Analysis of incidence and clinical characteristics of osteonecrosis of femoral head in patients with systemic lupus erythematosus treated with glucocorticoid: A descriptive study based on a prospective cohort / 中国修复重建外科杂志

OBJECTIVE@#To describe the disease characteristics of osteonecrosis of the femoral head (ONFH) in patients with systemic lupus erythematosus (SLE) who experiencing prolonged glucocorticoid (GC) exposure.@*METHODS@#Between January 2016 and June 2019, 449 SLE patients meeting the criteria were recruited from multiple centers. Hip MRI examinations were performed during screening and regular follow-up to determine the occurrence of ONFH. The cohort was divided into ONFH and non-ONFH groups, and the differences in demographic baseline characteristics, general clinical characteristics, GC medication information, combined medication, and hip clinical features were compared and comprehensively described.@*RESULTS@#The age at SLE diagnosis was 29.8 (23.2, 40.9) years, with 93.1% (418 cases) being female. The duration of GC exposure was 5.3 (2.0, 10.5) years, and the cumulative incidence of SLE-ONFH was 9.1%. Significant differences ( P<0.05) between ONFH and non-ONFH groups were observed in the following clinical characteristics: ① Demographic baseline characteristics: ONFH group had a higher proportion of patients with body mass index (BMI)<20 kg/m 2 compared to non-ONFH group. ② General clinical characteristics: ONFH group showed a higher proportion of patients with cutaneous and renal manifestations, positive antiphospholipid antibodies (aPLs) and anticardiolipin antibodies, severe SLE patients [baseline SLE Disease Activity Index 2000 (SLEDAI-2K) score ≥15], and secondary hypertension. Fasting blood glucose in ONFH group was also higher. ③ GC medication information: ONFH group had higher initial intravenous GC exposure rates, duration, cumulative doses, higher cumulative GC doses in the first month and the first 3 months, higher average daily doses in the first 3 months, and higher proportions of average daily doses ≥15.0 mg/d and ≥30.0 mg/d, as well as higher full-course average daily doses and proportion of full-course daily doses ≥30.0 mg/d compared to non-ONFH group. ④ Combined medications: ONFH group had a significantly higher rate of antiplatelet drug use than non-ONFH group. ⑤ Hip clinical features: ONFH group had a higher proportion of hip discomfort or pain and a higher incidence of hip joint effusion before MRI screening than non-ONFH group.@*CONCLUSION@#The incidence of ONFH after GC exposure in China's SLE population remains high (9.1%), with short-term (first 3 months), medium-to-high dose (average daily dose ≥15 mg/d) GC being closely associated with ONFH. Severe SLE, low BMI, certain clinical phenotypes, positive aPLs, and secondary hypertension may also be related to ONFH.

Corticosteroid associated lupus pancreatitis

SUMMARY The relationship between acute pancreatitis and the administration of glucocorticoids is unclear because most reported cases have been diagnosed with systemic vascular diseases, such as systemic lupus erythematosus, which may be responsible for pancreatitis. A 22-year-old woman with eye involvement of a newly diagnosed systemic lupus erythematosus was admitted to our hospital. Pulse intravenous methylprednisolone therapy was given at 1mg/kg day for 3 days, and oral prednisolone at 40 mg/day thereafter. During pulse steroid therapy, she had abdominal pain, back pain, distention, nausea, and vomiting. Her physical examination was compatible with acute abdomen and peritonitis. Abdomen Computerized Tomography scan revealed diffuse liquid perihepatic and perisplenic area with heterogeneity around the mesentery. Due to the symptoms of acute abdomen, explorative laparotomy was performed. There was diffuse free fluid in the abdomen and edematous changes were observed around the pancreas. Amylase and lipase from intraabdominal fluid were studied and found to be high. The postoperative prednol dose was reduced carefully. On the sixth postoperative day, the drain was removed, and the patient was discharged without any problem. Physicians should keep in mind that acute pancreatitis may also be a cause of differential diagnosis of newly developed abdominal pain in patients receiving pulse steroid therapy with a normal level of serum amylase and lipase.

