Evidence Of Systemic Lupus Erythematosus Research Articles

Predictors of flare-related inpatient or emergency department stay in systemic lupus erythematosus: A real-world analysis of Medicaid claims in the United States.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by multisystem inflammation. Medical management of SLE is based on reducing inflammation and tissue damage in the affected organs; however, medications used to treat SLE have been found to contribute to additional organ damage. Therefore, finding new ways to predict and prevent flares that require an inpatient (IP) stay or emergency department (ED) visit is critical for reducing the clinical and economic burden in patients with SLE. To identify risk factors of SLE flares requiring an IP/ED visit among a Medicaid-insured population with SLE. This retrospective study included patients from the Merative MarketScan Medicaid database (2013-2019). To capture patients at all stages of their SLE journey, all SLE claims for a patient were captured, and the index date was randomly selected among those claims that were at least 12 months after the first evidence of SLE. Patients were required to be continuously enrolled 1-year pre-index (year 1) and post-index (year 2). Demographics, clinical characteristics, and health care use and costs were measured in year 1, and flares requiring an IP/ED visit were identified in year 2 using the Garris algorithm. Multivariable logistic regression and classification and regression tree (CART) modeling were used to identify year 1 predictors and combination of factors, respectively, associated with flares-related IP/ED visits. Of the 8,083 patients included in the study, 37.6% of patients (n = 3,039) had a flare. Logistic regression identified ED visits in year 1 as one of the strongest predictors of flares-related IP/ED visits in year 2 (odds ratio = 2.19 [95% CI = 1.93-2.49]). SLE treatment progression to biologics (0.54 [0.42-0.70]) was the strongest predictor of decreased odds. Other strong predictors included other neurological disorders (1.63 [1.43-1.87]), Black race (1.49 [1.32-1.68]), chronic kidney disease/renal failure (1.35 [1.10-1.66]), and opioid use (1.30 [1.17-1.45]). CART modeling identified patients with an ED visit, an IP admission, and a diagnosis of Elixhauser Comorbidity Index-defined other neurological disorders in year 1 as having the highest probability of a flare-related IP/ED visit in year 2 (probability = 0.708), whereas patients without an ED visit had the lowest probability (probability = 0.185). Patients with the highest risk of a flare that required an IP/ED visit were those with a prior ED visit, IP admission, and other neurological disorders. Modeling also identified patients with prior opioid use, Black patients, and patients without SLE medications as subgroups with a high risk of a flare requiring an IP/ED visit.

Lupus hands mimicking psoriatic arthritis.

We report a case of a 68-year-old woman with chronic and severely destructive arthritis for 8 years with imaging features mimicking psoriatic arthritis (PsA) but serological evidence of systemic lupus erythematosus. Both the lupus panniculitis-like rash and the presence of interstitial lung disease were considered manifestations of systemic involvement of SLE.

Subclinical C1q Nephropathy Combined with Possible Donor-Derived IgA Deposition in a 1-Year Kidney Allograft Biopsy: A Case Report

Few previous studies have reported immune-complex nephropathy that has not been classified as a specific phenotype in kidney allografts. We report a case of a de novo subclinical "full-house" pattern of deposition in a pediatric transplantation recipient with possible donor-derived IgA deposition. A five-year-old boy underwent living kidney transplantation due to congenital kidney and urinary tract anomalies. A one-hour implantation biopsy revealed IgA deposition. A four-month protocol biopsy finding showed less intense IgA deposition, in contrast with the one-hour biopsy, and trace para-mesangial deposits. A one-year protocol biopsy demonstrated a full-house deposition pattern and massive electron-dense deposits with minor glomerular changes. At the time of the one-year biopsy, kidney function was stable, with no urinalysis abnormalities. No evidence of systemic lupus erythematosus was observed in clinical and serologic examinations. Mesangial IgG, IgM, C3, and C1q deposition was codominant, and IgA deposition was weaker. We diagnosed this case as C1q nephropathy combined with remaining donor-derived IgA deposition. Few studies have reported C1q nephropathy in kidney allograft; further accumulation of cases is required. To distinguish between donor-derived and de novo glomerular lesions, it is important to assess the serial histologic findings of immunofluorescence and electron microscopy. Here, we report a rare case of subclinical C1q nephropathy with possible donor-derived IgA nephropathy.

