Fever and Rash¶
Chapter 21 | Part 2 – Cardinal Manifestations & Presentation · Part 2 – Cardinal Manifestations & Presentation · Chapter 21
Key Clinical Points¶
- Koplik's spots (1- to 2-mm white or bluish lesions with erythematous halo on buccal mucosa) are pathognomonic for measles and typically appear during the first 2 days of symptoms.
- Rubella rash spreads from hairline downward and clears as it migrates; in contrast, measles becomes confluent.
- Rocky Mountain spotted fever (RMSF) rash begins on wrists and ankles and spreads centripetally to involve palms and soles later in the disease.
- Secondary syphilis presents as a copper-colored, scaly, and prominent rash on palms and soles; it is never vesicular in adults.
- Nikolsky's sign (epidermis slips off with lateral pressure) is characteristic of Staphylococcal scalded-skin syndrome and Stevens-Johnson syndrome (SJS).
- Erythema marginatum (rheumatic fever) consists of erythematous annular papules and polycyclic plaques occurring in waves over the trunk and proximal extremities.
- DRESS syndrome typically occurs 2-3 days after exposure in previously sensitized individuals, or 2-3 weeks later; it is characterized by eosinophilia and atypical lymphocytes.
- Stevens-Johnson syndrome (SJS) involves 30% of the epidermis.
- Kawasaki disease presents with a strawberry tongue, conjunctivitis, edema of hands/feet, and a rash similar to scarlet fever in children <8 years old.
- MIS-C (Multisystem inflammatory syndrome in children) shares features with Kawasaki disease and occurs 2-6 weeks following acute SARS-CoV-2 infection.
DEFINITION & OVERVIEW¶
• Overview: Rashes reflecting systemic disease are classified based on lesion morphology and distribution. These rashes differ from localized skin eruptions (e.g., cellulitis, impetigo) which may also present with fever.
• Classification of Rash Types: - Centrally distributed maculopapular - Peripheral - Confluent desquamative erythematous - Vesiculobullous - Urticaria-like - Nodular - Purpuric - Ulcerated - With eschars
• Lesion Morphology Definitions: - Macules: Flat lesions defined by an area of changed color (e.g., a blanchable erythema). - Papules: Raised, solid lesions ≤ 5 mm in diameter with a flat, plateau-like surface. - Nodules: Lesions > 5 mm in diameter with a more rounded configuration. - Wheals (urticaria, hives): Papules or plaques that are pale pink and may appear annular; nonvasculitic wheals are transient, lasting < 24 h. - Vesicles: Lesions ≤ 5 mm. - Pustules: Raised lesions containing purulent exudate. - Ulcer: Defect in the skin extending at least into the upper layer of the dermis. - Eschar (tâche noire): Necrotic lesion covered with a black crust. - Palpable purpura: Raised lesion due to inflammation of the vessel wall (vasculitis) with subsequent hemorrhage. - Petechiae: Purpuric lesions ≤ 3 mm in diameter.
EPIDEMIOLOGY¶
• Viral Infections: - Measles: Nonimmune individuals; characterized by Koplik's spots. - Rubella: Nonimmune individuals; avoid in pregnant women due to risk of congenital abnormalities. - Erythema infectiosum (fifth disease): Common in children 3–12 years old; occurs in winter and spring. - Exanthem subitum (roseola): Typically affects children < 3 years old. - Primary HIV infection: Individuals recently infected with HIV. - Infectious mononucleosis: Adolescents, young adults. - Hand-foot-and-mouth disease: Summer and fall; primarily children < 10 years old. - Varicella (chickenpox): Typically affects children; 10% of adults susceptible; common in late winter/spring. - West Nile virus: Mosquito bite; rare blood transfusion or transplant. - Zika virus: Mosquito bite; less common sexual transmission or blood transfusion. - Human parvovirus B19 infection.
