TWENTY-NINTH ISSUE
March 1, 2023
Long-term Outcomes After Rituximab Treatment for Patients With Systemic Sclerosis: Follow-up of the DESIRES Trial With a Focus on Serum Immunoglobulin Levels
JAMA Dermatology
Patients may have their DESIRES granted with Rituximab for systemic sclerosis!
Systemic sclerosis (SSc) is being treated with rituximab with increasing frequency. However, long-term treatment response and markers of such response are unknown. In a single-center extension study of the DESIRES trial, 29 patients with SSc continued to receive IV rituximab (375 mg/m2) every 4 weeks, for a total of 96 weeks.
What did they find?
Main Takeaways: Long-term rituximab treatment may improve skin and lung fibrosis in SSc. This response may be correlated with low serum immunoglobulins.
Systemic sclerosis (SSc) is being treated with rituximab with increasing frequency. However, long-term treatment response and markers of such response are unknown. In a single-center extension study of the DESIRES trial, 29 patients with SSc continued to receive IV rituximab (375 mg/m2) every 4 weeks, for a total of 96 weeks.
What did they find?
- Significant improvement in modified Rodan skin score (MRSS), a measure of skin sclerosis, after 1 and 3 rounds of rituximab (median IQR change -7 (-8.5 to -4), p<0.001), which was sustained through 96 weeks
- Improvement in MRSS was significantly correlated with decrease in serum IgA levels (r = 0.64, p<0.001)
- Significant improvement in forced vital capacity (FVC%), a measure of lung function, after 1 and 3 rounds of rituximab (median IQR change 1.85 (0.13 - 5.68), p<0.001), which was sustained through 96 weeks
- Greater improvement in FVC% predicted was associated with a lower IgM (median [IQR] change 7.2 [3.8-8.9] IgM vs 3.6 [1.4-6.2] IgG and IgA, p=.003)
Main Takeaways: Long-term rituximab treatment may improve skin and lung fibrosis in SSc. This response may be correlated with low serum immunoglobulins.
A scoring system for assessing risk of discoid lupus erythematosus progression to severe systemic lupus erythematosus
Journal of The American Academy of Dermatology
Lupus progression… hanDLE with care!
Discoid lupus erythematosus (DLE) is the most common form of cutaneous lupus erythematosus (CLE), an autoimmune skin condition that can progress to systemic lupus erythematosus (SLE). Researchers wanted to know which risk factors are the most likely predictors of disease progression to severe SLE (sSLE).
In a retrospective cohort study, researchers analyzed 30 patients with DLE who progressed to sSLE and 134 patients who did not.
What did they find?
Main Takeaway: Patients who were ≤ 25 at time of DLE diagnosis, were Fitzpatrick phototypes V or VI, or had ANA titers of ≥ 1:320 were found to have a higher risk of progression to sSLE.
Discoid lupus erythematosus (DLE) is the most common form of cutaneous lupus erythematosus (CLE), an autoimmune skin condition that can progress to systemic lupus erythematosus (SLE). Researchers wanted to know which risk factors are the most likely predictors of disease progression to severe SLE (sSLE).
In a retrospective cohort study, researchers analyzed 30 patients with DLE who progressed to sSLE and 134 patients who did not.
What did they find?
- Factors associated with increased risk of progression to sSLE included:
- age ≤ 25 years at the time of DLE diagnosis (OR, 2.8; 95% CI, 1.1-7.0)
- Fitzpatrick phototypes V or VI (OR, 2.7; 95% CI, 1.1- 7.0)
- ANA titers of ≥ 1:320 (OR, 15; 95% CI, 3.3- 67.3)
- Using the above 3 factors, researchers created a scoring system by weighting each variable according to its odds ratio (OR), with a score of 0 conferring no risk of developing sSLE and higher scores conferring increased risk
- The scoring system had a high negative predictive value (NPV) but lower positive predictive value (PPV); a score of ≤ 1 was associated with a NPV of 100% and a PPV of 31%, whereas a score of 6 was associated with a NPV of 89% and a PPV of 47%
- There was a 40% risk of progression to sSLE among patients who scored 6 or higher
Main Takeaway: Patients who were ≤ 25 at time of DLE diagnosis, were Fitzpatrick phototypes V or VI, or had ANA titers of ≥ 1:320 were found to have a higher risk of progression to sSLE.
