Senior Report 7.1

Case Presentation by Dr. Kristi Maso

8 week old male presents to the ED with his mother who states the child has been irritable while feeding for 3 weeks, but worse today.  She states she took him to his PCP 3 weeks ago and was diagnosed with acid reflux, however his irritability and sweating while feeding continued despite being started on zantac.   Today when feeding the child turned blue in the face and according to mom seemed to “start breathing hard and really fast.”  She became nervous and brought him to the ED.  The child has been otherwise healthy.  He is having normal bowel movements and wet diapers.  No fever, vomiting, or diarrhea.

PMH: GERD
PSH: None
FH: No HTN, DM, or asthma
Birth Hx: Patient was full term, born at 39 weeks via normal spontaneous vaginal delivery
SH: Child lives at home with mom and dad. There is no smoking in the home and he does not go to daycare.

Physical exam:
BP: not attainable child is crying,  HR: 170,  RR: 45,  T: 36.7,  Spo2: 90% on room air
Constitutional:  Child is crying and irritable, he has a blue tint to his face.
Eyes: PERRL, EOMI, conjunctiva are pink without pallor
Cardiovascular: Tachycardic rate and regular rhythm. + holosystolic murmur, no rubs or gallops. No S3 appreciated. Good palpable radial pulses bilaterally.
Respiratory: + accessory muscle use. Crackles at the lung bases bilaterally.  Faint expiratory wheezing.
Gastrointestinal:  Abdomen is soft, non tender, nondistended. The liver is palpable 1cm below the costal margin.
Skin: Ashen color, no rash

Labs/imaging:  A chest  xray is obtained in the ED which showed mild cardiomegaly with mild pulmonary vascular congestion. Because of this an EKG was ordered .

Senior 7.1

All laboratory studies are still pending at this time.

Questions:

1)     Based on the patient’s history and EKG findings, which of the following is the most likely diagnosis?
a) Viral Myocarditis
b) Congenital Dilated Cardiomyopathy
c) Mitral Valve Prolapse
d) Anomolous Left Coronary Artery from Pulmonary Artery

e) Total Anomolous Pulmonary Venous Return

2)     Which of the following is the treatment of choice for this child when presenting to the ED?
a) Place patient on 100% O2
b) IV Lasix
c) Bolus 20cc/kg to increase venous return
d) Blood cultures and broad spectrum IV antibiotics
e) Breathing treatments of albuterol and ipratropium x3

3)     Which of the following sign or symptom is least likely to be found on exam for this condition?
a) Heart murmur
b) Enlarged cardiac silhouette
c) Tachycardia
d) Poor feeding
e)Diaphoresis

 

Answers

1) D
2) B
3) A

Discussion: This EKG is diagnostic of a congenital anomaly called Anomolous Left Coronary Artery from Pulmonary Artery (ALCAPA).  ALCAPA is a serious congenital anomaly that occurs in about 1 in 300,000 live births.  In normal anatomical development the left and right coronary arteries come off the aorta, however in children with ALCAPA during development the left coronary instead comes off the pulmonary artery resulting in left ventricular dysfunction secondary to ischemia once the pulmonary pressures decrease as expected after birth.  Clinically, irritability increases as myocardial oxygen consumption increases (usually at times of feeding or crying).  States of increased oxygen demand lead to infarction of the anterolateral left ventricular free wall which causes mitral valve papillary muscle dysfunction and variable degrees of mitral insufficiency.

Facts about ALCAPA:

  • Usually diagnosed within the first 2 months of life – when pulmonary artery resistance drops to adult level.   (in fetal development the pulmonary artery pressure equals that of the systemic circulation so fetus gets adequate perfusion of the myocardium from the pulmonary artery through the anomalous coronary,  BUT after birth does the pulmonary artery contains only desaturated blood at low pressure which isn’t enough to perfuse the left ventricle especially at times of high demand like feeding or crying)
  • As pulmonary resistance decreases the left coronary artery blood blow travels back into the pulmonary artery essentially “stealing” blood from the ventricle causing worsening ischemia and infarction of the anterolateral free wall of the left ventricle.
  • Presents in a way similar to common pediatric conditions such as infantile colic, food intolerance, gastroesophageal reflux, and bronchiolitis.
  • Patients present in symptoms of heart failure and evidence of myocardial ischemia on EKG is pathognomic for the condition.   Cardiomegaly can be seen on chest xray.

EKG Findings:
Electrocardiogram almost always shows evidence of anterolateral myocardial infarction in the symptomatic patients. Inverted T waves can be seen in leads I and aVL. The left ventricular surface leads (V 5 -V 6 ) may also show deep Q waves and exhibit elevated ST segments and inverted T waves.  EKG is pathognomonic for ALCAPA and cannot be missed by ED physicians.

Signs:

  • Abnormal heart rhythm
  • Enlarged heart
  • Tachycardia
  • Murmur (holosystolic secondary to mitral regurg) –  RARE

Symptoms:

  • Blue or purple tint to gums, tongue, skin and nails (cyanosis)
  • Poor eating and poor weight gain
  • Crying with feeds
  • Rapid breathing or shortness of breath
  • Profuse sweating, especially with feeding
  • More sleepiness than normal
  • Unresponsiveness (the baby seems “out of it” at times)

Treatment:
Initial management is supportive but temporary. This includes diuretics, afterload agent, inotropes as needed, similar to treatment of CHF in adults.  The DIFFERENCE is the use of oxygen.  Using 100% O2 may further reduce pulmonary vascular resistance and worsen coronary steal from the right coronary artery into the pulmonary arteries. Oxygen saturations in the mid 80’s is permissible in these patients.

