Moffitt Pearls 8.15.17 – Anaphylaxis and Drug Reactions

Case Summary:

Thank you to Karen for presenting a mystery case of a young man with hx of asthma, seasonal allergies and eczema p/w perioral edema, itching and profound hypotension concerning for anaphylaxis! We discussed the importance of early therapy for anaphylaxis, drug reaction patterns and the possibility of serum sickness in the setting of Bactrim exposure and the atypical nature of her presentation.

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Key Pearls

  1. Anaphylaxis is a Type 1 IgE mediated hypersensitivity reaction that usually occurs within in minutes of an allergen exposure.
    • Volume and IM epinephrine are mainstays of therapy and should NOT be delayed.
  2. Drug reactions are often delayed days to weeks from drug exposure (make sure to review a log) and are mediated by Type IV hypersensitivity.
  3. Angioedema may be manifested by IgE mediated (Type I Hypersensitivity) drug reaction
    • IgE-mediated reactions tend to become more severe & progress toward anaphylaxis (Bactrum as in our case) upon re-exposure to causative agent

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Classification of Allergic Reactions

Type Description Mechanism Clinical Features
I Anaphylactic Usually IgE dependent release of vasoactive substances (histamine, prostaglandins and leukotrienes) Anaphylaxis (definition below), Angioedema, urticarial, GI Sx and bronchospasm
II Antibody (AB)-dependent cytotoxicity Antigen/Haptan associated with cell binds AB -> cell/tissue damage Hemolytic anemia, Interstitial nephritis
III Immune Complex Disease Formation of Antigen-Antibody (AB) Complexes Causes damage Serum Sickness
IV Cell-mediated or Delayed Hypersensitivity Antigen sensitizes T cells, then mediates tissue injury Delayed dermatitis or drug reaction

Drug Reaction Patterns Discussed

SJS (< 10 % body surface area)/TEN (>30% body surface area)

  • Mucosal involvement required, occurs usually within 8 weeks of drug exposure

DRESS

  • Systemic involvement (fever, adenopathy elevated LFTs) driven by eosinophilia; Reaction begins 2-6 weeks after exposure to offending drug

AGEP

  • Reaction often occurs 48-72 hours after drug exposure

Fixed Drug Eruption

  • Usually without mucosal involvement, occurs anytime – days to weeks after drug exposure

Erythroderma

  • >90% of body surface area involved; ddx wide and includes drugs ~ 20% cases and malignancy (Cutaneous T-cell lymphoma)

anap

 

Moffitt Pulmonary Report Pearls 8.14.17

Thank you to Luis for presenting a case of an elderly woman with history of bronchiectasis and MAC presenting with fevers, cough and chest pain. We were joined by Bhavika Kaul from pulmonary!

Key Pearls

  1. Ditty pearl: Use ABCD2 score (age > 60, BP >140, clinical features, duration > 60 min & DM) to decide whom to admit after TIA. For a score > 2 hospitalization recommended given higher risk (> 4 %) of 2 day CVA.
  2. Faget sign (sphygmothermic dissociation) is described as a temperature-pulse dissociation and is often a sign intracellular organisms with typhoid fever being a common boards question. MOST common cause of fever, HR dissociation… beta-blockade.
  3. Diagnosis of MAC requires BOTH microbiology and the appropriate clinical context (more details below).

Diagnosis of MAC in the Non-HIV Patient

  • Microbiology
    1. Induced sputum with at least 2 positive cultures  Or
    2. At least 1 bronchial lavage Or
    3. Transbronchial biopsy with mycobacterium
  1. Clinical Context:
    1. Pulmonary symptoms, nodular or cavitary opacities on CXR or CT scan with multiple nodules and bronchiectasis   AND
    2. Exclusion of other diagnoses

Treatment of MAC

  • Remember that macrolides are the cornerstone of therapy and you DO NOT want to use Azithromycin as a single agent given risk for resistance and partial treatment.
    • Hence, avoid azithro as single drug coverage or part of treatment for superimposed CAP in patient with possible MAC
  • For most patients being treated for MAC pulmonary disease require a three-drug combination regimen
    • Selection depends, in part, on susceptibility to macrolides; most MAC isolates are macrolide susceptible.
    • Antimycobacterial treatment is difficult to tolerate (weight benefits & risks) & continued until sputum cultures are consecutively negative for at least 12 months. 

