Safety issues with cyclosporine.
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Cyclosporine↗
Biomedical subjects
C N Ellis
Publications and source records attributed to C N Ellis.
Multiple warty dyskeratomas of the scalp.
Two patients presented with the unusual condition of multiple warty dyskeratomas on the scalp. Biopsies of affected skin stained positive with human keratin monoclonal antibodies HKN-6 and -7, specific for cortex and inner root sheath of normal human hair, respectively. Multiple warty dyskeratomas are a rare occurrence and their aetiopathogenesis remains elusive. Positive immunohistochemical staining of a lesion with antikeratin antibodies HKN-6 and -7, specific for human hair keratin, suggests a follicular origin for warty dyskeratoma.
Aged↗
Failure of topical polymyxin B to improve mild plaque psoriasis.
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Administration, Topical↗
Proceedings of the Psoriasis Combination and Rotation Therapy Conference. Deer Valley, Utah, Oct. 7-9, 1994.
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Administration, Cutaneous↗
A comparison of the efficacy and safety of adapalene gel 0.1% and tretinoin gel 0.025% in the treatment of acne vulgaris: a multicenter trial.
BACKGROUND: Adapalene is a new synthetic retinoid analogue developed for the topical treatment of acne vulgaris. OBJECTIVE: The study was designed to compare the efficacy and safety and adapalene gel 0.1% with tretinoin gel 0.025% in the treatment of grade II to II facial acne vulgaris. METHODS: Three hundred twenty-three patients were enrolled in this investigator-masked, randomized, parallel group, multicenter trial. Patients applied the test materials to the entire facial area daily, for a period of 12 weeks. Efficacy and cutaneous tolerance were assessed at baseline and weeks 2,4,8, and 12. Efficacy was determined by investigator counts of noninflammatory open and closed comedones, and inflammatory papules and pustules, as well as global improvement. Cutaneous tolerance was evaluated by erythema, scaling, and dryness, along with burning and pruritus. RESULTS: Staring at weeks 2 and 4, adapalene gel produced numerically greater lesion reductions than did tretinoin gel for all lesion types. At week 12, the mean percent reduction in the different lesion counts was as follow: 49% versus 37% for total lesions (p<0.01); 46% versus 33% for noninflammatory lesions (p=0.02); 48% versus 38% for inflammatory lesions (p=0.06) in adapalene and tretinoin gel treatment groups, respectively. Cutaneous side effects were limited to a mild "retinoid dermatitis" occurring in both treatment groups; however, patients treated with adapalene gel tolerated this therapy significantly better than those treated with tretinoin gel. Laboratory test evaluations (hematology, blood chemistries, urinalysis) were performed in 54 patients before and after 3 months of treatment. No clinically significant changes were observed. CONCLUSION: Adapalene gel 0.1% applied once daily was significantly more effective in reducing acne lesions and was better tolerated than tretinoin gel 0.025% in the treatment of acne vulgaris.
Acne Vulgaris↗
Topical tretinoin (retinoic acid) improves early stretch marks.
BACKGROUND AND DESIGN: Stretch marks are disfiguring lesions usually caused by excessive stretching of skin. We investigated the response of early, clinically active stretch marks to topical 0.1% tretinoin (retinoic acid) cream. In a double-blind, randomized, vehicle-controlled study, 22 patients applied either 0.1% tretinoin (n = 10) or vehicle (n = 12) daily for 6 months to the affected areas. Patients were evaluated by physical examination monthly and by analysis of biopsy specimens of stretch marks obtained before and at the end of therapy in comparison with untreated normal skin. RESULTS: After 2 months, patients treated with tretinoin had significant improvements in severity scores of stretch marks compared with patients who received vehicle (P < .05). After 6 months, eight (80%) of the 10 tretinoin-treated patients had definite or marked improvement compared with one (8%) of the 12 vehicle-treated patients (P = .002). Targeted stretch marks in patients treated with tretinoin had a decrease in mean length and width of 14% and 8%, respectively, compared with an increase of 10% (P < .001) and 24% (P = .008), respectively, in patients who received vehicle. There were no significant differences in various measures of quality and quantity of dermal collagen and elastic fibers in stretch marks when tretinoin and vehicle treatments were compared. CONCLUSIONS: Topical application of tretinoin significantly improves the clinical appearance of early, active stretch marks. The processes that are responsible for the clinical improvement remain unknown.
