Today, we talked about the case of a middle-aged man from the Philippines who presented with a one year progressive pruritic rash involving the face, arms, and legs as well as a distal symmetric peripheral neuropathy, found to have lepromatous leprosy on skin biopsy!
Mycobacterium leprae and lepromatosis like to grow in cooler areas, so infection often manifests in the skin and the peripheral nerves.
Transmission is likely via respiratory route, through broken skin, and by touching armadillos!
Early recognition and treatment is important to prevent injury to peripheral nerves.
DDx for rash + neuropathy
Lyme (usually cranial nerves, radiculopathy)
Zoster (tends to be painful rather than pruritic and localized to a dermatome)
WNV (flaccid paralysis)
Our patient presented with a pruritic rash and largely a distal symmetric peripheral neuropathy. We generated the following Venn diagram in report to help us with the diagnosis:
AKA Hansen’s disease
Infection caused by mycobacterium leprae and mycobacterium lepromatosis, separate species that cause similar clinical disease. They are both obligate intracellular parasites.
Involves the skin and peripheral nerves
Early treatment is important to prevent involvement of the eyes, hands, and feet due to neuropathy. The neuropathy is often non-reversible.
205 new cases detected in the US in 2010. 75% among immigrants (most commonly India, Brazil, Indonesia, Bangladesh, and Nigeria)
Unknown but probably respiratory route especially in lepromatous leprosy. Sometimes can transmit through broken skin. Also from armadillos.
Most people do NOT develop disease after exposure. Risk factor for disease development include older age, genetic influences, and immunosuppression.
Grows in cooler areas
Described in categories pertaining to how much bacillary burden of disease is present with tuberculoid being the least amount and lepromatous having the highest disease burden.
Hypopigmented or reddish patches on the skin
Typically involve the earlobes with nodular thickening and distributed symmetrically on the body in lepromatous leprosy.
Diminished sensation or loss of sensation within skin patches
Paresthesias of hands/feet
Neuropathy occurs early in disease course
Painless wounds or burns on the hands or feet
Lumps or swelling on the earlobes or face
Tender, enlarged peripheral nerves
Late findings in disease course:
Weakness of the hands with claw fingers, foot drop, facial paralysis, lagophthalmos (can’t close eyes completely due to CN7 palsy), lack of eyebrows/eyelashes, collapsed nose, perforated nasal septum.
Intermittent bacteremia can lead to focal lesions in various organs (liver, bone marrow, testicles and larynx)
Consider it in patients with skin lesions and/or enlarged nerve(s) accompanied by sensory loss.
No reliable blood or skin tests available.
Usually clinical and skin biopsy
Goal: Prevent and/or minimize injury to peripheral nerves!
Often times it’s loss of sensation but later can progress to painful neuropathy
Dapsone plus rifampin for tuberculoid leprosy. Clofazimine is added for lepromatous leprosy.
Duration can be up to 24 months
Treat neuritis with steroids for a prolonged course
Make sure to screen for G6PD deficiency before prescribing dapsone
Monitor liver function with rifampin
Clofazimine (causes phototoxicity) is not available in US pharmacies and must be obtained from the NHDP.
May take a few years for skin lesions to resolve completely with treatment
Very curable, low relapse rates, typically no drug resistance
Thanks to John for presenting the case of a middle-aged woman with metastatic renal cell carcinoma who presented with subacute diffuse weakness and constipation, found to have symptomatic hypercalcemia, treated with IV fluids and zoledronic acid.
A third of patients with malignancy develop hypercalcemia in their disease course. Hypercalcemia of malignancy is associated with very poor prognosis (~50% 30 day mortality).
Constipation plus polyuria is the most specific symptom combination for hypercalcemia
Denosumab is superior to zoledronic acid in treating hypercalcemia of malignancy and is safe to use in renal failure.
One way to quickly determine the etiology of hypercalcemia from your chemistry panel is to look at the chloride to phosphate ratio. A ratio > 33 is highly suggestive of a PTH or PTHrP mediated process.
