Ovarian function in patients with systemic lupus erythematosus:Pathogenesis,drug application and prospective therapies

Systemic lupus erythematosus(SLE)is a chronic autoimmune disease in which multiple organs are damaged that prevails in fertile women.Currently,glucocorticoids and immunosuppressants are widely used to treat SLE patients.However,ovarian dysfunction occurs following the use of these drugs in women with SLE.Here,we summarize recent progress in terms of understanding ovarian injury,the effects of drug application and strategies to improve ovarian function in women with SLE.This review could be helpful to precisely cure SLE in women desiring to have offspring.

Life course changes provoked by chronic disease: A study on everyday life for patients with systemic lupus erythematosus

Objective:This study examined patients with systemic lupus erythematosus(SLE)as a means to explore the impacts of chronic disease on life courses.Methods:A semi-structured in-depth interviews were conducted with nine patients in China in 2017;participants were included based on their having or having had facial butterfly erythema.Results:The study focused on both the disease's impact on the patients'health and on their daily lives.Four core themes emerged:visible changes in the patient's bodies,social dilemmas,"the encouragement of disease",and a new perspective on the relationship between disease and health.One important finding was that the occurrence of a chronic disease did not have only negative repercussions;some patients felt that there were advantages to being sick.Chronic disease resulted in a reworking of daily life.The patients developed a self-referential model of healing.Conclusion:The distinct interpretations of the same disease offered by different patients served to yield a more complete understanding of the disease.People with SLE adjust their thinking about the disease based on personal feelings as well as experiences and pursue a dialogue on their illness based on the disease pattern unique to them.The meaning that disease had for the patients was not limited to negative connotations.

An atypical presentation of Kikuchi-Fujimoto disease mimicking systemic lupus erythematosus: case report and literature review

Purpose: To report a case of atypical Kikuchi-Fujimoto disease (KFD) that illustrates several overlapping features with systemic lupus erythematosus (SLE). Methods: A case is reported followed by a review of the current literature. Case report: A 16-year-old boy with an unusual manifestation of Kikuchi-Fujimoto disease (KFD) is described. The patient presented with fever, weight loss and severe abdominal pain, due to extensive necrotizing retroperitoneal and mesenteric lymphadenopathy. During the course of his illness, he developed several symptoms suggestive of systemic lupus erythematosus (SLE): a pericardial effusion, cotton wool spots on the retina and antibodies against nuclear antigens (ANA), Smith (Sm) and ribonucleoprotein (RNP) antigens. However, no additional features of SLE were found. The patient subsequently fully recovered within two months, without initiation of immunosuppressive therapy. His autoantibodies became negative five months after initial presentation and he remains well at his 23 month follow up visit. Discussion: We hypothesize that the autoantibodies developed by our patient were secondary to self-antigen induced autoimmunity related to his extensive tissue necrosis. Despite initially having clinical features suggestive of SLE, our patient’s full and spontaneous recovery strongly supports the diagnosis of KFD. This illustrates the need for careful diagnosis, in order to avoid unnecessary and potentially toxic treatment with immunosuppressive agents.

Histone H1/MBP hydrolysing antibodies - novel potential marker in diagnosis of disease severity in systematic lupus erythematosus patients

Recently we have shown the presence of catalytically active IgGs, capable to cleave histone H1 and bovine myelin basic protein (MBP), in blood serum of SLE patients. Here we present data that demonstrate the correlation between a) proteolytic activity towards histone H1 and MBP of IgG-antibodies from blood serum of SLE patients and b) disease severity level in these patients. IgGs were isolated from blood serum by chromatography on protein G-sepharose. Commercial preparations of bovine myelin basic proteins (MBP) and calf thymus histone H1 were used as substrates. Analysis of the proteolytic activity showed that 16 of 38 lgG-preparations (42,1%) obtained from blood serum of SLE patients were capable of cleaving both histone H1 and MBP with different efficiency. It was revealed that the presence in blood serum of lgGs possessing proteolytic activity towards both histone H1 and bMBP closely correlates with manifestation of the disease severity in SLE patients.

