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Abstract: Parenteral gold has historically been used to treat several conditions, including rheumatoid arthritis. Gold administration leads to a variety of cutaneous reactions, including chrysiasis, which is a permanent blue-grey hyperpigmentation of the skin due to dermal gold deposition. In this report, we describe the case of a patient who received parenteral gold injections 22 years before the onset of her chrysiasis for the treatment of rheumatoid arthritis. Biopsy of the macules showed dermal gold deposits aggregating around a melanocytic nevus, as well as around preexisting osteoma cutis. To the authors' knowledge, this is the first report in the literature describing a case of chrysiasis with gold deposits concentrated around a melanocytic nevus and an area of osteoma cutis., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Localized chrysiasis is rare and can occur in two settings: after localized or traumatic implantation of elemental gold or gold salts or after localized laser or light therapy in someone who has been previously exposed to systemic gold therapy. We report a unique case of localized chrysiasis with associated aluminum salt deposition and sclerosing lipogranulomas because of previous injections of aurothioglucose (Solganal®). The unique histopathologic findings seen in this case have not been previously reported., (Published 2015. This article is a U.S. Government work and is in the public domain in the USA.)

Objective: For reasons of insufficient quality of the raw material, aurothioglucose was withdrawn from the Dutch market at the end of 2001. Aurothiomalate became available as an alternative preparation. We followed a cohort of patients during the first year after switching from aurothioglucose to aurothiomalate to study efficacy and tolerability., Methods: Patients were observed at baseline and at 3 and 12 months after switching. At each visit, data on adverse drug reactions (ADR), withdrawal, and disease activity were collected., Results: In total 120 patients were included [age 63(SD 15) yrs, 68% female, 93% with rheumatoid arthritis, duration of disease 15 (SD 9) years, 82% IgM rheumatoid factor-positive, with 9 (SD 9, range 0.1-45) yrs of previous aurothioglucose therapy]. Nineteen patients (16%) reported an ADR taking aurothiomalate not previously experienced with aurothioglucose, the most frequently reported being pruritus, dermatitis/stomatitis, and chrysiasis/hyperpigmentation. Twenty-nine patients (24%) withdrew from aurothiomalate within 12 months of followup for reasons of inefficacy (14%), ADR (7%), or disease in state of remission (3%). Kaplan-Meier estimates show aurothiomalate survival rates of 78.5% after 12 months. No statistically significant differences between the disease activity indicators during followup visits compared with the baseline visit were detected for the patients continuing aurothiomalate., Conclusion: Within the first 12 months after switching from aurothioglucose, 24% of patients withdrew from aurothiomalate. Sixteen percent of patients reported novel ADR. For the population continuing to take aurothiomalate no clinically relevant changes in disease activity were recorded after switching.

Thrombocytopenia is a well-known side effect following intramuscular gold therapy in patients with rheumatoid arthritis. Thrombocytopenia may occur at any time and it can be irreversible and sometimes fatal despite cytotoxic or immunosuppressive therapy. We describe two patients who presented with haemorrhagic diathesis on the day after the administration of aurothioglucose. The thrombocytopenia in these patients was caused by aurothioglucose-induced antibody-mediated platelet destruction. Both patients made an uneventful recovery and the platelet count returned to normal within several weeks without further treatment. Antibody-detecting tests were repeated five years later and could not demonstrate the presence of antibodies. Also after incubation with aurothioglucose no antibodies could be demonstrated.

We describe the case of a 78-year old woman, with rheumatoid arthritis, 3 years of regular parenteral gold administration and Chrysiasis. Chrysiasis is a rare permanent pigmentation of the skin resulting from the parenteral administration of gold. The cause of the pigmentation is multifactorial and not fully established at the moment.

We describe the case of a 78-year old woman, with rheumatoid arthritis, 3 years of regular parenteral gold administration and Chrysiasis. Chrysiasis is a rare permanent pigmentation of the skin resulting from the parenteral administration of gold. The cause of the pigmentation is multifactorial and not fully established at the moment.

