Hemorrhagic shock secondary to GI bleed with recent PCI for NSTEMI on DAPT… Did I mention severe aortic stenosis as well? How about all of these in one patient at the same time? 11/29/2018

Narges presented a very complicated patient, who presents with 2 days of abdominal pain and melena. He had a PCI 4 days prior with a drug-eluting stent deployed at the LAD, and he was discharged on aspirin and ticagrelor (PLATO trial, superior to clopidogrel). On presentation he was in hemorrhagic shock, with notable hematochezia on exam, encephalopathy, and a 4/6 systolic murmur with carotid radiation which turned out to be an undiagnosed severe aortic stenosis.

To briefly summarize his main problem list:

  1. Hemorrhagic shock secondary to UGIB
  2. CAD with recent NSTEMI s/p DES to LAD x1 on DAPT
  3. Severe aortic stenosis, newly diagnosed

Question is, what to do if you see a patient like this? Let’s break it down.


 

Antiplatelet and PCI

  • Drug eluting stents (DES) are designed to have lower rates of late re-stenosis than bare metal stents (BMS), but they are at higher risk for in-stent thrombosis due to delayed endothelialization.
  • Some terminology:
    • Stent re-stenosis:
      • Gradual narrowing of the stent segment, usually occurs 3-12 months after stent placement.
      • Can present as recurrent angina vs full blown MI
    • Stent thrombosis
      • Abrupt thrombotic occlusion of a previously patent stent, usually catastrophic MI
  • Duration of DAPT? It depends! Per the 2016 ACC/AHA guidelineDAPT.png

In a nut shell:

Elective PCI in stable CAD:

  • BMS: At least 1 month of DAPT
  • DES: At least 6 months of DAPT

Exact duration is yet to be determined; there is some evidence of decreased stent restenosis (DAPT trial) with longer duration of DAPT but at the expense of all cause mortality and bleeding complications. There are also newer studies (i.e. ARCTIC Interruption) that found no benefits with longer duration of DAPT.

For PCI in setting of ACS, however, the guideline is different:

Anti-platelet duration in setting of ACS

  • Medical Therapy: At least 12 months of DAPT
  • PCI (BMS or DES, doens’t matter): At least 12 months of DAPT
  • CABG: Also at least 12 months of DAPT

In patients with high bleeding risk or personal history of bleeding and/or long term NSAID use, preemptive prophylaxis with a PPI can be considered. If bleeding risk is significant, you can potentially decrease DAPT duration to at least 6 months, on a case-to-case basis.

Now keep in mind our patient has a DES deployed 4 days ago and he’s now bleeding…


GI Bleed

Risk Factors

  • Alcohol
  • NSAID
  • Anticoagulation
  • Cirrhosis
  • Cancer

Presentation

  • UGIB: BUN/Cr ratio > 30 usually (not sensitive but specific), melena (gut transit of blood)
  • LGIB: bright red hematochezia, lower BUN/Cr ratio, but do not be fooled, can be seen in brisk UGIB (especially in this patient).

Management

  • Airway protection
  • Large bore IVs (18 G), Cordis, IO (they work wonders in a pinch!)
  • Fluid resuscitation
  • Anti-acid (i.e. Protonix)
  • Octreotide if suspecting variceal bleed, if catastrophic variceal bleed, consider deployment of a Blakemore/Minnesota tube
  • Antibiotics for primary SBP prophylaxis if cirrhotic
  • Blood product administration
  • GI consultation, urgency depending on clinical status, EGD

High risk features on Endoscopy

The patient underwent EGD and a duodenal ulcer that was actively bleeding was found. There are certain features of an ulcer that we can use to risk stratify and determine how likely intervention will be successful, and how likely the ulcer will rebleed. This is the Forrest Classification, first published in the Lancet in 1974. Our patient in this case is class 1B, and he ended by rebleeding twice requiring additional endoscopic intervention.

Picture1

Source: Alzoubaidi DLovat LBHaidry R. Management of non-variceal upper gastrointestinal bleeding: where are we in 2018? 

Failure of endoscopic therapy

  • Predictors: active bleeding at time of endoscopy, visible vessel, > 2cm, posterior duodenal ulcers, and gastric ulcers on the lesser curvature are associated with higher risk of treatment failure/rebleeding.
  • First line: 2nd endoscopic intervention
  • If recurrent bleeding persists, surgical options or IR embolization should be considered

The key question here is, when to resume DAPT? The decision will have to be individualized and most would recommend restarting ASAP as soon as patient is clinically stable… At the same time, pt has one other newly diagnosed problem that makes his management tricky…


aorticvalvearea-classification-aorticstenosis-meangradient-cardiology-original

Source: grepmed

Severe Aortic Stenosis

Criteria:

  1. Area < 1cm2
  2. Mean trans valvular gradient > 40 mmHg
  3. Peak velocity > 4m/s

Referral to Cardiology because it is actually more complicated than this, there is also pseudo severe where AVR is not recommended, Low flow AS, low gradient AS, or both LF LG AS.

  • Pseudo-severe: mild to moderate AS, low gradient, underlying myocardial dysfunction leading to poor valve opening. No benefit in AVR
  • LF LG AS:
    • AVA < 1cm2, but gradient < 35mmHg
    • Must distinguish from pseudo severe AS. Do dobutamine stress echo
      • If AVA remains the same, gradient inc, confirms true severe AS
      • If AVA improves while mean gradient remains the same, this is pseudo-severe AS, manage medically.

Epidemiology

  • < 70: Suspect bicuspid aortic valve
  • > 70: Progressive valvular fibrosis/calcification
  • Developing country: Rheumatic fever

Pathophysiology

  • Over time leads to LV hypertrophy (concentric), muscle hypertrophy. Leads to heart failure over time.