Lasix: Given IV is 1mg/kg.

Definitive treatment is surgery which entails cutting the LCA from the pulmonary artery and trying to reattach to aorta or anastomose with subclavian.

Intern Report 7.3

Case Presentation by Dr. Jeffrey Van Laere, MD

HPI: 5 year-old girl with who presents to the emergency department as a transfer from an outside hospital with abdominal pain and diarrhea for 2 days. The patient reports worsening abdominal pain, which she describes as 6/10, diffuse, but worse in the right lower quadrant. She also reports “nearly constant” diarrhea that is non-bloody and watery. Patient states that she feels nauseous, but has had no vomiting.

ROS:
Negative for fever, vomiting, chest pain, shortness of breath, hematochezia.
Positive for diarrhea, abdominal pain, nausea.

PMH: None
PSH: Tonsillectomy and Adenoidectomy
Medications: None
Social History: Immunizations up to date. Grandmother with recent illness, lives in nursing home.

Physical Exam
Vitals: P 126  BP 112/64  RR 18  T 37.4  O2 98%
General: Well developed, well nourished female, lying still, appears uncomfortable.
HEENT: Dry mucosal membranes, no mucosal lesions, EOMI, PEERL
Resp: CTAB
CV: Tachycardic, RRR, no M/G/R
GI: Soft, Mild diffuse tenderness. Negative Murphy’s sign and pain at McBurny’s point. No hepatosplenomegaly.
MS: Full range of motion in extremities, no clubbing, cyanosis or edema.
Neuro: AAOx4, normal reflexes in biceps, triceps and Achilles tendons. Light touch sensation intact.

Labs
Na: 137
K:  4.7
Cl: 103
CO2:  25
BUN: 32.4
Cr: 2.6
Gluc: 87

WBC: 37.2
Hgb: 9.2
Hct: 27.6
Plt: 23

LDH: 1286

7.4 pic

Question #1: After reviewing the patient’s laboratory values, you return to discuss the results with the family. What do you think is the most likely diagnosis?
A) Thrombotic Thrombocytopenic Purpura
B) Hemolytic Uremic Syndrome
C) Clostridium difficile Infection
D) Appendicitis

Question #2: After discussing the diagnosis with the family, they are concerned and ask what the next step is in treating this?
A)  Platelet transfusion
B) Start IV fluids and IV antibiotics
C) Supportive care
D) Consult General Surgery

Question #3: After discussion of the treatment plan with the family, they are comforted by knowledge of this disease.  You discuss the concerns you have for this patient. What is the most serious complication of this disease?
A) Renal Failure
B) Dehydration
C) Arthritis
D) Bleeding

Answers & Discussion

1) Answer:  B – Hemolytic Uremic Syndrome
Hemolytic Uremic Syndrome is a multi-system disorder resulting in acute renal failure, thrombocytopenia, and microangiopathic hemolytic anemia.  The differential diagnosis for HUS includes TTP, DIC, appendicitis, gastroenteritis, and SLE. HUS and TTP share microangiopathic hemolysis, renal failure, and thrombocytopenia, however TTP will include a history of being febrile and neurologic changes in 40% of cases. While the patient may have symptoms of an infectious diarrhea, c difficile is an extremely rare cause of HUS. Appendicitis is a common cause of abdominal pain and leukocytosis, however this does not account for the patient’s thrombocytopenia, presence of schistocytes on peripheral smear, and elevated LDH.

2) Answer: C – Supportive care
While HUS is often associated with an infectious diarrhea, use of antibiotics for treatment is contraindicated, as it will increase the risk of development of HUS. Transfusion of platelets is contraindicated, as the thrombocytopenia is seen secondary to a consumptive process. Platelet transfusion will only exacerbate the underlying condition. As this is an infective process, there are no surgical indications, thus no need for a surgical consult.

3) Answer: A – Renal Failure
The pathogenesis of HUS includes the development of microthrombi that will migrate to the kidneys and deposit in the parenchema of the kidney. This will cause acute renal failure. These patients may develop hypertension, peripheral edema, oliguria or anuria. It is recommended to follow the patient’s renal function closely, as dialysis may be necessary. Dehydration is common in any diarrheal illness, but the majority of patients will survive the acute phase of the illness. Long term, up to one third of patients will have mild chronic kidney dysfunction. Many patients will develop purpura secondary to thrombocytopenia, however bleeding is not known to be a common cause of mortality in HUS. Arthritis is not associated with HUS.

Discussion

Hemolytic-Uremic Syndrome is one of the most common causes of acute renal failure in children. It commonly presents early in life, with a mean age of presentation being 3 years old, but it may present later into childhood. The most common cause of HUS is E. coli O157:H7, however it may also be caused by Shigella, S. pneumonia, Pseudomonas, HIV, or as a result of medications.

Patients will often present early with watery diarrhea, abdominal pain, and possibly fever. As the disease develops, approximately day 2-5, the patients may develop bloody diarrhea. After the initial course of gastroenteritis, the patients will later develop the triad of thrombocytopenia, hemolytic anemia, and acute renal insufficiency.

The pathophysiology of HUS stems from injury to the renal vascular endothelium. There is an initial injury to the endothelium, followed by deposition of complement, platelets, and fibrin. This deposition will cause narrowed renal vessels that will cause injury to RBCs and the microangiopathic hemolytic anemia. The result of this hemolysis will be seen through elevated LDH, as well as schistocytes, tear drop cells, and burr cells on peripheral smear.