• Bacterial & Rickettsial Infections: - Epidemic typhus: Exposure to body lice; Rickettsia prowazekii. - Endemic (murine) typhus: Exposure to rat or cat fleas; Rickettsia typhi. - Scrub typhus: Mite transmission; Orientia tsutsugamushi. - Rickettsial spotted fevers: Tick vector; includes R. conorii, R. australis, R. sibirica, and R. africae. - Human monocytotropic ehrlichiosis: Tick-borne; common in U.S. Southeast/Midwest. - Leptospirosis: Water contaminated with animal urine. - Lyme disease: Ixodes tick vector. - STARI: Amblyomma americanum (Lone Star tick) bite. - Typhoid fever: Contaminated food/water. - Rat-bite fever: Rat bite; primarily in Asia. - Relapsing fever: Ticks or body lice. - African trypanosomiasis: Tsetse fly bite. - Arcanobacterial pharyngitis: Children and young adults.
• Other Conditions: - Systemic lupus erythematosus (SLE): Young to middle-aged women; triggered by sun exposure. - Still's disease: Children and young adults. - Dengue fever: Mosquito bite; tropical/subtropical regions. - Chikungunya fever: Aedes spp. mosquito bites; tropical/subtropical. - Erythema multiforme: HSV or Mycoplasma pneumoniae; drug intake (sulfa, phenytoin, penicillin). - Bacterial endocarditis: Abnormal heart valve; IV drug use. - COVID-19: SARS-CoV-2 infection. - MIS-C: SARS-CoV-2 infection in children/adolescents. - Scarlet fever: Children 2–10 years old; follows Group A streptococcal pharyngitis. - Kawasaki disease: Children < 8 years old. - Streptococcal toxic shock syndrome: Severe Group A infections (e.g., necrotizing fasciitis). - Staphylococcal toxic shock syndrome: Toxin-producing S. aureus; fever > 39°C (>102°F). - Staphylococcal scalded-skin syndrome: Toxin-producing S. aureus; children < 10 years or adults with renal dysfunction. - Exfoliative erythroderma: Adults > 50; more common in men. - DRESS: Individuals unable to detoxify arene oxides; includes HHV6 viremia. - SJS/TEN: Uncommon in children; more common in HIV, SLE, or slow acetylators. - Pseudomonas folliculitis: Hot tub/swimming pool exposure. - Varicella: Children; 10% of adults susceptible. - Variola (smallpox): Nonimmune individuals exposed to smallpox. - Chronic meningococcemia, Dissemined gonococcal infection, RIME.
DIAGNOSTIC APPROACH¶
• Patient History: - Immune status and immunization history. - Medications taken within the previous month (especially anticonvulsants or antimicrobials). - Specific travel history and residence in endemic areas. - Exposure to domestic/other animals and animal/arthropod bites. - Recent dietary exposures. - Presence of cardiac abnormalities or prosthetic material. - Exposure to ill individuals. - Sexual exposure history. - Site of onset, direction, and rate of spread of the rash.
• Physical Examination: - Close attention to rash morphology and identification of salient features. - Determination of lesion type (macules, papules, etc.). - Assessment of distribution (central vs. peripheral). - Evaluation of configuration (annular or target). - Analysis of arrangement of lesions.
TABLES & FIGURES¶
• Table 1: Diseases Associated with Fever and Rash (Centrally Distributed Maculopapular Eruptions) - Rubeola (Measles): Paramyxovirus; distinct lesions becoming confluent from hairline down; Koplik's spots. - Rubella: Togavirus; clears as it spreads; Forchheimer spots. - Erythema infectiosum: Human parvovirus B19; "slapped-cheeks" followed by lacy reticular rash. - Roseola (HVM6/7): Human herpesvirus 6 or 7; children < 3 years; rash follows resolution of fever. - Primary HIV: Non-specific macules and papules; pharyngitis, adenopathy. - Infectious Mononucleosis (EBV): Maculopapular eruption; petechiae in some cases. - Drug Reactions: 2–3 days or 2–3 weeks post-exposure; eosinophilia. - Epidemic Typhus: Rickettsia prowazekii; maculopapular to confluent with petechiae. - Scrub Typhus: Orientia tsutsugamushi; eschar at site of bite.
