Snapshot A 23-year-old woman with past medical history of multiple allergies leading to facial swelling presents with marked difficulty breathing, abdominal pain, and swelling of the face and neck. On physical exam, her extremities are also noted to be markedly swollen (picture). She is immediately sedated for intubation to maintain patency of airway. Chart review reveals newly-started ACE-inhibitor. She is given epinephrine, fluids, and fresh frozen plasma. Introduction Disorder of complement, causing angioedema Genetics autosomal dominant Pathogenesis C1 esterase inhibitor deficiency C1 esterase inhibitor inhibits kallikrein-kinin pathway remember kallikrein activates bradykinin bradykinin ↑ vasodilation ↑ permeability ↑ pain ACE-inhibitors are contraindicated ACE inactivates bradykinin ACE-inhibitors allows ongoing bradykinin, causing angioedema Epidemiology attacks begin during childhood Risk factors family history of angioedema family history of those contraindicated with ACE-inhibitors autoimmune conditions Presentation Symptoms/physical exam recurrent episodes of angioedema without urticaria as opposed to anaphylaxis, which typically has urticarial angioedema of the face, oropharynx, extremities, or abdomen angioedema of GI tract severe abdominal pain GI upset worst at 24 hours resolves over 48-72 hours often preceded by prodrome fatigue flu-like symptoms not responsive to epinephrine (epi-pen) or antihistamines Evaluation Best initial test ↓ C4 and C2 levels if C4 are normal, C1 inhibitor deficiency is unlikely To confirm diagnosis if ↓ C4 ↓ C1 inhibitor antigenic levels ↓ C1 inhibitor functional levels Differential Diagnosis Anaphylaxis Allergic angioedema Facial cellulitis SVC syndrome Treatment Anaphylaxis presents very similarly to angioedema and often cannot be differentiated immediately in an emergency room setting therefore, patients are often initially treated with medications for anaphylaxis given urgent, life-threatening nature of anaphylaxis epinephrine fluid replacement anti-histamines Assess airwa, even after administering treatment intubate if necessary As soon as possible, especially if epinephrine and anti-histamines are not effective, administer medications for hereditary angioedema plasma-derived C1 inhibitor recombinant human C1 inhibitor fresh frozen plasma if above are not available Prognosis, Prevention, and Complications Prognosis mortaliy >30% in those with laryngeal angioedema angioedema is unpredictable Complications small bowel obstruction compartment syndrome death by asphyxiation
QUESTIONS 1 of 2 1 2 Previous Next Lab Values Blood Hematologic Cerebrospinal Sweat, Urine, and BMI Blood, Plasma, Serum Reference Range ALT 8-20 U/L Amylase, serum 25-125 U/L AST 8-20 U/L Bilirubin, serum (adult) Total // Direct 0.1-1.0 mg/dL // 0.0-0.3 mg/dL Calcium, serum (Ca2+) 8.4-10.2 mg/dL Cholesterol, serum Rec: < 200 mg/dL Cortisol, serum 0800 h: 5-23 μg/dL //1600 h: 3-15 μg/dL 2000 h: ≤ 50% of 0800 h Creatine kinase, serum Male: 25-90 U/LFemale: 10-70 U/L Creatinine, serum 0.6-1.2 mg/dL Electrolytes, serum Sodium (Na+) 136-145 mEq/L Chloride (Cl-) 95-105 mEq/L Potassium (K+) 3.5-5.0 mEq/L Bicarbonate (HCO3-) 22-28 mEq/L Magnesium (Mg2+) 1.5-2.0 mEq/L Estriol, total, serum (in pregnancy) 24-28 wks // 32-36 wks 30-170 ng/mL // 60-280 ng/mL 28-32 wk // 36-40 wks 40-220 ng/mL // 80-350 ng/mL Ferritin, serum Male: 15-200 ng/mLFemale: 12-150 ng/mL Follicle-stimulating hormone, serum/plasma Male: 4-25 mIU/mL Female: premenopause: 4-30 mIU/mL midcycle peak: 10-90 mIU/mL postmenopause: 40-250 pH 7.35-7.45 PCO2 33-45 mmHg PO2 75-105 mmHg Glucose, serum Fasting: 70-110 mg/dL2-h postprandial:<120 mg/dL Growth hormone - arginine stimulation Fasting: <5 ng/mLProvocative stimuli: > 7ng/mL Immunoglobulins, serum IgA 76-390 mg/dL IgE 0-380 IU/mL IgG 650-1500 mg/dL IgM 40-345 mg/dL Iron 50-170 μg/dL Lactate dehydrogenase, serum 45-90 U/L Luteinizing hormone, serum/plasma Male: 6-23 mIU/mL Female: follicular phase: 5-30 mIU/mL midcycle: 75-150 mIU/mL postmenopause 30-200 mIU/mL Osmolality, serum 275-295 mOsmol/kd H2O Parathyroid hormone, serume, N-terminal 230-630 pg/mL Phosphatase (alkaline), serum (p-NPP at 30° C) 20-70 U/L Phosphorus (inorganic), serum 