RESUMO A relação entre pancreatite aguda e a administração de glicocorticoides é incerta pois a maioria dos casos relatados foram diagnosticados com doenças vasculares sistêmicas, como lúpus eritematoso sistêmico, que pode causar pancreatite. Uma paciente de 22 anos com envolvimento ocular e lúpus eritematoso sistêmico recém-diagnosticado foi admitida em nosso hospital. Pulsoterapia intravenosa com metilprednisolona 1mg/kg foi administrada por 3 dias. Depois disso, a paciente foi tratada com prednisolona oral 40 mg/dia. Durante a pulsoterapia com corticoides, a paciente apresentava dor abdominal, dor nas costas, distensão, náusea e vômitos. O exame físico era compatível com quadro de abdome agudo e peritonite. Tomografia computadorizada do abdome revelou líquido difuso na região perihepática e periesplênica, com heterogeneidade ao redor do mesentério. Devido aos sintomas de abdome agudo, foi realizada laparotomia exploradora. Havia líquido livre difuso no abdome e alterações edematosas foram observadas em torno do pâncreas. A amilase e lipase do líquido intra-abdominal foram analisadas e consideradas elevadas. A dose pós-operatória de prednol foi reduzida com cuidado. No sexto dia de pós-operatório, o dreno foi retirado, e a paciente recebeu alta sem qualquer problema. Médicos devem lembrar que a pancreatite aguda também pode ser uma causa de diagnóstico diferencial para dor abdominal recém-desenvolvida em pacientes recebendo pulsoterapia com corticoides e com níveis normais de amilase e lipase séricas.

CD4+CD69+ T cells and CD4+CD25+FoxP3+ Treg cells imbalance in peripheral blood, spleen and peritoneal lavage from pristane-induced systemic lupus erythematosus (SLE) mice

Abstract Background: Adaptive immune cells, including CD4+CD69+ and CD4+CD25+FoxP3+ regulatory T (Treg) cells, are important for maintaining immunological tolerance. In human systemic lupus erythematosus (SLE), CD4+CD25+FoxP3+ Treg cells are reduced, whereas CD69 expression is increased, resulting in a homeostatic immune imbalance that may intensify autoreactive T cell activity. To analyze the mechanisms implicated in autotolerance failure, we evaluated CD4+CD69+ and CD4+CD25+FoxP3+ T cells and interleukin profiles in a pristane-induced SLE experimental model. Methods: For lupus induction, 26 female Balb/c mice received a single intraperitoneal 0.5 ml dose of pristane, and 16 mice received the same dose of saline. Blood and spleen samples were collected from euthanized mice 90 and 120 days after pristane or saline inoculation. Mononuclear cells from peripheral blood (PBMC), peritoneal lavage (PL) and splenocytes were obtained by erythrocyte lysis and cryopreserved for further evaluation by flow cytometry using the GuavaEasyCyte TM HT. After thawing, cells were washed and stained with monoclonal antibodies against CD3, CD4, CD8, CD25, CD28, CD69, FoxP3, CD14 and Ly6C (BD Pharmingen TM). Interleukins were quantified using Multiplex® MAP. The Mann-Whitney test and the Pearson coefficient were used for statistical analysis, and p < 0.05 considered significant. Results: Compared with the controls, SLE-induced animals presented increased numbers of CD4+CD69+ T cells in the blood on T90 and T120 (p = 0.022 and p = 0.008) and in the spleen on T120 (p = 0.049), but there were decreased numbers in the PL (p = 0.049) on T120. The percentage of Treg was lower in blood (p < 0.005 and p < 0.012) on T90 and T120, in spleen (p = 0.043) on T120 and in PL (p = 0.001) on T90. Increased numbers of CD4+ CD69+ T cells in the PL were positively associated with high IL-2 (p = 0.486) and IFN-γ (p = 0.017) levels, whereas reduced Treg cells in the blood were negatively correlated with TNFα levels (p = 0.043) and positively correlated with TGFβ1 (p = 0.038). Conclusion: Increased numbers of CD4+CD69+ T cells and reduced numbers of CD4+CD25+FoxP3+ Treg cells with an altered interleukin profile suggests loss of autotolerance in pristane-induced lupus mice, which is similar to human lupus. Therefore, this model is useful in evaluating mechanisms of cellular activation, peripheral tolerance and homeostatic immune imbalance involved in human SLE.

