Age-related Epstein-Barr Virus-associated Lymphoproliferative Disorder Masquerading as Systemic Lupus Erythematosus

Age-related Epstein-Barr virus (EBV)-positive B-cell lymphoproliferative disorder (LPD) occurs in elderly patients without immunodeficiency. An 81-year-old woman without any known immunodeficiency was examined for fever, rash, arthritis, thrombocytopenia, pleural and pericardial effusions, lymphadenopathy, and positive autoantibodies, which satisfied the classification criteria for systemic lupus erythematosus (SLE). However, a lymph node biopsy revealed EBV-LPD, and she was diagnosed with age-related EBV-LPD. In young individuals, EBV infection is a major differential diagnosis of SLE, but to our knowledge, this is the first reported case of age-related EBV-LPD mimicking SLE. We should therefore consider EBV-related disorders in the differential diagnosis of SLE even in elderly individuals.     

Characteristics of patients with systemic lupus erythematosus (SLE) and non-Hodgkin’s lymphoma (NHL)

Patients with systemic lupus erythematosus (SLE) are at increased risk of developing non-Hodgkin’s lymphoma (NHL), but features of SLE associated with NHL are not well described. The objective of this study was to describe SLE characteristics, laboratory serologies, and medication histories in patients who subsequently develop NHL. Two thousand twenty patients with SLE were identified using the online Partners’ patient database research tool between October 1992 and June 2005. We confirmed the diagnoses of SLE and NHL and sought details of medical history and treatment by medical record review. Eleven patients with NHL without coexisting rheumatoid arthritis, Sjögren’s, or HIV were identified; seven of these (64%) had a diffuse large B cell lymphoma subtype, and 83% of those stained were Epstein–Barr virus (EBV) negative. The mean duration of SLE at NHL diagnosis was 17.8 years (range 1.6–41.8), and the mean Systemic Lupus International Collaborative Clinics/American College of Rheumatology damage index was 1.9. Seven patients (64%) had SLE hematologic involvement, four had anti-dsDNA antibodies, and four had anti-phospholipid antibodies. One patient had significant renal disease. All patients had arthritis and had received antimalarial therapy. Five of 11 patients had received other treatments for SLE, including cyclophosphamide, imuran, methotrexate, and/or sulfasalazine. Diffuse large B cell lymphoma was the most common subtype of NHL, and most were EBV negative. Although disease duration was fairly long and end organ damage moderately severe in this group of patients, renal disease and the use of immunosuppressive chemotherapeutic agents were rare and did not appear to confer an increased risk of NHL development.     

A case report of systemic lupus erythematosus combined with Castleman’s disease and literature review

Although lymph node enlargement is common in active systemic lupus erythematosus (SLE), lymph node examination is frequently ignored in the diagnosis of SLE. Clinical presentation and abnormal laboratory findings are often sufficient for SLE diagnosis, not to mention that the specific histological finding of lymph node necrosis in SLE is rarely seen, and the follicular hyperplasia is usually considered as nonspecific. However, since the late 1990s, a few cases of SLE lymphadenopathy have been reported exhibiting a Castleman’s disease (CD) morphology, which was discovered in lymph node biopsies. Here we report a similar case of SLE combined with CD in a 23-year-old girl who displayed systemic symptoms, including systemic lymphadenopathy and abnormal laboratory findings indicating the active phase of SLE. A biopsy of neck lymphnodes showed histopathological features of CD. The patient responded very well to the prednisolone treatment. Based on the related literature review, we would like to stress the possibility of CD in patients with SLE lymphadenopathy.     

Long-term membranous glomerulonephritis as the presenting manifestation of systemic lupus erythematosus in a patient with human immunodeficiency virus infection

The coexistence of human immunodeficiency virus (HIV) infection and systemic lupus erythematosus (SLE) is unusual, but the occurrence of SLE after HIV infection is even less common. Both conditions share similar clinical features including constitutional symptoms, facial rash, oral ulcers, alopecia, arthralgias, arthritis, seizures, cytopenias, glomerulonephritis, and antinuclear and antiphospholipid antibodies. This clinical overlap makes the diagnosis of SLE in a patient with pre-existing HIV infection difficult. Furthermore, immune complex glomerulonephritis with features resembling lupus nephritis has been described in HIV-positive patients. We present the case of a 45-year-old Hispanic woman with long-standing HIV infection who developed membranous glomerulonephritis with histological features of lupus nephritis. Five years after onset of renal disease she developed clinically evident SLE.     

