2d:I[856015,["/_next/static/immutable/chunks/1xzisbplk9czp.js","/_next/static/immutable/chunks/3j2i1faptc_-9.js","/_next/static/immutable/chunks/0fma7nlq6immz.js","/_next/static/immutable/chunks/08tq8rmv423j5.js","/_next/static/immutable/chunks/1chr5wkk3j58k.js","/_next/static/immutable/chunks/37kmmh_zm4dov.js","/_next/static/immutable/chunks/311zvdjfxff-f.js","/_next/static/immutable/chunks/1a_hqhrsle_n_.js"],"default"] 2e:T76b7,

Summary Table

Domain	Details
Risk Factors	Unvaccinated or incompletely vaccinated children, immunocompromised patients (HIV/AIDS, malignancy, chronic steroid use), vitamin A deficiency, travel to endemic regions, close contacts of confirmed cases
Etiology	Paramyxovirus (genus Morbillivirus), single-stranded negative-sense RNA virus; transmitted via respiratory droplets and aerosolized particles; one of the most contagious human pathogens (R0 = 12-18)
Patient Presentation	High fever (often > 40 C) with the classic triad of cough, coryza, and conjunctivitis ("the 3 C's"), followed by a maculopapular rash spreading craniocaudally (head to toe)
Classic Physical Exam	Koplik spots: blue-white papules on an erythematous base on the buccal mucosa (pathognomonic, appear 1-2 days before the rash); erythematous, blanching maculopapular rash starting on the face and hairline, spreading downward to the trunk and extremities; non-purulent conjunctivitis; cervical lymphadenopathy
Key Diagnostic Results	Measles-specific IgM serology (positive at rash onset); RT-PCR of nasopharyngeal swab or urine; marked leukopenia with lymphocytopenia; multinucleated giant cells (Warthin-Finkeldey cells) on tissue biopsy
Management	Supportive care (antipyretics, hydration); Vitamin A supplementation (200,000 IU for children >= 12 months) for all confirmed cases; ribavirin reserved for severe/immunocompromised cases; post-exposure prophylaxis with MMR vaccine (within 72 hours) or immunoglobulin (within 6 days)
Keywords	"3 C's" (cough, coryza, conjunctivitis), Koplik spots, craniocaudal rash, maculopapular, paramyxovirus, vitamin A, febrile exanthem, post-auricular rash onset, Warthin-Finkeldey giant cells

1. Pathophysiology

Measles is caused by the Morbillivirus, a member of the Paramyxoviridae family. It is a single-stranded, negative-sense RNA virus with an envelope containing two critical surface glycoproteins: the hemagglutinin (H) protein, which binds to host cell receptors (CD46, SLAM/CD150, and nectin-4), and the fusion (F) protein, which mediates viral entry by fusing with the host cell membrane.

Transmission occurs through aerosolized respiratory droplets, and the virus can remain suspended in air for up to 2 hours after an infected person leaves the room. This explains why measles is extraordinarily contagious, with a basic reproductive number (R0) of 12 to 18, meaning a single infected individual can transmit the virus to 12-18 susceptible contacts. After inhalation, the virus initially infects epithelial cells of the respiratory tract and local dendritic cells and alveolar macrophages. These immune cells then carry the virus to regional lymph nodes, where the first round of viral replication occurs.

This is followed by a primary viremia (days 2-3 post-infection), during which the virus disseminates via the bloodstream to the reticuloendothelial system (spleen, liver, bone marrow, and additional lymph nodes). A secondary viremia (days 5-7) then spreads the virus to the skin, respiratory tract, and other organs, producing the clinical disease. The incubation period from exposure to symptom onset is typically 10 to 14 days.

The prodromal phase (lasting 2-4 days) is characterized by the "3 C's": cough, coryza, and conjunctivitis, along with high fever. These symptoms reflect direct viral cytopathic damage to respiratory and conjunctival epithelium. During this phase, Koplik spots appear on the buccal mucosa, which represent focal areas of epithelial necrosis and are considered pathognomonic for measles. Koplik spots typically appear 1-2 days before the rash and fade 1-2 days after the rash emerges.

