Systemic lupus erythematosus with various clinical manifestations in a patient with hereditary angioedema: a case report.

BACKGROUND: Hereditary angioedema (HAE) is an inherited disease characterized by recurrent angioedema without urticaria or pruritus. The most common types of HAE are caused by deficiency or dysfunction in C1 esterase inhibitor (C1-INH-HAE). The association between C1-INH-HAE and systemic lupus erythematosus (SLE) is known; however, variations in the underlying pathophysiology, disease course, and treatment in this population remain incompletely understood. CASE PRESENTATION: A 31-year-old Japanese woman with a prior diagnosis of HAE type 1 based on the episodes of recurrent angioedema, low C1 inhibitor antigen levels and function, and family history presented with new complaints of malar rash, alopecia, and arthralgias in her hands and elbows. She later developed fever, oral ulcers, lupus retinopathy, a discoid rash localized to her chest, and malar rash. Investigations revealed positive antinuclear antibody, leukopenia, thrombocytopenia, hypocomplementemia, and nephritis. Based on these findings, she was diagnosed with SLE according to the 2019 European League Against Rheumatism/American College of Rheumatology classification criteria. There did not appear to be a correlation between HAE disease activity and the timing of presentation with SLE, because HAE disease activity had been stable. The patient was able to achieve and maintain remission with immunosuppressive therapy including prednisolone, hydroxychloroquine, and tacrolimus. CONCLUSIONS: Our patient presented with a variety of symptoms, including fever and cytopenia in addition to mucocutaneous, joint, ocular, and renal lesions. It is important to better characterize the clinical characteristics of SLE in patients with C1-INH-HAE, and to clarify the mechanisms of SLE in this population.

Effect of add-on hydroxychloroquine therapy on serum proinflammatory cytokine levels in patients with systemic lupus erythematosus.

We investigated the effect of hydroxychloroquine (HCQ) as an add-on treatment to immunosuppressants on the expression of proinflammatory cytokines in patients with systemic lupus erythematosus. Serum levels of tumor necrosis factor (TNF)-α, interleukin (IL)-2, IL-6, IL-8, vascular endothelial growth factor (VEGF)-A, monocyte chemotactic protein-1 (MCP-1), macrophage inflammatory protein-1α (MIP-1α), and interleukin 1 receptor antagonist (IL-1ra) were measured immediately before and 3 months after treatment with oral HCQ. Among the 51 patients enrolled in the study, HCQ treatment led to significantly reduced serum levels of TNF-α, IL-6, IL-8, VEGF-A, IL-1ra, and IL-2 (p < 0.0001; p = 0.0006; p = 0.0460, p = 0.0177; p < 0.0001; p = 0.0282, respectively) and to decreased (but not significantly) levels of MIP-1α (p = 0.0746). No significant changes were observed in the serum MCP-1 levels before and after HCQ administration (p = 0.1402). Our results suggest that an add-on HCQ treatment modulates the expression of proinflammatory cytokines even in systemic lupus erythematosus patients with low disease activity.

Preterm birth is strongly affected by the glucocorticoid dose during pregnancy in women complicated by systemic lupus erythematosus.

BACKGROUND: This study aimed to investigate the effect of glucocorticoid doses on adverse pregnancy outcomes (APOs) in women complicated by systemic lupus erythematosus (SLE). METHODS: We investigated 74 pregnancies complicated by SLE or SLE-dominant mixed connective tissue disease. The pregnancies were managed from conception to delivery in our institution. We retrospectively evaluated whether the mean glucocorticoid dose during pregnancy is associated with APOs, including preterm birth (PB), low birth weight (LBW), and light-for-date (LFD). We also calculated the cut-off dose of glucocorticoid that affected APOs. RESULTS: All APOs occurred in 35 (50.7%) patients, with 14 cases of PB, 23 cases of LBW, and 10 cases of LFD. Patients with all APOs or PB had a higher dose of glucocorticoid during pregnancy than patients without all APOs or with full-term birth (P = 0.03, P <  0.01, respectively). Logistic regression analysis for all APOs and PB showed that the cut-off values of the mean glucocorticoid dose were 6.5 and 10.0 mg/day, respectively. Patients who delivered LBW or LFD newborns showed no significant difference in the glucocorticoid dose used during pregnancy than patients without LBW or LFD newborns. Patients who delivered LBW newborns were more likely to have used glucocorticoids during pregnancy (P <  0.01). CONCLUSIONS: In pregnancies complicated by SLE, a relatively lower dose of glucocorticoid than previously reported is significantly related to APOs, especially PB. Therefore, the disease activity of patients with SLE should be managed with the appropriate lower dose of glucocorticoid during pregnancy.

