Question Question

• This child has had a sore throat and fever for 3 days. The appearance of the throat is shown. What do you see?

Answer Answer

• A membrane has formed on the tonsils and pharynx;

Question Question

• What are the possible causes?

Answer Answer

• The first consideration must be diphtheria. Other possibilities are:

• Infectious mononucleosis, and• Streptococcal pharyngitis will be considered

later • After tonsillectomy the appearances may

resemble a membrane.

Question Question

• What is the cause of the membrane in diphtheria?

Answer Answer

• Corynebacteria diphtheriae multiplying in the mucosa produce a potent cytotoxin which causes necrosis of tissue. The resultant severe inflammatory reaction results in swelling and obstruction, and enlargement of the neck glands. With virulent strains, toxin is absorbed into the blood stream and can affect the heart, nervous system and kidneys.

Question Question

• What are the clinical features of diphtheria?

Answer Answer

• Sore throat, stridor & airway obstruction

• A white to grey membrane

• “bull neck”• Myocarditis

• Sore throat may be followed by severe stridor and airway obstruction.

• A white to grey membrane, which bleeds on attempted removal, is seen in the throat or nose.

Contd

continuedcontinued

• Neuropathy: bulbar paralysis, or peripheral weakness

• Nephropathy• Thrombocytopaenia

& disseminated intravascular coagulation

• There may be massive enlargement of the neck due to oedema around the enlarged neck glands ("bull neck")

• Myocarditis may develop in the first or second week

Contd

continuedcontinued

• Neuropathy - bulbar paralysis, or peripheral weakness - may ensue 3-8 weeks after the onset.

• Toxicity to the kidneys may manifest as albuminuria or as frank renal failure.

• There may be thrombocytopaenia and disseminated intravascular coagulation.

DiphteriaDiphteria

Bambang MulyawanBambang MulyawanFK-UMMFK-UMM

DEFINISIDEFINISI

• DIFTERIA ADALAH:PENYAKIT INFEKSI AKUT SANGAT MENULAR,DISEBABKAN CORYNEBACTERIUM DIPHTHERIAE , DITANDAI PEMBENTUKAN PSEUDO - MEMBRAN PADA KULIT DAN/ ATAU MUKOSA.

DiphtheriaDiphtheria

• An acute infection by Corynebacterium diphtheriae (Klebs-loecffler Bacillus)

• Predominantly in upper respiratory tract

• The patognomonic sign is a pseudomembran

• grayish-white color, which contains fibrin and necrotic tissue;

• hard to remove, easily bleeding

18831883 : Klebs found the bacteria in : Klebs found the bacteria in

pseudomembran pseudomembran

18841884 : Loeffler grew the bacteria: Loeffler grew the bacteria

18881888 : The bacteria makes toxin: The bacteria makes toxin

18941894 : Von Behring found the antitoxin: Von Behring found the antitoxin

19131913 : Immunization against the disease: Immunization against the disease

EpidemiologyEpidemiology

• Transmission : by contact with infected person or ‘carrier’ through droplet infections

• Food contamination are rare (milk)

• Incubation period : 2-6 days

• Endemic or epidemic: Indonesia is endemic

• Infant < 6 month seldom

• Peak incidents at age : 2-5 years

• Age > 10 years : has lower incidents

Jumlah Kasus Difteria dan Kematian di Beberapa Rumah Sakit Jumlah Kasus Difteria dan Kematian di Beberapa Rumah Sakit Propinsi di IndonesiaPropinsi di Indonesia

RSCM RSHS RSWS RSK RSU PMH

Tahun Kasus *m% Kasus *m% Kasus *m% Kasus *m% Kasus *m%

1991 22 50,0 28 10,7 0 0 70 8,6 32 21,9

1992 25 32,0 26 7,7 12 0 34 5,9 19 26,3

1993 19 26,3 18 0 7 0 12 0 16 62,5

1994 16 18,8 12 0 10 10 8 0 13 46,2

1995 12 25,0 6 0 4 0 9 11,1 7 14,3

1996 7 28,6 3 0 1 0 11 0 14 42,9

Etiology Etiology Corynebacterium diphtheriaeCorynebacterium diphtheriae

• Positive gram, nonmotile, nonsporulating• Three colony type: gravis, intermediate,

mitis has low fatality rate• Direct staining : methyl blue, neisser, toluidine

blue• Bacilli parallel group / “V”• Culture : media blood agar contains kalium

telurit

ETIOLOGIETIOLOGI

• Corynebacterium diphtheriae• kuman batang Gram-positif• Tidak bergerak• Pleimorfik• Tidak berkapsul• Tidak membentuk spora• Mati pd pemanasan 60 der.C • Tahan dalam keadaan beku dan kering• Dg pewarnaan : tampak dalam susunan palisade

