Severe Complications Due to Biopolymers in a Patient With Autoimmune Disease: A Case Report and Review of the Literature

We would like to thank Wang et al. [1] for their comments on our case report [2]. They highlight the fact that patients presenting with parkinsonism may fell into either idiopathic Parkinson’s disease (PD) or syndromes of secondary parkinsonism such as drug-induced parkinsonism, vascular parkinsonism, parkinsonism concomitant with autoimmune diseases, etc. [1]. In their comment, Wang et al. [1] dispute the diagnosis of idiopathic PD in our patient, since we haven’t provided some clinical, imaging, and laboratory data. Therefore, we would like to clarify that the diagnosis of idiopathic PD in our case was made 5 years prior to diagnosis of myasthenia gravis and rheumatoid arthritis. Apart from the initial clinical presentation of unilateral tremor, rigidity, and slowness of movement, the patient had had a brain MRI that was normal, and a DAT scan which was abnormal. Moreover, the patient’s symptoms had a very good response on levodopa. Five years after the diagnosis of PD, the patient was admitted because of progressive weakness in the flexion of his neck. During his admission, which lead to the diagnosis of myasthenia gravis and rheumatoid arthritis and details of which have been published in our case report [2], he had been screened for autoimmune disorders. The following antibodies were all negative; anti-nuclear antibodies (ANA), anti-doublestranded DNA (anti-dsDNA), perinuclear anti-neutrophil cytoplasmic antibodies (P-ANCA), cytoplasmic anti-neutrophil cytoplasmic antibodies (C-ANCA), anti-cardiolipin (ACLG and ACLM), anti-thyroid peroxidase (anti-TPO), anti-thyroglobulin (anti-TG). Moreover, his thyroid hormones titers (T3, T4, and TSH) were within normal limits. Finally, we must mention that the following paraneoplastic antibodies were also negative; Hu (ANNA-1), Ri (ANNA2), Yo (PCA-1), PNMA2 (Ma2/Ta), CV2 (CRMP-5), amphiphysin, recoverin, SOX1 (AGNA), zic4, and Tr (DNER). In conclusion, we agree with Wang et al. that it is always important to be careful before diagnosing idiopathic PD, especially when causes of secondary parkinsonism have not been excluded. As mentioned above, with this letter, we would like to clarify that our patient had a diagnosis of idiopathic PD, which was diagnosed 5 years before the diagnosis of rheumatoid arthritis and myasthenia gravis.

In this study, we assessed 75 patients with myasthenia gravis (MG) for coexistent autoimmune diseases (ADs) and for the characteristic autoantibodies that are associated with the most relevant forms of ADs. The demographic and clinical characteristics of the patients were recorded. In all patients, thyroid function tests, thyroid autoantibodies, and other autoantibodies were studied. The diagnosis of autoimmune thyroid disease (AITD) was made based on the clinical features, physical examination, and laboratory findings. The diagnoses of rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) were made in accordance with the revised criteria of American College of Rheumatology. The presence of other ADs were also recorded which was based on whether or not the patient already had a diagnosis of ADs; or, whether it was detected during the period of the study based on clinical findings and/or laboratory abnormalities. Thirty-nine patients (52%) had autoantibody positivity in their sera. Thyroid autoantibodies and antinuclear antibodies were the main autoantibodies detected. In twenty one of these patients, a diagnosis of AD could not be confirmed. Eighteen patients (24%) had a confirmed diagnosis of a coexisting AD. These ADs included AITD (16%), RA (4%), SLE (2.6%), and Lambert-Eaton myasthenic syndrome (1.3%). In ten patients, the diagnosis of ADs had been established before the development of MG; 8 of the patients included those who were newly diagnosed with ADs in the course of the management of MG. MG has an increased frequency of coexisting ADs. Autoantibodies that are characteristic for ADs can be found in the patients without the presence of any of the clinical findings of ADs. Clinical attention towards the management of ADs is especially needed during the follow-up of patients with MG.