The Clinicopathologic Spectrum of Membranous Nephropathy with Lupus-Like Features

Introduction: The pathologic features of membranous lupus nephritis (MLN) are occasionally encountered in secondary membranous nephropathy (sMN) without overt clinical evidence of systemic lupus erythematosus. Moreover, some sMN with lupus-like features (lupus-like membranous nephropathy [LL-MN]) have a clinical presentation more typical of primary membranous nephropathy (pMN). Based on the confounding clinical and pathologic presentation, it is unclear how to categorize and treat these patients. Methods: We performed immunohistochemical staining for recently discovered target antigens associated with MN -NELL-1, THSD7A, and EXT1/2 and compared the clinicopathologic presentation of patients with LL-MN to those with pMN and MLN. Results: From 2015 to 2020, there were 21 patients with MLN and 99 with MN, of which 59% were diagnosed pMN and 41% sMN. 44% of sMN patients showed lupus-like features (LL-fx). All LL-MN patients were negative for PLA2R and NELL1, but 12% were positive for EXT1/2. 50% of LL-MN patients had an identifiable systemic disease, of which 56% were autoimmune disease (AD) and 44% infection. Compared to pMN, LL-MN had a higher incidence of underlying AD (p = 0.02). Within pMN, 24% also had LL-fx (LL-pMN), and all but 1 were PLA2R- (78%) or NELL1-positive (15%). Only 5% of pMN patients had an AD, 66% of which showed LL-fx. Most idiopathic LL-MN were treated and behaved clinically similarly to pMN. There were no differences in outcome in terms of progression toward end-stage renal disease or mortality between LL-MN versus pMN and MLN. Conclusion: LL-MN appears to have a significant association with underlying AD and has a subset showing EXT1/2 positivity, whereas most LL-pMN and idiopathic LL-MN likely represent an atypical pathologic presentation of pMN.

MO249: Characteristics of Glomerulonephritis (GN) with Dominant C1Q Precipitation Compared to Corresponding GN without C1Q Staining on Immunofluorescent Examination

Abstract BACKGROUND AND AIMS Although C1q nephropathy (C1QN) was introduced three decades ago, the clinical significance and renal outcomes of C1QN remain unclear. Furthermore, it is uncertain whether the diagnosis of C1QN could be a new pathologic entity with clinical meanings. This study aimed to compare the clinical characteristics of the GN reclassified into C1QN based on the criteria described by Jennette and Falk (Pediatr Nephrol 2010: 25: 1385–1396) and corresponding GN not included in C1QN. METHOD We enrolled 21 212 patients with native kidney biopsy between 1979 and 2018 from 18 hospitals throughout Korea, retrospectively. We primarily adopted the findings and diagnosis by the pathologist in each hospital and then reclassified into C1q nephropathy (C1QN) on the basis of the criteria as follows: (i) presence of ≥ 2 + C1q in the mesangium on immunofluorescence (IF), (ii) corresponding mesangial or para-mesangial electron dense deposits on electron microscopy (EM), and (iii) lack of clinical and pathological evidence of systemic lupus erythematosus. Among 21212 patients, 77 patients were selected as C1QN with the criteria; however, six patients were excluded because of presence of primary diseases, such as renal amyloidosis, Henoch-Schölein Nephritis and systemic vasculitis, and myeloma cast nephropathy. The data of final outcomes, incidences of end-stage renal disease (ESRD) and death, were gathered from each hospital’s data registry, from the ESRD registry of the Korean Society of Nephrology, and from the Statistics of Korea, and were merged based on the identifier of Koreans. The follow-up duration for ESRD was 69.1 ± 67.8 months and, for mortality, 77.9 ± 65.5 months. RESULTS There were pathologic findings of 71 patients reclassified into C1QN including 41 (57.7%) males. Mean age of patients were 42.9 ± 18.9 years. There were 9 (12.7%) patients with DM and 39 (54.9%) hypertensive patients. The levels of creatinine, eGFR, and UPCR were 1.24 ± 0.92 mg/dL, 84 ± 43 mL/min/1.73 m2 and 2.58 ± 2.80 g/g creatinine, respectively. There were 22 (31.0%) patients with eGFR < 60 mL/min/1.73 m2 and 22 (31.0%) patients with UPCR ≥ 3.5 g/g creatinine. There were various pathologic diagnoses classified into C1QN, such as, original C1QN (21), IgA nephropathy (IGAN) (21), membranous nephropathies (MN) (11), focal segmental glomerulosclerosis (7), mesangial glomerulopathy (6), diabetic nephropathy (3), minimal change lesion (1), and acute tubulointerstitial nephritis (1). We compared the characteristics among the pathologic finding classified into C1QN, the pathologic finding without C1q stain, and the pathologic finding with non-dominant C1q stain which did not fulfill the criteria of C1QN. The identified GNs, which included enough number of patients to compare, were FSGS, IGAN and MN. Some differences of clinico-pathologic findings and incidence of ESRD were not evident after re-analysis with groups matched age and gender with 1:3 manner between the GN re-categorized into C1QN and the corresponding GN without C1q staining. The only difference was lesser amount of proteinuria in MN patients re-classified into C1QN compared with MN patients without C1q staining. Immunoglobulins showed higher intensity in IF staining of C1QN compared with non-C1QN of the corresponding GN. Intensity of C3 was also higher in IGAN and MN re-categorized into C1QN compared with the corresponding IGAN and MN not included in C1QN, respectively. CONCLUSION Reclassification into C1QN with the pre-defined criteria did not indicate a different clinico-pathologic identity based on comparison with the original diagnosis of GN. Activation of C1q, presumed activation of classical complement pathway in kidney tissues, in so-called C1QN could not be classified into new disease entity. Further studies on this topic are needed.

