Bertrand Lioger

Systemic inflammatory and autoimmune manifestations associated with myelodysplastic syndromes and chronic myelomonocytic leukaemia: a French multicentre retrospective study

OBJECTIVE We describe myelodysplastic syndrome (MDS)-associated systemic inflammatory and autoimmune diseases (SIADs), their treatments and outcomes and the impact of SIADs on overall survival in a French multicentre retrospective study. METHODS In this study, 123 patients with MDS and SIADs were analysed. RESULTS Mean age was 70 years (s.d. 13) and the male:female ratio was 2. The SIADs were systemic vasculitis in 39 (32%) cases, CTD in 31 (25%) cases, inflammatory arthritis in 28 (23%) cases, a neutrophilic disorder in 12 (10%) cases and unclassified in 13 cases (11%). The SIADs fulfilled the usual classification criteria in 75 (66%) cases, while complete criteria were not reached in 21 (19%) cases. A significant association was shown between chronic myelomonocytic leukaemia (CMML) and systemic vasculitis (P = 0.0024). One hundred and eighteen (96%) SIAD patients were treated (91% with steroids), with an 83% response to first-line treatment, including 80% for steroids alone. A second-line treatment for SIADs was required for steroid dependence or relapse in 48% of cases. The effect of MDS treatment on SIADs could be assessed in 11 patients treated with azacytidine and SIAD response was achieved in 9/11 (80%) and 6/11 (55%) patients at 3 and 6 months, respectively. Compared with 665 MDS/CMML patients without SIADs, MDS/CMML patients with SIADs were younger (P < 0.01), male (P = 0.03), less often had refractory anaemia with ring sideroblasts (P < 0.01), more often had a poor karyotype (16% vs 11%, P = 0.04) and less frequently belonged to low and intermediate-1 International Prognostic Scoring System categories, but no survival difference was seen between patients with MDS-associated SIADs and without SIADs (P = 0.5). CONCLUSION The spectrum of SIADs associated to MDS is heterogeneous, steroid sensitive, but often steroid dependent.

Antineutrophil cytoplasmic antibody-associated vasculitides and IgG4-related disease: A new overlap syndrome

OBJECTIVE Atypical manifestations have been described in patients with ANCA-associated vasculitides (AAV), such as pachymeningitis, orbital mass or chronic periaortitis. Because these manifestations have been associated to the spectrum of IgG4-related disease (IgG4-RD), we hypothesized that both diseases could overlap. METHODS We conducted a European retrospective multicenter observational study including patients fulfilling ACR and Chapel Hill criteria for AAV and IgG4-RD Comprehensive Diagnostic Criteria. RESULTS Eighteen patients were included (median age 55.5years, 13 men). AAV and IgG4-RD were diagnosed concomitantly in 13/18 (72%) patients; AAV preceded IgG4-RD in 3/18 (17%) while IgG4-RD preceded AAV in 2/18 (11%). AAV diagnoses included granulomatosis with polyangiitis in 14 (78%), microscopic polyangiitis in 3 (17%), and eosinophilic granulomatosis with polyangiitis in one case. IgG4-RD diagnosis included definite IgG4-RD in 5 (28%) cases, probable IgG4-RD in 5 (28%) and possible IgG4-RD in 8 (44%). IgG4-RD manifestations were chronic periaortitis in 9/18 (50%) patients, orbital mass and tubulointerstitial nephritis in 4 (22%) cases, prevertebral fibrosis in 3 (17%), pachymeningitis and autoimmune pancreatitis in 2 (11%) cases. Patients required median number of 2 (range 0-4) lines of immunosuppressants in combination with glucocorticoids. During the follow-up (median 49,8months, range 17,25-108months), AAV manifestations relapsed in 10/18 (56%) cases and IgG4-RD lesions in 5/18 (28%). When used, mainly for relapses, rituximab showed response in all cases. CONCLUSION AAV and IgG4-RD may overlap. Clinicians should consider that atypical manifestations during AAV could be related to IgG4-RD rather than to refractory granulomatous or vasculitic lesions.

Autoimmune and inflammatory diseases associated with chronic myelomonocytic leukemia: A series of 26 cases and literature review

We wanted to describe the characteristics, treatment and outcome of autoimmune and inflammatory diseases (SAIDs) associated with chronic myelomonocytic leukemia (CMML), and conducted a French multicenter retrospective study and a literature review. We included 26 cases of CMML (median age 75 years, 54% female), 80% with CMML-1. CPSS score was low (0 or 1) in 75% of cases. SAIDS was systemic vasculitis in 54%. Diagnosis of the 2 diseases was concomitant in 31% cases, and CMML was diagnosed before SAIDs in 12 cases (46%). First line treatment for SAIDs consisted mostly of steroid, with 85% of response. Second-line treatment was needed in 40% cases. Six patients received hypomethylating agents, with 66% response on SAIDs. A literature review found 49 cases of CMML-associated SAIDs, in whom SAIDs was systemic vasculitis in 29% cases. Hence, vasculitis is the most frequent SAIDs associated with CMML. After initial response to steroids, recurrence and steroid-dependence were frequent. Hypomethylating agents may be interesting in this context.

