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Martin Rudwaleit

Publications and source records attributed to Martin Rudwaleit.

At least 19 recordsLinked to original sources

Coronary vasospasm-induced acute diastolic dysfunction in a patient with Raynaud's phenomenon.

We present the case of a patient with severe dyspnea and Raynaud's phenomenon. We could clarify, using invasive techniques including left ventricular conductance catheterization and coronary ergonovine provocation, that isolated diastolic dysfunction induced by coronary vasospasm were responsible for the symptoms. Systolic function was not affected. Short-term infusions with the prostacyclin analogue iloprost, known to act as a disease-modifying agent in patients suffering from Raynaud's phenomenon, led to an improvement of cardiac function. Thus, episodes of dyspnea in patients with Raynaud's phenomenon might be also interpreted as a coronary ischemia equivalent, which may belong to a visceral form of Raynaud's phenomenon and which are sensitive to iloprost infusions.

Coronary Vasospasm↗

Inflammatory back pain in ankylosing spondylitis: a reassessment of the clinical history for application as classification and diagnostic criteria.

OBJECTIVE: Back pain associated with ankylosing spondylitis (AS) is referred to as inflammatory back pain (IBP). The value of the clinical history in differentiating IBP from mechanical low back pain (MLBP) has been investigated in only a few studies. In this exploratory study, we sought to evaluate the individual features of IBP and to compose and compare various combinations of features for use as classification and diagnostic criteria. METHODS: We assessed the clinical history of 213 patients (101 with AS and 112 with MLBP) younger than 50 years who had chronic back pain. Single clinical parameters and combinations of parameters were compared between the AS and MLBP patient groups. RESULTS: Morning stiffness of >30 minutes' duration, age at onset of back pain, no improvement in back pain with rest, awakening because of back pain during the second half of the night only, alternating buttock pain, and time period of the onset of back pain were identified as independent contributors to IBP. Importantly, none of the single parameters sufficiently differentiated AS from MLBP. In contrast, several sets of combined parameters proved to be well balanced between sensitivity and specificity. Among these, a new candidate set of criteria for IBP, which consisted of morning stiffness of >30 minutes' duration, improvement in back pain with exercise but not with rest, awakening because of back pain during the second half of the night only, and alternating buttock pain, yielded a sensitivity of 70.3% and a specificity of 81.2% if at least 2 of these 4 parameters were fulfilled (positive likelihood ratio 3.7). If at least 3 of the 4 parameters were fulfilled, the positive likelihood ratio increased to 12.4. CONCLUSION: A new set of criteria for IBP performed better than previous criteria in AS patients with established disease. A prospective study is needed to validate the diagnostic properties of the new candidate criteria set in patients with early disease.

Activities of Daily Living↗

Immunohistologic analysis of zygapophyseal joints in patients with ankylosing spondylitis.

OBJECTIVE: Zygapophyseal joints of the spine are often affected in ankylosing spondylitis (AS). In this study, we undertook a systematic immunohistologic evaluation of the immunopathology of the zygapophyseal joints in patients with advanced AS. METHODS: We obtained zygapophyseal joints from 16 AS patients undergoing polysegmental correction of kyphosis and from 10 non-AS controls (at autopsy). Immunohistologic analysis of the bone marrow was performed by analyzing the number of infiltrating T cells (CD3, CD4, CD8), B cells (CD20), osteoclasts (CD68), bone marrow macrophages (CD68), and microvessel density (CD34) per high-power field. RESULTS: Zygapophyseal joints from 6 of 16 AS patients, but from none of the controls, exhibited 2 or more CD3+ T cell aggregates, signifying persistent inflammation. Interstitial CD4+ and CD8+ T cells were significantly more frequent in AS patients compared with non-AS controls (P = 0.002 and P = 0.049, respectively). While there was no clear difference between the number of CD20+ B cells in AS patients overall compared with controls, there was a significant difference when persistently inflamed joints from patients with AS were compared with joints without active inflammation from patients with AS or joints from controls (both P = 0.03). Microvessel density in bone marrow from AS patients with active inflammation was significantly higher than that in bone marrow from controls. CONCLUSION: This immunohistologic study of bone marrow from zygapophyseal joints demonstrates persistent inflammation in the spine of patients with AS, including those with longstanding disease. The findings of increased numbers of T cells and B cells and neoangiogenesis suggest that these features play a role in the pathogenesis of AS.

