Drug-induced Causes Research Articles

Imaging of Multifocal and Diffuse Sclerotic Bone Lesions

Sclerotic bone lesions are encountered commonly in clinical practice. The differential diagnosis remains broad and includes traumatic, vascular, infectious, drug-induced, neoplastic, metabolic, myeloproliferative, developmental, and miscellaneous causes. This article seeks to discuss the various imaging findings in the most commonly encountered multifocal and diffuse sclerotic bone lesions with emphasis on differentiating features through imaging and clinical correlation.

Acquired idiopathic anhidrosis: A diagnosis often missed

Acquired idiopathic anhidrosis (AIA) is an uncommon entity characterized by anhidrosis in the absence of any neurologic or sweat gland abnormalities. The aim of this study was to characterize the clinical profile in a cohort of patients diagnosed with AIA at a tertiary dermatologic center. We retrospectively evaluated cases seen during a 10-year period. Inclusion criteria included all cases of generalized or partial anhidrosis with no obvious causes, confirmed by provocative starch-iodine sweat test. Ectodermal dysplasias, poral dysfunction from chronic dermatoses, autonomic dysfunction, and drug-induced causes were excluded. Fifteen Chinese patients were diagnosed with AIA, mostly healthy young men with no significant medical or drug history, with variable extent of body surface area involvement. Serum immunoglobulin E, a complete blood cell count, thyroid function test, and antinuclear antibody levels were unremarkable. Anhidrotic areas revealed normal eccrine appendages with mild perivascular and perieccrine lymphocytic infiltrate. There were no neurologic abnormalities. This was a retrospective study. Our study shows that AIA seems to be a heterogeneous group with no major dysfunction other than anhidrosis. Proper recognition and evaluation is paramount, especially for at-risk populations, so that appropriate measures on the prevention of heat injuries can be instituted.

Problem based review: The patient presenting with hyponatraemia

Hyponatraemia is the most common electrolyte anomaly and is associated with significant morbidity and mortality. Patients with severe hyponatraemia often present to acute medical units with non-specific symptoms which can progress to overt neurological manifestations. There are many causes of hyponatriaemia, the most common being drug-induced causes, particularly thiazide diuretics, and the Syndrome of Inappropriate ADH Secretion (SIADH). Initial assessment should include a careful evaluation of the patient’s volume status, which helps to identify the most likely cause. This article utilises a recent case which presented to our AMU to illustrate the importance of a careful and systematic assessment of patients presenting to hospital with hyponatraemia. The new vasopressin receptor antagonists are explored as an option for the management of severe hyponatraemia.

Saudi Guidelines on the Diagnosis and Treatment of Pulmonary Hypertension: Pulmonary arterial hypertension associated with connective tissue diseases.

The explosive growth of medical literature on pulmonary hypertension (PH) has led to a steady increase in awareness of this disease within the medical community during the past decade. The recent revision of the classification of PH is presented in in the main guidelines.Group 1 PH or pulmonary arterial hypertension (PAH) is a heterogeneous group and includes PH due to inheritable, drug-induced, and toxin-induced causes and to such underlying systemic causes as connective tissue diseases, human immunodeficiency viral infection, portal hypertension, congenital heart disease, and schistosomiasis.Systemic sclerosis (SSc) is an autoimmune multisystem disorder, which affects over 240 persons per million in the United States.[1] Its manifestations are not confined to the skin but may also involve the lungs, kidneys, peripheral circulation, musculoskeletal system, gastrointestinal tract, and heart.The outcome of PAH associated with SSc is worse when compared to other subtypes of PAH.In this review, we summarize available information about the pulmonary vascular and cardiac manifestations of SSc with special emphasis on their prognostic implications as well as the peculiarity of their detection.

