gold salts are important disease modifying antirheumatic drugs in the treatment of rheumatoid arthritis ( ra ) . however , toxicities with injectable gold are common , occuring in about 3040% of patients with ra in the long - term use of gold salts . the most common side effect of gold salts is mucocutaneous reactions , such as dermatitis , mouth ulcers or pruritus , which account for 6080% of all gold - associated toxicities . hepatotoxicity and isolated neutropenia which were developed simultaneously after gold therapy is a rare complication . we report a patient with rheumatoid arthritis who developed an unusual combination of hepatotoxic reactions and neutropenia as side effects of injectable gold . a 62-year - old woman with a 9-year history of rheumatoid arthritis ( ra ) was admitted to our hospital due to swelling and pain of both knees for several months , despite receiving antirheumatic drugs . she had an allergy to barbiturates and diabetes mellitus for 3 years , managed with metformin . the temperature was 37c , the pulse was 70 /minute , the respiration was 17 /minute and the blood pressure was 140/90 mmhg . there were no significant changes in vital signs after gold injections . physical examination revealed swelling , heat and redness of the wrists and knees at the time of admission . screens of hematological and biochemical profiles , including liver function , revealed normal except normocytic normochromic anemia ( hemoglobin concentration 9.5 mg / dl ) , thrombocytosis ( 566,000 /mm ) and elevated alkaline phosphotase level ( 218 iu / l , reference value 30110 ) . the erythrocyte sedimentation rate was 57 mm / h by the wintrobe method , and rheumatoid factor estimation by nephelometric method revealed 88 iu / ml ( reference value < 20 ) . the c - reactive protein was 10.6 mg / dl ( reference value < 0.8 ) . x - ray examination of the hands revealed erosions and partial bony fusions involving both wrists . radiographs of the knees showed effusion , erosions , periarticular osteoporosis , narrowing of the joint spaces and osteophytes at the articular margins . she had been managed with sulfasalazine ( 1 g / day ) , bucillamine ( 200 mg / day ) , piroxicam ( 20 mg / day ) , triamcinolone ( 2 mg / day ) in stable dosages and intermittent intra - articular corticosteroid injections . it was decided to commence treatment with gold injection and she was tested with 12.5 mg of intramuscular sodium aurothiomalate and administered 25 mg of gold on the next day inadvertently . after that , aurothiomalate was given twice at a weekly dose of 50 mg ( total cumulative dose 137.5 mg ) . although her arthritic symptoms had improved a little bit , she complained of malaise , dyspepsia , nausea and transient pruritus . after injection of the last dose , transient palmar erythema was noticed on both palms . all symptoms and signs disappeared 3 days after each gold injection . laboratory examinations after the last gold injection showed a leukocyte count of 2,200 /mm ( differentiation : 79% neutrophils , 18% lymphocytes , 2% monocytes , 0% eosinophils , 1% basophils ) , normochromic anemia ( hemoglobin concentration 9.4 mg / dl , mean corpuscular volume 88 fl ) and normal platelet count ( 376,000 /mm ) . additional laboratory examinations yielded no evidence of hepatitis a , b or c , cytomegalovirus or epstein - barr virus infection . antinuclear antibodies and liver disease specific antibodies such as anti - mitochondrial , anti - smooth muscle and anti - liver - kidney microsomal 1 ( lkm1 ) antibodies were negative . serum immunoglobulin levels were the following : immunoglobulin g ( igg ) 1260 mg / dl ( reference value 7511560 ) , iga 231 mg / dl ( reference value 82453 ) , igm 112 ( reference value 46304 ) , igd 11 iu / ml ( reference value < 100 ) and ige 3.4 iu / ml ( reference value 0200 ) . therapy consisted of discontinuation of potentially hepatotoxic drugs ( aurothiomalate , sulfasalazine , bucillamine , piroxicam , metformin ) and a treatment with prednisone 7.5 mg / day . approximately six weeks after cessation of gold injection , liver function tests became normalized except for alkaline phosphotase level , and then sulfasalazine , bucillamine , piroxicam , triamcinolone and metformin were resumed . in addition , neutropenia was recovered to 6,900 /mm at 5 weeks after cessation of gold injections ( figure 2 ) . she has had an uneventful recovery and her arthritis of the knees was treated by total knee replacement . forestier in 1929 pioneered the use of gold for the treatment of ra , assuming that both conditions might have a common infectious cause . the benefit of gold treatment in ra has been well documented over the past years . however , less