Acquired von Willebrand Syndrome in a Male with Systemic Lupus Erythematosus Presented with Mucocutaneous Bleeding and Treated with rFVIIa

Background: Systemic lupus erythematosis (SLE) is a disorder with multiple organ involvement. Haematological abnormalities have been addressed in it, but acquired von Willebrand syndrome is a rarer phenomenon in current disease. The Case: We report acquired von Willebrand syndrome and SLE in a man with brown rash on face, gingival bleeding, easy bruising and epistaxis and laboratory finding of decreased complement, high level of anti-nuclear antibody and anti-DNA. These findings confirmed the diagnosis of SLE. He underwent kidney biopsy and experienced severe pain at the site of biopsy, but the ultra-sonography evaluation showed small sub capsular haematoma at the site of biopsy. During the next 48 hours, gradually APTT prolongation was continued and haematocrit dropped. In spite of FFP infusion and taking tranexamic acid every eight hours, there wasn’t any improvement in haemostatic condition. He received Methylprednisolone and Cyclophosphamid pulses. The patient underwent surgery to roll out vascular complication, but there wasn’t any vascular problem. On the third day, recombinant activated factor VII was infused every two hours until oozing was stopped.

Suicide risk in systemic lupus erythematosus:A narrative review

Introduction:Despite the medical and scientific advances,the disease’s restrictions and the perception of personal and social losses related to its course reinforce fear and generate intense suffering in lupus patients.Psychiatric comorbidities,especially major depressive episodes,are highly prevalent during systemic lupus erythematosus.Among them,suicide is a behavior that is much more common than we believe.Objective:To perform a narrative review on suicidal behavior associated with systemic erythematosus lupus(SLE).Results:Studies have shown an increased risk of suicide among patients with chronic diseases and psychiatric disorders,especially depression.However,suicide cannot be attributed only to a higher prevalence of depression and other mental illnesses.Therefore,it is necessary to learn more about the suicide risk factors present in patients with lupus to work on secondary prevention and avoid the premature loss of lives and the additional suffering of families and surrounding communities.The coordination between the studies on suicidal behavior and its intricate network of individual and sociocultural factors and the studies on this multisystem autoimmune disease with a broad manifestation spectrum,lupus,creates new and essential field research.Conclusions:Non-psychiatrist office-based physicians,health clinics,or wards dedicated to the treatment of SLE should recognize and handle the suicide risk factors on their patients to reduce the suffering caused by this disease.

Ankle-Brachial Index in Systemic Lupus Erythematosus:A Senegalese Case-Control Study

Systemic lupus erythematosus (SLE) is associated with accelerated atherosclerosis and increasing cardiovascular risk which is recognized as a major cause of morbidity and death. Whether subclinical atherosclerosis has been evaluated by several methods, there are very limited data about Ankle-Brachial Index (ABI) in patients with systemic lupus erythematosus. The aim of the present study was to compare this index, between SLE patients and controls. We conducted a case-control study in the Department of Internal Medicine of our institution during the period from August 1, 2017 to December 31, 2018. We included 100 subjects, including 50 SLE patients and 50 control cases. This included 44 women and 6 men in patients with an identical distribution in controls. The mean age was 33.5 ± 11.3 years for cases and 33.3 ± 11.3 years (p-value: 0.93) for controls subjects. There was higher frequency of cardiovascular risk factors such as dyslipidemia (p-value at 0.009), low level of serum HDL-cholesterol (p-value??0.001), hypertriglyceridemia (p-value at 0.000) and hyperuricemia (p-value at 0.000) in patients with SLE. Overweight/obesity was higher in controls subjects (p-value at 0.028). There was no statistically significant difference in the frequency of diabetes-mellitus, smoking and high blood pressure. The abnormally ABI was recorded in 19 patients with SLE (38%) and 8 controls (16%) with a p-value: 0.01 and odds ratio: 3.22. Eight patients (16%) and four controls (8%) had low ABI without significant difference (p-value: 0.11 but odds-ratio at 2.98). Eleven patients with SLE (22%) and five controls (10%) had high ABI (p-value: 0.05 and odds-ratio: 3.24). In patients with SLE only disease activity (cSLEDAI) at the inclusion of the study was correlated?to abnormal ABI.?Conclusion:?This study showed an increasing prevalence of abnormal ABI in black African patients with SLE compared to controls with a correlation between disease activity and abnormal ABI.

