Pediatric Fever with Rash: Comprehensive Diagnostic Guide

1. Measles (Rubeola)
Category: Viral Exanthem
Key Features:
  • High fever (up to 40.5°C)
  • 3 C's: Cough, Coryza, Conjunctivitis
  • Koplik's spots (pathognomonic)
  • Maculopapular rash: Face → trunk → extremities
Diagnostic Points:
  • IgM antibodies
  • RT-PCR from nasopharyngeal swab
  • Viral culture
  • Travel/exposure history crucial
2. Rubella (German Measles)
Category: Viral Exanthem
Key Features:
  • Low-grade fever
  • Lymphadenopathy (postauricular, occipital)
  • Pink maculopapular rash: Face → trunk → extremities
  • Milder than measles
Diagnostic Points:
  • Rubella-specific IgM
  • Rising IgG titers
  • PCR from nasopharyngeal swab
  • Important in pregnant contacts
3. Roseola Infantum (HHV-6)
Category: Viral Exanthem
Key Features:
  • High fever for 3-5 days
  • Rash appears as fever resolves
  • Rose-pink macular rash
  • Typically affects 6-24 months old
Diagnostic Points:
  • Clinical diagnosis
  • PCR for HHV-6 if needed
  • Characteristic fever pattern
  • Rash timing diagnostic
4. Varicella (Chickenpox)
Category: Viral Exanthem
Key Features:
  • Moderate fever
  • "Dew drops on rose petals" appearance
  • Pruritic vesicular rash in different stages
  • Centripetal distribution
Diagnostic Points:
  • Clinical diagnosis usually sufficient
  • Tzanck smear
  • PCR from vesicular fluid
  • VZV IgM/IgG
5. Hand, Foot, and Mouth Disease
Category: Viral Exanthem
Key Features:
  • Low-grade fever
  • Vesicular lesions on palms, soles
  • Oral ulcers
  • Usually caused by Coxsackievirus A16
Diagnostic Points:
  • Clinical diagnosis
  • PCR from vesicular fluid
  • Viral culture
  • Distribution pattern diagnostic
6. Erythema Infectiosum (Fifth Disease)
Category: Viral Exanthem
Key Features:
  • Low-grade or no fever
  • "Slapped cheek" appearance
  • Lacy reticular rash on extremities
  • Caused by Parvovirus B19
Diagnostic Points:
  • Clinical appearance often diagnostic
  • Parvovirus B19 IgM
  • PCR for Parvovirus B19
  • Important in pregnant contacts
7. Zika Virus Infection
Category: Viral Exanthem
Key Features:
  • Mild fever
  • Maculopapular rash
  • Conjunctivitis
  • Joint pain
Diagnostic Points:
  • RT-PCR in acute phase
  • Zika virus IgM
  • Travel history crucial
  • Consider in endemic areas
8. Dengue Fever
Category: Viral Exanthem
Key Features:
  • High fever
  • Biphasic fever pattern
  • Petechial rash in recovery phase
  • Severe muscle/joint pain
Diagnostic Points:
  • NS1 antigen test
  • Dengue IgM/IgG
  • Complete blood count
  • Monitor for warning signs
9. Chikungunya
Category: Viral Exanthem
Key Features:
  • High fever
  • Maculopapular rash
  • Severe arthralgia
  • Headache
Diagnostic Points:
  • RT-PCR in early phase
  • Chikungunya IgM
  • Travel history
  • Distinguished from dengue
10. Infectious Mononucleosis
Category: Viral Infection
Key Features:
  • Fever
  • Maculopapular rash (especially with ampicillin)
  • Lymphadenopathy
  • Pharyngitis
Diagnostic Points:
  • Monospot test
  • EBV-specific antibodies
  • Complete blood count
  • Liver function tests
11. Scarlet Fever
Category: Bacterial Infection
Key Features:
  • High fever
  • "Sandpaper" rash
  • Strawberry tongue
  • Pastia's lines in skin folds
  • Associated with Group A Streptococcus
Diagnostic Points:
  • Rapid strep test
  • Throat culture
  • ASO titers
  • Monitor for complications
12. Meningococcemia
Category: Bacterial Infection - Emergency
Key Features:
  • High fever with rapid onset
  • Petechial/purpuric rash
  • Rapid progression
  • Signs of meningitis
Diagnostic Points:
  • Blood culture
  • CSF analysis
  • PCR for N. meningitidis