Antigens, CD↗

Concepts and epidemiology of spondyloarthritis.

The term 'spondyloarthritides' (SpA) comprises ankylosing spondylitis (AS), reactive arthritis, arthritis/spondylitis with inflammatory bowel disease, and arthritis/spondylitis with psoriasis. The main links between these diseases are an association with HLA-B27 and a similar clinical picture. Patients normally present with chronic low back pain or asymmetrical arthritis, predominantly of the lower limbs, and an overlap of these symptoms often occurs. AS is regarded as the most severe subtype. Recent attention has focused on earlier diagnosis of AS among patients with chronic low back, and this is becoming more important as effective therapies for early treatment have become available. AS is a disease of young people, normally starting in the third decade of life. The incidence and prevalence rates of AS, and of SpA as a whole, are strongly dependent and are directly correlated to the prevalence of HLA-B27 in a given population. Incidence rates of 0.5-8.2/100 000 population and prevalence rates of 0.2-1.2% have been described for AS, and about double these figures have been reported for SpA.

Early Diagnosis↗

Ankylosing spondylitis and bowel disease.

Between 5 and 10% of cases of ankylosing spondylitis (AS) are associated with inflammatory bowel disease (IBD), either Crohn's disease or ulcerative colitis. A much larger percentage of AS patients have subclinical gut inflammation manifested either by endoscopic findings or by histology. The association with HLA-B27 is less strong in IBD-associated AS than in idiopathic AS, and there is evidence for an association between gut inflammation in AS with the Crohn's-disease-related CARD15 mutations. Despite the different genetics, the immunopathology suggests common inflammatory pathways in gut and joint inflammation in AS, and in gut inflammation in AS and IBD. Although this observation is of interest to unravel the pathophysiology of the disease, systematic screening of AS patients by ileocolonoscopy is not indicated in the absence of gut symptomatology as only a small proportion of AS patients with subclinical gut inflammation will develop overt IBD over time. Treatment of AS associated with IBD with non-steroidal anti-inflammatory drugs (NSAIDs) is problematic because of concerns of potential re-activation of IBD by NSAIDs. Major advances have been made in recent years with the establishment of anti-tumour necrosis factor (TNF) therapy in AS, the other spondyloarthritides and IBD. Anti-TNF agents are of particular relevance to AS patients with concomitant IBD who are at risk of exacerbation of the underlying bowel disease when treated with NSAIDs. In IBD, infliximab, unlike etanercept, is effective in treating clinical symptoms, inducing and maintaining remission, and mucosal healing. Adalimumab appears to be effective in treating both AS and IBD; however, official approval is pending. Currently, infliximab is the drug of choice for the treatment of patients with active AS associated with IBD.

Colitis, Ulcerative↗

Brucella endocarditis in prosthetic valves.

Human brucellosis is a multiple organ disease that presents with fever and is most often transmitted via contaminated, unpasteurized goat milk and cheese. In chronic cases, focal complications (eg, spondylitis, neurobrucellosis and endocarditis) are frequently seen. Although the disease may be severely debilitating, the mortality rate is low. Fatal cases are often due to endocarditis. Because Brucella endocarditis is a rare complication (2% to 5%), therapeutic considerations are based on single-case experiences only. Therapy includes long-term antibiotic treatment using combinations of various antimicrobial drugs and surgical valve replacement when required. A case of Brucella endocarditis complicated by the infection of two valvular prostheses implanted after involvement of the mitral and aortic valve due to rheumatic fever is described. The patient was successfully treated by a medical and surgical approach. Therapeutic strategies in Brucella endocarditis are discussed in light of the current literature.

Anti-Bacterial Agents↗

Correlation of histopathological findings and magnetic resonance imaging in the spine of patients with ankylosing spondylitis.

