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BackgroundWe describe the early experiences of adults with systemic rheumatic disease who received the COVID-19 vaccine.MethodsFrom 2 April to 30 April 2021, we conducted an online, international survey of adults with systemic rheumatic disease who received COVID-19 vaccination. We collected patient-reported data on clinician communication, beliefs and intent about discontinuing disease-modifying antirheumatic drugs (DMARDs) around the time of vaccination, and patient-reported adverse events after vaccination.ResultsWe analysed 2860 adults with systemic rheumatic diseases who received COVID-19 vaccination (mean age 55.3 years, 86.7% female, 86.3% white). Types of COVID-19 vaccines were Pfizer-BioNTech (53.2%), Oxford/AstraZeneca (22.6%), Moderna (21.3%), Janssen/Johnson & Johnson (1.7%) and others (1.2%). The most common rheumatic disease was rheumatoid arthritis (42.3%), and 81.2% of respondents were on a DMARD. The majority (81.9%) reported communicating with clinicians about vaccination. Most (66.9%) were willing to temporarily discontinue DMARDs to improve vaccine efficacy, although many (44.3%) were concerned about rheumatic disease flares. After vaccination, the most reported patient-reported adverse events were fatigue/somnolence (33.4%), headache (27.7%), muscle/joint pains (22.8%) and fever/chills (19.9%). Rheumatic disease flares that required medication changes occurred in 4.6%.ConclusionAmong adults with systemic rheumatic disease who received COVID-19 vaccination, patient-reported adverse events were typical of those reported in the general population. Most patients were willing to temporarily discontinue DMARDs to improve vaccine efficacy. The relatively low frequency of rheumatic disease flare requiring medications was reassuring.

Endometriotic cells contain the full complement of steroidogenic genes for de novo synthesis of estradiol from cholesterol, which is stimulated by PGE2 via enhanced binding of SF1 to promoters of StAR and aromatase genes in a synchronous fashion.

Aberrant aromatase expression in stromal cells of endometriosis gives rise to conversion of circulating androstenedione to estrone in this tissue, whereas aromatase expression is absent in the eutopic endometrium. In this study, we initially demonstrated by Northern blotting transcripts of the reductive 17beta-hydroxysteroid dehydrogenase (17betaHSD) type 1, which catalyzes the conversion of estrone to 17beta-estradiol, in both eutopic endometrium and endometriosis. Thus, it follows that the product of the aromatase reaction, namely estrone, that is weakly estrogenic can be converted to the potent estrogen, 17beta-estradiol, in endometriotic tissues. It was previously demonstrated that progesterone stimulates the inactivation of 17beta-estradiol through conversion to estrone in eutopic endometrial epithelial cells. Subsequently, 17betaHSD type 2 was shown to catalyze this reaction, and its transcripts were detected in the epithelial cell component of the eutopic endometrium in secretory phase. Because 17beta-estradiol plays a critical role in the development and growth of endometriosis, we studied 17betaHSD-2 expression in endometriotic tissues and eutopic endometrium. We demonstrated, by Northern blotting, 17betaHSD-2 messenger ribonucleic acid (RNA) in all RNA samples of secretory eutopic endometrium (n=12) but not in secretory samples of endometriotic lesions (n=10), including paired samples of endometrium and endometriosis obtained simultaneously from eight patients. This messenger RNA was not detectable in any samples of proliferative eutopic endometrium or endometriosis (n=4) as expected. Next, we confirmed these findings by demonstration of immunoreactive 17betaHSD-2 in epithelial cells of secretory eutopic endometrium in 11 of 13 samples employing a monoclonal antibody against 17betaHSD-2, whereas 17betaHSD-2 was absent in paired secretory endometriotic tissues (n=4). Proliferative eutopic endometrial (n=8) and endometriotic (n=4) tissues were both negative for immunoreactive 17betaHSD-2, except for barely detectable levels in 1 eutopic endometrial sample. Finally, we sought to determine whether deficient 17betaHSD-2 expression in endometriotic tissues is due to impaired progesterone action in endometriosis. We determined by immunohistochemistry the expression of progesterone and estrogen receptors in these paired samples of secretory (n=4) and proliferative (n=4) eutopic endometrium and endometriosis, and no differences could be demonstrated. In conclusion, inactivation of 17beta-estradiol is impaired in endometriotic tissues due to deficient expression of 17betaHSD-2, which is normally expressed in eutopic endometrium in response to progesterone. The lack of 17betaHSD-2 expression in endometriosis is not due to alterations in the levels of immunoreactive progesterone or estrogen receptors in this tissue and may be related to an inhibitory aberration in the signaling pathway that regulates 17betaHSD-2 expression.

Estrogen is the most important known factor that stimulates the growth of endometriosis. Estrogen delivery to endometriotic implants was classically viewed to be only via the circulating blood in an endocrine fashion. We recently uncovered an autocrine positive feedback mechanism, which favored the continuous production of estrogen and prostaglandin (PG)E 2 in the endometriotic stromal cells. The enzyme, aromatase, is aberrantly expressed in endometriotic stromal cells and catalyzes the conversion of C 19 steroids to estrogens, which then stimulate cyclooxygenase-2 to increase the levels of PGE 2 . PGE 2 , in turn, is a potent inducer of aromatase activity in endometriotic stromal cells. Aromatase is not expressed in the eutopic endometrium. Aromatase expression in endometriosis and its inhibition in eutopic endometrium are controlled by the competitive binding of a stimulatory transcription factor, steroidogenic factor-1, and an inhibitory factor, chicken ovalbumin upstream promotertranscription factor to a regulatory element in the aromatase P450 gene promoter. In addition, we find that endometriotic tissue is deficient in 17β-hydroxysteroid dehydrogenase type 2, which is normally expressed in eutopic endometrial glandular cells and inactivates estradiol-17β to estrone. This deficiency is another aberration that favors higher levels of estradiol-17β in endometriotic tissues in comparison with the eutopic endometrium. The clinical relevance of local aromatase expression in endometriosis was exemplified by the successful treatment of an unusually aggressive form of recur- Endocrine-Related Cancer (1999) 6 293-301 rent endometriosis in a postmenopausal woman using an aromatase inhibitor.