Esomeprazole-induced central fever with severe myalgia.

OBJECTIVE: To report a case of central fever associated with severe myalgia following esomeprazole. CASE SUMMARY: A 64-year-old man presented with intense cephalalgia; severe, diffuse myalgia; and fever (>40 degrees C) after esomeprazole initiation for treatment of gastritis. Five hours after ingestion of the first esomeprazole pill (40 mg), the patient developed fever associated with cephalalgia and myalgia. This condition lasted about 40 hours and disappeared spontaneously. Symptoms partially responded to acetaminophen. Four days later, the patient received a second dose of esomeprazole 40 mg. Subsequently, 4 hours later, fever (>40 degrees C), headache, and difficulty in the movement of all parts of the body recurred. Neurologic examination was negative except for a minor state of disorientation. All reflexes were normal or slightly decreased. No skin lesions or breathing difficulty was noted. Routine blood tests were normal. Again, symptoms resolved spontaneously about 40 hours later. DISCUSSION: The temporal connection between esomeprazole intake and the onset of fever suggests a probable causal link, as confirmed by the Naranjo probability scale. However, the pathogenic mechanism remains unclear. Considering that esomeprazole is able to cross the blood-brain barrier, its peak serum concentration is reached 90-180 minutes after oral administration, and its serum half-life is approximately 2 hours, we assume that the appearance of fever with accompanying neurologic and muscular symptoms might result from the drug interference with the hypothalamic regulatory center of body temperature. CONCLUSIONS: Hyperpyrexia of central origin associated with intense cephalalgia and myalgia may occur as an adverse effect of esomeprazole therapy.

Myalgias and arthralgias associated with paclitaxel.

Paclitaxel-induced myalgias and arthralgias occur in a significant fraction of patients receiving therapy with this taxane, potentially impairing physical function and quality of life. Paclitaxel-induced myalgias and arthralgias are related to individual doses; associations with the cumulative dose and infusion duration are less clear. Identification of risk factors for myalgias and arthralgias could distinguish a group of patients at greater risk, leading to minimization of myalgias and arthralgias through the use of preventive therapies. Optimal pharmacologic treatment and possibilities for the prevention of myalgias and arthralgias associated with paclitaxel are unclear, partially due to the small number of patients treated with any one medication. The effectiveness of nonsteroidal anti-inflammatory drugs (NSAIDs) is the most frequently documented pharmacologic intervention, although no clear choice exists for patients who fail to respond to NSAIDs. However, the increasing use of weekly paclitaxel could necessitate daily administration of NSAIDs for myalgias and arthralgias and leave patients at risk for adverse effects. This concern may also limit the use of corticosteroids for the prevention and treatment of paclitaxel-induced myalgias and arthralgias. Data from case reports suggest that gabapentin (Neurontin), glutamine, and, potentially, antihistamines (e.g., fexofenadine [Allegra]) could be used to treat and/or prevent myalgias and arthralgias. Given the safety profile of these medications, considerable enthusiasm exists for evaluating their effectiveness in the prevention and treatment of paclitaxel myalgias and arthralgias, particularly in the setting of weekly paclitaxel administration.

Weekly 1-h paclitaxel infusion in patients with recurrent endometrial cancer: a preliminary study.

BACKGROUND: The aim of this study was to evaluate the toxicity and efficacy of weekly paclitaxel in patients with recurrent endometrial cancer. METHODS: Nine patients with recurrent endometrial cancer who had previously received chemotherapy or radiotherapy participated in the study, between May 1999 and August 2001. Paclitaxel was given at a dose of 70 mg/m(2) as a 1-h infusion every week for at least 20 consecutive weeks unless lesions became progressive. Intravenous dexamethasone and cimetidine and oral diphenhydramine were administered 30 min before paclitaxel infusion. RESULTS: The nine patients received a total of 149 cycles of therapy. No hypersensitivity reactions were elicited. Grade 3 leukopenia, neutropenia, and anemia occurred in 22%, 33%, and 33% of the patients, respectively. Granulocyte colony-stimulating factor was required for two patients and no patients experienced febrile neutropenia. Neurotoxicity was commonly observed. Grade 1 peripheral neuropathy and myalgias were observed in 78% and 11% of the patients, respectively. No grade 3 or higher nonhematological toxicities were observed. Partial responses were seen in six of the nine patients (67%). The median progression-free interval was 8 months (range, 0-12 months) and the median overall survival was 10 months (range, 4-24 months). CONCLUSION: Weekly 1-h paclitaxel administration is considered safe and effective as a salvage therapy for recurrent endometrial cancer, with this schedule and delivery making its use more convenient and easier in the outpatient setting. The current results support further evaluation.

Drug-induced myopathies.

Drug-induced muscle disorders represent a broad clinical spectrum, from asymptomatic elevated serum creatine kinase levels to life-threatening myopathies. An increasing number of drugs have been suspected or identified as myotoxic. It would be unrealistic to attempt to list them. In clinical practice, an iatrogenic origin must be discussed in any patient presenting with muscle symptoms in as much as drug-induced myopathies are usually reversible after discontinuation of the offending compound. The clinical and histopathological features depend on the causative agent and individual susceptibility to a given compound. Apart from isolated myalgias, drug-induced myopathies can be divided into five major categories: necrotising myopathies mainly due to lipid-lowering drugs; inflammatory myopathies, including polymyositis (especially associated with thiol compounds) and maphrophagic myofasciitis; mitochondrial myopathies, mainly due to antiretroviral nucleoside analogues; corticosteroid myopathy; and various forms of painless neuromyopathies. In some cases (e.g., statin-induced myopathies), risk factors have been clearly identified and preventive measures have been recommended.