Association between autoimmune pancreatitis and systemic autoimmune diseases

AIM: To investigate the association between autoimmune pancreatitis (AIP) and systemic autoimmune diseases (SAIDs) by measurement of serum immunoglobulin G4 (IgG4). METHODS: The serum level of IgG4 was measured in 61 patients with SAIDs of different types who had not yet participated in glucocorticosteroid treatment. Patients with an elevated IgG4 level were examined by abdominal ultrasonography (US) and, in some cases, by computer tomography (CT). RESULTS: Elevated serum IgG4 levels (919 ± 996 mg/L) were detected in 17 (28%) of the 61 SAID patients. 10 patients had Sj gren's syndrome (SS) (IgG4: 590 ± 232 mg/L), 2 of them in association with Hashimoto's thyroiditis, and 7 patients (IgG4: 1388 ± 985.5 mg/L) had systemic lupus erythematosus (SLE). The IgG4 level in the SLE patients and that in patients with SS were not significantly different from that in AIP patients (783 ± 522 mg/L). Abdominal US and CT did not reveal any characteristic features of AIP among the SAID patients with an elevated IgG4 level. CONCLUSION: The serum IgG4 level may be elevated in SAIDs without the presence of AIP. The determination of serum IgG4 does not seem to be suitable for the differentiation between IgG4-related diseases and SAIDs.

Differential Diagnosis and Association of Acquired Immunodeficiency Syndrome and Systemic Erythematous Lupus: A Brief Review

Acquired immunodeficiency syndrome and lupus erythematosus are multisystem diseases that can affect several organs and systems at different stages of disease evolution. Both diseases share common clinical manifestations, which may lead to diagnostic difficulties, especially at the onset of the disease. Another additional challenge is when there is an association of the two pathologies. The objective of this brief review is to describe the clinical manifestations of the diseases and to make considerations regarding the moment of onset of symptoms. Knowledge of these common manifestations and their peculiarities may alert clinicians to possible diagnoses and avoid errors in the evaluation and conduction of these patients.

Difficulties in the Management of Systemic Autoimmune Diseases in Saint-Louis Du Senegal through the Analysis of a Series of 70 Observations

Introduction: Systemic Autoimmune Diseases (SAID) long considered very rare in Africa are increasingly the subject of publications. The objective of this work is to identify the difficulties in the management of these pathologies in an internal medicine department in northern Senegal by analyzing the epidemiological, clinical-biological, therapeutic and evolutionary aspects of SAID. Methods: This was a descriptive cross-sectional study carried out in the internal medicine department of the Saint-Louis University Hospital Center. Included were all the files of patients followed in outpatient and/or hospitalization for autoimmune diseases according to the criteria of the American College of Rheumatology, during the period from January 2017 to December 2020. The data were analyzed using SPSS software version 21.0. As the study was descriptive, no statistical test was performed. Results: Out of 3800 patients, 70 presented SAID, i.e. a hospital prevalence of 1.8%. Polyarthritis was the first reason for consultation in 97% followed by skin manifestations in 8%. The patients had positive anti-nuclear autoantibodies in 88% of cases. Rheumatoid arthritis was the predominant condition (71%) followed by systemic lupus erythematosus (SLE) (15%) and undifferentiated autoimmune diseases in 10%. Eleven percent (11%) of patients had an associated autoimmune disease. Corticosteroids were used in the treatment of these conditions in 97% of cases and methotrexate was the most prescribed immunosuppressant (54%). Thirty-two percent (32%) of patients are lost to follow-up. Conclusion: SAID are diverse and under diagnosed;they are characterized by diagnostic delay above all linked to access to specialists and sometimes to the high cost of paraclinical examinations, in particular immunology. Treatment remains based primarily on corticosteroid therapy and conventional immunosuppressants in the face of the unavailability of biotherapies.

