Hospital Universitario "Dr. José Eleuterio González", Av. Gonzalitos No. 235 Nte, Col. Mitras Centro, Monterrey, Nuevo León, C.P. 64460, México.
Rheumatol Int. 2020 Oct;40(10):1717-1724. doi: 10.1007/s00296-020-04668-4. Epub 2020 Aug 14.
Systemic lupus erythematosus (SLE) is an autoimmune disease, characterized by multi-organ symptomatology. 16% of the patients with autoimmune thrombocytopenia have SLE and are associated with high mortality. Intravenous methylprednisolone or high-dose steroids are the first-line treatments in those patients who experienced life-threatening bleeding or have a severely low platelet count, whereas a second line includes splenectomy, as well as other immunosuppressive agents as monotherapy or combined therapy, including azathioprine, cyclophosphamide, cyclosporine, and mycophenolate mofetil. However, response rates of these therapies vary considerably. Rituximab (RTX) became a useful tool in the treatment of autoimmune diseases, due to the decrease of autoantibodies production. In addition, there is evidence that low doses of RTX (100 mg IV per week for 4 weeks) can have a similar effect compared to the standard dose. The objective of this study was to describe the response to low doses of RTX in patients with lupus-induced thrombocytopenia. We present a report of four female patients with newly diagnosed SLE, accompanied by purpuric syndrome and severe thrombocytopenia (< 30 × 109/L) as the clinical debut that was refractory to glucocorticoids (GC) therapy and treated with low doses of RTX. By week 5, complete response (> 100 × 109/L) was achieved in two patients, partial response (> 50 × 109/L) in 1 patient, and no response in one patient. There is little information on the treatment of SLE-associated autoimmune thrombocytopenia. The most extensive study found at the time of our search was the study of 10 Asian patients. They found that 80% of the patients responded by week four and maintained until week 24 of follow-up. At week 36, a follow-up for two patients showed relapse; this occurred on patients with the most disease duration (> 5 years) and was associated with a lower response rate. In contrast, our study with four patients found that half of them presented a complete response: one patient added concomitant therapy with azathioprine (AZA) and another patient without the concomitant therapy. A third patient with a partial improvement, this was seen by week five of treatment. Moreover, a fourth patient who did not have a response by week five of treatment presented a clinical response in subsequent appointments with a count of > 100 at week 24. Those patients who required concomitant use of AZA were patients who had positive antiphospholipid serology. The use of low-dose RTX for the management of severe thrombocytopenia refractory to GC in patients with SLE has a good response. It could be a safe, economical, and effective therapy.
系统性红斑狼疮(SLE)是一种自身免疫性疾病,其特征为多器官症状。16%的自身免疫性血小板减少症患者患有 SLE,并且与高死亡率相关。对于经历危及生命的出血或血小板计数严重降低的患者,静脉注射甲基强的松龙或大剂量类固醇是一线治疗方法,而二线治疗包括脾切除术以及其他免疫抑制剂作为单一疗法或联合疗法,包括硫唑嘌呤、环磷酰胺、环孢素和霉酚酸酯。然而,这些疗法的反应率差异很大。利妥昔单抗(RTX)由于减少了自身抗体的产生,成为治疗自身免疫性疾病的有用工具。此外,有证据表明,低剂量 RTX(每周静脉注射 100 毫克,共 4 周)与标准剂量相比具有相似的效果。本研究的目的是描述低剂量 RTX 对狼疮诱导的血小板减少症患者的反应。我们报告了 4 例新诊断为 SLE 的女性患者,伴有紫癜综合征和严重血小板减少症(<30×109/L)作为临床首发症状,对糖皮质激素(GC)治疗有抗药性,并接受了低剂量 RTX 治疗。到第 5 周时,2 例患者完全缓解(>100×109/L),1 例患者部分缓解(>50×109/L),1 例患者无反应。关于治疗狼疮相关自身免疫性血小板减少症的信息很少。在我们检索到的最广泛的研究是对 10 名亚洲患者的研究。他们发现,80%的患者在第 4 周时出现反应,并持续到第 24 周的随访。在第 36 周,对两名患者进行了 2 年的随访,结果显示复发;这种情况发生在疾病持续时间最长(>5 年)的患者中,与较低的反应率相关。相比之下,我们对 4 名患者的研究发现,其中一半患者完全缓解:一名患者同时使用了硫唑嘌呤(AZA),另一名患者未同时使用该药物。第三名患者部分改善,这是在治疗的第 5 周观察到的。此外,一名在第 5 周治疗时未出现反应的患者在第 24 周的后续就诊中血小板计数超过 100,出现了临床反应。需要同时使用 AZA 的患者是抗磷脂抗体血清学阳性的患者。在对 SLE 患者中 GC 耐药的严重血小板减少症患者使用低剂量 RTX 进行治疗具有良好的反应。这可能是一种安全、经济且有效的治疗方法。