Clinicopathological Pattern of Non-lupus Full House Nephropathy.

Background and Aims:Full-house immunofluorescence in a kidney biopsy is a common observation in lupus nephritis (LN) and was previously used synonymously with the diagnosis of LN. Though a minority of the patients will develop features suggestive of SLE during follow-up, a majority of the patients will continue without any clinical or serological evidence of systemic lupus erythematosus (SLE) over time. Our aim to conduct this study was to work up the clinicopathological spectrum of these “full-house” nephropathies (FHN) which were not due to lupus nephritis.Methods:A total of 6244 renal biopsies were evaluated at SGPGIMS Lucknow from January 2007 to December 2017 for full-house immunofluorescence. All those patients who had no clinical or serological evidence of SLE at the time of renal biopsy or at any time during follow up were included.Results:Among 498 patients with full house immunofluorescence, 81 patients had no clinical or serological evidence of SLE at the time of renal biopsy or at any time during follow up. The prevalence of non-lupus FHN in this study was 19.4%, and the major diagnoses were membranous nephropathy (25.9%), IgAN (22.2%), MPGN (14.8%), DPGN (12.3%), Crescentic GN (12.3%), Amyloidosis (8.6%), C1q nephropathy (3.7%).Conclusions:Full-house nephropathy (FHN), not otherwise suggestive of lupus nephritis, can also be found in a number of other conditions. Non-lupus full house nephropathy is an umbrella term for such cases which do not satisfy the standard criteria of SLE. This will prevent misclassifying these patients into SLE and further prevent them from unnecessary immunosuppression protocols.

Lineage-Specific Functionality of an Interferon Regulatory Factor 5 Lupus Risk Haplotype: Lack of B Cell Intrinsic Effects.

