Concomitant atypical knee gout and seronegative rheumatoid arthritis:A case report

BACKGROUND Gout and seronegative rheumatoid arthritis(SNRA)are two distinct inflammatory joint diseases whose co-occurrence is relatively infrequently reported.Limited information is available regarding the clinical management and prognosis of these combined diseases.CASE SUMMARY A 57-year-old woman with a 20-year history of joint swelling,tenderness,and morning stiffness who was negative for rheumatoid factor and had a normal uric acid level was diagnosed with SNRA.The initial regimen of methotrexate,leflunomide,and celecoxib alleviated her symptoms,except for those associated with the knee.After symptom recurrence after medication cessation,her regimen was updated to include iguratimod,methotrexate,methylprednisolone,and folic acid,but her knee issues persisted.Minimally invasive needle-knife scope therapy revealed proliferating pannus and needle-shaped crystals in the knee,indicating coexistent SNRA and atypical knee gout.After postarthroscopic surgery to remove the synovium and urate crystals,and following a tailored regimen of methotrexate,leflunomide,celecoxib,benzbromarone,and allopurinol,her knee symptoms were significantly alleviated with no recurrence observed over a period of more than one year,indicating successful management of both conditions.CONCLUSION This study reports the case of a patient concurrently afflicted with atypical gout of the knee and SNRA and underscores the significance of minimally invasive joint techniques as effective diagnostic and therapeutic tools in the field of rheumatology and immunology.

Potential of (18)~F-FDG-PET as a valuable adjunct to clinical and response assessment in rheumatoid arthritis and seronegative spondyloarthropathies

AIM: To evaluate the role of fluorine-18-labeled fluorodeoxyglucose positron emission tomography (18F-FDG PET) in various rheumatic diseases and its potential in the early assessment of treatment response in a limited number of patients. METHODS: This study involved 28 newly diagnosed patients, of these 17 had rheumatoid arthritis (RA) and 11 had seronegative spondyloarthropathy (SSA). In the SSA group, 7 patients had ankylosing spondylitis, 3 had psoriatic arthritis, and one had non-specific SSA. Patients with RA were selected as per the American College of Rheumatology criteria. One hour after FDG injection, a whole body PET scan was performed from the skull vertex to below the knee joints using a GE Advance dedicated PET scanner. Separate scans were acquired for both upper and lower limbs. Post-treatment scans were performed in 9 patients in the RA group (at 6-9 wk from baseline) and in 1 patient with psoriatic arthropathy. The pattern of FDG uptake was analysed visually and quantified as maximum standardized uptake value (SUVmax) in a standard region of interest. Metabolic response on the scan was assessed qualitatively and quantitatively and was correlated with clinical assessment. RESULTS: The qualitative FDG uptake was in agreement with the clinically involved joints, erythrocyte sedimentation rate, C-reactive protein values and the clinical assessment by the rheumatologist. All 17 patients in the RA group showed the highest FDG avidity in painful/swollen/tender joints. The uptake pattern was homogeneous, intense and poly-articular in distribution. Hypermetabolism in the regional nodes (axillary nodes in the case of upper limb joint involvement and inguinal nodes in lower limb joints) was a constant feature in patients with RA. Multiple other extra-articular lesions were also observed including thyroid glands (in associated thyroiditis) and in the subcutaneous nodules. Treatment response was better appreciated using SUVmax values than visual interpretation, when compared with clinical evaluation. Four patients showed a favourable response, while 3 had stable disease and 2 showed disease progression. The resolution of regional nodal uptake (axillary or inguinal nodes based on site of joint involvement) in RA following disease modifying anti-rheumatoid drugs was noteworthy, which could be regarded as an additional parameter for identifying responding patients. In the SSA group, uptake in the affected joint was heterogeneous, low grade and nonsymmetrical. In particular, there was intense tendon and muscular uptake corresponding to symptomatic joints. The patients with psoriatic arthritis showed intense FDG uptake in the joints and soft tissue. CONCLUSION: 18F-FDG PET accurately delineates the ongoing inflammatory activity in various rheumatic diseases (both at articular and extra-articular sites) and relates well to clinical symptoms. Different metabolic patterns on FDG-PET scanning in RA and SSA can have important implications for their diagnosis and management in the future with the support of larger studies. FDG-PET molecular imaging is also a sensitive tool in the early assessment of treatment response, especially when using quantitative information. With these benefits, FDG-PET could play a pivotal clinical role in the management of inflammatory joint disorders in the future.

