Laurie A. MacPhail

Thalidomide for the treatment of oral aphthous ulcers in patients with human immunodeficiency virus infection

BACKGROUND In patients with advanced human immunodeficiency virus (HIV) infection, aphthous ulceration of the mouth and oropharynx can become extensive and debilitating. Preliminary reports suggest that thalidomide may promote the healing of oral aphthous ulcers. METHODS We performed a double-blind, randomized, placebo-controlled study of thalidomide as therapy for oral aphthous ulcers in HIV-infected patients. The patients received a four-week course of either 200 mg of thalidomide or placebo orally once per day. They were evaluated weekly for the condition of the ulcers, their quality of life, and evidence of toxicity. Assays were performed for plasma tumor necrosis factor alpha (TNF-alpha), soluble TNF-alpha receptors, and HIV RNA. RESULTS Sixteen of 29 patients in the thalidomide group (55 percent) had complete healing of their aphthous ulcers after four weeks, as compared with only 2 of 28 patients in the placebo group (7 percent; odds ratio, 15; 95 percent confidence interval after adjustment for group sequential testing, 1.8 to 499; unadjusted P<0.001). Pain diminished and ability to eat improved with thalidomide treatment. The adverse effects noted with thalidomide included somnolence and rash (7 patients each), and 6 of the 29 patients discontinued treatment because of toxicity. Thalidomide treatment increased HIV RNA levels (median increase, 0.42 log10 copies per milliliter; increase with placebo, 0.05; P=0.04). With thalidomide treatment there were unexpected increases in the plasma concentrations of TNF-alpha and soluble TNF-alpha receptors. CONCLUSIONS Thalidomide is an effective treatment for aphthous ulceration of the mouth and oropharynx in patients with HIV infection.

Effect of highly active antiretroviral therapy on frequency of oral warts

To investigate changes in the pattern of oral disease associated with highly active antiretroviral therapy (HAART), we assessed the frequency of these lesions in our clinic over 9 years. We retrospectively studied 1280 patients seen between July, 1990, and June, 1999, and related oral findings to medication use, immune function, and viral load. We found significant decreases in oral candidosis, hairy leucoplakia, and Kaposis sarcoma over time, but no change in the occurrence of aphthous ulcers. There was an increase in salivary-gland disease and a striking increase in warts: three-fold for patients on antiretroviral therapy and six-fold for those on HAART (p=0.01). This pattern of oral disease in a referral clinic suggests that an increase in oral warts could be occurring as a complication of HAART.

Thalidomide for the treatment of esophageal aphthous ulcers in patients with human immunodeficiency virus infection

A multicenter, double-blind, randomized, placebo-controlled clinical trial was conducted to determine the safety and efficacy of thalidomide for treating esophageal aphthous ulceration in persons infected with human immunodeficiency virus (HIV). Twenty-four HIV-infected patients with biopsy-confirmed aphthous ulceration of the esophagus were randomly assigned to receive either oral thalidomide, 200 mg/day, or oral placebo daily for 4 weeks. Eight (73%) of 11 patients randomized to receive thalidomide had complete healing of aphthous ulcers at the 4-week endoscopic evaluation, compared with 3 (23%) of 13 placebo-randomized patients (odds ratio, 13.82; 95% confidence interval, 1.16-823.75; P=.033). Odynophagia and impaired eating ability caused by esophageal aphthae were improved markedly by thalidomide treatment. Adverse events among patients receiving thalidomide included somnolence (4 patients), rash (2 patients), and peripheral sensory neuropathy (3 patients). Thalidomide is effective in healing aphthous ulceration of the esophagus in patients infected with HIV.

THE PRO-SELF MOUTH AWARE PROGRAM : AN EFFECTIVE APPROACH FOR REDUCING CHEMOTHERAPY-INDUCED MUCOSITIS

Many oncology patients receive chemotherapy drugs that have the potential to induce oral mucositis. If mucositis is not prevented, patients will have to manage the problems associated with mucositis: pain, local infection, and decreased ability to take fluids or food. At the time of this writing, clinical approaches for mucositis management are variable and generally ineffective. The mouth care program, PRO-SELF: Mouth Aware (PSMA), presented in this article, was found to be a significant component of a self-care program that may have reduced the incidence of chemotherapy-induced mucositis. The PSMA program has three dimensions: (a) didactic information, (b) development of self-care exercises (skills), and (c) supportive interactions with a nurse in the setting where the patients are receiving their treatment. This program focuses on decreasing the direct (i.e., incidence and severity of mucositis) and indirect morbidities of oral mucositis (i.e., number of local infections, level of discomfort/pain, and disruption in fluid and/or food intake). It provides the critical dimensions (i.e., specific information, self-care exercises, and nurse support) to promote the prevention of mucositis. The PSMA program is designed to provide patients with a definitive self-care repertoire to manage chemotherapy-induced mucositis in the home without the direct supervision of a health care provider.

Recurrent aphthous ulcers in association with HIV infection: Description of ulcer types and analysis of T-lymphocyte subsets

This study was conducted to characterize the recurrent aphthous ulcers (RAU) found in association with human immunodeficiency virus (HIV) infection, to examine evidence for increased severity of the ulcers with HIV disease, and to determine whether increased severity is associated with abnormalities of peripheral blood lymphocyte subsets. Seventy-five HIV-seropositive patients with RAU were followed for up to 2 years, and lymphocyte subsets were analyzed in 42. Minor, herpetiform, and major ulcer types were seen, but unexpectedly, 66% of the patients had the usually uncommon herpetiform and major types. These types were temporally associated with symptomatic HIV disease. Patients with major RAU were significantly more immunosuppressed than those with minor or herpetiform RAU in that they had fewer CD4 and CD8 lymphocytes (p less than 0.05). The lesion of RAU is considered to represent a local breakdown in immunoregulation. The systemic immune imbalance seen with HIV disease may amplify the local defect and lead to more severe ulcers.

