What’s the story behind flaky scalp?

雙和醫院皮膚科 曾德朋醫師

http://pgbeautyscience.com/defining-issues.php

• A normal scalp has few flakes and healthy looking, smooth skin

• Dandruff is characterized by patches of loosely adherent flakes, usually

accompanied by itching

• Seborrheic dermatitis, the flakes have progressed to being greasy with a

yellow color. Inflammatory changes (surface erythema)

Textbook of Cosmetic Dermatology, 3rd Edn: Taylor & Francis: New York, 2005

Journal of Investigative Dermatology Symposium Proceedings (2007) 12, 10-14

A normal scalp

Background

• Dandruff and its more severe manifestation, seborrheic

dermatitis, affect approximately half of the adult population

globally, irrespective of gender, nationality or ethnicity. (Cardin,

1998)

• D/SD is a treatable but not curable condition.

• Commensally scalp yeast, Malassezia globosa

• Parakeratosis, inflammation and scaling seen at the hair-

follicle opening

• Hydrolysis of sebaceous triglycerides yielding free fatty acids

(esp. unsaturated ones)

• barrier disruption

• Itchy, erythema, skin flaking and dryness

Background

• The prevalence is higher in immune-compromised patients than

in healthy adults (Smith et al., 1994).

• Seborrheic dermatitis has been reported to occur in 3–5% of

immunocompetent adults, compared with 30–33% of AIDS

patients (Farthing and Staughtom, 1985).

• Some additional symptoms: pruritus (66%), irritation (25%), and

the feeling of a tight or dry scalp (59%) (Elewski, 2005).

• The classical signs of dandruff are loosely adherent, small white

or gray flakes, whereas seborrheic dermatitis is often associated

with yellowish, oily scales.

Textbook of Cosmetic Dermatology, 3rd Edn: Taylor & Francis: New York, 2005

A three-factor causal model for dandruff and seborrheic dermatitis

Role of sebaceous gland activity

•Increased incidence during infancy (cradle cap), low incidence after infancy

until puberty, increase in adolescence and young adulthood, and a decrease

later in life.

•When secreted, sebum consists of triglycerides and esters, which are broken

down by microbes into diglycerides, monoglycerides, and free fatty acids. The

free fatty acids play a key role in initiation of the irritant response at the base

of D/SD.

•The role of sebaceous secretion also underlies the impact of stress and

hormones on D/SD. It is well known that these are affecters of human sebum

secretion and therefore impact D/SD.

Sebum Textbook of Cosmetic Dermatology, 3rd Edn: Taylor & Francis: New York, 2005

Sebum Textbook of Cosmetic Dermatology, 3rd Edn: Taylor & Francis: New York, 2005

Role of Malassezia

•Dandruff, seborrheic dermatitis, pityriasis versicolor and Malassezia folliculitis,

and exacerbation of atopic dermatitis and psoriasis.

•The improvement in flaking following treatment is highly correlated with the

reduction in the level of scalp Malassezia (Schwartz et al., 2004).

•Using an advanced molecular technique, terminal fragment length

polymorphism, identified M. globosa and M. restricta as the predominant

species present on the scalp of D/SD sufferers.

•Malassezia globosa and M. restricta predominate on dandruff scalp, that oleic

acid alone can initiate dandruff-like desquamation

•M. globosa is the most likely initiating organism by virtue of its high lipase

activity, and that an M. globosa lipase is expressed on human scalp.

Role of Malassezia

•One sign/symptom associated with D/SD that has only recently been

described is that some properties of the hair fibers on the scalp can be

negatively impacted by the poor scalp skin physiology associated with D/SD

(paralleling similar observations for the scalp psoriasis)

•Comparison of the hairs from D/SD and normal populations demonstrated

D/SD-derived hair to be more narrow, with a more brittle surface and less

shine.

•D/SD can also contribute to increased rates of hair loss, which may be

directly due to the presence of Malassezia.

