Connective Tissue Diseases

TUESDAY, Oct. 10, 2023 (HealthDay News) -- COVID-19 is associated with an increased risk for autoimmune and autoinflammatory connective tissue disorders, according to a study published online Oct. 6 in JAMA Network Open.Sung Ha Lim, M.D., from the Yonsei University Wonju College of Medicine in South Korea, and colleagues examined the incidences and risks for autoimmune and autoinflammatory connective tissue disorders after COVID-19 in a retrospective population-based study. The analyses included 354,527 individuals with COVID-19 and 6,134,940 controls.The researchers found that the COVID-19 group had significantly increased risks for alopecia areata, alopecia totalis, antineutrophil cytoplasmic antibody-associated vasculitis, Crohn disease, and sarcoidosis (adjusted hazard ratios [95 percent confidence intervals], 1.12 [1.05 to 1.19], 1.74 [1.39 to 2.17], 2.76 [1.64 to 4.65], 1.68 [1.31 to 2.15], and 1.59 [1.00 to 2.52], respectively). The severity of COVID-19 was associated with the risks for alopecia totalis, psoriasis, vitiligo, vasculitis, Crohn disease, ulcerative colitis, rheumatoid arthritis, adult-onset Still disease, Sjögren syndrome, ankylosing spondylitis, and sarcoidosis."Our study comprehensively investigated the risks of autoimmune and autoinflammatory connective tissue disorders in patients with COVID-19 compared with controls, highlighting these disorders as potential post-COVID-19 sequelae," the authors write. "Long-term management of patients with COVID-19 should include evaluation of subsequent development of autoimmune and autoinflammatory connective tissue disorders."

Autoimmune, Autoinflammatory Connective Tissue Disorders Increased After COVID-19

WEDNESDAY, June 28, 2023 -- Systemic sclerosis (SSc) sine scleroderma (ssSSc) accounts for almost 10 percent of patients with SSc, according to a study published online June 28 in JAMA Dermatology.Alain Lescoat, M.D., Ph.D., from the University of Rennes in France, and colleagues characterized the clinical phenotype of patients with ssSSc compared with patients with limited cutaneous SSc (lcSSc) and diffuse cutaneous SSc (dcSSc) in a study based on information from the international EUSTAR database.Data were included for 4,263 patients with SSc; 376 (8.8 percent) were classified as having ssSSc. The researchers found that at the last available visit, patients with ssSSc had a lower prevalence of previous or current digital ulcers compared to the 708 patients with lcSSc and 708 patients with dcSSc (28.2 percent versus 53.1 and 68.3 percent, respectively) and lower prevalence of puffy fingers (63.8 percent versus 82.4 and 87.6 percent, respectively). The prevalence of interstitial lung disease was similar in ssSSc and lcSSc and was significantly higher in dcSSc (49.8 and 57.1 percent, respectively, versus 75.0 percent). In ssSSc, skin telangiectasias were associated with diastolic dysfunction (odds ratio, 4.778). Positivity for anti-Scl-70 antibodies was the only independent factor for the onset of skin fibrosis in ssSSc (odds ratio, 3.078). After up to 15 years of follow-up, the survival rate was higher in patients with ssSSc versus lcSSc and dcSSc (92.4 percent versus 69.4 and 55.5 percent, respectively)."The positivity for anti-Scl-70 was the only independent parameters associated with the onset of skin fibrosis in ssSSc, strengthening the relevance of antibody subtypes to predict the trajectory of skin involvement in patients with SSc," the authors write.Several authors disclosed ties to the biopharmaceutical industry.

Patients with ssSSC had lower prevalence of previous or current digital ulcers, puffy fingers compared to those with lcSSc, dcSSc

Systemic Sclerosis Sine Scleroderma Accounts for ~10 Percent With Systemic Sclerosis

The Morphea Activity Measure (MAM) scoring tool is reliable and valid for measuring pediatric morphea disease activity, according to a study published online Feb. 8 in
 
 JAMA Dermatology
 
 .




 Maria Teresa García-Romero, M.D., M.P.H., from the National Institute of Pediatrics in Mexico City, and colleagues developed and validated the MAM scoring tool to evaluate morphea disease activity for use in clinical and research settings.




 Fourteen survey respondents who were experts in morphea were involved in the development phase. A final tool was developed after two rounds using a Delphi consensus method, which included 10 items that were indicative of morphea activity. The researchers conducted a validation phase among 14 patients, two dermatologists, and six pediatric dermatologists. Good interrater and intrarater agreement was seen for MAM total scores, with intraclass correlation coefficients of 0.844 and 0.856, respectively. Moderately strong correlations were seen between the MAM and the modified Localized Scleroderma Severity Index and Physician Global Assessment of Activity. In qualitative interviews, evaluators agreed that the tool was easy to use, measured morphea disease activity at a single time point, and should be responsive to changes in disease activity over time.