Administration, Cutaneous↗
The safety of etretinate as long-term therapy for psoriasis: results of the etretinate follow-up study.
BACKGROUND: Etretinate is an aromatic retinoid given orally to treat severe psoriasis, a chronic disease that often requires long-term therapy. OBJECTIVE: We assessed the safety of long-term therapy with etretinate for psoriasis. METHODS: This 5-year prospective study of a cohort of 956 patients with psoriasis treated with etretinate assessed the frequency of adverse events in relation to total use and in relation to the frequency of these events in control populations. RESULTS: Our data do not provide evidence for an increased risk of cardiovascular disease, cancer, diabetes, or inflammatory bowel disease in association with long-term etretinate use. Although some patients reported that joint problems improved with the use of etretinate, a greater number associated the use of etretinate with joint problems. CONCLUSION: With proper patient selection and monitoring, long-term etretinate therapy (up to 4 years) does not appear to be accompanied by a substantial increased risk of major adverse effects.
Adult↗
Two concentrations of topical tretinoin (retinoic acid) cause similar improvement of photoaging but different degrees of irritation. A double-blind, vehicle-controlled comparison of 0.1% and 0.025% tretinoin creams.
BACKGROUND AND DESIGN: The efficacy of topical tretinoin (all-trans-retinoic acid) in treating photoaging is well established. Questions that remain are (1) whether irritation causes all or part of the improvement; (2) the concentration of tretinoin that maximizes clinical response with minimal side effects; and (3) the effects of long-term treatment on components of the cutaneous immune system. To address these issues, 99 photoaged patients completed a 48-week study using 0.1% tretinoin cream (n = 32), 0.025% tretinoin (n = 35), or vehicle (n = 32) once daily in a double-blind manner. Before and after treatment, we assessed histologic features, keratinocyte expression of HLA-DR and intercellular adhesion molecule-1, numbers of epidermal Langerhans' cells and epidermal and dermal T lymphocytes, and vascularity as measured by dermal endothelial cell area. RESULTS: Both 0.1% and 0.025% tretinoin produced statistically significant overall improvement in photoaging of the face compared with vehicle; there were no clinically or statistically significant differences in efficacy between the two concentrations of tretinoin. After 48 weeks, 0.1% and 0.025% tretinoin produced similar statistically significant epidermal thickening (by 30% and 28%, respectively) compared with vehicle (11% decrease) and increased vascularity (by 100% and 89%, respectively) compared with vehicle (9% decrease). By various analyses, irritant side effects (erythema and scaling) were statistically significantly greater with 0.1% tretinoin than with 0.025% tretinoin. No significant changes occurred in any immunologic markers when tretinoin and vehicle treatments were compared. CONCLUSIONS: Tretinoin 0.1% and 0.025% produce similar clinical and histologic changes in patients with photoaging, despite significantly greater incidence of irritation with the higher concentration. The separation between clinical improvement and irritation suggests that mechanisms other than irritation dominate tretinoin-induced repair of photoaging in humans.
Aged↗
Duration of remission during maintenance cyclosporine therapy for psoriasis. Relationship to maintenance dose and degree of improvement during initial therapy.
