Educational Session: Life-Threatening Pediatric Rashes

Transcription

1 Educational Session: Life-Threatening Pediatric Rashes Richard M. Cantor, MD, FAAP, FACEP 3/22/2010 4:30 PM - 5:30 PM

2 Cutaneous Signs of Serious Illness Richard Cantor MD FAAP/FACEP Associate Professor of Emergency Medicine and Pediatrics Director, Pediatric Emergency Services Medical Director, Upstate Poison Center Upstate Medical University Syracuse, NY

3 Newborn Threats

4 A 1 month old with fever?

5 Omphalitis Circumferential redness, warmth and tenderness around base of cord Foul drainage may be seen Caused by Strep A, Staph aureus, Gram negative rods Treatment Admission for IV antibiotics after full septic work up

6 Fever in a 5 Day Old

7 Illustrative Case 5 day old infant with a one-day history of poor breastfeeding, lethargy and a temp of 38.7C Examination significant for mild lethargy, mild jaundice and a few scattered petechiae on the chest Sepsis work-up done and the CSF showed a WBC of 2/mm3 and a RBC count 17/mm3

8 Illustrative Case CSF WBC = 2/mm3 and a RBC count 17/mm3 Glucose 62 Protein 68 WBC = 12,000 1% lymphocytes, 3% segmented neutrophils and 96% mononuclear cells After two days of negative bacterial cultures, intravenous antibiotics (ampicillin and cefotaxime [Claforan]), and clinical improvement, he was discharged home

9 Skin Manifestations

10 Illustrative Case On the 7 th day of life, the infant experienced a seizure Admitted with rapid decline and multiorgan failure Died the following day Positive cultures for HSV-1 from multiple sites (nasopharyngeal swab, liver biopsy) His mother also had a positive culture for HSV-1 from a breast lesion

11 Neonatal Herpes

12 Epidemiology Incidence approximately 1 per 3,000 to 20,000 live births A woman who experiences a primary episode of genital HSV during the third trimester has a 33% chance of transmitting the virus to her infant Of known infected infants, only 30% have mothers who had symptomatic HSV or a sexual partner with clinical infection Many neonatal infections result from asymptomatic cervical shedding of virus

13 Clinical Presentation Three subtypes of natally acquired or postnatally acquired infection have been identified disease localized to the skin, eye or mouth encephalitis, with or without skin, eye or mouth involvement disseminated infection that involves multiple sites, including the central nervous system, lung, liver, adrenals, skin, eye or mouth

14 Clinical Presentation Presentation is nonspecific irritability, lethargy, fever or failure to feed at about one week of age Infants often do not have skin lesions (less than 50 percent of infants with encephalitis or disseminated disease) By the time diagnosis is made, many infants have severe disease and have developed complications When diagnosis is delayed, mortality is high despite antiviral therapy

15 Skin Manifestations

16 CNS Pathology

17 Diagnosis of HSV Infections Diagnosis requires a high index of suspicion HSV infections should be considered in all neonates who present in the first month of life with nonspecific symptoms such as fever, poor feeding, lethargy or seizure Mandatory work up Culture any vesicular rash Culture blood, urine and CSF (for HSV as well) Culture eyes, nose and rectum for viral etiologies

18 Complications of Neonatal Herpes Simplex Virus Infections Seizures Psychomotor retardation Spasticity Blindness Learning disabilities Death Jacobs RF. Neonatal herpes simplex virus infections Semin Perinatol 1998;22:64-71.

19 Mortality Factors Virtually no mortality among infants with disease limited to the skin, eyes and mouth mortality increases to 15% among infants with encephalitis and 57% among infants with disseminated disease, even with antiviral therapy Long-term morbidity is common in infants who survive with encephalitis or disseminated disease, and may include seizures, psychomotor retardation, spasticity, blindness or learning disabilities

20 Herpes in Summary A vital consideration in all neonatal (<28days) septic workups Careful skin exam in all cases Part of the differential for all neonatal somatic compromises (fever, ;ethargy, poor feeding, seizures, hypothermia) Acyclovir is indicated

