Treatment of extraintestinal manifestations in inflammatory bowel disease.

Inflammatory bowel disease (IBD) is a systemic disease associated with a large number of extraintestinal manifestations (EIM). EIM are present in 15-20% of patients with ulcerative colitis and in 20-40% of patients with Crohn's disease. The management of EIM is best provided by a multidisciplinary team, which includes specialists in the affected organ systems with training in the treatment of IBD. Therapeutic strategy is often empirical. This is explained by the paucity of randomized-controlled studies for the specific treatment of EIM in IBD and by the fact that treatment models are based on extrapolation from patients with similar conditions but without IBD. For most EIM, the mainstay of therapy is the treatment of the underlying active IBD. However, some EIM such as axial arthritis, pyoderma gangrenosum, uveitis and primary sclerosing cholangitis run a clinical course independent of IBD activity and need specific therapy (e.g. TNF antagonists in ankylosing spondylitis and skin manifestations). This review summarizes the conventional and novel (e.g. anti-TNF) treatment modalities, and the therapeutic implications for the management of extraintestinal symptoms in IBD, in order to assist clinicians in optimizing treatment strategies for IBD patients with EIM.

Positive IgG Western Blot for Borrelia burgdorferi in Colombia

In order to evaluate the presence of specific IgG antibodies to Borrelia burgdorferi in patients with clinical manifestations associated with Lyme borreliosis in Cali, Colombia, 20 serum samples from patients with dermatologic signs, one cerebrospinal fluid (CSF) sample from a patient with chronic neurologic and arthritic manifestations, and twelve serum samples from individuals without clinical signs associated with Lyme borreliosis were analyzed by IgG Western blot. The results were interpreted following the recommendations of the Centers for Diseases Control and Prevention (CDC) for IgG Western blots. Four samples fulfilled the CDC criteria: two serum specimens from patients with morphea (localized scleroderma), the CSF from the patient with neurologic and arthritic manifestations, and one of the controls. Interpretation of positive serology for Lyme disease in non-endemic countries must be cautious. However these results suggest that the putative "Lyme-like" disease may correlate with positivity on Western blots, thus raising the possibility that a spirochete genospecies distinct from B. burgdorferi sensu stricto, or a Borrelia species other than B. burgdorferi sensu lato is the causative agent. Future work will focus on a survey of the local tick and rodent population for evidence of spirochete species that could be incriminated as the etiologic agent.

Clinical manifestations in patients with SOS1 mutations range from Noonan syndrome to CFC syndrome.

Noonan syndrome (NS) and cardio-facio-cutaneous (CFC) syndrome are autosomal dominant disorders characterized by heart defects, facial dysmorphism, ectodermal abnormalities, and mental retardation. There is a significant clinical overlap between NS and CFC syndrome, but ectodermal abnormalities and mental retardation are more frequent in CFC syndrome. Mutations in PTPN11 and KRAS have been identified in patients with NS and those in KRAS, BRAF and MAP2K1/2 have been identified in patients with CFC syndrome, establishing a new role of the RAS/MAPK pathway in human development. Recently, mutations in the son of sevenless gene (SOS1) have also been identified in patients with NS. To clarify the clinical spectrum of patients with SOS1 mutations, we analyzed 24 patients with NS, including 3 patients in a three-generation family, and 30 patients with CFC syndrome without PTPN11, KRAS, HRAS, BRAF, and MAP2K1/2 (MEK1/2) mutations. We identified two SOS1 mutations in four NS patients, including three patients in the above-mentioned three-generation family. In the patients with a CFC phenotype, three mutations, including a novel three amino-acid insertion, were identified in one CFC patient and two patients with both NS and CFC phenotypes. These three patients exhibited ectodermal abnormalities, such as curly hair, sparse eyebrows, and dry skin, and two of them showed mental retardation. Our results suggest that patients with SOS1 mutations range from NS to CFC syndrome.

