The Irregular Border

We are at an exciting time in medicine. A nearly exponential increase in the understanding of biology, chemistry, and pharmacology figuratively strains the digital shelves that hold all of this knowledge, while giant leaps in information technology mean that it is all accessible with a few taps of a smartphone. Modern medicine has more answers than ever before, and a new era of evidence-based decision-making has taken hold, bringing light and clarity to dark, unknown realms.

And yet, all is not well in this exciting new world of data and reason: there is unrest. There is increasing interest in so-called alternative medicine, which can be defined in a number of ways, but perhaps most pointedly as medicine that is simply not evidence-based. Both patients and practitioners are clearly interested in this domain and this is in striking contrast to the bright, shining edifice of evidence-based medicine. Indeed, studies indicate some 50% of dermatology patients - our patients - have tried one or more forms of alternative medicine.[i],[ii]

If modern medicine is so great - and it clearly is - why are people seeking these alternatives? Three major motivations seem to lie at the root of this movement:

• diseases that are not curable;
• explanations that are unsatisfying; and
• treatments that are thought to be unsafe and/or only symptomatic.

Another reason may have to do with the experience of seeing a doctor in the modern day: rushed, harried, and often more focused on the computer than on the patient. This is probably not how our forebears envisioned the art of medicine being practiced. In Dermatology - perhaps particularly so - these are all strongly represented: Many of our diseases are chronic and incurable; much of our understanding of the pathophysiology is incomplete; thus, many of our explanations fall short; and we have many treatments that only offer a temporary reprieve from a condition and yet still have many potential side effects.

Sadly, it does not seem likely that these conditions will be going away anytime soon for the majority of dermatologic diseases, which brings us to this column. Each month we hope to explore different diseases and treatments, looking into alternative approaches and their rationale. We will focus on the evidence: It may be surprising how much evidence is actually available in some areas. And, as we delve deeply, the line between alterative and mainstream may become a bit blurrier than it seemed at first blush. Above all else, we hope that it is stimulating and useful, for both skeptic and believer.

NEXT: Atopic dermatitis: fertile ground for alternative medicine

Atopic dermatitis (AD)

As we all know too well, this chronic, relapsing, itchy condition often begins in the first years of life, but may affect patients of all ages. Its etiopathogenesis is complex and still not fully understood, but the most recent research points to a combination of skin barrier dysfunction, immunologic aberrations, microflora imbalance, and abnormalities in the perception of itch.[iii],[iv] While intellectually stimulating, such a confusing collection of pathology defies a clear and simple explanation when patients ask: “Why do I have this disease?” And that is, unfortunately, no small number: AD affects up to 20% of children in developed countries and recent estimates are as high as 10% of adults having some form of eczema as well.[v]

The conventional approach to treatment for AD includes addressing the four main areas of dysfunction with moisturization, anti-inflammatory agents, anti-microbials, and anti-pruritic therapy. Allergen identification and avoidance of triggers is also helpful when possible.[vi] Generally speaking, most patients respond favorably to such regimens and the risks associated with conventional therapies are limited.

More recently, however, there has been increased scrutiny of topical corticosteroids: highly effective though they may be, but with a significant number of concerning side effects that make them undesirable for certain patients. This perception may lead to poor adherence to the plan, with more than one third of patients admitting to nonadherence to treatment in the setting of topical corticosteroid phobia in one study.[vii] Additionally, there is a perception that their effect - as well as that of the topical calcineurin inhibitors - is only symptomatic, and fails to address the “root” of the problem.

This makes for very fertile ground for alternative medicine, with many possible theories and approaches. We will limit ourselves to a few that have some decent evidence for potentially being useful, and also look at two that seem likely to be unhelpful, although they are frequently discussed.

NEXT: Useful alternatives

Sunflower seed oil

The skin barrier is of critical importance in AD, and is likely the primary issue in at least some types of eczema. Sunflower (Helianthus annus) seed oil is rich in linoleic acid, a fatty acid that can help maintain the skin barrier and decrease transepidermal water loss, both of which could be helpful for the barrier dysfunction in AD.[viii] Studies have also demonstrated anti-inflammatory properties of sunflower seed oil which would address another important aspect of AD.[viii]

When put to the test, the evidence points to at least a modest effect in AD. A study of 86 children with moderate AD randomized to corticosteroids with or without a sunflower-oil-containing cream found a significant impact on lichenification and excoriation, decreased corticosteroid use, and improved quality of life compared to the control group.[ix]

Another study of 19 adults randomized to receive olive oil to one arm versus sunflower seed oil to the other found that the olive oil actually caused a worsening of the barrier function and erythema. Sunflower seed oil, on the other hand, preserved skin barrier function and improved hydration.[x] Safe and inexpensive, sunflower oil seems a reasonable consideration for any patient with AD, so long as there is not a known sunflower seed allergy.