21 Things That Don t Blanch

22 A 4 year old with limp and unexplained bruising?

23 Henoch-Schonlein Purpura (HSP) IgA mediated small vessel vasculitis No clear etiologic agent has been described preceding URI, bacteria (GABHS, C. jejuni, Yersinia, Mycoplasma) Palpable purpura - buttocks / lower extremities

24 Henoch-Schonlein Purpura (HSP) Transient migratory arthritis in 2/3 of cases - large joints Renal involvement (25%) proteinuria / hematuria/ hypertension Also associated with the development of abdominal pain and intussusception Treatment -NSAIDS for the arthritis

25 A 10 year old with fever, headache and a non blanching rash?

26 Rocky Mountain Spotted Fever The most common rickettsial infection in the United States tick spread Reported from every state with most cases occurring in the east and midwest Principal pathology involves widespread vasculitis Commonly includes fever, rash, headache and myalgia

27 Rocky Mountain Spotted Fever The rash is present in 90% of patients, progressing from the extremities towards the trunk The rash may begin in a macular form with eventual progression to petechiae, involving the palms and the soles

28 Rocky Mountain Spotted Fever Complications include shock, renal failure and hemostatic complications Thrombocytopenia is common as well as LFT anomalies Treatment for ALL children is Doxycycline

29 Meningococcemia

30 Introduction Mortality / morbidity from meningococcal disease has changed very little since the 1950s N. meningitidis - the 2nd leading cause of meningitis in the United States The majority of cases of meningococcal infection occur in young children and teenagers Nasopharyngeal carriage

31 Epidemiology CDC reports = 2,500-3,500 cases annually Case fatality rate = 6 to 12% Disease rates 10 times higher in children < 2 years than in the overall population Highest in February and March; lowest in September

32 Carriage Rates 2% of children younger than 2 years 5% of children up to 17 years 20-40% of young adults are carriers Overcrowded conditions (eg, schools, military camps) can significantly increase the carrier rate

33 Pathogenesis Endotoxin releases tumor necrosis factor-alpha, interleukin 1, interleukin 6, and interferon-gamma severe hypotension reduced cardiac output increased endothelial permeability multiple organ failure massive DIC death

34 Culture Level of bacteremia is high when primary manifestation of infection is meningitis, concentration of organisms in the blood may be low compared to the CSF frequency of positive blood cultures can vary from 50-60% frequency of positive CSF cultures is much higher (80 to 90 percent)

35 History Follows a URI Headache, nausea, vomiting, myalgias, and arthralgias Not all patients appear toxic May be difficult to distinguish from a viral syndrome Fulminant presentation hemorrhagic eruption, hypotension, and cardiac depression may be apparent within hours

36 Physical Petechiae are the most common sign, in 50-60% of patients most often located on the extremities and trunk but may progress to involve any part of the body may appear in groups under areas of pressure

37 Physical Pustules, bullae, and hemorrhagic lesions with central necrosis can develop Stellate purpura with a central gunmetal-gray hue is characteristic Large maplike purpuric and necrotic areas related to the development of DIC are characteristic of fulminant meningococcemia

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40 Physical Noncutaneous physical findings Altered mental status Neck stiffness Irritability Seizures Gait disturbance Nausea/Vomiting Unstable vital signs

41 Differential Bacterial sepsis (gonococcemia, Haemophilus influenzae infectionstreptococcus pneumoniae infection) Endocarditis (Staphylococcus aureus infection) Rocky Mountain spotted fever Viral illness, especially with enterovirus infection Toxic shock syndrome Leptospirosis

42 Penicillin Penicillin G - at 300,000 units/kg per day with an upper limit of 24 million units/day usual dose in adults is 4 million units IV q 4 hrs First reports of N. meningitidis resistant to penicillin appeared in 1988

43 Chloramphenicol Chloramphenicol (100 mg/kg per day IV up to a maximum dose of 4 g/day) is an effective substitute for the penicillin-allergic patient increasing resistance to chloramphenicol worldwide could change this recommendation

44 Cephalosporins Cefotaxime, ceftriaxone, and ceftazidime have all proven successful in the treatment of pediatric meningococcal meningitis achieve levels in the CSF several orders of magnitude higher than the MICs of the organism to these agents

