Abstract Introduction Neuropsychiatric systemic lupus erythematosus (NPSLE) as described by the American College of Rheumatology (ACR) research committee includes 19 neuropsychiatric syndromes divided into neurologic syndromes of the central, peripheral, and autonomic nervous system and the psychiatric syndromes observed in patients with SLE in which other causes have been excluded. These symptoms may precede the onset of SLE or can occur at any time during the course of SLE. Guillain-Barré syndrome which is classified under the peripheral involvement has been rarely associated with SLE. Objective Guillain-Barré syndrome as an initial presentation of SLE has been reported in only a few cases. The isolated presentation of GBS may delay the diagnosis of SLE and its management. Methods We report a case of Guillain-Barré syndrome presenting as an initial manifestation of SLE, followed later by a succession of revelations of multi-visceral involvement. Case Report Z a 13-year-old girl, with no medical history, who presented to the emergency department with worsening muscle weakness in the lower limbs that appeared 15 days ago with an inability to walk for 3 days. The parents reported two episodes of fever, mouth ulcers, arthralgia accompanied by profound asthenia and behavioral disorder with visual hallucinations and nightmares preceding this episode. On initial physical examination revealed a generalized weakness of the lower exttremities. Sensory loss was variable in both her leg and feet. The deep tendon reflexes of her lower limbs were absent. A general physical examination revealed no other neurological, or organic findings. Respiratory and cardiac functions were within normal limits. A diagnosis of post-infectious Guillain-Barré syndrome was made, especially since she had an upper respiratory infection and viral serologies were initiated. Seven days after admission, the patient’s condition and neurological status worsened; She had a persistent fever with a maximum temperature at 40 °C, resistant to antipyretics. She had oedema of the lower limbs, hepatomegaly and splenomegaly. The hematological assessment revealed normocytic anaemia at 8.5 g/l, leukopenia with lymphopenia (500 cells/mm2) and thrombocytopenia (50 000 cells/mm2) with acute renal failure. Proteinuria >3 g/24h. A chest X-ray revealed moderate bibasilar pleural effusion and moderate pericardial effusion. Brain magnetic resonance imaging revealed no abnormalities. We suspected a macrophage activation syndrome (MAS) secondary to SLE. The inflammatory and autoimmune assessment were contributory with: antinuclear antibodies 1/1000 homogeneous fluorescence, positive anti-ribosome antibodies, reduced complement C3 and C4 fraction, serum ferritin > 3000 ng/ml, hypofibrinogenemia 1.3 g/l and D-dimer 3500 ng/ml. Patient fulfilling the ACR SLE criteria, with a severe multivisceral form: mucocutaneous, articular, neurological, renal, cardiac, hematological associated with MAS. Despite immunoglobulin and high-dose methylprednisolone, our patient died before the first session of plasmapheresis and first dose of cyclophosphamide. Discussion Neurolupus is a severe form of SLE with very high disease activity. Inaugural clinical presentation was not typical (SGB), but diagnosis was early after acute and severe revelation of other organic damage. Our patient presented with MAS as severe SLE whose short-term prognosis was compromised. Conclusion Pediatric neurolupus would be very heterogeneous and more severe than that of adults according to the few published pediatric series. Guillain-Barré syndrome revealing SLE is uncommon. In addition to this disorder, there are psychotic crises which are rarely mentioned during the initial clinical manifestations and which are a source of diagnostic difficulties, especially if they are isolated.