e166 SECTION XV Pediatric Critical Care Board Review Questions 2 Which immune cell plays the greatest role as an antigen pre senting cell? A CD41 T lymphocyte B CD81 T lymphocyte C Macrophage D Natura[.]
e166 S E C T I O N XV Pediatric Critical Care: Board Review Questions Which immune cell plays the greatest role as an antigen presenting cell? A CD41 T lymphocyte B CD81 T lymphocyte C Macrophage D Natural killer cell E Neutrophil Preferred response: C homeostasis in the setting of CARS can sometimes be achieved by treatment with immunostimulatory agents like interferon gamma (IFN-g) or granulocyte macrophage colony stimulating factor (GM-CSF) Rationale Innate immune cells of myeloid lineage typically serve as antigen presenting cells, with monocytes, macrophages, and dendritic cells played the greatest role in antigen presentation While neutrophils are capable of presenting antigen, their primary role in host defense is through phagocytosis, intracellular killing, and release of reactive oxygen species Natural killer cells’ role in antigen presentation is limited, and they effect killing primarily through the release of lytic enzymes T lymphocytes are the recipients, not initiators, of antigen presentation 1 A 15-year-old previously healthy African-American female is admitted to the PICU for a prolonged seizure Her blood pressure in the emergency department was 160/100 mm Hg On examination, she has an erythematous rash on her face crossing the nasal bridge, palatal ulcers, swelling of her elbows and wrists, and 21 pitting edema of the lower extremities Thorough evaluations for infection and malignancy are negative The antinuclear antibody (ANA) is positive with a 1:1280 titer Which of the following sets of laboratory values are most consistent with this patient’s underlying diagnosis? A Elevated C3 and C4, positive antimyeloperoxidase (MPO) antibody B Low C3 and C4, positive anti-Smith antibody C Normal C3 and low C4, positive anti-p155/140 antibody D Normal C3 and C4, negative anti-dsDNA antibody Preferred response: B Which of the following immunologic test results is most strongly associated with the immunoparalyzed phenotype? A Absolute lymphocyte count 1000 cells/uL B Low plasma IL-6 level C Markedly elevated ex vivo lipopolysaccharide (LPS)induced TNF-a production capacity D Monocyte HLA-DR expression of 20% Preferred response: D Rationale Monocyte HLA-DR expression ,30% has been repeatedly associated with increased risks for secondary infection and death from multiple forms of critical illness The immunoparalyzed phenotype is often associated with reduced ex vivo lipopolysaccharide (LPS)-induced TNF-a production capacity and high levels of circulating proinflammatory and antiinflammatory cytokines Lymphopenia, as defined by an absolute lymphocyte count ,1000 cells/uL, is a measure of adaptive immune suppression that is also consistent with immunoparalysis Which statement best describes the dynamic inflammatory response in critical illness? A A marked and persistent CARS response is beneficial to the patient B Restoration of the SIRS/CARS balance can require immunostimulatory treatment C The CARS response affects the adaptive immune system more than the innate D The SIRS/CARS balance is easily quantified in the clinical laboratory Preferred response: B Rationale The systemic inflammatory response syndrome/compensatory antiinflammatory syndrome (SIRS/CARS) balance can be measured through specialized testing of cytokines as well as markers of innate immune cell function such as monocyte HLA-DR expression and ex vivo LPS-induced cytokine production capacity High levels of systemic inflammation (SIRS) and immune suppression (CARS) often occur simultaneously, with a marked and persistent CARS response being frequently associated with adverse outcomes from critical illness Restoration of immunologic Chapter 106: Pediatric Rheumatologic Disease Rationale Systemic lupus erythematosus (SLE) is a multi-system autoimmune disease Incidence is higher in African-American and Hispanic females in the United States relative to other demographic groups The patient in this vignette has clinical features suggestive of SLE: malar rash, painless oral ulcers, arthritis, and evidence of significant kidney dysfunction (pitting edema and hypertension) Her uncontrolled lupus nephritis has caused her to develop posterior reversible encephalopathy syndrome (PRES) More than 95% of SLE patients have a positive ANA; however, the ANA is not specific for SLE and can be positive in other autoimmune conditions, infections, and