Presentation

  • Asx
  • Sx: SAD syncope, angina, dyspnea

Management

  • TAVR (transcatheter) vs SAVR (surgical), TAVR is non-inferior (PARTNER A, PARTNER B, SURTAVI trials) but has other complications to consider,
  • Can think about the transcatheter approach in high surgical risk patients.

In setting of hypotension

  • Patients with critical AS are highly preload dependent:
  • Cardiac Output (CO) = Heart Rate (HR) x Stroke Volume (SV). In patients with severe AS, CO is fixed due to physiologic limitations of a small outlet.
    • Increasing HR can help with CO but you run the risk of increasing myocardial O2 demands…
    • Also in terms of volume, pts with severe AS usually has a degree of diastolic dysfunction (decreased compliance due to a hypertrophied ventricle). As you can imagine, if you push too much fluids into a non-compliant system, back up can occur leading to pulmonary edema thus respiratory failure…
  • Choice Pressors: no absolute contraindication to any but phenylephrine has been suggested in some anesthesia text books as first line
    • Rationale: Pure alpha, increases DBP (diastolic blood pressure), which in turns inc coronary perfusion pressure (CPP = DP – PCWP (LVEDP))
    • Won’t induce tachycardia (if anything induces a mild reflexive bradycardia which decreases myocardial O2 demands).
    • Epi has been associated with higher incidences of arrhythmias

Neutropenia and Acute Diarrhea… It’s not C.diff, it’s Norovirus (11/28/18)

Elise presented a case of a middle age man with recently diagnosed pancreatic adenocarcinoma on chemo presenting with acute loose watery stools (“too many to count”) and abdominal discomfort. He appeared septic on presentation and was found to be neutropenic. Unfortunately (or fortunately) it is not the typical C.diff colitis, but actually norovirus!


Acute Diarrhea

Definition: defined as watery stool 3x in 24 hours, < 14 days duration

Most are infectious in etiology in an acute setting

Other causes: Ingested osmoles, malabsorption

Clues

  • Secretory: High volume, watery, no systemic symptoms, usually due to small intestinal involvement
    • Most common causes are viral (rota and noro), enterotoxin, ETEC, or vibrio chlolarae.
    • Negative fecal WBC
  • Invasive: Smaller volume, bloody/mucoid, tenesmus + LLQ pain, systemic symptoms.
    • Site of involvement is the colon. Common causes are Shigella, Campylobacter, EHEC, Entamoeba histolytica
    • Positive fecal WBC
  • Importance of vomiting: Usually indicates the ingestion of a pre-formed toxin or a viral infection. Examples:
    • Staph aureus
    • B. cereus
    • Norovirus
    • Certain parasites

Non-bloody/Watery

  • Norovirus (very common)
  • Rotavirus, enteric adenovirus, astrovirus (usually in immunocompromised adults)
  • diff (can be bloody/inflammatory)
    • Nosocomial vs community acquired
  • Clostridium perfringens (2nd most common cause of foodborne bacterial infection)
    • Associated with outbreaks in restaurants and catering facilities
    • Usually mild symptoms.
    • Associated with improperly cooked or stored meat.
    • Self-limited, supportive care often suffices
  • Enterotoxigenic E.coli (ETEC): AKA traveler’s diarrhea
    • Cruise ships, foreign countries, fecal contimation or food or water from an infected person.
  • Giardia lamblia:
    • Water & food borne outbreaks
    • Sx: 7-14 days incubation post exposure.
    • Presentation: Foul smelly stools, cramps, bloating.
    • Tx: Supportive + Metronidazole, Tinidazole, albendazole
  • Cryptosporadium
    • One of the most common parasitic foodborne diarrhea
    • Endemic in cattle, usually transmitted via infected animal or person. Food/water borne outbreaks also common.
    • Presentation: Severe, dehydrating watery diarrhea but self-limited in immunocompetent hosts.
    • Immunocompromised: More severe
  • Other bacterial
    • Staph aureus, Bacillus cereus: enterotoxins, acute diarrhea + vomiting
    • Listeria monocytogenes: Can cause systemic symptoms/spread
    • Cyclospora: Associated with sporadic outbreaks due to imported raspberries and basil.
    • Aeromonas: Distributed in watery environments, suspect if contact with fresh or brackish water.
  • Other viral: Hepatitis A

Inflammatory: bloody or mucoid diarrhea, with associated fever, abd pain. Presence of inflammatory cells in the stool. More likely bacterial.

  • Salmonella: Nontyphoidal, leading cause of acute inflammatory diarrhea
    • Association: Poultry, eggs, milk products, animal contacts
    • Incubation: 8 – 72 hours
    • Presentation: diarrhea is usually non-bloody, N/V, fever.
  • Campylobacter
    • Undercooked poultry
    • Watery or hemorrhagic diarrhea, 2-5 days after exposure
    • Association: Guillain-Barre, reactive arthritis
  • Shigella: Dysenteric diarrhea
    • Colonic infection, person to person or fecal oral transmission.
    • Mucoid or bloody diarrhea, 3-7 days after exposure.
  • EHEC: Enterhemorrhagic E.coli
    • Association: HUS
    • Presentation: Watery/progressively bloody diarrhea, 3-4 days post exposure, abd pain + fever.
  • Yersinia
    • Uncommon, can be transmitted via undercooked pork, unpasteurized milk, fecally contaminated water. 1-14 days after exposure
    • Associated with concurrent pharyngitis.
  • Others: Entamoeba histolytica, noncholera vibrios, CMV, HSV
    • CMV & HSV: Dx has to be confirmed by biopsy. Suspect these in immunocompromised patients.

Neutropenia and GI symptoms

Neutropenic enterocolitis (typhilitis), cytotoxic agent-related diarrhea, any viral/bacterial infection, but for typhilitis specifically:

Epidemiology

  • Associated with hematologic malignancies or ingestion of food contaminated with C. perfringens
  • Pre-existing bowel wall abnormalities increases risk (i.e. diverticulitis, tumor, previous surgery).

