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Received: 18 April 2020    Accepted: 7 May 2020

DOI: 10.1111/jocd.13488

REVIEW ARTICLE

Pityriasis capitis: Causes, pathophysiology, current modalities,

and future approach

Umang Sheth B.Pharm  | Payal Dande M.Pharm, PhD

SVKM's NMIMS, School of Pharmacy &

Technology Management, Shirpur Campus,
Shirpur, India
Correspondence
Payal Dande, Mukesh Patel Technology
Park, Babulde, Bank of Tapi River, Mumbai-
Agra Highway, Shirpur- 425 405, Dist.
Dhule, Maharashtra, India.
Email: payal.dande@nmims.edu
Abstract
Background: Pityriasis capitis commonly known as dandruff is one of the most com-
mon and widely seen dermatological disease that affects majority of the world popu-
lation. It is more than superficial flaking, as it leads to significant structural changes
in the stratum corneum and inflammatory biomarkers. Various intrinsic and extrin-
sic factors, such as Malassezia yeast, host epidermal conditions, sebaceous secre-
tion, and abnormal immune responses, are found to contribute to the pathogenesis.
Regardless of wide research, detail understanding, and treatment modalities, it still
remains to be a cause of concern due to its recurring nature.
Aims: The objective of this study is to enhance the understanding of its wide causes,
pathophysiology, current treatment, and future approach.
Methods: The article also aims at evaluating various promising anti-dandruff agents
that can be further researched to become the leads in anti-dandruff therapy.
Results & Conclusion: The article summarizes the current knowledge on dandruff
and present new facts and evidences in order to spread awareness, create potential
for new herbal treatment options, and effectively control the most commercially ex-
ploited scalp disorder.

KEYWORDS

anti-dandruff agents, dandruff, herbal drugs, Malassezia, Pityriasis capitis

1 |  I NTRO D U C TI O N a normal scalp, while Figure 2(B) depicts dandruff-affected scalp

Pityriasis Capitis is a scalp disorder affecting more than half of the
global population. A survey in the United States showed that 50
million people mainly in the prepubertal age suffer from dandruff
annually and the prevalence is sharply increasing due to rapid ur-
banization.1 It varies in severity and tends to affect men more than
women. It occurs more frequently in adolescents, young adults,
and again in senior adults over 50 years of age. 2 It is also found to
be seasonal: occurring mainly in winter and least during summer
(Figure 1).
Dandruff causes itchy, flaking skin with mild inflammatory re-
action. It is a mild form of seborrheic dermatitis, and its severity
varies from mild dandruff to exfoliative erythroderma requiring a
well-established line of treatment. Given below Figure 2(A) shows
with flaky skin.
2 | R ATI O N A LE / E TI O LO G Y
There are several extrinsic and intrinsic factors that seem to play
a role in causing P capitis (dandruff). Extrinsic factors include lack
of physical hygiene, excessive use of hair sprays, gels, wax, creams,
persistent aesthetical disturbances, and exposure to dust and dirt.
Intrinsic factors majorly include increased microbial flora, individual
susceptibility, allergy, sensitivity, hormonal imbalances, genetic pre-
disposition, and metabolic products of some essential amino acids
such as tryptophan as well as immunosuppression. Figure 3 highlights
some of the major intrinsic and extrinsic factors causing dandruff.

J Cosmet Dermatol. 2020;00:1–13. wileyonlinelibrary.com/journal/jocd© 2020 Wiley Periodicals LLC     1 |

