Eculizumab Salvage Therapy for Antibody‐Mediated Rejection in a Desensitization‐Resistant Intestinal Re‐Transplant Patient

The presence of elevated calculated panel reactive antibody (cPRA) and anti‐HLA donor specific antibodies (DSA) are high risk factors for acute antibody‐mediated rejection (AAMR) in intestinal transplantation that may lead to graft loss. Eculizumab has been used for the treatment of AAMR in kidney transplantation of sensitized patients that do not respond to other treatment. Here, we report a case where eculizumab was used to treat AAMR in a desensitization‐resistant intestinal re‐transplant patient. A male patient lost his intestinal graft to AAMR 8.14 years after his primary transplant. He received a second intestinal graft that had to be explanted a month later due to refractory AAMR. The patient remained highly sensitized despite multiple treatments. He received a multivisceral graft and presented with severe AAMR on day 3 posttransplantation. The AAMR was successfully treated with eculizumab. The patient presently maintains an elevated cPRA level above 90% but his DSAs have decreased from 18 000 MFI (mean fluorescent intensity) to below the positive cut‐off value of 3000 MFI and remains rejection free with a 2‐year follow‐up since his multivisceral transplant. Eculizumab offers an alternative to treat AAMR in intestinal transplantation in desensitization‐resistant patients.     

Anakinra is a possible alternative in the treatment and prevention of acute attacks of pseudogout in end-stage renal failure

We describe the case of a 71-year-old man with recurrent pseudogout attacks affecting multiple joints. He had end-stage renal failure that contra-indicated the use of non-steroidal anti-inflammatory drugs and was resistant to therapy with glucocorticoids. Based on the recent findings that interleukin (IL)-1β is involved in crystal-induced inflammation, the patient received anakinra, a specific IL-1 inhibitor, in order to treat an acute attack of pseudogout. In addition, anakinra was administered as preventive therapy 3 days per week after each hemodialysis session. Under this treatment, he did not present any severe episode of arthritis after a follow-up of 8 months. This observation suggests that anakinra is efficacious and safe for the prevention of crystal-induced arthritis in patients with severe renal failure.     

Performance of existing risk scores around heart transplantation: validation study in a 4‐year cohort

Several risk scores exist to help identify best candidate recipients for heart transplantation (HTx). This study describes the performance of five heart failure risk scores and two post‐HTx mortality risk scores in a French single‐centre cohort. All patients listed for HTx through a 4‐year period were included. Waiting‐list risk scores [Heart Failure Survival Score (HFSS), Seattle Heart Failure Model (SHFM), Meta‐Analysis Global Group in Chronic Heart Failure (MAGGIC), Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients with Heart Failure (OPTIMIZE‐HF) and Get With The Guidelines‐Heart Failure (GWTG‐HF)] and post‐HTx scores Index for Mortality Prediction After Cardiac Transplantation (IMPACT and CARRS) were computed. Main outcomes were 1‐year mortality on waiting list and after HTx. Performance was assessed using receiver operator characteristic (ROC), calibration and goodness‐of‐fit analyses. The cohort included 414 patients. Waiting‐list mortality was 14.0%, and post‐HTx mortality was 16.3% at 1‐year follow‐up. Heart failure risk scores had adequate discrimination regarding waiting‐list mortality (ROC AUC for HFSS = 0.68, SHFM = 0.74, OPTIMIZE‐HF = 0.72, MAGGIC = 0.70 and GWTG = 0.77; all P‐values <0.05). On the contrary, post‐HTx risk scores did not discriminate post‐HTx mortality (AUC for IMPACT = 0.58, and CARRS = 0.48, both P‐values >0.50). Subgroup analysis on patients undergoing HTx after ventricular assistance device (VAD) implantation (i.e. bridge‐to‐transplantation) (n = 36) showed an IMPACT AUC = 0.72 (P < 0.001). In this single‐centre cohort, existing heart failure risk scores were adequate to predict waiting‐list mortality. Post‐HTx mortality risk scores were not, except in the VAD subgroup.     