than 50% of patients treated with parenteral gold remain on gold after 5 years , with approximately 60% of terminations of treatment attributable to toxicity . adverse reactions develop in about one third of patients with ra treated with injectable gold . most complications are trivial , consisting primarily of localized dermatitis , stomatitis , transient hematuria , and mild proteinuria . more serious adverse reactions include the hematopoietic system , kidneys , liver or other vital organs . a systematic search of the english literature for the last 30 years yielded less than 30 documented cases of gold related hepatotoxicity . in most patients , the hepatic damage appeared during the early stages of gold therapy and after relatively small total doses . most cases showed cholestasis with jaundice , pruritus , rash , fever and abdominal complaints . summarized 24 well - documented cases of gold salt related hepatotoxicity in the english literature for the last 30 years . they consisted of 11 patients with cholestasis , 2 patients with hepatitis , 3 patients with necrosis , 1 patient with pericholangitis and 1 patient with cholestasis and necrosis together . the patient with a fatal outcome died of pulmonary insufficiency due to bronchopneumonia and fibrosing alveolitis . the first is an idiosyncratic side effect that is not dose - related and occurs even after small doses of gold . the second mechanism is a direct toxicity due to gold accumulation in the lysosomes of hepatic macrophage . this mechanism is dose related and occurs late in the course of therapy , without biochemical or structural evidence of cholestasis . the relevance of this finding is , however , unclear since uncomplicated gold therapy also results in gold accumulation in many organs , especially in cells of the reticuloendothelial system in the liver and kidney in previous reports , therapy for gold - induced hepatotoxicity has always consisted of discontinuation of the drug . sometimes corticosteroids , including our own , were started either to minimize liver damage or to control ra activity . other rare complications of gold are hematologic complications that include eosinophilia , leukopenia or agranulocytosis , thrombocytopenia , anemia , pancytopenia , and aplastic anemia . the most feared complication is severe pancytopenia or bone marrow aplasia with reported mortality of 6180% . in the past , the mortality rate was very high , but prognosis has been improved by aggressive therapy , including bone marrow transplantation , antithymocyte globulin or granulocyte colony - stimulating factor . the prevalence of leukopenia is low , and the extent and duration of white cell reductions are variable . they were divided into 3 groups according to commonly used clinical criteria : 3 patients developed felty s syndrome , 8 gold myelotoxicity and 14 mild , chronic benign granulocytopenia . the mechanisms involved in gold induced marrow suppression are unclear but include a direct toxic effect and an immune etiology . to our knowledge , there is only one previous case report that demonstrated hepatitis and neutropenia simultaneously secondary to gold thiomalate therapy for rheumatoid arthritis . in our case , hepatitis without jaundice and neutropenia after gold injection developed concurrently in the early phase of gold injections . although most hepatic injury after gold injections is associated with cholestatsis , there was no jaundice but hepatitis was dominant in our case . liver biopsy and bone marrow biopsy were not done because clinical symptoms and serologic signs were mild and showed improvement with time . the isolated neutropenia in our case was abrupt onset and occurred in the early times of gold injections , and also showed rapid recovery . so it was possible that in our patient , gold might act as a mild bone marrow depressant . we had prescribed piroxicam , bucillamine , sulfasalazine and metformin for about 3 years , but they were less likely to cause any hepatic problems and isolated neutropenia , as those drugs were continued throughtout the patient s illness . in conclusion , hepatotoxicity and isolated neutropenia on gold therapy are very rare but well - documented side effects . close observation for these complications should be considered , especially in the early phase of gold injections .
gold salts have been used for many years in the treatment of rheumatoid arthritis . 
 the common side effects are mucocutaneous reactions , but hepatotoxic reaction and isolated neutropenia are rare complications . 
 we report a 62-year - old woman with rheumatoid arthritis who had developed hepatitis and neutropenia simultaneously after receiving 137.5 mg of sodium aurothiomalate .