Adolescent with fever and atypical presentation Galit - - PowerPoint PPT Presentation

Galit Livnat-Levanon

Carmel Medical Center

Adolescent with fever and atypical presentation

פיח" ילוי פ2016

הרקמ תגצה

הזנמנא

ןב17םינש , אירבדב"כ ותלבק םרט םייעובש : תלחמםוח ,תלזנ , לועישלושלשו , עובש רחאל(םוח םע )הליהקב הזח םוליצ עצוב : הללצה לאמשמ, לחוה לופיטןיטנמגואב ימופ , לפוטעובש ךשמב. רואלןוימל הנפוה םימוחה ךשמה .

• לש לקשמב הדירי ןייצל שי5ק"ותלחמ ךלהמב ג.
• םיטוזקא תומוקמב לויט ללוש , וא הזחב םיבאכ ללוש

ימד חיכ .ותביבסב םילוח אלל.

Adolescent with fever and atypical presentation Galit Livnat-Levanon

ליהק הזח םוליצה23/8/2015

Adolescent with fever and atypical presentation Galit Livnat-Levanon

הרקמ תגצה

םידדמ:םוח :38.5 ,תומישנ :30הקדל ,היצרוטס : 96% ריוואברדח . ותקידבב :הלוח הארנ ,ררמצמ , אלל יוריג ינמיס ילאיגנינמ , החירפע הנידע" תיב פןטבו הזח. תואירל הנזאהב :תויצטיפירק םיסיסבבוד"צ . אלל גניבאלק . הדבעמ :סב" ד PLT=553000 WBC 10,500 (76%PMN) , CRP=8 ,הניקת האלמ הימיכ.

Adolescent with fever and atypical presentation Galit Livnat-Levanon

הלבקב הזח םוליצ30.8.2015

Adolescent with fever and atypical presentation Galit Livnat-Levanon

• לופיטל רבעומןיטנמגואב

IV + תפסוהלינזא.

• ותלבק רחאל םיימוי ,םימוח םע ךישממ , עיפומ באכ הייארו שאר

הלופכ ,הרכהה בצמב יוניש וא לובלב אלל. םייניב םוכיס

• אירב רענ ,יצחו םייעובש תכשמנה תיטוקא הלחמ ,לקשמב הדירי ,

לופיט םע רופיש אלליטויביטנא

• הזח םוליצב לאמשמ הללצה
• םוח + שאר באכ +היפולפיד

תלדבמ הנחבאב:

• MENINGITIS
• ENCEPHALITIS
• SINUSITIS

הרקמ רואית ךשמה

• BRAIN ABSCESS
• ADEM
• MS

Adolescent with fever and atypical presentation Galit Livnat-Levanon

הרקמ רואית ךשמה

תבחרהרוריב

• םייניע ץועי- הליזפהשדח המיאתמה לש השלוחל((Abducens

Cranial Nerve VI , שאר יבאכ לע תונולתו םוח תלחמ תוחכונב ץלמומ : ו הימדה LP

• הקידב תיגולוריונהניקת
• קא" וקאו גבל-םיניקת
• MRI ח םע חמ.נ :ןיקת
• MULTIPLEX VIRAL PCRילילש חיכ.
• היגולורס:

Rickettsia, Q fever הידימלכ- תילילש , המזלפוקימ- IGM יבויח

• PAN BACTERIAL PCRחיכ :המזלפוקימל יבויח
• תוברת םדתוילילש

Adolescent with fever and atypical presentation Galit Livnat-Levanon

• רחאל5םילחמ זופשא ימי ,דרוי םוחה , הליזפה

תפלוח , אללשאר יבאכ .

• ותקידבב םויבורורחש :בוטב שח ,םיניקת םידדמ ,

היצרוטס99%רדח ריוואב.

• םייניע אפור תקידב + תיגולוריונ הקידבהניקת.
• תואירה תקידבב : אלל תמשנ, הבוט ריווא תסינכ

הוושווד"צ םירוחרח אלל וא םיפוצפצתויצטיפירק.