As previously discussed, the most important aspects of treatment are supportive therapy and early peritoneal dialysis. Given the patient’s acute renal insufficiency and diarrhea, you should rehydrate the patient, but be cautious to avoid fluid overloading.  It is also important to follow the patient’s hyperkalemia and treat appropriately. Although these patients are often anemic, pRBCs are usually held until hemoglobin falls below 6 g/dL, and platelets are avoided unless life-threatening bleeding or procedures are necessary. Although there have been no studies, it is currently recommended that antibiotics be avoided due to concern for verotoxin release and worsening symptoms with administration.  An important distinction in treatment between TTP and HUS is that plasmapheresis is used with TTP, and may be used with suspected HUS that exhibits neurologic involvement.

Recommended Reading
Rosen, P., Marx, J. A. (2014). Chapter 122. Disorders of Hemostasis. p. 1609-1612 Rosen’s emergency medicine: Concepts and clinical practice

Rosen, P., Marx, J. A. (2014). Chapter 174. Genitourinary and Renal Tract Disorders. p. 2222-2223 Rosen’s emergency medicine: Concepts and clinical practice.

Fauci, A. S., & Harrison, T. R. (2012). Harrison’s online: Featuring the complete contents of Harrison’s Principles of internal medicine, 18th edition. Chapter 115. Disorders of Platelets and Vessel Wall. New York: McGraw-Hill, Medical Pub. Division.

Intern Report 7.2

Case Presentation by Dr. Hannah Ferenchick, MD

Chief complaint: “My lip is swollen”

A 34-year-old man presents to the ED for lip swelling that has been present for several hours. The patient states that at work earlier today he was removing a car bumper. It came loose and popped up and hit the patient in the lip. At the time, the patient had no bleeding or pain in the area. However, 1-2 hours after this, the patient stated that his lip became irritated and then swollen. Patient states that for the last few hours his lip has stayed swollen. Patient denies pain in this area, trouble swallowing or trouble breathing. The patient states that for the last few months he has had periodic issues with swelling. He states he has swelling randomly occur on his side and under his arms. In addition, he has occasional scrotal swelling. These areas of swelling are self resolving. He has a history of hypertension, for which he previously was on lisinopril. However, his PCP switched him to amlodipine since these swelling episodes began. Patient denies any recent fevers, chills, chest pain, shortness of breath, abdominal pain, diarrhea, constipation, dysuria, penile discharge, headache, increased urination or thirst, hives or urticaria.

ROS: negative except as noted per HPI

PMH: Hx of hypertension
PSH: negative
Meds: Amlodipine 5 mg BID
Allergies: No known medication allergies
FH: Hypertension
SH: Drinks alcohol socially, denies cigarette smoking and illicit drug use

PE: vitals: T 98.7, HR 78, BP 156/89, RR 18, pulse ox 100% RA, weight 241, 5’ 9’’
General: Well-appearing, overweight male, appropriate for stated age, resting in bed comfortably, no acute distress
HEENT: Normocephalic, atraumatic. PERRLA. No erythema or exudates in posterior oropharynx. Patient’s upper lip is swollen and edematous, no erythema noted. No abrasions, lesions or urticaria noted. Tongue is non edematous, Mallampati grade II. No tracheal deviation or neck masses.
Cardio: RRR, S1 and S2 heard, no murmurs
Respiratory: Lungs clear to auscultation bilaterally
Abdomen: Soft, non tender, non distended. Positive bowel sounds
Musculoskeletal: +2 radial and DP pulses bilaterally. No pitting edema in lower extremities.
Skin: No rashes, hives or lesions noted
Neuro: Alert and orientated X3

7.2

Questions:

1. Which of the following is the most likely diagnosis?
A. Allergic angioedema
B. Drug-induced angioedema
C. Hereditary angioedema
D. Idiopathic angioedema

2. Which of the following is considered an indication for screening for c1 inhibitor disorders?
A. Recurrent angioedema with urticaria
B. Recurrent unexplained episodes of colicky abdominal pain
C. History of angioedema with ACE-inhibitor use
D. History of refractory anaphylaxis

3. First line treatment of acute attacks of angioedema in adults with known c1-inhibitor deficiency includes which of the following?
A. 0.5 mg epipinephrine IM
B.  Ranitidine 50 mg IV
C. C1-esterase inhibitor (Berinert®) 20 units/ kg
D. 2 units fresh frozen plasma

Answers and Discussion

1)  The answer is C. The patient is having angioedema without related symptoms of a hypersensitivity reaction. Therefore, the most likely cause is a C1 inhibitor deficiency disorder, either hereditary angioedema or acquired C1 inhibitor deficiency (which is very rare and most commonly associated with lymphoproliferative disorders).

The patient has no signs of hypersensitivity reaction such as urticaria, wheezing or hypotension. Therefore, this is not likely due to an allergic-type reaction. The patient was taking lisinopril, which is known to cause angioedema due to the inhibition of ACE, and subsequent increased production of bradykinin. However, the patient stopped his ACE-I and continued to have symptoms which makes this diagnosis less likely. Finally, idiopathic angioedema is a diagnosis of exclusion.