(bentuk L atau V), atau formasi huruf Cina• Tumbuh aerob, baik di media K-tellurit / Loeffler

Corynebacteria diphtheriaeCorynebacteria diphtheriae

G+, club shaped, pleomorphic, aerobic rod

Figure 24.6

DiphtheriaDiphtheria

Pathogenesis of DiphtheriaPathogenesis of Diphtheria

• Encounter – Corynebacterium diphtheriae encountered only from other people (carriers)

• Entry – respiratory droplets; organism colonizes pharynx

• Spread • Multiplication • Evasion of host immune response –

adhesins; toxin may kill phagocytes contributing to pseudomembrane

• Damage – inflammation; circulating toxin• Transmission – aerosolized droplets; fomites

PathogenesisPathogenesis

• The bacilli multiply in upper respiratory tract

• Vulva, skin, conjunctiva, umbilicus, ear, are rare

• Pseudomembrane and toxin :

local spread out

PATOGENESIS & PATOFISIOLOGISPATOGENESIS & PATOFISIOLOGIS

• C.diphtheriae mukosa/kulit : berkembang pd permukaan mukosa sal.nafas atas, memproduksi toksin merembes ke sekeliling, mel. pemb. limfe dan darah ke seluruh tubuh.

• Toksin menempel pd membran sel, meng-inaktivasi enzim, sel akan mati / nekrosis di daerah kolonisasi kuman.

PATOGENESIS & PATOFIOLOGIS PATOGENESIS & PATOFIOLOGIS ( lanjutan )( lanjutan )

• Sbg.respons : inflamasi lokal, memben-tuk bercak eksudat meluas : eksudat fibrin. Terbentuk membran yg melekat erat, kelabu kehitaman. Membran terdiri dari : fibrin, sel radang, eritrosit, epitel. Sukar diangkat mudah berdarah. Infeksi II dpt terjadi pd. pseudomembran ini ( Strep.pyogenes).

PATOGENESIS & PATOFISIOLOGIS PATOGENESIS & PATOFISIOLOGIS (lanjutan)(lanjutan)

• Membran dan jar.edematus dpt.me- nyumbat jalan nafas. ( laring/cabang trakeobronkus :ggn nafas –sufokasi )

• Toksin kerusakan organ tu. jantung, saraf, ginjal. Miokarditis dlm 10 – 14 hari, manifes-tasi saraf stl 3 – 7 minggu.

Clinical manifestationsClinical manifestations

• Generally : moderate – fever; but conditions are generally weak

malaise headache

• Specific localized manifestation : - running nose - dispnoe - stridor

• Local (caused by inffected tissue by exotoxin)

MANIFESTASI KLINISMANIFESTASI KLINIS

• Bervariasi : tanpa gejala s/d penyakit hipertoksik serta fatal. Faktor yg berpengaruh : - imunitas penjamu thd toksin - virulensi kuman - toksigenitas C.diphtheriae - lokasi anatomis penyakit - umur, peny.sistemik penyerta, - peny. di nasofaring sebelumnya

MANIFESTASI KLINIS (lanjutan)MANIFESTASI KLINIS (lanjutan)

• Masa tunas 2 – 6 hari• Pasien datang biasanya stl beberapa

hari dg keluhan sistemik.• Demam jarang melebihi 38.9 der.C• Manifestasi lain tergantung pd lokalisa-

si peny.difteri ( hidung, tonsil, faring, laring, kulit, vulvovaginal, konjungtiva, telinga ).

ImmunityImmunity

• Shick test: does someone has the antitoxin ?

(+) lower antitoxin titers

(-) immunity ; higher anti toxin titers

• Congenital passive immunity

“absolute” in 3 months 15% : (+) shick test

“parsial” in 6 months 50% : (+)

Distribution according to spot of the affected tissueDistribution according to spot of the affected tissue

1. Nasal diphtheria (2%) • running nose purulosanguinous secretion

2. Tonsil and pharynx (faucial diphtheria) 75%

- likely to attack adenoid, uvula and palatum mole

- subfebril temperature – pseudomembran- sore throat, odinophagia- might change the voice, disphagia - regional lymph node

3. Laryngo – trocheal (25%)• wide spread of pharynx infection• severe upper respiratory tract

obstruction tracheotomy

4. Cutaneous diphtheria • the area of auricular, conjunctiva,• umbilicus, vagina

DIFTERIA HIDUNGDIFTERIA HIDUNG

• Menyerupai common cold, pilek ringan dg/tanpa gej.sistemik.