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2       SHETH and DANDE
2.1 | Extrinsic causes
The potential extrinsic causes for dandruff are continuous exposure
to sunlight, poor hygiene, overuse of shampoo, cosmetic products
such as hair sprays, gels, creams, frequent combing, and environ-
3
mental pollutants.
Further persistent aesthetical disturbance and psychological
trauma promotes negative socio-economic impact and leads to the
overgrowth of yeast and cause dandruff.
2.2 | Intrinsic factors
Skin cells are formed persistently on the scalp, so the shedding of
dead skin cells is a typical procedure. With dandruff, skin cells are
shed at a quicker rate than ordinary. Oil from the scalp makes the
skin cells clump together and show up as white flakes.
The scalp has a biotic network out of which Staphylococcus
spp., Propionibacterium spp., and Malassezia spp are known com-
ponents. However, certain studies have shown that the presence
of dandruff is closely associated with the disequilibrium in the pro-
portion of these major fungal and bacterial population colonizing
the scalp.4
Malassezia (etiological factor) is a yeast that is present on healthy
as well as dandruff-afflicted scalps. The central dandruff hypothe-
sis remains that this lipophilic yeast, Malassezia previously known
as Pityrosporum, is the main causative agent of dandruff.5 However,
on the dandruff-afflicted scalp, the levels of Malassezia increase to
almost double their normal level.6 It has been found that some met-
abolic products of tryptophan produced by Malassezia, for example,
indole derivatives, are the main cause of dandruff.
Dandruff can also be caused due to individual susceptibility and
allergy sensitivity. Heredity only plays a small role in developing a
predisposition for this condition.
According to cosmetic dermatologists, other probable causes
like stress, poor diet, genetic disposition, hormonal imbalances, and
infections further contribute to developing dandruff.7
2.3 | Immunosuppresive diseases and
Pityriasis capitis
Some people with low immunity are more susceptible to dandruff,
while others face intermittent clearing cycles and occasional flare-
ups of the condition. There could be various reason of weaken im-
munity. It could be due to immunosuppressive disease or drugs.
High prevalence and reoccurrence of dandruff in patients with im-
munosuppressive disorders suggest the relationship between fungal
growth Malassezia and the immune system.8
Immunosuppressive diseases such as AIDS, sickle cell anemia,
cancer, Parkinson's disease, multiple sclerosis, and mood depres-
sion result in aggravation of P capitis. Research suggests that stress
can reduce the effectiveness of the immune system, and thus, it is
possible that by inhibiting the immune system, stress could poten-
tially contribute to dandruff.9
However, Malassezia infections can manifest as superficial lo-
calized or can cause systemic infections in immune-compromised
hosts.10 Research suggests that immune response and inflammation
show the presence of host susceptibility factors, allowing the transi-
tion of M furfur to its pathogenic form.11
3 | PATH O PH YS I O LO G Y O F C AU SATI V E
AG E NT S
Dandruff is an improper cluster or collation of corneocytes caused
due to pathophysiological changes in the stratum corneum of
the scalp.12Increased research on dandruff has suggested that
Malassezia yeasts are responsible for initiating inflammatory and
hyperproliferative response of the epidermis. The pathogenesis of
dandruff consists of four pathophysiological events namely interac-
tion of Malassezia with the epidermis, initiation and propagation of
mild inflammation, disruption and differentiation of the epidermis,
and functional skin barrier disruption as shown in Figure 4.13
Sebaceous glands are microscopic exocrine glands which se-
crete an oily matter, the secretion being maximum on the scalp,
face, and cheek. In general, bacteria and fungus require lipid en-
vironment to grow and so it is generally found in the areas with
many sebaceous glands. The sebum secretion is a complex mix-
ture of wax esters, saturated and unsaturated fatty acids, tri-
glycerides, sterol esters, squalene, and sapienic acid (primitive to
humans).14 The secretion of sebum is under hormonal control, and
thus, hormonal imbalance may lead to over secretion of sebum.
The commensal microbes such as Malassezia, propionibacterium,
and staphylococcus on the scalp feed on this sebum, breaking the
triglycerides and esters into monoglycerides and free fatty acids
including oleic acid. The free fatty acids that are formed cause skin
irritation leading to scalp hyperproliferation which further leads
to formation of dandruff. Thus, people who suffer from dandruff
generally have an over active sebaceous glands, which make their
scalp oily.15 The investigations exhibit that the increased number
of scalp microorganisms found in dandruff occurs as secondary
part to increased nutrients.16
There are 14 described species of the yeast namely M globosa, M
obtusa, M restricta, M furfur, M slooffiae, M capre, M yamotaensis, M
japonica, M equina, M dermatis, M pachydermatis, M cuniculi, M nana
and M sympodialis.10 Their growth may be exacerbated by the hyper-
secretion of sebum and hyperproliferation of the stratum corneum.
Out of these, Malassezia globosa and Malassezia restricta predomi-
nate on dandruff scalp.17 M globosa is considered to be the initiat-
ing organism by virtue of its high lipase activity and is expressed
as M globosa lipase on the human scalp.18 Another important one is
M furfur that can grow in yeast phase as well as mycelia phase. The
organism requires a complex lipid environment for growth which ex-
plains its occurrence on the skin.19 One of the probable reasons for
more studies on M furfur is because of its ability to form filaments
SHETH and DANDE |
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F I G U R E 1   Graphical abstract of I; causes and solutions

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4       SHETH and DANDE
(A) (B)
F I G U R E 3   Major extrinsic and intrinsic factors causing dandruff
when it becomes its pathogenic form, making it more researchable
and interesting.
Mating of Malassezia species may also be considered to be a vital
part of pathogenesis of dandruff formation. Various researches
prove that Malassezia species complete their sexual cycle during
growth on human scalp. 20-22 It is believed that their close relatives
Malassezia species may potentially complete their life cycle on human
skin. Human skin presents an environment with a temperature below
the physiological temperature and that would immobilize cells, thus
facilitating the mating process.
4 |  C U R R E NT TR E ATM E NT
The current anti-dandruff agents contain antifungal, keratolytic,
anti-inflammatory, anti-sebum, and antibacterial agents such as
given below. 23
1. Antifungal agents: zinc pyrithione, imidazoles.
F I G U R E 2   A, Normal scalp B,
Dandruff-affected scalp
2. Anti-keratostatic or keratolytic agents: tar, selenium sulfide, sali-
cylic acid, sulfur compounds.
3. Anti-inflammatory agents: corticosteroids.
4. Anti-sebum agents: acting on sebaceous glands to slow down cell
and oil production based on mechanism of action. Examples in-
clude vitamin A derivatives such as isotretinoin and anti-andro-
gens such as cyproterone acetate.
5. Immunomodulator agents: pimecrolimus, tacrolimus.
Following Table 1 gives a brief description on anti-dandruff ther-
apy, their mechanism of action, and major side effects. 24,25
4.1 | Antifungal agents
The current treatment includes various topical antifungal agents
that aims to kill and reduce the level of Malassezia similarly alleviate
the activity of sebaceous glands. Major topical antifungal agents that
are used to control the dandruff condition include imidazole deriva-
tives, zinc pyrithione (1-hydroxy-2-pyridinethiones and their salts, in
particular zinc salts), sulfur, piroctoneolamine, and undecylenic acid
derivatives.
The azoles represent the largest class of antifungal agents used
in the treatment of dandruff. Azoles act by intervening ergosterol
biosynthesis. They inhibit the Cyp-450 enzyme responsible for
conversion of lanosterol to ergosterol. Inhibition of ergosterol syn-
thesis disrupts the membrane function and increases the permea-
bility. Thus, they are found to work against both Candida albicans
and Malassezia furfur. It affects the cell wall, leak out the content of
fungal cell and leads to the cell death.
Other topical antifungal operators, for example, the allylamines
(terbinafine), benzylamines (butenafine), and hydroxypyridones (ci-
clopirox), have likewise been compelling. 26
Treatment of zinc pyrithione (ZPT) in dandruff patients de-
creases the quantity of Malassezia on the scalp, thereby reducing the
flaking. High level of zinc causes inhibition in the growth of microbial
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F I G U R E 4   Schematic diagram for pathophysiology of Pityriasis capitis