Serum matrix metalloproteinase 3 in detecting remitting seronegative symmetrical synovitis with pitting edema syndrome: A case report

We report a case of remitting seronegative symmetrical synovitis with pitting edema(RS3 PE) syndrome in a 71-year-old woman. She referred to our hospital with finger stiffness, edema of both hands and feet, pain of bilateral shoulder, wrist, metacarpophalangeal, proximal interphalangeal, and ankle joints. Rheumatoid factor was negative, human leukocyte antigen-B7 antigen was positive. Moreover, matrix metalloproteinase 3(MMP-3) was high. She was diagnosed with RS3 PE syndrome, and treatment with prednisolone(15 mg/d) was started. One week after prednisolone treatment initiation, CRP decreased to negative, and joint pain was almost completely resolved. However, hand stiffness persisted, and MMP-3 level was still high. Thus, prednisolone dose was increased to 20 mg/d, and the stiffness resolved. Twenty days after treatment initiation, MMP-3 was normalized. MMP-3 was more indicative of RS3 PE syndrome symptoms than CRP. Thus, MMP-3 seems to be more sensitive to RS3 PE syndrome symptoms.

Unusual presentation of Brucellosis:Afebrile,culture positive Brucellosis and culture positive,seronegative Brucellosis

Objective:To investigate the unusual presentation of brucellosis.Methods:This prospective study was carried out on 46 patients suspected to brucellosis.The diagnosis was made with isolation of brucella species by Bone Marrow culture.Results:Among 40 culture positive patients,there were two unusual presentations of brucellosis: Afebrile culture positive and culture positive seronegative brucellosis.Conclusion:Some brucellosis patients would not match with criteria for diagnosis of brucellosis.Although it is needed to have positive serology or culture for diagnosis of brucellosis but sometimes,it is the clinical experiences,which help to diagnose and treat these kinds of patients.

Seronegative spondyloarthropathy-associated inflammatory bowel disease

Seronegative spondyloarthropathy(SpA)usually starts in the third decade of life with negative rheumatoid factor,human leukocyte antigen-B27 genetic marker and clinical features of spinal and peripheral arthritis,dactylitis,enthesitis and extra-articular manifestations(EAMs).Cases can be classified as ankylosing spondylitis,psoriatic arthritis,reactive arthritis,enteropathic arthritis,or juvenileonset spondyloarthritis.Joint and gut inflammation is intricately linked in SpA and inflammatory bowel disease(IBD),with shared genetic and immunopathogenic mechanisms.IBD is a common EAM in SpA patients,while extraintestinal manifestations in IBD patients mostly affect the joints.Although individual protocols are available for the management of each disease,the standard therapeutic guidelines of SpA-associated IBD patients remain to be established.Nonsteroidal anti-inflammatory drugs are recommended as initial therapy of peripheral and axial SpA,whereas their use is controversial in IBD due to associated disease flares.Conventional disease-modifying anti-rheumatic drugs are beneficial for peripheral arthritis but ineffective for axial SpA or IBD therapy.Anti-tumor necrosis factor monoclonal antibodies are effective medications with indicated use in SpA and IBD,and a drug of choice for treating SpA-associated IBD.Janus kinase inhibitors,approved for treating SpA and ulcerative colitis,are promising therapeutics in SpA coexistent with ulcerative colitis.A tight collaboration between gastroenterologists and rheumatologists with mutual referral from early accurate diagnosis to appropriately prompt therapy is required in this complex clinical scenario.

Seronegative autoimmune hepatitis in childhood

Comprehensive guidelines on seropositive autoimmune hepatitis have been published for both adults and children,although these guidelines comprise only limited knowledge about seronegative autoimmune hepatitis.Autoimmune hepatitis presents as an acute or chronic progressive disease and poor outcomes are inevitable if left untreated.The absence of autoantibody positivity,hypergammaglobulinemia and lack of comprehensive algorithms makes seronegative autoimmune hepatitis a mysterious disease.In general,seronegative autoimmune hepatitis often presents with acute hepatitis,and its treatment and prognosis similar to seropositive autoimmune hepatitis.The present review focuses on the known characteristics of seronegative autoimmune hepatitis in childhood,and those of which current knowledge is vague.

