JAMA Dermatology

<jats:sec id="ab-doi240049-4"><jats:title>Importance</jats:title><jats:p>Few studies have investigated the association between COVID-19 and autoimmune and autoinflammatory connective tissue disorders; however, research with long-term observation remains insufficient.</jats:p></jats:sec><jats:sec id="ab-doi240049-5"><jats:title>Objective</jats:title><jats:p>To investigate the long-term risk of autoimmune and autoinflammatory diseases after COVID-19 over an extended observation period.</jats:p></jats:sec><jats:sec id="ab-doi240049-6"><jats:title>Design, Setting, and Participants</jats:title><jats:p>This retrospective nationwide population-based study investigated the Korea Disease Control and Prevention Agency–COVID-19–National Health Insurance Service (K-COV-N) cohort. Individuals with confirmed COVID-19 from October 8, 2020, to December 31, 2022, and controls identified among individuals who participated in the general health examination in 2018 were included in the analysis.</jats:p></jats:sec><jats:sec id="ab-doi240049-7"><jats:title>Exposures</jats:title><jats:p>Confirmed COVID-19.</jats:p></jats:sec><jats:sec id="ab-doi240049-8"><jats:title>Main Outcomes and Measures</jats:title><jats:p>Incidence and risk of autoimmune and autoinflammatory connective tissue disorders in patients after COVID-19. Various covariates, such as demographic characteristics, general health data, socioeconomic status, and comorbidity profiles, were balanced using inverse probability weighting.</jats:p></jats:sec><jats:sec id="ab-doi240049-9"><jats:title>Results</jats:title><jats:p>A total of 6 912 427 participants (53.6% male; mean [SD] age, 53.39 [20.13] years) consisting of 3 145 388 with COVID-19 and 3 767 039 controls with an observational period of more than 180 days were included. Alopecia areata (adjusted hazard ratio [AHR], 1.11 [95% CI, 1.07-1.15]), alopecia totalis (AHR, 1.24 [95% CI, 1.09-1.42]), vitiligo (AHR, 1.11 [95% CI, 1.04-1.19]), Behçet disease (AHR, 1.45 [95% CI, 1.20-1.74]), Crohn disease (AHR, 1.35 [95% CI, 1.14-1.60]), ulcerative colitis (AHR, 1.15 [95% CI, 1.04-1.28]), rheumatoid arthritis (AHR, 1.09 [95% CI, 1.06-1.12]), systemic lupus erythematosus (AHR, 1.14 [95% CI, 1.01-1.28]), Sjögren syndrome (AHR, 1.13 [95% CI, 1.03-1.25]), ankylosing spondylitis (AHR, 1.11 [95% CI, 1.02-1.20]), and bullous pemphigoid (AHR, 1.62 [95% CI, 1.07-2.45]) were associated with higher risk in the COVID-19 group. Subgroup analyses revealed that demographic factors, including male and female sex, age younger than 40 years, and age 40 years and older, exhibited diverse associations with the risk of autoimmune and autoinflammatory outcomes. In addition, severe COVID-19 infection requiring intensive care unit admission, the Delta period, and not being vaccinated were associated with higher risk.</jats:p></jats:sec><jats:sec id="ab-doi240049-10"><jats:title>Conclusions and Relevance</jats:title><jats:p>This retrospective cohort study with an extended follow-up period found associations between COVID-19 and the long-term risk of various autoimmune and autoinflammatory connective tissue disorders. Long-term monitoring and care of patients is crucial after COVID-19, considering demographic factors, disease severity, and vaccination status, to mitigate these risks.</jats:p></jats:sec>

Post-acute sequelae of COVID-19: understanding and addressing the burden of multisystem manifestations.

Lancet Respir Med

Global burden of COVID-19: situational analysis and review.

Hum Antibodies

COVID-19-related acute kidney injury: incidence, risk factors and outcomes in a large UK cohort.

BMC Nephrol

COVID-19 and cardiovascular comorbidities.

Exp Clin Endocrinol Diabetes

Tüberk Toraks

COVID-19 and autoimmune diseases.

Curr Opin Rheumatol

SARS-CoV-2, the autoimmune virus.

Autoimmun Rev

Autoimmune and autoinflammatory connective tissue disorders following COVID-19.

JAMA Netw Open

Risk of autoimmune diseases following COVID-19 and the potential protective effect from vaccination: a population-based cohort study.

EClinicalMedicine

Data resource profile: the National Health Information Database of the National Health Insurance Service in South Korea.

Int J Epidemiol

Cohort Profile: The National Health Insurance Service-National Sample Cohort (NHIS-NSC), South Korea.