Serial measurement of presepsin,procalcitonin, and C‐reactive protein in the early postoperative period and the response to antithymocyte globulin administration after heart transplantation

Differentiation between systemic inflammatory response syndrome and sepsis in surgical patients is of crucial significance. Procalcitonin (PCT) and C‐reactive protein (CRP) are widely used biomarkers, but PCT becomes compromised after antithymocyte globulin (ATG) administration, and CRP exhibits limited specificity. Presepsin has been suggested as an alternative biomarker of sepsis. This study aimed to demonstrate the role of presepsin in patients after heart transplantation (HTx). Plasma presepsin, PCT, and CRP were measured in 107 patients serially for up to 10 days following HTx. Time responses of biomarkers were evaluated for both noninfected (n=91) and infected (n=16) patients. Areas under the concentration curve differed in the two groups of patients for presepsin (P<.001), PCT (P<.005), and CRP (P<.001). The effect of time and infection was significant for all three biomarkers (P<.05 all). In contrast to PCT, presepsin was not influenced by ATG administration. More than 25% of noninfected patients had PCT above 42 μg/L on the first day, and the peak concentration of CRP in infected patients was reached on the third post‐transplant day (median 135 mg/L). Presepsin seems to be as valuable a biomarker as PCT or CRP in the evaluation of infectious complications in patients after HTx.     

Anti‐IL‐2R blockers comparing with polyclonal antibodies: Higher risk of rejection without negative mid‐term outcomes after ABO‐incompatible kidney transplantation

There is no recommendation regarding the type of induction therapy to use in ABO‐incompatible (ABOi) kidney transplantation. The aim of this retrospective study was to compare the outcome of ABOi living donor kidney transplant (LDKT) recipients who received either polyclonal antibodies or anti‐interleukin‐2 receptor (IL‐2R) blockers as an induction agent. All ABOi HLA‐compatible patients that received a LDKT between 03/11 and 03/18 in three French transplantation center (Paris Saint‐Louis, Paris Necker, and Toulouse) were included in the study. Fifty‐eight patients were given polyclonal antibodies and 39 patients received anti‐IL‐2R blockers. We identified by a Cox proportional hazard model the use of polyclonal antibodies as a protective factor against acute rejection (HR = 0.4, 95%CI [0‐0.9], P < .05). However, pathological findings on protocol biopsies at 1 year were similar in both groups, as were patient and graft survivals, renal function, and complications. We conclude that the acute rejection rate was significantly higher in patients given anti‐IL‐2R blockers compared to polyclonal antibodies. However, in our series, there was no negative impact on mid‐term outcome.     

Successful simultaneous liver‐kidney transplantation for renal failure associated with hereditary complement C3 deficiency

Hereditary complement C3 deficiency is associated with recurrent bacterial infections and proliferative glomerulonephritis. We describe a case of an adult with complete deficiency of complement C3 due to homozygous mutations in C3 gene: c.1811delT (Val604Glyfs*2), recurrent bacterial infections, crescentic glomerulonephritis, and end‐stage renal failure. Following isolated kidney transplantation he would remain C3 deficient with a similar, or increased, risk of infections and glomerulonephritis. As C3 is predominantly synthesized in the liver, with a small proportion of C3 monocyte derived and kidney derived, he proceeded to simultaneous liver‐kidney transplantation. The procedure has been successful with restoration of his circulating C3 levels, normal liver and kidney function at 26 months of follow‐up. Simultaneous liver‐kidney transplant is a viable option to be considered in this rare setting.     

