February 7th 2020: Differential Diagnosis for Leg Ulcers

Leg Ulcers

Over 90% of leg ulcers caused by Venous Insufficiency, Arterial Insufficiency or Neuropathic cause. The differential for the remaining 10% is broad.
Venous Insufficiency:
Tend to occur mid-calf to ankle. Area just above the medial and lateral malleolus most commonly affected
Shallow with irregular borders
Pain is mild to moderate
May have surrounding venous stasis dermatitis
Diagnosis made clinically
Peripheral Arterial Disease:
Tend to occur distally on toe or on pressure areas such as heel, malleoli and shin (areas with the poorest blood flow)
Well-demarcated edges, “punched out” appearance” often with overlying eschar
Pain typically severe
Often complain of claudication symptoms, have shiny legs with decreased hair and diminished peripheral pulses
Diagnosis confirmed with ABI testing
Neuropathic Ulcers:
Most commonly occurring in diabetic patients but also seen in many other conditions that lead to peripheral neuropathy
Typically occur over pressure points on the foot and heal.
Have a “punched out” appearance and typically occur with a  thick callus
Painless
Diagnosis: Clinical but sensory exam can confirm peripheral neuropathy
Everything Else:
When your patient doesn’t fall into one of these 3 common buckets (or a combination of the above such as the diabetic with PAD) the differential is broad. In most cases the underlying pathophysiology has to do with fact that some process is leading to poor blood flow to the affected tissue. Differential includes the following categories:
Physical Injury
Pressure sore
Thermal Injury (burn or severe cold)
Radiation Injury
Factitial (self-injury)
Infection:
Many causes including bacterial, mycobacterial, fungal (aspergillus endemic fungi), spirochete (tertiary syphilis) and protozoal (leishmanias) infections. Some common causes to mention include:
Ecythyma: A deep form of Impetigo classically caused by Strep and Staph
Ectyhyma Gangrenosum: an infection of the media and adventitia of arteries and venules most commonly caused by Pseudomonas but can be seen with a range of organisms (bacterial and others)
Can also have secondary infection of ulcers that occur for other reasons
Vasculitis:
Many different causes including: Henoch Schonlein Purpura, Polyarteritis Nodosa, Granulomatosis with Polyangitis, SLE, Rheumatoid Vasculitis
Hypercoagulable Conditions:
Numerous inherited and acquired causes, notably including anti-phospholipid syndrome
Pyoderma Gangrenosum:
A neutrophilic dermatosis often associated with an underlying systemic disorder
Tends to have a real nasty and ugly appearance, often starts as a pustule that develops into a bulla, then ulcerates with purulent drainage
Is diagnosis of exclusion.
Malignancy
Squamous cell, basal cell, melanoma, cutaneous lymphoma, Kaposis sarcoma
Drugs:
Warfarin skin necrosis, HIT, hydroxyurea, along with others
Other:
Spider bite, Calciphylaxis, along with others

February 7th 2020: Pathophysiology and Management of Insomnia

Defining Insomnia and its Pathophysiology:
  • Melatonin release is inhibited by blue light.  Note that white light (usual overhead lights contains blue light)
  • Insomnia: difficulty falling asleep (sleep initiation) or staying asleep (sleep maintenance) with consequence (symptoms)
  • Why do people get insomnia?  There are two competing forces in the brain.  Neurotransmitters that promote wakefulness (serotonin, norepinephrine, histamine, glutamate) and sleepiness (melatonin and adenosine)
  • Adenosine builds steadily during the day and is responsible for sleep initiation.  Melatonin is responsible for sleep maintenance rather than initiation.
  • Caffeine blocks adenosine receptors, which inhibits sleepiness
  • Often insomnia is more of an issue of excessive wakefulness, not inadequate sleepiness.  This is why a good history is important for identifying wakefulness triggers (stimulants, anxiety, light).
CBT for Insomnia
  • stimulus control: uses Pavlovian conditioning to restrict the bed for sleeping; the patient should be advised to get out of the bed after 20 minutes and do something distracting
  • sleep restriction: sleep deprivation is the best cure for insomnia; determine when the patient is falling asleep and tell the patient to go to sleep at that time while still waking at the same time (do not go lower than 6 hours to avoid adverse effects) 

