A febrile girl with tonsillitis

Sukit Rungapinan, MD., Department of Pharmacology
Jaruk Hanprasertpong, MD., Department of Otolaryngology
Virat Sirisanthana M.D., Department of Pediatrics
Patient: An 8-year-old girl, Address: country side of Chiang Mai province
CC : Fever for 10 days and sore throat for 6 days

PI:
> 10 days PTA, she had an acute onset of high-graded fever. She took paracetamol but the fever and headache remained.
> 6 days PTA, she was seen by a doctor who gave a diagnosis of acute tonsillitis (injected and enlarged tonsils, body temperature 40 C, CBC: Hb 11.0 gm%, HCt 34%, WBC 4,600/cu.mm, N 68%, B 1%, L 29%, platelets 177,000/cu.mm). She was given intramuscular lincomycin 450 mg and oral amoxycillin 250 mg 3 times a day. High intermittent fever persisted.
> 2 days PTA, she developed rashes over the trunk, arms, and thighs. She also had various nonspecific symptoms, including faintings, mild nausea, periumbilical abdominal pain, diarrhea, mild sore throat, nonproductive cough, and severe bitemporal headache.
> On admission day, the fever persisted and her sore throat got worse.


Past History:
The girl had history of cleft lip and cleft palate which were repaired since she was 3 months old. She has routinely attended pediatric odontologist to have her teeth corrected. Her immunization status was up to date. There was no family history of similar illness. She usually plays around her house where grass and tree wildly grow on humid ground.


Physical examination:
VS: T 39.5 C, pulse rate108/min, RR 24/minm, BP=100/60 mmHg., BW 20 Kg
GA: looked sick, but fully concious
Skin: faint maculopapular rashes were observed over arms and thighs (fig.1). An ulcer with black crust on erythematous base was seen over her right shoulder region (fig. 2-3). Its size was approximately 8.0 mm in diameter. The lesion was not tender.
Lymph nodes: multiple enlarged lymph nodes (fig 4) were palpable as follows:
  > two predominately large (1.3 and 1.2 cm in diameter, respectively) on right supraclavicular area and on the lower portion of right posterior triangle of her neck
  > multiple small lymph node(less than 5 mm in diameter) in chain along both sides of posterior triangle of the neck could be palpated
All nodes were soft, non-tender, movable, and smooth surface.
ENT examination revealed surgical scar at philtrum and palate. Enlarged tonsils grade III/IV with hyperemia which extended on anterior tonsillar pillars and soft palate were detected (fig. 5). There was no exudative patch. Her pharynx was not injected. Her conjunctiva was normal.
Chest: Heart sound: WNL, Lungs: no adventitious sound
Abdomen: palpable liver (4 cm below right costal margin, span 13 cm.), spleen was not palpable
NS: WNL
 
Figure 1 maculopapular rash
Figure 2A black crusted ulcer at the right shoulder
Figure 3 Closed up the ulcer
Figure 4 Cervical and supraclavicular lymphadenopathy
Figure 5 Injected and enlarged tonsils with hyperemic soft palate

Active Problem list:
  1. Prolonged fever for 10 days
2. Nonspecific systemic complaints: faintings, nausea, abdominal pain, diarrhea, sore throat, cough, headache, poor appetite
3. Generalized maculopapular rash
4. Cervical and supraclavicular lymphadenopathy
5. Injected and enlarged tonsils with hyperemic soft palate
6. A black crusted ulcer at the right shoulder
7. Hepatomegaly