Induction chemotherapy with cemiplimab in a patient with coexistent vulvar cancer and autoimmune disease: A case report

#### Clinical Question Should GPs use anti-citrullinated peptide antibody testing instead of rheumatoid factor for diagnosing rheumatoid arthritis? Early diagnosis and treatment of rheumatoid arthritis (RA) is important in preventing long-term damage and disability. RA should be suspected largely on the basis of clinical findings, such as persistent joint pain, swelling, and stiffness. Further investigations, particularly in primary care, may contribute to the diagnosis. Rheumatoid factor (RF) is an autoantibody associated with RA and its presence has traditionally been used to support the diagnosis. However, RF has a low specificity in primary care and cannot be used to rule in or rule out disease. In contrast, anti-citrullinated peptide antibody (ACPA) has emerged as an alternative serological test, as it has greater specificity and may be preferable to RF in the diagnosis of RA.1 However, it is not yet generally available in primary care. RFs are autoantibodies directed against the Fc region of immunoglobulin IgG. RA is associated with the presence of RF in many, but not all cases. Raised levels are also found in other autoimmune diseases, for example, Sjogren’s syndrome and type 2 cryoglobulinaemia, in infection, and in healthy individuals. ACPAs, also called anti-cyclic citrullinated peptide (anti-CCP) antibodies, are reactive to the amino acid citrulline and are also present in the sera of patients with RA.2 The ACPA test is a laboratory-based enzyme-linked immunosorbent assay (ELISA). Point-of-care testing devices for both RF and ACPA are currently being developed. RA is a destructive inflammatory joint disease with an estimated UK prevalence of 1.2% in females and 0.4% …

Background The treatment of early rheumatoid arthritis (RA) should not be delayed. However, aggressive therapy is often introduced only when rheumatogists feel confident enough in their diagnosis of RA. Objectives We sought the confidence of both office-based-rheumatologists (OBR) and a college of 5 experts in their diagnosis of early-RA. Methods 270 patients with early-onset ( Results 35/270 patients (13%) were still unclassified by their OBR. RA was diagnosed in 114 (42%), spondylarthropathy in 56 (21%), and miscellaneous other disorders in 65 (24%). The OBR confidence in their final diagnosis of RA was 7,5 ± 2,3 (68/114 patients with a confidence of 8/10 or more). A collegial diagnosis of certain RA (N = 57) or probable RA (N = 41) was made for 98 patients. The strength of OBR confidence in the diagnosis of RA was strongly correlated to that of the college (r = 0,892). Conversely, the fulfilment of 4 ACR criteria for RA since the first visit was associated with an only slight increase in final OBR confidence (7,9 ± 2,1). Conclusion Although only 13/114 (11%) patients finally classified as RA changed from diagnosis during follow-up, the final confidence of OBR in their diagnosis of RA were below 8/10 in 40%, and was only slightly improved by the fulfilment of ACR criteria. This emphasises the need for a close follow-up of these patients during the first years and the use of RA criteria for the classification of early arthritis.

PurposesTo assess whether the positive predictive value (PPV) of first-time rheumatoid arthritis (RA) diagnosis registration in the Danish National Patient Registry increases when data are linked to the RA treatment codes and to assess the PPV of first-time RA diagnoses according to RA serological subtypes.MethodsParticipants from the Danish Diet, Cancer, and Health cohort with at least one RA diagnosis, registered at one of the Central Denmark Region hospitals in the Danish National Patient Registry during the period 1977–2016, were identified. Register-based RA diagnoses were verified by scrutinizing medical records against RA classification criteria or clinical case RA. PPVs for overall RA, seropositive RA, and other RA were calculated for two models: first-time RA diagnosis registration ever in the Danish National Patient Registry and first-time RA diagnosis registration ever where subsequently a prescription had been redeemed for a synthetic disease-modifying antirheumatic drug.ResultsOverall, 205 of 311 first-time register-based RA diagnoses were verified (PPV: 61.9%; 95% CI: 56.9–67.0). Regarding RA serological subtypes, 93 of 150 register-based seropositive RA (PPV: 62.0; 95% CI: 53.9–69.5) and 36 of 144 other RA (PPV: 25.0; 95% CI: 18.5–32.8) were confirmed. When register-based RA diagnosis codes were linked to RA treatment codes, the PPVs increased substantially: the PPV for overall RA was 87.7% (95% CI: 82.5–91.5), the PPV for seropositive RA was 80.2% (95% CI: 71.6–86.7), and the PPV for other RA was 41.1% (95% CI: 30.2–52.9).ConclusionThe first-time RA diagnoses in the Danish National Patient Registry should be used with caution in epidemiology research. However, linking registry-based RA diagnoses to the subsequent RA treatment codes increases the probability of identifying true RA diagnoses, especially overall RA and seropositive RA.

Backgroundearly diagnosis of rheumatoid arthritis (RA) is difficult as no single clinical manifestation, laboratory test, or imaging study results allow a diagnosis of RA to be made with certainty.Objectivesto detect...

