rifampin and Autoimmune-Diseases

Primary biliary cirrhosis (PBC) is a chronic cholestatic autoimmune liver disease that predominantly affects middle-aged women. It is characterized by slowly progressive destruction of the small intrahepatic bile ducts together with portal inflammation, and this initially leads to fibrosis and later to cirrhosis. It is currently accepted that the pathogenesis of PBC is multifactorial with genetic and environmental factors interplaying to determine the disease onset and progression. In addition to antimitochondrial antibody (AMA), which is the hallmark of PBC and is detected in at least 90% of the patients, other autoantibodies (antinuclear antibody, anti-smooth muscle antibody and rheumatoid factor, etc.) may also be found in the patients. There is no correlation between the titer of AMAs and the disease severity. Most patients are diagnosed either during the asymptomatic phase of PBC or after presenting with non-specific symptoms. Pruritus and fatigue are the most common symptoms of PBC. The prognosis of PBC has improved significantly during the last few decades. Patients are now diagnosed earlier in its clinical course, they are more likely to be asymptomatic at diagnosis and they are more likely to receive medical treatment. A wide variety of drugs have been assessed for the treatment of this condition: such immunosuppressive agents as corticosteroids, cyclosporine and azathioprine have a weak effect on the disease's natural history. Ursodeoxycholic acid (UDCA) is the only currently approved medical treatment. For PBC patients with end-stage liver disease or an unacceptable quality of life, liver transplantation is the only accepted therapeutic option. Early diagnosis and treatment of PBC are important because effective treatment with UDCA has been shown to delay disease progression and improve rate survival in the early stage.

Topics: Autoimmune Diseases; Cholagogues and Choleretics; Cholestadienes; Cholic Acids; Female; Humans; Liver Cirrhosis, Biliary; Male; Middle Aged; Prevalence; Rifampin

Linear IgA bullous dermatosis (LABD) is an autoimmune subepidermal blistering disease that may be associated with drug exposure.. Our purpose was to compare the clinical, pathologic, and immunofluorescence findings in drug-induced LABD with those in the idiopathic type.. Six patients with an acute drug eruption were identified who had linear IgA deposition at the basement membrane zone (BMZ). Lesional tissue was examined by brightfield microscopy, and perilesional tissue was examined by direct immunofluorescence (DIF). The presence of circulating BMZ antibody was assayed by indirect immunofluorescence (IIF) on monkey esophagus (ME) and salt-split human skin (SS).. Histopathologic examination showed subepidermal bullae with varying numbers of inflammatory cells. DIF showed linear IgA at the BMZ; three of the patients also had weak deposition of C3 at the BMZ. Serum from five patients was studied by IIF. One patient had circulating IgA BMZ antibodies in a titer of 1:80 on ME, localized to the dermal side on SS. All patients were free of lesions within 5 weeks after discontinuation of the drug.. Drug-induced LABD is a self-limited eruption characterized by linear deposition of IgA without IgG at the BMZ. Most patients lack circulating antibodies. The distribution of lesions and the course of the disease differ from those of idiopathic LABD.

Topics: Aged; Autoimmune Diseases; Basement Membrane; Captopril; Drug Eruptions; Female; Humans; Immunoglobulin A; Male; Phenytoin; Rifampin; Skin; Skin Diseases, Vesiculobullous; Somatostatin; Trimethoprim, Sulfamethoxazole Drug Combination; Vancomycin

Topics: Acetyltransferases; Adult; Aged; Autoimmune Diseases; Biotransformation; Chemical and Drug Induced Liver Injury; Drug Therapy, Combination; Enzyme Induction; Female; Humans; Isoniazid; Liver; Middle Aged; Pregnancy; Rifampin

Upadacitinib (ABT-494) is a selective Janus kinase 1 inhibitor being developed for treatment of auto-immune inflammatory disorders. This work evaluated effects of high-fat meal, cytochrome P450 (CYP) 3A inhibition, CYP induction, and organic anion transporting polypeptide (OATP) 1B inhibition on upadacitinib pharmacokinetics.. Two Phase 1 evaluations were conducted, each in 12 healthy subjects. In Study 1, using a randomized, two-sequence crossover design, a 3 mg dose of upadacitinib (immediate-release capsules) was administered alone under fasting conditions, after high-fat meal, or on Day 4 of a 6-day regimen of 400 mg once-daily ketoconazole. In Study 2, a 12 mg upadacitinib dose was administered alone, with the first, and with the eighth dose of a 9-day regimen of rifampin 600 mg once daily. Upadacitinib plasma concentrations were characterized.. Administration of upadacitinib immediate-release capsules after a high-fat meal decreased upadacitinib C. Strong CYP3A inhibition and broad CYP induction result in a weak and moderate effect, respectively, on upadacitinib exposures. OATP1B inhibition and administration of upadacitinib immediate-release formulation with food does not impact upadacitinib exposure.

