An atypical presentation for primary sclerosing cholangitis

We describe the clinical course of a group of patients with primary sclerosing cholangitis who at presentation were diagnosed to have autoimmune hepatitis. The history of one such patient is described in detail. We also compare this atypical sclerosing cholangitis (group I) to typical sclerosing cholangitis (group II) and to autoimmune hepatitis with (group III) and without (group IV) cholestasis. At presentation, mean AST in groups I and III was similar and significantly higher than in group II (P < 0.05). Mean ALP was higher in sclerosing cholangitis than in autoimmune hepatitis but not significantly so. Triaditis was present in all patients in groups I, III, and IV. Piecemeal necrosis and multilobular collapse/fibrosis were equally frequent in groups I, III, and IV. Only the response to corticosteroids helped differentiate among groups. Groups III and IV responded by normalizing AST. In group I, AST improved, but never became normal. As ALP became disproportionately abnormal (ALP-predominant pattern), cholangiography was performed, and the diagnosis of primary sclerosing cholangitis was made in all group I patients. We recommend that cholangiography be performed early in patients with suspected autoimmune hepatitis who partially respond to corticosteroids and develop an ALP-predominant pattern.     

Osteoid osteoma in a three-year-old child--a case report

Osteoid osteoma is an uncommon tumour in the very young. We present a case of osteoid osteoma in a three-year-old boy, who was treated as a case of sclerosing osteomyelitis of the femur. Because of persistent pain and lack of response to treatment, further radiological investigation confirmed the diagnosis to be that of an osteoid osteoma.     

MR cholangiography in primary sclerosing cholangitis

OBJECTIVE: The purpose of this study was to evaluate the ability of MR cholangiography to reveal the characteristics of biliary abnormalities found in primary sclerosing cholangitis. CONCLUSION: Our results suggest that MR cholangiography could be useful in the diagnosis of primary sclerosing cholangitis. Slightly dilated peripheral bile ducts unconnected to the central ducts in several hepatic segments are a characteristic MR sign of primary sclerosing cholangitis. However, other studies are necessary to establish the usefulness of MR cholangiography in relation to other imaging techniques for evaluating primary sclerosing cholangitis.     

Sclerosing cholangitis and biliary tract calculi--primary or secondary?

The clinical features of 61 patients with sclerosing cholangitis were reviewed. This group included 23 patients with biliary tract calculi, commonly considered as excluding the diagnosis of primary sclerosing cholangitis. The aim of this study was to compare these 23 patients (group A) with 38 patients with sclerosing cholangitis free of calculi (group B). Both groups had the following features in common: (i) age at presentation, (ii) incidence of inflammatory bowel disease, (iii) extent of radiological disease, (iv) prevalence of HLA-B8 and DR3 haplotype, (v) incidence of cholangiocarcinoma, and (vi) progression to hepatic transplantation (mean follow up 49.9 months). All patients in group A were symptomatic at diagnosis compared with 23 of the 38 patients (61%) in group B. Recurrent ascending cholangitis occurred in 12 patients in group A (52%) and two patients (5%) in group B. The similarity between the two groups was maintained when the nine patients in group A who developed calculi after sclerosing cholangitis was diagnosed were excluded. It is concluded that choledocholithiasis is part of the spectrum of primary sclerosing cholangitis and that it is not necessary to invoke choledocholithiasis as the initial lesion of the bile ducts in such patients.     