  • Immediate antibiotic treatment
13. Toxic Shock Syndrome
Category: Bacterial Toxin-Mediated
Key Features:
  • High fever
  • Diffuse erythroderma
  • Hypotension
  • Multisystem involvement
Diagnostic Points:
  • Blood cultures
  • Complete metabolic panel
  • Coagulation studies
  • Source identification crucial
14. Staphylococcal Scalded Skin Syndrome
Category: Bacterial Toxin-Mediated
Key Features:
  • Fever
  • Tender erythema
  • Superficial desquamation
  • Nikolsky sign positive
Diagnostic Points:
  • Clinical diagnosis
  • Skin biopsy if unclear
  • Blood culture
  • Monitor fluid status
15. Rocky Mountain Spotted Fever
Category: Rickettsial Disease
Key Features:
  • High fever
  • Maculopapular → petechial rash
  • Wrists/ankles → central spread
  • Headache, myalgia
Diagnostic Points:
  • Serologic testing
  • PCR from skin biopsy
  • Tick exposure history
  • Early treatment crucial
16. Lyme Disease
Category: Bacterial Infection
Key Features:
  • Low-grade fever
  • Erythema migrans
  • Bulls-eye appearance
  • Multiple lesions in disseminated disease
Diagnostic Points:
  • Two-tier testing
  • ELISA followed by Western blot
  • Tick exposure history
  • Geographic consideration
17. Mycoplasma Infection
Category: Bacterial Infection
Key Features:
  • Fever
  • Stevens-Johnson-like rash
  • Pneumonia
  • Mucositis
Diagnostic Points:
  • PCR from throat swab
  • Serology (IgM, IgG)
  • Chest X-ray
  • Cold agglutinins
18. Rat-Bite Fever
Category: Bacterial Infection
Key Features:
  • Relapsing fever
  • Maculopapular/petechial rash
  • Arthralgia
  • Exposure history
Diagnostic Points:
  • Blood culture
  • Gram stain
  • Animal exposure history
  • Consider in pet rat owners
19. Typhoid Fever
Category: Bacterial Infection
Key Features:
  • Step-ladder fever pattern
  • Rose spots on abdomen
  • Relative bradycardia
  • Hepatosplenomegaly
Diagnostic Points:
  • Blood culture
  • Widal test
  • Stool culture
  • Travel history important
20. Cat Scratch Disease
Category: Bacterial Infection
Key Features:
  • Low-grade fever
  • Primary inoculation lesion
  • Regional lymphadenopathy
  • Cat exposure history
Diagnostic Points:
  • Bartonella henselae serology
  • PCR from lymph node
  • Lymph node biopsy
  • Cat exposure history
21. Ehrlichiosis
Category: Rickettsial Disease
Key Features:
  • High fever
  • Maculopapular rash
  • Severe myalgia
  • Tick exposure
Diagnostic Points:
  • PCR testing
  • Peripheral blood smear
  • Serologic testing
  • Monitor blood counts
22. Gonococcal Disease
Category: Bacterial Infection
Key Features:
  • Fever
  • Pustular skin lesions
  • Arthritis
  • Adolescent consideration
Diagnostic Points:
  • Culture from lesions
  • NAAT testing
  • Joint fluid analysis
  • Screen for other STIs
23. Secondary Syphilis
Category: Bacterial Infection
Key Features:
  • Low-grade fever
  • Copper-colored rash
  • Palms/soles involvement
  • Lymphadenopathy
Diagnostic Points:
  • RPR/VDRL
  • Treponemal tests
  • Dark field microscopy
  • CSF analysis if indicated
24. Relapsing Fever
Category: Bacterial Infection
Key Features:
  • Recurring fever episodes
  • Petechial rash
  • Jaundice
  • Tick/louse exposure
Diagnostic Points:
  • Blood smear during fever
  • PCR testing
  • Exposure history
  • Geographic consideration
25. Leptospirosis
Category: Bacterial Zoonosis
Key Features:
  • Biphasic fever
  • Conjunctival suffusion
  • Petechial rash
  • Exposure to contaminated water
Diagnostic Points:
  • MAT (gold standard)
  • ELISA IgM
  • PCR in early phase
  • Liver/kidney function tests
26. Kawasaki Disease
Category: Vasculitis
Key Features:
  • High fever ≥5 days
  • Polymorphous rash
