.
The most common clinical presentation of sarcoidosis is pulmonary related.
In asymptomatic individuals with incidental hilar LAD, there is no indication for LN bx to diagnose sarcoidosis because 2/3 of cases resolve spontaneously without treatment. Close follow up is needed to ensure that patients do not develop symptoms.
Similarly, Lofgren syndrome (arthritis, erythema nodosum, hilar LAD, and fevers) and Heerfordt’s syndrome (uveoparotid fever) are clinically consistent with sarcoidosis and there is no indication for LN biopsy.

DDx for unilateral facial droop

CNS lesion
- Especially if forehead is spared. However, keep in mind that a stroke involving the region of pons which houses the nucleus of CN7 would mimic Bell’s palsy!
PNS lesion
- Infections
  - Zoster
  - HIV
  - Lyme
  - Syphilis
- Malignancy
  - Parotid tumors
  - Acoustic neuroma/schwannoma
  - Lymphoma or other mass compressing CN7
- Infiltrative/autoimmune
  - Sjogren’s syndrome
  - Sarcoidosis

Sarcoidosis

Multisystem granulomatous disorder of unknown etiology
3-4 x more common in blacks
Overall prevalence is 10-20 per 100,000 people
Pathophys
- Aberrant formation/accumulation of non-caseating granulomas
Clinical presentation
- Age of onset is 20-60 years
- Often discovered incidentally on a CXR
- Most common organ involved is the lung (cough, SOB, CP) with ILD being the most common type of lung involvement. 30% of patients present with extrathoracic manifestations.
- Fatigue, malaise, fever, and weight loss are common
- Lofgren’s syndrome: arthritis, erythema nodosum, b/l hilar LAD
- Heerfordt’s syndrome: parotid gland enlargement, facial palsy, fever, anterior uveitits
Diagnosis
- No biopsy needed in the following
  - Asymptomatic with hilar LAD
  - Lofgren’s syndrome
  - Heerfordt’s syndrome
- Otherwise, biopsy the easiest site to access. Keep in mind that erythema nodosum does not have granulomas and would not help in diagnosing sarcoidosis.
- Lab abnormalities that may be present:
  - Anemia
  - Leukopenia, eosinophilia, thrombocytopenia
  - ESR and CRP may be elevated
  - Hypercalciuria is more common than hypercalcemia
  - Moderate elevation in ALP suggests diffuse granulomatous hepatic involvement
  - Hypergammaglobulinemia and a positive RF (not usually part of routine work up)
  - ACE levels are elevated in 75% of untreated patients with sarcoid but has poor sensitivity and insufficient specificity (10% false positive rate with cocci, DM2, TB, hyperthyroidism, lung cancer, pneumoconiosis, etc.)
Organs that may be impacted in sarcoid
- Pulmonary: occurs in over 90% of patients. Bilateral hilar LAD as well parenchymal disease. Can present with a restrictive spirometry pattern due to underlying fibrosis, pulmonary HTN
- Cutaneous: can be disfiguring can be macules, papules, plaques and erythema nodosum
- Liver/Spleen: a high alkaline phosphatase level suggests granulomatous liver disease
- Neurologic: Noted in 5% of cases. MRI with contrast can help with diagnosis. Complications:
  - Cranial-nerve palsies (20-50%) → most common
  - Headache
  - Ataxia
  - Encephalopathy
  - Granulomatous meningitis
  - Weakness
  - Seizures
  - Neuroendocrine dysfunction
- Optho: anterior uveitis most common manifestation
- Cardiac: Typically cardiomyopathy, can also see arrhythmias (tachy or brady).
- Renal: Can have hypercaliuria (more common than hypercalcemia) and renal calculi
- Bone: chronic arthritis and cysts resembling rheumatoid, and diffuse granulomatous myositis.
Treatment/monitoring:
- Asymptomatic? Follow up outpatient q3-4 months and annually thereafter to monitor for development of symptoms.
- Symptomatic? Start steroids, re-evaluate q1-2 months
- Refer to this NEJM article for organ specific treatments.
Chronic complications of pulmonary sarcoid
- VTE is more common than the average patient population
- Chronic pulmonary aspergillosis
- Pulmonary HTN due to advanced fibrosis
Prognosis
- Up to 80% of patients with hilar LAD spontaneously improve on their own!
- With more symptomatic disease or more extrapulmonary manifestations, prognosis declines to less than 30% remission.
- Overall mortality is <5%

Morning Report

ECG Report!