系统性红斑狼疮合并淋巴瘤临床特征

目的探讨系统性红斑狼疮(SLE)合并恶性淋巴瘤(ML)的临床特点。方法回顾1998年1月至2012年2月北京协和医院收治的9例SLE合并ML患者的临床资料,分析其临床表现、实验室检查指标、淋巴瘤病理分型、治疗及预后。结果 SLE合并ML患者共9例,占同期SLE入院患者的0.18%;其中女性患者7例,男性患者2例;SLE平均发病年龄43.1岁(24～57岁),SLE平均确诊年龄为44.7岁(29～57岁),淋巴瘤平均确诊年龄为48.7岁(39～63岁),SLE发病到合并淋巴瘤病程均数为3.8年(1～15年)。淋巴瘤病理类型以非霍奇金淋巴瘤(NHL)为主,共7例,占77.8%(7/9),且淋巴瘤结外受累多见,共7例,占77.8%(7/9)。淋巴瘤在消化系统、呼吸系统、骨髓等部位均可发生,其中胃肠道受累3例,支气管和肺受累2例,骨髓受累2例。SLE合并ML患者中100%出现关节痛、淋巴结肿大及发热。实验室检查结果发现9例患者中6例补体减低,9例乳酸脱氢酶升高,5例红细胞沉降率(ESR)升高大于100mm/h。SLE合并ML的患者6例对化疗敏感,4例死亡,2例死因均为淋巴瘤消化道受累;2例诊断淋巴瘤放弃治疗后死亡。结论当SLE患者出现不明原因持续发热、淋巴结肿大、ESR持续大于100mm/h,乳酸脱氢酶持续偏高者需警惕SLE合并淋巴瘤的可能。当SLE合并淋巴瘤时结外受累多见,SLE合并ML多数对化疗敏感,但消化道受累时预后差。     

Systemic lupus erythematosus in a rhesus macaque

We describe the clinical course and histopathologic findings in a rhesus macaque (Macaca mulatta) which developed a systemic inflammatory disorder resembling systemic lupus erythematosus (SLE). The manifestations of the SLE included antinuclear antibody, hemolytic anemia, membranoproliferative glomerulonephritis, and arthritis. To our knowledge, spontaneously occurring SLE has not previously been described in nonhuman primates.     

Early onset multiple myeloma in a patient with systemic lupus erythematosus: a case report and literature review

Patients with systemic lupus erythematosus (SLE) are at increased risk for various plasma cell dyscrasias, but the coexistence of SLE and multiple myeloma (MM) are rarely reported to date. Due to the rarity, the clinical features of MM associated with SLE have not been elucidated, and the pathogenesis under this association remains unclear. In this report, we investigate a 31-year-old woman with 5-year history of SLE, who is diagnosed as IgA λ-type MM with multiple lymph node involvement. We discuss the clinical features of MM in SLE by reviewing previous cases and possible mechanisms connecting the two conditions.     

Lupus erythematosus proliferative glomerulonephritis in fetus

We report the case of a fetus with proliferative glomerulonephritis in the context of maternal systemic lupus erythematosus (SLE). The pattern of the renal lesions correspond to the class III of revisited WHO classification of glomerulonephritis in SLE. Amniotic fluid analysis showed a high level of albumin and the presence of anti-Ro and anti-DNA antibodies that were possibly responsible for the renal injury.     

Membranous glomerulonephritis with extra-renal disorders in children.

Thirty of 85 children with membranous glomerulonephritis (MGN) had associated extraglomerular disorders. The relation of these associations to membranous glomerulonephritis (MGN) is discussed. The causal relationship of acute hepatitis (5 cases), persistent hepatitis B antigenemia (6 cases), systemic lupus erythematosus (2 cases) and syphilis (1 case) may be ascertained; in similar conditions a definite antigen (Ag) has been found in MGN deposits. The association with SS or SA hemoglobinopathy (3 cases) ans with a preceding streptococcal infection (4 cases) raises the possible responsibility of renal tubular epithelium (RTE) Ag and of a streptococcal Ag. D-penicillamine therapy (1 case) is a well-known cause of MGN although the acting Ag remains unknown. Four children had serum sickness-like symptoms, two had hematologic disorders and two had proximal tubular dysfunction, one of them with proven anti-tubular and anti-alveolar basement membrane antibodies. A decrease in plasma C4, Clq, and factor B with normal C3 was frequently observed. The multiple Ag previously described as causative of MGN are recalled. The prevalent incidence of HBsAg is stressed, and the necessity for further investigations in patients with MGN in order to find an underlying disease is emphasized.     