Interstitial lung disease occurring shortly after tocilizumab infusion in a patient with polyarticular juvenile idiopathic arthritis: a case report.

BACKGROUND: Tocilizumab has been shown to be effective for treatment of juvenile idiopathic arthritis (JIA). To our knowledge, this is the first reported case of interstitial lung disease occurring shortly after tocilizumab infusion in a patient with JIA. CASE PRESENTATION: A 14-year-old female patient with polyarticular JIA developed interstitial lung disease after intravenous and subcutaneous administration of tocilizumab. Her condition improved with glucocorticoid therapy. CONCLUSION: Our results suggest that increased interleukin-6 levels in the blood following tocilizumab treatment may be linked to development of interstitial lung disease.

Two cases of refractory eosinophilic granulomatosis with polyangiitis wherein mepolizumab was effective against pulmonary and ear lesions.

Recently, mepolizumab, an interleukin (IL)-5 inhibitor, has been indicated for the treatment of eosinophilic granulomatosis with polyangiitis (EGPA) refractory to standard therapies. However, no reports have compared the efficacy of mepolizumab according to symptoms and organ lesions. Herein, we report two cases in which mepolizumab was highly effective in the management of EGPA with lung lesions and otitis media refractory to treatment with multiple immunosuppressive agents. These two cases suggest that mepolizumab is effective in treating pulmonary and ear lesions in EGPA.

The development of rapidly progressive glomerulonephritis associated with both antineutrophil cytoplasmic antibody-associated vasculitis and anti-glomerular basement membrane nephritis in the course of nontuberculous mycobacterium infection: a case report.

BACKGROUND: Antineutrophil cytoplasmic antibodies (ANCA) and Anti-glomerular basement membrane (GBM) antibodies often induce rapidly progressive glomerulonephritis (RPGN). Some reports have demonstrated RPGN with the sequential appearance of ANCA then anti-GBM antibodies, suggesting that ANCA may induce the development of anti-GBM antibodies. Whereas, many reports have shown that the development of ANCA is associated with various infectious diseases, such as non-tuberculous mycobacterial infection. CASE PRESENTATION: A 65-year-old woman with pulmonary non-tuberculous mycobacterial (NTM) infection was monitored without treatment. One year later, serum myeloperoxidase (MPO)- ANCA were elevated (14.1 U/mL (normal value < 3.0 U/ml)). A high fever and RPGN appeared 1 year later, and serum MPO-ANCAs were 94.1 U/mL. Anti-GBM antibodies were also detected. A renal biopsy revealed crescentic glomerulonephritis with linear deposits of IgG and C3c along the GBM and interstitial inflammation with endarteritis of arterioles. The diagnosis was RPGN associated with anti-GBM nephritis and ANCA-associated vasculitis. CONCLUSION: This report shows that preceding NTM infection may have induced ANCA and anti-GBM antibodies and caused the development of RPGN.

Effect of biologic disease-modifying anti-rheumatic drugs for patients with rheumatoid arthritis who hope to become mothers.

OBJECTIVES: We examined the effect of biologic disease-modifying anti-rheumatic drugs on the time to pregnancy in patients with rheumatoid arthritis who hope to become mothers. Additionally, we evaluated adverse pregnancy outcomes and risk factors of these drugs. METHOD: We retrospectively investigated 25 pregnancies of 19 patients who were taking disease-modifying anti-rheumatic drugs. In 15 pregnancies, patients continued biologic disease-modifying anti-rheumatic drugs until conception (group A). In 10 pregnancies, patients discontinued biologic disease-modifying anti-rheumatic drugs and conventional synthetic disease-modifying anti-rheumatic drugs at the time of planning to conceive (group B). We used tumor necrosis factor inhibitors (certolizumab pegol and etanercept) for group A patients. RESULTS: The mean time to pregnancy was shorter in group A than in group B (5.9 ± 3.8 vs 11.0 ± 6.5 months, P = 0.04). The mean birth weight of newborns was lighter in group B than in group A (2446.5 ± 352.4 vs 2969.4 ± 459.9 g, P = 0.007). There were no significant differences in the rates of preterm birth, light-for-date, and premature rupture of the membranes between the groups. In patients with preterm birth or light-for-date newborns, the mean dose of corticosteroids during pregnancy was significantly higher compared with that in those with full-term birth or non-light-for-date newborns (P = 0.02, P < 0.01, respectively). CONCLUSIONS: In patients with rheumatoid arthritis who hope to conceive, continuing biologic disease-modifying anti-rheumatic drugs at the time of conception could shorten the time to pregnancy. Using biologic disease-modifying anti-rheumatic drugs before pregnancy does not affect abortion, preterm birth, light-for-date, and premature rupture of the membranes.