New-onset Autoimmune Diseases Research Articles

Characteristics and predictors of Long Covid in children: a 3-year prospective cohort study

Children can develop Long Covid, however long term outcomes and their predictors are poorly described in these patients. The primary aim is to describe characteristics and predictors of Long Covid in children assessed in-clinics up to 36 months post-SARS-CoV-2 infection, as well as investigate the role of vaccines in preventing Long Covid, risk of reinfections and development of autoimmune diseases. Children aged 0-18 years old with confirmed SARS-CoV-2 infection were invited for a prospective follow-up assessment at a peadiatric post-covid clinic in Rome, Italy, at serial intervals (3-, 6-, 12-, 18-, 24- and 36-months post-infection onset, between 01/02/2020 and 28/02/2024). Long Covid was defined as persistence of otherwise unexplained symptoms for at least three months after initial infection. 1319 patients were initially included, 1296 reached the 3 months follow-up or more. Of the patients who underwent multiple follow-ups, 23.2% (301), 169 (13.2%), 89 (7.9%), 67 (6.1%), 47 (7.1%) were diagnosed with Long Covid at 3-6-12-18-24 months, respectively For the primary outcome of Long Covid at three months, age >12 years (P<0.001, OR 11.33, 95% CI 4.2; 15.15), comorbidities (P=0.008, OR 1.83, 95% CI 1.06; 2.44), being infected with original variants (P<0.001, OR 4.77, 95% CI 2.46; 14.47), female sex (P<0.001, OR 1.62, 95% CI 1.02; 1.89) were statistically significant risk factors. Age >12 years (P=0.002, OR 9.37, 95% CI 1.58; 8.64), and infection with original (P=0.012, OR 3.52, 95% CI 1.32; 8.64) and alfa (P<0.001, OR 4.09, 95% CI 2.01; 8.3) SARS-CoV-2 variants remained statistically significant risk factors for Long Covid duration for at least 18 months. Vaccination was associated with a lower risk of long covid at 3, 6 and 12 months for older children and a lower risk of reinfections. Being infected with the original SARS-CoV-2 variant was associated with a higher risk of new-onset autoimmune diseases ((P=0.035, 95% CI 1.12; 2.4). One patient was diagnosed with Long Covid after a re-infection. This is the longest follow-up study of children with SARS-CoV-2 infection, showing a significant and long-lasting burden of Long Covid in the pediatric population. Our findings highlight the urgent need of investing in pediatric Long Covid in order to find effective diagnostic and therapeutic approaches, as well can inform preventive strategies in case of future pandemics. This study has been funde by Pfizer non-competitive grant, granted to DB (#65925795).

Pregnancy complications and new-onset maternal autoimmune disease.

Autoimmune diseases disproportionately impact women and female-specific aspects of reproduction are thought to play a role. We investigated the time-varying association between pregnancy complications and new-onset autoimmune disease in females during the reproductive and midlife years. We conducted a population-based cohort study of 1704553 singleton births to 1072445 females in Ontario, Canada (2002-17) with no pre-existing autoimmune disease. Pregnancy complications were preeclampsia, stillbirth, spontaneous preterm birth and severe small for gestational age (SGA). Royston-Parmar models were used to estimate the time-varying association between pregnancy complications and a composite of 25 autoimmune diseases from date of delivery to date of autoimmune disease diagnosis or censoring at death, loss of health insurance, or 31 March 2021. Models were adjusted for baseline socio-demographics, parity and comorbidities. At 19 years (median = 10.9 years of follow-up), cumulative incidence of autoimmune disease was 3.1% in those with a pregnancy complication and 2.6% in those without complications. Adjusted hazard ratio (AHR) curves as a function of time since birth were generally L-shaped. Universally, risks were most elevated within the first 3 years after birth [at 1 year: preeclampsia AHR 1.22, 95% confidence interval (CI) 1.09-1.36; stillbirth AHR 1.36, 95% CI 0.99-1.85; spontaneous preterm birth AHR 1.30, 95% CI 1.18-1.44; severe SGA AHR 1.14, 95% CI 0.99-1.31] and plateaued but remained elevated thereafter. Prior history of pregnancy complications may be an important female-specific risk factor to consider during clinical assessment of females for possible autoimmune disease to facilitate timely detection and treatment.

What is causing this patient's urticaria?