Revisão sistemática da indução de autoanticorpos e lúpus eritematoso pelo infliximabe / Systematic review of infliximab-induced autoantibodies and systemic lupus erythematosus

Nesta revisão sistemática abordamos a indução de autoanticorpos e lúpus eritematoso pelo infliximabe, analisando estudos que dosaram vários autoanticorpos antes e após o uso do infliximabe em diversas doenças (artrite reumatoide, espondilite anquilosante, artrite psoriásica e doença de Crohn). Nossa busca foi realizada em nove bases de dados (Pub-Med, ScienceDirect, Scopus, Web of Knowledge, Scirus, Cochrane, EMBASE, Scielo e LILACS). Foram encontradas 998 referências; 24 artigos foram separados na íntegra, dos quais 10 foram excluídos por não entrarem em nossos critérios de seleção. A escolha dos artigos foi realizada por dois revisores, e as divergências foram resolvidas por um terceiro revisor. Incluímos estudos de fase IV, com no mínimo três meses de duração. No total foram estudados 760 pacientes; o fator antinuclear, o anticorpo anti-DNA de dupla hélice e os antígenos extraídos pela salina foram os mais verificados. De todos os pacientes, apenas 10 (1,3%) apresentaram manifestações clínico-laboratoriais de lúpus induzido por infliximabe.

The present systematic review aims to discuss infliximab-induced autoantibodies and subsequent onset of systemic lupus erythematosus (SLE) through the analyses of primary reports measuring autoantibodies both before and after the administration of infliximab for the treatment of several diseases - e.g., rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, and Crohn's disease. Our literature search was performed in nine databases - PubMed, Science Direct, Scopus, Web of Knowledge, Scirus, Cochrane, EMBASE, Scielo and LILACS, and the search query retrieved 998 primary reports, from which 24 articles were selected and further narrowed down to 14, based on our inclusion criteria. Two independent reviewers performed the article selection and a third reviewer solved discrepancies. Our inclusion criteria comprised primary reports of phase IV clinical trials with duration of at least three months. In total, 760 patients were evaluated and the most prevalent assays performed in the studies were anti-nuclear antibodies (ANA), anti-double stranded DNA antibodies (anti-dsDNA), and antibodies to saline-extracted antigens (ENA panel). Of all patients evaluated, 10 (1.3%) showed clinical signs and laboratorial evidence of infliximabinduced SLE.

Autoinmunidad inducida por drogas: a propósito de un caso / Drug-induced auto-immunity: on account of a case

Se presenta el caso de una paciente de 35 años con antecedentes de enfermedad de Basedow-Graves, en tratamiento con propiltiouracilo (PTU), consumidora de pasta base y cocaína, que ingresa por fenómenos trombóticos en extremidades. Presenta en forma brusca falla respiratoria severa, que requiere manejo en UCI. Al laboratorio inmunológico destacan: ANA (+), AntiDNA (+), Anti-Ro (+), Anti-cardiolipinas IgG (+). Se realiza una revisión de las entidades autoinmunes más frecuentes asociadas al uso de drogas.

It presents the case of a 35-year old patient with a history of Basedow Graves disease, under treatment with Propiltiouracile (PTU), crack and cocaine user, who was admitted on thrombotic phenomena in her limbs. She presents sudden severe respiratory failure that requires handling at ICU. Under immunologic lab tests, the following stand out: ANA (+), Anti-DNA (+), Anti-Ro (+), Anti-cardiolipines IgG (+). A checkup is made of the most frequent auto-immune entities associated to drug abuse.

Methimazole-Induced Bullous Systemic Lupus Erythematosus: A Case Report

Bullous systemic lupus erythematosus (SLE) is a kind of LE-non-specific bullous skin disease that is rarely induced by a medication. We describe the first case of bullous SLE to develop after administration of methimazole. A 31-yr-old woman presented with generalized erythematous patches, multiple bullae, arthralgia, fever, conjunctivitis, and hemolytic anemia. Biopsy of her bulla showed linear deposition of lgG, lgA, C3, fibrinogen, and C1q at dermo-epidermal junction. She was diagnosed as bullous SLE and treated with prednisolone, dapsone, hydroxychloroquine, and methotrexate. Our experience suggests that SLE should be considered as a differential diagnosis when bullous skin lesions develop in patients being treated for hyperthyroidism.

Artropatias iatrogênicas droga-induzidas / Iatrogenic drug-induced arthropathy

Um grupo de pacientes idosos apresenta várias doenças, levandoa consumir inúmeras drogas. Por outro lado, o metabolismo dessasdrogas se encontra bastante alterado pelas condições especiais doprocesso de envelhecimento. Portanto, um determinado sintoma aser combatido pode não ser causado pela devida doença, mas sim,por algum tipo de droga que o paciente esteja usando. Este capítulotem como escopo enumerar as síndromes reumáticas que podem seruma conseqüência das várias drogas administradas aos idosos.