Blood dendritic cell levels associated with impaired IL‐12 production and T‐cell deficiency in patients with kidney disease: implications for post‐transplant viral infections

Reduced pretransplant blood myeloid dendritic cell (mDC) levels are associated with post‐transplant BK viremia and cytomegalovirus (CMV) disease after kidney transplantation. To elucidate potential mechanisms by which mDC levels might influence these outcomes, we studied the association of mDC levels with mDC IL‐12 production and T‐cell level/function. Peripheral blood (PB) was studied in three groups: (i) end stage renal disease patients on hemodialysis (HD; n = 81); (ii) chronic kidney disease stage IV‐V patients presenting for kidney transplant evaluation or the day of transplantation (Eval/Tx; n = 323); and (iii) healthy controls (HC; n = 22). Along with a statistically significant reduction in mDC levels, reduced CD8⁺ T‐cell levels were also demonstrated in the kidney disease groups compared with HC. Reduced PB mDC and monocyte‐derived DC (MoDC) IL‐12 production was observed after in vitro LPS stimulation in the HD versus HC groups. Finally, ELISpot assays demonstrated less robust CD3⁺ INF‐γ responses by MoDCs pulsed with CMV pp65 peptide from HD patients compared with HC. PB mDC level deficiency in patients with kidney disease is associated with deficient IL‐12 production and T‐cell level/function, which may explain the known correlation of CD8⁺ T‐cell lymphopenia with deficient post‐transplant antiviral responses.     

Decreasing plasma soluble IL‐1 receptor antagonist and increasing monocyte activation early post‐transplant may be involved in pathogenesis of delayed graft function in renal transplant recipients

Sadeghi M, Daniel V, Naujokat C, Schmidt J, Mehrabi A, Zeier M, Opelz G. Decreasing plasma soluble IL‐1 receptor antagonist and increasing monocyte activation early post‐transplant may be involved in pathogenesis of delayed graft function in renal transplant recipients
Clin Transplant 2010: 24: 415–423. © 2009 John Wiley & Sons A/S. Abstract: Delayed graft function (DGF) increases the risk of acute allograft rejection and may affect long‐term graft survival. We compared pre‐transplant, early post‐transplant, and late post‐transplant serum creatinine (Cr) and plasma levels of neopterin, cytokines, and cytokine receptors/antagonists in patients with DGF (n = 39), slow graft function (SGF) (n = 43), or immediate graft function (IGF) (n = 30). Three and eight days post‐transplant, plasma neopterin (p < 0.001; p < 0.001), Soluble Interleukin‐6 (IL‐6) receptor (R) (p = 0.002; p = 0.001), and IL‐10 (p = 0.003; p = 0.001) were higher in DGF than IGF patients. One month post‐transplant, plasma neopterin (p < 0.001) and IL‐10 (p < 0.001) were higher in DGF than IGF patients. Three days post‐transplant, the results indicated reduced sIL‐1 receptor antognist (RA) production in DGF patients (p = 0.001). Simultaneously, plasma sIL‐6R and IL‐10 increased in DGF (p < 0.001; p = 0.003) and SGF (p = 0.007; p = 0.030) patients, indicating increased production of sIL‐6R and IL‐10. Lower sIL‐1 production in DGF than IGF patients early post‐transplant might promote the increased production of monocyte‐derived neopterin, sIL‐6R, and IL‐10. This monocyte/macrophage activation might induce inflammation in the graft and subsequently cause an impairment of graft function. Blocking of monocyte activity after renal transplantation may be considered a potential approach for improving graft outcome.     

Progressive Multifocal Leukoencephalopathy in a Heart Transplant Recipient Following Rituximab Therapy for Antibody‐Mediated Rejection

We report the case of a male heart transplant recipient who developed acute antibody‐mediated rejection and was treated with 5 weeks of a rituximab‐containing regimen. Two months later he presented with progressive motor and cognitive impairments and was diagnosed with progressive multifocal leukoencephalopathy (PML). He was treated with reduction of his immunosuppressive medications, mirtazapine, IVIG and plasmapheresis. He died within weeks. We reviewed the current literature on PML and its association with immunosuppression, highlighting its impact in the setting of solid organ transplantation and considering the potential effect of newer biologic drugs on the incidence of this devastating disease in the transplant population.     

