Diagnostic Dilemmas in Pediatric Infectious Disease: a Case-Based Discussion

Educational Objectives

The goal of this program is to improve management of pediatric infectious diseases. After hearing and assimilating this program, the clinician will be better able to:

1. Differentiate the clinical features of Kawasaki disease from those of multisystem inflammatory syndrome in children.
2. Administer antibiotic treatment in a timely fashion to patients with rickettsial disease.
3. Select the appropriate diagnostic tests for tuberculosis in children.

Summary

Fever and Rash

Case report 1: a 3 yr old boy has a 5-day history of fever ≤102°F; acetaminophen lowers the fever but it returns after 2 hr; the patient is irritable and does not want to be held or touched; maculopapular rash is concentrated on the chest, but is present on the face and extremities; the patient developed a rash on his trunk, arms and legs on the second day of fever; swollen hands and red eyes developed on the third of fever; the patient has no sick contacts and no travel history; exposure to new foods, animals, bug bites, fresh water is negative; the patient has no past medical history (and family history is non-contributory) and growth curves are normal; appetite is normal; the patient is of Japanese ethnicity, lives at home with his parents, and is the only child; physical examination — the patient is tired-appearing, irritable, has bilateral conjunctivitis, cracked lips, and red tongue; a 2 cm mobile and nontender lymph node was observed along the cervical chain; fever reduced after administration of antipyretics, but the patient remained tachycardic; the patient has non-labored respiration and the abdomen is soft and nontender and nondistended; the patient’s hands and feet are swollen

Differential diagnosis: Kawasaki disease, multisystem inflammatory syndrome in children (MIS-C), rickettsial disease, Streptococcus disease, measles, and adenovirus

Diagnosis and treatment: the patient was diagnosed with Kawasaki disease (KD); worse outcomes have been observed in patients with Kawasaki disease if treatment (eg, intravenous immunoglobulins [IVIG]) is delayed for ≥10 days; steroids may be administered with IVIG

Management of fever: echocardiography should be performed on patients with fever to detect coronary artery aneurysm; patients with fever for 4 to 5 days are not treated as emergency cases; symptoms may be observed and assessed before treatment; clinicians should be cautious when treating patients <2 yr of age presenting with tachycardia and fever that is nonresponsive to treatment; KD may cause aneurysms, which are difficult to bypass in infants because of the lack of veins for grafting

Case report 2: a 3 yr old boy has a 5-day history of fever ≤102°F; acetaminophen lowers the fever but it returns after 2 hr; the patient is irritable and does not want to be held or touched; the patient developed a rash on his trunk, arms and legs on the second day of fever; swollen hands and red eyes are present; abdominal pain is significant; stools are watery; the patient's family had upper respiratory infections (URI) 3 wk previous; patient has no travel history; exposure to new foods, animals, bug bites and fresh water is negative; family history is non-contributory; the patient’s ethnicity is White, he lives at home and was previously healthy; the patient's family refused vaccination for COVID-19

Epidemiology: patients who did not have a URI may later develop asymptomatic COVID-19 infection and eventually MIS-C; the risk of White children between toddler age and young school age in North American developing KD is 20 per 100,000 persons; the risk for Japanese children of the same age is 200 per 100,000 persons

Physical examination: the patient is irritable and appears tired; bilateral conjunctivitis, cracked lips, red tongue are observed; lymph nodes are not swollen; the patient’s respirations are nonlabored when not crying; the abdomen is soft and nontender and nondistended; the patient’s hands and feet are swollen; maculopapular rash is present

Differential diagnosis: KD, MIS-C, rickettsial disease, Streptococcus disease, measles, and adenovirus; the diagnosis is MIS-C

MIS-C: patients with MIS-C should be referred for evaluation to the emergency department; patient was referred for echocardiography and administered IVIG and steroids

Case report 3: a 14 yr old boy has a 5 day history of fever; fever reduces temporarily with acetaminophen; the patient has a headache; a rash developed on the trunk, arms and legs on the second day of fever, and red eyes on the third day of fever; the patient describes itchy bumps on ankles; no skin contacts; the patient recently spent time hiking in Japan; exposure to animals or new food is negative; the patient lives at home with parents, who were born in Japan; physical examination — patient is irritable and tired appearing; bilateral conjunctivitis is present; patient is tachycardic; hands and feet are swollen; raised bug bite marks and excoriated scabs on ankles are present; the patient was diagnosed with scrub typhus

Rickettsial disease: a rickettsial laboratory panel may be ordered for suspected cases of rocky mountain spotted fever or murine typhus; treated with doxycycline; murine typhus is caused by Rickettsia typhi and is endemic in Southern California (transmitted by fleas); children with murine typhus often do not require treatment, but treatment may shorten the course of illness; scrub typhus may lead to encephalitis and cardiac issues; urgent treatment with doxycycline is required for patients with scrub typhus and rocky mountain spotted fever; lack of direct contact with animals should not preclude considering rickettsial disease

Tuberculosis

Case report 4: a 10 mo old boy presents with low grade fever (<101°F) that began 2 to 3 days previous, and persistent cough that began 10 days previous; the patient is losing weight and has poor appetite and energy levels; the patient lived with his grandfather, who recently died of lung cancer; exposure to new foods, animals, bug bites, fresh water, and well water is negative; the patient has no past medical history and family history is noncontributory; the patient is white, lives at home and is the only child; immunizations are reported to be up to date

Diagnosis: differential diagnosis — community acquired pneumonia, bronchiolitis, tuberculosis (TB), influenza, and pertussis; chest x-ray was normal and showed diffused interstitial markings; patient was diagnosed with TB

