Acitretin-induced pneumonia: an underestimated complication of treatment of psoriasis

INTRODUCTION: Retinoids are known to induce side effects which can be severe. Alveolar and interstitial pneumonia of uncertain pathogenesis can rarely occur when retinoid are used among patients with psoriasis. EXEGESIS: We report an observation of acute respiratory distress beginning 26 days after introduction of acitretin, a second-generation retinoid. Treatment withdrawal and corticotherapy allow a spectacular amelioration of respiratory conditions. CONCLUSION: Pneumonia induced by retinoid must be known as a side effect of treatment of psoriasis.     

Severe hepatitis induced by cyproterone acetate: role of corticosteroids. A case report

Cyproterone acetate (CPA) is an oral anti-androgen commonly used to treat advanced prostate cancer. A variety of hepatotoxic reactions has been reported with CPA. Here we describe a case of a male patient who developed severe drug-induced hepatotoxicity during the treatment with CPA. The case, presenting sub-acute hepatitis, was characterized by a rapid evolution of cirrhosis and a protracted activity during the period of a few months despite the treatment withdrawal and an apparent benefits of corticosteroids, suggesting their indication in life threatening cases.     

Effects of retinoid therapy on insulin sensitivity, lipid profile and circulating adipocytokines

OBJECTIVE: In vitro and in vivo models indicate that all-trans retinoic acids influence glucose and lipid metabolism. We aimed to evaluate the effects of chronic treatment with acitretin, an all-trans retinoic acid, on glucose metabolism, lipid profile and adiponectin and resistin levels. DESIGN: Ten normoglycemic, normolipemic patients affected with psoriasis vulgaris were studied before and after 1 and 3 months of oral treatment with 35 microg of acitretin. METHODS: Glucose metabolism, lipid profile, and adiponectin and resistin levels were evaluated in basal conditions and after acitretin treatment. Ten healthy subjects matched for age, body mass index (BMI) and insulin sensitivity were studied as controls. RESULTS: One-month acitretin treatment reduced psoriasis activity, insulin sensitivity, evaluated as QUICKI values (0.364 +/- 0.034 versus 0.329 +/- 0.051; P < 0.05) and HOMA-IR index (1.53 +/- 0.73 versus 2.59 +/- 1.41; P < 0.05), and high-density lipoprotein (HDL)-cholesterol levels (45.2 +/- 11.7 versus 39.4 +/- 10.4 mg/dl; P = 0.01). The impairment in glucose and lipid homeostasis was transient and not associated to BMI variations. Adiponectin levels did not change during the treatment, while resistin levels, which were higher in untreated patients than in controls (9.4 +/- 4.4 versus 6.2 +/- 2.1 ng/ml; P = 0.05), fell within the normal range after 1 and 3 months of therapy. The normalization of resistin levels occurred without significant changes in circulating tumor necrosis factor alpha (TNFalpha) levels, which persisted elevated throughout the treatment. CONCLUSIONS: Treatment with a low dose of acitretin induced a mild, transient reduction of insulin sensitivity and HDL-cholesterol levels that was not related to modifications of adiponectin, resistin and TNFalpha levels. Although the role of resistin in humans remains elusive, the levels of this adipocytokine seem to be affected, at least in part, by retinoids.     

Fatal hepatic necrosis due to pyrimethamine-sulfadoxine (Fansidar)

Pyrimethamine-sulfadoxine has been associated with severe and fatal cutaneous reactions as well as transient liver damage. We report the case of a patient who died of progressive hepatic failure caused by pyrimethamine-sulfadoxine administration. In addition, we summarize reports made to the Food and Drug Administration since 1982 that focus on hepatotoxic reactions to pyrimethamine-sulfadoxine. We suggest that fatal hepatic injury can occur after treatment with pyrimethamine-sulfadoxine and that physicians who prescribe the drug should be aware of this possibility.     

Hepatotoxicity associated with sustained-release niacin.

Niacin (nicotinic acid) is a widely used agent in the treatment of hyperlipidemias characterized by elevated low-density lipoprotein and very-low-density lipoprotein. The tendency of the conventional crystalline niacin to cause flushing has limited its use in many patients. Sustained-release (SR) niacin preparations are increasingly utilized due to a lower incidence of flushing and convenient dosing frequency. Although gastrointestinal and hepatotoxic side effects are common to both formulations, they are more frequent and occasionally more severe with the SR preparations. We describe a patient who developed an acute illness characterized by hypothermia, hypotension, metabolic acidosis, and severe hepatic dysfunction 2 days after substitution of an SR preparation for a previously well-tolerated crystalline niacin.     

Hepatotoxicity induced by cyproterone acetate： A report of three cases

INTRODUCTION Androgen deprivation therapy in the form of either orchiectomy or treatment with endogenous estrogens or luteinizing hormone releasing hormone (LHRH) analogues alone or coupled with antiandrogens, produces regression of prostate cancer cells …     

A case of meglumine iodipamide hepatotoxicity.

