Autoimmune thyroid disease modifies the clinical expression of hand osteoarthritis in older people: a third National Health and nutrition examination survey study.

Introduction: The risk factors linked to hand osteoarthritis (OA) that contribute to its distinct symptoms and clinical presentation are not thoroughly understood. This study aimed to examine whether the autoimmune thyroid disease (AITD) autoantibodies, anti-thyroid peroxidase antibody (TPOAb), and anti-thyroglobulin antibody (TgAb), associate with hand OA and symptomatic hand OA in the Third National Health and Nutrition Examination Survey (NHANES III). Materials and methods: We included 2,429 persons from NHANES III ≥60 years of age. Data on hand OA or symptomatic hand OA were examined with respect to their associations with TPOAb and TgAb. Log-binomial and modified Poisson regression models were fit to examine the associations between the anti-thyroid autoantibodies and hand OA or symptomatic hand OA. Results: Higher levels of TPOAb were associated with a higher prevalence of symptomatic hand OA in the unadjusted (PR = 1.182, p = 0.024) and adjusted models after controlling for age, gender, and diabetes (PR = 1.174, p = 0.039). This association was no longer significant when positive TPOAb was considered a categorical variable with four levels and compared with negative TPOAb. TgAb showed a trend toward being positively associated with symptomatic hand OA (p < 0.10). When positive TgAb was considered a categorical variable with four levels and compared with negative TgAb, the highest quartile was associated with a higher prevalence of symptomatic hand OA than negative TgAb in the unadjusted (PR = 2.242, p = 0.008) and adjusted models (PR = 2.045, p = 0.038). There was no significant association between TPOAb or TgAb and hand OA. Conclusion: Higher levels of TPOAb may be associated with the presence of symptomatic hand OA in persons ≥60 years old. Persons ≥60 years old with the highest quartile levels of TgAb may be more likely to present with symptomatic hand OA.

Autoimmune thyroid disease and rheumatoid arthritis: where the twain meet.

Autoimmune thyroid disease (AITD) is the most prevalent autoimmune disease. It shares multiple genetic, clinical, and serologic characteristics with rheumatoid arthritis (RA). Although frequently described as a classic form of single-organ autoimmunity, the AITD disease burden in a subset of patients extends well beyond the thyroid gland. This review explores the complex interaction between the two diseases and the clinical consequences when they overlap. Beyond the well-known effects of AITD on thyroid function in RA, there is mounting evidence of the association of both conditions impacting the presentation and outcomes of diabetes, metabolic syndrome, and cardiovascular disease. An increasing number of studies suggest that there are negative effects of AITD on RA disease activity both in the presence and in the absence of thyroid dysfunction. Recent evidence suggests that AITD may not only worsen the cumulative damage of RA through higher disease activity but may also worsen secondary osteoarthritis changes. Less well-known is the significant association between AITD and chronic widespread pain syndromes including fibromyalgia. Importantly, the presence of fibromyalgia, which is increased in RA patients, appears to be further increased when it overlaps with AITD. Lastly, we probe the possible influence of AITD interacting with RA on fertility and clinical depression. Key Points • Autoimmune thyroid disease is the most common autoimmune disease and is frequently associated with rheumatoid arthritis. • Autoimmune thyroid disease can present with osteoarthritis, inflammatory arthritis, and chronic widespread pain syndromes. • The co-occurrence of autoimmune thyroid disease and rheumatoid arthritis may worsen disease activity and exacerbate other disease manifestations including cardiovascular disease, fertility, and depression. • The overlap of rheumatoid arthritis with autoimmune thyroid disease needs further research and should be sought in general clinical practice.

Association of the anti-thyroid peroxidase antibody with chronic hand pain in older adults in the Third National Health and Nutrition Examination Survey: a cross-sectional study.

Background: Autoimmune thyroid disease (AITD) is the commonest autoimmune disease. Although viewed as a classic form of single-organ autoimmunity, AITD is increasingly associated with non-thyroid sequelae including musculoskeletal manifestations and chronic pain syndromes. However, large population-based studies are needed. Objectives: To examine the relationships between chronic hand pain and the AITD autoantibodies, anti-thyroid peroxidase antibody (TPOAb), and anti-thyroglobulin antibody (TgAb), in the Third National Health and Nutrition Examination Survey (NHANES III). Design: This is a cross-sectional study. Methods: We examined data from NHANES III on 4820 persons aged 60 years or older with respect to hand pain and its association with TPOAb and TgAb. Log-binomial regressions were fit to examine the associations between the anti-thyroid autoantibodies and hand pain. Results: Positive TPOAb was associated with a higher prevalence of hand pain than negative TPOAb [prevalence ratio (PR) = 1.158, p = 0.048] in the unadjusted model. This association was no longer significant after controlling for age, body mass index, gender, and diabetes (p = 0.313). When positive TPOAb was considered as a categorical variable with four levels, the highest quartile was associated with hand pain in the unadjusted (PR = 1.489, p = 0.005) and adjusted models (PR = 1.325, p = 0.042). There was no significant association between TgAb and hand pain when covariates were controlled for. Conclusion: TPOAb may be associated with the presence of chronic hand pain in persons aged over 60 years, especially at higher serum levels.

