Profile of Autoantibodies and Clinical Symptoms in Guinean Patients with Connective Tissue Diseases

Connective tissue diseases (CTDs) are Autoimmune diseases (AIDs) characterized by the appearance of autoantibodies, which are diagnostic markers. Investigations of these autoantibodies play a major role in the management of several autoimmune diseases. The objective of this study was to describe the profile of anti-ENA antibodies according to the clinical symptoms of mixed CTDs in Conakry teaching Hospital. We performed a cross-sectional study during six months. A total of 20 patients was recruited and we measured antibodies using the ELISA technique. The mean age of our patients was 36.5 years, with a predominance of females. Cutaneous and rheumatological signs were the main clinical manifestations. SLP was the most frequent CTDs;the threshold of ENA antibodies positivity was higher in scleroderma with and SLP. Anti-ENA identification reveals the frequency of anti-SSA (83.33%), anti-U1RNP (66.66%) and anti-histone (50%) antibodies. Antinuclear antibodies (ANA) react with various components of the cell nucleus. Their detection is of major interest in the diagnosis of CTDs. Our results highlight the importance of determining the specificity of these antibodies to guide differential diagnosis.

Hydroxychloroquine-induced renal phospholipidosis resembling Fabry disease in undifferentiated connective tissue disease: A case report

BACKGROUND Fabry disease is a kind of lysosomal storage disease resulting from deficient activity of the lysosomal hydrolase alpha-galactosidase A(GLA). A mutation in the GLA gene leads to a loss of activity of alpha-galactosidase A. Some drugs,such as hydroxychloroquine, can cause pathological changes similar to those usually seen in Fabry disease.CASE SUMMARY We report the case of a 41-year-old female patient who was diagnosed with undifferentiated connective tissue disease in 2008. Hydroxychloroquine treatment started 2 years ago, and proteinuria and hematuria increased. Renal biopsy demonstrated renal phospholipidosis. Zebra bodies and myelin figures were found by renal electron microscopy and were initially thought to be indicators of Fabry disease. A genetic analysis of the patient and her family members did not reveal mutations in the GLA gene, supporting a diagnosis of hydroxychloroquine-induced renal phospholipidosis.CONCLUSION This report reveals one of the adverse effects of hydroxychloroquine. We should pay more attention to hydroxychloroquine-induced renal phospholipidosis.

Connective Tissue Diseases on the Elderly Population in Dakar Hospital Setting

Introduction: Immunosenescence contributes to the development of auto-antibodies. However, while the prevalence of some autoantibodies increases with age, the incidence of connective tissue diseases decreases with age. This study aims to determine the clinical and paraclinical characteristics of connective tissue diseases in the elderly population. Materials and Methods: We conducted a retrospective and descriptive study, from March 2010 to March 2021, in the Internal Medicine Department of Aristide Le Dantec Hospital, including all the medical records of patients followed up for connective tissue disease and whose symptomatology began at an age greater than or equal to 65 years. Epidemiological, clinical, paraclinical, therapeutic and evolutionary data were collected from a pre-established survey form and then processed using SPSS software. Results: Overall, 22 cases were collected out of 275 seen on consultation. They involved 16 women and 6 men, aged between 65 and 85 years with a median of 70 years. The mean duration of the clinical picture was 15.7 months with extremes of 1 and 96 months. The clinical symptoms were joint pain in 21 patients associated with dry eye and mouth syndrome in seven cases and one patient underwent isolated dry eye and mouth syndrome. Joint involvement was deforming in 13 patients. Poor general condition was noted in 20 patients. Biology showed anemia in 14 patients, hyperleukocytosis (2 patients) and thrombocytosis (5 patients). The sedimentation rate (SR) was accelerated in 9 patients and the C-reactive protein (CRP) was positive in 12 patients. Immunology showed a positive Latex test (3 patients/6), Waaler-Rose reaction (8 patients/13), anti-cyclic citrullinated peptides (anti-CCP) antibodies (11 patients/11), anti-nuclear antibodies (2 patients/4). Anti-extractable nuclear antigens (anti-ENA) antibody testing in 4 patients showed positive anti-U1RNP (1 case), anti-SSA and anti-SSB (1 case). Plain X-Rays of the hands, wrists and feet showed destructive lesions in 16 patients. The diagnosis of rheumatoid arthritis (RA) was set in 21 patients, one of which was associated with Sjogren’s syndrome (SS) and one with primary Sjogren’s syndrome. Treatment was based on prednisone (21 cases), methotrexate (17 patients), and hydroxychloroquine (9 patients). The evolution was remarkable in 10 patients. Conclusion: Autoimmune diseases in the elderly are uncommon compared to the young adult population. In our study, we only found cases of rheumatoid arthritis and Sjogren’s syndrome. As the population ages, connective tissue diseases may be increasingly diagnosed.