Interferon regulatory factor 5 (IRF5) is widely recognized as a risk locus for systemic lupus erythematosus (SLE). Risk gene and IRF5 activation is triggered through toll-like receptor signaling. In myeloid cells, this leads to production of type I interferon and inflammatory cytokines, with enhanced production in cells of individuals harboring IRF5 risk alleles. Mouse models have also demonstrated the importance of IRF5 in B cell function, particularly plasma cell differentiation and isotype switching. Here, we evaluated the major SLE risk haplotype of IRF5 on the functional attributes of freshly isolated B cells from human subjects who do not have evidence of SLE or other forms of autoimmunity. We took this approach to avoid the complications of studying genotype-phenotype relationships in B cells that have been chronically exposed to an inflammatory disease environment before isolation. We focused on B cell endophenotypes that included gene expression, antibody secretion, class switching, and apoptotic susceptibility. We performed IRF5 overexpression studies, genetic reporter assays and electro-mobility shift assays on B and myeloid cell lines. Somewhat surprisingly, the results of our analyses indicate that IRF5 risk genotypes do not have a B cell intrinsic effect on these B cell functions. By contrast, we confirmed that the IRF5 risk and non-risk haplotypes exert differential effects in myeloid cells, including an increased susceptibility to apoptosis conferred by the risk haplotype. We also demonstrated an increased binding of the transcription factor specificity protein 1 to an insertion/deletion present in the risk haplotype. Our findings raise the specter that genetic risk alleles can have complex and unexpected lineage-specific effects, and these must be carefully considered when guiding or developing therapies based on understanding disease risk haplotypes.

Prevalence of antinuclear antibodies in hidradenitis suppurativa.

The purpose of this study was to investigate the prevalence of antinuclear antibody (ANA) positivity in a cohort of patients with hidradenitis suppurativa (HS), and to assess the frequency of seroconversion during treatment with tumor necrosis factor (TNF)-α inhibitor therapy. This prospective study was conducted through the Wound Etiology and Healing (WE-HEAL) Study. Immunofluorescence ANA testing was performed at baseline, and repeated when clinically indicated. ANA titers of ≥1:160 were considered positive. Data were collected on demographics and disease activity scores including the Hurley stage, the HS Sartorius score (HSS) and the active nodule (AN) count. At the time of data lock, 73 patients with a confirmed diagnosis of HS were enrolled, and four (5.4%) had baseline positive ANA. None of the patients had clinical evidence of systemic lupus erythematosus or other autoimmune diseases. There were no significant differences in demographics, baseline HSS (43.25±47.55 compared to 59.48±56.67, P=0.58) or AN count (3.25±3.20 compared to 3.45±2.36, P=0.87) in the ANA positive group. Of the 69 patients who were ANA negative at enrollment, 31 (45%) received TNF-α inhibitor therapy. During follow up, one patient developed drug-induced lupus secondary to TNF-α inhibitor use. Additionally, one patient seroconverted to ANA positive without sequelae and one patient developed drug-induced hepatitis secondary to TNF-α inhibitor use. The prevalence of baseline ANA positivity in this HS population was similar to that seen in the general population (5.4%). The rate of seroconversion and drug-induced complications in this population were low.

Predominant but silent C1q deposits in mesangium on transplanted kidneys - long-term observational study

BackgroundC1q nephropathy (C1qN) was first described as glomerular disease characterized by predominant meangial C1q deposits in patients with proteinuria and no evidence of systemic lupus erythematosus. Several studies, however, revealed the clinical heterogeneity of C1qN, showing some cases with normal urinalysis. To confirm the existence of cases with predominant mesangial C1q deposits and negative or mild proteinuria and/or hematuria, we investigated renal graft biopsy specimens showing negative to mild proteinuria (less than or equal to 1+ by dip stick test) and/or hematuria.MethodsEligible participants were kidney transplant cases who corresponded to the criteria for C1qN and were followed more than 10 years. Their medical records were reviewed to determine the age at detection of predominant mesangial C1q deposits, gender, original renal disease and reason for renal graft biopsy, blood pressure, degree of proteinuria and hematuria, and serum creatinine levels.ResultsFrom 414 cases in adults and children, five pediatric patients (the male to female ratio, 1:1.5) were eligible. At the time when predominant mesangial C1q deposits were detected, 2 cases presented with mild proteinuria without hematuria, but the other 3 cases showed normal urinalysis. Light microscopy revealed minor glomerular abnormality in all the cases. Immunofluorescent study showed predominant mesangial C1q deposits with IgG, IgM and C3 in all cases. All selected specimens presented electron dense-depos in the mesangium. Ten years later from the detection, 2 cases continued to be normal urinalysis and 3 cases had mild proteinuria without hematuria. During this follow-up period, no cases presented with persistent proteinuria and/or hematuria greater than or equal to 2+ by dip stick test. And no cases developed systemic lupus erythematosus. Follow-up renal graft biopsies were performed once in 2 cases 8 years later from the detection. They showed minor glomerular abnormalities. C1q deposit disappeared in one case. In another case, immunofluorescent study was not examined.ConclusionsThis long-term observational study on transplanted kidneys confirms the existence of cases with predominant but silent C1q deposits in the mesangium who have negative or mild proteinuria.