Cutaneous T-Cell Lymphoma–Like Drug Eruption in an HIV-Positive Patient Taking Vancomycin and Rifampin

Cutaneous T-cell pseudolymphoma (CTPL) is a benign reactive T-cell lymphoproliferative subtype of pseudolymphoma. Some variants of CTPL can resemble the plaques of mycosis fungoides (MF). The vast majority of drug-induced cases have been associated with anticonvulsants. There is only one report in the literature documenting a case of vancomycin-induced CTPL. We report a cutaneous T-cell lymphoma-like eruption in a human immunodeficiency virus (HIV)-positive patient recently started on vancomycin and rifampin. A skin biopsy showed several histologic features of MF with immunohistochemical and T-cell receptor gene rearrangement studies suggestive of CTPL. This atypical T-cell reaction mimicking MF completely resolved on cessation of rifampin followed by vancomycin. Considering drug-induced causes of MF-like histologic changes is crucial to prevent unnecessary treatment for MF.

QT interval abnormalities: risk factors and perioperative management in long QT syndromes and Torsades de Pointes

Electrophysiological abnormalities of the QT interval of the standard electrocardiogram are not uncommon. Congenital long QT syndrome is due to mutations of several possible genes (genotype) that result in prolongation of the corrected QT interval (phenotype). Abnormalities of the QT interval can be acquired and are often drug-induced. Torsades de Pointes (TP) is an arrhythmia that is a result of aberrant repolarization/QT abnormalities. If not recognized and corrected quickly, QT interval abnormalities may precipitate potentially fatal ventricular dysrhythmias. The main mechanism responsible for the development of QT prolongation is blockade of the rapid component of the delayed rectifier potassium current (I kr), encoded for by the human-ether-a-go-go-related gene (hERG). The objectives of this review were (1) to describe the electrical pathophysiology of QT interval abnormalities, (2) to differentiate congenital from acquired QT interval abnormalities, (3) to describe the currently known risk factors for QT interval abnormalities, (4) to identify current drug-induced causes of acquired QT interval abnormalities, and (5) to recommend immediate and effective management strategies to prevent unanticipated dysrhythmias and deaths from QT abnormalities in the perioperative period.

