Juvenile lupus-like with negative serology: a clinical dilemma and diagnostic challenge

Systemic lupus erythematosus (SLE) is an autoimmune disorder that can affect various organs. Juvenile-onset SLE (jSLE) may be more severe than the adult-onset form, but the diagnosis and classification remain challenging due to the complex nature of the condition and its resemblance to other conditions. Antinuclear antibodies (ANA) are the immunological hallmark of SLE, but their limited specificity poses challenges. The 2019 (European Alliance of Associations for Rheumatology/American College of Rheumatology) SLE proposed a weighted multi-criteria system for classifying SLE, with ANA serving as an entry criterion. However, seronegative SLE, in which a patient's clinical features and laboratory values are consistent with SLE but their ANA serology test is negative, is a rare subtype of SLE that has been reported in several cases worldwide. Here, we present two rare cases of jSLE in 13- and 11 years old girls with negative ANA. The first case presented as lupus cerebritis and lupus nephritis (LN) class IV and V which showed improvement with treatment. The other one was also diagnosed as LN class IV but showed poor outcome despite aggressive immunosuppressive treatment. These cases highlight the importance of considering lupus-like symptoms in children with negative serology and the need for further research into current diagnostic protocols and calls for a re-evaluation using a more inclusive set of criteria that does not centralize immunological serology.