Hydroxychloroquine levels in pregnancy and materno-fetal outcomes in Systemic Lupus Erythematosus patients.

OBJECTIVES: Data about hydroxychloroquine (HCQ) levels during pregnancy are sparse. We assessed HCQ whole blood levels at first trimester of pregnancy as a potential predictor of maternal and obstetric/fetal outcomes in patients with systemic lupus erythematosus (SLE). METHODS: We included pregnant SLE patients enrolled in the prospective GR2 study receiving HCQ, with at least one available first-trimester whole-blood HCQ assay. We evaluated several cut-offs for HCQ whole blood levels, including ≤200 ng/ml for severe non-adherence. Primary outcomes were maternal flares during the second and third trimesters of pregnancy, and adverse pregnancy outcomes (APOs: fetal/neonatal death, placental insufficiency with preterm delivery, and small-for-gestational-age neonates). RESULTS: We included 174 patients (median age: 32.1 years, IQR 28.8-35.2). Thirty (17.2%) patients had flares, 4 (2.3%) being severe. APOs occurred in 28 patients (16.1%). There were no significant differences in APOs by HCQ level for either those with subtherapeutic HCQ levels (≤500 ng/ml vs >500 ng/ml: 23.5% vs 14.3%, p = 0.19) or those with non-adherent HCQ levels (≤200 ng/ml vs >200 ng/ml: 20.0% vs 15.7%, p = 0.71). Similarly, the overall rate of maternal flares did not differ significantly by HCQ level cut-off, but patients with subtherapeutic (HCQ ≤500 ng/ml: 8.8% vs 0.7%, p = 0.02) and non-adherent HCQ levels (≤200 ng/ml: 13.3% vs 1.3%, p = 0.04) had significantly more severe flares. CONCLUSION: In this large prospective study of pregnant SLE patients, first-trimester subtherapeutic (≤500 ng/ml) and severe non-adherent (≤200 ng/ml) HCQ levels were associated with severe maternal flares, but not with APOs. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02450396.

Efficacy and safety of targeted therapies in VEXAS syndrome: retrospective study from the FRENVEX.

OBJECTIVES: Vacuoles, E1 enzyme, X-linked, autoinflammatory and somatic (VEXAS) syndrome is an adult-onset autoinflammatory disease associated with somatic ubiquitin-like modifier-activating enzyme 1 (UBA1) mutations. We aimed to evaluate the efficacy and safety of targeted therapies. METHODS: Multicentre retrospective study including patients with genetically proven VEXAS syndrome who had received at least one targeted therapy. Complete response (CR) was defined by a clinical remission, C-reactive protein (CRP) ≤10 mg/L and a ≤10 mg/day of prednisone-equivalent therapy, and partial response (PR) was defined by a clinical remission and a 50% reduction in CRP levels and glucocorticoid dose. RESULTS: 110 patients (median age 71 (68-79) years) who received 194 targeted therapies were included: 78 (40%) received Janus kinase (JAK) inhibitors (JAKi), 51 (26%) interleukin (IL)-6 inhibitors, 33 (17%) IL-1 inhibitors, 20 (10%) tumour necrosis factor (TNFα) blockers and 12 (6%) other targeted therapies. At 3 months, the overall response (CR and PR) rate was 24% with JAKi, 32% with IL-6 inhibitors, 9% with anti-IL-1 and 0% with TNFα blockers or other targeted therapies. At 6 months, the overall response rate was 30% with JAKi and 26% with IL-6 inhibitors. Survival without treatment discontinuation was significantly longer with JAKi than with the other targeted therapies. Among patients who discontinued treatment, causes were primary failure, secondary failure, serious adverse event or death in 43%, 14%, 19% and 19%, respectively, with JAKi and 46%, 11%, 31% and 9%, respectively, with IL-6 inhibitors. CONCLUSIONS: This study shows the benefit of JAKi and IL-6 inhibitors, whereas other therapies have lower efficacy. These results need to be confirmed in prospective trials.