This article describes a teenage patient who was referred to a pediatric endocrinologist after her workup for recurring urticaria revealed a suppressed thyroid-stimulating hormone level and positive microsomal thyroid peroxidase antibodies. The patient's laboratory results revealed an autoimmune cause for the urticaria as a result of new-onset autoimmune thyroid disease.

New-onset autoimmune thyroid disease following COVID-19.

New-onset autoimmune thyroid disease following COVID-19.

Autoimmune Disorders Associated With Surgical Remission of Cushing's Disease : A Cohort Study.

Glucocorticoids suppress inflammation. Autoimmune disease may occur after remission of Cushing's disease (CD). However, the development of autoimmune disease in this context is not well described. To determine 1) the incidence of autoimmune disease in patients with CD after surgical remission compared with patients with nonfunctioning pituitary adenomas (NFPAs) and 2) the clinical presentation of and risk factors for development of autoimmune disease in CD after remission. Retrospective matched cohort analysis. Academic medical center/pituitary center. Patients with CD with surgical remission and surgically treated NFPA. Cumulative incidence of new-onset autoimmune disease at 3 years after surgery. Assessment for hypercortisolemia included late-night salivary cortisol levels, 24-hour urine free cortisol (UFC) ratio (UFC value divided by the upper limit of the normal range for the assay), and dexamethasone suppression tests. Cumulative incidence of new-onset autoimmune disease at 3 years after surgery was higher in patients with CD (10.4% [95% CI, 5.7% to 15.1%]) than in those with NFPAs (1.6% [CI, 0% to 4.6%]) (hazard ratio, 7.80 [CI, 2.88 to 21.10]). Patients with CD showed higher prevalence of postoperative adrenal insufficiency (93.8% vs. 16.5%) and lower postoperative nadir serum cortisol levels (63.8 vs. 282.3 nmol/L) than patients with NFPAs. Compared with patients with CD without autoimmune disease, those who developed autoimmune disease had a lower preoperative 24-hour UFC ratio (2.7 vs. 6.3) and a higher prevalence of family history of autoimmune disease (41.2% vs. 20.9%). The small sample of patients with autoimmune disease limited identification of independent risk factors. Patients achieving surgical remission of CD have higher incidence of autoimmune disease than age- and sex-matched patients with NFPAs. Family history of autoimmune disease is a potential risk factor. Adrenal insufficiency may be a trigger. Recordati Rare Diseases Inc.

New-onset autoimmune disease after COVID-19.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) may trigger autoimmune disease (AD) through initial innate immune activation with subsequent aberrations in adaptive immune cells leading to AD. While there are multiple reports of incident AD diagnosed after COVID-19, the risk in the context of key circulating strains is unknown. TriNetX, a global, federated, health research network providing access to electronic medical records across 74 healthcare organizations, was utilized to define an adult cohort between January 1, 2020, and March 3, 2023. Exposure was defined as COVID-19 diagnosis (ICD-10 code or positive laboratory test). Age- and sex-propensity score-matched controls never had COVID-19 diagnosed. Outcomes were assessed 1 month to 1 year after the index date. Patients with AD prior to or within 1 month after the index date were excluded from the primary analysis. Incidence and risk ratios of each AD were assessed. A total of 3,908,592 patients were included. Of 24 AD patients assessed, adjusted risk ratios for eight AD patients who had COVID-19 were higher compared to those who had no COVID-19. Cutaneous vasculitis (adjusted hazard ratio (aHR): 1.82; 95% CI 1.55-2.13), polyarteritis nodosa (aHR: 1.76; 95% CI 1.15-2.70), and hypersensitivity angiitis (aHR: 1.64; 95% CI 1.12-2.38) had the highest risk ratios. Overall, psoriasis (0.15%), rheumatoid arthritis (0.14%), and type 1 diabetes (0.13%) had the highest incidence during the study period, and of these, psoriasis and diabetes were more likely after COVID-19. The risk of any AD was lower if COVID-19 was diagnosed when Omicron variants were the predominant circulating strains. A positive antinuclear antibody was more likely and predictive of AD after COVID-19. SARS-CoV-2 may be a potential trigger for some AD, but the risk for AD may decrease with time given the apparent lower risk after infection with Omicron variants.

