Snapshot A 6-month-old boy presents with a past medical history of skin infections presents with difficulty breathing, high fever, and nonproductive cough. He is immediately started on broad-spectrum antibiotics. On further questioning, his family history includes a maternal uncle dying at age 20 from overwhelming pneumonia. Sputum is induced with hypertonic saline inhalation, and eventual staining shows Pneumocystis. He is immediately started on IVIG. Introduction Inherited primary combined B- and T-cell immunodeficiency characterized by increased levels of IgM Genetics X-linked recessive mutation in gene that codes for CD40 ligand (CD40L) Pathogenesis CD40L is expressed on activated T-helper cells defect in humoral immunity CD40L is necessary to induce B-cells to undergo Ig class-switching from IgM to IgG, IgA, and IgE see illustration above defect cell-mediated immunity CD40L also required for maturation of T-cells, dendritic cells, and macrophages Symptoms onset by 1 year, often with Pneumocystis infections most diagnosed before 4 years Presentation Symptoms severe pyogenic infections early in life chronic diarrhea opportunistic infections pneumonia Pneumocystis Cryptosporidium CMV echovirus encephalitis pancytopenia common fatigue infection pallor bleeding Evaluation Ig levels ↑ IgM ↓ IgA, IgG, and IgE due to defect in class-switching Diagnosis confirmed with flow cytometry deficient expression of CD40L on activated T-helper cells normal T- and B-cells CBC neutropenia thrombocytopenia possible Differential Diagnosis Bruton agammaglobulinemia CVID SCID Treatment Prophylaxis of Pneumocystis Regular IVIG replacement Prognosis, Prevention, and Complications Prognosis 20% survival rate past young adulthood leading cause of death pneumonia encephalitis malignancy Complications increased risk of autoimmunity increased risk of malignancies HCC carcinoid tumor infection bronchiectasis
QUESTIONS 1 of 4 1 2 3 4 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 . = + Sorry, this question is for PEAK Premium Subscribers only Upgrade to PEAK (M1.IM.74) A 3-month-old is referred to a pediatric immunologist by his pediatrician for further workup of recurrent sinopulmonary infections which have not abated despite adequate treatment. During the workup flow cytometry demonstrates a decrease in normal CD40L cells. Based on these findings, the immunologist decides to pursue a further workup and obtains immunoglobulin levels. Which of the following immunoglobulin profiles is most likely to be observed in this patient? Review Topic QID: 106685 1 Increased IgE; Decreased IgG, IgM 2% (3/122) 2 Decreased IgE, IgM, IgA, IgG 12% (15/122) 3 Increased IgE, IgA; Decreased IgM 7% (8/122) 4 Increased IgE 2% (3/122) 5 Increased IgM; Decreased IgG, IgA, IgE 73% (89/122) M1 Select Answer to see Preferred Response PREFERRED RESPONSE 5 (M1.IM.126) A 3-year-old boy presents to the pediatrics clinic for follow-up. He has a history of severe pyogenic infections since birth. Further workup revealed a condition caused by a defect in CD40 ligand expressed on helper T cells. This congenital immunodeficiency has resulted in an inability to class switch and a poor specific antibody response to immunizations. Which of the following best characterizes this patient's immunoglobulin profile? Review Topic QID: 105524 1 Increased IgE 0% (0/13) 2 Decreased IgA 0% (0/13) 3 Decreased Interferon gamma 0% (0/13) 4 Increased IgE and IgA; and decreased IgM 0% (0/13) 5 Increased IgM; decreased IgG, IgA, and IgE 92% (12/13) M1 Select Answer to see Preferred Response PREFERRED RESPONSE 5 Sorry, this question is for PEAK Premium Subscribers only Upgrade to PEAK