INTRODUCTION:

Alopecia is a condition that causes baldness on the head or other regions of the body where hair is ordinarily found. Low self-esteem brought on by the distressing disease has a negative psychological and social impact on sufferers. Alopecia areata is a common cause of hair loss that is characterised by an abrupt beginning of non-scarring hair loss in often clearly defined areas that can range in size from small patches to large or, less frequently, diffuse involvement. Most people experience hair loss or alopecia at some point in their lives, and more and more patients are seeking treatment. The most prevalent types of alopecia include androgenic (common baldness), alopecia areata, and chemotherapy-induced alopecia. Numerous factors, such as stress, hormones, nutrition, various illnesses, and prescription drugs for cancer are causes of the diseases.

The distinction between normal and pathological hair loss in paediatric patients can be thought about using a fundamental understanding of hair biology. The root of the hair is anchored in the follicle, an involution of the epidermis, and the proteinaceous shaft makes hair up. Hair loss is caused by a variety of reasons, including genetics, hormones, exposure to the environment, drugs, and nutrition. A multimodal strategy is necessary for treating hair loss, and using CAM may have additional advantages. The cycle of the hair follicle depends on vitamins and trace minerals, which also act as hormones, antioxidants, immunomodulators, and cofactors for enzymes to maintain homeostasis.¹

Alopecia and hair loss Although hair shedding is a normal everyday occurrence, it cannot be the primary cause of hair loss. Genetic programming determines each hair's cycle, which includes growth, stabilisation, ageing, and shedding. A human head typically loses 50–125 hairs every day (depending on sex), yet the majority of them will grow back during the resting stage since the follicle itself is not destroyed (14). When loss outweighs regrowth or regrowth is unhealthily weak, trouble sets in. It is possible to classify 100 hair losses per day as "normal" rather than pathogenic. But a pathological effluvium develops when there is a daily hair loss of more than 100.²

HAIR GROWTH CYCLE

Anagen, catagen, telogen, and exogen are the four phases in the cyclical growth of hair. Anagen, catagen, telogen, and shedding are the stages of normal hair follicles' growth, degeneration, resting, and shedding cycles (exogen).

Anagen: True anagen starts 4 weeks after birth and is the growth phase. True anagen starts 4 weeks after birth and is the growth phase. The stem cells present within the bulge region begin to proliferate at the onset of anagen to produce a new lower HF. The anagen growth phase of human scalp hairs can last between 2 and 8 years.

Catagen: Catagen is the time of the HF's rapid involution, during which the lower two thirds of the HF rapidly deteriorate over the course of two to three weeks, leaving only club hair encased in an epithelial cap.

Telogen: Following catagen, telogen is the phase of HF cycling during which hair is shed or lost. Mice have extremely synchronised HF cycling across their skin when they are young, but this synchrony is lost as they get older.

Exogen: Old hair shafts can be passively lost by mechanical forces, but exogenous shedding is typically an active process.^3,4

Figure 1. Changes in hair shaft and dermal papilla during hair cycle.³

Figure 2 Several causes of Alopecia. ⁵

TYPE OF ALOPECIA:

Baldness or alopecia can be classified as follows:

As there are several origins of the disorder, there are numerous varieties of alopecia. There are several common kinds of alopecia, including trichotillomania, androgenic alopecia, alopecia areata, chemotherapy-induced alopecia (CIA), anagen effluvium, and telogen effluvium.⁶

1. Androgenic alopecia:

Although AGA is frequently referred as as "male pattern baldness," both men and women can be severely affected by the disorder. Women often experience widespread hair loss over the top of their scalp, but men typically exhibit hairline regression around the temples and balding at the vertex. In men, typical androgenic hair loss starts above the vertex, or crown, of the head. In men, typical androgenic hair loss starts above the vertex, or crown, of the head. Although males can also develop this pattern, female AGA is sometimes referred to as "female pattern baldness." Similar to its male counterpart, it primarily produces widespread thinning without hairline recession and hardly ever results in total hair loss. Androgenic alopecia affects 70% of all males and roughly 40% of women during their lifetimes, according to Urysiak-Czubatka.Male individuals who do not develop baldness generally produce less quantities of the 5-alpha reductase enzyme. Androgenic alopecia affects people of Caucasian origin more than other races.⁷

Mechanism:

Dihydrotestosterone, a potent androgen, is created when the enzyme 5-alpha reductase breaks down testosterone in the gonads and other regions of the body like the liver and brain (DHT). The body converts about 10% of the testosterone it produces into DHT. 11 DHT, a sex steroid similar to testosterone, has a higher binding affinity than other androgens and accelerates the balding process (binds easily lasting for 53 minutes were as testosterone lasts for only 35 minutes). As androgens link to hair follicle receptors, follicles gradually weaken and shrink, which kills the cells that make up the follicles. The interaction of androgens with hair follicles causes a shorter telogen lifespan and a longer anagen lifespan.⁸