• Table 2: Peripheral Eruptions - Rocky Mountain spotted fever (RMSF): Rickettsia rickettsii; rash on wrists/ankles, then centripetally to palms/soles; may become petechial. - Secondary Syphilis: Treponema pallidum; copper-colored, scaly papery eruption; never vesicular in adults. - Chikungunya: Chikungunya virus; maculopapular on trunk and extremities. - Hand-foot-and-mouth disease: Coxsackevirus A16/Enterovirus 71; tender vesicles on hands/feet.
• Table 3: Specific Syndromes - Kawasaki Disease: Idiopathic; strawberry tongue, conjunctivitis, edema of hands/feet; children < 8 years. - Streptococcal Toxic Shock Syndrome: Group A Streptococcus; often clariniform rash; multiorgan failure. - Staphylococcal Toxic Shock Syndrome: S. aureus; extensive erythema of mucosal surfaces; fever > 39°C (>102°F). - Staphylococcal Scalded-Skin Syndrome (SSSS): S. aureus; Nikolsky's sign; children < 10 years or adults with renal dysfunction. - Exfoliative Erythroderma: Underlying conditions (psoriasis, etc.); adults > 50; more common in men.
• Table 4: Other Conditions - Varicella: VZV; macules → papules → vesicles → pustules; itchy. - Pseudomonas "hot-tub" folliculitis: Pseudomonas aeruginosa; pruritic, vesicular/pustular lesions. - Variola (Smallpox): Variola major virus; distinct distribution on face and extremities. - Mpox: Monkeypox virus; similar to smallpox but typically milder; 2022 outbreak included cases in Europe and U.S.
• Table 5: Petechial Rashes - Acute Meningococcemia: N. meningitidis; petechiae, purpura fulminans (black necrotic lesions). - Purpura Fulminans: Severe DIC; large erythema → hemorrhagic bullae → black necrotic lesions. - Dissemined Gonococcal Infection: N. gonorrhoeae; 1–5 mm papules → hemorrhagic pustules with gray necrotic centers. - Enteroviral Petechial Rash: Echovirus 9 or Coxsackievirus A8. - Viral Hemorrhagic Fever: Arenaviruses/Bunyaviruses/Flaviviruses; petechial rash, shock, hemorrhage.
KEY PEARLS & HIGH-YIELD POINTS¶
• Pathognomonic Signs: - Koplik's spots → Measles. - Nikolsky's sign → S. aureus scalded-skin syndrome or SJS. - Strawberry tongue/conjunctivitis/hand edema → Kawasaki disease (children < 8 years). - Copper-colored, scaly rash on palms/soles → Secondary syphilis.
• Diagnostic Distinctions: - RMSF: Centripetally spreading from wrists/ankles to palms/soles; petechial progression. - SJS vs. TEN: TEN is a maximal variant of SJS, involving sloughing of the entire epidermis (confluent desquamation). - DRESS: Look for eosinophilia and atypical lymphocytes in patients with drug exposure (2–3 days or 2–3 weeks).
• Clinical Indicators: - Eschar at bite site → Rickettsialpox (African tick-bite fever). - Slapped-cheeks appearance → Erythema infectiosum. - Purpura fulminans → Severe DIC, often with N. meningitidis. - SJS/TEN: SJS involves 30% of the epidermis; TEN is a maximal variant involving sloughing of the entire epidermis.
