Today, we talked about the fascinating case of a middle-aged man presenting with subacute cough, night sweats, and 15 pound weight loss, found to have bilateral hilar LAD on CXR and CT concerning for pulmonary sarcoidosis. While awaiting LN biopsy, he developed L sided Bell’s palsy with MRI showing inflammation of CN5 and CN7 as well as nodular dural thickening of the trigeminal cave concerning for neurosarcoidosis. LN biopsy showed non-caseating granulomas and he was subsequently started on high dose steroids for neurosarcoidosis.
Sarcoidosis is a multisystem granulomatous disorder of unknown etiology.
The most common clinical presentation of sarcoidosis is pulmonary related.
In asymptomatic individuals with incidental hilar LAD, there is no indication for LN bx to diagnose sarcoidosis because 2/3 of cases resolve spontaneously without treatment. Close follow up is needed to ensure that patients do not develop symptoms.
Similarly, Lofgren syndrome (arthritis, erythema nodosum, hilar LAD, and fevers) and Heerfordt’s syndrome (uveoparotid fever) are clinically consistent with sarcoidosis and there is no indication for LN biopsy.
DDx for unilateral facial droop
Especially if forehead is spared. However, keep in mind that a stroke involving the region of pons which houses the nucleus of CN7 would mimic Bell’s palsy!
Lymphoma or other mass compressing CN7
Multisystem granulomatous disorder of unknown etiology
3-4 x more common in blacks
Overall prevalence is 10-20 per 100,000 people
Aberrant formation/accumulation of non-caseating granulomas
Age of onset is 20-60 years
Often discovered incidentally on a CXR
Most common organ involved is the lung (cough, SOB, CP) with ILD being the most common type of lung involvement. 30% of patients present with extrathoracic manifestations.
Fatigue, malaise, fever, and weight loss are common
Otherwise, biopsy the easiest site to access. Keep in mind that erythema nodosum does not have granulomas and would not help in diagnosing sarcoidosis.
Lab abnormalities that may be present:
Leukopenia, eosinophilia, thrombocytopenia
ESR and CRP may be elevated
Hypercalciuria is more common than hypercalcemia
Moderate elevation in ALP suggests diffuse granulomatous hepatic involvement
Hypergammaglobulinemia and a positive RF (not usually part of routine work up)
ACE levels are elevated in 75% of untreated patients with sarcoid but has poor sensitivity and insufficient specificity (10% false positive rate with cocci, DM2, TB, hyperthyroidism, lung cancer, pneumoconiosis, etc.)
Organs that may be impacted in sarcoid
Pulmonary: occurs in over 90% of patients. Bilateral hilar LAD as well parenchymal disease. Can present with a restrictive spirometry pattern due to underlying fibrosis, pulmonary HTN
Cutaneous: can be disfiguring can be macules, papules, plaques and erythema nodosum
Liver/Spleen: a high alkaline phosphatase level suggests granulomatous liver disease
Neurologic: Noted in 5% of cases. MRI with contrast can help with diagnosis. Complications:
Cranial-nerve palsies (20-50%) → most common
Optho: anterior uveitis most common manifestation
Cardiac: Typically cardiomyopathy, can also see arrhythmias (tachy or brady).
Renal: Can have hypercaliuria (more common than hypercalcemia) and renal calculi
Bone: chronic arthritis and cysts resembling rheumatoid, and diffuse granulomatous myositis.
Asymptomatic? Follow up outpatient q3-4 months and annually thereafter to monitor for development of symptoms.
Clinical Pearls from our first ever (and hopefully monthly) ECG Report!
Make sure to always work through an ECG in a systematic way in order to avoid missing key information.
Remember that you might not see any p waves (or retrograde P waves) in AVRT and AVNRT. Both of these rhythms would be fast and regular. A fib, by contrast, would be irregular.
Hypercalcemia presents with a shortened QT and a loss of the ST segment on ECG. But make sure you are ruling out an MI because often times the loss of ST segment resembles a STEMI.
Whenever you see a downward p wave in lead I, think of two diagnoses:
Limb lead reversal
Easiest way to distinguish between dextrocardia and limb lead reversal is to look at the QRS amplitude as you move across the precordium. If the amplitude is decreasing as you advance from V1 to V6, then the diagnosis is dextrocardia because you are moving away from the heart. If the amplitude is not changing or increasing, then the diagnosis is limb lead reversal.