Objective: We assessed nitritoid reactions, which are a well recognized side effect of chrysotherapy that occur in roughly 5% of patients taking gold sodium thiomalate (GST)., Methods: Between January 1996 and January 2000, 8 patients followed in our gold monitoring program at Mary Pack Arthritis Centre experienced nitritoid reactions observed by the clinic nurse. We undertook a chart review to determine the risk factors, timing, course, and outcome of nitritoid reactions., Results: Patients' ages ranged from 36 to 69 years, and 7 of 8 were women. Duration of gold therapy prior to nitritoid reactions ranged from 13 months to 13 years. Seven had previously had mucocutaneous reactions, and one experienced gold dermatitis following a nitritoid reaction. Two of 8 patients were taking angiotensin converting enzyme inhibitor agents. Seven reactions were classified as mild, and one was a severe reaction with hypotension, syncope, and angina., Conclusions: Management includes a high index of suspicion in patients experiencing nausea, flushing, or dizziness following gold injections, switching from GST to gold sodium aurothioglucose, injection in the recumbent position, and observation for 20 minutes after injections in individual patients.

The purpose of our study was to investigate the significance of the presence of anti-Ro antibodies found by us in an earlier study of rheumatoid arthritis (RA) patients with gold-induced side effects. Sera of 29 anti-Ro (SSA) positive RA patients who had gold-induced side effects were studied. All sera were examined by Western blot using recombinant antigens, encoding the Ro 60 kD and the La proteins. HLA typing was done in all patients. Thirteen patients reacted only with the Ro 52 kD antigen and all had severe skin eruptions caused by gold therapy. Another ten patients who reacted only with the Ro 60 kD antigen had other side effects to gold (six had proteinuria and four leucopenia). Six patients who reacted to all three antigens (Ro 52 kD, Ro 60 kD and La) had secondary Sjögren's syndrome. No significant statistical differences were noted in the incidence of HLA-DR3 between the subgroups of patients. Our data indicated that antibodies to the Ro 52 kD antigen are associated with skin eruptions in RA patients treated with gold.

We report a case of gold pulmonary toxicity in a patient with adult-onset Still's disease with dyspnea on exertion and a normal chest radiograph. Withdrawal of gold therapy resulted in complete resolution of pulmonary toxicity in our patient without the need for additional steroid therapy.

Gold inhibits the Type I deiodinase that provides the bulk of circulating T3 in humans. We prospectively studied thyroid function in patients receiving increasing parenteral cumulative gold doses. Eight consecutive euthyroid patients with rheumatoid or psoriatic arthritis who were initiating intramuscular gold therapy were enrolled. Serum thyroid hormone levels (total T4, T3, and rT3) and TSH were measured for each subject at various levels during gold therapy. For analysis, the free T4 and free T3 indices, TSH concentrations, and T4/T3 ratios were correlated with cumulative gold dose. Neither individual nor pooled linear regressions showed a significant correlation between cumulative gold dose and any of the thyroid function parameters. Thyroid function is not affected in patients receiving up to 1500 mg of gold compounds. The most likely explanation for this is that gold principally accumulates in the Kupffer cells and renal cortex and these cells do not express Type I deiodinase.

Objective: To describe causality, morphology, course, and risk factors of mucocutaneous reactions to gold., Methods: A prospective study of 74 patients with rheumatoid arthritis starting with gold thioglucose., Results: Thirty-nine patients experienced an episode of gold dermatitis. Sixteen patients continued gold treatment. The estimated treatment withdrawal at 1 year was 26%. The clinical picture was variable and nonspecific. Gold dermatitis was associated with HLA-B35 and disease duration., Conclusion: Mucocutaneous reactions to gold are nonspecific, therefore a causality assessment is necessary. Incidence is high, but treatment can often be continued with dose reduction and local steroids. The predictive value of risk factors is low.

We report about the case of a 74-year-old woman who suffered diffuse alveolar damage and consecutive lethal pulmonary failure after gold therapy for rheumatoid arthritis. This is the fourth documented case of fatal pulmonary failure following gold therapy. The clinical findings were dominated by severe dyspnoea that warranted respirator therapy shortly after admission. Chest radiographs showed progressing confluent perihilar patchy infiltrates that suggested interstitial involvement. Steroid therapy had only a short-lasting effect on the respiratory failure, the patient died in prolonged hypoxic circulatory failure. Post-mortem examination showed the organotypical findings of diffuse alveolar damage in proliferative stage with advanced pulmonary fibrosis. With the discontinuation of gold medication and early steroid therapy, this disease which is based on immunological pathomechanisms is usually reversible. Both the knowledge of this entity and early diagnosis are essential for a promising therapeutic intervention.

