Clinical Health Updates

Low dose (40 mg/d) doxycycline effective for acne rosacea

Clinical Question:
Is low-dose doxycycline effective in the treatment of acne rosacea?

Bottom Line:
Low-dose doxycycline (40 mg controlled-release) is more effective than placebo in the treatment of acne rosacea. Side effects were minimal. Less than one fourth of actively treated patients reported near or complete clearing of their lesions, however, so many patients may still request alternative treatment, including a higher dose of doxycycline. (LOE = 1b)

Reference:
Del Rosso JQ, Webster GF, Jackson M, et al. Two randomized phase III clinical trials evaluating anti-inflammatory dose doxycycline (40-mg doxycycline, USP capsules) administered once daily for treatment of rosacea. J Am Acad Dermatol 2007;56:791-802.

Study Design:
Randomized controlled trial (double-blinded)

Synopsis:
The optimal dose of doxycycline necessary to treat acne rosacea is unknown. These investigators enrolled 537 patients in 2 separate studies conducted at different times to randomly receive in a double-blind manner (concealed allocation assignment) doxycycline (40 mg controlled-release daily) or matched placebo. Eligible patients were otherwise healthy adults, 18 years or older, with moderate to severe rosacea (10 to 40 papules and pustules, telangiectasia, moderate to severe erythema, and 2 or fewer nodules). Individuals blinded to treatment group assignment assessed the primary efficacy end point, defined as the mean change from baseline in total inflammatory lesion count (papules + pustules + nodules). The mean total lesion count at baseline was 20. In addition, patients were rated according to whether their disease was completely clear or near clear. Follow-up occurred for 97% of subjects at 16 weeks. Using intention-to-treat analysis, the mean change from baseline lesion score was significantly lower in the doxycycline group than in the placebo group (-1.8 vs -5.9 and -9.5 vs -4.3 in studies 1 and 2, respectively). Significantly more subjects in the doxycycline group also reported near or complete clearing of their lesions (22.3% vs 12.3%; number needed to treat = 9; 95% CI, 6-23). Adverse events were minimal to mild in both treatment groups.

Duct tape ineffective for common viral warts

Clinical Question:
Is duct tape an effective treatment for common viral warts in adults?

Bottom Line:
Occlusion with transparent duct tape is no more or less effective than occlusion with moleskin. The low success rate overall argues against any effect for occlusion. One interesting suggestion is that since hypnosis has been shown to be an effective treatment, perhaps that is the mechanism by which duct tape occlusion works, and perhaps adults are less suggestible than children. While this may not be the final word on this topic, it is discouraging news for the good folks at the American Duct Tape Council.

Reference:
Wenner R, Askari SK, Cham PM, et al. Duct tape for the treatment of common warts in adults: a double-blind randomized controlled trial. Arch Dermatol 2007; 143: 309-13.

Study Design:
Randomized controlled trial (double-blinded)

Synopsis:
The authors evaluated the efficacy of duct tape occlusion therapy for the treatment of common warts in adults. They did a double-blind controlled clinical intervention trial in a Veterans Affairs medical center. A total of 90 immunocompetent adult volunteers with at least 1 wart measuring 2 to 15 mm were enrolled between October 1, 2004, and July 31, 2005. Eighty patients completed the study. Patients were randomized by a computer-generated code to receive pads consisting of either moleskin with transparent duct tape (treatment group) or moleskin alone (control group). Patients were instructed to wear the pads for 7 consecutive days and leave the pad off on the seventh evening. This process was repeated for 2 months or until the wart resolved, whichever occurred first. Follow-up visits occurred at 1 and 2 months. Complete resolution of the target wart. Secondary outcomes included change in size of the target wart and recurrence rates at 6 months for warts with complete resolution. There were no statistically significant differences in the proportions of patients with resolution of the target wart (8 [21%] of 39 patients in the treatment group vs 9 [22%] of 41 in the control group). Of patients with complete resolution, 6 (75%) in the treatment group and 3 (33%) in the control group had recurrence of the target wart by the sixth month.