Fun Fact!

50% of patients with advanced HIV patient (CD4 <50) with a positive sputum culture for MAC who are NOT TAKING MAC ppx will get disseminated infection (fevers, weight loss, rising LFTs and cytopenias).


 Differential Diagnosis for Bronchiectasis

  • Chronic infections
  • Chronic aspiration
  • History of childhood infections
  • Cystic fibrosis
  • Cigarette smoking
  • Inflammatory – Rheumatoid Arthritis and Sjogren’s Syndrome
  • Allergic bronchopulmonary aspergillosis (ABPA)
  • Ciliary dyskinesia

Evernote: https://www.evernote.com/shard/s462/sh/52c9c737-6173-4108-8804-5652964366f4/7bc8596565dd78a597987d8d5f322ff4

VA AM report 8.14.17: Hyponatremia hiding mediastinitis

Case summary: Kelly Sydell paid us a visit this morning to tell us about a great case– a 74M with PMH aortic stenosis s/p recent aortic valve replacement, who presented with mild hyponatremia with a difficult volume exam, as well as mild incisional erythema and was found to have post-operative Salmonella mediastinitis.

Top pearls:

  1. The most common cause of mediastinitis in the modern era is a post-operative complication of thoracic or cardiac surgery; the majority are monomicrobial and nosocomial.
  2. Chest CT scan with contrast is the radiologic test of choice in diagnosing mediastinitis, as symptoms and exam findings can be subtle (as in this patient), and mediastinal widening on CXR is not sensitive in post-operative mediastinitis (but interestingly IS more sensitive in mediastinitis from other causes!).
  3. LT and Goop reminded us that during the AIDS epidemic, we learned that non-typhoidal Salmonella has a predilection for aortitis and mycotic aneurysm, particularly in the setting of atherosclerosis.

Post-operative mediastinitis

  • In the olden days, most mediastinitis arose from esophageal perforation, contiguous spread of oropharyngeal infection, penetrating trauma or hematogenous spread
  • Now, most cases are the consequence of cardiac or thoracic surgery
  • Incidence post-operatively ranges from 0.5-4% and depends on both patient factors (e.g. DM, obesity) and operative characteristics (e.g. how long the sterum is open)
  • Bacteriology (majority nosocomial and mono microbial):

mediastinitis

  • More atypical causes: fungi, Legionella, Mycoplasma hominis, or Nocardia and Mycobacterium tuberculosis
  • Presentation can be fulminant and acute or mild and subacute-to-chronic
  • Patients present with:
    • fever
    • tachycardia
    • chest pain
    • sternal instability
    • signs of sternal wound infection
    • purulent discharge
    • majority with leukocytosis and 50% with +BCx
  • Physical exam findings can be subtle; if suspicious, mediastinal widening on CXR is insensitive for post-operative mediastinitis (more sensitive for non-post-op causes), so radiologic test of choice is CT chest with contrast
  • Treatment:
    • surgical debridement with either primary or secondary closure
    • antibiotics for 2-6 weeks (vanc/zosyn–> narrow pending intra-operative cultures)

UptoDate

Dubert M, Pourbaix A, Alkhoder S, Mabileau G, Lescure F-X, Ghodhbane W, et al. (2015) Sternal Wound Infection after Cardiac Surgery: Management and Outcome. PLoS ONE 10(9): e0139122.


Salmonella and the vasculature

  • Vascular infections due to Salmonella can involve the thoracic and abdominal aorta, as well as coronary arteries, peripheral arteries, or vascular grafts and prosthetic valves.
  • Aortic infections are much more frequent, and the majority of these involve the abdominal aorta.
  • Nearly all cases of aortitis due to Salmonella result in formation of an aneurysm or, less commonly, in enlargement of a previously existing aneurysm
  • Most patients with aortitis due to Salmonella have preexisting atherosclerotic disease at the site of the subse- quently infected aneurysm
  • Mediastinitis due to Salmonella is rare and morbid, as it is strongly associated with concomitant aortitis, mycotic aneurysm, and rupture.