Amisulpride-Induced Macrocytic Anemia

Back to table of contents Previous article Next article LettersFull AccessAmisulpride-Induced Macrocytic AnemiaSujit Sarkhel, M.B.B.S., M.D., D.P.M., Samir Kumar Praharaj, M.B.B.S., M.D., D.P.M., and Sayeed Akhtar, M.B.B.S., M.D., D.N.B.Sujit SarkhelSearch for more papers by this author, M.B.B.S., M.D., D.P.M., Samir Kumar PraharajSearch for more papers by this author, M.B.B.S., M.D., D.P.M., and Sayeed AkhtarSearch for more papers by this author, M.B.B.S., M.D., D.N.B.Published Online:1 Jan 2013https://doi.org/10.1176/appi.neuropsych.12010001AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail To the Editor: Amisulpride, an atypical antipsychotic used in treatment of both positive and negative symptoms of schizophrenia, has a benign adverse-effect profile.1 Commonly reported adverse effects include dose-related extrapyramidal syndromes, gastrointestinal, and sexual problems.2 A summary of product characteristics3 for amisulpride does not report any hematological toxicity. A PubMed search did not reveal any such association. We report a case of macrocytic anemia induced by amisulpride that reversed after discontinuation of the drug.Case ReportThe patient, a 29-year-old man, diagnosed with paranoid schizophrenia 10 years ago, presented with wandering behavior, suspiciousness, and unprovoked violence. Mental status revealed guarded attitude and constricted affect with grandiose and persecutory delusions. His mother had paranoid schizophrenia. His baseline investigations including complete hemogram; liver and renal function tests were normal. The patient responded to a combination of depot zuclopenthixol injection 200 mg every 3 weeks and olanzapine 7.5 mg/day without any emergent adverse effect. However, because of prominent negative symptoms, olanzapine was discontinued and tablet amisulpride 100 mg/day was added. After 2 months, he reported fatigability and, on examination, pallor was noted. Complete hemogram revealed macrocytic anemia (Hb 4.6 gm/dl; PCV 14.9%; MCV 119.2 fl; MCH 39.2 pg; MCHC 32.9%). There was no history of alcohol abuse, and nutritional status was adequate. His liver and renal function tests were within normal range. A possibility of amisulpride-induced macrocytic anemia was considered and the drug was discontinued, after which the affected hematological parameters normalized. A Naranjo ADR probability scale score of 4 suggested a possible association.4DiscussionIn our case, macrocytic anemia appeared within a few weeks of exposure to amisulpride, which improved after discontinuation of the suspected offending agent. Before initiation of amisulpride, baseline hematological indices were normal. There was no change in dietary intake during this period. Also, no folate or vitamin supplement was prescribed. Therefore, it is possible that amisulpride was the offending agent in our case.Macrocytic anemia is commonly associated with folate and vitamin B12 deficiency, among others. Besides alcohol, drug-induced causes of macrocytic anemia include sulphasalazine, methotrexate, hydantoins, valproate, and oral contraceptives.5–8 Although the exact mechanism is not known, folate deficiency, either by inhibition of absorption or interference with metabolism, has been commonly hypothesized.8 A similar mechanism is likely to have caused macrocytic anemia in our case.The recent edition of Meyler’s Side Effects of Psychiatric Drugs9 does not list any hematological adverse effects with amisulpride. Thus, our case study exemplifies that rare adverse effects, not previously reported in pre-marketing trials or post-marketing efficacy and safety studies, may occur during clinical use.Institute of Psychiatry, Institute of Postgraduate Medical Education and Research (IPGMER), Kolkata, IndiaDept. of Psychiatry, Kasturba Medical College, Manipal, Karnataka, IndiaCentral Institute of Psychiatry, Kanke, Ranchi, Jharkhand, IndiaCorrespondence: Samir Kumar Praharaj, M.B.B.S., M.D., D.P.M.; e-mail: [email protected]co.inReferences1 Leucht S: Amisulpride a selective dopamine antagonist and atypical antipsychotic: results of a meta-analysis of randomized controlled trials. Int J Neuropsychopharmacol 2004; 7(Suppl 1):S15–S20Crossref, Medline, Google Scholar2 Coulouvrat C, Dondey-Nouvel L: Safety of amisulpride (Solian): a review of 11 clinical studies. Int Clin Psychopharmacol 1999; 14:209–218Crossref, Medline, Google Scholar3 Solian SPC: (Date of revision March 2008); available at http://www.sanofi-aventis.co.uk/products/Solian_SPC.pdf; accessed on July 29, 2011Google Scholar4 Naranjo CA, Busto U, Sellers EM, et al.: A method for estimating the probability of adverse drug reactions. Clin Pharmacol Ther 1981; 30:239–245Crossref, Medline, Google Scholar5 Stebbins R, Bertino JR: Megaloblastic anaemia produced by drugs. Clin Haematol 1976; 5:619–630Medline, Google Scholar6 Grieco A, Caputo S, Bertoli A, et al.: Megaloblastic anaemia due to sulphasalazine responding to drug withdrawal alone. Postgrad Med J 1986; 62:307–308Crossref, Medline, Google Scholar7 Kornberg A, Segal R, Theitler J, et al.: Folic acid deficiency, megaloblastic anemia and peripheral polyneuropathy due to oral contraceptives. Isr J Med Sci 1989; 25:142–145Medline, Google Scholar8 Greer JP, Foerster J, Rodgers GM, et al.: Wintrobe’s Clinical Hematology, 12th Edition. Philadelphia, PA, Lippincott, Williams & Wilkins, 2009Google Scholar9 Aronson JK: Meyler’s Side Effects of Psychiatric Drugs. Oxford, UK, Elsevier, 2009Google Scholar FiguresReferencesCited byDetailsCited byAntipsychotic Drugs Volume 25Issue 1 Winter 2013Pages E10-E11 Metrics PDF download History Published online 1 January 2013 Published in print 1 January 2013

Unexplained Falls Are Frequent in Patients with Fall-Related Injury Admitted to Orthopaedic Wards: The UFO Study (Unexplained Falls in Older Patients)