Pharmacologic treatments for Insomnia

  • Classes of drugs for sleep: melatonin and melatonin receptor agonists, anti-histamine, anti-depressants, benzodiazepines, benzodiazepine receptor antagonists, anti-psychotics, orexin antagonists
  • if the patient has any component of anxiety start an SSRI first (sertraline and lexapro are good options as they are less activating)
  • Anti-depressants, mirtazepine and low-dose doxepin are sedating without being anti-cholinergic which makes them better than trazodone and amitriptyline
  • Benzodiazepine receptor agonists: Ambien, Lunesta and Sonata; these are better options than BZD’s; Sonata is shorter acting than Ambient and Lunesta
  • Avoid anti-psychotics for insomnia
  • Orexin antagonists: suvorexant and lemborexant (orexin deficiency causes narcolepsy)

January 31st: NonBacterial Thrombotic Endocarditis (NBTE)

Nonbacterial Thrombotic Endocarditis (NBTE)

Also called Libman-Sacks Endocarditis and marantic endocarditis
Epidemiology:
Rare
Most commonly affects patients with:
  • Advanced Malignancy (up to 80% of cases)
    • Most commonly Adenocarcinoma
    • Up to 10% of patients with Mucinous secreting pancreatic Adenocarcinoma develop NBTE
  • SLE (Lupus)
Also seen rarely in:
  • Antiphospholipid Syndrome
  • Rheumatoid Arthritis
  • Sepsis (particularly in setting of DIC)
  • Severe burns
Pathogenesis:
  • Thought to require both endothelial damage to heart valve and a prothombotic state
Clinical Presentation:
  • Typically asymptomatic until Embolization occurs and majority of complications are due to embolization
  • Up to 50% of patients develop embolic phenomena
  • NBTE vegetations are more likely to dislodge than infective endocarditis vegetations due to lack of inflammatory reaction at attachment site and hence they are “less sticky”
  • Common Embolization sites include spleen, kidney, skin, extremities. But also commonly lead to Strokes due to CNS emboli
  • Valvular dysfunction is rare
Workup:
  • 3 sets of blood cx prior to antibiotics to evaluate for infection
  • Consider PCR testing for Coxiella, legionella, Brucella etc if Cultures negative
  • If infection thought to be unlikely based on this workup then:
    • Workup for Hypercoagulable state including:
      • Lupus anticoagulant
      • Coags, Fibrinogen, D-Dimer to evaluate for DIC
      • Search for e/o malignancy and SLE by history/exam
        • Age appropriate cancer screening a must, further evaluation as appropriate
        • Consider SLE workup: ANA, ENA panel
Treatment:
  • Anticoagulation: Based on clinical experience and retrospective studies the recommendation is to anticoagulate these patients as long as no contra-indication exists
  • Anticoagulation indicated whether or not they have embolized given the high risk of developing embolic disease
  • LMW Heparin recommended over Warfarin or DOACS
    • Studies suggested LMWH superior to Warfarin
    • DOACS not studied

References:

Bauer, Kenneth, et al. “NonBacterial Thrombotic Endocarditis.” UpToDate, 2 May 2019, www.uptodate.com/contents/nonbacterial-thrombotic-endocarditis

January 17th: Approach to Flank Pain and Nephrolithiasis

Differential for flank pain:

  • GI: cholecystitis, appendicitis, diverticulitis, constipation
  • Urologic: nephrolithiasis, pyelonephritis
  • Reproductive: testicular torsion in males, ovarian torsion in females, ovarian cyst rupture, PID
Workup:
  • Urinalysis w/ microscopic
  • Urine culture
  • CBC/chem 7
  • CT renal stone protocol provides more prognostic and characterizing information than a renal US, which only tells you if there is hydro and potentially can see some stones.  CT will allow you to determine size of stone and thereby likelihood of passing the stone.
  • If you’re sure the patient likely has a stone or if the patient has a history of stones, you can use a renal US to confirm.
Management of nephrolithiasis:
  • IV hydration
  • Toradol is first-line for pain control
  • Anti-emetics
  • As an outpatient counsel them to drink 3L a day, avoid diet sodas, low sodium, eat plenty of calcium (calcium supplements for vegans), DASH diet is really good for stones
Indications for emergent intervention of nephrolithiasis/ureterolithiasis:
  • fever +/- high suspicion for infection
  • sepsis
  • intractable symptoms often end up requiring stenting
  • solitary kidney with elevated Cr
  • percutaneous nephrostomy vs ureteroscopy:  very sick/ ICU patients often need PCN by IR because they cannot tolerate anesthesia needed for ureteroscopy/stenting
Interesting Tid-bits:
What’s a passable stone?:
  • almost definitely without question:  4mm or less
  • per guidelines: less than 10mm
Dark urine is different from bloody urine.  Bloody urine should be bright red.
Shock wave lithotripsy is not readily available, but is still an effective method of decompression.  However, they should be carefully chosen because they have a higher risk of needing a secondary procedure.  It is also not without untoward effects.   The shock waves can cause microvascular damage to the kidney.
Flomax has been proven scientifically to have no effect, however, we often still offer it simply to provide patients with a targeted medication.  However, note that flomax does not help non-obstructing intra-renal stones.