Pathophysiology

  • Infection of the bowel wall, usually the cecum but can involve ascending colon & ileum, leading to tissue necrosis

Presentation

  • Neutropenic
  • Fever, mean of 3 weeks after cytotoxic chemo
  • Abd pain, distension, N/V, watery/bloody diarrhea
  • Usually RLQ pain, can mimic appendicitis.

Diagnosis

  • CT

Management

  • 4th gen cephalosporins i.e. cefepime + Flagyl, surgery is generally avoid but indicated if e/o perforation

Prognosis

  • 50% mortality

Norovirus

Epidemiology:

  • Most common viral cause of gastroenteritis worldwide, all age range affected
  • 19-21 million cases every year in the US
  • Unclear reason, peak incidence during winter months.
  • Food born outbreaks is common: leafy greens, fruits, shell fish.

Pathophysiology/Transmission

  • Fecal oral transmission, RNA virus
  • Different genotypes exist with further sub-groups, tend to have a preference for certain blood type.
  • Incubation: 24-48 hours, affects the small intestines
  • Very infectious, can cause full blown infection even if exposed to a small amount (< 100 viral particles)
  • Extremely stable in the environment, resists freezing or heating up to 60 degrees C, disinfection requires chlorine or EtOH
  • Viral shedding is max over the first 24-48 hours, and pts can continue to shed for up to weeks

Presentation

  • Duration: 48-72 hours
  • Watery diarrhea, N/V, abd pain.
  • Vomiting usually prominent
  • Usually self-limiting but can be severe in immunocompromised patients

Diagnosis

  • Stool PCR

Management

  • Supportive
  • Contact plus isolation
  • Notify infection control (contact plus isolation)
  • If you have been exposed to someone with norovirus and you are symptomatic, PLEASE CALL IN SICK since this illness is highly contagious. Notify us and employee health. You have to be asymptomatic for at least 48 hours, and you have to be cleared by employee health, prior to returning to work.

Necrotizing Fasciitis & Ludwig’s Angina

Thanks to Joe for presenting the case of an elderly man with no known medical history who presented with acute AMS, found to have L facial swelling and crepitus, eventually diagnosed with necrotizing Ludwig’s angina!


Clinical Pearls

  • Necrotizing fasciitis (NF) is a surgical diagnosis and involves infection of muscle and subcutaneous fat.
  • CT is a useful tool to help with diagnosis and in one case series had a 100% sensitivity and >80% specificity for diagnosing NF.
  • LRINEC or Laboratory Risk Indicator for NF is a lab-based risk assessment tool to help risk stratify patients with possible NF.  It has a sensitivity of 80% and specificity of 67%.  It should NOT supplant your clinical judgement.
  • Ludwig’s angina refers to any infection of the submandibular space (not just NF).  Normally the treatment for Ludwig’s angina is antibiotics.  In the case of NF, urgent surgical debridement is necessary.  In spite of antibiotics and debridement, head and neck necrotizing infections are associated with a high mortality rate (~40%).
    • In patients with Ludwig’s angina, always involve anesthesia AND ENT to help secure airway. Oral intubation is associated with higher rates of laryngospasm in these patients so oftentimes nasal intubation is preferred.

Deep neck infections:

Capture

Necrotizing fasciitis

  • Background
    • Infection of deep tissues, specifically muscle fascia and subcutaneous fat.
    • Two main types
      • Type 1: polymicrobial
        • More common in elderly and those with significant comorbidities including diabetes, immunocompromised states, PVD, etc.
        • Blood cultures are positive in ~20% of patients.
      • Type 2: monomicrobial (usually GAS but can be other beta-hemolytic strep and MRSA)
        • Can be seen in any age group and without any underlying disease.
  • Clinical manifestations
    • Remember that you do not need to have a penetrating injury for NF.  Oftentimes, blunt trauma is the preceding history and overlying tissue does not show any signs of infection, leading to the “pain out of proportion to exam” finding.
    • Systemic signs of toxicity (including hypotension and shock), rapid progression, crepitus.
    • LRINEC or the Laboratory Risk Indicator for NF is a lab-based risk assessment tool to help risk stratify patients with possible NF.
      • It has a sensitivity of 80% and specificity of 67%.  It should NOT supplant your clinical judgement.
    • CT scan is highly sensitive (100% in one case series of 67 patients) and specific for differentiating NF from celllulitis.
    • Ultimately, NF is a surgical diagnosis so consult surgery early if you are concerned about the diagnosis and before waiting for imaging in an unstable patient!
  • Treatment
    • Early surgical intervention and debridement
    • Empiric antibiotics
      • Beta lactam/beta lactamase inhibitor or carbapenem PLUS
      • vancomycin or other similar drug for MRSA coverage PLUS
      • clindamycin
        • Eagle effect: at high bacterial loads, there is reduced efficacy of beta-lactam antibiotics for strep pyogenes infections due to reduced exposure of penicillin binding protein on the bacteria.  Clindamycin works better in these situations and does not rely on the penicillin binding protein site.
        • Toxin neutralization: clindamycin has the ability to suppress synthesis of bacterial toxins that cause systemic symptoms in patients with NF.
    • Other therapies such as hyperbaric oxygen and IVIG have not shown reliable evidence of benefit in studies and are not currently recommended by the IDSA.
  • Prognosis
    • Mortality is high even with appropriate treatment (up to 45%).

References: 

Refer to this amazing review by NEJM for more info on NF.

 

Acute Rheumatic Fever

Today, we talked about the very interesting case of a middle-aged man who presented with acute migrating oligoarthritis, found to be febrile with an inflammatory synovial fluid and elevated ASO titers consistent with acute rheumatic fever!