All-cause and cause-specific mortality risks associated with alopecia areata: a Korean nationwide population-based study.

JAMA Dermatol

Autoimmune inflammatory rheumatic diseases post–COVID-19 vaccination.

Int Immunopharmacol

Long-term cardiovascular outcomes of COVID-19.

Nat Med

Status and characteristics of the SARS-CoV-2 variant outbreak in the Republic of Korea in January 2021.

Public Health Weekly Report

A review of heart failure in patients with COVID-19.

Heart Fail Clin

Front Epidemiol

The role of cytokines and chemokines in severe acute respiratory syndrome coronavirus 2 infections.

Front Immunol

Patients with COVID-19 exhibit different immunological profiles according to their clinical presentation.

Int J Infect Dis

Characteristics and prognostic factors of disease severity in patients with COVID-19: the Beijing experience.

J Autoimmun

Prognostic value of interleukin-18 and its association with other inflammatory markers and disease severity in COVID-19.

Cytokine

Autoimmunity, COVID-19 Omicron variant, and olfactory dysfunction: a literature review.

Diagnostics (Basel)

The Omicron (B.1.1.529) SARS-CoV-2 variant of concern does not readily infect Syrian hamsters.

Antiviral Res

Clinical and experimental evidence suggest Omicron variant of SARS-CoV-2 is inherently less pathogenic than delta variant independent of previous immunity.

Eur J Med Res

Risk of autoimmune diseases in patients with COVID-19: a retrospective cohort study.

Vaccine-induced autoimmunity: the role of molecular mimicry and immune crossreaction.

Cell Mol Immunol

Infection and Autoimmunity

A possible role for autoimmunity through molecular mimicry in alphavirus mediated arthritis.

Sci Rep

Untangling COVID-19 and autoimmunity: identification of plausible targets suggests multi organ involvement.

Mol Immunol

SARS-CoV-2–specific immune response and the pathogenesis of COVID-19.

Int J Mol Sci

Molecular mimicry, bystander activation, or viral persistence: infections and autoimmune disease.

Clin Microbiol Rev

Systems immunology analysis reveals the contribution of pulmonary and extrapulmonary tissues to the immunopathogenesis of severe COVID-19 patients.

The type I interferon response in COVID-19: implications for treatment.

Nat Rev Immunol

Systemic lupus erythematosus after coronavirus disease-2019 (COVID-19) infection: case-based review.

Egypt Rheumatol

New onset systemic lupus erythematosus after COVID-19 infection: a case report.

AME Case Rep

New diagnosis of systemic lupus erythematosus after COVID-19 vaccination: a case report and review of literature.

JAAD Case Rep

Axial spondylarthritis following COVID-19 infection.

BMJ Case Rep

Rheumatoid arthritis occurring after coronavirus disease 2019 (COVID-19) infection: case based review.

COVID-19 infection and rheumatoid arthritis: mutual outburst cytokines and remedies.

Curr Med Res Opin

Analysis of the potential relationship between COVID-19 and Behcet’s disease using transcriptome data.

Medicine (Baltimore)

Rheumatologists’ perspective on coronavirus disease 19 (COVID-19) and potential therapeutic targets.

Clin Rheumatol

New-onset vitiligo following COVID-19 disease.

Skin Health Dis

Vitiligo following COVID-19: a case report and review of pathophysiology.

Vitiligo pathogenesis and emerging treatments.

Dermatol Clin

Virol Immunol J

COVID-19 and oxidative stress.

Biochemistry (Mosc)

New-onset bullous pemphigoid in a COVID-19 patient.

Case Rep Dermatol Med

Bullous pemphigoid outcome is associated with CXCL10-induced matrix metalloproteinase 9 secretion from monocytes and neutrophils but not lymphocytes.

J Allergy Clin Immunol

Three case reports of post immunization and post viral Bullous Pemphigoid: looking for the right trigger.