Multiple reports on the co-existence of autoimmune diseases and myasthenia gravis (MG) have raised considerable concern. Therefore, we reviewed autoimmune diseases in MG to explore their clinical presentations and determine whether the presence of autoimmune diseases affects the disease severity and treatment strategies for MG. We reviewed all the major immune-mediated coexisting autoimmune conditions associated with MG. PubMed, Embase and Web of Science were searched for relevant studies from their inception to January 2023. There is a higher frequency of concomitant autoimmune diseases in patients with MG than in the general population with a marked risk in women. Most autoimmune comorbidities are linked to AChR-MG; however, there are few reports of MuSK-MG. Thyroid disorders, systemic lupus erythematosus, and vitiligo are the most common system autoimmune diseases associated with MG. In addition, MG can coexist with neurological autoimmune diseases, such as neuromyelitis optica (NMO), inflammatory myopathy (IM), multiple sclerosis (MS), and autoimmune encephalitis (AE), with NMO being the most common. Autoimmune diseases appear to develop more often in early-onset MG (EOMG). MS coexists more commonly with EOMG, while IM coexists with LOMG. In addition, MG complicated by autoimmune diseases tends to have mild clinical manifestations, and the coexistence of autoimmune diseases does not influence the clinical course of MG. The clinical course of neurological autoimmune diseases is typically severe. Autoimmune diseases occur most often after MG or as a combined abnormality; therefore, timely thymectomy followed by immunotherapy could be effective. In addition, thymoma-associated AChR MG is associated with an increased risk of AE and IM, whereas NMO and MS are associated with thymic hyperplasia. The co-occurrence of MG and autoimmune diseases could be attributed to similar immunological mechanisms with different targets and common genetic factor predisposition. This review provides evidence of the association between MG and several comorbid autoimmune diseases.

Rheumatoid arthritis (RA), an autoimmune disease of unknown etiology, is a serious threat to the health of middle-aged and elderly people. Although western medicine, traditional medicine such as traditional Chinese medicine, Tibetan medicine and other ethnic medicine have shown certain advantages in the diagnosis and treatment of RA, there are still some practical shortcomings, such as delayed diagnosis, improper treatment scheme and unclear drug mechanism. At present, the applications of artificial intelligence (AI)-based deep learning and cloud computing has aroused wide attention in the medical and health field, especially in screening potential active ingredients, targets and action pathways of single drugs or prescriptions in traditional medicine and optimizing disease diagnosis and treatment models. Integrated information and analysis of RA patients based on AI and medical big data will unquestionably benefit more RA patients worldwide. In this review, we mainly elaborated the application status and prospect of AI-assisted deep learning and cloud computation-oriented western medicine and traditional medicine on the diagnosis and treatment of RA in different stages. It can be predicted that with the help of AI, more pharmacological mechanisms of effective ethnic drugs against RA will be elucidated and more accurate solutions will be provided for the treatment and diagnosis of RA in the future.

Die Untersuchung synovialer Veränderungen kann zur Diagnose von Gelenkerkrankungen und von systemischen Erkrankungen beitragen. Die Domäne der histopathologischen Diagnostik stellt die Abgrenzung tumoröser von entzündlichen Läsionen dar. Daneben können Kristallarthropathien und bestimmte Stoffwechselerkrankungen sicher diagnostiziert werden. Unter dem histologischen Bild einer granulomatösen Synovialitis können neben einer mykobakteriellen Infektion Sarkoidosen und Fremdkörperreaktionen sowie selten genetische Erkrankungen beobachtet werden. Amyloidosen können auch in der Tunica synovialis subtypisiert werden. Molekulare Methoden erlauben die schnelle und sichere Diagnostik septischer Arthritiden und eine Keimtypisierung. Mittels dieser Methoden können auch reaktive Arthritiden klassifiziert werden, da auch hier häufig DNA oder RNA bestimmter Keime in Gewebe oder Gelenkflüssigkeit nachgewiesen werden kann. Die Diagnose der rheumatoiden Arthritis basiert auf den American College of Rheumatology(ACR)-Kriterien. Molekulare Methoden, wie die Mikro-RNA-Technologie oder proteomische Methoden können die Diagnose unterstützen.