In a 56-year-old woman with granulomas of gold thioglucose in her hips, who developed insulin autoimmune syndrome, the relationships among the frequency or severity of hypoglycemic attacks, serum insulin (IRI) concentration, and characteristics of insulin antibodies were investigated during the clinical course with steroid treatment and two resection operations for the gold-thioglucose granulomas. When hypoglycemia was severe, the total IRI level was elevated, and Scatchard analysis showed that a high-affinity (k1), low-capacity (b1) population of antibodies had a relatively low affinity constant and very high binding capacity compared with the same population of antibodies in insulin-treated diabetic patients. When the attacks were relieved by steroid treatment and/or granuloma resection operation, the total IRI level was decreased and the high-affinity (k1), low-capacity (b1) population of antibodies showed a higher affinity constant and a lower binding capacity than those during the attacks. This indicated that the antibodies changed their characteristics to release insulin into the serum. The k1/b1 population of insulin antibodies with the lower affinity constant and higher binding capacity may easily release human insulin into the serum, leading to hypoglycemia. The longitudinal change of the k1/b1 population suggests a clonal change of the B cells producing the insulin antibody in insulin autoimmune syndrome.

Adverse immune reactions develop in up to 30% of patients treated with gold compounds. However, sensitization to gold(I) drugs is rarely demonstrated by in vivo or in vitro testing. Recent data from a mouse model provides evidence that gold(I) is oxidized to gold(III) before T cells are sensitized. To study the diagnostic value of skin tests, patch testing with various gold compounds - including gold(I) and gold(III) - was performed in 50 patients with rheumatoid arthritis treated with gold(I) drugs. Positive patch test reactions to either gold(I) or gold(III) compounds were not detected. In contrast, the lymphocyte transformation test (LTT) revealed a gold(III)-induced response in one of the 7 patients being tested. We conclude that patch testing fails to indicate T cell sensitization to gold(I) drugs in rheumatoid arthritis patients. The in vitro response to gold(III) obtained by LTT supports the hypothesis that biooxidation of gold(I) compounds may play a crucial role for sensitization.

A case of severe colitis requiring subtotal colectomy following administration of 35 mg Solganal b for intractable arthritis is described. Abdominal pain and watery diarrhea developed six weeks after the last dose of gold. Colonoscopy revealed mucosal edema and ulceration of the entire colon. Supportive measures failed and the patient required subtotal colectomy. Review of the literature revealed 29 cases, ranging in severity from limited ileal involvement to fulminant panenteritis. Most of the patients responded to intravenous fluids, steroids, and antibiotics, but four required surgery. The case described is notable for the delay in appearance of abdominal symptoms following the cessation of gold therapy. The mechanism of injury is unknown. Abdominal complaints in a patient who has received gold therapy, especially parenteral, merit strict attention, even if occurring several weeks after the final dose, and the diagnosis of gold colitis should be entertained.

A case of gold salt-induced oral lichen planus is reported. The oral lesions were successfully managed with a topical corticosteroid rinse. Gold salts, oral symptoms, and the use of the systemic inducing agent/immunosuppressant in combination with a topical corticosteroid are reviewed.

Lichenoid eruptions appearing in two women receiving chrysotherapy (Solganal B oleosum R) a described. The morphological diagnosis, distribution of skin eruptions, histological and immunological features and monoclonal antibodies (Leu 4, Leu 2A and Leu 3A) against several cell surface markers were studied. Individual lesions were not distinguishable from idiopathic lichen planus, with some features typical for gold lichenoid eruptions: hyperpigmentation, psoriasiform eruptions, and hair loss. Histopathological and immunological examination of biopsy specimens with monoclonal antibodies generally confirms clinical impressions. The authors suggest similar pathogenetic mechanisms in the development of idiopathic lichen planus and of lichenoid eruptions after gold therapy.

The long-term use of second-line antirheumatic drugs was prospectively studied in a consecutive sample of 245 patients with recently diagnosed rheumatoid arthritis. A survival analysis was done in which treatment termination due to side-effects and to insufficient therapeutic effect were used as index causes. Cumulative drug 'survival' of aurothioglucose with treatment termination due to toxicity was significantly less compared with hydroxychloroquine. With regard to lack of efficacy as index cause, the administration time of hydroxychloroquine was significantly less than that of either aurothioglucose or sulphasalazine. Treatment termination due to lack of efficacy or combined insufficient therapeutic response and toxicity proved to be influenced by the initial disease activity and by the rank order of prescription.