Coconut oil

Bacterial infection (usually with staphylococcus) is a major issue in AD. Coconut oil (Cocos nucifera) has been shown to address another closely-related issue in atopic dermatitis: staphylococcal colonization. In a randomized controlled trial it was found to clear an impressive 95% of staphylococcal colonization in patients with AD.[xi] When put to a more clinical test, it actually outperformed mineral oil in treating pediatric AD over 8 weeks in a randomized trial thus,[xii] making it an interesting alternative consideration.

Topical vitamin B12

Beyond topical corticosteroids and calcineurin inhibitors (which appear to do much of their work via anti-inflammatory pathways), there is not much in the armamentarium to combat the itch of AD. Antihistamines are often unhelpful, and a variety of over-the-counter cooling preparations offer only limited relief. Vitamin B12 (cobalamin) is a powerful scavenger of nitric oxide-which has been linked to triggering pruritus-making it a compelling consideration for treating AD. Additionally, in vitro studies have demonstrated that B12 suppresses the cytokine production of T lymphocytes and multiple inflammatory cytokines, also promising for AD therapy.[xiii]

When put to the test, a double-blinded randomized control trial of topical B12 in children with AD found significant improvement in the active group over the placebo at 2 and 4 weeks.[xiv] Another randomized trial of 49 AD patients found that the B12 group had significantly better improvement in AD compared to placebo control.[xiii] The concept of a safe, topically applied vitamin for AD is very attractive, even if just as an adjunctive therapy, much in the same way that niacinamide is now frequently found in moisturizers targeted towards acne and rosacea.

Acupuncture, acupressure

Generally considered a part of Traditional Chinese Medicine, acupuncture and acupressure build upon the idea that energy meridians in the body can become unbalanced and that by stimulating certain points (“acupoints”) with needles, pressure, magnets, or even lasers, the flow can be restored and rebalanced.[xv]

From a conventional standpoint, there are studies that show clear changes in specific brain areas with acupuncture, and evidence that there is endorphin production with acupuncture, suggesting a neurocutaneous connection.[xvi] While formal acupuncture would require a specially trained practitioner, more limited versions could be performed by nearly anyone, including patients themselves.

The study that got me excited about acupuncture was actually not in atopic dermatitis at all, but rather for the intractable itch of uremic pruritus. 40 patients with severe, refractory pruritus related to kidney failure were randomized to acupuncture at one point (Large Intestine 11, located near the antecubital fossa) three times weekly or acupuncture at a sham point for 1 month. At 1 month and 3 months, the itch was significantly lower in the actual acupuncture group (p<0.001), suggesting a real effect.[xvii]

Inspired by that study, we carried out a pilot study of acupressure-a tiny titanium bead that was massaged on that same acupuncture spot by the patient instead of a needle inserted by an acupuncturist-in 15 adults with moderate-severe AD.[xviii] This investigator blinded randomized controlled trial found a significant decrease in itch at 4 weeks compared to control (p=0.04). Interestingly, some of my patients who were participants in the study tell me that they continue to massage the area when they feel itchy to this day! Further work is required to substantiate this, but perhaps there is something to it.

NEXT: Not-so-promising alternatives

Evening primrose oil and borage oil

Finally, we have discussed many promising ideas, and perhaps it’s also important to close the door on some not-so-promising ones. Evening primrose oil and borage oil both have a somewhat mixed set of evidence from trials. The rationale being that these natural oils are rich in gamma-linolenic acid, which may benefit the skin barrier and may have anti-inflammatory and anti-itch properties.[xix] However, the Cochrane Review published a fairly definitive report in 2013[xx] that summarized the evidence for both agents thus far and concluded:

“Oral borage oil and evening primrose oil lack effect on eczema; improvement was similar to respective placebos used in trials… [W]e concluded that further studies on EPO or BO for eczema would be hard to justify.”

This is a powerful statement, to be sure, but in some ways a welcome one. With so many possibilities and relatively limited resources to test them all, crossing something off the list is actually good news and allows us to focus on things that may yet hold promise but require more research.

[i] Jensen P. Use of alternative medicine by patients with atopic dermatitis and psoriasis. Acta Derm Venereol. 1990;70(5):421-4.

[ii] Simpson EL, Basco M, Hanifin J. A cross-sectional survey of complementary and alternative medicine use in patients with atopic dermatitis. Am J Contact Dermat. 2003 Sep;14(3):144-7.