The maculopapular rash that follows is largely an immune-mediated phenomenon. It results from the host's T-cell response targeting virus-infected endothelial cells in dermal capillaries, producing perivascular inflammation. The rash characteristically begins on the face and behind the ears (post-auricular region), then spreads downward to the trunk and extremities over 3-4 days. This craniocaudal progression is a key discriminator from other febrile exanthems. The rash typically fades in the same order it appeared (face first), sometimes leaving a brownish discoloration or fine desquamation.

A critical concept is measles-induced immune suppression. The virus has a tropism for CD150/SLAM-expressing memory lymphocytes, and infection leads to the destruction of pre-existing memory B and T cells. This phenomenon, called "immune amnesia," can persist for months to years after acute infection and leaves the patient vulnerable to secondary bacterial infections. This explains why post-measles pneumonia and otitis media are so common and why measles is associated with increased all-cause mortality for 2-3 years following infection.

Complications vary by age and immune status. Pneumonia (either primary viral or secondary bacterial) is the most common cause of measles-related death. Acute post-infectious encephalitis occurs in approximately 1 in 1,000 cases, typically 1-2 weeks after the rash, and is caused by an autoimmune demyelinating process. A rare but uniformly fatal late complication is subacute sclerosing panencephalitis (SSPE), a progressive degenerative CNS disease that manifests 7-10 years after the initial infection, caused by persistent defective measles virus in the brain.

2. Classification and Clinical Manifestation

Clinical Phases of Measles

Phase	Timing	Key Features
Incubation	Days 1-14 after exposure	Asymptomatic; virus replicating in lymphoid tissue; primary and secondary viremia
Prodrome	Days 10-14 (lasts 2-4 days)	High fever (stepwise increase, can reach > 40 C), cough, coryza, conjunctivitis (the "3 C's"), malaise, anorexia; Koplik spots appear near the end of the prodrome
Exanthem (Rash)	Days 14-17 (lasts 5-6 days)	Erythematous, blanching maculopapular rash; begins at the hairline and face, spreads craniocaudally; fever peaks on day 1-2 of rash, then defervesces; patient is most infectious from 4 days before to 4 days after rash onset
Recovery	Days 18-21+	Rash fades in order of appearance (head to toe); desquamation and brownish staining may persist; cough may linger for 1-2 weeks

Classification by Severity

Category	Description
Uncomplicated Measles	Self-limiting course with fever, the 3 C's, Koplik spots, and rash resolving within 7-10 days
Modified Measles	Occurs in patients with partial immunity (e.g., passively acquired maternal antibodies in infants, prior partial vaccination); milder symptoms, atypical rash pattern, Koplik spots may be absent
Atypical Measles	Historically seen in patients who received the older killed-virus vaccine (no longer used); presents with high fever, peripheral (rather than central) rash that may be vesicular/petechial, and pneumonitis; rash spreads from extremities to trunk (reverse of typical)
Severe/Complicated Measles	Accompanied by one or more complications (see below)

Complications

Complication	Frequency / Notes
Pneumonia	Most common cause of death; can be primary giant cell (Hecht) pneumonia or secondary bacterial (Streptococcus pneumoniae, Staphylococcus aureus); occurs in ~6% of cases
Otitis media	Most common overall complication (~7-9%); secondary bacterial infection of the middle ear
Laryngotracheobronchitis (Croup)	Common in young children; caused by direct viral involvement of the airway
Diarrhea/Dehydration	Particularly problematic in malnourished children and in resource-limited settings
Febrile seizures	Occur in ~0.1-0.5% of cases; generally benign and self-limiting
Acute post-infectious encephalitis	~1 in 1,000 cases; occurs 1-2 weeks after rash onset; autoimmune demyelination; mortality ~10-15%, neurologic sequelae in ~25% of survivors
Subacute sclerosing panencephalitis (SSPE)	~1 in 10,000-100,000 cases; onset 7-10 years after infection; progressive cognitive decline, myoclonus, seizures; uniformly fatal; caused by defective measles virus persisting in the CNS
Measles keratoconjunctivitis	Can cause corneal scarring and blindness, particularly in vitamin A-deficient populations
Hemorrhagic measles (Black measles)	Rare, severe form with DIC, hemorrhagic skin lesions, and high mortality