Pregnancy after heart transplantation: a well‐thought‐out decision? The Quebec provincial experience – a multi‐centre cohort study

Despite reports of successful pregnancies in heart transplant (HTx) recipients, many centers recommend their patients against maternity. We reviewed our provincial experience of pregnancy in HTx recipients by performing charts review of all known gestations following HTx in the province of Quebec (Canada), stratified between planned and unplanned pregnancies. Long‐term survival was compared to HTx recipient women of childbearing age who did not become pregnant. Eighteen pregnancies, 56% unplanned, occurred in eight patients, 10.1 (2.6–27.0) years after HTx. Immunosuppression was CNI‐based, with a mean dose increase of 48.3% (tacrolimus) and 26.5% (cyclosporine), without rejection. Cardiometabolic complications were high compared to the general Canadian population, including preeclampsia (15.4% vs. 5.5%), hypertension (38.5% vs. 4.6%), and diabetes (15.4% vs. 5.6%). Mean gestational age was 35.1 (23.4–39.6) weeks (72.2% live births; 53.8% prematurity). Mean birthweight was 2418 (660–3612) g. Serum creatinine increased during pregnancy, becoming significant after delivery (P = 0.0239), and returning to preconception level in all but three patients within a year. After 4.6 (1.2–17.2) years of follow‐up, two rejection episodes occurred in one patient. Long‐term mortality was similar to overall HTx women (Kaplan–Meier; P = 0.8071). Pregnancy in HTx carries high cardiometabolic complications and decreased kidney function, but is feasible with acceptable outcomes and no impact on mother's survival.     

Circulating delta‐like Notch ligand 1 is correlated with cardiac allograft vasculopathy and suppressed in heart transplant recipients on everolimus‐based immunosuppression

Cardiac allograft vasculopathy (CAV) causes heart failure after heart transplantation (HTx), but its pathogenesis is incompletely understood. Notch signaling, possibly modulated by everolimus (EVR), is essential for processes involved in CAV. We hypothesized that circulating Notch ligands would be dysregulated after HTx. We studied circulating delta‐like Notch ligand 1 (DLL1) and periostin (POSTN) and CAV in de novo HTx recipients (n = 70) randomized to standard or EVR‐based, calcineurin inhibitor‐free immunosuppression and in maintenance HTx recipients (n = 41). Compared to healthy controls, plasma DLL1 and POSTN were elevated in de novo (P < .01; P < .001) and maintenance HTx recipients (P < .001; P < .01). Use of EVR was associated with a treatment effect for DLL1. For de novo HTx recipients, a change in DLL1 correlated with a change in CAV at 1 (P = .021) and 3 years (P = .005). In vitro, activation of T cells increased DLL1 secretion, attenuated by EVR. In vitro data suggest that also endothelial cells and vascular smooth muscle cells (VSMCs) could contribute to circulating DLL1. Immunostaining of myocardial specimens showed colocalization of DLL1 with T cells, endothelial cells, and VSMCs. Our findings suggest a role of DLL1 in CAV progression, and that the beneficial effect of EVR on CAV could reflect a suppressive effect on DLL1. Trial registration numbers— SCHEDULE trial: ClinicalTrials.gov NCT01266148; NOCTET trial: ClinicalTrials.gov NCT00377962.     

Late pancreatic panniculitis in a simultaneous pancreas kidney transplant patient with failed allografts

We present a rare case of pancreatic panniculitis in a 59‐year‐old male simultaneous pancreas–kidney (SPK) recipient with failed allografts. The patient presented with fever and painful erythematous nodules on his leg 1 month after stopping all immunosuppression. A thorough infectious and rheumatological workup was negative. He had pancreas rejection 4 years after SKP transplant and was restarted on dialysis after 14 years when his renal allograft failed due to chronic allograft nephropathy. His chronic immunosuppression (tacrolimus, azathioprine) was stopped and prednisone was weaned over 3 months at that time. A skin biopsy revealed saponification of the subcutaneous fat with inflammation pathognomonic of pancreatic panniculitis. Concurrent allograft pancreatitis confirmed with elevated lipase and a computed tomography scan finding of peripancreatic graft stranding and atrophic native pancreas. He was started on pulse steroid therapy for 3 days followed by oral taper. This resulted in dramatic resolution of all skin lesions and normalization of lipase levels within 1 week, followed by resumption of low‐dose tacrolimus and azathioprine. This is an extremely rare occurrence of panniculitis in pancreas allograft after 10 years of pancreatic failure associated with stopping immunosuppression.     