Systemic lupus erythematosus and lymphoma

2 cases of non-Hodgkin's lymphoma developing in young women with systemic lupus erythematosus (SLE) are described. The interval between the diagnosis of SLE and the development of lymphoma was 4 years and 4 months, respectively. In 1 patient the lymphoma was localised primarily in the lung. It is suggested that the development of lymphadenopathy in a patient with SLE should be an indication for early lymph node biopsy.     

Intravascular lymphoma in a patient with systemic lupus erythematosus: a case report

Intravascular lymphoma IVL is a rare and aggressive disorder characterized by proliferation of large lymphoid cells (most commonly B-cells) within the lumen of small vessels of nearly every organ. Obliteration of vessels leads to the different clinical signs, being cutaneous lesions and neurological signs the most frequent presentations, whereas lymph node and reticuloendothelial system involvement is typically absent. No association with SLE has been described up to the present. We report a case of IVL in a patient with systemic lupus erythematosus (SLE) involving skin, central nervous system (CNS) and bone marrow.     

Induction of systemic lupus erythematosus by interferon-gamma in a patient with rheumatoid arthritis.

The development of systemic lupus erythematosus (SLE) after 38 months of therapy with recombinant human interferon gamma (rIFN-gamma) was observed in a patient with rheumatoid arthritis. In addition to glomerulonephritis and a butterfly rash, previously negative tests for antinuclear, anti-dsDNA and anti-Sm antibodies became positive. We assume that rIFN-gamma induced the de novo development of SLE in our patient.     

Deficiency in EBV-induced gene 3 (EBI3) in MRL/ lpr mice results in pathological alteration of autoimmune glomerulonephritis and sialadenitis

MRL/lpr mice develop a systemic autoimmune disease that is reminiscent of systemic lupus erythematosus (SLE) and Sjögren’s syndrome in humans. To investigate the role of IL-27 in the development of autoimmune disorders in MRL/lpr mice, we disrupted the EBV-induced gene 3 (EBI3), which is a subunit of IL-27. Consequently, the pathophysiology of glomerulonephritis and sialadenitis, which develops in MRL/lpr mice, was drastically changed. EBI3^?/? MRL/lpr mice developed disease that resembles human membranous glomerulonephritis (MGN), not diffuse proliferative glomerulonephritis (DPGN), with a predominance of IgG1 in glomerular deposits, and different type sialadenitis from Sjögren’s syndrome, with IgG1 producing plasma cell infiltration in salivary glands, accompanied by increased IgG1 and IgE in the sera. T cells in these mice displayed significantly reduced IFN-γ production along with elevated IL-4 expression. Loss of EBI3 thus favors Th2-type autoimmune responses, suggesting that the Th1/Th2 balance may be a pivotal determinant of phenotypes of human autoimmune diseases.     

Systemic lupus erythematosus as the concomitant manifestation of angioimmunoblastic T-cell lymphoma

Herein we report a case of the simultaneous occurrence of angioimmunoblastic T-cell lymphoma (AITL) and systemic lupus erythematosus (SLE) in a 76-year-old woman. She presented with fever, night sweats, and general malaise. A laboratory examination revealed leukopenia, anemia, polyclonal hypergammaglobulinemia, hypocomplementemia, positive results for anti-nuclear antibodies and anti-double strand DNA (anti-dsDNA) antibodies, and mild proteinuria. A computed tomography scan of the abdominal cavity showed multiple swollen intra-abdominal and intra-pelvic lymph nodes. A biopsy specimen obtained from the peri-iliac lymph node confirmed the diagnosis of AITL, while renal biopsy results were consistent with lupus nephritis, International Society of Nephrology and Renal Pathology Society class V. These results indicated that our patient developed SLE concomitantly with AITL. These findings will lead to further understanding of the pathogenic mechanism of SLE.     

Reactivation of Epstein-Barr virus in patients with systemic lupus erythematosus

A link between Epstein-Barr Virus (EBV) and systemic lupus erythematosus (SLE) has been suggested. However, recent advances in molecular technology now permit more detailed analysis. Sera from SLE patients were tested for antibodies to several EBV antigens and had a significantly higher prevalence of immunoglobulin G antibodies against EBV early antigens than in normal or disease controls. This suggests that recent EBV infection or virus reactivation was occurring in these patients.     