in a subset of healthy children Specific antibodies for SLE include anti-dsDNA and anti-Smith antibodies An elevated dsDNA can be a marker of SLE activity Not all patients with SLE have anti-Smith or anti-dsDNA antibodies; however, when present they are both highly suggestive of this underlying diagnosis Anti-dsDNA antibodies are strongly associated with proliferative SLE nephritis Complement levels (C3 and C4) are usually low in active SLE due to consumption from immune complex formation Antimyeloperoxidase (MPO) antibody is typically associated with microscopic polyangiitis (MPA), an ANCA (antineutrophil cytoplasmic antibodies)-associated small vessel vasculitis Anti-p155/140 antibody is a specific antibody in juvenile dermatomyositis (JDM) and can be helpful in predicting clinical course It can occur in overlap syndromes but is not specific for SLE A 10-year-old male with juvenile idiopathic arthritis (JIA) is on maintenance treatment with a biologic medication He develops a fever of 103°F and respiratory distress Evaluation confirms disseminated histoplasmosis Which of the following medications is most likely associated with his infectious complication? A Abatacept B Anakinra C Infliximab D Tocilizumab Preferred response: C CHAPTER 136 Board Review Questions Rationale Biologic medications are widely used in the treatment of pediatric rheumatic conditions Given their various mechanisms of modulating and suppressing the immune system, patients on these medications must carefully be monitored for development of infection Additionally, certain biologic medications have several noninfectious potential side effects These medications are often used to treat JIA as well as other rheumatologic diseases TNFalpha inhibitors such as infliximab have been associated with increased risk of bacterial viral infections, as well as infections that require granuloma formation, such as tuberculosis and histoplasmosis TNF-alpha inhibitors are also associated with possible drug-induced lupus syndromes, and infusion or injection site reactions Anakinra, an IL-1 inhibitor used primarily in systemic onset JIA and macrophage activating syndrome (MAS), has been associated with increased viral infections such as varicella and herpesvirus (HSV), but has not been associated with more severe bacterial infections nor endemic mycoses Tocilizumab, an IL-6 blocker, may be used to treat systemic or polyarticular JIA and can be associated with severe bacterial infections, abdominal perforation and lipid abnormalities, but has not been associated with histoplasmosis Importantly, blockade of IL-6 blunts the acute phase response and thus C-reactive protein (CRP) levels may be normal in patients on tocilizumab even in the face of invasive infections associated with drug induced lupus A 5-year-old patient presents to the PICU with encephalopathy, distended abdomen, and petechial rash The patient has been experiencing fevers with an erythematous rash for the past weeks Labs demonstrate pancytopenia, transaminitis, and elevated serum creatinine Which of the follow sets of results would most strongly suggest macrophage activation syndrome (MAS) as the underlying etiology of his acute deterioration? A ADAMTS13 activity , 10% and D-dimers 10 mg/mL B C-reactive protein (CRP) 20 mg/dL and elevated antiPR3 antibody level C Negative antinuclear antibody (ANA) and elevated anticardiolipin IgG D Serum ferritin 10,000 ng/mL and normal red blood cell (RBC) morphology Preferred response: D Rationale Macrophage activation syndrome (MAS) is a form of secondary hemophagocytic lymphohistiocytosis (HLH) and a common complication of rheumatologic diseases, primarily systemic JIA Clinically, MAS can resemble sepsis, thrombotic thrombocytopenic purpura (TTP), malignancy, or other rheumatologic conditions such as lupus The etiology of pancytopenia is thought to be hemophagocytosis by activated macrophages in the bone marrow, liver, and spleen; as such RBC morphology is often normal as opposed to TTP where microangiopathic hemolytic anemia leads to schistocytes Coagulopathy results from excessive consumption of fibrinogen which may also cause a characteristic drop in erythrocyte sedimentation rate (ESR) or normalization of a previously elevated ESR Severe hyperferritinemia is characteristic of MAS and helps differentiate it from other inflammatory conditions e167 Mild to moderately elevated ferritin (500–1000 ng/mL) and an elevated ESR could be seen in active systemic JIA (without MAS) or sepsis However, in the setting of a rising ferritin (especially if 10,000 ng/mL), the diagnosis of MAS must be considered Additional labs that would suggest MAS include demonstration of hemophagocytosis in bone marrow or other tissue, elevated D-dimers, lactic acid dehydrogenase (LDH), triglycerides, low natural killer (NK) cell function, and elevated soluble IL-2 receptor levels Absent or severely reduced ADAMTS13 suggests TTP as an etiology A negative ANA and elevated anticardiolipin antibodies could be seen in the setting of severe infection and could be related to hypercoagulability but are not helpful to distinguish MAS from other etiologies While CRP is often elevated in MAS, an anti-PR3 level would be very suspicious for granulomatosis with polyangiitis (GPA) vasculitis as an underlying condition Although MAS can theoretically complicate any rheumatologic disorder, these labs alone would not necessarily indicate MAS physiology A 2-year-old presents to the PICU with a second lacunar stroke after a year of intermittent fevers, livedo-like rash, and hepatomegaly Initial hypercoagulability workup was unrevealing This child would be most likely to have a mutation in which of the following genes? A Autoimmune regulatory enzyme (AIRE) B CECR1 C FOX-P3 D NALP3 Preferred response: B Rationale A mutation in CECR1 (the gene encoding the protein adenosine deaminase 2) leads to deficiency of adenosine deaminase (DADA2) This syndrome is one of the monogenic autoinflammatory syndromes which presents in early childhood with lacunar strokes, livedo-like rash, necrotizing vasculitis, and hypogammaglobulinemia Autoinflammatory syndromes are the result of genetic defects in innate immune system pathways that cause episodic or persistent inflammation Symptoms depend on the specific syndrome, but generally involve recurrent or prolonged fevers associated with multiorgan involvement The majority of these syndromes presents at a young age and can be distinguished based on characteristic symptoms Defects in AIRE lead to a syndrome of multiorgan autoimmunity known as autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) or chronic cutaneous candidiasis These patients often present with hypoparathyroidism, adrenal failure, and chronic fungal infections, but not strokes Defects in FOX-P3 expression lead to defective T-regulatory cell function These patients also present in infancy or early childhood but with severe diarrhea, eczematous rash, and early onset type diabetes NALP3 gene mutations are found in patients with neonatal-onset multisystem inflammatory disease (NOMID, aka CINCA syndrome) Infants with NOMID present with neurologic findings, but these tend to be aseptic meningitis and sensorineural hearing loss, not strokes These patients often exhibit more urticarial rashes and may have episodes of systemic inflammation triggered by cold exposure e168 S E C T I O N XV Pediatric Critical Care: Board Review Questions In critically ill patients with rheumatic diseases, such as systemic lupus erythematosus, granulomatosis with polyangiitis, catastrophic antiphospholipid antibody syndrome, and macrophage activation syndrome, which of the following therapies is not typically part of the initial management in the ICU? A Azathioprine B Cyclophosphamide C High-dose IV pulse methylprednisolone D Rituximab Preferred response: A Rationale Aggressive treatment is essential and can be lifesaving in severely ill patients with newly diagnosed or flaring rheumatic diseases In the ICU setting, treatment is typically initiated with high-dose pulse IV methylprednisolone (30 mg/kg/day, maximum dose 1000 mg), administered over hour for consecutive days In addition to steroids, agents such as cyclophosphamide and rituximab are also used in patients with severe disease Plasmapheresis is an additional therapy that has been shown to reduce mortality rates in several of the rheumatic diseases Although azathioprine is an important therapy, it is typically used in patients with less severe disease as well as for long-term disease control It is rarely introduced in the ICU setting A 6-year-old boy with known systemic onset juvenile arthritis that was previously well controlled with low-dose prednisone and methotrexate has recently had an intercurrent illness from which he has been slow to recover During the 24 hours prior to admission, he has become progressively more lethargic, has had a sustained fever of 38.9°C, and has bruised and bled easily Laboratory studies in the emergency department before transfer to the intensive care unit show an erythrocyte sedimentation rate of 26 