Fluorine-18-FDG PET and technetium-99m antigranulocyte antibody scintigraphy in chronic osteomyelitis

The aim of this study was to assess the usefulness of PET with 2-18F-fluoro-2-deoxy-D-glucose (FDG), as compared to immunoscintigraphy (IS) with 99mTc-labeled monoclonal antigranulocyte antibodies (AGAbs), in the detection of chronic osteomyelitis. METHODS: Fifty-one patients suspected of having chronic osteomyelitis in the peripheral (n = 36) or central (n = 15) skeleton were evaluated prospectively with static FDG PET imaging and combined 99mTc-AGAb/99mTc-methylene diphosphonate (MDP) bone scanning within 5 days. FDG PET and IS were evaluated in a blinded and independent manner by visual interpretation, which was graded on a five-point scale of two observers' confident diagnosis of osteomyelitis. Receiver operating characteristic (ROC) curve analysis was performed for both imaging modalities. The final diagnosis was established by means of bacteriologic culture of surgical specimens and histopathologic analysis (n = 31) or by biopsy and clinical follow-up over 2 yr (n = 20). RESULTS: Of 51 patients, 28 had osteomyelitis and 23 did not. According to the unanimous evaluation of both readers, FDG PET correctly identified 27 of the 28 positives and 22 of the 23 negatives (IS identified 15 of 28 positives and 17 of 23 negatives, respectively). The area under the ROC curve was 0.97/0.97 (reader 1/reader 2) for FDG PET and 0.87/0.90 for IS, with a high degree of interobserver concordance (K-values were 0.96 for FDG PET and 0.91 for IS). In the central skeleton, the ROC curve area was 0.98/1.00 for FDG PET and 0.71/0.77 for IS (p<0.05). On the basis of ROC analysis, the overall accuracies of FDG PET and IS in the detection of chronic osteomyelitis were 96%/96% and 82%/ 88%, respectively. With regard to the optimal threshold values, sensitivity and specificity were 100%/97% and 95%/95% with FDG PET, compared to 86%/92% and 77%/82% with IS, respectively. CONCLUSION: In the peripheral skeleton, both FDG PET and combined 99mTc-AGAb/99mTc-MDP scanning are appropriate imaging modalities to diagnose chronic osteomyelitis. FDG PET additionally allows reliable differentiation between osteomyelitis and infection of the surrounding soft tissue. In the central skeleton within active bone marrow, FDG PET is highly accurate and superior to AGAb imaging in the diagnosis of chronic osteomyelitis, which frequently presents as a nonspecific photopenic lesion at scintigraphy with labeled white blood cells.     

Rare initial manifestation and differential diagnosis of primary sclerosing cholangitis

BACKGROUND: Primary sclerosing cholangitis is most often diagnosed in middle-aged men who are suffering from inflammatory bowel diseases. CASE REPORT: A young, previously healthy woman presents with icterus of acute onset, high transaminases and positive hepatitis B virus serology. Ultrasound and nuclear magnetic resonance images demonstrate multiple liver tumors. After acute viral hepatitis as well as primary or secondary malignant liver tumors have been excluded as underlying diseases, diagnosis of primary sclerosing cholangitis is made. CONCLUSION: Differential diagnosis of primary sclerosing cholangitis should also be considered in cases with untypical primary presentation.     

Tumor necrosis factor-alpha, interleukin-6, and interleukin-8 secretion and the acute-phase response in patients with bacterial and tuberculous osteomyelitis

Osteomyelitis, or bone infection, is a major worldwide cause of morbidity. Treatment is frequently unsatisfactory, yet little is known about pathogenesis of infection. Plasma tumor necrosis factor (TNF), interleukin (IL)-6, and IL-8 concentrations were measured before and after lipopolysaccharide stimulation of whole blood from patients with bacterial and tuberculous osteomyelitis and from controls. Patients with bacterial and tuberculous osteomyelitis mounted an acute-phase response and were anemic and febrile. However, plasma IL-6 concentrations were significantly elevated in only tuberculous osteomyelitis patients (vs. controls, P < .05). IL-6 concentrations correlated with erythrocyte sedimentation rate, C-reactive protein level, and plasma albumin concentration, all acute-phase markers. There were no other correlations between cytokine concentrations and clinical data. Following ex vivo stimulation, TNF, IL-6, and IL-8 were secreted equally by patients and controls. In summary, tuberculous osteomyelitis is characterized by elevated systemic IL-6 concentrations associated with an acute-phase response. For further insight into immunopathology of osteomyelitis, studies on infected bone are required.     

