Functional Decline in Peripheral Arterial Disease
Peripheral arterial disease (PAD) may be stratified in severity by the ankle-brachial index (ABI), measured by dividing the ankle systolic BP by the brachial systolic BP. Normally, this number is 1 or greater. Progressive atherosclerotic disease reduces the index, with a number < 0.9 considered indicative of PAD.
Observational studies from prior decades may have given the impression that PAD is a relatively static disorder, with as few as 15-30% of subjects experiencing symptom progression over intervals as long as 10 years. However, the lack of discernible symptomatic worsening might actually reflect a reduction in activities which induce symptoms, rather than lack of disease progression.
McDermott and colleagues studied subjects older than age 55 (n = 676) with PAD as demonstrated by ABI < 0.9. Functional status over time was measured by means of the 6-minute walk performance, usual-pace walking velocity, and fastest-pace walking velocity.
The presence of PAD, whether symptomatic or not, was associated with decrements in the 6-minute walk performance over time. For symptomatic PAD patients, performance declines were proportional to the degree of baseline ABI.
Even amongst asymptomatic persons with PAD, the likelihood of ultimately being unable to walk was almost 4-fold greater than persons without PAD. Previous guidance that minimized the importance of disease progression may have overlooked and seriously underestimated the functional consequences of even asymptomatic PAD.
McDermott MM, et al. JAMA 2004;292:453-461.
Topical Capsaicin for Chronic Pain
Topical analgesics, such as capsaicin (CAP), methylsalicylate, and transdermal lidocaine, are agents which are applied topically for a local effect, as opposed to agents applied topically for a systemic effect (eg, transdermal fentanyl). Topical analgesics have recently enjoyed greater application in primary care, perhaps to some degree due to the endorsement of agencies such as the American College of Rheumatology, whose guidelines include CAP as foundation therapy for osteoarthritis of the knee.
Mason and colleagues performed a metaanalyses of double-blind placebo controlled trials of CAP used for neuropathic pain (6 trials; n = 656) or musculoskeletal pain (3 trials, n = 368). Clinical success was defined as approximately a 50% reduction in pain. Adverse effects monitored included local adverse events and withdrawal due to adverse events.
CAP was superior to placebo for both pain syndromes. For example, the mean number of persons achieving at least 50% reduction in neuropathic pain at 4 weeks was 57% vs 42% with placebo, and similar results were seen in musculoskeletal syndromes.
The rate of adverse events leading to withdrawal was 13% in CAP subjects (3% in placebo). Overall, 54% of patients experienced some adverse local event in 4-8 week trials. Although the positive effects of CAP are modest, some patients achieve substantial benefit, and CAP treatment may reduce the need for concomitant systemic pharmacotherapy.
Mason L, et al. BMJ USA 2004;4: 349-358.
Topical Tacrolimus Therapy for Vitiligo
Vitiligo (VIT) is a disorder characterized clinically by one or more skin sites of depigmentation caused by loss of melanocyte activity. Demonstrated etiologies include genetic factors, autoimmune disorders, and viral infections, although in most cases the underlying pathology remains elusive. Recently, the role of blood and cutaneous cytokine expression in VIT has received increasing attention, resulting in recognition of alterations in interleukin and tumor necrosis factor alfa in these patients.
Tacrolimus (TAC) is a topical immunomodulator currently used to treat atopic dermatitis. Its putative primary mechanism is immune modulation by inhibition of T-cell activation, resulting in decreased proinflammatory cytokine production and release. Based upon favorable results from a small pilot study in VIT, Grimes et al performed this trial of TAC in subjects with VIT.
All subjects (n = 19) applied TAC as 0.1% ointment twice daily for 24 weeks. In addition, they used sunscreen (SPF 30 with Parsol 1789) each morning. VIT disease severity was assessed on a 6-point scale.
The degree of repigmentation varied with tissue site, with greatest success on the face and neck (68% experiencing greater than 75% repigmentation). Cytokine expression (which was elevated at baseline) showed a significant decrease over time with use of TAC. Tacrolimus shows promise as a therapeutic tool for VIT.
Grimes PE, et al. J Am Acad Dermatol 2004;51:52-61.
Dr. Kuritzky, Clinical Assistant Professor, University of Florida, Gainesville, is Associate Editor of Internal Medicine Alert.