Review Article

Premature Graying of Hair: A Comprehensive Review and Recent Insights

Abstract Kavita Poonia,

Background: Hair symbolizes well‑being and self‑expression, with graying occurring naturally among Mala Bhalla1
different racial groups at varying ages. Premature graying has psychological and societal impacts, Department of Dermatology,
influencing self‑esteem and quality of life. Gray hair usually advances gradually and is permanent, Venereology and Leprology,
with occasional reports of natural repigmentation. Premature graying of hair (PMGH) results from a All India Institute of Medical
complex interplay of genetic, environmental, and cellular factors. Materials and Methods: Studies Science, Bathinda, Punjab,
exploring links between gray hair and conditions such as osteopenia, hearing loss, smoking, obesity, 1
Department of Dermatology,
dyslipidemia, and cardiovascular disease have yielded mixed results. Despite continuous research Venereology and Leprology,
into the causes of gray hair, effective, evidence‑based treatments are lacking and still need to be Government Medical College
and Hospital, Chandigarh, India
improved. Conclusion: Herein, we reviewed the causes, mechanisms, risk factors, psychosocial
effects, and emerging therapies for PMGH.

Keywords: Canities, genetic, graying, oxidative stress, premature, treatment

Introduction Clinical presentation of gray hair:

Hair symbolizes well‑being and plays Canities, or hair whitening, primarily results
a vital role in social communication, from an optical phenomenon. As a result of
significantly shaping one’s physical the reflection or refraction of the incident
appearance and self‑perception. Graying of light, the pale‑yellow keratin appears white.[5]
hair, or canities, is a natural aging process Gray hair retains some color due to scattered
that occurs at different ages depending on melanosomes. However, white hair lacks
racial backgrounds. On average, Caucasians them entirely. Compared to pigmented hair,
start graying at around 34 years, while in gray hair tends to be thicker, rigid, and more
Blacks, it begins at around 43.9 years. challenging to manage. Gray hair also grows
Graying of hair may be labeled as faster and thickens more noticeably.[6] Gray
premature in Caucasians when it takes hair is particularly susceptible to damage
place before the age of 20 years, while in from UV radiation, necessitating increased
individuals of Black descent, the defined photoprotection.[7] In addition, structural
age may be before 30 years. There is alterations in the hair fiber make it challenging
no well‑defined threshold for premature for gray hair to maintain artificial color.[8]
graying of hair (PMGH) in the Asian Graying of hair differs between the genders.
population.[1,2] In women, it typically begins along the
PMGH has several psychological and hairline boundaries, whereas in men, it Address for correspondence:
sociocultural consequences, affecting first becomes noticeable at the temples Dr. Mala Bhalla,
self‑esteem, body image, and overall and sideburns before spreading to the Professor, Department of
entire scalp and eventually the occiput.[9] Dermatology, Venereology
quality of life due to society associating and Leprology, Government
gray hair with aging and compromised The rate of graying varies across different Medical College and
health. This phenomenon challenges our parts of the body. Scalp hair is usually Hospital, Chandigarh, India.
understanding of hair biology, genetics, affected first, followed by facial hair and, E‑mail: malabhalla@yahoo.
subsequently, body hair. Pubic, axillary, and co.in
and aging processes.[3,4] In this review,
we explore the various aspects of PMGH, chest hair retain pigmentation for a longer
including its causes, mechanisms, potential duration. This pattern may be attributed Access this article online
risk factors, psychosocial effects, and to discrepancies in the dispensing of
Website: https://journals.lww.
emerging treatments. melanocyte precursors during melanoblast com/idoj
migrations in embryonic development.[10] DOI: 10.4103/idoj.idoj_807_23
Quick Response Code:
This is an open access journal, and articles are
distributed under the terms of the Creative Commons How to cite this article: Poonia K, Bhalla M.
Attribution‑NonCommercial‑ShareAlike 4.0 License, which Premature graying of hair: A comprehensive review
allows others to remix, tweak, and build upon the work and recent insights. Indian Dermatol Online J
non‑commercially, as long as appropriate credit is given and the 2024;15:721-31.
new creations are licensed under the identical terms.
Received: 25-Oct-2023. Revised: 27-Jan-2024.
For reprints contact: [email protected] Accepted: 25-Mar-2024. Published: 30-Aug-2024.

© 2024 Indian Dermatology Online Journal | Published by Wolters Kluwer - Medknow 721
 Poonia and Bhalla: Premature graying of hair

