Enfermedad de Wilson: presentación hepática y revisión bibliográfica / Wilson's disease: liver presentation and literature review / Doença de Wilson: apresentação hepática e revisão de literatura

Resumen: La Enfermedad de Wilson es un trastorno genético raro que puede presentarse a cualquier edad y se caracteriza por el depósito de cobre a nivel hepático y cerebral. La afectación hepática abarca desde formas asintomática hasta falla hepática fulminante o cirrosis. Su diagnóstico precoz tiene implicancias pronósticas ya que el tratamiento puede lograr un balance negativo de cobre, permitir el control sintomático y prevenir la progresión de la enfermedad. Se presenta el caso de un hombre de 27 años, con dolor abdominal, en el que se hizo el diagnóstico de Enfermedad de Wilson a partir de una hipertransaminasemia leve. Los hallazgos que orientaron al diagnóstico fueron una cupruria aumentada por inducción con D-penicilamina y una cuantificación de cobre en tejido hepático seco elevada. Con un estadio de fibrosis leve, se comenzó tratamiento con D-penicilamina con buena tolerancia y la normalización de las alteraciones bioquímicas.

Abstract: Wilson's disease is a rare genetic disorder that can occur at any age and is characterized by copper deposition in the liver and brain. Liver involvement ranges from asymptomatic forms to fulminant hepatic failure or cirrhosis. Its early diagnosis has prognostic implications since the treatment can achieve a negative copper balance, allow symptomatic control and prevent the progression of the disease. We present the case of a 27-year-old man with abdominal pain, who was diagnosed with Wilson's disease from mild hypertransaminasemia. The findings that led to the diagnosis were an increased cupruria by induction with D-penicillamine and a quantification of copper in elevated dry liver tissue. With a stage of mild fibrosis, treatment with D-penicillamine was started with good tolerance and normalization of biochemical alterations.

Resumo: Doença de Wilson é uma doença genética rara que pode ocorrer em qualquer idade e é caracterizada pela deposição de cobre no fígado e no cérebro. O envolvimento do fígado varia de formas assintomáticas a insuficiência hepática fulminante ou cirrose. Seu diagnóstico precoce tem implicações prognósticas, uma vez que o tratamento pode alcançar um balanço negativo do cobre, permitir o controle sintomático e prevenir a progressão da doença. Apresentamos o caso de um homem de 27 anos com dor abdominal, diagnosticado com doença de Wilson de hipertransaminasemia leve. Os achados que levaram ao diagnóstico foram aumento da cuprúria por indução com D-penicilamina e quantificação de cobre em tecido hepático seco elevado. Com uma fase de fibrose leve, o tratamento com D-penicilamina foi iniciado com boa tolerância e normalização das alterações bioquímicas.

D-penicillamine Induced Elastosis Perforans Serpiginosa / 대한피부과학회지

No abstract available.

Nefropatía membranosa secundaria a exposición laboral con mercurio metálico

Las nefropatías tóxicas secundarias a la exposición ocupacional a metales han sido ampliamente estudiadas. La nefropatía membranosa por mercurio es poco frecuente.La intoxicación ocupacional con mercurio sí es frecuente, siendo las principales formas de presentación las manifestaciones clínicas neurológicas. La afectación renal secundaria a la exposición crónica a mercurio metálico puede desarrollar enfermedad glomerular por depósito de inmunocomplejos. La glomerulopatía membranosa y a cambios mínimos son las más frecuentemente comunicadas.Se presenta el caso de un paciente con exposición ocupacional a mercurio metálico, con síndrome nefrótico y biopsia renal con glomerulopatía membranosa que presentó respuesta favorable luego del tratamiento quelante e inmunosupresor.

Toxic nephrophaties secondary to occupational exposure to metals have been widely studied, including membranous nephropathy by mercury, which is rare. Occupational poisoning by mercury is frequent, neurological symptoms are the main form of clinical presentation. Secondary renal involvement in chronic exposure to metallic mercury can cause glomerular disease by deposit of immune-complexes. Membranous glomerulopathy and minimal change disease are the most frequently reported forms. Here we describe the case of a patient with occupational exposure to metallic mercury, where nephrotic syndrome due to membranous glomerulonephritis responded favorably to both chelation and immunosuppressive therapy.