Fluconazole-resistant Candida in AIDS patients: Report of two cases

Oropharyngeal candidiasis develops in up to 95% of patients with acquired immunodeficiency syndrome. Oral fluconazole is frequently prescribed for persons who are human immunodeficiency virus-seropositive as initial or suppressive therapy for oropharyngeal and esophageal candidiasis or as suppressive therapy for cryptococcal meningitis. We report two cases of oropharyngeal candidiasis, caused by Candida albicans, which developed in two patients with acquired immunodeficiency syndrome who had taken fluconazole for extended periods. In addition to the clinical resistance we observed, isolates of the organism appeared to be resistant in vitro to fluconazole and ketoconazole.

Risk Factors for Chemotherapy-Induced Oral Mucositis: Dental Appliances, Oral Hygiene, Previous Oral Lesions, and History of Smoking

Oral mucositis is one of the dose-limiting toxicities of several chemotherapy (CTX) agents. There are suggested risk factors that could influence the development of mucositis. The presence of dental appliances, history of oral lesions, or smoking have the potential to irritate the oral mucosa and produce breaks in the integrity of the mucosa. The purposes of this study were to determine if there were differences in the incidence, severity, and time to onset of CTX-induced mucositis in oncology outpatients who wore dental appliances, had a history of oral lesions, had varying oral hygiene/care practices, and had a history of smoking and those who did not. Patients who were initiated a course of CTX that included stomatotoxic agents were followed for three complete cycles of CTX. They were instructed on how to examine their mouths for mucositis, to contact, and then visit their outpatient settings if it occurred. Clinicians corroborated the presence of mucositis, and the Eilers Oral Assessment Guide was used by clinicians to determine the severity. Of 332 outpatients, almost half (46%) wore some type of dental appliance, 32% had a history of oral lesions, 10% were currently smoking, and 63% had a history of smoking. Oral hygiene/care practices varied: 81% brushed their teeth two or more times a day, 29% flossed at least daily, 11% had visited their dentist within 2 months of beginning CTX, and 10% had their teeth professionally cleaned within two months of beginning CTX. There was a 31% (n = 104) incidence of CTX-induced mucositis. No significant differences were found in the incidence between patients who wore dental appliances, had a history of oral lesions, had a history of smoking, and practiced different hygiene/care and patients who did not. Of 104 patients who developed mucositis, the average severity rating was 13.05 +/- 2.88 (+/-SD) (a normal mouth is rated at 8) and the average time to onset was 22.3 +/- 21.46 days. There were no significant differences found in severity or time to onset of mucositis between patients who wore dental appliances, had a history of oral lesions, had a history of smoking, and practiced different dental hygiene/care and patients who did not. Although not significant, there were interesting differences in the time to onset across the suggested risk factors (e.g., patients who had visited a dentist or who had their teeth professionally cleaned within 2 months before beginning before CTX developed mucositis 7.4 and 10.6 days sooner, respectively, than patients who did not). These findings suggest that risk factors for the development of CTX-induced mucositis are not as simple and direct as clinicians may believe.

Mechanisms for radiation-induced oral mucositis and the consequences.

Radiation therapy remains the primary method of treatment for patients with head and neck cancer. The tissue destruction and functional alterations in the oral cavity lead to the development of oral mucositis. The purpose of this review is to describe the mechanisms, risk factors, prevalence, and magnitude of radiation therapy-related oral mucositis and its morbidities in patients with head and neck cancer. The review concludes with a discussion of the implications for clinical practice. This review provides cancer nurses with the information necessary to identify patients with head and neck cancer who are at high risk for oral mucositis and the significant comorbidities associated with this complication of radiation therapy.

A Research Review of the Current Treatments for Radiation-Induced Oral Mucositis in Patients With Head and Neck Cancer

PURPOSE/OBJECTIVES To review the research studies on the current treatments for radiation therapy-(RT-) induced mucositis in patients with head and neck cancer. DATA SOURCES MEDLINE search of the literature from 1966-2001. DATA SYNTHESIS Four types of agents (i.e., antimicrobial, coating, anti-inflammatory, and cytokine-like agents) have been evaluated for the management of RT-induced oral mucositis in patients with head and neck cancer. Most of the published studies had relatively small sample sizes and used inconsistent measures to evaluate the extent and severity of oral mucositis. Therefore, definitive conclusions regarding the effectiveness of any of the agents tested in the prevention and treatment of RT-induced oral mucositis cannot be drawn. CONCLUSIONS Oral mucositis remains the most common complication among patients with head and neck cancer. Although a number of strategies and products are being investigated and new directions are promising, the therapies tested to date have not produced consistent results. IMPLICATIONS FOR NURSING The most effective measure to treat RT-induced mucositis in patients with head and neck cancer is frequent oral rinsing with a bland mouthwash, such as saline or a sodium bicarbonate rinse, to reduce the amount of oral microbial flora. Dental care, consistent oral assessments, and the initiation of a standardized oral hygiene protocol before the initiation of cancer treatment are the most effective approaches for oral mucositis.

Acyclovir-resistant, foscarnet-sensitive oral herpes simplex type 2 lesion in a patient with AIDS

We report the case of an immunocompromised patient with AIDS in whom developed a perioral and several intraoral HSV 2 lesions that persisted for more than 1 year. The virus was resistant to acyclovir but was sensitive to foscarnet. Viral isolates were thymidine kinase negative. The lesions resolved with intravenous foscarnet therapy given over a 15-week period, and when last seen, 8 months after foscarnet was discontinued, the patient had not had a recurrence.