Vaskulitiden

Within the framework of the 2012 Chapel Hill Consensus Conference (CHCC) the subdivision of the heterogeneous group of diseases collectively known as vasculitis established in 1994 was revised and expanded with the aim of standardization of the nomenclature. Evidence-based criteria for the primary diagnosis of vasculitis do not currently exist. In vascular surgery the forms of vasculitis affecting medium and large size vessels are important differential diagnoses. Giant cell arteritis which often also simultaneously affects extracranial arteries is one of the most important differential diagnoses of peripheral artery occlusive disease (PAOD) with an age-dependent increase in prevalence. In cases of gastrointestinal, renal and coronary macroangiopathy in middle-aged patients, the presence of polyarteritis nodosa although rare has to be considered. Highly associated with nicotine consumption and often accompanied by superficial thrombophlebitis, thromboangiitis obliterans should be considered as a special form of vasculitis when infrapopliteal occlusive artery disease is present in younger patients.     

A new international classification of childhood vasculitis

There has been, for many years, a need for an acceptable classification of childhood vasculitis as well as criteria for classifying specific sub-categories of vasculitic disease affecting the young. Hitherto, there has been, with certain exceptions, much reliance on adult classification systems and criteria that have not proved entirely satisfactory. A recent International Consensus Conference held in Vienna in June 2005 attempted to rectify this state of affairs. It resulted in a new proposal for childhood vasculitis classification and proposals of classification criteria for several important categories of childhood vasculitis including Henoch–Schonlein purpura, Kawasaki disease, polyarteritis nodosa (with additionally definitions for cutaneous and microscopic polyarteritis), Wegener granulomatosis and Takayasu arteritis. The process involved the Delphi technique to gather a wide spectrum of opinion from pediatric rheumatologists and nephrologists followed by the Consensus Conference attended by a group of pediatricians with extensive vasculitis experience where nominal group techniques were utilized to agree on a general classification and classification criteria for individual childhood vasculitides. The consensus that was reached will hopefully provide pediatricians with a valuable tool in the study of childhood vasculitides but will require appropriate validation using patient and control groups.     

Fibromyalgia: mechanisms and potential impact of the ACR 2010 classification criteria

Fibromyalgia is a disorder characterized by chronic widespread pain in the presence of widespread tenderness, and multiple somatic symptoms. Since the publication of the American College of Rheumatology (ACR) 1990 classification criteria for fibromyalgia, research has proliferated and, in a relatively short period, investigators have begun to unravel the etiology and long-term impact of this complex condition. Although the ACR 1990 criteria have been central to fibromyalgia research during the past two decades, a number of practical and philosophical objections have been raised in relation to them. Principally these objections have centered on the use (or lack thereof) of the tender point examination, the lack of consideration of associated symptoms, and the observation that fibromyalgia might represent the extreme end of a pain continuum. In developing the ACR 2010 criteria, experts have sought to address these issues and to simplify clinical diagnosis. An implicit aim was to facilitate more rigorous study of etiology. The purpose of this Review is to summarize research to date that has described the epidemiology, pathology and clinical course of fibromyalgia, and to assess the probable impact of the ACR 2010 criteria on future research efforts.     

Overview of the 2012 revised International Chapel Hill Consensus Conference nomenclature of vasculitides

The nomenclature and classification of vasculitis has been difficult and controversial for many decades. This is problematic both for research on vasculitis as well as clinical care of patients with vasculitis. The first (1994) International Chapel Hill Consensus Conference on the Nomenclature of Systemic Vasculitides (CHCC) proposed names and definitions for the most common forms of vasculitis. Since then, there have been substantial advances in our understanding of vasculitis and changes in medical terminology. In addition, CHCC 1994 did not propose a nomenclature for some relatively common forms of vasculitis, such as vasculitis secondary to other diseases. To address these issues, a second International Chapel Hill Consensus Conference was held in 2012. The goals were to change names and definitions as appropriate, and add important categories of vasculitis not included in CHCC 1994. This overview summarizes the 2012 CHCC and points out the changes compared to the 1994 CHCC. Notable changes include the introduction of new terms such as granulomatosis with polyangiitis, eosinophilic granulomatosis with polyangiitis and immunoglobulin A vasculitis and the inclusion of categories for variable vessel vasculitis and secondary forms of vasculitis.     

