rifampin and Lupus-Erythematosus--Systemic

Topics: Animals; Anti-Glomerular Basement Membrane Disease; Anti-Inflammatory Agents; Antibodies; Captopril; Drug Hypersensitivity; Environmental Exposure; Glomerulonephritis; Gold; Heroin; Humans; Hydrocarbons; Hypersensitivity, Delayed; Hypersensitivity, Immediate; Immune Complex Diseases; Kidney Diseases; Kidney Glomerulus; Lupus Erythematosus, Systemic; Mercury; Nephritis, Interstitial; Penicillamine; Penicillins; Rifampin

Iberdomide is a cereblon E3 ligase modulator capable of redirecting the protein degradation machinery of the cell towards the elimination of target proteins potentially driving therapeutic effects. In vitro studies demonstrated that iberdomide predominantly undergoes oxidative metabolism mediated by cytochrome P450 (CYP) 3A4/5 but had no notable inhibition or induction of CYP enzymes. Consequently, the potential of iberdomide as a victim of drug-drug interactions (DDI) was evaluated in a clinical study with healthy subjects.. A total of 33 males and 5 females with 19 subjects per part were enrolled. Part 1 evaluated the pharmacokinetics (PK) of iberdomide alone (0.6 mg) and when administered with the CYP3A and P-gp inhibitor itraconazole (200 mg twice daily on day 1 and 200 once daily on days 2 through 9). Part 2 evaluated the PK of iberdomide alone (0.6 mg) and with CYP3A4 inducer rifampin (600 mg QD days 1 through 13). Plasma concentrations of iberdomide and the active metabolite M12 were determined by validated liquid chromatography-tandem mass spectrometry assay.. Coadministration of iberdomide with itraconazole increased iberdomide peak plasma concentration (C. Caution should be taken when coadministering iberdomide with strong CYP3A inhibitors. Coadministration of iberdomide with strong CYP3A inducers is not advised.. Clinical trial identification number is NCT02820935 and was registered in July 2016.

Topics: Adult; Area Under Curve; Cytochrome P-450 CYP3A; Cytochrome P-450 CYP3A Inducers; Cytochrome P-450 CYP3A Inhibitors; Drug Interactions; Female; Healthy Volunteers; Heterocyclic Compounds, 4 or More Rings; Humans; Immunologic Factors; Itraconazole; Lupus Erythematosus, Systemic; Male; Microsomes, Liver; Middle Aged; Morpholines; Multiple Myeloma; Phthalimides; Piperidones; Rifampin; Young Adult

The incidences of infection with Mycobacterium tuberculosis and Cryptococcus neoformans in immunocompromised patients have increased, but there are few documented cases of their coexistence. We present the case of a 9-year-old female with systemic lupus erythematosus (SLE), treated with prednisone and cyclophosphamide, who was admitted to the emergency department with a 2-week history of fever, headache, malaise, fatigue, and diplopia 3 years after diagnosis. Physical examination showed limitation of abduction of the right eye, Kernig and Brudzinski signs, and hyporeflexia. Magnetic resonance imaging showed hyperdense lesions located in the caudate nucleus, and lumbar puncture showed pleocytosis, a low glucose level, and increased protein level. Cerebrospinal fluid culture identified C. neoformans and PCR detect M. tuberculosis. Treatment was started with isoniazid, rifampin, pyrazinamide, ethambutol, and amphotericin B. We found two similar reports in adults, but no data were found for either pediatric or SLE patients.

Topics: Amphotericin B; Antitubercular Agents; Child; Coinfection; Cryptococcosis; Cryptococcus neoformans; Ethambutol; Female; Humans; Immunocompromised Host; Isoniazid; Lupus Erythematosus, Systemic; Meningoencephalitis; Mycobacterium tuberculosis; Pyrazinamide; Rifampin