Diagnostic tests: chest x-ray revealed a miliary pattern, which is often seen in children <5 yr of age with TB; patients are at high-risk; patients may be tested for TB with, eg, purified protein derivative test (PPD), interferon-γ release assays (IGRAs)(T-SPOT, QuantiFERON-TB Gold); children have different sensitivities for diagnostic tests at different ages; IGRAs are appropriate for children >5 yr of age, except in cases of immune issues; the PPD test is appropriate for children <2 yr of age PPD; the white blood cell profile of children in this age range does not generate an interferon response that is able to be detected; use of both tests is recommended for children from 2 to 5 yr of age; IGRAs are specific for tuberculosis, but PPD tests results may be positive if the patient has a non-tuberculosis mycobacteria infection; the Bacillus Calmette-Guerin (BCG) vaccine may produce a false positive result with a PPD test; BCG vaccine status should not be used to make a definitive diagnosis of tuberculosis

Treatment: the RIPE (rifampin, isoniazid, pyrazinamide, and ethambutol) regimen; RIPE therapy may initiated in children <5 yr of age before results from bacterial cultures are complete; patients at high risk for TB are admitted and gastric or sputum aspirates are used for testing; children >10 yr of age normally are able to produce sputum from coughing; RIPE therapy is recommended to be continued in children <5 yr of age until ≥3 samples have no growth of acid-fast bacillus (AFB) for 6 wk, the AFB stain test has no growth, and ≥2 samples tested by polymerase chain reaction are negative; stain and culture results must be separately considered; a positive stain does not imply a positive culture; a patient with a negative stain may have a positive culture; hemoptysis indicates, eg, epistaxis, a bleeding ulcer, lung lesions; differentiate between lesions in the larynx or lesions in the esophagus may be difficult on x-ray; computed tomography may be indicated; miliary pattern TB does not cause hemoptysis in children; hemoptysis and the presence of cavitary lesions in the upper lobes of the lungs in teenagers and young adults strongly indicates TB

Take-home points: Kawasaki disease, MIS-C and Rickettsial disease present with similar findings (eg, fever, rash); exposures to insects and arachnids and travel history must be determined; ethnicity may contribute to differential diagnosis and clinical suspicions; key laboratory findings include peripheral white blood cells, lymphocytes and sodium levels; patients with KD may have leukocytosis and thrombocytosis; patients do not have low sodium levels; patients with MIS-C may have thrombocytopenia, leukopenia and low sodium levels; patients with fever and low sodium levels with recent travel to a region that is endemic for rickettsial disease should be immediately treated with doxycycline; TB — obtaining history of exposure is essential for patients with fever and cough; patients <5 yr of age with TB present in the differential diagnosis should be referred to the emergency department for testing and treatment

Readings

Kang HK, Jeong BH, Lee H, et al. Clinical significance of smear positivity for acid-fast bacilli after ≥5 months of treatment in patients with drug-susceptible pulmonary tuberculosis. Medicine (Baltimore). 2016; 95(31):e4540. doi:10.1097/MD.0000000000004540; Kay AW, Islam SM, Wendorf K, Westenhouse J, Barry PM. Interferon-γ release assay performance for tuberculosis in childhood. Pediatrics. 2018;141(6):e20173918. doi:10.1542/peds.2017-3918; Peter JV, Sudarsan TI, Prakash JA, et al. Severe scrub typhus infection: clinical features, diagnostic challenges and management. World J Crit Care Med. 2015; 4(3):244-250. Published 2015 Aug 4. doi:10.5492/wjccm.v4.i3.244; Sotgiu G, Centis R, D'ambrosio L, et al. Tuberculosis treatment and drug regimens. Cold Spring Harb Perspect Med. 2015; 5(5):a017822. Published 2015 Jan 8. doi:10.1101/cshperspect.a017822; Sundel RP, Petty RE. Kawasaki disease. Textbook of Pediatric Rheumatology. 2011; 505-520. doi:10.1016/B978-1-4160-6581-4.10033-0; Zhang QY, Xu BW, Du JB. Similarities and differences between multiple inflammatory syndrome in children associated with COVID-19 and Kawasaki disease: clinical presentations, diagnosis, and treatment. World J Pediatr. 2021;17(4):335-340. doi:10.1007/s12519-021-00435-y.

Disclosures

For this program, members of the faculty and planning committee reported nothing relevant to disclose.

Acknowledgements

Dr. Smit was recorded at Pediatrics in the Islands: Clinical Pearls 2022, held June 25 to July 1, 2022, and presented by the American Academy of Pediatrics, California Chapter 2, and Children's Hospital Los Angeles Medical Group. For more information about upcoming CME activities from this presenter, please visit https://www.chla.org/cme-conferences. Audio Digest thanks the speakers and presenters for their cooperation in the production of this program.

CME/CE INFO

Accreditation:

The Audio- Digest Foundation is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

The Audio- Digest Foundation designates this enduring material for a maximum of 1.75 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Audio Digest Foundation is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center's (ANCC's) Commission on Accreditation. Audio Digest Foundation designates this activity for 1.75 CE contact hours.

Lecture ID:

PD684101

Expiration:

This CME course qualifies for AMA PRA Category 1 Credits™ for 3 years from the date of publication.

Instructions:

To earn CME/CE credit for this course, you must complete all the following components in the order recommended: (1) Review introductory course content, including Educational Objectives and Faculty/Planner Disclosures; (2) Listen to the audio program and review accompanying learning materials; (3) Complete posttest (only after completing Step 2) and earn a passing score of at least 80%. Taking the course Pretest and completing the Evaluation Survey are strongly recommended (but not mandatory) components of completing this CME/CE course.

Estimated time to complete this CME/CE course:

Approximately 2x the length of the recorded lecture to account for time spent studying accompanying learning materials and completing tests.