Systemic lupus erythematosus (SLE) is a chronic systemic autoimmune disease of unknown etiology that can affect nearly any organ system and so pathophysiology involves an inappropriate innate and adaptive immune response [1]. When neurological and psychiatric symptoms are present, a condition known as neuropsychiatric systemic lupus erythematosus (NPSLE), with a prevalence reaching up to 95%, it becomes a disease with poorer prognosis, higher mortality rate and reduced quality of life [2]. The central nervous system (CNS) involvement occurs due to an ischemic or autoantibody related inflammatory mechanism resulting in blood-brain barrier disfunction, leading to increased permeability and passive diffusion of autoantibodies and other immune mediators [2], [3]. The most common clinical manifestations are cognitive impairment (up to 80%), mood disorder (up to 80%), anxiety (up to 40%) and headache (up to 28.3%) [3]. Leukoencephalopathy or leukodystrophy-like phenotype is rarely described in patients with SLE [3].

Leukodystrophies are a group of rare genetically determined disorders, with high debilitating potential, which affect the white matter of the central nervous system. They are usually progressive diseases with a broad clinical spectrum and so far, no curative treatment has been found. At this point, the management is often symptomatic and palliative with a multidisciplinary team of specialists [4]. The importance of a proper differential diagnosis among these pathologies relies on the possibility of acute and effective treatment for autoimmune diseases with better outcomes. In the case of leukodystrophy-like phenotype in NPSLE, aggressive and early treatment is required with corticosteroids and intravenous cyclophosphamide, improving the clinical outcome, without evidence of motor deficit in most of the cases described.

Of those patients with NPSLE, up to 75% present with MRI abnormalities [3], most commonly white matter lesions in deep subcortical and periventricular areas. These lesions are often found in frontal and parietal lobes, with isolated punctate and an asymmetrical pattern, and usually non-enhancing [3]. Leukodystrophy-like phenotype in NPSLE, resembling inherited or acquired leukodystrophies, diseases that mainly affect the white matter of the CNS, discloses diffuse, confluent and bilateral, essentially symmetrical, white matter abnormalities [4], [5]. This radiological pattern of leukoencephalopathy is considered rare in NPSLE and only a few cases have been described until now, and none of which in Latin America [6], [7], [8], [9], [10], [11], [12], [13], [14], [15], [16], [17], [18], [19], [20], [21], [22], [23], [24], [25], [26], [27], [28], [29], [30].

Considering its severity, NPSLE remains a diagnostic challenge, as it lacks defined criteria, being based on clinical assessment and biomarker tests such as serological, immunological, electrophysiological, and neuroimaging studies [31]. Neuroimaging remains a non-invasive method and is considered the gold standard in NPSLE evaluation [31]. Due to the rare presentation of diffuse white matter abnormalities in NPSLE, we report five cases from a single-center with leukodystrophy-like phenotype in NPSLE, in order to highlight this phenotype of severe NPSLE. Additionally, a systematic review of the literature about this unusual presentation, considering its main demographic, radiological and clinical characteristics, was also performed.