Efficacy and Safety of Botulinum Toxin in Adults with Raynaud's Phenomenon Secondary to Systemic Sclerosis: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study.

OBJECTIVE: To determine whether a single session of botulinum toxin type A (BTA) injections into both hands more effectively decreases the frequency of systemic sclerosis-associated Raynaud's phenomenon (SSc-RP) episodes than placebo. METHODS: This multicenter, randomized, double-blind, placebo-controlled, parallel-group phase III trial in patients with SSc-RP assessed the effect of 50-unit BTA or placebo injections into the palms of both hands around each neurovascular bundle during 1 session in winter. The primary end point was the between-group difference in the median change in the number of RP episodes from baseline (day 0) to 4 weeks postinjection. Values between the groups were compared with the Wilcoxon rank-sum test. RESULTS: The intent-to-treat analysis included 46 BTA-treated patients and 44 placebo recipients. At 4 weeks after assigned treatment injections, the median number of daily RP episodes decreased comparably in the BTA and placebo groups (median change -1 episode/day [interquartile range (IQR) -1.5, 0 episodes/day] and -1 episode/day [IQR -2.5, 0 episodes/day], respectively) (P = 0.77 versus placebo). Moreover, change in Raynaud's Condition Score, quality of life assessed by Health Assessment Questionnaire disability index, and hand function assessed by shortened Disabilities of the Arm, Shoulder, and Hand (QuickDASH) and Cochin Hand Function Scale from baseline to follow-up weeks 4, 12, and 24 did not differ significantly between groups. The BTA group experienced transient hand muscle weakness significantly more frequently (P = 0.003). CONCLUSION: Neither the primary nor secondary end points were reached, and our results do not support any beneficial effect of palmar BTA injections to treat SSc-RP.

High prevalence of early asymptomatic venous thromboembolism in anticoagulated COVID-19 patients hospitalized in general wards.

Coronavirus disease 2019 (COVID-19) is associated with coagulation activation and high incidence of venous thromboembolism (VTE) in severe patients despite routine thromboprophylaxis. Conflicting results exist regarding the epidemiology of VTE for unselected anticoagulated COVID-19 patients hospitalized in general wards. The aim of this study was to evaluate the prevalence of asymptomatic deep venous thrombosis (DVT) in unselected patients with COVID-19 recently hospitalized in general wards. We performed a systematic complete doppler ultrasound (CDU) at a median 4 days after admission in 42 consecutive COVID-19 patients hospitalized in general wards of our university hospital, irrespective of D-Dimer level, and retrospectively collected clinical, biological and outcome data from electronic charts. Thromboprophylaxis was systematically applied following a French national proposal. In our population, the prevalence of asymptomatic DVT was 19% (8/42 patients), with distal thrombosis in 7/8 cases and bilateral DVT in 4/8 cases. Symptomatic pulmonary embolism was detected in 4 (9.5%) patients, associated to DVT in one case. Compared to patients without DVT, patients with DVT were older and experienced poorer outcomes. In conclusion, prevalence of asymptomatic DVT is high in the first days of hospitalization of unselected COVID-19 patients in general wards and may be related to poor prognosis. Individualized assessment of thromboprophylaxis and early systematic screening for DVT is warranted in this context.

Thoracic aorta involvement in giant cell arteritis: a case-control analysis of morphological data at diagnosis.

OBJECTIVES: Giant cell arteritis (GCA) is a cause of potentially fatal aortic aneurysms. Descriptive data on thoracic aorta measurements at the beginning of the disease are lacking. We aimed to compare aortic diameters between a recently diagnosed GCA population and an age- and sex-matched control group. METHODS: Patients with GCA and with an available thoracic CT concomitant with diagnosis were included. Controls were patients matched for age and sex and hospitalised in the same care centre for pneumonia. The main criteria were the anteroposterior and lateral diameters of the ascending thoracic aorta, which were measured by a blinded evaluator. RESULTS: 90 cases and 90 controls were included. Each group comprised 30 males and 60 females for a mean age of 75.1±9 and 75.7±10.1 years old. At the time of GCA diagnosis no difference was found between the two groups (anteroposterior diameter 37.1±5 mm for cases vs. 36.7±5 mm for controls, p=0.6; lateral diameter 36.6±5 mm for cases vs. 35.9±4 mm for controls, p=0.3). Thoracic aorta diameter was not significantly higher in patients with aortitis at diagnosis (n=44) than in cases without aortitis (n=46). CONCLUSIONS: Morphologic comparison of thoracic aorta at diagnosis of GCA with an age- and sex-matched control population showed no significant difference. Morphologic evaluation of aorta cannot predict accurately the occurrence of aortic aneurysm. Systematic follow-up according to current recommendations is thus justified.