Characteristics and Management of IgA Vasculitis (Henoch-Schonlein) in Adults Data From 260 Patients Included in a French Multicenter Retrospective Survey

Data on adult IgA vasculitis (Henoch‐Schönlein) (IgAV) are scarce. This survey was designed to better define the clinical spectrum of IgAV and efficacy of treatments in a French patient population.

Characteristics and management of IgA vasculitis (Henoch-Schönlein purpura) in adults: Data from the 260 patients included in the IGAVAS survey

Data on adult IgA vasculitis (Henoch‐Schönlein) (IgAV) are scarce. This survey was designed to better define the clinical spectrum of IgAV and efficacy of treatments in a French patient population.

Risk factors associated with intracranial hemorrhage in adults with immune thrombocytopenia: A study of 27 cases.

LMW iron dextran over 1 hr. An additional 30-min infusion time was used for each 500 mg beyond the traditional 1 gram dose and premedication use was only recommended with >2 drug allergies. We conducted a retrospective cohort study of adults receiving iron dextran for the first time at a cancer center located on the campus of a regional academic medical center. Patients were divided into shortened infusion (rate 12 mg/min) and extended infusion (rate <12 mg/min) iron dextran groups. Infusion time was based on rounding up to the nearest 500 mg dose. A total of 241 were screened for inclusion, 34 of whom were excluded (20 previously received iron dextran, 6 concurrent chemotherapy, 4 incomplete time information, 3 experienced an AE during test dose, and 1 did not receive iron dextran). Of those who met inclusion, 92 (45%) received the extended infusion and 115 (55%) received the shortened infusion. At baseline, there were no statistically significant differences between groups with the exception of more females (81.5% vs. 67.8%; P 5 0.026) and premedication use (81.5% vs. 46.9%; P< 0.001) in the extended infusion group. The most common indications for parenteral iron were gastrointestinal or uterine bleeding (35%) and cancer (28%). AEs and AEs requiring medication intervention were not significantly different between groups (Table I). The most common AEs were abdominal pain and nausea. Throat itching occurred in two (both in the extended infusion group) and led to infusion discontinuation in one. The univariate analysis of baseline characteristics to identify correlation with AEs only detected a significant association with celiac disease. Celiac disease, as well as those variables that differed significantly at baseline between the two groups (female sex and premedication use), were incorporated into the multiple logistic regression. In that analysis, celiac disease remained the only characteristic significantly associated with increased risk of developing an AE (OR 39.9, 95% CI 3.8–417.4; P 5 0.002). Of the four with celiac disease in the study, three developed an AE. There were also no significant differences between groups with regard to average increase in hemoglobin or any of the iron indices (Table I). Chair time was significantly less, by an average of 1.7 hr, in the shortened infusion group (Table I). The results of this study show that there is no difference in AEs and effectiveness between shortened and extended infusion iron dextran. AEs were relatively uncommon and nonlife threatening. After controlling for gender and premedication use, celiac disease was the only baseline characteristic significantly associated with an increased likelihood of an AE. Although previous studies have not reported a relationship between celiac disease and AEs, it may be related to the immune-mediated nature of the disease. However, this association should be viewed cautiously as there were only four (1.9%) with celiac disease. Notably, premedication use did not significantly reduce the risk of developing an AE. While premedication use did decline significantly after protocol implementation, it is suspected that many continued to receive premedication because of provider comfort. Antihistamines were the most commonly administered premedication, despite the lack of evidence and their ability to cause AEs themselves [4]. While it is difficult to differentiate, it is possible that many of the AEs experienced were secondary to anti-histamine use rather than iron dextran. Those with >2 drug allergies made up a relatively large percentage of the population (12%) but, unlike the previous study, we found no significant association between multiple drug allergies and AEs. This could be explained by premedication use in this group, although this is common practice in many studies and the protective effect of premedication is not convincing [3,5]. Finally, the switch to shortened infusion iron dextran also has the advantage of significantly less chair time. This time savings is beneficial as it allows more to receive treatment and requires less time spent in clinic. Additionally, it improves reimbursement rates, as a clinic is often paid more for the first hour of infusion than subsequent hours. Although several studies have assessed the safety and effectiveness of shortened infusion iron dextran, this study is unique in that it directly compares extended versus shortened infusion in a general population [3,5,6]. Limitations include the retrospective nature and infrequency of severe AEs. Since severe AEs are exceedingly rare, especially with the disappearance of HMW formulations, it is logistically challenging to collect a sample size that would have a high likelihood of capturing such events. Future studies are necessary to further elucidate risk factors associated with developing an AE in order to identify if certain populations may benefit from premedication. In summary, iron dextran is a convenient parenteral treatment option that allows for total iron deficit repletion, which is particularly beneficial for those who live in rural areas or have difficulty getting into clinic. Although historical concerns regarding serious iron dextran AEs have led to standard extended infusion times, the results of this study support the transition to shortened infusion as safe, effective, and associated with significant chair time savings.