Reference Tables¶
TABLE 21-1 Diseases Associated with Fever and Rash DISEASE Centrally Distributed Maculopapular Eruptions Acute…¶
Harrison's 22e, p.138
| DISEASE | ETIOLOGY | DESCRIPTION | GROUP AFFECTED/ EPIDEMIOLOGIC FACTORS |
CLINICAL SYNDROME | CHAPTER |
|---|---|---|---|---|---|
| Centrally Distributed Maculopapular Eruptions | |||||
| Acute meningococcemiaa | — | — | — | — | 160 |
| — | — | — | — | ||
| Rubeola (measles, first disease) (Fig. 21-1, Fig. A1-2, Fig. A1-3) |
Paramyxovirus | Discrete lesions that become confluent as rash spreads from hairline downward, usually sparing palms and soles; lasts ≥3 days; Koplik’s spots |
Nonimmune individuals |
Cough, conjunctivitis, coryza, severe prostration |
211 |
| Togavirus | Spreads from hairline downward, clearing as it spreads; Forchheimer spots (palatal petechiae) |
Nonimmune individuals |
Adenopathy, arthritis | ||
| Erythema infectiosum (fifth disease) (Fig. A1-1) |
Human parvovirus B19 | Bright-red “slapped-cheeks” appearance followed by lacy reticular rash that waxes and wanes over 3 weeks; rarely, papular- purpuric “gloves-and-socks” syndrome on hands and feet |
Most common among children 3–12 years old; occurs in winter and spring |
Mild fever; arthritis in adults; rash following resolution of fever |
202 |
| Human herpesvirus 6 or, less commonly, the closely related human herpesvirus 7 |
Diffuse maculopapular eruption over trunk and neck; resolves within 2 days |
Usually affects children <3 years old |
Rash following resolution of fever; similar to Boston exanthem (echovirus 16); febrile seizures may occur |
||
| Primary HIV infection (Fig. A1-6) |
HIV | Nonspecific diffuse macules and papules most commonly on upper thorax, face, collar region; less commonly, urticarial or vesicular lesions; oral or genital ulcers |
Individuals recently infected with HIV |
Pharyngitis, adenopathy, arthralgias |
208 |
| Epstein-Barr virus | Diffuse maculopapular eruption historically in ~5% of cases increasing to ~90% of cases when antibiotics, particularly ampicillin, given, but recent observed rates of ~20% without antibiotics and little increase with antibiotics; urticaria, petechiae in some cases; periorbital edema (50%); palatal petechiae (25%) |
Adolescents, young adults |
Hepatosplenomegaly, pharyngitis, cervical lymphadenopathy, atypical lymphocytosis, heterophile antibody |
||
| Other viral exanthems | Echoviruses 2, 4, 9, 11, 16, 19, 25; coxsackieviruses A9, B1, B5; etc. |
Wide range of skin findings that may mimic rubella or measles |
Affects children more commonly than adults |
Nonspecific viral syndromes |
210 |
| Drugs (antibiotics, anticonvulsants, diuretics, etc.) |
Intensely pruritic, bright-red macules and papules, symmetric on trunk and extremities; may become confluent |
Occurs 2–3 days after exposure in previously sensitized individuals; otherwise, after 2–3 weeks (but can occur anytime, even shortly after drug is discontinued) |
Variable findings: fever and eosinophilia |
||
| Epidemic typhus | Rickettsia prowazekii | Maculopapular eruption appearing in axillae, spreading to trunk and later to extremities; usually spares face, palms, soles; evolves from blanchable macules to confluent eruption with petechiae; rash evanescent in recrudescent typhus (Brill-Zinsser disease) |
Exposure to body lice; occurrence of recrudescent typhus as relapse after 30–50 years |
Headache, myalgias; mortality rates 10–40% if untreated; milder clinical presentation in recrudescent form |
192 |
| Rickettsia typhi | Maculopapular eruption, usually sparing palms, soles |
Exposure to rat or cat fleas |
Headache, myalgias | ||
| Scrub typhus | Orientia tsutsugamushi | Diffuse macular rash starting on trunk; eschar at site of mite bite |
Endemic in South Pacific, Australia, Asia; transmitted by mites |
Headache, myalgias, regional adenopathy; mortality rates up to 30% if untreated |
192 |