Ankylosing spondylitis (AS) is a chronic inflammatory disease which affects primarily the sacroiliac joints and the spine. In patients with active disease, magnetic resonance imaging (MRI) of the spine shows areas of bone marrow edema, the histopathological equivalent of which is unknown. In this study we correlate inflammation in the spine of patients with AS as revealed by histological examination with bone marrow edema as detected by MRI. We have compared the histopathological findings of zygapophyseal joints from 8 patients with AS (age: 30 to 64, disease duration 7 to 33 years) undergoing spinal surgery with findings in MRI. For histopathological analysis, we quantified infiltrates of CD3+, CD4+ and CD8+ T cells as well as CD20+ B cells immunohistochemically. Bone marrow edema was evaluated in hematoxylin and eosin stained sections and quantified as the percentage of the bone marrow area involved. All patients with AS showed interstitial mononuclear cell infiltrates and various degrees of bone marrow edema (range from 10% to 60%) in histopathological analysis. However, in only three of eight patients histopathological inflammation and edema in the zygapophyseal joints correlated with bone marrow edema in zygapophyseal joints of the lumbar spine as detected by MRI. Interestingly, two of these patients showed the highest histological score for bone marrow edema (60%). This first study correlating histopathological changes in the spine of patients with AS with findings in MRI scans suggests that a substantial degree of bone marrow inflammation and edema is necessary to be detected by MRI.

Adult↗

Clinical response to discontinuation of anti-TNF therapy in patients with ankylosing spondylitis after 3 years of continuous treatment with infliximab.

We analyzed the clinical response and the time to relapse after discontinuation of continuous long-term infliximab therapy in patients with ankylosing spondylitis (AS). After 3 years of infliximab therapy, all AS patients (n = 42) discontinued treatment (time point (TP)1) and were visited regularly for 1 year in order to assess the time to relapse (TP2). Relapse was defined as an increase to a value >or= 4 on the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and a physician's global assessment >or= 4 according to the recommendations of the Assessments in Ankylosing Spondylitis (ASAS) working group. After 52 weeks, 41 of the 42 patients (97.6%) had to be reinfused because of relapse. The mean change in the BASDAI between TP1 and TP2 was 3.6 +/- 1.7 and that in the physician's global assessment was 4.4 +/- 1.8 (both P < 0.001). The mean time to relapse was 17.5 weeks (+/- 7.9 weeks, range 7 to 45). Ten patients (24%) showed a relapse within 12 weeks and 38 patients (90.5%), within 36 weeks. After 52 weeks, only one patient had remained in ongoing remission without further treatment with anti-tumor-necrosis factor. Patients who were in partial remission according to the ASAS criteria and those with normal C-reactive protein levels at the time point of withdrawal had longer times to relapse after discontinuation of the treatment. Retreatment with infliximab was safe and resulted in clinical improvement in all patients to a state similar to that before the treatment was stopped. Discontinuation of long-term therapy with infliximab eventually led to relapse of disease activity in all patients but one.

Antibodies, Monoclonal↗

Application of the OMERACT filter to scoring methods for magnetic resonance imaging of the sacroiliac joints and the spine. Recommendations for a research agenda at OMERACT 7.

Magnetic resolution imaging (MRI) is a promising tool in the assessment of inflammation and structural damage in clinical trials in ankylosing spondylitis (AS). The ASAS/OMERACT MRI in AS working group, a collaborative initiative of rheumatologists and musculoskeletal radiologists with a special interest in this field, collected data on all available scoring methods for both sacroiliac (SI) joints and spine, and tested them with respect to the OMERACT filter. These data were presented together with the technical specifications of all methods at the OMERACT 7 conference. In addition, the results of 2 separate experiments on the inter-reader reliability of scoring methods to assess activity in SI joints, and on the comparison of STIR sequence versus T1 post-gadolinium (Gd) sequence for the spine, were presented. Thereafter, 8 groups discussed these data and proposed a research agenda, each on a different topic. This information was reported back to all participants and a prioritized research agenda was compiled by voting. Research on scoring methods for assessing disease activity, in both the spine and SI joints, was considered most important. Research on assessing structural damage was considered less important. The specific process and results of this initiative are discussed.

Biomedical Research↗

Scoring sacroiliac joints by magnetic resonance imaging. A multiple-reader reliability experiment.

