USMLE Step 3 (Fach) / Pediatrics (Lektion)

First Aid Step 3

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• Breast milk jaundice Pathophysiology: increased concentration of β-glucuronidase in breast milk → ↑ deconjugation and reabsorption of bilirubin → persistence of physiologic jaundice Clinical features: onset within 2 weeks after birth; lasts for 4-13 weeks. Total bilirubin levels may reach 19-20 mg/dL. Treatment:- Continued breastfeeding and supplementation with formula feeds  - Phototherapy if required   
• Breastfeeding jaundice Pathophysiology: insufficient breast milk intake  → lack of calories and inadequate quantities of bowel movements to remove bilirubin from the body → ↑ enterohepatic circulation → increased reabsorption of bilirubin from the intestines Clinical features: onset within 1 week Treatment: increase breastfeeding sessions, rehydration
• Suspected foreign body ingestion 1. X-ray PA & lateral - CT scan if object not visible on x-ray 2. High-risk features (Patient has respiratory or obstructive symptoms; object is a button battery, magnet, or sharp item) → Endoscopic removal 2. No high-risk features → Serial x-rays- No transit → Endoscopic removal- Object moving distally → No intervention
• Infantile colic Etiology: - Gastrointestinal (e.g., overfeeding or underfeeding, aerophagia, cow's milk intolerance), biologic (e.g., increased serotonin levels, tobacco exposure, dysfunctional motor regulation related to immaturity), and psychosocial (e.g., exposure to stress) factors are suspected Clinical features:- Healthy and thriving infant- Paroxysmal episodes of loud and high pitched crying- Hypertonia (e.g., clenched fists) during episodes- Infant is not easily consoled Diagnosis: crying that lasts ≥ 3 hours per day, ≥ 3 days per week, for ≥ 3 weeks in an otherwise healthy infant <3 months Treatment:- Reassurance  - Trial of various feeding and soothing techniques   The 5 S’s for soothing crying babies:- Swaddling- Side/Stomach position (done under close supervision only) - Shushing sounds - Swinging- Sucking
• Neonatal infection and sepsis Etiology:- Early-onset infection/sepsis: ≤ 72 hours after delivery  → Common causes: chorioamnionitis, bacterial colonization of the maternal genital tract (pathogen transfer to the infant)→ Common pathogens: group B Streptococcus and E. coli; less common are Listeria monocytogenes, Staphylococcus aureus, Enterococcus, and Haemophilus influenzae.- Late-onset infection/sepsis: > 72 hours after delivery→ Common causes: nosocomial infection→ Common pathogens: group B Streptococcus and E. coli; less common are coagulase-negative Staphylococcus, Staphylococcus aureus, Klebsiella, Pseudomonas Risk factors:- Maternal→ Fever→ PROM, premature labor→ Infections (e.g., UTI)- Fetal:→ Premature birth, low birth weight, low Apgar score→ Difficult delivery→ Asphyxia→ Intravascular catheter or nasal cannula (in late-onset sepsis) Clinical features:- Irritability, lethargy, poor feeding- Temperature changes (fever and hypothermia both possible)- Cardiocirculatory: tachycardia, hypotension, poor perfusion, and delayed capillary refill > 3 sec  - Respiratory: tachypnea, dyspnea (e.g., expiratory grunting), apnea (more common in preterm infants)- Skin tone: jaundiced and/or bluish-gray (indicates poor perfusion) Diagnosis:- Blood cultures or urine culture for suspected UTI- Blood tests: Leukocytopenia or leukocytosis, thrombocytopenia, ↑ CRP- Lumbar puncture: test cerebrospinal fluid for possible meningitis  - Chest x-ray: may reveal clear signs of pneumonia (e.g., segmental infiltrates) but more often nonspecific with diffuse opacities Management:- Supportive care (cardiopulmonary monitoring and support)- Broad-spectrum antibiotics: IV ampicillin and gentamicin→ Indications: clinical suspicion, confirmed or suspected maternal infection (e.g., chorioamnionitis)→ Adapt therapy according to antibiogram results
• Neonatal respiratory distress syndrome Incidence:- 1% of all newborns- 10% of all preterm babies Etiology: Impaired synthesis and secretion of surfactant Risk factors:- Premature birth- Genetic predisposition- Scheduled cesarean section  - Maternal diabetes mellitus  - Hydrops fetalis- Multifetal pregnancies Clinical features:- History of premature birth- Onset of symptoms: usually manifests immediately after birth  - Signs of increased breathing effort→ Tachypnea→ Nasal flaring and moderate to severe subcostal/intercostal and jugular retractions  → Typical expiratory “grunting”  - Auscultation: decreased breath sounds- Cyanosis due to peripheral hypoxic vasoconstriction Diagnostics:- Chest x-ray: diffuse, fine, reticulogranular (ground-glass) densities, with low lung volumes and air bronchograms- Blood gas analysis: Hypoxia with respiratory acidosis; can also lead to increased lactate levels- Prenatal testing for NRDS: Amniocentesis. Markers of fetal lung immaturity:→ Lecithin-sphingomyelin ratio < 1.5  → Foam stability index < 0.48→ Low surfactant-albumin ratio- Microscopic findings: Hyaline membranes lining the alveoli with engorged and congested capillary vessels Treatment:- Ventilation→ Nasal CPAP with a PEEP of 3-8 cm H2O  → If respiratory insufficiency persists, intubation with mechanical ventilation and O2 inhalation  - Endotracheal administration of artificial surfactant within 2 hours postpartum  - Supportive measures: IV fluid replacement; stabilization of blood sugar levels and electrolytesPhysiologic O2 saturation in neonates is around 90% instead of 100%. A saturation of 100% is considered toxic for the neonate!