The p300/CBP Inhibitor A485 Normalizes Psoriatic Fibroblast Gene Expression In Vitro and Reduces Psoriasis-Like Skin Inflammation In Vivo
Journal of Investigative Dermatology
“I have an epigenetics joke but it may leave an imprint on you” –DrChromo
Psoriasis is a chronic inflammatory skin disease characterized by well-demarcated plaques with an overlying silvery scale. Fibroblasts have an important role in regulating the immune response and are thought to play a role in psoriasis. Interestingly, psoriasis tends to affect certain areas more than others (for example, the extensor surfaces). This tendency to recur in the same regions suggests a role of epigenetic changes (meaning changes to gene expression without changing the actual DNA sequence; think chromatin remodeling, histone modifications, DNA methylation, etc.) in the affected skin.
What did they find?
Main Takeaway: Epigenetics plays a role in psoriasis and targeting epigenetic reprogramming may be an exciting new therapeutic avenue to pursue.
Psoriasis is a chronic inflammatory skin disease characterized by well-demarcated plaques with an overlying silvery scale. Fibroblasts have an important role in regulating the immune response and are thought to play a role in psoriasis. Interestingly, psoriasis tends to affect certain areas more than others (for example, the extensor surfaces). This tendency to recur in the same regions suggests a role of epigenetic changes (meaning changes to gene expression without changing the actual DNA sequence; think chromatin remodeling, histone modifications, DNA methylation, etc.) in the affected skin.
What did they find?
- When growing cells from psoriatic lesions in vitro, fibroblasts continued to appear abnormally, even after several passages
- Transcriptomic profiling of fibroblasts from psoriatic skin identified the upregulation of several genes, such as ITGA4 and a spliced form of fibronectin EDA FN
- Screening of small-molecule epigenetic modifying drugs identified that CBP/p300 inhibitors were capable of reducing expression of aberrantly upregulated genes in psoriatic fibroblasts, including ITGA4 and EDA FN
- Administration of CBP/p300 inhibitors to a mouse model of psoriasis reduced skin inflammation, immune cell recruitment, and the production of inflammatory cytokines
Main Takeaway: Epigenetics plays a role in psoriasis and targeting epigenetic reprogramming may be an exciting new therapeutic avenue to pursue.
innovations in dermatology
This Article Will Scratch Your Itch!
Atopic dermatitis (AD) is a common, chronic inflammatory skin disease that typically manifests in childhood and may proceed to adulthood. Pruritis in AD induces scratching which furthers the redness and inflammation to the area, leading to a cycle of flare ups and remissions. Previously, a group of researchers designed an advanced acousticmechanic wearable sensor (ADAM) mounted to the dorsal hand to detect scratching in a pediatric cohort with high accuracy. To further evolve this innovation, the researchers have developed an AI-algorithm that quantifies scratching occurrences and sleep metrics for adults with AD.
What did they find?
- Home sleep monitoring was performed on 11 participants with AD through wearing the ADAM sensor on the dorsum of the dominant hand, as well as through infrared camera footage
- The AI-algorithm was proven to detect nocturnal scratch events with a 93% sensitivity and 100% specificity
- This ADAM device allowed researchers to determine a relationship between scratch events per hour and total sleep time (TST, R=-0.69) as well as scratch events per night and TST (R=-0.54), which had been challenging with other wrist mounted systems
- A correlation was found between increased scratch events and increased wake after sleep onset (R=0.64)
Limitations: A small sample size of patients with AD was utilized for this study. Creating a larger sample size will enhance the validity and reliability of the AI-algorithm.
Main takeaway: Use of ADAM sensor in conjunction with an AI-algorithm will be useful to clinically evaluate scratching behavior in diseases where itch is prominent and can further physician decision making when treating patients.