** Primary hyperPTH is the most common cause of hypercalcemia in the outpatient setting. Malignancy is the most common cause of hypercalcemia in the inpatient setting.
Treatment of hypercalcemia:
No treatment if asymptomatic
Avoid exacerbating factors
If chronic/asymptomatic ⇒ same tx as Ca <12
If acute/symptomatic ⇒ same tx as Ca 14-18
IVF – lots!
Lasix only if concurrent renal/heart failure
Bisphosphonate (zoledronic acid >>pamidronate if malignancy. Denosumab if refractory to ZA or severe renal impairment)
We discussed the case of a middle aged woman admitted with AMS, found to have AGMA and respiratory alkalosis with work up revealing ASA toxicity, managed with HD!
In suspected ASA toxicity, check serum levels every 2 hours until two consecutive levels decrease from peak value
The goal in treatment of ASA overdose is to keep ASA in its charged and deprotonated state which has less end organ toxicity.
Give bicarb with the goal of maintaining urine pH of 7.5-8 and serum pH <7.60.
Treat hypokalemia aggressively (see below).
Patients with ASA overdose have a high minute ventilation so avoid intubation if possible to allow them to maintain their minute ventilation.
Call renal early for HD if indicated ⇒ AMS, cerebral/pulmonary edema, fluid overload, kidney injury, severe acidemia, ASA level >100 mg/dL, or clinical deterioration in spite of aggressive management
Management of ANY patient with suspected toxic ingestion:
ABCs (Airway, Breathing, Circulation)
Call Poison Control! (1800 222-1222)
Can patient get Activated Charcoal? (usually only within 1 hour of ingestion)
Check Utox, Salicylate screen, acetaminophen screen, +- alcohol and volatile screen if suspected. You don’t want to miss a potential co-ingestion!
Remember that ASA can be found in other compounds like topical salicyclic acid, herbal medications, bismuth subsalicyclate (part of Pepto-Bismol), and Oil of Wintergreen so don’t forget about those topical medications!
Most sensitive vital sign abnormality in early ASA overdose is tachypnea with hyperventilation.
Classic acid/base abnormality is anion gap metabolic acidosis with respiratory alkalosis (see below)
How does ASA work?
Inhibition of cyclooxygenase results in decreased synthesis of prostaglandins, prostacyclin, and thromboxanes. This contributes to platelet dysfunction and gastric mucosal injury
Stimulates the chemoreceptor trigger zone to cause Nausea and Vomiting
Activates the respiratory center in the medulla leading to hyperventilation and respiratory alkalosis
Interferes with cell metabolism (Krebs cycle and decouples oxidative phosphorylation) leading to metabolic acidosis
Reaches peak concentration within 1 hour of ingestion. Takes longer with the enteric coated formulations
Detox occurs normally by the liver and then metabolites are excreted by the kidney. In OD, liver is overwhelmed so more of the drug becomes dependent on renal excretion (slow and can take up to 30 hours).
Nausea and vomiting
Hyperpnea (tachypnea and hyperventilation)
Hyperthermia (due to disturbances with oxidative phosphorylation)
Lethargy and confusion
Making the diagnosis
Check salicylate level and if elevated, check levels every two hours until two consecutive levels decrease from peak , value is less <40, and patient is asymptomatic.
<30 = therapeutic, >40 = toxic, >100 = absolute indication for HD regardless of symptoms
Check serum creatinine– ASA is renally excreted so significant renal failure will change management.