Clinical Pearls

  • Nonsuppurative manifestations of GAS infection include acute rheumatic fever (ARF), acute GN, and Scarlet fever.
  • Use the modified Jones Criteria to help you diagnose ARF and treat early if high suspicion for the disease (do not wait for titers to come back).
  • Late complications of ARF include rheumatic heart disease (10-20 years after infection) and Jaccoud arthropathy.
  • Treatment of ARF involves NSAIDs for arthritis, PCN G IM x 1 dose for acute presentation and then monthly for prophylaxis, and patient education about oral hygiene to prevent endocarditis and need for prophylaxis before invasive procedures.

Differential diagnosis for a migratory arthritis

  • Rheumatic fever
  • Infective endocarditis
  • Vasculitis (IgA, cryo, ANCA associated)
  • SLE 
  • Acute leukemia
  • Serum sickness
  • Viral arthritis
  • Bacteremia (staph, strep, mening/gonococcal)
  • Pulmonary infections (mycoplasma, histoplasma)
  • Lyme
  • Whipple’s

Nonsuppurative complications of GAS infection

  • ARF
  • Scarlet fever
  • Acute GN

Rheumatic fever 

  • Nonsuppurative sequela that occurs 2-4 weeks after GAS pharyngitis
  • Epi
    • More common in children 5-15 years of age
    • More common in resource limited settings
  • Pathogenesis:
    • Poorly understood, ?molecular mimicry
  • Clinical manifestations:
    • Two primary manifestations of disease

Two manifestations of ARF

(Table above from UpToDate)

  • Late sequelae
    • Rheumatic heart disease (10-20 years after infection), primary involves the mitral valve >aortic valve.
      • Leading cause of cardiovascular death in the first 5 decades of life in resource limited settings
    • Jaccoud arthropathy
  • Diagnosis:
    • Revised Jones criteria (joint and cardiac manifestations can only be counted once).
      • Major
        • Carditis and valvulitis (clinical or subclinical) – 50-70%
          • Usually pancarditis. Valvulitis especially of mitral and aortic valves, shown as regurg on echo.
          • Carey Coombs murmur: short mid-diastolic murmur heard loudest at the apex
        • Arthritis (migratory, involving large joints) – 35-66%, earliest symptom
          • Several joints affected in quick succession, each inflamed for a day or two to one week. Most common are knees, ankles, elbows, and wrists.
        • CNS involvement (Sydenham chorea) – 10-30%
        • Subcutaneous nodules – 0-10%
        • Erythema marginatum – <6% 
      • Minor
        • Arthralgia
        • Fever >38.5
        • Elevated acute phase reactants (ESR, CRP)
        • Prolonged PR interval on EKG
      • Diagnosis requires evidence of prior GAS infection plus:
        • 2 major OR
        • 1 major + 2 minor criteria OR
        • 3 minor criteria (only if patient has history of prior episode of ARF)
      • In a high prevalence setting, slightly modified criteria are used.
    • Labs:
      • Prior GAS infection through either
        • Throat culture
        • Positive rapid strep antigen test
        • Elevated or rising ASO titers
      • Treatment
        • Goals
          • Symptomatic relief of acute disease manifestations
            • Arthritis: NSAIDs
            • Carditis: if severe, heart failure treatments
          • Eradication of GAS
            • IM PCN G benzathine x 1
            • Contacts (throat culture test and treat if positive)
          • Ppx against future GAS infection to prevent progression of cardiac disease
            • PCN G IM once a month
            • For 5 years or until 21 years of age (whichever is longer)
            • If ARF with carditis and residual heart disease
              • 10 years or until 40 years, sometimes even lifelong
            • Education
              • Oral health
              • Ppx before any invasive procedures

Stroke from CNS TB induced vasculitis!

Thanks to Katie for presenting the interesting case of a young man with history of disseminated TB with TB meningitis and hydrocephalus requiring VP shunts, admitted for acute LUE weakness, L homonymous hemianopsia, and memory impairment, found to have acute strokes in multiple vascular territories due to TB related CNS vasculitis!


Clinical Pearls

  • Remember that arterial dissection is the most common cause of stroke in a young patient.
  • CNS vasculitis can be primary or secondary to a systemic illness.  It typically presents with infarcts in multiple vascular territories.  Treatment involves immunosuppression with high dose steroids + cytoxan/rituxan.
  • CNS vasculitis is the most common cause of severe neurologic deficit in patients with TB meningitis.
  • Vasculitis in CNS TB is the result of a hypersensitivity reaction to proteins released from the bacteria.
  • TB meningitis requires an extended course of anti-TB treatment, generally up to 1 year or more.  Serial LPs are obtained to monitor adequate response to therapy.

Etiologies of stroke in a young adult

CNS TB:

Three main manifestations:

  1. TB meningitis (most common presentation in low incidence settings like the US)
  2. Intracranial tuberculoma
  3. Spinal tuberculous arachnoiditis

Spillage of tubercular protein into the subarachnoid space results in an intense hypersensitivity reaction and inflammation resulting in

  • Proliferative arachnoiditis (fibrous mass encasing cranial nerves and vessels adjacent to it)
  • Vasculitis with resultant aneurysm, thrombosis, and infarction
  • Communicating hydrocephalus 

