Ver el código de «TORCH infections»

==Background==
*TORCH infections is an acronym for a group of congenital and perinatal infections that share overlapping clinical features in the newborn: Toxoplasmosis, Other (syphilis, varicella, parvovirus B19, Zika), Rubella, Cytomegalovirus (CMV), and Herpes simplex virus (HSV).<ref name="StatPearls">Jaan A, Rajnik M. TORCH Complex. ''StatPearls''. NCBI. 2023.</ref> These infections account for approximately 2-3% of all congenital anomalies and may cause fetal death, prematurity, growth restriction, and devastating multisystem disease.<ref name="StatPearls"/> The emergency physician's role is to recognize the nonspecific clinical pattern that suggests congenital infection, initiate time-sensitive empiric treatment (especially acyclovir for HSV), and arrange appropriate confirmatory testing and specialist consultation.
*TORCH infections are transmitted from mother to fetus/neonate via:
** Transplacental (during pregnancy) — most TORCH agents
** Peripartum (during delivery) — HSV (~85% of neonatal HSV cases), HIV
** Postpartum (breast milk, close contact) — CMV, HIV
* Earlier gestational infection generally causes more severe fetal damage; later infection causes higher transmission rates but often milder disease<ref name="AMBOSS">Congenital TORCH infections. ''AMBOSS''. 2024.</ref>
*Neonatal cholestasis occurs in ~1 in 2,500 live births; infections account for ~11% of cases (see [[Neonatal hepatitis]])<ref name="Gottesman">Gottesman LE, et al. Etiologies of conjugated hyperbilirubinemia in infancy: systematic review. ''BMC Pediatr''. 2015;15:192.</ref>

===The "TORCH titer" — limitations===
*A blanket "TORCH titer" panel (IgG screening) is of '''limited clinical utility''' and is '''not recommended as a primary diagnostic strategy'''<ref name="StatPearls"/>
*Neonatal IgG largely reflects maternal antibodies transferred across the placenta and does not confirm neonatal infection
* Pathogen-specific testing (IgM, PCR) directed by clinical suspicion is far more useful
*If clinical syndrome suggests congenital infection, investigate each pathogen individually with the most appropriate rapid diagnostic test

==Clinical features==
===Shared/overlapping features (the congenital infection pattern)===
* Intrauterine growth restriction (IUGR)/small for gestational age
* Hepatosplenomegaly
* Jaundice (conjugated hyperbilirubinemia — see [[Neonatal hepatitis]])
* Petechiae, purpura, or thrombocytopenia ("blueberry muffin" rash — dermal erythropoiesis)
* Microcephaly
* Chorioretinitis
* Sensorineural hearing loss
* Intracranial calcifications
* Anemia
* Seizures

Many neonates with congenital infection are asymptomatic at birth but develop sequelae (hearing loss, developmental delay, chorioretinitis) weeks to years later.<ref name="AMBOSS"/>

===Pathogen-specific features===

====Toxoplasmosis (''Toxoplasma gondii'')====
*Classic triad: '''chorioretinitis + hydrocephalus + diffuse intracranial calcifications'''<ref name="StatPearls"/>
*Calcifications tend to be diffuse/scattered (compare CMV: periventricular)
*Chorioretinitis is the most common late finding — may appear months to years after birth
* Macrocephaly (from hydrocephalus) distinguishes from most other TORCH agents which cause microcephaly
*Most neonates are asymptomatic at birth; untreated disease leads to progressive neurologic and ocular damage
*Maternal risk: cat litter, undercooked meat, contaminated soil/water

====Congenital syphilis (''Treponema pallidum'')====
* Early (<2 years): hepatosplenomegaly, jaundice, rhinitis (snuffles — blood-tinged nasal discharge), maculopapular rash (palms/soles), osteochondritis/periostitis, generalized lymphadenopathy, funisitis (inflammation of umbilical cord), condylomata lata
* Late (>2 years): Hutchinson teeth (notched, peg-shaped incisors), saddle nose, frontal bossing, interstitial keratitis, saber shins, sensorineural deafness, high palatal arch
* Hydrops fetalis in severe cases
*Periostitis may be visible on skeletal X-rays (an important diagnostic clue)

