Severe enterovirus infections in patients with immune-mediated inflammatory diseases receiving anti-CD20 monoclonal antibodies.

OBJECTIVE: Patients with X linked agammaglobulinemia are susceptible to enterovirus (EV) infections. Similarly, severe EV infections have been described in patients with impaired B-cell response following treatment with anti-CD20 monoclonal antibodies (mAbs), mostly in those treated for haematological malignancies. We aimed to describe severe EV infections in patients receiving anti-CD20 mAbs for immune-mediated inflammatory diseases (IMIDs). METHODS: Patients were included following a screening of data collected through the routine surveillance of EV infections coordinated by the National Reference Center and a review of the literature. Additionally, neutralising antibodies were assessed in a patient with chronic EV-A71 meningoencephalitis. RESULTS: Nine original and 17 previously published cases were retrieved. Meningoencephalitis (n=21/26, 81%) associated with EV-positive cerebrospinal fluid (n=20/22, 91%) was the most common manifestation. The mortality rate was high (27%). EV was the only causal agents in all reported cases. Patients received multiple anti-CD20 mAbs infusions (median 8 (5-10)), resulting in complete B-cell depletion and moderate hypogammaglobulinemia (median 4.9 g/L (4.3-6.7)), and had limited concomitant immunosuppressive treatments. Finally, in a patient with EV-A71 meningoencephalitis, a lack of B-cell response to EV was shown. CONCLUSION: EV infection should be evoked in patients with IMIDs presenting with atypical organ involvement, especially meningoencephalitis. Anti-CD20 mAbs may lead to impaired B-cell response against EV, although an underlying primary immunodeficiency should systematically be discussed.

Intravenous immunoglobulins for the treatment of prolonged COVID-19 in immunocompromised patients: a brief report.

Primary humoral deficiency and secondary B-cell depletion may lead to prolonged Sars-Cov-2 infection due to a decreased viral clearance. Prolonged infection is mainly driven by the lack of anti-Sars-Cov-2 immunoglobulin (IVIg) especially in patients with no vaccine response. Anti-spike immunoglobulin can be provided by infusion of convalescent patients' plasma: recent studies highlighted that commercial immunoglobulin show high titers of neutralizing IgG. We conducted a single center retrospective cohort. We included 9 patients (6 males, median age 74 years old): one patient with X-linked agammaglobulinemia and 8 patients treated with rituximab (2 granulomatosis with polyangiitis, 1 neuromyelitis optica, 4 low grade B-cell lymphoma and 1 EBV post-transplant lymphoproliferative disorder). Mean serum globulin was 4 ± 1.6 g/L. 7/8 had received at least 3 doses of mRNA anti-Sars-Cov-2 vaccine (median 4) with no response (anti-Spike IgG 0 for 6 patients). In this specific population requiring oxygen therapy but no intensive care support, the administration of IVIg was well tolerated and provided a swift improvement of clinical status, a significant decrease of inflammation associated to the an improvement of radiological patterns. Our results suggest that immunoglobulin could be used as a salvage therapy as an alternative to convalescent plasma but highly stringent patient selection is required due to the worldwide shortage of IVIg.

A case of restitution ad integrum in Gorham-Stout disease.

Gorham-Stout disease (or "vanishing bone" disease) is a rare mono or polyostotic disease of unknown etiology, characterized by intraosseous angiomatous proliferation leading to bone resorption. We report the case of a 17-year-old woman presenting with symptomatic osteolytic lesions of the frontal vault. Imaging was suggestive of Gorham-Stout disease without argument for other diagnoses. An unusual evolution of the "vanishing bone" lesions was observed on the scan after one year, with a full recovery of the lytic lesions. This report shows for the first time a spontaneous restitutio ad integrum of bone matrix in Gorham-Stout disease.

Azacitidine for patients with Vacuoles, E1 Enzyme, X-linked, Autoinflammatory, Somatic syndrome (VEXAS) and myelodysplastic syndrome: data from the French VEXAS registry.