Intranuclear delivery of the transcription modulation domain of Tbet-improved lupus nephritis in (NZB/NZW) F1 lupus-prone mice

Excessive expression of Tbet and IFNγ is evidence of systemic lupus erythematosus (SLE) in lupus patients. In this study, the nucleus-transducible form of Transcription Modulation Domain (TMD) of Tbet (ntTbet-TMD), which is a fusion protein between Protein Transduction Domain Hph-1 (Hph-1-PTD) and the TMD of Tbet comprising DNA binding domain and isotype-specific domain, was generated to inhibit Tbet-mediated transcription in the interactomic manner. ntTbet-TMD was effectively delivered into the nucleus of the cells and specifically inhibited Tbet-mediated transcription without influencing the differentiation of other T cell subsets and signaling events for T cell activation. The severity of nephritis was significantly reduced by ntTbet-TMD as effectively as methylprednisolone in lupus-prone mice. The number of Th1, Th2 or Th17 cells and the secretion of their cytokines substantially decreased in the spleen and kidney of lupus-prone mice by ntTbet-TMD treatment. In contrast to methylprednisolone, the marked increase of Treg cells and the secretion of their immunosuppressive cytokine were detected in the spleen of (NZB/NZW) F1 mice treated withntTbet-TMD. Thus, ntTbet-TMD can improve nephritisin lupus-prone mice by modulating the overall proinflammatory microenvironment and rebalancing Tcell subsets, leading to new immune therapeutics for Th1-mediated autoimmune diseases.

Complete Remission from C1q Nephropathy with Disappearance of C1q Deposition after Steroid Therapy

C1q nephropathy is a rare glomerular disease, defined by characteristic mesangial C1q immune deposition seen in immunofluorescence microscopy with no serological evidence of systemic lupus erythematosus. C1q nephropathy can be diagnosed with a subsequent biopsy, as with IgA nephropathy. There are some cases with an initial diagnosis of hematuria and proteinuria with minimal disease changes, focal segmental glomerulonephritis, and mesangial proliferative glomerulonephritis, but lacking C1q nephropathy, in which C1q deposition on immunofluorescence subsequently develops. We report a case that was diagnosed as diffuse mesangial proliferative glomerulonephritis, but a subsequent biopsy showed C1q nephropathy, with C1q deposition in both immunohistochemistry and electron microscopy (EM). We treated the C1q nephropathy with methylprednisolone and confirmed the disappearance of C1q depositions by both immunohistochemistry and EM in a follow-up biopsy. Keywords: Complement C1q; Glomerulonephritis; Methylprednisolone 중심 단어: Complement c1q; ì‚¬êµ¬ì²´ì‹ ì—¼; Methylprednisolone

Possible evidence of systemic lupus erythematosus and periodontal disease association mediated by Toll-like receptors 2 and 4.

Toll-like receptors (TLRs) participate in the innate immune response and trigger the immune responses of the body. Systemic lupus erythematosus (SLE) is an autoimmune disease of unknown aetiology, characterized by an excessive autoimmune response in the body affecting the connective tissues. The disease is possibly triggered by both environmental aetiological factors and pathological organic processes such as exposure to sunlight, chronic infectious processes and genetic factors. Conversely, periodontal disease is an infectious disease caused by microorganisms in the oral cavity, resulting in a chronic inflammatory process which continuously stimulates the immune response, thus causing damage to the periodontal tissues. The expression of both TLR-2 and TLR-4 receptors are increased in both SLE and periodontal disease. Periodontitis might trigger excessive activation of immune response occurring in SLE by maintaining a high expression of TLRs, leading in turn to the acceleration of the onset and progression of autoimmune reactions. In addition, periodontal treatment is able to reduce the expression of these receptors and therefore the symptoms of SLE. Here we discuss the possible interaction between SLE and periodontitis, and suggest further studies evaluating common features in both factors that could explored, due to morbidity and mortality of SLE and the high incidence of periodontal infections around the world.