Hair follicular pigmentary unit and melanogenesis This segregation of melanocyte subpopulations during
skin development has significant implications for
Immature melanoblasts, originating from the neural
understanding the melanocyte replenishment during the
crest, migrate into the skin during embryogenesis to give
hair cycle, the function of melanocyte stem reservoirs,
rise to melanocytes in both the epidermal and follicular
and the aging‑related changes in pigmentation, including
melanin units. As hair follicles mature, melanoblast/
the depletion of functional melanocytes contributing to the
melanocyte descendants, referred to as “transit” or
graying process.[16]
“transient‑amplifying” melanocytes, proliferate in the
epidermis and then migrate into the developing hair follicle. Aging of the follicular melanin unit
Within the follicle, these melanocytes can either remain
A hair follicle goes through various stages throughout
dopa‑oxidase‑positive cells (actively expressing tyrosinase)
the life span, resulting in different hair types. Fine,
or persist as dopa‑oxidase‑negative cells, depending on
unpigmented lanugo hair appears in fetal development,
their specific follicular location.[11]
which later transforms into shorter vellus hair, still lacking
The hair follicular melanin unit synthesis involves pigmentation. Subsequently, this vellus hair progresses
specialized cell types, molecular pathways, and cellular to intermediate hair with subtle pigmentation, eventually
organelles. It resides within the immune‑privileged forming long, thick terminal hair in adulthood.[10]
proximal hair bulb influenced by DP (dermal papilla)
The pigmentary unit of hair follicles is particularly
fibroblasts.[12] The ratio of melanocytes to keratinocytes
susceptible to age‑related alterations. Typically, hair
in the hair bulb is approximately 1:5, while the basal
color begins in its lightest shade during early childhood
epidermal layer adjacent to the DP maintains an almost
and gradually darkens even before puberty begins. This
equal 1:1 ratio. In contrast, the epidermal melanin unit has
darkening trend continues through adolescence and young
a 1:36 ratio.[13]
adulthood until it eventually culminates in the onset of
Melanocytes in the hair bulb are distinct from epidermal gray hair or canities. Hormones, particularly androgens and
ones in size, dendritic structure, rough endoplasmic estrogens, significantly influence this process.[19]
reticulum and Golgi activity, and the production of
larger melanosomes. Unlike epidermal melanocytes,
Etiopathogenesis of PMGH
where melanin granules disintegrate in differentiating The etiopathogenesis of premature canities involves a
keratinocytes, granules transferred to follicular cortical complex interaction of genetic, environmental, cellular,
keratinocytes undergo minimal digestion, contributing to and biochemical factors. While our understanding of this
hair pigmentation’s distinct appearance and longevity.[14] phenomenon continues to evolve, several key mechanisms
that contribute to the premature loss of hair pigmentation
In adult hair follicles, the pigmentation process
have been identified.[20]
encompasses an interface among follicular melanocytes,
cortical/medullary keratinocytes, and DP fibroblasts. This Role of reactive oxygen species in PMGH
process comprises melanogenesis in hair bulb melanocytes,
then pigmented granules pass on to cortical and medullary Reactive oxygen species (ROS) and their role in premature
keratinocytes and the development of pigmented hair hair graying are a significant research focus, providing insights
shafts.[15,16] into the underlying mechanisms. During the active growth
phase known as anagen, robust melanogenesis occurs within
Unlike continuous epidermal melanogenesis, follicular hair follicles, involving the synthesis of melanin through the
melanogenesis is synchronized with the hair growth oxidation of tyrosine and dihydroxyphenylalanine. However,
cycle, occurring during the anagen phase, stopping during this melanogenesis process generates ROS as by‑products,
catagen, and remaining dormant in telogen.[15] Anagen disrupting normal cellular functions and leading to oxidative
typically lasts 3–5 years, with a monthly hair growth stress in melanocytes.[21,22]
rate of approximately 1 cm. Immature melanocytes
Antioxidant defense mechanisms in the body, for example,
re‑differentiate during early anagen, likely recruited from
enzymatic antioxidants such as superoxide dismutase and
an emerging reservoir in the upper layer of the outer root
catalase, play a central part in neutralizing free radicals
sheath. Active melanogenesis begins during anagen III,
and protecting melanocytes from damage.[23] Nevertheless,
with tyrosinase activity becoming evident. Pigment transfer
with aging, a decline in antioxidant activity and increased
to cortical keratinocytes starts in anagen IV and continues
oxidative species production create an imbalance,
through anagen V and VI. As anagen VI concludes, hair
contributing to oxidative stress‑related melanocyte
follicle regression begins, primarily affecting the hair
dysfunction. These findings assist the theory that oxidative
follicle pigmentary unit with melanocyte dendrite retraction
stress has a role in hair graying.[24]
and reduced melanogenic activity while keratinocyte
multiplication persists. Hence, the hair shaft closest to the Oxidative stress triggers changes in gene expression,
scalp remains non‑pigmented.[17,18] affecting genes such as B‑cell lymphoma 2 (BCL‑2),

722 Indian Dermatology Online Journal | Volume 15 | Issue 5 | September-October 2024

 Poonia and Bhalla: Premature graying of hair

TRP‑2, TRP1, microphthalmia‑associated transcription reducing melanin production. Although its mechanism is
factor (MITF), and PAX 3. BCL‑2, important for regulating not fully understood, chloroquine specifically seems to
and countering cell death in oxidative stress‑prone decrease pheomelanin production.[20]
environments, gains significance in graying. In vivo mouse 2. Smoking: Smoking and PMGH are linked through the
models (with bcl‑2−/− phenotype) have demonstrated production of substantial ROS, which accelerates hair
faulty melanogenesis and enhanced apoptosis, including follicle aging. Unfortunately, smoking also causes hair
reduced MITF expression, suggesting BCL‑2’s role in hair loss apart from graying. Testing on DP cells of balding
graying.[25,26] individuals revealed higher markers of oxidative stress
and DNA damage.[32]
Elevated oxidative stress reduces BCL‑2 expression,
3. UV radiation: UV radiation plays a significant role
leading to cell death and decreased active hair follicles.
in PMGH by inducing oxidative stress through the
In addition, ROS negatively affects BCL‑2 levels.[27]
production of ROS. This oxidative stress can harm
Similarly, Shi et al.[28] conducted a study on premature hair melanocytes, disrupt melanin production, and trigger
graying, analyzing pigmented and gray hair from a similar cellular responses, contributing to hair graying. UVA
Chinese population (n = 9). Their Western blot findings can cause biochemical damage, resulting in changes
revealed distinct gene expression levels for melanogenesis to hair color, while UVB leads to protein depletion,
genes (TRP1, MITF, and PAX3), notably higher in causing structural damage to the hair shaft’s
pigmented hair follicles. cuticle.[33]
Genetic factors: Several genes play essential roles in 4. Nutritional: Hair can undergo reversible
normal hair pigmentation, including BCL‑2, TRP‑2, hypopigmentation due to a deficiency of various
TRP1, MITF, and telomerase. Among these, BCL‑2 nutritional factors. In the context of premature graying,
and MITF are crucial for preserving melanocyte stem one study found significantly lower zinc levels
cells (MSCs) and serve as indicative markers of MSCs. in individuals with PMGH compared to a control
MITF deficiency and Pax 3 and Sox 10 genes directly group.[34] A recent study on a youthful Indian population
contribute to PMGH development.[25,26] MITF‑mutant noted reduced serum levels of ferritin, calcium, and
mice experience progressive hair graying due to hemoglobin in those predisposed to PMGH.[35] Another
reduced melanocyte numbers, eventually leading to study identified a correlation between lower serum
widespread depigmentation. Harris et al.[29] unveiled a vitamin B12 levels in individuals with PMGH.[36]
novel role for MITF in suppressing innate immune gene Similarly, Sonthalia et al.[37] established a strong link
expression, thereby impeding hair graying. Their findings between PMGH, family history, vitamin B12 deficiency,
demonstrated that artificially enhancing the innate immune and hypothyroidism. In a study involving 35 students,
response in animals resulted in substantial melanocyte Bhat et al.[38] examined various hematological
stem cell loss and an increased prevalence of gray hair. parameters, including serum ferritin, hemoglobin,
In addition, telomerase has a notable role in PMGH, calcium, total iron‑binding capacity, iron, vitamin D3,
supported by observations that telomerase‑deficient mice and vitamin B12, confirming the significant role of
exhibit a higher proportion of gray hair than control vitamin D3 deficiency in PMGH. Fatemi Naieni et al.[39]
mice.[30] emphasized the importance of metal ions, especially
copper ions, which are essential for tyrosinase activity
Several syndromes can lead to PMGH, either directly and normal hair coloration. They observed lower levels
or indirectly, often associated with impaired DNA repair of these metal ions in serum samples from individuals
mechanisms, rendering individuals more susceptible to with PMGH.
oxidative stress.
Association of PMGH with systemic diseases
External factors
Several studies have investigated the link between PMGH
External factors can be categorized as physical and and various health conditions. The Copenhagen City Heart
chemical influences. Physical factors involve exposure to study observed an increased likelihood of heart attack in men
ultraviolet (UV) radiation, smoking, chronic alcoholism, with non‑pigmented hair compared to those with pigmented
chronic illness, a sedentary lifestyle, and psychological hair, but it did not find a connection between PMGH and
stress. In contrast, chemical factors encompass the early mortality.[40] Similarly, further studies also reported
utilization of synthetic dyes and pharmaceutical drugs.[31] associations between PMGH and cardiovascular diseases,
1. Drugs: Certain chemotherapeutic drugs (tyrosine kinase while Glasser’s study did not find such a link.[41‑43] A recent
inhibitors (sunitinib, pazopanib, dasatinib)), antiepileptics study showed elevated levels of IL‑6 and TNF‑α in patients
(phenytoin and phenobarbital), antiandrogen (tamoxifen), with premature canities and stated that these could be useful
immunomodulators (interferon), and antimalarials markers to assess the risk of adverse cardiovascular events.[44]
(chloroquine and hydroxychloroquine) can trigger PMGH Aggarwal et al.[45] identified PMGH as a substantial indicator
by inhibiting c‑kit receptor activity in melanocytes, of cardiovascular disease in smokers.