Incidence and Severity of Acute Cellular Rejection in Recipients Undergoing Adult Living Donor or Deceased Donor Liver Transplantation‡

Living donor liver transplantation (LDLT) may have better immunological outcomes compared to deceased donor liver transplantation (DDLT). The aim of this study was to analyze the incidence of acute cellular rejection (ACR) after LDLT and DDLT. Data from the adult‐to‐adult living donor liver transplantation (A2ALL) retrospective cohort study on 593 liver transplants done between May 1998 and March 2004 were studied (380 LDLT; 213 DDLT). Median LDLT and DDLT follow‐up was 778 and 713 days, respectively. Rates of clinically treated and biopsy‐proven ACR were compared. There were 174 (46%) LDLT and 80 (38%) DDLT recipients with ≥1 clinically treated episodes of ACR, whereas 103 (27%) LDLT and 58 (27%) DDLT recipients had ≥1 biopsy‐proven ACR episode. A higher proportion of LDLT recipients had clinically treated ACR (p = 0.052), but this difference was largely attributable to one center. There were similar proportions of biopsy‐proven rejection (p = 0.97) and graft loss due to rejection (p = 0.16). Longer cold ischemia time was associated with a higher rate of ACR in both groups despite much shorter median cold ischemia time in LDLT. These data do not show an immunological advantage for LDLT, and therefore do not support the application of unique posttransplant immunosuppression protocols for LDLT recipients.     

Association of cigarette smoking with albuminuria in the United States: the third National Health and Nutrition Examination Survey

BACKGROUND: The association of cigarette smoking with albuminuria has been reported but not examined in a representative U.S. population. No study has evaluated the association between serum cotinine (a biological marker for tobacco exposure) and kidney damage. METHODS: A cross-sectional analysis was conducted among 15,719 adult participants of the third National Health and Nutrition Examination Survey to assess the association between smoking exposure and kidney damage. Smoking was assessed by self-reported lifetime cigarette use and serum cotinine. Kidney damage was assessed by urine albumin-to-creatinine ratio (ACR), with albuminuria defined as ACR of > or =17 microg/mg in males and > or =25 microg/mg in females. RESULTS: The analysis included 13,121 with normal albumin (mean ACR 6.3 microg/mg) and 2,414 with albuminuria (mean ACR 143 microg/mg); hypertension was prevalent in 27% and 59%, respectively. Former smoking was similar between groups (21%), while current smoking was more common in persons with albuminuria (26%) compared to normal ACR (21%). Adjusted for other risk factors, among hypertensives, current smokers were 1.85 (95% CI: 1.29, 2.64) times more likely to have albuminuria than never smokers. Current smokers with a > or =40 pack-year history were at highest risk for albuminuria. Among non-smoking hypertensives, those exposed to passive smoke (highest versus lowest quartile of serum cotinine) were 1.41 (95% CI: 1.04, 1.90) times more likely to have albuminuria. Former smoking with cessation of > or =1 year among hypertensives was not associated with albuminuria. Among non-hypertensives, smoking and albuminuria were not consistently associated. CONCLUSION: Current and passive smoking, but not former smoking, were associated with the presence of albuminuria in the general U.S. population with hypertension, indicating a benefit to the kidney from smoking cessation.     

