An uncommon cause of fever in a patient with hyperthyroidism.

Fever as an indicator of disease has always been and remains a clinical symptom of great importance. It may be a manifestation of any inflammatory process of the thyroid and also may be presenting feature of thyroid storm. Melioidosis, is an infection caused by the gram negative bacterium Burkholderia pseudomallei and the commonest co-morbidity observed in India is diabetes mellitus. Here we present a case of Graves disease (hyperthyroidism) who was referred by primary care physician with history of prolonged fever of more than one month duration and later diagnosed to have melioidosis. It is important in primary care setting as family physicians need to be aware of this infection as it can affect many organs and early diagnosis and treatment will result in cure of this condition. Copyright:

Introduction

Melioidosis is an emerging infection in India, especially in males from rural areas, with diabetes and alcoholism being the commonest risk factors. Both sepsis with bacteremia and localized disease involving joints and focal abscesses are common. Melioidosis is more prevalent in immunosuppressed populations with diabetes mellitus or malignancy.[1] The commonest co-morbid condition observed was diabetes mellitus (80%) in a case series of 114 of whom 25 had liver abscesses who succumbed to their illnesss.[2] Prolonged febrile illness may be the presenting symptom in Melioidosis. Primary care and family physician needs to be aware of this infection as early diagnosis and treatment will reduce the morbidity associated with this condition.

A 32-year-old woman referred by a primary care physician presented with a history of prolonged fever of 40 days duration. She was a homemaker with no known contact to animals, farming, or gardening. She had two to three spikes of fever with chills per day with temperatures recorded up to 38°C. She had a history of receiving quinolones and penicillin group of drugs for febrile illness. She was earlier diagnosed to have hyperthyroidism and was on medical treatment with carbimazole. System symptom review was unremarkable. On examination, she was malnourished with BMI of 19.5 kg/m2. She was febrile with a temperature of 38.2°C, had tachycardia of 120 beats per minute with regular rhythm. She had a grade-2 diffuse goiter and there was no ophthalmopathy or dermopathy. Rest of the examination was essentially normal.

Investigations revealed normocytic anemia with a hemoglobin 10.2 gm/dL and rest of the cell lines were normal. She had an elevated C- reactive protein of 114 ng/L (N <3) and ESR of 70 mm/hour (N 0–15). Her blood smear examination was negative for a malarial parasite. Her liver function was normal except for low albumin of 2.5 gm/dL (N 3.5–4.4) and an albumin-globulin ratio reversal (total protein 8 gm/dL). Her TSH was <0.008 mIU/L (N 0.4–4.2) with free T4 of 3.4 (N 0.8–2 ng/dL). Her urine examination, chest radiograph, and electrocardiogram were non-contributory. Serial blood cultures were also collected. She was started on carbimazole 30 mg/day and also on a beta-blocker.

Her ultrasound abdomen and pelvis showed a heterogenous hypoechoic lesion in the right lobe of liver (3.7 cm × 6.5 cm × 6.3 cm) seen as multicystic with thick internal septae with demonstrable internal vascularity along the septae in the right lobe of liver. Her contrast-enhanced computerized tomogram [Figure 1] displayed heterogeneously enhancing liver lesion with honeycombing filling defect. A similar hypodense lesion was evident in the spleen. The honeycomb lesions in liver and spleen prompted the possibility of melioidosis. An ultrasound-guided aspirate from the liver lesion and blood culture [Figure 2] revealed the presence of gram-negative bacterium Burkholderia pseudomallei. A diagnosis of melioidosis on the background of hyperthyroidism was made.

Figure 1

CT scan showing heterogeneously enhancing liver lesion with honeycombing filling defect

Figure 2

B. pseudomallei colonies in MacConkey agar

She was started on parenteral ceftzadime and doxycycline. She made a dramatic improvement with resolution of fever within a week and on discharge, she was advised to continue the antibiotics (ceftazidime and co-trimaxazole) and antithyroid medication under the supervision of her primary care physician. She was scheduled for a review after one month.

The melioidosis was named from the Greek “melis”(distemper of asses) and “eidos”(resemblance) by Stanton and Fletcher in 1932.[3] It is a potentially fatal illness caused by the soil saprophyte gram-negative bacterium Burkholderia pseudomallei and is found in contaminated water and soil and spreads to humans through inhalation and inoculation. A high index of suspicion to detect melioidosis in the early stages and administer appropriate antibiotics is needed.[4] It is probably underreported from Indian continent and most cases have been reported from southwestern coastal Karnataka and northeastern Tamil Nadu.[2]

As elsewhere, the majority of cases have type-2 diabetes mellitus and occupational exposure to the environment.[5] Most present with community-acquired pneumonia and/or bacteremia, especially during heavy rainfall. The high seropositivity rate (29%) in Karnataka and isolation of B. pseudomallei from the environment in Tamil Nadu and Kerala confirm India as melioidosis-endemic although the full extent of the distribution of the organism across the country is unknown.[6]

Laboratory diagnosis of melioidosis can be difficult. Suspect colonies on 10% sheep blood agar which are oxidase-positive and motile are subjected to agglutination using in-house B. pseudomallei anti-sera, rabbit derived which usually expedites the diagnosis.[7] The current treatment protocol of melioidosis comprises two phases. The first is the acute phase, the aim of which is to stop patients from dying of overwhelming sepsis and the second is the eradication phase, to kill any residual bacteria and to minimize the risk of infection relapsing. The combination of agents used, duration of therapy, and need for adjunct modalities depends on the type, severity, and antimicrobial susceptibility of infection.[8910] Treatment failure has been defined in studies as fever for longer than 14 days or bacteremia for longer than 7 days. The drugs recommended in the acute phase are ceftazidime 40 mg/kg intravenous every 6 h or 8 h for 2–4 weeks plus cotrimoxazole 10/50 mg/kg (up to 320/1600 mg) every 12 h. An effective alternative is meropenem 25 mg/kg every 8 h as in case of neuromelioidosis, persistent bacteremia. The drugs recommended in the oral eradication phase are cotrimoxazole and amoxycillin-clavulanic acid and doxycycline.[9] In conclusion, primary care and family physician needs to be aware of this condition which can present as prolonged febrile illness in the presence of conditions such as diabetes mellitus or hyperthyroidism. Early detection and treatment will significantly reduce the morbidity and mortality associated with this infection.

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