3.0-4.5 mg/dL Prolactin, serum (hPRL) < 20 ng/mL Proteins, serum Total (recumbent) 6.0-7.8 g/dL Albumin 3.5-5.5 g/dL Globulin 2.3-3.5 g/dL Thyroid-stimulating hormone, serum or plasma .5-5.0 μU/mL Thyroidal iodine (123I) uptake 8%-30% of administered dose/24h Thyroxine (T4), serum 5-12 μg/dL Triglycerides, serum 35-160 mg/dL Triiodothyronine (T3), serum (RIA) 115-190 ng/dL Triiodothyronine (T3) resin uptake 25%-35% Urea nitrogen, serum 7-18 mg/dL Uric acid, serum 3.0-8.2 mg/dL Hematologic Reference Range Bleeding time 2-7 minutes Erythrocyte count Male: 4.3-5.9 million/mm3Female: 3.5-5.5 million mm3 Erythrocyte sedimentation rate (Westergren) Male: 0-15 mm/hFemale: 0-20 mm/h Hematocrit Male: 41%-53%Female: 36%-46% Hemoglobin A1c ≤ 6 % Hemoglobin, blood Male: 13.5-17.5 g/dLFemale: 12.0-16.0 g/dL Hemoglobin, plasma 1-4 mg/dL Leukocyte count and differential Leukocyte count 4,500-11,000/mm3 Segmented neutrophils 54%-62% Bands 3%-5% Eosinophils 1%-3% Basophils 0%-0.75% Lymphocytes 25%-33% Monocytes 3%-7% Mean corpuscular hemoglobin 25.4-34.6 pg/cell Mean corpuscular hemoglobin concentration 31%-36% Hb/cell Mean corpuscular volume 80-100 μm3 Partial thromboplastin time (activated) 25-40 seconds Platelet count 150,000-400,000/mm3 Prothrombin time 11-15 seconds Reticulocyte count 0.5%-1.5% of red cells Thrombin time < 2 seconds deviation from control Volume Plasma Male: 25-43 mL/kgFemale: 28-45 mL/kg Red cell Male: 20-36 mL/kgFemale: 19-31 mL/kg Cerebrospinal Fluid Reference Range Cell count 0-5/mm3 Chloride 118-132 mEq/L Gamma globulin 3%-12% total proteins Glucose 40-70 mg/dL Pressure 70-180 mm H2O Proteins, total < 40 mg/dL Sweat Reference Range Chloride 0-35 mmol/L Urine Calcium 100-300 mg/24 h Chloride Varies with intake Creatinine clearance Male: 97-137 mL/minFemale: 88-128 mL/min Estriol, total (in pregnancy) 30 wks 6-18 mg/24 h 35 wks 9-28 mg/24 h 40 wks 13-42 mg/24 h 17-Hydroxycorticosteroids Male: 3.0-10.0 mg/24 hFemale: 2.0-8.0 mg/24 h 17-Ketosteroids, total Male: 8-20 mg/24 hFemale: 6-15 mg/24 h Osmolality 50-1400 mOsmol/kg H2O Oxalate 8-40 μg/mL Potassium Varies with diet Proteins, total < 150 mg/24 h Sodium Varies with diet Uric acid Varies with diet Body Mass Index (BMI) Adult: 19-25 kg/m2 Calculator ( ) xy AC 7 8 9 ÷ 4 5 6 × 1 2 3 - 0 . = + (M1.IM.74) A 47-year-old male presents to the emergency department with facial swelling and trouble breathing. These symptoms began this morning and progressively worsened over the past several hours. Vital signs are as follows: T 37.7, HR 108, BP 120/76, RR 20, and SpO2 96%. Physical examination reveals nonpitting swelling of the face, hands, and arms as well as edema of the tongue and mucus membranes of the mouth and pharynx. The patient reports several episodes of mild facial swelling that occurred during childhood between the ages of 5-18, but he does not recall seeing a physician or receiving treatment for this. His medical history is otherwise negative, except for mild hypertension for which his primary care physician initiated lisinopril 2 weeks ago. This patient most likely has which of the following underlying abnormalities? Review Topic QID: 106671 1 MHC class I deficiency 11% (4/37) 2 Defective lysosomal storage proteins 8% (3/37) 3 Lack of NADPH oxidase 0% (0/37) 4 Defect in cytoskeletal glycoprotein 3% (1/37) 5 Deficiency of C1 esterase inhibitor 68% (25/37) M1 Select Answer to see Preferred Response PREFERRED RESPONSE 5 (M1.IM.21) A 23-year-old female presents to the emergency room with diffuse swelling. Her boyfriend is especially concerned because her face has begun to swell (Figure A). Her tongue is also swollen and she is beginning to have trouble breathing. If her symptoms are due to a congenital syndrome and not a medication side effect, which of the following would be true regarding this patient's disease? Review Topic QID: 104232 FIGURES: A 1 Caused by deficiency in C1 esterase inhibitor 62% (30/48) 2 Caused by deficiency in C3 10% (5/48) 3 Caused by deficiency in C5-C8 8% (4/48) 4 Caused by deficiency in decay accelerating factor 4% (2/48) 5 Danazol is contraindicated in this disease as it may worsen symptoms 6% (3/48) M1 Select Answer to see Preferred Response PREFERRED RESPONSE 1