Azacitidine can be effective in myelodysplastic syndromes (MDS) associated with inflammatory/autoimmune diseases. Vacuoles, E1 Enzyme, X-linked, Autoinflammatory, Somatic syndrome (VEXAS) is a new monogenic autoinflammatory syndrome caused by somatic ubiquitin-like modifier-activating enzyme 1 (UBA1) mutation, often associated with MDS, whose treatment is difficult and not yet codified. Based on a French nationwide registry of 116 patients with VEXAS, we report the efficacy and safety of azacitidine treatment in 11 patients with VEXAS with MDS. Clinical response of VEXAS to azacitidine was achieved in five patients (46%), during 6, 8+, 12, 21, 27+ months respectively, suggesting that azacitidine can be effective in selected patients with VEXAS and associated MDS.

Case Report: TNFα Antagonists Are an Effective Therapy in Cardiac Sarcoidosis.

Introduction: Cardiac sarcoidosis (CS) is a life-threatening disease in which clear recommendations are lacking. We report a case series of CS successfully treated by tumor necrosis factor (TNF)α antagonists. Methods: We conducted a single-center retrospective study of our patients with CS treated by TNFα antagonists. Results: Four cases (4/84, 4.7%) were found in our database. Mean age was 40 years (range 34-53 years), and all were Caucasian men. Mean follow-up was 54.75 months (range 25-115 months). All patients received corticosteroid therapy (CT) and immunosuppressive therapy (IT). TNFα antagonists (infliximab or adalimumab) were started after the first or second CS relapse under CT and IT. One patient experienced relapse under TNFα antagonists (isolated decreased left ventricular ejection) and responded to a shorter interval of TNFα antagonist infusion. CT was discontinued in three patients treated with TNFα antagonists without relapse or major cardiac events during follow-up. No serious adverse event occurred in our case series, possibly due to dose sparing and frequent arrest of CT. Conclusion: TNFα antagonists were effective in refractory and/or relapsing CS treated by corticosteroids and/or immunosuppressive agents, without serious adverse events, and should be considered earlier in CS treatment scheme.

Use of Biologics to Treat Relapsing and/or Refractory Eosinophilic Granulomatosis With Polyangiitis: Data From a European Collaborative Study.

OBJECTIVE: To describe the efficacy and safety of biologics for the treatment of eosinophilic granulomatosis with polyangiitis (EGPA). METHODS: A retrospective European collaborative study was conducted in patients with EGPA who received treatment with biologics for refractory and/or relapsing disease. RESULTS: Among the 147 patients with EGPA included in the study, 63 received rituximab (RTX), 51 received mepolizumab (MEPO), and 33 received omalizumab (OMA). At the time of inclusion, the median Birmingham Vasculitis Activity Score (BVAS) was 8.5 (interquartile range [IQR] 5-13) in the RTX group, while the median BVAS in the OMA group was 2 (IQR 1-4.5) and the median BVAS in the MEPO group was 2 (IQR 1-5). In patients receiving RTX, the median BVAS declined both at 6 months (median 1, IQR 0-4.5) and at 12 months (median 0, IQR 0-2), and the frequency of remission, partial response, treatment failure, and stopping treatment due to adverse events was 49%, 24%, 24%, and 3%, respectively. For the treatment of glucocorticoid (GC)-dependent asthma, patients who received MEPO had a much better GC-sparing effect and overall response than did patients who received OMA. The frequency of remission, partial response, treatment failure, and stopping treatment due to adverse events was 15%, 33%, 48%, and 4%, respectively, in the OMA group and 78%, 10%, 8%, and 4%, respectively, in the MEPO group. Remission rates at 12 months were 76% and 82% among patients receiving MEPO at a doses of 100 mg and 300 mg, respectively. CONCLUSION: These results suggest that RTX could be effective in treating relapses of EGPA vasculitis. MEPO is highly effective with a good safety profile in patients with GC-dependent asthma. Our data suggest that 100 mg MEPO monthly could be an acceptable dosage for first-line therapy in selected instances of EGPA, recognizing, however, that this has not been compared to the validated dosage of 300 mg monthly.

