[Corneal chrysiasis. Gold salt deposits in the cornea in a patient with rheumatoid arthritis. An analysis with confocal microscopy]. / Crisiasis corneal. Depósitos corneales de sales de oro en paciente con artritis reumatoide. Análisis con microscopía confocal.

CASE REPORT: A 60-year-old woman with rheumatoid arthritis of 20 years onset, on treatment with monthly intramuscular gold salts (GS) for the last 7 years. She complained of suffering from halo vision, and the examination showed a visual acuity of 0.6 in both eyes (BE). The slit lamp showed some deposits in the stroma with scattered golden granulated, without any further inflammatory reaction. DISCUSSION: GS deposits are dose-dependent and reversible, although very slowly. In this article, we introduce, for the first time, evidence of deposits of GS in all layers of the cornea, predominantly in the corneal stroma and in the endothelium.

Clinically relevant patch test results in patients with burning mouth syndrome.

BACKGROUND: Patients with a sore or burning mouth associated with clinically normal oral mucosa present a difficult diagnostic challenge. OBJECTIVE: The objective of this study was to assess the value of patch testing in patients with burning mouth syndrome. METHODS: We retrospectively reviewed the results of patch testing to an oral series in patients with burning mouth syndrome seen at Mayo Clinic, Rochester, Minnesota, between January 2000 and April 2006. RESULTS: Of 195 consecutive patients with a burning or sore mouth, 75 had patch testing to an oral series, and 28 of these patients (37.3%) had allergic patch test reactions. The most common allergens were nickel sulfate hexahydrate 2.5%, balsam of Peru, and gold sodium thiosulfate 0.5%. On follow-up, 15 patients reported improvement, 4 removed or avoided the offending dental metal, and 6 avoided the dietary allergen. Thirteen patients did not improve; 6 avoided identified allergens, but without improvement; 1 removed dental metals without symptom change; and 5 avoided test-positive dietary allergens but without improvement. The remaining 7 nonresponders had nonrelevant patch test results or did not avoid allergens. CONCLUSIONS: Patch testing can identify patients who may be allergic to dental metals or dietary additives and who may benefit from removal or avoidance of these.

Effects of aurothiomalate and gold(III) complexes on spontaneous motility of isolated human oviduct.

Organic gold complexes have different biological activity, depending on their potential for interactions with key functional molecules.The aim of this study was to investigate potential of several newly synthesized organic gold complexes to influence spontaneous motility of the Fallopian tubes.The effects of [Au(bipy)Cl(2)](+) (dichloride(2,2'-bipyridyl)aurate(III)-ion), aurothiomalate, [Au(DMSO)(2)Cl(2)]Cl and DMSO on spontaneous motility of Fallopian tubes were tested on the isolated tube segments in vitro. Aurothiomalate (from 2.9 × 10(-9) to 4.9 × 10(-4) M/l), [Au(bipy)Cl(2)]Cl (from 3.3 × 10(-9) to 4.2 × 10(-5) M/l) and DMSO (from 1.9 × 10(-8) to 1.0 × 10(-5) M/l) did not affect spontaneous contractions of the isolated Fallopian tube ampulla, while [Au(DMSO)(2)Cl(2)]Cl (from 2.9 × 10(-9) to 4.2 × 10(-5) M/l) showed concentration-dependent increase (stimulation) of spontaneous contractions of the isolated Fallopian tube isthmus, and remained without effect on the isolated ampulla.The drugs designed as organic gold complexes with weaker bonds between the gold itself and organic part of a molecule could adversely affect motility of the Fallopian tubes, and theoretically fertility of women taking such drugs in their reproductive age.

Characterization of patients with arthritis referred for gold therapy in the era of biologics.

