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.
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.
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!
Exam findings for hypothermiachange 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.
↑ HR, ↑ RR, ↑ BP, hyperventilation
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…)
Humidified inspired air
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
Passive, external (see above) PLUS
Forced heated air
Warm water immersion
Warm humidified air (42°C)
Warm IV fluids (42°C)
Body cavity lavage (in trauma patients only)
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
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.
Any of the above (passive external, active external, active internal) and/or
Etiologies of hypothermia:
Items in red above are the most common causes of hypothermia.
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
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)
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!
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
Rare, not enough data
Small cohort: median age 48 years, 77% men
MEN Type 1: Younger presentation, 20s
Pancreatic islet cell origin
Generally benign, single vs multiple
Rare to be malignant (10%)
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
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
High insulin level
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.
Localized lesion: Surgical resection is curative
Octreotide: Inhibits growth hormone secretion, can switch to Q-monthly formulation
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)
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.
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!)
Our doctor-in-training, Jacqueline, presented a case of a 46yo man with a complicated abdominal surgical history, as well as schizophrenia, who presents with acute onset vague abdominal pain. He could not provide any remarkable history (other than abd pain and losing a bag of coins), and his exam was otherwise benign except for mild diffused abdominal pain…
The mystery was resolved on a radiography.
Foreign Body Ingestion
Mostly in kids, peaks 1-2 years of age
Adults: Typically, accidental (95% of cases) usually related to fish, chicken bones, or toothpicks. More common in older adults, pts with mental illnesses, intoxicated, or inmates (drug trafficking, packers vs stuffers).
Most frequent cause of esophageal obstruction = food bolus on existing stricture
Chest pain/abdominal pain
Fever, shock (perforation)
Imaging, clinical history
Will depend on stability, the location, nature of the objects ingested, and progression.
Expectant management for most blunt objects, ~ 70-80% of objects will pass by day 4. Consider surgical/endoscopic intervention if failure to progress
Local necrosis secondary to pressure, electrical current, or caustic chemicals.
Ulceration can occur within 2-4 hours
Perforation can be seen as early as 4-8 hours
VERY IMPORTANT to distinguish between coin batteries (thicker, concentric circles) vs coins (thinner, confluent)!
Higher chance of complications if multiple magnets and/or metallic objects were ingested.
Can react with metal external of the body and cause injury
Localized bowel necrosis, obstruction
Prompt removal endoscopically if in esophagus or stomach.
Beyond stomach: Surgery if symptomatic or failure to progress
Single magnet: Expectant management, serial XR, monitor progress, don’t be around anything ferromagnetic
High risk of perforation/injury if in esophagus, medical emergency
Immediately endoscopic removal if in esophagus
Stomach/proximal duodenum: still consider urgent endoscopic removal, complication risk varies from as low as 10% to 40%
Beyond and failure to progress: Surgical intervention recommended.
Packers vs Stuffers
Packers: Carefully PACKING illicit substances into packages, lower chance of leakage (image adapted from Vectortoons.com)
Stuffers: Hastily STUFFING illicit substances to hide evidence from law enforcement (image adapted from Family Guy), higher chance of content leakage.
Packers: Whole-bowel irrigation safe and feasible
Opioid (CNS depression, hypoventilation, pinpoint pupils): IV Naloxone 0.05 in nonapneic patients, 0.2 – 1mg in apneic patients. Larger doses may be required if pt ingested a large amount of heroin.
Sympathomimetic (agitation, hypertension, hyperthermia): Symptomatic management, airway monitoring, temperature control. AVOID pure beta blockers. Can consider GI decontamination but consult Poison Control.
If suspecting ingestion of potentially toxic substance, don’t hesitate to call Poison Control!
Sarasa presented a case of a young woman with recently diagnosed pulmonary TB on HREZ presenting with worsening dyspnea and voice changes. Her fiberoptic endoscopy of the upper airway was normal. She was found on CT to have tissue thickening and stranding in the mid/lower trachea as well as a small tracheal diverticula, very suspicious for endobronchial TB!