•Anti-dandruff shampoos with anti-fungal actives appear to reduce hair loss

even in androgenic alopecia populations

Malassezia: The Impact of the structure and Function of epidermis

•Closely associated with flakes and parakeratotic cells

•The quantity correlates with flaking severity

•Hyper-proliferative nature of the epidermis in D/SD, increased turnover rate and

thicker epidermis

•The corneocyte envelope structure: irregular and highly invaginated due to the

lack of synchronization between proliferation and differentiation in D/SD

•Epidermal lipids are affected by D/SD

•Lamellar structure formed by ceramides is replaced with a much wider,

unstructured lipid material

•Sebaceous lipids are altered

•Free fatty acids are released by Malassezia –derived lipase activity :

primary initiators of inflammation.

Malassezia fungi

Textbook of Cosmetic Dermatology, 3rd Edn: Taylor & Francis: New York, 2005

Barrier

Breach

Textbook of Cosmetic Dermatology, 3rd Edn: Taylor & Francis: New York, 2005

Treatment strategies for D/SD

Role of individual susceptibility

•Fatty acid metabolite of Malassezia, oleic acid, induces flaking in dandruff-

susceptible patients, but not in non-susceptible patients.

•Physical factors, nutritional disorders, drugs, and neurotransmitter

abnormalities are additional aggravating factors. The difference between

dandruff-susceptible and non-susceptible individuals remains unclear.

•Multiple possibilities exist, including innate differences in stratum corneum

barrier function, skin permeability, and immune response to free fatty acids

or proteins and polysaccharides from Malassezia.

Dandruff and seborrheic dermatitis (D/SD)

1. Considered the same basic condition differing only in magnitude

2. Heredity plays only a small role in developing a predisposition for

the condition

4 Sequential pathophysiological phases:

• Malassezia ecosystem and interaction with

the epidermis

• Initiation and propagation of inflammation

• Disruption of proliferation and

differentiation processes of the epidermis

• Physical and functional skin barrier

disruption

Acta Derm Venereol 2013; 93: 131–137.

Malassezia

In 1873 Rivolta suggested that yeasts were

also present in dandruff. Malassez

subsequently described both oval and round

spores in scalp scales from patients with

dandruff and in recognition of his discovery

the genus Malassezia was described in 1889

The pathogenesis of seborrhoeic dermatitis and dandruff

– the current status

the original scientific observations linked both diseases with the yeast that we now

know as Malassezia

Biomolecular changes

Elevated levels of the cytokines from D/SD lesions: IL-la, IL-Iß, IL-2, IL-4, IL-6,

IL-10, IL-12, TNF-a and IFN-y vs. skin from normal volunteers.

Tracking the above

biomarkers before and

after treatment with a

commercial 1%

potentiated ZPT shampoo

•Decreased inflammatory biomarkers quantified (IL-lra/IL-la, IL-8 and histamine) ->

normalization of the skin inflammatory state

•Involucrin decreased while terminal differentiation products keratins 1, 10 and 11

increased.

•HSA decreased ->barrier function returning to normal and consistent with

structure/function level intercellular lipids responsible for barrier function also

increased significantly

These new D/SD measures support the inclusion of D/SD in the broad group of

inflammatory dermatoses, including psoriasis, atopic dermatitis and acne. These

conditions have different triggering events, but share the pathophysiology of

inflammation, proliferation and skin barrier impairment.

Adherent Scalp Flaking Score (ASFS)

• The scalp is divided into eight sections

• Adherent of flakes on scalp using a 1 to 10 (increment of 2 units) scale.

• Loose flake in the hair are not considered in the grading.

• Total 1 to 80 units.

Assessment of disease severity

• ASFS method reliability: reproducible demonstration of the efficacy

of a 1% potentiated ZPT shampoo

• ASFS method relevance: self-perception assessments

• ASFS method reproducible across graders

• Assessment of flakiness

• Ultraviolet (UV) examination of the skin

• Measurement of specular light reflectance (SLR)

• Perception of scaliness resulted from increased light

scattering and specular reflectance at skin surface.

• Near-UV light (375 nm)

• Before and after daily applications of clobetasol propionate 0.05%

shampoo (Clobex) for 1 week

Therapies for Dandruff/Seborrheic Dermatitis

• Treatments to control dandruff and seborrheic dermatitis can be divided

into three main classes on the basis of their mechanisms of action; these

include keratolytic, antimicro- bial, and antiproliferative agents.

• Effective anti-dandruff shampoos

• A potent anti-fungal active system

• An efficient scalp delivery system

• Retain the anti-fungal materials after rinsing and optimize their

spatial delivery

• Zinc pyrithione (ZPT): most common anti-fungal used in AD shampoos, first

discovered in late 1950s.

