TONSILOPHARYNGITIS DIPHTHERIAE COMPLICATED WITH DIPHTHERITIC MYOCARDITIS IN 13 YEARS OLD GIRL AT DR. KARIADI HOSPITAL SEMARANG-INDONESIA

TONSILOPHARYNGITIS DIPHTHERIAE COMPLICATED WITH DIPHTHERITIC MYOCARDITIS IN 13 YEARS OLD GIRL AT DR. KARIADI HOSPITAL SEMARANG-INDONESIA Disusun oleh : Teguh Oky Fachrozy SNIM : 11.2014.353Stase : THT RS Bayukarta - KarawangABSTRACTBackground : Diphtheria is a frequent upper respiratory tract illness caused by Coryne-bacterium diphtheriae characterized by sore throat, low fever, malaise, anorexia and pseudo-membrane on the tonsils, pharynx, larynx and nasal cavity. Case description: It was reported that 13 years old girl from Kudus referred to Dr. Kariadi Hospital with sore throat, low fever, hoarseness, cough, anorexia and malaise. Patient has history of immunization completely. Physical examination indicates enlarged tonsil grade II and pseudo-membranous in the area of the tonsils, uvula, and pharynx. There was no bull neck. Results: The result of throat swab culture and Neisser staining were positive, Blood agar, and Telurit agar culture lead to the performance Coryne-bacterium diphtherias colonies. From the result of the ECG, CK-MB and Troponin I show myocarditiss sign. Patient should be in strict isolation room until 3 times of cultures show negative results. The theraphy was ADS 80,000 unit i. v. (DAT treatment), penicillin procaine 50000-100000 IU/kg/day intramuscularly for 10 days and was given prednisone for reducing inflammatory reaction that can lead to airway obstruction. INTRODUCTIONDiphtheria is an acute, communicable disease caused by exotoxin producing Corynebacterium diphtheriae. Review of pathology in archived cases and the literature shows that C.diphtheriae usually localizes in the upper respiratory tract, ulcerates the mucosa, and induces the formation of an inflammatory pseudomembrane.

The exceedingly potent toxin is absorbed into the circulation and damages remote organs, potentially resulting in death.Materials and methodsCase report The case reported 13-year 8-month old girl hospitalized since January 31th 2013 until February 18th 2013. Her main complaint was sore throat (referred from Kudus Hospital with membranous tonsillitis suspected diphtheria). Since 4 days before hospitalization, the girl suffered from fever, low-grade fever, no seizure, no shivering, cough (+), disphagia (-), no discharge from ears, no nose bleeding, no gums bleeding, no ptechie, no nausea, no vomite, no gastrointestinal and urinary tract complaints.Three days before hospitalization, The doctor suggested to bring her to ENT specialist. Two days later, the girl suffered from difficulty in speaking and sore throat increased. From physical examination in emergency room, there were tonsil enlargement grade II and grayish patch pseudo-membranous in the area of the tonsils, uvula, and pharynx. There was no bull neck. The result of throat swab culture and Neisser staining were positive. Blood agar and Telurit agar culture lead to the performance Corynebacterium diphtherias colonies.ContinuedGeneral conditions were conscious, spontaneous breathing, and no retraction. Heart rate was 98 beats/minute and regular with good pulse. Respiratory rate was 28 times/minutes. Body temperature was 36,70C and blood pressure was 100/65 mmHg. Head was mesocephal, eyes were no conjunctival anemic, no icteric. Nasal flare was negative, no nasal discharge, mouth was no cyanotic with tonsil enlargement T2-2, hyperemis, grayish pseudomembrane in tonsils, uvula, and pharynx, no lymph neck enlargement, no bullneck, tenderness (+).Laboratory examinations on January 31th 2013 were Hb 10.5 g/%l, Ht 35.2%, leucocytes 20.200/mmk, erythrocyte 3.97million/mmk, thrombocyte 119.000/mmk, MCV 88.8 fl, MCH 26.30 pg, MCHC 29.70 gr/dl, cells count E0/B0/Bt0/Li77/Mo16, CKMB 35 U/l. ECG showed sinus arithymia. Chest X-ray showed normal. Results of cardiology consultation were sinus arythmia with suggestion for checking CKMB, troponin T, ECG monitoring, and bed rest.Riwayat kehamilanShe was born from G2P2A0 mother, 27 years old, aterm. Her mother got medical check up to midwife more than 4 times during pregnancy regularly and received vitamin, iron supplementation, and TT injection for twice. There was no history of illness during pregnancy. Basic immunization was complete.Her father is a mechanic with average income is of IDR. 1.000.000,-/month and her mother is a housewife.