Temporal Arteritis Revealing Antineutrophil Cytoplasmic Antibody-Associated Vasculitides: A Case-Control Study.

OBJECTIVE: Temporal arteritis (TA) is a typical manifestation of giant cell arteritis (GCA). Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAVs) are rarely revealed by TA manifestations, leading to a risk of misdiagnosis of GCA and inappropriate treatments. This study was undertaken to describe the clinical, biologic, and histologic presentations and outcomes in cases of TA revealing AAV (TA-AAV) compared to controls with classic GCA. METHODS: In this retrospective case-control study, the characteristics of patients with TA-AAV were compared to those of control subjects with classic GCA. Log-rank test, with hazard ratios (HRs) and 95% confidence intervals (95% CIs), was used to assess the risk of treatment failure. RESULTS: Fifty patients with TA-AAV (median age 70 years) were included. Thirty-three patients (66%) presented with atypical symptoms of GCA (ear, nose, and throat involvement in 32% of patients, and renal, pulmonary, and neurologic involvement in 26%, 20%, and 16% of patients, respectively). Blood samples were screened for ANCAs at the time of disease onset in 33 patients, and results were positive in 88%, leading to a diagnosis of early TA-AAV in 20 patients. The diagnosis of AAV was delayed a median interval of 15 months in 30 patients. Compared to controls with GCA, patients with TA-AAV were younger (median age 70 years versus 74 years), were more frequently men (48% versus 30%), and had high frequencies of atypical manifestations and higher C-reactive protein levels (median 10.8 mg/dl versus 7.0 mg/dl). In patients with TA-AAV, temporal artery biopsy (TAB) showed fibrinoid necrosis and small branch vasculitis in 23% of patients each, whereas neither of these characteristics was evident in controls with GCA. Treatment failure-free survival was comparable between early TA-AAV cases and GCA controls, whereas those with delayed TA-AAV had a significantly higher risk of treatment failure compared to controls (HR 3.85, 95% CI 1.97-7.51; P < 0.0001). CONCLUSION: TA-AAV should be considered diagnostically in cases of atypical manifestations of GCA, refractoriness to glucocorticoid treatment, or early relapse. Analysis of TAB specimens for the detection of small branch vasculitis and/or fibrinoid necrosis could be useful. Detection of ANCAs should be performed in cases of suspected GCA with atypical clinical features and/or evidence of temporal artery abnormalities on TAB.

Large-vessel vasculitis diagnosed between 50 and 60 years: Case-control study based on 183 cases and 183 controls aged over 60 years.

BACKGROUND: Age at onset of large-vessel vasculitis (LVV) is commonly used to distinguish giant cell arteritis (GCA) and Takayasu arteritis (TA). However, LVV between age 50 and 60 years may be difficult to classify. METHODS: We conducted a retrospective study including LVV aged between 50 and 60 years at onset (LVV50-60, cases) and compared them to LVV aged over 60 years (LVV>60, controls). LVV was defined histologically and/or morphologically. Controls fulfilled ACR 1990 criteria for GCA or presented isolated aortitis. RESULTS: We included 183 LVV50-60 and 183 gender-matched LVV>60. LVV50-60 had more frequent peripheral limb manifestations (23 vs. 5%), and less frequent cephalic (73 vs. 90%) and ocular signs (17 vs. 27%) than LVV>60. Compared to LVV>60, CT angiography and PET/CT scan were more frequently abnormal in LVV50-60 (74 vs. 38%, and 90 vs. 72%, respectively), with aorta being more frequently involved (78 vs. 47%). By multivariate analysis, absence of cephalic symptoms, presence of peripheral limb ischemia and aorta involvement, and increased CRP level were significantly associated with LVV50-60 presentation compared to LVV>60. At last follow-up, compared to LVV>60, LVV50-60 received significantly more lines of treatment (2 vs. 1), more frequent biologics (12 vs. 3%), had more surgery (10 vs. 0%), and had higher prednisone dose (8.8 vs. 6.5 mg/d) at last follow-up, CONCLUSION: LVV onset between 50 and 60 years identifies a subset of patients with more frequent aorta and peripheral vascular involvement and more refractory disease compared to patients with LVV onset after 60.