2) The answer is B. GI attacks in hereditary angioedema (HAE) present as intermittent episodes of GI colic, nausea, vomiting and diarrhea. These symptoms result from bowel wall edema. GI attacks are experienced by most patients with HAE and may be the only presenting symptoms in up to ¼th of these patients. The presence of urticaria is associated with allergic angioedema, which is caused by hypersensitivity reactions. These are triggered by common allergens and rarely physical stimuli such as trauma or temperature changes. The inhibition of angiotensin-converting enzyme by ACE-inhibitors results in decreased metabolism of substance P and bradykinin, which contributes to tissue inflammation and can lead to angioedema. These patients often tolerate ARBs well. Refractory anaphylactic shock may require a continuous infusion of epipinephrine in the treatment if intramuscular epipinephine and volume expansion with normal saline have not succeeded in normalizing vital signs. However, it is not an indication for HAE screening.

 3) The answer is C. Cinryze and berinert are C1 inhibitor concentrates derived from plasma. They are among first line therapies for C1 inhibitor deficiency angioedema. Other medications that are also considered first line include icatibant, which is a synthetic bradykinin receptor antagonist and ecallantide, a recombinant plasma kallikrein inhibitor that blocks the production of bradykinin by inhibiting plasma kallikrein. It is approved in US for treatment of acute attacks of HAE in patients 16 yrs and older. Cinreyze is technically not FDA approved for acute angioedema attacks, but is being has been used in Europe with success. IM epinephrine is typically not thought to be helpful in C1-inhibitor deficiency cases. It does not address the known pathophysiologic mechanism of underlying C1ID, although it may help decrease mucosal edema. It is considered first line in the treatment of allergic angioedema. H2 antihistamines are indicated in the treatment of allergic angioedema. Finally, FFP has c1 inhibitor and has been reported to be effective in acute attacks. It is considered 2nd line in treatment of HAE, to be used when first line medications are not available.

Discussion:
The differential diagnosis for this patient includes allergic reaction/anaphylaxis, drug-induced angioedema, allergic contact dermatitis, hereditary angioedema, acquired C1-esterase deficiency angioedema and idiopathic angioedema. Allergic reactions and anaphylaxis often present with systemic symptoms involving multiple organ systems simultaneously, such as wheezing, urticaria, and hypotension. The patient does not exhibit any of these, which makes this diagnosis unlikely. Drug induced angioedema is associated with ACE-inhibitors and NSAIDs. However, the patient had stopped his ACE-inhibitor without resolution of his angioedema. Allergic contact dermatitis often presents as erythematous, scaly plaques and occurs in association with cosmetic and topical pharmaceuticals. Idiopathic angioedema is a diagnosis of exclusion and therefore not appropriate in this case. The most likely cause of this patient’s presentation is a bradykinin-induced angioedema, either hereditary angioedema or acquired C1-esterase deficiency.

Angioedema results from vasodilation and edema of the deeper dermal and subcutaneous layers of the skin. The skin may appear normal color or pink due to the swelling being located in deeper layers of the skin. Angioedema may cause pain and is not necessarily associated with pruritus. The majority of angioedema is caused by hypersensitivity reactions commonly triggered by allergens, referred to as allergic angioedema (or mast cell mediated angioedema). Mast-cell mediated angioedema often presents with other systemic signs of mast cell mediator release: urticaria, pruritus, bronchospasm, and hypotension. The patient had none of these symptoms; therefore the most likely cause of this patient’s presentation is a bradykinin-induced angioedema. These are nonallergic types of angioedema and are caused by bradykinin excess. The distinction between mast-cell mediated angioedema and bradykinin induced angioedema is crucial for treatment and management of the disease. The causes of bradykinin-induced angioedema include hereditary angioedema (HAE), acquired C1 inhibitor deficiency and ACE inhibitors. In the case of HAE and ACID, the deficiency of C1 inhibitor results in increased bradykinin levels. These types of angioedema do not respond to the typical treatments for allergic hypersensitivity reactions such as steroids, antihistamines and IM epipinephrine. As always, early airway stabilization is key in management.

Although this patient was not currently demonstrating any signs of airway compromise, ENT was consulted in the emergency department.  They did a bedside bronchoscopy, which showed some signs of edema at the base of the tongue. Therefore, they recommended that the patient be observed in the ICU for 24 hours, with a low threshold for intubation and cricothyroidotomy tray at bedside. Patient was given methylprednisone 125 mg IV, zantac 25 mg IV and Benadryl 25 mg IV push in the emergency department and was admitted to the ICU. Patient was given Decadron 10 mg q8hr, zantac 50 mg Q8 hours and Benadryl 50 mg IV Q8 hours. Patient did well overnight, with no signs of airway compromise. Repeat bronchoscopy was done the following day which showed significant improvement in edema. Therefore, patient was cleared by ENT and discharged home with a 5-7 day course of Zantac and Benadryl, as well as a prescription for Medrol dose pack and close follow-up with allergy/immunology for evaluation of possible genetic or environmental causes of his angioedema.

References:
Atkinson, JP., Cicardi, M,  Zuraw, B. Hereditary angioedema: Treatment of acute attacks. In: UpToDate, Saini S (Ed), UpToDate, Waltham, MA, 2013.

Atkinson, JP., Cicardi, M,  Zuraw, B. Hereditary angioedema: Epidemiology, clinical manifestations, exacerbating factors, and prognosis. In: UpToDate, Saini S (Ed), UpToDate, Waltham, MA, 2013.

Cicardi, M. Acquired C1 inhibitor deficiency: Clinical manifestations, epidemiology, pathogenesis, and diagnosis. In: UpToDate, Saini S (Ed), UpToDate, Waltham, MA, 2013.