Botulinum might be more effective than nitroglycerine in anal fissure

Clinical Question:
Is type A botulinum toxin more effective than nitroglycerine ointment in treating chronic anal fissure?

Bottom Line:
In this study, botulinum toxin (Botox, Dysport) appeared slightly more effective than topical nitroglycerine in managing chronic anal fissures.

Reference:
Brisinda G, Cadeddu F, Brandara F, Marniga G, Maria G. Randomized clinical trial comparing botulinum toxin injections with 0.2 per cent nitroglycerin ointment for chronic anal fissure. Br J Surg 2007;94:162-167.

Study Design:
Randomized controlled trial (single-blinded)

Synopsis:
In recent years treatment of chronic anal fissure has shifted from surgical to medical. These authors compared the ability of two non-surgical treatments-botulinum toxin injections and nitroglycerin ointment-to induce healing in patients with idiopathic anal fissure. One hundred adults were assigned randomly to receive treatment with either type A botulinum toxin (30 units Botox or 90 units Dysport) injected into the internal anal sphincter or 0.2 per cent nitroglycerin ointment applied three times daily for 8 weeks. After 2 months, the fissures were healed in 46 (92 per cent) of 50 patients in the botulinum toxin group and in 35 (70 per cent) of 50 in the nitroglycerin group (P=0.009). Three patients in the botulinum toxin group and 17 in the nitroglycerin group reported adverse effects (P<0.001). Those treated with botulinum toxin had mild incontinence to flatus that lasted 3 weeks after treatment but disappeared spontaneously, whereas nitroglycerin treatment was associated with transient, moderate-to-severe headaches. Nineteen patients who did not have a response to the assigned treatment crossed over to the other therapy.

Effective treatments for rosacea

Clinical Question:
What treatments are effective for rosacea?

Bottom Line:
There is evidence that topical metronidazole and azelaic acid are effective. There is some evidence that oral metronidazole and tetracycline are effective. More well-designed, randomized controlled trials are required to provide better evidence of the efficacy and safety of other rosacea therapies.

Reference:
van Zuuren EJ, Gupta AK, Gover MD, Graber M, Hollis S. Systematic review of rosacea treatments. J Am Acad Dermatol 2006;online:Nov 3.

Study Design:
Meta-analysis (randomized controlled trials)

Synopsis:
These investigators thoroughly searched multiple databases — including MEDLINE, EMBASE, The Cochrane Registry of Clinical Trials, Science Citation Index, and reference lists — and consulted with experts. They also searched unpublished literature through correspondence with authors and pharmaceutical companies. Two reviewers independently performed searches and assessed articles for eligibility. Disagreement was resolved by consensus discussion. From a total of 71 possible clinical trials, the authors included 29 randomized trials meeting appropriate criteria for high quality (8) and intermediate quality (21). Fourteen trials used adequate blinding to treatment allocation and 17 used intention-to-treat analysis. Only data on outcome measures from trials on topical metronidazole, topical azelaic acid, and oral tetracycline could be pooled. The primary outcome measure, quality of life, was not assessed in any of the studies and only a few studies assessed the participant?s own opinion regarding rosacea severity. The following medications were significantly superior to placebo: topical metronidazole, benzoyl peroxide 5%/erythromycin 3% gel, benzoyl peroxide 5%/clindamycin 1% gel, benzoyl peroxide alone, azelaic acid, and sodium sulfacetamide10%/sulfur 5%. Oral tetracycline was significantly better than placebo by physician assessment, but not by patient assessment. There was no significant difference in efficacy between topical metronidazole and azelaic acid or between topical metronidazole and oral tetracycline. Rilmenidine and permethrin were not significantly better than placebo.

Betamethasone, calcipotriol best for intertriginous psoriasis

Clinical Question:
What is the best treatment for psoriasis?