Screening for Occult Cancer in Patients With Unprovoked Venous Thromboembolism: A Systematic Review and Meta-analysis of Individual Patient Data.

BACKGROUND: Screening for cancer in patients with unprovoked venous thromboembolism (VTE) often is considered, but clinicians need precise data on cancer prevalence, risk factors, and the effect of different types of screening strategies. PURPOSE: To estimate the prevalence of occult cancer in patients with unprovoked VTE, including in subgroups of different ages or those that have had different types of screening. DATA SOURCES: MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials up to 19 January 2016. STUDY SELECTION: Prospective studies evaluating cancer screening strategies in adults with unprovoked VTE that began enrolling patients after 1 January 2000 and had at least 12 months of follow-up. DATA EXTRACTION: 2 investigators independently reviewed abstracts and full-text articles and independently assessed risk of bias. DATA SYNTHESIS: 10 eligible studies were identified. Individual data were obtained for all 2316 patients. Mean age was 60 years; 58% of patients received extensive screening. The 12-month period prevalence of cancer after VTE diagnosis was 5.2% (95% CI, 4.1% to 6.5%). The point prevalence of cancer was higher in patients who had extensive screening than in those who had more limited screening initially (odds ratio [OR], 2.0 [CI, 1.2 to 3.4]) but not at 12 months (OR, 1.4 [CI, 0.89 to 2.1]). Cancer prevalence increased linearly with age and was 7-fold higher in patients aged 50 years or older than in younger patients (OR, 7.1 [CI, 3.1 to 16]). LIMITATION: Variation in patient characteristics and extensive screening strategies; unavailability of long-term mortality data. CONCLUSION: Occult cancer is detected in 1 in 20 patients within a year of receiving a diagnosis of unprovoked VTE. Older age is associated with a higher cancer prevalence. Although an extensive screening strategy initially may detect more cancer cases than limited screening, whether this translates into improved patient outcomes remains unclear. PRIMARY FUNDING SOURCE: None. (PROSPERO: CRD42016033371).

Clinicopathologic characteristics, treatment, and outcomes of tubulointerstitial nephritis and uveitis syndrome in adults: A national retrospective strobe-compliant study.

Tubulointerstitial nephritis and uveitis (TINU) syndrome is a rare disease, defined by the association of idiopathic acute TINU. The aim of our work was to determine the characteristics of adult TINU syndrome in France, and to assess factors (including treatment) influencing medium-term prognosis.We conducted a nationwide study including 20 French hospitals. Clinical, laboratory, and renal histopathologic data of 41 biopsy-proven TINU syndromes were retrospectively collected. The patients were diagnosed between January 1, 1999 and December 1, 2015.Twenty-five females and 16 males were included (F/M ratio: 1.6:1). The median age at disease onset was 46.8 years (range 16.8-77.4) with a median serum creatinine level at 207 µmol/L (range 100-1687) and a median estimated glomerular filtration rate (eGFR) at 27 mL/min per 1.73 m (range 2-73). Twenty-nine patients (71%) had a bilateral anterior uveitis and 24 (59%) had deterioration in general health at presentation. Moderate proteinuria was found in 32 patients (78%) (median proteinuria 0.52 g/24 h; range 0.10-2.10), aseptic leukocyturia in 25/36 patients (70%). The evaluation of renal biopsies revealed 41 patients (100%) with an acute tubulointerstitial nephritis, 19/39 patients (49%) with light to moderate fibrosis and 5 patients (12%) with an acute tubular necrosis. Thirty-six patients (88%) were treated with oral corticosteroids. After 1 year of follow-up, the median eGFR was 76 mL/min per 1.73 m (range 17-119) and 32% of the patients suffered from moderate to severe chronic kidney disease. Serum creatinine (P < 0.001, r = -0.54), serum bicarbonate and phosphate levels (respectively, P = 0.01, r = 0.53; and P = 0.04, r = 0.46), and age (P = 0.03, r = -0.37) at the 1st symptoms were associated with eGFR after 1 year. During the 1st year 40% of patients had uveitis relapses. The use of oral corticosteroids was not associated with a better kidney function but was associated with fewer uveitis relapses (P = 0.44 and 0.02, respectively).In our study, 32% of patients were suffering from moderate to severe chronic kidney disease after 1 year of follow-up, and 40% had uveitis relapses during this follow-up. This work also suggests that oral corticosteroids are effective for the treatment of TINU syndrome's uveitis.

