Multisystem Inflammatory Syndrome (MIS-C) — Differential Diagnosis — Clinical Pathway: Emergency, ICU and Inpatient

Differential Diagnosis for patient with possible Multisystem Inflammatory Syndrome in Children (MIS-C)
ED Fever Pathway
Differential Diagnosis	Clinical Features
Bacterial Infections/Sepsis	Patients appear clinically ill Associated with vital sign abnormalities, poor perfusion, and mental status changes Evaluate for focal source, e.g., skin/soft tissue, meningitis, pneumonia Obtain appropriate bacterial cultures See Common Features of Shock in Children See ED Sepsis Pathway for management recommendations
Toxic Shock Syndrome	Signs and symptoms develop rapidly Source of infection may not be clinically evident (e.g.,Staphylococcal TSS); consider menstrual vs non-menstrual etiologies Presentation: Fever/chills Hypotension Diffuse erythrodermic rash Can have multiorgan system involvement, including diarrhea, hepatitis, and acute kidney injury injury
Staph Scalded Skin Syndrome (SSSS)	Common in children under the age of 6 Significant skin pain and erythema of the skin folds Generalized erythema of the skin as the disease progresses Flaccid bullae with erosions at the area of friction Fever, irritability and malaise
Kawasaki Disease	Commonly presents in children under the age of 6 and share many clinical features of MIS-C Fever with notable irritability Rash Non-purulent conjunctival injection Cervical lymphadenopathy Extremity changes including edema See Kawasaki Disease Pathway
Ricketsial Illnesses	More common in spring and summer months (tick-borne illnesses) RMSF: fever, headache, followed by rash (macules &arrowr; petechiae starting on wrists/ankles progressing to trunk, palms and soles involved later; 10-20% never develop rash; lab findings include thrombocytopenia and hyponatremia Ehrlichia/anaplasma: fever, headache, rash; typical lab findings include leukopenia or thrombocytopenia
Viral Infections	Nonspecific presentation of MIS-C may overlap with many viral illnesses Adenovirus Enterovirus (particularly in the summer months) EBV HHV6 in infants/young children
Myocarditis	Clinical signs of cardiogenic shock (cold extremities, diminished pulses/capillary refill, hypotension) Elevated troponin ST changes on EKG Cardiac dysfunction on echo Often associated with arrhythmias
Serum Sickness	Commonly presents following exposure to a drug or therapeutic agent Fever Rash Arthralgias

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The clinical pathways are based upon publicly available medical evidence and/or a consensus of medical practitioners at The Children’s Hospital of Philadelphia (“CHOP”) and are current at the time of publication. These clinical pathways are intended to be a guide for practitioners and may need to be adapted for each specific patient based on the practitioner’s professional judgment, consideration of any unique circumstances, the needs of each patient and their family, and/or the availability of various resources at the health care institution where the patient is located.

Accordingly, these clinical pathways are not intended to constitute medical advice or treatment, or to create a doctor-patient relationship between/among The Children’s Hospital of Philadelphia (“CHOP”), its physicians and the individual patients in question. CHOP does not represent or warrant that the clinical pathways are in every respect accurate or complete, or that one or more of them apply to a particular patient or medical condition. CHOP is not responsible for any errors or omissions in the clinical pathways, or for any outcomes a patient might experience where a clinician consulted one or more such pathways in connection with providing care for that patient.