Severe heterotopic ossification in a seronegative spondyloarthritis patient after cervical Bryan disc arthroplasty: A case report

BACKGROUND Cervical disc arthroplasty(CDA)is an alternative treatment to traditional interbody fusion that maintains postoperative cervical spine mobility.However,the CDA postoperative period is impacted by osteolysis,subsidence,metallosis,or heterotopic ossification(HO).We report a case of severe HO in a seronegative spondyloarthritis patient after cervical Bryan disc arthroplasty.CASE SUMMARY A 34-year-old man received hybrid surgery for C4-C5 and C5-C6 arthroplasty with Bryan discs and C6-C7 arthrodesis with polyetheretherketone cage due to traumatic herniation of the intervertebral disc(HIVD).After four years,cervical spine radiographs revealed severe HO around the Bryan discs over the C4-C5 and C5-C6 levels.The magnetic resonance image revealed HIVD over the C3-C4 level with spinal cord compression.Seronegative spondyloarthritis was diagnosed after consultation with a rheumatologist.A second CDA for the adjacent segment disease HIVD with Baguera C disc over the C3-C4 level achieved an excellent outcome.CONCLUSION Minimizing intraoperative tissue trauma and achieving postoperative interbody stability avoid soft tissue traction to prevent HO formation after CDA.

Reversal of IgM deficiency following a gluten-free diet in seronegative celiac disease

Selective Ig M deficiency(s IGMD)is very rare;it may be associated with celiac disease(CD).We present the case of an 18-year-old man with s IGMD masking seronegative CD.Symptoms included abdominal pain,diarrhea and weight loss.Laboratory tests showed reduced Ig M,DQ2-HLA and negative anti-transglutaminase.Villous atrophy and diffuse immature lymphocytes were observed at histology.Tissue transglutaminase m RNA mucosal levels showed a 6-fold increase.The patient was treated with a gluten-free diet(GFD)and six months later the symptoms had disappeared,the villous architecture was restored and mucosal tissue transglutaminase m RNA was comparable to that of healthy subjects.After 1 year of GFD,a complete restoration of normal Ig M values was observed and duodenal biopsy showed a reduction of immature lymphocytes and normal appearance of mature immune cells.

Increased Activity of NK Cells and Plasmacytoid Dendritic Cells in HIV-Exposed Seronegative (ESN) Individuals

The mechanisms involved in resistance to HIV-1 infection, especially the role of innate immune response, have not been thoroughly explored in individuals who are repeatedly exposed to HIV-1, but do not get the infection, termed as Exposed sero-negative or ESN. Frequency and activation state of natural killer (NK) cells and plasmacytoid dendritic cells (pDC) in ESNs from North India were compared with those in recently infected HIV positives (RHIV), chronically infected HIV positives (HIV+) and healthy controls (HC). The activation state of NK cells in terms of cytokine response (IFNγ & TNFα) was significantly higher in ESNs compared to the healthy controls, recently infected HIV+ and chronically infected HIV+. Although the number of circulating pDC in different study groups was not significantly different, yet these cells seem to have significantly higher activation state in terms of IFNα production (ex-vivo in response to CpG ODN) in ESNs when compared with other groups. Increased activation status of NK cells and pDC in Exposed but Seronegative individuals indicates their continuous stimulation with HIV antigens due to regular exposure with infected partners and which might be imparting resistance to viral infection in these individuals.

Seronegative Myasthenia Gravis and a Biermer’s Anemia:A Rare Association

We report a rare association of seronegative myasthenia gravis and a Biermer’s anemia (or pernicious anemia). A Senegalese patient of 31 years has been followed for a vitamin B12 deficiency anemia, 12 months before his hospitalization in our department. She has been admitted for an intense and invalidating fatigability in spite of the correction of anemia, associated to a right ptosis. This clinical picture has electively been improved to the prostigmine test. The electromyography had revealed a compatible decrement with a diagnosis of myasthenia. The positivity of the antibodies anti gastric parietal cells and the twice negativity of the antibody against acetylcholine receptor (AChR) and muscle-specific kinase (MuSK) had permitted to deduct a diagnosis of seronegative myasthenia and Biermer’s anemia. The evolution was favorable under substitutive B12 vitamin therapy associated to corticotherapy and azathioprine. We insist on the research and the early treatment of a myasthenia, in a context of Biermer’s anemia, before suggestive clinical signs in spite of the negativity of the anti-Rach antibodies and anti-Musk.