TA B L E 1   Current topical agents for dandruff treatment

Class Medication Mechanism Side effects

Azoles Ketoconazole Inhibition of fungal cell wall synthesis Severe itching, burning, redness, pain
Fluconazole Prolonged skin retention
Clotrimazole Irritation, burning at site of application
Sertaconazole Contact dermatitis, pruritus
Bifonazole Allergic skin inflammation
Miconazole Irritant contact dermatitis, itching,
burning sensation
Allylamine Terbinafine (systemic) Interferes with synthesis of ergosterol by Rare tachycardia and insomnia
Benzylamine Butenafine inhibiting squalene 2,3-epoxidase Dryness, swelling
Organosulfur Zinc pyrithione Increases cellular copper and interferes with Irritant contact dermatitis in
iron-sulfur proteins approximately 3% patients
Hydroxypyridones Ciclopirox olamine Inhibition of metal-dependent enzymes Itching, burning sensation
Keratolytic agents Selenium sulfide Cytostatic and keratolytic Orange-brown scalp discoloration
Coal tar Disperses scales, diminishes epidermal Itching, burning sensation
multiplication and dermal penetration
Anti-inflammatory Corticosteroids Penetrate the stratum corneum with limited Acne, weight gain.
agents increase in the sebum level in the serum.
Anti-sebum agents Isotretinoin Reduces sebum production and stabilizes Dry scalp
keratinization.
Immunomodulators Pimecrolimus Reduces the ability of mast cells to release Risk of skin malignancy and lymphoma
Tacrolimus chemicals that promote inflammation with prolonged use.
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6       SHETH and DANDE
cell by binding to intracellular proteins. ZPT was also found to me-
diate growth inhibition through causing an increase in copper in the
Malassezia species. Saunders et al (2011) showed that incubation of
zinc pyrithione with the scalp fungus Malassezia globosa also leads
to a copper imbalance, suggesting that the increased intracellular
copper is the source of efficacy against the fungi associated with
P capitis. 27
4.2 | Role of zinc in immunity
Zinc is identified to play a vital role in the immune system, and
zinc-deficient persons are extremely susceptible to a variety of
Malassezia species. Zinc is a potent mediator of host resistance to
infection. Due to low toxicity of zinc at high doses, 28 therapeutic use
of zinc as an immunomodulator along antifungal agent may serve as
a novel approach.
4.3 | Keratolytic agents
Keratolytic agents such as selenium sulfide reduce the keratinocyte
adhesion as well as hyperkeratosis, thereby increasing the absorp-
tion of antifungal agents. 29
Tar is used as a second-line therapy as it decreases the number
and size of epidermal cells and diminishes epidermal multiplication
and dermal penetration thereby reducing the Malassezia colonization.
However, it has limitations such as staining, odor, and messiness in
its application. 30
4.4 | Anti-inflammatory agents
Corticosteroids are used to reduce any inflammation or dry skin.
Topical corticosteroids pervade the stratum corneum and achieve
sufficient concentration in the skin without reaching high serum
fixations.
Topical steroid (such as hydrocortisone and betamethasone),
topical lithium salts, and topical calcineurin inhibitor treatment (such
as tacrolimus and pimecrolimus) were found to reduce the symptoms
of seborrheic dermatitis.31
4.5 | Anti-sebum agents
In normal quantities, sebum is an oily substance that has the func-
tion of protecting the skin from dehydration. It also has antibacterial
properties. The presence of excessive sebum results in an alteration
of the hydrolipid equilibrium of the skin. Anti-sebum agents such as
antiseptic lotions, lotions with fat-soluble substances (to dissolve
fats), lotions with lipid (oil-based) solvents, and soothing lotions
(amino acids, sulfur, pine tar) may be used to control sebum secre-
tion. Moreover, an astringent action should be applied to sebaceous
glands to block them from producing too much sebum and to neu-
tralize the foul odor caused by the superficial oxygenation of lipids
(fats) produced by seborrhea.32
4.6 | Immunomodulators
Tacrolimus and pimecrolimus inhibit calcineurin and have been
effective in the treatment of P capitis. Both drugs exhibit an anti-
inflammatory action by inhibiting cytokine production; however,
tacrolimus possesses strong fungicidal activity in vitro against
Malassezia. Tacrolimus and pimecrolimus are mainly for short-term
use in patients with seborrheic dermatitis.33
5 | LI M ITATI O N S O F CU R R E NT
TR E ATM E NT
The anti-dandruff agents are found in different combination and are
available in the various forms such as shampoos, lotions, condition-
ers, and creams containing a combination of synthetic and natural
components.
The synthetic anti-dandruff agents have been demonstrated to
cause baldness, premature hair graying, hair loss, and inflamed hair
follicles. Most medicated formulations carry risks of side effects
such as dryness of hair/skin, associated cytostasis, and eczema.34
The common synthetic excipients used in shampoos such as par-
abens, propylene glycol, and olefin sulfonate have proven to be dan-
gerous to entire human anatomy as they play a role in development
of cancer. Sodium lauryl sulfate, an ingredient present in 90% of the
shampoos, causes cataract in adult and improper eye development
in children, corrodes hair follicles, and impairs the ability of hair to
grow.
Anti-dandruff shampoos are able to fight the dandruff causing
fungi but they are unable to prevent the reoccurrence of dandruff,
hence “Anti- Dandruff” may be a misnomer. The other drawback
from commercial antifungal is the adverse drug interactions with
other medications and their high cost in pharmacies.
Current approach of using topical antifungal, anti-inflammatory,
anti-sebum, and keratolytic agents is targeting the symptoms how-