Magnetic resonance imaging (MRI) of the sacroiliac (SI) joints and the spine is increasingly important in the assessment of inflammatory activity and structural damage in clinical trials with patients with ankylosing spondylitis (AS). We investigated inter-reader reliability and sensitivity to change of several scoring systems to assess disease activity and change in disease activity in patients with AS. Twenty sets of consecutive MRI, derived from a randomized clinical trial comparing an active drug with placebo and selected on the basis of the presence of activity at baseline, were presented electronically to 7 experienced readers from different countries (Europe, Canada). Readers scored the MRI by 3 different methods including: a global score (grading activity per SI joint); a more comprehensive global score (grading activity per SI joint per quadrant); and a detailed scoring system [Spondyloarthritis Research Consortium of Canada (SPARCC) scoring system], which scores 6 images, divided into quadrants, with additional scores for "depth" and "intensity." A fourth and a fifth scoring system were constructed afterwards. The fourth method included the SPARCC score minus the additional scores for "depth" and "intensity," and the fifth method included the SPARCC slice with the maximum score. Inter-reader reliability was investigated by calculating intraclass correlation coefficients (ICC) for all readers together and for all possible reader pairs. Sensitivity to change was investigated by calculating standardized response means (SRM) on change scores that were made positive. Overall inter-reader ICC per method were between 0.47 and 0.58 for scoring status, and between 0.40 and 0.53 for scoring change. ICC per possible reader pairs showed much more fluctuation per method, with lowest observed values close to zero (no agreement) and highest observed values over 0.80 (excellent agreement). In general, agreement of status scores was somewhat better than agreement of change scores, and agreement of the comprehensive SPARCC scoring system was somewhat better than agreement of the more condensed systems. Sensitivity to change differed per reader, but in general was somewhat better for the comprehensive SPARCC system. This experiment under "real life," far from optimal conditions demonstrates the feasibility of scoring exercises for method comparison, provides evidence for the reliability and sensitivity to change of scoring systems to be used in assessing activity of SI joints in clinical trials, and sets the conditions for further validation research in this field.

Humans↗

An elevated level of IL-10- and TGFbeta-secreting T cells, B cells and macrophages in the synovial membrane of patients with reactive arthritis compared to rheumatoid arthritis.

A relative high secretion level of IL-10 and a low secretion of TNF-alpha has been described in the synovial fluid and peripheral blood of patients with reactive arthritis (ReA), possibly contributing to the persistence of bacteria. The role of TGF-beta is less clear. We investigated these cytokines in the synovial membrane of patients with ReA and rheumatoid arthritis (RA) and tried to identify their cellular source. We used sections from the synovial membrane of 4 ReA and 4 RA patients which were double stained with immunofluorescence antibodies against cell surface markers for T cells (CD3), macrophages (CD68) and B cells (CD20) in combination with antibodies against intracellular cytokines TNF-alpha, IFN-gamma, TGF-beta, IL-4 and IL-10, and quantified these using a fluorescence microscope. A lower number of TNF-alpha-secreting cells were found in ReA compared to RA: CD3+: 1.78 +/- 0.54% versus 5.02% +/- 0.47% (p = 0.034). CD68+: 2.86 +/- 0.52 versus 5.37 +/- 0.53% (p = 0.034), CD20+ : 3.02 +/- 0.42% versus 3.58 +/- 0.48% (p > 0.05). A higher number of IL-10 positive cells were found in ReA compared to RA: CD3+: 3.27 +/- 1.5% versus 1.13 +/- 0.50% (p = 0.034), CD68+ 1.23 +/- 0.75% versus 0.83 +/- 0.35% (p > 0.05), CD20+: 3.70 +/- 1.6% versus 1.6 +/- 1.1% (p > 0.05). A difference between ReA and RA was also found for TGF-beta+ T cells: CD3+ 7.86 + 1.5% versus 1.78 + 0.35% (p = 0.032); CD20+: 7.91 + 2.1% versus 2.1 + 2.8% (p > 0.05), CD68+: 7.81% + 1.24% versus 2.12 + 0.28% (p = 0.032). In conclusion, we saw a different cytokine secretion pattern in the synovial membrane of ReA and RA. For T cells in ReA we found a cytokine secretion profile typical for T regulatory cells 1 (Tr1), with an elevated level of IL-10- and TGF-beta-secreting cells. Whether this is due to a more general difference in TNF-alpha, IL-10 or TGF-beta production which is genetically determined or regulated by T cells remains to be determined.

Antigens, CD↗

Successful short term treatment of patients with severe undifferentiated spondyloarthritis with the anti-tumor necrosis factor-alpha fusion receptor protein etanercept.