To evaluate the incidence of unexplained falls in elderly patients affected by fall-related fractures admitted to orthopaedic wards, we recruited 246 consecutive patients older than 65 (mean age 82 ± 7 years, range 65–101). Falls were defined “accidental” (fall explained by a definite accidental cause), “medical” (fall caused directly by a specific medical disease), “dementia-related” (fall in patients affected by moderate-severe dementia), and “unexplained” (nonaccidental falls, not related to a clear medical or drug-induced cause or with no apparent cause). According to the anamnestic features of the event, older patients had a lower tendency to remember the fall. Patients with accidental fall remember more often the event. Unexplained falls were frequent in both groups of age. Accidental falls were more frequent in younger patients, while dementia-related falls were more common in the older ones. Patients with unexplained falls showed a higher number of depressive symptoms. In a multivariate analysis a higher GDS and syncopal spells were independent predictors of unexplained falls. In conclusion, more than one third of all falls in patients hospitalized in orthopaedic wards were unexplained, particularly in patients with depressive symptoms and syncopal spells. The identification of fall causes must be evaluated in older patients with a fall-related injury.

A 54 year-old man with a chronic cough — Chronic cough: don't forget drug-induced causes

A 54 year-old man consults about a long-standing cough: his wife encouraged him to attend as she was tired of hearing him cough all the time. He is a bit vague about when it started, but it must be ‘nearly a year’. He has consulted his usual general practitioner about the cough three times. Eight months ago he presented with a ‘chesty’ cough associated with a feverish illness and an upper respiratory tract infection; he was prescribed a course of antibiotics which he thinks might have slightly improved the cough, though it did not fully resolve. Two subsequent consultations resulted in a further course of antibiotics and a trial of a salbutamol inhaler, neither of which appear to have made any difference. The clinical notes record that his chest was ‘clear’ at each of these consultations. He describes himself as ‘generally well’, though he has been tired recently which he attributes to the long hours he is working. He smoked for about 15 years but quit in his mid-thirties.

Pathogenesis of HIV‐associated sensory neuropathy: evidence from in vivo and in vitro experimental models

HIV-associated sensory neuropathy (HIV-SN) is a frequent neurological complication of HIV infection and its treatment with some antiretroviral drugs. We review the pathogenesis of the viral- and drug-induced causes of the neuropathy, and its primary symptom, pain, based on evidence from in vivo and in vitro models of HIV-SN. Viral coat proteins mediate nerve fibre damage and hypernociception through direct and indirect mechanisms. Direct interactions between viral proteins and nerve fibres dominate axonal pathology, while somal pathology is dominated by indirect mechanisms that occur secondary to virus-mediated activation of glia and macrophage infiltration into the dorsal root ganglia. The treatment-induced neuropathy and resulting hypernociception arise primarily from drug-induced mitochondrial dysfunction, but the sequence of events initiated by the mitochondrial dysfunction that leads to the nerve fibre damage and dysfunction are still unclear. Overall, the models that have been developed to study the pathogenesis of HIV-SN, and hypernociception associated with the neuropathy, are reasonable models and have provided useful insights into the pathogenesis of HIV-SN. As new models are developed they may ultimately lead to identification of therapeutic targets for the prevention or treatment of this common neurological complication of HIV infection.

Many faces of angioedema

Angioedema of the intestinal tract is an infrequent but well-described cause of abdominal pain that can occur because of inherited, acquired, allergic, or drug-induced causes. Hereditary angioedema (HAE) is a genetic disorder that causes recurrent attacks of severe edema of various body parts, including the intestinal tract. Moderate to severe abdominal pain occurs in 43-93% of such attacks due to intestinal edema. Laryngeal edema is a potentially life-threatening manifestation. Failure to recognize and diagnose HAE or other causes of intestinal angioedema can lead to years of delay in diagnosis, and in the case of HAE, often to unnecessary abdominal surgeries. Recognizing the typical history of recurrent attacks of abdominal pain, oropharyngeal/laryngeal angioedema or cutaneous angioedema, family history of similar symptoms, association of attacks with stress or menses, and exacerbation of attacks after administration of estrogens or angiotensin-converting enzyme inhibitors will increase diagnostic accuracy. Interdisciplinary treatment is often necessary after the diagnosis of HAE, first with acute management in the emergency room or the intensive care unit, followed by either drug prophylaxis against future attacks using a C1-esterase inhibitor concentrate or attenuated androgens and discontinuation of medications known to trigger attacks. Newer drugs approved for treatment of acute attacks may have future roles in the prevention of attacks if further studies support their efficacy. Gastroenterologists in particular should maintain a high index of suspicion for the possibility of HAE or other causes of intestinal angioedema in patients with a history of recurrent abdominal pain.