February 27, 2019 vmcimchiefs Leave a comment

Clinical Pearls from our first ever (and hopefully monthly) ECG Report!

Make sure to always work through an ECG in a systematic way in order to avoid missing key information.
Remember that you might not see any p waves (or retrograde P waves) in AVRT and AVNRT. Both of these rhythms would be fast and regular. A fib, by contrast, would be irregular.
Hypercalcemia presents with a shortened QT and a loss of the ST segment on ECG. But make sure you are ruling out an MI because often times the loss of ST segment resembles a STEMI.
Whenever you see a downward p wave in lead I, think of two diagnoses:
- Dextrocardia
- Limb lead reversal
Easiest way to distinguish between dextrocardia and limb lead reversal is to look at the QRS amplitude as you move across the precordium. If the amplitude is decreasing as you advance from V1 to V6, then the diagnosis is dextrocardia because you are moving away from the heart. If the amplitude is not changing or increasing, then the diagnosis is limb lead reversal.
The presence of > 2 mm coved precordial ST-segment elevation (leads V₁through V₃) with T wave inversions is suggestive of Brugada morphology. In a patient with history of syncope, ventricular arrhythmias, or family history of Brugada syndrome, this is consistent with a diagnosis of Brugada syndrome and would require ICD placement.

Have an interesting ECG? Save them/send them our way for our next ECG report!

Morning Report

Multiple Myeloma

February 26, 2019 vmcimchiefs Leave a comment

Thanks to Erica for presenting the case of a middle aged man who presented with acute back pain and B symptoms after trauma to his back, found to have stage 3B multiple myeloma.

Clinical Pearls

Remember that majority of cases of acute low back pain (<6 weeks) is due to musculoskeletal etiologies that spontaneously improve on their own. Imaging and further diagnostic work up is not indicated unless there are red flags (see below).
A straight leg test is more useful when negative as it has a high negative predictive value for ruling out radiculopathy. False positive rates are quite high.
Unexplained anemia and worsening renal function in the outpatient setting should trigger a work up for multiple myeloma.
The most common presenting symptoms for MM are anemia (73%), bone pain (58%), and renal insufficiency (48%).
In diagnosing MM, sensitivity increases with each added test: SPEP (82%) → IFE (93%) → FLC/UPEP (97%). The other 3% that would not be diagnosed with these tests have a non-secretory MM (monoclonal increase in plasma cells in bone marrow that do not produce immunoglobulins or light chains).

Red flags for acute low back pain:

Focal neurologic complaints/deficits
History of cancer
Age >50 years
Fever not explained by another cause
History of recent bacteremia or IVDU
Steroid use
Weight loss
Pain that is worse at night
No relief with bed rest or pain lasting >1 month

Multiple Myeloma: refer to this prior blog post. Other info below:

Diagnostics:

SPEP: picks up M protein or elevated immunoglobulins (heavy + light chain) in the serum. You can diagnose over 80% of patients with MM using an SPEP.
IFE: identifies the specific type of immunoglobulin that is elevated with its light chain.
Free light chains (FLC): measures the amount of free light chains not bound to a heavy chain floating around in the blood. Normally people have about a 2:1 ratio of kappa to lambda chains. In light chain only multiple myeloma, there is a disproportionate increase in one type over the other and the ratio will be off. If there is an increase in both light chains but the ratio is normal, think kidney disease!
- Keep in mind that the reason to check FLC when you suspect MM is to diagnose those people who are only producing light chains and not whole immunoglobulins that would have been picked up by SPEP/IFE.
UPEP: measures light chains dumped in the urine (Bence Jones protein)

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Morning Report

Thrombocytopenia and ITP

February 26, 2019 vmcimchiefs Leave a comment

Thanks to Connie for presenting the case of an elderly woman who presented with petechial bleeding, found to have a platelet count of 15, with work up revealing possible Evans’ Syndrome as well as bladder cancer!

Clinical Pearls

Think of thrombocytopenia as a problem with platelet production, platelet destruction, sequestration, or lab problem.
ITP is a diagnosis of exclusion. It can be a primary process due to autoimmune platelet destruction, or triggered by an associated condition (secondary ITP).
Remember that decadron is superior to prednisone in treatment of ITP based on this meta-analysis.
TPO mimetics are best as a last resort and more useful in maintenance of remission rather than inducing remission.