January 9th 2020: Bacterial Meningitis Pearls

Indications for Head CT prior to LP:
While many of us learned in Medical School that you need to get a HCT prior to an LP this is only needed in specific circumstances as outlined by the 2004 IDSA guidelines on Bacterial Meningitis. Patients with any of the following require a HCT prior to an LP.
  • Immunocompromised state (eg, HIV infection, immunosuppressive therapy, solid organ or hematopoietic cell transplantation)
  • History of central nervous system (CNS) disease (mass lesion, stroke, or focal infection)
  • New onset seizure (within one week of presentation)
  • Papilledema
  • Abnormal level of consciousness
  • Focal neurologic deficit

In the absence these presenting signs/symptoms you should not get a HCT as it can delay time to LP and antibiotics. If a HCT is not needed order Blood cultures and have the LP done STAT and start antibiotics + steroids as soon as these are done. If a HCT is needed order blood cultures STAT and start antibiotics + steroids prior to HCT and LP in order to avoid delay in antibiotics.

Empiric Antibiotic Coverage for Community Acquired Meningitis

From the 2004 IDSA guidelines:

  • Age 2-50 y/o: Vancomycin + Ceftriaxone
  • Age>50 y/o: Vancomycin + Ceftriaxone + Ampicillin

Note that Age >50 you need Ampicillin coverage for Listeria.

It is also important to know that Vancomycin is necessary to cover Ceftriaxone resistant Strep Pneumoniae

Indications for Steroids:

The evidence for use of steroids in bacterial Meningitis largely comes from a 2002 NEJM Paper “Dexamethasone in adults with bacterial meningitis” by de Gans et al. IDSA guidelines summarize it as follows:

“A total of 301 adults were randomized to receive dexamethasone (10 mg q6h for 4 days) or placebo, the first dose being administered 15-20min prior to the first antimicrobial dose. At 8 weeks after enrollment, the percentage of patients with an unfavorable outcome (15% vs. 25%;P= .03 ) and death (7% vs. 15%; P = .04) was significantly lower in the dexamethasone group. Among the subgroup of patients with pneumococcal meningitis, benefit was evident in those who received adjunctive dexamethasone, with a lower percentage of unfavorable outcomes (26% vs. 52%; P =.006 ) and deaths (14% vs. 34%; P = .02 ). Benefits were not seen in other sub groups with meningitis caused by other meningeal pathogens, although patient numbers in those groups were small. In all groups, dexamethasone appeared to be the most beneficial in patients with moderate-to-severe disease on the Glasgow Coma Scale.”

Based on this data current recommendations are to start Dexamethasone 0.15mg/kg Q6H for 2-4 days, with first dose given at the time of antibiotics. Dexamethasone should only be continued if CSF gram stain reveal gram= positive diplococci or/if blood or CSF cultures grow Strep pneumonia

The guidelines mention that some experts only recommend Dexamethasone if the GCS is </= 11 given that these patients appeared to derive the largest benefit in a subgroup analysis of the NEJM paper, however current IDSA guideline recommend giving Dexamethasone regardless of GCS out of concern that assessment of GCS may delay administration of steroids.

January 9th 2020: Workup and Management of PMR/GCA

History questions to ask if concerned for GCA:

  • vision changes? (look for diplopia, monocular vision loss)
  • pain characteristics? (commonly sharp, temporal in location, can be unilateral or bilateral, constant, severe)
  • jaw claudication? tongue claudication? (people often tire of chewing)
Laboratory workup for GCA: 
  • CMP, CBC, CRP, ESR (can use either CRP or ESR if one or the other is unremarkable, but the other marker is elevated), temporal artery ultrasound (a new diagnostic test becoming more available and is already available at Duke), temporal artery biopsy, vitamin D (because patient will potentially need bisphophanate while on steroids)
  • Also make sure to get BPs in both arms and both legs since GCA can cause pressure differentials
  • Can do a PET scan in the case of a difficult diagnosis to look for inflammation in the large arteries
 