• Transient tachypnea of the newborn (wet lung disease) Reversible respiratory disorder Etiology: Most commonly occurs in full-term neonates delivered by cesarean section. These infants often have fluid-filled lungs.   Clinical features:- Diffuse crackles are heard on examination. Diagnostics:- X-ray shows fluid in the lung fissures and increased lung volumes. Treatment: supportive care (e.g., supplemental oxygen, neutral thermal environment, adequate nutrition)
• Meconium aspiration syndrome Neonates with meconium aspiration are usually post-term rather than preterm infants An unresponsive neonate and green amniotic fluid establish the diagnosis and serve as indications for emergency intubation and endotracheal drainage. Other signs include:- Increased lung volume- Asymmetric, patchy opacities- Pleural effusion
• Bronchopulmonary dysplasia (BPD) Chronic lung disease primarily found in premature infants exposed to prolonged mechanical ventilation and oxygen therapy for neonatal RDS Etiology: immature lung with exposure to ventilation → barotrauma, oxygen toxicity, inflammation- History of infant requiring mechanical ventilation > 28 days Clinical features:- Seen in infants < 32 weeks- Persistence of symptoms similar to NRDS (e.g., tachypnea, grunting, nasal flaring); episodes of desaturation Diagnostics:- Chest x-ray: diffuse, fine granular densities; atelectasis- Histology: atelectasis, fibrosis, emphysematous alveolar changes Therapy: controlled oxygenation, diuretics, consider glucocorticoids
• Congenital diaphragmatic hernia Etiology: Impaired development and/or fusion of embryonic structures (pleuroperitoneal membrane) → defect in the diaphragm persists during fetal development → displacement of abdominal contents into the pleural cavity  → compression of lung tissue  → pulmonary hypoplasia Clinical features:- Presentation depends on the degree of pulmonary hypoplasia and pulmonary hypertension  - Respiratory distress (e.g., nasal flaring, tachypnea, cyanosis, intercostal retractions, grunting)  - Barrel-shaped chest, scaphoid abdomen, and auscultation of bowel sounds in the chest- Absent breath sounds on the ipsilateral side  - Mediastinal shift: shift of heart sounds/apex beat to the right side- Possible syndromic dysmorphism (e.g., craniofacial, spinal dysraphism, cardiac) Diagnostics:- Antenatal ultrasound: most cases are diagnosed on routine antenatal ultrasound→ Fluid-filled stomach/bowel seen in the thorax→ Peristalsis may also be noted in the chest, confirming the diagnosis.→ Esophageal compression can cause polyhydramnios→ Hydrops fetalis may also be seen in severe cases  - Chest x-ray:→ Abdominal contents, air/fluid-filled bowel, and poorly aerated lung in the ipsilateral hemithorax→ Mediastinal shift to the right + compression of the contralateral lung→ In doubtful cases, a naso-gastric tube is inserted and a chest radiograph is taken: the feeding tube will be seen in the thorax.→ In right-sided CDH: the liver appears as an intrathoracic soft tissue mass + absence of the normal intra-abdominal liver shadow Treatment:- Prenatally diagnosed CDH: Antenatal glucocorticoids  Postnatal therapy:- Correction of hypoxemia→ Intubation + mechanical ventilation: indicated in all infants with CDH  → Extracorporeal life support (ECLS)- Gastric decompression: insertion of a nasogastric tube + continuous suction  - Inotropic support may be required to maintain blood pressure- Surfactant administration: in infants born < 34 weeks of gestation and x-ray findings suggesting neonatal respiratory distress syndrome- Surgical repair (thoracotomy or laparotomy): Indicated in all cases of CDH→ Timing: after the infant is stabilized, often after 24-48 hours  → Procedure: reduction of the hernial contents + primary closure of the defect  
• Congenital toxoplasmosis Transmission:- Mother: Cat feces, Raw or insufficiently cooked meat, Unpasteurized milk (especially goat milk)- Fetus: Transplacental transmission→ Third trimester: ∼ 70% transmission rate→ First trimester: ∼ 15% transmission rate Clinical features:- Classic triad of toxoplasmosis1. Chorioretinitis (a form of posterior uveitis)  2. Diffuse intracranial calcifications3. Hydrocephalus- Petechiae and purpura (blueberry muffin rash)  - Fever- Seizures- Jaundice- Hepatosplenomegaly- Lymphadenopathy- Pneumonitis- Thrombocytopenia Sequelae of congenital toxoplasmosis:- Epilepsy- Intellectual disability- Visual disabilities (chorioretinitis → increased risk of retinal lesions, cataracts, and glaucoma)Diagnostics:- PCR for T. gondii DNA in amniotic fluid  - Newborn→ CT/MRI: intracranial calcifications, hydrocephalus, ring-enhancing lesions  → T. gondii-specific IgM antibodies (CSF, serum)→ PCR for T. gondii DNA (CSF, serum)→ Ophthalmological evaluation: chorioretinitis   Treatment- Mother: immediate administration of spiramycin- Fetus: When confirmed or highly suspected, switch to pyrimethamine, sulfadiazine, and folinic acid.  - Newborn: pyrimethamine, sulfadiazine, and folinic acid
• Congenital syphilis Early congenital syphilis (onset < 2 years of age)  - Hepatomegaly and jaundice- Rhinorrhea with white or bloody nasal discharge  - Maculopapular rash on palms and soles  - Skeletal abnormalities (e.g., metaphyseal dystrophy, periostitis)- Generalized lymphadenopathy (nontender) Late congenital syphilis (onset > 2 years of age)- Typical facial features: saddle nose, frontal bossing, short maxilla- Dental findings: Hutchinson's teeth (notched, widely spaced teeth); mulberry molars (poorly developed first molars)  - Eyes and ears: interstitial keratitis, sensorineural hearing loss- Skin: rhagades (perioral fissures), gummas- Skeletal: saber shins (anterior bowing of the tibia), painless arthritis in knees and other joints- Neurological: cranial nerve palsies (e.g., CN VIII defect causing deafness), intellectual disability, hydrocephalusDiagnosis:- Newborn and mother→ Initial test: RPR or VDRL (serum)→ Confirmatory test: dark-field microscopy or PCR of lesions or bodily fluids  - Fetus: repeated ultrasound examinations (placentomegaly, hepatomegaly, ascites, and/or hydrops fetalis)  Treatment:- 14 days of IV penicillin G for both pregnant women and newborns
• Congenital listeriosis Transmission:- Mother: Contaminated food: especially raw milk products- Fetus: Transplacental transmission from an infected mother/Direct contact with infected vaginal secretions and/or blood during delivery Clinical features:- Increased risk of premature birth and spontaneous abortion- Early-onset syndrome: granulomatosis infantiseptica→ Severe systemic infection characterized by disseminated abscesses (may develop in any organ system)→ Most common findings: respiratory distress and skin lesions→ Signs of meningitis may already develop. Transmission during birth or postnatally (via contact with the mother or contaminated environment)- Late-onset syndrome (5 days to 3 weeks after birth): Listeria meningitis/encephalitis Diagnosis:- Culture from blood or CSF samples (pleocytosis)   Treatment:- IV ampicillin and gentamicin (for both mother and newborn)