Kikuchi-Fujimoto disease:A comprehensive review

Kikuchi-Fujimoto disease,a rare form of necrotizing lymphadenitis,is an uncommon,benign,self-limiting disorder of obscure etiology.It affects mostly young adults of both genders.Clinically,it presents with fever and lymphadenopathy of a firm to rubbery consistency frequently involving cervical lymph nodes while weight loss,splenomegaly,leucopenia,and elevated erythrocyte sedimentation rate feature in severely affected patients.Cutaneous involvement occurs in about 30%-40%of cases as facial erythema and nonspecific erythematous papules,plaques,acneiform or morbilliform lesions of great histologic heterogeneity.Both Kikuchi-Fujimoto disease and systemic lupus erythematosus share an obscure and complex relationship as systemic lupus erythematosus may occasionally precede,develop subsequently,or sometimes be associated concurrently with Kikuchi-Fujimoto disease.It is often mistaken for non-Hodgkin lymphoma while lupus lymphadenitis,cat-scratch disease,Sweet’s syndrome,Still’s disease,drug eruptions,infectious mononucleosis,and viral or tubercular lymphadenitis are other common differentials.Fine needle aspiration cytology mostly has features of nonspecific reactive lymphadenitis and immunohistochemistry studies usually show variable features of uncertain diagnostic value.Since its diagnosis is exclusively from histopathology,it needs to be evaluated more carefully;an early lymph node biopsy will obviate the need for unnecessary investigations and therapeutic trials.Its treatment with systemic corticosteroids,hydroxychloroquine,or antimicrobial agents mostly remains empirical.The article reviews clinicoepidemiological,diagnostic,and management aspects of KFD from the perspective of practicing clinicians.

IFIH1 and DDX58 gene variants in pediatric rheumatic diseases

BACKGROUND The IFIH1 gene codes the MDA5 protein and the DDX58 gene codes the RIG-I receptor.Both proteins are parts of the interferon(IFN)I signaling pathway and are responsible for antiviral defense and innate immune response.IFIH1 and DDX58 polymorphisms are associated with a spectrum of autoimmune diseases.Rare gain-of-function IFIH1 mutations have been found in Singleton-Merten and Aicardi-Goutières syndrome,while DDX58 mutation can cause atypical Singleton-Merten syndrome.AIM To characterize children with pediatric rheumatic diseases(PRD)carrying DDX58 or IFIH1 variants.METHODS Clinical exome sequencing was performed on 92 children with different PRD.IFIH1 and DDX58 variants have been detected in 14 children.IFN-I score has been analyzed and the clinical characteristics of patients have been studied.RESULTS A total of seven patients with systemic lupus erythematosus(SLE)(n=2),myelodysplastic syndrome with SLE features at the onset of the disease(n=1),mixed connective tissue disease(MCTD)(n=1),undifferentiated systemic autoinflammatory disease(uSAID)(n=3)have 5 different variants of the DDX58 gene.A common non-pathogenic variant p.D580E has been found in five children.A rare variant of uncertain significance(VUS)p.N354S was found in one patient with uSAID,a rare likely non-pathogenic variant p.E37K in one patient with uSAID,and a rare likely pathogenic variant p.Cys864fs in a patient with SLE.Elevated IFN-I score was detected in 6 of 7 patients with DDX58 variants.Seven patients had six different IFIH1 variants.They were presented with uSAID(n=2),juvenile dermatomyositis(JDM)(n=1),SLElike disease(n=1),Periodic fever with aphthous stomatitis,pharyngitis,and adenitis syndrome(n=1),and systemic onset juvenile idiopathic arthritis(n=1).Three patients have VUS p.E627X,one patient has benign variant p.I923V.Rare VUS p.R595H was detected in the JDM patient.Another rare VUS p.L679Ifs*2 and previously not reported variant p.V599Ffs*5 were detected in the patient with uSAID.One patient with uSAID has rare VUS p.T520A.All patients had elevated IFN-I scores.CONCLUSION Rare compound-heterozygous IFIH1 variant(p.L679Ifs*2 and p.V599Ffs*5),heterozygous IFIH1 variant(p.T520A)and heterozygous DDX58 variant(p.Cys864fs)are probably disease causative for uSAID and SLE.The majority of patients with different DDX58 and IFI1 variants had hyperactivation of the IFN I signaling pathway.

