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Paediatric Emergency Rounds Presenting Complaint: “My child has a RASH”. Kelly Millar. Overview of Topics. Varicella in the immunocompromised host Fever and petechiae Acute exfoliating conditions. A) wait and see B) oral acyclovir C) IV acyclovir D) VZIG E) call ID!?!. CASE 1
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Paediatric Emergency RoundsPresenting Complaint: “My child has a RASH” Kelly Millar
Overview of Topics • Varicella in the immunocompromised host • Fever and petechiae • Acute exfoliating conditions
A) wait and see B) oral acyclovir C) IV acyclovir D) VZIG E) call ID!?! CASE 1 3 yo on prednisone (2 mg/kg/d) for nephrotic syndrome 5 yo sibling just diagnosed with chicken pox No prev Varivax, no hx of CP infection What would you do?
CASE 2 • 3 yo on prednisone (2mg/kg/d) for nephrotic syndrome • just diagnosed with chicken pox • First lesion noted in past 24 hours • A) wait and see • B) oral acyclovir • C) IV acyclovir • D) VZIG • E) call ID!?! What would you do?
CASE 3 • 3 yo on flovent (125ug) 2 puffs BID for asthma maintenance • Just diagnosed with chicken pox • First lesion noted in past 24 hours • What if this child had received a 5 day course of prednisone (2mg/kg) 3 weeks ago? • A) wait and see • B) oral acyclovir • C) IV acyclovir • D) VZIG • E) call ID!?! What would you do?
How well are physicians doing? • General practice survey of the management of chickenpox: appropriate targeting of antiviral therapy. Shepherd et al. Family Practice (2001) 18(3):249-52 • Only 61.8% used antivirals when clear indication to do so • 32.6% used antivirals when not indicated
Varicella Exposure • Defined as household, play, or classroom contact with person who has varicella or who develops varicella within 48 hours • transmitted to 85-90% of susceptible household contacts • May be acquired after close physical contact with person with zoster
Varicella Prophylaxis Strategies • Varivax • VZIG • Acyclovir?
Varicella Prophylaxis - Varivax • Live attenuated • Seroconversion rates: • Children: > 95% after 1 dose • >13yrs: 80% after 1 dose, 99% after 2 doses • 3-5% develop localized lesions, another 3-5% generalized lesions (rarely transmissable) • Evidence for post-exposure prophylaxis if given within 72 hrs post-exposure
Varicella Prophylaxis - VZIG • Highly effective when given within 96 hrs of exposure • 10-15% have mild breakthrough infection • Prolongs incubation period (if admitted, must be isolated for 35 days post exposure)
Varicella Prophylaxis - Acyclovir • 3 recent studies on po acyclovir prophylaxis for healthy household contacts: • Acyclovir given for 5-7 days starting on day 7 post-exposure (coincides with viremia) • Decreases the rate of clinical varicella by 65% • Problem: Low varicella antibody titres • ? Protection against reinfection • ? Predisposition to early zoster
Varicella Prophylaxis - Acyclovir • No data for efficacy in immunocompromised patients • ? Possible role if VZIG unavailable or if patient presents > 96 hrs post-exposure
Who needs post-exposure prophylaxis? • No history of varicella PLUS one of: • Newborns whose mothers developed lesions from 5 days prior to 48 hrs post delivery • Pregnant women • Immunocompromised – high dose steroids in past 30 days, chemotherapy, BMT, immunosuppressives, congenital cellular immunodeficiencies, HIV
What about steroids? • Low dose: • < 1mg/kg/day prednisolone or equivalent • < 20 mg/day total prednisolone or equivalent • Inhaled steroids • High Dose: • > 1 mg/kg/day or > 20mg per day total of prednisolone or its equivalent • Beware of anabolic steroid users
What PEP should be used? In the immunocompromised? • If present within 96 hours post-exposure: • GIVE VZIG • If present after 96 hours post-exposure: • Consider acyclovir • Possible role for combined VZIG + po acyclovir In the healthy patient? • May offer Varivax within 72 hours of exposure
Treatment of Varicella:Who should receive acyclovir? * Initiate therapy within 24 hours of onset of rash
Treatment of Varicella:Who should receive acyclovir? • IV therapy should also be given to all severely ill patients regardless of risks • Severe disease = pneumonitis, hepatitis, encephalopathy, DIC, SIADH • Visceral dissemination is heralded by high fever, extensive rash, & severe abdominal or back pain
Why not use acyclovir for everyone? • Reduces mean # lesions from 347 to 294 • Fever defervesces 1 day earlier • No reduction in 2° bacterial infections, pneumonitis or cerebellitis • Does not reduce household transmission • S/E – headache, nausea, vomiting, rash • 1% - acute encephalopathy • ↑ risk in underlying neuro/renal disorders
Herpes Zoster • IV acyclovir for severely immunocompromised • PO acyclovir for mildly immunocompromised • Involvement of opthalmic branch of trigeminal: • po acyclovir (IV if < 2 years of age) • Optho consult
A) wait and see B) oral acyclovir C) IV acyclovir D) VZIG E) call ID!?! CASE 1 3 yo on prednisone (2 mg/kg/d) for nephrotic syndrome 5 yo sibling just diagnosed with chicken pox No prev Varivax, no hx of CP infection What would you do?