Severe neuromuscular complications possibly associated with amlodipine.

OBJECTIVE: To document a case of severe, progressive myopathy, myalgias, arthralgias, and weakness possibly caused by amlodipine in a patient with benign essential hypertension. CASE SUMMARY: A 52-year-old white woman with asthma and newly diagnosed hypertension was initiated on zafirlukast therapy for asthma and amlodipine therapy for hypertension. Two months later, the patient reported severe, generalized muscle and joint pain, muscle stiffness, and weakness. The zafirlukast was discontinued without resolution of symptoms. Laboratory tests revealed an elevated C-reactive protein. The amlodipine dosage was increased. Her symptoms persisted and further laboratory tests revealed a positive anti-nuclear antibody screen, and negative single- and double-stranded DNA antibody tests. After another amlodipine dosage increase, the patient experienced a sudden onset of left-sided facial numbness, facial weakness, and a severe headache.The patient was admitted to rule out a possible cerebrovascular event or a metabolic neurologic process. Magnetic resonance imaging showed no abnormalities. The patient discontinued the amlodipine and reported complete resolution of the neurologic symptoms after 4 days. One month later, zafirlukast was reinitiated without a return of symptoms. CONCLUSIONS: Amlodipine was not initially suspected as a cause of these symptoms because these effects are not commonly associated with amlodipine therapy. However, due to the temporal relationship and progression of symptoms with increasing amlodipine dosage, drug-related causes were eventually explored. Review of the medical literature suggests myalgias and arthralgias may be adverse effects common to dihydropyridine calcium-channel antagonists.

Absent neutrophil alkaline phosphatase in the eosinophilia myalgia syndrome associated with L-tryptophan use.

The clinical constellation of leukocytosis, thrombocytosis, and low or absent stainable neutrophil alkaline phosphatase (NAP) is considered characteristic of chronic myelogenous leukemia (CML). CML with eosinophilic differentiation (eosinophilic leukemia) is well described, and leukemia and other clonal hematologic malignancies are associated with the syndrome of eosinophilic fasciitis. We describe leukocytosis, thrombocytosis, eosinophilia, mild basophilia, and absent stainable NAP, initially suggesting the diagnosis of CML in a patient with the eosinophilia myalgia syndrome associated with L-tryptophan use, a condition resembling eosinophilic fasciitis. Cytogenetic and molecular genetic studies failed to demonstrate a clonal proliferation of eosinophils.

Eosinophilic fasciitis is clinically distinguishable from the eosinophilia-myalgia syndrome and is not associated with L-tryptophan use.

Induration of the skin develops in a majority of patients with the eosinophilia-myalgia syndrome associated with L-tryptophan, and bears striking clinical and histopathological resemblance to eosinophilic fasciitis (EF). These similarities have led to the suggestion that eosinophilia-myalgia syndrome and EF are the same disease. To study the relationship of eosinophilia-myalgia syndrome and EF, we ascertained the prevalence of L-tryptophan use in a cohort of patients with EF, and compared their clinical and laboratory findings to those of patients with eosinophilia-myalgia syndrome associated cutaneous involvement. None of 11 patients who were diagnosed as having EF between 1970 and 1989 used L-tryptophan containing preparations prior to the onset of their illness. Marked clinical and laboratory test differences were observed between patients with EF and eosinophilia-myalgia syndrome. Patients with eosinophilia-myalgia syndrome had a more acute onset, more severe symptoms, higher frequency of rash and of pulmonary, cardiac, gastrointestinal, neurologic, myopathic and thyroid involvement compared to patients with EF. Corticosteroid therapy resulted in improvement of cutaneous involvement in 88% of patients with EF but it was only partially successful in patients with eosinophilia-myalgia syndrome. Hospitalization and fatalities occurred only among patients with eosinophilia-myalgia syndrome. These observations demonstrate that eosinophilia-myalgia syndrome is a more severe disease with multisystemic involvement that can be clinically distinguished from EF. In contrast to eosinophilia-myalgia syndrome, EF is not associated with L-tryptophan ingestion.

Prevention of succinylcholine myalgias: a meta-analysis.

Meta-analysis is a term used to describe statistical methods for evaluating a series of research reports; this analysis transcends the limitations that may be inherent in each of the individual studies summarized. Forty-five research reports of clinical trials for the prevention of myalgias after succinylcholine were assembled. Four classes of preventive drugs (nondepolarizing muscle relaxants, benzodiazepines, succinylcholine in "self-taming" doses, and local anesthetics) were reported in detail sufficient to allow for inclusion in a meta-analysis of clinical efficacy. Each study was summarized by determining the difference in the incidence of myalgias on the first postoperative day between treatment and control groups. A random-effects variance components approach was used. Seven meta-analyses were performed (atracurium, d-tubocurarine, gallamine, pancuronium, diazepam, succinylcholine in self-taming doses, and lidocaine). For each meta-analysis there was statistically significant heterogeneity among studies. Atracurium, d-tubocurarine, gallamine, pancuronium, diazepam, and lidocaine all significantly decreased the frequency of myalgias by about 30%. Succinylcholine in self-taming doses alone was not efficacious.