Treatment and prevention of cerebrovascular disorders in children

Opinion statement Cerebrovascular disorders are an important cause of mortality and chronic morbidity in children. Ischemic stroke is more common than cerebral venous thrombosis and hemorrhagic stroke in children. Several medical disorders have been associated with stroke in children, and a thorough evaluation of underlying causes is needed to determine the best treatment and prevention strategy. The treatment and prevention of stroke in children is not well studied, and current recommendations are based on adult studies, nonrandomized trials, or expert opinion. Children with stroke require immediate, special attention and if possible should be stabilized and transferred to an institution that can offer pediatric neurovascular expertise and care. All children with stroke should be referred to or have their care managed by a pediatric neurologist. The treatment of stroke in adults is well studied, and when applicable this evidence should be considered in the treatment of children with stroke. Data from animal and adult stroke studies have demonstrated a benefit for the aggressive treatment of infection, fever, blood pressure, hypo/hyperglycemia, intracranial pressure, and seizures, and should be applied to children with stroke. The use of thrombolytic, antithrombotic, and antiplatelet therapies is based on adult studies, cohort studies, and/or expert opinion. Two consensus guidelines regarding the treatment of arterial ischemic stroke and cerebral venous thrombosis were recently published and recommend the use of anticoagulants or antiplatelet agents in the acute setting, depending on the underlying cause of stroke. The evidence for the primary prevention of stroke in children is restricted to sickle cell disease (SCD) and derived from the Stroke Prevention in Sickle Cell Study Project studies. Long-term chronic transfusion therapy to maintain hemoglobin S levels below 30% is indicated in children with SCD and intracranial stenosis. It has also been recently determined that chronic transfusion therapy should not be stopped in children with SCD and an increased risk for stroke. The recurrence rate of arterial ischemic stroke (AIS) in children ranges from 6% to 30% and is highest among children with recurrent transient ischemic attack, cardiac disease, arteriopathies, and metabolic and coagulation abnormalities. Recommendations for secondary prevention are based on adult studies and the underlying pathophysiology of the stroke. Antiplatelet therapy (aspirin 1–5 mg/ kg/day) is recommended in most children with a history of AIS. Although there is minimal evidence to support its use in children, anticoagulation may be indicated in AIS associated with extracranial arterial dissection, prothrombotic disorders, cardiac disease, severe intracranial stenosis, and recurrent AIS while on antiplatelet therapy.     

Bilateral ureteral stricture from polyarteritis nodosa

A case of bilateral, asynchronous ureteral stricture from polyarteritis nodosa is described. Two cases of unilateral ureteral stricture from polyarteritis nodosa have been reported previously. Ureteral obstruction not associated with retroperitoneal fibrosis is rare with polyarteritis nodosa.     

Marked Differences in acute cellular rejection rates between living-donor and deceased-donor liver transplant recipients

BACKGROUND.: Due to ongoing organ donor shortage, an increasing number of adult live-donor liver transplants (LDLT) are being performed. The aims of this study were to compare the incidence of ACR between recipients of live- and deceased-donor liver transplants, and to note any differences in ACR among related and unrelated living-donor recipients. METHODS.: Sixty-four adults undergoing LDLT between 1998-2001 were closely matched with a deceased recipient. Statistical comparisons in ACR between the live- and deceased-donor groups were based on the differences between the ACR rates of each LDLT patient and the corresponding matched deceased recipient. Analyses were performed separately for pairs in which the living donor was not related to the recipient, was a nonsibling relative, or was a sibling. RESULTS.: Live- and deceased-donor recipients underwent a similar number of liver biopsies. In all, 16/50 (32%) of the biopsied LDLT patients had ACR compared to 36/49 (73%) of the deceased-donor recipients. ACR rates of living donors and their deceased-donor matches did not differ significantly for the unrelated living donors, but did differ for the nonsibling related (P=0.03) and the sibling LDLT (P=0.03). The results were similar when comparing rates of high-degree ACR for unrelated, nonsibling related, and sibling pairs. High-degree ACR differences in the sibling LDLT group were significantly greater than in the nonsibling group (P=0.05). CONCLUSIONS.: Rates of ACR and high-degree ACR are decreased in living-related liver transplant recipients. This difference is likely genetically related as ACR rates are lower in recipient-donor pairs of increasing genetic similarity.     