 "The MAM has potential as an outcome measure for use in both clinical and research settings," the authors write. "Further study, including a larger validation study and longitudinal testing to measure responsiveness to change, is warranted."




 Several authors disclosed financial ties to the biopharmaceutical and medical technology industries.




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Moderately strong correlations seen between MAM and modified Localized Scleroderma Severity Index, Physician Global Assessment of Activity

Morphea Activity Measure Reliable, Valid for Disease Activity

Lenabasum is well tolerated for the treatment of amyopathic dermatomyositis, according to a phase 2 study published online Oct. 1 in the
 
 Journal of Investigative Dermatology
 
 .




 Victoria P. Werth, M.D., from the University of Pennsylvania Perelman School of Medicine in Philadelphia, and colleagues evaluated the safety and efficacy of lenabasum in patients with refractory cutaneous dermatomyositis. The analysis included 22 participants randomly assigned to lenabasum (11 participants) or placebo (11 participants) for a regimen of lenabasum daily for 28 days (all participants) and then either lenabasum or placebo twice per day for 56 days.




 The researchers observed no serious or severe adverse events related to lenabasum, and no participants discontinued the study. In the lenabasum group, the adjusted least-squares mean for Cutaneous Dermatomyositis Disease Area and Severity Index activity decreased more, with the difference reaching significance on day 113.




 "Current treatments, which are limited and can involve frequent and costly intravenous infusions, are not always effective in treating its dermatological manifestations and can produce side effects," Werth said in a statement. "Our research showed that the cannabinoid receptor type 2 agonist lenabasum works to improve the skin of patients with amyopathic dermatomyositis in a short period of time. The identification of a well tolerated and effective oral medication greatly expands treatment options for patients with refractory skin disease."




 The study was partially funded by Corbus Pharmaceuticals, the developer of lenabasum, and several authors disclosed financial ties to the company.




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Results of phase 2 study suggest clinical benefit and favorable safety profile, warranting further study of lenabasum for DM

Lenabasum Studied for Refractory Cutaneous Dermatomyositis

For patients with cutaneous lupus erythematosus (CLE), normal-appearing skin is a type I interferon-rich, prelesional environment, according to a study published in the April 27 issue of
 
 Science Translational Medicine
 
 .




 Allison C. Billi, M.D., Ph.D., from the University of Michigan in Ann Arbor, and colleagues analyzed normal-appearing skin, lesional skin, and circulating immune cells from lupus patients via integrated single-cell RNA sequencing and spatial RNA sequencing to examine CLE immunopathogenesis.




 The researchers found that in patients with lupus, normal-appearing skin represented a type I interferon-rich, prelesional environment. Interferon-induced gene expression changes were seen in all major skin cell types and altered predicted cell-cell communication networks. In addition, lupus-enriched CD16 dendritic cells underwent interferon education in the skin, yielding proinflammatory phenotypes.




 "These interferon-educated immune cells seem to be priming many different cell types in the skin to overreact to stimuli with excessive inflammatory responses, manifesting as disfiguring skin lesions," Billi said in a statement. "We don't yet know all of the stimuli that can tip the balance and precipitate these rashes, but ultraviolet light certainly appears to be one of them."




 Several authors disclosed financial ties to the biopharmaceutical industry.




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Normal-appearing skin is type I interferon-rich environment; interferon-induced gene expression changes seen in all major skin type cells

Normal-Looking Skin Involved in Cutaneous Lupus Erythematosus

How do you dose IVIG for dermatomyositis with and without myopathy?

The dose of IVIG for DM is sort of same for whether it's skin or muscle, and it is 2 grams/kg total dose, which can be equally divided on anything from two to five days. In my practice I do divide that over a three day period, and I repeat it every four weeks for the first six months. And depending on clinical response, after six months, if a patient has sort of either gone into remission or they've improved complete significantly, you can decrease the dose to 1 gram per kg body weight again on three divided three days. So IVIg is a good option for both DM with or without muscle involvement, and certainly for skin DM it's very efficacious.

For patients with extensive skin disease from dermatomyositis, are you still trying traditional immunosuppressants prior to moving to IVIG?

I do move to IVIG a lot sooner. IviG was approved recently by the FDA for dermatomycitis, so that certainly made it easier to get insurance approval. Pre FDA approval. Getting IViG was a little hard, and the insurance sort of made you go through the wringer of trying other immune suppressants. But certainly IVig has a great role in skin DM, which isn't responsive to other immune therapies. So I really move to IVIG sometimes even as a first step if a patient has really bad DM involving the skin, and often as a second line if they haven't responded to one conventional immune suppressant, just because sometimes insurance gives me a hard time.

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How do you dose IVIG for dermatomyositis with and without myopathy?

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For patients with extensive skin disease from dermatomyositis, are you still trying traditional immunosuppressants prior to moving to IVIG?

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