Dual autoimmune diseases:Rheumatoid arthritis with systemic lupus erythematosus and Type 1 diabetes mellitus with multiple sclerosis

Autoantibodies and inflammation are the hallmarks of autoimmune diseases(ADs).Organ-specific and nonorgan-specific ADs are divided according to whether the autoimmune reaction is directed against a specific tissue(e.g.,thyroid in Hashimoto's thyroiditis)or widely expressed antigens(e.g.,cell nuclei in systemic lupus erythematosus[SLE]).SLE is distinguished by the presence of circulating autoantibodies and immune complex deposition,both of which can induce inflammatory damage to many organs.Rheumatoid arthritis(RA),sometimes called inflammatory arthritis,is a systemic AD that affects the joints and causes synovitis.Multiple sclerosis(MS)is a central nervous system inflammatory disease with various neurological and autoimmune symptoms.Links have been reported between RA and SLE as well as between Type 1 diabetes mellitus and MS.Identification of shared genes and biological processes could aid in the discovery of possible treatment targets in these dual ADs.This review article explores the molecular nature and familial inheritance of dual ADs.

Effect of Rituximab Versus Mycophenolate Mofetil or Cyclophosphamide as Control in Lupus Nephritis:A Meta-Analysis

Objective:To evaluate the effects of rituximab versus mycophenolate mofetil or cyclophosphamide as control in lupus nephritis by meta-analysis.Methods:A systematic search was carried out up to January 2022,obtaining 7 studies involving 645 participants with lupus nephritis at the commencement of the investigation;198 of them were treated with rituximab,while 447 were treated with mycophenolate mofetil or cyclophosphamide.We determined the odds ratio(OR)and mean difference(MD)with 95%confidence index(CI)to compare rituximab’s efficacy to that of mycophenolate mofetil or cyclophosphamide as control in lupus nephritis using random-or fixed-effects model by dichotomous or continuous techniques.Results:The rituximab group showed significantly higher complete renal remission rate(OR=2.52;95%CI 1.30-4.91,P=0.006)and total renal remission rates(OR=2.22;95%CI 1.36-3.63,P=0.001)than the control group.However,there was no significant difference in terms of end Systemic Lupus Erythematosus Disease Activity Index(SLEDAI)score(MD-1.16;95%CI-2.88-0.57,P=0.19),proteinuria(MD-0.31;95%CI-0.70-0.09,P=0.013),and serum creatinine(MD 0.01;95%CI-0.04-0.07,P=0.64)between the rituximab group and the control.Conclusion:Rituximab exhibited significantly greater complete renal remission rate and total renal remission rates,with no significant difference in terms of shorter-end SLEDAI,proteinuria,and serum creatinine,compared with the control in individuals with lupus nephritis.

Therapeutic efficacy of anti-CD19 CAR-T cells in a mouse model of systemic lupus erythematosus

Dysregulated B-cell activation plays pivotal roles in systemic lupus erythematosus(SLE),which makes B-cell depletion a potential strategy for SLE treatment.The clinical success of anti-CD19 CAR-T cells in treating B-cell malignancies has attracted the attention of researchers.In this study,we aimed to investigate the feasibility of applying anti-CD19 CAR-T cell therapy to SLE treatment in a mouse disease model.We constructed murine anti-CD19 CARs with either CD28 or 4-1BB as the intracellular costimulatory motif and evaluated the therapeutic function of the corresponding CAR-T cells by infusing them into MRL-lpr mice.Furthermore,anti-CD19 CAR-T cells were transferred to MRL-lpr mice before the onset of disease to determine their role in SLE prevention.According to our observations,compared with antibody treatment,the adoptive transfer of our anti-CD19 CAR-T cells showed a more sustained B-cell-depletion effect in MRL-lpr mice.The transfer of syngeneic anti-CD19 CAR-T cells not only prevented disease pathogenesis before the onset of disease symptoms but also displayed therapeutic benefits at a later stage after disease progression.We also tried to optimize the treatment strategy and found that compared with CAR-T cells with the CD28 costimulatory motif,CAR-T cells with the 4-1BB costimulatory motif showed better therapeutic efficiency without cell enrichment.Taken together,these results show that anti-CD19 CAR-T cell therapy was effective in the prevention and treatment of a murine model of SLE,indicating its potential for clinical use in patients.