 

Soravia-Dunand, VA et al. Aortitis Due to Salmonella: Report of 10 Cases and Comprehensive Review of the Literature. Clinical Infectious Diseases 1999;29:862–8.

 

Fernández-Ayala M1, Nan D, Gutierrez JA, Fariñas MC. Postoperative mediastinitis due to Salmonella. Scand J Infect Dis. 2003;35(1):67-8.


Approach to hyponatremia

Just a reminder that until robots take over medicine and improve our volume exams, there exists a very nifty volume-independent hyponatremia algorithm found here (Rabih version) and here (Rachel Stern version)!

 

ZSFG AM Report 8/14/2017: Management of Severe ARDS

Thank you to Josh Shak and Jesse Fitzpatrick for presenting a case of severe ARDS. Also thank you to Vincent and Alison, our pulm/crit care fellows for dropping knowledge bombs left and right in report. Amazing!

Top Pearls:

  1. Proning and paralysis are the two interventions in severe ARDS that have been consistently linked with improved mortality.
  2. Consider 4 parameters when considering whether you can give diuretics in a patient with severe ARDS (cardiac output, urine output, need for pressors, and volume status)
  3. Remember that high-flow can be used in hypoxemic respiratory failure.

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ARDS:
  • Onset within one week of known insult
    • Direct injury: PNA, aspiration, pulmonary contusion, fat emboli, near drowning, post lung transplantation
    • Indirect injury: Sepsis, severe trauma, shock, drug overdose, DIC, pancreatitis, TRALI
  • Bilateral infiltrates on CXR not fully explained by effusions, nodules, or lung collapse
  • Resp failure not fully explained by heart failure or volume overload (PCWP <18)
  • Hypoxemia:
Severity: (PaO2/FiO2 ratio)
  • Mild: ratio 200-300
  • Mod: ratio 100-200
  • Severe: <100
Treatment:
  • Ventilation w/ ARDSNet Protocol: Less lung compliance, so goal is to reduce barotrauma, allow permissive hypercapnia
    • Volume/pressure limited ventilation: NEJM 2000- Small tidal volumes (6mL/kg ideal body weight) are associated with reduced mortality of 31% compared to conventional VT patients (12mL/kg) that have a mortality of 40%. Plateau pressure goal <30 cmH2O. If plateau pressure higher, decrease VT in 1ml/kg increments
    • Oxygenation: Goal PaO2 55-80 mmHg or O2 sat 88-95%. Two grids – low PEEG (ARMA trial) vs. high PEEP (ALVEOLI, LOV, Express trials). Chose strategy based on clinical scenario to avoid oxygen toxicity but if poor cardiac squeeze / chest tube / other reason to want lower PEEP keep that in mind
    • Minimize acidosis: pH >7.30. Adjust respiratory rate (max 35), consider bicarb to keep pH at goal
    • I:E ratio: Goal 1:1-1:3. Adjust flow rate and inspiratory flow to achieve this goal
  • Refractory hypoxemia on ARDSNet protocol
    • Neuromuscular blockade: NEJM 2010, single RTC showed mortality benefit of cisatracurium – decreases O2 consumption and improves synchrony (when given upfront)
    • Recruitment maneuvers: Transiently increase PEEP to recruit atelectatic lung – MD at bedside bc can become transiently hypotensive bc decreased preload, also increased risk barotrauma
    • Conservative fluid management: NEJM 2007- FACTT RCT showed that conservative fluid strategy with diuresis (goal CVP <4, PCWP <8) resulted in better oxygenation, fewer days on vent (of note, trial excluded patients with hypotension, on pressors, with oliguric renal failure, or on HD). So general concept is to maintain MAP >65 and avoid hypoperfusion, but better to be dry than wet in ARDS – fluid restrict and use diuretics
    • Inhaled epoprostenol (flolan) / inhaled nitric oxide: Vasodilation- temporarily improves oxygenation, but no mortality benefit
    • Tham/Bicarb: Minimizes acidosis, but no mortality benefit
    • Proning: NEJM 2013, PROSEVA group- French trial showed reduction in mortality if proning done early
    • ECMO: Lung replacement therapy with extracorporeal membrane oxygenation (ECMO)

 

Sources:

  • Thank you to Laura Huppert for sharing this outline/Summary for ARDS including references for many of the trials!