• Topical corticosteroids, calcineurin inhibitors and various fungistatic

compounds have proven efficacy

• Removal of scales

• Reducing the adherence of the Malassezia yeasts to corneocytes and

inhibiting their colonization of the skin

•In adults with seborrhoeic dermatitis of the scalp, antifungal preparations

containing ketoconazole improve symptoms compared with placebo.

•Bifonazole and selenium sulphide are also likely to be effective

•Terbinafine is unknown for it’s therapeutic effect: no RCTs.

•Topical corticosteroids: Insufficient RCT evidence; however, there is consensus

that topical corticosteroids are effective in treating seborrhoeic dermatitis of

the scalp in adults.

•Tar shampoo may reduce scalp dandruff and redness compared with placebo.

Clinical evidence April, 2010

Ketoconazole shampoo compared with placebo Ketoconazole shampoo is

more effective than placebo at improving scalp symptoms such as scaling,

itching, redness, and dandruff at 4 weeks in people with seborrhoeic

dermatitis of the scalp (moderate-quality evidence).

Bifonazole shampoo compared with placebo Bifonazole shampoo may be

more effective at improving symptoms such as scaling and pruritus, and

overall symptom severity at 6 weeks in people with seborrhoea or

seborrhoeic dermatitis of the scalp (low-quality evidence).

Clinical evidence April, 2010

Selenium sulphide shampoo compared with placebo Selenium sulphide

shampoo may be more effective at reducing dandruff, and at increasing

response to treatment at 29 days, in people with moderate to severe dandruff

(low-quality evidence).

Tar shampoo compared with placebo Tar shampoo is more effective than

placebo at improving dandruff and redness at 29 days in people with

seborrhoeic dermatitis or dandruff (moderate-quality evidence).

Clobetasol propionate shampoo 0.05% compared with placebo Clobetasol

propionate shampoo 0.05% applied twice weekly for 2.5, 5, or 10 minutes may

be more effective at 4 weeks in improving total symptom severity scores. (very

low-quality evidence).

-Comment: Although limited evidence is available from a single small RCT

concerning clobetasol propionate shampoo 0.05%, there is consensus that

topical corticosteroids are effective in treating seborrhoeic dermatitis of the

scalp in adults.

Clinical evidence April, 2010

Clinical evidence April, 2010

Topical therapies:

•Antifungals: first publication in 1984 on the use of ketoconazole in

seborrheic dermatitis.

•Ketoconazole shampoo 2% is superior to 1% and can be used once-

weekly s maintenance therapy for scalp seborrheic dermatitis.

•Bifonazole 1% cream + 40% urea for scalp seborrheic dermatitis

•Miconazole used either alone or in combination with hydrocortisone.

•Ciclopirox: both antifungal and anti-infalmmatory properties.

Combinations of ciclopirox 1.5% shampoo with salicylic acid 3% or zinc

pyrithione 1% are also effective. Statistical non-inferiority of ciclopirox in

comparison with ketoconazole has been demonstrated.

Corticosteroids

For severe seborrheic dermatitis, low- or medium-potency topical corticosteroids can

be used when beginning treatment, either alone or in combination with an antifungal

agent, to limit inflammation.

Zinc Pyrithione

Zinc pyrithione 1% shampoo in comparison with ketoconazole 2% shampoo has

produced inferior results, whereas selenium sulphide exhibited similar efficacy

Tacrolimus

•Topical tacrolimus 0.1%: an open-label 4-week randomized study against

betamethasone 17-valerate lotion and zinc pyrithione 1% shampoo in 83 patients

with seborrheic dermatitis of the scalp.

•Tacrolimus ointment demonstrated greater prolonged efficacy than topical steroids,

but exhibited shorter durability of improvement than zinc pyrithione shampoo.

•Due to the increased viscosity of the tacrolimus ointment, treatment was

inconvenient to use on the scalp.

Selenium Sulphide

In a randomized double-blind trial, selenium sulfide 2.5% was tested against

ketoconazole 2% and placebo in 246 patients with moderate to severe dandruff.

Both ketoconazole and selenium sulfide shampoos were effective, but ketoconazole

was better tolerated.

Tars have been used since the ancient times. Hippocrates first described the

use of pine tar in medicine.