The presence of > 2 mm coved precordial ST-segment elevation (leads V1through V3) with T wave inversions is suggestive of Brugada morphology. In a patient with history of syncope, ventricular arrhythmias, or family history of Brugada syndrome, this is consistent with a diagnosis of Brugada syndrome and would require ICD placement.
Have an interesting ECG? Save them/send them our way for our next ECG report!
Thanks to Erica for presenting the case of a middle aged man who presented with acute back pain and B symptoms after trauma to his back, found to have stage 3B multiple myeloma.
Remember that majority of cases of acute low back pain (<6 weeks) is due to musculoskeletal etiologies that spontaneously improve on their own. Imaging and further diagnostic work up is not indicated unless there are red flags (see below).
A straight leg test is more useful when negative as it has a high negative predictive value for ruling out radiculopathy. False positive rates are quite high.
Unexplained anemia and worsening renal function in the outpatient setting should trigger a work up for multiple myeloma.
The most common presenting symptoms for MM are anemia (73%), bone pain (58%), and renal insufficiency (48%).
In diagnosing MM, sensitivity increases with each added test: SPEP (82%) → IFE (93%) → FLC/UPEP (97%). The other 3% that would not be diagnosed with these tests have a non-secretory MM (monoclonal increase in plasma cells in bone marrow that do not produce immunoglobulins or light chains).
Red flags for acute low back pain:
Focal neurologic complaints/deficits
History of cancer
Age >50 years
Fever not explained by another cause
History of recent bacteremia or IVDU
Pain that is worse at night
No relief with bed rest or pain lasting >1 month
Multiple Myeloma: refer to this prior blog post. Other info below:
SPEP: picks up M protein or elevated immunoglobulins (heavy + light chain) in the serum. You can diagnose over 80% of patients with MM using an SPEP.
IFE: identifies the specific type of immunoglobulin that is elevated with its light chain.
Free light chains (FLC): measures the amount of free light chains not bound to a heavy chain floating around in the blood. Normally people have about a 2:1 ratio of kappa to lambda chains. In light chain only multiple myeloma, there is a disproportionate increase in one type over the other and the ratio will be off. If there is an increase in both light chains but the ratio is normal, think kidney disease!
Keep in mind that the reason to check FLC when you suspect MM is to diagnose those people who are only producing light chains and not whole immunoglobulins that would have been picked up by SPEP/IFE.
UPEP: measures light chains dumped in the urine (Bence Jones protein)
Thanks to Connie for presenting the case of an elderly woman who presented with petechial bleeding, found to have a platelet count of 15, with work up revealing possible Evans’ Syndrome as well as bladder cancer!
Think of thrombocytopenia as a problem with platelet production, platelet destruction, sequestration, or lab problem.
ITP is a diagnosis of exclusion. It can be a primary process due to autoimmune platelet destruction, or triggered by an associated condition (secondary ITP).
Remember that decadron is superior to prednisone in treatment of ITP based on this meta-analysis.
TPO mimetics are best as a last resort and more useful in maintenance of remission rather than inducing remission.
Severe megaloblastic anemia (folate/B12 deficiency)
Today we talked about the case of a young woman who presented after suicide attempt by ingestion of multiple prescription medications, found to be obtunded, initially in status epilepticus and later with exam findings concerning for serotonin syndrome.
Continuous EEG is indicated if a patient is not returning to baseline mentation 15 mins after a seizure to rule out non-convulsive status epilepticus.
Status epilepticus is defined as a seizure lasting > 5 mins or > 2 discrete seizures between which there is incomplete recovery of consciousness.
Treatment of status epilepticus involves acute management with IV/IM benzos, urgent long-term control with IV fosphenytoin (preferred), phenytoin, or valproic acid. Remember that keppra is more useful in suppressing future seizures than treating an acute episode.
Serotonin syndrome is a clinical diagnosis and manifests with neuromuscular activation like tremors, hyperreflexia, and clonus (generally worse in lower extremities). Use Hunter’s criteria to help with diagnosis.
When is continuous EEG needed?
If patient is not returning toward baseline in 15 mins after a seizure, goal is to rule out nonconvulsive seizures
How to define status?
