tetracycline and Crohn-Disease

The aim of this study was to critically assess all available evidence suggesting an association between antibiotic exposure and new onset of inflammatory bowel disease (IBD).. This systematic review was conducted according to the PRISMA statement and eligible studies were identified through search of PubMed, Embase and the Cochrane Library. Data on patient demographics, antibiotic exposure and confounding factors were analyzed. The Newcastle-Ottawa Scale (NOS) was used to assess the quality of eligible studies.. A total of 15 observational studies (10 case control and five cohort) including 8748 patients diagnosed with IBD were systematically reviewed. Antibiotic exposure was mostly associated with Crohn's disease but not with ulcerative colitis. In particular, penicillin's, cephalosporins, metronidazole and fluoroquinolones were most commonly associated with the onset of Crohn's disease. The impact of tetracycline-family antibiotics on the pathogenesis of IBD was not clear.. There may be an association between antibiotic exposure and the development of IBD; especially Crohn's disease. Even though, clinicians should be cautious when prescribing certain antibiotic regimens to patients with a strong family history of IBD, it should be emphasized that available data are not granular enough to reach any definitive conclusions.

Topics: Anti-Bacterial Agents; Colitis, Ulcerative; Crohn Disease; Fluoroquinolones; Humans; Metronidazole; Penicillins; Risk; Tetracycline

Microbes are detected by the pathogen-associated molecular patterns through specific host pattern recognition receptors. Nucleotide-binding oligomerization domain-containing protein 2 (NOD2) is an intracellular pattern recognition receptor that recognizes fragments of the bacterial cell wall. NOD2 is important to human biology; when it is mutated it loses the ability to respond properly to bacterial cell wall fragments. To determine the mechanisms of misactivation in the NOD2 Crohn mutants, we developed a cell-based system to screen for protein-protein interactors of NOD2. We identified heat shock protein 70 (HSP70) as a protein interactor of both wild type and Crohn mutant NOD2. HSP70 has previously been linked to inflammation, especially in the regulation of anti-inflammatory molecules. Induced HSP70 expression in cells increased the response of NOD2 to bacterial cell wall fragments. In addition, an HSP70 inhibitor, KNK437, was capable of decreasing NOD2-mediated NF-κB activation in response to bacterial cell wall stimulation. We found HSP70 to regulate the half-life of NOD2, as increasing the HSP70 level in cells increased the half-life of NOD2, and down-regulating HSP70 decreased the half-life of NOD2. The expression levels of the Crohn-associated NOD2 variants were less compared with wild type. The overexpression of HSP70 significantly increased NOD2 levels as well as the signaling capacity of the mutants. Thus, our study shows that restoring the stability of the NOD2 Crohn mutants is sufficient for rescuing the ability of these mutations to signal the presence of a bacterial cell wall ligand.

Topics: Acetylmuramyl-Alanyl-Isoglutamine; Animals; Cell Wall; Crohn Disease; Gene Expression Regulation; Half-Life; HCT116 Cells; HEK293 Cells; HSP70 Heat-Shock Proteins; Humans; Mutation; NF-kappa B; Nod2 Signaling Adaptor Protein; Protein Binding; Protein Stability; Signal Transduction; Tetracycline

There is increasing evidence that Escherichia coli organisms are important in Crohn's disease (CD) pathogenesis. In CD tissue they are found within macrophages, and the adherent-invasive CD ileal E. coli isolate LF82 can replicate inside macrophage phagolysosomes. This study investigates replication and antibiotic susceptibility of CD colonic E. coli isolates inside macrophages. Replication of CD colonic E. coli within J774-A1 murine macrophages and human monocyte-derived macrophages (HMDM) was assessed by culture and lysis after gentamicin killing of noninternalized bacteria and verified by electron microscopy (EM). All seven CD colonic isolates tested replicated within J774-A1 macrophages by 3 h (6.36-fold +/- 0.7-fold increase; n = 7 isolates) to a similar extent to CD ileal E. coli LF82 (6.8-fold +/- 0.8-fold) but significantly more than control patient isolates (5.2-fold +/- 0.25-fold; n = 6; P = 0.006) and E. coli K-12 (1.0-fold +/- 0.1-fold; P < 0.0001). Replication of CD E. coli HM605 within HMDM (3.9-fold +/- 0.7-fold) exceeded that for K-12 (1.4-fold +/- 0.2-fold; P = 0.03). EM showed replicating E. coli within macrophage vacuoles. Killing of HM605 within J774-A1 macrophages following a 3-h incubation with antibiotics at published peak serum concentrations (C(max)) was as follows: for ciprofloxacin, 99.5% +/- 0.2%; rifampin, 85.1% +/- 6.6%; tetracycline, 62.8% +/- 6.1%; clarithromycin, 62.1% +/- 5.6% (all P < 0.0001); sulfamethoxazole, 61.3% +/- 7.0% (P = 0.0007); trimethoprim, 56.3% +/- 3.4% (P < 0.0001); and azithromycin, 41.0% +/- 10.5% (P = 0.03). Ampicillin was not effective against intracellular E. coli. Triple antibiotic combinations were assessed at 10% C(max), with ciprofloxacin, tetracycline, and trimethoprim causing 97% +/- 0.0% killing versus 86% +/- 2.0% for ciprofloxacin alone. Colonic mucosa-associated E. coli, particularly CD isolates, replicate within macrophages. Clinical trials are indicated to assess the efficacy of a combination antibiotic therapy targeting intramacrophage E. coli.