Post-marketing surveillance for the safety of the 9-valent human papillomavirus vaccine: a retrospective real-world study in China

ABSTRACTBackgroundThe 9-valent human papillomavirus (9vHPV) vaccine was introduced in China in 2018. This study was conducted to monitor the occurrence of new-onset autoimmune diseases (AIs) in Chinese women vaccinated with the 9vHPV vaccine and adverse pregnancy outcomes in infants born to mothers with inadvertent pregnancy exposure.Research design and methodsWomen who received the first dose of the 9vHPV vaccine at age 16–26 years in Ningbo between January 2019 and March 2021 were monitored in the Ningbo Regional Health Information Platform. New-onset cases of seven pre-specified AIs diagnosed within six months after vaccination were collected. Cases of stillbirth and 23 major congenital anomalies diagnosed within three months of birth in target infants were collected.ResultsA total of 102,670 doses of the 9vHPV vaccine were administered to 41,609 women who had received no other HPV vaccine. New-onset AIs were diagnosed in 36 women, comprising 21 Hashimoto’s, 11 Graves’, and 4 uveitis disease cases. Among 50 women with maternal vaccination exposure, no stillbirths were observed. One case of microtia was observed.ConclusionsIn this first post-marketing surveillance of the 9vHPV vaccine in China, no safety signals were identified when putting the results in context to published data.

New Onset Autoimmune Diseases after the Sputnik Vaccine.

The vertiginous advance for identifying the genomic sequence of SARS-CoV-2 allowed the development of a vaccine including mRNA-based vaccines, inactivated viruses, protein subunits, and adenoviral vaccines such as Sputnik. This study aims to report on autoimmune disease manifestations that occurred following COVID-19 Sputnik vaccination. Patients and Methods: A retrospective study was conducted on patients with new-onset autoimmune diseases induced by a post-COVID-19 vaccine between March 2021 and December 2022, in two referral hospitals in Mexico City and Argentina. The study evaluated patients who received the Sputnik vaccine and developed recent-onset autoimmune diseases. Results: Twenty-eight patients developed recent-onset autoimmune diseases after Sputnik vaccine. The median age was 56.9 ± 21.7 years, with 14 females and 14 males. The autoimmune diseases observed were neurological in 13 patients (46%), hematological autoimmune manifestations occurred in 12 patients (42%), with thrombotic disease observed in 10 patients (28%), and autoimmune hemolytic anemia in two patients (7.1%). Rheumatological disorders were present in two patients (7.1%), and endocrine disorders in one patient (3.5%). Principio del formulario Conclusion: Although the COVID-19 Sputnik vaccine is generally safe, it can lead to adverse effects. Thrombosis and Guillain-Barre were the most frequent manifestations observed in our group of patients.

Incident autoimmune diseases in association with SARS-CoV-2 infection: a matched cohort study.

To investigate whether the risk of developing an incident autoimmune disease is increased in patients with prior COVID-19 disease compared to those without COVID-19, a large cohort study was conducted. A cohort was selected from German routine health care data. Based on documented diagnoses, we identified individuals with polymerase chain reaction (PCR)-confirmed COVID-19 through December 31, 2020. Patients were matched 1:3 to control patients without COVID-19. Both groups were followed up until June 30, 2021. We used the four quarters preceding the index date until the end of follow-up to analyze the onset of autoimmune diseases during the post-acute period. Incidence rates (IR) per 1000 person-years were calculated for each outcome and patient group. Poisson models were deployed to estimate the incidence rate ratios (IRRs) of developing an autoimmune disease conditional on a preceding diagnosis of COVID-19. In total, 641,704 patients with COVID-19 were included. Comparing the incidence rates in the COVID-19 (IR=15.05, 95% CI: 14.69-15.42) and matched control groups (IR=10.55, 95% CI: 10.25-10.86), we found a 42.63% higher likelihood of acquiring autoimmunity for patients who had suffered from COVID-19. This estimate was similar for common autoimmune diseases, such as Hashimoto thyroiditis, rheumatoid arthritis, or Sjögren syndrome. The highest IRR was observed for autoimmune diseases of the vasculitis group. Patients with a more severe course of COVID-19 were at a greater risk for incident autoimmune disease. SARS-CoV-2 infection is associated with an increased risk of developing new-onset autoimmune diseases after the acute phase of infection. Key Points • In the 3 to 15 months after acute infection, patients who had suffered from COVID-19 had a 43% (95% CI: 37-48%) higher likelihood of developing a first-onset autoimmune disease, meaning an absolute increase in incidence of 4.50 per 1000 person-years over the control group. • COVID-19 showed the strongest association with vascular autoimmune diseases.

