The addition of topical doxepin to corticosteroid therapy: an improved treatment regimen for atopic dermatitis.
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Biomedical subjects
Publications and source records attributed to D L Breneman.
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BACKGROUND: Topical corticosteroids are often used in the treatment of psoriasis, but long-term use may be associated with serious adverse events such as tachyphylaxis or atrophy of the skin. Tazarotene, a new topical retinoid, has demonstrated significant clinical benefits but can cause mild to moderate local irritation. OBJECTIVE: We evaluate whether a combination treatment of topical tazarotene and a topical corticosteroid would increase efficacy while reducing the incidence of local adverse events associated with a topical retinoid. METHODS: Three hundred patients enrolled in an investigator-masked study were randomly assigned to 1 of 4 treatment groups: tazarotene 0.1% gel in combination with placebo cream, or with a low-, mid-, or high-potency corticosteroid cream, for 12 weeks of treatment and a posttreatment follow-up at week 16. RESULTS: Tazarotene 0.1% gel in combination with a mid- or high-potency corticosteroid, when compared with tazarotene plus placebo cream, achieved significantly greater reductions in scaling, erythema, and overall lesional severity, and a decreased incidence of adverse events. CONCLUSION: All tazarotene combinations (including tazarotene plus placebo) were highly effective in rapidly reducing the severity of psoriasis. Combining tazarotene with a topical corticosteroid increased efficacy while reducing the incidence of local adverse events.
Cutaneous pseudolymphoma refers to a heterogeneous group of benign reactive T- or B-cell lymphoproliferative processes of diverse causes that simulate cutaneous lymphomas clinically and/or histologically. The inflammatory infiltrate is bandlike, nodular, or diffuse and is composed predominantly of lymphocytes with or without other inflammatory cells. Depending on the predominant cell type in the infiltrate, cutaneous pseudolymphomas are divided into T- and B-cell pseudolymphomas. Cutaneous T-cell pseudolymphomas include idiopathic cutaneous T-cell pseudolymphoma, lymphomatoid drug reactions, lymphomatoid contact dermatitis, persistent nodular arthropod-bite reactions, nodular scabies, actinic reticuloid, and lymphomatoid papulosis. Cutaneous B-cell pseudolymphomas include idiopathic lymphocytoma cutis, borrelial lymphocytoma cutis, tattoo-induced lymphocytoma cutis, post-zoster scar lymphocytoma cutis, and some persistent nodular arthropod-bite reactions. This review attempts to discuss current aspects of the classification, pathogenesis, clinical spectrum, histopathologic and immunohistochemical diagnosis, and laboratory investigations for clonality in the various types of cutaneous pseudolymphomas.
The efficacy and safety of a new formulation of metronidazole 1 percent cream applied once daily was compared to vehicle cream in a double-blind, randomized, parallel group, ten-week clinical study. The results showed that metronidazole 1 percent cream was significantly better than vehicle in reducing the lesions of rosacea, improving erythema, and physician's global rosacea scores. The incidence of adverse events related to the skin was low.
OBJECTIVE: To compare the safety and efficacy of cetirizine with that of hydroxyzine and placebo in the treatment of chronic idiopathic urticaria. DESIGN: A 4-week multicenter, randomized, double-blind, double-dummy, placebo-controlled safety and efficacy study. SETTING: Patients were treated in a variety of allergy practice settings. PATIENTS: The study population consisted of 188 patients who were at least 12 years of age, with symptomatic chronic idiopathic urticaria that had occurred episodically for at least 6 weeks. INTERVENTIONS: Patients were given either cetirizine 10 mg once daily, hydroxyzine 25 mg tid, or placebo for 4 weeks. MAIN OUTCOME MEASURES: Patients and investigators used a 4-point scale to evaluate symptoms of urticaria and adverse effects of treatment. Ratings were compared among those taking cetirizine, hydroxyzine, or placebo. RESULTS: After 1 day of treatment, patients randomized to receive cetirizine 10 mg/d exhibited a reduction in the number of episodes of urticaria (and a reduction in pruritus) compared with patients who received hydroxyzine 25 mg tid and patients who received placebo (p = 0.002). The number of urticarial episodes in patients treated with hydroxyzine did not reach significance until day 2 (p = 0.001). Compared with patients who received placebo, patients who received cetirizine and those who received hydroxyzine showed reductions during weeks 1, 2, and 3 and at end-point analysis in the number and size of lesions and in the severity of pruritus (p < 0.04). Patient and physician evaluations at the end of week 4 revealed an improvement in urticarial symptoms for the hydroxyzine and cetirizine groups compared with the placebo group (p < 0.001). Four patients in the hydroxyzine group, 1 patient in the cetirizine group, and 1 patient in the placebo group discontinued the study because of sedation. No patient withdrew because of lack of efficacy. CONCLUSIONS: Cetirizine 10 mg once daily was equivalent to hydroxyzine 25 mg tid in controlling the symptoms of patients with chronic urticaria, as assessed by patient and investigator evaluations.