Initial laboratory investigations:
  CBC: Hb 9.2 g/dl, Hct 28 %, WBC=5,200/cu.mm (N 80%, L 20%), platelets 131,000/cu.mm
Peripheral blood smear for malarial pigment: negative
U/A: WNL
Since the provisional diagnosis of "scrub typhus" was made, the therapeutic diagnosis was started with oral doxycycline 2.2 mg/kg/dose given every 12 hrs (for the first 2 doses) . The fever dramatically subsided as presented in figure 6 . Twelve hours later, she became more cheerful and her appetite returned.
Therefore, doxycycline (2.2 mg/kg/day div q 12 hrs) was continued. The hyperemic soft palate and tonsils subsequently faded off. The tonsils were slightly decreased in size 36 hours after doxycycline. The
Lymph nodes and liver remained palpable at the time of the discharge from the hospital on day 3 of the treatment. Doxycycline was continued for 14 days.
Figure 6 Temperature chart
Follow-up: Seven days after the discharge (10 days after doxycycline) she was followed up. She was afebrile and had no rash. The lesion (i.e., eschar) moderately reduced in size. Her tonsils and lymph nodes became normal size for age (tonsils grade II/IV, Pic 10). Liver was just palpable below right costal margin.

Other laboratory investigations :
 

> Weil-Felix test (acute sample ...day 10 of fever): OX-2=1:40, OX-K=1:20, OX-19=1:40 (negative)
> Serum Immunofluorescent antibody titer (IFA) for Orientia tsutsugamushi (scrub typhus) and murine tuphus (acute sample ...day 10 of fever): < 50 (negative)
> The convalescent serum sample was not obtained.
Discussion
  Scrub typhus is a febrile illness caused by Orientia tsutsugamushi, an obligate intracellular bacterium in the Rickettsiaceae family. The organism is transmitted during the bite of trombiculid mites (chigger). Field rodents are the reservoir hosts. Scrub typhus is confined to a definite geographic region. It extends from northern Japan and far eastern Russia in the north, to northern Australia in the south, and to Pakistan and Afghanistan in the west. In 2000, there were 3,914 cases (6.34 cases per 100,000 population) of scrub typhus reported to the Thai Ministry of Public Health (MOPH). The true incidence is probably much higher since tests for anti-O. tsutsugamushi antibody are available in only a few medical centers in Thailand. ...........furthur readings: ref 1-2. Epidemiologic, clinical and laboratory features of scrub typhus in 30 Thai children seen at Chiang Mai University Hospital will be published in April (ref 3)

Discussion 1: Diagnosis and differential diagnosis of a patient with "eschar "
  > Although this case had no serologic verification, the course of illness, systemic manifestations, a typical eschar, and therapeutic response led to the diagnosis of scrub typhus without difficulty.
Tularemia, spotted fever rickettsiosis, and anthrax can present with eschars but by the epidemiology and clinical course they could be excluded in this case.
> Eschar is a very useful sign in making the diagnosis. Although eschar was described as an ulcer, surrounded by a red areolar and often covered by a dark scab, some did not have the dark scab. They were found in moist intertriginous areas, such as the genitalia and the perineum.
>Eschar, if carefully searched, was seen in 25-75% of patients with scrub typhus.

Discussion 2: Where should we search for? "eschar"
  Eschar occurs as the result of mite (chigger) bite. Since the chigger is small (<5 mm) and the bite is neither painful nor ichy, the history of the bite was not usually obtained. The mite lives in bushes. When it contact human skin, it moves anti-gravity (i.e, from the contact site upward to the head). When it hits the obstacles such as the intertriginous areas, it bites. The common sites found are genitalia and perineum, neck, inguinal area, umbilicus, and axilla.

Discussion 3: How can scrub typhus present with tonsillitis?
 

After mite bite (inoculation) the rickettsiae multiply and spread to the adjacent lymphoid structures.
The lymph nodes from the neck/shoulder region drained into nearly ipsilateral superficial cervical lymph node and deep cervical lymph node. Then, there are communications from intraoral structure (tonsil and nasopharynx), cervical lymph nodes, to the the contralateral neck.
> Tonsillitis, cervical and supraclavicular lymphadenopathy in this case, represented the regional lymphadenopathy in scrub typhus.


