Pediatrics
Certification Exam Review Online

Educational Objective:

Recognize the signs and symptoms of Wiskott-Aldrich syndrome.

Key Point:

Wiskott-Aldrich syndrome presents in males with eczema, thrombocytopenia, and recurrent infections. This X-linked recessive disease causes a defect in humoral immunity, thereby predisposing persons with the disease to infections with encapsulated organisms.

Explanation:

The most likely diagnosis is Wiskott-Aldrich syndrome, which is an X-linked recessive disorder that results in eczema, thrombocytopenia, and increased susceptibility to infections in affected infant males. The genetic defect causes an impaired humoral immune response, thereby increasing the patient's risk for infection from encapsulated organisms such as Streptococcus pneumoniae. During thein the first year of life,patients will present with recurrent infections, including otitis media, pneumonia, and meningitis. They also have an impaired response to vaccines for encapsulated organisms. As infants, patients with thrombocytopenia may have prolonged bleeding from circumcision or bloody diarrhea. The disease is usually fatal by adolescence, but it can be cured via bone marrow transplant.

SCID is a group of disorders that results from various genetic mutations (including adenosine deaminase deficiency) that result in the absence of T-cell mediated immunity. Those with SCID have underdeveloped or absent lymphoid tissues. Infants present in the first few months of life with failure to thrive and recurrent viral and bacterial infections. SCID may be inherited as an X-linked or autosomal recessive adenosine deaminase deficiency.

Ataxia telangiectasia results from a mutation on chromosome 11 that results in progressive cerebellar ataxia, oculocutaneous telangiectasias, and humoral and cellular immunodeficiency--most commonly, the absence of immunoglobulin A. Affected individuals also have recurrent sinopulmonary infections.

References:

Buckley R. Primary combined antibody and cellular immunodeficiencies. In: Kliegman RM, et al, eds. Nelson Textbook of Pediatrics. 20th ed., 2016:1022-1032.

MacGinnitie A, et al. Allergy and immunology. In: Zitelli BJ, et al, eds. Zitelli and Davis' Atlas of Pediatric Physical Diagnosis. 6th ed., 2012:111-144.

Educational Objective:

Identify target levels for factor replacement.

Key Point:

The target level of factor activity after replacement for a serious injury is 100%.

Explanation:

In a patient with hemophilia who has a life-threatening injury or major hemorrhage, factors should be replaced to raise the factor level to 100% activity. For mild to moderate bleeding, factors levels should be replaced to aim for a level between 35% and 50%.

Hemophilia is a coagulopathy caused by factor VIII deficiency (hemophilia A) or factor IX deficiency (hemophilia B). These 2 types are X-linked recessive disorders, and patients present with prolonged partial thromboplastin time.

Hemophilia A and B are the most common severe inherited bleeding disorders. Hemophilia A is due to a deficiency of factor VIII and hemophilia B to a deficiency of factor IX. The inadequate formation of thrombin leads to failure to form a tight fibrin clot. Partial thromboplastin time is prolonged.

Children with hemophilia may hemorrhage with circumcision or during venipuncture, or they may develop joint or intracranial bleeding with minor injuries. The condition is diagnosed by measuring factor VIII and IX levels. Treatment for moderate to severe bleeding is with factor supplementation.

Reference:

Scott JP, Flood VH. Hereditary clotting factor deficiencies (bleeding disorders). In: Kliegman RM, et al, eds. Nelson Textbook of Pediatrics. 20th ed., 2016:2384-2389.

Educational Objective:

Describe the rash associated with idiopathic thrombocytopenic purpura.

Key Point:

Children with ITP usually present acutely with petechiae, purpura, and a low platelet count.

Explanation:

ITP is an autoimmune disease occurring in previously healthy children with a history of a recent viral infection. This child presented with an acute onset of purpura and petechiae and has a low platelet count.

Manifestations of the disease may include epistaxis, menorrhagia, or intracranial hemorrhage. No therapy is indicated for patients with mild symptoms, but first-line therapy is intravenous immunoglobulin if significant bleeding is present or the platelet count is below 20,000/μL. Intravenous anti-D therapy may be used for Rh-positive patients. Splenectomy is reserved for second-line therapy in resistant or recurrent cases. The prognosis is worse in older children.

TTP presents with fever, microangiopathic hemolytic anemia, thrombocytopenia, abnormal renal function, and central nervous system changes. It can appear clinically similar to HUS but is rare in children.

HSP is a vasculitis of the skin, gastrointestinal tract, and kidneys. The child may have a purpuric rash on his or her legs and buttocks. Children with HSP may have a normal or elevated platelet count.

A child with ALL may appear ill, and he or she could have pancytopenia in most cell lines as well as an elevated white blood cell count.

Reference:

Scott JP. Platelet and blood vessel disorders. In: Kliegman RM, et al, eds. Nelson Textbook of Pediatrics. 20th ed., 2016:2400-2407.

This represents a type II open fracture. Type II and type III open fractures require antibiotic coverage with a first-generation cephalosporin plus additional gram-negative coverage for skin flora of the groin with an aminoglycoside.

Monitoring of peak vancomycin concentrations is not recommended. The most accurate and practical measurement to guide dosing is a serum trough obtained once vancomycin has reached steady state concentrations, prior to the fourth dose.

Optimal trough concentrations in pediatric patients have not been established. In adults with serious methicillin-resistant Staphylococcus aureus (MRSA) infections, vancomycin trough concentrations of 15-20 micrograms/mL are recommended. The ratio of the area under the curve (AUC) to the minimum inhibitory concentration (MIC) is the best predictor of vancomycin efficacy. One study showed that an AUC/MIC ratio of >400 was associated with better outcomes than were AUC/MIC ratios <400. A serum trough of 15-20 micrograms/mL is needed to achieve an AUC/MIC ratio >400 if the MIC of the organism is <1 in adult studies.

Vancomycin doses of 40 mg/kg/day in children do not consistently reach the target AUC/MIC ratio of 400. Doses of 60 mg/kg/day (or 15 mg/kg every 6 hours) were shown to increase the likelihood of reaching this target, and are recommended for empiric dosing in serious MRSA infections in children. In addition, a loading dose of 20-25 mg/kg was shown to be safe in adults and may be considered in children with serious infections.

References:

Liu et al. Clinical Practice Guidelines by the Infectious Diseases Society of America for the Treatment of Methicillin-Resistant Staphylococcus Aureus Infections in Adults and Children. Clinical Infectious Diseases 2011. 52(3): 285.

2009 Report of the Committee on Infectious Diseases, American Academy of Pediatrics Red Book 27th edition, 2009.

Frymoyer, A et al. Prediction of Vancomycin Pharmacodynamics in Children With Invasive Methicillin-Resistant Staphylococcus aureus Infections: A Monte Carlo Simulation. Clinical Therapeutics 2010; 32(3): 534-541.

Jimenez-Truque, Natalia; Thomsen, Isaac; Saye, Elizabeth; and Creech, Buddy. Should Higher Vancomycin Trough Levels Be Targeted for Invasive Community-Acquired Methicillin-Resistant Staphylococcus Aureus Infections in Children? The Ped Infect Dis Journal April 2010: 29(4); 368-370.