Primary Hodgkin disease of the ileum complicating Crohn disease

BACKGROUND: Primary gastrointestinal lymphoma currently is considered to be an uncommon complication of chronic inflammatory bowel disease. All tumors reported in which recently developed techniques, such as immunohistochemical markers, were used for lymphoma classification proved to be non-Hodgkin lymphomas. Gastrointestinal lymphomas developing in Crohn disease are a very heterogeneous group, with tumors of both B-cell and T-cell lineage represented, along with some tumors of equivocal phenotype. By contrast, gastrointestinal lymphomas complicating ulcerative colitis all have proved to be so-called polymorphic B-cell lymphomas. METHODS: The current report describes another case of primary gastrointestinal lymphoma complicating chronic inflammatory bowel disease occurring in the ileum of a 34-year-old man with a 3-year history of Crohn disease. RESULTS: Histopathologic findings were in keeping with nodular sclerosing Hodgkin disease. Broad birefringent collagen bands divided the tumor into well-defined nodules consisting of typical Reed-Sternberg cells and lacunar variants admixed with a polymorphous lymphoid infiltrate. By immunohistochemical studies, Reed-Sternberg cells and lacunar variants stained positively for Leu-M1 (CD15) and Ber H2 (CD30). The background lymphocytes were primarily of T-cell phenotype. CONCLUSIONS: To the knowledge of the authors, this article reports the first case of primary gastrointestinal Hodgkin disease in association with chronic inflammatory bowel disease that has been confirmed by immunohistochemical studies.     

Bone disease in patients with primary sclerosing cholangitis: prevalence, severity and prediction of progression

BACKGROUND/AIMS: Osteopenia is a common complication in some chronic cholestatic liver diseases. Our aims were to determine the prevalence and severity of bone disease in patients with primary sclerosing cholangitis; and identify risk factors to predict the presence and progression of osteopenia. METHODS: Eighty-one patients involved in a randomized trial of ursodeoxycholic acid were analyzed. Bone mineral density of the lumbar spine was determined at entry and at annual intervals. RESULTS: Bone mineral density of the lumber spine in primary sclerosing cholangitis patients was significantly lower than expected when compared to normal values adjusted for age, sex and ethnic group at entry (p<0.005), and after 1 year (p<0.05), 2 years (p<0.05), 4 years (p<0.005) and 5 years of follow-up (p<0.005). Seven patients (8.6%) had bone mineral density of the lumber spine below the fracture threshold at entry. These patients were significantly older, had a longer duration of inflammatory bowel disease and more advanced primary sclerosing cholangitis. The rate of bone loss in primary sclerosing cholangitis patients and expected in normal controls was 0.01+/-0.02 g x cm(-2) x year(-1) and 0.003+/-0.003 g x cm(-2) x year(-1), respectively (p = NS), and was similar in patients receiving placebo and ursodeoxycholic acid. Age was the only variable inversely related with baseline bone mineral density of the lumber spine (p<0.0001). None of the variables predicted progression of the bone disease. CONCLUSIONS: Severe osteoporosis occurs in few patients with primary sclerosing cholangitis, but it should be suspected in patients with longer duration of inflammatory bowel disease and more advanced liver disease. Its presence, severity and progression cannot be accurately evaluated by routine clinical, biochemical, or histological variables. Ursodeoxycholic acid does not affect the rate of bone loss in primary sclerosing cholangitis.     