BACKGROUND: Cyclosporine therapy is highly effective in the treatment of psoriasis. To minimize side effects, the lowest effective dosage for maintenance therapy should be sought. METHODS: We selected 61 patients who had achieved clearing or near-clearing of psoriasis during an induction phase of cyclosporine therapy. We then randomly assigned them in a double-blind fashion to receive one of two dosages of cyclosporine (1.5 or 3 mg/kg per day) or placebo for maintenance treatment. For each patient, the time to relapse was the time from the start of maintenance therapy until the patient showed a two-point worsening of psoriasis on a seven-point scale, up to a maximum of 4 months, when the study ended. RESULTS: Sixty patients completed the maintenance study. The mean time to relapse was significantly longer in the 3-mg/kg group (12 +/- 1 weeks) than in the 1.5-mg/kg group (9 +/- 1 weeks; P = .04) and the placebo group (7 +/- 1 weeks; P = .002); the latter two groups were not significantly different (P = .3). When the study ended, 57% of the 3-mg/kg group had not relapsed, compared with 21% and 5% of the 1.5-mg/kg and placebo groups, respectively. The following factors were associated with longer remissions: less psoriasis at the start of maintenance dosing (r = .40, P = .002); lower dosage of cyclosporine to achieve clearing or near-clearing during induction (r = -.30, P = .02); higher maintenance dosing (r = .38, P = .004); and smaller differences between the induction and maintenance dosages (r = -.41, P = .002). Patients' laboratory values improved compared with those at induction, and no patient experienced important clinical side effects during maintenance dosing. CONCLUSIONS: After clearing or near-clearing is achieved in patients with severe psoriasis, 3 mg/kg per day is a reasonable dosage to choose for maintenance. Patients who are more responsive to cyclosporine (as measured by greater clearing of psoriasis at lower induction dosages) tend to have longer remissions.
Adult↗
Sulfasalazine therapy for psoriatic arthritis: a double blind, placebo controlled trial.
OBJECTIVE: Psoriatic arthritis (PsA) is often poorly responsive to 2nd line antirheumatic drug therapy. Sulfasalazine has recently gained wide acceptance in the treatment of rheumatoid arthritis, and beneficial effects have also been noted in ankylosing spondylitis and reactive arthritis. We report a double blind placebo controlled study of sulfasalazine in PsA. METHODS: Twenty-four patients with active PsA were randomized to receive either sulfasalazine (3 g/day) (n = 10) or placebo (n = 14) for 8 weeks, in a double blind manner, followed by an 8 week open label crossover phase for nonresponding placebo patients. RESULTS: Compared with placebo controls, sulfasalazine treated patients were significantly improved at Weeks 4 and 8 with respect to physician (p < 0.01) and patient (p < 0.05) global assessments. Duration of morning stiffness was significantly decreased at Week 8 (p < 0.01). Clinical variables of disease activity returned to baseline after a 4 week drug washout period in 5 evaluable patients. Six patients in the placebo group crossed over to an 8 week open label phase and demonstrated significant improvements in joint scores, 50 ft walking time, and global patient assessment. Sulfasalazine treated patients also showed significant improvements in cutaneous involvement. CONCLUSION: Sulfasalazine was effective in PsA, with efficacy observed as early as the 4th week of treatment. Longterm studies are needed to determine whether such therapy can modify disease outcome.
Activities of Daily Living↗
Topical tretinoin (retinoic acid) treatment of hyperpigmented lesions associated with photoaging in Chinese and Japanese patients: a vehicle-controlled trial.
BACKGROUND: Hyperpigmented lesions are a predominant component of photoaging in Chinese and Japanese persons. Topical 0.1% tretinoin cream improves the hyperpigmentation associated with photoaging in Caucasian persons. OBJECTIVE: Our purpose was to assess the efficacy of 0.1% tretinoin cream treatment of hyperpigmented lesions associated with photoaging in Chinese and Japanese patients. METHODS: Forty-five photoaged patients (23 Chinese, 22 Japanese) completed a double-blind, randomized study in which 21 applied 0.1% tretinoin cream and 24 applied vehicle cream once daily to face and/or hands for 40 weeks. Patients' hyperpigmented lesions were evaluated clinically and by colorimetry throughout the study and by histologic analysis of skin biopsy specimens taken before therapy and at the end of treatment. RESULTS: At the end of treatment, hyperpigmented lesions of the face and hands were lighter or much lighter in 90% of patients receiving tretinoin compared with 33% receiving vehicle (p < 0.0001). Colorimetry demonstrated significant lightening of lesions after tretinoin compared with vehicle (p < 0.05). Histologic analysis of hyperpigmented lesions demonstrated a statistically significant 41% decrease in epidermal pigmentation with tretinoin therapy as compared with a 37% increase in the vehicle group (p = 0.0004). No patient withdrew for adverse effects. CONCLUSION: By clinical, colorimetric, and histologic evaluation, 0.1% tretinoin cream significantly lightens the hyperpigmentation of photoaging in Chinese and Japanese patients.
