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

• A membrane has formed on the tonsils

and pharynx;
 Question

• What are the possible causes?

 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

• What is the cause of the membrane in

diphtheria?
 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

• What are the clinical features of diphtheria?

 Answer

• Sore throat, stridor & • Sore throat may be

airway obstruction followed by severe
• A white to grey stridor and airway
membrane obstruction.
• “bull neck” • A white to grey
• Myocarditis membrane, which
bleeds on attempted
removal, is seen in
the throat or nose.

Contd
 continued

• There may be
• Neuropathy: bulbar massive
paralysis, or enlargement of the
peripheral weakness neck due to oedema
• Nephropathy around the
• Thrombocytopaenia enlarged neck
& disseminated glands ("bull neck")
intravascular • Myocarditis may
coagulation develop in the first
or second week

Contd
 continued
• 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.
Diphteria

Bambang Mulyawan
FK-UMM
 DEFINISI

• DIFTERIA ADALAH:PENYAKIT
INFEKSI AKUT SANGAT
MENULAR,DISEBABKAN
CORYNEBACTERIUM DIPHTHERIAE ,
DITANDAI PEMBENTUKAN PSEUDO
- MEMBRAN PADA KULIT DAN/ ATAU
MUKOSA.
 Diphtheria
• 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
1883 : Klebs found the bacteria in
pseudomembran
1884 : Loeffler grew the bacteria
1888 : The bacteria makes toxin
1894 : Von Behring found the antitoxin
1913 : Immunization against the disease
 Epidemiology

• 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
Propinsi 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
Corynebacterium 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
 ETIOLOGI
• 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 diphtheriae
G+, club shaped, pleomorphic, aerobic rod
Diphtheria

Figure 24.6
 Pathogenesis 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
 Pathogenesis

• The bacilli multiply in upper respiratory tract

• Vulva, skin, conjunctiva, umbilicus, ear, are
rare
• Pseudomembrane and toxin :
local  spread out
 PATOGENESIS & 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
( 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
(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 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 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)

• 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 ).
 Immunity

• 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 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 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 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
(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 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
KULIT,VULVOVAGINAL,KONJUNGTIVA, DAN
TELINGA

• 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
 Toxin

• 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
 Laboratory

• Decrease of Hb and erythrocyte

• Leucocytosis, PMN
• Urine:
• mild albuminuria
• founded as thorax-hialyn sediment ,
• erythrocyte, leukocyte
 Diagnosis

1. Clinical manifestations.
2. Direct preparation / positive culture of
throat swab.
3. Immunization history
 DIAGNOSIS
• 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 diagnosis

• Nasal diphtheria
• Corpus alienium
• Syphilis congenital

• Faucial diphtheria
• Tonsillitis follicularis (lacunaris)
• Fever
• general conditions
• regional lymph node
• direct preparation / culture
 DIAGNOSIS 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 / 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 (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 )
 Complications
• 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  Tracheotomy

• Dyspnea, cyanosis
• Irritability
• Stridor inspiratory
• Retraction
- epigastrium
- intercostals
- suprasternal
 PENGOBATAN
• 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 )
• 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.
 Treatment

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.
 Treatment

- Corticosteroid = anti infection, anti allergy, anti

edema,
- Prednisone 2mg/KgBW, stop by tapp off.

• Paralysis = Strychnine ¼ mg , vit BI100mg  10

subsequent days.
 Prognosis

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
 Prognosis

5. Antitoxin

1st day 0.3% (mortality)

2nd days 4%
3rd days 12%
> 4th days 25%
 Attention

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
 PROGNOSIS

• 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.