Differentials
Streptococcus pneumoniae sepsis
SIGNS / SYMPTOMS
Purpura fulminans is more characteristic in meningococcemia than in sepsis caused by other bacterial pathogens.
INVESTIGATIONS
Blood or other body fluid cultures diagnostic.
Staphylococcus aureus sepsis
SIGNS / SYMPTOMS
Purpura fulminans is more characteristic in meningococcemia than in sepsis caused by other bacterial pathogens.
INVESTIGATIONS
Blood or other body fluid cultures diagnostic.
Streptococcus pyogenes sepsis
SIGNS / SYMPTOMS
Purpura fulminans is more characteristic in meningococcemia than in sepsis caused by other bacterial pathogens.
INVESTIGATIONS
Blood or other body fluid cultures diagnostic.
Coronavirus disease 2019 (COVID-19)
SIGNS / SYMPTOMS
Residence in or travel history to an area with local transmission of COVID-19, or close contact with a suspected or confirmed case in the 14 days prior to symptom onset.
May be difficult to distinguish clinically from bacterial pneumonia. In addition to fever, cough, and dyspnea, other common presenting symptoms include sore throat, myalgia, fatigue, and altered sense of taste and/or smell.
Patients with respiratory distress may have tachycardia, tachypnea, or cyanosis accompanying hypoxia.
INVESTIGATIONS
Real-time reverse transcription polymerase chain reaction (RT-PCR): positive for SARS-CoV-2 RNA.
It is not possible to differentiate COVID-19 from other causes of pneumonia on chest imaging.
Streptococcal pharyngitis
SIGNS / SYMPTOMS
Pharyngeal erythema and, frequently, tonsillar exudates and tender cervical adenopathy. Although the onset is abrupt, the infection does not progress rapidly.
INVESTIGATIONS
Throat culture or antigen detection is positive for beta-hemolytic S pyogenes.
Gonococcemia
SIGNS / SYMPTOMS
Typically presents with septic arthritis, tenosynovitis, and tender pustular skin lesions. Infections are most common in women and often begin within a week of the start of a menstrual period. Unlike meningococcemia, disseminated gonococcemia rarely progresses rapidly.
INVESTIGATIONS
Urethral, cervical, rectal, and oropharyngeal cultures, nucleic acid amplification tests, or blood cultures indicate gonococcal infection.
Leptospirosis
SIGNS / SYMPTOMS
The disease course may be bimodal, with fever, meningitis, and a rash, which may be hemorrhagic, developing several days after improvement in initial symptoms. Hepatitis, jaundice, interstitial nephritis, and myocarditis are common in severe Leptospira infections but are rare in meningococcal infections.
INVESTIGATIONS
Serologic testing confirms leptospirosis.
Rocky Mountain spotted fever
SIGNS / SYMPTOMS
Typically progresses more slowly than meningococcemia. The rash of Rocky Mountain spotted fever (RMSF) begins on the distal extremities and spreads proximally.
INVESTIGATIONS
Hyponatremia, hypoalbuminemia, and mild hepatitis are common laboratory abnormalities. Serologic testing confirms RMSF.
Ehrlichiosis
SIGNS / SYMPTOMS
Typically progresses more slowly than meningococcemia. Rash is uncommon, especially in adults.
INVESTIGATIONS
Serologic testing confirms ehrlichiosis. Inclusion bodies (morulae) may be seen in peripheral blood leukocytes.
Anaplasmosis
SIGNS / SYMPTOMS
Typically progresses more slowly than meningococcemia. Rash is uncommon.
INVESTIGATIONS
Serologic testing confirms anaplasmosis. Inclusion bodies (morulae) may be seen in peripheral blood leukocytes.
Infective endocarditis
SIGNS / SYMPTOMS
Bacterial endocarditis infrequently progresses rapidly to septic shock or meningitis, and patients typically have a longer duration of fever prior to presentation. A new or changed heart murmur, septic emboli, immunologic sequelae such as glomerulonephritis, and splenomegaly are common in endocarditis and not observed with meningococcal infections.
INVESTIGATIONS
Echocardiography typically demonstrates a valvular or intracardiac abnormality.
Toxic shock syndrome
SIGNS / SYMPTOMS
Nonpurulent conjunctivitis, pharyngitis, and erythroderma or a scarlatiniform rash that later desquamates are characteristic of toxic shock syndrome (TSS). Gastrointestinal complaints, hepatitis, severe muscle pain, elevated serum creatine kinase (CK), and renal abnormalities are more common in TSS than in meningococcal infections. Focal pyogenic infections may be observed in patients with TSS, particularly those caused by staphylococci.