[iii] Kabashima K. New concept of the pathogenesis of atopic dermatitis: interplay among the barrier, allergy, and pruritus as a trinity. J Dermatol Sci. 2013;70(1):3–11.

[iv] Kong HH, Oh J, Deming C, Conlan S, Grice EA, Beatson MA, Nomicos E, Polley EC, Komarow HD; NISC Comparative Sequence Program, Murray PR, Turner ML, Segre JA. Temporal shifts in the skin microbiome associated with  disease flares and treatment in children with atopic dermatitis. Genome Res. 2012 May;22(5):850-9.

[v] Silverberg JI, Hanifin JM. Adult eczema prevalence and associations with asthma and other health and demographic factors: a US population-based study. J Allergy Clin Immunol. 2013 Nov;132(5):1132-8.

[vi] Lio PA, Lee M, LeBovidge J, Timmons KG, Schneider L. Clinical management of atopic dermatitis: practical highlights and updates from the atopic dermatitis practice parameter 2012. J Allergy Clin Immunol Pract. 2014 Jul-Aug;2(4):361-9

[vii] Aubert-Wastiaux H, Moret L, Le Rhun A, et al. Br J Dermatol. 2011;165(4):808-814.

[viii] Eichenfield LF, Mccollum A, Msika P. The benefits of sunflower oleodistillate (SOD) in pediatric dermatology. Pediatr Dermatol. 2009;26(6):669-75.

[ix] Msika P, De Belilovsky C, Piccardi N, et al. New emollient with topical corticosteroid-sparing effect in treatment of childhood atopic dermatitis: SCORAD and quality of life improvement. Pediatr Dermatol. 2008 Nov-Dec;25(6):606-12.

[x] Danby SG, AlEnezi T, Sultan A, Lavender T, Chittock J, Brown K, Cork MJ. Effect of olive and sunflower seed oil on the adult skin barrier: implications for neonatal skin care. Pediatr Dermatol. 2013 Jan-Feb;30(1):42-50. doi: 10.1111/j.1525-1470.2012.01865.x.

[xi] Agero AL, Verallo-Rowell VM. A randomized double-blind controlled trial comparing extra virgin coconut oil with mineral oil as a moisturizer for mild to moderate xerosis. Dermatitis. 2004 Sep;15(3):109-16.

[xii] Evangelista MT, Abad-Casintahan F, Lopez-Villafuerte L. The effect of topical virgin coconut oil on SCORAD index, transepidermal water loss, and skin capacitance in mild to moderate pediatric atopic dermatitis: a randomized, double-blind, clinical trial. Int J Dermatol. 2014 Jan;53(1):100-8. doi: 10.1111/ijd.12339.

[xiii] Stücker M, Pieck C, Stoerb C, et al. Topical vitamin B12--a new therapeutic approach in atopic dermatitis-evaluation of efficacy and tolerability in a randomized placebo-controlled multicentre clinical trial. Br J Dermatol. 2004 May;150(5):977-83.

[xiv] Januchowski R. Evaluation of topical vitamin B(12) for the treatment of childhood eczema. J Altern Complement Med. 2009 Apr;15(4):387-9.

[xv] Kampik G. Acupuncture, Theory and practice. Fortschr Med. 1976 Apr 8;94(10):559-62.

[xvi] Lu DP, Lu GP. An Historical Review and Perspective on the Impact of Acupuncture on U.S. Medicine and Society. Med Acupunct. 2013 Oct;25(5):311-316.

[xvii] Che-Yi C, Wen CY, Min-Tsung K, Chiu-Ching H. Acupuncture in haemodialysis patients at the Quchi (LI11) acupoint for refractory uraemic pruritus. Nephrol Dial Transplant. 2005 Sep;20(9):1912-5.

[xviii] Lee KC, Keyes A, Hensley JR, Gordon JR, Kwasny MJ, West DP et al. Effectiveness of acupressure on pruritus and lichenification associated with atopic dermatitis: a pilot trial. Acupuncture in medicine: journal of the British Medical Acupuncture Society 2012;30:8-11.

[xix] Morse NL, Clough PM. A meta-analysis of randomized, placebo-controlled clinical trials of Efamol evening primrose oil in atopic eczema. Where do we go from here in light of more recent discoveries? Curr Pharm Biotechnol. 2006 Dec;7(6):503-24

[xx] Bamford JT, Ray S, Musekiwa A, van Gool C, Humphreys R, Ernst E. Oral evening primrose oil and borage oil for eczema. Cochrane Database Syst Rev. 2013 Apr 30;4:CD004416