Leprosy is a contagious and chronic systemic granulomatous disease caused by the bacillus Mycobacterium leprae. To our knowledge, no case of leprosy in a childhood-onset systemic lupus erythematosus (c-SLE) patient has been reported. For a period of 31 years, 312 c-SLE patients were followed at the Pediatric Rheumatology Unit of our University Hospital. One of them (0.3%) had tuberculoid leprosy skin lesions during the disease course and is here reported. A 10-year-old boy from Northwest of Brazil was diagnosed with c-SLE based on malar rash, photosensitivity, oral ulcers, lymphopenia, proteinuria, positive antinuclear antibodies, anti-double-stranded DNA, anti-Sm and anti-Ro/SSA autoantibodies. He was treated with prednisone, hydroxychloroquine and intravenous cyclophosphamide, followed by mycophenolate mofetil. At 12-years-old, he presented asymmetric skin lesions characterized by erythematous plaques with elevated external borders and hypochromic center with sensory loss. Peripheral nerve involvement was not evidenced. No history of familial cases of leprosy was reported, although the region where the patient resides is considered to be endemic for leprosy. Skin biopsy revealed a well-defined tuberculoid form. A marked thickening of nerves was observed, often destroyed by granulomas, without evidence of Mycobacterium leprae bacilli. At that time, the SLEDAI-2K score was 4 and he had been receiving prednisone 15 mg/day, hydroxychloroquine 200 mg/day and mycophenolate mofetil 3 g/day. Paucibacillary treatment for leprosy with dapsone and rifampicine was also introduced. In conclusion, we have reported a rare case of leprosy in the course of c-SLE. Leprosy should always be considered in children and adolescents with lupus who present skin abnormalities, particularly with hypoesthesic or anesthesic cutaneous lesions.

Topics: Adolescent; Autoantibodies; Child; Dapsone; Humans; Leprostatic Agents; Leprosy, Paucibacillary; Lupus Erythematosus, Systemic; Male; Mycobacterium leprae; Rare Diseases; Rifampin

Topics: Antibiotics, Antitubercular; Humans; Lupus Erythematosus, Systemic; Male; Middle Aged; Rifampin; Skin

Topics: Acute Disease; Antitubercular Agents; Drug Combinations; Female; Humans; Isoniazid; Lupus Erythematosus, Systemic; Middle Aged; Pyrazinamide; Rifampin; Steroids; Tuberculosis, Cutaneous; Tuberculosis, Miliary

A 75-year-female with a history of Isoniazid (INH) therapy for latent tuberculosis, was admitted with a 4-week duration of dyspnea, cough, and pleuritic chest pain. She was treated with intravenous antibiotics for a diagnosis of pneumonia. Her stay was complicated by development of recurrent, exudative eosinophilic pleural effusions (EPEs). When symptoms continued to worsen and she developed joint pain and anasarca and did not respond to the antibiotics, a rheumatologic work-up was performed. She was found to have positive anti-double stranded-DNA antibodies and anti-histone antibodies; thus, a diagnosis of drug-induced lupus, secondary to INH, was made. INH was discontinued, and the patient was started on prednisone; within weeks her symptoms resolved. This case illustrates a unique side effect of INH that caused exudative EPEs and drug-induced lupus with positive anti-dsDNA.

Topics: Aged; Antibodies, Antinuclear; Antitubercular Agents; DNA; Drug Substitution; Eosinophilia; Exudates and Transudates; Female; Glucocorticoids; Humans; Isoniazid; Latent Tuberculosis; Lupus Erythematosus, Systemic; Pleural Effusion; Prednisone; Rifampin; Treatment Outcome

The case of a 56-year-old woman, with a previous history of systemic lupus erythematosus (SLE), later diagnosed as also affected by active dermatomyositis (DM) associated with tuberculosis (TB) is reported. Since TB is a contra-indication to receive immunosuppressive therapy for DM/SLE, intravenous immunoglobulins (IVIG) with low-dose steroids and anti-TB therapy were administered with excellent clinical results. This report underlines the crucial role of IVIG in the treatment of critical patients suffering from connective tissue disorders associated with severe infections.