A 56-year-old woman with granulomas of gold thioglucose in her hips exhibited recurrent bouts of hypoglycemic attacks. The first attack occurred 2 years after the last injection of gold thioglucose, when large amounts of extractable insulin and human insulin-specific antibody were noted in her serum. Histological examination of the resected granulomas showed marked infiltration of lymphocytes, plasma cells, and macrophages containing yellowish-brown granules, which proved to be gold by electron microscopy using X-ray microanalysis. After resection of the granuloma, however, the frequency of the hypoglycemic attacks decreased remarkably as well as the levels of both extractable insulin and human insulin-specific antibody.

Benefits and risks of gold therapy in patients with juvenile chronic arthritis (JCA) were reviewed. An improvement of laboratory and clinical parameters was observed in eight out of the 16 children of the sample (10 boys and 6 girls). The side effects were noticed in 5 patients, but only in one of these children gold therapy had to be stopped due to alopecia areata. Corticosteroid dose was significantly reduced in 7 out of the 11 patients. It is concluded that gold salts may be effectively applied as primary therapy in children with JCA, with no more risk than in adults.

Secondary antibody deficiency is one of the rare adverse effects of chrysotherapy in rheumatoid arthritis. The plasma levels of all immunoglobulins fall into ranges significantly lower than the tolerable physiological minimum. The long-lasting panhypogammaglobulinemia can increase the risk of infection in the patient and, therefore, should be closely monitored. Hence, a record of immunoglobulin levels before and during therapy with gold compounds seems to be mandatory.

A 56 year old woman with rheumatoid arthritis developed relapsing thrombocytopenia during successive treatments with aurothioglucose, sulphasalazine, and hydroxychloroquine. The presence of IgM or IgG antibodies or immune complexes reactive with autologous platelets could not be shown. Relapsing thrombocytopenia may indicate a genetically determined HLA-DR3 and B8 aberrant immunological response to stimuli such as certain second line drugs.

Auranofin (triethylphosphine gold) was administered to 21 patients with juvenile rheumatoid arthritis during an open-ended, open-label, noncontrolled trial designed to establish safety and preliminary efficacy. Initial dosage was 0.1 mg/kg/day; incremental increases to 0.2 mg/kg/day were allowed. Aspirin (80 mg/kg/day), tolmetin (20 to 40 mg/kg/day), and naproxen (400 to 600 mg/m2/day) were allowed as rapidly acting anti-inflammatory agents. All patients attained measurable plasma concentrations of gold during the study. Clinically significant improvement (greater than 25%) occurred in more than half the patients with regard to the number and severity of joints with swelling, pain on motion, and tenderness. The number of joints with active arthritis decreased by at least 25% in nine of the 19 patients. Group mean changes between the initial and final visit indicated improvement in all articular disease indices measured. Eleven of 16 patients with an elevated erythrocyte sedimentation rate showed decreases of at least 25%. The group given the higher dosage had a greater proportion of responders with decreases in erythrocyte sedimentation rate. Four of six patients whose sera contained rheumatoid factor showed decreases in its titer. Discontinuation of auranofin was necessary in two patients because of headaches and because of hematuria and anemia associated with a severe flare of polyarticular disease, respectively. The results from this trial are sufficiently encouraging to merit a double-blind trial of auranofin in children with juvenile rheumatoid arthritis.

Seventy-four Israeli patients with rheumatoid arthritis (RA) were studied for possible association between HLA antigens and adverse reactions to gold treatment (aurothioglucose). HLA-B35 was significantly increased in patients who developed gold induced mucocutaneous lesions. These results are in accord with earlier reports, despite the different genetic background of the Israeli RA population and the different type of gold compound used.