TB Meningitis

  • 1% of all TB cases, 5% of all extrapulmonary TB cases
  • 15-40% mortality rate
  • Clinical manifestations
    • 3 stages:
      • Prodromal phase: malaise, headache, low grade fever, personality changes
      • Meningitic phase: meningismus, headache, vomiting, lethargy, confusion, CNS signs, some motor deficits
      • Paralytic phase: stupor, coma, seizures, hemiparesis (death within 5-8 weeks)
  • Diagnosis:
    • Characteristic CSF findings of low glucose, elevated protein, lymphocytic pleocytosis 
    • CSF AFB smear and culture: in general, a minimum of 3 serial LPs should be performed, as diagnostic yield increases f
    • Nucleic acid tests: Xpert MTB/RIF assay should be submitted in the setting of high clinical suspicion and negative AFB staining.
  • Treatment
    • Intensive phase (2 months): four drugs RIPE. Ethambutol has poor CNS penetration so some use fluoroquinolones instead.
    • Continuation phase (7-10 months)
    • Steroids
      • A review of 9 trials on 1337 patients found that use of steroids reduced death and disability by ~25%.
      • Benefit higher if started earlier in disease process.
      • Treat for 8 weeks, slow taper.
    • Stroke
      • A retrospective study in Stroke 2018 on patients with TB meningitis found that those >40, with concurrent HTN, dysplipidemia, and DM were more likely to have this complication. Some small case series showing benefit in reducing future strokes with the use of Aspirin.
      • No role for tPA.


Acute encephalopathy… found to have thrombocytopenia and evidence of microangiopathic hemolytic anemia… A case of TTP! 11/19/2018

Bri presented a case of a gentleman with multiple medical comorbidities with a recent lap chole presenting with confusion. His labs were significant for anemia, thrombocytopenia, elevated indirect bilirubin, elevated LDH, and undetectable haptoglobin. A smear revealed numerous schistocytes concerning for MAHA. ADAMTS13 levels were found to be very low, and the presence of an ADAMTS13 inhibitor was detected as well. This presentation is consistent with thrombotic thrombocytopenic purpura (TTP)!


Common differential for microangiopathic hemolytic anemia (MAHA):

  • DIC
  • HELLP/Eclampsia
  • TTP/HUS, atypical HUS
  • Mechanical heart valves
  • Severe B12 deficiency

TTP

Epidemiology

  • Rare, most often > 40 in adults, congenital ADAMTS13 deficiencies can be seen in kids (Upshaw-Schulman Syndrome, autosomal recessive)
  • 2:1 female to male predominance

Pathophysiology

  • Non-immune mediated platelet and RBC destruction due to mechanical shearing of platelets and RBC when they pass through platelet/fibrin deposits on small vessel walls in absence of ADAMTS13 activity.
  • Further consumption of plts via formation of microthrombi in small arterioles/capillaries, brain/heart/kidneys are especially affected.
  • ADAMTS13 cleaves VWF, preventing large multimer formation on vessel walls

ADAMTS

J Evan Saldler. Von Willebrand factor, ADAMTS13, and thrombotic thrombocytopenic purpura. Blood 2008 112:11-18; doi: https://doi.org/10.1182/blood-2008-02-078170

Causes

  • Idiopathic
  • Drug-induced (Immunosuppressants, chemo)
  • Pregnancy (preeclampsia/eclampsia)
  • Hemorrhagic colitis
  • HUS: more likely in kids, more commonly presents with AKI and in higher severity. Associated with E.coli O157:H7 infection and some strains of Shigella
  • Atypical HUS: very similar to TTP but differnet pathophys (congenital complementary activation defect)

Presentation

  • Pentad of FATRN: < 1/3, can be indolent (days to weeks of malaise)
    • Fever( 10%)
    • Anemia (100%)
    • Thrombocytopenia (100%)
    • Renal dysfunction, more common in HUS
    • Neuro (encephalopathy): More common in TTP (53%), less in HUS
  • Triad that’s almost always present:
    • LDH elevation
    • Schistocytes
    • Thrombocytopenia
  • Sx: Non-specific, encephalopathy, abd pain, N/V, diarrhea, arrhythmia.
  • Exam: SICK compared to pts with ITP.

Diagnosis

  • Thrombocytopenia
  • E/O hemolysis: Anemia, polychromasia, elevated retic, reduced hepato, elevated LDH, elevated indirect bilirubin
  • Fibrinogen is normal (although early DIC can also be relatively normal)
  • PT/PTT are normal (vs elevated in DIC!)
  • Low ADAMTS13 level (<10%) is highly specific for TTP
  • ADAMTS13 inhibitor usually seen in adults, suggestive of autoimmune related deficiency of ADAMTS13. Generally responsive to immune suppression.

Management

  • Emergent consultation with specialists, coordinate with MICU, Heme/Onc, and Renal! 
  • FFP can be given to temporize things, fastest treatment option
  • DO NOT TRANSFUSE PLATELETS
  • 90% mortality without tx
  • Emergent PLEX: reduces mortality to 20-30%, but those who survive the initial episode can have relapses 20-50% of the time.
    • Low ADAMTS13 activity and higher titers of ADAMTS13 inhibitor are associated with worse prognosis.
    • Plasma exchange usually continued until e/o dz activity has decreased (nrl plt, nrl LDH)
  • Immune suppression with corticosteroids, rituximab can be considered in refractory cases.
  • For HUS, tx is mainly supportive +/- dialysis but Eculizumab can be used.

 

Neurosyphilis? Wait… reactive arthritis!

Thanks to Tim for presenting the interesting case of a middle-aged man with h/o inadequately treated syphilis who presented with neck stiffness worse in the mornings, back pain, and blurry vision, admitted for presumed neurosyphilis.  Exam revealed inflammation of T2/T3 joints, L SI joint tenderness, and an inflamed R foot with dactylitis of the 3rd and 4th digits.  Further history revealed a recent gonorrhea/chlamydia for which he was treated and HLA B27 positivity consistent with reactive arthritis!  He was started on NSAIDs with significant improvement of symptoms.