3. Diagnostic Workup

Test	Role	Timing / Notes
Measles-specific IgM serology	Best Initial Test (standard of care)	Obtain at rash onset; may be falsely negative if drawn in the first 72 hours of rash; sensitivity improves 3-4 days after rash onset; consider repeat testing if initially negative
RT-PCR (viral RNA detection)	Most Accurate / Confirmatory Test	Nasopharyngeal swab, throat swab, or urine; detectable from the prodrome through several days after rash onset; also allows genotyping for epidemiologic tracking
Measles-specific IgG serology (acute and convalescent)	Confirmatory (retrospective)	4-fold rise in IgG titers between acute (at rash onset) and convalescent (2-4 weeks later) sera; useful when IgM result is equivocal
Viral culture	Reference laboratory use	Slow (takes days); not used for routine clinical diagnosis; mainly for viral genotyping
CBC	Supportive	Leukopenia with lymphocytopenia is characteristic
Tissue biopsy (rarely needed)	Pathologic confirmation	Warthin-Finkeldey multinucleated giant cells in lymphoid tissue or respiratory epithelium

The standard approach to diagnosing measles begins with clinical recognition of the classic triad (cough, coryza, conjunctivitis) with a craniocaudal maculopapular rash and high fever, particularly in an unvaccinated patient or one with known exposure. In most clinical and public health settings, measles-specific IgM serology is the best initial test. It should be drawn at the time of rash onset. However, a key caveat is that IgM can be falsely negative if obtained within the first 72 hours of rash onset, so if clinical suspicion remains high and the initial IgM is negative, repeat testing 3-4 days later is recommended.

RT-PCR from a nasopharyngeal or throat swab (or urine) is the most accurate confirmatory test. It is highly sensitive and allows genotyping, which is critical for distinguishing between wild-type measles and vaccine-strain virus, and for epidemiologic surveillance. RT-PCR can detect viral RNA from the prodromal phase through approximately 7-10 days after rash onset. For this reason, public health guidelines recommend obtaining both serology (IgM) and a viral specimen for RT-PCR whenever measles is suspected.

A paired acute and convalescent IgG titer showing a 4-fold rise provides retrospective confirmation, which is useful in diagnostically challenging cases but is less practical in acute management.

On laboratory studies, expect to see leukopenia (white blood cell count often below $4,000/\mu L$) with a predominant lymphocytopenia, reflecting the virus's tropism for lymphocytes. This finding can help distinguish measles from bacterial infections that typically produce leukocytosis. Thrombocytopenia may also be present in severe cases.

Histopathology is rarely needed for diagnosis, but when tissue is examined, Warthin-Finkeldey giant cells (multinucleated reticuloendothelial giant cells formed by fusion of virus-infected lymphoid cells) are pathognomonic. These can be found in the tonsils, adenoids, appendix, and respiratory epithelium.

Imaging is generally unnecessary unless complications are suspected. A chest radiograph should be obtained if the patient has persistent fever, tachypnea, or hypoxia suggesting pneumonia. Findings in measles pneumonia can range from interstitial infiltrates to lobar consolidation (if secondary bacterial pneumonia is present).

4. Management and Treatment

Intervention	Details
Supportive care	Antipyretics (acetaminophen or ibuprofen for fever), adequate oral hydration, rest, airborne isolation precautions
Vitamin A	All confirmed cases: 200,000 IU orally once daily for 2 days (age >= 12 months); 100,000 IU for ages 6-11 months; 50,000 IU for ages < 6 months
Antibiotics	Only if secondary bacterial infection is present (e.g., bacterial pneumonia, otitis media); choice based on likely pathogen
Ribavirin	Reserved for severe or life-threatening measles in immunocompromised patients; not standard for uncomplicated cases
Post-exposure prophylaxis (PEP)	MMR vaccine within 72 hours of exposure for eligible contacts; Immunoglobulin (IG) within 6 days of exposure for high-risk individuals (infants < 12 months, pregnant women, immunocompromised patients)
Airborne isolation	From 4 days before rash to 4 days after rash onset (standard); immunocompromised patients should remain isolated for the duration of illness

Acute Stabilization and Supportive Care: There is no antiviral therapy with proven efficacy for routine measles. Management is primarily supportive. Fever should be treated with acetaminophen (paracetamol) 10-15 mg/kg/dose every 4-6 hours or ibuprofen 10 mg/kg/dose every 6-8 hours as needed. Adequate fluid intake must be maintained, especially in children at risk for dehydration due to fever, poor oral intake, or diarrhea.