Renal Sarcoidosis Presenting as Acute Kidney Injury With Granulomatous Interstitial Nephritis and Vasculitis

Among the various renal manifestations of sarcoidosis, granulomatous inflammation confined to the tubulointerstitial compartment is the most commonly reported finding. We present the case of a 66-year-old man with acute kidney injury, hypercalcemia, mild restrictive pulmonary disease, and neurologic signs of parietal lobe dysfunction. Kidney biopsy showed diffuse interstitial inflammation with noncaseating granulomas that exhibited the unusual feature of infiltrating the walls of small arteries with destruction of the elastic lamina, consistent with granulomatous vasculitis. The findings of granulomatous interstitial nephritis on kidney biopsy, hypercalcemia, and possible cerebral and pulmonary involvement in the absence of other infectious, drug-induced, or autoimmune causes of granulomatous disease established the diagnosis of sarcoidosis. Pulse methylprednisolone followed by maintenance prednisone therapy led to improvement in kidney function, hypercalcemia, and neurologic symptoms. Vasculocentric granulomatous interstitial nephritis with granulomatous vasculitis is a rare and under-recognized manifestation of renal sarcoidosis.

Enzyme Histochemical Assessment of Mitochondrial Functions in Patients with Myopathic form of Limb-Girdle Syndrome

Isolated mitochondrial myopathy is characterized by slowly progressive limb-girdle muscle weakness and resembles other muscle disorders like muscular dystrophy or inflammatory myopathy on clinical grounds. Identification of abnormal mitochondria in the muscle tissue is required for the diagnosis of isolated mitochondrial myopathy. Therefore, this study was done with aim to identify patients with isolated mitochondrial myopathy among those with limb-girdle muscle syndromes of undefined cause. Forty-eight consecutive patients with limb-girdle muscle disease from 2008 to 2010 were screened for Duchenne/Becker muscular dystrophy gene deletion, metabolic myopathy, and drug-induced and endocrine causes. Twenty patients without an identifiable cause were subjected to muscle biopsy for hematoxylin and eosin staining and enzyme histochemistry. Clinical, biochemical, and electrophysiological features in all these patients with limb-girdle muscle disease were nonspecific, and no conclusion regarding the underlying cause could be drawn from these investigations. On hematoxylin and eosin staining, 12 patients were diagnosed as muscular dystrophy, inflammatory myopathy with characteristic appearance of polymyositis was diagnosed in 4 patients, and 3 patients had normal muscle histology. After enzyme histochemistry, one patient was identified having mitochondrial myopathy. A brief case summary of the only patient diagnosed as isolated mitochondrial myopathy in our study is presented.

Autoimmune Hepatitis Presenting with Profound Hyperferritinemia and Transaminitis