• Pathologic jaundice Causes of pathologic indirect hyperbilirubinemia:- Hemolytic:→ Infection or sepsis (infections in the newborn)→ Hematomas (e.g., from vacuum-assisted delivery, vitamin K deficiency bleeding)  → Hemolytic disease of the newborn (ABO incompatibility, Rhesus incompatibility)→ RBC structural defects (spherocytosis, hereditary elliptocytosis)→ Ineffective erythropoiesis (thalassemias)→ Glucose-6-phosphate dehydrogenase deficiency- Nonhemolytic:→ Hyperbilirubinemia syndromes (e.g., Crigler-Najjar syndrome, Gilbert's syndrome)→ Glucuronyl transferase deficiency  → Increased enterohepatic circulation: e.g., high GI obstruction (pyloric stenosis, bowel obstruction)→ Other causes: medication, hypothyroidism, malnutrition, polycythemia Causes of pathologic direct hyperbilirubinemia:- Decreased bilirubin excretion: → Intrahepatic cholestasis: Sepsis, Hepatitis A, Hepatitis B, TORCH infections, Cystic fibrosis→ Extrahepatic cholestasis: Biliary atresia, Choledochal cyst, Tumors/strictures- Intrahepatic pathologies: Infectious hepatitis, Metabolic diseases (Dubin-Johnson syndrome, Rotor syndrome), Galactosemia, Alpha-1-Antitrypsin deficiency, Hypermethioninemia), Idiopathic neonatal hepatitis, Alagille syndrome   Clinical features:- Onset of jaundice: can appear < 24 hours after birth; can persist > 1 week in term infants and > 2 weeks in preterm infants- Acute bilirubin encephalopathy (onset within first days of life) → Lethargy, hypotonia (floppy infant syndrome), poor feeding→ Fever, shrill cry→ Stupor, apnea, seizures→ Possibly fatal if neurotoxicity is severe- Kernicterus/chronic bilirubin encephalopathy (develop over first years of life)  → Cerebral paresis, hearing impairment, vertical gaze palsy→ Movement disorder (athetosis)→ Apparent intellectual and developmental disabilities  → Dental enamel hypoplasia Treatment:1. Phototherapy- Phototherapy is the primary treatment in neonates with unconjugated hyperbilirubinemia.- Indications:→ Increase of total serum bilirubin above the threshold for phototherapy (children > 95th percentile on nomogram (e.g., > 15 mg/dL in a 48-hour-old term infant, > 20 mg/dL in 96-hour-old infant))  - Contraindication: ↑ direct (conjugated) bilirubin → danger of “bronze baby” syndrome  - Continued until total bilirubin levels < 15 mg/dL  - Adequate fluid supplementation to prevent dehydration- Eye protection against UV light- Side effects: Diarrhea, dehydration, Changes in skin hue (bronzing) and skin rashes2. Exchange transfusion- Most rapid method for lowering serum bilirubin concentrations- Indications:→ Threshold in a 24-hour-old term baby is a total serum bilirubin value > 20 mg/dL  → Inadequate response to phototherapy, or a rapid rise in the total serum bilirubin level (> 1 mg/dL/hour in less than 6 hours)→ Acute bilirubin encephalopathy→ Hemolytic disease, severe anemia- Exchange blood in quantities of 5-20 mL via an umbilical venous catheter until total serum bilirubin is < 95th percentile on nomogram.3. IV immunoglobulin- Used in cases with immunologically mediated conditions, or in the presence of Rh, ABO, or other blood group incompatibilities that cause significant neonatal jaundice- Dose range for IVIG: 500-1000 mg/kg
• Eczema Epidemiology:- About 10-15% of all children are affected- Onset of symptoms usually occurs between 3-6 months of age Triggers:- Exposure to indoor dust- Heat- Extremely dry or humid climate  - Emotional stress- Infections- Skin irritation Clinical features:- Main symptoms: intense pruritus and dry skin  - Infantile AD (age < 2 years):→ Eczema: over the cheeks, face, head, and extensor surfaces of the extremities that usually spares the diaper area→ May begin as cradle cap  → Dennie-Morgan fold: increased folds below the eye  - Childhood AD (age 2 to 12 years):→ Eczema: flexural creases (antecubital fossa and popliteal fossa), skin folds, extensor surface of hands→ Lesions usually become lichenified (lichenification is thickening of the skin with accentuated skin markings) - Adult/adolescent AD (age > 12 years):→ Lichenified lesions and pruritus of flexor surfaces of the extremities→ Adult AD may also present as nummular eczema (coin-shaped lesions over skin surface, usually 1-3 cm in diameter) Associated findings:- Atopic triad: triad of asthma, allergic rhinitis, and atopic dermatitis- Xerosis- White dermographism: a physical finding of transiently blanched skin after skin stroking. - Dermatographism: formation of urticaria after minor pressure is applied to the skin, likely mediated by local histamine release.- Hertoghe sign: thinning or loss of the outer third of the eyebrows Treatment:- Avoid triggers: Allergic trigger factors (pets, dust mites, pollen, certain foods), Irritants (clothing, chemicals), Heat- Keep the skin moist- Breast feeding recommended during infancy- Manage/eliminate stress- Mild AD: Emollients, Topical steroids (mild potency)- Moderate AD: Emollients, Topical steroids (intermediate potency), Topical calcineurin inhibitors- Severe AD: Emollients, Topical steroids (high potency), Topical calcineurin inhibitors, Phototherapy (narrow band UVB), Systemic therapy Complications:- Secondary infections→ Bacterial: staphylococcal skin infections  → Viral: eczema herpeticum→ Mycosal: tinea (especially Trichophyton rubrum)- Psychosocial complications: Sleep problems, Decreased quality of life
• Erythema toxicum neonatorum Erythema toxicum is a benign, self-limiting rash that appears within the first week of life. Etiology: unknown (probable contributing factors: immature sebaceous glands and/or hair follicles) Clinical features:- Small, red macules and papules that progress to pustules with surrounding erythema- Located on trunk and proximal extremities; spares the palms of hands and soles of feet Diagnosis:- Based on clinical appearance of rash- Biopsy or smear of pustula (rarely necessary): ↑ eosinophils Treatment: observation only Prognosis: typically resolves without complications within 7-14 days
• Congenital dermal melanocytosis (Mongolian spot) Benign blue-gray pigmented skin lesion of newborns Neonatal prevalence:- Asian and Native American: 85-100%- African American: > 60%- Hispanic: 46-70% - White: < 10% Pathogenesis: melanocytes migrating from the neural crest to the epidermis during development become entrapped in the dermis Clinical features:- Blue-gray pigmented macule (may also be green or brown)- Diameter: typically < 5 cm, may be > 10 cm- Location: most common on the back, also seen on the buttocks, flanks, and shoulders Diagnosis: Based on clinical appearance- It is important to document the diagnosis of Mongolian spots, as they may resemble bruises and lead to false suspicions of child abuse Prognosis: usually resolves spontaneously during childhood (typically by the age of 5)
• Congenital melanocytic nevi Epidemiology: 1/20,000 births Clinical features:- Vary in size: < 1.5 cm to > 40 cm; > 40 cm in size = giant congenital melanocytic nevus).- Light to darkly pigmented lesion- Often with increased hair growth Treatment: surgical excision or laser treatment (depending on type and size of lesion) Prognosis: Large nevi are at risk of degeneration → frequent follow-up
• Milia neonatorum Tiny epidermal papules on the face caused by the buildup of keratin and sebaceous secretions. These pinhead-sized lesions resolve without treatment.
• Infantile seborrheic dermatitis Onset: occurs shortly after birth   Clinical features:- Erythematous (or salmon-colored) scaling plaques → greasy, yellow, adherent scales- Location: scalp (common; also known as cradle cap), forehead, nose, external ear, umbilical area, or intertriginous areas- Pruritus (rarely)- Usually a clinical diagnosis Differential diagnosis:- Atopic dermatitis: While seborrheic dermatitis typically presents during the first 3 months of life, atopic dermatitis tends to appear at a later stage. - Diaper dermatitis: usually spares intertriginous areas (skin folds) Treatment:- Usually resolves spontaneously without medical therapy- Regular bathing, use of baby shampoos, and application of an emulsifying ointment may help relieve symptoms.- Topical corticosteroids (low potency) and ketoconazole in severe cases Complications (rare):- Erythroderma- Leiner disease: most severe form of infantile seborrheic dermatitis presenting with erythroderma, recurrent diarrhea, and failure to thrive  
• Measles (Rubeola) Epidemiology:- Distribution: Measles typically occurs in regions with low vaccination rates and in developing countries.- Peak incidence: < 12 months of age  - Infectivity: ∼ 90%; highly contagious 5 days before and up to 4 days after the onset of exanthem.  Clinical features:- Incubation period: 2 weeks after infection- Prodromal stage (catarrhal stage)→ Duration: lasts ∼ 4-7 days→ Presentation: Coryza, Cough, and Conjunctivitis (the “3 Cs”)  → Fever  → Koplik spots: Pathognomonic enanthem of the buccal mucosa. Tiny white or bluish-gray spots, resembling "grains of sand", on an irregular erythematous background.- Exanthem stage→ Duration: appears 1-2 days after enanthem and lasts ∼ 7 days→ High fever, malaise  → Generalized lymphadenopathy→ Erythematous maculopapular, blanching, partially confluent exanthem  → Usually begin in the face, frequently behind the ears along the hairline→ Disseminates to the rest of the body towards the feet (palm and sole involvement is rare)→ The rash begins to fade after ∼ 5 days of onset; leaving a brown discoloration and desquamation in severely affected areas Diagnostics:- CBC: ↓ leukocytes, ↓ platelets- Gold standard: Serology detection of Measles-specific immunoglobulin M (IgM) antibodies   Treatment:- Symptomatic treatment  - Vitamin A supplementation  - PEP in patients without prior vaccination