COVID-19 Induced Mixed Connective Tissue Disease (MCTD)—Case Report

Mixed connective tissue disease (MCTD) is a rare systemic autoimmune disorder that damages multiple organs simultaneously and is associated with chronic inflammation, in which the signs of systemic sclerosis, systemic lupus erythematosus, and polymyositis can co-occur. Its distinctive feature and the basis for the diagnosis of MCTD is the presence of an antibody against the uridine-rich RNP of the cell nucleus (Anti-U1-RNP). It has been observed that intercurrent infections can trigger autoimmune diseases, however, the fact that viral infections—such as SARS-CoV-2—induce them is currently poorly understood. The present study raises the etiological role of the SARS-CoV-2 virus in the development of the disease. Authors describe the case of a 38-year-old patient in good general condition, who was diagnosed with mixed connective tissue disease three months after COVID-19 infection.

Targeted treatment strategy for patients with severe pulmonary hypertension secondary to connective tissue diseases

Background:Pulmonary arterial hypertension(PAH)associated with connective tissue diseases(CTD)(CTD-PAH)remains a difficult challenge in clinical practice.We aimed to evaluate the effects of targeted vasodilators in patients with severe CTD-PAH.Methods:The data of 53 patients with severe CTD-PAH hospitalized at the Department of Rheumatology and Immunology,The Affiliated Drum Tower Hospital of Nanjing University Medical School,were retrospectively reviewed.Patients were followed up for an average of 2 years to track their outcomes.The efficacy of treatment and the survival rate of patients with severe CTD-PAH were determined.Results:Among the causes of severe CTD-PAH,systemic lupus erythematosus(SLE)was the most common(39.6%),and the age at onset in patients with SLE-PAH was younger than that of patients with other CTD.Bosentan was more effective than sildenafil in reducing pulmonary artery pressure,improving cardiac function,and increasing survival time.Combination therapy with targeted vasodilators significantly improved the prognosis of patients with severe CTD-PAH compared with monotherapy.Conclusions:Patients with severe CTD-PAH should be treated early with targeted vasodilators.In this study,bosentan was superior to sildenafil.Combined treatment might be an option for severe CTD-PAH.

Metagenomic next-generation sequencing for pneumocystis jirovecii pneumonia in patients with connective tissue disease

Background:Accurate diagnosis of Pneumocystis jirovecii pneumonia(PJP)is challenging,and the delayed diagnosis of PJP is associated with high mortality in patients with connective tissue disease(CTD).Metagenomic next-generation sequencing(mNGS)technology facilitates etiological diagnosis of various infectious diseases,with promising application in diagnosing PJP.This study aimed to investigate the value of mNGS using bronchoalveolar lavage fluid(BALF)for diagnosing PJP infection.Methods:Data from 55 patients with CTD and suspected pulmonary infection was retrospectively collected and analysed.A PJP group and non-PJP group were formed.The clinical manifestations,laboratory test results,treatment methods,and outcomes were summarized.BALF mNGS results were compared with traditional pathogen tests(TPT)and serum 1,3-beta-D-glucan(BDG)testing.Results:The mean age of PJP patients was 54 years,and 59%(10/17)of the patients were female.A significant difference was found between the average daily dose of prednisone administered to the PJP group and non-PJP group(25 mg vs.16 mg,P<0.001).The PJP group had a significantly higher incidence of dyspnoea(88%[15/17]vs.16%[6/38],P<0.001)and elevated serum BDG level(167.73 vs.30.67 pg/mL,P<0.001).BALF mNGS was more sensitive than both TPT(100%[95%confidence interval{CI}:77.1%-100%]vs.11.8%[95%CI:2.1%-37.7%],P<0.001)and serum BDG(100%[95%CI:77.1%-100%]vs.85.7%[95%CI:42%-99.2%],P<0.001).BALF mNGS was more specific than serum BDG(89.5%[95%CI:74.3%-96.6%]vs.46.7%[95%CI:22.3%-72.6%],P=0.493).Co-infection with cytomegalovirus(CMV)was more common in the PJP patients than in the non-PJP patients(59%[10/17]vs.11%[4/38],respectively,P<0.001).Conclusion:BALF mNGS technology is highly effective for diagnosing PJP in patients with CTD and identifying co-infections.