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The introduction of new surgical techniques and other therapeutic modalities has markedly influenced the use of ionizing radiation therapy in dermatology. X-rays and electron beams are now used only for a limited number of indications in carefully selected patients. Since surgical approaches have gained popularity in the treatment of skin tumors, not all dermatologists are familiar with the benefits of ionizing radiation for patients with cutaneous neoplasms and certain other skin disorders. This article reviews modern indications for radiation therapy in dermatology. Important physical and biologic factors, radiation side effects, radiation protection measures, and therapeutic results will also be discussed. Although the use of radiotherapy in dermatology has in large part been supplanted in recent years by other forms of treatment, ionizing radiation continues to be an essential therapeutic alternative for many cutaneous tumors and some skin diseases. It is important to be familiar with the principles of radiotherapy so that optimal therapy can be selected for individual patients.
BACKGROUND AND DESIGN: The combination of nicotinamide and tetracycline has been anecdotally reported to be effective in the treatment of bullous pemphigoid. We conducted a randomized, open-labeled trial comparing the combination of 500 mg of nicotinamide, three times daily, and 500 mg of tetracycline four times daily, with prednisone therapy in 20 patients with bullous pemphigoid. The study was divided between an 8-week acute phase with fixed drug dosages and a 10-month follow-up phase in which study medications were tapered based on patient response. RESULTS: Eighteen of 20 patients enrolled in the study were treated, two patients were unavailable for follow-up. Twelve patients were treated with the combination of nicotinamide and tetracycline and six patients were treated with prednisone. There were five complete responses, five partial responses, one nonresponder, and one patient with disease progression in the nicotinamide and tetracycline group compared with one complete response and five partial responses in the prednisone group. There were no statistically significant differences in response parameters between the two groups. All five patients in the nicotinamide and tetracycline group receiving long-term follow-up remained disease free during medication tapering, while three patients in the prednisone group had repeated disease flare-ups with steroid tapering. Adverse effects in the nicotinamide and tetracycline group included gastrointestinal upset (two patients) and transient renal failure (one patient). In the prednisone group, there was one occurrence each of hypertension, erosive gastritis, multiple decubitus ulcers, osteomyelitis, deep venous thrombosis, and death related to sepsis. Two patients required insulin therapy for hyperglycemia. CONCLUSIONS: The combination of nicotinamide and tetracycline appears to be a useful alternative to systemic steroids in the treatment of bullous pemphigoid.
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Six double-blind, independently randomized studies evaluated the efficacy and safety of calcium mupirocin ointment in eliminating nasal carriage of Staphylococcus aureus among health care workers. Healthy volunteers with stable nasal carriage of S. aureus (n = 339) received either calcium mupirocin ointment (n = 170) or an identical placebo ointment (n = 169) intranasally for 5 days. Nasal carriage was eliminated 48-96 hours after completion of treatment in 130 (91%) of 143 evaluable volunteers receiving mupirocin but in only 8 (6%) of 142 evaluable volunteers receiving placebo. The 85% crude difference represents a 90% pooled (adjusted) estimate of the risk difference (95% confidence interval, 0.86-0.95) and a risk ratio of 16 (P < .0001). This effect of treatment with mupirocin was observed consistently (risk ratio, 8-32) in all six centers. In addition, 96 of the 130 mupirocin-treated volunteers and 1 of the 8 placebo-treated volunteers who were culture-negative at the end of therapy remained free of S. aureus 4 weeks after treatment. Adverse events in each treatment arm were mild and equally frequent. These data, consistent across six institutions, demonstrate that calcium mupirocin ointment administered intranasally for 5 days is safe and effective in eliminating stable nasal carriage of S. aureus.
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Pruritus is a significant problem for many patients undergoing long-term hemodialysis. Topical capsaicin depletes and prevents the reaccumulation of substance P in peripheral sensory neurons. Substance P functions in the transmission of pain and probably itch sensations. An open-label, uncontrolled trial and a double-blind, vehicle-controlled trial were conducted to evaluate the efficacy and safety of capsaicin 0.025% cream in the treatment of localized areas of pruritus in patients undergoing long-term hemodialysis. Eight of nine evaluable patients in the open-label trial reported marked relief or complete resolution of itching during the study period, and two of five evaluable patients in the double-blind trial reported complete resolution of itching in the capsaicin-treated arm with no or minimal improvement in the vehicle-treated arm. Twelve patients in the open-label trial and two in the double-blind trial were unevaluable. No serious treatment-related adverse reactions occurred.