Definition: TB that involves the tracheobronchial tree
More common among patients with extensive pulmonary TB, especially with cavitary lesions, can occur in 10-40% of patients but less common now with anti-TB therapy.
For some reason more likely to occur in women in second to third decades of life.
Usually seen in main and upper bronchi, but in 5 % of cases: involves the lower trachea
Unclear but thought to be by either direct extension of pulmonary disease into the bronchi, spread via infected sputum, or hematogenous/lymphatic spread.
Cough, CP, hemoptysis, wheezing (low pitch), fatigue, fever, dyspnea. Can mimic foreign body aspiration, non-resolving pneumonia, or malignancy.
Can have significant sputum production, leading to bronchorrhea (> 500mL/day of sputum)
Diagnosis: CT and bronchoscopy are methods of choice for dx, with bronch being the most validated for confirming the diagnosis.
XR: Can be normal in 10-20% of cases
CT: Can demonstrate endobronchial lesions, stenosis (up to 2/3 of patients), or fistulas.
Bronchoscopy: able to visualize stenosis and biopsy. Can interview if severe symptomatic stenosis.
Same as for other forms of TB but also prevent tracheobronchial stenosis
Intensive Phase: HREZ (aka RIPE) x 2 months
Ex: 2HREZ/4HR = standard regimen, 2 months of HREZ (RIPE), followed by 4 months of isoniazid and Rifampin
Specific for endobronchial TB
Shown improvement in outcome (prevention of bronchial compression) in children.
Some data on shortening healing time and decrease severity of bronchial stenosis
Nebulized INH or streptomycin, mixed data
Surgery: Usually indicated for stenosis or stricture. Balloon dilatation, stenting, ablation, resection, cryosurgery.
Severe tracheobronchial stenosis sometimes requires pneumonectomy or lobectomy
Distinctive entity, also more prevalence in younger patients, most commonly presents with dysphonia (96%), odynophagia (25%), and stridor (9%). True vocal cords, epiglottis, and false vocal cords are most commonly involved.
Drug Resistance and TB
Drug-resistance TB: resistant to one or more anti-TB drugs
Mono-resistant: single agent
Poly-resistant: resistant to multiple drugs, but susceptible to either INH or rifampin but not both
MDR: R to INH and rifampin + others.
XDR-TB: Extensively drug resistant TB: resistant to INH, rifampin, fluoroquinolones + either aminoglycosides or capreomycin or both.
If suspecting resistant, strategy usually is to add at least 2 additional drugs. Adding single drug inc risk for resistance.
Management of drug-resistant TB:
Tx of MTB PCR will be based on susceptibility data
Conventional: 20-26 months treatment, with an intensive phase with at least 5 effective drugs for at least 6 months after negative sputum, followed by a continuation phase of at least 4 drugs for 18-24 months
Shorten version for 9-12 months if no extra-pulmonary manifestation and susceptible to quinolones.
Thanks to Barnie for presenting the case of a middle-aged woman who was admitted with acute onset of SOB, found to have submassive PE.
Risk stratification tools are helpful in estimating the pre-test probability of PE. The best and most validated is Wells criteria.
YEARS items is a newer tool that was studied in an RCT in the Netherlands and found to lower the number of CTPA scans ordered by 14% without a significant impact on rates of missed PE diagnoses.
For patients at low risk of PE according to Wells, PERC is useful in ED or outpatient setting to rule out PE without ordering a d-dimer (see graphic below).
Age-adjusted d-dimer is age x 10 for patients older than 50 years. This accounts for the increase in d-dimer baseline related to aging. ADJUST-PE trial showed that age-adjusted d-dimer leads to higher specificity without subsequent VTE.
Studies have shown an 11.6% reduction in CTPA scans with the use of this correction factor without an appreciable increase in missed diagnoses of PE.
Think of PE in three broad categories:
Massive PE = hemodynamically unstable ⇒ anticoagulation + thrombolysis
Low risk PE = hemodynamically stable, no RV strain ⇒ anticoagulation. Use the PESI score to determine if your patient can be treated outpatient.