ever not effective to eradicate the root cause.
6 | N OV E L TO PI C A L D RU G D E LI V E RY
S YS TE M S FO R A NTI - DA N D RU FF AG E NT S
The conventional antifungal agents are found to be ineffective due
to their poor bioavailability and short duration at their site of appli-
cation which further affects the complete elimination of organisms
and thereby increasing tolerance causing the reoccurrence. Hence,
newer drug delivery forms are being researched to resolve the bio-
availability and specificity issues. Novel drug delivery systems such
as liposomes, transfersomes, niosomes, and pharmacosomes have
SHETH and DANDE
found to be able to localize the drug activity at the site of action
thereby lowering its concentration at the other sites in body. Thus,
novel drug delivery systems are being evaluated for its enhanced
therapeutic efficacy and stability.
Liposomes serve as a drug vesicular carrier for improving the
delivery of variety of therapeutic agents to the target sites in the
body.35 These are microscopic vesicles comprising phospholipid
bilayer. These carriers enhance the therapeutic index of drug and
thereby its therapeutic efficacy. They have advantage of being bio-
compatible, completely biodegradable, nontoxic, and flexible vesi-
cles but have high cost of production, probabilities of leakage and
36
may have fusion of encapsulated drug/ molecules. Vivek Dave
et al showed that liposomal loaded ketoconazole with neem extract
showed synergistic effect and had a great potential in the treatment
37
of seborrheic dermatitis.
Micelles are nanosized colloidal conveys with a hydrophobic
center and hydrophilic shell. They are utilized as pharmaceutical
transporters for water-insoluble medications and are alluring med-
ication bearers providing increased bioavailability. Manish Kumar
et al proved the use of miconazole nitrate loaded micellar gel for
enhanced topical delivery of deep seated fungal infections. The per-
meability and solubility of miconazole nitrate was found to have in-
creased due to micellization.38
Transfersomes are an ultra-deformable lipid aggregates, com-
posed of lipids and biocompatible membrane softeners having a
smaller particle size than liposomes. These vesicles are capable of
penetrating the skin and have an inner aqueous region surrounded
by a lipid bilayer. Transfersomes act by penetrating the stratum
corneum by either intracellular or transcellular route producing an
“osmotic gradient.” These vesicles migrate into the hydrated deeper
layers as they can easily squeeze through pores of stratum corneum
due to its elastic nature. One of the advantages of transfersomes
includes the presence of highly flexible membrane which permits
transfersomes to squeeze through the pores smaller than their own
diameter, while limitations include chemical instability as drug deliv-
39
ery vehicle.
Microemulsions are transparent, thermodynamically stable, and
isotropic liquid dispersions, making them promising colloidal trans-
porter frameworks for topical and transdermal administration of
medications. The upsides of topical microemulsions incorporate im-
proving dissolvability of medications, high thermodynamic stability,
40
simplicity of arrangement, and low expenses. Microemulsions of
poorly water-soluble antifungal drugs miconazole, ketoconazole, and
itraconazole were designed and developed by Puranajoti et al using
either mineral oil or olive oil as an oil phase.41
Solid lipid nanoparticles (SLNs) are transporters in which the
medication is entrapped inside a solid lipid center framework.
Cases of these lipids are triglycerides, diglycerides, mono-
glycerides, unsaturated fats, steroids, and waxes. 39 Points of
interest of lipid nanoparticles are that the lipids used in their
preparation are physiological lipids and that they can be prepared
utilizing natural solvent free techniques.42 Surajit Das et al proved
that topical gel formulation of imidazole drug-loaded SLNs can be
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      7
used for sustained/prolonged topical delivery of imidazole anti-
fungal drugs.43
Silver nanoparticles, in contrast to silver ions, serve as a better
alternative owing to slow and long-term release of ions by oxida-
tion. Silver nanoparticles act as a potential fungistatic material for
containing and eradicating scalp-related diseases such as dandruff.
Research carried out by Mohammed F Anwar et al showed that sil-
ver nanoparticles exhibit excellent anti-dandruff activity and were
considered superior to tested drugs in therapeutic efficacy. Their
mechanism of action was found out to be easy entry into the cel-
lular organization by breaching cell membrane.44 Silver nanoparti-
cles synthesized from Solanum trilobactum leaf extract using green
chemistry approach were also found to be effective in dandruff
treatment 45
Following Table 2 encompasses the novel topical drug delivery
systems for anti-dandruff agents;
7 | H E R BA L TR E ATM E NT S
Herbal drugs serve as the best alternative for patients with dandruff
who prefer a natural product. A wide range of active constituents
of various plants including vitamins, phyto-hormones, essential oils,
bioflavonoids, enzymes, amino acids, tannic acid, fruit acids, and gly-
cosides are gaining importance in anti-dandruff remedies.49
The following Table 3 gives systematic information regarding
natural anti-dandruff agents and their uses.
1. Aloe barbadensis, commonly known as aloe vera, belonging to
family Asphodelaceae, has potent antimicrobial, antifungal, and
antiviral properties attributed to the natural anthraquinones,
saponins, and a polysaccharide called acemannan.72 Grindley
D, Reynolds T (1986) confirmed that the gel extract from
the parenchymatous cells in the leaf pulp of Aloe vera is