Topics: Adult; Area Under Curve; Autoimmune Diseases; Cross-Over Studies; Cytochrome P-450 CYP3A; Cytochrome P-450 CYP3A Inducers; Cytochrome P-450 CYP3A Inhibitors; Diet, High-Fat; Dietary Fats; Drug Interactions; Fasting; Female; Food-Drug Interactions; Healthy Volunteers; Heterocyclic Compounds, 3-Ring; Humans; Janus Kinase 1; Ketoconazole; Liver-Specific Organic Anion Transporter 1; Male; Middle Aged; Protein Kinase Inhibitors; Rifampin; Young Adult

Pemphigus vulgaris (PV) is a rare life-threatening condition of the pemphigus group of autoimmune blistering diseases. Systemic glucocorticoids are the cornerstone of management for PV, but complications can arise from their long-term use. We report a case of recurrence of a well-controlled case of PV that could not be alleviated by a combination of steroids, mycophenolate mofetil, and high-dose intravenous immune proteins. The patient had developed numerous complications during previous glucocorticoid therapy, including hypertension, diabetes, glaucoma, cataracts, optic nerve atrophy, aseptic necrosis of the femoral head, osteoporosis, and pulmonary tuberculosis. We determined that recurrence of PV and treatment resistance were consequences of the interaction between the antitubercular agent rifampicin that the patient was taking and corticosteroids. Pemphigus vulgaris was quickly controlled after the rifampicin was discontinued.

Topics: Autoimmune Diseases; Crime; Humans; Immunosuppressive Agents; Mycophenolic Acid; Pemphigus; Rifampin

We hypothesize that a large group of medical conditions of unknown etiology including leukemia, multiple myeloma, myelodysplastic and autoimmune disorders, may be associated with or caused by an obscure group of intracellular obligate parasitic bacteria named Ehrlichia/Anaplasma (EA). Ensconced in the stem cells of the bone marrow, EA may disrupt the normal development and function of many of the cells of immunity, manifesting itself as different syndromes. Recent studies of the activity of EA suggest direct effects on the immune system consistent with the manifestations of leukemia. We reference here three leukemia patients with direct or indirect evidence of EA infection. Moreover, EA have been shown to be most sensitive to rifamycins. Two moribund leukemia patients with levels of platelets and white cells incompatible with life were treated with therapeutic doses of Rifampin. Though they did not survive, their condition improved dramatically for a time, suggesting Rifampin provided some therapeutic benefit. We assert that these results warrant more extensive study.

Topics: Adolescent; Anti-Bacterial Agents; Autoimmune Diseases; Blood Platelets; Ehrlichia; Ehrlichiosis; Female; Humans; Immune System; Leukemia; Male; Middle Aged; Multiple Myeloma; Myelodysplastic Syndromes; Polycythemia Vera; Polymerase Chain Reaction; Rifampin

Reactivation of latent tuberculosis infection (LTBI) is an important complication in patients treated with tumor necrosis factor-alpha (TNF-α) blocking agents. However, the best method for LTBI detection before initiation of anti-TNF therapy remains to be determined.. From January 2010 to August 2013, anti-TNF therapy was initiated in 426 patients with immune-mediated inflammatory diseases (IMIDs). Tuberculin skin test (TST) and Quantiferon-TB Gold In Tube (QFT-GIT) assay were performed before starting anti-TNF treatment. LTBI was defined as a positive TST (induration ≥ 10 mm) or as a positive QFT-GIT result. Patients were followed up until December 2013.. The positive TST and QFT-GIT rates were 22.3% (95/426) and 16.0% (68/426), respectively, yielding a total of 27.0% (115/426) of positive LTBI results. LTBI treatment was initiated in 25.1% (107/426) and was completed in 100% (107/107) of patients. During a median 294 days of follow-up, active TB occurred in 1.4% (6/426) of the patients with negative TST and QFT-GIT results at baseline.. The either test positive strategy, using both TST and QFT-GIT assay, is acceptable for LTBI screening before commencing anti-TNF therapy in patients with IMIDs.