Administration, Topical↗
Psychosocial correlates of the treatment of photodamaged skin with topical retinoic acid: a prospective controlled study.
BACKGROUND: The psychosocial aspects of the treatment of photodamaged skin have received little attention. OBJECTIVE: We prospectively examined the psychosocial correlates of the treatment of mildly to severely photodamaged skin. DESIGN: Sixty subjects (age, 53.3 +/- 1.3 years [mean +/- standard error]; 35 receiving retinoic acid and 25 the inactive vehicle) completed a battery of psychosocial ratings before starting therapy and after 24 weeks of therapy with retinoic acid or vehicle. RESULTS: Before therapy, the subjects had pathologically high obsessive-compulsiveness scores (measured by the Brief Symptom Inventory [BSI]). From before to after therapy, the retinoic acid group reported decreased obsessive-compulsiveness (BSI) (p = 0.01), and decreased phobic anxiety (BSI) (p = 0.04), whereas the vehicle group reported an increase (p < 0.05) in both these symptom dimensions. CONCLUSION: High obsessive-compulsiveness (BSI), which is associated with excessive perfectionism and need for control, probably predisposed the subjects to seek treatment of their wrinkles. In the retinoic acid group but not the vehicle group there was an improvement in obsessive-compulsiveness and decreased anxiety in previously anxiety-provoking situations.
Administration, Cutaneous↗
A prospective study of renal structure and function in psoriasis patients treated with cyclosporin.
The impact of long-term cyclosporin therapy on kidney structure and function was evaluated in psoriasis patients with normal baseline renal function. Patients received cyclosporin at an average dose 3.9 mg/kg/day for up to three years and underwent serial kidney biopsies and measurements of iothalamate clearance and serum creatinine concentration. Kidney biopsy specimens (assessed on a scale of 0 to 4 where 0 = normal and 4 = severe) from 19 cyclosporin-treated patients as compared to 38 age-matched transplant donors showed increased interstitial fibrosis (1.9 +/- 0.2 vs. 0.3 +/- 0.1, P < 0.0001) and tubular atrophy (1.6 +/- 0.2 vs. 0.3 +/- 0.1, P < 0.0001) at one year. Eleven patients had a second biopsy after an additional two years of cyclosporin treatment demonstrating additional interstitial fibrosis (1.8 +/- 0.2 to 2.4 +/- 0.3, P = 0.002) and tubular atrophy (1.4 +/- 0.2 to 1.9 +/- 0.2, P = 0.053), and the onset of cyclosporin-associated arteriolopathy (0 to 0.5 +/- 0.2, P = 0.02). Quantitative digital morphometric analysis of trichrome-stained specimens also showed increased interstitial fibrosis (22.5 +/- 1.5 to 32.0 +/- 2.0% of interstitial area, P = 0.0008). Iothalamate clearance declined at an average rate of -3.1 ml/min/1.73 m2 per year (95% CI -5.8, -0.3) during the period of cyclosporin treatment. The slope of reciprocal serum creatinine declined by -0.06 dl/mg per year (95% CI -0.08, -0.04). Chronic cyclosporin treatment of otherwise healthy psoriasis patients is associated with progressive renal structural injury and reduced glomerular filtration rate.