Topics: Animals; Anti-Bacterial Agents; Cell Line; Cells, Cultured; Colon; Crohn Disease; Culture Media; Escherichia coli; Humans; Macrophages; Mice; Microbial Sensitivity Tests; Monocytes; Mucous Membrane

The efficacy of a 5-day intensive intravenous regimen (IVR), used as treatment for severely active Crohn's disease in 49 patients, has been evaluated retrospectively. The value of such systemic therapy has not been reported before. Immediate remission was achieved in 38 (76%) patients with no significant difference between those with established disease and those seen for the first time. Patients with ileocolonic disease had the poorest response. There was no apparent change in the natural history of the Crohn's disease after IVR therapy. Nevertheless, this is a safe and effective method of achieving remission in most sick patients with severely active Crohn's disease.

Topics: Adolescent; Adult; Aged; Crohn Disease; Drug Therapy, Combination; Female; Humans; Hydrocortisone; Infusions, Parenteral; Male; Metronidazole; Middle Aged; Prednisolone; Recurrence; Retrospective Studies; Tetracycline; Time Factors

Between 4% and 14% of patients with intestinal Crohn's disease (CD) may manifest the typical oral changes of this disorder. These changes include labial and intraoral inflammatory tissue hyperplasia with fissuring ("cobblestoning") and swelling. In addition, angular cheilitis and regional lymphadenopathy may be present. We report two cases of oral CD in brothers, in whom the unusual symptoms of metallic dysguesia and gingival bleeding were prominent features. Despite the well-recognized familiar incidence of CD, a review of the literature shows that in no previous case reports has familial oral CD been noted. Successful symptomatic and objective treatment results were obtained with a mouthwash preparation of triamcinolone acetonide, tetracycline, and lidocaine.

Topics: Adult; Biopsy; Crohn Disease; Drug Combinations; Dysgeusia; Gingiva; Humans; Lidocaine; Male; Mouth Diseases; Mouth Mucosa; Mouthwashes; Taste Disorders; Tetracycline; Triamcinolone Acetonide

Crohn's disease of the vulva is a rare disease, only eight cases having been described in the literature (Parks, Morson & Pegum, 1965; Mountain, 1970; Ansell & Hogbin, 1973; Devroede et al., 1975; Kao, Paulson & Askin, 1975; Levine, Barton & Grier, 1982). Two additional cases are presented, one of whom is the sixth reported with metastatic Crohn's disease of the vulva.

Topics: Adult; Crohn Disease; Female; Humans; Tetracycline; Vulva; Vulvitis

Thirty-six unselected patients were investigated 3-24 years (mean, 7.8 years) after small-bowel resection for Crohn's disease (mean small intestinal resection, 105 cm). Iliac crest bone biopsies after in vivo tetracycline double-labelling showed a markedly reduced trabecular bone mass (controls, 0.25 +/- 0.06; patients, 0.15 +/- 0.05; p less than 0.01). The average bone remodeling and osteoid mineralization was normal, and only two patients demonstrated signs of frank but slight osteomalacia. The mean serum levels of the three vitamin D metabolites 25-hydroxyvitamin D, 24,25-dihydroxyvitamin D, and 1,25-dihydroxyvitamin D were normal. The observed reduction in trabecular bone mass may theoretically be followed by an increased risk of spontaneous fractures.