Evernote:

  • ARDS: https://www.evernote.com/shard/s509/sh/cb6c79be-7831-4f91-b27b-64adb933d76c/f899c44e2a65b98100f54fb2744f2728

ZSFG AM Report Pearls 8/11/17: Localizing the Lesion in Cirrhosis

Thank you to Scott Goldberg for presenting a case of a patient with new onset ascites who was found to have cirrhosis on ultrasound with questions about the utility of liver biopsy

Top Pearls:

  • Consider pre-sinusoidal, sinusoidal, and post-sinusoidal approach to a differential for elevated portal pressures in patients with new ascites
  • Other etiologies of ascites outside of elevated portal HTN, include peritoneal disease and hypoalbuminemia

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A Framework for New Ascites:

  • There are many approaches and frameworks for ascites. One approach is thinking about elevated portal HTN versus other causes of ascites not due to portal hypertension
    • Other approaches include thinking about alterations in hydrostatic vs. oncotic pressures
  • Within elevated portal pressures, there is a separate differential that can be broken down into:
    • Pre-sinusoidal
    • Sinusoidal
    • Post-sinusoidal
  • Non-elevated portal pressure ascites can also be broken down into:
    • Generalized hypoalbuminemia
    • Peritoneal disease

Portal HTN

Elevated Portal Pressure Ascites:

  • Pre-Sinusoidal: Portal vein thrombosis, Splenic vein thrombosis (complication of pancreatitis, pancreatic tumor), Developmental abnormalities (polycystic liver disease, AV fistulas), Biliary disease (biliary cirrhosis, PSC), Neoplastic occlusion of intrahepatic portal vein (lymphoma, CLL, epithelial malignancy), Granulomatous processes (schistosomiasis, sarcoidosis)
  • Sinusoidal: Infiltrative disease into the space of Disse (amyloid, light chain deposition, ,mastocytosis), Fibrosis of space of Disse (NASH, viral hepatitis, CMV, schisto, toxins), compression of space of Disse (hypertrophied hepatocytes)
  • Post-Sinusoidal: Budd-Chiari, vascular malignancies, Cardiac causes (constrictive pericarditis, restrictive cardiomyopathy)

Space of Disse

Non-Elevated Portal Pressure Ascites:

  • Hypoalbuminemia: Nephrotic syndrome, Protein-losing enteropathy, Severe malnutrition
  • Peritoneal Disease: malignant ascites, infectious peritonitis, eosinophilic gastroenteritis, starch granulomatous peritonitis, peritoneal dialysis

Sources:

Evernote:

VA ICU Report 8.11.17: ACS and EtOH withdrawal

Case Summary

Thanks to our ICU team for presenting an interesting case of a 74M with esophageal CA c/b low grade GIB who presented with ACS and found to have triple vessel disease


Top pearls

  1. Peripheral arterial disease commonly co-occurs with CAD –> check pulses in your patients presenting with chest pain.
  2. The complications of a femoral access  include pseudoaneurysm, AVM and RP hematoma. Cholesterol embolization syndrome is a delayed complication.
  3. In patients with CAD,  be more aggressive with controlling the sympathetic surge that accompanies alcohol withdrawal.

EtOH withdrawal

Check out this graph about the manifestations of EtOH withdrawal  – courtesy of Anna Parks!

