Atypical clinical presentation of systemic juvenile idiopathic arthritis or Still's disease: a report of two cases

Juvenile idiopathic arthritis (JIA) constitutes a group of arthritis of unknown origin that begins before the age of 16 years. Still´s disease is the systemic form of this condition. Its clinical presentation is marked by fever, rash and sometimes joint pain, in the absence of evidence of another aetiology of the fever. We present the cases of two boys aged 4 and 10 years admitted for fever, with a cerebral origin for the first and no infectious site for the second. Fever persisted after antimalarial treatment and adequate antibiotics. Ferritinaemia, elevated sedimentation rate, lactate dehydrogenase (LDH), triglycerides, and increased serum transaminases, all in the absence of evidence of other inflammatory or malignant diseases were suggestive of Still's disease. Both children received a corticosteroid therapy with progressive dose reduction associated to methotrexate during treatment. Fever disappeared within a few hours after initiation of corticosteroid therapy, with considerable improvement in clinical state. To the best of our knowledge, these cases are among the rare cases of childhood Still disease reported in sub-Saharan Africa. These cases highlight the importance of investigating non-infectious causes of persistent fever in children, in a context of infectious disease endemicity.

Systemic juvenile idiopathic arthritis (SJIA) is distinguished by a systemic involvement and a particularly severe inflammatory syndrome. Its diagnosis is based on major criteria such as a hectic fever, a typical rash during febrile peaks, both associated or not with symmetrical or non-symmetrical polyarticular involvement. Minor criteria such as dysphagia, odynophagia, poly lymphadenopathy, hepatomegaly and splenomegaly may complete the picture [2]. On paraclinical, it is common to note an increase in ferritinaemia with a fall in its glycosylated beta fraction, very high C-reactive protein (CRP) and sedimentation rate indicating significant biological inflammation.
In addition, hepatic cytolysis, increased lactate dehydrogenase (LDH) and hypertriglyceridemia are not uncommon.
The diagnosis is made after excluding other possible causes of fever in children [2,3]. This is because fever is the major symptom of several diseases such as malaria and various bacterial infections; infections which are very frequent in children in low/middle income countries like Cameroon. This situation leads to excessive use of antimalarials and antibiotics, due to the persistence of fever [4]. We  The chest X-ray showed no infection site, the right hip ultrasound showed intra-articular effusion and the abdominal ultrasound found no lymphadenopathy. The diagnosis of Still disease was made. As soon as the first dose of corticosteroids was administered at 1mg/kg, there was a regression of the fever within 24 hours. In addition to corticosteroid therapy, bedrest was recommended during periods of relapses with a diet low in salt, sugar, fat, and the gradual addition of methotrexate at a low dose (10 mg/m 2 of body surface area). With this treatment, the progression was favourable.

Discussion
SJIA is part of a heterogeneous group of early arthritis in children less than 16 years of age, whose causes are unknown. Based on the clinical presentation and the biological workups, there are 07 different forms [3]. JIA can start with fever, associated with arthritis or not.
Both patients presented with fever but no arthritis, although this occurred in the second patient 08 days later. Physical examination and blood tests generally help to exclude the infectious and malignant causes of fever. This is particularly important in low/middle-income countries where these infectious causes are endemic, and represent the main aetiologies of fever [5]. Faced with the persistence of fever after proper antibiotic and antimalarial treatment, it is therefore important to look for evidence of an inflammatory disease in general, and SJIA in particular.
The management of SJIA is generally multidisciplinary. The objective of this management is to guarantee, in the most severe forms, the vital and functional prognosis while limiting the inflammatory process and pain. All these using the treatment with the least risk of intolerance. A progression towards a macrophage activation syndrome is to be feared because the mortality rate linked to this complication stands at 5-8% [2]. As a result, even though non-steroidal anti-inflammatory drugs or general corticosteroids are most often the preferred treatment during the first weeks of the disease, the progression is towards the increasingly frequent and early recourse to methotrexate and even to biological treatment using anti-interleukin 1 or 6 [6].
The favorable response of patients to interleukin 1 and 6 inhibitors confirms the role of interleukin 1 in the etiopathology of SJIA. SJIA can rightly be considered an auto-inflammatory syndrome [7]. Our patients rather benefited from treatment with methotrexate. It should be noted that JIA can also occur in patients on immunosuppressive therapy [8,9]. However, this was not the case of our patients.

Conclusion
Cases of SJIA are rarely documented in sub-Saharan African literature.
This auto inflammatory pathology with a fearsome complication is not often mentioned. Inflammatory causes should be investigated in cases of persistent fever in children in malaria endemic areas, even in the absence of osteoarticular signs. The diversity in clinical presentation shows the need for more research to be done on the pathophysiology of this condition.