mm/h (the last recorded value month earlier was 54 mm/h), prolonged prothrombin time and partial thromboplastin time, a platelet count of 20,000/µL, and an aspartate aminotransferase and alanine aminotransferase value of greater than 2000 IU/L Which two additional diagnostic tests should be included in the initial workup of this patient to confirm the diagnosis and guide medical management? A Complement levels and antinuclear antibody (ANA) B Creatinine and renal biopsy C Ferritin and bone marrow aspiration D White blood cell count and hematocrit Preferred response: C Rationale This boy most likely has macrophage activation syndrome, a complication of his systemic onset juvenile idiopathic arthritis, possibly precipitated by an intercurrent infection Further tests to confirm this diagnosis include a ferritin level test, which is usually markedly elevated, and a bone marrow aspiration to demonstrate the typical hemophagocytic changes The differential diagnosis includes an infectious process causing disseminated intravascular coagulation He should be treated with empiric antibiotics, although therapy for macrophage activation syndrome is initiated, which includes pulses of methylprednisolone, 30 mg/kg/day, and cyclosporine, to mg/kg/day In addition, he should receive supportive therapies, such as correction of his coagulopathy A 15-year-old girl who recently arrived from a refugee camp in Africa is admitted from the emergency department because of severe respiratory distress She is severely anemic (hemoglobin, 4.9 g/dL), and her chest radiograph shows generalized patchy infiltrates She has no gastrointestinal symptoms, and a rectal examination is negative for occult blood Her urinalysis shows red cells and 31 proteinuria The primary indication for emergently ordering blood products for this patient includes which of the following? A She needs an emergent blood transfusion because of heart failure caused by severe anemia B She may have an occult upper gastrointestinal hemorrhage that has become life-threatening C She may have catastrophic bleeding following a renal biopsy that is indicated to diagnose her underlying disease process D She may have a life-threatening pulmonary hemorrhage resulting from an underlying pulmonary-renal syndrome Preferred response: D Rationale Although the differential diagnosis for this patient includes iron deficiency anemia, malnutrition with severe infection, a marrow infiltrative process or aplasia, severe hemolytic anemia, or acute blood loss, a pulmonary-renal syndrome with life-threatening pulmonary hemorrhage should be suspected Besides a full review of all organ systems and evaluation for other causes of her symptoms, this patient should be tested for Goodpasture syndrome (antiglomerular basement membrane antibodies), a vasculitic syndrome such as Wegener granulomatosis or microscopic polyangiitis (ANCA, proteinase-3, and myeloperoxidase), and lupus (ANA, complements, and dsDNA antibodies) See the Rationale for question in this chapter for a summary of the pulmonary, renal, and laboratory findings in the most common pulmonaryrenal syndromes Supportive therapy, which may require intubation, mechanical ventilation with high positive end-expiratory pressure, and blood transfusions, should be initiated for this patient Clinical judgment regarding treatment with corticosteroids and other immunosuppressive therapies in addition to antibiotics is indicated CHAPTER 136 Board Review Questions e169 Pulmonary-Renal Syndromes Other Organ System Involvement Laboratory Findings Pauci-immune necrotizing glomerulonephritis Sinus, airways Usually cANCA positive (PR3) Pulmonary hemorrhage Pauci-immune necrotizing glomerulonephritis Skin, CNS Usually pANCA positive (MPO) Goodpasture syndrome Pulmonary hemorrhage Anti-GBM-positive glomerulonephritis None Anti-GBM positive SLE Pulmonary hemorrhage Proliferative or membranous changes; marked immune complex deposition Multisystem disease ANA positive, anti-dsDNA positive, anti-Sm positive, low complements Diagnosis Pulmonary Findings Renal Findings GPA Cavitating lung lesions, pulmonary hemorrhage MPA ANA, Antinuclear antibody; GBM, glomerular basement membrane; GPA, granulomatosis with polyangiitis; MPA, microscopic polyangiitis; MPO, myeloperoxidase; PR3, proteinase-3; SLE, systemic lupus erythematosus Chapter 107: Bacterial and Fungal Infections An 8-year-old girl has been intubated and mechanically ventilated for days due to influenza virus associated acute respiratory distress syndrome Today her ventilator requirement