Remember that the most common EKG finding in PE is normal sinus rhythm! The most common abnormal EKG finding is sinus tachycardia. S1Q3T3 pattern is only seen in 10% of patients with PE.
Suggested algorithm for diagnostic work up of suspected PE:
Remember that the scoring tools above are only there to add to your clinical judgment, not replace it!
Recent study in the Lancet looked at the utility of a different diagnostic algorithm, using the three most predictive items on Wells together with d-dimer. Compared to Wells, this diagnostic tool led to a 14% reduction in unnecessary CTPA!
Remember that clot burden does not factor into the treatment categories of PE. Low clot burden in a patient with baseline cardiopulmonary disease can still lead to hemodynamic compromise and would be considered massive PE.
Submassive PE treatment is an area of much debate. A famous trial (PEITHO trial) in 2014 randomized 1006 patients to receive heparin + placebo vs heparin + tenecteplase (European version), and found a >50% reduction in combined death and cardiovascular collapse at 7 days but a > four-fold increase in risk of major bleed including intracranial hemorrhage. Subsequent meta-analyses (and this one) found that the risk of major bleeding was highest in people >65 years of age. So treatment decisions here are tricky and require consulting multiple services!
Signs of RV strain:
S1Q3T3: this is a sign of cor pulmonale and can be seen in a number of conditions in addition to PE
Bronchospasm (really bad asthma)
McConnell’s sign (regional wall motion abnormality sparing the RV apex)
Not sensitive but helpful in distinguishing RV strain due to chronic pulmonary HTN from RV strain due to acute PE
Narges presented a case of a late-middle age woman with history of recurrent pancreatitis, chronic alcohol use, who presents with worsening leg swelling, nausea/vomiting, and chest pain in setting of increased alcohol intake from bereavement. She increased her alcohol intake from “several drinks” a day to a fifth of hard liquor per day for the past few weeks. She was incidentally found to have a severely elevated Transferrin Sat, and genetics study revealed HFE mutation consistent with hemochromatosis.
For those of us illiterate in EtOH… A standard drink is defined as:
Hereditary: Up to 10% of Caucasians in US and Western Europe are thought to be heterozygous. Homozygous roughly 0.5%.
Symptomatic median age around age 40 for males, later for females due to higher iron loss.
Disorder of iron storage, that results in increased intestinal iron absorption and iron deposition.
Iron deposition leads to organ damage.
Most commonly secondary to mutant HFE (human hemochromatosis protein).
HFE codes a protein involved in cellular iron sensing and intestinal iron absorption regulation.
Autosomal recessive with variable penetrance.
Heterozygotes are asymptomatic and are not at risk of iron-overload.
Homozygous patients have variable disease penetrance, thought to be relatively low.
***Key point: Just because someone has the mutation (can be incidentally found on genetic sequencing) does not mean they will have the disease (iron build up in the body leading to end organ damage).
Alcohol intake is a major risk factor for development of liver disease for patients with HFE mutation. Iron overload thought to potentiate effect of alcohol induced liver toxicity
Liver damage occurs without inflammation, but hence HH can occur in setting without elevated AST/ALT.
At least 43% of HH pts have other underlying causes i.e. fatty liver, alcohol, HBV/HCV, that leads to elevated transaminases and liver cirrhosis.
Most common mutant is C282Y, if heterozygous, not at risk for developing progressive or symptomatic iron overload.
Homozygous C282Y are at risk but again penetrance is variable.
Homozygous H63D are generally not at risk but might have minor abnormalities in iron studies. If symptomatic, usually has other underlying process i.e. alcohol (such as this patient).
Secondary iron overload (seen in frequent transfusions due to ineffective erythropoiesis)
Takes time to develop end-organ damage. Patients are usually asymptomatic until they have 20+ g of iron built up in the body (average iron content of an adult is 4-5g).
Early: Non-specific, weakness, weight loss, skin hyperpigmentation (bronze skin), abd pain, loss of libido.