Anakinra effectiveness in refractory polyserositis: An Italian multicenter study

ObjectivesPolyserositis is an inflammatory condition involving different serosal membranes at the same time, specifically the pericardium, pleura, and peritoneum with exudates in the respective cavities. Treatment with non-steroidal anti-inflammatory drugs (NSAIDs), colchicine and glucocorticoids may be effective in patients with polyserositis, but relapses often occur when these drugs are tapered or discontinued. The interleukin (IL)-1 receptor antagonist anakinra has shown a beneficial effect in idiopathic recurrent pericarditis, mostly in unresponsive patients who develop steroid dependence and/or colchicine resistance. To date, there are no data suggesting the best therapy for managing acute episodes and/or relapses of polyserositis. On this basis, we performed a retrospective study aimed at evaluating the effectiveness and safety profile of anakinra in treating patients with refractory polyserositis.MethodsPatients with idiopathic polyserositis or rheumatic diseases presenting inflammation of 2 or more serous membranes were included. Serositis had to be confirmed by imaging tests comprising either echocardiography, abdominal ultrasound, chest or abdomen computed tomography and/or chest x-ray scan. We included patients with polyserositis who started anakinra from January 2011 to January 2019 due to a poorly controlled disease despite treatment with NSAIDs, conventional immunosuppressant drugs, or the need to minimize oral corticosteroids intake. Erythrocyte sedimentation rate (ESR), C reactive protein (CRP), and imaging tests, were recorded to monitor serositis at baseline and either at 3, 6 and 12-month follow-up. Patients with malignancies and infectious diseases were excluded from the analysis.ResultsForty-five patients with recurrent polyserositis (23 women) (mean age 43.2 ± 15.8 years and mean disease duration 23.1 ± 28 years) were analysed. Polyserositis was idiopathic in 26 (57.8%) patients. Thirteen patients suffered from autoinflammatory diseases, whereas 6 were affected by autoimmune diseases. Combination treatment with colchicine and NSAIDs at anakinra baseline was administered in 38/45 (84.4%) and 37/45 (82.2%) patients, respectively. After starting anakinra, 84.5% of patients experienced a resolution of serositis with a dramatic decrease in ESR and CRP (P < 0.001, for both) already at 3 months, furthermore the same beneficial effect was observed up to 12 months. No relapse was seen at 3 months, whereas the median number of relapses at 6 and 12 months was 0 (interquartile range 0-1). Glucocorticoids were discontinued in 22/45 (48.9%) patients already after 3 months (P < 0.001). After 12 months 32/37 (86.5%) patients were steroid-free. Similarly, NSAIDs use significantly was decreased at 3 months (7/45 [15.6%] patients, P < 0.001), whereas at 12-month follow-up no patient was on NSAIDs. Urticarial rashes at anakinra injection site occurring in 3 patients were the most common adverse events.ConclusionsAnakinra appeared to be a safe and useful therapeutic choice for patients refractory to optimal anti-inflammatory therapy (NSAIDs, colchicine and corticosteroids), allowing not only a dramatic reduction of recurrences but also of corticosteroids use. Anakinra was effective both in the idiopathic forms of polyserositis and in those with an underlying rheumatic disease, suggesting a common pathogenic pathway leading to serositis onset.     