Bile duct bacterial isolates in primary sclerosing cholangitis: a study of explanted livers

BACKGROUND/AIMS: The pathogenesis of the inflammatory lesion in primary sclerosing cholangitis is unknown. The clinical picture is characterized by i.a. episodes of fever, the cause of which also remains speculative. Previous studies of bacterial isolates in the liver or bile ducts in primary sclerosing cholangitis have had the shortcoming of possible contamination associated with the sampling. The aim of this study was to investigate whether bile and bile duct tissue, obtained under sterile conditions in connection with liver transplantation, contain bacteria. METHODS: We studied bile from bile duct walls and bile collected from the explanted livers of 36 patients with primary sclerosing cholangitis and 14 patients with primary biliary cirrhosis. RESULTS: Positive cultures were obtained from 21 of 36 primary sclerosing cholangitis patients, but from none of the primary biliary cirrhosis patients. The number of bacterial strains was inversely related to the time after the last endoscopic retrograde cholangiography. Treatment with antibiotics or intraductal stent, or the occurrence of fever before liver transplantation did not seem to influence the culture results, whereas antibiotic treatment in connection with endoscopic retrograde cholangiography may possibly have reduced the number of isolates in the cultures. Alpha-haemolytic Streptococci were retrieved as late as 4 years after the last endoscopic retrograde cholangiography. Retrospective analysis of liver laboratory tests after endoscopic retrograde cholangiography did not indicate a deleterious effect of the investigation. CONCLUSIONS: The data suggest that antibiotics should be given routinely in connection with endoscopic retrograde cholangiography. They also raise the question of a possible role of alpha-haemolytic Streptococci in the progression of primary sclerosing cholangitis.     

Ceptral voice analysis: link with perception and stroboscopy

Osteomyelitis of the clavicle or the sternoclavicular joint is a rare complication of subclavian vein catheterization. Soft tissue infections around the puncture site occur frequently and respond well to topical and antibiotic treatment. If symptoms persist for several weeks, osteomyelitis or sternoclavicular pyo-arthrosis should be considered. Bone and gallium scintigraphy scans and computerized tomography scans are helpful diagnostic measures.     

Synthesis and binding-analysis of 5E-[19-(2-bromoacetoxy)methyl]25-hydroxyvitamin D3 and 5E-25-hydroxyvitamin D3-19-methyl[(4-azido-2-nitro)phenyl]glycinate: novel C19-modified affinity and photoaffinity analogs of 25-hydroxyvitamin D3

In addition to fibrillary glomerulonephritis (FGN), Congo red negative mesangial fibrils may commonly be seen in sclerosing glomerular diseases. Rarely, these nonspecific mesangial fibrils (NMF) may mimic fibrils in FGN and cause a differential diagnostic pitfall. Following an interesting case of sclerosing crescentic glomerulonephritis with abundant NMF (which is presented in some detail) we have reviewed our renal biopsy files for a period of two and a half years and found additional 16 cases where the presence of NMF warranted studies to exclude FGN and other diseases with fibrillary deposits. The immunofluorescence pattern characteristically seen in FGN was not present in any of these cases. Our data confirm that mesangial fibrillary material seen ultrastructurally in sclerosing glomeruli with negative or nonspecific immunofluorescence (IF) represents a nonspecific reaction of the mesangial matrix to chronic glomerular injury. The presence of NMF should not lead to the erroneous diagnosis of FGN. Negative or nonspecific immunofluoresence, localization to the mesangium in a usually segmental fashion, and the more bundle-like than random arrangement of fibrils are helpful diagnostic hints in differentiating NMF from fibrils in FGN.     

Invasive streptococcal infection as a complication of chickenpox

Two girls aged 11 months and 6 years, presented with an invasive group A streptococcal (GAS) infection during the course of primary varicella. The infant had severe cellulitis of the left arm and leg, fever and bacteraemia. She developed osteomyelitis of ulna and tibia. The 6-year-old girl had a fever > 38.5 degrees C, hypotension, an acute respiratory distress syndrome, liver function abnormalities, and positive cultures of blood and joints. Her clinical picture was compatible with a GAS-associated toxic shock syndrome. If during the course of primary varicella persistent fever, secondary fever or pain in one or more extremities occurs, invasive bacterial infection by GAS or Staphylococcus aureus should be considered, even in the absence of skin infection or cellulitis.     