2. Alopecia areata:

Alopecia areata is a frequent kind of autoimmune hair loss that can strike at any age and has a lifetime prevalence of about 2%. People who have a personal or family history of other autoimmune diseases like thyroid illness or vitiligo are more likely to develop AA in their lifetime. When people with alopecia areata experience an entirely hairless scalp, things start to become worse (alopecia totalis). Alopecia universalis, a condition caused by alopecia areata, is characterised by the loss of hair throughout the entire body. When the right bodily signals are assumed, alopecia areata may not typically result in the death of hair follicle cells because hair frequently grows back after recovery.⁹

Mechanism:

Investigations into the genetic causes of AA are still ongoing, however T lymphocytes coordinated at hair follicles intervened in organ-explicit immune system infection. The aetiology of AA has been linked to genes that regulate T-cell proliferation and activation, such as CTLA4, interleukins (IL2/IL21), human leukocyte antigens, and natural killer cell-activating ligands. Affected individuals and experimental mice models have autoantibodies to HF structures at the anagen stage.¹⁰

Figure 3.(A) Single, well-defined patch of hair loss characteristic of alopecia areata (AA). (B) Pathognomonic exclamation point hairs in AA. (C) Light microscopic appearance of a tapered hair removed from the scalp of patient with rapidly progressive AA.¹⁰

Cancer chemotherapy induces apoptosis in rapidly dividing cells within delicate tissues, it is linked to serious adverse effects (such as the hematopoietic system, the epithelia of the digestive tract and other organs) This apoptosis heavily relies on p53, also referred to as "the guardian of the genome," which builds up in vulnerable cells after a variety of stresses and causes growth arrest or induces programmed cell death. The matrix keratinocytes that are growing and generating the hair shaft in the bulb of the anagen HF are impacted by chemotherapy. The HF enters a dystrophic catagen stage as a result of damage to proliferating cells, which compromises the integrity of the hair shaft and results in hair loss. The majority of hair in HF is in the anagen phase at any given moment, and after chemotherapy, these hair are rapidly destroyed, with considerable apoptosis observed in the proximal bulb region. Chemotherapy-induced DNA damage causes the afflicted cells to rapidly accumulate the p53 protein, which is then followed by an overexpression of the genes that encode Fas, IGF-BP3, and Bax, all of which are responsive to p53. Anthracyclines (like doxorubicin), taxanes (like taxol), alkylating substances (like cyclophosphamide), and the topoisomerase inhibitor etoposide all cause moderate-to-severe CIA.¹¹

90% of scalp hair that is in the anagen stage after chemotherapy is converted to telogen, which causes club hair to fall out without replacement. In the hair cycle, this causes shorter anagen periods and longer telogen phases. Because cycling follicular stem cells are often unaffected by the medicine and will develop a new hair follicle, which will subsequently produce a new hair strand, hair that has been lost due to chemotherapy typically comes back once the patient stops taking the medication.¹²

HAIR CYCLE DISTURBANCES:

Anagen effluvium:

The disorder causes growing hair in the anagen stage to become shady (anagen arrest). Anagen effluvium can be caused by chemotherapy or other drugs, just like chemotherapy-induced alopecia. The disorder results in anagen hair loss, which prolongs the telogen phase for as long as the patient is receiving treatment.¹³

Telogen effluvium:

It might be challenging to tell a diffuse, non-inflammatory hair loss disorder from female pattern hair loss. In most cases, telogen effluvium is preceded by a few months by an initiating stimulus, such as psychological stress, childbirth, weight loss, or pharmaceuticals (e.g., interferons, antihyperlipidemic drugs, derivatives of retinol, anticoagulants). Rather than the causal agent itself, the severity and length of exposure determine the effluvium level. Telogen effluvium may be acute (lasting less than six months), chronic (lasting more than six months), or persistently chronic.¹⁴

Loose Anagen Syndrome (LAS):

A somewhat uncommon cause of hair loss called loose anagen syndrome is characterised by anagen hairs that are poorly anchored to the follicle, frequently causing painless hair loss when gently pulled.¹⁵

Short Anagen Syndrome (SAS):

Due to a reduced growth phase of the hair cycle, the short anagen syndrome is a rare cause of apparent hair loss in youngsters. Typically sporadic at birth, this disease can occasionally be passed down by an autosomal dominant gene.¹⁵

TRAUMATIC HAIR LOSS:

Trichotillomania:

The impulse control disorder trichotillomania is characterised by compulsive, repetitive, and self-inflicted hair pulling from the scalp, brows, and/or other areas of the body (19, 31). Although trichotillomania can affect children as young as six, its prevalence peaks between the ages of nine and thirteen, with a strong female predominance^.16

FIGURE 4 | Patchy hair loss characterized by irregular borders and hairs in various stages of regrowth in a child with trichotillomania.¹⁶

Traction alopecia:

It is caused by persistent (continuous or recurrent) tension on the hair, frequently from hairstyles. The hairline frequently experiences hair loss. A complete history may aid in the diagnosis. Usually, tensional straining activities on the hair that cause hair breaking cause traction alopecia. Due to their strong desire to seem decent, middle-aged women are particularly affected by attempting various hairstyles.¹⁷