Lúpus induzido por drogas: da imunologia básica à aplicada: [revisão] / Drug-induced lupus: from basic to spplied immunology: [review]

O lúpus induzido por drogas (LID) é descrito como o desenvolvimento de sintomas semelhantes ao do lúpus eritematoso sistêmico idiopático, temporalmente relacionado à exposição a drogas, havendo, comumente, a resolução do quadro com a suspensão do medicamento desencadeante. A associação mais clássica é feita com a procainamida e a hidralazina. Recentemente, com a introdução de novas drogas na prática clínica, tem sido relatado um aumento no número de medicamentos implicados como causadores da doença, e a lista atual inclui quase uma centena de drogas relacionadas à ocorrência de LID. Embora descrito há mais de 60 anos, o mecanismo imunológico básico do LID ainda não está totalmente compreendido. Há várias hipóteses para o processo de indução de auto-imunidade pelas drogas, e o fenômeno geralmente é interpretado como uma inapropriada ativação do sistema imunitário. Entre as diversas teorias propostas, as mais aceitas são: a inibição da metilação do ácido desoxirribonucléico (DNA) por algumas drogas, o que permitiria a ativação das células T; a oxidação de certas substâncias pelos monócitos, gerando metabólitos ativos que ocasionariam ativação das células apresentadoras de antígenos e/ou a interferência dos metabólitos de determinadas drogas com a tolerância do sistema imune. Novos estudos são necessários para a melhor compreensão da imunopatogenia do LID, objetivando desenvolver tratamentos específicos com base no melhor conhecimento dos mecanismos patogênicos.

Drug-induced lupus (DIL) has been described as the development of idiopathic systemic lupus erythematous-like symptoms, temporarily associated to the exposition to drugs, and as a rule, the condition is improved with the suspension of the triggering medication. The most classical association is with procainamide and hydralazine. Recently, with the introduction of new drugs in the clinical practice, an increase on the number of medications associated with the occurence of the disease has been reported, and the current list includes almost one hundred drugs associated to the occurrence of DIL. The basic DIL immunologic mechanism, although described for more than 60 years, is not yet fully understood. There are several hypotheses for the drug-induced autoimmunity process, and the phenomenon is generally interpreted as an inappropriate activation of the immune system. Among the several theories proposed, the most accepted ones are: the inhibition of the DNA methylation by some drugs, what would allow the activation of T-cells; the oxidation of some substances by monocytes, what would generate active metabolites that in turn would lead to the activation of antigen-presenting cells and/or the interference of the metabolites of some drugs with the immune system tolerance. Further studies should be conducted in order to elucidate the DIL immunopathogeny with the objective of developing specific treatments based on the better knowledge on the pathogenic mechanisms.

Etanercept-Induced Systemic Lupus Erythematosus in a Patient with Rheumatoid Arthritis

Tumor necrosis factor (TNF) is known to play a critical role in the pathogenesis of rheumatoid arthritis (RA). Etanercept is a recombinant soluble fusion protein of TNF type II receptor and IgG, which acts as a specific TNF- antagonist. Anti-TNF-therapy has been an important advance in the treatment of RA. However, induction of autoantibodies in some proportion of patients treated with TNF inhibitors raised concerns for development of systemic autoimmune diseases such as systemic lupus erythematosus (SLE). Although new autoantibody formation is common with anti-TNF therapy, there are only rare reports of overt SLE, most of which manifested without major organ involvement and resolved shortly after discontinuation of the therapy. We describe a 55-yr-old Korean woman who developed overt life threatening SLE complicated by pneumonia and tuberculosis following etanercept treatment for RA. This case is to our knowledge, the first report of etanercept-induced SLE in Korea.

Amiodarone-induced systemic lupus erythematosus.

Drug-induced lupus is not a very common entity. Drugs like hydralazine, procainamide have been reported to induce lupus, but so far there is no case report of amiodarone-induced lupus in Indian literature. A case of atrial fibrillation in an elderly man who came with systemic features of lupus after amiodarone therapy for one and half years is reported.

