Multimodal imaging diagnosis and analysis of prognostic factors in patients with adult-onset Coats disease

AIM:To describe the multimodal imaging features,treatment,and outcomes of patients diagnosed with adultonset Coats disease.METHODS:This retrospective study included patients first diagnosed with Coats disease at≥18 years of age between September 2017 and September 2021.Some patients received anti-vascular endothelial growth factor(VEGF)therapy(conbercept,0.5 mg)as the initial treatment,which was combined with laser photocoagulation as needed.All the patients underwent best corrected visual acuity(BCVA)and intraocular pressure examinations,fundus color photography,spontaneous fluorescence tests,fundus fluorescein angiography,optical coherence tomography(OCT),OCT angiography,and other examinations.BCVA alterations and multimodal image findings in the affected eyes following treatment were compared and the prognostic factors were analyzed.RESULTS:The study included 15 patients who were aged 24-72(57.33±12.61)y at presentation.Systemic hypertension was the most common associated systemic condition,occurring in 13(86.7%)patients.Baseline BCVA ranged from 2.0 to 5.0(4.0±1.1),which showed improvement following treatment(4.2±1.0).Multimodal imaging revealed retinal telangiectasis in 13 patients(86.7%),patchy hemorrhage in 5 patients(33.3%),and stage 2B disease(Shield’s staging criteria)in 11 patients(73.3%).OCT revealed that the baseline central macular thickness(CMT)ranged from 129 to 964μm(473.0±230.1μm),with 13 patients(86.7%)exhibiting a baseline CMT exceeding 250μm.Furthermore,8 patients(53.3%)presented with an epiretinal membrane at baseline or during follow-up.Hyper-reflective scars were observed on OCT in five patients(33.3%)with poor visual prognosis.Vision deteriorated in one patient who did not receive treatment.Final vision was stable in three patients who received laser treatment,whereas improvement was observed in one of two patients who received anti-VEGF therapy alone.In addition,8 of 9 patients(88.9%)who received laser treatment and conbercept exhibited stable or improved BCVA.CONCLUSION:Multimodal imaging can help diagnose adult-onset Coats disease.Anti-VEGF treatment combined with laser therapy can be an option for improving or maintaining BCVA and resolving macular edema.The final visual outcome depends on macular involvement and the disease stage.

Managing adult-onset Still's disease in pregnancy:A case report

BACKGROUND Adult-onset Still’s disease(AOSD)is a rare systemic inflammatory disorder characterized by fever,arthritis,skin rash,and systemic symptoms.The etiology of AOSD is unknown;however,it is thought to be related to immune dysregulation.Although a rare disease,AOSD can significantly impact reproductive health,particularly during pregnancy.This case study assesses the implications of pregnancy in a patient with AOSD,as well as the potential for heredity of the disease.Neonatal hemophagocytic lympho-histiocytosis(HLH)is a rare and lifethreatening disorder characterized by hyperinflammation and uncontrolled activation of immune cells,leading to multiple organ dysfunction.This case report aimed to introduce neonatal HLH from a mother with AOSD.CASE SUMMARY This case study presents a 29-year-old female with AOSD who became pregnant and gave birth to a premature infant who was diagnosed with neonatal HLH.AOSD can significantly impact pregnancy and childbirth,as it may become more severe during pregnancy,with an increased risk of fetal loss and preterm birth.The management of AOSD during pregnancy involves the use of nonsteroidal anti-inflammatory drugs and glucocorticoids,as well as immunosuppressive agents in severe cases.However,the use of immunosuppressive agents during pregnancy may be associated with potential risks to the fetus.The hereditary implications of AOSD are unclear;however,available evidence suggests that genetic factors may play a role in the disease development.CONCLUSION AOSD can have significant implications for pregnancy and childbirth,including an increased risk of fetal loss and preterm birth.Neonatal HLH,a complication of AOSD in pregnancy,requires prompt diagnosis and management.Women with AOSD who are considering pregnancy should discuss their options with their healthcare provider and develop a management plan that addresses the potential risks to both mother and fetus.