Tran, Paul T. and Muelleman, Robert. “Allergy, hypersensitivity, angioedema and anaphylaxis.” In. Rosen’s Emergency Medicine: Concepts and Clinical Practice 8th ed. Ed. Marx. 2014.

COW A1.2

COW

*CASE OF THE WEEK*

HPI: 2-year-old boy with a history of eczema presents after a possible clonidine ingestion. The mother states that she put the child ton bed and upon checking on him later in the night, found him with an open pill bottle of 0.1 mg clonidine tablets. She apparently had left her purse reachable to the child. She is not sure if and how many pills the child ingested. Incident occurred at 11:00PM. The mother noticed the patient became lethargic and limp;  therefore, she brought him to the SG ED.

ROS: unable to obtain

PMH: Eczema

PSH: None

Meds: None

Social History: Lives at home with mother, shots UTD

Do you have a list of medications in the home?

Physical Exam

Blood pressure: 116/62, Pulse 123, Temperature 36.7, respiratory rate 20.

General:  Well nourished, Well developed, difficult to arouse with stimulation

Eye: Pupils are small, 2  mm, equal and reactive.

HENT:  Normocephalic, Atraumatic.

Respiratory:  Lungs CTA bilaterally.

Cardiovascular:  Tachycardic, S1 auscultated, S2 auscultated, No rub, No murmur, No gallop, Good pulses equal in all extremities, Normal peripheral perfusion, No edema.

Gastrointestinal:  Soft, Non-tender, Non-distended, Normal bowel sounds, No organomegaly.

Musculoskeletal:  Normal range of motion, No swelling, No deformity.

Integumentary:  Warm, Dry.

Neurologic:  Normal deep tendon reflexes, Not alert,  No clonus or other abnormal movements, Moving all four extremeties, Non focal exam.

LABS: 

ABG: 7.29/32/86/15

White count 6, hgb 10.9

APAP, salicylate undetectable

Electrolytes normal; What was the AG?

QUESTION 1:

ANSWER: G. Clonidine is a peripheral and central alpha 2 and imidazoline agonist that inhibits sympathetic outflow from the CNS leading to hypotension, bradycardia, and depressed mental status. In overdose, clonidine can initially cause peripheral vasoconstriction and hypertension due to peripheral alpha 2 agonism. The hypertension is usually asymptomatic and can last for many hours.   The hypertension  may be abruptly followed by hypotension. If in the rare instance hypertension needs to be controlled, phentolamine is the drug of choice. However, a short-acting calcium channel blocker may be utilized (more sound then an alpha blocker for an alpha agonist?). Beta 2 agonists (albuterol, clenbuterol) leads to vascular smooth muscle relaxation and cardiac stimulation leading to hypotension and tachycardia.  Adenosine antagonists (caffeine, theophylline) causes hypotension, tachycardia, and  seizures. Yohimbine is an alpha 2 antagonist (see answer to next question).

QUESTION 2:

ANSWER: B. Dexmedetomidine (Precedex ®) is a central alpha2 and imidazoline agonist that is increasing in popularitydue to its sympatholytic, analgesic, sedative properties, and its “lack of respiratory depression”.  High doses of dexmedetomidine lead to bradycardia, hypertension, and hypotension. Abrupt discontinuation of dexmedetomidine can lead to hypertension, tachycardia and agitation similar to a “clonidine withdrawal” syndrome.  Etomidate and thiopental are GABA agonists, propofol is a GABA agonist and NMDA antagonist, and ketamine is a pure NMDA antagonist.

QUESTION 3:

ANSWER: B.  Imidazolines agonize the  imidazoline receptor found presynaptically that reduces sympathetic outflow from the CNS. Technically, Imidazolines and clonidine both agonize alpha2 and imidazoline receptors and imidazoline receptors may be more responsible for hypotension.  ImidAZOLE-ring chemicals are found in antifungals (e.g. fluconazole) and midazolam. Methylxanthines (e.g. caffeine, theophylline) release catecholamines (leading to mostly B1 and B2 receptor agonism), antagonize adenosine (CNS stimulation and seizures), and inhibit phosphodiesterase.  Non-dihydropyridines (diltiazem and verapamil) are calcium channel blockers and will lead to hypotension and bradycardia, as will beta antagonists, but through a different mechanism than clonidine.

BONUS QUESTION 4:

ANSWER: C.  Yohimbine and tolazoline are alpha adrenergic antagonists. Case reports are conflicting about tolazoline’s effectiveness.  Aconitine is the toxin found in monkshood and acts as a sodium channel opener. Briefly, toxicity appears similar to digoxin toxicity with paresthesias and without hyperkalemia.  Cytisine is a nicotinic agonist found in the mescal bean, broom, and golden chain.  Cyproheptadine is an antihistamine,  serotinin antagonist, and antimuscarinic agent which is employed clinically for serotonin syndrome.

Hospital Course:

Upon arrival the patient was noted to be lethargic. Although the patient would respond to vigorous stimulation, the patient would become obtunded when not being stimulated. Thus, the patient was intubated for airway protection and sedated with ketamine and midazolam.  He was transferred to the Children’s PICU.

The patient was extubated the following day.  His lowest heart rate was 58. Blood pressure remained normal and stable.