What is a normal ESR?  Divide patient’s age by 2 and add 10
 
Management of GCA:
  • first-line: high-dose steroids (1mg/kg daily with maximal dose of 60mg)
  • alternatives: MTX, Tocilizumab (anti-IL-6 agent)
  • Note that tocilizumab is starting to be used alongside steroid therapy and studies are ongoing
  • Trend ESR to ensure that it is coming down, but treatment should be based on symptoms, not ESR trend
A few interesting notes on GCA:
  • The ability of a temporal artery biopsy to diagnose GCA generally does not go down over time.  Don’t worry about if a few days have passed and you and your patient still want to get the biopsy.  Steroids will not destroy the yield (don’t let the surgeons mislead you!).  It may reduce the inflammatory cells, but the pathognomonic arterial architecture will remain.
  • Fundoscopic exam in patients with GCA should show evidence of optic disc ischemia (in the form of pallor) and edema (all due to vasculitis and thrombosis of the vessel feeding the optic nerve)
  • Temporal artery ultrasound is now available at Duke.  Neuro-Ophthalmology generally performs the temporal artery ultrasound/  Findings look like a “halo sign” when pushing down on the artery.  If the ultrasound is highly suggestive of GCA, you may even be able at some point to forgo temporal artery biopsy.
History questions to ask if concerned for PMR:
  • morning stiffness?
  • proximal muscle weakness? (trouble lifting arms/brushing hair)
  • hip pain? (can test hip range of motion in elderly by having them seated and internally/externally rotating hip by swinging foot lateral and medial)
Treatment of PMR:
  • steroids: 12.5-25mg daily for 2-4 weeks, then taper by 1mg per week
  • patients generally improve rapidly (within hours of steroid dose)
  • MTX is a possible alternative, but less effective
  • tocilizumab trials are under way for PMR

ATS/IDSA 2019 Updates to CAP Guidelines

Sputum stain and culture/Blood Cultures:

-NOT recommended for CAP in the outpatient setting

-Recommended for inpatients:

-Classified as severe CAP

-Empirically treated for MRSA and P. Aeruginosa

-Previously infected with MRSA or P. Aeruginosa

-Hospitalized and received IV Abx during the hospitalization or in the last 90 days.

Legionella and S. Pneumo urine antigen

-Recommendation is to NOT routinely test in adults with CAP except in:

-Cases with epidemiological factors (outbreaks and recent travel)

-Severe CAP

Procalcitonin

-Empiric abx should be initiated in adults with clinically suspected and radiographically confirmed CAP regardless of initial serum procal

Prediction Tools for inpatient vs outpatient

-Pneumonia Severity Index over CURB-65

-PSI identifies larger proportions of patients as low risk and has a higher discriminative power in predicting mortality.

 

Ectopic ACTH

The summary is that CRF/CRH (corticotropin-releasing factor/hormone) is produced by the hypothalamus and passes to the corticotrope cells in the anterior pituitary via the hypophyseal portal system. CRH stimulates corticotrope cells in the anterior pituitary to produce a long peptide called POMC (pro-opiomelanocortin). CRH also stimulates the cleavage of POMC into multiple things but the final products include ACTH,  beta-lipotropin, and melanocyte stimulating hormone (MSH).  ACTH then is released into the blood stream and causes the secretion of glucocorticoids from the adrenal cortex, typically in response to stress.

The reason for hyperpigmentation in adrenal insufficiency is related to increased production of POMC (due to negative feed back from glucocorticoid deficiency) and therefore MSH which results in increased melanin synthesis, causing hyperpigmentation. It appears that in the process of protein cleavage of POMC, it is first cleaved into the ACTH protein and then cleaved again to the MSH protein.
I found a nice review article attached about the work-up of patients  with suspected Cushing Syndrome. Cushings
Ectopic ACTH syndrome –  accounts for approximately 20% of ACTH-dependent CS cases. As Jeremy had mentioned, finding the source of the tumor is very important as this disease can be cured. It appears that about 80% of cases have complete remission.
Sources:
-Tumors of the lung (small cell, bronchial carcinoid tumors) – about 50% of cases.
-Non-lung neuroendocrine tumors – ~23% of cases
              -Thymic tumors
              -Pancreatic
              -Gastrointestinal carcinoids
-Medullary thyroid carcinomas – 7.5% of cases
-Pheochromocytoma – 2.5% of cases
It appears that the DOTATATE scan which is a somatostatin-analog radiolabeled with gadolinium for PET shows the highest sensitivity among molecular imaging for detecting neuroendocrine tumors in ectopic ACTH production.