responsible for anti-dandruff treatment.73 Aloe has a pH of
6 which is similar to the pH of skin, thus permitting simple
infiltration of the scalps corneal stratum.
2. Azadirachta indica, commonly known as neem, belonging to fam-
ily Meliaceae, has been found to have the properties of a blood
purifier and high antibacterial activity. It is used for a number of
medicinal purposes. Neem has been shown to inhibit dermato-
phyte. Prabha Manju M et al (2012) showed that chloroform and
methanolic extracts of Azadirachta indica showed maximum an-
tifungal activity and exhibit MIC 1 mg/mL.74 This anti-adhesive
mechanism is responsible for antifungal activity. Beauty experts
say that neem extracts can be used in several ways to treat dan-
druff. Chewing neem leaves every morning is considered to be
the best way to get rid of dandruff.
3. Phyllanthus emblica, commonly known as amla, belonging to
family Euphorbiaceae, contains vitamin C which is effective in
dandruff treatment as it prevents accumulation of dandruff on
scalp. The fresh juice of E officinalis was found to be most effec-
tive against the M furfur and M Globosa. The in vitro diameter
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8       SHETH and DANDE
Delivery system Drugs
Liposomes Miconazole nitrate
Micelle Clotrimazole, fluconazole, and
econazole nitrate
Microemulsions Itraconazole, ketoconazole(o/w),
fluconazole
Vesicular delivery Econazole nitrate (ethosomes),
system miconazole nitrate (liposomes)
Proniosomes Miconazole and itraconazole
Solid lipid Clotrimazole and miconazole
nanoparticles
Silver Nanoparticles Solanum trilobactum leaf extract
of the highest zone of inhibition was found to be 22 mm and
20 mm, respectively, and the results of aqueous and ethanol
extract showed appreciable antifungal activity as confirmed by
P. Sivagurunathan et al (2016).3 The MOA suggest the additive
effect of amino acids for nourishing the scalp by the water hold-
ing capacity. The general and medicinal uses include astringent,
laxative, diuretic, and rich source of vitamin C. Fruit in dried
powdered form is used to promote hair growth, prevent prema-
ture graying of hair, and control dandruff.
4. Mentha piperita, commonly known as peppermint, belonging to
family labiatae, is a characteristic disinfectant specialist, which
reinforces the scalp's well-being by clearing out dead skin and
microbes. Peppermint oil has remedial properties for restor-
ing the scalp to its regular pH levels. This pH adjusting impact
diminishes dryness and flakiness, which is normally the reason
for irritation and dandruff. Peppermint oil for scalp health effec-
tively kills Malassezia cultures leads to reducing dandruff symp-
toms. Mentha piperita contains tannins which are inhibitory to
bacteria, fungi, and yeast growth. Rajinder Singh et al. (2015) in
their research paper showed significant antibacterial activity of
Mentha oil and its different extracts against gram positive and
gram negative bacteria.75
5. Glycyrrhiza glabra, commonly known as liquorice, belonging to
the family Leguminoseae, contains glycyrrhizin and can help re-
63
duce the scalp's secretion of oils. The effects of dandruff can
be minimized by reducing the oils in the scalp.
6. Citrus limon, commonly known as lemon, belonging to family
Citrus, particularly lemon, found to be powerful against skin
conditions like dandruff.76 It is rich in vitamin C and helps to
re-establish the balances of the skin. Lemon juice acts as an
TA B L E 2   Novel topical drug delivery
Advantages of delivery
systems for anti-dandruff agents
system
Localized drug delivery,
increased bioavailability,
and enhanced permeation36
Increase efficacy of topical
drugs for superficial fungal
infections 46
Enhances percutaneous
absorption of the drug47
Increase the lipidic
components of topical
drugs into the stratum
corneum39
Enhances residence time of
drugs in the epidermis and
stratum corneum42
Good carriers for lipophilic
drugs 48
Green synthesized AgNPs
using S trilobactum have
great potential in dandruff
treatment45
effective cleansing agent and removes excess sebum and dan-
druff particles. Dandruff has also been linked with zinc defi-
ciency. According to Curejoy Editorial (2017), small amounts of
zinc in lemon juice could also add to its effectiveness against
dandruff. Lemon juice & henna extract and lemon & amla com-
binations are considered to show the best synergistic activity
against Malassezia furfur.
7. Apis mellifeca, commonly known as honey, belonging to family
Apidae, has rich anti-oxidant properties which prevents damage
to the scalp. It also comprises antibacterial and antimicrobial
qualities which prevent scalp infections and soothe issues like
dandruff allowing for unhindered hair growth.
8. Honey and its constituents have been shown to modulate cy-
tokine production by a range of cells. This is due to the anti-
microbial properties of honey which contribute to skin healing
by enhancing the skin immune system to fight infection or sup-
pressing inflammation in the skin.61
9. Eucalyptus globulus, commonly known as eucalyptus, belonging
to family Myrtaceae, promotes shine and increases circulation to
the scalp. Hemraj Vashist et al (2012) showed that the essential
oil of fresh plant leaves obtained by hydrodistillation procedure
is responsible for treating dandruff.77 The oil contains more than
80% cineol, with different constituents as p-cymene, alpha-
pinene, limonene, and geraniol.78
10. Olea europaea, commonly known as olive oil, belonging to fam-
ily Oleaceae, can temporarily remove dandruff flakes. Olive oil
when applied in the scalp can soak into thick, scaly scalp that
cause persistent dandruff issues and moisturize dry areas that
may be flaking off. It contains vitamins A, E, and K that repair
damaged hair and clarifies hair follicles.66
SHETH and DANDE |
      9

