Genetics

RT @ericdeinmd Mucosal Hypothesis RA #RNL26 Demoruelle ACPA can predate RA development Nam et al: non-specific jt pain: 42% developed RA in 12 mos Circiumaro et al: MSK complaints 38% devel RA in 36 mo APIPPRA: 29% at 12 mo, 37% at 24 mo, StopRA 18% in 12 mo, 33% at 36 mo https://t.co/DxGhhFL1gO
Dr. John Cush @RheumNow( View Tweet )
RT @ericdeinmd Mortality risk in RA #RNL26 Myasoedova Premature deaths in up to 1/4 of pts Decline in mortality in RA after year 2000 Full siblings of RA also high mortality (shared genetic or environ factors affect risk?) Risks: Seropositivity, esp ACPA, CRP, extra-artic https://t.co/ytm6odmtgR
Dr. John Cush @RheumNow( View Tweet )
The challenge may be that lupus has multiple endotypes with variable rates of progression/trajectories. Can you Prevent SLE? Dr. David Karp lecturing at UTSW @drdavidkarp @utswrheum https://t.co/BA4KRKebIv
Dr. John Cush @RheumNow( View Tweet )
RA outcomes according to onset: typica RA vs undifferentiated inflam arthritis (UIA) or palindromic rheumatism (PR). Progress to RA = RA > UIA > PR. PR has more +FHx & ACPA; UIA more females w/ Knee Sxs. Best remission rates w/ PR onsets. https://t.co/JJRCdKcs1u https://t.co/n385f6EF59

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Dr. John Cush @RheumNow( View Tweet )
🧬 PAPA Syndrome: When Sterile Inflammation Mimics Infection (Pyogenic Arthritis, Pyoderma gangrenosum, Acne) •A rare monogenic autoinflammatory disease •Caused by gain-of-function mutations in PSTPIP1 🧠 Pathophysiology •Mutant PSTPIP1 → increased interaction with pyrin https://t.co/tJ4INdgfky

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Ravi Kumar @RheumattDoc( View Tweet )
A 2 yr. old female pt reported w/ a a novel P435S gain-of-function variant in TLR7 (thought pathogenic in SLE) - pt dx w/ juvenile SLE, recurrent infection, and neuroinflammatory features. A review of 12 other TLR7 GOF variants revealed similar SLE associations. https://t.co/NU553QwCtj
Dr. John Cush @RheumNow( View Tweet )
2025

The 2025 Rheumatology Year in Review

Jack Cush, MD

The year 2025 presented numerous advances in rheumatology and related inflammatory and autoimmune disorders ranging from several new groundbreaking FDA approvals/indications, drug developments, game-changing guidelines and practices that will impact patient care for rheumatic diseases.

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A 2 yr. old female pt reported w/ a a novel P435S gain-of-function variant in TLR7 (thought pathogenic in SLE) - pt dx w/ juvenile SLE, recurrent infection, and neuroinflammatory features. A review of 12 other TLR7 GOF variants revealed similar SLE associations. https://t.co/TGgKDQ0D7F
Dr. John Cush @RheumNow( View Tweet )
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2026 Resolutions (1.9.2026)

Jack Cush, MD

Dr. Jack Cush reviews the news, announcements and journal articles from this past week on RheumNow.com. More on Variable bendability, a better way to treat RA, and a novel advance for GLP1a in PsA; and 2026 Resolutions!

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HLA-B27: still the most important genetic factor in axSpA susceptibility, but has lower frequency African American, South American & Middle Eastern pop. B27 discerns clinical subsets of SpA and PsA, particularly acute anterior uveitis or axSpA with psoriasis, https://t.co/Yg7DBOTW8o
Dr. John Cush @RheumNow( View Tweet )
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Disease Activity Criteria for Adult-Onset Still's Disease: EULAR Points to Consider

Jack Cush, MD

EULAR has published a "points to consider" (PtCs) guidance on the development of criteria for the assessment of the disease activity in adult-onset Still’s disease (AOSD).

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RHEUM Survey> In RA, seropositivity correlates best with what?

Dr. John Cush @RheumNow( View Tweet )

Retrospective cohort study of 546 DM or clinically amyopathic DM pts. 5 factors were signif assoc w/ cancers (1 point ea): 1) TIFF-1-γ Ab (OR 3.8), poikiloderma (OR 3.1), DM subtype (2.8), anemia (2.4), but ILD was protective (OR 0.39). Markedly elevated DM cancer risk seen w/ https://t.co/OdygNQY2u3
Dr. John Cush @RheumNow( View Tweet )
Hematologic Malignancies Increased in Systemic Sclerosis Swedish national study found that among a cohort of systemic sclerosis (SSc) patients a two-fold increase risk of hematological malignancies was seen. https://t.co/K1WuMC0mXI https://t.co/MGkvwESqIe