Observasi rawat On the 5th day, the patient was still dispneu, sore throat, and hoarseness. She looked ill appearance. Pseudo-membrane was still positive in uvula, bleeding (+), but showed improvement. Tonsil was T2-2, hiperemis (+). Throat swab culture was still positive for Corynebacterium diphtheriaOn the 7th days, Physical examination of tonsil showed T2- T2 hyperemic, pseudo-membrane was still positive in uvula but showed improvement. Suggestion swab and culture daily until 3 times examination showed negative. There was no Corynebacterium diphtheriae colonization in both of throat swab and culture. Prednisone began to be tapering off 2-2-1 tablets (25 mg). On the 8th days, Second throat swab and culture showed no Corynebacterium diphtheriae colonization.On the 9th days, Third throat swab and culture showed no Corynebacterium diphtheriae colonization. On the 10th day, Tonsil was T1-1 and was not hiperemis. Procaine penicillin injection was stopped after 10 days administration.On the 12th day, sore throat was improvement but she was still cough.On 13th day, the patient complained about hoarseness. Antibiotic have been switched to erythromycin oral 3x500 mg. She was programmed to indirect laryngoscope and consulted to pediatric cardiology. She was assessed myocarditis diphtheria and received prednisone 6-5-5 tablets.On the 15th day, the patient was still hoarseness. The result of indirect laryngoscopy showed laryngitis.On the 16th day, laboratory result of CKMB showed 23 U/l. Electrocardiography showed sinus rhythm, normoaxis deviation, T-inverted in lead II, III, V3- V6 and depression of ST segment in lead II, V4- V6.On the 17th day, the patient had no complaint.On the 19th day, electrocardiography showed sinus rhythm, normoaxis deviation, T inverted in lead II, III, V3-V6 and depression of ST segment in lead II. The patient got improvement and had no complaint. So she discharged from hospital and had to control to policlinic.RESULTS AND DISCUSSIONSIn this case, swab staining and culture were positive for Corynebacterium diphtheria and the patient was diagnosed with tonsilopharyngitis diphtheria. Pathology of diphtheriaC. diphtheria is usually transmitted by direct contact or by sneezing or coughing. In populations with a high rate of immunization, improved coverage in children has shifted the age distribution of those afflicted to unimmunized or poorly immunized adults. Furthermore, relatively increased isolation of nontoxigenic strains of C. diphtheria versus toxigenic strains is noted when immunization rates are improved. Diphtheria commonly affects the tonsils, pharynx, and larynx. The C. diphtheria remains in the superficial mucosa or skin and elaborates its exotoxin. The diphtheria exotoxin, a potent 62 kd polypeptide inhibits protein synthesis leading to local tissue necrosis. The exotoxin is absorbed into the mucous membranes and causes destruction of epithelium and a superficial inflammatory response.Expression of the gene is regulated by the bacterial host and is iron dependent. In the presence of low concentrations of iron, the gene regulator is inhibited, resulting in increased toxin production.As toxin concentrations increase, the toxic effects extend beyond the local area due to distribution of the toxin by the circulation.3 Diphtheria toxin does not have a specific target organ, but myocardium and peripheral nerves are most affected.Human diphtheria infection may terminate with acute cardiac failure or may prove fatal weeks later during convalescence.Examination of heart tissues after death demonstrates cardiac damage in many cases, although the pathologic lesions are varied and inconsistent, perhaps representing a spectrum of changes related to cumulative exposure to toxin. When toxin concentrations are low, the heart chambers may be dilated with no effusion or malformation.No other inflammatory cells are observed. Conduction tissue lesions are not extensive. Abnormalities of coronary vessels, endocardium, or epicardium are not seen.Clinical presentationClassic diphtheria is an upper-respiratory tract illness characterized by sore throat, low- grade fever, and an adherent pseudo-membrane of the tonsil(s), pharynx, and/or nose. The disease can involve almost any mucous membrane.The infection most often manifests as membranous naso-pharyngitis or obstructive laryngotracheitis.C. diphtheria disseminates from the skin or respiratory tract and causes invasive systemic infections including bacteremia, endocarditis and arthritisIn this casethe girl suffered from low grade fever, sore throat, cough, disphagia, hoarseness, difficult in speaking and in the course of disease, the girl was dispneu. From physical examination, there were stridor, tonsil enlargement T2-2, hyperemic, and an adherent grayish-white pseudo-membranous in the area of the tonsils, uvula, and pharynx.These clinical manifestations were corresponded to tonsilopharyngitis diphtheria.Early symptoms include malaise, sore throat, anorexia and low- grade fever. Two to three days later the membrane appears in the pharyngeal/tonsillar area.In cases of severe disease the individual may also develop edema of the submandibular areas and the anterior neck, along with lymphadenopathy, giving the characteristic bullneck appearance.