TA B L E 3   Natural anti-dandruff agents

Ingredient Source Part used Active constituents Function/Uses

Aloe vera Aloe barbadensis Leaf Salicylic acid Hydrates, heals, and soothes the
scalp50
Amla Phyllanthus emblica Fruit Phyllemblin, ascorbic acid, and Reverses gray hair, adds shine, and
gallic acid thickens hair51
Argan oil Argania spinosa Nut kernels Tocopherol, ferulic acid Promotes hair growth and moisturizes
the scalp52
Arnica Arnica montana Flowers Pseudoguaianolide Hair tonic and stimulates hair follicles53
sesquiterpene lactones,
thymol
Bahera Terminallia bellirica Dried ripe fruits Ellagic acid, gallic acid Inhibitory effect due to gallic acid 54
Burdock Arctium lappa Root Sterols, tannins Treatment of seborrhea55
Cade oil Juniperus oxycedrus Wood of shrub Cadinene, cadinol Enriches hair follicles, antimicrobial
properties56
Datura Datura metel Juice Hyoscine (scopolamine) Juice is applied against dandruff57
Shikakai Acacia concinna Leaf, bark and Vitamin A,D,E,K, saponins Promotes hair growth, removes
fruit pods dandruff and lice from the hair58
Fenugreek Trigonella foenum Seeds Nicotinic acid, lecithin Seeds are softened and used as
poultice59
Henna Lawsonia inermis Leaf Lawsone, gallic acid, tannins Anti-inflammatory, fungicidal, and
antibacterial properties60
Honey Apis mellifeca Honey comb Hydroxypropyltrimonium Treats microbial infections of the scalp
and immunomodulatory properties61
Lemon Citrus limon Juice Limonene, linalool, cineole, The acidic effect of the juice has high
citric acid potential to inhibit fungal growth62
Liquorice Glycyrrhiza glabra Root Glycyrrhizin, liquiritin Reduces scalp secretion of oils63
Mango Mangifera indica Kernels Mangiferin, myrcene Ground kernels mixed with milk acts as
anti-dandruff agent64
Neem Azadirachta indica Leaf Azadirachtin, meliantriol Antifungal activity due to anti-
adhesive mechanism65
Olive oil Olea europaea Leaf Oleic acid, squalene, Anti-inflammatory effect66
polyphenols
Onion Allium cepa Juice Allicin, diallyl sulfide, alliin Promotes hair growth, strengthens
roots of hair.
Promising antifungal activity67
Peppermint oil Mentha piperita Leaves Menthol, menthone Natural hair thickening properties and
nourishes damaged hair
Powerful antimicrobial agent68
Reetha Sapindus mukorossi Dry de-seeded Triterpene, oleanane, Antibacterial and anti-inflammatory
fruits dammarane and tirucullane activity69
saponins
Snakegourd Trichosanthes Leaves Carotenes Moisturizes the scalp70
cucumerina
Eucalyptus Eucalyptus globulus Leaf 1,8-cineol, α-pinene Potential anti-dandruff activity71