E015 A case of ocular myasthenia gravis seen by rheumatology as suspected mononeuritis multiplex in an adult male shortly after Pfizer-BioNTech SARS-CoV-2 vaccination

Abstract Background/Aims Myasthenia gravis (MG) is an antibody-mediated autoimmune disease targeting proteins at the postsynaptic membrane of the neuromuscular junction. MG is thought to occur in genetically susceptible individuals following an environmental trigger. SARS-CoV-2 infection has been associated with new-onset autoimmune disease, new-onset MG, and exacerbations of pre-existing MG, with molecular mimicry between SARS-CoV-2 epitopes and autoantigen-induced autoreactivity thought to be part of the underlying mechanism. We report a case of new-onset ocular MG following first dose Pfizer-BioNTech BNT162b2 SARS-COV2 vaccination which was referred to rheumatology as suspected mononeuritis multiplex. Methods A 53-year-old man of East Asian ethnicity presented to the emergency department (ED) with sudden onset diplopia and left lateral gaze restriction 7 days after receiving his first dose of the Pfizer-BioNTech BNT162b2 SARS-COV2 vaccination. He had longstanding myopia and dry eyes but no other medical history, no regular medications or significant family history. He was a current smoker, with a 50-pack year history. He did not drink alcohol or use any recreational drugs. He was found to have an isolated left VI cranial nerve (CN) palsy with an otherwise normal ocular and physical examination. Blood tests were unremarkable apart from raised cholesterol, and he was discharged with a suspected self-limiting microvascular CN lesion. Three weeks later he presented to ED with worsening diplopia, increasingly restricted eye movements, headache, nausea, vomiting and blurred vision. Ophthalmology assessment noted new right sided CN III and VI palsy, persistent left CN VI palsy, and vertical diplopia in all fields of gaze. Neurological and physical examination were normal. Bloods including an autoimmune screen were unremarkable. SARS-CoV-2 Spike antibodies were positive consistent with SARS-CoV-2 vaccination but not infection. Intracranial and thoracic imaging were unremarkable. He was referred to and seen by both rheumatology and neurology as a case of suspected mononeuritis multiplex. Results A diagnosis of ocular MG was confirmed with positive serum acetylcholine receptor antibodies, and he was started on prednisolone, and pyridostigmine to good effect. Daily forced vital capacity (FVC) showed no respiratory muscle involvement, and nerve conduction studies and electromyography were normal, excluding secondary generalisation. Conclusion A review of the literature found 14 reported cases of new-onset MG all within 4 weeks following SARS-CoV-2 vaccine. Whilst these cases provide interesting insights into the pathogenesis of autoimmune conditions such as MG, they are not epidemiological studies to inform vaccine safety. Ultimately, current evidence suggests that the risks of SARS-COV-2 infection outweigh the risk of vaccine-related adverse events, therefore we suggest clinicians should be aware of potential new-onset autoimmune conditions, but support the safety of SARS-COV2 vaccination. Further, research into possible immunological mechanisms behind this phenomenon, including identifying potential epitopes inducing molecular mimicry, could help establish the likelihood of a causative link. Disclosure A. Storrie: None. R.M. Hum: None. J. Lilleker: None. P. Ho: None.

A case of ANCA-associated vasculitis in a 16-year-old female following SARS-COV-2 infection and a systematic review of the literature

BackgroundAntineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a rare form of vasculitis in children. SARS-CoV-2, the virus that causes COVID-19 infection, seems to trigger autoimmunity and new-onset autoimmune disease in pediatric and adult patients. We present a case of new-onset AAV following COVID-19 infection in an adolescent patient, and we review the literature of AAV following COVID-19 infection.Case presentationAn adolescent female with a history of asthma was diagnosed with mild COVID-19 infection and subsequently developed persistent cough, wheezing, hearing loss, arthralgias, and rash. Her imaging and laboratory workup showed pulmonary nodules and cavitary lesions, elevated inflammatory markers, negative infectious testing, and positive ANCA. She was treated with glucocorticoids, rituximab, and mycophenolate mofetil. At six-month follow-up, she had improvement in her symptoms, pulmonary function tests, imaging findings, and laboratory markers.ConclusionsWe report the second case of new-onset anti-PR3, C-ANCA vasculitis and the fourth case of pediatric-onset AAV following COVID-19 infection. A systematic review of the literature found 6 cases of new-onset AAV in adults after COVID-19 infection. Pediatric and adult patients who develop AAV post COVID-19 infection have few, if any, comorbidities, and show marked radiographic and symptomatic improvement after treatment. There is increasing evidence for COVID-19-induced autoimmunity in children and our case highlights the importance of considering AAV in a child following a recent COVID-19 infection because timely treatment may improve clinical outcomes.