Transfusion in critically ill children: an ongoing dilemma

Transfusion of blood products is a cornerstone in managing many critically ill children. Major improvements in blood product safety have not diminished the need for caution in transfusion practice. In this review, we aim to discuss the interplay between benefits and potential adverse effects of transfusion in critically ill children by including 65 papers, which were evaluated based on previously agreed selection criteria. Current practice on transfusing critically ill children is mainly founded on the basis of adult studies, common practices with cut‐off values, and expert opinions, rather than evidence‐based medicine. Paediatric patients have explicit physiological challenges and requirements to be addressed. Critically ill children often suffer from anaemia, have substantial iatrogenic blood loss with subsequent transfusions, and are at a higher risk of complications, often due to human errors. Transfusion in children is associated with increased morbidity. A restrictive transfusion strategy is not associated with increased morbidity. Thus, transfusion in paediatrics should be considered a high‐risk treatment and requires individual clinical assessment. Current level of evidence support the notion that in most stable cases, despite high severity of illness (cyanotic children and neonates excluded), a restrictive haemoglobin threshold of 70 g/l (4.3 mmol/l) is no more harmful than to transfuse at a liberal trigger, e.g. haemoglobin 95 g/l (5.9 mmol/l). Thus, balanced against potential benefits and often its necessity, a restrictive approach may be appropriate due to the associated risks of transfusion.     

Clinical response and temporal patterns of acute cellular rejection: relationship to chronic transplant nephropathy

Abstract The association between acute cellular rejection (ACR) and the development of chronic rejection has been the subject of much debate. Studies have suggested that the two phenomena may be linked, or, conversely that there may be no association at all. In order to clarify this relationship the outcome of 284 renal allografts were examined. The transplants were all performed at a single institution between April 1989 and December 1991, allowing a minimum follow up of 5 years. ACR was classified into three clinical response groups: (1) fully responsive to therapy (type 1 ACR), (2) partially responsive (type 2) and (3) ACR requiring treatment with ATG or OKT3 (type 3). Acute and chronic rejection were determined by histological (Banff) criteria. Chronic transplant nephropathy (CTN) occurred significantly more frequently in those with late ACR after day 60 than in those who had early rejection (53.5% versus 17.3%, respectively, P < 0.00001). Acute rejection that was fully responsive to therapy (type 1) had no association with CTN, but partially responsive rejection and rejection requiring seconD-line treatment were both significantly associated with CTN ( P < 0.0001 and P < 0.001, respectively). This study suggests that it is the clinical behaviour and response to treatment of ACR that is paramount in determining the onset of chronic rejection, and not the mere presence or absence of the clinical phenomenon.     

Utility of an immune cell function assay to differentiate rejection from infectious enteritis in pediatric intestinal transplant recipients

The Cylex Immune Cell Function Assay measures cell‐mediated immunity based on ATP production by stimulated CD4 + cells. We hypothesized that this test would discriminate acute cellular rejection (ACR) from infectious enteritis (IE) in pediatric intestinal transplant (ITx) recipients with allograft dysfunction. We retrospectively analyzed 224 Cylex assays drawn in 47 children who received 53 ITx. Samples were classified as stable, ACR, or IE based on clinical status. ATP values were analyzed using Kruskal–Wallis and t‐tests. Overall, there was a statistically significant difference in ATP values based on clinical status (p = 0.03); however, overlap was observed between groups. The median ATP value during ACR was significantly greater than during stable periods (p = 0.02). No difference was seen in IE vs. stability (p = 0.8). The difference in median ATP value in ACR vs. IE approached significance (p = 0.1). Relative to previous levels, ACR episodes were associated with a median ATP increase of 101 ng/mL and IE episodes with a decrease of 3 ng/mL (p = 0.3). These data indicate that the Cylex assay has limited utility in differentiating ACR from IE, largely due to interpatient variability. Following longitudinal intrapatient trends may be an adjunctive tool in discriminating IE from ACR and guiding immunosuppression adjustments in select patients.     