Indian Dermatology Online Journal | Volume 15 | Issue 5 | September-October 2024 723

 Poonia and Bhalla: Premature graying of hair

Some studies have suggested that PMGH is associated with Table 1: Differentiating features from various
low bone mineral density, although more recent research differential diagnoses
contradicts this association.[46,47] A recent study explored the Differential Distinguishing features of Premature
correlation between hearing loss and PMGH, explaining diagnosis Graying Hair
that patients with PMGH experienced hearing impairment Diffuse gray hair
at higher frequencies. This suggests that PMGH is a causes
noteworthy risk factor and warrants further investigation.[48] Oculocutaneous Lack of pigmentation in skin, hair, and eyes;
Another study correlated family history and obesity not albinism commonly involves vision impairment
only with the prevalence but also with the severity of Hermansky‑Pudlak Albinism, bleeding tendencies, and lung
PMGH.[32] Obesity has been independently linked to syndrome fibrosis; platelet dysfunction may also be
systemic oxidative stress, with many detrimental effects present.
attributed to this increased oxidative burden. Furthermore, Chediak‑Higashi Albinism, recurrent bacterial infections,
obesity seems to influence melanogenesis through syndrome and giant granules in white blood cells;
immunodeficiency.
hormonal pathways.[49] It has been proposed by Morpurgo
Tietz syndrome Albinism affecting skin and hair; hearing loss
et al.[50] that leptin resistance in obese individuals elevates may be associated.
melanocyte‑stimulating hormone antagonists, leading Griscelli syndrome Silver hair due to pigmentary dilution;
to reduced melanogenesis and a diminished ability for immunodeficiency and neurological
melanocyte DNA repair. abnormalities in some types.
Paik et al.[51] and Sharma et al.[52] found decreased Elejalde syndrome Characterized by silvery‑gray hair; associated
with developmental delays, intellectual
HDL‑cholesterol levels in PMGH patients, while Kocaman
disability, and facial dysmorphism.
et al.[53] identified hyperlipidemia as an independent
Menke’s syndrome Sparse, light‑colored hair with a texture
predictor of PMGH. Similarly, Chakrabarty et al.[54] resembling steel wool; often accompanied by
observed raised LDL and lower HDL levels in PMGH cases hair shaft abnormalities.
compared to controls. However, these differences, although Metabolic Phenylketonuria, histidinemia, and
statistically significant, had minimal clinical relevance. disorders homocystinuria may lead to light‑colored hair.
Differential diagnosis Associated with metabolic abnormalities
Oasthouse disease Linked to methionine metabolism;
Distinguishing gray hair from other hypopigmented hair characterized by light hair and recurring
disorders is essential [Table 1]. The latter can occur in edema
localized or diffuse patterns. Conditions characterized Localized causes of
by reduced pigment include oculocutaneous albinism, gray hair (Poliosis)
Hermansky‑Pudlak syndrome, Chediak‑Higashi syndrome, Vitiligo Depigmented skin patches.
and Tietz syndrome. Syndromes related to disrupted Autoimmune condition where melanocytes
melanosomal transfer, such as Griscelli, Elejalde, and are destroyed.
Chediak‑Higashi syndromes, can result in distinct silver Piebaldism Congenital pigmentary disorder.
hair. In Menke’s syndrome, hair is scanty, light in color, Characterized by depigmented and
and has a texture resembling steel wool, often accompanied hyperpigmented skin areas and localized
by structural abnormalities. Metabolic disorders such as white patches of hair
phenylketonuria, histidinemia, and homocystinuria can Wardenburg Genetic disorder with sensorineural deafness,
also lead to light‑colored hair. Oasthouse disease, linked to Syndrome pigmentary disturbances, and often
heterochromia iridis (different‑colored irises).
methionine metabolism, is characterized by light hair and
Woolf Syndrome Rare genetic condition with
recurring edema.[55]
hypopigmentation,
Localized gray hair, also called poliosis, can occur in hair abnormalities, and hearing loss.
conditions such as vitiligo, piebaldism, Wardenburg Ziprkowski Syndrome involving localized poliosis,
syndrome, Woolf’s syndrome, Ziprkowski‑Margolis Margolis ocular abnormalities, and hearing loss; a rare
syndrome, and tuberous sclerosis.[56] If a specific area of syndrome and poorly understood condition.
hair suddenly turns white, clinicians should investigate Tuberous sclerosis Neurocutaneous disorder with skin lesions,
the possibility of depigmentation in the underlying skin intellectual disabilities, and the development
to rule out vitiligo. Reports of abrupt overnight graying of benign tumors in various organs.
of hair (canities subita) have been associated with vitiligo, Sudden graying Vitiligo, telogen effluvium, and alopecia
telogen effluvium, and alopecia areata.[57‑60] of hair (canities areata
subita)
Scoring for PMGH
There is currently no standardized scoring system to important for monitoring the response to therapy and
evaluate the severity of PMGH, which is particularly assessing the efficacy of drugs.[61] Various scoring systems

