BACKGROUND: The management of systemic lupus erythematosus (SLE) during pregnancy remains a challenge currently. Identifying early predictors of adverse pregnancy outcomes in SLE patients can help to develop treatment plan and improve prognosis. The aim of this study is to explore the clinical and laboratory variables in the early pregnancy that can predict adverse neonatal and maternal outcomes, thereby facilitating the grading management of SLE.
METHODS: A retrospective analysis was conducted on 126 pregnant women with SLE who were admitted to Zhongnan Hospital of Wuhan University between January 2017 and December 2022. All enrolled patients were diagnosed (including newly diagnosed and previously diagnosed) during first trimester of pregnancy and their clinical records, laboratory results and pregnancy outcomes were reviewed. The association between the clinical and laboratory characteristics of patients at 12 gestational age and the adverse neonatal (ANOs) as well as maternal outcomes (AMOs) were analyzed.
RESULTS: A total of 117 live births (92.8%) were recorded in the study. ANOs occurred in 59 (46.8%) cases, including fetal loss in 9 cases (7.1%), preterm birth in 40 cases (31.7%), small for gestational (SGA) in 15 cases (11.9%), and complete heart block in 2 cases (1.5%). Univariate analysis showed that disease activity index (P < 0.0001), lupus nephritis (P = 0.0195), anti-SSB positivity (P = 0.0074) and hypocomplementemia (P = 0.0466) were related to ANOs. However, multivariate analysis showed that only disease activity during early pregnancy was an independent predictor for ANOs (OR = 7.053, 95% CI: 1.882 to 26.291, P = 0.004). In addition, 48 patients experienced AMOs during subsequent trimester, including 24 (19.0%) patients with disease flare and 23 (18.3%) patients with pre-eclampsia. Unplanned pregnancy (P = 0.010), active disease (P = 0.0004), new onset SLE (P = 0.0044) and lupus nephritis (P = 0.0009) were associated with AMOs in univariate analysis, while disease activity was identified as an independent risk factor for AMOs (OR = 2.553, 95% CI: 1.012-6.440, P = 0.047).
CONCLUSIONS: Active disease in early pregnancy is associated with adverse pregnancy outcomes. For patients with high risk factor for ANOs and AMOs, more intensive treatment and follow-up should be a wise measure. Especially for those who suffer from active disease, they should be fully informed and given the option to terminate or continue their pregnancy.

OBJECTIVE: Systemic Lupus Erythematosus (SLE) often causes damage to small nerve fibers, leading to distressing painful and autonomic symptoms. Despite this, Small Fiber Neuropathy (SFN) remains an underrecognized complication for SLE patients. In this cross-sectional study, we aimed to assess SFN in patients with SLE and to explore its correlations with immunologic disease features and clinical manifestations.
METHODS: We recruited 50 SLE patients (1 male to 12.5 females, aged 20-80 years) reporting painful disturbances. We conducted a comprehensive clinical and neurophysiological evaluation, using Nerve Conduction Studies and Quantitative Sensory Testing. Additionally, we carried out an extensive laboratory assessment of disease-related serological parameters. We also performed a thorough skin biopsy analysis, investigating somatic and autonomic innervation while detecting complement and inflammatory cell infiltrates within the skin.
RESULTS: Out of 50 patients, 19 were diagnosed with SFN, primarily characterized by a non-length-dependent distribution; 7 had a mixed neuropathy, with both large and small fiber involvement. Patients with SFN were younger than patients with a mixed neuropathy (p = .0143); furthermore, they were more likely to have a history of hypocomplementemia (p = .0058) and to be treated with cyclosporine A (p = .0053) compared to patients without neuropathy. However, there were no significant differences in painful and autonomic symptoms between patients with and without SFN.
CONCLUSIONS: This study highlights the relevant frequency of SFN with a non-length-dependent distribution among SLE patients experiencing painful symptoms. Indeed, SFN emerges as an early manifestation of SLE-related neuropathy and is closely associated with hypocomplementemia, suggesting a potential pathogenic role of the complement system. Moreover, SFN may be influenced by disease-modifying therapies. However, the precise role of SFN in shaping painful and autonomic symptoms in patients with SLE remains to be fully elucidated.