There have been only two reports of severe hepatotoxic reaction caused by meglumine iodipamide. Lately we experienced such a reaction in an 66-year old female with chronic intrahepatic cholestasis. After drip infusion cholangiography was performed by infusing 40 ml. of 50% meglumine iodipamide (Biligrafin) intravenously, the patient developed nausea and abdominal pain. Her serum transaminase rose to more than 2,000 K-A units on the third day and gradually returned to normal by the 18th day. The macrophage migration inhibition test of her blood was positive for meglumine iodipamide. Accordingly some delayed type of hypersensitivity in the above reaction could be considered. When a larger amount than a recommended dose of meglumine iodipamide is infused in cholangiography, a severe hepatotoxic reaction might be induced, especially in icteric cases.     

Effects of chronic retinoid administration on pituitary function

It has been reported that retinoids may affect hypothalamic-pituitary-thyroid axis, causing central hypothyroidism. In the present study, we evaluated pituitary function in 11 male psoriatic patients at baseline and after 1 and 3 months of treatment with acitretin (all-trans retinoic acid, 35 mg/day). Serum LH, FSH, testosterone, cortisol, GH and IGF-I levels were not affected by the treatment. By contrast, we observed a significant decrease in TSH levels (from 0.92 +/- 0.3 to 0.80 +/- 0.3 mU/I, p < 0.05) at 1 month, that reverted to baseline after 3 months. No change in free T4 (FT4) levels occurred, while free T3 (FT3) levels were reduced at 1 and 3 months (from 6.7 +/- 0.5 to 6.2 +/- 0.3 and 6.1 +/- 0.6 pmol/l; p < 0.05, respectively). Moreover, acitretin treatment induced a significant reduction of PRL levels after 3 months (from 182 +/- 70 to 150 +/- 56 mU/l, p < 0.05). During treatment, no change in TSH and PRL response either to TRH or dopamine infusion was observed. In conclusion, we demonstrated that treatment with low dose of acitretin induced a series of hormonal modifications that, in addition to a mild and transient reduction of TSH levels, included a persistent reduction of FT3, probably due to changes in thyroid hormone metabolism, and a decrease in PRL levels.     

Hepatitis on High Dose Isoniazid: Reintroduction of the Drug in Severe Tuberculous Meningitis

Hepatitis developed in two patients treated with high doses (1000 mg/day) of isoniazid for severe tuberculous meningitis. Isoniazid was discontinued and later read-ministered in gradually increasing intrathecal and subsequently oral doses, up to the final dose of 400 mg/day. Transaminases remained normal, during 12 months on this dose, suggesting dose dependence of hepatotoxicity or a metabolic adaptation to the injury. Continued isoniazid treatment can be important in similar cases and it may become possible, if oral or intrathecal doses significantly lower than the initial hepatotoxic ones, are used.     

Hepatotoxicity of parenteral gold therapy in rheumatoid arthritis: a case report and review of the literature.

We report a case of severe hepatotoxic reaction during gold therapy for rheumatoid arthritis. The previous literature on this condition is reviewed and the possible mechanisms of gold-induced hepatotoxicity are discussed.     

A strategy to improve the detection of drug-induced hepatotoxicity.

AIMS: To report a new strategy for the detection of hepatotoxic adverse drug reactions (ADRs) in hospitalized patients improving the results obtained with other methods. DESIGN: The model is based on the identification of a single alert signal in various target clinical departments over a 12-month period. Each patient was later interviewed following a set protocol. The main results analyzed were the drugs suspected of ADR; causal relationship between suspected drugs and ADRs; ADR severity, and incidence of hepatotoxic ADR/100,000 inhabitants. SUBJECTS: Population served by a university-affiliated urban teaching hospital (519,381 inhabitants). RESULTS: The overall ratio of confirmed/suspected ADRs was high (35/80). The most commonly reported drug was amoxicillin-clavulanic acid (4 cases). With regard to causality, 2 suspected cases were classified as definite and 14 as probable. The distribution according to the severity of hepatotoxicity was 6 severe and 29 mild cases. The incidence of hepatotoxic ADRs/100,000 inhabitants as revealed by our method was much higher versus voluntary report (6.74 and 1.79, respectively). CONCLUSIONS: Our method has proven effective for improving the detection of hepatotoxic ADRs, and may be extended to other types of adverse reactions.     

Liver damage due to N-propyl-ajmalin bitartrate (NPAB)]

The authors report on four cases of immediate hepatotoxic reaction following diagnostic re-exposure. In checking 27 patients who had received NPAB treatment for the first time, four were found to have a hepatotoxic reaction that developed within 13--20 days after beginning the treatment. In view of the significance of NPAB for the treatment of cardiac rhythm disorders, further such studies are required in order to define the actual risk involved in this procedure.     

Prolonged cholestasis due to trimethoprim sulfamethoxazole.

