Effect of remission, clinical remission with active serology, and glucocorticoid dosage on the pregnancy outcome of pregnant patients with systemic lupus erythematosus.

BACKGROUND: Remission is a key treatment target in systemic lupus erythematosus (SLE) management. Given the direct correlation between lupus flares and elevated risks of adverse pregnancy outcomes (APOs), securing remission before conception becomes crucial. However, the association between clinical remission with active serology, and the risk of APOs is not thoroughly understood. Additionally, determining the optimal glucocorticoid dosage during pregnancy to mitigate APO risks remains under-researched. This study investigated the risk of APOs in relation to remission/serological activity status in patients in clinical remission/glucocorticoid dosage. METHODS: Pregnant patients with SLE, who were followed up at two Japanese tertiary referral centers, and had their remission status assessed at conception, were included in this study. We categorized the patients into two groups based on whether they achieved Zen/Doria remission at conception and analyzed the APO ratio. We also examined the influence of serological activity in pregnant patients with clinical remission and analyzed the optimal glucocorticoid dosage to minimize the APO ratio. RESULTS: Of the 96 pregnancies included, 59 achieved remission at conception. Pregnant patients who achieved remission showed a significant decrease in the APO ratio compared with those who did not. (overall APO: odds ratio (OR) 0.27, 95% confidence interval (CI) 0.11-0.65, p < 0.01, maternal APO: OR 0.34, 95%CI 0.13-0.85, p = 0.021, neonatal APO: OR 0.39, 95%CI 0.17-0.90, p = 0.028). Conversely, no statistical difference was observed in the APO ratio based on serological activity in pregnant patients with clinical remission. (overall APO: OR 0.62, 95%CI 0.21-1.79, p = 0.37, maternal APO: OR 1.25, 95%CI 0.32-4.85, p = 0.75, neonatal APO: OR 0.83, 95%CI 0.29-2.39, p = 0.73). A glucocorticoid dose of prednisolone equivalent ≥ 7.5 mg/day at conception correlated with increased APO. (overall APO: OR 3.01, 95%CI 1.23-7.39, p = 0.016, neonatal APO: OR 2.98, 95% CI:1.23-7.22, p = 0.016). CONCLUSIONS: Even with active serology, achieving clinical remission can be a clinical target for reducing APOs in patients who wish to conceive. In addition, if clinically feasible, reducing the glucocorticoid dosage to < 7.5 mg/day before conception could be another predictive factor.

A retrospective analysis of the safety of tacrolimus use and its optimal cut-off concentration during pregnancy in women with systemic lupus erythematosus: study from two Japanese tertiary referral centers.

BACKGROUND: Tacrolimus is one of the major treatment options for systemic lupus erythematosus (SLE) and is considered to be a pregnancy-compatible medication. Since little is known about tacrolimus safety during pregnancy complicated by SLE, this study was designed. METHODS: We included SLE pregnant patients who were followed up at two Japanese tertiary referral centers. We performed multivariate logistic regression analysis to assess each adverse pregnancy outcome (APO) risk. Moreover, we assessed the influence of tacrolimus on the APO ratio in pregnant patients with lupus nephritis, and the impact of combined tacrolimus-aspirin therapy on the APO ratio relative to patients exclusively administered tacrolimus. RESULTS: Of the 124 pregnancies, 29 were exposed to tacrolimus. Multivariate analysis showed no statistical difference in APO ratio. (overall APO: adjusted odds ratio [aOR], 0.69; 95% confidence interval [CI], 0.23-2.03; p = 0.50; maternal APO: aOR, 1.17; 95% CI, 0.36-3.83; p = 0.80; neonatal APO: aOR, 1.10; 95% CI, 0.38-3.21; p = 0.86; PROMISSE APO: aOR, 0.50; 95% CI, 0.14-1.74; p = 0.27). Blood pressure and estimated glomerular filtration rate (eGFR) during pregnancy and after delivery did not differ between the two groups. Receiver operating characteristic (ROC) curve showed that tacrolimus concentration > 2.6 ng/ml was related to reduced preterm birth rate. (AUC = 0.85, 95% CI: 0.61-1.00, sensitivity: 93% and specificity: 75%). Regarding effect of tacrolimus on lupus nephritis during pregnancy, tacrolimus showed no increased risk of APO, blood pressure or eGFR during pregnancy and after delivery. (overall APO: OR, 1.00; 95% CI, 0.25-4.08; p = 0.98; maternal APO: OR 1.60, 95% CI, 0.39-6.64; p = 0.51; neonatal APO: OR, 0.71; 95% CI, 0.17-3.03; p = 0.65, PROMISSE APO: OR, 0.50; 95% CI, 0.08-3.22; p = 0.47). Tacrolimus-aspirin combination therapy showed a protective tendency against hypertensive disorders during pregnancy, preeclampsia and low birth weight. CONCLUSIONS: Tacrolimus use during pregnancy with SLE and lupus nephritis showed no significant influence on APO, blood pressure, or renal function; therefore tacrolimus may be suitable for controlling lupus activity during pregnancy. In addition, when using tacrolimus during pregnancy, we should aim its trough concentration ≥ 2.6 ng/ml while paying careful attention to possible maternal side effects of tacrolimus. TRIAL REGISTRATION: Retrospectively registered.