increased significantly due to worsening oxygenation index and chest radiographic findings She is febrile, and her endotracheal aspirate is thick, yellow-brown in color, and contains numerous polymorphonuclear cells and gram-positive cocci in clusters Which of the following would be an inappropriate antimicrobial to initiate at this time? A Clindamycin B Daptomycin C Linezolid D Trimethoprim-sulfamethoxazole E Vancomycin Preferred response: B Rationale Staphylococcus aureus coinfection is common in patients infected with influenza virus and is thought to develop in the setting of virus-induced impaired immunity S aureus-influenza coinfection has been associated with significant mortality, and therefore prompt antistaphylococcal coverage is strongly indicated in cases of suspected or proven S aureus superinfection The patient in this vignette demonstrates clear signs of ventilator-associated pneumonia, characterized by change in clinical and radiographic parameters paired with concerning microbiologic results Each of the antibiotics listed above contain antistaphylococcal coverage, with typically high levels of methicillin-resistant Staphylococcus aureus (MRSA) coverage, although exact susceptibilities vary geographically However, daptomycin binds to and is inactivated by pulmonary surfactant, thereby limiting its utility in treating respiratory infections A 5-year-old boy with lupus nephritis and stage chronic kidney disease is admitted to the PICU in septic shock with decreasing urine output over the last hours Which of the following antibiotic regimens is associated with significantly greater nephrotoxicity and should be avoided in this high-risk patient? A Cefepime and vancomycin B Ceftazidime and vancomycin C Ceftriaxone and vancomycin D Meropenem and vancomycin E Piperacillin-tazobactam and vancomycin Preferred response: E Rationale Children with septic shock are at high-risk for developing acute kidney injury (AKI); particular caution should be taken in patients with septic shock and preexisting chronic kidney disease Each of the antimicrobial regimens listed above provide broadspectrum gram-positive and gram-negative coverage and, after considering other patient specific factors, could be suitable in the treatment of septic shock However, ample data suggest that the combination of piperacillin-tazobactam with vancomycin is highly associated with AKI and therefore should be avoided in patients at high-risk for renal injury The combined risk associated with this combination is greater than the sum of the risks of each antibiotic; in other words, they appear to multiply each other’s renal toxicity When possible, suitable alternative antimicrobial regimens should be employed in order to lessen the risk of AKI A previously healthy 3-year-old child presents with a 2-day history of fever, two episodes of emesis, mild sore throat, and decreased urine output She is admitted to PICU with confusion, cool extremities, tachycardia, and an excoriated, crustedover bug bite on the leg with surrounding erythema Laboratory tests revealed elevated white blood cell count, elevated transaminases, and a lactate of mmol/L Preliminary blood culture grows gram-positive cocci in chains You suspect toxic shock Which antimicrobial should be added to her current regimen of vancomycin and ceftriaxone to enhance efficacy? A Clindamycin B Gentamicin C Linezolid D Piperacillin-tazobactam Preferred response: A Rationale A member of the lincosamide family, clindamycin inhibits the growth of bacteria by binding to the 50S subunit of the ribosome In children with infection caused by strains of S aureus or group A streptococcus that are suspected to produce toxin-mediated disease (e.g., toxic shock syndrome, necrotizing fasciitis), clindamycin is often used in conjunction with a b-lactam agent to stop toxin production as quickly as possible Retrospectively collected data suggest improved outcomes in patients treated with the combination Gentamicin is utilized as combination therapy for enhanced gram-negative coverage as is piperacillin-tazobactam The macrolide azithromycin has enhanced efficacy for atypical e170 S E C T I O N XV Pediatric Critical Care: Board Review Questions organisms and respiratory infections Linezolid would be an appropriate choice for a vancomycin-resistant organism A 10-year-old boy with acute lymphoblastic leukemia is transferred to the PICU from the oncology ward with fever, neutropenia, progressive dyspnea, and hypoxia with progressive infiltrates on chest radiograph He has been on broad-spectrum