Anatomical and functional considerations in total claviclectomy

There should be no hesitation in performing a total claviclectomy. It is the treatment of choice in cases of ch. pyogenic osteomyelitis of the clavicle and other lesions which demand sacrificing the bone. There was no functional impairment of the shoulder joint or the girdle. There is usually no major postoperative complication and no residual disability. In children, regeneration of bone takes place from the periosteal tube.     

Ursodeoxycholic acid does not improve the clinical course of primary sclerosing cholangitis over a 2-year period

BACKGROUND: Ursodeoxycholic acid has been shown to be a useful agent in the clinical management of patients with primary biliary cirrhosis and autoimmune chronic active hepatitis. Its efficacy is presumed to be based upon its ability to act as a detergent and to incite a choleresis. Recent additional data suggest it also reduces HLA antigen expression on liver and biliary epithelial cells and impairs T cell reactivity. METHODS: A randomized controlled study of 59 patients with primary sclerosing cholangitis was performed over a 24 months period with 3 groups being studied. Group I consisted of 20 patients who were given ursodeoxycholic acid 300 mg orally twice a day; group II consisted of 19 patients who were given colchicine 0.6 mg orally BID; and group III was an untreated medical control group. All three groups were seen at regular 3-month intervals and had quarterly, annual and terminal studies performed to assess their disease status. RESULTS: No difference between groups was evident after two full years of therapy when parameters of liver injury, liver function, liver size and hepatic copper content were compared between groups. Similarly, no difference in ERCP findings was evident between groups either at entry or after two years of therapy. CONCLUSIONS: These data suggest that ursodeoxycholic acid is no better than colchicine or simple medical follow-up. Thus, neither ursodeoxycholic acid or colchicine can be considered to be effective therapies for primary sclerosing cholangitis.     

Diagnosis of osteomyelitis. Accuracy and limitations of antigranulocyte antibody imaging compared to three-phase bone scan

Thirty-seven patients with suspected osteomyelitis in conjunction with diabetic gangrene (N = 14, group 1), arthroplasty (N = 8, group 2), and various diseases (N = 15, group 3) were examined. Three-phase bone scans, followed by granulocyte imaging using I-123 labeled anti-NCA 95 monoclonal antibodies, were performed to evaluate and compare the diagnostic accuracy of both procedures. Final diagnosis was established histologically, bacteriologically, or by both methods either through the clinical course or by long-term follow-up in patients in group 1. Osteomyelitis was proven in 17 out of the 37 patients. Bone and antigranulocyte imaging demonstrated positive results in all patients with osteomyelitis (sensitivity 100% for each method). No signs of skeletal infection were found in 20 patients. Fifteen of these patients had no antigranulocyte antibody accumulation, resulting in 75% specificity. Ten patients without infection had normal three-phase bone imaging results (specificity 50%). Antigranulocyte imaging results were negative in 6 out of 10 patients without osteomyelitis in groups 2 and 3 whose bone imaging results were questionable. However, because of identical bone and granulocyte imaging results, no increase of diagnostic accuracy could be obtained by additional granulocyte imaging in patients with diabetic gangrene. Final diagnoses of false-positive antigranulocyte studies were aseptic osteonecrosis (N = 2), loosening of prostheses, gouty arthritis, and pain after arthrolysis. In summary, antigranulocyte antibody imaging offered high sensitivity and acceptable specificity for the diagnosis of osteomyelitis. Diagnostic accuracy can be improved through the adjuvant use of antigranulocyte imaging for patients with suspected osteomyelitis, especially when radiographic and scintigraphic results are questionable or unreliable.     

What is the association of primary sclerosing cholangitis with sex and inflammatory bowel disease in Turkish patients?