Vitamin A Supplementation: This is one of the most tested points in exam vignettes. Vitamin A significantly reduces morbidity and mortality from measles, particularly in children with vitamin A deficiency. The WHO and AAP recommend vitamin A for all children with measles, regardless of their country of residence.

The dosing schedule is age-based and given orally once daily for 2 consecutive days:

Children >= 12 months of age: 200,000 IU per dose
Children 6-11 months of age: 100,000 IU per dose
Children < 6 months of age: 50,000 IU per dose

A third dose should be given 2-4 weeks later if there is clinical evidence of vitamin A deficiency (e.g., xerophthalmia, Bitot spots). The mechanism of benefit relates to vitamin A's role in maintaining mucosal epithelial integrity and supporting T-cell-mediated immune responses.

Management of Complications: For secondary bacterial infections (pneumonia, otitis media), antibiotics should be chosen based on the most likely pathogen. Amoxicillin is a reasonable first-line agent for otitis media. For community-acquired bacterial pneumonia superimposed on measles, empirical coverage for Streptococcus pneumoniae and Staphylococcus aureus with an appropriate beta-lactam (e.g., amoxicillin-clavulanate or a parenteral cephalosporin if hospitalized) is indicated.

Ribavirin is an antiviral agent that has shown in vitro activity against measles virus. Its clinical use is limited to severe measles in immunocompromised patients, such as those with HIV/AIDS or patients on immunosuppressive therapy. It is not standard care for uncomplicated measles.

Acute post-infectious encephalitis is managed with supportive care, seizure management, and monitoring for elevated intracranial pressure. There is no established antiviral treatment for measles encephalitis. SSPE has no curative therapy; intrathecal interferon-alpha and inosiplex have been tried with limited benefit.

Post-Exposure Prophylaxis (PEP): This is a high-yield management question. The choice of PEP depends on the time since exposure and the patient's immune status:

MMR vaccine should be given within 72 hours of exposure to susceptible individuals aged >= 6 months (this includes the early "zero dose" at 6-11 months, which does not count as a routine vaccine dose and requires re-vaccination at 12-15 months).
Immunoglobulin (IG) should be given within 6 days of exposure for individuals who cannot receive MMR, including: infants < 6 months, pregnant women, and severely immunocompromised patients. The dose is 0.5 mL/kg IM (maximum 15 mL) or 400 mg/kg IV for immunocompromised patients.
If more than 6 days have passed since exposure, neither MMR nor IG is effective as PEP.

Infection Control: All patients with suspected or confirmed measles must be placed on airborne isolation precautions (negative-pressure room, N95 respirators for healthcare workers). The infectious period extends from 4 days before to 4 days after rash onset. Immunocompromised patients may shed virus for a prolonged period and should remain in isolation for the entire duration of their illness.

5. Differential Diagnosis and Distractors

Differential	Why It Is Similar	Key Discriminator
Rubella (German Measles)	Also a viral exanthem with maculopapular rash and fever in an unvaccinated patient	Rubella has a milder prodrome without the severe "3 C's"; rash is more diffuse and shorter-lived (3 days, hence "3-day measles"); posterior auricular and postoccipital lymphadenopathy are prominent; no Koplik spots; Forchheimer spots (petechiae on soft palate) may be present instead
Roseola (HHV-6)	Febrile illness in a young child followed by a diffuse maculopapular rash	In roseola, the rash appears after the fever breaks ("fever, then rash"), while in measles, rash appears while the fever is still high; roseola typically affects children aged 6-24 months; no Koplik spots; no 3 C's
Erythema Infectiosum (Parvovirus B19)	Rash illness in a child that can be confused with measles	Rash in parvovirus B19 starts on the cheeks ("slapped cheek" appearance), then develops a reticular (lace-like) pattern on the trunk and extremities; patient is usually afebrile or mildly febrile by the time rash appears; no Koplik spots
Kawasaki Disease	High fever with conjunctivitis and rash in a child	Kawasaki features bilateral non-exudative conjunctivitis (similar to measles) but also includes strawberry tongue, lip cracking, cervical lymphadenopathy, and extremity changes (edema, erythema, desquamation of hands/feet); no Koplik spots; no coryza
Scarlet Fever (Group A Strep)	Fever with a diffuse erythematous rash	Scarlet fever rash has a sandpaper texture, starts in the groin/axilla (not face), and features Pastia lines (linear petechiae in skin folds) and strawberry tongue; presence of pharyngitis and positive rapid strep test; no Koplik spots
Drug Eruption	Diffuse maculopapular rash with fever	Drug reactions have a temporal association with new medication exposure (especially antibiotics like ampicillin, anticonvulsants); rash is often pruritic; no Koplik spots; no 3 C's; eosinophilia may be present
Infectious Mononucleosis (EBV) with ampicillin rash	Maculopapular rash with fever and pharyngitis	The rash in EBV is classically triggered by ampicillin/amoxicillin administration; posterior cervical lymphadenopathy, tonsillar exudates, hepatosplenomegaly, and atypical lymphocytes on blood smear distinguish it; heterophile antibody (Monospot) positive
Secondary Syphilis	Diffuse maculopapular rash that can involve palms and soles	Secondary syphilis rash involves the palms and soles (measles typically does not); history of painless genital ulcer (primary chancre) weeks prior; condylomata lata, mucous patches; positive treponemal and non-treponemal serology