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PURPOSE: This phase II study was undertaken to assess the efficacy and toxicity of alternating administration of pentostatin (deoxycoformycin [DCF]) and interferon alfa-2a (IFN) in patients with advanced or refractory mycosis fungoides (MF) or the Sézary syndrome (SS). PATIENTS AND METHODS: Forty-one patients underwent therapy with alternating cycles of DCF 4 mg/m2 intravenously (IV) days 1 through 3 and IFN 10 million U/m2 intramuscularly (IM) day 22, and 50 million U/m2 intramuscularly (IM) days 23 through 26. Twenty-nine patients had not responded to prior chemotherapy or total-skin electron-beam irradiation (TSEB), six had not responded to topical therapies, and six had no previous treatment. RESULTS: Two patients achieved a complete response (CR) and 15 achieved a partial response (PR), for an overall response rate of 41% (95% confidence interval, 26% to 58%). No responses were observed in the seven patients with visceral involvement. The median progression-free survival of patients who responded was 13.1 months. IFN-related constitutional symptoms were reported in 39% of patients; severe toxicities included cardiomyopathy in one patient, acute and chronic pulmonary dysfunction in four, and reversible mental status changes in two. Seven patients developed herpes zoster during therapy and six had staphylococcal bacteremia. CONCLUSION: These results suggest that the combination of DCF and IFN is an active regimen in MF patients without visceral involvement.
Topical mechlorethamine hydrochloride is commonly used in the treatment of mycosis fungoides and has been formulated in both aqueous and ointment vehicles. Two concerns regarding the topical application of mechlorethamine hydrochloride relate to the adequacy of skin coverage that can be attained by the patient and the extent to which others in the patient's household might be exposed to the drug. In this study six patients applied either aqueous or ointment vehicles containing a fluorescent dye. Subsequent examination of the skin under a Wood's lamp revealed a significant percentage of body surface area to be missed during application; several areas were noted to be missed most commonly. These observations have led to specific alterations in instructions given to patients regarding drug application. Examination of the surrounding environment showed minimal evidence of contamination.
A transdermal patch for the OTC antihistamine, triprolidine (TP), might provide benefits in terms of increased efficacy and reduced sedative side effects. However, concerns over potential irritant or allergic contact sensitization (ACS) skin reactions necessitated through skin toxicity testing before and during initial clinical development. Initial effort was expended on development of a binary vehicle delivery system comprised of TP in 0.5% oleic acid (OA) in propylene glycol (PG). Rabbit skin irritation and Buehler guinea pig skin sensitization testing indicated that this TP/OA/PG formula had both skin irritation and ACS potential. Both tests underestimated, to some degree, the skin toxicities observed in later clinical testing. In clinical tests, skin irritation was due mainly to the OA/PG vehicle, but was enhanced in the presence of high TP concentrations. Of 26 subjects enrolled in a rising dose clinical pharmacokinetics study, one subject exposed twice to TP/OA/PG presented with delayed skin reactions suggestive of ACS. Positive diagnostic patch test results for this subject and four out of five other twice-exposed study subjects suggested that the TP/OA/PG formula had a very high ACS potential. Subsequent predictive clinical patch testing was conducted with a buffered aqueous TP formula which provided in vitro skin penetration of the drug equivalent to the TP/OA/PG formula. These clinical studies demonstrated that TP itself had no significant irritation potential but still induced ACS reactions in a high proportion of test subjects. The incidence of adverse skin reactions to TP was considered to be too high relative to the degree of improved therapeutic benefit of this delivery form. On this basis, all technology development effort was discontinued.
BACKGROUND: -The anticonvulsant hypersensitivity syndrome is characterized by the development of fever, rash, lymphadenopathy, and hepatitis, and is associated with leukocytosis and eosinophilia. This article describes the unusual development of a follicular pustular eruption in two patients as a manifestation of this syndrome. OBSERVATIONS: -This pustular eruption most commonly develops on the face and scalp but may subsequently become generalized. While cultures of the pustules are negative, biopsy specimens reveal a dilated follicular infundibulum filled with neutrophils. Recognition of cutaneous pustulation as a potential manifestation of this syndrome is important, as a generalized pustular eruption developing in a febrile patient can easily be confused with an infectious process. CONCLUSIONS: -The anticonvulsant hypersensitivity syndrome may present with a follicular pustular eruption rather than the more commonly associated macular or papular rash or erythroderma. The three most commonly used anticonvulsants, phenytoin, phenobarbital, and carbamazepine, can each produce an identical hypersensitivity reaction. In addition, in vitro testing has demonstrated that approximately 80% of patients tested to all three medications had positive reactions to each. Furthermore, with in vitro testing researchers are able to predict which anticonvulsants are safe to use, thereby allowing for prospective individualization of therapy. However, this technology is not yet available for widespread use.
The human immunodeficiency virus type 1 (HIV-1) has been isolated from a number of body fluids, including semen, tears, cerebrospinal fluid, saliva, breast milk, alveolar fluid, and vaginal fluid, but it has not been isolated from fluid-containing skin lesions. We report the isolation of HIV-1 from cutaneous blister fluid in a patient with concomitant HIV-1 infection and porphyria cutanea tarda. Although transmission of HIV-1 through casual contact has not been reported, appropriate precautions should be taken to avoid direct contact with cutaneous fluid-containing lesions in HIV-1-positive patients.