Risk of Autoimmune Diseases Following Optic Neuritis: A Nationwide Population-Based Cohort Study.

ObjectivesOptic neuritis is (ON) is believed to be an immune-mediated disease; however, the association between optic neuritis and autoimmune diseases remains unclear. This study aimed to identify the incidence rate and adjusted hazard ratio (aHR) of autoimmune diseases in patients with optic neuritis.MethodsThis nationwide, population-based, retrospective cohort study collected patients’ data between 1999 and 2013 from the National Health Insurance Research Database in Taiwan. A total of 9,235 patients were included. Using 1:4 propensity scoring, 1,847 patients were enrolled in the optic neuritis group and 7,388 in the non-optic neuritis group according to age, sex, comorbidities, and corticosteroid use. Follow-up was started from the index date and the endpoint was a diagnosis of new-onset autoimmune diseases including, myasthenia gravis (MG), psoriatic arthritis (PsA), systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and ankylosing spondylitis (AS).ResultsThe Kaplan-Meier curves depicted that patients with optic neuritis had a higher cumulative incidence of autoimmune diseases than patients without optic neuritis. Cox proportional hazard regression showed that patients with optic neuritis were at a high risk of autoimmune diseases (aHR: 1.40; 95% C.I., 1.05–1.87), including MG (aHR: 4.16, 95% C.I.: 1.33–12.94), SLE (aHR: 3.33, 95% C.I.: 1.24–8.97), and AS (aHR: 2.86, 95% C.I.: 1.54–5.31). Subgroup analysis provided that patients with optic neuritis aged below 65 years (aHR: 1.42, 95% C.I.: 1.03–1.96) or who were females (aHR: 1.59, 95% C.I.: 1.11–2.27) had a significantly increased risk of autoimmune diseases compared to respective controls. The use of corticosteroids reduced the risk of autoimmune diseases in patients with optic neuritis (aHR for corticosteroids non-users: 1.46, 95% C.I.: 1.03–2.07).ConclusionPatients with optic neuritis presented with a high risk of autoimmune diseases such as MG, SLE, and AS, especially patients with optic neuritis who were young or females. Corticosteroids attenuated the link between optic neuritis and subsequent autoimmune diseases.

P237 New-onset systemic lupus erythematosus following COVID-19 vaccination: a report of two cases

Abstract Background/Aims There is a growing number of reports of new-onset autoimmune disease or complications of underlying autoimmune disorders following COVID-19 infection and vaccination. Methods We describe two cases of systemic lupus erythematosus (SLE) that developed de novo in two female patients shortly after receiving their COVID-19 vaccinations. Results The first case is a 29-year-old female with no prior medical history. One week following her COVID-19 Pfizer/BioNTech vaccination, she developed widespread pruritus, fatigue, myalgia, arthralgia, fever and night sweats. Blood tests showed pancytopenia and she was referred for an urgent haematology opinion due to lymphoma. Positron Emission Tomography/computed tomography (PET/CT) demonstrated widespread lymphadenopathy. Bone and lymph node biopsy showed reactive changes only. Her symptoms progressed with polyarticular inflammatory arthritis, oral ulceration, Raynaud’s, pleuritic chest pain, palmar purpuric rash, and a widespread tender urticarial rash. Further investigations showed low complement C3/C4, anti-double stranded DNA antibody titre (dsDNA) &amp;gt;200 IU/mL, positive Anti-Ro antibody, positive Anti-La antibody, weakly positive anti-RNP antibody and an Anti-C1q antibody &amp;gt;400 units/ml with a urine protein/creatinine ratio (PCR) of 39 mg/mmol. A diagnosis of SLE with urticarial vasculitis was made and she commenced Hydroxychloroquine in addition to weaning prednisolone (60mg). A skin biopsy confirmed lupus vasculitis. Despite high dose prednisolone, urine PCR increased over 2 weeks from 39 to 84 mg/mmol. Renal biopsy demonstrated class 3 lupus nephritis. She was pulsed with 500mg IV methyl prednisolone over 3 days and commenced mycophenolate 1g BD. Within weeks she was in clinical remission. The second case is a 70-year-old female with a past medical history of diverticulosis, uterine fibroids and small hand joint osteoarthritis. She presented with a sudden onset, 6-week history of bilateral symmetrical small and large joint synovitis that developed 8 days following the first dose of the COVID-19 Oxford-AstraZeneca vaccine. Her investigations showed reduced lymphocyte counts (0.9 109/L), raised CRP 26 mg/L and ESR 32 mm/hr. Antinuclear antibodies were weakly positive with a homogenous pattern. DsDNA titre was raised at 175 IU/mL and C4 reduced at 0.14 g/L. There was no proteinuria or any evidence of major internal organ involvement. She was started on a short reducing course of oral prednisolone given the severity of her presenting clinical features. Her symptoms improved, with no recurrence on stopping steroids but she has continued elevation in DsDNA; a conservative management approach is being adopted. Conclusion Both cases met the EULAR/ACR and SLICC classification criteria for SLE. There was a clear temporal association between the onset of SLE symptoms and COVID-19 vaccination. Our cases raise the possible association/causation of SLE following COVID-19 vaccination. Potential mechanisms include immune responses elicited by the COVID-19 vaccination, triggering autoimmunity in genetically predisposed individuals. Further research and data from registries are required. Disclosure J. Beynon: None. M. Alsharkawy: None. L. Sammut: None. J. Ledingham: None.