45 The child with a non-blanching rash: how likely is meningococcal disease? L C Wells Arch Dis Child 2001;85:

46 Methods A total of 233 infants and children up to 15 years of age presenting with a non-blanching rash were studied over a period of 12 months Clinical features and laboratory investigations were recorded at presentation The ability of each to predict meningococcal infection was examined

47 Results 11% had proven meningococcal infection Children with meningococcal infection were more likely to be ill, pyrexial (>38.5 C), have purpura, and a capillary refill time of more than two seconds than non-meningococcal children No child with a rash confined to the distribution of the superior vena cava had meningococcal infection Investigations were less helpful, although children with meningococcal infection were more likely to have an abnormal neutrophil count and a prolonged international normalised ratio No child with a C reactive protein of less than 6 mg/l had meningococcal infection

48 Conclusions Most children with meningococcal infection are ill, have a purpuric rash, a fever, and delayed capillary refill Children with a non-blanching rash confined to the distribution of the superior vena cava are very unlikely to have meningococcal infection Measurement of C reactive protein may be helpful no child with a normal value had meningococcal infection Lack of fever at the time of assessment does not exclude meningococcal disease

49 A 4 year old Asian child with a cough?

50 Coining Asian folk remedy to treat respiratory infections Edge of coin or spoon scrapes skin to release toxins Often confused with abuse Cao gio (SE Asia) or Quat sha (China)

51 Tips of the Iceberg

52 A 6 year old on Cefaclor?

53 Erythema Multiforme Hypersensitivity reaction 2 presentations: Minor - skin lesions only (EM Minor or Hebra s Disease) Major - systemic symptoms and severe involvement of mucous membranes (Stevens Johnson)

54 Erythema Multiforme Associated with many pathogens Herpes simplex Mycoplasma Drug exposure Mononucleosis

55 Erythema Multiforme Simple EM generally resolves over 10 to 14 days Target lesions may demonstrate symmetrical distribution over elbows, knees and extensor surfaces Simple EM should be managed conservatively with oral antihistamines Joint involvement may respond to a pulse of systemic steroids

56 Stevens-Johnson Syndrome

57 Stevens-Johnson Syndrome Presents with 7 to 10 days of fever, headache, malaise, and target lesions of the skin Mucous membrane degeneration is also noted with pan-mucosal involvement Patients with SJS should be admitted for intravenous hydration and intensive dermatologic care

58 A 3 year old with 4 days of hyperpyrexia?

59 Kawasaki Syndrome Acute self limiting multisystem disease of unknown etiology Peak incidence is months 80% cases less than 4 years Reported outbreaks in 2-3 year cycles

60 Kawasaki Syndrome Fever for at least 5 days Conjunctivitis Polymorphous rash Oral cavity changes (red, cracked lips, strawberry tongue, diffuse mucosal injection) Cervical adenopathy

61 Kawasaki Syndrome Peripheral extremity changes: Erythema and induration of hands and feet Desquamation from fingers or toes Findings cannot be explained by another disease process

62 Kawasaki Syndrome Acute (7-15 days), subacute (10-25 days), and convalescent phases (6-10 weeks) Lab abnormalities are nonspecific Thrombocytosis in the subacute phase Elevated ESR and CRP

63 Kawasaki Syndrome Management CXR and ECG Cardiology consult IV Gamma Globulin (2gm/kg over 7-8 hours) Aspirin ( mg/kg/d) until fever resolves

64 The World of Staph and Strep

65 The Spectrum of Gram Positive Diseases GABHS Pharyngitis Impetigo Cellulitis / Abscess Staphylococcal Scalded Skin Syndrome Scarlet Fever Toxin Mediated Diseases Toxic Shock Syndrome Localized infections

66 Not ever getting back into day care?

67 Impetigo The most common skin infection in childhood Considered an extremely infectious disease Represents an interruption in the epithelial border resulting in colonization by bacteria May complicate any dermatologic problem

68 Impetigo S. aureus and S. pyogenes, rarely others Begins as a tiny papule with rapid development of golden crusting Frequently starts under the nose and spreads by autoinnoculation to other body parts Regional lymph nodes are often involved Associated with acute glomerulonephritis (non preventable)

69 Impetigo Topical antibiotics may be utilized yet are less effective than oral forms Treatment must include consideration for the presence of S. aureus Bactroban (mupirocin) has shown promise as a single topical treatment for simple impetigo