Adult↗
Topical retinoic acid (tretinoin) for melasma in black patients. A vehicle-controlled clinical trial.
BACKGROUND AND DESIGN: Melasma is an acquired, masklike, facial hyperpigmentation. The pathogenesis and treatment of melasma in black (African-American) patients is poorly understood. We investigated the efficacy of topical 0.1% all-trans-retinoic acid (tretinoin) in the treatment of melasma in black patients. Twenty-eight of 30 black patients with melasma completed a 10-month, randomized, vehicle-controlled clinical trial in which they applied either 0.1% tretinoin or vehicle cream daily to the entire face. They were evaluated clinically (using our Melasma Area and Severity Index), colorimetrically, and histologically. RESULTS: After 40 weeks, there was a 32% improvement in the Melasma Area and Severity Index score in the tretinoin treatment group compared with a 10% improvement in the vehicle group. Colorimetric measurements showed lightening of melasma after 40 weeks of tretinoin treatment vs vehicle. Lightening of melasma, as determined clinically, correlated well with colorimetric measurements. Histologic examination of involved skin revealed a significant decrease in epidermal pigmentation in the tretinoin group compared with the vehicle group. Side effects were limited to a mild "retinoid dermatitis" occurring in 67% of tretinoin-treated patients. Among the patients in this study in comparison with comparably recruited white patients, melasma was reported to have begun at a later age and was more likely to be in a malar distribution. CONCLUSIONS: This controlled study demonstrates that topical 0.1% tretinoin lightens melasma in black patients, with only mild side effects.
Adult↗
Topical tretinoin (retinoic acid) therapy for hyperpigmented lesions caused by inflammation of the skin in black patients.
BACKGROUND AND METHODS: Irregular disfiguring skin hyperpigmentation due to inflammation may develop in black persons. We investigated the treatment of this hyperpigmentation with topical tretinoin (0.1 percent retinoic acid cream). Fifty-four subjects completed a 40-week randomized, double-blind, vehicle-controlled study. Twenty-four subjects applied tretinoin daily to the face, arms, or both areas, and 30 subjects applied vehicle cream. At base line and after 40 weeks of treatment, each subject's post-inflammatory hyperpigmented lesions and normal skin were assessed by clinical and colorimetric evaluations and by analysis of biopsy specimens. RESULTS: The facial post-inflammatory hyperpigmented lesions of the tretinoin-treated subjects were significantly lighter after the 40 weeks of therapy than those of the vehicle-treated subjects (P < 0.001); overall improvement was first noted after four weeks of tretinoin treatment. At the end of treatment, colorimetry demonstrated a 40 percent lightening of the lesions toward normal skin color in the tretinoin-treated lesions, as compared with an 18 percent lightening in vehicle-treated lesions (P = 0.05). The epidermal melanin content in the lesions decreased by 23 percent with tretinoin and by 3 percent with vehicle (P = 0.24). Normal skin was minimally lightened by tretinoin as compared with vehicle, according to both clinical evaluation (0.1 vs. -0.1 unit change on an 8-point scale; P = 0.055) and colorimetry (P < 0.001). Retinoid dermatitis developed in 12 of the 24 tretinoin-treated subjects who completed the study (50 percent) and in 1 tretinoin-treated subject who withdrew from the study, but diminished as the study progressed. CONCLUSIONS: Topical application of tretinoin significantly lightens post-inflammatory hyperpigmentation and, to a clinically minimal but statistically significant degree, lightens normal skin in black persons.
Administration, Cutaneous↗
Clinical significance of diminutive polyps of the rectum and sigmoid colon.
A retrospective review of 637 consecutive colonoscopies with polypectomy in 526 patients was performed to determine the association of small polyps of the rectum and sigmoid colon with more proximal colonic neoplasms. All colonic polyps were proximal to the sigmoid colon in 117 procedures. Proximal neoplasms were found in 32 percent of patients with a single polyp in the rectum or sigmoid colon. The incidence increased to 83 percent for those with three or more polyps. The occurrence of proximal colonic neoplasms was not affected by the size or histologic type of the rectosigmoid polyps. These findings would suggest that total colonic evaluation be considered in all patients with a polyp in the rectum or sigmoid colon regardless of the size or histologic type of the polyp.