A Case of Microscopic Polyangiitis Complicated by Mucormycosis: A Dangerous Balancing Act.

Microscopic polyangiitis (MPA) is a rare antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis marked by renal involvement, which often leads to rapidly progressive glomerulonephritis. Immunosuppressive treatment is necessary to prevent irreparable organ damage. On the other hand, mucormycosis is a rare and devastating opportunistic fungal infection with a high mortality rate in both immunosuppressed and immunocompetent individuals. It requires a high index of suspicion at the time of diagnosis since any delay in treatment may lead to severe morbidity or death. Here, we present the case of a diabetic patient diagnosed with MPA who received partial induction treatment, subsequently developed mucormycosis, survived, yet required continued immunosuppressive treatment for active MPA while imaging was concerning for a persistent mucormycosis infection. This case highlights the barriers to early mucormycosis detection specific to vasculitis patients, mucormycosis considerations unique to the rheumatologic population, and discusses how to balance immunosuppressive treatment in the setting of a deadly opportunistic infection.

Association of anti-thyroid antibodies with radiographic knee osteoarthritis and chondrocalcinosis: a NHANES III study.

OBJECTIVES: To examine the relationships between radiographic knee osteoarthritis (RKOA), symptomatic radiographic knee osteoarthritis (sRKOA), and chondrocalcinosis, as outcome variables, and the autoimmune thyroid disease (AITD) autoantibodies, anti-thyroid peroxidase antibody (TPOAb) and anti-thyroglobulin antibody (TgAb), in the Third National Health and Nutrition Examination Survey (NHANES III) data source. METHODS: NHANES III provided data on 2291 persons over the age of 60 years that included the osteoarthritis variables of interest RKOA, sRKOA and chondrocalcinosis, and the thyroid autoantibodies TPOAb and TgAb. A log-binomial regression model was fit to examine the relationships between anti-thyroid autoantibodies and RKOA. Modified Poisson regression models were employed for the thyroid autoantibodies compared to sRKOA and chondrocalcinosis. RESULTS: Patients with higher levels of TPOAb were more likely to have chondrocalcinosis [prevalence ratio (PR) 1.247, 95% confidence interval (CI) 1.051, 1.479, p = 0.012]. A piecewise regression analysis indicated that this relationship between TPOAb and chondrocalcinosis was only observed when TPOAb was above 35 IU/ml (PR 1.482, 95% CI 1.233, 1.781, p < 0.001). Levels equal to or below 35 IU/ml were not associated with chondrocalcinosis. TPOAb was not associated with RKOA or sRKOA, and TgAb was not significantly related to any of the outcomes. CONCLUSION: There was no association of AITD autoantibodies TPOAb and TgAb with RKOA or sRKOA. However, there may be an association of TPOAb with the presence of chondrocalcinosis.

Rapid Implementation of a Multidisciplinary COVID-19 Cytokine Storm Syndrome Task Force.

OBJECTIVE: Patients with coronavirus disease 2019 (COVID-19) can progress to a state of unregulated inflammation called cytokine storm syndrome (CSS). We describe formation and operation of a COVID-19 multidisciplinary consultation service that was allowed to individualize treatment for critically ill patients with COVID-19 during the pandemic. METHODS: Institutional experts from different subspecialties formed a COVID-19 CSS task force at Montefiore Medical Center, Bronx, NY. They agreed on a set of four clinical and six laboratory parameters that can help early identify COVID-19 CSS. We describe the formation and implementation of the COVID-19 task force. The case series description of the COVID-19 CSS consultation cohort highlights consultation volume, baseline characteristics, clinical and laboratory parameters, and how biologic treatments were allocated to these patients. RESULTS: Between April 4,2020, and May 7,2020, the COVID-19 CSS task force was formed, consisting of adult and pediatric rheumatologists and allergy and immunology physicians. The task force evaluated a total of 288 patients, of whom 197 (68%) were male, the median (interquartile range [IQR]) age was 62 (51-70) years, 122 (42%) were Hispanic, and 88 (31%) were Black or African American. The common presenting symptoms in all referred patients were dyspnea (85%) and diarrhea (80%). Thirty-one patients who received biologic therapy were younger, with a median (IQR) age of 53 (32-63) years, as opposed to 62.5 (52-70) years in the nonbiologic group (P = 0.008). A higher proportion receiving biologics was in the critical care setting (26 [84%] vs 151 [59%]; P = 0.006). CONCLUSION: To the best of our knowledge, this is the first multidisciplinary collaborative effort to provide individualized patient recommendations for evaluation and treatment of patients with COVID-19 who may have CSS. This working model helped to devise an approach that may have identified patients who were most likely to benefit from biologic therapy in the absence of evidence-based guidelines.