Purpose: Case: A 79-year-old male presented with a 3-week history of fatigue, painless jaundice, dark urine, clay-colored stools, and involuntary 5-kg weight loss. His history was negative for alcohol use, cancer, known liver disease, highrisk sexual practices, blood transfusions, intravenous drug use, or ill contacts. Labs showed AST=1305U/L, ALT=667U/L, alkaline phosphatase=284U/L, total bilirubin=32.5mg/dL, direct bilirubin=25.8mg/dL, INR=1.6, and ferritin level=16,900mcg/L. Abdominal CT showed cirrhotic liver configuration and abdominal ultrasound was unremarkable. Viral and drug-induced causes for hepatitis were excluded. Liver biopsy revealed lymphoplasmacytic infiltration without evidence of hemophagocytic syndrome or iron overload, suggesting autoimmune hepatitis (AIH) (Figure 1). Further lab evaluation revealed total protein=5.7 g/dL, albumin=2.6 g/dL, gamma-globulin=1.8 g/dL, positive antinuclear antibody=3.1U and negative anti-smooth muscle antibody. Prednisone 60 mg daily was started with initial decline of AST and ALT to the 100-300 level ranges. Despite 3 weeks of treatment, his mentation continued to decline from acute liver and renal failure. Given his poor prognosis, he received palliative care until his death. Discussion: This case highlights an unusual presentation of AIH in which an elderly male presented with extreme hyperferritinemia and liver failure. Previous data suggests that the differential diagnosis for liver disease with extremely elevated ferritin levels is limited and includes hemochromatosis, Still's disease, and hemophagocytic syndrome. The marked ferritin elevation in the setting of AIH has not, to our knowledge, been previously reported. Our case demonstrates that AIH should be considered in the differential when evaluating a patient with hyperferritinemia liver disease. The clinical presentation of AIH is markedly variable and liver failure can result if treatment is delayed.Figure 1: Liver biopsy suggests AIH. Biopsy shows moderate lymphoplasmacytic infiltrate and marked bile ductular proliferation. The zone 3 areas show focal hepatocyte necrosis.

PGE2-regulated wnt signaling and N -acetylcysteine are synergistically hepatoprotective in zebrafish acetaminophen injury

Acetaminophen (APAP) toxicity is the most common drug-induced cause of acute liver failure in the United States. The only available treatment, N-acetylcysteine (NAC), has a limited time window of efficacy, indicating a need for additional therapeutic options. Zebrafish have emerged as a powerful tool for drug discovery. Here, we developed a clinically relevant zebrafish model of APAP toxicity. APAP depleted glutathione stores, elevated aminotransferase levels, increased apoptosis, and caused dose-dependent hepatocyte necrosis. These outcomes were limited by NAC and conserved in zebrafish embryos. In a targeted embryonic chemical screen, prostaglandin E2 (PGE2) was identified as a potential therapeutic agent; in the adult, PGE2 similarly decreased APAP-associated toxicity. Significantly, when combined with NAC, PGE2 extended the time window for a successful intervention, synergistically reducing apoptosis, improving liver enzymes, and preventing death. Use of a wnt reporter zebrafish line and chemical genetic epistasis showed that the effects of PGE2 are mediated through the wnt signaling pathway. Zebrafish can be used as a clinically relevant toxicological model amenable to the identification of additional therapeutics and biomarkers of APAP injury; our data suggest combinatorial PGE2 and NAC treatment would be beneficial for patients with APAP-induced liver damage.

Drug allergy

Drug allergy is one type of adverse reaction to drugs and encompasses a spectrum of hypersensitivity reactions with heterogeneous mechanisms and clinical presentations. A thorough history is essential to the management of drug allergy. Laboratory testing has a very limited role in the management of drug allergy. Graded dose challenges and procedures to induce drug tolerance might be required in patients with drug allergy when there is a definite need for a particular agent. Management of reactions to specific agents, including beta-lactam antibiotics, sulfonamides, local anesthetics, radiocontrast media, angiotensin-converting enzyme inhibitors, nonsteroidal anti-inflammatory drugs, and biologic modifiers, will be discussed in further detail.

Mutism as the Presenting Symptom: Three Case Reports and Selective Review of Literature

Mutism, defined as an inability or unwillingness to speak, resulting in an absence or marked paucity of verbal output, is a common clinical symptom seen in psychiatric as well as neurology outpatient department. It rarely presents as an isolated disability and often occurs in association with other disturbances in behavior, thought processes, affect, or level of consciousness. It is often a focus of clinical attention, both for the physician and the relatives. Mutism occurs in a number of conditions, both functional and organic, and a proper diagnosis is important for the management. We hereby present three cases, who presented with mutism as the presenting symptom and the differential diagnosis and management issues related to these cases are discussed. The authors also selectively reviewed the literature on mutism, including psychiatric, neurologic, toxic-metabolic, and drug-induced causes.