Thrombocytopenia DDx

Decreased production
- Aplastic anemia
- MDS
- Drugs
- Alcohol
- Cirrhosis
- Leukemia
- Severe megaloblastic anemia (folate/B12 deficiency)
- Myelofibrosis
- Granulomas
- Solid malignancy mets to the bone
Increased destruction
- Immune mediated
  - Primary ITP
  - Secondary
    - Infection: HIV
    - Rheum d/o: SLE, APLS
    - Lymphoproliferative process: CLL, lymphomas
    - Drugs
    - Post-transfusion purpura (alloimmune process)
- Non-immune mediated
  - MAHA (DIC, HUS/TTP)
  - Plavix
  - Vasculitis
  - HELLP
  - Infections: sepsis, CMV, EBV, malaria, rickettsia, ehrlichiosis, dengue, Hanta virus, etc.
  - CVVH
Sequestration due to hypersplenism
Pseudo-thrombocytopenia: clumping due to EDTA anticoagulated tubes (confirm by request blood draw in citrate coated tubes)

Thrombocytopenia work up

Good history and review of meds, infections, prior history of autoimmune disorders
Check CBC, coags and peripheral smear!
- Spherocytes ⇒ AIHA, hypersplenism
- Schistocytes ⇒ MAHA
- Pancytopenia ⇒ aplastic anemia, MDS, leukemias, etc.

Immune Thrombocytopenic Purpura (ITP)

Check out our thorough post on this topic here.

Morning Report

Status Epilepticus & Serotonin Syndrome

February 20, 2019 vmcimchiefs Leave a comment

Today we talked about the case of a young woman who presented after suicide attempt by ingestion of multiple prescription medications, found to be obtunded, initially in status epilepticus and later with exam findings concerning for serotonin syndrome.

Clinical Pearls

Continuous EEG is indicated if a patient is not returning to baseline mentation 15 mins after a seizure to rule out non-convulsive status epilepticus.
Status epilepticus is defined as a seizure lasting > 5 mins or > 2 discrete seizures between which there is incomplete recovery of consciousness.
Treatment of status epilepticus involves acute management with IV/IM benzos, urgent long-term control with IV fosphenytoin (preferred), phenytoin, or valproic acid. Remember that keppra is more useful in suppressing future seizures than treating an acute episode.
Serotonin syndrome is a clinical diagnosis and manifests with neuromuscular activation like tremors, hyperreflexia, and clonus (generally worse in lower extremities). Use Hunter’s criteria to help with diagnosis.

Status Epilepticus

When is continuous EEG needed?
- If patient is not returning toward baseline in 15 mins after a seizure, goal is to rule out nonconvulsive seizures
How to define status?
- > 5 mins OR
- > 2 discrete seizures between which there is incomplete recovery of consciousness
Non-convulsive status epilepticus
- Suspect if LOC not improving by 10 mins after cessation of movement
- Mental status remains abnormal for 30-60 mins after movement cessation
- Dx requires a 24-hour EEG (we don’t have one ☹)
- Treatment is the same as generalized status epilepticus, but prognosis is worse (mortality 65% vs 27%)
Treatment of status
- Assessment and supportive treatment
- Initial pharmacologic therapy
  - Ativan (2 mg IV q1-2 mins), total dose 0.1mg/kg
    - Watch out for respiratory depression and hypotension
    - Alternatives: versed 0.2mg/kg IM, valium 0.2mg/kg IV
- Urgent long-term control
  - Fosphenytoin (preferred): 20 mg/kg at 150mg/min
    - Give extra 10 mg/kg if not responding
    - Dephosphorylates into phenytoin. It’s more soluble in water and less likely to precipitate in the skin and vessels.
  - Phenytoin: 20mg/kg at 50mg/min (slower than fospheny)
    - If infused too fast, can irritate skin/vessels causing skin necrosis
  - Valproic acid: 20mg/kg at 5 mg/kg/min
    - Sometimes the preferred choice in patients with known generalized epilepsy b/c phenytoin can provoke absence seizures in that population.
  - What about Keppra?
    - Technically not FDA approved for status. It has weak evidence to support its use. More useful in suppressing subsequent seizures after status has been controlled.