Successful Treatment of Rapidly Progressive Lupus Nephritis Associated with Anti-MPO Antibodies by Intravenous Immunoglobulins

We report a case of systemic lupus erythematosus (SLE) associated with crescentic glomerulonephritis and myeloperoxidase-specific anti-neutrophil cytoplasmic antibodies (MPO-ANCA). A 34-year-old Japanese female patient diagnosed with SLE developed rapidly progressive renal failure and nephrotic syndrome. Haemodialysis was required to restore renal function. Methylprednisolone pulse therapy followed by plasmapheresis did not suppress the progression of renal failure, so she was treated with high-dose intravenous immunoglobulin (IV-IG) therapy, which was well tolerated and effectively prevented renal failure. A renal biopsy showed diffuse proliferative lupus nephritis (WHO classification IVc) with predominant crescent formation and scant subendothelial immune deposits. These findings indicate that, in addition to lupus nephritis, which usually results from the deposition of circulating or locally formed immune complexes, MPO-ANCA may be involved in the pathogenesis of crescentic glomerulonephritis. Furthermore, we propose that IV-IG is an effective therapy for MPO-ANCA-related renal crisis in lupus nephritis. Received: 10 December 1997 / Accepted: 23 July 1998     

Simultaneous presentation of hemophagocytic syndrome and mesenteric vasculitis in a patient with systemic lupus erythematosus

We report an 18-year old female patient with systemic lupus erythematosus (SLE), who developed fever, pancytopenia, abdominal pain, and watery diarrhea. Computed tomography (CT) and bone marrow aspirate revealed lupus mesenteric vasculitis (LMV) and hemophagocytic syndrome (HPS). Serologic tests for Epstein–Barr virus (EBV) indicated its reactivation. This case demonstrates that HPS and concomitant LMV associated with viral reactivation can occur as clinical manifestations of SLE flare.     

Chronic intestinal pseudo-obstruction associated with biliary tract dilatation in a patient with systemic lupus erythematosus

We present the case of a 57-year old female patient diagnosed with systemic lupus erythematosus (SLE) along with glomerulonephritis and chronic intestinal pseudo-obstruction (CIPO). Dilatation of bile and pancreatic ducts not associated with malignant or litiasic obstruction is reported. The combination of bile duct associated with CIPO in a patient with lupus has not been previously reported in the literature and it probably suggests a smooth muscle dysmotility.     

The risk of lymphoma development in autoimmune diseases: a meta-analysis

BACKGROUND: The risk of development of non-Hodgkin lymphoma (NHL) in autoimmune patients has been investigated in several cohort studies. These studies revealed inconclusive results. To shed some light on this controversy, we conducted a meta-analysis of all available cohort studies linking systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and primary Sj?gren syndrome (pSS) to the risk of NHL development. METHODS: We searched the PubMed database (1974 to April 2005) for English-language cohort studies using the key words systemic lupus erythematosus, SLE, rheumatoid arthritis, RA, Sj?gren syndrome, or SS; non-Hodgkin lymphoma; and relative risk, RR, standardized incidence rate, or SIR. All cohort studies that used established diagnostic criteria for SLE, RA, and pSS; had histologic confirmation of NHL; and provided standardized incidence rates (SIRs) were included in the meta-analysis. RESULTS: The 20 studies chosen for the analysis included 6 for SLE, 9 for RA, and 5 for pSS. Overall, the meta-analysis suggested extreme heterogeneity among the studies (P < .01; I2 > 70%), high risk of NHL development for pSS (random effects SIR, 18.8; 95% confidence interval [CI], 9.5-37.3); moderate risk for SLE (random effects SIR, 7.4; 95% CI, 3.3-17.0); and lower risk for RA (random effects SIR, 3.9; 95% CI, 2.5-5.9). In RA, the random effects SIRs of NHL with conventional antirheumatic treatment, cytotoxic treatment, and treatment with a biological agent were 2.5 (95% CI, 0.7-9.0), 5.1 (95% CI, 0.9-28.6), and 11.5 (95% CI, 3.7-26.9), respectively. CONCLUSIONS: Rheumatic disease may present a potential risk factor for development of NHL. In this regard, we focused on the underlying pathophysiologic mechanisms related to lymphomagenesis in pSS, SLE, and RA, to justify the varying potential for and background of NHL development.     

Kikuchi's disease and systemic lupus erythematosus: case report and review

The case of a 50-year-old male with a clinical syndrome consistent with systemic lupus erythematosus (SLE), generalized lymphadenopathy, and renal involvement is presented. The pathologic examination of an excised supraclavicular lymph node showed necrotizing lymphadenitis. Although necrotizing lymphadenitis is a well-known characteristic of SLE lymphadenitis, the main histologic and immunophenotypic findings of our case showed the presence of distinctive Kikuchi's lymphadenitis.