70 The Strep Cell Wall

71 Was the bath too hot?

72 Bullous Impetigo Characterized by clear thin-walled blisters which eventually erode and form coin lesions Surprising little surrounding erythema is noted Rapid spread is characteristic Generally a benign infection but should be considered a systemic illness in neonates

73 Bullous Impetigo Treatment is essentially the same as simple impetigo Antibiotics effective against Staphylococcus should be utilized Neonates should be admitted for intravenous antibiotic therapy

74 A 6 month old with sunburn?

75 Scalded Skin Syndrome (Ritter s Disease) Usually seen in children under the age of 5 Presents with fever and irritability and sensitive skin Generalized erythema progresses to bullae formation and desquamation of large sheets of skin The skin may often be rubbed off in thin layers (Nikolsky s sign)

76 Scalded Skin Syndrome (Ritter s Disease) Caused by an exfoliative toxin elaborated by certain strains of staphylococcus The primary staphylococcal infection may be anywhere Treatment involves oral antibiotics and strict attention to skin care Many cases necessitate admission to replace insensible fluid losses

77 A 12 year old with epigastric abdominal pain?

78 Scarlet Fever (Scarlatina, Second Disease) Streptococcal oropharyngeal infection with systemic systems Characterized by fever, malaise, and pharyngitis Rash progresses from neck to trunk to extremities Circumoral pallor and strawberry tongue

79 Scarlet Fever (Scarlatina, Second Disease) Characteristic sandpaper feel with profound erythema Petechiae in linear arrangement (Pastia s lines) 5 to 7 days later desquamation may occur

80 Teen Trouble

81 Case History A 14 year old girl presents with fever Present for 2 days with a Tmax of 40C Mild headache, malaise, migratory myalgias, nonbilious emesis, nonbloody diarrhea, sore throat No sick contacts/travel Mid menses Not sexually active No significant PMH

82 Case PE Vitals: T 39C, HR 120, RR 16, BP 80/50 HEENT: marked conjunctival/pharyngeal erythema w/ o exudate Chest: Hyperactive precordium Abdomen: Generalized non focal tenderness Ortho: WNL, some tenderness to thighs and calves Neuro: Irritable Skin: Generalized erythema

83 The Rash (erythroderma)

84 Labs CBC: WBC, H/H WNL---Platelets 80,000 BMP: BUN 60, Creat 2.8 CK markedly elevated LFT s abnormal Urinalysis: 10 WBC, gram stain negative ECG: sinus tachycardia

85 Problem List Shock Fever Transaminitis Azotemia Myositis

86 Toxic Shock Syndrome

87 TSS: CDC Case Definition Fever T >38.9C (102.0F) Hypotension Systolic blood pressure 90 mmhg for adults or less than fifth percentile by age for children <16 years of age Orthostatic drop in diastolic blood pressure 15 mmhg Rash Diffuse macular erythroderma Desquamation 1-2 weeks after onset of illness, particularly involving palms and soles

88 CDC Case Definition Multisystem involvement (3 or more of the following organ systems) GI: Vomiting or diarrhea at onset of illness Muscular: Severe myalgia / CPK elevation >2X Mucous membranes: Vaginal, oropharyngeal, or conjunctival hyperemia Renal: BUN or serum creatinine >2 X normal, or pyuria (>5 WBC/hpf) Hepatic: Bilirubin or transaminases >2 X the normal Hematologic: Platelets <100,000/L CNS: Disorientation or alterations in consciousness without focal neurologic signs

89 CDC Case Definition Negative results on the following Blood, throat, or CSF cultures for another pathogen (blood cultures may be positive for Staphylococcus aureus) Serologic tests for Rocky Mountain spotted fever, leptospirosis, or measles

90 Epidemiology TSS associated with S. aureus first described in a series of pediatric cases in 1978 Incidence rose sharply in documented cases of menses-related TSS (declining) Clinical illness arose during menstrual periods and was associated with the use of highly absorbent tampons

