Mirizzi Syndrome

By vmcimchiefs

Thanks to Richard for presenting the case of a middle-aged man who presented with acute onset of lower back pain, intermittent abdominal pain, and emesis, found to be septic, work up revealing Mirizzi syndrome causing acute cholangitis which led to klebsiella bacteremia and L spine osteomyelitis! Whoosh!

Clinical Pearls

  • Klebsiella is found along the GI tract and can cause UTIs, pneumonias, osteomyelitis, GI infections, and surgical site wound infections.
  • Charcot triad of pain, fever, and RUQ pain is found in only ~50% of patients who present with acute cholangitis.  So do not rule out the diagnosis if someone doesn’t have all three.
  • Mirizzi syndrome is rare and can be accompanied by acute chonagitis, acute cholecystitis, or acute pancreatitis.  Management involves antibiotics to treat a concurrent infection in the biliary tree as well as surgical resection of the gallbladder and impacted stone.

Differential for hyperbilirubinemia:

Hyperbilirubinemia breakdown

Remember that the most common reasons for conjugated hyperbilirubinemia are extrahepatic causes and include the following:

  • Stones (30-70%)
  • Malignancy (10-50%)
  • Benign biliary strictures (5-30%)
  • Biliary stent obstruction (~20%)

Cholangitis

Most common bacteria:

  • E coli (25-50%)
  • Klebsiella (15-20%)
  • Enterococcus (10-20%)
  • Enterobacter (5-10%)

Clinical manifestations

  • Charcot’s triad (~50% have all 3)
    • Fever
    • Abdominal pain
    • Jaundice
  • Reynold’s pentad: (rare, ~5%)
    • Above PLUS
    • Hypotension
    • AMS
  • Cholestatic LFT pattern ⇒ can progress to hepatocellular LFT pattern

Assessment of disease severity

  • Severe (suppurative) cholangitis — Acute cholangitis is considered severe if it is associated with the onset of dysfunction in at least any one of the following organs/systems:
    • Cardiovascular dysfunction – Hypotension requiring pressors
    • AMS
    • Respiratory dysfunction – PaO2/FiO2 ratio <300
    • Renal dysfunction – Oliguria, serum creatinine >2.0 mg/dl
    • Hepatic dysfunction – Prothrombin time-international normalized ratio >1.5
    • Hematological dysfunction – Platelet count <100,000/mm
  • Moderate acute cholangitis — Acute cholangitis is defined as moderate if it is associated with any two of the following:
    • Abnormal WBC count (>12,000/mm3, <4,000/mm3)
    • Fever 39°C (102.2°F)
    • Age (≥75 years)
    • Hyperbilirubinemia (total bilirubin ≥5 mg/dl)
    • Hypoalbuminemia
  • Mild acute cholangitis — Mild acute cholangitis does not meet the criteria for moderate or severe cholangitis at initial diagnosis.

Management

  • For moderate to severe cases, consider admission to the ICU and urgent ERCP/GB decompression.
  • For mild cases, admit to the floor and monitor closely
  • Antibiotics
    • To cover gram negatives, narrow based on sensitivities
    • Duration is typically 7-10 days.
  • Address predisposing cause
    • Elective cholecystectomy after infection has resolved in those with gallstones

Mirizzi syndrome

Obstruction of the common bile duct from extrinsic compression, often from swelling or infection in the cystic duct, which can share a sheath with the CBD.

  • Commonly diagnosed intraoperatively in patients undergoing GB surgery
  • Presentations
    • Pain (54-100%)
    • Jaundice (24-100%)
    • Cholangitis (6-35%)
    • Acute cholecystitis (1/3 of patients)
    • Acute pancreatitis (rare)
  • Labs
    • Elevated bili and ALP
    • Leukocytosis if concurrent cholecystitis, cholangitis, or pancreatitis
  • Diagnosis
    • Imaging
      • Dilatation of the biliary system above the gallbladder neck
      • Presence of impacted stone in GB neck
      • Normal diameter below level of stone
    • US (23-46% sensitive)
    • CT abdomen (can r/o malignancy but sensitivity is 42%, specificity 99%)
    • MRCP (highest sensitivity)
  • Management
    • Surgery
    • Sometimes ERCP can be diagnostic and therapeutic as a temporizing measure to surgery or if patient is too high risk and unsuitable for surgery
    • Antibiotics for treatment of concurrent cholangitis or cholecystitis

mirizzi-syndrome-5-638

Source: https://www.slideshare.net/mohamedfazly31/mirizzi-syndrome-70749345

Nephrotic Syndrome Secondary to Minimal Change Disease (12/3/2018)

By vmcimchiefs

Narges presented a case today with a middle age woman with uncontrolled insulin dependent diabetes Type 2, multiple malignancies s/p resection, presenting with acute anasarca and shortness of breath developed over a few days. She was anasarcic up to the mid back on presentation, with an albumin of 0.9 (baseline of 3.8 a month ago). Her UA had 3+ protein and a urine protein/Cr ratio of 23. If you’re thinking nephrotic syndrome, that’s right! Biopsy revealed the diagnosis of minimal change disease (MCD) with concurrent ATN!