  Outpatient Treatment of Alcohol Use Disorder

Outpatient Treatment of Alcohol Use Disorder

Screening: CAGE questions have fallen out of favor as they tend to only capture patients with severe alcohol dependence (as opposed to at risk use).  USPTF now recommends using AUDIT-C. The AUDIT-C consists of three questions and is recommended screening tool in the primary care setting. The USPSTF recommends screening all patients >18 for alcohol use disorder. If you only have time for one question, ask “How often do you drink > 4-5 drinks in one sitting for women, 60+ older or > 6 drinks in one sitting for men.” The calculator of can be found here.

 

These three questions make up the AUDIT-C:

 

●How often do you have a drink containing alcohol?

 

●How many drinks containing alcohol do you have on a typical day when you are drinking?

 

●How often do you have six or more drinks on one occasion?

 

Medications: There are three FDA approved medications to treat alcohol use disorder: naltrexone (vivitrol = long acting injectable form), acamprosate, and disulfiram. This table from MKSAP does a nice job outlining each medication (see table).

A few key points:

·         Naltrexone

o    Avoid in patients with cirrhosis. It has known liver toxicity. Consider stopping this medication if liver enzymes are > 10x upper limit of normal. It’s also an opioid antagonist, so do NOT use this drug in patients with ongoing opiod use.

o    Starting dose = 50mg

·         Acamprosate

o    Not used often given TID dosing (666mg TID)

o    Avoid in patients with renal disease (GFR < 30). If CKD 3 or greater, will require dose reduction

 

We also talked about a few off-label options, including gabapentin and topiramate.

·         Gabapentin: For outpatients at risk of withdrawal (e.g. hx of prior withdrawal, high intake) or with ongoing use, Dr. Brown recommend starting gabapentin at 300mg PO qhs and then quickly up-titrate to 300mg PO TID à 600mg PO TID.

·         Topomax: 75mg to 300mg daily. Dr. Brown does not exceed 200mg PO daily. Side effects: mental slowing, kidney stones, tingling sensation (related to carbonic anhydrase). Not typically used for withdrawal treatment.

Acute Liver Injury

Adapted from Dr. Cunningham’s case during intern report.

Per the American College of Gastroenterology guidelines, The R-value is defined as serum ​alanine aminotransferase (ALT) / upper limit of normal (ULN) divided ​by serum alkaline phosphatase (Alk phos) / ULN. This value is helpful to discern the pattern of liver injury in someone presented with a transaminitis. The image below is adapted from MD calc on how to interpret the value. Basically, an R – value ≥ 5 is defined as hepatocellular, R <2 is cholestatic and 2 < R < 5 is mixed.
https://www.mdcalc.com/r-factor-liver-injury
As talked about in report, AST/ALT ratio is also important in helping to find an etiology to a liver injury. AST/ALT ratio > 2 is suggestive of alcoholic liver disease, particularly in the setting of an elevated GGT. Other causes of high AST/ALT ratios are listed below.
-Occasionally in non-alcoholic steatohepatitis
-Hepatitis C cirrhosis
-Wilsons disease
-Viral hepatitis
-Rhabdomyolysis (AST comes from tissues other than the liver, such as muscle).
Lastly, indications for SBP prophylaxis are listed below. Adapted from uptodate.

-Patients with cirrhosis and gastrointestinal bleeding. Antibiotic prophylaxis in this setting has been shown to decrease mortality in randomized trials.

-Patients who have had one or more episodes of SBP. In such patients, recurrence rates of SBP within one year have been reported to be close to 70 percent.

-Patients with cirrhosis and ascites if the ascitic fluid protein is <1.5 g/dL (15 g/L) along with either impaired renal function or liver failure. Impaired renal function is defined as a creatinine ≥ 1.2 mg/dL (106 micromol/L), a blood urea nitrogen level ≥ 25 mg/dL (8.9 mmol/L), or a serum sodium ≤130 mEq/L (130 mmol/L]). Liver failure is defined as a Child-Pugh score ≥9 and a bilirubin ≥ 3 mg/dL (51 micromol/L).