Rheumatic associations of autoimmune thyroid disease: a systematic review.

To investigate specific disease patterns in the rheumatic manifestations associated with autoimmune thyroid disease (AITD) through a systematic literature review. We performed a systematic review using the Medline OVID, PubMed, EMBASE, and Web of Science databases through May 2018 for experimental and observational studies that explored the association of AITD with degenerative joint disease (DJD), osteoarthritis (OA), chronic widespread pain (CWP) and fibromyalgia syndrome (FMS), and seronegative inflammatory arthritis (IA). A total of 2132 articles were identified. After title and abstract screening and removal of duplicates, 66 articles were retrieved for full text review. Eighteen studies were deemed eligible for inclusion. Six observational studies reported up to 45% prevalence of DJD in AITD. Hand and spinal DJD were reportedly associated with higher odds of AITD. Twelve observational studies were retrieved reporting up to 62% prevalence of FMS in AITD patients. Four studies described the occurrence of seronegative IA in AITD patients. The rheumatic associations of AITD may manifest specific patterns of disease distinct from those of other well-defined autoimmune syndromes and contribute significantly to disease burden.

The prevalence and distribution of the amyloidogenic transthyretin (TTR) V122I allele in Africa.

BACKGROUND: Transthyretin (TTR) pV142I (rs76992529-A) is one of the 113 variants in the human TTR gene associated with systemic amyloidosis. It results from a G to A transition at a CG dinucleotide in the codon for amino acid 122 of the mature protein (TTR V122I). The allele frequency is 0.0173 in African Americans. METHODS: PCR-based assays to genotype 2767 DNA samples obtained from participants in genetic studies from various African populations supplemented with sequencing data from 529 samples within the 1000 Genomes Project. RESULTS: The rs76992529-A variant allele was most prevalent (allele frequency 0.0253) in the contiguous West African countries of Sierra Leone, Guinea, Ivory Coast, Burkina Faso, Ghana, and Nigeria. In other African countries, the mean allele frequency was 0.011. CONCLUSIONS: Our data are consistent with a small number of founder carriers of the amyloidogenic TTR V122I (p.Val142Ile) allele in southern West Africa, with no apparent advantage or disadvantage of an allele carrying newborn reaching adulthood. In U.S. African Americans, the allele represents a significant risk for congestive heart failure late in life. If clinical penetrance is similar in African countries with high allele frequencies, then cardiac amyloidosis could also represent a significant cause of heart disease in the elderly in those populations.

Association of spinal degenerative disc disease with thyroid autoimmunity.

OBJECTIVES: Autoimmune thyroiditis (ATD) has been linked to various forms of arthritis. The relationship with spinal degenerative disc disease (DDD) is not known. We studied the association between ATD and spinal DDD. METHODS: We performed a cross-sectional analysis of patients who had data on both anti-thyroid peroxidase antibodies (TPOAb) and anti-thyroglobulin antibodies (TgAb) from January 1997 to January 2014 in Clinical Looking Glass (CLG), a data analysis software platform. Spinal DDD was confirmed by radiological diagnosis. RESULTS: Of the 7698 patients for whom the TPOAb and TgAb values were available, 4383 patients with complete data for the following covariates; age, gender, race, ethnicity, smoking, diabetes, body mass index and thyroid stimulating hormone (TSH) levels, were included. Thirty-three percent had ATD, while 67% did not. The unadjusted odds ratio (OR) of having spinal DDD with ATD was 1.5 (95% confidence interval (CI)1.3, 1.7), p<0.001. After adjustment for covariates, ATD remained associated with a higher frequency of spinal DDD, OR 1.8 (95% CI 1.6, 2.2), p<0.001. Stratifying by BMI and TSH levels showed similar results. Additional analyses excluding patients with known connective tissue diseases and spondyloarthritis (SpA) also showed consistent results. CONCLUSIONS: ATD is associated with increased frequency of spinal DDD independent of BMI and TSH levels, and among those without connective tissue diseases or SpA. This finding suggests that there may be an important link between thyroid autoimmunity and spinal DDD.