Figure 5 | Fringe sign (A) and tenting (B) are clinical findings suggestive of traction alopecia. ¹

APLASIA CUTIS CONGENITA (ACC):

Alopecia with associated scarring at birth is a hallmark of the very uncommon heterogenous group of illnesses known as Aplasia Cutis Congenita (ACC). Location and pattern of skin absence, the existence of accompanying abnormalities (such as trisomy 13 or 4p-syndrome, cleft lip and palate), and the route of inheritance all contribute to the clinical subgroups.¹⁸

Other Congenital Alopecia:

Transient Neonatal Hair Loss (TNHL):

Neonatal occipital alopecia, a relatively common condition, and the emergence of bald patches in other areas are all included in transient neonatal hair loss. The vertex and temporoparietal regions of healthy neonates' scalps were noted to have distinct and well-described male patterns.¹⁹

Congenital Triangular Alopecia (CTA):

Congenital triangle alopecia, also known as temporal triangular alopecia or Brauer nevus, is an uncommon type of alopecia that mostly affects frontotemporal regions. It is non-progressive and non-scarring. Lesions are triangular or lancet shaped, and the affected region is completely hairless except for a few vellus hairs. The majority of lesions are unilateral, primarily on the left side, although 7.5-20% of them can also be bilateral. ²⁰

Figure 6. A single, subcentimeter aplasia cutis congenita lesion on the vertex of the scalp.²⁰

Congenital Atrichia and Hypotrichosis:

A category of uncommon congenital illnesses known as congenital atrichia and hypotrichosis appear with hair loss or reduced hair volume caused by mutations in the human hairless gene that are autosomal recessive.²¹

Treatment For Alopecia:

Table 1 | Some Important clinical findings of alopecias to aid in diagnosis.²²

Type of hair loss	Loss of follicular ostia	Pattern	Scale	Erythema	Trichoscopy	Trichogram	Classic findings
Androgenetic alopecia	No	Patchy, usually vertex or temporoparietal regions	No	No	Thin and vellus hairs, hair shaft thickness diversity, perifollicular pigmentation, yellow dots	Diversity of hair shaft thickness	Vellus hairs within patches, ↑ androgen levels, ± family history
Alopecia areata	No	Patchy, diffuse, or complete hair loss	No	None to mild	Yellow dots, exclamation mark hairs	Tapered hair	“Exclamation point” hairs, ± nail pitting, ± family history of AA
Anagen effluvium	No	Diffuse	No	No			Occurs days or weeks after inciting event
Telogen effluvium	No	Diffuse	No	No		Increased percentage of clubbed hairs	+) hair pull test if active disease

Table 2. Drug discovery for different types of alopecia. ²³

Drug (Trade name)	M, F, Both, animal	Class/route	Mechanism
ANDROGENIC ALOPECIA Minoxidil (Rogaine)	Both; approved	Vasodilator, ATPsensitive potassium channel opener; topical	Increases blood flow to HF,stimulates VEGF and PGE2
Finasteride (Propecia)	Both, approved M	5-α-reductase (5-α-R) inhibitor; oral, topical, mesotherapy	Inhibits 5-α-R2
Flutamide (Eulexin, Flutamin, Cytomid)	F	Nonsteroidal antiandrogen; Oral	Androgen receptor antagonist
ALOPECIA AREATA Hydrocortisone (Cortizone)	Both; approved	Corticosteroid; topical; intradermal injection, oral	Anti-inflammatory, immunosuppressive.
Dinitrochlorobenzene	Both	Local irritant; topical	Triggering sensitization counteracting autoreactive T cells
CHEMOTHERAPY-INDUCE ALOPECIA Cyclosporin A (Neoral)	Rats	Inhibitor of T cells; topical	Binds to cyclophilin and inhibits calcineurin; possibly increases P-glycoporotein
Calcitriol, 1,25- dihydroxyvitamin D-3 (Topitriol)	Rats	Active metabolite of vitamin D; topical	Stimulates differentiation in HF

Table 3. Nondrug therapies for alopecia^.23

Treatment	Mechanism	Application
Hair transplantation	Replaces old with new HF	AGA
LLLT	Stimulates HF and stem cells, protects HF from dying	AGA, AA, CIA
Follicular neogenesis	Dissociated epidermal and dermal cells in suspension reconstitute on a matrix	AGA
Fractional laser	Induction of thermal micro-wounds stimulates HF	AGA
Platelet rich plasma	Mixed growth factors in dalteparin and protamine microparticles	AGA
Stem cells	Skin derived progenitor cells	AGA

Nutrient	Effect on hair growth
Zinc	Indicated to patchy surface alopecia
Iron	Carries oxygenated blood to the hair follicle cells
Vitamine A, B, C, D, E	Prevents free radicals, Improves shininess, helps absorption of iron, helps absorption of iron, helps absorption of iron.