Risk of connective—tissue disease in men with testicular or penile prostheses：a preliminary study

AIM: To help clarifying the possibility of connective-tissue diseases in men with penile or testicular prostheses. METHODS: Eight patients underwent inflatable penile prostheses and 15, testicular prostheses consented to the study. Their medical records were reviewed and a follow-up interview and physical and serological examinations were performed. RESULTS: In patients with penile prostheses, there was no abnormal antinuclear antibody (ANA) or IgM elevation. The serum levels of the rheumatoid factor (RF), C4, IgA and IgG were abnormal in one patient, and the levels of erythrocyte sedimentation rate (ESR) and C3, abnormal in two. Four had elevated IgE. In patients with testicular prostheses, there was no abnormal RF, ANA or IgM. The serum levels of ESR and IgA were abnormal in two, and three had abnormal C4, ten abnormal C3, and eleven decreased IgG. All had increased IgE. Men with penile prostheses had higher serum levels of IgG and IgM than those with testicular prostheses (P=0.001, P=0.016, respectively). The rates of abnormal values of IgE and IgG were higher in men with testicular prostheses than in men with penile prostheses (P=0.008, P=0.009, respectively). Physical examination was normal in all patients and nobody had documented symptoms pertinent to connective-tissue diseases. CONCLUSION: Our findings suggest that the risk of connective-tissue diseases is not higher in patients wearing prostheses as the ANA is negative and there is no apparent manifestation suggestive of connective-tissue diseases.

Transient positive antimitochondrial M2 in sera of patients with connective tissue diseases after intravenous immunoglobulin infusions

Background:Although antinuclear antibodies(ANAs),anti‐SSA and anti‐Ro52,are present in immunoglobulin preparations,it is unknown whether intravenous immunoglobulin(IVIG)therapy influences the testing of serum autoantibodies in patients with connective tissue diseases(CTDs).The present study aimed to investigate the dynamic change over time of serum ANA‐related autoantibodies in patients with CTDs receiving IVIG therapy.Methods:Serum ANA‐related autoantibodies were monitored in two patients with CTD before IVIG therapy and at different times after therapy.These autoantibodies were tested in different batches of immunoglobulin preparations from seven pharmaceutical companies.Results:One patient developed a new ANA pattern(cytoplasmic dense fine speckled pattern,AC‐19)just after IVIG therapy.Both patients developed de novo positivity for AMA‐M2 and anti‐SSA,but returned negative 1 month after IVIG therapy.The residual liquid in patients'immunoglobulin preparations showed positive ANAs with a high titer of AC‐19(1:640),a low titer of the nuclear fine speckled pattern(AC‐4,1:80),positive AMA‐M2,and positive anti‐SSA.ANA‐related autoantibodies were tested in 16 batches of immunoglobulin preparations and all had positive ANAs with two patterns:AC‐19(1:640 or 1:320)and AC‐4(1:80).AMA‐M2 and anti‐SSA were positive in 100%of the batches.Conclusion:Our study highlights high‐titer AMA‐M2 autoantibodies in immunoglobulin preparations and suggests their transient transfer into a patient's circulation via IVIG therapy.To avoid incorrect clinical decisions based on postinfusion antibody titers,our data recommend retesting 1–2 months after high‐dose IVIG immunomodulatory treatment.