The transcription, translation, transport-trail and autoimmunity: Guilt by association.

The autoimmune connective tissue diseases (ACTD) are a group of diseases which share clinical features and genetic inheritance. They are characterized by systemic autoimmunity and autoantibody production with a striking predilection for cellular components involved in transcription, translation and cellular transport. Although multiple triggers of autoimmunity have been proposed for this group of diseases including microbial agents such as viruses and bacteria, drugs, ultraviolet light, environmental toxins, stress, hormones and heavy metals, the prominence of autoantibodies to components of the transcription, translation, cellular transport-trail (TTTT) suggests that the agent(s) triggering the autoimmune response potentially utilize the TTTT. For the ACTD, viruses and viral agents are the likely triggers of autoimmunity as a result of aberrant viral latency with the production of autoantibodies to the components of the cellular TTTT machinery through multiple mechanisms, perhaps including molecular mimicry, bystander activation and epitope spreading.

Prevalence of the amyloidogenic transthyretin (TTR) V122I allele in 14 333 African-Americans.

BACKGROUND: Transthyretin (TTR) V122I (rs76992529) is one of 111 variants caused by point mutations in the coding sequence of the human TTR gene that are associated with systemic amyloidosis. It results from a G to A transition at a CG dinucleotide in codon 142(122 of the mature protein) of the gene and has been described almost exclusively in people of African descent. Several series have reported allele frequencies from 0.015 to 0.020 in African-Americans. OBJECTIVE: To define more accurately the frequency of the TTR V122I variant allele in the African-American population. METHODS: DNA isolated from blood spots from 1688 New York State African-American newborns was genotyped for the TTR V122I allele. We also compiled new data from the Jackson Heart Study and previously unpublished data from the Dallas Heart Study, plus data from a San Diego "wellness study", providing 15 650 additional allelotypes to those already reported. RESULTS: Among the New York newborns, the TTR V122I allele was present in 65/3376 alleles (allele prevalence 0.0193). The combined available data from all the non-selected African-American cohorts showed the TTR variant allele to be present in 451/26 062 alleles (allele prevalence of 0.0173), slightly but not significantly lower than our previously published estimates. CONCLUSIONS: The allele prevalence for TTR V122I in African-Americans is 0.0173. Of African-Americans under age 65, 3.43% carry at least one copy of the variant amyloidogenic allele.

Association of antithyroid peroxidase antibody with fibromyalgia in rheumatoid arthritis.

To investigate how autoimmune thyroiditis (ATD) affects the clinical presentation of established rheumatoid arthritis (RA) with particular reference to fibromyalgia and chronic widespread pain (CWP). A cohort of 204 patients with RA for whom the presence or absence of autoimmune thyroid antibodies was documented was examined for the relationships between thyroid autoantibodies and fibromyalgia or CWP. We identified 29 % who tested positive for antithyroid peroxidase antibodies (TPOAb). The anti-thyroglobulin antibody (TgAb) was found in 24 %. Among the thyroid autoantibody-positive patients, 40 % had a diagnosis of fibromyalgia or CWP versus 17 % for antibody negative patients. Logistic regression analyses (adjusted by age, sex, diabetes and BMI) indicated that TPOAb-positive patients were more likely to have fibromyalgia or CWP, with an odds ratio (OR) of 4.641, 95 % confidence interval (CI) (2.110-10.207) P < .001. Adjusting for spinal degenerative disc disease did not change the association with fibromyalgia, OR 4.458, 95 % CI (1.950-10.191), P < .001. The OR between TgAb and fibromyalgia was not significant (P > .05). Additional logistic regression analyses (adjusted by age, sex and BMI) indicated a significant relationship between TPOAb and fibromyalgia or CWP in patients without diabetes and those without hypothyroidism (OR of 4.873, 95 % CI (1.877-12.653), P = .001 and OR of 4.615 95 % CI (1.810-11.770), P = .001, respectively). There may be a positive association between the ATD antibody TPOAb, and fibromyalgia syndrome and CWP in patients with established RA.

Rheumatic symptoms in autoimmune thyroiditis.