INVESTIGATIONS
Blood cultures are positive in about half of patients with streptococcal TSS and 5% with staphylococcal TSS.
Enteroviral infection
SIGNS / SYMPTOMS
Rashes are most commonly erythematous and maculopapular but may be petechial. Stomatitis is characteristic of group A Coxsackie viruses.
INVESTIGATIONS
Cerebrospinal fluid (CSF) from patients with enteroviral meningoencephalitis typically reveals mild lymphocytic pleocytosis, mildly elevated or normal glucose, and normal protein concentration. Enterovirus may be isolated from blood, CSF, stool, throat, or urine. Enteroviral nucleic acid may be detected in CSF.
Epstein-Barr virus
SIGNS / SYMPTOMS
Cervical and generalized adenopathy, hepatosplenomegaly, and hepatitis are common. Severe illness is rare.
INVESTIGATIONS
Epstein-Barr virus (EBV) infection is diagnosed serologically. Nucleic acid detection may confirm EBV in immunocompromised patients.
Cytomegalovirus
SIGNS / SYMPTOMS
Beyond the neonatal period, a hemorrhagic rash is unusual. Pharyngitis, cervical adenopathy, and hepatosplenomegaly are common. Severe illness, with pneumonitis, chorioretinitis, enteritis, hepatitis, meningoencephalitis, coagulopathy, and pancytopenia, occurs in neonates and immunocompromised patients.
INVESTIGATIONS
Cytomegalovirus infection is confirmed by serology, viral culture, antigen detection, or nucleic acid amplification.
Human parainfluenza virus
SIGNS / SYMPTOMS
Respiratory symptoms, including pharyngitis, rhinitis, and cough, are prominent. Rash is uncommon, but petechiae may be present.
INVESTIGATIONS
Parainfluenza virus infection may be confirmed by viral culture, antigen detection, or nucleic acid amplification.
Respiratory syncytial virus
SIGNS / SYMPTOMS
There may be an ongoing community outbreak. Respiratory symptoms, including pharyngitis, rhinitis, and cough, are prominent. Rash is uncommon, but petechiae may be present.
INVESTIGATIONS
Respiratory syncytial virus infection may be confirmed by viral culture, antigen detection, or nucleic acid amplification.
Influenza
SIGNS / SYMPTOMS
There may be an ongoing community outbreak. Respiratory symptoms, including pharyngitis, rhinitis, and cough, are prominent. Rash is uncommon, but petechiae may be present.
INVESTIGATIONS
Influenza may be confirmed by viral culture, antigen detection, or nucleic acid amplification.
Dengue/yellow fever
SIGNS / SYMPTOMS
There may be a history of travel to an endemic area 1 to 12 days prior to symptoms. Hepatitis and jaundice are more common in viral hemorrhagic fevers than in meningococcal infections.
INVESTIGATIONS
Serologic testing confirms a viral hemorrhagic fever.
Immune thrombocytopenia
SIGNS / SYMPTOMS
Typically, lack of fever or other signs of infection.
INVESTIGATIONS
Bone marrow aspirates or biopsy, assays for the presence of antiplatelet antibodies or evaluation for other autoimmune disorders, and tests for coagulation factor deficiencies confirm immune thrombocytopenia.
Henoch-Schonlein purpura
SIGNS / SYMPTOMS
Palpable purpuric rash, most commonly on the lower extremities; abdominal pain and vomiting; joint pain; and swelling and edema of the distal extremities, scalp, and scrotum.
INVESTIGATIONS
Hematuria and proteinuria are common. Skin biopsy demonstrates a leukocytoclastic vasculitis.
Thrombotic thrombocytopenic purpura
SIGNS / SYMPTOMS
Fever less common than in meningococcemia.
INVESTIGATIONS
Microangiopathic hemolytic anemia, thrombocytopenia (platelets <50 × 10⁹/L), elevated serum LDH concentration, and hyperbilirubinemia are typical.
Aplastic/myelodysplastic syndromes
SIGNS / SYMPTOMS
Fever less common than in meningococcemia but may be present in patients with secondary infections. Most patients have physical and laboratory findings suggestive of their primary disorder, such as bleeding from mucosal sites and pancytopenia.
INVESTIGATIONS
Typical laboratory findings of bone marrow failure syndromes include pancytopenia and evidence of abnormal hematopoiesis on bone marrow exam.
Bone marrow infiltration by malignancy
SIGNS / SYMPTOMS
Most patients have physical and laboratory findings suggestive of their primary disorder, such as weight loss, splenomegaly, adenopathy, and pancytopenia.
INVESTIGATIONS
Examination of peripheral blood and/or bone marrow confirms malignancy.
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