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Fever, Rash and Acute Kidney Injury in a 10-year-old Girl

Carr, Jeremy P. J. MB BS*; McCloskey, Kathleen M MB BS*; Campbell, Janine MB BS, PhD; Efron, Daryl MB BS, MD*

The Pediatric Infectious Disease Journal: February 2014 - Volume 33 - Issue 2 - p 227
doi: 10.1097/INF.0000000000000090
Your Diagnosis, Please

Supplemental Digital Content is available in the text.

*Department of General Pediatrics; and Department of Haematology, Royal Children’s Hospital Melbourne, Victoria, Australia. E-mail:

The authors have no conflicts of interest to disclose.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (

A 10-year old girl presented to a regional hospital in southern Australia with a 24-hour history of fever, rigors, lower abdominal pain, vomiting and headache. Her medical history was significant only for attention deficit hyperactivity disorder treated with clonidine. She had no sick contacts and had not recently travelled interstate or overseas.

Her vital signs included a temperature of 39.2°C, heart rate of 110 beats/min, blood pressure of 100/70 mmHg and respiratory rate of 22 breaths/min. On examination, the patient was alert and orientated. Abdominal palpation elicited generalized tenderness. Cardiopulmonary and neurological examinations were normal. There was no rash present.

Initial investigation results showed hemoglobin of 15.5 g/dL, platelet count of 114 × 109/L and white blood cell count of 6 × 109/L, with a differential of 90% neutrophils, 5% bands and 5% lymphocytes. Bilirubin was 26 μmol/L (normal: 0–15) and C-reactive protein was 315 mg/L (normal: <8). Hepatic transaminases, electrolytes, blood urea nitrogen and creatinine were all normal. Because of the concern of appendicitis, an abdominal ultrasound was performed and was normal, although the appendix itself was not visualized. She was discharged home with simple analgesia but returned the following day with ongoing abdominal and back pain, myalgias, headaches, delirium, sore throat and a truncal rash.

On reevaluation, the patient was hypothermic (temperature of 35.5°C) and tachycardic (heart rate of 120 beats/min). Blood pressure, respiratory rate and oxygen saturation were all normal. She was irritable, disinterested in her surroundings and at times, incoherent. She was also unable to walk due to calf and thigh pain. Abdominal examination revealed periumbilical and suprapubic tenderness with voluntary guarding. There was mild photophobia but no neck stiffness. She had widespread, small, blanching erythematous papules that were most prominent on her abdomen. There were no petechiae. Several small lymph nodes were palpable in her axilla. She had not passed urine since her initial presentation.

Repeat laboratory investigations revealed thrombocytopenia (platelet count of 10 × 109/L), acute kidney injury [creatinine of 231 μmol/L (normal: 30–80) and blood urea nitrogen of 23 mmol/L ( normal: 2.1–6.5), hypoglycemia of 1.3 mmol/L (normal: 3.3–5.8) and hepatic dysfunction with alanine aminotransferase of 41 U/L (normal: 0–30), aspartate aminotransferase of 125 U/L (normal: 0–30), alkaline phosphatase of 321 U/L (normal: 85–390) and bilirubin of 99 μmol/L (normal: 0–15)]. The patient also had evidence of coagulopathy with INR of 1.7 (normal: <1.3), fibrinogen of 6.4 g/L (normal: 2.0–4.0) and APPT of 23 seconds (normal: 26–36). The white blood cell count was 12.4 × 109/L, with a differential of 92% neutrophils and 8% lymphocytes. C-reactive protein was 462 mg/L, and creatinine kinase was 2546 IU/L (40–240). Examination of the urine demonstrated leucocytes of 20 × 106/L, red blood cells of 50 × 106/L and moderate proteinuria with urine protein to creatinine ratio of 1.8 (normal: < 0.2). Her chest radiograph was normal.

The patient received fluid resuscitation, 50 mg of intravenous hydrocortisone and empiric antibiotic therapy with intravenous cefotaxime and vancomycin. She was transferred to a tertiary-level pediatric hospital. On arrival, she was normothermic but hypotensive with a blood pressure of 84/47 mmHg. She was also lethargic, confused and distressed due to abdominal pain. Generalized edema and cool peripheral extremities were noted. She was given a 50 mL/kg bolus of normal saline to correct her hypotension. Cefotaxime was continued, and flucloxacillin, doxycycline and oseltamavir were added empirically to her treatment regimen.

She was admitted to the Intensive Care Unit for management of her altered mental status and oliguric acute kidney injury. Her urine output was 0.6 mL/kg/h over the first 24 hours in the hospital, maintained with judicious intravenous fluid therapy. On hospital day 2, the patient developed hypertension with a blood pressures up to 159/51 mmHg (95th percentile for age: 119/78 mmHg). Her edema worsened and was associated with a 10% gain in total body weight. The patient defervesced 48 hours after commencing antimicrobial therapy, but became progressively more delirious. An MRI/MRA of the brain was performed to exclude an intracranial bleed or a vasculitic process, and this was normal. On hospital day 4, she developed petechiae, most prominently on her distal lower limbs and buttocks, which progressed to purpura. She remained thrombocytopenic and developed a normochromic anemia (hemoglobin of 6.1 g/dL), requiring several transfusions of platelets and packed red blood cells. A direct Coombs test was negative, lactate dehydrogenase was 1365 U/L (normal: 313–618) and haptoglobin and urinary myoglobulin were both normal. The peripheral blood film contained no schistocytes and only rare red cell fragments, and ADAMTS13 activity was normal, making hemolytic uremic syndrome/thrombotic thrombocytopenic purpura unlikely. Abdominal ultrasound demonstrated splenic size at the upper limit of normal, nonspecific prominence of the portal tracts and diffusely echogenic kidneys. There was no growth from blood cultures. Additional negative test results included: leptospirosis polymerase chain reaction; Neisseria meningitidis polymerase chain reaction; influenza polymerase chain reactionand serologies for rickettsiae, ehrlichiosis, Q fever and locally relevant arboviruses (Barmah Forest Virus, Murray Valley Encephalitis Virus, Ross River Virus and Kunjin Virus). A biopsy of the purpuric skin lesions showed mild mid-dermal perivascular lymphocytosis and negative immunofluorescence staining, in particular for immunoglobulin A, excluding Henoch-Schonlein Purpura.

Her peripheral blood film on arrival (Fig., Supplemental Digital Content 1, along with additional history provided clues to the diagnosis.

For denouement see p. 231

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