Case Report: Rhupus (The Association of Systemic Lupus Erythematosus and Rheumatoid Arthritis): About 2 Cases

Introduction: The association of systemic lupus erythematosus and rheumatoid arthritis (rhupus) is a rare clinical condition. Throughout the world, 287 cases of Rhupus have been described. We report two new observations of two patients who presented predominantly distal erosive polyarthritis with positive anti-Sm antibodies in one case and SmRNP in the other case. Observations: Case 1: 37 years old patient, with a recent diagnosis of pulmonary tuberculosis. She has since 8 months an inflammatory, bilaterally and symmetrical polyarthralgia without deformation or ankylosing synovitis, associated with malar erythema without other abnormalities. Immunological tests showed: positive Rheumatoid factor at 158 IU/ml, positive Anti-CCP at 550 IU/ml, and positivity of antinuclear at 1/1280 nuclear fluorescence with a strong presence of anti-Sm >8 IU/ml. The diagnosis of rhupus was concluded, without serious visceral involvement. Case 2: A 28-year-old patient, married with 3 children, with bilateral, symmetrical, deforming and chronic polyarthritis affecting large and small joints, which had been evolving for over 5 years without cutaneous abnormality associated. Paraclinical investigations showed: a biological inflammatory syndrome. Immunology was positive, with rheumatoid factors at 78 IU/ml, anti-CCP at 561 IU/ml, antinuclear antibodies at 1/1280 with positive anti-SmRNP and anti-SSA/Ro52, and a positive direct Coombs test. Joint ultrasound revealed tenosynovitis of the extensors and common flexors of the fingers, erosions and synovitis of multiple PPIs. The diagnosis of rhupus was based on the presence of 10 ACR criteria for RA and 8 ACR/EULAR 2019 criteria for SLE. Conclusion: Rheumatoid arthritis is a rare autoimmune disease combining features of both systemic lupus erythematosus and rheumatoid arthritis in the same patient, often sequentially. Despite a growing number of case reports and series, a consensus on the classification of SLE arthritis is still lacking, and diagnostic criteria for rhupus do not exist. These cases of rhupus must be recognized, as the vital and/or functional prognosis may be different from SLE alone or isolated RA.

Short- and Long-term Outcomes in Patients with Connective Tissue Diseases Undergoing Percutaneous Coronary Intervention

Background： Coronary artery disease （CAD） is a leading cause of morbidity and mortality in patients with connective tissue diseases （CTDs）. Risk factors and clinical characteristics in these patients are not equivalent to those in traditional CAD patients. The objective of this study was to report short- and long-term clinical outcomes in a consecutive series of patients with CTD who underwent percutaneous coronary intervention （PC1） with stent implantation. Methods： The study group comprised 106 consecutive patients with CTD who underwent PCI in Beijing Friendship Hospital between January 2009 and June 2012. Medical records were analyzed retrospectively including clinical basic material, coronary angiogram data, and the incidence of major adverse cardiac events （MACEs） during the short- and long-term （median 3 years） follow-up. Results： Ninety-two of the patients （86.8%） had one or more traditional CAD risk lhctors. Multivessel disease was present in more than 2/3 of patients （73.6%）. Tbe left anterior descending coronary artery was the most commonly affected vessel （65. 1%）. Five bare-metal stents and 202 drug-eluting stents were implanted. After a median follow-up period of 36 months, thirteen patients （12.3%） died from cardiac causes, the rate of stent thrombosis was 9.4%, and the rate of target vessel revascularization （TVR） was 14.2%. Multivariate analysis revealed that hypertension （hazard ratio [HR] = 3.07, 95% confidence interval [CI]： 1.30-7.24, P = 0.041 ）, anterior myocardial infarction （HR - 2.77. 95% CI： 1.06-7.03, P = 0.04）, longer duration of steroid treatment （HR - 3.60, 95% CI： 1.43-9.08, P 0.032）, and C-reactive protein level 〉10 mg/L （HR 3.98, 95% CI： 1.19 12.56, P = 0.036） were independent predictors of MACEs. Conclusions： Patients with CTD and CAD may have severe coronary lesions. PCI in these patients tends to result in an increased rate of stent thrombosis and TVR during long-term follow-up, which may be influenced by traditional and nontraditional risk factors.

The ASD that Wouldn’t Go Away:An Unusual Case of ASD Device Failure in a Patient with Marfan Syndrome

Marfan syndrome patients have connective tissue abnormalities that predispose them to intracardiac defects and postoperative complications.We present a case of late onset ASD device failure secondary to device movement within the atrial septum in a girl with Marfan syndrome.This case study suggests that further studies are necessary to determine the optimal device and approach for ASD repair in this patient cohort.