• הדבעמ תרזוח :ס"ד,הימיכ-תוניקת .

CRP=0.9

הרקמ רואית ךשמה

Adolescent with fever and atypical presentation Galit Livnat-Levanon

רורחש םרט םוליצ3.9.2016

Adolescent with fever and atypical presentation Galit Livnat-Levanon

הנחבא :המזלפוקימהינומואינפעמ תוברועמ םע"מ

MYCOPLASMA PNEUMONIA

• The smallest free-living microorganisms, lack cell wall, more

than 100 species (17 human pathogens) PATHOGENESIS: adherence proteins attach to the epithelial membranes (affinity for respiratory tract) → injury to epithelial cells and their cilia by hydrogen peroxide and superoxide

• Cytotoxin (CARDS) direct damage to respiratory tract

→ influx of inflammatory cells→ pro-inflammatory cytokines

• Immune-mediated: antibodies against mycoplasma antigens

act as autoantibodies - cross reaction with human red cells and brain cells

Adolescent with fever and atypical presentation Galit Livnat-Levanon

Adolescent with fever and atypical presentation Galit Livnat-Levanon

MYCOPLASMA PNEUMONIA

EPIDEMIOLOGY

• Person to person by infected respiratory droplets
• Incubation period ~ three weeks
• Year-round, most frequently fall and winter
• Can be epidemic (families 80%, children are the reservoir)
• M. pneumoniae accounts for 20% of acute pneumonia in

middle and high school students CLINICAL FEATURES Gradual onset with: headache, malaise, and low-grade fever

• Physical examination: minimal findings

Adolescent with fever and atypical presentation Galit Livnat-Levanon

Respiratory tract disease

• Cough: 75-100% intractable, nonproductive only 3-10%

develop pneumonia

• Pharyngitis (6-59 %), rhinorrhea (2-40%), and ear pain (2-35%).

Possible relation to asthma:

• *M. pneumoniae implicated in the exacerbation of asthma
• # Isolated the bacteria in higher prevalence among asthmatics
• M. pneumoniae infection may worsen asthma symptoms and

can produce wheezing in children who do not have asthma.

• The mechanism behind development of the disease is still

unknown

*Biscardi,S., etal. Mycoplasma pneumoniae and asthma in children. Clin. Infect.Dis 2004 # Smith-Norowitz,T.A. etal.. Asthmatic children have increased specific anti-Mycoplasma pneumoniae IgM but not I Gg or IgE-values independent of history of respiratory tract infection. Pediatr.Infect.Dis. 2013

Adolescent with fever and atypical presentation Galit Livnat-Levanon

Mycoplasma and asthma

Chlamydia pneumoniae, and mycoplasma pneumoniae: Are they related to severe asthma in childhood? Objective: To determine the frequency of these triggers and their relationship to severe asthma. Methods: 82 children , three study groups: Group 1: severe asthma, Group 2: stable asthma and Group 3: control group. Serological tests (IgG and IgM) for both C. pneumoniae and M. pneumoniae. Results: M. pneumoniae IgM was observed in 6/27 (22.2%) in Group 1, 2/29 (6.9%) in Group 2 and 0/26 in the Control Group (p = 0.01).

• M. pneumoniae IgG was observed in 7/27 (25.9%) in Group 1, 4/29

(13.7%) in Group 2 and 0/26 in the Control Group (p < 0.05). Conclusions: M. pneumoniae and C. pneumoniae may play a role in the development of severe asthma

Iramain R et al. J Asthma. 2016 Aug

Adolescent with fever and atypical presentation Galit Livnat-Levanon

Mycoplasma pneumoniae in children with acute and refractory asthma

OBJECTIVES: To identify the frequency of M pneumoniae in respiratory secretions of children with and without asthma METHODS: 143 (53 patients with acute asthma, 26 patients with refractory asthma, and 64 healthy controls; age range 5-17 years) Detection of M pneumoniae using CARDS toxin antigen capture and PCR. Immune responses were determined by IgG and IgM RESULTS: M pneumoniae in 64% of patients with acute asthma, 65% with refractory asthma, and 56% of healthy controls. Children with asthma had lower antibody levels compared with healthy controls CONCLUSION: M pneumoniae is common in children, detection is associated with worsening asthma, and children with asthma may have poor humoral immune responses to M pneumoniae.

