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Defining Issues







ADVANCES IN SCIENCE

FLAKE FAKE-OUT: TRUE CAUSE FOUND
After 100 Years, Research Uncovers A Case of Mistaken Identity

Fungi are ancient troublemakers, but the suspicion that they might cause disease is only about 100 years old. When Louis Charles Malassez (French microbiologist: 1842-1909) first saw a yeast-like substance lurking in the scales of a patient with seborrheic dermatitis,1 he was at the forefront of mycology, but the view was far from clear. Now a century later, there are new resources in the scientific toolkit, and genetic research is finally providing the means to accurately identify the precise microfloral component that Malassez first saw. Recent genetic research into this all-too-common scalp irritant has turned up new evidence that the fungus causing the problem is not what it first appeared to be. Formerly identified as Pityrosporum ovale, an antiquated term that is no longer used,2 and later misidentified as Malassezia furfur, the fungus producing seborrheic dermatitis/dandruff actually belongs to a sister species and is not M. furfur. Using genome-based methodology, researchers at P&G Beauty collared the true culprit, Malassezia globosa. More importantly, in making a clearer identification, they uncovered the fungus' mode of operation and documented the cycle that causes excessive scalp desquamation. Their pioneering work corrects decades of guessing and inaccurate attribution.  

Scientists proved that lipophilic M. globosa is the fungal component of seborrbeic dermatitis/dandruff. The accurate identification of this fungal yeast is so recent that the terminology in most medical references and textbooks is out of date.

  

  

  

  

  

Scientists proved that lipophilic M. globosa is the fungal component of seborrbeic dermatitis/dandruff. The accurate identification of this fungal yeast is so recent that the terminology in most medical references and textbooks is out of date.

CORRECT CLASSIFICATION


When Pityrosporum was reclassified (1996) into seven species of the Malassezia genus,3,4,5,6 Malassezia furfur, which is the most easily cultured species, was thought to be the organism behind seborrheic dermatitis/dandruff. M. furfur is ubiquitous and known to cause disease, but specialists were baffled by an inconsistency. M. furfur infections occurring on other body parts look very different from the scalp desquamation associated with seborrheic dermatitis/dandruff.

Persisting with their questioning, researchers became even more curious when they amplified the fungal ribosomal gene cluster ITS I and ITS II regions from each DNA sample and analyzed the fragment sizes to differentiate each Malassezia species. They could not observe Malassezia furfur in their analysis of the scalp fungi.7 Instead, they found that two previously unsuspected fungi predominated: M. restricta and M. globosa, eliminating M. furfur from the list of suspects. Yeast growth on the human scalp turned out to be much more nuanced than first expected.

WHY HAD SCIENTISTS BEEN MISLED BY M. FURFUR?

Finding M. globosa present in dandruff seemed to contradict older research that had been dependent upon culturing scalp microflora in a Petri dish to find the resident fungi. Previous studies had shown that M. furfur was present. When closer analysis revealed previously undetected species, scientists realized that they were seeing something new that had been there all along. M. globosa had eluded diagnosis for years because it did not culture well, whereas M. furfur actually thrives in a Petri dish environment, multiplies rapidly and totally obscures evidence of other species. Because M. globosa thrives in the much more exclusive cultural niche of the disease-susceptible scalp, the species evaded discovery until gene-sequencing research revealed its presence. The case for M. globosa was further substantiated by the following factors: • Malassezia are known to be lipophilic; they are nourished by scalp sebum.

  • M. globosa is the Malassezia species with the highest lipase activity of those found on human beings, and it is frequently present on the scalp of dandruff patients and in seborrheic dermatitis scale.
  • Although M. restricta is the most numerous inhabitant of the human scalp, it has significantly less lipase activity, so it has been ruled out as a probable cause.
  • When M. globosa consumes sebum triglycerides, this particular species releases skin-irritating unsaturated fatty acids (i.e., oleic acid, found to induce dandruff in human subjects).