OBJECTIVE: Anti-tumor necrosis factor-a (TNF-alpha) therapy has been successfully used in patients with active ankylosing spondylitis (AS) and other subtypes of spondyloarthritis (SpA). Treatment options for patients with severe forms of undifferentiated spondyloarthritis (uSpA), a rather frequent SpA subset, are limited. In this open study we examined the efficacy of the TNF-alpha receptor fusion protein etanercept in patients with uSpA. METHODS: Ten patients classified to have uSpA according to modified European Spondylarthropathy Study Group criteria in a severe and active stage of disease were included in the study and received etanercept in a dosage of 25 mg two times a week for 12 weeks, followed by an observation period of 12 weeks. The following outcome variables were used: Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Functional Index (BASFI), pain on a numerical rating scale, disability by the Funktionsfragebogen Hannover (FFbH), a validated questionnaire to assess functional disability, and quality of life (Medical Outcome Study Short Form-36, SF-36). The primary outcome variable was defined as >or= 50% improvement of the BASDAI. RESULTS: Treatment with etanercept resulted in a >or= 50% regression of disease activity in 60% (95% CI 31-83%) of the patients. The mean BASDAI at baseline of 6.1 (range 3.7-9.2) dropped significantly to 3.5 at Week 12 (0.8-8.7; p = 0.01). Function, spinal pain, peripheral arthritis, enthesitis, quality of life, and acute phase reactants improved similarly. The FFbH improved from 62.8% to 69.7%. After cessation of anti-TNF therapy, 4 out of 8 patients relapsed after an average of 4.5 weeks (range 3-6). Two patients went into longstanding remission. No severe adverse events or major infections were observed. CONCLUSION: This study strongly suggests that treatment with etanercept has short term efficacy in patients with active and severe uSpA. Since it is known that 30-50% of uSpA patients develop AS over time, it will be important to study whether this can be prevented by anti-TNF-alpha therapy.

Adult↗

Down-regulation of the nonspecific and antigen-specific T cell cytokine response in ankylosing spondylitis during treatment with infliximab.

OBJECTIVE: Treatment of active ankylosing spondylitis (AS) with the monoclonal tumor necrosis factor alpha (TNF alpha) antibody infliximab is highly clinically effective. This study was undertaken to investigate the precise mechanism of action of anti-TNF alpha treatment in AS. METHODS: Cytokine expression of CD4+ and CD8+ T cells was investigated before and 6 and 12 weeks after the start of treatment in 10 patients treated with infliximab, and before and after 6 weeks of treatment and 6 weeks after placebo was switched to infliximab in 10 patients treated initially with placebo. Peripheral blood mononuclear cells (PBMCs) were stimulated for 6 hours either nonspecifically with phorbol myristate acetate (PMA)/ionomycin or antigen specifically with a pool of 46 overlapping 18-mer peptides derived from the G1 domain of aggrecan. Cells were stained for T cell surface markers CD4 and CD8 and for the intracellular cytokines interferon-gamma (IFN gamma), TNF alpha, interleukin-4 (IL-4), and IL-10. Positive cells were quantified by flow cytometry. For monocyte-derived cytokines, PBMCs were stimulated with lipopolysaccharide (LPS) for 18 hours and TNF alpha and IL-10 in the supernatant were measured by enzyme-linked immunosorbent assay. RESULTS: Compared with baseline, infliximab treatment induced a significant decrease at 12 weeks in the number of CD4+ and CD8+ T cells that were positive for IFN gamma and TNF alpha upon PMA/ionomycin stimulation (P = 0.005). A significant reduction had already begun to occur at 6 weeks. No change in the percent IFN gamma or TNF alpha positivity among CD4+ and CD8+ subpopulations was observed after 6 weeks in patients treated with placebo. However, when these patients began infliximab treatment after 6 weeks of receiving placebo, there was a similar significant decrease in IFN gamma and TNF alpha production by CD4+ and CD8+ T cells (P < 0.05). Furthermore, infliximab treatment induced a significant reduction in the number of IFN gamma+ and TNF alpha+ CD8+ T cells (P = 0.005 at week 6 and week 12) after antigen-specific in vitro stimulation with G1-derived peptides. Between-group analysis showed that the change in the expression of IFN gamma and TNF alpha in both CD4+ and CD8+ T cells was significantly different between the infliximab and placebo groups (P = 0.001 for all variables). There was no change in the number of IL-10+ or IL-4+ T cells during treatment. No significant change in the production of TNFalpha and IL-10 upon in vitro stimulation of PBMCs with LPS was detectable during infliximab treatment. CONCLUSION: Infliximab down-regulates both IFN gamma and TNF alpha secreted by T cells but does not induce a change in cytokines produced by monocytes during 3 months of treatment. This is likely to be a relevant mechanism for the clinical efficacy of this therapy.