• Sekret hidung : serosanguinus – mukopurulen – shg lecet pd nares dan bibir atas.

• Membran putih pada septum nasi.• Absorpsi toksin lambat, gej.sistemik ti-

dak nyata diagnosis lambat dibuat.

DIFTERIA TONSIL FARINGDIFTERIA TONSIL FARING

• Anoreksia, malaise, demam ringan, nyeri menelan.

• 1 – 2 hari timbul membran melekat, putih kelabu menutup tonsil dan dinding faring, uvula, palatum molle, atau ke bawah : laring & trakea.

• Dpt terjadi limfadenitis servikalis dan submandibular, dpt edema jar. lunak leher luas : bullneck

DIFTERIA TONSIL FARING DIFTERIA TONSIL FARING (lanjutan)(lanjutan)

• Pada kasus berat :gagal nafas/sirkulasi. Paralisis palatum molle : kesukaran menelan

dan regurgitasi. Stupor, koma, bahkan kematian dpt terjadi

dlm 1 minggu – 10 hari.• Pada kasus sedang: penyembuhan ber-

angsur, dapat dg penyulit miokarditis dan neuritis .

• Kasus ringan : membran lepas dlm 7-10 hr, penyembuhan sempurna

DIFTERIA LARINGDIFTERIA LARING

• Biasanya perluasan difteria faring• Gjl. obstruksi sal.nafas atas menyolok

(retraksi suprasternal,interkostal dan supraklavikular ).

• Klinis = infectious croup lain ( nafas bunyi, stridor progresif, suara parau, batuk kering.

• Kematian mendadak terjadi jika ada pelepasan membran yg menutup jalan nafas

DIFTERIA DIFTERIA KULIT,VULVOVAGINAL,KONJUNGTIVA, DAN KULIT,VULVOVAGINAL,KONJUNGTIVA, DAN

TELINGATELINGA

• Tidak lazim ( unusual )• Kulit : tukak,tepi jelas, membran pada

dasarnya, cenderung menahun• Mata : lesi di konjungtiva (kemerahan),

edema dan membran pd konj.palpebra• Telinga: otitis eksterna, sekret purulen dan

berbau

ToxinToxin

• Exotoxin could cause general or local symptom

• Lymphogenic and hematogenic spread to the regional lymph node, heart, kidney and nerve tissue

• Pathology : • enlargement and edematous of regional lymph node (“bull

neck”)

• heart myocardium inflammation and degeneration

• kidney and liver local necrotic, interstitial nephritis (seldom)

• nerves myelin sheet destruction and degeneration , edematous of the axon

LaboratoryLaboratory

• Decrease of Hb and erythrocyte

• Leucocytosis, PMN

• Urine: • mild albuminuria

• founded as thorax-hialyn sediment ,

• erythrocyte, leukocyte

DiagnosisDiagnosis

1. Clinical manifestations.

2. Direct preparation / positive culture of

throat swab.

3. Immunization history

DIAGNOSISDIAGNOSIS

• Didasarkan atas pemeriksaan klinis. Penundaan pengobatan dg menunggu hasil laboratorium akan membahayakan jiwa pasien.

• Diagnosis pasti : isolasi C.diphtheriae, dg pembiakan pd media Loeffler dilanjutkan dg tes toksinogenisitas scr in-vivo ( marmut ) dan in-vitro (Elek )

Differentials diagnosisDifferentials diagnosis

• Nasal diphtheria • Corpus alienium• Syphilis congenital

• Faucial diphtheria• Tonsillitis follicularis (lacunaris)

• Fever

• general conditions

• regional lymph node

• direct preparation / culture

DIAGNOSIS BANDINGDIAGNOSIS BANDING

• Dift. hidung : rhinorhea, benda asing dlm hidung, snuffles (lues kongenita)

• Dift. faring : tonsilitis membranosa akut o.k. streptokokus, mononukleosis infeksiosa, tonsilitis membranosa non- bakterial, tonsilitis herpetika primer, blood dyscrasia, pasca tonsilektomi

• Dift. laring : laringitis, spasmodic croup, angioneurotic edema, benda asing di laring

• Dift. kulit : impetigo dan infeksi kulit o.k.strepto/stafilikokus.

