Drug-induced aseptic meningitis (DIAM) has been reported as an uncommon adverse reaction with numerous agents. It is a diagnosis of exclusion, and clinical signs and CSF findings vary greatly. The body of evidence regarding DIAM is largely in the form of anecdotal case reports and must be interpreted carefully bearing this in mind. The major categories of causative agents are nonsteroidal anti-inflammatory drugs, antimicrobials, intravenous immunoglobulin, intrathecal agents, vaccines and a number of other less frequently reported agents. There appears to be an association between DIAM and connective tissue disease, particularly systemic lupus erythematosus, and ibuprofen. There are 2 major proposed mechanisms for DIAM. The first involves direct irritation of the meninges by intrathecal administration of the drug, and the second involves immunological hypersensitivity to the drug, most likely type III and type IV hypersensitivity. Recognition and diagnosis of DIAM is important, as it is treatable by withdrawal of the drug and recurrence is prevented. The outcome of DIAM is generally good, usually without long term sequelae. This article describes the case reports of DIAM in the current literature and discusses the diagnosis and management of this rare complication.

Drug-induced aseptic meningitis: diagnosis and management.

Azole antifungals are first-line options in the prophylaxis and treatment of invasive fungal infections. They are often used for prolonged (weeks to months) periods of time, particularly in patients with hematologic malignancies, or in those who have received a solid organ or hematopoietic stem cell transplant. Long-term use of azoles is associated with hepatotoxicity and hormone-related effects, including gynecomastia, alopecia, decreased libido, oligospermia, azoospermia, impotence, hypokalemia, hyponatremia, and (rarely) adrenal insufficiency. Voriconazole and posaconazole have been associated with peripheral neuropathies, and itraconazole and voriconazole with pancreatitis. In addition, voriconazole has been associated with periostitis, phototoxic reactions, and squamous cell carcinoma. Since many at-risk patients are commonly receiving multiple medications, it can be difficult for care providers to identify antifungal agent causality or contribution to patient symptoms. Knowledge and recognition of adverse events caused by azoles, leading to dose reduction or discontinuation, can generally reverse these adverse events.

Adverse Effects Associated with Long-Term Administration of Azole Antifungal Agents.

Itraconazole is an orally administered triazole antifungal agent. Its spectrum of activity includes dermatophyte, dimorphic and dematiaceous fungi, yeasts, and some moulds. In clinical trials, mycological cure was attained in approximately 70 to 80, > or = 70 and > or = 80% of patients with, respectively, fingernail and toenail onychomycosis (200 mg/day for 3 months), dermatophytosis (100 mg/day for 2 to 4 weeks) and vaginal candidiasis (400 mg/day for 1 day or 200 mg/day for 3 days). Approximately 20 to 30% of patients with onychomycosis may relapse after completion of therapy; relapse rate data are limited for the other indications. Recently developed intermittent regimens of itraconazole (400 mg/day for 1 week per month for 3 to 4 months) appear to have similar efficacy to standard regimens in the treatment of onychomycosis. Shorter, higher dosage itraconazole treatment regimens (200 or 400 mg/day for 1 week) are also beneficial in dermatomycoses. Discrepancies and limitations of study design hamper conclusions about efficacy relative to other antifungal drugs. Newer intermittent and short course higher dosage itraconazole regimens have also not been evaluated in comparative studies. Available studies show that the efficacy of itraconazole appears to be greater than that of griseofulvin, but similar to or lower than that of terbinafine in patients with dermatophyte onychomycosis or cutaneous fungal infections. Moreover, the efficacy of itraconazole may be similar to or lower than that of fluconazole in the treatment of cutaneous mycoses. Comparative data from patients with acute vaginal candidiasis suggest that itraconazole is at least as effective as intravaginal clotrimazole and oral fluconazole, and superior to intravaginal econazole. These results require confirmation. Prescription-event monitoring data indicate that itraconazole is generally well tolerated. Gastrointestinal disturbances, dizziness and headache occur most commonly; liver toxicity has been rarely described. Its usefulness in some clinical situations may be limited because of its ability to interact with various therapeutic agents. In conclusion, itraconazole along with other established agents should be considered a first-line treatment for patients with extensive or recalcitrant cutaneous fungal infections, mixed dermatophyte and Candida onychomycosis or vaginal candidiasis. It is currently considered a second-line drug for dermatophyte onychomycosis; the use of newer intermittent itraconazole treatment regimens may, however, extend its role in the management of this condition. Although itraconazole offers greater benefit than conventional therapies (griseofulvin and ketoconazole) in terms of efficacy and tolerability, wider clinical experience is required to determine its merits relative to the newer agents, terbinafine and fluconazole.