Identification of HIV-1 specific T lymphocyte responses in highly exposed persistently seronegative Chinese

Background Studies of highly exposed persistently seronegative （HEPS） individuals may provide valuable information on mechanisms of protection and on vaccine design. Cellular immune responses play a critical role in containing human immunodeficiency virus. However, the cellular immune responses in HEPS individuals have not been thoroughly assessed at the entire viral genome level. Methods Ten HEPS Chinese with a history of frequent penetrative vaginal intercourse （mean frequency, at least once a week）, with some unprotected sexual contact occurring in the weeks or days immediately before enrollment, 25 HIV-1 seropositive individuals, 10 HIV-1-seronegative healthy individuals with low-risk sexual behavior and no history suggestive of exposure to HIV-1 infection were enrolled. HIV-1-specific T cell responses were comprehensively analyzed by an interferon- 7 Elispot assay against 770 overlapping peptides spanning all HIV-1 proteins. Results HIV-1-specific T-cell responses of interferon- 7 secretion were identified in 3 （30%） out of 10 HEPS individuals; the specific cytotoxic T lymphocytes were targeted at Pol （2/10）, Env （2/10）, and Tat （1/10）. HIV-1-specific T-cell responses of interferon- ~ secretion were identified in 20 （80%） out of 25 seropositive intravenous drug users （IDUs）, revealing that all HIV-1 proteins and protein subunits could serve as targets for HIV-1-specific CD8^＋ T cell responses with 85% recognizing Gag, 80% recognizing Nef, 75% recognizing Pol, 60% recognizing Env, 55% recognizing Vpu, 45% recognizing Vpr, 20% recognizing Vif, 20% recognizing Tat and 15% recognizing Rev in these seropositive individuals. None of the seronegative healthy individuals gave the positive T-cell responses. Conclusions About 30% of HEPS Chinese mounted HIV-1 specific T cell immune responses. Cell-mediated immunity against HIV-1 may be developed through non-productive infections.

Seronegative Autoimmune Hepatitis

Autoimmune hepatitis(AIH)is a relatively rare liver disease with varying worldwide incidence of from 0.7 to 2 per 100,000 people.It is characterized by the presence of auto-antibodies.However,an average of 10% of AIH cases have AIH symptoms and pathology but lack autoimmune serology.For such seronegative AIH(snAIH)cases,there is currently no established diagnostic algorithm for diagnosis.and improper or delayed diagnosis of snAIH can lead to no or inappropriate treatment that results in progression to fulminant hepatitis or cirrhosis.This review aims to review the current literature and to present an update of seronegative autoimmune hepatitis,including its pathophysiology,clinical presentation,methods of diagnosis,and treatment in order to increase awareness and emphasize the necessity for timely management.

A REPORT ON 8 SERONEGATIVE CONVERTED HIV/AIDS PATIENTS WITH TRADITIONAL CHINESE MEDICINE

Since February 1990, during the treatment of HIV/AIDS patients in Tanzania, seronegative conversion （SNC） occurredin 8 HIV/AIDS patients after medication with traditional Chinese medicine. Among them, 7 cases have been checked with PCR amplifying assay and 5 patients with p24 antigen. The 8 cases were reported in this article.

Posterior reversible encephalopathy syndrome due to seronegative systemic lupus erythematosus

Posterior reversible encephalopathy syndrome(PRES)is a neurotoxic state coupled with a unique computed tomography or magnetic resonance imaging(MRI)appearance.Recognized in the setting of a number of complex conditions(preeclampsia/eclampsia,allogeneic bone marrow transplantation,organ transplantation,autoimmune disease and high-dose chemotherapy)in the imaging,clinical and laboratory features of this toxic state are becoming better elucidated.We are presenting a case of PRES due to seronegative systemic lupus erythematosus,with MRI findings of diffuse vasogenic edema.

Prevalence of occult hepatitis B virus infection

Occult hepatitis B virus(HBV) infection(OBI) is characterized by the persistence of HBV DNA in the liver tissue in individuals negative for the HBV surface antigen.The prevalence of OBI is quite variable depending on the level of endemic disease in different parts of the world,the different assays utilized in the studies,and the different populations studied.Many studies have been carried out on OBI prevalence in different areas of the world and categories of individuals.The studies show that OBI prevalence seems to be higher among subjects at high risk for HBV infection and with liver disease than among individuals at low risk of infection and without liver disease.