Background and objective: Rheumatoid arthritis is an autoimmune disease. This study investigated the potential value of combining cartilage oligometric matrix protein, anti-cyclic citrullinated protein, and 14-3-3 eta protein with traditional biomarkers to reduce the diagnostic gap. Methods: This case-control study included 46 male and female patients and 42 age- and gender-matched adults as control group. The biomarkers were measured using ELISA technique. Results: Tests for anti-cyclic citrullinated protein and cartilage oligometric matrix protein are excellent tools to diagnose rheumatoid arthritis because anti-cyclic citrullinated protein and cartilage oligometric matrix protein are associated with the highest ROC area. The validity of the test for 14-3-3 eta protein, which is a good test to predict rheumatoid arthritis, ranks second. The optimum cut-off values for high cartilage oligometric matrix protein, high anti-cyclic citrullinated protein, and high 14-3-3 eta protein were ≥0.242µg/L, ≥0.566ng/L, and ≥0.145ng/L, respectively. 14-3-3η protein, cartilage oligometric matrix protein status as a parallel combination which is considered as a wonderful combination in classification criteria for rheumatoid arthritis. Parallel combination, both criteria two tests are positive, namely “high cartilage oligometric matrix protein (≥0.242) + high 14-3-3η protein (≥0.145)” was associated with a perfect test, that the patients have rheumatoid arthritis (sensitivity 100%, specificity 100%, accuracy 100%, positive predictive value at pre-test probability 50% and 90% = 100%). A positive test using this combination is 100% diagnostic and establishes a possible diagnosis of rheumatoid arthritis with 100%, while a negative test would exclude a possible diagnosis of rheumatoid arthritis with 100% confidence. Conclusion: Results confirmed that high serum level of cartilage oligometric matrix protein, anti-cyclic citrullinated protein, and 14-3-3 eta protein are significantly associated with increased risk for rheumatoid arthritis, demonstrating the potential value of combining these new biomarkers with traditional biomarkers to enhance diagnostic sensitivity and specificity and ultimately reduce the diagnostic gap.

Statins have antiinflammatory/immunomodulatory effects that may be useful in preventing rheumatoid arthritis (RA), but previous observational studies about the risk of RA with statin use yielded conflicting results. The aim of this study was to determine whether high-intensity statin treatment is associated with reduced risk of RA. Using data from the UK Clinical Practice Research Datalink, we performed a nested case-control analysis in a population-based cohort of patients who began receiving statins between 1997 and 2009 and were followed up until a first diagnosis of RA, death, end of registration with the physician's practice, or end of January 2011. For each case of RA, 10 age-, sex-, and calendar year-matched controls were randomly selected from risk sets. We estimated the hazard ratio (HR) of incident RA in the highest quintile of duration-weighted average statin intensity compared to the lowest, using conditional logistic regression. Models were adjusted for smoking status, total cholesterol level, obesity, history of cardiovascular disease, coexistent autoimmune disease, hypothyroidism, and persistence with treatment. The cohort included 528,654 new users of statins, with 1,357 new cases of RA occurring during a mean follow-up of 3.3 years, for an incidence rate of 7.9 per 10,000 person-years. Cases were more likely to be smokers, to have other autoimmune diseases, and to have had lower total cholesterol levels at baseline. The incidence of RA was lower in the highest statin intensity quintile (adjusted HR 0.77 [95% confidence interval 0.63-0.95]) in comparison to the lowest quintile. In this large population-based study, high-intensity statin treatment was associated with a reduced risk of RA in comparison to low-intensity statin treatment.