• Erythema infectiosum (fifth disease) Peak incidence: 5-15 years Pathogen: Human parvovirus B19   Disease course- Incubation period: 4-14 days- Infectivity: Only contagious before onset of rash- Asymptomatic in ∼ 25% of cases Clinical symptoms:- Mild cold‑like symptoms  - Exanthem: 2-5 days following the onset of cold‑like symptoms  - Initial diffuse redness of the face with perioral sparing (slapped‑cheek rash)- Spread of exanthem to the extremities and trunk→ Initially confluent and maculopapular; adopts a lace‑like, reticular appearance over time as it clears.→ Associated with mild pruritus (in ∼ 50% of cases)→ Fades after ∼ 7–10 days; may be recurrent over several weeks (becoming more pronounced after exposure to sunlight or heat) - Third phase with rash that varies with exposure to sun or heat and resolves spontaneously after several weeks.Parvovirus B19-associated arthritis:- Epidemiology: affects < 10% of children and up to 60% of adults (♀ > ♂) infected with parvovirus B19  - Arthralgia with symmetrical, nondestructive polyarthritis, particularly in the joints of the fingers, hand, knee, and ankle  - Usually resolves after 3-4 weeks Diagnostics:- Erythema infectiosum is typically a clinical diagnosis (i.e., slapped‑cheek or lace‑like appearance of rash) in children.- Adults: Lab tests only if diagnosis is unclear→ Antibody testing- Differentiating between parvovirus B19‑associated arthritis and acute rheumatoid arthritis may require additional tests- Patients with transient aplastic crisis and immunocompromised patients→ CBC with reticulocytes: ↓ Reticulocytes (0–1%), ↓ Hemoglobin below patient's baseline by ≥ 2 g/dL (aplastic crisis) or (< 8 g/dL) (severe anemia as in pure red cell aplasia)→ Initial diagnostic test: viral DNA testing (nucleic acid amplification testing (NAAT) such as PCR of blood or bone marrow) → Adjunctive diagnostic test: serologic antibody testing (in immunocompetent adults)   Treatment:- Treatment is not necessary in most cases, as the disease is often self-limiting- Analgesics and nonsteroidal anti‑inflammatory drugs (NSAIDs)- Short course of low‑dose prednisone for parvovirus B19‑associated arthritis
• Roseola infantum Epidemiology:- Most frequent in infants and young children- Peak incidence: 6 months to 2 years   Pathogen: HHV-6 (and in rare cases HHV-7)- Incubation period: 5-15 days Clinical features:- Febrile phase→ Duration: 35 days→ Abrupt onset of high fever, in some cases > 40ºC (104ºF)  → Frequent cause of emergency room visits for febrile illness→ Cervical, postauricular, and/or occipital lymphadenopathy→ Inflamed tympanic membranes→ Nagayama spots: papular enanthem on the uvula and soft palate→ Mild upper and lower respiratory symptoms (pharyngitis, cough, etc.)→ Vomiting and/or diarrhea→ Conjunctivitis and edema of the eyelid- Exanthem phase→ Duration: 1-3 days→ Characteristic presentation: subsequent sudden decrease in temperature and development of a patchy, maculopapular exanthem→ Rose-pink in color; blanches upon pressure→ Nonpruritic (DDx: drug allergy!)→ Originates on the trunk; sometimes spreads to the face and extremities Diagnostics: clinical Treatment:- Symptomatic treatment (e.g., fluids and possibly acetaminophen to reduce fever)
• Mumps Epidemiology:- Sex: ♂ = ♀ for parotitis (however, males are three times more likely to have CNS complications)- Peak incidence: 5-14 years of age Clinical features:- Incubation period: 16-18 days- Asymptomatic course in ∼ 20% of cases- Nonspecific or predominantly respiratory symptoms in ∼ 50% of cases- Prodrome: → Duration: 3-4 days→ Low-grade fever, malaise, headache- Classic course (in ∼ 30% of cases): inflammation of the salivary glands, particularly parotitis  → Duration of parotitis: at least 2 days (may persist > 10 days)→ May initially present with local tenderness, pain, and earache→ Swelling on one side is initially observed. During the course of disease, both salivary glands are usually swollen. → Usually self-limiting with a good prognosis (unless complications arise) Diagnostics: Laboratory tests, if available, should be conducted to confirm the suspected cases (especially if presentation is atypical or there is a mumps outbreak).- Positive serology confirms the diagnosis: IgG and/or IgM  - Relative lymphocytosis- ↑ CRP, ↑ ESR- ↑ amylase Treatment:- Symptomatic therapy: Medication for pain and fever (e.g., acetaminophen), bedrest, adequate fluid intake, avoidance of acidic foods and drinks, ice packs to soothe parotitis Complications:- Orchitis (< 10% of cases; most common complication in post-pubertal males)→ Primarily unilateral, although bilateral in ∼ 15% of cases→ Sudden onset of fever, nausea, vomiting→ On examination: swollen and tender affected testicle(s)→ May lead to atrophy and, in rare cases, infertility  - Aseptic meningitis (1-10% of cases): predominantly mild course; usually no permanent sequelae  - Encephalitis (< 1% of cases): Reduced consciousness, seizures, neurological deficits: cranial nerve palsy, hemiplegia, sensorineural hearing loss (rare)- Acute pancreatitis (< 1% of cases): Vomiting, nausea, upper abdominal pain, ↑ Lipase in addition to ↑ amylase, Diabetes mellitus type I (delayed complication)  
• Congenital adrenal hyperplasia CAH is caused by autosomal recessive defects in enzymes that are responsible for the production of cortisol.There are three subtypes of CAH:- 21β-hydroxylase (∼ 95% of CAH)- 11β-hydroxylase (∼ 5% of CAH)- 17α-hydroxylase (rare) 21β-hydroxylase:- Hypotension  - XX genotype: → Female pseudohermaphroditism: clitoromegaly and/or male external genitalia along with a uterus and ovaries  → Precocious puberty  → Virilization, irregular menstrual cycles, infertility  - XY genotype: Normal male external genitalia at birth, Precocious puberty   11β-hydroxylase- Hypertension- XX genotype: → Female pseudohermaphroditism: clitoromegaly and/or male external genitalia along with a uterus and ovaries  → Precocious puberty  → Virilization, irregular menstrual cycles, infertility  - XY genotype: Normal male external genitalia at birth, Precocious puberty   17α-hydroxylase:- Hypertension- XX genotype: → Normal female external genitalia at birth→ Delayed puberty (primary amenorrhea) or sexual infantilism  - XY genotype: → Male pseudohermaphroditism: female external genitalia with a blind-ending vagina and intra-abdominal testes at birth  → Delayed puberty or sexual infantilism All:- Hypoglycemia  - Adrenal crisis → vomiting and diarrhea → dehydration- Failure to thrive  - Hyperpigmentation in areas that are not exposed to sunlight (e.g., palm creases, mucous membranes of the oral cavity, genitalia) is a common feature in all forms of CAH.   Diagnostics:- Screening is conducted by measuring 17-hydroxyprogesterone (also for newborns).  - If steroid precursors are not elevated at baseline but CAH is still suspected, administer exogenous ACTH (cosyntropin) and measure again (see ACTH stimulation test).  → Hypocortisolism is seen in all forms of CAH, and cortisol levels remain low even after administration of cosyntropin.- Specific patterns of electrolyte and/or acid-base disorders are associated with specific enzyme deficiencies. Treatment:- Glucocorticoid replacement therapy is indicated in all forms of CAH.  - Lifelong daily regimen→ Hydrocortisone in neonates and children→ Prednisolone or dexamethasone in adolescents and adults- Steroid stress dosing- 21β-hydroxylase deficiency: Lifelong fludrocortisone therapy (aldosterone substitution), sodium chloride (salt) supplements, especially during infancy and childhood- 11β-hydroxylase deficiency: Spironolactone to block mineralocorticoid receptors, reduced dietary sodium intake- 17α-hydroxylase deficiency: Spironolactone to block mineralocorticoid receptors, estrogen replacement therapy for female genotype; may be started in early puberty, reduced dietary sodium intake- Salt-wasting CAH: Fluid resuscitation with intravenous normal saline, intravenous dextrose in patients with significant hypoglycemia, immediate administration of glucocorticoid replacement therapy