Incidence of acute cellular rejection following granulocyte colony‐stimulating factor administration in lung transplantation: A retrospective case‐cohort analysis

Granulocyte colony‐stimulating factor (GCSF) is an option to treat leukopenia in lung transplant recipients. Conflicting evidence exists regarding its effects on acute cellular rejection (ACR). A retrospective, case‐cohort study was conducted to assess whether the use of GCSF in lung transplant recipients is associated with an increased incidence of ACR. Patients had to have received at least one dose of GCSF but were excluded if they received GCSF within 30 days prior to transplant or received a lymphocyte‐depleting agent within 14 days of GCSF administration. Thirty‐five patients who received GCSF within 3 months of transplant met inclusion criteria and 105 patients were identified as controls based on a 1:3 allocation scheme. Incidence of ACR was 57.1% in the GCSF group versus 50.5% in the control group (relative risk (RR)=1.13; 95% CI, 0.80 to 1.59; P=.48). At 3 months post‐transplant, 74.3% of the GCSF group had a dose reduction or discontinuation of their antiproliferative agent versus 17.1% of the control group (RR=4.33; 95% CI, 2.73 to 6.89; P<.0001). Rejection severity and incidence of infections was similar among groups. These findings show that GCSF administration within 3 months following lung transplantation was not associated with a higher incidence or severity of ACR.     

Juvenile relapsing periarteritis nodosa and streptococcal infection

Classic polyarteritis nodosa is a multisystem inflammatory disease associated with necrotizing vasculitis of small and medium arteries. In most cases, the causes of polyarteritis nodosa remain unknown, but viruses (HBV, HCV, HIV) and microbes (especially streptococcus) have been considered as etiologic or contributing factors. A 13-year-old boy was admitted with fever, skin lesions, polyarthritis and muscle involvement. A muscle biopsy demonstrated a necrotizing vasculitis and antistreptolysin titre was tremendously increased. His condition improved following the administration of oral steroids but he experienced relapses 5 and 12 years later when penicillin withdrawal was attempted. The flares were accompanied by a major increase of antistreptolysin titre and response to corticosteroid was obtained. He is currently 38 years old and he remains well on prophylactic penicillin. Polyarteritis nodosa in children may occur after a streptococcal infection. It may be prudent to consider penicillin prophylaxis in patients with periarteritis nodosa when a streptococcal etiology is documented or highly suspected.     

Performance of the American College of Rheumatology/European League Against Rheumatism 2010 criteria for the diagnosis of rheumatoid arthritis in Chinese patients

ObjectivesTo evaluate the ability of American College of Rheumatology (ACR) 2010 classification criteria to diagnose rheumatoid arthritis (RA) compared to the widely used ACR 1987 criteria in Chinese patients.MethodsFour hundred and four patients suffering from arthritis were included in the study. Two hundred and twenty-one of them were classified as RA patients and 183 had alternative diagnoses. The patients were further subdivided into three groups according to their disease duration of within one year, one to two years or more than two years. The diagnostic value of ACR/EULAR 2010 criteria for RA was evaluated by comparing the sensitivity and specificity with those of ACR 1987 criteria in these patients.ResultsThe sensitivity and specificity of ACR/EULAR 2010 criteria for diagnosing RA were 95% and 92.9%, respectively. In contrast, the sensitivity and specificity of ACR 1987 criteria were 81.4% and 92.9%, respectively. The efficacy of ACR/EULAR 2010 criteria was superior to the ACR 1987 criteria by comparing their area under the curves (AUC) (0.940, 95% CI [0.912, 0.967] vs. 0.872, 95% CI [0.835, 0.909]). The recognition accuracy of ACR/EULAR 2010 criteria was higher than that of ACR 1987 criteria (94.5% vs. 86.6%, P < 0.05). Inter-rater analysis showed that agreement of the two criteria was substantial (Kappa = 0.744, P < 0.001). For patients with disease duration within one year, one to two years and over two years, the sensitivities of ACR 1987 criteria were 69.2%, 81.3% and 89.9%, while the specificities were 94.4%, 90.6% and 92%, respectively. The corresponding sensitivities of ACR/EULAR 2010 criteria in these patients were 91%, 93.8% and 98.2%, while the corresponding specificities were 94.4%, 96.6% and 89.3%, respectively. The advantage of ACR/EULAR 2010 criteria over 1987 criteria in higher sensitivity was remarkable particularly in patients with disease duration within one year (P < 0.001).ConclusionsThe ACR/EULAR 2010 criteria is more accurate in RA diagnosis compared to the ACR 1987 criteria by elevating the sensitivity while preserving the specificity, especially in patients with disease duration within one year. The ACR/EULAR 2010 criteria may serve as new diagnostic tools in daily clinical practice.     