724 Indian Dermatology Online Journal | Volume 15 | Issue 5 | September-October 2024

 Poonia and Bhalla: Premature graying of hair

have been used in different studies [Table 2], but none is help not only in delineating the underlying cause but also
standardized or universally accepted as yet. A commonly in counseling the patient [Figure 1].
used scoring system in different studies is the hair Management: Despite extensive molecular research,
whitening score (HWS), wherein gray/white hair is used to effective treatments for canities still need to be discovered.
determine the percentage of hair whitening: Oral therapies have been attempted with inconsistent
1. Trace: <25% outcomes, often supported only by anecdotal reports rather
2. Mild: 25%–50% than robust clinical trials. It is alarming that the number
3. Moderate: 50%–75% of patients seeking treatment for PMGH and its significant
4. Manifest: 75%–100% psychological and social impact.[69] Consequently, patients
5. Complete: 100% are frequently prescribed supplements comprising
multivitamins, antioxidants, and minerals such as biotin,
Approach to a patient with PMGH: Flowchart
calcium pantothenate, zinc, copper, and selenium on an
Though PMGH is a condition of cosmetic concern, it may empirical basis.[70] However, it is crucial to acknowledge
need a detailed history and evaluation to exclude other that the systematic evidence supporting their efficacy
associated conditions. Some baseline investigations may remains relatively weak.

Figure 1: Approach to a patient with PMGH

Indian Dermatology Online Journal | Volume 15 | Issue 5 | September-October 2024 725

 Poonia and Bhalla: Premature graying of hair

Table 2: Scoring system used in different studies for grading of severity of premature graying of hair
Authors Year Scoring system used Place of study
Jo et al.[9] 2012 Grade 1: <20% Korea
Grade 2: 20%–40%
Grade 3: 40%–60%
Grade 4: 60%–80%
Grade 5: >80%
Bhat et al.[38] 2013 Mild: <50 gray hair India
Moderate: 50–100
Severe: >100
Erdoğan et al.[62] 2013 Hair whitening score (HWS) Turkey
1 (Trace): <25%
2 (Mild): 25%–50%
3 (Moderate): 50%–75%
4 (Manifest): 75%–100%
5 (Complete): 100%
Kocaman et al.[53] 2013 Hair whitening score (HWS): defined according to the percentage of gray/white hairs Turkey
1: pure black
2: black > white
3: black=white
4: white > black
5: pure white
A gray/white‑hair scale was used to determine the percentage of hair whitening.
1 (Trace): <25%
2 (Mild): 25%–50%
3 (Moderate): 50%–75%
4 (Manifest): 75%–100%
5 (Complete): 100%
Shin et al.[32] 2014 Severity was based on the number of gray hairs on a self‑reported basis. Korea
No gray hair
Mild: <10 gray hair
Moderate: 10–100 gray hair
Severe: >100 gray hair
Singal et al.[61] 2016 Score 1: assigned to under 10% gray hair/cm2 India
Score 2: 10%–30% gray hair/cm2
Score 3: >30% gray hair/cm2
El‑Sheikh et al. [63]
2018 Hair whitening score (HWS) Egypt
1 (Trace): <25%
2 (Mild): 25%–50%
3 (Moderate): 50%–75%
4 (Manifest): 75%–100%
5 (Complete): 100%
Texture and diameter of gray hair fibers were also assessed
Sharma et al.[64] 2018 0 gray hair India
Mild: <10 gray hair
Moderate: 10–100 gray hair
Severe: >100 gray hair
Thompson et al.[65] 2019 severity of graying (0, 1–10, 11–100, and >100 self‑reported gray hairs) United States
Kiafar et al.[66] 2020 The number of gray hair/100 hair was used for grading Iran

Contd...

726 Indian Dermatology Online Journal | Volume 15 | Issue 5 | September-October 2024

 Poonia and Bhalla: Premature graying of hair

Table 2: Contd...
Authors Year Scoring system used Place of study
Acer et al.[67] 2020 The number of graying hairs was classified as <10, 10–100, and >100 to determine Turkey
the severity of PHG.
Agarwal et al.[68] 2020 Hair whitening score (HWS) based on the extent of gray hair India
1: pure black
2: black > white
3: black=white
4: white > black
5: pure white