  • Conjunctival injection
  • Oral changes
  • Cervical lymphadenopathy
  • Extremity changes
Diagnostic Points:
  • Clinical criteria based diagnosis
  • Elevated inflammatory markers
  • Echocardiogram mandatory
  • Monitor for coronary aneurysms
27. Systemic Juvenile Idiopathic Arthritis
Category: Autoimmune
Key Features:
  • High spiking fever
  • Salmon-pink evanescent rash
  • Arthritis
  • Lymphadenopathy
Diagnostic Points:
  • Ferritin levels
  • Complete blood count
  • Joint imaging
  • Exclude infections
28. Henoch-Schönlein Purpura
Category: Vasculitis
Key Features:
  • Low-grade fever
  • Palpable purpura
  • Abdominal pain
  • Arthralgia
Diagnostic Points:
  • Clinical diagnosis
  • Skin biopsy if unclear
  • Urinalysis monitoring
  • Renal function tests
29. Stevens-Johnson Syndrome
Category: Severe Drug Reaction
Key Features:
  • High fever
  • Severe mucocutaneous involvement
  • Target lesions
  • Often drug-triggered
Diagnostic Points:
  • Clinical presentation
  • Skin biopsy
  • Drug history crucial
  • Monitor fluid/electrolytes
30. DRESS Syndrome
Category: Severe Drug Reaction
Key Features:
  • High fever
  • Extensive rash
  • Eosinophilia
  • Internal organ involvement
Diagnostic Points:
  • RegiSCAR criteria
  • Complete blood count
  • Liver function tests
  • Drug history essential
31. Serum Sickness
Category: Immune Complex Disease
Key Features:
  • Fever
  • Urticarial rash
  • Joint pain
  • Following medication/antiserum
Diagnostic Points:
  • Clinical diagnosis
  • C3/C4 levels
  • Drug/antiserum history
  • Inflammatory markers
32. Acute Rheumatic Fever
Category: Post-Streptococcal
Key Features:
  • Fever
  • Erythema marginatum
  • Migratory arthritis
  • Carditis
Diagnostic Points:
  • Jones criteria
  • ASO titers
  • ECG/Echocardiogram
  • Prior strep history
33. Sweet Syndrome
Category: Neutrophilic Dermatosis
Key Features:
  • Fever
  • Tender erythematous plaques
  • Neutrophilia
  • Associated conditions
Diagnostic Points:
  • Skin biopsy
  • Complete blood count
  • Search for underlying cause
  • Inflammatory markers
34. PFAPA Syndrome
Category: Periodic Fever Syndrome
Key Features:
  • Periodic fever
  • Aphthous stomatitis
  • Pharyngitis
  • Cervical adenitis
Diagnostic Points:
  • Clinical diagnosis
  • Pattern recognition
  • Exclusion of other causes
  • Response to steroids
35. CAPS (Cryopyrin-Associated Periodic Syndromes)
Category: Autoinflammatory
Key Features:
  • Recurrent fever
  • Urticaria-like rash
  • Cold-triggered symptoms
  • Joint/CNS involvement
Diagnostic Points:
  • Genetic testing (NLRP3)
  • Family history
  • Clinical features
  • Response to IL-1 blockers
36. TRAPS (TNF Receptor Associated Periodic Syndrome)
Category: Autoinflammatory
Key Features:
  • Prolonged fever episodes
  • Migratory rash
  • Periorbital edema
  • Severe myalgia
Diagnostic Points:
  • TNFRSF1A gene testing
  • Inflammatory markers
  • Family history
  • Response to biologics
37. MIS-C (Multisystem Inflammatory Syndrome in Children)
Category: Post-Infectious Inflammatory
Key Features:
  • High fever
  • Polymorphic rash
  • Multi-organ dysfunction
  • Post-COVID association
Diagnostic Points:
  • CDC/WHO criteria
  • SARS-CoV-2 serology
  • Inflammatory markers
  • Cardiac evaluation
38. Primary Hemophagocytic Lymphohistiocytosis
Category: Immune Dysregulation
Key Features:
  • Persistent fever
  • Variable rash
  • Hepatosplenomegaly
  • Cytopenias
Diagnostic Points:
  • HLH-2004 criteria
  • Ferritin levels
  • Genetic testing
  • Bone marrow examination
40. Langerhans Cell Histiocytosis
Category: Histiocytic Disorder
Key Features:
  • Fever
  • Seborrheic-like rash
  • Bone lesions
