Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024141 (systemic lupus erythematosus)
 44,322 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Allergic disorders commonly occur in patients with systemic lupus erythematosus (SLE) and allergies to some drugs may occasionally be related to disease flares. We evaluated the prevalence of several types of allergy in 132 patients with SLE and their families and compared the SLE patients with a control group of 66 patients with non-lupus disorders. Total IgE levels were tested in 117 SLE patients and 61 controls. Eighty-three of the 132 SLE patients (63%) had a history of at least one type of allergic disorder. This prevalence was significantly higher (P < 0.0001) than that of the control group (20 of 66 controls). The prevalence of drug allergy (38% vs. 17%; P < 0.005), skin allergy (36% vs. 17%; P < 0.01) and insect allergy (14% vs. 2%; P < 0.02) were significantly higher in SLE patients when compared with controls. Family members of SLE patients had an increased prevalence of at least one type of allergy (55% vs. 24%; P < 0.0001), allergic rhinitis (30% vs. 14%; P < 0.02), asthma (25% vs. 9% P < 0.02), and both rhinitis or asthma (44% vs. 20%; P < or = 0.002). The presence of allergy both in the patient and in the family was more frequent in SLE patients than controls (42% vs. 15%; P < 0.001). We found no differences in total IgE levels between the two groups. Drug, skin and insect allergies were particularly frequent in SLE patients. We also found a high prevalence of rhinitis and asthma in their families.
Lupus 1993 Jun
PMID:Allergic disorders in systemic lupus erythematosus. 836 10

Carbamazepine is an anticonvulsant which is associated with a significant incidence of hypersensitivity reactions including agranulocytosis. We have postulated that many drug hypersensitivity reactions, especially agranulocytosis and lupus, are due to reactive metabolites generated by the myeloperoxidase (MPO) (EC 1.11.1.7) system of neutrophils and monocytes. This led to a study of the metabolism and covalent binding of carbamazepine with MPO/H2O2/Cl- and neutrophils. Metabolism and covalent binding were observed in both systems and the same pathway appeared to be involved; however, the metabolism observed with the MPO system was approximately 500-fold greater than that observed with neutrophils. The metabolites identified were an intermediate aldehyde, 9-acridine carboxaldehyde, acridine, acridone, choloroacridone, and dichloroacridone. We postulate that the first intermediate in the metabolism of carbamazepine is a carbonium ion formed by reaction of hypochlorous acid (HOCl) with the 10,11 double bond. Although we have no direct proof for the proposed carbonium ion, it provides the most likely mechanism for the observed ring contraction. Iminostilbene, a known metabolite of carbamazepine, was also metabolized by a similar pathway leading to ring contraction; however, the rate was much faster and the first step may involve N-chlorination and a nitrenium ion intermediate. These data confirm that carbamazepine is metabolized to reactive intermediates by activated leukocytes. Such metabolites could be responsible for some of the adverse reactions associated with carbamazepine, especially reactions such as agranulocytosis and lupus which involve leukocytes.
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PMID:Carbamazepine metabolism to a reactive intermediate by the myeloperoxidase system of activated neutrophils. 838 60

Systemic rheumatic symptoms occur with widely different frequencies as a side effect of long-term therapy with some 39 medications currently in use. Because symptoms are nonspecific, subjective, and protean, diagnosis of drug-induced lupus (DIL) requires awareness of this risk of chronic medication. However, laboratory features and the characteristic of full recovery after discontinuing treatment are helpful in differentiating drug-induced from spontaneous lupus or other syndromes. Drug-induced lupus is probably mediated by reactive drug metabolites, not the ingested medications, and susceptibility to neutrophil-mediated oxidative transformation is a property of ten lupus-inducing drugs reported so far. Mechanisms for DIL modeled after drug hypersensitivity reactions are unsupported experimentally and inconsistent with the features of DIL. However, several new lines of investigation using mouse models have opened up promising leads into the origin of autoreactive T cells and disease development in DIL.
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PMID:Etiology and mechanisms of drug-induced lupus. 1050 55