6. Traps and High-Yield Pearls

The most common way students get measles questions wrong is by failing to recognize the chronologic relationship between Koplik spots and the rash. Koplik spots appear during the prodromal phase, 1-2 days before the rash, and fade shortly after the rash emerges. If the vignette describes a child in the prodromal phase (fever, cough, coryza, conjunctivitis with white spots on the buccal mucosa), the diagnosis is measles even though the rash has not yet appeared. Students who are anchored to the rash as the defining feature will miss this.

A second common trap involves the direction of rash spread. Measles rash spreads craniocaudally (head to toe). If a vignette describes a rash starting on the trunk or extremities and spreading upward, this should point away from measles and toward alternative diagnoses such as atypical measles, drug eruption, or secondary syphilis.

Students also frequently forget that vitamin A is indicated for all children with measles, not just those in developing countries or those with malnutrition. The exam tests whether you know to include vitamin A supplementation as part of the standard management plan.

Another tested concept is the timing of post-exposure prophylaxis. The critical cutoffs are: MMR vaccine within 72 hours and immunoglobulin within 6 days of exposure. Knowing who qualifies for which (pregnant women and immunocompromised patients get IG, not MMR) is a frequently examined decision point.

The concept of immune amnesia is increasingly tested in more advanced board-style questions. Students should understand that measles does not simply resolve. The destruction of memory lymphocytes leaves the patient immunologically vulnerable for months to years afterward, which is why measles vaccination prevents not only measles itself but also reduces overall childhood mortality from other infections.

Finally, be aware of the SSPE trap: if a vignette presents an adolescent with progressive cognitive decline, myoclonus, and behavioral changes with a history of measles in infancy, the answer is SSPE. Students may be drawn toward other neurodegenerative conditions, but the history of early measles infection combined with the long latency period is the critical clue.

The core competency being tested with measles questions is the ability to recognize the disease based on its clinical staging (prodrome with Koplik spots followed by craniocaudal rash), to distinguish it from other childhood exanthems using key discriminators, and to apply the correct management (vitamin A for all, PEP timing, and isolation precautions).

1e:["$","$L2d",null,{"article":{"id":"44a27870-d7eb-4e1b-82c3-e68daa00cbcd","title":"Measles","content":"$2e","category":"Dermatovenereologi","created_at":"2026-06-09T06:01:03.74977+00:00","status":"published","subcategory":null},"questionCount":2,"sections":[{"id":"section-pathophysiology","num":"01","title":"Pathophysiology"},{"id":"section-classification-and-clinical-manifestation","num":"02","title":"Classification and Clinical Manifestation"},{"id":"section-diagnostic-workup","num":"03","title":"Diagnostic Workup"},{"id":"section-management-and-treatment","num":"04","title":"Management and Treatment"},{"id":"section-differential-diagnosis-and-distractors","num":"05","title":"Differential Diagnosis and Distractors"},{"id":"section-traps-and-high-yield-pearls","num":"06","title":"Traps and High-Yield Pearls"}],"hasSummaryTable":true}]