Itraconazole. A reappraisal of its pharmacological properties and therapeutic use in the management of superficial fungal infections

Tinnitus and hearing loss, both reversible and irreversible, are associated both with acute intoxication and long term administration of a large range of drugs. The mechanism causing drug-induced ototoxicity is unclear, but may involve biochemical and consequent electrophysiological changes in the inner ear and eighth cranial nerve impulse transmission. Over 130 drugs and chemicals have been reported to be potentially ototoxic. The major classes are the aminoglycosides and other antimicrobials, anti-inflammatory agents, diuretics, antimalarial drugs, antineoplastic agents and some topically administered agents. Prevention of drug-induced ototoxicity is generally based upon consideration and avoidance of appropriate risk factors, as well as on monitoring of renal function, serum drug concentrations, and cochlear and auditory functions before and during drug therapy. Ototoxicity, although not life-threatening, may cause considerable discomfort to patients taking ototoxic drugs, and in some cases drug discontinuation may be necessary to prevent permanent damage. Much research has been performed to investigate the causes and mechanisms of ototoxicity, to try to prevent this complication. Despite these efforts, ototoxicity still occurs, and there is much work to be done in order to understand the mechanism of ototoxicity of different drugs and to prevent hearing loss and tinnitus in the future.

Drug-Induced Tinnitus and Other Hearing Disorders

Methods and compositions for inhibition of angiogenesis with EM-138

INTRODUCTION: Extra-cutaneous manifestations of neutrophilic dermatosis are rare. Symptomatic cases are usually multiform and confusing. We report a case with an aseptic lymph node abscess associated with pyoderma gangrenosum. CASE REPORT: A 28-year-old woman with past history of pyoderma gangrenosum was seen for abdominal symptoms and fever related to an epigastric mass. Due to signs indicating abscess formation, surgery was performed and led to total regression of the symptomatology. Recurrence was evidenced 3 months later with skin lesions which were negative on bacteriological examinations. The diagnosis of lymph node manifestations of pyoderma gangrenosum was retained. General corticotherapy was very effective. Relapse occurred again 6 years later and was treated with thalidomide. DISCUSSION: Lymph node involvement has been described in Sneddon-Wilkinson's disease associated with pyoderma gangrenosum. In neutrophilic dermatosis, pulmonary manifestations appear to be the least exceptional of the extra-cutaneous lesions. The pathophysiology has not been elucidated although recent hypotheses suggest that G-CSF could be involved. Corticotherapy is remarkably effective in most cases but thalidomide could be an interesting alternative treatment.

Aseptic adenitis in pyoderma gangrenosum

Vertigo and hypokalemia. Two rare side effects of itraconazole

Aseptic meningitis during pyrazinamide therapy for lupus erythematosus

Meningite aseptique sous pyrazinamide lors de lupus erythemateux

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Aseptic adenitis in pyoderma gangrenosum

Vertigo and hypokalemia. Two rare side effects of itraconazole

Aseptic meningitis during pyrazinamide therapy for lupus erythematosus

Meningite aseptique sous pyrazinamide lors de lupus erythemateux