Efficacy of tocilizumab highlighted by FDG-PET/CT in a patient with relapsing polychondritis-associated aortitis.

Relapsing polychondritis (RP) is a rare systemic inflammatory disease primarily affecting the ears, nose and tracheobronchial tree cartilage, but also the cardiovascular system. Cardiovascular complications are the second cause of mortality in RP. We report the case of a woman with a corticosteroid-resistant RP-associated aortitis, who was successfully treated with tocilizumab (TCZ). The FDG-PET/CT was a useful tool for diagnosing aortitis and assessing the effect of biotherapy. We conducted a systematic literature review confirming this is the first case of rapid and sustained remission in a patient with corticosteroid-resistant RP-associated aortitis after TCZ treatment administered as a first-line immunotherapy. However, further studies are needed to confirm the beneficial effect of TCZ used in this life-threatening condition.

Adult Onset Asthma and Periocular Xanthogranuloma (AAPOX), a Rare Entity With a Strong Link to IgG4-Related Disease: An Observational Case Report Study.

Adult onset asthma and periocular xanthogranuloma (AAPOX) is a rare non-Langerhans histiocytosis characterized histopathologically by a periocular infiltration of foamy histiocytes and Touton giant cells. Benign hyperplasia with plasma cell infiltration is classically described in eyelids or lymph nodes of AAPOX patients. It is also a characteristic feature of IgG4-related disease (IgG4-RD), a new entity defined by an IgG4-bearing plasma cell infiltration of organs.To determine if AAPOX syndrome shares clinical, biological, and histopathological characteristics with IgG4-RD, we used the comprehensive clinical diagnostic criteria for IgG4-RD in a retrospective case series of three consecutive patients with histologically-proven AAPOX. Patients who were diagnosed with AAPOX at a French academic referral center for orbital inflammation between November 1996 and March 2013 were enrolled. Biopsies from ocular adnexa or other organs were systematically reexamined. For each patient, clinical and serological data, radiologic findings, and treatment were retrospectively analyzed.Two AAPOX patients fulfilled all of the diagnostic criteria for a definite IgG4-RD. One patient who lacked the serological criteria fulfilled the criteria of a probable IgG4-RD.These 3 cases of AAPOX patients fulfilled the IgG4-RD comprehensive clinical diagnostic criteria. To our knowledge, this is the first observational case report study to clearly show a strong relationship between IgG4-RD and AAPOX syndrome.

Adult-onset asthma associated with periocular xanthogranuloma: new diagnostic and therapeutic approaches in a very rare systemic disease.

PURPOSE: To report some novel findings concerning the systemic manifestations and treatment of adult-onset asthma and periocular xanthogranuloma, a rare type of non-Langerhans histiocytosis that can lead to important visual dysfunction. METHODS: A retrospective case series of 2 patients was evaluated for orbital and systemic manifestations using fluorodeoxyglucose positron emission tomography/CT and/or orbital MRI. Histological specimens were reviewed in all patients. Oral prednisone was initiated at 1 mg/kg daily and gradually tapered to a minimum effective dose. Efficacy was assessed on the basis of an objective observation of decreased swelling. RESULTS: One patient displayed original uptake foci involving intrathoracic lymphadenopathies, the trajectory of the paraumbilical vein and perirectal fat. Low-dose prednisone was able to induce a durable response in the authors' patients. CONCLUSIONS: Fluorodeoxyglucose positron emission tomography/CT may be useful for the diagnostic workup and follow-up assessment of patients with adult-onset asthma and periocular xanthogranuloma. Oral corticosteroids can be used successfully as first-line treatment in such patients.

Pregnancies in systemic necrotizing vasculitides: report on 12 women and their 20 pregnancies.