On the 13th day, the patient complained about hoarseness. Then she was programmed to indirect laryngoscope. The result of indirect laryngoscope showed laryngitis.Diagnosis of diphtheriaDiagnosis is usually made based on history, clinical presentation, and swab staining and culture as it is essential to begin therapy as soon as possible.Diphtheria should be suspected based on the following clinical clues :

mildly painful tonsillitis and/or pharyngitis with associated membrane, especially if the membrane extends to the uvula and soft palate; adenopathy and cervical swelling, especially if associated with the membranous pharyngitis and signs of systemic toxicity; hoarseness and stridor; palatal paralysis; serosanguinous nasal discharge with associated mucosal membrane; and temperature elevation rarely in excess of 39.4C (103F). Other toxin mediated complications of diphtheria are toxic cardiomyopathy which occurs in 1025% of patients with respiratory diphtheria and is responsible for 5060% of deaths. Neurotoxicity and renal damage can also occur.Centre for Disease Control and Prevention (CDC 2010) defines diphtheria as :

Probable: In the absence of a more likely diagnosis, an upper respiratory tract illness with an adherent membrane of the nose, pharynx, tonsils, or larynx; and absence of laboratory confirmation; and lack of epidemiologic linkage to a laboratory confirmed case of diphtheria. Confirmed: An upper respiratory tract illness with an adherent membrane of the nose, pharynx, tonsils, or larynx; and any of the following: isolation of Corynebacterium diphtheriae from the nose or throat; or histopathologic diagnosis of diphtheria; or epidemiologic linkage to a laboratory confirmed case of diphtheria. In this casebased on history of illness, the patient suffered from low-grade fever and cough (+) since 4 days before hospitalization . One day later, she was sore throat, disphagia, and hoarseness. The parents take her to physician again and she was diagnosed tonsillitis. Two days later, the girl suffered from difficulty in speaking and sore throat increased.From physical examination result, there were tonsil enlargement grade II and an adherent grayish-white pseudo-membranous in the area of the tonsils, uvula, and pharynx. The result of indirect laryngoscope showed laryngitis.The result of throat swab culture and Neisser staining were positive, Blood Telurit agar culture lead to the performance Corynebacterium diphtherias colonies. According to CDC classification, the patient was categorized to confirmed diphtheria because there were upper respiratory tract illness with an adherent membrane of the nose, pharynx, tonsils, or larynx with positive culture for Corynebacterium diphtherias colonies (level of evidence 1)treatmentThe treatment of diphtheria is divided into general and specific treatment. The general treatments includes: 1) isolation, 2) bed rest at least 2-3 weeks, 3) soft or liquid food depending on the state of the patient, 4) cleanliness of respiratory track and liquid absorption, and 5) electrocardiography control 2-3 times a week for 4-6 weeks to detect myocarditis earlier. The specific treatment aims to neutralize toxin produces by diphtheria bacilli and kill diphtheria bacilli producing toxin (level of evidence 3)In this casethe decision to treat not only based on clinical manifestation but also from microbiology examination on the first admission in emergency unit.Furthermore, swab of pseudo-membranous area were taken to confirm for diphtheriae cultures too. She was placed in isolation room in PINERE until having obtained the results of 3 times negative cultures and took bed rest in hospital.

In this caseFor nutritional support, the patient received 6x300 cc liquid diet I via NGT with the need of energy was 1900 kcal per day, 285 grams of carbohydrates, 60 grams of protein, and 58 grams of lipid.For specific treatment, the patient received procaine penicillin injection of 2 million unit (right and left buttom) for 10 days, DAT 80.000 unit, ketorolac injection 3x30 mg. Per-oral : paracetamol 4-6x500 mg (if T>38oC), prednisone 40 mg daily (3-3-2 tablets) for reducing inflammatory reaction that can lead to airway obstruction. The most effective treatment for diphtheria is early administration of diphtheria antitoxin (DAT), along with appropriate antimicrobial therapy to eliminate the corynebacteria from the site of infection thus stopping ongoing toxin- production the results of 3 times negative cultures, and/or at least 24 hours after completing treatment and show an improvement of symptoms, finally the patient was getting improvement clinically and then transferred to the inpatient ward. Finally there is no growth in culture and Neisser staining result during the fourth until sixth day hospitalization. complicationToxin mediated complications of diphtheria are toxic cardio-myopathy which occurs in 10 25% of patients with respiratory diphtheria and is responsible for 5060% of deaths. Neurotoxicity and renal damage can also occur. Some of these features may present up to six weeks after the onset of the illness suggesting an immunological basis for the pathophysiologic mechanism for these delayed features of diphtheriaAcute mortality is due to toxin-mediated diphtheritic cardio-myopathy, suffocation by the pseudo- membrane, disseminated intravascular coagulation, and renal failure.Prognosis Diphtheria is associated with high mortality. For those in whom the disease is recognized on the first day and appropriate treatment instituted mortality is 1% but those in whom such treatment is delayed till the fourth day mortality rises to 20%

In this case, the patient had good outcome and prognosis was good with no mortality. Its due to an early recognition, prompt ADS administration, better care, and monitoring. The patient should be monitored closely for complications and checked for routine blood biochemistry including CPK-MB, SGOT, Troponin-T, and ECG monitoring Level of evidenceThey reported that the immediate cause of death was myocarditis (85%), airway compromise (11.1%) and septic shock due to nosocomial sepsis. Inadequate immunization, hypotension at admission and presence of any complication like airway compromise, myocarditis and renal failure had a significant adverse effect on outcome (P