Herb-induced acute bone marrow intoxication and interstitial nephritis superimposing glomerular C1q deposition in a patient with paroxysmal nocturnal hemoglobinuria.

Paroxysmal nocturnal hemoglobinuria is a rare disease of the red blood cell membrane that renders it lyzable by the complement system, leading to chronic intravascular hemolysis. Renal hemosiderosis is a well-known complication of intravascular hemolytic anemia and can lead to acute kidney injury and renal failure. The use of herbal medicine is common worldwide. The nephrotoxicity of herbal remedies can take several forms, which include acute kidney injury and acute and chronic interstitial nephritis. In addition, the use of herbal remedies can result in bone marrow toxicity and suppression. C1q nephropathy is an uncommon form of glomerular disease characterized by dominant or co-dominant glomerular immunofluorescence positivity for C1q in the absence of clinical and serological evidence of systemic lupus erythematosus, and has various clinical presentations and outcome. Here, we report a patient of undiagnosed paroxysmal nocturnal hemoglobinuria who consumed herbal medicine of unknown constituents and clinically presented with anemia and acute kidney injury. The pathological findings of bone marrow and renal biopsies that include bone marrow intoxication, severe renal hemosiderosis and acute interstitial nephritis and kidney injury, as well as co-dominant glomerular deposition of C1q, are discussed. In addition, we discuss and hypothesize the possible pathogenesis of glomerular C1q deposition in the setting of paroxysmal nocturnal hemoglobulinuria.

C1q nephropathy in India: a single-center study.

C1q nephropathy (C1qN) is defined by conspicuous C1q deposits in the glomerular mesangial regions of patients who do not have any evidence of systemic lupus erythematosus (SLE). We present our experience with C1qN over the last three years. In total, 1775 native renal biopsies were reviewed and dominant/co-dominant C1q mesangial deposits in patients with absence of clinical and/or serological evidence of SLE were considered as C1qN. Their clinical profile and renal function status were studied and correlated. C1qN was observed in 11 patients (0.61%), and included eight males and three females; the mean age was 36.6 years. The most common presentation was nephrotic syndrome. Hematuria was noted in eight patients (72%). The mean serum creatinine was 2.78 mg/dL. Hypertension was seen in two patients (18%). Mesangial proliferative glomerulonephritis (MePGN) was the most common histological pattern, followed by focal and segmental glomerulosclerosis and other lesions. The common codeposits along with C1q were IgM, followed by C3 and others. MePGN had better prognosis than others. To conclude, C1qN was noted in 0.61% of all renal biopsies with bimodal age distribution and may present as podocytopathy or non-podocytopathy. The prognosis depends on the morphological pattern and C1q deposits per se are not prognostic indicators.

C1q nephropathy in the setting of granulomatosis with polyangiitis treated with tacrolimus.

C1q nephropathy in the setting of granulomatosis with polyangiitis treated with tacrolimus.

AB1369 What is the evidence-based for future policy decisions regarding biologics in sle? A structured review of the literature

BackgroundThe introduction of biologics in Rheumatoid Arthritis (RA) had a dramatic impact on pharmaceutical budgets. Policy-makers initially struggled to make informed resource allocation decisions on use of biologics due to...

Exacerbation of latent lupus: is the culprit acid-fast bacilli or antitubercular therapy?

Typical as well as atypical presentations of systemic lupus erythematosus are being increasingly recognized due to improved diagnostic methods. In a tuberculosis-endemic country like India, it was traditionally believed that the occurrence of tuberculosis in lupus was due to the chronic immunosuppression caused by lupus or because of the use of steroids or isoniazid-induced lupus. Increasingly several patients with no recorded predisposition to lupus with a history of treatment for tuberculosis are coming with evidence of systemic lupus erythematosus rather than a drug-limited story. Whether the development of an autoimmune state is a mere conjecture or the presence of acid-fast bacilli in the body for a prolonged duration causes complex antigenic interactions leading to an antigenic response needs to be looked into. We present a report of three such patients and review the pathogenetic interactions that could possibly explain the role of mycobacterial antigens as a putative antigen in the pathogenesis of lupus.