OBJECTIVES: To describe pregnancies of women with systemic necrotizing vasculitides (SNVs), i.e. PAN, WG, Churg-Strauss syndrome (CSS) or microscopic polyangiitis (MPA), followed over the past 15 years at four French centres. METHODS: Retrospective analysis of women whose SNV appeared during pregnancy or who became pregnant after SNV diagnosis. RESULTS: Among the 12 women identified, one experienced rupture of pancreatic artery microaneurysms at 27 weeks revealing PAN, leading to surgical haemostasis and caesarean delivery. Eleven others started 19 pregnancies after SNV diagnosis (8 in four WG, 6 in three CSS, 1 each in three PAN and 2 in one MPA); 14 conceived during vasculitis remission. Two ended in first-trimester abortions, four miscarried; the remaining 13 pregnancies yielded 14 live newborns (1 twin pregnancy), with 7 pre-term births. Life-threatening complications occurred during 3 of these latter 13 pregnancies and required caesarean delivery. The twin pregnancy (in a CSS patient with initial vasculitis-related cardiac involvement, but in remission at conception) was complicated by transient maternal cardiac failure at 32 weeks. One WG patient with vasculitis-related renal damage developed thrombotic microangiopathy-associated renal impairment at 32 weeks, and another WG patient had severe pneumonia at 37 weeks. Other pregnancies were uneventful or with minor vasculitis manifestations. CONCLUSION: Pregnant SNV patients should be monitored closely, because miscarriages and pre-term births are not uncommon. Pregnancy does not seem to have a major impact on vasculitis activity. However, life-threatening manifestations can occur, especially in patients with vasculitis-related cardiac or renal damage.

Transient elastography as a screening tool for liver fibrosis and cirrhosis in a community-based population aged over 45 years.

BACKGROUND: Liver stiffness measurement (LSM) has been used to measure fibrosis in patients with various types of chronic liver diseases. However, its usefulness as a screening procedure in apparently healthy people had not been evaluated to date. METHODS: 1358 subjects >45 years old from a general population attending for a medical check-up were consecutively enrolled in the study. All subjects were submitted to medical examination and laboratory tests in addition to LSM, performed on the same day by a single operator. Subjects with LSM values >8 kPa were referred to a liver unit for further investigations. RESULTS: 168 subjects were not considered for analysis due to missing data (n=23), LSM failure (n=51) or unreliable LSM values (n=94). Among the 1190 remaining subjects, 89 (7.5%) had LSM >8 kPa including nine patients with LSM >13 kPa. Despite the fact that normal liver tests were observed in 43% of them (38 out of 89), a specific cause of chronic liver disease was found in all cases. Non-alcoholic fatty liver disease (NAFLD) was the likely cause of chronic liver disease in 52 patients, alcoholic liver disease (ALD) in 20, and both causes were associated in seven additional patients. Hepatitis C virus and hepatitis B virus chronic hepatitis was documented in five and four cases, respectively, and primary biliary cirrhosis in one. Liver biopsy was obtained for 27 patients, including the nine patients with LSM >13 kPa, who were diagnosed with liver cirrhosis due to ALD (n=5), chronic hepatitis C (n=3) or chronic hepatitis B (n=1). The 18 remaining biopsies showed liver fibrosis in all cases except one (isolated steatosis), with ALD and NAFLD being present in six and eight cases, respectively. CONCLUSION: LSM proved to be a useful and specific procedure to screen for cirrhosis in the general population and to detect undiagnosed chronic liver disease in apparently healthy subjects.

Takayasu disease revealed by bilateral loss of vision.

PURPOSE: Takayasu arteritis is a nonspecific granulomatous inflammatory arteriopathy of unknown cause, most frequently diagnosed in young Asian women. The authors present an atypical initial presentation of Takayasu disease with bilateral loss of vision in a young Haitian man. METHODS: Case report. RESULTS: The presenting feature was bilateral loss of vision, a result of malignant hypertensive retinopathy and choroidopathy. Systemic evaluation disclosed inflammatory signs and renal artery obstruction which caused the malignant hypertension. CONCLUSION: This case, involving an unusual presentation of Takayasu disease, illustrates how a malignant hypertensive retinopathy and choroidopathy led to the ultimate diagnosis of Takayasu disease.

Successful treatment of idiopathic orbital inflammation with infliximab: an alternative to conventional steroid-sparing agents.

Therapy for orbital pseudotumor, also called idiopathic orbital inflammation, is nonspecific and mainly based on the use of corticosteroids. Two patients with steroid-dependent idiopathic orbital inflammation, one with myositis and the other with dacryoadenitis, and intolerant of standard steroid sparing agents (methotrexate or azathioprine), were treated with infliximab, a monoclonal antitumor necrosis factor alpha antibody. In both patients, orbital manifestations disappeared following treatment. After follow-up for at least 20 months, the 2 patients still receiving infliximab remained event free. Infliximab enabled steroid tapering to less than 5 mg per day, suggesting that infliximab could constitute an alternative to conventional steroid sparing agents.