Hypocomplementemic urticarial vasculitis syndrome (HUVS) is a rare autoimmune disorder characterized by chronic urticaria, systemic vasculitis, and hypocomplementemia, posing significant diagnostic challenges due to its overlap with common conditions and varied systemic manifestations. We report the case of a 36-year-old female with a history of post-birth cerebral hemorrhage and seizure disorder, who presented with abdominal pain, diarrhea, and subtle urticarial lesions. Initial investigations by gastroenterology suggested inflammatory bowel disease (IBD), but persistent symptoms and evolving cutaneous signs prompted further evaluation. A skin biopsy demonstrated leukocytoclastic vasculitis, while serological tests showed hypocomplementemia and positive antineutrophil cytoplasmic antibodies (ANCA), confirming HUVS. The patient\'s management included high-dose corticosteroids and mycophenolate mofetil, with partial symptom relief. Subsequent introduction of rituximab markedly improved her gastrointestinal and dermatological symptoms, highlighting its effectiveness in treating refractory HUVS. This case emphasizes the necessity for vigilance, interdisciplinary collaboration, and personalized treatment adaptations in managing HUVS.

Multiple myeloma (MM) is a plasma cell malignancy belonging to the class of monoclonal gammopathies that leads to end-organ damage myeloma events that encompass anemia, the presence of lytic bone lesions, hypercalcemia, and renal insufficiency. However, there are very few reported cases of patients with low complements in the context of MM and renal failure. Traditionally, low complements in glomerular disease are associated with conditions such as membranoproliferative glomerulonephritis, cryoglobulinemia, systemic lupus erythematous, and post-infectious glomerulonephritis. Despite its rarity, physicians should maintain a high degree of suspicion and consider MM as a potential cause of low complements in patients with renal injury. In this case report, we present a patient with a history of MM associated with acute kidney injury with hypocomplementemia, an atypical presentation of myeloma in MM.

Hematologic abnormalities are common manifestations of SLE, although neutropenia is observed less frequently and is not included in the classification criteria. Nonetheless, neutropenia is a risk factor for infections, especially those caused by bacteria or fungi. We aimed to evaluate the impact of neutropenia in SLE through a systematic investigation of all infections in a large cohort of well-characterized patients, focusing on neutropenia, lymphopenia, and hypocomplementemia. Longitudinal clinical and laboratory parameters obtained at visits to the Rheumatology Unit, Linköping University Hospital, and linked data on all forms of healthcare utilization for all the subjects included in our regional SLE register during 2008-2022 were assessed. Data regarding confirmed infections were retrieved from the medical records. Overall, 333 patients were included and monitored during 3,088 visits to a rheumatologist during the study period. In total, 918 infections were identified, and 94 occasions of neutropenia (ANC < 1.5 × 109/L) were detected in 40 subjects (12%). Thirty neutropenic episodes in 15 patients occurred in association with infections, of which 13 (43%) required in-hospital care, 4 (13%) needed intensive care, and 1 (3%) resulted in death. Bayesian analysis showed that patients with ≥ 1 occasion of neutropenia were more likely to experience one or more infections (OR = 2.05; probability of association [POA] = 96%). Both invasiveness (OR = 7.08; POA = 98%) and severity (OR = 2.85; POA = 96%) of the infections were significantly associated with the present neutropenia. Infections are common among Swedish SLE patients, 12% of whom show neutropenia over time. Importantly, neutropenia is linked to both the invasiveness and severity of infections. Awareness of the risks of severe infections in neutropenic patients is crucial to tailor therapies to prevent severe illness and death.

Adult-onset Still\'s disease (AOSD) causes fever, rash, pharyngalgia, and arthralgia through autoinflammation. Its complement titer has not previously received attention because this usually increases during the inflammatory process. Our female patient in her 60s was admitted to the hospital with fever, rash, arthralgia, and pharyngalgia. Her white blood cell count was 19,130/μL, hemoglobin was 11.0 g/dL, platelet count was 26.0 × 104/μL, and ferritin titer was 6,175 ng/mL. Anti-nuclear antibodies and anti-neutrophil cytoplasmic antibodies were negative. The presence of infectious diseases and malignancies was excluded. She was diagnosed with hypocomplementemia at the onset of AOSD because of her low complement component 4 (C4) titer (<5.0 mg/dL). Her complement component 3 (C3) titer was 104.5 mg/dL, which was within normal limits. There was no sign of thrombotic microangiopathy (TMA) or hemophagocytosis. She was treated with high-dose corticosteroids, including pulse methylprednisolone therapy, cyclosporine, methotrexate, and intravenous immunoglobulin, but was resistant to these, and her disease repeatedly flared up. Treatment with intravenous cyclophosphamide eventually led to remission. Post-treatment, her C4 titer increased to within the normal range. Although hypocomplementemia with TMA or hemophagocytosis has been reported in AOSD patients, our patient showed no sign of either at disease onset. Hypocomplementemia of AOSD may be a sign of high disease activity and could be a predictive marker for resistance to standard therapy.

