Studies yield clues to pathology, treatment of rosacea

Miami Beach, Fla. - New knowledge regarding rosacea’s pathology may explain why some newer treatment strategies appear effective, while pointing the way for additional approaches, according to an expert who spoke at the American Academy of Dermatology’s annual meeting.

Among the most exciting developments in researchers’ understanding of rosacea is the recently reported neurogenic subtype of rosacea, says Frank C. Powell, M.D., a consultant dermatologist at the Charles Institute of Dermatology, University College Dublin.

In this regard, he says, several studies suggest that this new subtype features the release of neurotransmitters in the skin (Scharschmidt TC, Yost JM, Truong SV, et al. Arch Dermatol. 2011;147(1):123-126).

Also intriguing is the question of how neurogenic rosacea interacts with the skin’s blood vessels to produce erythema and flushing, he says.

“It is postulated that neurotransmitters lead to vasodilatation in the skin, and the release of neurotransmitters that cause stinging and burning,” Dr. Powell says.

Additionally, research has shown that administering pituitary adenylate cyclase-activating polypeptide (PACAP), a neuropeptide which helps regulate blood vessels, into the skin causes flushing, swelling and itching (Schwab VD, Sulk M, Seeliger S, et al. J Investig Dermatol Symp Proc. 2011;15(1):53-62). Therefore, Dr. Powell says, blocking PACAP may reduce redness and flushing in rosacea.

By the same token, he says, “Topical brimonidine gel is a vasoconstrictor that studies have shown is effective in the management of the erythema associated with rosacea. This further supports the concept of the neurogenic pathway of inflammatory erythema in rosacea.”

Mites and more

Dr. Powell notes that recent research suggests that the innate immune system is hyperactive in the skin of patients with rosacea (Yamasaki K, Gallo RL. J Investig Dermatol Symp Proc. 2011;15(1):12-15; Yamasaki K, Gallo RL. J Dermatol Sci. 2009;55(2):77-81).

Furthermore, Dr. Powell says many studies substantiate that the population of Demodex folliculorum mites is greatly elevated in the skin of patients with rosacea. He poses the question whether the elevated mite population could be triggering the immune response in patients with rosacea.

“Studies show that anti-Demodex therapy achieves positive clinical results in those patients,” he says. One such study involved 60 patients with resistant rosacea and high Demodex counts. They were randomized to treatment with either ivermectin or ivermectin and metronidazole. After four weeks, the proportions of patients in these groups who achieved complete remission were 45 and 71 percent, respectively (Salem DA, El-Shazly A, Nabih N, et al. Int J Infect Dis. 2013;17(5):e343-e347. Epub 2013 Jan 5).

Somewhat similarly, “We ourselves have performed some studies showing that the mites can modify the immune response in patients with rosacea  (Lacey N, Delaney S, Kavanagh K, Powell FC. Br J Dermatol. 2007;157(3):474-481. Epub 2007 Jun 26).

In this regard, one study suggests that a defect in innate or induced immunity allows the proliferation of Demodex mites in the skin. When the mite population reaches critical levels, they cause trauma or breaches in the affected follicles of the face, which provokes an exaggerated immune response that can result in the formation of papules and pustules (Forton FM. J Eur Acad Dermatol Venereol. 2012;26(1):19-28).

Inflammation reduction

Unlike in acne, Dr. Powell adds, “The inflammatory lesions that develop in people with rosacea are sterile. They don’t tend to contain bacteria. Therefore, we believe that the antibiotics used in rosacea work by reducing inflammation rather than killing bugs.”

Additionally, “There is a genetic predisposition toward rosacea” he says. “About 15 percent or more of people with rosacea have a family history of rosacea. It seems to be particularly common in Caucasians and those with a Celtic background (Chosidow O, Cribier B. Ann Dermatol Venereol. 2011;138 Suppl 3:S179-S183). It’s very uncommon in people with darkly pigmented skin.”

Research also shows that patients with rosacea have irregularities in their transient receptor potential ion channels of vanilloid type (TRPV). This is important because factors such as heat or topical capsaicin, which trigger rosacea symptoms and promote flushing, can activate TRPV channels, Dr. Powell says.

In one study, investigators used immunohistochemistry and other tests to show that patients with erythematotelangiectatic rosacea (subtype one) showed genetic expression of TRPV1, while the patients with papulopustular rosacea (subtype two) showed genetic expression of TRPV2 (Sulk M, Seeliger S, Aubert J, et al. J Invest Dermatol. 2012;132(4):1253-1262). Accordingly, these investigators write, TRP ion channels may be targets for the treatment of rosacea. Dr Powell says that these genetic studies also could lend credence to the growing evidence suggesting that the different subtypes of rosacea may in fact be inherently different but related conditions.

Disclosures: Dr. Powell reports no relevant financial interests.