Infundibuloneurohypophysitis Associated With Sjögren Syndrome Successfully Treated With Mycophenolate Mofetil: A Case Report.

Hypophysitis is an inflammatory disorder of the pituitary gland and corticosteroids are usually recommended as the first-line treatment. Hypophysitis related to primary Sjögren syndrome (pSS) is uncommon. We describe the unusual case of a patient with infundibuloneurohypophysitis associated with pSS successfully treated with mycophenolate mofetil (MMF).We describe a case of a 60-year-old man with a medical history of pSS presented with central diabetes insipidus and panhypopituitarism. Magnetic resonance imaging (MRI) revealed a thickening of the pituitary stalk and intense enhancement of the posterior pituitary, pituitary stalk, and hypothalamus. We diagnosed infundibuloneurohypophysitis associated with pSS. Hormonal replacement was started immediately and MMF was introduced without corticosteroids. After 9 months of treatment, MRI of the pituitary revealed a complete regression of the nodular thickening of the pituitary stalk, with normal enhancement and appearance of the pituitary. The pituitary axes had completely recovered, whereas the diabetes insipidus was partially restored. Our findings suggest that MMF is an effective alternative to corticosteroids for the treatment of lymphocytic hypophysitis associated with an autoimmune disease. Furthermore, this report could contribute to extend the spectrum of the neurological and endocrinological manifestations of pSS.

Ovarian thrombosis and uterine synechiae after arterial embolization for a late postpartum haemorrhage.

BACKGROUND: We report two unusual separate complications after uterine artery embolization for a late postpartum haemorrhage. This report appeared important to us in view of the apparent absence of any other publications on this topic. CASE PRESENTATION: We report the case of a 25-year-old woman, gravida 3, para 1, admitted for uterine bleeding 7 days after a spontaneous delivery at term, in our university hospital. A suction curettage and then, after persistent bleeding, uterine artery embolization were necessary. Immediately after the embolization, a bilateral ovarian thrombosis occurred, subsequently followed by amenorrhea, due to uterine synechiae, and depression. Hysteroscopic surgery was performed to remove the adhesions. A complete work-up for thrombophilia showed a heterozygous mutation of the factor V gene R506Q. The pathology examination found subinvolution of the placental bed. One month after treatment of the synechiae (and insertion of a copper IUD for contraception), the woman's menstrual cycle returned to normal. Her clinical examination 19 months later was normal. CONCLUSIONS: This case teaches us that one rare complication can hide another! It is important to consider the diagnosis of subinvolution of the placental bed in cases of late PPH and to know the complications associated with vascular artery embolization in order to provide the most rapid and least invasive treatment.

Successful treatment with azathioprine of relapsing Rosai-Dorfman disease of the central nervous system.

Rosai-Dorfman disease (RDD) is a rare non-Langerhans histiocytosis that usually presents with lymphadenopathy. Although isolated involvement of the CNS was considered to be uncommon, numerous cases have been reported in recent years. For RDD of the CNS, the treatment consists, in general, of surgery. In cases of partial resection or relapse, chemotherapy regimens, corticosteroids, and/or radiotherapy have yielded negative results. The authors describe the case of a 57-year-old man with a history of chronic Q fever who presented with aphasia and partial seizure. Computed tomography of the brain revealed a left frontotemporal lesion that was suggestive of a meningioma. The lesion was partially resected and histopathological evaluation revealed the presence of RDD. Nineteen months later, a Jacksonian seizure prompted MRI evaluation, which disclosed a local recurrence of the tumor. Computed tomography and FDG-PET demonstrated that the RDD involved no other site, but the presence of ileitis, noted on ileoscopy, led to the diagnosis of Crohn disease. Treatment with the purine analog azathioprine was initiated, leading to an objective and sustained response in both the RDD tumor and ileitis over 35 months of follow-up. This case report highlights the potential use of a purine analog in cases of relapsing RDD of the CNS and a possible common defect of macrophage regulation in RDD, Crohn disease, and Q fever.