Clinical Pearls:

  • Neurosyphilis is most commonly seen in HIV positive patients and can present at any time after infection.
  • Early neurosyphilis occurs within the first year after infection and involves the CNS, meninges, and vasculature
    • Neurosyphilis presents with posterior uveitis or pan-uveitis whereas reactive arthritis presents with anterior uveitis
  • Late neurosyphilis occurs >10 years after infection and involves the brain and spinal cord parenchyma
  • The four main spondyloarthropathies are ankylosing spondylitis, psoriatic arthritis, reactive arthritis, and IBD-related arthritis.
  • The genital pathogen most commonly associated with reactive arthritis is chlamydia trachomatis.
    • HLA B27 is positive in 30-50% of patients
    • Mainstay of treatment is NSAIDs
    • Disease typically lasts 3-5 months.

 

Syphilis

Clinical manifestations and treatment of different stages of syphilis

Neurosyphilis manifestations

  • Refer to this prior post
  • Early (w/n first year of infection)
    • CSF, meninges, vasculature
    • Symptomatic meningitis
    • Ocular syphilis (posterior uveitis, panuveitis)
    • Meningovascular syphilis
      • Arteritis of any sized vessel which can lead tostroke or spinal cord infarction
  • Late
    • Brain and spinal cord parenchyma
      • General paresis (10-25 years after initialinfection)
        • Progressive dementia
        • Psychiatric symptoms
      • Tabes dorsalis (>20 years after initialinfection)
        • CSF may be completely normal
        • Affects dorsal columns
        • Symptoms
          • Sensory ataxia
          • Argyll-Robertson pupil
          • Lancinating pains
  • Diagnosis
    • Non-treponemal tests (poor sensitivity but highspecificity)
      • VDRL
      • RPR
    • Treponemal tests
      • FTA-ABS
      • Syphilis EIA
    • In an HIV negative patient with suspectedneurosyphilis and a non-reactive CSF-VDRL, one can establish the diagnosis with
      • CSF lymphocytes >5 cells/microL
      • CSF protein concentration >45

Reactive Arthritis

  • Epimiology
    • Young adults, M:F equal
  • Typically follows GI or urogenital infections (several days to weeks after infection)
    • Chlamydia trachomatis (most common genital infection associated)
    • Yersinia
    • Salmonella
    • Shigella
    • Campylobacter
    • E coli
    • C diff
    • Chlamydia pneumoniae
  • Manifestations
    • Mono- or oligoarticular pattern of arthritis,often involving the lower extremities, sometimes associated with dactylitis and enthesitis
    • The triad of arthritis, urethritis, andconjunctivitis is only present in a subset of patients (formerly called Reiter’s syndrome)
    • Ocular manifestions: conjunctivitis, less frequently anterior uveitis, episcleritis, and keratitis.
    • Other: 
      • Skin: keratoderma blennorhagica, erythema nodosum
      • Circinate balanitis 
      • Nail changes resembling psoriatic arthritis
  • Lab
    • E/o of antecedent or concomitant infection
    • Elevated acute phase reactants
    • Positive HLA-B27 (present in 30-50% of patients)
    • Inflammatory synovitis
    • Imaging consistent with enthesitis or arthritis
  • Treatment
    1. Treat any ongoing concurrent infection
    2. NSAIDs (first line)
    3. Steroids (if refractory to NSAIDs)
    4. DMARDS (for chronic reactive arthritis)
    5. Anti-TNF (last resort)
  • Prognosis
    • Duration is typically 3-5 months
    • >6 months duration is considered chronic reactive arthritis
    • Most remit completely or have little active disease w/n 6-12 months after presentation
    • 15-20% may experience more chronic persistent arthritis

Spontaneous Bacterial Peritonitis secondary to… Acinetobacter? 11/14/2018

Our doctor-in-training Jacqueline presented a middle man with infrequent medical care, with a history of heavy alcohol use, who presents with generalized swelling and anorexia. He was septic on presentation with a distended abdomen. Ascitic fluid anlysis was concerning for bacterial peritonitis, and blood cultures (4/4 bottles) were positive for acinetobacter with OXA resistance marker!


Spontaneous bacterial peritonitis

Important to distinguish between Spontaneous bacterial peritonitis (SBP) vs Secondary bacterial peritonitis (also SBP but for the sake of clarity, SBP from this point on will refer to spontaneous bacterial peritonitis)

  • Secondary: Bacterial peritonitis secondary to something else besides spontaneous, i.e. bowel perforation, surgery.
    • 100% mortality without surgical intervention. Surgical risk is high but patient mortality is almost guaranteed without surgery!
    • If Spontaneous BP, mortality can approach 80% with abdominal surgery.
  • Diagnosis: history, fluid analysis
  • Cultures from peritoneal fluid usually polymicrobial (gut flora)
  • Tertiary bacterial peritonitis: Persistence of peritonitis or abscess following adequate treatment of primary or secondary peritonitis

Epidemiology

  • Pts with cirrhotic ascites, suspect SBP in all these patients, and also pts with ascites suffering from a GIB.
  • Organisms: E.coli, Klebsiella, strep pneumo are most common, usually single organism
  • Less common: Acinetobacter, pseudomonas, proteus
  • If polymicrobial of anaerobes, suspect secondary bacterial peritonitis
  • Rarely fungal but they have been described, poor prognosis.

Presentation

  • S/S of ascites
  • May have fever, malaise, encephalopathy, decompensated liver cirrhosis, peritoneal signs sometimes.
  • Frequently an instigator for hepatorenal syndrome in cirrhotic patients.

