Chrysiasis: Gold Aggregates Around a Nevus and Osteoma Cutis.

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.

Localized chrysiasis, aluminum salt deposition and dystrophic calcification a decade after gold injections.

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.

Parenteral gold preparations. Efficacy and safety of therapy after switching from aurothioglucose to aurothiomalate.

OBJECTIVE: For reasons of insufficient quality of the raw material, aurothioglucose was withdrawn from the Dutch market at the end of 2001.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.

Two patients with acute thrombocytopenia following gold administration and five-year follow-up.

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.

[Chrysiasis]. / Chrysiasis.

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.

Nitritoid reactions: case reports, review, and recommendations for management.

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.

[Chrysiasis]. / Chrysiasis.

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.

Anti-Ro (SSA) antibodies in rheumatoid arthritis patients with gold-induced side effects.

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.

Gold pulmonary toxicity in a patient with a normal chest radiograph.

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.

Prospective studies of thyroid function in patients receiving gold 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.

Mucocutaneous reactions to gold: a prospective study of 74 patients with rheumatoid arthritis.

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.

[Fatal diffuse alveolar damage after gold medication]. / Letaler diffuser Alveolarschaden nach Goldmedikation.

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.

Longitudinal changes of serum insulin concentration and insulin antibody features in persistent insulin autoimmune syndrome (Hirata's disease).

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.