Nephrotic Syndrome

Some definitions

  • Nephrotic range proteinuria: > 3.5g proteinuria per day or spot urine protein/cr ratio of > 3.5
  • Nephrotic syndrome: Above + symptoms (edema, HLD, hypoalbuminemia, lipiduria, etc)

Epidemiology

  • Most common primary cause of nephrotic syndrome in adults in the US is FSGS
  • Most common secondary cause of nephrotic syndrome in adults in the US is Diabetic Nephropathy

Presentation

  • AKI (underlying glomerulonephritis vs hypovolemia vs sepsis vs ATN)
  • Hypercoagulability (loss of anticoagulant proteins namely antithrombin III, C, S)
  • Hyperlipidemia (reactive hepatic synthesis of proteins due to hypoproteinuria)
  • Malnutrition (gut edema, dec body weight, edema) leading to anemia, osteomalacia, vitamin D deficiency
  • Immunocompromise (inc risk for infection due to hypoimmunogammopathy)
  • Edema (low oncotic pressure due to hypoalbuminemia)

Diagnosis

  • 24 urine protein > 3.5g is diagnostic
  • Spot urine protein/cr ratio > 3.5 is also diagnostic
  • Exactly cause will require additional work up, to be discussed below in differential

General Management Strategies

  • Proteinuria control (ACEi, ARB)
  • BP Control
  • Volume Control (Diuretics, low salt)
  • HLD: usually resolves with disease control, can use statins
  • Immunosuppresion for primary causes
  • Treat underlying secondary causes

Differential Diagnosis

Picture1

Source: Grepmed

The three most commonly encountered causes, besides diabetic nephropathy, are:

Capture

Minimal Change Disease

As seen in this patient, is typically seen in pediatric population and it is the most common cause of nephrotic syndrome in kids < 8-10 years old. It only accounts for 10% of cases of nephrotic syndrome in adults.

Presentation

  • Acute onset edema
  • Higher incidences of thrombotic events in adults
  • AKI common, at higher risk for ATN

Diagnosis

  • Biopsy, electron microscopy with podocyte effacement

Management

  • Corticosteroids: initial course of 6-8 weeks in adults, 1.5mg/kg/day
  • Cyclosporine for non-responders
  • Other options: mycophenolate (Cellcept), azathioprine (but pt is already on this, Imuran!)

Prognosis

  • 80-90% of patients respond to initial corticosteroid therapy
  • Up to 50% can recur

Focal Segmental Glomerulosclerosis (FSGS)

Epidemiology

  • Higher incidence among African Americans (5 times more likely than White)
  • Associated with HIV (collapsing variant), heroin (30x risk)

Diagnosis

  • Biopsy: focal and segmental hyalinization of the glomeruli, often with immunostaining showing IgM and complement (C3) deposits in a nodular and coarse granular patter

Management

  • Primary: Immunosuppression, corticosteroids +/- cyclosporine, tacrolimus + plasma exchange
  • Secondary: Treat underlying cause

Prognosis: Poor

  • > 50% develop renal failure within 10 years of diagnosis, and 20% develop ESRD within 2 years despite treatment
  • May recur after kidney transplantation.
  • Heroin addicts with FSGS: can experience complete remission if they STOP EARLY.

Membranous Nephropathy

Epidemiology

  • Associated with malignancy i.e. lymphoma, colon cancer, lung cancer
  • Most cases are idiopathic

Diagnosis

  • Biopsy
  • Microscopy: Thickened capillary loops
  • Immunoassay: Granular IgG & C3 depositions in the subepithelial layer

Management

  • Immunosuppression similar to above, treat any secondary causes

Prognosis

  • Generally pretty god, 30-40% treated go into complete remission, 30-50% go into partial remission. Treatment can be prolonged.
  • Treating secondary causes also can induce remission.

Note that there are some other causes that can present with both nephrotic and nephritc features, i.e. membranoproliferative glomerulonephritis. Complement levels are NORMAL in MCD, FSGS, and MN, while complement levels are low in MPGN.

Primary anticoagulation for patients with nephrotic syndrome can be considered in some cases but not routinely done. Please refer to this article for reference.

 

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

By vmcimchiefs

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 D, Lovat LB, Haidry R. Management of non-variceal upper gastrointestinal bleeding: where are we in 2018? Frontline Gastroenterology Published Online First: 09 February 2018. doi: 10.1136/flgastro-2017-100901

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)

By vmcimchiefs

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

By vmcimchiefs

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

By vmcimchiefs

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!

By vmcimchiefs

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.