Background: Systemic lupus erythematosus (SLE) is an autoimmune disease with a high degree of variability at onset, making it difficult to reach a correct and prompt diagnosis.

Objectives: To present the difficulties faced by the clinician in making a SLE diagnosis, based on the characteristics at study entry of an Italian cohort of SLE patients with recent onset as compared to two similar cohorts.

Methods: Beginning on 1 January 2012 all patients with a diagnosis of SLE (1997 ACR criteria) and a disease duration less than 12 months were consecutively enrolled in a multicenter prospective study. Information on clinical and serological characteristics was collected at study entry and every 6 months thereafter.

Results: Our cohort consisted of 122 patients, of whom 103 were females. Among the manifestations included in the 1997 American College of Rheumatology (ACR) criteria, cutaneous, articular and hematologic symptoms were the most prevalent symptoms at study entry.

Conclusions: Data from the literature confirm that the diagnosis of SLE is challenging, and that SLE is a severe disease even at onset when a prompt diagnosis is necessary for initiating the appropriate therapy.