Evolution of nonspecific duodenal lymphocytosis over 2 years of follow-up

AIM: To assess the evolution of duodenal lymphocytosis(DL), a condition characterized by increased intraepithelial lymphocytes(IELs), over 2 years of follow-up.METHODS: Consecutive patients undergoing upper endoscopy/histology for abdominal pain, diarrhea, weight loss, weakness or other extraintestinal features compatible with celiac disease(CD) were included. Evaluation of IELs infiltrate in duodenal biopsy sampleswas carried out by CD3-immunohistochemistry and expressed as number of positive cells/100 enterocytes. Diagnostic agreement on the IELs count was tested by calculating the weighted k coefficient. All patients underwent serological detection of autoantibodies associated with CD: Ig G and Ig A anti-tissue transglutaminase and endomysium. Each patient underwent further investigations to clarify the origin of DL at baseline and/or in the course of 2 years of follow-up every six months. Autoimmune thyroiditis, intestinal infections, parasitic diseases, bacterial intestinal overgrowth, hypolactasia and wheat allergy were detected. Colonoscopy and enteric magnetic resonance i m a g i n g w e r e p e r f o r m e d w h e n n e c e s s a r y. R i s k factors affecting the final diagnosis were detected by multinomial logistic regression and expressed as OR.RESULTS: Eighty-five patients(16 males, 69 females, aged 34.1 ± 12.5 years) were followed up for a mean period of 21.7 ± 11.7 mo. At baseline, endoscopy/duodenal biopsy, CD3 immunohistochemistry revealed: > 25 IELs/100 enterocytes in 22 subjects, 15-25 IELs in 37 and < 15 IELs in 26. They all had negative serum anti-transglutaminase and anti-endomysium, whilst 5 showed Ig G anti-gliadin positivity. In the course of follow-up, 23 developed CD seropositivity and gluten sensitivity(GS) was identified in 19. Other diagnoses were: 5 Helicobacter pylori infections, 4 jejunal Crohn's disease, 1 lymphocytic colitis and 1 systemic sclerosis. The disease in the remaining 32 patients was classified as irritable bowel syndrome because of the lack of diagnostic evidence. At multivariate analysis, the evolution towards CD was associated with an IELs infiltrate > 25(OR = 1640.4) or 15-25(OR = 16.95), human leukocyte antigen(HLA) DQ2/8(OR = 140.85) or DQA1*0501(OR = 15.36), diarrhea(OR = 5.56) and weakness(OR = 11.57). GS was associated with IELs 15-25(OR = 28.59), autoimmune thyroiditis(OR = 87.63), folate deficiency(OR = 48.53) and diarrhea(OR = 54.87).CONCLUSION: DL may have a multifactorial origin but the IELs infiltrate and HLA are strong predictive factors for CD development and a clinical diagnosis of GS.

A Needs-Based Rheumatologist Education Program on Treating to Target in Psoriatic Arthritis and Spondyloarthropathy: Insights and Challenges

Objectives: To determine if comparative practice data and education for rheumatologists would change physician behavior for monitoring and treating psoriatic arthritis (PsA) and spondyloarthritis (SpA). Methods: Participating rheumatologists each performed a chart audit on 20 patients with PsA and SpA. Accredited education (determined by a survey and chart audits) and results of chart audits (comparing to other rheumatologists) were provided for each participant (intervention). Eight months later, a repeat chart audit by each participant was conducted on another 20 PsA and SpA patients. Changes in measurements collected, treatment given and patient characteristics pre and post intervention were analyzed. Results: Nine rheumatologists received the intervention. At baseline, most routinely monitored PsA and SpA for clinical and laboratory markers. In PsA, there was no change post-intervention in performing SJC (96%), TJC (≥91%), ESR (≥70%), CRP (≥73%), and CDAI (25%). In SpA, there were increased measurements of inflammatory markers (54% pre vs. 61% post for CRP), more NSAID use and decreased physical exam measures and HAQ but no significant changes. There were no major treatment differences pre and post intervention including NSAIDs, DMARDs and biologics. Conclusions: The rheumatologists frequently performed measurements of disease activity, did not change significantly with educational intervention so there may have been little room for improvement and many patients were already in a low disease state. Calculation of composite scores did not increase in PsA. The validity of physical exam and BASDAI as a measurement of disease activity were noted as concerns in applying a treat-to-target approach in SpA. Significance and Innovation: This study did not show a significant change in behavior for rheumatologists who had education based on care gaps and needs assessment in psoriatic arthritis and spondyloarthropathy. The rheumatologists identified that disease activity is difficult to determine with usual care in SpA and thought some measures lacked validity.

Effects of Glyke in Treating 60 HIV-Infected Patients

Using Giyke, a Chinese Materia Medica, in treating 60 human immunodeticiency virus in-fected patients. the total effective rate was 35%. the rates of immunological improvement and stabilitywere 68. 3% - 90% , while those of symptoms amelioration were 35% - 64% respectively. Polymerasechain reaction was used to check one of two patients and revealed positive. Experimental study showedGlyke could inhibit simian immunodeficiency virus as well as enhance the patient's immune function.