HLA antigens and toxicity to gold and penicillamine in rheumatoid arthritis.
One hundred sixty-eight patients with rheumatoid arthritis treated with chloroquine (n = 87), gold salts (n = 133) and/or penicillamine (n = 77) were investigated for possible associations between HLA antigens and toxic reactions. Patients with 2 or more side effects to gold and/or penicillamine had a significantly increased frequency of antigens HLA-B8 and DR3 compared to patients with one or without adverse reactions. Proteinuria to gold or penicillamine was significantly associated with HLA-B8 (relative risk [RR] 4.2) and DR3 (RR 14.0) whereas nonnephrologic side effects to gold or penicillamine were associated with B7 and DR2 (RR 3.5 and 2.8). Patients with skin reactions to gold had a significantly greater frequency of HLA-B7. We found no correlation between chloroquine side effects and any HLA antigen. The results suggest a genetic predisposition to toxic reactions to gold or penicillamine based on an immunologic dysregulation.
D000328:Adult; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000235:genetics; D002738:Chloroquine / Q000009:adverse effects* / Q000627:therapeutic use; D005260:Female; D005787:Gene Frequency; D005819:Genetic Markers; D006052:Gold Sodium Thiomalate / Q000009:adverse effects* / Q000627:therapeutic use; D006680:HLA Antigens / Q000235:genetics*; D015793:HLA-B7 Antigen; D015795:HLA-B8 Antigen; D015803:HLA-DR3 Antigen; D015804:HLA-DR4 Antigen; D000949:Histocompatibility Antigens Class II / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D010396:Penicillamine / Q000009:adverse effects* / Q000627:therapeutic use; D012306:Risk
D005819:Genetic Markers; D006680:HLA Antigens; D015793:HLA-B7 Antigen; D015795:HLA-B8 Antigen; D015803:HLA-DR3 Antigen; D015804:HLA-DR4 Antigen; D000949:Histocompatibility Antigens Class II; D006052:Gold Sodium Thiomalate; D002738:Chloroquine; D010396:Penicillamine