Glomerulonephritis penicillamine

Penicillamine onset may be seen in 1 to 3 months, and most responses occur within 6 months. Early adverse effects include skin rash, metallic taste, hypogeusia, stomatitis, anorexia, nausea, vomiting, and dyspepsia. Glomerulonephritis may occur, which manifests as proteinuria and hematuria. Penicillamine is usually reserved for patients who are resistant to other therapies because of the rare but potentially serious induction of autoimmune diseases (e.g., Goodpasture s syndrome, myasthenia gravis). 

Brown Norway rat HgCl2 AU-salts D-Penicillamine Nevirapine HCB IC-glomerulonephritis Skin pathology, dermatitis Polyclonal IgE AutoAb (Type IV-collagen, ANA, 1 anti-ACh, thyroglobulin) Systemic inflamatory response with autoimmune symptoms... 

Nitrofurantion D-Penicillamine Peripheral neuritis Autoimmunity drug-induced SLE, myasthenia gravis, pemphigus, glomerulonephritis, Goodpasture s disease... 

Although rare, cases of renal lupus syndrome and pemphigus blisters have also been reported as a consequence of D-penicillamine-induced immune complexes (Ntoso et al., 1986 Bigazzi, 1988), as well as with other drugs. With renal lupus syndrome, secondary glomerulonephritis may result if granular IgG antibodies are produced and deposited on the basement membranes. In patients with pemphigus blisters, autoantibodies to the intercellular substance of the skin have been recovered from the sera, and dermal biopsies have demonstrated intracellular deposits or... 

Ntoso, K.A., Tomaszewski, J.E., Jimenez, S.A. and Neilson, E.G. (1986). Penicillamine-induced rapidly progressive glomerulonephritis in patients with progressive systemic sclerosis successful treatment of two patients and a review of the literature. Amer. J. Kidney Dis. 8 159-163. 

Penicillamine-induced lupus-like syndrome can be associated with proliferating glomerulonephritis with mesangial involvement and interstitial infiltrates (213,219). In such cases antibodies to native DNA can be found. 

In rare cases penicillamine can cause extracapillary glomerulonephritis with more extensive and serious glomerular injury leading to progressive and persistent renal insufficiency. One such patient has been described with a review of 26 similar published cases (233). 

Three case reports from Belgium and France have illustrated the fact that rarely proliferative crescent-forming extracapillary glomerulonephritis and renal insufficiency can also occur (236,237). AH three patients had taken penicillamine for systemic sclerosis. Antimyeloperoxidase antineutrophil cjdoplasm antibodies were found in aU three one patient also had alveolar hemorrhage (that is Goodpasture s syndrome). 

A 56-year-old woman with systemic sclerosis taking penicillamine 750 mg/day had homogeneous antinuclear antibodies and antibodies to native DNA. Her manifestations of vasculitis were glomerulonephritis with renal insufficiency, pulmonary hemorrhage, and bilateral hemothorax (that is similar to Goodpasture s syndrome). 

In a 69-year-old man with penicillamine-induced crescentic glomerulonephritis ANCA tests were repeatedly negative (353). He had been taking penicillamine up to 750 mg/day for systemic sclerosis. 

DotmeUy S, Levison DA, Doyle DV. Systemic lupirs erythematosus-like syndrome with focal proliferative glomerulonephritis during D-penicillamine therapy. Br J Rheumatol 1993 32(3) 251-3. 

Almirall J, Alcorta I, Botey A, Revert L. Penicillamine-induced rapidly progressive glomerulonephritis in a patient with rheumatoid arthritis. Am J Nephrol 1993 13(4) 286-8. 

Karpinski J, Jothy S, Radoux V, Levy M, Baran D. D-penicillamine-induced crescentic glomerulonephritis and antimyeloperoxidase antibodies in a patient with scleroderma. Case report and review of the literature. Am J Nephrol 1997 17(6) 528-32. 

Macarron P, Garcia Diaz JE, Azofra JA, Martin de Francisco J, Gonzalez E, Fernandez G, Sampedro J. D-penicillamine therapy associated with rapidly progressive glomerulonephritis. Nephrol Dial Transplant 1992 7(2) 161-4. 

Bindi P, Gilson B, Aymard B, Noel LH, Wieslander J. Antiglomerular basement membrane glomerulonephritis following D-penicillamine-associated nephrotic syndrome. Nephrol Dial Transplant 1997 12(2) 325-7. 

Honkanen E, Tornroth T, Pettersson E, Skrifvars B. Membranous glomerulonephritis in rheumatoid arthritis not related to gold or D-penicillamine therapy a report of four cases and review of the literature. Clin Nephrol 1987 27(2) 87-93. 

Marchand-Courville S, Dhib M, Fillastre JP, Godin M. Glomerulonephrites extracapillaires secondaires a la D-penicillamine. A propos d une observation et revue de la litterature. [Extracapillary glomerulonephritis secondary to D-penicillamine. Apropos of 1 case and review of the literature.] Nephrologie 1998 19(l) 25-32. 

Marlier S, Gisserot O, Yao N, Hecht M, Paris JF, Carh P, Chagnon A. Glomerulonephrite extracapillaire lots d un traitement par D-peniciUamine. [Extra-capiUary glomerulonephritis induced by D-penicillamine therapy.] Presse Med 1999 28(13) 689-90. 

In usual doses, 600-800 mg/day, pyritinol has a profile of adverse reactions reminiscent of that of penicillamine (2,3). Some 40% of users have adverse reactions, leading to withdrawal in about 23% of the total. The most common are non-specific rashes and stomatitis in addition, pemphigus, lichen planus, and photosensitivity have occurred. Gastrointestinal symptoms (diarrhea, gastral-gia, nausea, loss of taste) can occur, but are less frequent than with penicillamine. Thrombocytopenia, reversible extramembranous glomerulonephritis with nephrotic syndrome (4), a myasthenia-like picture, and acute polymyositis with positive rechallenge have also been described (5). 

Some degree of renal damage occurs in about 10% of patients taking tiopronin (1-3,5,6). As with penicillamine, proteinuria can progress to nephrotic syndrome (13,14). Biopsy may show minimal change membranous glomerulonephritis and granular depositions of IgG and C3 (13,15). 

A drug-induced systemic lupus erythematosus (SEE) with proliferative glomerulonephritis has also been described in patients treated with D-penicillamine [111, 157]. Systemic lupus erythematosus syndrome is induced in approximately 2% of patients treated with D-penicillamine [112,158]. Unlike other forms of drug-induced systemic lupus erythematosus, anti-double-strand DNA anhbodies and/or hypocomplementemia are seen in D-penicillamine-induced systemic lupus erythematosus syndrome [111, 156]. Nephropathy is rare in D-penicillamine-induced systemic lupus erythematosus syndrome [111]. Walshe [112] reported that 8 patients developed the serological change of systemic lupus erythematosus of 120 patients with Wilson s disease treated with D-penicillamine, but none of them showed nephropathy. 

Devogelaer J-P, Pirson Y, Vandenbroucke J-M, Cosyns J-P, Brichard S, Deuxchaisnes CN. D-penicillamine induced crescentic glomerulonephritis Report and review of the literature. J Rheumatol 1987 14 1036-1041. 

Banfi G, Imbasciati E, Guerra L, Mihatsch MJ, Ponticelli C. Extracapillary glomerulonephritis with necrotizing vasculitis in D-penicillamine treated patients with rheumatoid arthritis. Nephron 1983 33 56-60. 

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