====Rubella (congenital rubella syndrome)====
*Classic triad: sensorineural deafness + cataracts + congenital heart disease (especially patent ductus arteriosus, pulmonary artery stenosis)<ref name="AMBOSS"/>
*"Blueberry muffin" rash (dermal erythropoiesis)
*Hepatosplenomegaly, thrombocytopenic purpura
*Microcephaly, intellectual disability
* Deafness is the most common single manifestation
*Rare in countries with effective vaccination programs; consider in unvaccinated/immigrant populations

====Cytomegalovirus (CMV) — the most common congenital infection====
*Most common congenital infection worldwide (~0.2-2% of live births)<ref name="AMBOSS"/>
* ~90% are asymptomatic at birth — but asymptomatic infants can still develop late-onset hearing loss and developmental delay
*Symptomatic disease: petechiae, hepatosplenomegaly, jaundice, microcephaly, periventricular calcifications (compare toxoplasmosis: diffuse), chorioretinitis, seizures
* Sensorineural hearing loss is the most important late complication — leading infectious cause of childhood hearing loss worldwide
*"Blueberry muffin" rash

====Herpes simplex virus (HSV) — the most acutely life-threatening====
* Most EM-critical TORCH infection due to rapid progression and high mortality without treatment<ref name="HSV_JHM">Schmit M, et al. Clinical progress note: Evaluation and management of neonatal herpes simplex virus disease. ''J Hosp Med''. 2023;18(6):548-555.</ref>
*Incidence: ~1 in 2,000-3,200 live births in the US
*~85% acquired peripartum (during delivery), ~10% postpartum, ~5% in utero
* Three clinical categories:

{| class="wikitable"
|-
! Category !! Frequency !! Typical onset !! Key features !! Mortality (with treatment)
|-
| '''SEM''' (skin, eyes, mouth) || ~45% || Day 7-14 || Vesicular rash (>80% have vesicles), [[keratoconjunctivitis]], oral ulcers || <1%
|-
| '''CNS''' || ~30% || Day 14-21 || Seizures (often focal), irritability, lethargy, poor feeding, bulging fontanelle; vesicles in only ~60% || ~4%
|-
| '''Disseminated''' || ~25% || Day 7-14 || Sepsis-like: [[DIC]], [[hepatitis]]/[[liver failure]], pneumonitis, shock; '''CNS involved in up to 75%'''; vesicles in only ~60% || ~30%
|}

* Critical pitfall: vesicular rash is '''absent''' in ~40% of CNS and disseminated disease — '''do not rely on vesicles to suspect HSV'''<ref name="HSV_JHM"/>
* Fever is often absent at presentation
*Any ill neonate <42 days of age with sepsis-like picture, seizures, or liver failure should be empirically treated with acyclovir

====Other "O" pathogens====
* Parvovirus B19: severe fetal anemia → hydrops fetalis (nonimmune); aplastic crisis; usually self-limited if live-born; may require intrauterine transfusion
* Varicella (VZV): congenital varicella syndrome (limb hypoplasia, cicatricial skin lesions, microcephaly, cortical atrophy, chorioretinitis); very rare with maternal vaccination
* Zika virus: microcephaly (often severe), ocular defects, arthrogryposis; epidemic setting; no specific treatment
* HIV: usually asymptomatic at birth; testing and prophylaxis per neonatal protocols

==Differential diagnosis==
===Neonate with the "congenital infection" pattern===
* Other TORCH infections (always consider the full panel when one is suspected)
*[[Neonatal sepsis]] (bacterial — ''E. coli'', GBS)
*[[Galactosemia]] (may mimic sepsis with liver failure; ''E. coli'' sepsis association)
*[[Tyrosinemia|Tyrosinemia type 1]] (liver failure + coagulopathy)
*[[Neonatal hemochromatosis]] (GALD)
*[[Biliary atresia]] (if jaundice is the presenting sign)
*Neonatal leukemia/neuroblastoma ("blueberry muffin" appearance)
*Hemophagocytic lymphohistiocytosis (HLH)
*Aicardi-Goutières syndrome (pseudo-TORCH — genetic condition mimicking congenital infection with calcifications + CSF lymphocytosis)