Périartérite noueuse juvénile à rechute et infection streptococcique

Juvenile relapsing periarteritis nodosa and streptococcal infection. Classic polyarteritis nodosa is a multisystem inflammatory disease associated with necrotizing vasculitis of small and medium arteries. In most cases, the causes of polyarteritis nodosa remain unknown, but viruses (HBV, HCV, HIV) and microbes (especially streptococcus) have been considered as etiologic or contributing factors. A 13-year-old boy was admitted with fever, skin lesions, polyarthritis and muscle involvement. A muscle biopsy demonstrated a necrotizing vasculitis and antistreptolysin titre was tremendously increased. His condition improved following the administration of oral steroids but he experienced relapses 5 and 12 years later when penicillin withdrawal was attempted. The flares were accompanied by a major increase of antistreptolysin titre and response to corticosteroid was obtained. He is currently 38 years old and he remains well on prophylactic penicillin. Polyarteritis nodosa in children may occur after a streptococcal infection. It may be prudent to consider penicillin prophylaxis in patients with periarteritis nodosa when a streptococcal etiology is documented or highly suspected.     

Is blood eosinophilia an effective predictor of acute rejection in living donor liver transplantation?*

Summary The association of blood eosinophilia with acute cellular rejection (ACR) after living donor liver transplantation has not been examined yet. The subjects were the 167 recipients who underwent liver biopsy (314 times). The blood eosinophil counts in the preoperative period (n = 167), 3 days before (n = 314) and on the day of biopsy (n = 314) were compared among the groups stratified by severity of ACR. Among 314 biopsy specimens, the 140 biopsy specimens were diagnosed with ACR. In the 140 ACR episodes, eosinophil counts before and after therapy was compared between the episodes that responded to therapy (n = 80) and those not (n = 60). The sensitivity and specificity of preoperative eosinophilia (eosinophil counts >130 mm(3)) to predict ACR was 33% and 65%, respectively. The eosinophil counts >400 mm(3) 3 days before and on the day of biopsy was associated with the severity of ACR (P < 0.0001). The sensitivity to predict ACR was 26% and 33%, and the specificity, 94% and 93%, respectively. There was no significant difference in changes of eosinophil counts between the steroid-responders versus the nonresponders. The present results suggested the limited role of eosinophilia as a predictor of ACR after living donor liver transplantation.     

Comparison of ACR 1987 and ACR/EULAR 2010 criteria for predicting a 10-year diagnosis of rheumatoid arthritis