TEACHING POINTS

  • Clonidine has been used for a variety of clinical purposes including: withdrawal treatment (opioids, etoh, benzos, and tobacco) and treatment of mania, ADHD, Tourette Syndrome, tics, hypertension, PTSD, motor spasticity, and rigidity from administration of large doses of opioid.
  • Other pharmacologically similar centrally acting alpha agonists include alpha-methydopa, guanfacine, tizanidine (Zanaflex ®) and guanabenz
  • Imidazolines are often employed as topical vasoconstrictors and more recently are used as antihypertensive agents (SEE TABLE BELOW)
  • Clonidine and dexmedetomidine not only stimulate alpha2 receptors presynaptically, but they also bind to imidazoline receptors.
  • Stimulation of alpha2 and imidazoline receptors, likely through various mechanisms, inhibit the release of noradrenaline and are often thought of as “sympatholytics”

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Presented by Dr. Andrew King. 

Intern Report 7.1

Case Presentation by Dr. Henry White

Chief Complaint: Headache and fever

History of Present Illness: 13 year old male presents complaining of a headache for the last 2 days and a fever 4 days. The headache gradually started it is global in distribution, constant ache, 6-8/10 over the last 24 hours, currently at a 7/10.  It improves with ibuprofen or acetaminophen, it is not aggravated by sight or sound, and he denies any vision or hearing changes. The fever has been ranged between 99-101 for the past 4 days.

The parents state he is currently being evaluated for a constellation of symptoms, but no diagnosis has been made.  These include microscopic hematuria and occasionally pink tinged urine for the last 3 weeks.  Sporadic bilateral conjunctivitis without uveitis per ophthalmology with no vision changes or pain.  He has had polymigratory arthralgias over the past month, mostly located in his elbows and knees, but also in the small joints of his hands, feet and ankles bilaterally, sparing hips and shoulders.  This pain improves with the ibuprofen.  He has also had a blotchy rash over legs, ankles and elbows, with lower extremities affected more than the upper.  Parents also deny any sick contacts, and say the patient was previously healthy before these symptoms started one month ago.

ROS:
General: Positive for fever and for 5 pound weight loss over last month with overall decreased activity level. Negative chills/sweats
HEENT: occasional epistaxis, no sore throat or congestion
Pulmonary: Intermittent cough, no dyspnea/wheezing
Cardiovascular: No chest pain
Gastrointestinal: Positive anorexia, no nausea/vomiting/diarrhea/constipation/blood in stool/melena, no abdominal pain
Musculoskeletal: no weakness or myalgias
Integumentary: no increased bruising or bleeding

Past Medical History: none – currently being worked up for above
Surgical History: none
Medications: ibuprofen, last dose 2 hours prior to arrival, acetaminophen, unknown eye drops
Allergies: none
Family History: hypertension
Social History: no alcohol/tobacco/other drugs, patient denies any sexual history

Physical Exam

Vitals: BP 125/76,HR 100,RR 14,T 100.1, 98% on RA, 5’2” weighing 122 lbs
General: Patient is lying on exam bed in obvious discomfort, holding his head with both hands

HEENT: normocephalic, scalp nontender to palpation, bilateral  conjunctivitis (represented below), EOMI without pain through visual range of motion, 20/20 vision b/l , MMM with no posterior oropharynx erythema or ulcerations

Neck: no lymphadenopathy noted, neck supple with no meningeal signs.

Pulmonary: Slight crackles over bilateral lower lung fields, no wheezes, good air exchange, no accessory muscle use or peripheral cyanosis

Cardiovascular: RRR with no r/g/m/c, 2+ D.P/Radial pulses b/l, brisk capillary refill

Abdomen: soft, nontender, nondistended

Genitourinary: normal, no inguinal adenopathy

Musculoskeletal: Musculoskeletal: Pain with active motion of elbows R>L, and ankles equal bilaterally, no pain with passive motion.  Able to ambulate normally but with significant amounts of pain.  5/5 strength in all extremities, good muscle tone in all limbs.  Joints nontender to palpation, no warmth, swelling or redness over any joint

Integumentary: Nonblanching, flat purpura over b/l lower extremities with concentrated over the anterior shin/ankles with some extension into soles of feet, as well as some over b/l elbows.  Not painful to palpation, some petechia noted over elbows/forearms.  No ecchymosis/abrasions/blisters noted, no involvement of torso or facial areas.

Neurological: AOx3, CN 2-7, 9-12 intact, speech fluid, heel to shin and finger to nose normal b/l, sensation intact to light touch over all extremities

case 7.1j

Question 1

This patient was admitted to Observation overnight, during which he developed some hemoptysis and epistaxis.  Bleeding stopped spontaneously, but patient was sent for chest CT that showed multiple cavitary lesions.  What is the most likely diagnosis in this patient?
a)  Kawasaki’s Disease
b)  Polymyalgia Rheumatica
c)  Wegner’s Granulomatosis
d)  Lyme Disease

Question 2

What is the gold standard for diagnosis of this disease?
a)  Biopsy
b)  ANCA
c)  Clinical diagnosis, no single lab test diagnostic
d)  Western Blot and ELISA serology

Question 3.