Check potassium level-need to treat hypokalemia aggressively (see below)
Other labs that can support diagnosis but not required
Coagulation studies (large overdose can cause hepatotoxicity and interfere with Vit K metabolism)
Lactate (can be elevated due to uncoupling of oxidative phosphorylation)
CXR if concern for pulmonary edema (potential complication of ASA overdose)
Treatment ASA overdose
Goal: keep salicylate (weak acid) in its charged and deprotonated form to prevent it from crossing into the blood brain barrier by maintaining alkalemia
Activated Charcoal if <1 hour from ingestion
AVOID intubation if possible (remember that these patients have high minute ventilation (RR x TV) due to ASA effect on the medulla and this can be hard to reproduce on the ventilator without causing significant auto-peep)
Volume resuscitation (be careful of pulmonary edema/cerebral edema)
Alkalinize urine with sodium bicarbonate
Sodium Bicarbonate 1-2 meQ/kg IV bolus followed by 100-150 meQ/D5W and titrated to maintain urine pH of 7.5 to 8.0 and continued until salicyclate level <30. It is OK to continue sodium bicarbonate even with alkalemia as long as pH<7.60. Alkalinizing the urine keeps ASA in the non-acidic form (Sal-), thus avoiding a lot of the complications of ASA overdose.
Treat hypokalemia aggressively to maintain alkalinization. If hypokalemia is not corrected, the body will reabsorb potassium and acidify the urine, which is the opposite of what we want.
Consider giving glucose for neuro-glycopenic symptoms (controversial but patient can have neuro-glycopenic symptoms due to low CNS glucose even with a normal serum glucose)
Today, we discussed the case of an elderly woman with significant history of vasculopathy and ESRD who presented with weakness, found to be bradycardic to 30s, hypotensive, and hyperkalemic to 7.2. Her hyperkalemia was treated with dialysis but she underwent cardiac cath due to up trending troponins, found to have a 100% occlusion of the RCA!
First step in managing a patient with bradycardia is ABCs!
First medication for symptomatic bradycardia is atropine. Remember that atropine works at the level of the AV node and higher so if the block is occurring somewhere below the AV node, then atropine will not be effective.
Other pharmaceutical agents are dopamine, epi, or isoproterenol
Anyone with bradycardia and unstable hemodynamics in spite of above treatments should receive transcutaneous pacing. This buys you time until you can place a transvenous pacemaker (less painful, more effective)
ECG has a low sensitivity but high specificity for hyperkalemia-induced cardiomyocyte instability.
ECG changes associated with hyperkalemia in progressive severity:
Peaked T waves
P wave widening, PR prolongation, P wave disappearance
QRS widening, AV block, bradycardia
Atropine (0.5 mg – 1 mg q3-5 mins for a total of 0.03 mg/kg)
If no improvement, consider dopamine or epi
If still symptomatic, then start transcutaneous pacing
In our patient, the cause was severe hyperkalemia as well as an RCA infarct. Given her clinical instability, and the potential for worsening hyperkalemia from cardiac catheterization alone, the team normalized her serum potassium before performing cardiac cath which led to the RCA MI diagnosis.
ECG changes are not sensitive for hyperkalemia and can miss up to 39% of patients even with a K of 7-9.
Sweet spot for potassium appears to be a mean K of 3.5 to 4.5 mEq/L. There is not a well-defined treatment threshold.
Bottom line for management: if you have the kidneys available, use the kidneys to excrete as much potassium as possible.
Newer agents like sodium zirconium and patiromer. Mix with water. Well tolerated and highly effective.
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.
EKG Changes in Hyperkalemia:
K > 5.5 ⇒ repolarization abnormalities:
Peaked T waves are the earliest sign
K > 6.5 ⇒ progressive paralysis of the atria:
P wave widens and flattens
PR segment lengthens
P wave eventually disappears
K > 7.0 ⇒ conduction abnormalities and bradycardia:
High-grade AV block, slow junctional and ventricular escape rhythms
Any kind of conduction block (bundle branch blocks, fascicular blocks)
Thanks to Grace for presenting the case of a middle aged man who presented with chronic weight loss, acute SOB, and splenomegaly on exam, found to have a WBC of 188 on work up and chest imaging concerning for leukostasis.
Most common cause of splenomegaly is portal HTN. But the ddx is broad (see schema below).