==Evaluation==
===ED workup for suspected congenital infection===
* CBC with differential: anemia, thrombocytopenia, atypical lymphocytes, neutropenia
* Hepatic panel: AST, ALT (may be markedly elevated in HSV hepatitis), bilirubin (fractionate)
* Coagulation studies: PT/INR, fibrinogen (DIC in disseminated HSV)
* Blood glucose: hypoglycemia (hepatic failure)
* BMP: electrolytes, renal function
* Blood culture (to exclude bacterial sepsis)
* Urinalysis and urine culture
* Lumbar puncture: CSF cell count, protein, glucose, HSV PCR, bacterial culture; HSV PCR on CSF is critical for diagnosis of CNS disease
* ALT specifically: markedly elevated ALT is a red flag for disseminated HSV (liver is a primary target organ)

===Pathogen-specific testing (initiate from ED based on clinical suspicion)===

{| class="wikitable"
|-
! Pathogen !! Best diagnostic test !! Key notes
|-
| '''HSV''' || '''HSV PCR''' (CSF, blood, surface swabs of mouth/eyes/nasopharynx/vesicles) || Start '''acyclovir empirically''' before results return; also send ALT, DIC labs
|-
| '''CMV''' || '''Urine CMV PCR''' or saliva CMV PCR || Must be collected within first '''3 weeks of life''' to distinguish congenital from postnatal infection
|-
| '''Toxoplasmosis''' || '''Toxoplasma-specific IgM and IgA''' in infant serum; '''PCR''' || IgG alone reflects maternal antibodies; ophthalmology and neuroimaging needed
|-
| '''Syphilis''' || '''RPR/VDRL''' (quantitative) on infant AND mother; '''treponemal test''' (FTA-ABS IgM) || Compare infant to maternal RPR titers; skeletal survey; LP if neurosyphilis suspected
|-
| '''Rubella''' || '''Rubella-specific IgM''' in infant serum || Maternal vaccination history is critical; viral culture/PCR of nasopharyngeal secretions
|-
| '''Parvovirus B19''' || '''Parvovirus IgM'''; '''PCR''' on blood || Reticulocyte count (aplastic crisis); fetal ultrasound for hydrops
|}

===Imaging===
* Cranial ultrasound (neonates): intracranial calcifications, ventriculomegaly, periventricular echogenicity
* CT head: more sensitive for calcifications; periventricular (CMV) vs diffuse (toxoplasmosis) distribution pattern
* MRI brain: most sensitive for cortical malformations (polymicrogyria in CMV), white matter disease
* Ophthalmologic examination: all suspected congenital infections require fundoscopic exam for chorioretinitis
* Skeletal survey: periostitis, osteochondritis (congenital syphilis)
* Audiology (ABR): arrange for all confirmed congenital infections, especially CMV

==Management==
===HSV — the ED emergency===
*'''Start IV acyclovir immediately''' in any neonate with suspected HSV — '''do not wait for PCR results'''<ref name="HSV_JHM"/>
* Dose: acyclovir 20 mg/kg/dose IV every 8 hours (= 60 mg/kg/day)
* Duration:
** SEM disease: 14 days IV
** CNS or disseminated disease: 21 days IV
**Repeat LP with CSF HSV PCR before stopping treatment in CNS disease; continue IV acyclovir until CSF PCR is negative<ref name="HSV_NIH">Herpes Simplex Virus: Pediatric OIs. ''NIH Clinical Guidelines''. 2024.</ref>
*After IV course: oral acyclovir suppressive therapy 300 mg/m²/dose TID for 6 months (reduces cutaneous recurrences and improves neurodevelopmental outcomes in CNS disease)
* Supportive care: IV fluids, correct DIC/coagulopathy (FFP, cryoprecipitate, platelets), respiratory support, seizure management, broad-spectrum antibiotics until bacterial sepsis excluded
* Monitor: CBC twice weekly (acyclovir-associated neutropenia in ~20%), daily creatinine (nephrotoxicity)
* Ophthalmology consult: herpetic keratoconjunctivitis requires topical trifluridine or ganciclovir in addition to systemic therapy

===Congenital syphilis===
* Aqueous penicillin G: 50,000 units/kg/dose IV every 12 hours (age <7 days) or '''every 8 hours''' (age ≥7 days) for '''10 days'''<ref name="StatPearls"/>
*Alternative: Procaine penicillin G 50,000 units/kg IM daily for 10 days (if IV not feasible)
*Normal neonate born to adequately treated mother (≥4 weeks before delivery): single dose benzathine penicillin G 50,000 units/kg IM may suffice
* No alternative to penicillin — penicillin-allergic infants require desensitization