Adenoma↗
Recombinant interferon gamma therapy for atopic dermatitis.
BACKGROUND: Atopic dermatitis is characterized by immunologic abnormalities including evidence for reduced interferon gamma production. Therapeutic options for treatment of atopic dermatitis are limited and unsatisfactory. Previous open trials have suggested efficacy for recombinant interferon-gamma (rIFN-gamma) in treatment of severe atopic dermatitis. We describe the results of treatment with rIFN-gamma, assessing clinical, immunologic, and laboratory safety parameters in 83 patients with moderate to severe atopic dermatitis. OBJECTIVE: Our purpose was to determine in a randomized, placebo-controlled, double-blind multicenter study the effects of recombinant human interferon gamma therapy in patients with atopic dermatitis. METHODS: Patients received 50 micrograms/m2 rIFN-gamma (n = 40) or placebo (n = 43) by daily subcutaneous injection for 12 weeks. Seventy-eight patients completed the treatment course; two patients receiving rIFN-gamma (one because of constitutional side effects) and three receiving placebo discontinued treatment before completion. Physician and patient overall response evaluations, clinical severity scores, body surface area involvement, and laboratory parameters were monitored throughout the trial. RESULTS: Patients in both treatment groups were similar except that the rIFN-gamma group was older and had a longer disease duration. Forty-five percent of rIFN-gamma-treated patients and 21% of placebo-treated patients achieved greater than 50% improvement in physicians' overall response evaluations (p = 0.016). As estimated by patients, responses also showed significant improvement in the rIFN-gamma group compared with the placebo group (53% vs 21%, p = 0.002). Significant reductions in erythema (p = 0.035) and in excoriations or erosions (p = 0.045) occurred in rIFN-gamma-treated patients. Other atopic symptoms such as conjunctivitis (p < 0.002) were also reduced in the rIFN-gamma group. Occasional headaches, myalgias, or chills occurred in 30% to 60% of rIFN-gamma-treated patients but were effectively prevented by pretreatment acetaminophen and by dosing at bedtime. Grade II granulocytopenia occurred in five rIFN-gamma patients but normalized with continued treatment. Reduction to alternate-day dosing was necessary for six patients in the rIFN-gamma group and two in the placebo group. Seven had mild elevations of hepatic transaminase levels that did not affect therapy. The mean eosinophil count was significantly reduced (p = 0.003), whereas a nonsignificant increase in serum IgE levels occurred in the active treatment group. CONCLUSION: This study demonstrated that rIFN-gamma given by daily subcutaneous injection over a 12-week period was safe, well accepted, and effective in reducing inflammation, clinical symptoms, and eosinophilia in severe atopic dermatitis.
Adolescent↗
Alcohol intake and treatment responsiveness of psoriasis: a prospective study.
BACKGROUND: Alcohol has been reported to be a risk factor in psoriasis mainly based on the observation that there is a higher prevalence of alcohol abuse in persons with psoriasis, especially in men. OBJECTIVE: We prospectively examined the relation between pretreatment average daily ethanol consumption and treatment outcome in inpatients with moderate to severe psoriasis. METHODS: The severity of psoriasis of 94 inpatients (48 men and 46 women) was assessed before and after treatment. Ethanol use was determined by obtaining the patients' reports of their average daily consumption of alcoholic beverages during the 6 months before admission. RESULTS: The average daily ethanol intake of more than 80 gm before treatment was more frequently associated with less treatment-induced improvement (less than 10%) (p = 0.02) in the percentage of the total body surface area affected by psoriasis in men but not in women. CONCLUSION: Ethanol abuse may have an adverse effect on treatment outcome in men with psoriasis.
Adult↗