LAB NOTES

THE ETIOLOGY: MALASSEZIA LIPASE ACTIVITY

As the Malassezia globosa microorganisms consume sebum, they leave behind oleic acid. Oleic acid is a component of human sebum that is intensely irritating when it is isolated, and oleic acid has been shown to induce dandruff-like flaking when scalp conditions are right.9, 10

This is the likely mechanism by which this organism induces dandruff. Yeast dines on sebum but leaves behind the oleic acid component, which causes irritation. The irritation causes underlying inflammation and flaking that compromise the skin's barrier function. 

 

Oleic acid induces sub-clinical abnormalities in the skin that are associated with unhealthy scalps.11 Researchers applied oleic acid to the scalps of dandruff-prone individuals, and the skin developed abnormally shaped corneocytes and excess lipid similar to the morphology that occurs in dandruff.

Electron microscopic analysis shows normal skin (top) and signs of hyperproliferation and subclinical abnormalities in the dandruff stratum corneum (middle, bottom). 

THE NOXIOUS TRIANGLE

Dandruff/Seborrheic Dermatitis Symptoms Depend Upon Three Conditions:

  • Susceptibility. An inborn tendency for skin to have an inflammatory response to oleic acid.
  • Sebum. Naturally occurring oils nourish fungi.
  • Scalp microflora. M. globosa flourishes under the right conditions.

The noxious triangle

TREATMENT

Susceptibility and sebum production are genetic and not readily changed, so topical treatment is the best option. Controlling the fungal cause of dandruff with pyrithione zinc (PTZ) medicated shampoo is the most efficient, least invasive treatment. Ordinary shampoo does not subdue the causative agent. It takes a fungicide that is efficacious on M. globosa and mild enough to avoid contributing to the irritation to clear the scalp and stop proliferation.12 By building a more comprehensive mechanism for dandruff etiology, P&G Beauty is able to differentiate among the fungal-specific anti-microbials and formulate treatments and hair styling products that are more efficacious and pleasant to use.

An efficacious seborrheic dermatitis/dandruff anti-microbial shampoo must provide anti-fungal and aesthetic benefits. 

An efficacious seborrheic dermatitis/dandruff anti-microbial shampoo must provide anti-fungal and aesthetic benefits.

BIOLOGICAL FACTS

ALL FLAKES ARE NOT ALIKE

M. globosa starts the cycle of seborrheic dermatitis and dandruff, whether mild or severe, and variants on the condition may share a common etiology. Frequent washing with a PTZ-medicated shampoo relieves most scalp seborrhea; however, many people think that they just have dry skin and are not aware of what their flaking condition is or that it can be relieved by proper treatment.

NORMAL HEALTHY SCALP

Skin cells usually turn over without calling attention to themselves. When flaking is not apparent, a fingernail lightly scraped on a healthy, unaffected scalp will loosen just a little bit of slightly oily white scale, showing normal skin turnover.

Normal healthy scalp 

Normal scalp

• Skin cell migration is 28 days
• Cells shed as single cells

 

DANDRUFF

Dandruff is a mild form of seborrheic dermatitis. Its hallmark is discarded stratum corneum cells clumped into oily white flakes that are all-too-obvious on dark clothes, in hair and on the scalp. The larger than normal flakes signal that the scalp is oily and cell turnover is accelerated. There are also changes to the skin that are not visible to the naked eye. While flakes make dandruff apparent, a patient may suffer itching and scalp tightness without visible evidence of cell hyperproliferation. Itch and a misleading sense that the scalp is dry are also symptoms that M. globosa is active and PTZ is an effective treatment.

Dandruff 

Dandruff

• Dandruff cell migration is 7-21 days
• Cells shed as clumps of 100-1,000 cells  

SEBORRHEIC DERMATITIS

Seborrheic dermatitis has the same etiology as dandruff, but it is an extremely severe form that requires medical treatment. In addition to regular shampooing with an efficacious fungicide such as PTZ, patients often require topical corticosteroid treatment to control erythema. The inflamed skin may also be intensely itchy and weeping. Flakes may be white or yellow. Flaking extends to hairy or smooth areas beyond the scalp. M. globosa is active and the skin is oily as it is in dandruff, but much more irritated.

