BackgroundThrombotic thrombocytopenic purpura (TTP) is a rare and life-threatening thrombotic microangiopathy characterized by microangiopathic haemolytic anemia, consumption thrombocytopenia and organ injury, particularly kidney failure and neurological manifestation1.Two forms are distinguished: the hereditary one, caused by a deficit of the metalloprotease ADAMTS13, and the idiopathic one characterized by the presence of antibodies directed against ADAMTS13. The second one is the most common. There are various subgroups of acquired TTP associated with HIV infection, sepsis, pregnancy, autoimmune disease, disseminated malignancies and drugs. Antiphospholipid syndrome (APS) is a clinical immunological condition characterized by thromboembolic events, repetead miscarriages or stillbirth and thrombocytopenia; it can be a primary disorder or due to connective tissue disease, in particular systemic lupus erythematosus2.ObjectivesWe describe a case of TTP associated with a primary APS. The real clinical challenge lies in the differential diagnosis between TTP and anti-phospholipid antibody syndrome.MethodsA 37-year-old man presented to the emergency department for short-term episodes of anesthesia of the right upper limb and face with spontaneous resolution. In his past medical history, he suffered of antiphospholipid syndrome treated with warfarin. Upon admission, blood tests revealed severe thrombocytopenia, haemolytic anemia with schistocytes on peripheral blood smear, low thrombin time and prolongation in the prothrombin time. Neurological symptoms were assessed by electroencephalogram and CT brain, resulted negative, while a brain MRI revealed acute-subacute ischemic stroke. Based on these findings we suspected a diagnosis of TTP, subsequently confirmed by reduced activity of ADAMTS-13 with borderline ADAMTS-13 inhibitory antibodies. Immunological testing confirmed positivity of antiphospholipid antibodies and antinuclear antibodies.ResultsAccording to the last guidelines3 about management of acute episode of TTP, immediate therapy with high-dose corticosteroids (prednisone 1 mg/kg) and plasmapheresis was started and then we added infusion of rituximab (375 mg/m2/week for 4 times). Efficacy of treatment was evaluated by weekly dosage of ADAMTS13 activity, with a gradual rise in values (3 → 78%) and improvement in symptoms and laboratory examination. After persistent remission, we gradually reduced steroid therapy. Few months later, in February 2021, patient developed a bilateral comunitary pneumonia, that required hospitalization, oxygen - therapy (also with C-PAP) and endovenous antibiotics. After two weeks patient was discharged from hospital in good clinical health and he was subjected to periodic outpatients visits. Disease activity was in remission, so steroid therapy was reduced and recently we added hydroxychloroquine for APS. Some days ago patient developed covid – 19 infection, despite vaccination, and he was treated with monoclonal antibodies, with good clinical response.ConclusionWe have described a rare clinical case of TTP, despite concomitant warfarin treatment for primary anti-phospholipid syndrome. A careful follow-up of these medical conditions is recommended for patient’s fragility and for the risk of related serious clinical complications.References[1]Saha M. et al. Thrombotic thrombocytopenic purpura: pathogenesis, diagnosis and potential novel therapeutics. J Thromb Haemost. 2017 Oct;15(10):1889-1900.[2]De Carvalho JF et al. Primary antiphospholipid syndrome with thrombotic thrombocytopenic purpura: a very unusual association. Lupus. 2009 Aug;18(9):841-4.[3]Zheng XL et al. ISTH guidelines for treatment of thrombotic thrombocytopenic purpura. J Thromb Haemost. 2020 Oct;18(10):2496-2502.Disclosure of InterestsNone declared

BackgroundLupus nephritis (LN) is one of the major organ involvement of Systemic Lupus Erythematosus (SLE), causing significant increase of morbidity, mortality and healthcare impact.1 According to international guidelines, immunosuppressive therapy is indicated for LN class III and IV, while class V usually do not require this treatment, less than there is a proteinuria in the nephrotic range, and so for class II, also with a risk of evolution in a more aggressive form.2 Immunosuppressive drugs commonly used are mycophenolate mofetil/mycophenolate acid (MMF/MPA) and cyclophosphamide for the initial treatment and MMF/MPA or azathioprine for the maintenance of remission. LN treatment is often difficult because of the drug adverse events and the comorbidities that make therapeutic choices very challenging.ObjectivesWe describe the case of a young woman with SLE and other major systemic comorbidities who developed severe LN. This case emphasizes the importance of considering patients in their complexity and the delicate role of the physician in tailoring the treatment strategy on the individual patient.MethodsA 36-year-old woman presented to our Department for lymphadenopathy, headache, epistaxis, fever and weight loss. In her past medical history, she had a cerebral abscess caused by Streptococcus Constellatus with residual left hemiplegia and cervical HPV-related high-grade dysplasia, treated by ring biopsy. Upon admission, blood tests revealed severe neutropenia and lymphocytopenia, thrombocytopenia and low complement; blood cultures were negative. A total body CT scan showed multiple lymphadenopathies. Lymph node and bone marrow biopsies were performed and histological examination was negative for hematological disease. The autoimmune panel was positive for antinuclear, anti-DNAn, anti-Sm, anti-U1RNP, anti-cardiolipin and anti-beta2glycoprotein antibodies. According to clinical and laboratory results, a diagnosis of SLE was made.ResultsHigh-dose corticosteroid therapy was started with good clinical response and improvement of blood tests. Because of the gynecological history, immunosuppressive therapy was not started, and a wait-and-see strategy with steroid tapering and careful follow-up was started. A few months later, the patient developed an increase of serum creatinine with proteinuria at nephrotic range. Thus, a kidney biopsy was performed with evidence of class III LN. Following this result, we started high-dose corticosteroid therapy, with only partial response. After executing colposcopy with biopsy, that was negative for HPV-related lesions, we decided to start MMF, continuing with a careful follow-up. After six months, proteinuria reduced but maintained on levels around 1 gr per day. Bearing in mind the growing number of studies reporting the efficacy of belimumab in LN 3,4, we added this drug to achieve a better disease control, continuing to closely monitor the patients and potential adverse events.ConclusionIn patients with LN the choice of the immunosuppressive therapy can be very challenging. A tailored approach to the individual patient may be the best option to improve the management of this complex disease.References[1]Gasparotto M. et al. Lupus nephritis: clinical presentations and outcomes in the 21st century. Rheumatology (Oxford). 2020 Dec 5;59(Suppl5):v39-v51[2]Fanouriakis A. et al. 2019 Update of the Joint European League Against Rheumatism and European Renal Association-European Dialysis and Transplant Association (EULAR/ERA-EDTA) recommendations for the management of lupus nephritis. Ann Rheum Dis. 2020 Jun;79(6):713-723.[3]Furie R. et al. Two-Year, Randomized, Controlled Trial of Belimumab in Lupus Nephritis. N Engl J Med. 2020 Sep 17;383(12):1117-1128.[4]Ward M. et al. Belimumab as Add-on Therapy in Lupus Nephritis. N Engl J Med. 2020 Sep 17;383(12):1184-1185.Disclosure of InterestsNone declared