The primary objectives of this study were to evaluate the safety and efficacy of the cyclooxygenase-2 inhibitor celecoxib in systemic lupus erythematosus (SLE) patients both with and without a self-reported sulfa drug allergy and to review the literature on the use of nonsteroidal agents in SLE subjects. A retrospective review of medical records was performed for 50 SLE patients seen by a community-based rheumatologist and treated with open label celecoxib in doses of 200-400 mg/day for a period of 1-9 months. A MEDLINE search of all articles pertaining to the use of NSAIDs in patients with SLE since 1966 was undertaken. We noted that, in this cohort of celecoxib-treated SLE patients from an office rheumatology practice, the majority demonstrated some improvement, and little toxicity was observed. SLE patients with self-reported sulfa allergies were not more likely to have adverse reactions to celecoxib than non-sulfa allergic patients. The literature review performed herein reveals that, although NSAID toxicity should be a continuing concern in an SLE population, structural dissimilarities between celecoxib and the sulfonamide antimicrobials may make true cross-allergenicity less likely to be a clinical problem. These results suggest that patients with SLE can be safely and effectively treated with celecoxib; however, further studies are needed to assess the effectiveness and safety of all NSAIDs in SLE.
Lupus 2002
PMID:Celecoxib for systemic lupus erythematosus: case series and literature review of the use of NSAIDs in SLE. 1213 71

Idiosyncratic reactions can affect many different organ systems, either as -an isolated event (e.g., hepatitis) or as part of a syndrome (e.g., drug hypersensitivity syndrome). Formation of reactive metabolites of drugs in conjunction with a decreased ability for detoxification is believed to be the initiating step in many idiosyncratic reactions. The drug hypersensitivity syndrome, defined by the presence of fever, rash and internal organ involvement, is estimated to occur in approx 1 in 1000 to 1 in 10,000 exposures with drugs such as anticonvulsants sulfonamide antibiotics, allopurinol, and dapsone. Symptoms usually start within 2-8 wk of drug initiation. Serum sicknesslike reaction, most frequently found after 7-14 d of drug exposure, is distinguished by a fever, cutaneous eruption and arthralgias. Medications such as cefaclor, minocycline and bupropion are most frequently implicated in this reaction. In contrast, drug-induced lupus can occur l-2 yr after initiation of medication. Drug-induced lupus is characterized by musculoskeletal complaints and fever and weight loss. Drugs most commonly associated with drug-induced lupus include procainamide, hydralazine, chlorpromazine, isoniazid, and minocycline. Management of patients who develop idiosyncratic reactions includes discontinuation of the implicated drug, initiation of corticosteroids (when appropriate), and symptomatic relief as required. Internal organ involvement, which may initially be asymptomatic, should be monitored. Confirmatory or diagnostic tests are not readily available in most areas, except for research purposes.
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PMID:Reactive metabolites and adverse drug reactions: clinical considerations. 1272 94

The acute clinical syndrome of toxic epidermal necrolysis (TEN) is currently thought to be a distinct clinical-pathological entity typically resulting from drug hypersensitivity. We describe an adult woman who experienced a fulminate pattern of apoptotic epidermal cell injury following tanning bed exposure while taking naproxen that resulted in a clinical presentation having combined features of drug-induced TEN and an infrequently recognized form of bullous cutaneous lupus erythematosus (LE). This case calls attention to the fact that TEN-like injury can occasionally be seen in settings other than drug hypersensitivity (e.g., LE, acute graft versus host disease) and illustrates the need for a unifying concept in this area. We therefore propose the term 'Acute Syndrome of Apoptotic Pan-Epidermolysis (ASAP)' to designate a clinical syndrome that is characterized by life-threatening acute and massive cleavage of the epidermis resulting from hyperacute apoptotic injury of the epidermis. We also review vesiculobullous skin disorders that can be encountered in LE patients and suggest a new classification scheme for such lesions.
Lupus 2004
PMID:Toxic epidermal necrolysis-like acute cutaneous lupus erythematosus and the spectrum of the acute syndrome of apoptotic pan-epidermolysis (ASAP): a case report, concept review and proposal for new classification of lupus erythematosus vesiculobullous skin lesions. 1564 50

