Pediatrics International | 2021
Brucellosis as a cause of hyperferritinemia in systemic arthritis
Abstract
Hyperferritinemia is rare in children. The causes in children include macrophage activation syndrome (MAS), infections, systemic-onset juvenile idiopathic arthritis (SJIA), catastrophic anti-phospholipid syndrome, primary hemophagocytic lymphohistiocytosis (HLH), and chronic iron overload. In SJIA, the exaggerated production of inflammatory cytokines can explain most of the features of the disease. In addition to disease exacerbation in SJIA, MAS, which is a well-known complication associated with SJIA, followed by infections, could also be implicated. Brucellosis is a common infection in Saudi Arabia due to ingestion of fresh dairy products. It has been reported to result in hyperferritinemia in addition to inducing MAS in healthy individuals. We describe here the case of a patient with an established diagnosis of SJIA who had been in remission on treatment for over a year when he developed brucellosis, which precipitated hyperferritinemia. This study was approved by the ethics board of King Abdullah International Medical Research Center (KAIMRC), and informed consent was obtained from the patient. A previously healthy 14-year-old male presented to our tertiary center with a high-grade fever for 1 month prior to presentation. His fever occurred daily, mainly in the evening, and it was associated with pain and swelling in multiple joints, including both hips, knee joints, the wrists, elbows, and temporomandibular joints (TMJ). In addition to extended periods of morning stiffness, he reported fatigability, loss of appetite, and unintended weight loss of 6 kg over a 6-month period. His systemic review was unremarkable, and he had no similar previous history. Physical examination revealed a well-looking, febrile boy with a bilateral scattered erythematous rash affecting the thighs. There was tenderness in both TMJs and active arthritis affecting both elbows, wrists, hips and knees. He had no lymphadenopathy or organomegaly, rest of examinations were unremarkable. The differential diagnoses included Epstein–Barr virus infection (EBV), cytomegalovirus infection (CMV), brucellosis, SJIA, and malignancy. Blood tests including inflammatory parameters were mentioned in Table S1, visit 1. Epstein–Barr virus infection (EBV) and CMV polymerase chain reactions (PCR) were negative. A bone-marrow aspiration and a biopsy were negative for leukemia and lymphoma. Hence, a diagnosis of possible SJIA was made, and the patient was started on prednisone 2 mg/kg/day divided doses, which resulted in a dramatic clinical improvement of his fever and arthritis. A summary of his visits’ record in the first year is provided in (Table S1). Almost a year later from the first presentation, the patient presented to the clinic with a history of daily fever persisting for 2 weeks and associated with fatigability and decreased appetite. There was no history of skin rash or joint symptoms. Further investigations and management are listed in Table S1, visit 7. He came for his regular follow up after two weeks but was not well during this visit; he was highly febrile, and he had arthritis affecting the right shoulder, the left hip, and bilateral sacroiliac joints. His blood tests were done, described in Table S1, visit 9, and they confirmed Brucella infection by Brucella abortus. The patient was admitted and started on three antibiotics: Gentamicin, doxycycline and rifampicin. The patient’s prednisone dose was increased to 10 mg twice daily, and methotrexate was stopped. Following two weeks in hospital he was discharged home to complete a 3 months’ course of antibiotics, and methotrexate was resumed at 15 mg p.o. weekly. Follow-up Brucella titers were 1:640 and 1:160 after 6 months and 12 months, respectively. The patient was followed for 2 years, during which he remained in remission and was taken off prednisone and subsequently methotrexate with no flare-up of his arthritis. Brucellosis is associated with high ferritin levels, which become normal after the primary infection is treated. The mechanism behind this could be related to the overproduction of activating cytokines, which contribute to macrophage activation, or could be due to a poorly regulated or inappropriate T-helper lymphocyte response to intracellular pathogens. In the literature, brucellosis can present in different ways and hyperferritinemia is one of its features, especially when associated with sHLH (Table 1). Clinicians should bear in mind this rare phenomenon, in some parts of the world, in the differential diagnosis of hyperferritinemia. Correspondence: Jubran Theeb Alqanatish, MD, Division of Rheumatology, Department of Pediatric, King Abdullah Specialized Children Hospital, King Abdulaziz Medical City, Riyadh, Saudi Arabia. Email: [email protected] Received 22 July 2020; revised 11 September 2020; accepted 28 September 2020. doi: 10.1111/ped.14492