Cogan syndrome: Characteristics, outcome and treatment in a French nationwide retrospective study and literature review

BACKGROUND Cogan syndrome is mainly treated with steroids. We aimed to determine the place of DMARDs and biologic-targeted treatments. PATIENTS AND METHODS We conducted a French nationwide retrospective study of patients with Cogan syndrome (n=40) and a literature review of cases (n=22) and analyzed the efficacy of disease-modifying anti-rheumatic drugs (DMARDs) and tumor necrosis factor α (TNF-α) antagonists. RESULTS We included 62 patients (31 females) (median age 37years [range 2-76]. At diagnosis, 61 patients (98%) had vestibulo-auditory symptoms, particularly bilateral hearing loss in 41% and deafness in 31%. Ocular signs were present in 57 patients (92%), with interstitial keratitis in 31 (51%). The first-line treatment consisted of steroids alone (n=43; 70%) or associated with other immunosuppressive drugs (n=18; 30%). Overall, 13/43 (30%) and 4/18 (22%) patients with steroids alone and with associated immunosuppressive drugs, respectively (p=0.8), showed vestibulo-auditory response; 32/39 (82%) and 15/19 (79%) ocular response; and 23/28 (82%) and 10/14 (71%) general response. Overall 61 patients had used a total of 126 lines of treatment, consisting of steroids alone (n=51 lines), steroids with DMARDs (n=65) and infliximab (n=10). Vestibulo-auditory response was significantly more frequent with infliximab than DMARDs or steroids alone (80% vs 39% and 35%, respectively), whereas ocular, systemic and acute-phase reactant response rates were similar. Infliximab was the only significant predictor of vestibulo-auditory improvement (odds ratio 20.7 [95% confidence interval 1.65; 260], p=0.019). CONCLUSION Infliximab could lead to vestibulo-auditory response in DMARDS and steroid-refractory Cogan syndrome, but prospective studies are necessary.

Acute Lower Limb Ischaemia and Diabetes in a Patient Treated with Anti-PD1 Monoclonal Antibody for Metastatic Melanoma.

We recommend thromboembolism prevention in cases of pre-existing diabetes, and particularly as regards ketoacidosis, in patients under pembrolizumab therapy.

Thymic Epithelial Tumor-Associated Cytopenia: A 10-Year Observational Study in France

Introduction: Thymic epithelial tumor (TET)‐associated cytopenia is rare but difficult to treat. Methods: We performed a multicenter, retrospective study of TET and associated forms of cytopenia in France. Cases were collected by the French National Reference Center for Autoimmune Cytopenia and the French National Thymic Malignancy Interest Group (Réseau Tumeurs Thymiques et Cancer) and through a call for cases by the French Society of Internal Medicine. Results: Thirty‐six cases were recorded between 2002 and 2014 and followed up for a median of 38 months (interquartile range, 23–106 months). Thirty‐two patients underwent surgery for TET, and 14 of the latter were in complete remission at last follow‐up. Cytopenia can occur before, simultaneously, or after diagnosis of TET. The most common types of cytopenia were pure red cell aplasia (in 30% of cases) and Good syndrome (GS) (also in 30% of cases). Eleven patients displayed two or more episodes of cytopenia. Eighteen patients received steroids as their first‐line treatment, leading to a complete response in nine. Other first‐line treatments (cyclosporine and rituximab) were less effective but should be considered as treatment options. Infections developed in 84% of the patients with GS; this did not appear to be related to the presence or absence of immunosuppressive treatment or chemotherapy. Eight patients died during the follow‐up period (two died of cytopenia and five of infections). Conclusions: The optimal treatment for TET‐associated cytopenia has not been clearly defined and the outcome does not appear to be correlated with TET progression. For GS, prophylactic immunoglobulin replacement therapy and prophylactic antibiotic therapy can be recommended.

Unusual skin manifestation of antiphospholipid syndrome.

A 30-year-old woman with antiphospholipid syndrome (APS) was admitted for arthralgia, skin ulceration (Figure 1) and auricular chondritis, 1 week after an intrauterine fetal death at 25th week of gestation. Physical examination showed …