Topics: Antitubercular Agents; Dermatomyositis; Female; Humans; Immunoglobulins, Intravenous; Immunologic Factors; Isoniazid; Lupus Erythematosus, Systemic; Middle Aged; Pyrazinamide; Rifampin; Tuberculosis

We describe a case of Mycobacterium haemophilum in an immunocompromised patient with systemic lupus erythematosus (SLE). Mycobacterium haemophilum is a recently described pathogen which has not been previously described either in SLE patients or patients on Mycophenolate Mofetil. Mycobacterium haemophilum can be difficult to diagnose, as it may not have the granulomas characteristic of atypical mycobacterial infections. Combination therapy with at least two drugs for several months is required and the outcome depends on the patient's underlying immunocompromised state. Our report highlights the need for early diagnosis and treatment of Mycobacterium haemophilum in immunocompromised patients with SLE.

Topics: Adult; Anti-Bacterial Agents; Antirheumatic Agents; Clarithromycin; Cyclophosphamide; Ethambutol; Female; Humans; Immunosuppressive Agents; Isoniazid; Leg; Lupus Erythematosus, Systemic; Muscle, Skeletal; Mycobacterium haemophilum; Mycobacterium Infections; Mycophenolic Acid; Rifampin

Rifampicin has been prescribed throughout the world for over 20 years, yet only four cases of rifampicin-induced lupus erythematosus (LE) have been reported. Rifampicin-induced LE is associated with combination therapy with clarithromycin or ciprofloxacin. These drugs are all metabolized through the cytochrome P450 liver enzyme system and combined usage may lead to higher rifampicin blood levels. Drug-induced LE differs from systemic LE; cutaneous manifestations, although uncommon, are an important clue to the diagnosis. We report a case of rifampicin-induced LE presenting with florid cutaneous features.

Topics: Aged; Antibiotics, Antitubercular; Drug Eruptions; Humans; Lupus Erythematosus, Systemic; Male; Rifampin

Topics: Adult; Antibiotics, Antitubercular; Antitubercular Agents; Drug Therapy, Combination; Female; Humans; Lupus Erythematosus, Systemic; Rifampin; Thrombocytopenia; Tuberculosis, Pulmonary

We have investigated changes in the pharmacokinetics of prednisolone caused by co-administration or discontinuation of rifampin. Serial IV pharmacokinetic studies of prednisolone (1 mg/kg) in groups of 3 patients over a 1 month period of rifampin co-treatment or after its withdrawal, revealed significant changes in the area under the curve, the total clearance, the non-renal clearance and the half-life. The changes in the pharmacokinetic parameters reached a 1.5 to 2-fold plateau after 2 weeks and the half maximal effect was attained within 5 days. Neither the volume of distribution nor the protein binding of prednisolone were significantly altered.

Topics: Adult; Drug Interactions; Female; Half-Life; Humans; Lupus Erythematosus, Systemic; Male; Metabolic Clearance Rate; Middle Aged; Nephrotic Syndrome; Prednisolone; Protein Binding; Rifampin; Time Factors

Topics: Adrenal Cortex Hormones; Adult; Colitis; Drug Therapy, Combination; Ethambutol; Feces; Female; Humans; Lupus Erythematosus, Systemic; Mycobacterium tuberculosis; Pyrazinamide; Rifampin; Tuberculosis, Gastrointestinal

Topics: Adult; Fever; Humans; Lupus Erythematosus, Systemic; Male; Rifampin

A 32-year-old man with systemic lupus erythematosus controlled by steroid therapy developed multifocal cutaneous abscesses caused by Mycobacterium scrofulaceum. The distribution and evolution of the lesions suggested hematogenous dissemination, but he exhibited no pulmonary or other visceral manifestations of systemic mycobacterial disease. The patient completed nine months of therapy with isoniazid and rifampin, and the lesions resolved within five months of presentation.

Topics: Abscess; Adult; Drug Resistance, Microbial; Drug Therapy, Combination; Humans; Isoniazid; Lupus Erythematosus, Systemic; Male; Mycobacterium avium; Rifampin; Tuberculosis, Cutaneous

Topics: Enzyme Induction; Female; Humans; Lupus Erythematosus, Systemic; Middle Aged; Prednisolone; Rifampin; Tuberculosis, Pulmonary