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)

Porphyria cutanea tarda is the most common disorder of porphyrin metabolism in the United States and Europe. This report presents the clinical, laboratory and pathologic features of 40 patients with porphyria cutanea tarda. Each patient was followed up for variable times during 1960-76 at the Clinical Research Center and the Dermatology Service of the Columbia-Presbyterian Medical Center; at the New York University Medical Center; or at the Rockefeller University Hospital. Earlier age at onset; diminution of alcohol ingestion as the major etiologic factor; and, an increased incidence in females indicate new environmental influences. The most frequently associated etiologic factor, aside from alcohol intake, was use of estrogens for contraception; postmenopausal syndrome; or treatment of prostatic carcinoma. Cutaneous findings in the patients included bullae (85%); increased skin fragility (75%); facial hypertrichosis (63%); hyperpigmentation (55%); sclerodermoid changes (18%); and, dystrophic calcification with ulceration (8%). Diabetes mellitus was found in 15%; systemic lupus erythematosus in 5%; elevated serum iron level in 62%; and, abnormal liver function test results in 60%. Histologic abnormalities were seen in liver biopsies of 34 patients. Phlebotomy is the treatment of choice. In 32 patients so treated, clinical remissions averaged 30.9 months. 31% (10 patients) had a relapse but additional phlebotomies resulted in 2nd remissions. Chloroquine and plasmaphoresis treatments were also briefly discussed.
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PMID:Porphyria cutanea tarda. Clinical features and laboratory findings in 40 patients. 46 34

Special effects and side effects of antirheumatic basic treatment and symptomatic drugs, lead to distinct indications in the management of rheumatic diseases. Chloroquine should mainly be administered in "lupoid" rheumatoid arthritis (R.A.), in systemic lupus erythematosus, and in less active initial stages of R.A., whereas gold and D-penicillamine should be used in more active early stages of R.A. In psoriatic arthritis there is no contraindication for gold D-penicillamine, however, is less effective. Immunosuppressive agents may be used in special cases of R.A. and connective tissude diseases. However, strict controls and special care are necessary. Additive organ disorders may lead to individual contra-indications for basic treatment. All these drugs are not harmless and need careful control. In "lupoid" R.A. corticoids are superior to nonsteroidal antirheumatic drugs. The association of the conversion of R.A. into necrotizing vasculitis has been suggested. There is, however, no proof for this assertion. The new nonsteroidal antirheumatic drugs are assumed to have less side effects, but their real position may be evaluated only after much longer periods of administration. Rare, but severe side effects, especially due to the hematopoetic system, are problbly caused by an incompatibility of the patient. One must not forget the advantages for millions of rheumatic patients. Also, in an age of an exaggerated desire for security, special consideration must be given to these advantages, so that the development of new antirheumatic drugs is not suppressed.
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PMID:[Differential indications in rheumatism therapy on the basis of well-known drug side effects]. 122 32

Chloroquine and hydroxychloroquine are widely used in diseases of connective tissue, especially in rheumatoid arthritis and systemic lupus erythematosus. However, various side effects are reported in many publications. In general these side effects are less important, e.g. those on the gastrointestinal tract and drug exanthema. Disorders of the haemopoetic system, the central nervous system, and peripheral neuromyopathy are rare. Only few reports exist about fetal damage. In contrary, severe problems result from eye complications such as reversible keratopathy and mostly irreversible retinopathy. If, however, chloroquine is administered, the necessity of exakt dosage and periodic ophthalmologic controls has to be stressed.
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PMID:[Complications in chloroquin therapy]. 124

We reviewed 71 patients with palindromic rheumatism. The average length of followup was 3.6 years. Fifty-one patients received antimalarial therapy. Forty-one of the 51 patients experienced marked improvement with 77.5% reduction in frequency and 63% reduction in duration of attacks. Sixteen out of the 71 patients developed persistent arthritis in the form of rheumatoid arthritis (12 patients), systemic lupus erythematosus (2 patients), Crohn's disease (1 patient) and asymmetric seronegative arthropathy (1 patient). Chloroquine therapy, therefore, seems effective in relieving palindromic rheumatism.
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PMID:Palindromic rheumatism: a response to chloroquine. 202 96

Chloroquine is a drug used mainly as an anti-malaria agent with many other pharmacological properties. It was given to a patient with chorea and disseminated lupus erytematosus seeking the anti-inflammatory effect of the drug. The unexpected result on chorea hastened its use in 7 other patients with the same success. Chloroquine seems to be an effective drug for the relief of chorea. The mechanism of action is unknown.
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PMID:[Chorea and chloroquine. A new treatment for an ancient malady]. 732 46

Chloroquine can prevent photosensitivity reactions, but its mechanism of action is poorly understood. To investigate if the drug may interfere with inflammatory or immunological mechanisms of the UV-induced erythema of photosensitive patients, we studied the localization of chloroquine in the skin and its effect on the epidermal/dermal expression of IL-1, TNF-alpha, IL-6 and ICAM-1 and the occurrence of different lymphoid cells in normal skin and UVB-induced erythema in 8 patients with photosensitive discoid and systemic lupus erythematosus and 4 patients with polymorphic light eruption (PMLE), before and during chloroquine treatment. Using a specific monoclonal antibody against chloroquine, we found a strong granular staining pattern of mainly keratinocytes in all biopsy specimens from normal and erythematous skin during chloroquine treatment. In non-irradiated skin, T lymphocytes, macrophages and HLA-DR expressing cells were sparsely distributed within the dermis in similar amounts before and during chloroquine treatment. In UVB-induced erythema an increase in the number of these cells, mainly located in the dermal perivascular area, was seen before medication. During chloroquine treatment such cellular infiltration was reduced. ICAM-1 expression was detected on the endothelium of dermal vessels but not on keratinocytes. The accumulation of chloroquine in the epidermis and the decreased cellular infiltration in erythematous skin during chloroquine treatment indicate a local anti-inflammatory effect. This effect may be due to either unspecific UV-protective properties of the drug or to some specific downregulating action by chloroquine on keratinocyte function.
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PMID:In situ localization of chloroquine and immunohistological studies in UVB-irradiated skin of photosensitive patients. 765 84