BMC Pediatr

Few studies have investigated the association between COVID-19 and autoimmune and autoinflammatory connective tissue disorders; however, research with long-term observation remains insufficient.
To investigate the long-term risk of autoimmune and autoinflammatory diseases after COVID-19 over an extended observation period.
This retrospective nationwide population-based study investigated the Korea Disease Control and Prevention Agency-COVID-19-National Health Insurance Service (K-COV-N) cohort. Individuals with confirmed COVID-19 from October 8, 2020, to December 31, 2022, and controls identified among individuals who participated in the general health examination in 2018 were included in the analysis.
Confirmed COVID-19.
Incidence and risk of autoimmune and autoinflammatory connective tissue disorders in patients after COVID-19. Various covariates, such as demographic characteristics, general health data, socioeconomic status, and comorbidity profiles, were balanced using inverse probability weighting.
A total of 6 912 427 participants (53.6% male; mean [SD] age, 53.39 [20.13] years) consisting of 3 145 388 with COVID-19 and 3 767 039 controls with an observational period of more than 180 days were included. Alopecia areata (adjusted hazard ratio [AHR], 1.11 [95% CI, 1.07-1.15]), alopecia totalis (AHR, 1.24 [95% CI, 1.09-1.42]), vitiligo (AHR, 1.11 [95% CI, 1.04-1.19]), Behçet disease (AHR, 1.45 [95% CI, 1.20-1.74]), Crohn disease (AHR, 1.35 [95% CI, 1.14-1.60]), ulcerative colitis (AHR, 1.15 [95% CI, 1.04-1.28]), rheumatoid arthritis (AHR, 1.09 [95% CI, 1.06-1.12]), systemic lupus erythematosus (AHR, 1.14 [95% CI, 1.01-1.28]), Sjögren syndrome (AHR, 1.13 [95% CI, 1.03-1.25]), ankylosing spondylitis (AHR, 1.11 [95% CI, 1.02-1.20]), and bullous pemphigoid (AHR, 1.62 [95% CI, 1.07-2.45]) were associated with higher risk in the COVID-19 group. Subgroup analyses revealed that demographic factors, including male and female sex, age younger than 40 years, and age 40 years and older, exhibited diverse associations with the risk of autoimmune and autoinflammatory outcomes. In addition, severe COVID-19 infection requiring intensive care unit admission, the Delta period, and not being vaccinated were associated with higher risk.
This retrospective cohort study with an extended follow-up period found associations between COVID-19 and the long-term risk of various autoimmune and autoinflammatory connective tissue disorders. Long-term monitoring and care of patients is crucial after COVID-19, considering demographic factors, disease severity, and vaccination status, to mitigate these risks.

Long-Term Risk of Autoimmune and Autoinflammatory Connective Tissue Disorders Following COVID-19.

Long-Term Risk of Autoimmune and Autoinflammatory Connective Tissue Disorders Following COVID-19

<jats:sec id="ab-doi230037-4"><jats:title>Importance</jats:title><jats:p>Data on the association between atopic dermatitis (AD) and inflammatory bowel disease (IBD) are inconsistent. Few studies have examined the association of AD or AD severity with risk of ulcerative colitis (UC) and Crohn disease (CD) separately.</jats:p></jats:sec><jats:sec id="ab-doi230037-5"><jats:title>Objectives</jats:title><jats:p>To examine the risk of new-onset IBD, UC, and CD in children and adults with AD.</jats:p></jats:sec><jats:sec id="ab-doi230037-6"><jats:title>Design, Setting, and Participants</jats:title><jats:p>This population-based cohort study assessed patients with AD matched with up to 5 controls on age, practice, and index date. Treatment exposure was used as a proxy for AD severity. Data were retrieved from The Health Improvement Network, a UK electronic medical record database, for January 1, 1994, to February 28, 2015. Data analysis was performed from January 8, 2020, to June 30, 2023.</jats:p></jats:sec><jats:sec id="ab-doi230037-7"><jats:title>Main Outcomes and Measures</jats:title><jats:p>Outcomes of interest were incident IBD, UC, and CD. Logistic regression was used to examine the risk for each outcome in children and adults with AD compared with controls.</jats:p></jats:sec><jats:sec id="ab-doi230037-8"><jats:title>Results</jats:title><jats:p>A total of 1 809 029 pediatric controls were matched to 409 431 children with AD (93.2% mild, 5.5% moderate, and 1.3% severe). The pediatric cohort ranged in median age from 4 to 5 years (overall range, 1-10 years), was predominantly male (936 750 [51.8%] controls, 196 996 [51.6%] with mild AD, 11 379 [50.7%] with moderate AD, and 2985 [56.1%] with severe AD), and with similar socioeconomic status. A total of 2 678 888 adult controls were matched to 625 083 adults with AD (65.7% mild, 31.4% moderate, and 2.9% severe). The adult cohort ranged in median age from 45 to 50 years (overall range, 30-68 years) and was predominantly female (1 445 589 [54.0%] controls, 256 071 [62.3%] with mild AD, 109 404 [55.8%] with moderate AD, and 10 736 [59.3%] with severe AD). In fully adjusted models, children with AD had a 44% increased risk of IBD (hazard ratio [HR], 1.44; 95% CI, 1.31-1.58) and a 74% increased risk of CD (HR, 1.74; 95% CI, 1.54-1.97), which increased with worsening AD; however, they did not have increased risk of UC (HR, 1.09; 95% CI, 0.94-1.27) except for those with severe AD (HR, 1.65; 95% CI, 1.02-2.67). Adults with AD had a 34% (HR, 1.34; 95% CI, 1.27-1.40) increased risk of IBD, a 36% (HR, 1.36; 95% CI, 1.26-1.47) increased risk of CB, and a 32% (HR, 1.32; 95% CI, 1.24-1.41) increased risk of UC, with risk increasing with worsening AD.</jats:p></jats:sec><jats:sec id="ab-doi230037-9"><jats:title>Conclusion and Relevance</jats:title><jats:p>In this cohort study, children and adults with AD had an increased risk of IBD, with risk varying by age, AD severity, and IBD subtype. These findings provide new insights into the association between AD and IBD. Clinicians should be aware of these risks, particularly when selecting systemic treatments for AD in patients who may have coincident gastrointestinal symptoms.</jats:p></jats:sec>