> 5 mins OR
> 2 discrete seizures between which there is incomplete recovery of consciousness
Non-convulsive status epilepticus
Suspect if LOC not improving by 10 mins after cessation of movement
Mental status remains abnormal for 30-60 mins after movement cessation
Dx requires a 24-hour EEG (we don’t have one ☹)
Treatment is the same as generalized status epilepticus, but prognosis is worse (mortality 65% vs 27%)
Treatment of status
Assessment and supportive treatment
Initial pharmacologic therapy
Ativan (2 mg IV q1-2 mins), total dose 0.1mg/kg
Watch out for respiratory depression and hypotension
Alternatives: versed 0.2mg/kg IM, valium 0.2mg/kg IV
Urgent long-term control
Fosphenytoin (preferred): 20 mg/kg at 150mg/min
Give extra 10 mg/kg if not responding
Dephosphorylates into phenytoin. It’s more soluble in water and less likely to precipitate in the skin and vessels.
Phenytoin: 20mg/kg at 50mg/min (slower than fospheny)
If infused too fast, can irritate skin/vessels causing skin necrosis
Valproic acid: 20mg/kg at 5 mg/kg/min
Sometimes the preferred choice in patients with known generalized epilepsy b/c phenytoin can provoke absence seizures in that population.
What about Keppra?
Technically not FDA approved for status. It has weak evidence to support its use. More useful in suppressing subsequent seizures after status has been controlled.
Clinical diagnosis. Serum serotonin concentrations do not correlate with clinical findings.
Severe disease can lead to DIC, rhabdo, renal failure, and ARDS.
Diagnostic criteria: use Hunter’s (84% sensitive, 97% specific)
Serotonin syndrome may be distinguished from other causes of agitated delirium on the basis of neuromuscular findings. Whereas patients with serotonin syndrome show signs of neuromuscular activation (eg, tremor, hyperreflexia and clonus that are greater in the lower extremities, ocular clonus, and increased muscle tone), patients with sympathomimetic toxicity or infections of the central nervous system lack these findings.
Supportive care and sedation
Chemical sedation preferred over physical restraint
High BP: esmolol or nitroprusside (Short acting). Avoid longer acting agents
Low BP: neo or epi. Avoid idirect agents like dopamine because they are converted to epi and norepi. When monoamine oxidase is inhibited, epi and norepi production at the cellular level is not controlled and could lead to an exaggerated HD response.
No benefit to Tylenol b/c increase in body temp is due to increased muscular activity rather than alteration in the hypothalamic temperature setpoint.
If temp >41.1, then sedate, paralyze, intubate
Histamine receptor antagonist. Also has weak anticholinergic activity
12 mg loading dose, then 2 mg q2h until clinical response is seen.
Is sedating (good) and can also cause transient hypotension.
Thanks to Jess for presenting the fascinating case of a middle-aged woman with family history of autoimmune disease who presented with acute onset of fatigue and abdominal pain, found to have vitiligo on exam. Work up revealed hyponatremia due to a secondary adrenal insufficiency, pancytopenia, and panhypopituitarism possibly due to a yet to be diagnosed autoimmune disorder!
Remember that hyponatremia is a problem of water regulation that can be compounded by low solute intake.
Primary adrenal insufficiency is disorder at the level of the adrenal glands and manifests with low sodium and high serum potassium levels.
Secondary adrenal insufficiency is disorder at the level of the pituitary and manifests with low/normal sodium and normal potassium levels (because low cortisol leads to high ADH levels and hyponatremia).
Make sure to do work up to rule out panhypopituitarism. Keep in mind that the most sensitive test for HPA access integrity is LH/FSH.
Tertiary adrenal insufficiency is disorder at the level of the hypothalamus and presents similarly to secondary AI.
Test for adrenal insufficiency with a cort-stim test and/or AM cortisol and ACTH levels.
Remember these three steps to working up hyponatremia:
Is there a sodium problem? check serum osm
Are the kidneys responding appropriately? check urine osm
Is ADH revved up for a hemodynamic reason? check urine Na
Failure of adrenal glands
Causes: Addison’s (most common in the US), infiltrative processes (TB, sarcoid), hemorrhage, toxins
Labs would show ↓Na and ↑potassium (b/c aldosterone is gone)
Failure of pituitary (low ACTH)
Causes: pituitary lesions, surgeries, TBI, drugs
Clinically may present with loss of other anterior pituitary hormones
Labs would show ↓Na (because low cortisol leads to high ADH levels) but normal potassium levels (b/c aldosterone is active)
Failure of hypothalamus (low CRH)
Causes: more commonly iatrogenic (cessation of high dose glucocorticoid therapy without taper) or post surgical interventions.