Lupus Enteritis

We report the case of a 25-year-old Iraqi woman who had multiple hospitalizations at an outside hospital for abdominal pain, nausea, and diarrhea without any evidence of systemic lupus erythematosus. Laboratory investigations finally showed a positive antinuclear antibody (1280), positive anti-dsDNA, anti-β2 glycoprotein I, low complement, positive Coombs tests, and leukopenia. A kidney biopsy showed ISN class II lupus nephritis. An ileal biopsy and angiogram were unremarkable. A computed tomography showed marked and dramatic bowel edema involving the small and large bowel ("target sign"), dilatation of intestinal segments, engorgement of mesenteric vessels ("comb sign"), and increased attenuation of mesenteric fat. These cardinal signs on computed tomography scan led to the correct diagnosis of lupus enteritis. Treatment was commenced with high-dose corticosteroids followed by mycophenolate mofetil, hydroxychloroquine, and then oral cyclophosphamide, but failed. The patient was eventually treated with the Euro-Lupus intravenous cyclophosphamide regimen, which resulted in significant clinical and radiological resolution.

Nephrotic Syndrome in a Multiple Sclerosis Patient Receiving Long-term Interferon Beta Therapy

Recombinant interferon α (IFN-α) and interferon β (IFN-β) are efficient drugs for clinical use in multiple sclerosis, hepatitis C virus infection, and malignant diseases. We report a case of a 40-year-old woman with relapsing-remitting multiple sclerosis who was treated with interferon beta-1b for several years before being admitted to our department with nephrotic-range proteinuria (protein excretion, 8.3 g/d) and serum albumin level of 2.9 g/dL without any clinical and laboratory change typical for a systemic autoimmune disease. The kidney biopsy led to the diagnosis of immune complex-mediated membranoproliferative glomerulonephritis with immunoglobulin and complement deposits visible by immunohistology, as well as subendothelial deposits and tubuloreticular inclusions evident by electron microscopy. Subsequently replacing interferon beta-1b with glatiramer acetate resulted in partial remission, with proteinuria decreasing to protein excretion of 1.0 g/d 2 months thereafter. The association of a focal mesangiocapillary glomerular change and immunoglobulin-complement deposits with tubuloreticular inclusions suggests lupus nephritis. To our knowledge, this is the first report of an interferon beta-1b-induced immune complex glomerulonephritis characterized by histologic, immunohistologic, and ultrastructural features that resembled lupus nephritis, but that occurred in a patient without evidence of systemic lupus erythematosus. Our review of experimental data and earlier case reports suggests a pathogenic role of recombinant IFN in some autoimmune diseases, especially those with the potency to induce systemic lupus erythematosus-like syndromes.

Successful Treatment of Subacute Lupus Erythematosus With Ustekinumab

A 58-year-old woman presented with a history of subacute cutaneous lupus erythematosus (SCLE) for the past 6 years, associated with photosensitivity, arthralgia, and fatigue. There was no evidence of systemic lupus erythematosus (SLE) or any history of exposure to drugs known to induce SCLE. Previous treatments included hydroxychloroquine sulfate, dapsone, prednisone, azathioprine, mycophenolate mofetil, topical corticosteroids, and tacrolimus 0.1% ointment, with limited benefit. Examination of the skin revealed erythematous and variably hyperkeratotic plaques (Figure, A) covering 70% of the body surface area. Laboratory test results were positive for SS-A/Ro and antinuclear antibodies (titer 1:640) but negative for SS-B/La and double-stranded DNA antibodies. Histopathologic analysis demonstrated vacuolar interface dermatitis, with a superficial and middermal perivascular and periadnexal inflammatory infiltrate consisting of mononuclear cells. There were faint deposits of mucin. Direct immunofluorescence revealed focal cytoid bodies and IgG and fibrin deposits at the dermoepidermal junction. This constellation of findings was consistent with the diagnosis of SCLE. THERAPEUTIC CHALLENGE