Real-world comorbidities of atopic dermatitis in the pediatric ambulatory population in the United States.

J Am Acad Dermatol

Major comorbidities of atopic dermatitis: beyond allergic disorders.

Am J Clin Dermatol

Real-world comorbidities of atopic dermatitis in the US adult ambulatory population.

Atopic dermatitis does not increase the risk of inflammatory bowel disease: a nationwide cohort study.

J Dermatol

Autoimmune disease comorbidities in patients with atopic dermatitis: a nationwide case-control study in Taiwan.

Pediatr Allergy Immunol

Bidirectional relationship between atopic dermatitis and inflammatory bowel disease: a systematic review and meta-analysis.

Inflammatory bowel disease is associated with an increased risk of inflammatory skin diseases: a population-based cross-sectional study.

Autoimmune disease concomitance among inflammatory bowel disease patients in the United States, 2001-2002.

Inflamm Bowel Dis

Autoimmune diseases in adults with atopic dermatitis.

Association between atopic dermatitis and autoimmune disorders in US adults and children: a cross-sectional study.

Occurrence of inflammatory bowel disease in patients with chronic inflammatory skin diseases: a cohort study.

Br J Dermatol

Comorbidities in adolescents with inflammatory bowel disease: findings from a population-based cohort study.

Pediatr Res

New-onset inflammatory bowel disease in adults with atopic dermatitis.

J Eur Acad Dermatol Venereol

An association between ulcerative colitis and atopic dermatitis, diseases of impaired superficial barriers.

J Invest Dermatol

Approach to the management of recently diagnosed inflammatory bowel disease patients: a user’s guide for adult and pediatric gastroenterologists.

Gastroenterology

The Read clinical classification.

Risk factors for diagnosis of psoriatic arthritis, psoriasis, rheumatoid arthritis, and ankylosing spondylitis: a set of parallel case-control studies.

J Rheumatol

Development and validation of an algorithm to accurately identify atopic eczema patients in primary care electronic health records from the UK.

Validity of psoriatic arthritis and capture of disease modifying antirheumatic drugs in the health improvement network.

Pharmacoepidemiol Drug Saf

Validation studies of the health improvement network (THIN) database for pharmacoepidemiology research.

Validity and completeness of the General Practice Research Database for studies of inflammatory bowel disease.

Risk of herpesvirus, serious and opportunistic infections in atopic dermatitis: a population-based cohort study.

Severe and predominantly active atopic eczema in adulthood and long term risk of cardiovascular disease: population based cohort study.

Atopic eczema in adulthood and mortality: UK population-based cohort study, 1998-2016.

Atopic eczema and obesity: a population-based study.

Association between atopic eczema and cancer in England and Denmark.

Atopic eczema and fracture risk in adults: a population-based cohort study.

Atopic eczema in adulthood and risk of depression and anxiety: a population-based cohort study.

J Allergy Clin Immunol Pract

Model building strategy for logistic regression: purposeful selection.

Ann Transl Med

Sensitivity analysis in observational research: introducing the E-value.

Ann Intern Med

Atopic dermatitis is associated with an increased risk for rheumatoid arthritis and inflammatory bowel disease, and a decreased risk for type 1 diabetes.

Atopic diseases are associated with development of inflammatory bowel diseases in Korea: a nationwide population-based study.

Clin Gastroenterol Hepatol

The bidirectional association between inflammatory bowel disease and atopic dermatitis: a systematic review and meta-analysis.

Dermatology

The pathogenicity of Th17 cells in autoimmune diseases.

Semin Immunopathol

Immunological decision-making: how does the immune system decide to mount a helper T-cell response?

Immunology

IL-25 (IL-17E) in epithelial immunology and pathophysiology.