Reversal of Severe Wilson Arthropathy by Liver Transplantation.

Wilson disease is associated with multisystem involvement. We describe a patient of Wilson disease with severe arthropathy, which completely reversed following liver transplantation. This is the first case report in literature describing the complete reversal of Wilson disease related arthropathy by liver transplantation.

Penicillamine-induced elastosis perforans serpiginosa with abnormal "lumpy-bumpy" elastic fibers in lesional and non-lesional skin.

Four types of elastosis perforans serpiginosa (EPS) have been described in literature: 1) idiopathic EPS, 2) reactive perforating elastosis associated with connective tissue disorders, 3) in some instances of pseudoxanthoma elasticum (PXE), disease-specific calcified elastic tissue is extruded, producing a clinical picture indistinguishable from other types, may also be seen in patients undergoing hemodialysis and 4) EPS induced by long-term treatment with D-penicillamine is observed in patients suffering from Wilson's disease. Long term D-penicillamine therapy causes an alteration in the dermal elastic tissue. D-penicillamine induced EPS has a distinctive histopathologic feature - serrated appearance of elastic fibers due to perpendicular budding from their surface giving a "lumpy-bumpy" look. D-penicillamine induced elastic fiber alteration may not always manifest clinically as EPS. We report a case of D-penicillamine induced widespread alteration in skin elastic tissue with distinct histopathologic features.

Juvenile scleroderma: experience in one institution.

Background: Scleroderma is a chronic connective tissue disease characterized by hardened or scaly skin and widespread abnormalities of the viscera, which is rare in the pediatric age group. Objective: In this study, we retrospectively reviewed 23 pediatric patients suffering systemic (SSc) and localized (LS) scleroderma. Methods: Twenty-three patients were enrolled and were diagnosed with SSc or LS from March 1993 to September 2009 in the Department of Pediatrics at Mackay Memorial Hospital in Taipei, Taiwan. These diagnoses were based on the criteria of the American College of Rheumatology and the clinicalmanifestations of hard skin. Data recorded included sex, age-at-onset, age-at-diagnosis, laboratory data, family history, trauma history, treatment, and outcomes. Results: Three patients suffered SSc and 20 patients had LS, including 16 girls and 7 boys. Mean age-at-onset was 6.55±3.28 years old. Antinuclear antibodies were positive in 15 patients. Tests for anti-Scl-70 antibodies were positive in 1 patient with SSc. One boy had en coup de sabre combined with a posterior fossa tumor. Twenty-two patients were treated with D-penicillamine. Oral prednisolone and methotrexate were added, if indicated. One girl with LS developed proteinuria after Dpenicillamine treatment. All patients with localized disease ultimately documented a softening of their skin lesions. Conclusions: While scleroderma is rare in children, the prognosis of SSc is poor but better than for adults. The prognosis for LS is usually benign, however, the skin may become progressively indurated and it may not only be a skin disease. No progression from LS to SSc was observed in our study.

Lead-induced peripheral neuropathy following ayurvedic medication.

Lead poisoning following intake of Ayurvedic medication is one of the recent areas of concern. We report a case of a 58-year-old type II diabetic man who was stable with diet control and 30 mg pioglitazone per day. He took Ayurvedic medication for generalized weakness and developed peripheral neuropathy following its intake. He was found to have high blood and urinary lead levels and was diagnosed to have subacute lead poisoning. He was treated with d-Penicillamine for 8 weeks, following which his lead levels became normal. The use of d-Penicillamine was proved highly effective in treating a case of lead poisoning.

Evaluation of lung infiltration score to predict postural hypoxemia in ventilated acute respiratory distress syndrome patients and the lateralization of skin pressure sore.