Inflammation of the pituitary
Four categories based on histologic findings:
Most common form
Seen in late pregnancy and post-partum period
Also associated with CTLA4 inhibitors like ipilimumab
Idiopathic or secondary to GPA, sarcoid, TB
Xanthomatous (most rare)
Headache out of proportion to exam findings
Preferential decrease in ACTH and TSH ⇒ adrenal insufficiency and hypothyroidism
Pituitary size eventually normalizes but pituitary loss of function is often permanent.
Thanks to Audris for presenting the case of a middle-aged man with vasculopathy on ACEi who presented with angioedema requiring intubation! We discussed the diagnostic work up and management of angioedema as well as hyperkalemia!
First order of business when suspecting angioedema is the ABCs!
Treat angioedema in the acute setting with H1 blockers and steroids, even if you are suspicious of a non-histaminergic pathway.
Always assess for concurrent anaphylaxis (hypotension or bronchospasm in addition to hives or angioedema). If anaphylaxis is present, then treatment involves IM 0.3-0.5 mg of 1:1000 dilution epinephrine (1mg/mL), repeat every 20 minutes until symptoms resolve (max 3 doses)
If you have access to a functioning kidney, favor loop diuretics over cation exchange binders (i.e. kayexalate) to lower serum potassium!
Patiramer is much better tolerated than kayexalate and has a more favorable side effect profile.
Calcium gluconate has a role in the treatment of hyperkalemia when EKG changes are present. Give a dose and repeat the EKG. If no improvement, repeat to a maximum of 3 doses until EKG has normalized.
3 pathophysiologic subtypes:
Mast cell/histamine mediated
Allergic reactions: food/insect stings, latex, drugs. Can also be idiopathic. IgE type 1 hypersensitivity
Direct mast cell release: drugs (opiates, contrast). IgE is not involved.
ASA/NSAIDs: via IgE or direct mast cell release
Chronic urticaria w/w/o angioedema
S/sx affecting organ systems other than the skin? Suspicious for anaphylaxis ⇒ give epi
Treatment: H1 blockers, glucocorticoids.
Inhibition of enzymes involved in the degradation of bradykinin, or deficiency/dysfunction of complement C1 inh
More prolonged time course, develops over 24-46 hours and resolves within 2-4 days
Relationship between trigger and onset of symptom is not as apparent
Not associated with other s/sx. More common to have abdominal pain due to bowel wall involvement.
Other drugs: sirolimus, everolimus, amiodarone, metoprolol, risperidone, paroxetine, and etanercept, inhaled cocaine.
Hypereosinophilic syndrome and Gleich syndrome
Agents that reduce serum potassium via transient intracellular shift:
Insulin: give with D50 if normoglycemic to avoid hypoglycemia and be sure to check FSG hourly for 4 hours after to ensure no hypoglycemia develops
Albuterol (10-20 mg) nebs: this is significantly higher than the dose we give in COPD (2.5 mg) and is equal to ~8 treatments! So make sure to continue the nebs when the patient arrives on the floor from the ER if they are still hyperkalemic.
NaHCO3: best for management of chronic hyperkalemia in the outpatient setting. In the acute management of hyperkalemia, alkalinization of serum with a large bicarb load can lead to a reduction in serum calcium levels. Lower serum calcium can lead to more cardiac membrane instability and fatal arrhythmias!
Agents that eliminate potassium from the body:
Loop diuretics: first choice if a functioning kidney is available!
Cation exchange binders: preferred when kidneys are not available
Patiramer (available at VMC), much more tolerable than kayexalate and highly effective at lowering serum potassium. Like kayexalate, it works over hours to days.
Sodium zirconium: similar to patiramer but not currently available
Kayexalate: not pleasant to take orally. Also carries with it the slight risk of colonic ischemia especially in post renal transplant patients and those with baseline colonic dysfunction (due to infection or inflammation).
Indication for using calcium gluconate: when EKG changes are noted. Repeat doses (maximum 3) until EKG changes have resolved.