Roles of IL-25 in type 2 inflammation and autoimmune pathogenesis.

IL-25 regulates Th17 function in autoimmune inflammation.

J Exp Med

Interleukin-25 inhibits interleukin-12 production and Th1 cell-driven inflammation in the gut.

Clinical presentation of Crohn’s, ulcerative colitis, and indeterminate colitis: symptoms, extraintestinal manifestations, and disease phenotypes.

Semin Pediatr Surg

Specificities of inflammatory bowel disease in childhood.

Best Pract Res Clin Gastroenterol

Differentiating ulcerative colitis from Crohn disease in children and young adults: report of a working group of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition and the Crohn’s and Colitis Foundation of America.

J Pediatr Gastroenterol Nutr

Endoscopic rectal sparing in children with untreated ulcerative colitis.

Indeterminate colitis: a significant subgroup of pediatric IBD.

Diagnostic considerations in pediatric inflammatory bowel disease management.

Gastroenterol Hepatol (N Y)

NOD2 and inflammation: current insights.

J Inflamm Res

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Nature

A frameshift mutation in NOD2 associated with susceptibility to Crohn’s disease.

Aberrant expression of bacterial pattern recognition receptor NOD2 of basophils and microbicidal peptides in atopic dermatitis.

Molecules

NOD2 and TLR2 ligands trigger the activation of basophils and eosinophils by interacting with dermal fibroblasts in atopic dermatitis-like skin inflammation.

Incidence and prevalence of inflammatory bowel disease in UK primary care: a population-based cohort study.

BMJ Open

Atopic eczema and major cardiovascular outcomes: a systematic review and meta-analysis of population-based studies.

Changing patterns in the epidemiology and outcomes of inflammatory bowel disease in the United Kingdom: 2000-2018.

Aliment Pharmacol Ther

Data on the association between atopic dermatitis (AD) and inflammatory bowel disease (IBD) are inconsistent. Few studies have examined the association of AD or AD severity with risk of ulcerative colitis (UC) and Crohn disease (CD) separately.
To examine the risk of new-onset IBD, UC, and CD in children and adults with AD.
This population-based cohort study assessed patients with AD matched with up to 5 controls on age, practice, and index date. Treatment exposure was used as a proxy for AD severity. Data were retrieved from The Health Improvement Network, a UK electronic medical record database, for January 1, 1994, to February 28, 2015. Data analysis was performed from January 8, 2020, to June 30, 2023.
Outcomes of interest were incident IBD, UC, and CD. Logistic regression was used to examine the risk for each outcome in children and adults with AD compared with controls.
A total of 1 809 029 pediatric controls were matched to 409 431 children with AD (93.2% mild, 5.5% moderate, and 1.3% severe). The pediatric cohort ranged in median age from 4 to 5 years (overall range, 1-10 years), was predominantly male (936 750 [51.8%] controls, 196 996 [51.6%] with mild AD, 11 379 [50.7%] with moderate AD, and 2985 [56.1%] with severe AD), and with similar socioeconomic status. A total of 2 678 888 adult controls were matched to 625 083 adults with AD (65.7% mild, 31.4% moderate, and 2.9% severe). The adult cohort ranged in median age from 45 to 50 years (overall range, 30-68 years) and was predominantly female (1 445 589 [54.0%] controls, 256 071 [62.3%] with mild AD, 109 404 [55.8%] with moderate AD, and 10 736 [59.3%] with severe AD). In fully adjusted models, children with AD had a 44% increased risk of IBD (hazard ratio [HR], 1.44; 95% CI, 1.31-1.58) and a 74% increased risk of CD (HR, 1.74; 95% CI, 1.54-1.97), which increased with worsening AD; however, they did not have increased risk of UC (HR, 1.09; 95% CI, 0.94-1.27) except for those with severe AD (HR, 1.65; 95% CI, 1.02-2.67). Adults with AD had a 34% (HR, 1.34; 95% CI, 1.27-1.40) increased risk of IBD, a 36% (HR, 1.36; 95% CI, 1.26-1.47) increased risk of CB, and a 32% (HR, 1.32; 95% CI, 1.24-1.41) increased risk of UC, with risk increasing with worsening AD.
In this cohort study, children and adults with AD had an increased risk of IBD, with risk varying by age, AD severity, and IBD subtype. These findings provide new insights into the association between AD and IBD. Clinicians should be aware of these risks, particularly when selecting systemic treatments for AD in patients who may have coincident gastrointestinal symptoms.

Risk of Inflammatory Bowel Disease in Patients With Atopic Dermatitis.

Risk of Inflammatory Bowel Disease in Patients With Atopic Dermatitis

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