• Precocious puberty The appearance of secondary sexual characteristics before the age of 8 years in girls and 9 years in boys. Classification:- Central precocious puberty (gonadotropin-dependent precocious puberty, true precocious puberty)- Peripheral precocious puberty (gonadotropin-independent precocious puberty, peripheral pseudopuberty) Central precocious puberty: precocious puberty with elevated GnRH levels- Etiology→ Idiopathic or constitutional (most cases)→ CNS lesions→ Pituitary gonadotropin-secreting tumors (rare)→ Systemic conditions: tuberous sclerosis, neurofibromatosis→ Obesity-related precocious sexual development due to increased levels of leptin in obesity- Diagnosis→ Basal LH and FSH: increased  → GnRH stimulation test (gold standard): Gonadotropin (LH und FSH) levels increase after intravenous administration of GnRH.  → Sex hormones: ♂: ↑ serum testosterone; ♀: ↑ serum estradiol→ Brain MRI/CT with contrast→ X-ray of the left hand  - Therapy: GnRH agonist (e.g., leuprolide, buserelin), with close monitoring of therapy   Peripheral precocious puberty- Etiology→ ↑ Androgen production, e.g.: Ovarian cyst (most common cause), Congenital adrenal hyperplasia, Virilizing ovarian and adrenocortical tumors, Leydig-cell tumor→ ↑ Estrogen production, e.g.: hCG-secreting germ cell tumors (e.g., granulosa cell tumor), adrenal gland tumors that produce estrogen, McCune-Albright syndrome  → ↑ β-hCG production: e.g., hepatoblastoma→ Primary hypothyroidism- Diagnosis→ Imaging: ultrasound of the pelvis, testicles, and abdomen→ Laboratory tests: ↑ Estrogen/testosterone (depending on the tumor), ↓ FSH, ↓ LH  → Tests to detect primary underlying causes: e.g., TSH, FT3, β-hCG, CT/MRI- Therapy→ Precocious puberty caused by excessive hormonal production from a tumor in the body: surgical removal→ Precocious puberty caused by CAH: cortisol replacement → Ovarian cysts: No intervention is necessary, as spontaneous resolution of ovarian cysts is common.
• Meningitis Etiology:- Otitis media- Sinusitis- CSF leak after head trauma or neurosurgery- Sepsis Risk factors:- Immunocompromise (e.g., due to AIDS, asplenia, heavy alcohol use disorder, chronic illness, cancer, sickle cell anemia, old age, pregnancy)- Crowded living conditions (e.g., college dormitories, military barracks, retirement homes (listeriosis), kindergartens)- Close contact with an infected person Newborns:- Group B streptococcus (most common but incidence decreasing because of screening and prophylaxis during pregnancy)- Escherichia coli- Listeria monocytogenes- Haemophilus influenzae Infants:- Streptococcus pneumoniae and Neisseria meningitidis (most common)- Haemophilus influenzae  - Listeria monocytogenes Children and teenagers:- Neisseria meningitidis (most common)- Streptococcus pneumoniae- Listeria monocytogenes- Haemophilus influenzae if not immunized   Clinical features: Neonates - Early symptoms: Lethargy, Muscle hypotonia, Irritability, Poor appetite, vomiting, Hyperthermia or hypothermia, Dyspnea, abnormal breathing patterns (e.g., Biot respiration)- Late symptoms: Fontanelle bulging, High-pitched crying, Seizures Diagnostics- Blood cultures should be performed before antibiotic therapy is started- Lumbar puncture → Approach: essential in all patients with suspected meningitis, unless there are signs of increased intracranial pressure, which include:  → History of space-occupying CNS lesions, hydrocephalus, CSF shunts, or CNS trauma→ Focal neurological deficits→ Altered mental status→ Seizures→ Papilledema- If LP is contraindicated: initiate empiric antibiotic treatment immediately and conduct CT before LP to rule out ↑ ICP   Management algorithm:1. Blood cultures2. Lumbar puncture for CSF Gram stain and culture  3. Immediate empirical treatment< 1 month: ampicillin PLUS aminoglycoside (e.g., gentamicin) PLUS third-generation cephalosporin (e.g., cefotaxime or ceftriaxone)> 1 month to < 50 years: vancomycin PLUS third-generation cephalosporin (e.g., cefotaxime or ceftriaxone)- Possibly dexamethasone: for suspected or confirmed HiB meningitis
• Kawasaki disease Clinical diagnosis requires fever for at least 5 days and:≥ 4 other specific symptoms, or< 4 specific symptoms if the coronary arteries are involved Specific symptoms- Erythema and edema of hands and feet, including the palms and soles (the first week)→ Possible desquamation of fingertips and toes (after 2-3 weeks)- Polymorphous rash, originating on the trunk- Painless bilateral “injected” conjunctivitis without exudate- Oropharyngeal mucositis→ Erythema and swelling of the tongue (strawberry tongue)→ Cracked and red lips- Cervical lymphadenopathy (mostly unilateral)Nonspecific symptoms may precede the onset of Kawasaki disease (e.g., diarrhea, fatigue, abdominal pain) Diagnostics:- Laboratory findings: ↑ ESR and CRP, Leukocytosis, Thrombocytosis- Echocardiography: for evaluating coronary artery aneurysms→ Minimal evaluation: should be performed at diagnosis, at 2 weeks, and at 6-8 weeks after onset Treatment:- IV immunoglobulin (IVIG) → High single-dose to reduce the risk of coronary artery aneurysms→ Most effective if given within the first 10 days following disease onset- High-dose oral aspirin  - IV glucocorticoids: may be considered in addition to standard treatment in high-risk patients, as they lower the risk of coronary involvement; also in cases of treatment-refractory disease
• Severe combined immunodeficiency (SCID) A rare genetic condition caused by numerous genetic mutations that result in the defective development of functional B cells and T cells.- X-linked recessive: Defective IL-2R gamma chain (most common SCID mutation)- Autosomal recessive: Adenosine deaminase (ADA) deficiency, Janus-associated kinase 3 (JAK3) deficiency Clinical features:- Normal at birth- Severe, recurrent infections: bacterial diarrhea, chronic candidiasis (thrush), viral and protozoal infections- Failure to thrive- Chronic diarrhea- Lymph nodes and tonsils may be absent Diagnosis:- Quantitative PCR: ↓ T-cell receptor excision circles (TRECs)- Flow cytometry: absent T cells  - CXR: absent thymic shadow- Lymph node biopsy: absent germinal centers Treatment:- IV immunoglobulins- PCP prophylaxis- Bone marrow transplant or stem cell transplantation- Avoidance of live vaccines- Confinement to sterile environments (hence “bubble boy disease”) Prognosis: often fatal in the first year of life if left untreated
• Wiskott-Aldrich syndrome (WAS) Genetic condition characterized by impaired function of T cells and thrombocytopenia Etiology: mutated WASp gene (X-linked recessive inheritance) → impaired signaling to actin cytoskeleton reorganization → defective antigen presentation Epidemiology: occurs primarily in males Clinical features:- Onset of symptoms: from birth- Classic triad:1. Eczema (high risk of atopic disorders)2. Bleeding diathesis3. Recurrent opportunistic infections with encapsulated organisms in the first years of life (e.g., otitis media)- Increased risk of autoimmune diseases and hematological malignancies (e.g., lymphoma, leukemia) Diagnosis:- Normal or ↓ IgG and IgM- ↑ IgE and IgA- Thrombocytopenia with small platelets- Genetic analysis (confirmatory test): mutated WASp gene Treatment:- IV immunoglobulin therapy- Prophylactic antibiotics- Platelet transfusions- Stem cell transplantation may be curative. Prognosis: shortened life expectancy
• Hyper-IgM syndrome A group of syndromes characterized by a class-switching defect of Th cells. Etiology:- X-linked recessive inheritance: Abnormal interaction between CD4 T cells and cells that express CD40 Clinical presentation- Recurrent sinopulmonary infections (commonly Pneumocystis jirovecii and Histoplasma)- Cryptosporidium enteritis (which may lead to biliary disease, cirrhosis, and cholangiocarcinoma)- CMV hepatitis- Failure to thrive Diagnosis:- ↓ IgG, IgA, IgE- Normal or ↑ IgM- Lymph node biopsy: absent germinal centers Treatment:- IV immunoglobulin therapy- Prophylactic antibiotics- Recombinant human granulocyte-colony stimulating factor- Stem cell transplantation may be curative.