11. Trichosanthes cucumerina, commonly known as snakegourd,
belonging to family Cucurbitaceae, is considered to be very ef-
fective in dandruff treatment as well as alopecia. This can be
attributed to the rich vitamin and mineral content, especially
high levels of carotenes which specialize in hair care. It is rec-
ommended that rubbing a healthy amount of juice in the scalp
and leaving it for half an hour stimulates the body to boost fluid
production and moisturizes the scalp.70
12. Juniperus oxycedrus, commonly known as cade oil, belonging to
family Cupressaceae, is distilled from the wood of the shrub and
has a dark color with a smoky aroma. Cade oil is used for its anti-
microbial and dermatological benefits like seborrheic dermatitis,
dandruff, lice, and other scalp problems. It is recommended that
adding 2 drops of cade oil in bathing water or mild shampoo can
act as a potent remedy for treating dandruff as it promotes the
growth of hair by enriching the hair follicles.56
 |
10       SHETH and DANDE

13. Allium cepa, commonly known as onion, belonging to family
Amaryllidaceae, contains proteins, allyl propyl disulfide, and dial-
lyl sulfide. Sharquie KE et al (2002) showed that the use of crude
onion juice gave considerably higher results with regard to dan-
druff treatment.79It also contains some mineral like potassium,
zinc, calcium, and magnesium.
14. Acacia concinna, commonly known as shikakai belonging to fam-
ily Leguminosae, helps in expelling dandruff and extremely viable
in expelling oil and dirt from hair. It has a naturally mild pH and is
a natural hair conditioner. Using pods and leaves of dry shikakai
is considered to be one of the upcoming remedies for dandruff
owing to its antifungal properties.58
15. Jasminum sambac, a flowering plant commonly known as Arabian
jasmine, belonging to the family Oleaceae, is abundant locally
in Southeast Asia and traditionally used as remedies for skin
problems such as acne, white head, and blackhead, that has
proven successful. The leaves of J sambac contain the secoiri-
doid glycosides, jasminin, quercetin, and rutin. As J sambac pos-
sesses antibacterial property, it can be used to treat acne and
skin infections. The callous extracts of J. sambac were also re-
ported to display antimicrobial activity against Staphylococcus
albus, Proteus mirabilis, Salmonella typhi, and Propionibacterium
acnes.80,81 The use of J sambac extract can be a potential additive
in skin and hair products to prevent Malassezia sp infection alto-
gether.Santhanam et al (2014) indicated that methanol extract
of flowers exhibited twice inhibitory effect against Malassezia sp
compared to leaves.82
8 | LI M ITATI O N S O F H E R BA L TR E ATM E NT
Although these herbal formulations are free of synthetic chemicals,
they have higher prices than conventional because the ingredients are
natural and scarce. The minimum inhibitory concentration (MIC) values
of plant extracts are much higher than synthetic agents which means
that more quantity of plant extracts are needed in the formulation in
order to inhibit the growth of microorganism which serves as a disad-
vantage as compared to synthetic treatment options which require very
little concentration of ingredients to show a similar inhibitory action.
9 | CO M PLE M E NTA RY A N D A LTE R N ATI V E
TR E ATM E NT S
According to the Ayurvedic system of medicine, dandruff is caused
due to the imbalance of all three doshas (Vata, Pitta, and Kapha),
Vata and Pitta imbalance being mainly responsible for its occurrence.
Ayurvedic medicines that can be used for treatment of dandruff
include Dhurdhurapatradi Thailam for external application, while
Gandhaka Rasayana is used as an internal medicine for the treat-
ment of dandruff. Gandhaka Rasayana is purified sulfur combined
with hydrating and antimicrobial properties which helps remove
dead surface of skin, making it ideal for the treatment of dandruff.83
One theory of Ayurveda also states that dandruff can be caused
due to the impurities in the blood which lead to the inadequate
nourishment of the scalp. Thus, Khadirarishta and Saribadyasavam

TA B L E 4   Marketed preparations
Active ingredient in percentage
Srno Dosage form Brand name quantity