One hundred and twelve patients with classical or definite rheumatoid arthritis (RA) were randomly assigned to receive either sodium aurothiomalate (GSTM) or auranofin (AF). Monthly clinical assessments (morning stiffness, grip strength, articular index, pain, quality of life) and concurrent hematological, biochemical, and urine studies were performed to monitor the efficacy/toxicity (E/T) ratio. Ninety-two patients have completed 3 months; 65, 6 months; 47, 9 months; and 30, 12 months. The groups were numerically balanced at each time period. Analysis of the 0-6 month period suggests that both drugs were equally and significantly beneficial after 3 months and that this was maintained at 6 months. Toxicity was as frequent in both groups but more serious in the GSTM group. The main side effects were gastrointestinal (diarrhea) in the AF group and mucocutaneous in the GSTM group. Half of the withdrawals (14 in each group) were because of side effects in the GSTM group and for inadequate therapeutic efficacy in the AF group. This study suggests that after 6 months of treatment the E/T ratio of AF is greater than or equal to that of GSTM. These conclusions will need to be confirmed during the ongoing longer observation period. A significant clinical difference between the 2 drugs is that in a given patient treated with GSTM, the onset of toxicity coincides with a good therapeutic effect. This relationship does not appear to exist during AF treatment.

The data from 310 patients treated with gold were analysed. The occurrence of side effects is lower than the average data in the literature: with "Solganal" 21.5%, with "Tauredon" 21%. The clinical importance of the differentiation of toxic and allergic side effects is pointed out. It seems possible to differentiate between the toxic-allergic and the dosage dependent, actually toxic side effects. In cases of toxicity caused by retarded metabolisation the use of the barbiturate enzyme induction made it possible to continue treatment.

A 70-year-old female with seronegative rheumatoid arthritis developed interstitial pneumonitis while on chrysotherapy. The reversibility of lung disease and favourable response to steroid treatment support the diagnosis of gold-induced lung disease and distinguish this entity from other forms of interstitial lung disease associated with rheumatoid arthritis. The relevant literature related to gold-induced lung disease is briefly reviewed.

We compared auranofin (AF) in a single blind multi-centre study with gold sodium thiomalate and D-penicillamine in the treatment of rheumatoid arthritis. Adult patients with disease duration 6-60 months without previous treatment with gold salts with persistent active disease, were included. Thirty-nine patients, 13 in each treatment group, have so far been entered. Cumulative toxicity data and some results of efficacy assessments in those completing 9 months of treatment are presented. AF is very well tolerated, judgment concerning efficacy must await the end of the trial.

In view of encouraging results from various reliable multicenter studies, an interesting new oral agent, auranofin (triethylphosphine gold), is believed to be a major advance towards more effective treatment of rheumatoid arthritis with mild adverse reactions. The present study evaluates the long-term efficacy of auranofin in 46 patients with active rheumatoid arthritis and attempts to delineate further the results of drug monitoring concerning adverse reactions. Six patients withdrew due to untoward and partially serious events, e.g. thrombocytopenia, colitis or pancreatic disease. In view of the high frequency of side effects which required immediate withdrawal of auranofin in 13%, with a total of 37% of patients experiencing adverse reactions, it should be kept in mind that oral gold therapy may be a two-edged sword and requires further critical drug monitoring.

Two hundred eight patients were studied in a prospective, controlled, double-blind multicenter trial comparing auranofin (AUR), gold sodium thiomalate (GST), and placebo. One hundred sixty-one patients completed at least 20 weeks of therapy. Response to a variety of measures of efficacy was generally modest for both gold treatment groups although improvement was continuing in both groups at the end of the study. There was statistically significant improvement with both gold preparations compared to placebo for the number of tender joints, the joint tenderness score, and physician assessment of disease severity. GST was also significantly better than placebo for the joint swelling score. GST demonstrated more improvement in patients with anemia and thrombocytosis compared to the other treatment groups and both gold preparations were superior to placebo in improvement of an elevated erythrocyte sedimentation rate. Twenty-seven percent of patients on GST were withdrawn from the study for adverse drug reaction with rash and stomatitis being the predominant cause. Only 6% of patients on AUR were withdrawn for untoward drug effect. The time of onset of the adverse reactions is discussed. The two gold preparations were similar in efficacy although AUR was better tolerated.

A 63-year-old woman with seropositive rheumatoid arthritis was successfully treated with auranofin for 12 months. Heavy proteinuria then developed and the drug was stopped. However, the proteinuria apparently became worse. This was later recognised to be a spurious effect due to the introduction of tolmetin. Renal biopsy showed a type I membranous glomerulonephropathy.