• Angina Plaut Vincent • fragile membrane, thick, smelly, not easy

bleeding • direct preparation Bacillus fusciformis

(+ gram)

• Laryngitis diphtheria• laryngitis acute / laryngo tracheitis• corpus alienum

PENYULIT / KOMPLIKASIPENYULIT / KOMPLIKASI

• Sebagai akibat: 1. inflamasi lokal 2. aktivitas eksotoksin (3). Infeksi sekunder

• Pengelompokan : obstruksi jalan nafas, dampak eksotoksin ( otot jantung, saraf dan ginjal ), infeksi II oleh bakteri lain

PENYULIT / KOMPLIKASI PENYULIT / KOMPLIKASI (lanj.)(lanj.)

• Obstruksi jalan nafas : o.k.tertutupnya jln nafas oleh membran difteri, edema tonsil , ,faring, submandibular, servikal

• Dampak toksin : miokarditis pd mg I – VI ( tu mg II ). Pada saraf :lm, bilateral, saraf motorik

• Infeksi II bakteri : penyulit ini jarang terjadi ( o.k. antibiotik )

ComplicationsComplications

• Cardiovascular system Occurred at the end of the first week or early of the 2nd week . ECG abnormality 20%.

• ST-segment mild depression; frequently T-wave inversion at lead 2 or more.

• Disturbances of conductions (bad prognosis)

• BBB (complete heart block)

• Cardiac Sign • tachycardia in the beginning.

• myocardium acute inflammation bradycardia

• Myocarditis• weakness of the 1st heart sound• heart hypertrophy• gallop rhythm.• systolic murmur

• Cardiac shock (usually in the 2nd week)• extensive myocardium damage decrease of

cardiac output shock

• Cardiac decompensation

• Urogenital system : nephritis.• Nerves system : 10% of patients

– Palate paralysis : voice changes/disphagia (1st/2nd week)

– Ophthalmologic muscles especially accommodation muscles • Strabismus• pupil dilatation • ptosis (3rd week and following

weeks)

• General paralysis affected the face , neck and extremities (after the 4th week).

• N. Phrenicus paralysis (4th-7th week) : cough, dyspnoe, thoracal breathing, cyanosis .

• Respiratory systems– Airway obstruction– Bronchopneumonia– Atelektasis

Airway obstruction Airway obstruction Tracheotomy Tracheotomy

• Dyspnea, cyanosis

• Irritability

• Stridor inspiratory

• Retraction

- epigastrium

- intercostals

- suprasternal

PENGOBATANPENGOBATAN• TUJUAN :

1. menginaktivasi toksin secepatnya 2. mencegah/me-minimal penyulit 3. mengeliminasi C.diphtheriae 4. mengobati infeksi penyerta/penyulit

• Umum : isolasi, istirahat, cairan dan diet adekuat, menjaga jln nafas, kelem-baban udara.

PENGOBATAN (lanjutan )PENGOBATAN (lanjutan )

• Khusus : 1. antitoksin ( Anti Diphtheria Serum ) 2. antibiotika : untuk membunuh bakt., menghentikan produksi toksin. Penisilin prokain 50.000-100.000 U/kgBB/hari selama 10 hari. 3. kortikosteroid : obst. nafas (bullneck) miokarditis.

TreatmentTreatment

1. General

- isolation , good nursing- observation of the complications- bed rest total

2. Specific

- A.D.S 100.000 UI- Antibiotic : PP 50.000 UI/KgBW.

TreatmentTreatment

- Corticosteroid = anti infection, anti allergy, anti edema,- Prednisone 2mg/KgBW, stop by tapp off.

• Paralysis = Strychnine ¼ mg , vit BI100mg 10 subsequent days.

PrognosisPrognosis

Depends on : 1. Age

2. Stadium

3. Localization

4. Bacteria pathogenicity (mitis has lower- virulency)

5. immunization status

6. Are there any complication ?

7. Antibiotic resisitence

PrognosisPrognosis

5. Antitoxin

1st day 0.3% (mortality)

2nd days 4%

3rd days 12%

> 4th days 25%

AttentionAttention

1. Totally bed rest (luminal 5 mg/KgBw, largactil 2mg/KgBw)

2. Throat swab

3. ECG each week

4. Urinary and hematological examination weekly

5. Pulse, respiratory, defecation

6. Airway obstruction

PROGNOSISPROGNOSIS

• Setelah ditemukannya ADS ( Anti Diftria Serum ) , prognosis baik.

• Kematian mendadak (Krugman ) : 1. obstr. jln nafas mendadak, terlepas-nya membran difteri 2. miokarditis dan gagal jantung 3. paralisis diafragma ok neuritis frenik.

• Miokarditis dan neuritis p.u. sembuh.