Seborrheic dermatitis 

Seborrheic dermatitis

• Cell migration is 7-21 days
• Cells shed as clumps of 100-1,000 cells
• It is a more severe case of dandruff
• It may also include erythema  

DRY SCALP

Dry scalp is extremely rare. Many who think that their scalp is dry, actually have the opposite problem, an oily scalp and dandruff/seborrheic dermatitis. Truly dry, peeling skin sheds transparent flakes that are barely visible rather than oily white to yellow flakes. Dry skin flakes are generally smaller than dandruff and the scalp is itchy, but not oily.

   

Dry Scalp

• Dry scalp skin cell migration is 28 days
• Dry skin flakes are typically clumps of 10-25 cells

 

SCALP PSORIASIS

Psoriasis is a medical condition quite different from seborrheic dermatitis in that cells reproduce ten times faster than normal and build up into patchy, thick, silvery plaques that are well defined. Psoriasis is an autoimmune disease of severe desquamation that does not respond to anti-fungal therapy.

 Scalp psoriasis Scalp Psoriasis  

THE PROBLEM IS WIDESPREAD

  • Noticeable flaking frequently responds to anti-fungal treatment.13 In clinical studies, PTZ proved efficacious on more than 90 percent of people with flaking scalps no matter what caused the desquamation.
  • Seborrheic dermatitis/dandruff is widespread, reportedly affecting 45-50 percent of the global population.14
  • Approximately half of those with moderate or severe dandruff claim they don't have it-many mistake their flakes for dry skin.
  • The onset of dandruff frequently occurs when sebum production rises at the beginning of puberty, and unless M. globosa is controlled, proliferation can continue throughout life.
  • More than 60 percent of men and women have had some flaking.
  • More than 50 percent of men and women have had an itchy scalp.
  • More than 40 percent of men and more than 50 percent of women report experiencing a greasy scalp.
  • Climate does not appear to be a factor; where air is cold and dry, the dehydrated flakes appear whiter and may seem more obvious, but actually, more cases are reported in summer/warm weather when the causative organism proliferates.
  • Dandruff is so widespread that Head & Shoulders® is the second most frequently purchased shampoo worldwide. (Globally, the leading non-medicated shampoo brand is Pantene®.)

EMOTIONAL ATTITUDES & BEHAVIORS

THE ULTIMATE BAD HAIR DAY

  • Flaking is a social liability.15 People know that often dandruff is more visible to friends and associates than to the sufferer. This is a potential source of embarrassment. In fact, according to a survey conducted in Japan and the US, more than 70 percent of people agree that they would feel embarrassed if they had noticeable dandruff and unexpectedly met someone they knew. Once discovered, flaky scalps send patients to their physicians for relief from unsightliness as well as from itching.
  • The stigma undermines confidence. More than 70 percent of dandruff sufferers agree that they feel less confident when they know that their scalp is flaking and they have to meet someone important, according to the same survey.
  • Scratching breaks hair.16 Constantly itchy skin can lead to broken hair, damaged from scratching. Just 15 minutes of scratching scars hair.
  • Teens suffer high rates of dandruff,17 but are often unaware of it:
    • Teens as young as 13 can have dandruff as severely as adults. 
    • Flake oiliness is higher in teens than in adults. 
    • M. globosa levels are higher in teens than in adults.
  • People with scalp conditions ask their hairdresser before they consult their dermatologist. Hair stylists frequently misdiagnose dandruff as sluggish scalp and dry hair, failing to recognize the need for an anti-fungal shampoo.
  • Hair washing habits may affect the incidence of dandruff.18 Popular hairstyles such as tight braiding and coiling often cannot be washed daily without destroying the elaborate beauty of the design. The lower washing frequency these intricate hairstyles require may allow sebum buildup, inadvertently nurturing M. globosa, and causing women of African descent to experience higher dandruff severity than other populations.
The chart illustrates differences in the prevalence of dandruff between Chinese and various U.S. populations.
The chart illustrates differences between Chinese and various US populations.

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