Oral therapy Latanoprost, an eye drop containing prostaglandin

F2a (PGF2a), has been associated with the repigmentation
P‑aminobenzoic acid and calcium pantothenate: Temporary
of gray hair after long‑term use. The repigmentation
hair darkening has been noted in individuals ingesting
process typically begins at the hair’s base and gradually
significant amounts of p‑aminobenzoic acid (PABA), though
the exact mechanism is unclear. A study of 460 patients extends along the entire length.[77]
with gray hair who took 100 mg of PABA three times a Hair plucking: Removing gray hair might be a sensible
day led to pigment restoration within 2–4 months in 82% of option when less than 10% of the hair is gray. In
patients. However, relapse occurred after discontinuation. addition, coloring, specifically the gray strands, could
Zarafonetis reported hair repigmentation with doses of 12– be contemplated, especially during the initial phases of
20 g of PABA.[71] graying, mainly when it is localized to the temples in men
Pasricha et al. reported success with vitamin supplements and the perimeter in women.[3]
such as 200 mg of daily calcium pantothenate (vitamin Hair colorant: With no effective topical or oral treatments
B5) in two young girls with PMGH hair. Over 29 and available, alternative approaches gain importance, such
13 months of follow‑up, they witnessed the transformation as plucking gray hair and using hair colorants to conceal
of 300 and 1069 gray hair into pigmented hair respectively. it. Hair colorants come in two categories: natural and
The hair follicles displayed a pigmented base and a gray tip, synthetic. Natural hair colors often contain ingredients
termed “converted hair.” In a separate study, they combined such as Henna, Amla, and false daisy. They are commonly
gray hair avulsion and supplementation, uprooting all gray safe but require regular reapplication due to the weaker
hair during each 3‑month follow‑up and trimming any color retention by gray hair. Synthetic hair dyes fall into
converted hair at the junction where it shifted from gray two main groups: oxidative and nonoxidative [Table 3].
to black. Their results indicated that the combination was Oxidative dyes, including permanent, semi‑permanent, and
more effective than using supplements alone.[72] auto‑oxidative types, are favored for their longer‑lasting
However, Brandaleone et al. used 200 mg of PABA, 100 mg color and ease of use. They effectively penetrate the hair
of calcium pantothenate, and 50 grams of brewer’s yeast for cortex. In contrast, nonoxidative dyes adhere to keratin but
8 months in patients with non‑pigmented hair with no success.[73] do not penetrate the hair cortex.[78,79]
In addition, Pavithran et al.[74] reported that solar PUVA was Anti‑aging compounds: Anti‑aging compounds for graying
useful in nearly two‑thirds of patients with PMGH hair. hair are continually being explored for their potential
Topical solutions benefits. Some promising compounds include green tea
polyphenols, selenium, copper, phytoestrogens, melatonin,
Palmitoyl tetrapeptide‑20 and Melitane and substances from traditional Chinese medicine (TCM)
Palmitoyl tetrapeptide‑20, an agonist for and Ayurvedic medicine. These compounds are of current
α‑melanocyte‑stimulating hormone (α‑MSH), has been interest in addressing the aging process of hair, particularly
studied in labs and among 15 men with PMGH. In those in relation to graying. Anti‑aging compounds prove
with PMGH, it increased melanin production in pulled hair ineffective in shampoos due to water dilution and short
within 3 months.[75] An additional α‑MSH agonist, melitane, contact time. Shampoos containing antioxidants such as
a biomimetic peptide, has also been considered for reversing vitamins C and E primarily safeguard the fatty substances
premature graying.[76] However, it is crucial to note that within the shampoo from oxidation, rather than providing
limited data regarding its effectiveness is available. protection to the scalp.[3,76]
Prostaglandins Future therapy
Prostaglandins are recognized as highly effective Stem cell approach: Melanocytes actively participating in
stimulants for melanocyte growth and melanin production. melanin production express a complete set of enzymes and

Indian Dermatology Online Journal | Volume 15 | Issue 5 | September-October 2024 727

 Poonia and Bhalla: Premature graying of hair

Table 3: Comparison between different categories of hair colorant

Hair coloring agent Properties Pros Cons
Permanent a. Contains three agents: developer, coupler and a. Long lasting result a. Contains ammonia and hydrogen
oxidant hydrogen peroxide b. Give intense color peroxide, which damage hair
b. Reacts and forms color within the hair fiber quality
c. Provide full coverage
c. Resists washing but may fade with time b. Regrowth of new hair require
touch‑ups
Semi‑permanent a. Contains small molecules such as para dyes a. Enhances natural a. Fades gradually with each wash
b. Penetrates the hair cortex color b. Limited coverage for gray
c. Provide natural and with some variation b. Low ammonia hair (<30%)
content
d. Applied on wet shampooed hair and left for
10–40 minutes then rinsed c. Less damaging than
permanent color
e. Resist‑ 6–10 shampoos wash (last for 4–6 weeks)
Demi‑permanent a. Contains three agents: developer, coupler a. More natural a. Damage hair quality, but less than
and oxidant. Instead of ammonia contains appearance permanent
ethanolamine or sodium carbonate b. Longer lasting than
b. Reacts and forms color within the hair fiber semi‑permanent
c. Last up to 20–25 shampoos c. Require less frequent
touch ‑ups
Temporary a. Contains large organic, water soluble molecules a. Natural, safe a. Wash out easily, require regular
b. Remains on hair shaft, do not penetrate b. Adds temporary reapplication
c. Applied on towel dried hair and left vibrancy and b. May stain clothing and towels
highlights c. Suitable only for less extensive
d. Washes out with next hair wash
involvement (<15%)

proteins involved in melanin biosynthesis. Consequently, mouse model with gray hair and observed repigmentation.
one potential long‑term strategy for addressing PMHG The increased pigmentation was linked to an 80% rise in
is analyzing the gene‑level expression of these proteins, melanocyte progenitor cell counts in hair bulbs. In addition,
particularly in stem cells.[80] Another study by Saha et al.[81] regrowth was observed with continued repigmentation even
discusses the utilization of a placental extract rich in C18:0 after discontinuing treatment and shaving the hair.[84]
sphingolipid to stimulate microphthalmia‑associated
Several medications have been identified as inducing
transcription factor (MITF) and initiate the activity of
repigmentation through diverse mechanisms. For instance,
dormant melanocyte stem cells in gray‑haired mice. In
drugs with anti‑inflammatory properties, including
addition, recent findings highlight the ability of flavonoids
thalidomide, lenalidomide, adalimumab, acitretin, etretinate,
such as sterubin, luteolin, and hydroxygenkwanin, known
prednisone, cyclosporin, cisplatinum, interferon‑α, and
for their antioxidant and anti‑inflammatory properties,
psoralen, play a role in this process.[85] Certain drugs, such
to scavenge free radicals and encourage melanogenesis
as latanoprost, erlotinib, imatinib, tamoxifen, and levodopa,
through the Wnt signaling pathway.[82]
stimulate melanogenesis.[86] In contrast, clofazimine
Laser: Improvement in hair pigmentation in a accumulates within tissues, leading to repigmentation, while
male‑pattern hair‑loss patient was observed when the mechanism of repigmentation induced by captopril
subjected to a combination treatment involving 1927‑nm remains unknown.[87] Notably, many of these medications
fractionated thulium laser therapy and intra‑perifollicular have been widely used for various indications, yet only
polydeoxyribonucleotide injections (PRDN). After a minority of individuals have reported experiencing hair
completing 12 sessions, there was a noticeable increase repigmentation. Furthermore, confirming drug‑induced
in pigmented hair follicles. This effect is attributed to the repigmentation is challenging as it typically requires
antioxidant properties of PRDN.[83] Nonetheless, these the hair to return to its original color after the drug is
study findings pertain to a single individual and require discontinued. However, this is practically impossible in
validation in a larger population. most cases as patients often continue the treatment. The
observed complexity in the pathways involved in hair
Drugs in development: The approach is to study the
melanogenesis and repigmentation suggests a complex
potential of neural‑crest‑derived stem cells, encouraging
interplay. Therefore, targeting a single pathway may not be
their differentiation into active melanocytes to rejuvenate
sufficient to reverse the process.[88]
the pigmentation of gray hair. A novel combination
compound named RT1640 (comprising cyclosporin A, A novel compound, designated as SkQs, consists
minoxidil, and a pigment‑promoting drug) was used in a of plastoquinone, a penetrating cation serving as an