• Ataxia telangiectasia (Louis-Bar syndrome) A DNA repair defect. Classic triad of 3 As:1. Progressive cerebellar ataxia  2. Spider angiomas: telangiectasias on face and conjunctivae3. IgA deficiency- Susceptibility to infections (e.g., otitis media, sinusitis, pneumonia)- Increased sensitivity to radiation- Increased risk of malignancy (lymphoma, leukemia, gastric carcinoma)- Other neurological symptoms: athetosis, chorea, myoclonus, neuropathy, slurred speech, oculomotor apraxia Treatment:- BMT for severe disease- IVIG for antibody deficiency.
• Bruton agammaglobulinemia (X-linked agammaglobulinemia) X-linked recessive disease that causes a complete deficiency of mature B lymphocytes. Epidemiology: occurs mainly in boys Etiology: defect of Bruton tyrosine kinase (BTK) expressed in B cells Clinical features:- Onset is > 4 months after birth because of the continual decrease of maternal IgG in fetal serum.- Hypoplasia of tonsils and other lymphoid tissue- Recurrent, severe pyogenic infections (e.g., pneumonia, otitis media), especially with encapsulated organisms (S. pneumoniae, N. meningitidis, and H. influenzae)- Hepatitis virus and enterovirus (e.g., Coxsackie virus) infection Diagnosis:- Flow cytometry: Absent or low levels of B cells (marked by CD19, CD20, and CD21), normal or high T cells- Absent lymphoid tissue (e.g., tonsils) Treatment:- IV immunoglobulins- Prophylactic antibiotics
• Selective IgA deficiency Definition: most common primary immunodeficiency that is characterized by a near or total absence of serum and secretory IgA Epidemiology: approx. 1:220 to 1:1000 Clinical features- Often asymptomatic- May manifest with sinusitis or respiratory infections (S. pneumoniae, H. influenzae), chronic diarrhea (Giardiasis)- Associated with gluten-sensitive enteropathy, inflammatory bowel disease, atopy- Anaphylactic reaction to products containing IgA Diagnosis:- Decreased serum IgA levels (< 7 mg/dL)- Normal IgG and IgM levels- Increased susceptibility to Giardia infection Treatment:- Treatment of infections- Prophylactic antibiotics- Intravenous infusion of IgA is not recommended because of the risk of anaphylactic reactions (caused by the production of anti-IgA antibodies).
• Common variable immunodeficiency (CVID) Primary immunodeficiency with low serum levels of all immunoglobulins despite phenotypically normal B cells Epidemiology:- Sex: ♀ = ♂- Onset: presents later than other B-cell defects (usually at 20-35 years of age) Etiology: B cells are phenotypically normal but are unable to differentiate into Ig-producing cells, resulting in low immunoglobulins of all classes. Clinical features:- Recurrent pyogenic respiratory infections, e.g., sinopulmonary infections (in rare cases, enteroviral meningitis)- Associated with a high risk of lymphoma, gastric cancer, bronchiectasis, and autoimmune disorders (e.g., rheumatoid arthritis, autoimmune hemolytic anemia, immune thrombocytopenia, vitiligo) Diagnosis:- Quantitative immunoglobulin levels: low levels of IgG, IgA, and IgM- Decreased number of plasma cells- Flow cytometry shows subsets of normal B and T cells- Poor response to immunizations Treatment:- Treatment of infections- Prophylactic antibiotics- IV immunoglobulins
• DiGeorge syndrome (22q11.2 deletion syndrome) Syndrome characterized by defective development of the third and fourth pharyngeal pouches leading to hypoplastic thymus and parathyroids Etiology: autosomal dominant; microdeletion at chromosome 22 (22q11.2) Clinical features:- Cardiac anomalies: congenital heart diseases, e.g., tetralogy of Fallot, persistent truncus arteriosus, ventricular septal defect (VSD), atrial septal defect (ASD)- Anomalous face: dysmorphic facial features, including prominent nasal bridge, hypoplastic wing of the nose, dysplastic ears, micrognathia (small lower jaw)  - Thymus aplasia/hypoplasia → recurrent infections due to T-cell deficiency (viral/fungal/PCP pneumonia)- Cleft palate- Hypocalcemia due to hypoparathyroidism → tetany Diagnosis:- Detection of 22q11.2 deletion via fluorescence in situ hybridization (FISH)- ↓ PTH and Ca2+- ↓ Absolute T-lymphocyte count- Delayed hypersensitivity skin testing- CXR: absence of thymic shadow Treatment:- Antibiotics, virostatics, and antimycotics- PCP prophylaxis- Consider bone marrow transplant and/or IVIG- Possible thymus transplantation   Prognosis: poor if not treated (patients usually do not survive beyond childhood)
• Autosomal dominant hyperimmunoglobulin E syndrome (Job syndrome) Defect in neutrophil chemotaxis Etiology: autosomal dominant: STAT3 mutation → decreased Th17 cells → defect in neutrophil/macrophage recruitment Clinical features:- Coarse facies- Abscesses, recurrent bacterial (staphylococcal) infections- Retained primary teeth- Hyper-IgE (eosinophilia)- Dermatologic (severe eczema)- Other features: Decreased bone density increases the risk of bone fractures following minor trauma. Diagnosis:- ↑ IgE- (Variable) eosinophilia- ↓ INF Treatment:- Antibiotics and prophylaxis (with penicillinase-resistant antibiotics)- IV immunoglobulin therapy
• IL-12 receptor deficiency Impaired Th response due to ↓ IL-12 receptors   Etiology: autosomal recessive Pathophysiology: Normally, antigen-presenting macrophages release IL-12 → Th cells transform to T1 type → release of IFN-γ to activate macrophagesDefective IL-12 receptors: macrophages cannot be activated by IFN-γ → no cytotoxicity in cells infected with intracellular pathogens (e.g., Mycobacteria, Salmonella) Clinical features:- The age of onset varies (depends on the age at exposure to causative pathogens): ∼ 1-3 years of age- Features of disseminated disease, especially tuberculosis (e.g., following administration of BCG vaccine)- Fungal infections Diagnosis: ↓ IFN-γ Treatment: antibiotics and IFN-γ therapy
• Chronic mucocutaneous candidiasis Impaired or absent T-cell response to Candida antigens Etiology: several congenital defects that result in impaired T-cell function- The majority of cases are caused by autoimmune regulator (AIRE protein) deficiency. Pathophysiology: defects in IL-17 and IL-17 receptors → impaired immune response to Candida infections Clinical features:- Noninvasive Candida infections of the skin, mucous membranes, and nails- Associated autoimmune disorders (e.g., immune thrombocytopenic purpura, rheumatoid arthritis) Diagnosis:- Usually clinical- Absent in vitro T-cell proliferation when exposed to Candida antigen- Absent cutaneous reaction to Candida antigen Treatment:- Antifungal therapy- Treatment of associated conditions
• IPEX syndrome (immune dysregulation, polyendocrinopathy, enteropathy, X-linked) A syndrome characterized by a dysfunctional regulatory T-cell lineage that leads to autoimmunity as a result of disrupted tolerance to self-antigens. Etiology:- X-linked recessive- Mutation in transcription factor FOXP3 → unchecked activation of T cells against host tissues Clinical features:- Classically presents in early infancy- Lymphadenopathy and/or chronic lymphoid tissue hypertrophy (e.g., enlarged tonsils)- Eczema- Autoimmune endocrine conditions (e.g., hyperthyroidism or hypothyroidism, type 1 diabetes mellitus)- Chronic diarrhea- Failure to thrive Diagnosis:- Primarily based on clinical examination and family history- Genetic testing: mutations in FOXP3- Flow cytometry: severely reduced or absent CD4+CD25+ regulatory T cells with otherwise normal T-cell populations Treatment:- Nutritional support- Immunosuppression: tacrolimus, cyclosporine, or sirolimus- Rituximab- Bone marrow transplant
