Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0033687 (proteinuria)
 24,015 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 61-year-old man suffering from active generalized scleroderma developed pemphigus foliaceus after 9 months of D-penicillamine therapy, 900-1200 mg daily. At the same time, he developed proteinuria. Upon discontinuation of the drug, the proteinuria quickly resolved, but the bullous disease was still active one year later, with development of fresh blisters and intercellular deposits of immunoglobulin G and complement C3. The theory is proposed that D-penicillamine alters the epidermal cement substance, rendering it antigenic and thus initiating a vicious circle.
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PMID:Penicillamine-induced pemphigus foliaceus. 7 71

Proteinuria and the nephrotic syndrome are well known to occur as complications of penicillamine therapy, but reports of penicillamine-induced pemphigus have been relatively few. This is the report of a case in which both complications occurred simultaneously.
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PMID:Penicillamine pemphigus and the nephrotic syndrome occurring simultaneously. 62 9

One hundred and forty patients with classic or definite rheumatoid polyarthritis were treated with N2 mercapto-propionly-glycine: thiopronine (Acadione) at an average dose of 1 g per day over a mean duration of 11.7 months + 10.7 months. The retrospective study of these cases, followed between 1980 and 1988 by the same medical team, permits to evaluate the long-term tolerance of the product. Adverse reaction, always subsiding were observed in 55 p. cent of the patients, requiring discontinuation of the treatment in 40 p. cent of the cases. These side effects occur in 3/4 of the cases, during the first 6 months of the treatment. The intolerance mainly affect skin and mucosae: 46 cases (32.8 p. cent) resulting in 32 instances (22.8 p. cent) discontinuation of the treatment because of stomatitis, pruritus, various types of erythema, pemphigus (1 case). Fourteen patients presented a renal failure (10 p. cent) requiring in 8 instances (5.7 p. cent) discontinuation of the thiopronine because of nephrotic syndrome (3 case) and proteinuria (5 cases). Haematological disorders were observed in 13 instances (9.2 p. cent), justifying, in 10 instances (7.1 p. cent) discontinuation of the treatment because of thrombopenia or leucothrombopenia. The other side effects observed are the following: digestive disorders 15 cases (10.7 p. cent) requiring discontinuation of the treatment in 3 instances (2.1 p. cent), agueusia in 6 instances (4.2 p. cent) requiring discontinuation of the treatment in one case; miscellaneous disorders 13.5 p. cent for which the responsibility of thiopronine is not precisely established (especially hepatic cholostasis, muscle disorders), requiring discontinuation the the treatment in 1.4 p. cent of the cases.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Long-term tolerability of tiopronin (Acadione) in the treatment of rheumatoid arthritis. Apropos of 140 personal cases]. 213 12

Many of the adverse reactions produced by penicillamine and other compounds with an active sulfhydryl group form a distinctive pattern when viewed as a class. Alterations in taste perception, mucocutaneous lesions, proteinuria due to immune-complex membranous glomerulopathy, and pemphigus are adverse reactions that have been encountered with all of the compounds discussed herein. Hematologic reactions such as neutropenia and thrombocytopenia occur rarely and with variable frequency. The angiotension converting enzyme inhibitor captopril has an active sulfhydryl group. When it was first given in high doses to patients with severe hypertension, adverse effects similar in pattern to those just outlined were reported. With reduced doses and more careful patient selection, the more serious reactions are no longer found, but disturbances of taste perception, rash, and oral mucosal ulcers are still encountered.
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PMID:Adverse effects profile of sulfhydryl compounds in man. 293 93

We studied D-penicillamine toxicity in 259 patients with systemic sclerosis treated since 1972. The average daily dose of 635 mg was given for a mean of 1.8 years. Of patients with systemic sclerosis, 47% has side effects from D-penicillamine treatment, similar to the 56% of 807 patients with rheumatoid arthritis in seven separate series. Individual manifestations of toxicity included rash, proteinuria, gastrointestinal symptoms, dysgeusia, oral ulcers, thrombocytopenia, and neutropenia. Four episodes each of myasthenia gravis and pemphigus occurred in our patients; both were reported rarely in patients with rheumatoid arthritis. Adverse effects occurred more frequently after rapid increases in dosage. Treatment had to be discontinued due to toxicity in 29% of patients with systemic sclerosis and in 33% of those with rheumatoid arthritis. Although toxic, with a high frequency of adverse effects, D-penicillamine can be used safely in the treatment of systemic sclerosis. Pemphigus and myasthenia gravis may occur more frequently with therapy for systemic sclerosis than with that for rheumatoid arthritis.
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PMID:The toxicity of D-penicillamine in systemic sclerosis. 293 30

An international multicentre study of adverse reactions to D-penicillamine was undertaken on 2879 patients exposed to the drug--1491 of them a prospective sample. The majority of patients were being treated for rheumatoid arthritis. Over a period of 18 months, 319 (21%) of patients in the prospective sample developed adverse reactions necessitating drug withdrawal; two thirds of these occurred during the first 3 months of treatment. The most frequently-occurring adverse reactions involved skin (6%), kidneys (4%), gastro-intestinal tract (4%) and haemopoiesis (3%). Adverse effects, considered to be serious by the reporting physician, included fever and leucopenia during the early weeks of treatment and, after some months of drug exposure, proteinuria, myasthenia gravis, dyspnoea and pemphigus. Two patients died, one of fulminating septicaemia and the other was found at autopsy to have had multiple lung abscesses following unexplained anaemia and hemiparesis.
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PMID:European League against Rheumatism study of adverse reactions to D-penicillamine. 293 13