Patients with antiphospholipid syndrome (APS) are prone to excessive postoperative morbidity and mortality after cardiovascular surgery because of its thromboembolic derangements. We present a case of coronary artery bypass grafting (CABG) in a patient with primary APS. He suffered from repetitive coronary occlusion after percutaneous transluminal coronary angioplasty (PTCA). Since his lupus anticoagulant level was found to be 217 s (normal, <50 s), he was diagnosed as the primary APS. He received steroid pulsation therapy with 1000 mg of prednisolone, double-filtration plasmapheresis (DFPP) and 50 mg of cyclophosphamide to attenuate the antibody activity. Four months after the last PTCA, he experienced chest pain and approximately 90% of stenosis in the left anterior descending (LAD) lesion was apparent, although the titer for the lupus anticoagulant was reduced to the normal range. He had drug allergy to ticlopidine hydrochloride and aspirin. Taken together, his disease was found to be resistant to these medical treatments, and surgical treatment was considered. Since cardiopulmonary bypass is known to exaggerate its coagulatory and fibrinolytic complications, off-pump CABG (OPCAB) was feasible in this case. The left internal thoracic artery (ITA) was anastomosed to the LAD using the off-pump technique. The procedure was successful, and the postoperative course for 3 years has been satisfactory without any cardiovascular complaints.
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PMID:Off-pump coronary artery bypass in a patient with the antiphospholipid syndrome. 1575 83

Autoantibodies and, less commonly, systemic rheumatic symptoms are associated with treatment with numerous medications and other types of ingested compounds. Distinct syndromes can be distinguished, based on clinical and laboratory features, as well as exposure history. Drug-induced lupus has been reported as a side-effect of long-term therapy with over 40 medications. Its clinical and laboratory features are similar to systemic lupus erythematosus, except that patients fully recover after the offending medication is discontinued. This syndrome differs from typical drug hypersensitivity reactions in that drug-specific T-cells or antibodies are not involved in induction of autoimmunity, it usually requires many months to years of drug exposure, is drug dose-dependent and generally does not result in immune sensitization to the drug. Circumstantial evidence strongly suggests that oxidative metabolites of the parent compound trigger autoimmunity. Several mechanisms for induction of autoimmunity will be discussed, including bystander activation of autoreactive lymphocytes due to drug-specific immunity or to non-specific activation of lymphocytes, direct cytotoxicity with release of autoantigens and disruption of central T-cell tolerance. The latter hypothesis will be supported by a mouse model in which a reactive metabolite of procainamide introduced into the thymus results in lupus-like autoantibody induction. These findings, as well as evidence for thymic function in drug-induced lupus patients, support the concept that abnormalities during T-cell selection in the thymus initiate autoimmunity.
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PMID:Drug-induced lupus. 1576 26

Drug allergies are heterogeneous and multifactorial diseases and are always the consequence of an exaggerated immune-mediated reaction. Previously described models of immunologic mechanisms (mainly based on Gell and Combs' classification) cannot fully explain the physiopathology of these diseases; it seems therefore important to identify risk factors. Clinical and biologic tests are helpful diagnostic tools but are limited in their sensitivity and reliability and are certainly not predictive. Epidemiologic data supply information concerning the prevalence of drug hypersensitivity: female gender, concomitant infections (HIV, herpes) and concurrent illnesses (systemic lupus erythematosus) are all significant risk factors. Another host-related factor is the genetic predisposition of patients and is currently under investigation in our laboratory. Most genetic studies concern HLA haplotype association or polymorphism in genes encoding drug-metabolising enzymes. A current study by our group seems to implicate polymorphisms within the promoter of IL-10, a cytokine with anti-inflammatory properties. The chemical properties of the drug and the treatment regimen also influence the development of drug allergies.
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PMID:Drug hypersensitivity: epidemiology and risk factors. 1701 25

Systemic lupus erythematosus is a chronic, relapsing autoimmune disease that can affect multiple organ systems. An increased prevalence of drug allergy has been reported in lupus patients compared with the general population. Using a cohort of 417 lupus patients, we found a history of sulpha allergy in 27.3% of patients. European-American lupus patients with sulpha allergy are about two times more likely to suffer from lymphopenia, two times more likely to have anti-Ro autoantibody, and four times less likely to have anti-nRNP antibodies compared with lupus patients without a reported sulpha allergy (P = 0.0075, 0.025, and 0.032, respectively). In African-American lupus patients, a history of sulpha allergy was associated with over three times increased odds of developing pericarditis (P = 0.005).
Lupus 2008 Mar
PMID:Sulpha allergy in lupus patients: a clinical perspective. 1837 60


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