Topics: Adult; Antibiotics, Antitubercular; Antitubercular Agents; Autoimmune Diseases; Female; Humans; Interferon-gamma Release Tests; Isoniazid; Latent Tuberculosis; Male; Middle Aged; Retrospective Studies; Rifampin; Tuberculin Test; Tumor Necrosis Factor-alpha

Topics: Aged; Arthritis, Infectious; Arthritis, Rheumatoid; Arthroplasty, Replacement, Knee; Autoimmune Diseases; Ciprofloxacin; Cloxacillin; Drug Therapy, Combination; Fatal Outcome; Humans; Immunocompromised Host; Knee Prosthesis; Male; Phlebitis; Postoperative Complications; Prosthesis-Related Infections; Pulmonary Embolism; Recurrence; Rifampin; Staphylococcal Infections; Staphylococcus; Virulence

Topics: Anti-Bacterial Agents; Antitubercular Agents; Autoimmune Diseases; Drug Therapy, Combination; Ethambutol; Female; Humans; Isoniazid; Lymph Nodes; Middle Aged; Mycobacterium tuberculosis; Purpura, Thrombocytopenic, Idiopathic; Pyrazinamide; Pyridoxine; Rifampin; Tuberculosis

Topics: Adult; Anemia, Hemolytic; Antitubercular Agents; Autoimmune Diseases; Biopsy; Drug Therapy, Combination; Ethambutol; Humans; Isoniazid; Male; Pyrazinamide; Rifampin; Tuberculosis, Lymph Node

Rifampicin-induced thrombocytopenia is reported in three patients with pulmonary tuberculosis. All three patients gave a definite history of having had prior exposure to rifampicin. Immunological studies in all three patients showed the presence of antiplatelet antibodies, resulting in thrombocytopenia. Moreover, binding of these antibodies to the platelet membrane was more avid in the presence of rifampicin, thereby implicating the drug. The avidity of the rifampicin-dependent antibodies was demonstrated by platelet aggregation inhibition test, and estimation of the rifampicin-dependent antibody was done by studying the platelet-associated immunoglobulin [PAlgG] by ELISA which was also used to quantitate antiplatelet antibodies. Immunofluorescence test was also performed to detect antiplatelet antibodies.

Topics: Adult; Antibiotics, Antitubercular; Autoantibodies; Autoimmune Diseases; Female; Hemagglutination Tests; Humans; Middle Aged; Platelet Aggregation; Rifampin; Thrombocytopenia; Tuberculosis, Pulmonary

A middle-aged male with lepromatous leprosy developed bouts of skin lesions of depigmented macules and patches of vitiligo, just following attacks of type II lepra reaction each time. In view of the present concept of autoimmunity playing a role in the pathogenesis of vitiligo as well as lepra reaction, their association in our patient appears to be more than fortuious. The depigmented macules persisted even after regression of skin lesions of leprosy following chemotherapy. The vitiligo macules responded partially to topical and systemic psoralen therapy.

Topics: Autoimmune Diseases; Clofazimine; Dapsone; Drug Therapy, Combination; Follow-Up Studies; Humans; Leprosy, Lepromatous; Male; Middle Aged; Rifampin; Vitiligo

It is suggested that the important drugs rifampicin and halothane and the raised glucose levels in diabetes mellitus exert injurous effects on cells through a lysosomal mechanism. Further evidence is given of by time rifampicin induction of beta-glucuronidase and beta-N acetylglucosaminidase and its possible relation to hepatitis and pancreatitis. On the basis of preliminary data halothane may cause hepatitis connected to lysosomal enzyme release in the presence of other aggravating factors common to the perioperative period. The onset of diabetic vascular complications may be related to the similar raised levels of lysosomal enzymes found in insulin, drug and diet controlled disease. Release of these enzymes into plasma may be a marker of important changes in the lysosome, whether due to enzyme induction or damage, and could be a primary mechanism of many disease processes including some thought to be mainly autoimmune in character. Routine estimation in the clinical laboratory along with existing cytoplasmic and microsomally derived enzymes in the chemical screen would be a useful way of surveying lysosomal changes in the wide spectrum of disease in a general hospital.

Topics: Acetylglucosaminidase; Autoimmune Diseases; Diabetic Angiopathies; Glucose; Glucuronidase; Halothane; Humans; Lysosomes; Rifampin

Topics: Adult; Antibodies; Antibody Formation; Autoimmune Diseases; Female; Humans; Male; Middle Aged; Rifampin; Tuberculosis, Pulmonary