OBJECTIVE: To describe the clinical characteristics of patients referred for gold therapy and determine the reason for referral. METHODS: We conducted a chart review of patients referred for gold at the Mary Pack Arthritis Program, Vancouver, Canada, from July 2007 to July 2009. RESULTS: The sample included 69 female and 12 male patients. Diagnosis was rheumatoid arthritis (RA) in 71/81, psoriatic arthritis in 5, juvenile idiopathic arthritis (JIA) in 2, Sjögren syndrome in 1, undifferentiated polyarthritis in 1, and spondyloarthritis in 1. Twenty of 81 patients had received gold before: 15 were referred for a second course, 4 a third course, and 1 a fourth course. Ten of 81 patients were referred for gold as their first disease-modifying antirheumatic drug (DMARD). Seventy-one had received prior DMARD: 1 prior DMARD in 22 patients, 2 in 24 patients, 3 in 15 patients, and > 3 in 6 patients. Four patients had received prior biologic therapy plus 2 to 4 prior DMARD. Twelve of 71 received gold monotherapy, 56/71 received gold/DMARD combinations, and 3 received gold/biologic/DMARD combinations. Reasons for referral included failure of other DMARD in 54 patients, limited DMARD options in 50 (chronic liver disease in 34, sulfa allergy in 7, high alcohol consumption in 5, and planning pregnancy in 4), physician choice in 12, previous benefit from gold in 10, benefit of clinic support in 10, inappropriate for biologics in 7, patient choice in 4, and failure of biologics in 3. CONCLUSION: The most common reasons for referral to gold clinic in 2007 to 2009 are failure of other DMARD and limited DMARD options due to underlying liver disease.

Gold sodium thiomalate for the treatment of rheumatoid arthritis in a patient with hepatitis B.

OBJECTIVE: To describe a case of gold sodium thiomalate use for the treatment of rheumatoid arthritis (RA) in a patient with hepatitis B. CASE SUMMARY: A 53-year-old Korean American woman with mild RA and chronic hepatitis B infection was treated for worsening RA symptoms with subcutaneous injections of gold sodium thiomalate for 21 months, with the dosage decreased from the initial 40 mg per week to 40 mg every 3 weeks after 51 weeks of successful treatment. She had undergone treatment for hepatitis B in the past with lamivudine; however, she had not received that medication for at least 1 year prior to initiating treatment with gold sodium thiomalate injections. During the treatment period she achieved remission of RA without a significant elevation of her liver enzyme levels or reactivation of hepatitis B. DISCUSSION: Two main factors influence drug product selection when considering the subset of RA patients with chronic hepatitis B infection: severity of liver function compromise and treatment status of chronic hepatitis B. Our patient did not demonstrate significant liver function compromise, but was not receiving viral suppressive treatment for hepatitis B; therefore, the use of many first-line nonbiologic disease-modifying antirheumatic drugs (DMARDs) was contra-indicated based on current guideline recommendations. Additionally, because the patient had refused viral suppressive therapy, there was great concern with the use of biological DMARDs and potential reactivation of hepatitis B. In the past, gold salts were the standard of care in treating RA until the development of the newer agents and there was some evidence that gold sodium thiomalate could be used with minimal risk of hepatotoxicity. CONCLUSIONS: Gold sodium thiomalate proved to be a safe and effective treatment option in a patient with RA and hepatitis B.

Corneal chrysiasis: in vivo confocal microscopy analysis.

PURPOSE: To describe the in vivo confocal microscopy corneal findings in a patient treated with gold sodium thiomalate. METHODS: A woman with rheumatoid arthritis who had been treated with gold sodium thiomalate for 32 years came to our center for an ophthalmologic examination about 5 years ago. Besides visual acuity, the examination included slit-lamp biomicroscopy, intraocular pressure, and funduscopy. Confocal microscopy was performed using Confoscan 4 (Nidek Technologies, Padova, Italy) with a 40x lens. RESULTS: Every layer of the cornea is affected by gold deposits with high reflectivity, especially in the anterior stroma, where they have a larger dimension. CONCLUSIONS: Corneal chrysiasis can be evaluated by confocal microscopy, giving information on corneal metabolism and physiology.

Investigation of contact allergy to dental metals in 206 patients.

BACKGROUND: Contact allergy to dental materials is poorly understood; clinical manifestations are heterogeneous. OBJECTIVE: To analyse positive patch test reactions to metals (as their alloys or salts) used in dentistry together with clinical symptoms and possible relevance to dental fillings. METHODS: We retrospectively analysed 206 patients who underwent patch testing with metals used in dentistry because of suspected contact allergy to them. RESULTS: Twenty-eight of 206 patients had positive patch test reactions to metals used in dentistry. The number of positive patch test reactions was highest for gold sodium thiosulfate, palladium chloride, and nickel sulfate (n = 10, respectively), followed by amalgam, ammoniated mercury, and cobalt chloride (n = 4, respectively) and amalgam-mixed metals (including copper, tin, zinc, and silicon), and ammonium tetrachloroplatinate (n = 1). Only 14 (7%) of 206 patients had a clinically relevant contact allergy with conditions of the oral mucosa (n = 7 with lichen planus and n = 7 with stomatitis) and positive patch test reactions to dental metals containing the suspected allergen. Improvement of symptoms was assessed in one patient with amalgam contact allergy 2 weeks after removal of dental fillings. CONCLUSIONS: Clinically relevant contact allergies to dental metals are infrequent. Gold sodium thiosulfate and palladium chloride presented the most frequent contact allergens.