Most common cause of a WBC 25k-75k is infection (C diff)
WBC >100k is leukemia until proven otherwise.
Leukostasis is symptomatic hyperleukocytosis, most commonly associated with AML.
Management involves lowering the WBC by leukapharesis, hydrea, and TKIs (if CML) and preventing TLS.
Defined as symptomatic hyperleukocytosis and is a hematologic emergency!
Mortality rate can be as high as 40% within the first week of presentation.
Clinical manifestations of ischemia primarily in CNS, MI, lungs, and kidneys. Can also see limb ischemia and priapism.
Malignancies at highest risk of leukostasis in order of prevalence:
AML (WBC >50k)
ALL (WBC >100k, though tends to present with TLS and DIC much more commonly than leukostasis)
CML (WBC >100k), generally if in myeloid blast crisis
CLL (WBC >400k)
FLUIDS, lots and lots of fluids
Cytoreduction: lowers the WBC
Leukapharesis: not readily available as it requires a dialysis line and trained nursing staff
Hydroxyurea: to lower the WBC
Tyrosine kinase inhibitors (especially for CML related leukostasis)
Induction chemo (for non-CML related leukostasis)
Prevent tumor lysis syndrome:
Uric acid lowering therapy
In hemodynamically stable patients AVOID TRANSFUSION – it’s like adding fuel to the fire and can worsen ischemia. Platelet transfusion is less dangerous than RBCs and you may have to do it before trialysis line placement.
↑K, ↑Phos, ↑uric acid, ↑creatinine, ↓calcium
Occurs in bulky or chemosensitive tumors with high proliferative rate (Burkitt’s lymphoma, acute leukemias, small cell lung cancer)
Allopurinol takes 1-2 days to show effect and does not reduce preexisting elevated uric acid levels so use rasburicase if uric acid already high or preemptively if TLS risk is high or if there is kidney injury.
HD if concern for renal damage
Causes of pseudohyperkalemia
Technique of blood drawing (tourniquets and fist pumping)
Thanks everyone for yet another high yield report on ECGs with Dr. Zhao! Here are the main pearls from today:
Remember that a negative p wave amplitude in lead I is seen in two diagnoses only: dextrocardia and limb lead reversal. To distinguish between the two, look at the amplitude of the QRS complexes as you advance through the precordial leads. In dextrocardia, you should see a loss of amplitude as you go from V1 to V6, because you are getting further away from the heart. In limb lead reversal, this is not the case.
Remember that ST depressions in anterior leads V2 and V3 should raise your suspicion for a posterior MI and prompt further evaluation with a posterior ECG!
When dealing with an irregularly irregular wide complex tachycardia, think of these three differential diagnoses:
Atrial fibrillation with aberrancy (i.e. with a bundle branch block)
QRS waves should largely look similar in morphology
Rates should not exceed 170 bpm because all conduction is still going down the AV node
Treatment: shock if unstable, AV nodal blocking agents or amiodarone
Atrial fibrillation with an accessory pathway (WPW, also known as a preexcitation pathway)
QRS waves have varying shapes because they are conducted down the accessory pathway and the AV node
Because the accessory pathway has a much shorter refractory period than the AV node, heart rate can be very high and >200 bpm.
Treatment: shock if unstable. Do NOT give AV nodal blocking agents (including amiodarone) because blocking the AV node can force all conduction down the much faster accessory pathway and lead to VF arrest. The agent of choice is IV procainamide.
QRS morphology varies (Torsades)
Rates should not exceed 170 bpm
Treatment: shock if unstable, otherwise amiodarone
Thanks to Brayden for presenting a case of a 48yo M with no significant medical or family history presenting with 2-3 months of LE edema, generalized weakness, malaise, myalgias, and arthralgias (general, no particular pattern). He was found to be anemic, and urine studies were notable for nephritic range proteinuria and microscopic hematuria. His complements levels were normal. Ultimately renal biopsy revealed the presence of crescents in the glomeruli, and MPO positivity indicating a P-ANCA related vasculitides. Based on his history, his final diagnosis is RPGN Type 3 secondary to most likely MPA.