Recent studies have elucidated the steps involved in the association of antigenic peptides with major histocompatibility complex (MHC) encoded proteins and have suggested how antimalarial compounds might influence this important site of immune activation. These steps of antigen presentation in the macrophage (or other antigen-presenting cells) include: (a) the partial proteolytic degradation of endogenous and exogenous proteins into peptides within the lysosome; (b) the synthesis of MHC class II (i.e. HLA-D associated) alpha, beta, and invariant (Ii) chains in the endoplasmic reticulum; (c) the initial association of alpha-Ii and beta-Ii chains in the endoplasmic reticulum and the transport of these complexes to the primary endosome; (d) the fusion of lysosomal vacuoles and endosomal vacuoles, allowing the mixtures of lysosomal enzymes, peptides, alpha-Ii and beta-Ii; (e) the displacement of Ii chains by peptides to form alpha-beta-peptide complexes in the endosome; and (f) the migration of alpha-beta-peptide complexes to the macrophage cell surface where they can stimulate CD4 T cells, resulting in release of cytokines. A low pH is required for digestion of the protein by acidic hydrolases in the lysosome, for assembly of the alpha-beta-peptide complex and for its transport to the cell surface. Chloroquine and hydroxychloroquine are weak diprotic bases that can diffuse across the cell membrane and raise the pH within cell vesicles. This background provides the underlying basis for the theory that antimalarials may act to prevent autoimmunity by the following putative mechanism.(ABSTRACT TRUNCATED AT 250 WORDS)
Lupus 1993 Feb
PMID:Mechanism of action of antimalarial drugs: inhibition of antigen processing and presentation. 809 45

The antimalarial agents chloroquine and hydroxychloroquine have been used widely for the treatment of rheumatoid arthritis and systemic lupus erythematosus. These compounds lead to improvement of clinical and laboratory parameters, but their slow onset of action distinguishes them from glucocorticoids and nonsteroidal antiinflammatory agents. Chloroquine and hydroxychloroquine increase pH within intracellular vacuoles and alter processes such as protein degradation by acidic hydrolases in the lysosome, assembly of macromolecules in the endosomes, and posttranslation modification of proteins in the Golgi apparatus. It is proposed that the antirheumatic properties of these compounds results from their interference with "antigen processing" in macrophages and other antigen-presenting cells. Acidic cytoplasmic compartments are required for the antigenic protein to be digested and for the peptides to assemble with the alpha and beta chains of MHC class II proteins. As a result, antimalarials diminish the formation of peptide-MHC protein complexes required to stimulate CD4+ T cells and result in down-regulation of the immune response against autoantigenic peptides. Because this mechanism differs from other antirheumatic drugs, antimalarials are well suited to complement these other compounds in combination drug therapy.
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PMID:Mechanism of action of hydroxychloroquine as an antirheumatic drug. 827 23

Chloroquine and hydrocychloroquine have been evaluated in 30 noninfectious disorders and conditions other than rheumatoid arthritis or lupus erythematosus; 12 of these have been subjected to well-designed controlled trials. It is concluded that chloroquines are safe and effective first line therapies for selected patients with porphyria cutanea tarda, cutaneous sarcoidosis, cutaneous manifestations of dermatomyositis, hyperlipidemias and thromboembolic prophylaxis for patients with antiphospholipid antibodies. Published experience with these and other diseases or syndromes are critically reviewed.
Lupus 1996 Jun
PMID:The use of chloroquine and hydroxychloroquine for non-infectious conditions other than rheumatoid arthritis or lupus: a critical review. 880 13

Antimalarials are beneficial therapeutic agents in systemic lupus and rheumatoid arthritis. These autoimmune diseases have abnormally low apoptosis of inflammatory cells. Both disorders have an abnormal angiogenesis. In the present report, antimalarials were demonstrated to selectively increase apoptosis of HUVECs in vitro. A 24-h exposure to 50 or 150 microM of the drugs was associated with a significant loss of substrate-adherent cells. Chloroquine exhibited an inhibitory effect on HUVEC proliferation over 7 days. Programmed cell death in HUVECs rendered nonadherent by chloroquine was confirmed by the induction of DNA fragmentation in floating cells. Northern blot analysis revealed a rapidly increased expression of the bcl-x(s) gene without any change in the expression of the bcl-2 gene, indicating that HUVECs under chloroquine were undergoing apoptosis. The onset of the apoptotic cascade in HUVECs appeared shortly after the addition of chloroquine. The effect of chloroquine on apoptosis was distinct from acute cell lysis and was restricted to HUVECs. Antimalarials also induced IL-1alpha production. In parallel, chloroquine alone did not increase the expression of IL-6. Anti-IL-1alpha Ab or IL-1Ra only marginally reversed chloroquine-induced depression of proliferation for the low drug concentration, but not the massive cell death effect at and above 50 microM. Taken together, these data may indicate that antimalarials repress angiogenesis. The autocrine mechanism involving IL-1alpha accounts only for a minor fraction of the full antiendothelial effect of chloroquine, which is mainly dependent on apoptosis.
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PMID:Mechanisms of action of antimalarials in inflammation: induction of apoptosis in human endothelial cells. 902 28


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