Anti-glomerular basement membrane diseases and thrombotic microangiopathy treated with rituximab.

A 68-year-old male patient presented with a 2-week history of malaise and anuria. Renal replacement therapy with haemodialysis was begun for acute kidney injury. His anti-glomerular basement membrane (anti-GBM) antibody titre was 3060 U/ml. Based on this finding, anti-GBM disease was diagnosed. Plasmapheresis and high-dose glucocorticoid therapy were begun, but his haemolytic anaemia and thrombocytopenia progressed. A disintegrin and metalloprotease with thrombospondin type 1 motif, 13 (ADAMTS-13) activity decreased to 33%, but no inhibitor was detected. Secondary thrombotic microangiopathy was suspected, and rituximab therapy was begun. The addition of rituximab is thought to have further reduced the anti-GBM antibodies, prevented recurrence, stabilised the platelet count, and facilitated the patient's withdrawal from plasmapheresis and glucocorticoid therapy. Rituximab may be a viable therapeutic option for anti-GBM diseases complicated with thrombotic microangiopathy.

Diagnosing Pollen-food Allergy Syndrome Allergologically in a Patient with Suspected Eosinophilic Gastroenteritis.

Pollen-food allergy syndrome (PFAS) consists of type I allergy to pollen and multiple food items that are cross-reactive to the pollen. PFAS typically occurs in the oral cavity and can co-occur with eosinophilic esophagitis. However, it is infrequently reported to present with symptoms of eosinophilic gastroenteritis (EGE), such as abdominal pain and eosinophilic infiltration of the gastrointestinal tract. We herein report a patient with a condition initially suspected of being EGE based on symptoms and pathological findings that was later diagnosed as PFAS associated with birch pollen. PFAS should be considered as a differential diagnosis in patients with EGE-like symptoms.

Sterile subconjunctival abscess in an HLA-B51-positive patient with ulcerative colitis.

PURPOSE: To report a rare case of aseptic abscess presenting as a subconjunctival abscess in an HLA-B51-positive patient with ulcerative colitis. OBSERVATIONS: A 25-year-old, male, Japanese patient with ulcerative colitis presented with an unilateral subconjunctival abscess. Infective endocarditis with endophthalmitis was suspected of being the cause, and systemic antimicrobial therapy was begun. The patient became critically ill and experienced the complication of heart failure with mitral valve perforation but improved dramatically with high-dose corticosteroids and intravenous infliximab following mitral valvuloplasty. His HLA typing was positive for HLA-B51. CONCLUSIONS AND IMPORTANCE: Both infectious and non-infectious etiologies should be considered in a patient with a subconjunctival abscess with systemic inflammation. An aseptic abscess can present as a subconjunctival abscess, and HLA-B51 may play a role in the pathogenesis of this rare condition.

TAFRO syndrome showing cholangitis on liver biopsy.

TAFRO syndrome is a systemic inflammatory disorder. TAFRO is an acronym that stands for thrombocytopenia, anasarca, fever, reticulin fibrosis, renal dysfunction, lymphadenopathy and hepatosplenomegaly. There are no reports of TAFRO syndrome describing cholangitis on liver biopsy. Herein, we report the first case of TAFRO syndrome with cholangitis. The patient was a 56-year-old man who presented with sudden onset abdominal pain and fever. His symptoms progressed to generalized edema, thrombocytopenia, hepatomegaly, and acute renal failure. Biopsies taken from the mediastinal lymph nodes and bone marrow showed the mixed type of multicentric Castleman's disease and mild reticulin fibrosis, respectively, compatible with TAFRO syndrome. His symptoms were temporarily relieved by steroid pulse therapy and tocilizumab. Fever and anasarca relapsed in a few weeks, however. He was then administered rituximab which resolved his symptoms almost completely.