IMG_1698.PNG

To summarize:

  • Patients can develop signs of withdrawal as early as 6 hours after their last drink
    • Initial symptoms and signs are that of sympathetic hyperactivity
      • Tremor, anxiety, tachycardia and tachypnea
  • Delirium tremors usually develops 72 hours after last drink and is characterized by
    • Altered sensorium
      • This is the distinguished feature of DTs
    • Increased autonomic dysfunction
  • Seizure
    • Risk increases after 24 hours
    • Most seizures are generalized tonic clonic and rarely last > 3  min
      • Rule out other causes of seizure that occur more commonly in patient with alcohol use disorder
        • Subdural hemorrhage
        • Nutritional deficiencies (pyroxidine > thiamine in terms of seizure risk)
        • Traumatic encephalopathy
          • This can create a nidus for seizure activity independent of EtOH use

Treatment

There is an increasing number of treatment options for EtOH withdrawal. It is helpful to divide these options into GABAergic agents versus GABA independent drugs.

  • The primary reason to do so is because GABA independent agents do not protect from EtOH withdrawal seizures

GABAergic agents

  1. Benzodiazepines
    • First line option for most patients
  2. Barbituates
    • Phenobarbital is an increasingly utilized option especially for patients being dc’d from the ED
  3. Propofol
    • Use this in patients who are intubated and experiencing EtOH withdrawal

GABA independent agents

  1. Dexmedetomidine
    • Central acting alpha blocker that reduces the CNS sympathetic outflow
    • This is a great adjunct to one of the agents above.
  2. Clonidine
    • Similar mechanism to above
    • Used less frequently
  3. Haldol
    • Increasingly used and incorporated in CIWA protocols specifically for agitation
      • Helps reduce BzD use
      • Caution with QTc prolongation
  4. Others
    • Gabapentin and Carbamazepine are other less frequently used adjuncts to reduce BzD requirement.

 

Moffitt Pearls – 8.11.17 – Saddle Nose Deformity, Upper GI Bleeding &Munchausen Syndrome

Thank you to HH and Neil for both presenting today! HH first presented a mini case of a patient who came in for a gout flare that was found to have a saddle nose deformity.

Neil then presented the interesting case of a young woman with a hx of gastric ulcers presented with epigastric pain and hematemesis who after extensive work-up including CT and EGD was found to have Munchausen syndrome!************************************************************************************

Key Pearls

  1. The differential diagnosis for saddle nose deformity falls into the classic triad of infectious, inflammatory and malignancy per table below.
  2. 80% of upper GU bleeds are due to four causes: peptic ulcer disease (35%), esophagogastric varices (30%), esophagitis (10%) and Mallory-Weiss tears (~5%).
  3. The management strategy for a pt. w/ munchausen syndrome is VERY difficult, but should include a single provider (w/ help from psychiatry) and goal to limit interventions + discuss diagnosis with patient in a supportive manner.

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Differential Diagnosis for Saddle Nose Deformities

Infectious Inflammatory Malignancy Other
Syphilis GCA (formerly Wegner’s) NK T-cell Lymphoma Trauma
Leprosy Sarcoidosis Locally invasive tumor (BCC) Cocaine
TB Relapsing polychondritis Lymphomatoid Granulomatosis Surgery
Cutaneous Leishmaniosis      
Septal abscess      

 Differential Diagnosis for Hematemesis AND Fever

  • Mallory-Weiss Tear
  • Peptic ulcer bleeds c/b perforation
  • Hemosuccus pancreaticus (pseudoaneurysm/aneurysm)
  • Upper GI Malignancy – hemobilia, widespread esophageal/gastric malignancy

Munchausen Syndrome or Factitious d/o Imposed on Self

  • Definition: Falsified general medical or psychiatric symptoms
  • Risk Factors: Females, Unmarried, Healthcare professional
  • Diagnostic Criteria (DSM-5):
  1. Falsification of physical or psychological signs or symptoms, or induction of injury or disease, associated with identified deception
  2. The individual presents himself or herself to others as ill, impaired, or injured
  3. The deceptive behavior is evident even in the absence of obvious external rewards
  4. The behavior is not better explained by another mental disorder, such as delusional disorder or another psychotic disorderPrognosis: Very poor even as multiple studies have shown limited benefit even with psychotherapy
  • Management: One provider should oversee pt with help of psychiatry w/ goal to limit interventions. One should be sure to exclude all possible medical conditions and then discuss diagnosis w/ pt in supportive manner