===Congenital toxoplasmosis===
* Pyrimethamine (loading dose 2 mg/kg/day for 2 days, then 1 mg/kg/day) + sulfadiazine (50 mg/kg/dose BID) + leucovorin (10 mg 3 times weekly) for 12 months<ref name="CDC_Toxo">Clinical Care of Toxoplasmosis. ''CDC''. 2024.</ref>
*Leucovorin (folinic acid) is mandatory to prevent pyrimethamine-induced bone marrow suppression
*'''Do NOT substitute folic acid for leucovorin''' — folic acid antagonizes pyrimethamine's therapeutic effect while leucovorin selectively rescues marrow
*Add corticosteroids (prednisone 0.5 mg/kg BID) if CSF protein >1 g/dL or vision-threatening chorioretinitis
* Weekly CBC while on pyrimethamine (monitor for neutropenia, anemia, thrombocytopenia)

===Congenital CMV===
* Valganciclovir (oral) or ganciclovir (IV) for moderate-to-severe symptomatic congenital CMV<ref name="AMBOSS"/>
*Valganciclovir 16 mg/kg/dose BID orally for 6 months is current standard
*Goal is to preserve hearing and neurodevelopmental outcomes
* Not routinely initiated in the ED — refer to infectious disease/neonatology for treatment decisions
*Monitor for neutropenia, thrombocytopenia, hepatotoxicity

===Congenital rubella===
* No specific antiviral treatment
*Supportive management of cardiac defects, cataracts, hearing loss
* Infectious for up to 1 year — isolation precautions; notify public health

===General supportive measures for all congenital infections===
*Vitamin K (if cholestatic — fat-soluble vitamin malabsorption)
*Treat [[Neonatal hepatitis|conjugated hyperbilirubinemia]] per workup
*Nutritional support (MCT-enriched formula if cholestatic)
*Seizure management
*Hearing evaluation (ABR) for all
*Ophthalmologic examination for all
*Developmental follow-up

==Disposition==
* All neonates with suspected congenital infection should be admitted — most will require NICU-level care
* HSV: start acyclovir in the ED; admit to NICU; infectious disease consultation
* Syphilis with positive RPR or symptomatic: admit; start IV penicillin after LP; involve infectious disease
* CMV, toxoplasmosis: admit for confirmatory testing, neuroimaging, ophthalmologic evaluation, and treatment initiation
* Well-appearing infant with isolated conjugated hyperbilirubinemia: may be evaluated urgently as outpatient (see [[Neonatal hepatitis]]) but ensure TORCH-specific testing is sent and follow-up is reliable
* Notify: congenital syphilis and rubella are reportable diseases — contact public health

==See Also==
*[[Neonatal hepatitis]]
*[[Neonatal jaundice]]
*[[Neonatal HSV]]
*[[Neonatal sepsis]]
*[[Biliary atresia]]
*[[Tyrosinemia]]
*[[Galactosemia]]
*[[Sensorineural hearing loss]]

==External Links==
*[https://www.ncbi.nlm.nih.gov/books/NBK560528/ StatPearls — TORCH Complex]
*[https://www.cdc.gov/toxoplasmosis/hcp/clinical-care/index.html CDC — Clinical Care of Toxoplasmosis]
*[https://pmc.ncbi.nlm.nih.gov/articles/PMC3685871/ PMC — Treatment of HSV Infections in Pediatric Patients]
*[https://pmc.ncbi.nlm.nih.gov/articles/PMC321459/ Clin Microbiol Rev — Neonatal Herpes Simplex Infection]
*[https://www.merckmanuals.com/professional/pediatrics/infections-in-neonates/neonatal-herpes-simplex-virus-hsv-infection Merck Manual — Neonatal HSV Infection]
*[https://clinicalinfo.hiv.gov/en/guidelines/hiv-clinical-guidelines-pediatric-opportunistic-infections/herpes-simplex-virus NIH — Herpes Simplex Virus: Pediatric OIs]

==References==
<references/>

[[Category:Pediatrics]]
[[Category:ID]]