Promiscuous interaction between gold-specific T cells and APCs in gold allergy.

Gold compounds clinically used as immunomodulators have high potential to evoke hypersensitivity reactions as an adverse effect. To explore the mechanism of gold allergy, we immunologically characterized T cells infiltrating skin rashes and generated 44 gold-specific T cell clones and lines from a rheumatoid arthritis patient who developed skin rashes and systemic symptoms after gold treatment. CD4(+) and CD8(+) cells predominantly infiltrating the skin rashes and some of the T cell clones and lines shared common Vbetas. These cells exhibited Th0-like, Th2-like, and Tc1-like cytokine profiles, and showed chemotactic activities for thymus and activation-regulated chemokine and IFN-gamma-inducible protein-10 corresponding to the cytokine profiles. T cell recognition of gold consisted of MHC-restricted and MHC-independent pathways. Blocking studies with anti-MHC Abs indicated that the groove of MHC in APCs, where Ags should ordinarily be settled, did not serve as a conjugating site of gold for these T cells in certain cases. These observations raise the possibility that gold-specific CD4(+) and CD8(+) T cells and APCs promiscuously interact under stimulation with gold, resulting in various clinical manifestations in gold allergy.

Gold therapy in women planning pregnancy: outcomes in one center.

OBJECTIVE: To review the experience and outcome of pregnancies in women taking gold while planning pregnancy. METHODS: We undertook a chart review of patients attending for gold injection and monitoring between January 1992 and April 2006. For women who became pregnant while being followed taking gold therapy, we extracted demographic, treatment, and disease activity data, information regarding pregnancy complications, outcome, and postpartum course. For details missing from the clinic records, patients were interviewed by the clinic nurse. RESULTS: Fourteen women experienced 20 pregnancies while being followed in the gold monitoring clinic. Mean age at the time of conception was 34.5 years (range 24-41), disease duration 8.5 years (1-16). Rheumatoid factor was positive in 9 of 14 women. Duration taking gold prior to conception was < 12 months in 7 pregnancies, 13-24 months in 4, 25-34 months in 2, and 2-10 years in 7 pregnancies. Four women continued taking gold until delivery. The rest of the women discontinued gold when they knew they were pregnant, with the exception of one who held her gold 4 weeks prior to conception. There were 5 spontaneous abortions in the first trimester; included were 2 spontaneous abortions in a woman with known Robertsonian chromosomal translocation. Sixteen babies were healthy including a pair of twins. One baby was born with weakness of one extraocular muscle requiring surgery; one had blocked tear ducts at birth. Rheumatoid arthritis (RA) flared during 3/15 completed pregnancies and postpartum and post-spontaneous abortion in 18/20 pregnancies. CONCLUSION: Our clinic experience and the published literature support the current practice that in patients with RA, gold may still be considered a treatment option in women planning pregnancy.

Interferon-gamma secreted from peripheral blood mononuclear cells as a possible diagnostic marker for allergic contact dermatitis to gold.

10% of patch-tested patients have a positive reaction to gold. Most lack clinical symptoms, but allergic contact dermatitis (ACD) to gold is increasing. In this study, 77 dermatological outpatients were divided into 3 groups depending on epicutaneous patch test outcomes: a group positive to gold (EPI+), a group negative to gold (EPI-), and a group with irritant reactions to gold (EPI-IR). Lymphocytes were stimulated in vitro with gold sodium thiosulfate. Proliferation was assessed using the lymphocyte transformation test (LTT), and cytokine secretion was assessed using a multibead array (Luminex; Linco Research Inc., St. Charles, MO, USA), in order to evaluate whether an in vitro method with high diagnostic accuracy could be devised. The EPI+ group showed a significantly increased secretion of interferon (IFN)-gamma, interleukin (IL)-2, and IL-13 and also showed a significantly higher stimulation indexes for LTT, compared to the other 2 subject groups. Sensitivity and specificity were calculated for all methods individually and combined, but IFN-gamma assessment alone was the most accurate method for identifying ACD to gold, with sensitivity and specificity of 81.8% and 82.1%, respectively. This method also identified 87.5% of the EPI-IR subjects as non-allergic. Therefore, assessment of secretion of IFN-gamma should be a valuable complement to patch test for diagnosing gold allergy.

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.