Diagnosis:

  • PMN > 250 cells/mL
  • Positive cultures/Gram-stain
  • Absence of secondary causes

Management:

  • Antibiotics:
    • Cefotaxime 2g Q8H
    • Ceftriaxone once daily is an alterative with some evidence trending toward improved survival and less ICU stay with 2g daily dosing vs 1g.
    • Cefepime 1-2g Q8H is an alternative as well esp for resistant pathogens.
    • Fluoroquinolones: Consider alternative if pt already on a quinolone for prophylaxis prior to developing SBP. Can use Cipro, Levo, or Moxi.
    • Carbapenems
    • Beta lactam/Beta lactamase inhibitors i.e. Zosyn
    • Duration: At least 5 days
  • Albumin: Recommended, RCT published in NEJM in 1999 established the administration of albumin decreases the incidence of renal failure with albumin + antibiotics as well as decrease in mortality.
    • Patients in the study who were most likely to benefit from albumin had:
      • Bili > 4
      • Cr > 1
      • BUN > 30
    • 1.5g albumin /kg on day 1, the 1.0g/kg on day 3. Dose limited to max of 100g
  • HRS (Hepatorenal syndrome): 1.0g/kg albumin days 1 & 2 and see if renal function improves (albumin challenge)

Prognosis

  • Renal failure can be seen in 30-40% of patients with SBP
  • Prognosis tends to be poor once HRS sets in
  • HRS
    • Type 1: Rapid progressive decline, 50% 1 month mortality
    • Type 2: More subacute/chronic, not associated with an inciting event, median survival 6 months

 Prophylaxis

  • Primary
    • Cirrhotics presenting with GIB should get primary prophylaxis, total duration of therapy x 7 days
    • Ascitic protein < 1.0 g/dL can also be considered (RCT published in Journal of Hepatology in 2008)
    • Ascitic protein <1 and Childs Pugh > 9 or T.bili > 3 or renal dysfunction: can also consider long-term primary prophylaxis, based on an RCT from Gastroenterology in 2007, drug of study was norfloxacin.
  • Secondary
    • Indicated after first episode of SBP, one year recurrence rate of 40-70%, mortality rate of 50-70%
    • Meds: Norfloxacin or cipro daily, Bactrim also an equivocal alternative
    • Life-long or until transplant

Please refer to this article for an overview of SBP.


Acinetobacter

Epidemiology:

  • Nosocomial, ICU
  • Tropical/humid environments
  • Water and soil
  • Certain strains can survive in a desiccated environment for weeks.

Presentation

  • Most commonly in ventilator associated pneumonia and blood stream infection (1.5% – 2.4%)
  • Others: Central line, catheters, surgical site infection
  • Can be contamination, pts and health care workers can be colonized
  • Can also present as endocarditis or meningitis or ocular infection (contact lens)
  • Peritonitis secondary to acinetobacter usually more common in peritoneal dialysis patients.

Risk Factors

  • Prior antibiotics, especially beta lactams, carbapenems, fluoroquinolones
  • Presence of catheters, ICU
  • PD (especially in setting of peritonitis secondary to actinobacteria)
  • Trauma, burn, immunosuppression

Resistance

  • Increasingly resistant, both acquired and inherent
  • ESBL phenotype also emerging

Management

  • 1st line: cephalosporin (ceftaz, cefepime), beta-lactam/beta lactamase inhibitor, carbapenems are highly effective, ampicillin0sulbactam is also very effective.
  • Sometimes combination therapy is used i.e. with a fluoroquinolone or aminoglycoside due to concerns of emerging and acquired resistance but limited data on combo therapy vs emergences of resistance or whether clinical outcome is improved.
  • Other possible options: minocycline, tigecycline, polymyxins

Prognosis

  • 2x more likely to die from a carbapenem resistant strain

Hypothermia and Myxedema Coma – 11/13/18

Thanks to Austin for presenting the case of an elderly woman with h/o psychiatric disorder who presented with acute/subacute onset of AMS, severe hypothermia, sinus bradycardia, and hypotension with work up revealing hypothyroidism suspicious for myxedema coma!


Clinical Pearls

  • Exam findings for hypothermia change depending on severity of hypothermia (see below).
  • It is crucial to measure core body temperature for accuracy especially when you are rewarming the patient (esophageal is the best, rectal/bladder are ok prior to rewarming but can remain low in spite of increasing core body temp so do not rely on these metrics alone)
  • Think of etiologies of hypothermia broadly within the categories of increased loss or decreased heat generation.
  • The most common causes of hypothermia are sepsis, exposure, and hypoglycemia.
  • The hallmarks of myxedema coma are AMS, hypothermia, and a precipitating event (i.e. infection, exposure, meds, etc.)
  • Myxedema coma is a medical emergency with a high mortality rate.  So consult endocrine early when you are suspecting it.
  • Always treat myxedema coma with levothyroxine AND steroids until you have ruled out a concurrent adrenal insufficiency.

HYPOTHERMIA

Types:

  • Mild (32-35°C)
    • Clinical manifestations
      • Shivering, rigors
      • ↑ HR, ↑ RR, ↑ BP, hyperventilation
      • Cold diuresis
        • Body’s attempt to preserve heat.  When peripheral vasoconstriction occurs to keep blood closer to vital organs, BP rises.  Kidneys see this rise in BP and act to correct it by dumping fluid! (Oh kidneys…)
    • Treatment
      • Passive, external
        • Blankets
        • Humidified inspired air
  • Moderate (28-32°C)
    • Clinical manifestations
      • ↓ shivering
      • Confusion, slurred speech
      • ↓ HR, hypoventilation
      • Can also start to notice other cardiac manifestations such as prolonged QTc, QRS, osborn (J) waves, ST elevations/depressions.
      • ↓ renal blood flow
    • Treatment
      • Passive, external (see above) PLUS
      • Active external
        • Forced heated air
        • Warm blankets
        • Warm water immersion
      • Active internal
        • Warm humidified air (42°C)
        • Warm IV fluids (42°C)
        • Body cavity lavage (in trauma patients only)
  • Severe (<28°C)
    • Clinical manifestations
      • NO shivering
      • Edema (due to poor renal blood flow) of extremities and lung
      • ↓ HR, ↓ BP (due to drop in cardiac output), hypoventilation, ventricular arrhythmias
      • Cardiac manifestations more common as with moderate hypothermia
      • AMS
      • Paradoxical undressing
        • mechanism is poorly understood but thought to be due to paralysis of the nerves regular vascular muscle tone leading to vasodilation and sensation of a heat flush which results in the patient wanting to take their clothes off.
    •  Treatment
      • Any of the above (passive external, active external, active internal) and/or
      • Extracorporeal
        • HD
        • ECMO

Etiologies of hypothermia:

Capture

Items in red above are the most common causes of hypothermia.