Context: Mechanical ventilation with positive end expiratory pressure (PEEP) is associated with unequal aeration of lungs in acute respiratory distress syndrome (ARDS) patients. Therefore, patients may develop asymmetric atelectasis and postural hypoxemia during lateral positioning. Aims: To validate proposed lung infiltration score (LIS) based on chest x-ray to predict postural hypoxemia and lateralization of skin sores in ARDS patients. Settings and Design: University hospital ICU. Prospective, observational study of consecutive patients. Materials and Methods: Sixteen adult patients of both genders on mechanical ventilation with PEEP for 24 to <48 hours. On chest x-ray, 6 segments were identified on each lung. The proposed LIS points (0- normal; 1- patchy infiltrates; 2- white infiltrates matching heart shadow) were assigned to each segment. Without changing ventilation parameters, supine, left and right lateral positions at 45° tilt were randomly changed. At the end of 20 minutes of ventilation in each position, we observed arterial oxygen saturation, hemodynamic and arterial blood gases. Later, position change protocol (4 hourly) was practiced in ICU, and skin pressure sore grading was noted within a week of ICU stay. Statistical Analysis Used: Nonparametric Bland and Altman correlation analysis, ANOVA and Student t test. Results: Arterial oxygenation (PaO 2 /FiO 2 = 313± 145.6) was significantly (P<0.01) higher in better lung (lower LIS)-down position than supine (PaO 2 /FiO 2 = 199± 70.2) or a better lung-up position (PaO 2 /FiO 2 = 165± 64.8). The positioning-related arterial oxygenation was significant (P< 0.05) at LIS asymmetry ≥3 between two lungs. Conclusions: The LIS mapping on chest x-ray was useful to differentiate between asymmetric lung disease and postural hypoxemia in ICU patients, which predisposed patients to early skin sore changes on higher LIS side.

Effect of Lead Intoxication and D-Penicillamine Treatment on Hematological Indices in Rats / Efectos de Intoxicación con Plomo y Tratamiento de D-Penicilamina en índices Hematológicos en Ratas

Lead is one of the most important environmental pollution which is toxic to many organ systems. D-penicillamine (D-P) is a chelator drug which is used for treatment of lead toxicity for several years. This study was conducted in order to evaluate the efficacy of D-P in reducing the effects of lead on hematological indices. This study was done on 36 male adult, 6-8 weeks albino Wistar rats in Gorgan University of Medical Sciences. At first male adult rats were exposed to lead acetate in their drinking water. After 8 weeks, 6 rats were selected and blood samples were prepared to assess the effects of lead toxicity. The remained lead exposed rats were divided into recovery and treatment groups where distilled water and D-P was administered for them, respectively. After lead exposure, red blood cell count increased slightly, but hemoglobin and hematocrite were decreased. Also MCV and MCH were significantly decreased (P<0.05). RDW, PDW and MPV were significantly higher in lead exposed rats (P<0.05). After recovery period, most of parameters were close to normal while there were no significant differences between recovery and treatment groups. This study showed that hematologic effects of lead are reversible and D-P administration do not play an important role in subchronic lead intoxication.

El plomo es uno de los más importantes contaminantes ambientales, tóxico para la mayoría de los sistemas orgánicos. La D-penicillamina (D-P) es una droga quelante, la cual se ha usado para el tratamiento de la toxicidad por plomo durante varios años. Este estudio fue dirigido para evaluar la eficacia de la D-P en la reducción de los efectos del plomo en los índices hematológicos. Este estudio se realizó en 36 machos adultos de ratas Wistar albinas de 6-8 semanas, en la Universidad de Ciencias Médicas de Gorgan, Irán. Al inicio, las ratas machos adultas fueron expuestas al acetato de plomo en el agua de beber. Después de 8 semanas, 6 ratas se seleccionaron para evaluar los efectos de la toxicidad del plomo en muestras sanguíneas. Las restantes ratas expuestas fueron divididas para su recuperación, a las cuales se les administró agua destilada y un grupo con tratamiento al que se le suministró D-P. Después de la exposición al plomo, el conteo de glóbulos rojos se incrementó ligeramente, pero la hemoglobina y el hematocrito disminuyeron. También el MCV y el valor de MCH disminuyeron significativamente (P< 0,05). Los valores de RDW, PDW y MPV fueron significativamente altos en las ratas expuestas al plomo (p< 0,05). Luego del periodo de recuperación, la mayoría de los parámetros se acercaron al valor normal y no hubo diferencias significativas entre el grupo recuperado y con tratamiento. Este estudio mostró que los efectos hematológicos del plomo son reversibles y la administración de D-P no juega un rol importante en la intoxicación subcrónica.