We describe a case of a young 32-year-old Indian female who presented with a solitary symptom of facial swelling for two months. The patient\'s blood test results showed hypocomplementemia and C1 INH deficiency and fell into the \"third type\" of acquired angioedema (AAE), leading to the diagnosis of systemic lupus erythematosus (SLE), with SLE inactivity at the time of presentation, which makes this an interesting case due to the rarity of such findings in our clinical settings.

Rheumatoid arthritis (RA) is a chronic inflammatory disorder with a wide clinical heterogeneity. Among its complications, rheumatoid vasculitis (RV) is notable for its severity and potential to involve multiple organ systems. A particularly serious manifestation of RV is ischemia, which is indicative of advanced vasculitic involvement and a significant risk of tissue damage. This case report describes an 83-year-old male with RA who presented with polyarticular joint pain and hand ischemia. Despite the initial diagnosis of RA exacerbation, worsening systemic symptoms without identifiable infectious causes and hypocomplementemia led to the diagnosis of RV exacerbation. Initial management with steroids showed temporary improvement. However, relapse after dose reduction prompted the administration of rituximab, an anti-cluster-of-differentiate-20 (anti-CD20) monoclonal antibody, which yielded favorable outcomes. This case underscores the importance of clinical vigilance in older patients with RA for signs, such as ischemic hands, emphasizing the pivotal role of early detection and intervention in RV management, particularly in community hospital settings.

OBJECTIVE: The objectives of this study were to assess the association between serological activity (SA) and clinical inactivity in SLE and to investigate whether SA predicts flare after the attainment of clinically inactive disease (CID) and remission.
METHODS: The longitudinal data of children from three paediatric rheumatology referral centres were retrospectively reviewed. CID was interpreted as the beginning of a transitional phase of clinical inactivity on a moderate glucocorticoid dose during which tapering was expected and defined as the absence of disease activity in clinical domains of SLEDAI, without haemolytic anaemia or gastrointestinal activity, in patients using <15 mg/day prednisolone treatment. Modified DORIS remission on treatment criteria were used to determine remission.
RESULTS: Of the 124 patients included, 89.5% displayed SA at onset. Through follow-up, the rate of SA decreased to 43.3% at first CID and 12.1% at remission. Among the patients with CID, 24 (20.7%) experienced a moderate-to-severe flare before the attainment of remission. While previous proliferative LN [odds ratio (OR): 10.2, P: 0.01) and autoimmune haemolytic anaemia (OR: 6.4, P: 0.02) were significantly associated with increased odds of flare after CID, SA at CID was not associated with flare. In contrast, 21 (19.6%) patients experienced flare in a median of 18 months after remission. Hypocomplementemia (OR: 9.8, P: 0.02) and a daily HCQ dose of <5 mg/kg (OR: 5.8, P: 0.02) during remission significantly increased the odds of flare.
CONCLUSIONS: SA during remission increases the odds of flare, but SA at CID does not. Suboptimal dosing of HCQ should be avoided, especially in children with SA in remission, to lower the risk of flares.

BACKGROUND: Postinfectious glomerulonephritis with C3-dominant glomerular deposition (C3-PIGN) involves C3-dominant glomerular deposition without immunoglobulin. Atypical C3-PIGN involves persistent hypocomplementemia. We investigated the clinical features and explored complement-related gene mutations in atypical PIGN patients.
METHODS: We enrolled atypical C3-PIGN patients and collected data regarding the clinical presentation and pathological characteristics and follow-up data. We measured the levels of complement associated antibodies and performed whole-exome sequencing (WES) to detect mutations in complement-related genes.
RESULTS: The analysis included six atypical C3-PIGN patients. All patients were antistreptolysin-O (ASO) positive. All patients had varying degrees of hematuria, and four patients had proteinuria. None of the patients were positive for complement-related antibodies. All patients possessed mutations of genes related to the complement pathway, including alternative complement pathway genes-CFI, CFH, CFHR3, CFHR5; the lectin pathway gene-MASP2; and the common complement pathway gene-C8A. The rare variant of CFHR3 has been reported in C3 glomerulonephritis. During 56-73 months of follow-up, the levels of urine markers in three patients recovered within 6 months, and the remaining patients had abnormal urine test results over 12 months. Patients who received glucocorticoid therapy recovered faster.
CONCLUSIONS: Our study suggested that complement-related gene mutations may be an important cause of persistent hypocomplementemia in atypical C3-PIGN patients. In addition to variations in alternate pathway-related genes, we also found variations in lectin pathway-related genes, especially MASP2 genes. Although the overall prognosis was good, atypical C3-PIGN patients exhibited a longer period for recovery. Our results suggested that atypical C3-PIGN patients should receive more medical attention and need testing for mutations in complement-related genes.