Topics: 24,25-Dihydroxyvitamin D 3; Adult; Aged; Bone and Bones; Calcifediol; Calcitriol; Crohn Disease; Dihydroxycholecalciferols; Female; Humans; Intestine, Small; Male; Middle Aged; Photometry; Postoperative Complications; Tetracycline; Vitamin D

Topics: Adolescent; Adult; Body Height; Body Weight; Child; Crohn Disease; Female; Flucytosine; Humans; Male; Middle Aged; Prednisone; Rifampin; Tetracycline

Continuous treatment with broad-spectrum antibiotics resulted in symptomatic improvement in 41 of 44 patients (93%) with Crohn's disease who were treated for 6 months or longer. Radiographic follow-up demonstrated evidence of improvement in 20 of 35 patients (57%) for whom posttherapy radiographs were available. Radiography demonstrated resolution of ulcerations, abdominal masses, stenosis, and in some patients restoration of a normal intestinal mucosal pattern. In some patients these changes occurred within weeks; in others, over a period of years. Patients with perianal fistulas and patients who had previously undergone surgery and had recurrence of their disease prior to treatment with antibiotics accounted for the therapy failures.

Topics: Adolescent; Adult; Ampicillin; Anti-Bacterial Agents; Cephalothin; Clindamycin; Crohn Disease; Drug Evaluation; Erythromycin; Female; Follow-Up Studies; Humans; Male; Middle Aged; Prednisone; Radiography; Tetracycline

The therapy of Crohn's disease in adolescence must balance the natural disease history of growth suppression, debilitation, and progression against possible drug-related adverse effects on growth and development. In contrast to published guidelines which usually suggest episodic and symptomatic treatment of relapses, we have attempted to suppress disease activity throughout adolescence. Sixteen consecutive adolescent patients treated with continuous medical therapy for a mean duration of 3.5 years are presented. Fourteen received long term prednisone therapy for maintenance of disease suppression. All 16 have been asymptomatic or have had only mild symptoms which did not interfere with regular activities. Only 1 subject had to be rehospitalized. He subsequently underwent bowel surgery. Aternate day corticosteroid administration has been attained in 11 patients; 10 are growing and developing at a normal rate. In total, 13 of 16 have achieved pubertal development appropriate for age. The 8 patients with distal ileal disease have had a consistently excellent response to medical therapy. There have been no major adverse effects from drug therapy. It is concluded that an effort to suppress disease activity continuously in adolsecents with Crohn's disease is warranted. Excellent symptomatic control and normal rate of growth can be expected in patients with primarily ileal disease.

Topics: Adolescent; Child; Crohn Disease; Drug Therapy, Combination; Female; Humans; Male; Prednisone; Sulfasalazine; Tetracycline

A 58-year-old white female who had regional enteritis for many years insidiously developed scleroderma. A review of the literature failed to reveal any previous reports of this combination of diseases. The possible etiologies of both diseases are discussed along with their overlapping clinical manifestations.

Topics: Colostomy; Contracture; Crohn Disease; Female; Hand Deformities, Acquired; Humans; Middle Aged; Postoperative Complications; Prednisone; Radiography; Recurrence; Scleroderma, Systemic; Tetracycline; Vitamins

Over the past 10 years, it has been well established that Crohn's disease may involve any segment of the gastrointestinal tract from the mouth to the anus and may also cause destructive extraintestinal lesions. Extensive cutaneous ulceration has recently been recognized as one of the rare extraintestinal complications. A case of chronic vulvar ulceration due to Crohn's disease is reported. The clinical manifestations and management of such a lesion are discussed.

Topics: Abscess; Adult; Aminosalicylic Acids; Biopsy; Buttocks; Colectomy; Complement Fixation Tests; Crohn Disease; Female; Humans; Ileostomy; Isoniazid; Pregnancy; Skin Ulcer; Steroids; Tetracycline; Vulva; Vulvar Diseases

Topics: Administration, Topical; Adolescent; Anti-Inflammatory Agents; Barium Sulfate; Biopsy; Crohn Disease; Epithelium; Humans; Hydrocortisone; Male; Mouth Diseases; Mouth Mucosa; Mouthwashes; Nystatin; Oral Manifestations; Physical Examination; Prednisone; Radiography; Sulfasalazine; Tetracycline; Ulcer

Topics: Actinomyces; Actinomycosis; Aged; Anus Diseases; Colitis, Ulcerative; Crohn Disease; Diabetes Mellitus; Diagnosis, Differential; Female; Follow-Up Studies; Humans; Male; Middle Aged; Penicillin G; Rectal Diseases; Rectal Fistula; Suppuration; Tetracycline

Topics: Adolescent; Adult; Agglutination Tests; Antibody Formation; Chloramphenicol; Crohn Disease; Female; Humans; Male; Middle Aged; Pasteurella; Pasteurella Infections; Streptomycin; Tetracycline

Topics: Adult; Cheek; Crohn Disease; Female; Gingiva; Humans; Mouth Mucosa; Oral Manifestations; Tetracycline

Topics: Adult; Cecal Diseases; Chloramphenicol; Crohn Disease; Female; Humans; Tetracycline

Topics: Crohn Disease; Humans; Oleandomycin; Prednisone; Tetracycline