A) wait and see B) oral acyclovir C) IV acyclovir D) VZIG E) call ID!?! CASE 1 3 yo on prednisone (2 mg/kg/d) for nephrotic syndrome 5 yo sibling just diagnosed with chicken pox No prev Varivax, no hx of CP infection What would you do?
CASE 2 • 3 yo on prednisone (2mg/kg/d) for nephrotic syndrome • just diagnosed with chicken pox • First lesion noted in past 24 hours • A) wait and see • B) oral acyclovir • C) IV acyclovir • D) VZIG • E) call ID!?! What would you do?
CASE 2 • 3 yo on prednisone (2mg/kg/d) for nephrotic syndrome • just diagnosed with chicken pox • First lesion noted in past 24 hours • A) wait and see • B) oral acyclovir • C) IV acyclovir • D) VZIG • E) call ID!?! What would you do?
CASE 3 • 3 yo on flovent (125ug) 2 puffs BID for asthma maintenance • Just diagnosed with chicken pox • First lesion noted in past 24 hours • What if this child had received a 5 day course of prednisone (2mg/kg) 3 weeks ago? • A) wait and see • B) oral acyclovir • C) IV acyclovir • D) VZIG • E) call ID!?! What would you do?
CASE 3 • 3 yo on flovent (125ug) 2 puffs BID for asthma maintenance • Just diagnosed with chicken pox • First lesion noted in past 24 hours • What if this child had received a 5 day course of prednisone (2mg/kg) 3 weeks ago? • A) wait and see • B) oral acyclovir • C) IV acyclovir • D) VZIG • E) call ID!?! What would you do?
Fever and Petechiae In prospective cohort studies, 1.8% of children with fever > 38° have petechiae
CASE • An 18 mo old child presents with a fever of 38.9° and is noted by nursing staff to have petechiae. Remaining vitals are normal. • You assess the child to be content and non-toxic in appearance. You note mild URTI Sx and multiple petechiae on the chest and arms. The remainder of your exam is unremarkable. • How will you proceed?
Evaluation of febrile children with petechial rashes: is there consensus among pediatricians? DG Nelson et al. Ped Inf Dis J 1998;17:1135-40. management is highly variable!
Why do we worry? • Fever and petechiae may be a harbinger of septicemia • In the past, many authorities recommended blood cultures, lp, and admission for empiric IV antibiotics until cultures returned! • These recommendations where based on published series of in-patients with fever and petechiae where invasive bacteria where detected at rates of up to 17% • Probable selection bias as examined only in-patients
Who needs further investigation and treatment? • Toxic, hypotensive, significant lethargy or irritability Straightforward • Well appearing child not so easy
Can we be more selective in the ED? Incidence of bacteremia in infants and children with fever and petechiae. Mandl et al. J Pediat 1997;131:398-404. • Prospective cohort study of all children ≤ 18yrs presenting to the ED with fever and petechiae over an 18 mo period • N = 411 • Clinical features recorded: general appearance, number of petechiae, position of petechiae, whether a mechanical cause for petechiae was present, purpura • Labs recorded: CBC, cultures, coags, CSF
Fever & petechiae (418) Excluded (7) Included (411) Admitted (63%) D/C home (37%) Sepsis (N=8) Antibiotics (66%) 2 Meningococcus Sepsis (0%) 1 Gp A Strep 3 no growth* 2 pneumococcus Mandl et al – Children’s Hosp, Boston CBC (97%) Culture (95%) Coags (64%) LP (53%)
Sensitivity Specificity PPV NPV ill appearing 1.00 0.88 0.11 1.00 abN WBC 1.00 0.64 0.05 1.00 pet. below nipples 1.00 0.40 0.02 1.00 purpura 0.83 0.97 0.31 0.99 prolonged INR 0.67 0.98 0.40 0.99 Mandl et al – Children’s Hosp, BostonDiagnostic predictors for invasive bacteremia
Mandl et al – Children’s Hosp, Boston • “well appearing children with petechiae, but no purpura and normal WBC and INR and exceedingly unlikely to have serious invasive bacteremia” • No children with petechiae limited to above the nipple line had bacteremia