Pregnancy outcomes in women with primary Sjögren's syndrome: an analysis of data from the multicentre, prospective, GR2 study.

BACKGROUND: Adverse pregnancy outcomes in women with primary Sjögren's syndrome have only been evaluated retrospectively using heterogeneous methods and with contradictory results. We aimed to describe adverse pregnancy, delivery, and birth outcome risks in pregnant women with primary Sjögren's syndrome compared with those of a matched general population in France, and to identify factors predictive of disease flares or adverse pregnancy outcomes. METHODS: We conducted a multicentre, prospective, cohort study in France using the GR2 (Groupe de Recherche sur la Grossesse et les Maladies Rares) registry. Women from the GR2 study were eligible if they had conceived before March, 2021, had primary Sjögren's syndrome according to the American College of Rheumatology and European Alliance of Associations for Rheumatology (EULAR) 2016 classification criteria, and had an ongoing pregnancy at 12 weeks of gestation. In women who entered in the registry with pregnancies before 18 weeks of gestation, we sought to identify factors associated with primary Sjögren's syndrome flare (≥3-point increase in EULAR Sjögren's Syndrome Disease Activity Index [ESSDAI] score) or adverse pregnancy outcomes (fetal or neonatal death, placental insufficiency leading to a preterm delivery [<37 weeks of gestation], or small-for-gestational-age birthweight). A matched controlled study compared adverse pregnancy, delivery, and birth outcome rates between pregnant women with primary Sjögren's syndrome from the GR2 registry and matched controls from the general population included in the last French perinatal survey (Enquête Nationale Périnatale 2016). FINDINGS: 1944 pregnancies were identified in the GR2 cohort, of which 106 pregnancies in 96 women with primary Sjögren's syndrome were included in this analysis. The median age at pregnancy onset was 33 years (IQR 31-36). 87 (83%) of 105 pregnancies (with ethnicity data) were in White women, 18 (17%) were in Black women; 92 (90%) of 102 had previous systemic activity (ESSDAI score of ≥1; data missing in four pregnancies), and 48 (45%) of 106 had systemic activity at inclusion. Of 93 pregnancies included at week 18 of gestation or earlier, primary Sjögren's syndrome flares occurred in 12 (13%). No baseline parameters were associated with primary Sjögren's syndrome flare. Four twin pregnancies and one medical termination were excluded from the adverse pregnancy outcome analysis; of the remaining 88, adverse pregnancy outcomes occurred in six (7%). Among pregnancies in women with data for antiphospholipid antibodies (n=55), antiphospholipid antibody positivity was more frequent among pregnancies with adverse outcomes (two [50%] of four pregnancies) compared with those without adverse outcomes (two [4%] of 51 pregnancies; p=0·023). Anti-RNP antibody positivity was also more frequent among pregnancies with adverse outcomes than those without, although this was not statistically significant. In the matched controlled study, adverse pregnancy outcomes occurred in nine (9%) of 105 pregnancies in women with primary Sjögren's syndrome and 28 (7%) of the 420 matched control pregnancies; adverse pregnancy outcomes were not significantly associated with primary Sjögren's syndrome (odds ratio 1·31, 95% CI 0·53-2·98; p=0·52). INTERPRETATION: Pregnancies in women with primary Sjögren's syndrome had very good prognoses for mothers and fetuses, with no overall increase in adverse pregnancy outcome risk compared with the general population. Women with antiphospholipid antibodies or anti-RNP antibodies require close monitoring, because these factors might be associated with a higher risk of adverse pregnancy outcomes. FUNDING: Lupus France, Association des Sclérodermiques de France, Association Gougerot Sjögren, Association Francophone Contre la Polychondrite Chronique Atrophiante, AFM-Telethon, Société Nationale Française de Médecine Interne, Société Française de Rhumatologie, Cochin Hospital, French Health Ministry, Fondation for Research in Rheumatology, Association Prix Véronique Roualet, Union Chimique Belge.