Topical treatment
1 Shampoo Dove Zinc pyrithione (1%)
Head and shoulders Zinc pyrithione (0.5%, 1%,1.5%)
Denorex Coal tar (2.5%)
Selsun Selenium sulfide (2.5%)
2 Cream Nizoral Ketoconazole (2%)
Lamisil Terbinafine (1%)
Lotrimin Clotrimazole (1%)
3 Gel Xolegel Ketoconazole (2%)
Loprox Ciclopirox (0.77%)
4 Hair oil Tvam Basil and neem
Trichup oil Rosemary oil and lemon oil
Himalaya Tea tree oil and rosemary
extract
Oral treatment
1 Tablets Nizoral Ketoconazole (200 mg)
Tricovel TricoLact, Lactobacillus
rhamnosus—LR04
2 Capsules Itrazole Itraconazole (100 mg)
SHETH and DANDE
are consumed for the detoxification of blood. Taking Panchakarma
detoxification procedures like Nasyam, Raktamokshana, Shirobasti,
Abhyanga, and Swedanam can be effective in the management of
dandruff.84
According to the Unani system of medicine, dandruff is also
called Huzaz/Abria and this condition arises because of Akhlat-e-
Radiyah (Morbid matter). Altaf Hussain Shah et al (2009) in their
study proved that the Unani formulation consisting of Althaea offi-
cinalis Linn (Khatmi), Cicerarietinum Linn (Nakhud), Viola odorata Linn,
and Viciafaba Linn (Baaqlaa) was equally effective as the standard
drug in reducing the symptoms of dandruff like itching and erythema
and that these ingredients have definite efficacy in the treatment of
dandruff.85
By following the Homeopathic system of medicine, patients
were able to reduce their dependency on the conventional treat-
ments. The principles of homeopathy are totally against the use of
localized topical treatment of skin diseases like dandruff because of
the temporary relief provided by these local applications thereby
suggesting root cause approach of a disease, with minimum side
effects. A few drugs which may be used to treat P capitis are arse-
nicum album, sepia, sulfur, calcarea carbonicum, graphites, meze-
reum, and so on. 86 Other homeopathic treatment options include
Thuja occidentalis which is used for white scaly dandruff, hair dry-
ness, and flakes falling off, and Kali Sulph for profuse creamish-yel-
low scaly dandruff.
According to the Chinese system of medicine, internal treat-
ment such known as Huang Lian Jie Du Tang (A traditional chinese
medicine to relieve inflammation and toxicity) is considered as an-
tiinflammatory, antifungal and antibacterial medicine which is used
to treat ‘damp heat and toxin type of dandruff'. Moisturizing herbs
such as raw Rhemannia and Scrophularia roots have some effect on
the bacterial overgrowth of certain strains of Staphylococcus that
are also present in the seborrheic dermatitis scalp. 87
10  | FU T U R E S CO PE A N D C H A LLE N G E S
The treatment of dandruff still remains to be a cause of concern due
to its recurring nature. Thus, there is a huge scope for research in
terms of novel formulations and drug discoveries. Future studies
should be directed to formulate effective anti-seborrheic therapies
with high frequency biostimulation treatments which disinfects the
skin and vascularises the follicles. Since topical antifungal agents
help in symptomatic relief, an intensive approach can be initiated
by evaluating the effectiveness of oral antifungal agents as a key
alternative treatment in the near future. As immunosuppression is
one of the major causes of recurrence, possible treatment with im-
munomodulatory drugs along with antifungal agents may lead to
effective dandruff treatment. Novel formulations with enhanced
bioavailability as well as clinical efficacy pose as potential drug de-
livery systems of future. Multi-targeted formulations are essentially
required to minimize the potential side effects and increase cosmetic
acceptance.
|
      11
11 | I M M U N O M O D U L ATI O N W ITH
A NTI FU N G A L AG E NT S —A N E W H O R IZO N
The limitations of conventional therapy can be minimized by mod-
ulating the immune responses of the host which may prove help-
ful in combatting this dermatological disorder. Immunomodulatory
therapy, in combination with existing antifungal therapy, will prove
to be an attractive option to enhance the immune system and aid
complete clearance of these pathogens. Additionally, as host im-
mune modulation and antifungal immunotherapy exhibit both ad-
vantages and limitations, comprehensive and methodical testing of
the efficacy of this synergistic combination from these categories
is in order. Down the road, there has to be comparative study be-
tween conventional antifungal agents and in combination with im-
munomodulatory agents to achieve targeted approach.88
A detailed research must be carried out to determine the impact
of fungal interactions in immunosuppressed individuals, which will
pave the way for future therapies to modulate the immune system
through modified antifungal therapy.89
According to Jung-Hyun Choi et al, the clinical implications of
immunomodulation effect of antifungal agents may have positive
outcomes if further research is carried out.90
The following Table 4 gives an account of a few marketed prepa-
rations of topical as well as oral anti-dandruff agents.
12 | CO N C LU S I O N
The current treatment of dandruff is focused entirely on symp-
tomatic treatment, while other etiological causes remain unex-
plored. This is the main reason why dandruff tends to reappear on
the scalp. Thus, attempts should be made to effectively treat dan-
druff by targeting the root cause using multi-targeted approach
with antifungal agents, anti-inflammatory, and immunomodulatory
agents.
AC K N OW L E D G M E N T S
We would like to thank the Management of SVKM's NMIMS School
of Pharmacy & Technology Management, Shirpur campus, India, for
their support and encouragement throughout the review process.
C O N FL I C T O F I N T E R E S T
The authors have no conflicts of interest.
ORCID
Umang Sheth  https://orcid.org/0000-0003-2309-169X
Payal Dande  https://orcid.org/0000-0003-3384-7454
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How to cite this article: Sheth U, Dande P. Pityriasis capitis:
Causes, pathophysiology, current modalities, and future
approach. J Cosmet Dermatol. 2020;00:1–13. https://doi.
org/10.1111/jocd.13488