Wood PR et al. Ann Allergy Asthma Immunol. 2013 May

Adolescent with fever and atypical presentation Galit Livnat-Levanon

Extra pulmonary disease

• Hemolysis, skin rash, joint involvement, GIT, CNS and

heart disease.

• CNS involvement — 0.1% of all patients, most frequently

in children, significant morbidity and mortality:  aseptic meningitis  meningoencephalitis (postencephalitic epilepsy)  peripheral neuropathy  transverse myelitis  cerebellar ataxia  cranial nerve palsies pathogenesis uncertain: Direct infection + immune- mediated

Objective: to characterize the neurologic complications

• f M. pneumoniae in children

Methods: All children admitted to hospital over a 16- year period with acute neurologic manifestations and PCR–confirmed M. pneumoniae Results: 365 children had M. pneumoniae in the CSF or respiratory tract by PCR, 42 (11.5%) had neurologic disease: encephalitis (52%), acute disseminated encephalomyelitis (12%), transverse myelitis (12%), and cerebellar ataxia (10%).

Samiah A. Al-Zaidy et al. Clinical Infectious Diseases , June 2015

Adolescent with fever and atypical presentation Galit Livnat-Levanon

Neurological Complications of PCR-Proven M. pneumoniae Infections in Children: Prodromal Illness Duration May Reflect pathogenetic Mechanism

Results: Two distinct disease patterns: 1. Prolonged prodrome (≥7 days), respiratory manifestations, IgM in peripheral blood, and detection of M. pneumoniae in the respiratory tract, but not the CSF 2. Brief (<7 days) or no prodrome, less frequent respiratory manifestations and IgM response, and detection of M. pneumoniae in the CSF, but not the respiratory tract. Conclusions: two separate pathogenetic mechanisms for M. pneumoniae–associated neurologic disease:

• ne related to direct infection of the central nervous system

and one indirect, likely immunologically mediated.

Adolescent with fever and atypical presentation Galit Livnat-Levanon

Samiah A. Al-Zaidy et al. Clinical Infectious Diseases , June 2015

Neurological Complications of PCR-Proven M. pneumoniae Infections in Children: Prodromal Illness Duration May Reflect pathogenetic Mechanism

Adolescent with fever and atypical presentation Galit Livnat-Levanon

Pathomechanisms in M. pneumoniae encephalitis

Narita M et al. Pathogenesis of neurologic manifestations of Mycoplasma pneumoniae infection. Pediatr Neurol 2009

Adolescent with fever and atypical presentation Galit Livnat-Levanon

Mycoplasma and ocular involvement

Ocular involvement :

• conjunctivitis
• third or sixth nerve palsies
• homonymous hemianopia
• nystagmus
• anterior uveitis
• optic neuropathy (rare)

Milla E, et al. Bilateral optic papillitis following Mycoplasma pneumoniae pneumonia. Ophthalmologica. 1998

Adolescent with fever and atypical presentation Galit Livnat-Levanon

Benign isolated abducens nerve palsy in Mycoplasma pneumoniae infection.

Case report: boy 26 months of age with benign acquired isolated bilateral abducens nerve palsy. the first report of Mycoplasma pneumoniae as the cause of benign isolated abducens nerve palsy in children

Wang CH et al. Pediatric Neurol 1998

Case report: 15-year-old male ,6-week of intermittent fever + night sweats, 5 kg weight loss, and fatigue with severe frontal retro-orbital headache & intermittent diplopia and blurry vision. The patient also developed cough & shortness of breath Chest X-ray: normal MRI: vasculitis of the middle cerebral arteries Serology: IGM was positive to M pneumoniae, titers increased

• ver fourfold within 3 weeks.