Coal tar was used for dermatologic conditions for well over 2000 years, when it was

referred to as ‘‘asphalt’’ by Dioscorides.

•Over the past century, coal tar has also been used in the treatment of scabies,

sarcoidosis, neurodermatitis, and pityriasis lichenoides chronica.

•Currently, it is employed mainly for chronic stable plaque psoriasis, scalp psoriasis,

seborrheic dermatitis, and atopic dermatitis.

•Coal tar preparations in seborrheic dermatitis avoid the use of corticosteroids.

•Coal tar gel use against Malassezia species. The in vitro fungistatic effects of coal tar

against Malassezia species has been found equivalent to ketoconazole gel.

Crude coal tar is one of 3 main types of tar, the others being wood tar (principally

pine, beech, birch, and juniper) and shale (bituminous tars/ichthammols).

Wood and shale tars lack contact sensitizing potential and/or photosensitizing

effects, both qualities that coal tar possesses.

•Wood tars: derived from the destructive distillation of pine, birch, beech, and

juniper, contain acetic acid or phenolcarbonic acids, with a relative absence

of toxic anthracene and pyridine derivatives.

•Polytar (Steifel, Coral Gables, Florida): A tar blend of coal tar, juniper tar

(cade oil), and pine tar has been used clinically for the treatment of psoriasis,

seborrheic dermatitis, and atopic dermatitis.

•In a 6-week, openlabel, noncomparative trial of 910 patients, topical scalp

treatment for seborrheic dermatitis was evaluated in patients using the

combination of a tar blend 1% shampoo (Polytar) and zinc pyrithione 1%

mixed in a shampoo base. Results showed a statistically significant decline in

mean dandruff score, with an 84.8% reduction at 6 weeks.

Superpotent corticosteroid applied as a short contact treatment.

•Would provide similar efficacy results to ketoconazole without

showing side effects?

INFANTILE SEBORRHEIC DERMATITIS

Infants with seborrheic dermatitis usually present with cradle cap. Within the first

few months of life, generally by weeks 3 to 5, the scalp can be covered with a

greasy, yellowwhite, thick scale often with fissuring and some erythema but without

alopecia.

Erythema desquamativum (Leiner’s disease) was originally described as a very rare

but severe form of seborrheic dermatitis in infants with erythroderma and

immunodeficiency.

TREATMENT OF INFANTILE SEBORRHEIC DERMATITIS

•For infants, the scalp tends to be the area with the most involvement, especially at

the vertex.

•SD will eventually resolve on its own without any treatment.

•Various regimens exist but in general daily use of simple emollients (mineral oil,

petrolatum, olive oil) or non-prescription shampoos alone or in combination will

soften the scale to allow it to be gently massaged away with fingers or

an infant brush.

•Ketoconazole 2% shampoo has been reported to be safe in infants less than 1 year

of age with no detectable serum levels of the drug or change in liver enzymes.

•Other reported treatments include over-the counter topical tar shampoos, selenium

sulfide shampoos, topical corticosteroids, and salicylic acid in shampoos

or in an emollient. (There are no large, randomized, control trials evaluating the

safety and efficacy of these regimens in infants. )

•With salicylic acid, there is some concern for potential systemic absorption.

FDA

•none approved for children younger than 2 years.

•Approved medications include:

•ciclopirox 0.77% gel (Loprox) twice a day for 4 weeks for ages older than 16

•ciclopirox 1%shampoo twice a week for 4 weeks for ages older than 16

•ketoconazole 2% foam (Exina) twice a day for 4 weeks for ages older than 12

•ketoconazole 2% gel (Xolegel) daily for 2 weeks for patients older than 12

•selenium sulfide 1% or 2.5% shampoo (Selsun) twice a week for 2 weeks for

ages older than 2

•sulfacetamide 10% lotion, cream, gel,wash, foam (Carmol Scalp Treatment,

Klaron, Ovace) daily for 8 to 10 days for ages older than 12

•sulfacetamide/ sulfur 10%/5% wash, cream, or gel (Plexion, Rosac, Rosula)

daily or twice daily for ages older than 12

•There are some topical corticosteroids approved for pediatric “corticosteroid

responsive dermatoses,” but none are specifically approved for seborrheic

dermatitis.

Thank You!