Atopic dermatitis and risk of autoimmune conditions: Population-based cohort study

Atopic dermatitis (AD) is associated with immune dysregulation, but epidemiologic data on the pattern of autoimmune comorbidity in people with AD are limited. We sought to determine the risk of autoimmune conditions in people newly diagnosed with AD. Retrospective cohort analysis (January 2009 to December 2018), using the UK-based Oxford-Royal College of General Practitioners Research and Surveillance Centre primary care database. We compared baseline prevalence and incidence after diagnosis of autoimmune conditions in 173,709 children and adults with new-onset AD and 694,836 age-, sex-, and general practitioner practice-matched controls. Outcomes were a composite of any autoimmune condition (Crohn disease, ulcerative colitis, celiac disease, pernicious anemia, type 1 diabetes, autoimmune hypothyroidism, Graves disease, psoriatic arthritis, rheumatoid arthritis, ankylosing spondylitis, systemic lupus erythematosus, Sjögren syndrome, vitiligo, alopecia areata, and multiple sclerosis) and each individual autoimmune condition. Preexisting autoimmune conditions were more common in people diagnosed with AD compared to controls (composite 5.8% vs 4.3%). Excluding people with preexisting autoimmune disease, there was an association between AD and incidence of new-onset autoimmune disease (composite adjusted hazard ratio [aHR] 1.28; 95% confidence interval [CI] 1.23-1.34). Risk was highest for more severe AD (aHR 1.99; 95% CI 1.77-2.23) than moderate AD (aHR 1.33; 95% CI 1.19-1.49) or mild AD (aHR 1.22; 95% CI 1.16-1.28). People with AD were at significantly increased risk of developing psoriatic arthritis, Sjögren syndrome, Crohn disease, vitiligo, alopecia areata, pernicious anemia, ulcerative colitis, rheumatoid arthritis, and hypothyroidism (aHR range 1.17-2.06), but not other autoimmune conditions. People with AD have an increased risk of multiple autoimmune conditions, especially those with more severe AD.

Coxiella burnetii Infection Associated With Thromboangiitis Obliterans-like Phenomena With Digital Autoamputation: A Case Report and Review of Q Fever-Associated Autoimmunity.

We present a case of a patient with chronic Q fever who presented with digital necrosis, autoamputations, and positive anticentromere antibody, mimicking a scleroderma vasculopathy or thromboangiitis obliterans. Coxiella burnetii infection has long been associated with the presence of autoantibodies and autoimmune phenomena including vasculitis. Clinicians should consider Q fever testing in patients with new-onset autoimmune diseases or autoantibodies and appropriate exposure histories.

Risk of new-onset autoimmune diseases in primary aldosteronism: a nation-wide population-based study.