Elevated ST2 levels are associated with antibody‐mediated rejection in heart transplant recipients

Soluble ST2 (sST2) is a novel biomarker of inflammation and fibrosis. Elevated sST2 levels (≥35 ng/mL) are associated with worse outcomes in patients with heart failure (HF). There are sparse data regarding the significance of sST2 levels after heart transplantation (HTx). The study aims were to evaluate trends in soluble ST2 levels after the resolution of HF status with HTx and association between post‐HTx sST2 levels and outcomes. Plasma sST2 levels were measured at baseline (median [IQR] of 118 days pre‐HTx) and 12 months post‐HTx in 62 subjects who were stratified into two groups by post‐HTx sST2 levels < or ≥35 ng/mL: “Group 1” or “Group 2,” respectively. Plasma sST2 levels were elevated in 58% of patients pre‐HTx and in 50% of patients post‐HTx. There was no association between elevated sST2 levels before and after HTx, and no significant differences in baseline characteristics between Group 1 and Group 2 patients. Group 2 as compared to Group 1 HTx recipients had significantly higher incidence of antibody‐mediated rejection (AMR) for the entire post‐transplant follow‐up period (32% vs 4%, P = 0.006). There was no association between post‐HTx sST2 level status and other post‐HTx outcomes including survival. In conclusion, elevated plasma sST2 levels after HTx are associated with increased risk for AMR.     

Immune activation‐ and regulation‐related patterns in stable hand transplant recipients

We assessed cell subsets and expression of a set of genes related to the T‐cell populations in peripheral blood mononuclear cells to elucidate whether immune status of stable hand transplant recipients (HTx) differs from stable kidney transplant recipients (KTx). The study was conducted on five HTx 4.8 ± 1.7 years after transplantation and 30 stable KTx 7.9 ± 2.4 years after transplantation as well as 18 healthy volunteers. The research involved PBMC gene expression analysis of CD4, CD8, CTLA4, GZMB, FOXP3, IL10, IL4, ILR2A, NOTCH, PDCD1, PRF1, TGF‐B, and TNF‐A genes on a custom‐designed low‐density array (TaqMan) as well as flow cytometry assessment of lymphocyte subpopulations. HTx presented significantly increased expression of immunomodulatory genes (TNF, IL10, GITR, and PDCD1) compared to KTx and controls. HTx revealed a proinflammatory molecular pattern with higher expression of NOTCH and CD8 compared to KTx and controls. KTx showed a reduced level of regulatory T cells compared to controls and HTx. Both HTx and KTx presented an increased number of CD8⁺ and CD8⁺CD28⁻ T cells compared to controls. Stable hand transplant recipients exhibit persistent immune activation with rejection‐related gene expression pattern counterbalanced by secondary induction of regulatory mechanisms.     

Immune checkpoint inhibitor therapy-associated graft intolerance syndrome in a failed kidney transplant recipient

Immune checkpoint inhibitors (ICPIs) are monoclonal antibodies against inhibitory receptors on T cells resulting in anticancer activity. In kidney transplant (KT) recipients, ICPI use has been associated with acute allograft rejection. In failed allografts, however, the effects of ICPIs are unknown. We present a case of a 66-year-old man with a history of diabetes, renal cell cancer, left native nephrectomy, and end-stage kidney disease. He received a deceased donor KT which failed after 6 years due to biopsy-proven recurrent diabetic nephrosclerosis. He was started on hemodialysis and his immunosuppression was gradually weaned off. A year later, he was diagnosed with renal cell cancer in his right native kidney requiring nephrectomy. He later developed metastasis and was started on combination ICPIs. He developed hematuria, allograft pain, and malaise consistent with graft intolerance syndrome 28 days after starting ICPIs. Urine culture and cystoscopy were normal. A computed tomography scan of his abdomen revealed an enlarged allograft with patchy enhancement. After a multidisciplinary discussion, he underwent transplant nephrectomy. Histopathology showed chronic active T cell–mediated rejection. As ICPI use becomes prevalent, practitioners need to be aware of its potential complications among KT recipients both with functioning and failed allografts.     