Hepatic Manifestations of Wilson Disease - CHUV Experience 2005-2010

Background and aim: Wilson disease (WD) is an inherited disorder ofhepatic copper excretion leading to toxic accumulation of copper in theliver as well as the brain, cornea, and other organs. The defect is due tomutations of the copper-transporting ATPase ATP7B. Here, we describethe adult cases of hepatic WD diagnosed at the CHUV between 2005and 2010.Methods: Clinical manifestions, results of diagnostic tests, and follow-upof adult patients with hepatic WD were recorded systematically.Results: Seven new adult cases of hepatic WD were diagnosed in ourcenter between 2005 and 2010. Three were women and 4 men, with amedian a ge at d iagnosis o f 24 (range, 1 8-56) years. Three patientspresented with acute liver failure (ALF), three with persistently elevatedliver function tests, and one with a dvanced cirrhosis. None hadneurological manifestations. Only one patient, presenting with ALF, had aKayser-Fleischer corneal ring. Median ceruloplasmin levels at diagnosiswere 0.13 (range, <0.03-0.30) g/l, median 24 h urinary copper excretion6.3 (range, 0.4-62.0) μmol/24 h, and median hepatic copperconcentration 591 (range, 284-1049) μg/g. At least one mutation in theATP7B g ene was i dentified in a ll patients. Allelic frequency of t hecommon H1069Q mutation was 14%. Two patients presenting with ALFand the one with advanced cirrhosis underwent successful l ivertransplantation. One patient with ALF recovered under chelator therapy.D-penicillamine was used as first-line chelator treatment, with a switch totrientine due to adverse effects in 2 out of 4 patients u nder l ong-termtreatment.Conclusions: The clinical presentation of WD and the performance ofdiagnostic tests are variable. A high index of suspicion i n clinicallycompatible situations i s key, with a combination of tests allowing thediagnosis of WD.

Chronology of extraintestinal manifestations relative to IBD diagnosis in the Swiss IBD Cohort

Background and Aims: Due to a p aucity of s uch data we aimed to a ssess the type and f requency o f extraintestinal manifestations ( EIM) in I BD p atients and to e valuate their chronologic behavior. Methods: A nalysis of d ata from t he Swiss Inflammatory Bowel Disease Cohort (SIBDCS) which c ollects data since 2 005 on a large sample o f IBD patients f rom hospitals and private practices across Switzerland. Results: A t total o f 1,143 patients were a nalyzed ( 572 (50%) female, mean age 42.1 ± 14.4 years), 629 with Crohn's disease (CD), 501 with ulcerative colitis (UC), and 13 with indeterminate colitis ( IC). Of t hese, 3 74 (32.7%) presented o ne to five E IM (65% w ith CD, 3 3% w ith UC, 2% w ith IC). O f those patients suffering from EIM, 4 1.7% p resented two, 1 2.4% t hree, 5 .3% four, and 3.2% f ive E IM d uring lifetime. T he initial EIM presented with the following frequencies: p eripheral a rthritis (PA) 6 3.4%, ankylosing spondylitis (AS) 8 .1%, primary sclerosing cholangitis (PSC) 6%, uveitis 5.7%, oral a phthosis 5.7%, erythema nodosum (EN) 5 %, other 3 .6%, pyoderma gangrenosum 1.8%, psoriasis 0.7%. In only 7.1% of cases, the EIM m anifested before IBD diagnosis was made (median time 28 months b efore IBD diagnosis, I QR 7 -60 months), in 9 2.9% EIM m anifested a fter e stablished IBD d iagnosis (median 72 months, IQR 9-147 months). Conclusions: EIM are a frequent problem in IBD patients. The vast m ajority of E IM m anifest a fter I BD d iagnosis has b een established. P eripheral a rthritis, a nkylosing spondylitis, a nd PSC represent the most frequent first manifestations of an EIM.

Clinical manifestations of mucous membrane pemphigoid in a tertiary center.

Mucous membrane pemphigoid (MMP) is a progressive inflammatory disease of autoimmune etiology. We performed a retrospective analysis of clinical signs and treatment on 16 patients. Conjunctival biopsies were performed in all patients and showed typical immuno-deposits at the basement membrane zone. The mean age at presentation was 69 years, 60 % were female.12 patients demonstrated ocular involvement (11 bilaterally). At the time of referral to our hospital, 92 % had reached an advanced stage III or IV. All patients presented conjunctival fibrosis with resultant fornix foreshortening. Trichiasis and symblepharon were found in 11 patients. Keratitis was found in 11 patients resulting in ulceration in 5 cases. Complications required surgical interventions included: entropion surgery (n = 2), tarsorrhaphy (n = 1), amniotic membrane transplantation (n = 2), keratoplasty (n = 1). Systemic immunomodulatory therapy is the treatment of choice. Dapsone (n = 8), steroids (n = 8), azathioprine (n = 5), cyclophosphamide (n = 2), mycophenolate mofetil (n = 4) and methotrexate (n = 1) were used concomitantly or consecutively. Early diagnosis can prevent ocular complications. Immunomodulatory therapy has provided an avenue for preserving vision. The management of MMP requires a multidisciplinary approach.