A Case of Lead Poisoning After Ingestion of Herb Pills / 대한산업의학회지

BACKGROUND: Lead is a common environmental metal and has been used for various purposes for a long time, leading to frequent reports of lead poisoning. The concern about lead poisoning starts has been mostly focused on occupational exposure and is linked to the prevention and management of lead exposure in refining and manufacturing processes. Nowadays, however, there is growing concern about nonoccupational lead exposure by many pollutants. Especially, lead poisoning by herb medicine has commonly been observed in clinics in Southeast Asia and South Korea. This case report contains diagnosis of inpatients who suffered from lead poisoning from a herb medicine, arthritis remedy and who complained of abdominal symptoms and dizziness. The study purpose was to awaken our healthful interest in lead poisoning. CASE REPORT: A 53-year-old female patient complaining of abdominal pain, dizziness, and numbness of hand and foot came to our hospital due to the continuation of her anemic finding symptoms while undergoing treatment at a secondary hospital. Her past medical history was unremarkable except she had taken herb pills for about a year which were administered by herb medicine to treat arthritis. Physical examination was unremarkable except for oral ulcer finding. Hemoglobin was 8.5 g/dl, reticulocyte count was 4.10%, bilirubin was 1.3 mg/dl (direct 0.3 mg/dl), and Zinc protoporphyrin 169.12 ug/dl. In urinalysis results, WBC increased to 30~39 /HPF, While AST/ALT, BUN/Cr, PT/aPTT, and nerve conduction velocity were normal. Basophilic stippling was observed through peripheral blood smear. The blood lead level was 80.4 microgram/dl and the urine lead level continued to increase to 541 microgram/l. Analysis of the pills that the patient had been taking showed that they contained 30 mg/g lead. By oral chelation therapy with D-penicillamine four times per day for five days, the patient's hemoglobin increased to 11.8 g/dl, while blood lead level decreased to 39.2 microgram/dl, and urine level to 196 microgram/l. Although the soles of her feet remained cold, but other symptoms and anemia finding were improved considerably. However, after discontinuing D-penicillamine medication, the blood lead level increased to 41.4 microgram/dl again. The further administration of D-penicillamine for five days reduced the blood lead level to 31.5 microgram/dl. At two years after the discontinuance of D-penicillamine, the followup findings were normal; hemoglobin was 13.1 g/dl, hematocrit 39.6%, reticulocyte count 1.22%, blood lead level 13.3 microgram/dl, and urine lead level 9.17 microgram/l. CONCLUSION: After taking herb medicine pills for one year, the patient was admitted to hospital chiefly complaining of abdominal pain, dizziness, and numbness of the hand and foot. The high blood and urine and lead levels and lead chemical analysis of the herb pills confirmed lead poisoning which was treated with D-penicillamine for five days. The follow-up result after two years indicated normal blood and urine lead levels.

Acetylized Racemization Process and Kinetics of D-penicillamine / 中国药房

OBJECTIVE:To study the process of acetylized racemization of D-penicillamine in the acidic condition. METHODS:The acetylized racemic mixture of D-penicillamine was prepared by racemizing acetyl chloride in acetic acid solu_tion with D-penicillamine as feedstock.The preparation process was optimized with the quantities of solvent and acetyl chloride,the reaction temperature,the reaction time etc.as parameters.The influence of reaction temperature,reaction time on the specific optical rotation in the acetylized process was determined and the kinetic equation of acylation process was computed. RESULTS:The optimal condition for racemization was the following,the quantity ratios of D-penicillamine-acetic acid -acetyl chloride were 1∶7∶2,the reaction temperature was 80℃ and the reaction time was 5h.The kinetic equation of acylation process fitted first order linear relation. CONCLUSION:This preparation process is mild and simple,and it offers direct feedstock for the preparation of D,L-penicillamine.

Early Onset of Minimal change Nephrotic Syndrome during Treatment with D-penicillamine in a Patient with Wilson s Disease

Wilson s disease is an autosomal recessive disorder characterized by degenerative changes in the brain, liver, and cornea. Treatment includes D-penicillamine, trientine, and zinc sulfate. D-penicillamine has been used frequently as first line therapy for Wilson s disease. However, nephrotoxicity can occur after D-penicillamine treatment. Among them membranous glomerulopathy is the most common histological abnormality but minimal change lesions have also been reported. Nephrotic syndrome is a late complication of D-penicillamine treatment but very rarely can occur within 2 months after treatment of D-penicillamine. We report the early development of minimal change nephrotic syndrome in a 3-year-old girl with Wilson s disease 3 weeks after initiation of D-penicillamine.