The association between hyperaldosteronism and autoimmune disorders has been postulated. However, long-term incidence of a variety of new-onset autoimmune diseases (NOAD) among patients with primary aldosteronism has not been well investigated. From Taiwan's National Health Insurance Research Database with a 23-million population insurance registry, the identification of primary aldosteronism, essential hypertension and NOAD as well as all-cause mortality were ascertained by a validated algorithm. From 1997 to 2009, 2319 primary aldosteronism patients without previously autoimmune disease were identified and propensity score-matched with 9276 patients with essential hypertension. Among those primary aldosteronism patients, 806 patients with aldosterone-producing adenomas (APA) were identified and matched with 3224 essential hypertension controls. NOAD incidence is augmented in primary aldosteronism patients compared with its matched essential hypertension (hazard ratio 3.82, P < 0.001, versus essential hypertension). Furthermore, NOAD incidence is also higher in APA patients compared with its matched essential hypertension (hazard ratio = 2.96, P < 0.001, versus essential hypertension). However, after a mean 8.9 years of follow-up, primary aldosteronism patients who underwent adrenalectomy (hazard ratio = 3.10, P < 0.001, versus essential hypertension) and took mineralocorticoid receptor antagonist (MRA) still had increased NOAD incidence (hazard ratio = 4.04, P < 0.001, versus essential hypertension). Primary aldosteronism patients had an augmented risk for a variety of incident NOAD and all-cause of mortality, compared with matched essential hypertension controls. Notably, the risk of incident NOAD remained increased in patients treated by adrenalectomy or MRA compared with matched essential hypertension controls. This observation supports the theory of primary aldosteronism being associated with a higher risk of multiple autoimmune diseases.

Safety of the AS04-adjuvanted human papillomavirus (HPV)-16/18 vaccine in adolescents aged 12–15 years: end-of-study results from a community-randomized study up to 6.5 years

ABSTRACT This manuscript discloses end-of-study safety data of a community-randomized controlled trial in Finland (NCT00534638), assessing the effectiveness of two vaccination strategies (gender-neutral versus females only) using the AS04-adjuvanted human papillomavirus (HPV)-16/18 (AS04-HPV-16/18) vaccine. The total vaccination cohort included 32,175 adolescents aged 12–15 y at vaccination of whom 14,837 received the AS04-HPV-16/18 vaccine and 17,338 received the hepatitis-B virus vaccine (control). Spontaneous reporting of serious adverse events (SAEs) combined with surveillance using nation-wide health registries showed an acceptable safety profile of the AS04-HPV-16/18 vaccine. During the study period (up to 6.5 y), the incidences (per 100,000 person-years) of reported SAEs considered as possibly related to vaccination were 39.1 (95% confidence interval [CI]: 25.3–57.7) and 39.8 (95%CI: 26.8–56.8) in the HPV and control groups, respectively. The most frequently reported new-onset autoimmune diseases (NOADs) were ulcerative colitis (incidence rates of 28.2 and 33.1 per 100,000 person-years in the HPV and control groups, respectively), insulin-dependent diabetes mellitus (21.9 and 37.1), Crohn’s disease (15.6 and 22.5), celiac disease (15.6 and 21.2), and juvenile idiopathic arthritis (14.1 and 15.9). Of 1,344 pregnancies reported (777 and 567 in the HPV and control groups, respectively), most resulted in elective termination (58.4% and 58.6%), birth of a live infant (32.7% and 32.3%), or in spontaneous abortion (8.0% and 7.9%). No major, registered congenital anomalies were identified. The incidence rates of NOADs and pregnancy outcomes were generally balanced between groups. No specific safety signals were identified in the population-based health registry surveillance.

AB007. Development and onset of autoimmune diseases in cutaneous lupus erythematosus patients

: Patients with systemic lupus erythematosus (SLE) harbor an increased risk for developing additional autoimmune diseases. A recent cross-sectional study reported that cutaneous lupus erythematosus (CLE) patients without SLE also had significantly elevated rates of co-existing autoimmune disease(s). In a case-control study, we characterized the timing and prevalence of autoimmune diseases in a group of 122 CLE patients in relation to their CLE diagnosis and identified demographic and clinical factors associated with the presence of additional autoimmune diagnosis. 117 patients with SLE were used as controls. At the time of lupus diagnosis, 12.3% of CLE and 16.2% of SLE patients had a prior-onset autoimmune disease (P=0.383). After lupus diagnosis, 19.7% of CLE and 17.95% of SLE patients had a new-onset autoimmune disease (P=0.687). For CLE patients, the most common prior-onset and new-onset diagnoses were autoimmune thyroid disease and SLE, respectively. Univariate analysis showed that patients with prior-onset disease were older (P=0.019) and more likely to be antinuclear antibody (ANA) positive (P<0.001) at CLE diagnosis. Patients with new-onset autoimmune disease were more likely to be ANA positive at any point during follow-up (P=0.001). Multivariate analyses showed that positive ANA was significantly associated with prior-onset [odds ratio (OR) 6.95, P=0.001] and new-onset autoimmune diagnosis (OR 5.65, P=0.003). These results demonstrated an elevated and persistent risk for acquiring autoimmune diseases in CLE patients similar to that seen for SLE patients. CLE patients with positive ANA histories have an even greater risk for additional autoimmune conditions, which may help providers focus their screenings.