91 Epidemiology 50% of reported TSS cases are nonmenstrual Seen in a variety of clinical situations Surgical / postpartum wound infections (27% of cases) Mastitis Septorhinoplasty/Sinusitis Osteomyelitis/arthritis Burns Cutaneous / subcutaneous lesions (especially of the extremities, perianal area, and axillae Respiratory infections following influenza

92 Epidemiology TSS occurs in children 50 cases in children 5 yrs were reported between 1979 and 1996 Patients < 2 yrs accounted for approximately half of these cases 62% had preceding cutaneous nonsurgical lesions

93 Staphylococcal toxic shock syndrome MRSA strains produce TSST-1 Organism produces several enzymes that induce inflammation and abscesses three syndromes food poisoning = S. aureus enterotoxin scalded skin syndrome = exfoliative toxin toxic shock syndrome = toxic shock syndrome toxin-1 (TSST-1) and other enterotoxins

94 Clinical Presentation Rapid symptom/sign development interval between menstruation and TSS is 2-3 days in post-surgical cases 2 days, although the onset has been reported as late as 65 days postoperatively

95 Hypotension All patients with definite TSS have fever >38.9C, hypotension, and skin manifestations decrease in SVR as well as nonhydrostatic leakage of fluid unresponsive to large amounts of IVF can persist for several days

96 Skin manifestations Erythroderma involves both the skin and mucous membranes diffuse, red, macular rash resembling sunburn also involves the palms and soles Conjunctival-scleral hemorrhage and hyperemia of the vaginal and oropharyngeal mucosa Some patients also experience loss of hair and nails one to two months later with regrowth by six months

97 Multiorgan system involvement Diffuse myalgias and weakness increase in serum creatine phosphokinase Profuse diarrhea Prerenal and intrinsic renal failure Hyponatremia Hypoalbuminemia Hypocalcemia Hypophosphatemia

98 Multiorgan system involvement Pulmonary edema / pleural effusions Depression of myocardial function Hepatic dysfunction Heme abnormalities ( anemia/thrombocytopenia) CNS Encephalopathy/seizure activity (cerebral edema) Persistent sequelae = headaches, memory loss, and poor concentration

99 Diagnosis % S. aureus isolated from mucosal / wound sites In contrast to streptococcal TSS, S.aureus rarely (5%) recovered from blood cultures Diagnosis based upon clinical presentation, utilizing the CDC case definition Confirmed case has all 6 clinical findings plus desquamation A probable case has 5/6 clinical findings present

100 Diagnosis Cultures from mucosal and wound sites should be obtained S. aureus isolates can be tested for toxin production in research laboratories Can analyze acute and convalescent serum for antibody responses to various S. aureus exotoxins Presence of a strain of S. aureus that produces toxin in a patient who does not have acute phase antibody to the toxin is highly suggestive of TSS

101 Differential Diagnosis Other diagnostic considerations streptococcal TSS - most often associated with severe pain and tenderness patients with streptococcal TSS may require immediate surgical debridement of the involved site

102 Differential Diagnosis RMSF Petechial rash, involves the extremities first, average of 3 days after the development of fever Meningococcemia meningitis seen and is rare in TSS Leptospirosis, dengue hemorrhagic fever, and typhoid fever

103 Management Surgical therapy Remove all vaginal FB Drain all wounds Supportive therapy Extensive fluid replacement (10-20 liters per day) Vasopressors (eg, dopamine and/or norepinephrine) may also be required

104 Antibiotic therapy Unclear whether antibiotics alter the course clindamycin suppresses protein synthesis and toxin synthesis (demonstrated in vitro) five different beta lactam antibiotics, including nafcillin and cephalosporins, increased measurable TSST-1, probably by lysis or increasing cell membrane permeability

105 Antibiotic therapy TSS due to methicillin-susceptible S. aureus clindamycin (600 mg IV every eight hours) plus oxacillin or nafcillin (2 g IV every four hours) TSS due to MRSA clindamycin (600 mg IV every eight hours) plus either vancomycin (15 mg/kg IV every 12 hours) or linezolid (600 mg PO or IV every 12 hours)

106 Streptococcal toxic shock syndrome

107 Definitions Invasive GAS infections defined as bacteremia pneumonia necrotizing fasciitis spontaneous gangrenous myositis Group A streptococcal TSS is defined as any GAS infection associated with the acute onset of shock and organ failure