Adult-Onset Still's Disease Misdiagnosed as Acute Fibrinous and Organizing Pneumonia: A Case Report and Literature Review

Adult-onset Stil's disease(AOSD)is a rare condition that lies between autoinflammatory syndrome and autoimmune disease.The main clinical manifestations include fever,chills,rash,joint swelling and pain,peripheral blood leukocytosis,splenomegaly,etc.It is a systemic disease affecting between 1 and 34 people per million.The average age of onset is 35 years old,with a slightly higher prevalence rate in women.Since AOSD lacks early specific symptoms and signs,non-specialist doctors have limited understanding of the disease,and patients are prone to clinical misdiagnosis,mistreatment,and delayed disease progression.This paper reports a patient whose AOSD was misdiagnosed as acute fibrinous and organizing pneumonia.

Hepatitis A virus-associated acute acalculous cholecystitis in an adult-onset Still’s disease patient:A case report and review of the literature

BACKGROUND Acute acalculous cholecystitis(AAC)is inflammation of the gallbladder without evidence of calculi.Although rarely reported,its etiologies include hepatitis virus infection(e.g.,hepatitis A virus,HAV)and adult-onset Still’s disease(AOSD).There are no reports of HAV-associated AAC in an AOSD patient.CASE SUMMARY Here we report a rare case of HAV infection-associated AAC in a 39-year-old woman who had a history of AOSD.The patient presented with an acute abdomen and hypotension.Elevated hepatobiliary enzymes and a thickened and distended gallbladder without gallstones on ultrasonography suggested AAC,but there were no signs of anemia nor thrombocytopenia.Serological screening revealed anti-HAV IgM antibodies.Steroid treatment did not alleviate her symptoms,and she was referred for laparoscopic cholecystectomy.The resected gallbladder was hydropic without perforation,and her clinical signs gradually improved after surgery.CONCLUSION AAC can be caused by HAV in AOSD patients.It is crucial to search for the underlying etiology for AAC,especially uncommon viral causes.

Adult-onset Still's disease evolving with multiple organ failure and death:A case report and review of the literature

BACKGROUND Adult-onset Still’s disease(AOSD)is a rare systemic inflammatory disease,which is characterized by daily fever and arthritis,with an evanescent rash and neutrophilic leukocytosis.To date,there has been no definite laboratory or imaging test available for diagnosing AOSD;the diagnosis is one of exclusion,which can be very challenging.In particular,AOSD patients may experience different complications affecting their clinical picture,management,and prognosis.The treatment of AOSD remains largely empirical and involves therapeutic agents.CASE SUMMARY We report the case of a 36-year-old woman who presented with fever,red rash,arthralgia,and sore throat.Her serum ferritin level and white blood cell count were markedly elevated,and the first diagnosis 22 years prior was"juvenile rheumatoid arthritis of systemic type".The patient was treated with prednisone,sulfasalazine,methotrexate,and leflunomide.After remission of her symptoms,the patient stopped taking the medications,and the disease recurred.Ultimately,the patient was diagnosed with adult-onset Still's disease.Relapse occurred several times due to self-medication withdrawal,and an interleukin-6 antagonist(tocilizumab/Actemra)was administered to control the disease.Recently,she was hospitalized because an incision did not heal,and the patient suddenly developed high fever and diarrhea during hospitalization.The patient's disease progressed violently and quickly developed into macrophage activation syndrome,disseminated intravascular coagulation,shock,and multiple organ failure.The patient had sudden cardiac arrest,and she died despite emergency rescue efforts.CONCLUSION AOSD patients need regular follow-up in the long-term treatment process,and must press formulary standard medication,and do not voluntarily withdraw or reduce the dose.Otherwise it may cause disease back-and-forth or serious lifethreatening complications.Meanwhile,strict management of trauma,infections,tumors,and other diseases may contribute to improved outcomes in patients with complications.

Adult-onset Still's disease: A case report

Rationale: Fever of unknown origin (FUO) is a frequently observed phenomenon in clinical practice. Definite diagnosis of FUO is a great challenge in clinical practice since potential causes for FUO involve more than 200 diseases. Adult-onset Still's disease is a defined clinical entity and a known rare cause of FUO. Patient's concern: A 19-year girl was referred to the clinic with the concern of intermittent fevers and shivering for almost a year despite multiple investigations and consultations. She had undergone intensive serologic, radiologic, laboratory investigations to exclude infectious diseases, connective tissue diseases, and malignancy, and all the investigation showed no conclusive diagnosis. Diagnosis: Adult-onset Stills disease. Intervention: Steroids and supportive treatment. Outcomes:The symptoms were relieved within three days, and the patient became asymptomatic. Lessons: Physicians need to be familiar with the diagnostic criteria of adult-onset Still's disease, or it shall remain a diagnostic dilemma. Besides, all shivers are not infections.