After a controlled, double blind multicenter trial of D-penicillamine in the treatment of rheumatoid arthritis, 148 patients were followed for an additional year in an open label trial. Complications of longterm D-penicillamine included rash, gastrointestinal manifestations, proteinuria, bone marrow depression, myasthenia gravis, myositis, acute febrile reaction and pemphigus foliaceus. With the exception of one patient with myasthenia gravis, all adverse reactions resolved after withdrawal of D-penicillamine. While the complications of D-penicillamine therapy are usually dose related, these reactions can occur at any time and at any dose. Continued and frequent longterm monitoring of D-penicillamine therapy is required.
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PMID:Toxicity of longterm low dose D-penicillamine therapy in rheumatoid arthritis. Cooperative Systematic Studies of Rheumatic Disease Group. 295 97

D-penicillamine (DPA) leads to side effects in different ways: collagen and elastin crosslinking are inhibited, which results in thin and vulnerable skin, cutis laxa, elastosis perforans serpiginosa, wound healing defects and embryopathy. Toxic influences effect thrombo- and leukocytopenia (incidence 5-15%), gastrointestinal disturbances (10-30%), changes or loss of taste (5-30%), loss of hair (1-2%), and partly proteinuria (5-20%). Acute hypersensitive reactions include DPA-allergy (2-10%). Severe adverse effects are autoimmune phenomena such as pemphigus, DPA-induced lupus erythematosus, polymyositis/dermatomyositis, membranous glomerulopathy and hypersensitivity pneumonitis (like Good-pasture's syndrome) and myasthenia (all less than 1%). In addition there are a number of rare side effects, often single observations. Risk factors include a genetic disposition (especially HLA-B8 and -DR3), poor sulphoxidizers and, to a certain degree, higher age. During pregnancy and in clinically relevant disturbances of bone marrow, liver and renal function DPA is contraindicated. The total incidence of side effects amounts to 30-60%, the withdrawal rate is 20-30%; therefore clear indications and a regular survey of DPA therapy are necessary.
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PMID:[D-penicillamine--side effects, pathogenesis and decreasing the risks]. 306 3

Selected adverse reactions of penicillamine encountered in our clinic since 1975 are described. They include: proteinuria (26 cases), lupus erythematosus (six cases), myasthenia gravis (two cases), pemphigus (three cases), obliterative bronchiolitis (two cases) and obstructive jaundice (one case).
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PMID:Selected adverse reactions of D-penicillamine. 672 28

Since their initial description in 1957, the interferons (IFNs) have been increasingly used to treat a wide array of diseases. Acute adverse effects, i.e. 'flu-like' syndromes, hypo- or hypertension, tachycardia, headache, myalgias and gastrointestinal disorders, occur within the first hour or day after starting treatment. They are seldom treatment-limiting and are easily manageable. Sub-acute and chronic effects develop after several days, usually within 2 and 4 weeks of therapy. The most typical is neurological toxicity, including fatigue/asthenia, and behavioural and cognitive changes. Such symptoms may seriously impair quality of life and result in treatment discontinuation. Seizures have seldom been described. Other infrequent central nervous system adverse effects include vertigo, cramp and oculomotor nerve paralysis. Distal paraesthesias and peripheral neuropathy have been reported. IFN-associated autoimmunity is quite rare but a matter of concern. Biological or clinical manifestations usually require several months to become apparent. Autoantibodies have been shown to develop in most patients but have been inconsistently associated with clinical symptoms of systemic lupus erythematosus, rheumatoid-like arthritis and thyroiditis. Both hypo- and hyperthyroidism have been described but are usually reversible. Other infrequent autoimmune reactions include diabetes, pemphigus and worsening of multiple sclerosis. Although several patients present with a pre-existing autoimmune disorder, no predisposing factor has been clearly established. While hypotension and tachycardia are the most frequent acute cardiovascular complications, a few additional cases of cardiac arrhythmias and myocardial ischaemia have been reported after a short course or several weeks of treatment. These latter complications do not appear to be dose-dependent or age-related. Isolated cases of congestive heart failure have also been described. Mild proteinuria has been observed in 15 to 25% of patients, but acute renal toxicity is uncommon. A transient rise in serum aminotransferase levels is frequently noted during the first stage of therapy, especially in patients receiving the highest dosages. Direct hepatotoxicity is extremely rare. Autoimmune hepatitis, which is ill-diagnosed as chronic viral hepatitis, and de novo induction of autoimmune hepatitis, account for the majority of liver diseases. Haematotoxicity is relatively common but mild to moderate, and develops gradually during the first weeks of treatment. Neutropenia is the most common haematological toxicity, but is usually not dose-limiting and resolves rapidly upon drug discontinuation. Myelosuppression, autoimmune and immune allergic haemolytic anaemias and thrombocytopenias have seldom been described. Cutaneous adverse effects comprised nonspecific erythema and hair loss and, less frequently, vasculitis, local ulcerations at the site of injection and exacerbation of psoriasis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Clinical toxicity of the interferons. 751 63


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