Breast Gigantism Induced by D-Penicillamine: Case Report

D-penicillamine, a chelating agent of copper, is the drug of choice for the treatment of Wilson's disease. Breast enlargement is a rare complication arising from its use, and we report a case of breast gigantism which developed after it had been used for ten months to treat this condition. Mammography demonstrated bilaterally enlarged dense breasts; ultrasonography, similarly, demonstrated enlargement, revealing the presence of a mass, shown at biopsy to be benign, in the left one.

Subcutaneous and Gastrointestinal Exposure to Metallic Mercury: Report of 2 Cases / 대한산업의학회지

BACKGROUND: Mercury poisoning presents a variety of clinical pictures depending on the chemical structure, the route of exposure, the amount absorbed and other individual factors. Therefore, the ingestive and subcutaneous absorption of elemental(metallic) mercury can be considered to be relatively harmless in contrast to the inhalation of mercury vapor. CASE REPORTS: A 72-year-old man presented to the department of urology due to tenderness, edema and a necrotic abscess of his penis after trauma. The soft tissue abscess required a surgical resection of the penis. For chelation therapy, oral D-penicillamine was administrated. 7 months later, he showed no subjective or objective signs of mercury poisoning. Another 5-yearold girl presented to the emergency department after accidental self-ingestion of elemental mercury. She was followed clinically and did not show any systemic mercury poisoning. CONCLUSION: The Mercury concentrations in the blood and urine were elevated in the case of subcutaneous exposure, but was unchanged in the case of ingestion. Subcutaneous and gastrointestinal exposure to metallic mercury has a minimal risk for systemic mercury poisoning, which is in contrast to the exposure by inhalation.

A Case of Minimal Change Nephrotic Syndrome Associated with D-penicillamine Therapy of Wilson's Disease / 대한소아소화기영양학회지

Wilson's disease is a treatable autosomal recessive inherited disorder of copper metabolism due to mutation of the copper transporting gene. The basic strategy of treatment is to reduce the amount of copper in the liver and other tissues by administering both a low copper diet and copper-chelating agents. D-penicillamine is the first choice as a copper-chelating agent. Some serious side effects could occur in 3~5% of all patients following D-penicillamine therapy. We report a 19 year-old male with Wilson's disease who developed nephrotic syndrome 6 months after the initiation of D-penicillamine therapy. Prednisolone was administered to control nephrotic syndrome and D-penicillamine was switched to trientine. Urinary remission was achieved within a week and maintained thereafter. Nephrotic syndrome was proven to be MCNS by kidney biopsy.

A case of myasthenia gravis in a patient with diffuse systemic sclerosis developed during D-penicillamine treatment / 대한류마티스학회지

D-penicillamine has been used to reduce skin thickening and prevent the development of significant organ involvement in the treatment of scleroderma. This drug has a number of serious adverse reactions including glomerulonephritis with nephrotic syndrome, aplastic anemia, thrombocytopenia, and myasthenia gravis. A 44-year-old woman was admitted for weakness of the extremity muscle during repeated use. Eight months before admission, she visited dermatology department of our hospital. She was diagnosed as having scleroderma. D-penicillamine was started for the treatment of skin lesions. Based on the fluctuation of proximal muscle weakness, high titer of acetylcholine receptor antibody and definite decremental response of Jolly test, she was diagnosed as myasthenia gravis. D-penicillamine was discontinued because of the suspicion of D-penicillamine induced myasthenia gravis. Muscle weakness improved after D-penicillamine was withdrawn. The development of reversible myasthenia gravis may be regarded as a part of general predisposition for autoimmune disease related to the D-penicillamine therapy.