BACKGROUND/AIMS: In the Western world, primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease that is associated with inflammatory bowel disease (IBD), particularly chronic ulcerative colitis and, to a lesser degree, Crohn's disease. The goal of this study was to determine the prevalence of PSC in Turkish patients with IBD and chronic amebic colitis, a disease that is endemic in Turkey. METHODOLOGY: During a 10-year period, between 1986 and 1996, a total of 81 IBD (64 ulcerative colitis and 17 Crohn's disease) patients and 127 patients with chronic amebic colitis were seen and evaluated with radiologic, serologic, immunologic and pathologic tests. Whenever a clinical or biochemical finding suggested the presence of co-existent hepatic and/or biliary disease, the patient was further evaluated by liver biopsy, auto-antibodies and endoscopic retrograde cholangiopancreatography (ERCP) to determine whether they also had PSC or some other form of liver disease. As a disease control group, a total of 752 patients with clinical and/or laboratory evidence of pancreaticobiliary disease were also studied. In 86 of these 752 patients (10%), a primary disorder of the biliary tree was diagnosed by ultrasonography, computed tomography, peritoneoscopy, liver biopsy, ERCP and abdominal laparotomy. In addition, all 86 patients of the control group were evaluated endoscopically in order to determine whether they had any associated gastrointestinal condition of the upper or lower gastrointestinal tracts. After establishing final diagnoses of IBD, amebic colitis and PSC, these patients were evaluated with respect to their socio-economic status. A high protein diet (1.8 gram/kg/day) was administered to those patients with chronic amebic colitis and IBD during the active period of the disease. RESULTS: Of the 208 patients (81 with IBD and 127 with chronic amebic colitis), no cases of PSC were identified. Of the 86 patients in the control group with primary biliary tract disease, 45 had a biliary system malignancy, 14 had primary biliary cirrhosis (PBC), 16 had PSC, 3 had Caroli's disease, 6 had a common bile duct cyst, and 2 had gallbladder adenomatosis. All but 1 of the 16 patients with PSC were female. CONCLUSIONS: These data suggest that, in contrast to findings in Western Europe and the USA, in Turkey: 1) PSC is not regularly associated with idiopathic IBD; 2) most patients with PSC are female; 3) PSC accounts for only 18% of patients with a primary disorder of the biliary tree; 4) the incidence of small-duct primary sclerosing cholangitis is greater than that reported in the literature; and, 5) the incidence of IBD and PSC in Turkey is relatively lower than in other countries.     

An unusual cause of low back pain. Osteomyelitis of the spinous process

STUDY DESIGN: A case report of osteomyelitis of the spinous process. OBJECTIVE: To describe the diagnosis and successful treatment of a patient with spinous process osteomyelitis. SUMMARY OF BACKGROUND DATA: Spinous process osteomyelitis is exceedingly rare and may be misdiagnosed as paraspinal muscle strain, discitis, or vertebral body osteomyelitis. The clinical presentation of spinous process osteomyelitis is subtle, laboratory findings are nonspecific, and radiographs are often normal. METHODS: The diagnosis, treatment, and outcome of two patients with spinous process osteomyelitis (an adult and a child) with insidious, nonspecific lumbar pain and fever are reviewed. RESULTS: Magnetic resonance imaging with and without gadolinium enhancement demonstrated increased signal of the spinous process with paraspinous musculature enhancement, a finding consistent with spinous process osteomyelitis. Biopsy results demonstrated the presence of staphylococcus aureus in the child and no organisms in the adult. Treatment with intravenous antibiotics led to resolution in both cases. CONCLUSIONS: The use of magnetic resonance imaging technology permitted the early and accurate diagnosis of spinous process osteomyelitis.     

Sir Colin MacKenzie and the Institute of Anatomy

Implant therapy can be used to build permanent restorations when there is loss of osseous and dental structures. In diffuse sclerosing osteomyelitis, permanent restorations utilizing implants could improve masticatory function. However, because of the probability of bone separation, the presence of an inadequate blood supply and the possibility of exacerbating the disease, implant therapy should be used with caution in the majority of patients. Certainly the operative sites should not be placed in the midst of these lesions. Questions exist as to their placement in unaffected portions of the jaws.