Do other out-patient studies agree? • The management of fever and petechiae: making sense of rash decisions. Brogan & Raffles. Arch Dis Child 2000;83:506-7. • Retrospectively and prospectively assessed the performance of a 5 factor screening test (N=55) • Factors = shock, lethargy, irritability, abnormal WBC, elevated CRP • 5 patients had bacterial sepsis • Sens 100%, Spec 60%, PPV 20%, NPV 100%
What about petechiae without fever? • LC Wells et al Arch Dis Child 2001 • Prospective cohort study of children aged <16 yrs presenting to the PED with non-blanching rash over a 12 month period • N=233, 15 excluded N = 218 • 11% bacteremia (all meningococcus)
Sensitivity Specificity PPV NPV ill appearing 79 (100) 81 (88) 35 (11) 97 (100) abN WBC 58 (100) 56 (64) 14 (5) 91 (100) Rash below nipple line 100 (100) 38 (40) 17 (2) 100 (100) purpura 83 (83) 88 (97) 47 (31) 98 (99) prolonged INR 58 (67) 96 (98) 67 (40) 94 (99) Wells et al - Nottingham *Fever > 37.5°: Sensitivity = 79%, NPV = 95
How should we approach the child with petechiae? • Clinical Risk Factors: • Toxic appearance, lethargy, irritability • Petechiae below the nipple line, purpura • Laboratory Risk Factors: • Abnormal WBC (<5000, >15000) • Elevated INR
How should we approach the child with petechiae? Safe approach: Draw CBC, coags and culture (+/- lp as clinically indicated) • if no risk factors, may D/C home (may consider a 4 hour observation period) • If any positive risk factors, admit for IV antibiotics pending culture results In a well-appearing child with no purpura and petechiae limited to the SVC area (with a plausable mechanism – ie. vomiting/coughing) – an argument could be made for not doing bloodwork
Acute Exfoliating Conditions • Toxic Epidermal Necrolysis (TEN) • Incidence ~ 1.3 per million • Staph Scalded Skin Syndrome (SSSS) • Incidence ~ unknown
Toxic Epidermal Necrolysis (TEN) • A life-threatening, exfoliating disease of the skin and mucous membranes • Hallmark is full-thickness necrosis of the epidermis with separation at the dermoepidermal junction
Relationship of TEN to other Exfoliating Conditions • Controversal relationship to: • Erythema multiforme minor • Erythema multiforme major • Stevens-Johnson syndrome • Unclear if TEN is distinct entity or severe form of EM major or SJS
TEN SJS EM Major Erythema Multiforme Minor A Spectrum of Illness?
Erythema Multiforme Minor • Erythematous, target-like lesions, occasionally with bullae, symmetrically involving extensor surfaces of limbs, palms and soles
EM Minor • Cause – hypersensitivity reaction (HSV, drugs) • Course –benign, self-limited, usually resolves in 5 – 15 days • Treatment – oral antihistamines and topical steroids may provide symptomatic relief • Skin tenderness is not typical and should alert to possibility of early TEN
Erythema Multiforme Major • Also thought to be a hypersensitivity reaction • As with EM minor, but with involvement of ≥2 mucosal surfaces (precedes rash by 1-2 days) • Pronounced constitutional symptoms common
Stevens-Johnson Syndrome • Is SJS is separate entity from EM major? • Some feel SJS is a distinct entity as the rash is more erythematous and less acral than EM major • EM major is more commonly triggered by infections and SJS by drugs
SJS vs TEN • Unsure if on same spectrum or distinct diseases • Some use %BSA to define with: <10% = SJS >30% = TEN • Histologically SJS has a much higher density cell infiltrate (T-lymphocytes) vs TEN (low density macrophages and dendrocytes)
TEN - Pathogenesis • Majority of cases are likely adverse drug reactions (foreign antigen response) • Mean time from drug to onset = 13.6 days • Higher risk drugs • NSAIDS [38%] • Antibiotics [36%] (sulfonamides) • Anticonvulsants [24%] (phenobarb, lamotrigene) • Corticosteroids [14%]