Outcome of Unclassified Inflammatory Rheumatism: Observation of 7 Cases in Dakar

Introduction: Unclassified inflammatory rheumatism is persistent inflammatory arthralgias with or without synovitis without sufficient classification criteria for an inflammatory rheumatism or a well-defined connective disease. Their outcome is variable and has been little studied in Africa. We report the epidemiological, paraclinical and evolutionary characteristics of seven cases of indeterminate polyarthritis. Material and Method: From January 2012 to May 2021, we selected all the files of patients followed up for unclassified inflammatory rheumatism and in whom a precise diagnosis was retained during the course of the disease. The diagnosis of unclassified inflammatory rheumatism was retained after biological, immunological and radiological explorations without specificities. Our study took place in the Internal Medicine Department of Aristide Le Dantec Hospital (HALD). Results: Seven cases out of 274 consulted were collected. They consisted of seven women with an average age of 39 years at the time of the first consultation (extremes: 19 and 67 years). All seven patients presented with inflammatory polyarthralgia or non-deforming, non-erosive peripheral polyarthritis, without extra-articular manifestations. A biological inflammatory syndrome was present in all seven patients. Autoantibodies (rheumatoid factor, ANA, anti-ENA and ACPA) were negative in all patients. The first-line treatments in all seven cases were hydroxychloroquine (200 - 400 mg/day) and prednisone (5 - 10 mg/day). Methotrexate was added in 3 cases. During follow-up, 2 cases progressed to Polyarthritis Rheumatoid (PR) after 3 and 4 years. Two cases progressed to Sjögren’s syndrome after 4 and 5 years. Two patients progressed to systemic scleroderma after 5 and 8 years. One patient progressed to lupus after 5 years. Conclusion: Regular follow-up is essential in IAN. It allows the early diagnosis of IJR or a well-differentiated connective tissue disease and ensures adequate management, especially early.

Calcinosis cutis in a young man with dermatomyositis

A 25-year-old man with known dermatomyositis was admitted to the University of Leipzig Medical Centre for the first time.The diagnosis was originally made abroad years ago.Current laboratory studies showed elevated C-reactive protein and creatine kinase.Antinuclear antibodies,anti-Mi-2 antibodies,anti-Jo-1 antibodies,and anti-Scl-70 antibodies were negative,and the rheumatoid factor was positive.Nailfold video capillaroscopy(NVC)revealed numerous arborized(or“bushy”)capillaries reflecting dermatomyositis-typical neoangiogenesis.Physical examination showed extensive calcinosis cutis on arms,legs,and trunk.

Advances in classification of aortic dissection

Background Aortic dissection remains one of the most acute and critical diseases in cardiac surgery,with high mortality and disability rates.In the 1960s,DeBakeyfirst proposed the classification of aortic dissection.Subsequently,various classifications of aortic dissection have been proposed.To facilitate clinicians and medical staff involved in the treatment of aortic dissection to make better assessment of the condition of aortic dissection patients and to make reasonable clinical decisions,we reviewed several current mainstream classification schemes.We hope that this paper inspires other researchers to propose a new,more suitable classification scheme for use in the clinical setting.

Clinical and laboratory features,treatment,and outcomes of macrophage activation syndrome in 80 children:a multi-center study in China