Successful treatment of adult-onset still disease caused by pulmonary infection-associated hemophagocytic lymphohistiocytosis: A case report

BACKGROUND Adult-onset still disease(AOSD) and hemophagocytic syndrome(HPS) are two inflammatory diseases with very similar clinical manifestations. HPS is one of the most serious complications of AOSD and its risk of death is very high. It is difficult to identify HPS early in patients with AOSD, but early identification and proper treatment directly affects the prognosis.CASE SUMMARY A 39-year-old male showed a high spiking fever and myalgia. Laboratory data revealed elevated white blood cell, serum ferritin, and neutrophil percentage.However, his fever failed to relieve after a clear diagnosis of AOSD caused by pulmonary infection and treatment by antibiotics and corticosteroids;further laboratory data showed elevated serum ferritin, C-reactive protein, erythrocyte sedimentation rate and triglyceride, as well as liver abnormalities. Bone marrow smear showed hemophagocytosis. Secondary HPS was definitely diagnosed. The high fever disappeared and the laboratory findings returned to normal values after treatment by high-dose intravenous methylprednisolone and methotrexate.CONCLUSION For AOSD patients with high suspicion of HPS, active examination needs to be considered for early diagnosis, and timely using of adequate amount of corticosteroids is the key to reducing risk of HPS death.

Atypical adult-onset Still’s disease with an initial and sole manifestation of liver injury: A case report and review of literature

BACKGROUND Adult-onset Still's disease(AOSD)typically presents with a high spiking fever,polyarthritis,transient maculopapular rash,neutrophilic leukocytosis,and hepatosplenomegaly.It has a wide spectrum of clinical symptoms ranging from mild to severe,with extensive involvement of almost every organ.Although liver involvement in the form of increased hepatic enzymes and bilirubin is common,no AOSD case with liver involvement as the initial manifestation of AOSD has been reported.CASE SUMMARY A 35-year-old woman presented to the hepatology department with progressively worsening jaundice for one week.Liver chemistry tests revealed a significantly increased liver enzymes and bilirubin level.Given that the clinical examination was unremarkable,liver biopsy was considered because the patient had a history of AOSD 6 years ago.Liver histopathology revealed that most hepatic lobules were still recognizable.Fusional necrosis was observed around most central veins.A few bridging necrotic zones were also found.Infiltration of multiple plasma cells were observed in the necrotic zone,and the reticular scaffold was still expanded.Additionally,no obvious fibrosis was observed in the portal area.Mild mixed inflammatory cell infiltration was noted in the interstitium of the portal area.Further examination was unremarkable except for a remarkably high level of ferritin.Collectively,a presumptive diagnosis of liver injury secondary to AOSD was made.The hepatic involvement responded well to glucocorticoid treatment.CONCLUSION This case highlights that hepatic involvement as an initial and sole manifestation could be a pattern of relapsed AOSD.The diagnosis of AOSD should be considered in the case of nonresolving liver injury after the exclusion of common etiologies for liver diseases.A liver biopsy can be useful for the differential diagnosis of liver injury associated with AOSD.

Systemic Diseases in Dakar (Senegal): Spectrum, Epidemiological Aspect and Diagnostic Time-Limit

Introduction: Systemic diseases have been the subject of few studies in the African literature and have probably been under-estimated. The objective of our study was to specify their spectrum, their epidemiological aspects and diagnostic delay in Internal Medicine Departments of Dakar (Senegal). Material and Method: It was a multicentric retrospective and descriptive study regarding all systemic diseases during 119 months from 1st January 2005 to 30 November 2014 in 5 hospital centers down Dakar. Systemic diseases were retained according to their international consensus criteria. Results: During the studying period, 726 patients were included with 632 women and 94 men (sex ratio of 0.14). The average age was 43.76 years. Inflammatory rheumatoid family history was noted in 10.06% of cases. Rheumatoid arthritis (RA) was the predominant affection, recorded on 564 patients, isolated or associated with other systemic diseases. It was followed in a decreasing order, in the systemic auto-immune diseases sub-groupe, by systemic lupus (56 cases), Sj?gren’s syndrome (32 cases), Systemic Sclerosis (26 cases), Idiopathic inflammatory myopathies (21 cases), Undifferentiated connective tissue diseases (20 cases), Anti Phospholipid’s syndrome (6 cases) and Mixed connective tissue disease (6 cases). A diagnosis of systemic vasculitis was recorded in 19 patients. The other systemic affections were represented by systemic sarcoidosis (8 cases), Adult-onset Still’s disease (03 cases), amyloidosis (02 cases) and 02 cases of systemic syndrome associated to immunodeficiency. The mean diagnostic delay duration before the diagnostic was 3.46 years. Conclusion: Systemic diseases in internal medicine are characterized by their diversity, the clear predominance of RA, and significant diagnostic delay.