Background:Finnish healthcare registers are used in medical research, but there is little data about the validity of these registers in rheumatology.Objectives:The aim of our study was to determine the validity of rheumatoid arthritis (RA) diagnoses in patients participating in the Finnish Biobanks.Methods:We reviewed the electronic patient charts of 125 patients with at least one visit with a diagnosis of seropositive RA, 125 patients with at least one visit with a diagnosis of seronegative RA and 250 age-and-sex matched controls. Patients were randomly selected from Finnish biobank participants. We evaluated whether the patients’ diagnosis of RA recorded in the hospital discharge registry at the participating hospital was correct according to chart review and expert opinion. In the control group it was investigated whether the diagnosis of RA was written in the patients’ chart, but the diagnosis code was not recorded.Results:The positive predictive value (PPV) of a single hospital registry diagnosis of seropositive RA was 0.74 but rose to 0.98 in patients with a special reimbursement for seropositive RA and 0.98 in anti-citrullinated protein antibody positive patients. For seronegative RA, the PPV of a diagnosis was 0.72 and in patients with a special reimbursement for seronegative RA 0.89. The PPV was higher in patients with more than one visit with the diagnosis: 0.92 if the patients had at least 5 visits with seropositive RA and 0.88 with at least 5 visits with seronegative RA. Negative predictive value for RA diagnosis was 0.99.Conclusion:These results demonstrate that the validity of RA diagnoses in healthcare registers can be markedly improved with data about special reimbursement for medication, number of visits and serological data.Disclosure of Interests:Antti Palomäki Consultant of: Pfizer, Speakers bureau: Pfizer, Sanofi, MSD, Johanna Paltta Consultant of: Lilly, Abbvie, Laura Pirilä Consultant of: Novartis, MSD Finland, Roche, Bristol-Myers-Squibb, Pfizer, Sanofi, Abbvie, Oy Eli LIlly Finland Ab, UCB Pharma Oy Finland, Jansen-Cilag, Mylan, Sandoz, Boehringer-Ingelheim, Paid instructor for: Boehringer -Ingelheim, MSD Finland, Speakers bureau: Boehringer-Ingelheim, Pfizer Finland, Hanna-Kaisa Heikkilä: None declared, Pia Isomäki Consultant of: Abbvie, BMS, Eli Lilly, MSD, Novartis, Pfizer, Roche, Sanofi, Johanna Huhtakangas Consultant of: Boehringer Ingelheim, Tuulikki Sokka-Isler: None declared, Oili Kaipiainen-Seppänen Speakers bureau: Boehringer Ingelheim, Kari Eklund Consultant of: Celgene, Lilly, Speakers bureau: Pfizer, Roche

Introduction: Type 1 diabetes mellitus (T1DM) is a common autoimmune disease among children and adolescents. The primary goal in the management of T1DM is to prevent acute and long-term complications by achieving good glycaemic control. Studies have highlighted the relation between glycaemic control and other factors, including age. Other studies have demonstrated that T1DM patients are at high risk of developing other autoimmune diseases, such as autoimmune thyroiditis and coeliac disease. On the other hand, T1DM can lead to many complications in paediatrics. Objectives: To investigate the relationship between metabolic control, acute and long-term complications and the coexistence of autoimmune diseases with T1DM among children and adolescents in Jeddah, Saudi Arabia. Materials and methods: This was a cross-sectional study that included 243 T1DM children and adolescents visiting the paediatric diabetes clinic at King Abdulaziz University Hospital, Jeddah, Saudi Arabia. Clinical and laboratory characteristics of the patients were all recorded. Metabolic control, complications and associated autoimmune diseases were evaluated. Results: The mean age of patients was 10.5±3.8 years and HbA1c level was 8.8%. Acute complications included ketoacidosis in 61.3% of the patients and hypoglycaemic attacks in 60.5%. Long-term complications included retinopathy, microalbuminuria and dyslipidaemia, which were detected in 6.2%, 16.9% and 19.3% of patients, respectively. Vitamin D deficiency was found in 77%, thyroid dysfunction was noted in 9.1% and coeliac disease in 6.2% of patients. A significant difference was found in pubertal and prepubertal age groups in terms of glycaemic control (P =0.001). Conclusions: The level of HbA 1c was found to be higher among the pubertal age group. A relationship between autoimmune diseases and gender were determined and vitamin D deficiency was highly prevalent in our population. Acknowledgements: Dr Abdulmoien Al-Agha for supervising this project.

Similar pathophysiological mechanisms within autoimmune diseases have stimulated searches for common genetic roots. Polyautoimmunity is defined as the presence of more than one autoimmune disease in a single patient. When three or more autoimmune diseases coexist, this condition is called multiple autoimmune syndrome (MAS). We analyzed the presence of polyautoimmunity in 1,083 patients belonging to four autoimmune disease cohorts. Polyautoimmunity was observed in 373 patients (34.4%). Autoimmune thyroid disease (AITD) and Sjögren's syndrome (SS) were the most frequent diseases encountered. Factors significantly associated with polyautoimmunity were female gender and familial autoimmunity. Through a systematic literature review, an updated search was done for all MAS cases (January 2006–September 2011). There were 142 articles retrieved corresponding to 226 cases. Next, we performed a clustering analysis in which AITD followed by systemic lupus erythematosus and SS were the most hierarchical diseases encountered. Our results indicate that coexistence of autoimmune diseases is not uncommon and follows a grouping pattern. Polyautoimmunity is the term proposed for this association of disorders, which encompasses the concept of a common origin for these diseases.