Background Macrophage activation syndrome(MAS)is a major cause of morbidity and mortality in pediatric rheumatology.We aimed to further understand the clinical features,treatment,and outcome of MAS in China.Methods A multi-center cohort study was performed in seven hospitals in China from 2012 to 2018.Eighty patients with MAS were enrolled,including 53 cases with systemic juvenile idiopathic arthritis(SJIA-MAS),10 cases of Kawasaki disease(KD-MAS),and 17 cases of connective tissue disease(CTD-MAS).The clinical and laboratory data were collected before(pre-),at onset,and during full-blown stages of MAS.We compared the data among the SJIA-MAS,KD-MAS,and CTD-MAS subjects.Results 51.2%of patients developed MAS when the underlying disease was first diagnosed.In patients with SJIA,22.6%(12/53)were found to have hypotension before the onset of SJIA-MAS.These patients were also found to have significantly increased aspartate aminotransferase(AST)and lactate dehydrogenase(LDH),as well as decreased albumin(P<0.05),but no difference in alanine aminotransferase,ferdtin,and ratio of ferritin/erythrocyte sedimentation rate(ESR)at onset of MAS when compared to pre-MAS stages of the disease.In addition,ferritin and ratio of ferritin/ESR were significantly elevated in patients at full-blown stages of SJIA-MAS compared to pre-MAS stage.Significantly increased ferritin and ratio of ferritin/ESR were also observed in patients with SJIA compared to in KD and CTD.Receiver-operating characteristic analysis showed that 12,217.5μg/L of ferritin and 267.5 of ferritin/ESR ratio had sensitivity(80.0%and 90.5%)and specificity(88.2%and 86.7%),respectively,for predicting full-blown SJIA-MAS.The majority of the patients received corticosteroids(79/80),while biologic agents were used in 12.5%(10/80)of cases.Tocilizumab was the most commonly selected biologic agent.The overall mortality rate was 7.5%.Conclusions About half of MAS occurred when the underlying autoimmune diseases(SJIA,KD,and CTD)were first diagnosed.Hypotension could be an important manifestation before MAS diagnosis.Decreased albumin and increased AST,LDH,ferritin,and ratio of ferritin/ESR could predict the onset or full blown of MAS in patient with SJIA.

Clinical parameters and outcomes of Pneumocystis jiroveci pneumonia in non-HIV/AIDS patients

Pneumocystis jiroveci pneumonia （PCP） is one of the most serious and potentially fatal infectionsencountered in immonosuppressed patients. It remains the most common cause of pulmonary morbidity and mortality in patients infected with human immunodeficiency virus （HIV）.

Analysis of Closed Claims in the Clinical Management of Rheumatoid Arthritis in Japan

Background： Despite an increasing awareness of the risk of medical errors, few data sources are available to highlight the characteristics and patterns of medical errors in the clinical management of rheumatoid arthritis （RA）. The present study aimed to evaluate medical malpractice claims associated with the management of RA and other atltoimmune connective tissue diseases （ACTDs）. Methods： We analyzed 38 ACTD-associated closed claims extracted from a total of 8530 claims processed between July 2004 and June 2014 by the Tokyo headquarters office of Sompo Japan Nipponkoa Incorporated, a leading malpractice insurer in Japan. Results： RA was the most common ACTD assessed in this study, accounting for 20 cases. Although the male-to-female ratio among these cases was 5：15, in accordance with the general demographic distribution of RA, the proportion of patients older than 60 years （77.8%） was relatively high as the general range of RA susceptibility is 30-50 years. The analysis of allegation types among RA cases revealed statistically significant differences from non-RA cases （Fisher＇s exact test） as well as the following key findings： diagnosis-related allegations were absent （P 〈 0.01 ）, whereas medication-related allegations were distinctively common （P=0.02）. Clinical processes related to the assessment process were most vulnerable to breakdown and leading to negligence identified with subsequent medication-related allegations, particularly among RA cases. Conclusions： The characteristics of malpractice claims associated with RA management, including the high frequency of medication-related allegations, breakdowns in the assessment process, and high claim numbers among patients older than 60 years, suggest the importance of caution exercised by physicians when administering immunosuppressants for the clinical treatment of RA.

Research progress on the pathogenesis of aortic dissection

Aortic dissection(AD) is a cardiovascular emergency with a high mortality rate, and the risk of death is estimated to increase by 1%-2% per hour. AD is complicated by variable clinical manifestations, and early detection and treatment can give more time for the treatment of patients.Hypertension is the most common cause of AD. In China, 65%-75% of patients with AD have poor blood pressure control. Patients with AD who are less than40 years of age are more likely to suffer from genetic diseases. Connective tissue disease(CTD) plays a dominant role in genetic diseases. Recently, inflammatory immunity, oxidative stress, obstructive sleep apnea-hypopnea syndrome(OSAHS), and other risk factors are being further studied. The new pathogenic factors should be explored to provide an accurate and effective prevention and treatment basis and new diagnostic methods and targets for drug therapy for AD.