Relationship Between Clinical and Immunological Features with Magnetic Resonance Imaging Abnormalities in Female Patients with Neuropsychiatric Systemic Lupus Erythematosus

Background：Conventional magnetic resonance imaging （MRI） is the preferred neuroimaging method in the evaluation ofneuropsychiatric systemic lupus erythematosus （NPSLE）.The purpose of this study was to investigate the association between clinical and immunological features with MRI abnormalities in female patients with NPSLE,to screen for the value of conventional MRI in NPSLE.Methods：A total of 59 female NPSLE patients with conventional MRI examinations were enrolled in this retrospective study.All patients were classified into different groups according to MRI abnormalities.Both clinical and immunological features were compared between MRI abnormal and normal groups.One-way analysis of variance was used to compare the systemic lupus erythematosus disease activity index （SLEDAI） score for MRI abnormalities.Multivariate logistic regression analysis investigated the correlation between immunological features,neuropsychiatric manifestations,and MRI abnormalities.Results：Thirty-six NPSLE patients （61%） showed a variety of MRI abnormalities.There were statistically significant differences in SLEDAI scores （P 〈 0.001）,incidence of neurologic disorders （P =0.001）,levels of 24-h proteinuria （P =0.001） and immunoglobulin M （P =0.004）,and incidence of acute confusional state （P =0.002）,cerebrovascular disease （P =0.004）,and seizure disorder （P =0.028） between MRI abnormal and normal groups.In the MRI abnormal group,SLEDAI scores for cerebral atrophy （CA）,cortex involvement,and restricted diffusion （RD） were much higher than in the MRI normal group （P 〈 0.001,P =0.002,P =0.038,respectively）.Statistically significant positive correlations between seizure disorder and cortex involvement （odds ratio [OR] =14.90;95% confidence interval [CI],1.50-151.70;P =0.023） and cerebrovascular disease and infratentorial involvement （OR =10.00;95% CI,1.70-60.00;P =0.012） were found.Conclusions：MRI abnormalities in NPSLE,especially CA,cortex involvement,and RD might be markers of high systemic lupus erythematosus activity.Some MRI abnormalities might correspond to neuropsychiatric manifestations and might be helpful in understanding the pathophysiology of NPSLE.

Sequential bilateral central retinal artery occlusion as the primary manifestation of systemic lupus erythematosus

Bilateral central retinal artery occlusion （CRAO） has been rarely reported as the primary manifestation in patients with systemic lupus erythematosus （SLE）. The severe retinal vaso-occlusive diseases usually cause devastating and permanent damage to visual function in spite of vigorous treatment. A 42-year-old Chinese woman presented with abrupt bilateral vision loss. The diagnosis of bilateral CRAO was suggested by the ocular presentation and fluorescein angiography. Laboratory studies showed positive results of antinuclear antibody, anti-Ro/SSA anti-La/SSB; decreased levels of C3, C4 complement and normal levels of antiphospholipides antibodies （APAs）. Her visual acuity deteriorated despite systemic steroid and immunosuppressant treatment. Severe vaso-occlusive retinopathy may be an earlier manifestation of SLE without elevated level of APAs.