Hematuria: First step is to see if there is actually RBC in the urine!
RBC Casts, proteinuria, AKI
No casts, no AKI
Porphyria, Beeturia, Rhabdomyolysis
All About Casts! Presence of certain casts in the urine can provide useful information.
Hyaline casts: Nephrotic syndrome, pre-renal azotemia, normal
Fatty oval bodies: Nephrotic syndrome
RBC casts: GN
Granular cast: ATN, interstitial nephritis, note that you can see ATN even without casts!
WBC cast: Interstitial nephritis, acute pyelonephritis, acute GN
Glomerular inflammatory leading to hematuria, variable range proteinuria, HTN, edema, RBC casts or dysmorphic RBC
Immune Complex Deposition GN
Typically LOW complement levels
SLE GN: ANA, DS-DNA
C3 way lower than C4
PIGN (post-infectious or strep GN, infection related GN): Streptococcal antibodies i.e. ASO, recent infection
Low C3, Low CH50, normal C4
Supportive care + antibiotics
Typically weeks after an infection but can occur during infection
IgA nephropathy: MOST COMMON, recent respiratory or GI infection, kidney biopsy with IgA deposits, normal complements
Cryglobulinemic GN: Cryoglobulin, HCV association
C4 way lower than C3
Membranoproliferative GN (MPGN): Complement activation, immune-staining positivity on biopsy
HSP (nrl complements), palpable purpura, abd pain. IgA, IgG, C3 deposition. Closely related to IgA Nephropathy but with systemic/extra-renal involvement.
Lung and renal involvement, young patients <30 are more likely to have involvement of both and older patients > 50 are more likely to present with isolated GN. Male predominance in younger patients and female predominance in older patients.
ANCA related GN aka Pauci-immune GN (PIGN)
NORMAL complement levels
Absent extra-renal disease: ANCA-associated crescentric GN
Respiratory sx, sinusitis, granulomas, C-ANCA/PR3: Granulomatosis with polyangiitis (GPA)
Asthma and eosinophilia, P-ANCA/MPO: EGPA
Biopsy: None to few immune deposits in the glomeruli in IF and EM. 96% will be positive for ANCA, the other 4% are ANCA-negative pauci-immune GN
Focal necrotizing, crescentic glomeruli
RPGN: Rapid renal failure with extensive crescent formation that can lead to ESRD within weeks to months. Can present in any age group.
Association: Goodpasture, SLE, GPA, idiopathic
Bx: Crescent formation in > 50-75% of glomeruli
IM: Linear IgG
Types: 3 types depending on immunofluorescence pattern.
Type 1: 20%, anti-GBM
Type 2: 25%, immune complex deposition, SLE, GSP, IgA nephropathy, acute proliferative GN
Type 3: Aka Pauci-immune GN, 55%, glomeruli damaged in unclear mechanism. Can be idiopathic or related to ANCA associated vasculitis like GPA, MPA, EPGA. Most common.
Kidney biopsy for definitive diagnosis but it can be deferred if a diagnosis can be determined via serologies or if pts have fibrotic kidneys, which makes the risks for that diagnostic piece of information outweigh the benefits.
Management of GN:
Treat underlying cause if any.
Immunosuppression: Usually high dose steroids + cyclophosphamide, rituximab may also be used. Plasmapheresis is also an option.
Initial therapy: Methyprednisolone 500-1000mg daily for 3 days
No different between use of rituxuimab vs cyclophosphamide (RAVE, RITUXVAS)
Cyclophosphamide: Available in PO formulation in a daily dosing, favored by some Nephrologist.
If left untreated, RPGN progresses to ESRD over weeks to months. Fewer crescents (<50%) is associated with slower progression.