728 Indian Dermatology Online Journal | Volume 15 | Issue 5 | September-October 2024

 Poonia and Bhalla: Premature graying of hair

antioxidant component that is designed to selectively 14. O’Sullivan JDB, Nicu C, Picard M, Chéret J, Bedogni B,
target mitochondria. Its efficacy has been demonstrated in Tobin DJ, et al. The biology of human hair greying. Biol Rev
2021;96:107–28.
inhibiting the progression of age‑related diseases, including
15. Slominski A, Paus R. Melanogenesis is coupled to murine
cataracts, retinopathy, glaucoma, balding, canities, and anagen: Toward new concepts for the role of melanocytes and
osteoporosis in animal studies.[3] the regulation of melanogenesis in hair growth. J Invest Dermatol
1993;101:90S‑7S.
Conclusions 16. Botchkareva NV, Khlgatian M, Jack Longley B,
PMGH is an interesting phenomenon of growing Botchkarev VA, Gilchrest BA. SCF/c-kit signaling is required
for cyclic regeneration of the hair pigmentation unit. FASEB J
cosmetic concern, with more patients seeking a solution 2001;15:645–58.
and treatment. There is a paucity of literature regarding 17. Sugiyama S. Mode of redifferentiation and melanogenesis
all aspects of this condition. More epidemiological and of melanocytes in mouse hair follicles. J Ultrastruct Res
experimental studies are required to unravel the mystery 1979;67:40–54.
so that more treatment options can be offered for the 18. Tobin DJ, Bystryn JC. Different populations of melanocytes
management. are present in hair follicles and epidermis. Pigment Cell Res
1996;9:304–10.
Acknowledgment 19. Van Neste D, Tobin DJ. Hair cycle and hair pigmentation:
Dynamic interactions and changes associated with aging. Micron
All authors have contributed to the preparation of the 2004;35:193–200.
manuscript. 20. Mahendiratta S, Sarma P, Kaur H, Kaur S, Kaur H, Bansal S,
et al. Premature graying of hair: Risk factors, co-morbid
Financial support and sponsorship conditions, pharmacotherapy and reversal—A systematic review
and meta-analysis. Dermatol Ther 2020;33:e13990.
Nil.
21. Trüeb RM. Oxidative stress in ageing of hair. Int J Trichology
Conflicts of interest 2009;1:6–14.
22. Acer E, Kaya Erdoğan H, Kocatürk E, Saracoğlu ZN, Alataş Ö,
There are no conflicts of interest. Bilgin M. Evaluation of oxidative stress and psychoemotional
status in premature hair graying. J Cosmet Dermatol
References 2020;19:3403–7.
1. Tobin DJ, Paus R. Graying: Gerontobiology of the hair follicle 23. Emerit I, Filipe P, Freitas J, Vassy J. Protective effect of
pigmentary unit. Exp Gerontol 2001;36:29–54. superoxide dismutase against hair graying in a mouse model.
Photochem Photobiol 2004;80:579‑82.
2. Sehrawat M, Sinha S, Meena N, Sharma P. Biology of hair
pigmentation and its role in premature canities. Pigment Int 24. Arck PC, Overall R, Spatz K, Liezman C, Handjiski B,
2017;4:7‑12. Klapp BF, et al. Towards a “free radical theory of graying”:
Melanocyte apoptosis in the aging human hair follicle is an
3. Pandhi D, Khanna D. Premature graying of hair. Indian J
indicator of oxidative stress induced tissue damage. FASEB J
Dermatol Venereol Leprol 2013;79:641–53.
2006;20:1567–9.
4. Triwongwaranat D, Thuangtong R, Arunkajohnsak S. A review
25. Lee JH, Fisher DE. Melanocyte stem cells as potential
of the etiologies, clinical characteristics, and treatment of
therapeutics in skin disorders. Expert Opin Biol Ther
canities. Int J Dermatol 2019;58:659–66.
2014;14:1569–79.
5. Daly S, Bianchini R, Polefka T, Jumbelic L, Jachowicz J.
26. Nishimura EK. Melanocyte stem cells: A melanocyte reservoir
Fluorescence and coloration of grey hair. Int J Cosmet Sci
in hair follicles for hair and skin pigmentation: Melanocyte stem
2009;31:347–59.
cells. Pigment Cell Melanoma Res 2011;24:401–10.
6. Hollfelder B, Blankenburg G, Wolfram LJ, Höcker H. Chemical
27. Azad N, Iyer AKV, Wang L, Lu Y, Medan D, Castranova V,
and physical properties of pigmented and non‑pigmented
et al. Nitric oxide–mediated Bcl‑2 stabilization potentiates
hair (?grey hair?). Int J Cosmet Sci 1995;17:87–9.
malignant transformation of human lung epithelial cells. Am J
7. Gao T, Bedell A. Ultraviolet damage on natural gray hair and its Respir Cell Mol Biol 2010;42:578–85.
photoprotection. J Cosmet Sci 2001;52:103–18. 28. Shi Y, Luo LF, Liu XM, Zhou Q, Xu SZ, Lei TC. Premature graying
8. Locke B, Jachowicz J. Fading of artificial hair color and its as a consequence of compromised antioxidant activity in hair bulb
prevention by photofilters. J Cosmet Sci 2005;56:407–25. melanocytes and their precursors. PLoS One 2014;9:e93589.
9. Kwon O, Jo S, Paik S, Choi J, Lee J, Cho S, et al. Hair graying 29. Harris ML, Fufa TD, Palmer JW, Joshi SS, Larson DM, Incao A,
pattern depends on gender, onset age and smoking habits. Acta et al. A direct link between MITF, innate immunity, and hair
Derm Venereol 2012;92:160–1. graying. Yamashita Y, editor. PLOS Biol 2018;16:e2003648.
10. Tobin D. Aging of the hair follicle pigmentation system. Int J 30. Buckingham EM, Klingelhutz AJ. The role of telomeres in the
Trichology 2009;1:83‑93. ageing of human skin: Telomeres and skin ageing. Exp Dermatol
11. Slominski A, Wortsman J, Plonka PM, Schallreuter KU, 2011;20:297–302.
Paus R, Tobin DJ. Hair follicle pigmentation. J Invest Dermatol 31. McDonough PH, Schwartz RA. Premature hair graying. Cutis
2005;124:13–21. 2012;89:161–5.
12. Tobin DJ. Human hair pigmentation biological aspects. Int J 32. Shin H, Ryu HH, Yoon J, Jo S, Jang S, Choi M, et al.
Cosmet Sci 2008;30:233–57. Association of premature hair graying with family history,
13. Fitzpatrick TB, Breathnach AS. [THE EPIDERMAL MELANIN smoking, and obesity: A cross‑sectional study. J Am Acad
UNIT SYSTEM]. Dermatol Wochenschr 1963;147:481–9. Dermatol 2015;72:321–7.