Bottom Line:
The 1% pimecrolimus was shown to be less potent than 0.1% betamethasone in the treatment of IP. Considering the adverse-effect profile of long-term application of corticosteroids, occasional or intermittent rescue therapy with short-term topical corticosteroids and maintenance with a less potent agent, such as 1% pimecrolimus or 0.005% calcipotriol, might be appropriate for patients with IP in general practice.

Reference:
Kreuter A, Sommer A, Hyun J, et al. 1% pimecrolimus, 0.005% calcipotriol, and 0.1% betamethasone in the treatment of intertriginous psoriasis. A double-blind, randomized controlled study. Arch Dermatol 2006;142:1138-1143.

Study Design:
Randomized controlled trial (double-blinded)

Synopsis:
IP occurs in the axillae, under the breasts, in the inguinal folds, and on the buttocks and genitals. It is very pruritic and is typically worsened by perspiration. Treatment options (all topical) include corticosteroids, pimecrolimus and tacrolimus, and calcipotriol. In this study, 80 patients with IP from a dermatology clinic were randomly assigned to receive either 1% pimecrolimus, 0.005% calcipotriol, 0.1% betamethasone valerate, or vehicle cream once daily for 4 weeks, followed by 6 weeks without treatment. The primary outcome was the Modified Psoriasis Area and Severity Index (M-PASI) measured at days 0, 14, 28, 42, and 70. Groups were balanced at the start of the study and analysis was by intention to treat. There were only 5 withdrawals, including 3 in the betamethasone group. The mean M-PASI scores decreased from 22.1 to 2.9 in the betamethasone group (86%), from 25.3 to 9.7 in the calcipotriol group (62%), from 19.5 to 11.5 in the pimecrolimus group (39.7%), and from 18.2 to 13.8 in the placebo group (21.1%). There were statistically significant differences between betamethasone and pimecrolimus and vehicle cream, and between calcipotriol and vehicle cream. There was no significant difference between pimecrolimus and vehicle cream. The authors of this study, funded by the manufacturer of pimecrolimus, play up the adverse effects of betamethasone and calcipotriol while ignoring the fact that adverse effects were actually most common in the pimecrolimus group. It is important to note that the European Medicines Agency, which checks the safety of drugs in the European Union, has warned doctors and patients using pimecrolimus about a possible risk of skin cancer and lymphoma.

Azelaic acid effective for papulopustular rosacea

Clinical Question:
Is azelaic acid safe and effective for the treatment of rosacea?

Bottom Line:
Azelaic acid in 20% cream and 15% gel formulations appears to be effective in the treatment of papulopustular rosacea, particularly in regard to decreases in mean inflammatory lesion count and erythema severity. Compared with metronidazole, azelaic acid appears to be an equally effective, if not better, treatment option.

Reference:
Liu RH, Smith MK, Basta SA, Farmer ER. Azelaic acid in the treatment of papulopustular rosacea: a systematic review of randomized controlled trials. Arch Dermatol 2006;142:1047-1052.

Study Design:
Meta-analysis (randomized controlled trials)

Synopsis:
Although rosacea is most commonly treated with topical metronidazole, azelaic acid is another option. The authors performed a thorough search of the literature to identify placebo-controlled trials of azelaic acid for rosacea, which included contacting authors of identified studies and experts on the condition. They identified 5 relevant randomized controlled trials with a total of 873 patients. The trials lasted between 2 months and 3 months; one was a “split face” comparison; the others used a parallel groups design. All of the studies were double-blinded and appropriately randomized, and the authors carefully described dropouts, withdrawals, and their statistical methods. The studies all used either 20% cream or 15% gel. Limitations in data reporting meant that the results of individual studies could not be combined in a meta-analysis. In a qualitative summary of the study results, the authors report that 4 of the 5 studies found statistically significant decreases in mean inflammatory lesion count and erythema severity compared with placebo. However, the treatment had no effect on the severity of telangiectasias.