Systemic lupus erythematosus (SLE) is considered to have a global occurrence of 2-8 new cases per 100.000 people, with a global prevalence at 30-50 cases per 100.000 people. Recent estimates however suggest these numbers have tripled in the last thirty years. Ages 15 to 45 are being primarily affected; male to female ratio is 1:8-10 with a predilection for younger females. A lingering disease with remissions and flares, SLE reaches a sustained remission in 25% of cases; up to 50% develop irreversible organ damage. The multiorgan spread marks the disease severity; multiple systems may be involved at once: pulmonary, cardiovascular, GI, ocular and renal involvement, skin, muscle and joint and psycho-neurologic affects. SLE is a systemic disease often difficult to diagnose and treat. Atypical presentations – with progressive evolution resistant to aggressive treatment strategies and associated to multiple comorbidities – only begin to describe the challenges when approaching the clinical aspects of a SLE. Multiple medical professionals have to contribute to the management of a patient with SLE due to the systemic nature of the disease. We hope the described case reflects the above-mentioned diagnostic challenges and peculiarities when dealing with this disease.