Prednisone‐free maintenance immunosuppression in obese kidney transplant recipients

Obese transplant recipients (BMI ≥ 30 kg/m²) have decreased posttransplant patient and graft survival compared with their nonobese counterparts. At the same time, many prednisone‐related side effects (eg, new‐onset diabetes) are similar to those associated with obesity. Using SRTR data, we studied outcomes associated with prednisone‐free maintenance immunosuppression (rapid discontinuation of prednisone—RDP). Between January 1, 2000, and December 31, 2014, 44 635 first transplant recipients with BMI ≥ 30 kg/m² had a first kidney transplant (28 176 DD; 16 459, LD); 12,994 (29%) were discharged from the hospital on a prednisone‐free protocol. We compared outcomes to those discharged on a protocol incorporating maintenance prednisone (intention‐to‐treat analysis). RDP‐treated obese first DD recipients had significantly better patient survival (HR, 0.88; CI, 0.81‐0.96) and graft survival (HR, 0.93; CI, 0.88‐0.99) compared with their counterparts on maintenance immunosuppression. Although not statistically significant, the same trends were seen for LD recipients. For both DD and LD recipients, there was no difference between groups for death‐censored graft survival, suggesting that the benefit of RDP was due to improved patient survival. Our findings suggest that kidney transplant recipients with BMI ≥ 30 kg/m² benefit from a protocol that incorporates RDP.     

Health‐related quality of life,social support,and caregiver burden between six and 120 months after heart transplantation: a Spanish multicenter cross‐sectional study

A multicenter cross‐sectional study was conducted to determine the current heart transplant (HTx) outcomes in Spain. Clinical and functional status, health‐related quality of life (HRQoL), social support, and caregiver burden were analyzed in 303 adult transplant recipients (77.9% males) living with one functioning graft. Mean age at time of HTx (SD) was 56.4 (11.4) years, and the reason for transplantation in all patients was congestive heart failure. All patients had received a first heart transplant 6 (±1), 12 (±2), 36 (±6), 60 (±10), or 120 (±20) months previously. Participants completed the Kansas City Cardiomyopathy Questionnaire (KCCQ), the EQ‐5D, the Duke‐UNC Functional Social Support Questionnaire, and the Zarit Caregiver Burden Scale. Reasonable HRQoL, social support, and caregiver burden levels were found at all time points, although a slight decrease in HRQoL was recorded at 120 months (p ≤ 0.033). Multivariate regression analyses showed that complications, comorbidities, and hospitalizations were associated with HRQoL (EQ‐5D: 48.4% of explained variance, F_4,164 = 38.46, p < 0.001; KCCQ overall summary score: 45.0%, F_3,198 = 54.073, p < 0.001). Patient functional capabilities and complications affected caregiver burden (p < 0.05). In conclusion, HTx patients reported reasonable levels of HRQoL with low caregiver burden. Clinical variables related to these outcomes included functional status, complications, and number of admissions.     

Myositis in a patient with familial Mediterranean fever and spondyloarthritis successfully treated with anakinra

Familial Mediterranean fever is an autosomal-recessive autoinflammatory disorder more commonly observed in Mediterranean populations and characterized by recurrent episodes of fever, serositis, myalgia and arthritis. There is rarely any association with spondyloarthritis. The most important long-term complication is progressive systemic type AA amyloidosis. Treatment with colchicine is effective in reducing the frequency of attacks and prevents the development of amyloidosis. However, 5% of cases are considered resistant to colchicine. We here describe the case of a 39-year-old man, with a history of arthritis, arthralgias, and sacroiliitis in the course of a familial Mediterranean fever. He is homozygous for the M694I mutation in the MEFV gene. He subsequently developed myositis of the right quadriceps muscle confirmed by magnetic resonance imaging, electromyography and histology. He had frequent and severe arthralgias, despite colchicine, then etanercept and adalimumab, impairing his quality of life. The patient was successfully treated with the IL-1 receptor antagonist anakinra with a dramatic improvement of muscular and articular symptoms. To our knowledge, our patient is the first patient with coexisting FMF, spondyloarthritis and myositis responding to anakinra treatment. Moreover this is the second case in the literature of myositis associated with familial Mediterranean fever.