Autoimmune thyroiditis (ATD) is generally regarded as a classic example of single organ autoimmunity with a high association with endocrine thyroid disorders. However, it is closely associated with several autoimmune diseases including rheumatologic syndromes and has long been known to have several rheumatic manifestations particularly in association with hypothyroidism. More recently, it has also been implicated in rheumatologic syndromes in the absence of hypothyroidism or subclinical hypothyroidism. There is also an emerging body of evidence that ATD is highly linked to chronic generalized pain syndromes including fibromyalgia. This review examines the rheumatic symptoms of ATD described in the current literature and discusses the clinical relevance of ATD in general rheumatology.

Fibromyalgia and chronic widespread pain in autoimmune thyroid disease.

Fibromyalgia and chronic widespread pain syndromes are among the commonest diseases seen in rheumatology practice. Despite advances in the management of these conditions, they remain significant causes of morbidity and disability. Autoimmune thyroid disease is the most prevalent autoimmune disorder, affecting about 10 % of the population, and is a recognized cause of fibromyalgia and chronic widespread pain. Recent reports are shedding light on the mechanisms of pain generation in autoimmune thyroid disease-associated pain syndromes including the role of inflammatory mediators, small-fiber polyneuropathy, and central sensitization. The gradual elucidation of these pain pathways is allowing the rational use of pharmacotherapy in the management of chronic widespread pain in autoimmune thyroid disease. This review looks at the current understanding of the prevalence of pain syndromes in autoimmune thyroid disease, their likely causes, present appreciation of the pathogenesis of chronic widespread pain, and how our knowledge can be used to find lasting and effective treatments for the pain syndromes associated with autoimmune thyroid disease.

Rheumatic manifestations of euthyroid, anti-thyroid antibody-positive patients.

The aim of this study is to define the rheumatic manifestations of euthyroid patients with chronic lymphocytic thyroiditis (CLT) but without a well-defined connective tissue disease. Forty-six consecutive patients with anti-thyroid peroxidase (αTPO) and/or anti-thyroglobulin antibodies (αTG), and normal thyroid function in the absence of a well-defined connective tissue disease were included in a case-cohort study. Arthralgias were a presenting complaint in 98 % of patients. Fibromyalgia syndrome was found in 59 % of patients. Raynaud's phenomenon occurred in 28 % and sicca symptoms in 26 % of patients. Two patients had seronegative arthritis resembling rheumatoid arthritis. Arthritis was radiographically present in 88 %, affecting the spine in 45 % of patients. Thyroid-stimulating hormone (TSH) levels positively correlated with levels of αTPO, but not with erythrocyte sedimentation rate (ESR) or αTG levels. A positive ANA was found in 24 % of patients. One patient developed subclinical hypothyroidism during the study. Rheumatic manifestations frequently occur in patients with CLT in the absence of overt thyroid dysfunction and mimic the presentation of the well-defined connective tissue diseases.

Rheumatic manifestations of autoimmune thyroid disease: the other autoimmune disease.

Autoimmune thyroid disease (AITD) is an inflammatory thyroiditis that in some cases is characterized by lymphocytic infiltration of the thyroid gland, also referred to as chronic lymphocytic thyroiditis or Hashimoto thyroiditis. Hashimoto thyroiditis is one of the commonest causes of hypothyroidism. Hypothyroidism has been associated with osteoarthritis (OA) and inflammatory forms of arthritis and with several well defined connective tissue diseases, which in turn can cause arthritis. The presence of arthritis in patients with AITD with normal thyroid function is now being increasingly recognized. There is also considerable evidence to suggest that AITD is highly associated with fibromyalgia syndrome. We review the current literature on the rheumatologic manifestations of AITD and describe the features in its presentation that set it apart from other forms of autoimmune arthritis.

JAK2 inhibition in murine systemic lupus erythematosus.

Systemic lupus erythematosus is a systemic autoimmune disease characterized by the presence of myriad autoantibodies, some with pathogenic potential, and diverse clinical manifestations. Involvement of the kidney is a major cause of morbidity and mortality in human lupus patients and in murine models of the disease. It is hoped that more specific inhibition of crucial disease pathways would improve patient response rates, while reducing the considerable rates of drug-related side effects associated with current therapy. IL-6 has a pivotal regulatory role in the development and maturation of long-lived plasma cells, one of the key cell types driving the lupus disease phenotype as the source for the majority of lupus-related autoreactive antibodies. In this study, Lu et al. target the IL-6 signal transduction pathway using a specific JAK2 inhibitor of the JAK-STAT pathway, CEP-33779. In murine lupus models, they show significant improvement in nephritis, and prolonged survival, in mice treated with CEP-33779. The study presents the promise of a novel pathway for therapeutic intervention in systemic lupus erythematosus using a medication administered orally.