The Koebner phenomenon on tattoos and piercings in a patient with cutaneous lupus: a case report and review of the literature.

The Koebner phenomenon is associated with cutaneous lupus erythematosus (CLE). A 20-year-old woman with a 10-year history of systemic lupus, treated with hydroxychloroquine and methotrexate, presented with features of chronic discoid lupus erythematosus (DLE) on the scalp, at the site of ear piercings, and on the temporal bone at the site of trauma from her jewelry. She also had subacute CLE (SCLE) lesions on old black tattoos. Histology and direct immunofluorescence confirmed CLE. We reviewed 13 cases of Koebner phenomenon on tattoos in patients with CLE (seven men, median age: 31.5 years) and none after piercings. Lesions developed within 1 week to 16 years after tattooing. Lesions may be isolated, precede, or be associated with other CLE lesions. They can appear secondarily on the tattoo. There is no specific color affinity, but cases have shifted from red to black, possibly when mercury was withdrawn from red inks. CLE on tattoos is a rare phenomenon that more often presents with DLE features than SCLE. Patients should be warned of the potential risk of developing lesions on tattoos. Immunosuppressive treatment needs to be taken into account if a patient wishes to get a tattoo. However, tattooing is not associated with severe complications.

Vaccination against influenza and pneumococcal infections in patients with autoimmune disorders under biological therapy: Coverage and attitudes in patients and physicians.

BACKGROUND: Patients under biological therapy for auto-immune disease are considered immunosuppressed and several recent recommendations highlight the need for vaccination against influenza and pneumococcal infections. The aims of this study were to evaluate influenza and pneumococcal vaccine coverage among patients receiving biological therapy and identify factors associated with vaccine uptake within this population. METHODS: A retrospective cross-sectional study was performed in adult patients attending hospitals for an auto-immune/inflammatory disease and treated with biological therapy. Vaccine uptake was evidenced from patient's medical records or from their pharmacist's records. Questionnaires about attitudes and knowledge regarding vaccinations were administered to patients and their physicians. Multivariable logistic regression was used to determine factors significantly associated with influenza and pneumococcal vaccine receipt. RESULTS: A total of 208 patients were included: 52% female and mean age 50.6 (± 14.7) years. Among them 173 completed the questionnaire while 72 physicians replied. Underlying inflammatory diseases were rheumatisms (46%), bowel diseases (31%) and skin diseases (23%). Vaccine uptake was 28% for influenza, 48% for pneumococcus and 22% received both vaccines. Main factors associated to positive uptake were receiving a prescription from a physician, as well as having a good knowledge of vaccines. Factors limiting vaccination were a negative attitude toward vaccines in general, and belonging to the group of inflammatory bowel diseases. CONCLUSIONS: Vaccine coverage for influenza and pneumococcal infections are low in the patients under biologics for auto-immune/inflammatory disease. Health policies should reinforce information and promotion of these vaccines among these patients but also the prescribers.

Breast metastasis of a squamous cell carcinoma of the uterine cervix mimicking inflammatory breast cancer.

Breast metastases from distant carcinoma are infrequent, and cervix carcinoma is rarely the primary lesion. We describe the first case of a cervical squamous cell carcinoma with breast metastasis mimicking an inflammatory breast cancer in a 74-year-old woman. Seventeen months after the treatment of a primary tumor, the patient developed breast lesions looking like an inflammatory breast tumor. After a 1-year delay due to the patient's refusal, pathological examination and immunohistochemistry confirmed the diagnosis of breast metastasis from a poorly differentiated squamous cell carcinoma. The volume of the breast was huge, associated with axillary lymphadenopathies and multiple lung metastases. Despite platinum-based chemotherapy, the disease progressed and the patient died rapidly, 3 months after the first chemotherapy cycle and 15 months after the first mammary symptoms. We review the literature concerning breast metastases from gynecologic cancers and, particularly, from cervical squamous cell carcinoma. Differential diagnosis of such lesions may be problematic but is essential to avoid unnecessary mutilating surgery and to institute the appropriate systemic therapy. The prognosis is poor.