Regulation of type I collagen and interstitial collagenase mRNA expression in human dermal fibroblasts by colchicine and D-penicillamine

Sclerosis is a disease process in which idiopathic hardening occurs in the skin and/or internal organs as a result of the accumulation of type I collagen, induced mainly by transforming growth factor-beta. Colchicine and D-penicillamine are widely used for its treatment. Their effects are known to be due to post-translational down-regulation of type I collagen synthesis, with colchicine also up-regulating interstitial collagenase. To determine whether or not they have any pre-translational effect on type I collagen and MMP-1, and also to observe their effects on the action of TGF-beta, cultured neonatal foreskin fibroblasts were treated with colchicine and D-penicillamine, singly and together. The amount of type I collagen and MMP-1 mRNA were quantitated by Northern blot hybridization. Colchicine suppresses the basal level of type I collagen mRNA but minimally stimulates the mRNA expression of MMP-1, whereas D-penicillamine does not have any significant effects on either. Colchicine was also able to significantly suppress the TGF-beta-induced up-regulation of type I collagen mRNA expression.

A Case of D-Penicillamine Induced Iga Nephropathy in a Patients with Scleroderma / 대한류마티스학회지

IgA nephropathy can occur rarely as a complication of D-penicillamine treatment, but it is exact pathogenesis remains unclear. If a patients has gross or microscopic hematuria during D-penicillamine treatment, D-penicillamine induced IgA nephropathy should be suspected as a cause of hematuria. In those cases, renal biopsy should be taken for diagnosis and proper management. We experienced a case of IgA nephropathy confirmed by renal biopsy in a 39-years-old female patient with scleroderma during D-penicillamine therapy and report this case with a review of literature.

Two Cases of Wilson's Disease Associated with Kayser-Fleicher Ring

Wilson's disease is an inborn error of copper metabolism which may be associated with hepatic cirrhosis and progressive degeneration of the central nervous system. The most common ophthalmologic finding in Wilson's disease is the Kayser-Fleischer ring. Other much less common physical signs include neurologic signs, endocrinologic abnormality. The Kayser-Fleischer ring occurs in the corneal periphery and is usually yellow- brown color. The Kayser-Fleischer ring.copper deposition at the level of the posteior position of Descemet's membran. The authours have recently experienced two cases of wilson's disease. One case. a 20-year-old girl, has Kayser-Fleischer rings in both eyes, amenorrhea, chronic active hepatitis and the other case, a 21-years-old girl, has dense yellow-green colored Kayser-Fleischer rings in both eyes, palilalia, and family relationship. Both cases have been treated with D-penicillaine and low copper diet. After treatment, clinical manifestation have been improved markedly at former case and the other cae is steady stage, but the Kayse-Fleischer rings have not disappeared yet in both cases.

Effects of Bucillamine on the Function of Human B Cell and T Cell / 대한류마티스학회지

OBJECTIVE: Bucillamine[N- (2-mercapto-2-methylpropionyl)-L-cysteine] (BUC) is a thiol compound that differs from D-pencillamine(DPC) in that it contains two free sulfhydryl groups. Clinical trials have suggested that the efficacy of BUC in rheumatoid arthritis(RA) is as effective as DPC, but the mechanism of action remains unclear. We therefore examined the effects of BUC on the in vitro function of human B cell and T cell in comparision to those of DPC. METHODS: The effect of BUC and DPC on Staphylococcus aureus Cowan 1 (SAC) induced IgM production by B cells from 11 healthy donors was examined. Phytohemagglutinin (PHA) induced proliferation and Interferon-r(IFN-r) and Interleukin-2 (IL-2) production by T cells was also examined. RESULTS: BUC and BUC-ID(SA981) suppressed the production of IgM at concentration of 0. 1-100 ug/ml, whereas DPC suppressed at concentration of 100 ug/ml. BUC and DPC inhibited PHA induced DNA synthesis of peripheral blood mononuclear cells(PBMCs) and T cell in a dose-dependent manner. DPC (10 ug/ml) significantly suppresed IFN-r production by PHA-stimulated T cells, but not suppressed IL-2 production, whereas BUC(10 ug/ml) not significantly suppressed IFN-r and IL-2 production. CONCLUSION: BUC has immunosuppressive effects inhibiting the function of B cells and T cell proliferation, whereas the action of DPC is targeted at T lymphocytes. BUC may be effective in rheumatoid factor positive RA patients who have not responded to treatment with DPC.