An Elderly Gentleman with Acute Lupus Pneumonitis as the Initial Manifestation of Systemic Lupus Erythematosus.

Systemic lupus erythematosus is a systemic autoimmune disease, with presentations that vary within a population and across the lifespan of an individual. The disease afflicts childbearing women more than men and uncommonly presents in the geriatric population. Lupus pneumonitis is rare, with a reported incidence of 1-4%. Herein, we discuss the case report of an elderly gentleman with biopsy-proven acute lupus pneumonitis (ALP) as an initial presentation of lupus. After starting high-dose steroids, the patient initially improved, though unfortunately endured a non-ST elevation myocardial infarction and recurrent gastrointestinal bleeding. Despite multiple interventions and a prolonged hospital course, his gastrointestinal bleeding persisted. He elected to go on home hospice and ultimately passed away due to ongoing gastrointestinal bleeding. As with our patient, elderly patients can pose a diagnostic dilemma with regard to late-onset lupus; multiple comorbidities and growing evidence that late-onset lupus may manifest with distinct clinical patterns from younger cohorts complicate diagnosis in these patients. It is critical to maintain a broad differential, which includes unusual rheumatic manifestations when management of common comorbidities fails to alleviate symptoms for an elderly patient. Failure to do so may result in delayed diagnosis of rheumatic disease and increased side effects related to treatment. Additionally, this case serves as a reminder that due to the complexity of rheumatic disease and the additional challenge of older patients with baseline comorbidities, sometimes palliative care options may be appropriate.

Effect of thrombopoietin receptor agonists on the apoptotic profile of platelets in patients with chronic immune thrombocytopenia.

Platelet survival depends upon mediators of apoptosis e.g., Bcl-xL, Bax, and Bak, which are regulated by thrombopoietin (TPO)-mediated AKT signaling. Thrombopoietin receptor (TPO-R) signaling might decrease platelet and/or megakaryocyte apoptosis and increase the platelet count. This study therefore explored anti-apoptotic effects of TPO-R-agonists in vivo on platelets of patients with immune thrombocytopenia. Patients received eltrombopag or romiplostim for two weeks. Total, immature, and large platelet counts were assessed as were Bcl-xL inhibitor assay; Bcl-xL Western blot; and flow cytometric (FACS) analysis of the AKT-signaling pathway. Eight/ten patients had platelet responses to eltrombopag and all three to romiplostim. Platelet sensitivity to apoptosis by Bcl-xL inhibition was greater in pretreatment patients than controls. This sensitivity normalized after one week of therapy, but surprisingly returned to pretreatment levels at week two. FACS analysis revealed increased AKT-pathway signaling after one week, followed by a decrease at week two. Platelet counts correlated with the Bcl-xL /Bak ratio. Platelet survival may be enhanced by TPO-R-agonists as a transient decrease in platelet sensitivity to apoptosis was accompanied by transient activation of AKT. However, this mechanism has only a short-lived effect. Megakaryocytes and platelets already present at the start of TPO-R-agonist treatment appear to respond differently than those generated de novo.

Improved regulatory T-cell activity in patients with chronic immune thrombocytopenia treated with thrombopoietic agents.

Immune thrombocytopenia (ITP) is an autoantibody-mediated bleeding disorder with both accelerated platelet destruction and impaired platelet production. We and others have described impaired regulatory CD4(+)CD25(hi) T cells (Treg) numbers and/or suppressive function in ITP patients. Clinical trials using thrombopoietic agents to stimulate platelet production have shown favorable outcomes in ITP patients, but information on the immunologic responses of treated patients are lacking. We studied the immunologic profile of chronic ITP patients before (n = 10) and during treatment with thrombopoietin receptor (TPO-R) agonists (n = 9). Treg activity, as measured by suppression of proliferation of autologous CD4(+) CD25(-) cells, was improved in patients on treatment (P < .05), and the improvement correlated with reduction in interleukin-2-producing CD4(+) cells, consistent with dampening of immune responses. There was a concomitant increase in total circulating transforming growth factor-ß1 (TGF-ß1) levels (P = .002) in patients on treatment, and the levels of TGF-ß1 correlated with the degree of improvement in platelet counts (r = .8, P = .0002). This suggests that platelets in patients on TPO-R treatment may play a role in improving Treg function, either directly or indirectly by enhanced release of TGF-ß1 as a result of greater platelet turnover. In conclusion, our findings suggest that thrombopoietic agents in patients with ITP have profound effects to restore immune tolerance.