antimicrobials, and you suspect invasive pulmonary aspergillosis Which antifungal would be ineffective in this patient? A Amphotericin B B Caspofungin C Fluconazole D Voriconazole Preferred response: C Rationale Fluconazole has no activity against Aspergillus Voriconazole is available in both parenteral and enteral formulations and remains the drug of choice for invasive aspergillosis Amphotericin and liposomal amphotericin, both FDA approved for Aspergillus infection, are excellent alternative therapies Amphotericin has numerous side effects, but the liposomal caspofungin—an echinocandin, although not recommended as first-line therapy—is FDA approved as salvage treatment for invasive aspergillosis, and there is some clinical data suggesting benefit when used in combination with voriconazole as part of the initial treatment of invasive aspergillosis Chapter 108: Life-Threatening Viral Diseases and Their Treatment A previously healthy 12-year-old child presents with fever and confusion after having a seizure A computed tomography (CT) scan of the head is normal Cerebrospinal fluid (CSF) studies revealed white blood cells, 100 with 80% lymphocytes and 20 % neutrophils; glucose, 40 mg/dL; protein, 85 mg/dL Bacterial culture and viral polymerase chain reaction (PCR) studies are pending This child should be empirically started on which of the following? A Meropenem and acyclovir B Vancomycin C Vancomycin and ceftriaxone D Vancomycin, ceftriaxone, and acyclovir Preferred response: D Rationale While this child could have bacterial meningitis, these CSF findings are most consistent with viral meningitis Given the high potential for morbidity and mortality with herpes simplex virus (HSV) encephalitis, acyclovir should be added while awaiting viral PCR results from the CSF Vancomycin and ceftriaxone are standard antibiotics for empiric treatment of bacterial meningitis in older children and adults Meropenem is unnecessary in a previously healthy adolescent 2 An 8-year-old child with a history of asthma presents with a 3-day history of fever, myalgias, vomiting, and increased work of breathing Chest radiograph reveals evidence of pneumonia He requires PICU admission due to the need for significant respiratory support Nasopharyngeal sample for respiratory viral PCR is positive for influenza A Which of the following is the preferred antimicrobial treatment for this child? A Acyclovir B Amantadine C Peramivir D Vancomycin E Trimethoprim/sulfamethoxazole Preferred response: C Rationale Intravenous peramivir is indicated as one dose for severe influenza A infection Oseltamivir would be an option as well if enteral therapy were acceptable Influenza exhibits widespread resistance to amantadine Antibiotics would not help with this child’s viral infection Acyclovir does not have activity against influenza virus A previously healthy 9-year-old female has a history of fever and has had symptoms of an upper respiratory tract infection for days On presentation she complains of shortness of breath, abdominal pain, and emesis Physical examination reveals a tired-appearing child with tachycardia and tachypnea She has nasal congestion, bilateral fine crackles on lung exam, and a gallop rhythm and ejection systolic murmur on cardiac exam Her abdominal exam is normal Which of the following is not a useful modality to support a diagnosis of acute myocarditis? A Chest radiograph (CXR) B Computed tomography (CT) of the chest C Echocardiogram D Electrocardiogram (ECG) Preferred response: B Rationale There is a wide spectrum in the clinical manifestations of myocarditis in children Findings of congestive heart failure are the most common feature CXR will reveal pulmonary edema and possibly cardiomegaly; ECG may characteristically show ST-T wave changes and dysrhythmias MRI and echocardiogram are used to demonstrate decreased contractility, ischemic changes, and pericarditis Chest CT scan is generally not used in the diagnosis of myocarditis ... hematocrit Preferred response: C Rationale This boy most likely has macrophage activation syndrome, a complication of his systemic onset juvenile idiopathic arthritis, possibly precipitated by... thick, yellow-brown in color, and contains numerous polymorphonuclear cells and gram-positive cocci in clusters Which of the following would be an inappropriate antimicrobial to initiate at this... encoding the protein adenosine deaminase 2) leads to deficiency of adenosine deaminase (DADA2) This syndrome is one of the monogenic autoinflammatory syndromes which presents in early childhood