Une cause rare de cyanose : sulfhémoglobinémie imputable au thiocolchicoside (Miorel ®)

An acquired abnormality of haemoglobin is among the many causes of cyanosis, especially in patients with no identified cardiorespiratory cause.A 50-year-old woman, suffering from amyotrophic lateral sclerosis, was hospitalised for dyspnoea. Physical examination revealed cyanosis that persisted despite oxygen therapy. Discordance between the reduced arterial oxygen saturation and normal arterial oxygen tension led to a search for a dyshaemoglobinaemia as a possible cause. Use of co-oxymetry with spectrophotometry revealed sulphaemoglobinaemia. Sulphaemoglobinaemia is due to irreversible incorporation of a thiol radical into the porphyrin ring of a haem group. This decreases the affinity of haemoglobin for oxygen and thus reduces oxygen carrying capacity. A drug-induced cause is often identified. However, no previously described cause for sulphaemoglobinaemia was identified in our patient. The patient was currently being treated with thiocolchicoside (Miorel((R))). Thiocolchicoside was suspected as the cause because its chemical structure contains an easily hydrolysable thiol radical. Withdrawal of thiocolchicoside led to regression of the sulphaemoglobinaemia.This report underlines the importance of searching for an acquired abnormality of haemoglobin (methaemoglobinaemia or sulphaemoglobinaemia) in patients with cyanosis resistant to oxygen, in the absence of any cardiorespiratory abnormality. This case is the first to suspect thiocolchicoside as a possible cause of sulphaemoglobinaemia.

Hypercaroténémie chez un nourrisson

Hypercarotenaemia is the consequence of high serum carotenoid levels, which are deposited in the stratum corneum and give a yellowish coloration to the skin. It can be distinguished from jaundice by the absence of colouring of the conjunctivae as well as orange discolouration of the palms and soles. We report a rare case of hypercarotenaemia in a child that began at the age of three months. Clinical signs and symptoms included yellowish discolouration of the skin, orange palms and soles, xerosis and pruritus. Hypercarotenaemia was confirmed by high levels of serum carotenoids. Serum vitamin A was normal. Dietary and drug-induced causes of hypercarotenaemia were excluded in this case, as well as other classical metabolic causes (renal insufficiency, malabsorption syndrome, diabetes, hypothyroidism). The child was placed on a low-carotenoids diet for six months, resulting in decreased serum carotenoid levels and regression of cutaneous signs and symptoms, especially pruritus. Although pruritus has never been reported in isolated hypercarotenaemia it is a classical sign of hypervitaminosis A. The mechanism of pruritus is not understood in this instance since vitamin A levels were normal. This case report is also unusual in that no classical cause of hypercarotenaemia was found, as a result of which we concluded on a likely defect in beta-carotene 15, 15'oxygenase, an enzyme involved in vitamin A production.

A Benchmark for Platelet Count Monitoring with Low-Molecular-Weight Heparin: Expanding Implementation of National Patient Safety Goals

Practitioners in US hospitals are implementing anticoagulation dosing and monitoring protocols to improve the safety of anticoagulation, consistent with National Patient Safety Goal 03.05.01. An audit of the Utrecht Patient Oriented Database of patients treated with low-molecular-weight heparin (LMWH) at the University Medical Center Utrecht revealed low compliance with platelet count monitoring as well as initial management of suspected heparin-induced thrombocytopenia (HIT). Limitations to this work included the inability to exclude other drug-induced causes of thrombocytopenia and their definition of the frequency of platelet count monitoring for compliance in patients given venous thromboembolism prophylaxis. Despite these limitations, the authors' work represents the first published report on extending the quality of heparin anticoagulation management to platelet count monitoring and evaluation for HIT in a large patient population. Clinicians should include evaluations of compliance with platelet count monitoring with unfractionated heparin and LMWH, as well as appropriateness of the initial management strategies for HIT, and direct thrombin inhibitor protocols in their patient safety practice assessments.