[Back pain without radiculitis as an initial manifestation of Lyme disease: two cases]. / Rachialgies sans radiculite révélant une maladie de Lyme: à propos de deux cas.

INTRODUCTION: The most frequent neurological expression of Lyme disease (borreliosis) during its secondary phase is meningoradiculitis, but atypical presentations occur. Lyme disease must be considered especially in endemic areas and during the summer (May-October). CASES: We report cases of two patients with unusual clinical presentations of neuroborreliosis. Both had acute inflammatory back pain, resistant to the usual analgesic treatment. Both patients responded negatively to questions about tick bites and erythema migrans. Laboratory tests revealed an inflammatory process in only one patient. Lyme disease was confirmed by lymphocytic meningitis and serological tests positive for Borrelia in blood (both cases) and cerebrospinal fluid (one case). Antibiotic treatment led to the disappearance of pain and the normalization of laboratory tests. DISCUSSION: Inflammatory back pain, even without radiculitis, may be related to Lyme disease in endemic areas.

Regressive aortic valve and infundibular tumors during idiopathic hypereosinophilic syndrome.

Fibroblastic endocarditis is a classic complication of prolonged hypereosinophilic syndrome, whatever the cause. In France, it is most frequently encountered in cases of idiopathic hypereosinophilic syndrome. It commonly involves the apex of the ventricles, with a clinical picture of restrictive cardiomyopathy of unfavorable prognosis, and the auriculoventricular valves. We report the case of a 77-year-old man in whom atypical cardiac involvement disclosed idiopathic hypereosinophilic syndrome. In addition to the usual features of obliteration of the apex and restrictive cardiomyopathy, echocardiographic examination showed severe left ventricular dysfunction and intracardiac tumors, one of which was unusually localized to an aortic valve. Treatment, which comprised strict control of the eosinophilic process, standard treatment for cardiac failure, and anticoagulation therapy, produced rapid and long-lasting improvement of his clinical status and left systolic and diastolic ventricular function, and on echocardiography the intracardiac tumors had totally disappeared. The patient suddenly died of septic shock 16 months after first being seen.

[Mesenteric venous thrombosis. A retrospective study of 23 cases]. / Thromboses veineuses mésentériques. Etude rétrospective de 23 cas.

UNLABELLED: Mesenteric venous thrombosis is uncommon. Diagnosis is difficult and much remains to be learned about clinical aspects, etiology and treatment options. PATIENTS AND METHODS: We conducted a retrospective study over 5 years concerning patients with isolated mesenteric venous thrombosis or with extension to the portal vein. RESULTS: Twenty-three patients (12 women), mean age 55 years, were included. Abdominal pain (96%), bowel obstruction (35%), fever (26%), diarrhea (17%), gastrointestinal bleeding (13%) were the most common symptoms at presentation. In 78% of patients, at least one underlying condition was identified: thrombophilia, oral contraceptive, cancer, paroxysmal nocturnal hemoglobinuria, essential thrombocythemia, intra-abdominal processes. CT scan and ultrasound diagnostic sensitivity were 89% and 57% respectively. Outcome was favorable for the 18 patients treated with anticoagulants (associated with surgery in 4 patients). Three patients with neoplasm died early. CONCLUSION: Mesenteric venous thrombosis must be kept in mind as a possible diagnosis in patients with abdominal pain. Predisposing factors are frequently associated and should be searched for. Early diagnosis, using CT scan or ultrasound, enables immediate anticoagulation and seems to improve outcome.