108 Virulence factors Exotoxins Strep pyrogenic exotoxins are elaborated by GAS These toxins induce cytotoxicity, pyrogenicity, and enhancement of the lethal effects of endotoxin M protein M protein - important virulence determinant of GAS, and strains lacking M protein are less virulent

109 Risk factors Minor trauma Injuries resulting in hematoma, bruising, or muscle strain Surgical procedures (eg, suction lipectomy, hysterectomy, vaginal delivery, bunionectomy, bone pinning, breast reconstruction, cesarean section Viral infections (eg, varicella, influenza) Use of nonsteroidal antiinflammatory drugs (NSAIDs)

110 Risk factors Varicella infection (eg, chicken pox) - major risk factor for invasive GAS infections including GAS TSS The rate of varicella-related invasive GAS infections as a % of all invasive GAS infections were: Prevaccine era (1993 to 1995) 27 percent During initial utilization (1996 to 1998) 16 percent Widespread vaccine use (1999 to 2001) 2 percent Association between NSAIDs and severe GAS infections is uncertain

111 Clinical Presentation Most common initial symptom of GAS TSS is diffuse or localized pain abrupt in onset, severe, and usually precedes tenderness or physical findings of soft tissue infection typically involves an extremity

112 Clinical Presentation Fever is the most common presenting sign Influenza like syndrome (20%) Confusion (55%) and coma / combativeness may be manifest in some patients 50% normotensive on presentation or admission, but become hypotensive within 4 hours

113 Clinical Presentation 80% have signs of soft tissue infection, followed by ecchymoses and sloughing of skin which progresses to necrotizing fasciitis or myositis in 70% GAS TSS is a very rare complication of streptococcal pharyngitis in adults, but may be more common in children A diffuse, scarlatina-like erythema occurs in only 10 percent of cases

114 Shock Shock at the time of admission or within 4-8 hrs is present in virtually all patients with GAS TSS Despite aggressive therapy, the systolic pressure remains depressed in 90% of patients after 8 hours

115 Laboratory findings Mild leukocytosis, band counts may reach 40-50% Creatinine elevation, precedes the development of hypotension in 40-50% Positive blood cultures (60%) Increase in the serum creatinine kinase concentration presence of necrotizing fasciitis or myositis

116 Differential Diagnosis Abrupt onset of shock in a previously healthy individual has a limited number of causes Staphylococcal TSS Gram-negative sepsis Rocky Mountain Spotted Fever Acute meningococcemia Leptospirosis Heat stroke

117 Diagnosis Working Group on Severe Streptococcal Infections - clinical guidelines for diagnosis: Isolation of GAS from a normally sterile site (eg, blood cerebrospinal, pleural, or peritoneal fluid, tissue biopsy, or surgical wound) plus Hypotension

118 Diagnosis Plus 2 or more of the following Renal impairment Coagulopathy Liver involvement ARDS Erythematous macular rash, may desquamate Soft tissue necrosis (eg, necrotizing fasciitis, myositis, or gangrene)

119 Management Surgical prompt exploration / debridement of suspected deep-seated S. pyogenes infection mandatory Hemodynamic support Massive amounts of intravenous fluids (10 to 20 L/ day), vasopressors (eg, dopamine and/or norepinephrine)

120 Antibiotic therapy Associated with high mortality / morbidity despite penicillin therapy Clindamycin has several potential advantages in treating GAS infections suppresses the synthesis of bacterial toxins facilitates phagocytosis of S. pyogenes by inhibiting synthesis of the antiphagocytic M-protein has a longer postantibiotic effect causes suppression of tumor necrosis factor

121 Choice of antibiotic therapy Definitive studies not available Clindamycin A carbapenem A combination drug containing a penicillin plus betalactamase inhibitor (eg, ticarcillin-clavulanate 3.1 g every four hours or piperacillin-tazobactam 4.5 g every six hours)

122 Summary Any infant less than 2 weeks being worked up for sepsis necessitates Herpes culture and treatment Prolonged febrile illnesses (over 4 days) may be Kawasaki in origin All petechial rashes are meningococcemic until proven otherwise; most will be viral or valsalvic Toxin mediated fever and hypotension may be secondary to either GABHS or Staph infections