Fatal evolution of systemic lupus erythematosus associated with Crohn's disease

Abstract: The authors describe the case of a young Brazilian woman who was treated of ileocolonic Crohn's disease sparing rectum, as confirmed by colonoscopy and histopathological examination. After a 4-years course of sulfasalazine treatment, she presented with skin facial lesions in vespertilio, fever, arthralgias and high titers of anti-ANA and LE cells. A sulfasalazine-induced lupus syndrome was diagnosed, because ofter sulfasalazine withdrawal and a short course of prednisone, the clinical symptoms disappeared and the laboratory tests returned to normal. Mesalazine 3 g/day was started and patient remained well for the next 3 years, when she was again admitted with fever, weakness, arthralgias, diplopy, strabismus and hypoaesthesia in both hands and feet, microhematuria, haematic casts, hypocomplementemia and high titers of autoimmune antibodies. A diagnosis of associated systemic lupus erythematosus was made. Although a pulsotherapy with methylprednisolone was started, no improvement was noticed. A cyclophosphamide trial was tried and again no positive results occurred. The patient envolved to severe clinical manifestation of general vasculitis affecting the central and peripheral nervous system and lungs, havaing a fatal evolution after 2 weeks. Although uncommon, the association of both disease may occur, and the authors call attention to this possibiliti, making a brief review of literature.

Lupus eritematoso sistêmico (LES) induzido por carbamazepina (CBZ): relato de caso / Systemic lupus erythematosus (LES) induced by carbamazepine (CBZ): repor a case

C. M. M. A., 32 a., fem, bca, severo atraso no desenvolvimento neuropsicomotor desde o nascimento. Iniciou, aos 13 anos, crises parciais complexas com ou sem generalizaçäo secundária. Foi submetida a vários esquemas medicamentosos sem controle completo das crises. Com a introduçäo de CBZ em 05/88, houve evidente reduçäo da frequência das crises. Em 11/89 passou a apresentar apatia, febre, emagrecimento (13 kg em 4 meses), náuseas, vômitos, rash malar e artrite de tornozelos. Laboratorialmente, o hemograma mostrou anemia miocrítica, Hb=9.8, Ht=31, VHS=100mm, células LE: 40 por cento , fator antinúcleo (FAN) = 10240 padräo periférico e homogêneo, anti SM-RNP-PO-LA-DNA negtivos; RX tórax mostrou finas áreas de atelectasia na base pulmonar direita. Com estes elementos, foi feito o diagnóstico de LES induzido por CBZ e introduzido 20mg de predinisona, com retirada lenta e gradual em 7 meses. Substituído a CBZ por valproato de sódio (VA), houve piora das crises, porém com desaparecimento da sintomatologia e normalizaçäo das provas laboratoriais, exceto a manutençäo da positividade do FAN, com títulos baixos (1:2560 - 05/91). Ressaltamos a importância de investigaçäo laboratorial para LES, em pacientes em uso de drogas antiepilépticas com manifestaçöes sistêmicas, particularmente em pacientes com retardo mental severo, cujos dados clínicos podem näo ser confiáveis. A evoluçäo favorável, na ausência de tratamento específico, e diminuiçäo significativa do FAN, após a suspensäo da CBZ, sugerem tratar-se de LES induzido por droga

Systemic lupus erythematosus during isoniazid therapy.

A case of systemic lupus erythematosus (SLE) in a young female which developed during the course of isoniazid therapy for pulmonary tuberculosis is described. SLE in this case is believed either to be induced or precipitated by isoniazid. Pertinent literature has been reviewed.

Lúpus induzido por insoniazida / Lupus induced by isoniazide

Grande número de drogas tem sido responsabilizado pela induçäo de auto-anticorpos; algumas dessas drogas säo capazes de induzir quadro clínico de LES, embora geralmente sem envolvimento renal ou de sistema nervoso. Os autores investigam a freqüência de induçäo de lúpus pela isoniazida em 20 portadores de tuberculose após três a seis meses da introduçäo dessa medicaçäo. Nenhum paciente apresentou quadro clínico sugestivo de lúpus após introduçäo da isoniazida e apenas três pacientes (15%) mostraram positividade do FAN. A freqüência dos anticorpos anti-histona e antiDNA desnaturado foi maior após inicio da terapêutica. Esses dados sugerem que o uso de isoniazida näo estaria associado à induçäo de lúpus clínico, embora essa droga seja capaz de induzir o aparecimento de anticorpos antinucleares

Lúpus induzido por procainamida / Lupus induced by procainamide

Os autores apresentam um caso de lúpus-símile induzido por procainamida, com sinais, sintomas e provas laboratoriais característicos desta síndrome. Comentam a fisiopatogenia, bem como o tratamento