Antibodies, Monoclonal↗

Biologic therapies in the spondyloarthritis: new opportunities, new challenges.

Therapeutic options for patients suffering from the more severe forms of spondyloarthritis have been rather limited in the last decades. There is now accumulating evidence that antitumor necrosis factor therapy is highly effective in spondyloarthritis, especially in ankylosing spondylitis and psoriatic arthritis. Based on the data recently published on more than 500 patients with ankylosing spondylitis and psoriatic arthritis, this treatment seems to be even more effective than in rheumatoid arthritis. The antitumor necrosis factor-alpha agents currently available, infliximab (Remicade), etanercept (Enbrel), and adalimumab (Humira), are approved for the treatment of rheumatoid arthritis in the United States and partly in Europe. The situation in spondyloarthritis is different from that of rheumatoid arthritis because there is an unmet medical need, especially in ankylosing spondylitis: no therapies with disease-modifying antirheumatic drugs are available for severely affected patients, especially with spinal disease. Thus, tumor necrosis factor blockers may even be considered a first-line treatment in a patient with active ankylosing spondylitis and psoriatic arthritis whose condition is not sufficiently controlled with nonsteroidal antiinflammatory drugs in the case of axial disease, and sulfasalazine or methotrexate in the case of peripheral arthritis. For infliximab, a dose of 5 mg/kg was required, and intervals between 6 and 12 weeks were necessary to suppress disease activity constantly-also a major aim for long-term treatment. The standard dosage of etanercept is 2 x 25 mg subcutaneously per week. There are no studies yet on adalimumab (standard rheumatoid arthritis dose, 20-40 mg subcutaneously every 1-2 weeks) in spondyloarthritis. Infliximab was very recently approved for AS in Europe. The efficacy of etanercept was first demonstrated in psoriatic arthritis, and it is now approved for this indication. A double-blind study has also been performed in ankylosing spondylitis, with similarly clear efficacy. There is preliminary evidence that both agents do also work in other spondyloarthritis, such as undifferentiated spondyloarthritis. Ideally, both agents will be approved soon for the short-term treatment of severe, uncontrolled spondyloarthritis. In parallel, studies should be performed to document the long-term efficacy of this treatment. There is hope that ankylosis may be preventable, but it remains to be shown whether patients benefit from long-term antitumor necrosis factor therapy and whether radiologic progression and ankylosis can be stopped. Severe adverse events have remained rare. Complicated infections including tuberculosis have been reported. These can be largely prevented by appropriate screening. At it stands now, the benefits of antitumor necrosis factor therapy in ankylosing spondylitis seem to outweigh these shortcomings.

Antibodies, Monoclonal↗

Congenital absence of the portal vein with splenomegaly and hypersplenism in a young woman.

Congenital absence of portal vein (CAPV) with a systemic shunt of enteric blood is a rare malformation. Twenty-seven cases have been reported to date; with the exception of 4 patients all cases had either liver anomalies or cardiac anomalies. CAPV is usually diagnosed before the age of 18 (25/27 cases). Here we present the case of a 33-year-old woman with CAPV without further anomalies. Beside suffering from circumscript scleroderma, splenomegaly and hypersplenism, the patient was otherwise healthy. Diagnosis was based on histological findings, angiography and CT scan. The liver biopsy showed portal tracts with inconspicuous arteries and bile ducts, but with severe loss of portal vein branches and minimal proliferation of bile ductules. In addition, the perivenular sinusoids were slightly dilated with focal parenchymal atrophy. Angiography showed a missing portal vein system and a missing splenic vein with drainage of the enteric blood through dilated perisplenic and perigastric collaterals to the azygos vein system. A CT scan revealed an empty liver hilus without portal vein. Here we discuss clinical aspects of this patient, show radiologic and histopathologic findings, and compare them to other cases in the literature.

Abnormalities, Multiple↗