Elevated levels of serum antibodies against alpha-1,6-glucan in patients with systemic lupus erythematosus or rheumatoid arthritis

This study was undertaken to investigate whether levels of anti-alpha-1,6-glucan antibodies in human sera correlate with rheumatoid arthritis(RA)and systemic lupus erythematosus(SLE).Serum samples were collected from patients with SLE(n=30),RA(n=30)and healthy adult volunteers.IgG,IgA and IgM levels against alpha-1,6-glucan were measured using enzyme linked immunosorbent assays.Anti-alpha-1,6-glucan IgG prevalence was raised in patients with active SLE(73.3%)and RA(60%)compared with healthy controls(13.3%).Strong correlation between anti-alpha-1,6-glucan-IgG levels and anti-perinuclear factor(r=0.642;p<0.05)in RA patients or anti-nuclear antibodies(r=0.675;p<0.05)in SLE patients was observed.No significant differences in anti-alpha-1,6-glucan-IgA or-IgM levels were noted between different groups.We conclude that anti-alpha-1,6-glucan-IgG levels were significantly elevated in patients with SLE or RA and positively correlated with disease activity.

Generalized megaviscera of lupus:Refractory intestinal pseudo-obstruction,ureterohydronephrosis and megacholedochus

Dilated dysfunction involving multiple visceral organs has been reported in patients with systemic lupus erythematosus(SLE).Chronic intestinal pseudo-obstruction(CIPO) resulting from intestinal smooth muscle damage has presented in conjunction with ureterohydronephrosis and, more rarely, biliary dilatation(megacholedochus).While the molecular pathogenesis is largely unknown, observed histo-pathologic features include widespread myositis, myocyte necrosis in the intestinal muscularis propria with subsequent atrophy and fibrosis, preserved myenteric innervations and little vasculitis.High dose immunosuppression usually results in resolution of symptoms with recovery of smooth muscle function, indicative of an autoimmune etiology.We report a patient with SLE who presented with intestinal pseudo-obstruction, ureterohydronephrosis and megacholedochus, and present images that illustrate megaviscera simultaneously involving all 3 visceral organs.Since the co-manifestation of all 3 is unusual and has been reported only once previously, wehave termed this rare clinical syndrome generalized megaviscera of lupus(GML).Although the SLE disease-activity parameters responded to aggressive immunomodulative therapy in our patient, clinical evidence of peristaltic dysfunction persisted in all involved viscera.This is a variation from the favorable outcomes reported previously in SLE patients with GML and we attribute this poor clinical outcome to disease severity and, most importantly, delayed clinical presentation.Since inflammation followed by atrophy and fibrosis are key aspects in the pathogenesis and natural history of GML, the poor response in our patient who presented late in the clinical course may be the result of ‘burnt out' inflammation with irreversible end-stage flbrosis.Thus, early recognition and timely initiation of treatment may be the key to recover visceral peristaltic function in patients with GML.

Phenotypic characterization of patients with activated PI3Kδ syndrome 1 presenting with features of systemic lupus erythematosus

Activated phosphoinositide 3-kinase d syndrome 1(APDS1)is a primary immunode-ficiency disease caused by gain-of-function mutations in PIK3CD.Clinical features of autoimmune disease have been reported in patients with APDS1.In this study,we reported three patients with APDS1 presenting with systemic lupus erythematosus(SLE)phenotype.The clinical manifestations included recurrent respiratory tract infection,lymphoproliferation,Coombs-positive hemolytic anemia,decreased complement fractions,positive antinuclear antibodies,renal complications related to SLE associated diseases,which met the clinical spectrum of APDS1 and the classification criteria of SLE.The immunological phenotype included an inversion in the CD4:CD8 ratio,an increase in both non-circulating Tfh CD4^(+)memory T and circulating Tfh populations,a low level of recent thymic emigrant T cells,overexpression of CD57 on T cells,and a decrease in B cells with fewer antibody class switch recombination.These phenotypes detected in patients with APDS1 presenting with SLE were resemble that in patients with APDS1 presenting without SLE.Meanwhile,we described the effect of glucocorticoids and rapamycin therapy on patients with APDS1.The phosphorylation of S6 at Ser235/236 was inhibited in patients with APDS1 who underwent glucocorticoids therapy,including two who presented with SLE phenotype.The phosphorylation of AKT at Ser473 and phosphorylation of S6 at Ser235/236 were inhibited in other patients with APDS1 who underwent rapamycin therapy.Here,we showed the coexistence of immunodeficiency and SLE phenotype in APDS1,and the inhibition of rapamycin in activated Akt-mTOR signaling pathway.