What is the mainstay of treatment for this disease?
a)  Doxycycline
b)  Long term corticosteroids
c)  Long term corticosteroids and cyclophosphamide
d)  IVIG and aspirin

Answers: 1. C, 2. A, 3. C

Answer Discussion

  1. The above vignette is a description of pediatric Wegner’s patient.  Definitely a challenging disease process with a lot of overlap with other conditions  It is a small vessel vasculitis classically taught to affect kidneys and lungs, but also can present with many other symptoms.   This patient presents with renal, pulmonary, cutaneous, and musculoskeletal symptoms.  Kawasaki’s disease is a large vessel vasculitis which classically presents as a high fever for more than 5 days with a predominance of conjunctivitis, mucous membrane involvement, and lymphadenopathy and potentially many other symptoms.  And while there are overlaps between kawasaki’s and Wegner’s, the low grade fever is more in line with Wegner’s.  Polymyalgia Rheumatica can also present with a large range of symptoms, with the arthralgias focused on the neck, shoulders and hips.  Lyme disease is a tick borne infection that can present during a spectrum of the disease process.  Early manifestations include a target rash and flu-like symptoms with later symptoms predominately affecting neurological and cardiac systems.
  2. While there are numerous tests to help rule in or out Wegner’s as the possible disease state, only a tissue sample can give the definitive diagnosis.  A sample taken from an active site of inflammation is diagnostic, and necessary due to the potential severe side effects of medical treatment.  ANCA testing is the laboratory test of choice, but only 82-94% sensitive.  Serology is the testing of choice for Lyme disease, and Kawasaki’s and Polymyalgia are clinically diagnosed and no single test is diagnostic.
  3. The mainstay of treatment for Wegner’s is steroids and immunosuppression with cyclophosphamide/methotrexate/rituximab.  This is important to know because Wegner’s patients undergoing treatment will be functionally immunosuppressed and at risk for overwhelming infections, even PCP.  Patients are also at risk for DVTs secondary to the disease progress, and untreated, the disease can be fatal by as little as 5 months.  Doxycycline is the first line treatment for Lyme disease.  Long term steroids are the treatment for Polymyalgia Rheumatica, but immunosuppressants are required for Wegner’s.  IVIG and aspirin are the treatment for Kawasaki’s.

Discussion:

This is a pediatric case of Granulomatosis with Polyangiitis (Wegner’s), a predominately small vessel vasculitis.  Though the two most common vasculitidies of childhood are Henoch-Schonlein purpura and Kawasaki disease, Wegner’s is a potentially lethal disease process if not treated appropriately.

The clinical presentation can be misleading as well, early symptoms are non-specific including fever, malaise, anorexia and weight loss as well as migratory arthralgias and can persist for months before other organ involvement.

Ocular symptoms can include conjunctivitis, scleritis, proptosis or uveitis

Wegner’s also can present with numerous ENT symptoms, including epistaxis, sinusitis, persistent rhinorrhea or even saddle nose deformity or laryngotracheobronchial stenosis.  Pulmonary manifestations can involve anything from intermittent coughing or wheezing to hemoptysis, dyspnea pulmonary fibrosis or pulmonary arterial hypertension with chest x-rays variably showing nodules, opacities and possibly infiltrates.  CT scan can show nodules, cavitary lesions or infiltrates

Cardiac and gastrointestinal symptoms are much less common, ex. pericarditis

Renal disease is one of the most common manifestations.  Glomerulonephritis develops in up to 80% of patients within the first 2 years, and is common at time of diagnosis.  ANCA positive patients are at greater risk for progression to end stage renal disease.  Other common signs are usually nephritic range proteinuria, hematuria, and AKI with cellular casts

Musculoskeletal disease usually presents as migratory arthralgias and myalgias

Cutaneous disease is present in up to half of cases and the most common lesion is leukocytoclastic angiitis – shown in example picture, but may also have focal necrosis/ulceration, hives, livida reticularis or tender nodules.

Nervous system involvement can present with cranial nerve abnormalities, CNS lesions or external ophthalmoplegia

There are multiple diagnostic criteria including the American College of Rheumatology (ACR) and Chapel Hill Consensus Conference Criteria (CHCC), both criteria are limited in distinguishing Wegner’s from Microscopic Polyangiitis, and recommend a definitive diagnosis with tissue biopsy from a site of active inflammation (lung/kidney).  Confirmation with biopsy is also indicated before starting a patient on immunosuppressant therapy with steroids and cyclophosphamide/methotrexate/rituximab etc.  ANCA is positive in 82-94% of cases.  Other lab values include an elevated ESR, elevated CRP, leukocytosis, normochromic normocytic anemia, thrombocytosis or thrombocytopenia and evidence of AKI.

CHCC guidelines might permit the diagnosis of Wegners in the absence of biopsy with:

  1. Radiographic evidence of pulmonary involvement for more than 1 month
  2. Upper airway symptoms for more than 1 month as listed above
  3. Glomerulonephritis
  4. ANCA positive

After remission induction, patients remain at risk for flare-ups, usually following an infection, and are also at increased risk for PCP or disseminated VZV.  Patients are also at increased risk for DVTs and long term side effects of the immunosuppressing medications.

Vasculitides Overview

Large Vessel Vasculitides

Temporal Arteritis: Commonly women in their 60’s/70’s.  Multiple systemic symptoms, as well as ischemic symptoms to branches of internal and external carotid.  30-40% also have Polymyalgia Rheumatica.  Lab assessment can include ESR, CRP, and anemia.  Treatment is corticosteroids, most effective within 24hrs of symptom onset.

Takayasu’s Arteritis (Pulseless disease): Chronic recurring disease affecting aorta and it’s branches. Primarily seen in young women.  Early diagnosis extremely difficult, symptoms are minor and nonspecific.  Later symptoms include uneven to absent pulses, claudication, retinopathy, strokes, and other ischemic type symptoms.  Treatment is prednisone, and further treatment may require immunosuppressants.

Medium Vessel Vasculitides

Polyarteritis Nodosa: Predominately in males in their 50’s/60’s, but can present at any age. Early symptoms include fevers, myalgias, arthralgias, and cutaneous manifestations (usually palpable purpura possibly with ulcerations), later manifestations include peripheral neuropathy and bowel ischemia.  Treatment is corticosteroids and add immunosuppressants if there is organ involvement.