Drug-induced liver injury due to trimethoprim sulfamethoxazole is rare and classified as an unpredictable or idiosyncratic type of hepatotoxic reaction. Early reports suggested that the pattern of liver injury in the majority of cases is mixed hepatocellular-cholestatic. The current report describes two cases of severe, prolonged cholestasis after treatment with trimethoprim sulfamethoxazole; intractable pruritus and abnormal liver test results lasted for 1-2 years after discontinuation of the drug. Liver biopsy specimens showed a cholestatic pattern of liver injury and only minimal hepatocellular necrosis or inflammation. Recent case reports suggest that cholestasis alone may occur after the use of trimethoprim sulfamethoxazole; these two additional cases show that cholestasis may be quite prolonged.     

Case Report: Chronic Liver Injury Related to Use of Bentazepam

Liver injury induced by benzodiazepines is rare and is classified as an unpredictable or idiosyncratic hepatotoxic reaction. Early reports indicated that in most cases the pattern of liver injury was cholestatic. We describe three patients with persistent increases in liver transaminase levels after several weeks of treatment with bentazepam, a benzodiazepine marketed in Spain for anxiety disorders. In all cases withdrawal of the drug was followed by resolution of transaminase level abnormalities. A liver biopsy (done in one patient only) showed histological evidence of severe chronic active hepatitis. In conclusion, these findings, together with two previously published case reports, suggest that a benzodiazepine can cause chronic hepatitis and argue in favor of using liver function tests to monitor all patients taking bentazepam.     

Methotrexate-induced cirrhosis requiring liver transplantation in three patients with psoriasis. A word of caution in light of the expanding use of this 'steroid-sparing' agent

Methotrexate has been used for many years to treat refractory psoriasis. Three cases of methotrexate-induced cirrhosis requiring orthotopic liver transplantation are presented to emphasize the importance of strict adherence to published criteria for patient selection, monitoring of cumulative drug dosages, and the performance of serial liver biopsies. Each patient had been treated with long-term methotrexate therapy (cumulative doses far in excess of 1.5 g) without undergoing serial liver biopsies, contrary to well-established treatment guidelines. Caution must be exercised in using methotrexate as a steroid-sparing agent in the treatment of inflammatory diseases because of its potential to cause severe hepatotoxic effects with long-term usage and cumulative doses above 1.5 g. Patients easily become psychologically dependent on the drug, and physicians need to guard against the false sense of security engendered by normal results on liver function studies.     

Severe hepatotoxicity by Indian Ayurvedic herbal products: A structured causality assessment

The case of a 64 year old female patient is presented who has treated herself for 9 months with various Indian Ayurvedic herbal products for her vitiligo and experienced a causally related severe hepatotoxicity (ALT, 601 U/L; AST, 663 U/L; Bilirubin, 5.0 mg/dL). After discontinuation, a rapid improvement was observed. Causality assessment with the updated CIOMS (Council for International Organizations of Medical Sciences) scale showed a probable causality (+8 points) for Bakuchi tablets containing extracts from Psoralea corylifolia leaves with psoralens as ingredients, as the primary candidate causing the hepatotoxic reaction. The degree of probability was lower with +6 points for other used herbs: Khadin tablets containing extracts from Acacia catechu leaves; Brahmi tablets containing Eclipta alba or Bacopa monnieri; and Usheer tea prepared from Vetivexia zizaniodis. The case is the first report of Indian Ayurvedic herbal products being potentially hepatotoxic in analogy to some other herbs.     

Cyclophosphamide-induced acute liver failure requiring transplantation in a patient with genetically deficient debrisoquine metabolism: a causal relationship?

Severe liver damage can occur after treatment with cyclophosphamide. The possible linkage to genetically deficient drug metabolic capacity is unknown. A 58-year-old woman with rheumatoid arthritis was treated with oral cyclophosphamide 50 mg twice daily for 2 months. Due to poor response the dose was doubled and liver failure requiring transplantation developed within weeks. After surgery PCR amplification using DNA from leukocytes showed that she was homozygous for the mutated allele CYP2D6B, which is predictive of the poor metaboliser phenotype for debrisoquine, occurring in 7% of Caucasians. Our patient may have accumulated high levels of the hepatotoxic 4-hydroxylated cyclophosphamide metabolite. Pharmacogenetic methods can help in exploring mechanisms of unexpected severe adverse effects.     

Initially obscure hepatotoxicity attributed to sildenafil

We describe a patient with a hepatotoxic reaction, presenting with general malaise, severe jaundice, and pruritus. This turned out to be caused by the, at first unrevealed, use of sildenafil. The injury seems to be hepatocanalicular, characterized by a hepatocellular liver test pattern, combined with extensive cholestasis on liver biopsy. One should bare in mind that the use of sildenafil may not be readily disclosed by the patient nor his doctor.     

Acitretin and AIDS-related Reiter's disease

A patient with AIDS presented with Reiter's syndrome. Arthritis and skin lesions responded poorly to nonsteroidal anti-inflammatory drugs and topical corticosteroid therapy. Dramatic improvement was seen 2 weeks after acitretine was added. When Reiter's syndrome recurred 11 months later despite treatment with highly active anti-retroviral drugs and an undetectable plasmatic viral load, acitretin without NSAID or topical treatment was again administered and was rapidly effective.