Indian Dermatology Online Journal | Volume 15 | Issue 5 | September-October 2024 729

 Poonia and Bhalla: Premature graying of hair

33. Seiberg M. Age-induced hair greying – the multiple effects of 52. Sharma N, Dogra D. Association of epidemiological
oxidative stress. Int J Cosmet Sci 2013;35:532–8. and biochemical factors with premature graying of hair:
34. Anggraini DR, Feriyawati L, Sitorus MS, Syarifah S. Analysis of A case‑control study. Int J Trichology 2018;10:211–7.
zinc and copper serum levels in premature hair graying at young 53. Kocaman SA, Cetin M, Durakoglugil ME, Erdogan T, Canga A,
age. Open Access Maced J Med Sci 2022;10:283–6. Cicek Y. The degree of premature hair graying as an independent
35. Chandran S, Simon SA, George AE. A clinical study of risk marker for coronary artery disease: A predictor of biological
premature canities and its association with hemoglobin, ferritin age rather than chronological age. Anadolu Kardiyol Derg Anatol
and calcium levels. Indian J Dermatol 2022;67:216–21. J Cardiol 2012;12:457‑63.
36. Mediratta V, Rana S, Rao A, Chander R. An observational, 54. Chakrabarty S, Krishnappa PG, Gowda DG, Hiremath J. Factors
epidemiological study on pattern of clinical presentation and associated with premature hair graying in a young Indian
associated laboratory findings in patients of premature hair Population. Int J Trichology 2016;8:11–4.
graying. Int J Trichology 2018;10:93‑5. 55. Van Geel N, Speeckaert M, De Schepper S, Lapeere H,
37. Sonthalia S, Priya A, Tobin DJ. Demographic characteristics and Speeckaert R, Chevolet I, et al. Hypomelanoses in children.
association of serum vitamin B12, ferritin and thyroid function J Cutan Aesthetic Surg 2013;6:65.
with premature canities in Indian patients from an urban skin 56. Dessinioti C, Stratigos AJ, Rigopoulos D, Katsambas AD.
clinic of North India: A retrospective analysis of 71 cases. Indian A review of genetic disorders of hypopigmentation: Lessons
J Dermatol 2017;62:304–8. learned from the biology of melanocytes. Exp Dermatol
38. Bhat RM, Sharma R, Pinto AC, Dandekeri S, Martis J. 2009;18:741–9.
Epidemiological and investigative study of premature graying of 57. Hoffmann E. Sudden turning gray of the hair caused by
hair in higher secondary and pre‑university school children. Int J fright, canities subita psychogenica. Z Haut Geschlechtskr
Trichology 2013;5:17–21. 1957;22:74–8.
39. Fatemi Naieni F, Ebrahimi B, Vakilian HR, Shahmoradi Z. 58. Shah VV, Aldahan AS, Mlacker S, Alsaidan M, Nouri K. Canities
Serum iron, zinc, and copper concentration in premature graying subita: Sudden blanching of the hair in history and literature. Int
of hair. Biol Trace Elem Res 2012;146:30–4. J Dermatol 2016;55:362–4.
40. Schnohr P, Lange P, Nyboe J, Appleyard M, Jensen G. Gray hair, 59. Tan SP, Weller RB. Sudden whitening of the hair in an
baldness, and wrinkles in relation to myocardial infarction: The 82‑year‑old woman: The ‘overnight greying’ phenomenon:
Copenhagen City Heart Study. Am Heart J 1995;130:1003–10. A memorable patient. Clin Exp Dermatol 2012;37:458–9.
41. Das S, Chander R, Garg T, Mendiratta V, Singh R, Sanke S. 60. Helm F, Milgrom H. Can scalp hair suddenly turn white? A case
Cardiovascular risk markers in premature canities. Indian J of canities subita. Arch Dermatol 1970;102:102–3.
Dermatol Venereol Leprol 2022;89:221–5. 61. Singal A, Daulatabad D, Grover C. Graying severity score:
42. Aggarwal A, Aggarwal S, Goel A, Sharma V, Dwivedi S. A useful tool for evaluation of premature canities. Indian
A retrospective case‑control study of modifiable risk factors and Dermatol Online J 2016;7:164–7.
cutaneous markers in Indian patients with young coronary artery 62. Erdoğan T, Kocaman SA, Çetin M, Durakoğlugil ME,
disease. JRSM Cardiovasc Dis 2012;1:1–8. Uğurlu Y, Şahin İ, et al. Premature hair whitening is an
43. Glasser M. Is early onset of gray hair a risk factor? Med independent predictor of carotid intima‑media thickness in young
Hypotheses 1991;36:404–11. and middle‑aged men. Intern Med 2013;52:29‑36.
44. Das S, Chander R, Garg T, Mendiratta V, Singh R, Sanke S. 63. El‑Sheikh AM, Elfar NN, Mourad HA, Hewedy ES. Relationship
Cardiovascular risk markers in premature canities. Indian J between trace elements and premature hair graying. Int J
Dermatol Venereol Leprol 2023;89:221‑5. Trichology 2018;10:278‑83.
45. Aggarwal A, Srivastava S, Agarwal M, Dwivedi S. Premature 64. Sharma N, Dogra D. Association of epidemiological
graying of hair: An independent risk marker for coronary artery and biochemical factors with premature graying of hair:
disease in smokers – A retrospective case control study. Ethiop J A case‑control study. Int J Trichology 2018;10:211‑7.
Health Sci 2015;25:123‑8. 65. Thompson KG, Marchitto MC, Ly BCK, Chien AL. Evaluation
46. Beardsworth SA, Kearney CE, Steel SA, Newman J, Purdie DW. of physiological, psychological, and lifestyle factors associated
Premature greying of the hair is not associated with low bone with premature hair graying. Int J Trichology 2019;11:153‑8.
mineral density. Osteoporos Int 1999;10:290–4. 66. Kiafar B, Taheri A, Isaac Hashemy S, Saki A, Mahdeianfar B,
47. Agarwal S, Choudhary A, Kumar A, Zaidi A, Mohanty S, Yadav S. Taghavi F, et al. Serum levels of lead and selenium in patients
A study of association of premature graying of hair and osteopenia with premature graying of the hair. J Cosmet Dermatol
in North Indian population. Int J Trichology 2020;12:75‑8. 2020;19:1513‑6.
48. Ozbay I, Kahraman C, Kucur C, Namdar ND, Oghan F. Is 67. Acer E, Kaya Erdoğan H, Kocatürk E, Saracoğlu ZN, Alataş Ö,
there a relationship between premature hair greying and hearing Bilgin M. Evaluation of oxidative stress and psychoemotional
impairment? J Laryngol Otol 2015;129:1097–100. status in premature hair graying. J Cosmet Dermatol
49. Page S, Chandhoke V, Baranova A. Melanin and melanogenesis 2020;19:3403–7.
in adipose tissue: possible mechanisms for abating oxidative 68. Agarwal S, Choudhary A, Kumar A, Zaidi A, Mohanty S,
stress and inflammation?: Melanogenesis to prevent Yadav S. A study of association of premature graying of hair
complications of obesity. Obes Rev 2011;12:e21–31. and osteopenia in North Indian Population. Int J Trichology
50. Morpurgo G, Fioretti B, Catacuzzeno L. The increased incidence 2020;12:75‑8.
of malignant melanoma in obese individuals is due to impaired 69. Kumar AB, Shamim H, Nagaraju U. Premature graying of hair:
melanogenesis and melanocyte DNA repair. Med Hypotheses Review with updates. Int J Trichology 2018;10:198–203.
2012;78:533–5. 70. Poonia K, Thami GP, Bhalla M, Jaiswal S, Sandhu J. Non
51. Paik S, Jang S, Joh H, Lim C, Cho B, Kwon O, et al. Association scarring diffuse hair loss in women: A Clinico-etiological study
between premature hair greying and metabolic risk factors: from tertiary care center in North-West India. J Cosmet Dermatol
A cross‑sectional study. Acta Derm Venereol 2018;98:748–52. 2019;18:401–7.