Efficacy of hepatitis B sero-vaccination in newborns of African HBsAg positive mothers.

BACKGROUND: Maternal-infant transmission of hepatitis B virus (HBV) during birth carries a high risk of chronic HBV infection in infants. Appropriate neonatal prophylaxis is effective in preventing perinatal transmission of HBV. The purpose of this study was to evaluate the protective efficacy of anti-HBV sero-vaccination in newborns of HBsAg positive mothers from Mayotte, French island in the Mozambican canal. PATIENTS AND METHODS: One-hundred newborns of HBsAg positive mothers were identified retrospectively on the basis of hospital medical record and hepatitis B immune globulin (HBIG) prescriptions review from 1994 to 2007. To determine the rate of protective efficacy of neonatal prophylaxis defined by anti HBs antibodies >10 IU/mL with negative HBsAg, anti HBc and HBV DNA testing, HBV serological markers were performed in vaccinated children. RESULTS: Eighty-three of 100 newborns (83%) were given a complete sero-vaccination. Maternal HBe Ag status at delivery (available in 93%) was positive in 56 (60%) of cases and HBV viral load (available in 57%) was <5 logIU/mL, between 5 and 7 logsIU/mL and >7 logsIU/mL in 23 (40.4%), 12 (21%) and 22 (38.6%), respectively. HBV markers in all children at a median age of 5 years [IQR 2-8] showed that 76% were protected with anti HBs >10 IU/mL, despite incomplete sero-vaccination in 12 infants; 6% of infants had anti-HBs and anti-HBc positivity with undetectable HBV DNA, 1% had isolated anti HBc while 14% were seronegative. Only 3% had evidence of immunoprophylaxis failure: 1 infant was HBsAg carrier and 2 had detectable HBV DNA without HBsAg (occult HBV infection). The only factor associated with sustained protective efficacy was on time serological control performed within one year of life, whereas maternal age, HBeAg status and HBV viral load on delivery were not. CONCLUSION: The anti-HBV sero-vaccination of newborns of HBsAg-positive mothers is fairly done in Mayotte and allows a high protection of mother-to-child transmission in a mean endemic area with fair safety. Screening of sero-vaccination failures has to be reinforced in order either to revaccinate or to treat infected children.

Behçet's disease in East African patients may not be unusual and is an HLA-B51 negative condition: a case series from Mayotte (Comoros).

OBJECTIVE: We aimed to report the presence of Behçet's disease in patients of East African ancestry, where there have been very few reports of the disease. METHODS: Case series of 14 patients, all of whom were born in the Comoros, reporting to the single primary general medicine department of Mayotte's island since 1998. All the patients but one satisfied the international group study criteria for Behçet disease. RESULTS: We report a series of 14 patients (13 unrelated) including 10 men and features of the disease. Two multicase family histories were elicited. Mean diagnosis delay was 5.5 ± 5.1 years. Behçet's disease presented mainly as neuro-Behçet in five patients including three with progressive brain stem syndrome, vascular disease in three patients, relapsing panuveitis in two patients, and rheumatic disease with mucocutaneous disease in four patients. Thirteen patients were tested and were found to be HLA-B51 negative. All the patients were treated with colchicine and most of them received additional immunosuppressive treatment, mainly glucocorticoids and azathioprine. However, after a mean 43-month follow-up, five had serious permanent disabling, one of whom had died of neuro-Behçet. CONCLUSIONS: Behçet's disease may be an under-reported, HLA-B51 negative, condition in native East African populations and appears to be often life-threatening and/or associated with severe damage in these patients. A high degree of awareness of physicians is necessary to shorten diagnostic delays and to improve the management of patients.