• Chronic granulomatous disease (CGD) Deficiency of superoxide production by polymorphonuclear neutrophils and macrophages Etiology:- X-linked recessive or autosomal recessive inheritance (2:1)- Defective phagocytic nicotinamide adenine dinucleotide phosphate (NADPH) oxidase- Defective ROS production: impaired ability to deactivate or kill ingested microorganisms- Decreased respiratory burst in neutrophils Clinical features:- Recurrent, severe infections (chronic skin, lymph node, bone, respiratory, GI, and urinary tract infections) with catalase-positive organisms (S. aureus, Nocardia spp., Escherichia coli, Candida, Klebsiella, Pseudomonas, Aspergillus, Serratia)- Anemia- Lymphadenopathy- Granulomas of the skin and GI/GU tract Diagnosis:- Neutrophil assay→ Dihydrorhodamine test (DHR): flow cytometry test showing abnormal NADPH oxidase activity (inability to metabolize dihydrorhodamine to fluorescent product, rhodamine → decreased green fluorescence)→ Nitroblue tetrazolium dye reduction test: negative.  - Hypergammaglobulinemia- Genotyping is confirmatory Treatment:- Treatment of infections- Life-long prophylactic antibiotics, e.g., TMP-SMX (for catalase-positive infections)- Glucocorticoids for severe inflammation- IFN-γ therapy  - Bone marrow transplant- Possibly gene therapy
• Leukocyte adhesion deficiency type 1 (LAD1) Genetic condition characterized by a defect in the leukocytic chemotaxis that results in decreased phagocyteactivity Etiology:- Autosomal recessive inheritance- Absence of the ß2-integrin leukocyte adhesion surface molecule LFA-1 (CD18) → Leukocytes are unable to migrate into tissues during infection or inflammation. Clinical features:- Recurrent nonsuppurative bacterial infections (e.g., skin and mucosal infections), impaired wound healing  - Wounds with minimal inflammation and no pus- Omphalitis- Delayed separation of the umbilical cord (> 2 weeks postpartum) Diagnosis:- Leukocytosis; however, neutrophils are absent at the site of infection!- Flow cytometry: absent CD18, CD11a, CD11b, and CD11c Treatment:- Prevention of further infections (e.g., adequate dental hygiene)- Treatment of infections- Bone marrow transplant
• Chédiak-Higashi syndrome Defect in neutrophil chemotaxis and microtubule polymerization dysfunction → defective phagosome-lysosome fusion Etiology: autosomal recessive; defective lysosomal trafficking regulator (LYST) gene Clinical features:- Recurrent pyogenic infections- Pathogens include S. pyogenes, S. aureus, and Pseudomonas spp.- Partial albinism- Progressive peripheral neuropathy- Hemophagocytic lymphohistiocytosis (can occur in the accelerated phase and is potentially fatal) Diagnosis:- Peripheral smear shows giant cytoplasmic granules in granulocytes and platelets- Mild coagulation abnormalities- Neutropenia Treatment: bone marrow transplant
• Terminal complement deficiency (C5-C9 deficiency) Inability to form antigen-antibody complex, resulting in defective opsonization and phagocytosis and inability to kill organisms Epidemiology: C5, C6, and C8 deficiency are the most common Etiology: autosomal recessive pattern Clinical features:- Recurrent pyogenic infections (e.g., meningococcal or gonococcal)- Associated with SLE and glomerulonephritis- Life-threatening sepsis may occur in prolonged disease. Diagnosis: CH50 assay screening test   Treatment:- Meningococcal vaccine- Prophylactic antibiotics
• C1 esterase inhibitor deficiency Autosomal dominant inheritanceUnregulated activation of kallikrein → ↑ bradykinin → angioedema Clinical features:- Recurrent angioedemas provoked by triggers, e.g., trauma, surgery, infections, and drugs- Airway edemas can be life-threatening. Diagnostics:- CH50 assay screening test- ↑ Bradykinin levels- Low C4 levels Treatment:- Acute: purified C1-INH concentrate, bradykinin-B2-receptor antagonist (icatibant), kallikrein inhibitor (ecallantide); FFP if other therapies are unavailable- Prophylaxis: long-term prophylaxis with attenuated androgens (e.g., danazol) or plasma-derived C1-INH concentrate
• Juvenile idiopathic arthritis Epidemiology:- Prevalence: 1/1000 children- Sex: ♀ > ♂- Age of onset: < 16 years Clinical features:- Arthritic symptoms: red, swollen joints, early morning stiffness, limited or painful joint movement  - Synovial thickening- Fever and other extra-articular manifestations (e.g., uveitis, rashes, nail changes, lymphadenopathy, hepatosplenomegaly) may be present depending on the type of JIA- Certain children may present with nonspecific features such as excessive crying, lethargy, decreased scholastic performance, and/or growing pains. Oligoarticular JIA: Arthritis involving ≤ 4 joints within 6 months of disease onset- Asymmetrical pattern- Large, weight-bearing joints (knee and ankle) are usually affected.  - Chronic anterior uveitis- Prognosis: Mostly good   Seronegative polyarticular JIA: Arthritis involving more than ≥ 5 joints within 6 months of disease onset Seropositive polyarticular JIA: Arthritis involving more than ≥ 5 joints within 6 months of disease onset- Rheumatoid nodules- RF positive Systemic JIA (Still's disease): Arthritis involving ≥ 1 joint ANDIntermittent fever that lasts for at least two weeks with fever spikes occuring on at least 3 consecutive days AND ≥ 1 extra-articular manifestation- Transient, migratory, salmon-pink rash  - Generalized lymphadenopathy- Splenomegaly and/or hepatomegaly- Serositis (peritonitis, pleuritis, and/or pericarditis) Diagnostics:- ↑ ESR is usually seen with all forms of JIA.- ↑ Acute phase reactants (e.g., CRP, ferritin) and leukocytosis are usually associated with systemic JIA.- ↑ ANA (antinuclear antigen) levels may be seen with oligoarticular, polyarticular, and psoriatic JIA.- Anti-CCP antibodies indicate a poor prognosis.  - CBC: Anemia, thrombocytosis, and/or leukocytosis are seen in the case of systemic JIA.  - Imaging (e.g., X-ray, ultrasound) of the affected joint  - Regular ophthalmological screening using slit lamp examination for anterior uveitis   Treatment:- First-line: NSAIDs  → Local intra-articular steroids (e.g., triamcinolone) are indicated in the case of active arthritis.- Second-line: Disease-modifying antirheumatic drugs (DMARDs)→ Therapy with DMARDs should be started as early as possible in the case of high disease activity.  → The DMARD of choice is determined on an individual basis with methotrexate being used in most cases.  - Biologic agents (e.g., etanercept, adalimumab, anakinra, tocilizumab) are indicated if the response to DMARDs is poor.  →  A short course of systemic glucocorticoid therapy may be prescribed in the severe cases Factors associated with a poor prognosis:- Early onset- Prolonged active systemic disease- Hip and/or wrist involvement- Polyarthritis- Symmetrical disease- Presence of RF- Presence of anti-CCP antibodies