Auranofin [S-triethylphosphine gold-2,3,4,6 tetra-O-acetyl-l-thio-beta-D-glucopyranoside) SK&F 39162) has been administered at 0.1-0.25 mg/kg/day as the sole remission-inducing drug to 46 children affected with juvenile chronic arthritis (JCA). There were 22 males and 24 females; 12 children were affected with pauciarticular onset JCA, 26 with polyarticular onset JCA and 8 with systemic onset JCA. Three sets of efficacy criteria were evaluated quarterly: eight clinical, (Ritchie Index, number of affected, swollen and limited joints, number of joint with increased temperature, morning stiffness, Steinbrocker functional class, physician's disease evaluation), three hematochemical and one therapeutical. In most patients a panel of immunological parameters was routinely performed inclusive of peripheral blood lymphocyte subsets, serum immunoglobulins and C3c-C4 complement components. Patients who showed a definite improvement of at least two out of the three orders of efficacy criteria were classified as responders to auranofin. Out of the 35 patients evaluable after at least six months of treatment there were 24 (68%) responders. Nonresponders had a basal higher level of serum IgA and a basal lower level of serum C4. Both responders and nonresponders presented a reduction of the T4/T8 ratio during auranofin treatment, while only in responders did the basal high levels of IgG and C3c show a definite decrease.

The prevalence of eosinophilia in 82 rheumatoid arthritis patients receiving gold sodium thiomalate (GSTM) and 30 patients receiving auranofin (AF) was determined in a retrospective study. Eosinophilia occurred in 21% taking GSTM and in 13% on AF. The simultaneous occurrence of toxicity and eosinophilia occurred in 14% receiving GSTM and in 10% receiving AF. In contrast, eosinophilia only occurred in 24% of those with suspected toxicity receiving GSTM and in 30% of those with suspected toxicity receiving AF. The value of eosinophilia as a marker of toxicity is discussed.

HLA phenotype frequencies were studied in 21 rheumatoid arthritis (RA) patients with haematotoxic reactions to aurothioglucose (AuTG) or D-penicillamine (DP), 65 matched RA controls and 277 healthy controls. Antigens B8 and DR3 were significantly increased in the toxic RA patient group as compared to both RA controls and healthy controls. These contrasts were strongest in the patients with AuTG-induced thrombocytopenia or leucopenia: all patients developing either reaction to this drug were B8- and/or DR3-positive (p less than 0.001), 7 (78%) being positive for both antigens. In the patient group with DP-induced reactions these antigens were also increased but these differences were not significant. In the latter group the prevalence of antigen DR4 was high, especially in the patient group with DP-induced thrombocytopenia, all 12 patients with this type of reaction being DR4 positive. Our data suggest that haematotoxic reactions to AuTG and DP develop primarily (or even exclusively) in genetically predisposed RA patients. Furthermore, the HLA phenotype contributing to an increased risk seems not to be the same for the two anti-rheumatic drugs studied.

Despite a progressively more favorable prognosis in systemic lupus erythematosus (SLE) a need remains for therapeutic agents with greater benefit and less toxicity than corticosteroids and immunosuppressive drugs. Therefore, we treated 16 patients with SLE but without renal diseases with auranofin, a drug with proved efficacy and safety in rheumatoid arthritis. A modest diminution in overall disease activity, as judged by the investigators, and a reduction in maintenance corticosteroid dosage was achieved. However, neither laboratory assessments nor more objective clinical measurements of SLE disease activity disclosed any improvement over baseline. One case each of proteinuria and thrombocytopenia was observed, most likely related to underlying disease and not the drug, suggesting that auranofin may be safe in patients with SLE. A controlled trial, utilizing a broader spectrum of patients with SLE, may be warranted.

A patient suffered chronic interstitial nephritis after receiving large quantities of gold salts for rheumatoid arthritis. Gold deposits were seen with transmission electron microscopy and confirmed by microprobe x-ray analysis both within renal tubular epithelial cells and interstitial macrophages and free within the renal interstitium. Clinical resolution of renal failure followed discontinuation of therapy with gold salts. Probable mechanisms of injury to renal tubular epithelial cells include uptake of gold by tubular epithelial cells and incorporation of gold into mitochondria, with subsequent cellular injury; interstitial deposits probably occur after necrosis of tubular epithelial cells, with release of gold into the interstitium and resultant inflammation. Thus, chronic interstitial nephritis can be added to the patterns of renal injury seen after gold therapy for rheumatoid arthritis.