Treatment: symptoms resolved within 48 hours of administration of doxycline, IVIG, and steroids

Alexandra Milloff Butler et al.Pediatric Annals, October 2014

Adolescent with fever and atypical presentation Galit Livnat-Levanon

A Persistently Febrile Adolescent with Headache and Vision Changes

Adolescent with fever and atypical presentation Galit Livnat-Levanon

PCR

• Diagnosis
• Infectious Diseases Society of America (IDSA):

serology or PCR for diagnosis of Mycoplasma.

• PCR from a nasopharyngeal specimen is the

diagnostic test of choice: rapid, highly sensitive and specific but…..does not distinguish disease from asymptomatic carriage (colonization rates of 5%–13.5%)

• In the context of respiratory illness, DNA can be

detected for a median of 7 weeks and for as long as several months after acute infection

• PCR of CSF fluid - low diagnostic yield

Thurman KA et al. Comparison of laboratory diagnostic procedures for detection of Mycoplasma pneumoniae in community outbreaks. Clin Infect Dis 2009

• Antibody titers begin to rise 7-9 days after infection

and peak at 3-4 weeks.

• Fourfold or greater increase in titer is indicative of

infection

• Enzyme immunoassay (EIA) is more sensitive in

detecting acute infection than culture and has sensitivity comparable to the PCR

• Cold agglutinins — nonspecific early IgM reaction

against the erythrocyte I antigen, elevated in 50% of adult, the accuracy in children is not known

• Culture — slow growing, difficult to isolate(2-3 weeks)

Adolescent with fever and atypical presentation Galit Livnat-Levanon

Diagnosis - Serology

Adolescent with fever and atypical presentation Galit Livnat-Levanon

Treatment

ABX: macrolide or tetracycline

• Azithromycin, Doxycycline (children ≥8 years)

Macrolide resistance: USA 2015=3.5-13.2%, Japan/China > 85% of M. pneumoniae pediatric cases are macrolide- resistant. Associated with severe clinical features and more extrapulmonary complications.

• Alternative treatments tetracyclines &

fluoroquinolones (levofloxacin)

Patrick M. Meyer Sauteur et al. Frontiers in Microbiology , March 2016

Adolescent with fever and atypical presentation Galit Livnat-Levanon

CNS treatment

• Antibiotics: no major therapeutic role in

immune mediated or neurotoxic disease.

• In observational studies: glucocorticoids, anti-

inflammatory drugs, diuretics, and plasma exchange have been used in addition to antibiotics without clear indication of benefit

Adolescent with fever and atypical presentation Galit Livnat-Levanon

Objectives: To determine whether antibiotics are effective in the treatment of childhood LRTI secondary to

• M. pneumoniae

Methods: RCTs comparing antibiotics (macrolide, tetracycline or quinolone classes) versus placebo, or antibiotics from any other class Results: 1912 children were enrolled (7 studies), clinical response did not differ between children randomized to a macrolide or non-macrolide ABX Conclusion: insufficient evidence to draw any specific conclusions about the efficacy of antibiotics

Samantha J Gardiner, John B Gavranich, Anne B Chang. The Cochrane Collaboration 2015

Antibiotics for community-acquired lower respiratory tract infections secondary to Mycoplasma pneumoniae in children

Take home message

• M. pneumoniae may have atypical

presentation

• Neurologic involvement: direct or immune

mediated

• Neurologic involvement without respiratory

manifestations

• Association with asthma?
• Diagnosis is not trivial

Adolescent with fever and atypical presentation Galit Livnat-Levanon

Galit Livnat-Levanon

Carmel Medical Center

פיח" ילוי פ2016

Thank you