Increased human neutrophil lipocalin and its clinical relevance in adult-onset Still’s disease

Background:Human neutrophil lipocalin(HNL)has been used extensively to differentiate acute bacterial infection from febrile diseases as a biomarker to reflect the activation of the neutrophil.The serum HNL levels in the adult-onset Still’s disease(AOSD)patients with and without infection,as well as the healthy controls(HCs),were analyzed statistically in this study to evaluate the value of HNL for the diagnosis of AOSD.Methods:A total of 129 AOSD patients were enrolled,from whom blood samples were drawn and the AOSD diagnosis was confirmed through the review of the medical records,where the systemic score,demographic characteristics,clinical manifestations,and laboratory parameters were also collected for the patients;in addition,a total of 40 HCs were recruited among the blood donors from the healthcare center with the relevant information collected.The HNL test was done for the blood samples with the enzyme-linked immunosorbent assay and the analyses were done for the correlations of HNL with clinical manifestations and diagnostic effectiveness.Results:The serum HNL increased significantly in the patients with only AOSD as compared with that in the HCs(139.76±8.99 ng/mL vs.55.92±6.12 ng/mL;P<0.001).The serum HNL level was correlated with the white blood cell(WBC)count(r=0.335,P<0.001),neutrophil count(r=0.334,P<0.001),erythrocyte sedimentation rate(r=0.241,P=0.022),C-reactive protein(r=0.442,P<0.0001),and systemic score(r=0.343,P<0.0001)in the AOSD patients significantly.Patients with fever,leukocytosis≥15,000/mm^(3),and myalgia in the HNL-positive group were observed relatively more than those in the HNL-negative group(P=0.009,P=0.023,and P=0.007,respectively).HNL was a more sensitive indicator than ferritin and C-reactive protein(CRP)to differentiate the AOSD patients with bacterial infection from AOSD-only patients,and the Youden index was 0.6 for HNL and 0.29 for CRP.Conclusion:Serum HNL can be used as a biomarker for the diagnosis of the AOSD,and HNL is also observed to be associated with the disease activity.

Pathogenesis,disease course,and prognosis of adult-onset Still’s disease:an update and review

Objective:Adult-onset Still's disease(AOSD)is a rare but clinically well-known polygenic systemic autoinflammatory disease.In this review,we aim to present frontiers in the pathogenesis,clinical features,diagnosis,biomarkers,disease course,prognosis,and treatment in AOSD.Data sources:We retrieved information from the PubMed database up to July 2019,using various search terms and relevant words,including AOSD and Still's disease.Study selection:We included data from peer-reviewed journals.Both basic and clinical studies were selected.Results:Pathogenesis of AOSD involves genetic background,infectious triggers,and immunopathogenesis,mainly the activation of macrophages and neutrophils followed by a cytokine storm.Diagnosis and prognosis evaluation of AOSD is still challenging;therefore,there is an urgent need to identify better biomarkers.Biologic agents,including interleukin(IL)-ip,IL-6,and tumor necrosis factor-a antagonists in the treatment of AOSD,have good prospect.Conclusion:This review highlights the advances in pathogenesis,potential biomarkers,disease course,and treatment in AOSD.

Intracranial infection accompanied sweet’s syndrome in a patient with anti-interferon-γautoantibodies:A case report

BACKGROUND Several reports of adult-onset immunodeficiency syndrome have been associated with anti-interferon-gamma(IFN-γ)autoantibodies(AIGAs).However,it is rare to find AIGAs with intracranial infections.CASE SUMMARY In this case study,we report a case of an AIGAs with intracranial infection and hand rashes considered Sweet’s syndrome.The patient presented to our hospital with a persistent cough,a fever that had been going on for 6 mo,and a rash that had been going on for a week.The patient started losing consciousness gradually on the fourth day after admission,with neck stiffness and weakened limb muscles.The upper lobe of the left lung had a high-density mass with no atypia and a few inflammatory cells in the interstitium.Brain magnetic resonance imaging and cerebrospinal fluid suggest intracranial infection.The pathology of the skin damage on the right upper extremity revealed an infectious lesion that was susceptible to Sweet’s disease.It has an anti-IFN-γautoantibody titer of 1:2500.She was given empirical anti-non-tuberculous mycobacterial and antifungal treatments.The patient had no fever,obvious cough,headache,or rash on the hand.She got out of bed and took care of herself following hospitalization and discharge with medicine.CONCLUSION Adults with severe and recurrent infections of several organs should be considered for AIGAs if no other known risk factors exist.AIGAs are susceptible to subsequent intracranial infections and Sweet’s syndrome.