  • Multi-system involvement
Diagnostic Points:
  • Skin/bone biopsy
  • CD1a/S100 staining
  • Skeletal survey
  • PET-CT if indicated
41. Acrodynia (Mercury Poisoning)
Category: Heavy Metal Toxicity
Key Features:
  • Low-grade fever
  • Pink, painful hands/feet
  • Photosensitivity
  • Hypertension
Diagnostic Points:
  • Blood/urine mercury levels
  • Environmental history
  • 24-hour urine collection
  • Neurological evaluation
42. Acrodermatitis Enteropathica
Category: Nutritional Deficiency
Key Features:
  • Fever
  • Periorificial dermatitis
  • Alopecia
  • Diarrhea
Diagnostic Points:
  • Zinc levels
  • Alkaline phosphatase
  • Skin biopsy
  • Response to zinc
43. Acute Generalized Exanthematous Pustulosis
Category: Drug Reaction
Key Features:
  • High fever
  • Sterile pustules
  • Rapid onset
  • Drug association
Diagnostic Points:
  • EuroSCAR criteria
  • Skin biopsy
  • Drug history
  • Differentiate from pustular psoriasis
44. Erythema Multiforme
Category: Immune-Mediated
Key Features:
  • Fever
  • Target lesions
  • Post-infectious/drug
  • Mucosal involvement
Diagnostic Points:
  • Clinical diagnosis
  • HSV PCR if indicated
  • Drug history
  • Skin biopsy if atypical
45. Familial Mediterranean Fever
Category: Autoinflammatory
Key Features:
  • Recurrent fever
  • Erysipelas-like erythema
  • Serositis
  • Ethnic predisposition
Diagnostic Points:
  • MEFV gene testing
  • Acute phase reactants
  • Family history
  • Colchicine response
46. Neonatal Lupus
Category: Autoimmune
Key Features:
  • Fever
  • Annular lesions
  • Heart block
  • Maternal antibodies
Diagnostic Points:
  • Anti-Ro/La antibodies
  • ECG/echocardiogram
  • Maternal history
  • Skin biopsy
47. Hyperimmunoglobulin D Syndrome
Category: Autoinflammatory
Key Features:
  • Recurrent fever
  • Cervical lymphadenopathy
  • Maculopapular rash
  • Early onset
Diagnostic Points:
  • MVK gene mutation
  • IgD levels
  • Mevalonic acid testing
  • Genetic counseling
48. CANDLE Syndrome
Category: Autoinflammatory
Key Features:
  • Recurrent fever
  • Violaceous eyelid edema
  • Lipodystrophy
  • Growth delay
Diagnostic Points:
  • PSMB8 gene testing
  • Interferon signature
  • Skin biopsy
  • Metabolic evaluation
49. Schnitzler Syndrome
Category: Autoinflammatory
Key Features:
  • Chronic fever
  • Urticarial rash
  • Bone pain
  • Monoclonal gammopathy
Diagnostic Points:
  • Strasbourg criteria
  • Serum protein electrophoresis
  • Bone scan
  • IL-1 blockade response
50. Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)
Category: Severe Drug Reaction
Key Features:
  • High fever
  • Extensive rash
  • Facial edema
  • Internal organ involvement
Diagnostic Points:
  • RegiSCAR criteria
  • Eosinophil count
  • Liver function tests
  • HHV-6 reactivation
51. Papular-Purpuric Gloves and Socks Syndrome
Category: Viral Infection
Key Features:
  • Fever
  • Edema and erythema of hands/feet
  • Petechial purpura
  • Parvovirus B19 association
Diagnostic Points:
  • Clinical diagnosis
  • Parvovirus B19 serology
  • Complete blood count
  • Self-limiting course
52. Rowell Syndrome
Category: Autoimmune
Key Features:
  • Fever
  • Lupus-like lesions
  • Erythema multiforme-like lesions
  • Chilblain-like lesions
Diagnostic Points:
  • ANA testing
  • Anti-Ro/La antibodies
  • Rheumatoid factor
  • Skin biopsy
53. Gianotti-Crosti Syndrome
Category: Post-Viral
Key Features:
  • Low-grade fever
  • Symmetric acral papules
  • Lymphadenopathy
  • Associated with various viruses
Diagnostic Points:
  • Clinical diagnosis
  • Viral studies if indicated
  • Liver function tests
  • Self-limiting course
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