• Henoch-Schonlein purpura Epidemiology:- Sex: ♂ > ♀- 90% of cases < 10 years old- Peak incidence: 6 years Etiology- Preceding infection→ > 75% of cases preceded by viral or bacterial infection 1-3 weeks prior→ Most commonly an upper respiratory tract infection caused by group A streptococcus→ GI infections also possible; many other organisms have also been associated with HSP- Genetic predisposition- Drugs (e.g., some antibiotics and antiarrhythmics) and vaccinations (e.g., yellow fever, cholera) Clinical features:- Skin (∼ 100% of cases): Symmetrically distributed, raised, erythematous macules or urticarial lesions that coalesce into palpable purpura (non-blanching skin lesions)→ Most common sites: the lower extremities, buttocks, and other areas of pressure or constraint (e.g., from socks or clothing)- Joints (∼ 75% of cases): arthritis/arthralgia, most common in the ankles and knees  - Gastrointestinal tract (∼ 60% of cases): → Colicky abdominal pain (may be severe enough to mimic an acute abdomen)→ Bloody stools or melena→ Nausea/vomiting- Kidneys (∼ 50% of cases): HSP nephritis with signs and symptoms of nephritic syndrome  - Scrotum (e.g., scrotal swelling, pain, and tenderness)- Central and peripheral nervous system (e.g., headaches, seizures, focal neurologic deficits, ataxia, intracerebral hemorrhage, central and peripheral neuropathy)- Respiratory tract (e.g., mild interstitial changes, pulmonary hemorrhage) Diagnostics: Clinical!- Laboratory tests: ↑ Platelet count, ↑ IgA in serum,↑ Creatinine and/or BUN, ↑ Inflammatory markers - Urinalysis: Hematuria, often with RBC casts, possibly proteinuria- Biopsy: reserved for patients with unusual skin presentations or severe renal involvement (e.g., persistent nephrotic syndrome)HSP is a unique cause of purpura without thrombocytopenia! Treatment:- Mild disease: No treatment necessary- Severe disease: Inpatient treatment→ Systemic glucocorticoids for severe abdominal pain not relieved by NSAIDs→ IV fluids to maintain hydration→ In case of severe renal disease: IV methylprednisolone pulse therapy Complications:- HSP nephritis may progress to nephrotic syndrome.  - Small bowel infarction or perforation- Intussusception  
• Ventricular septal defect (VSD) Epidemiology: The most common congenital heart defect (4/1000 live births) Etiology:- Genetic syndromes: Down syndrome, Edward syndrome, Patau syndrome  - Fetal alcohol syndrome- Intrauterine infection (e.g., TORCH) Clinical findings:- Small defects: usually asymptomatic- Medium-sized or large defects:→ Lead to cardiac failure in the first 2-3 months of life- Palpation: Hyperdynamic precordium may be detected in hemodynamically relevant defects.  - Harsh holosystolic murmur over the left lower sternal border; typically louder in small defects  - Becomes louder with maneuvers that increase left ventricular afterload (e.g., handgrip) because of increased left-to-right shunting- Mid-diastolic murmur over cardiac apex  - Systolic thrill  - Loud pulmonic S2 (if pulmonary hypertension develops) Diagnostics:- Doppler echocardiography: confirms diagnosis; evaluation of defect size and shunt volume; exclusion of other anomalies- ECG: signs of right heart hypertrophy- Chest x-ray: → Enhanced pulmonary vascular markings, left atrial and ventricular enlargement→ In later stages, enlarged right ventricle and pulmonary artery (due to elevated PVR) Treatment:- Small VSDs: rarely require surgical interventions → small to moderate defects often heal spontaneously; follow-up echocardiography recommended- Symptomatic and large VSDs: Surgical (patch) repair in children < 1 year of age with signs of pulmonary hypertension and older children who did not improve with medical therapy 
• Atrial septal defect (ASD) Etiology:- Down syndrome- Fetal alchohol syndrome- Holt-Oram syndrome   Clinical features:- Small defects: usually asymptomatic- Large defects: Palpitations  - ASDs typically manifest with advancing age.   Auscultation:- Systolic ejection murmur over the left second ICS sternal border  - Widely split second heart sound (S2) over the left second ICS, which is fixed (does not change with respiration, normal S1- Soft mid-diastolic murmur over the lower left sternal border   Diagnostics:- Echocardiography (confirmatory test): to visualize the defect, its extent, and shunt volume- ECG: vertical or right axis, P pulmonale, right bundle branch block (complete or incomplete), signs of right heart hypertrophy, PR prolongation- Chest x-ray: enlarged right atrium, ventricle, and pulmonary arch; increased pulmonary vasculature Treatment:- In childhood, spontaneous closure may occur.- Patch repair: Indicated in symptomatic children with significant left-to-right shunt→ Surgical or via percutaneous transcatheter procedure
• Patent ductus arteriosus (PDA) Epidemiology:- Sex: ♀ > ♂ (2:1) Etiology- In 90% of cases, PDAs occur as isolated defects; in 10% of patients, PDAs occur with other congenital heart defects.  - Premature infants  - Infants born at high altitude- Maternal rubella infection during pregnancy- Maternal prostaglandin administration- Trisomies (Down, Patau, and/or Edwards syndrome) Clinical features:- Small PDA: asymptomatic with normal findings on physical examination  - Large PDA: Nonspecific symptoms (e.g., failure to thrive) and symptoms of heart failure in infancy- Heaving, laterally displaced apical impulse  - Bounding peripheral pulses, wide pulse pressure (pulsus celer et altus)- Auscultatory findings: loud continuous murmur (“machinery” murmur); best heard in the left infraclavicular region   Diagnostics:- Echocardiography (confirmatory test)→ Shows left cardiac enlargement (in larger PDAs)→ Doppler: assesses degree of shunt and pulmonary artery pressure→ Color Doppler: demonstrates blood flow from the aorta into the pulmonary artery- ECG: normal in small PDA; left axis deviation due to LVH in large PDA- Chest x-ray: prominent pulmonary artery and aortic knob along upper left heart border; increased pulmonary markings - Cardiac catheterization and angiography: only necessary prior to repair or in more complex CHDs Treatment:- Observation: Regular evaluation of the heart and pulmonary vasculature is indicated in patients with a small PDA without evidence of left-sided heart volume overload.- Elective ductal closure→ Symptomatic PDAs→ Left heart enlargement or mild to moderate pulmonary hypertension  → Techniques: a) Pharmacologic closure (in premature infants): Infusion of indomethacin or ibuprofenb) In infants > 5 kg: percutaneous catheter occlusion or surgical ligation  - Administer prostaglandin (PGE1) if the PDA is needed for survival (e.g., in transposition of the grand vessels, tetralogy of Fallot, hypoplastic left heart).

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