730 Indian Dermatology Online Journal | Volume 15 | Issue 5 | September-October 2024

 Poonia and Bhalla: Premature graying of hair

71. Chris Zarafonetis JD. Darkening of gray hair during Biological patterning and therapeutic potentials. Exp Dermatol
para‑amino‑benzoic acid therapy*. J Invest Dermatol 2019;28:395–405.
1950;15:399–401. 81. Saha B, Singh SK, Mallick S, Bera R, Datta PK, Mandal M,
72. Pasricha JS. Effect of grey hair evulsion on the response to et al. Sphingolipid‑mediated restoration of Mitf expression
calcium pantothenate in premature grey hairs. Indian J Dermatol and repigmentation in vivo in a mouse model of hair graying.
Venereol Leprol 1986;52:77–80. Pigment Cell Melanoma Res 2009;22:205‑18.
73. Brandaleone H, Main E, Steele JM. Effect of calcium 82. Taguchi N, Yuriguchi M, Ando T, Kitai R, Aoki H, Kunisada T.
pantothenate and para‑aminobenzoic acid on the gray hair of Flavonoids with Two OH groups in the B‑ring promote
humans. Exp Biol Med 1943;53:47–9. pigmented hair regeneration. Biol Pharm Bull 2019;42:1446‑9.
74. Pavithran K. Puvasol therapy in premature greying of hair. 83. Choi YJ, Cho S, Kim YK, Kim DS. Improvement of hair graying
Indian J Dermatol Venereol Leprol 1986;52:74–5. during a treatment of male pattern hair loss using 1,927‑nm
75. Almeida Scalvino S, Chapelle A, Hajem N, Lati E, Gasser P, fractionated thulium laser energy and polydeoxyribonucleotide
Choulot J, et al. Efficacy of an agonist of α - MSH, the injections. Med Lasers 2017;6:37–40.
palmitoyl tetrapeptide-20, in hair pigmentation. Int J Cosmet Sci 84. Anderson ZT, Palmer JW, Idris MI, Villavicencio KM, Le G,
2018;40:516–24. Cowart J, et al. Topical RT1640 treatment effectively reverses
76. Sakhiya J, Sakhiya D, Patel M, Daruwala F. Case report on gray hair and stem cell loss in a mouse model of radiation-
premature hair graying treated with Melitane 5% and oral hair induced canities. Pigment Cell Melanoma Res 2021;34:89–100.
supplements. Indian J Pharmacol 2019;51:346‑9. 85. Sadighha A, Zahed GM. Hair darkening after treatment with
77. Bellandi S, Amato L, Cipollini EM, Antiga E, Brandini L, cyclosporin in a patient with psoriasis. J Eur Acad Dermatol
Fabbri P. Repigmentation of hair after latanoprost therapy. J Eur Venereol 2008;22:1239‑41.
Acad Dermatol Venereol 2011;25:1485‑7. 86. Grichnik JM, Burch JA, Burchette J, Shea CR. The SCF/KIT
78. Kaur K, Kaur R, Bala I. Therapeutics of premature pathway plays a critical role in the control of normal human
hair graying: A long journey ahead. J Cosmet Dermatol melanocyte homeostasis. J Invest Dermatol 1998;111:233‑8.
2019;18:1206–14. 87. Philip M, Samson JF, Simi PS. Clofazimine‑induced hair
79. Singh R, Madke B, Bansod S, Yadav N. Premature graying of pigmentation. Int J Trichology 2012;4:174‑5.
hair: A concise review. Cosmoderma 2021;1:65. 88. Yale K, Juhasz M, Atanaskova Mesinkovska N.
80. Qiu W, Chuong CM, Lei M. Regulation of melanocyte Medication‑induced repigmentation of gray hair: A systematic
stem cells in the pigmentation of skin and its appendages: review. Skin Appendage Disord 2020;6:1‑10.

Indian Dermatology Online Journal | Volume 15 | Issue 5 | September-October 2024 731