Paradoxical gastrointestinal reactions in patients taking tumor necrosis factor inhibitors: a rare event that broadens the histologic spectrum of medication–associated injury

Tumor necrosis factor (TNF) inhibitors are widely used in the therapy of certain autoimmune disorders. Paradoxical immunologic reactions manifesting as new-onset autoimmune disease or exacerbation of the underlying condition have been reported in association with these drugs. In this study, we reviewed gastrointestinal biopsies and clinical findings in patients with rheumatologic disease on TNF inhibitor therapy and compared to patients with rheumatologic disease not on TNF inhibitors. Eighteen biopsies from 9 patients treated with TNF inhibitor therapy and 249 biopsies from 120 control patients not treated with TNF inhibitors were included. Among patients taking a TNF inhibitor, 55.6% were female, and the median age was 47 (range, 30-67 years). Four (44.4%) patients were taking etanercept, 4 (44.4%) adalimumab, and 1 (11.1%) certolizumab pegol. Of the 120 control patients, 75 (62.5%) were female and the median age was 62 (range, 26-85 years). Paradoxical reactions were observed in 3 (33.3%) of 9 patients on TNF inhibitors, including 2 (22.2%) with inflammatory bowel disease-like changes and 1 (11.1%) with sarcoid-like granulomas. All 3 patients showed symptomatic and histologic improvement or resolution after discontinuation of therapy. These reactions were not observed in any of the control patients (P = .0002). Our results indicate that among patients with rheumatologic disease, paradoxical reactions of the gastrointestinal tract are associated with TNF inhibitor therapy. Knowledge of this association is important because symptoms and histologic features may improve following medication switch.

Post-licensure safety surveillance study of routine use of quadrivalent meningococcal diphtheria toxoid conjugate vaccine (MenACWY-D) in infants and children

BackgroundMenactra® vaccine (MenACWY-D) was licensed in the United States in 2005 for persons 11–55 years of age, in 2007 for children 2–10 years of age, and in 2011 for infants/toddlers 9–23 months of age. We conducted two studies at Kaiser Permanente Northern California (KPNC), an integrated health care organization, to assess the safety of MenACWY-D in 2–10-year-olds and 9–23-month-olds receiving the vaccine during routine clinical care. MethodsWe conducted observational, retrospective studies of MenACWY-D in 2–10-year-olds (October 2007–October 2010) and in 9–23-month-olds (June 2011–June 2014). We monitored all subjects for non-elective hospitalizations, emergency department visits, and selected outpatient outcomes (specified neurological conditions, hypersensitivity reactions and new-onset autoimmune diseases) up to 6 months after vaccination, depending on the study. Using a self-control risk-interval design, we calculated incidence rate ratios (IRRs) comparing outcomes during the post-vaccination risk interval (0–30 days) with those during more remote post-vaccination comparison intervals (31–60 and 31–180 days [children] or 31–75 days [infants/toddlers]). ResultsThere were 1421 children aged 2–10 years and 116 infants/toddlers aged 9–23 months who received MenACWY-D. Approximately 30% of the 2–10-year-olds and 67% of the 9–23-month-olds were considered at increased risk of meningococcal disease. Among 2–10-year-olds, there was 1 hospitalization on post-vaccination day 5 for fever, which was considered possibly related to vaccination. The only significantly elevated outcome among 2–10-year-olds was cellulitis/abscess (2 cases occurred during the risk interval versus 0 during comparison interval; IRR not evaluable [NE], 95% CI: 1.42, NE). After medical record review, the 2 cases were considered unrelated to vaccination. Among 9–23-month-olds, no outcomes were significantly elevated after vaccination and there were no hospitalizations. There were no deaths observed during the three-year accrual and subsequent six-month surveillance period for either study. ConclusionsImmunization of infants and young children with MenACWY-D vaccine was not associated with any new safety concerns; however, these small studies had limited power to detect rare or uncommon safety events.ClinicalTrials.gov Identifiers are NCT00728260 and NCT01689155.