Lab findings:

  • Less reliable since labs have to be warmed prior to processing
    • ABG is often inaccurate
    • Coagulopathy may be masked
    • Hyperkalemia due to rewarming

Complications of rewarming:

  • Hypotension due to peripheral vasodilation
  • Ileus and urinary retention
  • Worsening coagulopathy
  • Arrhythmias
  • Hyperkalemia
  • Core temperature after-drop (a condition in which cold peripheral blood gets shunted to the core and results in further decline in temperature.  You can avoid this by active internal rewarming like warmed IV fluids)

MYXEDEMA COMA 

Learn all about it from our prior blog post here.

Metastatic… Insulinoma? 11/7/2018

Yonglu presented a middle age man with no medical history presenting with syncope. In the preceding months, he has been having non-specific fatigue, decreased exercise tolerance, dizziness, and diaphoresis. He was found to be hypoglycemic after this syncopal episode, and in the hospital his labs were consistent with hyperinsulinism when he was in a hypoglycemic state. CT revealed diffuse liver masses concerning for HCC, as well as a lesion on his left iliac crest appearing to be an osteosarcoma. He was also found to have a pancreatic mass as well…

Three malignant processes? Octreotide scan revealed increased uptake at these regions, and biopsy of the liver revealed a diagnosis of a neuroendocrine tumor!


Hypoglycemia

When we think about hypoglycemia, its pattern can actually give us a clue.

  • Fasting: Most common
  • Post-prandial: non-insulinoma pancreatogenous hypoglycemia syndrome (NIPHS), post-bariatric surgery hyperinsulinemic hypoglycemia
  • Both: Insulin autoantibody, insulinoma

hypoglycemic-differential-hypoglycemia-malignancy-diagnosis-original

Source: grepmed


Insulinoma

Epidemiology

  • Rare, not enough data
  • Small cohort: median age 48 years, 77% men
  • MEN Type 1: Younger presentation, 20s

Pathophysiology

  • Pancreatic islet cell origin
  • Generally benign, single vs multiple
  • Rare to be malignant (10%)

Presentation

  • Pattern: fasting hypoglycemia mainly but can be both
  • May have some sympathoadrenal sx i.e. palpitations, diaphoresis (seen in this patient), tremulousness
  • Likes to spread to liver, rarely can have bony mets (~13%)

Whipple’s Triad: Presence of all three demonstrates “true” hypoglycemia

  • Symptoms of hypoglycemia
  • Low plasma glucose at time of symptoms
  • Relief of symptoms when glucose is back to normal

Diagnosis

  • Evidence of inappropriately high serum insulin during episode of hypoglycemia
  • 72 hour fasting plasma glucose test: Supervised fast in order to bring on hypoglycemia in order to evaluate etiology. If pt has underlying hyperinsulinism, 95-99% of the time they will be hypoglycemia within 48 hours of fasting.
    • Blood test is drawn when pt has sx of hypoglycemia
    • Test: Glucose, insulin, proinsulin, and c-peptide level.
    • Normal: suppression of endogenous insulin
    • Abnormal: Inappropriately elevated insulin, pro-insulin, and c-peptide in setting of hypoglycemia.
  • Octreotide scan: Increased uptake seen in tumors of neuroendocrine etiology, more sensitive than US, CT, or MRI for detection of somatostatin receptor positive tumors
  • Evidence of hyperinsulinism
    • Low BHB
    • High insulin level
    • High C-peptide
    • High pro-insulin
  • Chromogranin A: used to help diagnose carcinoid tumors (NET of the digestive tract and lungs). Nowadays carcinoid is generally used to refer to well differentiated NETs originating in the lungs. GI tract tumors are now termed NET.

Management

  • Localized lesion: Surgical resection is curative
  • Hypoglycemia
    • Somatostatin analogy
      • Octreotide: Inhibits growth hormone secretion, can switch to Q-monthly formulation
      • Lanreotide
    • Diazoxide: Diminishes insulin secretion, side effects include hirsutism and edema
  • Radiation therapy: Data also limited in utility but can be consider if evidence of bony mets (which is also rare for NET)
  • Chemo:
    • Minority of NET, namely high-grade, well differentiated with Ki67 index > 20%, are rare and there is no consensus on how to treat these patients. These patients generally respond poorly to platinum/etoposide based regimens used to treat most NETs.
    • Other options: Temozolomide, Sunitinib (RTK inhibitor), Everolimus (mTOR inhibitor)

Helpful table for hypoglycemia work up.

Beta-hydroxybutyrate (BHB) is by product of alternate metabolism (more specifically ketone bodies) in a fasting state, so it can be elevated in setting of prolonged fasting (not just DKA).

Also thanks to Arathi for pointing out that insulin has a negative feedback on this process, hence in a hyperinsulinemic state (despite concurrent hypoglycemia), beta hydroxybutyrate would be very low!

Insulinomas can appear like hypoglycemia secondary to oral glycemic agents, but the key is the oral glycemic agent screen would be positive in the latter case!

IGF-omas can cause s/sx hypoglycemia due to similarity with insulin. Expect IGF2 levels to be elevated in such cases and elevated BHB.

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Please refer to this helpful review article if you want to know more about NETs!

Also please refer to this paper for a case report on AFP-producing pancreatic NET (AFP elevated in this patient!)