Serotonin syndrome:

Clinical diagnosis. Serum serotonin concentrations do not correlate with clinical findings.
Severe disease can lead to DIC, rhabdo, renal failure, and ARDS.
Diagnostic criteria: use Hunter’s (84% sensitive, 97% specific)
DDx
- NMS
- Anticholinergic toxicity
- Malignant hyperthermia
- Sympathomimetic intoxication
- Sedative-hypnotic withdrawal
- Meningitis
- Encephalitis
Serotonin syndrome may be distinguished from other causes of agitated delirium on the basis of neuromuscular findings. Whereas patients with serotonin syndrome show signs of neuromuscular activation (eg, tremor, hyperreflexia and clonus that are greater in the lower extremities, ocular clonus, and increased muscle tone), patients with sympathomimetic toxicity or infections of the central nervous system lack these findings.
Treatment
- Supportive care and sedation
  - Chemical sedation preferred over physical restraint
- Autonomic instability
  - High BP: esmolol or nitroprusside (Short acting). Avoid longer acting agents
  - Low BP: neo or epi. Avoid idirect agents like dopamine because they are converted to epi and norepi. When monoamine oxidase is inhibited, epi and norepi production at the cellular level is not controlled and could lead to an exaggerated HD response.
- Hyperthermia
  - No benefit to Tylenol b/c increase in body temp is due to increased muscular activity rather than alteration in the hypothalamic temperature setpoint.
  - If temp >41.1, then sedate, paralyze, intubate
- Antidote: cyproheptadine
  - Histamine receptor antagonist. Also has weak anticholinergic activity
  - 12 mg loading dose, then 2 mg q2h until clinical response is seen.
  - Is sedating (good) and can also cause transient hypotension.

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Morning Report

Hyponatremia due to secondary adrenal insufficiency

February 19, 2019 vmcimchiefs Leave a comment

Thanks to Jess for presenting the fascinating case of a middle-aged woman with family history of autoimmune disease who presented with acute onset of fatigue and abdominal pain, found to have vitiligo on exam. Work up revealed hyponatremia due to a secondary adrenal insufficiency, pancytopenia, and panhypopituitarism possibly due to a yet to be diagnosed autoimmune disorder!

Clinical pearls

Remember that hyponatremia is a problem of water regulation that can be compounded by low solute intake.
Primary adrenal insufficiency is disorder at the level of the adrenal glands and manifests with low sodium and high serum potassium levels.
Secondary adrenal insufficiency is disorder at the level of the pituitary and manifests with low/normal sodium and normal potassium levels (because low cortisol leads to high ADH levels and hyponatremia).
- Make sure to do work up to rule out panhypopituitarism. Keep in mind that the most sensitive test for HPA access integrity is LH/FSH.
Tertiary adrenal insufficiency is disorder at the level of the hypothalamus and presents similarly to secondary AI.
Test for adrenal insufficiency with a cort-stim test and/or AM cortisol and ACTH levels.

Hyponatremia

Remember these three steps to working up hyponatremia:

Is there a sodium problem? check serum osm
Are the kidneys responding appropriately? check urine osm
Is ADH revved up for a hemodynamic reason? check urine Na

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Adrenal insufficiency

Primary AI:

Failure of adrenal glands
Causes: Addison’s (most common in the US), infiltrative processes (TB, sarcoid), hemorrhage, toxins
Labs would show ↓Na and ↑potassium (b/c aldosterone is gone)

Secondary AI:

Failure of pituitary (low ACTH)
Causes: pituitary lesions, surgeries, TBI, drugs
Clinically may present with loss of other anterior pituitary hormones
Labs would show ↓Na (because low cortisol leads to high ADH levels) but normal potassium levels (b/c aldosterone is active)

Tertiary AI:

Failure of hypothalamus (low CRH)
Causes: more commonly iatrogenic (cessation of high dose glucocorticoid therapy without taper) or post surgical interventions.

Hypopituitarism

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Hypophysitis:

Inflammation of the pituitary
Four categories based on histologic findings:
- Lymphocytic
  - Most common form
  - Seen in late pregnancy and post-partum period
  - Also associated with CTLA4 inhibitors like ipilimumab
- Granulomatous
  - Idiopathic or secondary to GPA, sarcoid, TB
- Plasmacytic (IgG4-related)
- Xanthomatous (most rare)
Clinical presentation
- Headache out of proportion to exam findings
- Preferential decrease in ACTH and TSH ⇒ adrenal insufficiency and hypothyroidism
Prognosis:
- Pituitary size eventually normalizes but pituitary loss of function is often permanent.

Findings	Sensitivity	Specificity	LR if Present	LR if Absent
Pulse Deficit	12-49%	82-99%	4.2	0.8