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Dr. John Cush @RheumNow( View Tweet )
Retrospective cohort study of 546 DM or clinically amyopathic DM pts. 5 factors were signif assoc w/ cancers (1 point ea): 1) TIFF-1-γ Ab (OR 3.8), poikiloderma (OR 3.1), DM subtype (2.8), anemia (2.4), but ILD was protective (OR 0.39). Markedly elevated DM cancer risk seen w/ https://t.co/r564RbZys2
Dr. John Cush @RheumNow( View Tweet )
Study of 489,569 UK Biobank participants (40 to 69yrs) betw 2006–2010 showed incident RA in 5404. Having self reported eating disorders (anorexia nervosa, bulimia, etc) was associated with a higher risk of developing RA (ad HR 1.76; 1.12–2.76), moreso in men (HR 5.09). https://t.co/GPV3YoE3kt
Dr. John Cush @RheumNow( View Tweet )
Myelodysplastic & chr myelomonocytic leukemia pts rarely get lupus. Review of 19 w/ SLE & 5 w/ CLE; these were older (65 yrs), more male (15M/9F), w/ less renal [10%] & articular [36%] Dz w/ less dsDNA [32%]. Thought to be clonal inflammatory, & not autoinflammatory, process. https://t.co/EAvkJm6GQs
Dr. John Cush @RheumNow( View Tweet )
Robinson et al has published that Epstein-Barr virus infects and reprograms autoreactive B cells to drive the systemic autoimmune response in SLE https://t.co/vjpvILrJOt https://t.co/JfcycqHvhl

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Dr. John Cush @RheumNow( View Tweet )
Genetic Risks and Severe Cutaneous Reactions to Allopurinol A matched cohort study shows that HLA-B*58:01 and HLA-A*34:02 are strongly associated with allopurinol-induced severe cutaneous adverse reactions (SCARs), these alleles were absent in more than one-third of those https://t.co/NLpHVhr9Ww
Dr. John Cush @RheumNow( View Tweet )
NHANES study of 4,622 adults, including 296 w/ RA, shows volatile organic compounds (VOCs) & metabolites (mVOCs) exposures increases the risk of #RA (OR: 1.23 - 1.37), especially in females. https://t.co/pBNLTRkyLn https://t.co/L6nVbYlBhD

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Dr. John Cush @RheumNow( View Tweet )
S.Korean study of 481 pts w/ myositis (IIM) - 12.9% (n = 62) had myositis-assoc. cancer. CA risk factos= older age, male, current smoking, dermatomyositis, TIF1γ; but lower risk w/ anti-synthetase synd, overlap myositis, arthritis, & ILD. SCRIM score had AUROC = 0.852 https://t.co/MdU1fRWWgS
Dr. John Cush @RheumNow( View Tweet )
Rheumatoid arthritis and the ‘big bang’ at #ACR25! Is there ‘bang for the buck’ using big data to help predict who will develop RA in at-risk populations and similarly to predict response to csDMARDs, TNFi and JAKi in RA? https://t.co/QDvdiP3q9R https://t.co/cz4j4vZkSd

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Dr. John Cush @RheumNow( View Tweet )
Needle in a haystack What T cell to target for #autoimmune diseases T cell repetoires (TCR) not all are sequenced and many can exist to present antigens Diff scales of approaches Implications CAR-T CD19 CD20 BCMA Treg HLAB27 etc! #ACR25 @ACRheum @RheumNow Alok Joglekar #26S08 https://t.co/Qgw8Akz1xk

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Janet Pope @Janetbirdope( View Tweet )
Will #PAD4 levels predict pts w #CCP positive #arthralgia who will develop #RA? Leeds study - 79 at risk pts PAD4 levels may predicting #rheumatoid #arthritis development #ACR25 @RheumNow @ACRheum abst#832 https://t.co/dnAA6z3NJQ

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Janet Pope @Janetbirdope( View Tweet )
#ACR25 Abstr#LB21 Are they novel somatic variants beyond #VEXAS in driving inflammation in undiagnosed SAID?Unbiased enrichment analysis in 265 UBA1-negative adults identified IDH1/2 hotspot mutations. Cd be used to screen esp those with cytopenia. Sorry pix not allowed @RheumNow

Md Yuzaiful Md Yusof @Yuz6Yusof( View Tweet )

Recent Blogs

Sexist Rheumatology

Kathryn H. Dao, M.D. , Jack Cush, MD
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Cush and Dao are at it again. This time it's whether men or women are better patients. Cush says men are better patients; Dao says Er, not so fast bub!  This is their light-hearted, gender biased debate on the best patients: Men vs. Women.

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Rx Updates (filtered for Topic)

Therapeutic Updates

The Impact of Obesity on Psoriatic Arthritis

Sponsored by Lilly Medical Affairs
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Image alt text: A person indoors raises one arm in a flexed pose while holding the elbow with the opposite hand. Is obesity common in your patients with PsA? Learn more about the intersection of disease pathogenesis between PsA and obesity and how weight intervention can affect PsA outcomes.
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