Adult-onset Still’s disease successfully treated with Chinese herbal medicine: A case report with 15-month follow-up

Adult-onset Still’s disease(AOSD) is a rare but clinically well-known, polygenic, and systemic autoinflammatory disease, which is characterized by spiking fever, evanescent skin rash, arthralgia, and sore throat.The application of non-steroidal anti-inflammatory drugs and glucocorticoids, which are first-line therapies of AOSD, is limited due to their side effects such as liver injury or disorder of blood glucose.Therefore, patients who suffer from systemic diseases in China prefer to seek help from Chinese herbal medicine(CHM), which is an important part of complementary and alternative medicine. In this case,we report a 28-year-old male badminton coach presenting with a 15-day history of fever and skin rash,accompanied by sore throat, fatigue, myalgia and chills. Additionally, hepatosplenomegaly, multiple lymphadenopathies, aminotransferase abnormality, and elevated inflammatory factor levels were observed during hospitalization. Infectious diseases, solid tumors, hematological diseases, and common autoimmune diseases were excluded. Not benefitting from antibiotic therapy, the patient was finally diagnosed with AOSD, after a careful examination, then showed rapid remission after a six-week treatment with CHM granules based on Xiaochaihu Decoction and Yinqiao Powder. After stopping the treatment, there was no relapse within a 15-month follow-up period. To the best of our knowledge, this is the first well-documented case of this successful treatment. The present case report suggests that CHM is a reliable choice for complementary and alternative therapy for AOSD, but confirming the utility of CHM for AOSD requires further support from prospective studies.

Torsades de pointes episode in a woman with high-grade fever and inflammatory activation: A case report

BACKGROUND QT interval prolongation can induce torsades de pointes(TdP),a potentially fatal ventricular arrhythmia.Recently,an increasing number of non-cardiac drugs have been found to cause QT prolongation and/or TdP onset.Moreover,recent findings have demonstrated the key roles of systemic inflammatory activation and fever in promoting long-QT syndrome(LQTS)and TdP development.CASE SUMMARY A 30-year-old woman was admitted with a moderate to high-grade episodic fever for two weeks.The patient was administered with multiple antibiotics after hospitalization but still had repeating fever and markedly elevated C-reactive protein.Once after a high fever,the patient suddenly lost consciousness,and electrocardiogram(ECG)showed transient TdP onset after frequent premature ventricular contraction.The patient recovered sinus rhythm and consciousness spontaneously,and post-TdP ECG revealed a prolonged QTc interval of 560 ms.The patient’s clinical manifestations and unresponsiveness to the antibiotics led to the final diagnosis of adult-onset Still’s disease(AOSD).There was no evidence of cardiac involvement.After the AOSD diagnosis,discontinuation of antibiotics and immediate initiation of intravenous dexamethasone administration resulted in the normal temperature and QTc interval.The genetic analysis identified that the patient and her father had heterozygous mutations in KCNH2(c.1370C>T)and AKAP9(c.7725A>C).During the 2-year follow-up period,the patient had no recurrence of any arrhythmia and maintained normal QTc interval.CONCLUSION This case study highlights the risk of systemic inflammatory activation and antibiotic-induced TdP/LQTS onset.Genetic analysis should be considered to identify individuals at high risk of developing TdP.

成人still病研究进展

成人still病（adultonsetstill’sdisease，AOSD）是一种复杂的涉及全身各系统的罕见炎症性疾病。主要临床表现包括发热、关节炎及皮疹。确切的发病机制到目前为止仍不清楚，由于该病的临床症状复杂多变且涉及全身各系统，容易引起漏诊和误诊。过去一直是一个排除性诊断，由于新的诊断标准出现，提高了不明原因发热患者中AOSD的诊断特异性及敏感性。近年来AOSD的临床生物学特征、免疫学研究及细胞因子靶向治疗取得显著成果，为A0sD的研究与探索增添了更大的希望。