ObjectiveTo compare the diagnostic accuracy of the 2010 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) and 1987 ACR criteria for rheumatoid arthritis (RA) in a cohort of patients with recent-onset arthritis followed-up for 10 years.MethodsOne hundred and sixty-four patients with recent-onset arthritis of less than 1 year's duration were included prospectively between 1995 and 1997. The diagnosis of RA was defined as having a diagnosis of RA made by the office-based rheumatologist 10 years after enrolment. We compared the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the criteria sets at baseline.ResultsAt baseline, 60 of the 164 patients had alternative diagnoses better explaining the arthritis and 13 had erosions typical for RA; of the 91 remaining patients, 33 had at least 6 ACR/EULAR points (indicating definite RA), and 58 had fewer than 6 points. The ACR/EULAR criteria had a quite similar sensitivity than the 1987 ACR criteria (33/57 [57.9%] for ACR/EULAR criteria vs 34/57 [59.6%] for the 1987 ACR criteria), but higher specificity, PPV, and NPV (95/107 [88.8%], 34/46 [73.9%], and 95/118 [80.5%], respectively) than the 1987 ACR criteria (80/107 [74.8%], 33/63 [52.4%], and 80/104 [76.9%], respectively).ConclusionACR/EULAR criteria performed substantially better than ACR 1987 criteria for predicting a diagnosis of RA after 10 years. Much of the improvement was ascribable to the use of exclusion criteria.Bullet points(1) The ACR/EULAR criteria had the same sensitivity, but higher specificity, PPV, and NPV than the 1987 ACR criteria; (2) Much of the improvement was ascribable to the use of exclusion criteria.     

Acute Cellular Rejection with CD20-Positive Lymphoid Clusters in Kidney Transplant Patients Following Lymphocyte Depletion

Lymphoid clusters (LC) containing CD20-positive B cells in kidney allografts undergoing acute cellular rejection (ACR) have been identified in small studies as a prognostic factor for glucocorticoid resistance and graft loss. Allograft biopsies obtained during the first episode of ACR in 120 recipients were evaluated for LC, immunostained with CD20 antibody, and correlated with conventional histopathologic criteria, response to treatment and outcome. LC were found in 71 (59%) of the 120 biopsies. All contained CD20 positive B cells that accounted for 5-90% of the LC leukocyte content. The incidence of LC was highest in the patients who had no lymphoid depletion or had been treated with Thymoglobulin preconditioning (79% vs. 75%, respectively) compared to 37% in patients pretreated with Campath (p = 0.0001). Banff 1a/1b ACR were more frequent in the LC-positive than the LC-negative group (96% vs. 80%, respectively; p = 0.0051). With a posttransplant follow-up of 953 +/- 430 days, no significant differences were detected between LC-postitive and LC-negative groups in time to ACR, steroid resistance, serum creatinine and graft loss. CD20+LC did not portend glucocorticoid resistance or worse short to medium term outcomes. CD20+LC may represent a heterogenous collection in which there may be a small still to be fully defined unfavorable subgroup.     

The impact of first untreated subclinical minimal acute rejection on risk for chronic lung allograft dysfunction or death after lung transplantation

Acute cellular rejection (ACR) is a significant risk factor for chronic lung allograft dysfunction (CLAD). Although clinically manifest and higher grade (≥A2) ACR is generally treated with augmented immunosuppression, management of minimal (grade A1) ACR remains controversial. In our program, patients with subclinical and spirometrically stable A1 rejection (StA1R) are routinely not treated with augmented immunosuppression. We hypothesized that an untreated first StA1R does not increase the risk of CLAD or death compared to episodes of spirometrically stable no ACR (StNAR). The cohort was drawn from all consecutive adult, first, bilateral lung transplantations performed between 1999 and 2017. Biopsies obtained in the first‐year posttransplant were paired with (forced expiratory volume in 1 second FEV₁). The first occurrence of StA1R was compared to a time‐matched StNAR. The risk of CLAD or death was assessed using univariable and multivariable Cox proportional hazards models. The analyses demonstrated no significant difference in risk of CLAD or death in patients with a first StA1R compared to StNAR. This largest study to date shows that, in clinically stable patients, an untreated first A1 ACR in the first‐year posttransplant is not significantly associated with an increased risk for CLAD or death. Watchful‐waiting approach may be an acceptable tactic for stable A1 episodes in lung transplant recipients.