Buerger’s Disease: Vaso-occlusive disease of young male smokers typically in lower extremities.  Symptoms can start as mild paresthesia’s/pain and progress to severe pain with claudication and possibly ulceration.  Treatment is abstinence from tobacco, and possibly calcium channel blockers.  Half of all patients who continue using tobacco need amputation.

Small Vessel Vasculitides

Behcet’s Disease: A chronic relapsing vasculitis that can affect large vessels, presents with oral/genital ulcers, skin lesions and possibly ophthalmologic/ neurologic/ gastrointestinal manifestations, and typically men between 25-35.  Oral ulcers are an early sign and required for diagnosis.  Kidney and cardiac involvement is rare, and diagnosis is by tissue biopsy. Treatment is focused on presenting symptoms.

Wegner’s Granulomatosis: discussed above

Churg-Strauss: It is a granulomatis vasculitis of multiple organs presenting as asthma and allergic rhinitis with eosinophilia.  Associated with allergy/atopic disorders.  Asthma usually presents during adulthood.  Pulmonary, ENT, and cutaneous symptoms predominate along with nonspecific symptoms of fever and weight loss.  Neurological and cardiac symptoms are also common.  Labs may show eosinophilia >1500/mm3, possibly p-ANCA, and chest x-ray may show Loffler’s syndrome/consolidation/cavitation.  Diagnosis is by tissue biopsy, and treatment is corticosteroids and possibly cyclophosphamide.

Microscopic Polyangiitis: Another ANCA positive vasculitis with a high degree of overlap with Wegner’s, with common symptoms of alveolar hemorrhage and glomerulonephritis, with the other most common symptoms including weight loss, mononeuritis multiplex, fever and cutaneous findings.  Diagnosis is by tissue biopsy, and treatment is corticosteroids and immunosuppressants.

Goodpasture’s Syndrome (Anti-GBM syndrome): Caused by the build-up of anti-glomerular basement membrane antibodies in the alveolar and glomerular basement membrane.   The disease has bimodal peak incidence during the 20’s and 50’s/60’s.

Like Wegner’s, initial symptoms include fever, malaise and arthralgia.  Hemoptysis occurs in 70% of cases, and glomerulonephritis is another frequent complication of the disease.  Notable tests include elevated ESR, UA with RBC casts, and Anti-GBM Ab positive.  Diagnosis is made with kidney biopsy, and treatment is corticosteroids and possibly immunosuppressants, and patients may end up requiring renal transplant if able to get anti-GBM antibodies to undetectable levels.

Henoch-Schonlein Purpura: Another small vessel vasculitis with a large degree of overlap with Wegner’s disease.  It typically involves the skin, gastrointestinal tract, and kidneys.  The disease predominately affects the pediatric population, and male to female ratio of 2:1.  Up to 2/3 of patients have a history of a respiratory infection 10 days before developing symptoms.  Classically, these symptoms include abdominal pain, fever, palpable purpura, hematuria and arthralgias. Gastrointestinal complaints in 70% with renal involvement in up to 50%.  Neurological involvement is rare.  Treatment is aimed at the underlying cause, if applicable, and multiple possible treatment regimens are currently being researched.  However, this disease is usually self limited, over the course of 6-8 weeks, and prolonged treatment may not be needed.

Key Points:

Wegner’s is a complex disease process potentially involving many different organ systems.  In medical school it was taught as the vasculitis that involves the kidneys and lungs, but it’s important to be aware that it can involve much more than those systems.

Missing the diagnosis can potentially have severe consequences in terms of morbidity and mortality.  Important lab/imaging work-up includes Urinalysis with microscopic analysis for urinary sediment and presence of blood, BMP (they know what these tests are for, CBC .  ANCA, ESR, CRP, LFTs, hepatits panel, HIV screen, and blood cultures as indicated to rule out other disease processes.  A baseline chest x-ray or possibly CT to assess pulmonary involvement.

Wegner’s Diagnosis is based on tissue biopsy.  Patients with suspected Wegner’s are an indication for admission and further work-up for diagnosis as well as medical treatment induction.

Patients being treated for Wegner’s are immunosuppressed and at risk for infections including disseminated VZV and PCP.  They are also at risk for DVT’s as well as numerous medication side effects.

References: 

  1. American Academy of Ophthamology – http://www.aao.org/theeyeshaveit/red-eye/immunologic-conjunctivitis.cfm
  2. John’s Hopkins Vasculitis Center – http://www.hopkinsvasculitis.org/types-vasculitis/microscopic-polyangiitis/
  3. Bosch et al, Treatment of Antineutorphil Cytoplasmic Antibody Associated Vasculitis – http://jama.jamanetwork.com/article.aspx?articleid=208292, JAMA 2007
  4. Lehrmann, Jill and Sercombe, Clare, Systemic Lupus Erythematosus and the Vasculitides, Rosen’s Emergency Medicine 7th edition
  5. Cabral et al, Classification and incidence of childhood vasculitis, uptodate.com updated June 5th 20013
  6. Falk et al, Clinical manifestations and diagnosis of granulomatosis with polyangiitis and microscopic polyangiitis, uptodate.com updated September 25th 2012
  7. Gnann Jr., John, Antiviral therapy of Varicella Zoster virus infections Chapter 65 of Human Herpesviruses: Biology, Therapy and Immunoprophylaxis 2007  http://www.ncbi.nlm.nih.gov/books/NBK47401/