Discussion 4: How can we make the definite diagnosis of scrub typhus?
O. tsutsugamushi does not grow on artificial media. Its isolation requires mice or chick embryo or tissue culture inoculation, which is potentially a hazardous. Thus, the diagnosis of scrub typhus relies mainly on serologic methods. The standard reference methods are the IFA test and the indirect immunoperoxidase test using yolk sac-propagated or cell culture-derived O. tsutsugamushi antigens.
The study by Brown et al (ref 4) showed that:
> For the Weil-Felix test:
  > The overall specificity at the titer 1:=>320 was 0.97
> The overall sensitivity at the titer 1:=>320 was 0.44
> With paired sera collected 3 or more days apart, a 4-fold rise to => 1:320 was 0.96 specific and 0.39 sensitive
> For the IFA test
  > The overall specificity of the at the titer 1:=>400 is 0.96
> The overall sensitivity of the IFA test at the titer 1:=>400 is 0.48
> With paired sera collected 3 or more days apart, a 4-fold rise to => 1:200 was 0.98 specific and 0.54 sensitive
The current serology test available in Thailand is the IFA test. The method was published in the handbook distributted by Ministry of Public Health (Ref.5). The Interpretation for the active infection is :
  > IgM or IgG titer 1:=>400 or
> With paired sera, a 4-fold rise to => 1:200

Discussion 5: Could this girl have murine typhus? (ref 2)
 

There are 3 rickettsial diseases in Thailand, scrub typhus, murine typhus and Thai tick typhus. All respond well to doxycycline as seen in this case. But;
> A patient with murine typhus does not present with "eschar" as in this case.
> A patient with Thai tick typhus usually have "petichial rash".

Discussion 6: What are the common severe manifestations of scrub typhus?
 

> pneumonitis
> meningitis


Discussion 7: Antimicrobial agents
 

Patient with scrub typhus or murine typhus or Thai tick typus responded well to doxycycline, tetracycline or chloramphenicol. Although cases of scrub typhus poorly responsive to doxyclicline and chloramphenicol had been recently reported from northern Thailand (ref 6). One recent randomized clinical trial had shown that rifampicin might be useful in treating these poorly responsive cases (ref 7).


References and suggested further readings
1. Watt G, Walker DH. Scrub typhus. In: Guerrant RL, Walker DH, Welter PF, editors. Essentials of tropical infections diseases. USA: Churchill Livingstone, 2001: 278-281.
2. วิรัต ศิริสันธนะ. โรคติดเชื้อ Rickettsiae. ใน: ทวี โชติพิทยสุนนท์, อุษา ทิสยากร (บรรณาธิการ). Update on Pediatric Infectious Diseases IV. กรุงเทพฯ : โรงพิมพ์ ชัยเจริญ; 2544. p.184-90. Click here for reprint in pdf file.
3. Sirisanthana V, Puthanakit T, Sirisanthana T. Epidemiologic, clinical and laboratory features of scrub typhus in 30 Thai children. Pediatr Inf Dis J 2003;22:April issue (In press)
4. Brown GW, Shirai A, Rogers C, Groves MG. Diagnostic criteria for scrub typhus: probability values for immunofluorescent antibody and Proteus OX-K agglutinin titres. Am J Trop Med Hyg 1983;32:1101-7.
5 มงคล เจนจิตติกุล. โรคติดเชื้อริคเค็ทเซีย (Rickettsial Infection). ใน: ไพจิตร์ วราชิต, ณัฎฐีวรรณ ปุ่มวัน, สมชาย แสงกิจพร (บรรณาธิการ). โรคติดต่อที่เป็นปัญหาใหม่:คู่มือการตรวจวินิจฉัยทางห้องปฏิบัติการ. สถาบันวิจัยวิทยาศาสตร์สาธารณสุข กรมวิทยาศาสตร์การแพทย์ กระทรวงสาธารณสุข; 2541. p.247-56.
6. Watt G, Chouriyagune C, Ruangweerayud R, Watcharapichat P, Phulsuksombati D, Jongsakul K, Teja-Isavadharm P, Bhodhidatta D, Corcoran KD, Dasch GA, Strickman D. Scrub typhus infections poorly responsive to antibiotics in northern Thailand. Lancet. 1996;348:86-9.
7. Watt G, Kantipong P, Jongsakul K, et al. Doxycycline and rifampicin for mild scrub-typhus infections in northern Thailand: a randomised trial. Lancet 2000;356:1057-61.


Final Diagnosis : Scrub typhus

BACK to Interesting  Case List