SAN FRANCISCO (July 30, 2015) – As research continues to reveal the many ways the human microbiome may affect human health, the potential role of Demodex mites in rosacea has come into sharper focus with new technology and may point to new approaches in patient care, according to experts at a roundtable on the clinical implications of Demodex in rosacea during the recent annual meeting of the American Academy of Dermatology.
“The controversy surrounding the role of Demodex mites in the pathophysiology of rosacea has been going on for over eight decades,” said Dr. James Del Rosso, adjunct clinical professor of dermatology at Touro University College of Osteopathic Medicine in Henderson, Nevada and a consultant to Galderma. “We are now finally seeing more research using advanced technological methods to better evaluate and quantify the potential connections between Demodex mites, rosacea, and other rosacea form facial eruptions. This is great news for dermatologists and their patients!”
Demodex mites are a normal part of the human microbiome but have often been found in more than four times greater numbers on the facial skin of rosacea sufferers, according to Dr. Frank Powell, consultant dermatologist at Mater Misericordiae Hospital in Dublin and former president of the European Academy of Dermatology and Venereology.
“Researchers have more recently discovered that while Demodex folliculorum and D. brevis live in the hair follicles and sebaceous glands of the facial skin, D. folliculorum is also found in the meibomian glands of ocular rosacea patients,” he said. “In the mites’ brief life span of 14 days, they live and reproduce in the pilosebaceous units, subsisting on sebum and cellular contents, and emerge from the follicles primarily at night.”
He suggested that a genetic predisposition for rosacea may be reflected in a different skin type with specific lipid qualities that allows Demodex to flourish in greater numbers.
Dr. Powell noted that the presence and quantity of Demodex can easily be determined by performing a skin surface or follicular biopsy, in which a glass slide coated with Super Glue® is applied to a 1-cm section of the face for 60 seconds, then slowly levered off. The mites often live deep within the follicle, and repeating the process up to four times may yield further evidence of Demodex, he said. Dr. Diane Thiboutot, professor of dermatology and Vice-Chair for Research at Penn State University and a consultant to Galderma, pointed out that while surface cells stick to the slide, follicular plugs stand out and may be clipped for further examination.
Recent research has identified a host of microscopic elements and interactions in the innate immune system that contribute to rosacea’s development, involving such substances as kallikreins, cathelicidins and mast cells, Dr. Thiboutot said. Importantly, she noted, many of the triggers of rosacea – ultraviolet light damage or bacterial antigens, as well as Demodex, for example – have one thing in common: They have been shown to activate the enzyme toll-like receptor-2 (TLR-2) signaling, which initiates a cascade of events that leads to the inflammatory signs and symptoms of rosacea, including papules and pustules. The challenge, however, is that TLR-2 activation is necessary to fight off pathogens, so wiping out its function would be counterproductive.
“The significance of the relationship between Demodex and rosacea has long been controversial, as it doesn’t fulfill certain traditional parameters for a causal association between a pathogen and a disease,” Dr. Thiboutot continued. “These parameters may have been superseded by more recent findings, and a recent review of 48 articles in the Archives of Dermatology concluded that the degree of Demodex infestation, as opposed to its simple presence, is an important factor in rosacea.”
She pointed out that rosacea and demodicosis are currently the only diseases widely associated with increased Demodex mites, although recent evidence suggests there may be others. Dr. Powell noted that increased Demodex numbers causing inflammation may be present in those whose immune systems are compromised, including individuals with malignancy, leukemia, HIV infection or pregnancy. Interestingly, he said, individuals who had significant acne when younger have often been observed to have rosacea later, supporting a possible genetic component in patients with skin that reacts to either Propionibacterium acnes or Demodex.
Dr. Del Rosso stressed that Demodex may play a role in the pathophysiology of rosacea, at least in some patients, and may influence the type and severity of visible manifestations of rosacea in different individuals. “The classic ‘subtypes’ of rosacea appear to reflect variations in inflammatory and immunologic responses which in some cases may be induced by Demodex mites,” he said. “For example, in one study, individuals with erythematotelangiectatic rosacea (subtype 1) were found to have higher facial counts of Demodex mites than those with papulopustular rosacea (subtype 2). It has been suggested that the higher Demodex counts lead to degradation of the follicular wall as the mites attempt to improve their survival. This loss of follicular wall integrity then triggers an immunologic response that reduces the number of Demodex mites, with papules and pustules subsequently emerging from the augmented perifollicular inflammation that occurs.”
Dr. Del Rosso noted that he has observed cases of patients with a more diffuse facial distribution of small papules, pustules and fine scaling than what is typical of rosacea. He has previously diagnosed these cases as demodicosis, as skin scrapings of the facial lesions have easily revealed multiple Demodex mites on light microscopy. Such patients are usually poorly responsive or only partially responsive to traditional rosacea therapies, he said, but have been effectively treated with oral ivermectin.
Ivermectin has been used for years as an anti-vermicidal and antiparasitic, and more recently has been shown to have anti-inflammatory actions as well. A large study on the action of topical ivermectin in patients with moderate to severe rosacea proved very effective, yielding physician assessments of clear or almost clear in 38.4 to 40.1 percent, and 64.9 to 65.7 percent mean reduction of inflammatory lesions of test subjects after 12 weeks, said Dr. Linda Stein Gold, director of dermatology clinical research at Henry Ford Hospital and a consultant to Galderma. “Something is happening that is different,” she said. “It would be useful to quantify the association between the mites, rosacea and this type of treatment.”
She noted that microbic organisms that live on Demodex mites may also be involved, as a recent study found an unexpected diversity of such microorganisms, including a total of 92 species, 36 of which were never before recorded on humans.
The roundtable participants agreed that further studies should be conducted to improve understanding of the presence of Demodex and its potential actions and interactions with other pathogenic factors in rosacea, as well as to provide knowledge for uniquely targeted therapy in clinical practice. The roundtable was sponsored by the National Rosacea Society with funding from Galderma Laboratories.
Microscopic Demodex mites are a natural part of the human microbiome – the ecological community of microorganisms that live within and on the body. Two species of Demodex are found in humans. D. folliculorum live in hair follicles, primarily on the face, as well as in the meibomian glands of the eyelids; D. brevis live in the sebaceous glands of the skin.
While D. folliculorum are found on the skin of all humans, they frequently occur in greater numbers in those with rosacea. While there has been much debate as to whether their increased numbers are a cause or result of rosacea, evidence appears to be mounting that an overabundance of Demodex may possibly trigger an immune response in people with rosacea, or that the inflammation may be caused by certain bacteria associated with the mites.
The mites are most plentiful in the same regions of the face that are most commonly affected by rosacea – the cheeks, nose, chin and forehead – and large quantities of mites have been found in biopsies of rosacea papules and pustules.
About the National Rosacea Society
The National Rosacea Society is the world’s largest organization dedicated to improving the lives of the estimated 16 million Americans who suffer from this widespread but poorly understood disorder. Its mission is to raise awareness of rosacea, provide public health information on the disorder and support medical research that may lead to improvements in its management, prevention and potential cure.
Comprehensive information and materials on rosacea are available on the NRS website at www.rosacea.org. The NRS may also be followed on Facebook, Twitter and Pinterest for up-to-date information and tips on rosacea. Further information may be obtained by writing the National Rosacea Society, 196 James Street, Barrington, Illinois 60010; via email at firstname.lastname@example.org; or by calling its toll-free number at 1-888-No-Blush.