DOI: http://dx.doi.org/10.26510/2394-0859.pbe.2017.21

Review Article

Advance approaches in alopecia

Anand Mohan, Mohd. Adil Khan, Suresh Chandra*

Department of Pharmacy, Pranveer Singh Institute of Technology, Bhauti, Kanpur Nagar, Uttar Pradesh, India

*For correspondence

Mr. Suresh Chandra,

Department of Pharmacy, Pranveer Singh Institute of Technology, Bhauti, Kanpur Nagar, Uttar Pradesh, India. Email: sureshcology81@ gmail.com

 

 

 

 

Received: 27 April 2017

Accepted: 12 May 2017

ABSTRACT

Alopecia is characterized by hair loss mainly on scalp some time on other resign of the body that has negative psychological and social impact on patients. Androgenetic alopecia and alopecia areata are common disorders. Androgenetic alopecia is the sensitivity of scalp follicles to dihydrotestosterone and alopecia areata is an autoimmune disorder. Current studies have explained the efficacy of corticosteroid therapy or the combination of ultraviolet A therapy and systemic corticosteroids for severe AA. Finasteride opens up new possibilities for the treatment of androgenetic alopecia. Current drug treatment approaches use regrowth stimulators such as minoxidil and finasteride for androgenetic alopecia, as well as corticosteroids, PUVA therapy for alopecia areata. Targeted delivery to the Hair follicle units helps faster targeting to cells that accelerate drug action by faster availability of drug, novel combination treatments combinations like tretinoin with minoxidil shows better results, gene therapy are new approaches that are under developing stage and giving satisfactory results on animal as well as humans.

Keywords: Minoxidil, Finasteride, Targeted delivery, Nanostructured lipid carrier, Gene therapy

Introduction

Hair, an important part of protection system of body, their root is deep inserted in dermis where it's follicle is controlled by erector pili muscle. It's ornament structure along with sebaceous gland. Hair is a dead part with no nerve connections. The hair follicle has the unique ability to regenerate itself. Hair follicle growth occurs in cycles. Each cycle consists of a long growing phase (anagen), a short transitional phase (catagen) and a short resting phase (telogen). At the end of the resting phase, the hair falls out (exogen) and a new hair starts growing in the follicle beginning the cycle again.2 Normally about 100 strands of hair reach the end of their resting phase each day and fallout. AA may be associated with other autoimmune diseases, particularly thyroid autoimmune disease such as Hashimoto's thyroiditis and Basedow's disease. The prevalence of thyroid disease in patients with AA ranges from 8% to 28%. Vitiligo, an autoimmune skin disease affecting melanocytes, is also associated with AA. The prevalence of vitiligo in AA patients is 3% to 8% compared with 1% in the United States population. These disease associations suggest a relationship between autoimmunity and AA.1

Types of alopecia

Androgenetic alopecia

Androgenetic alopecia (AGA) is the most common form of hair loss. When it affects women, it leads to diffuse alopecia over the mid-frontal scalp (female pattern hair loss). This process is a result of hair follicle miniaturization within follicular units. It represents a progressive reduction in diameter, pigmentation and length of the hair shaft.3

Alopecia areata

Alopecia areata (AA) is a non-scarring autoimmune, inflammatory scalp, and/or body hair loss condition. Based on the extent of hair loss, the hair loss pattern of AA can be described as single delimited patches; patchy AA, in which there is a partial loss of scalp hair; alopecia-totalis (AT), in which 100% of scalp hair is lost; or alopecia-universalis (AU), in which there is a 100% loss of all scalp and body hair.4

Telogen effluvium

Telogen effluvium (TE) is an increased loss of normal club hairs that occurs by a perturbation of the hair cycle. It was first described by Kligman in 1961 and his hypothesis was that whatever the cause of hair loss, the follicle tends to behave in a similar way, causing premature termination of anagen.5,6 The true incidence is unknown because many cases are subclinical.7 Common causes of TE include iron deficiency, drugs and stress.

Causes

Alopecia areata is an autoimmune disease. An autoimmune disease develops when the immune system mistakes healthy cells for foreign substances. Researchers don't know what triggers the immune system to attack hair follicles, so the exact cause of this condition isn't known. However, it most often occurs in people who have a family history of other autoimmune diseases. There are many causes of hair loss including disease and genetic condition. Studies confirms that it is stressful condition are one of major cause of hair loss.8 Increased levels of androgens in hair follicles can lead to a shorter cycle of hair growth and the growth of shorter and thinner strands of hair. Additionally, there is a delay in the growth of new hair to replace strands that are shed. Researchers suspect that several genes play a role in androgenetic alopecia, variations in only one gene-AR have been confirmed in scientific studies. The AR gene provides instructions for making a protein called an androgen receptor. Androgen receptors allow the body to respond appropriately to dihydrotestosterone and other androgens.

Diagnosis

Hair loss conditions with distinct clinical manifestations, such as typical AA and AGA, can be easily diagnosed based on the pattern of hair loss or the shape of fallen out hair shafts. However, some hair loss conditions are not diagnosable just by routine clinical evaluations. Dermoscopy is a useful device that enhances the diagnostic capacity in some hair loss conditions of AA there is a genetic predisposition to alopecia areata.9 About 20% of people with alopecia areata have a family history.10

Treatment

For androgenetic alopecia

Minoxidil

Minoxidil, BID, (2% or 5% solution, 5% foam) was the first drug to become available for treating scalp hair loss.11 Originally discovered for oral use as an antihypertensive agent, Minoxidil was surprisingly found to induce hair growth in patients. This unexpected side effect led to the development of a topical Minoxidil-containing lotion for alopecia treatment. The mechanism(s) by which minoxidil promotes hair growth is still not fully understood.12-15 Philpot and coworkers recently showed that minoxidil stimulates regrow thin hair follicle cultures where a blood supply is absent.16 Data derived from multiple, double-blind, placebo controlled trials, involving over 2000 males between the ages of 18 and 50 years, showed that twice daily application of 2% minoxidil solution over one year produced moderate to dense regrowth in approximately 30 to 35% of patients.17

Finasteride

Finasteride, (1 mg PO qd) is a specific inhibitor of type II, 5-α reductase.11 This intracellular enzyme converts testosterone into dihydrotestosterone which affects hair follicle regression. By reducing scalp tissue levels of dihydrotestosterone, Finasteride treatment suppresses male pattern hair shedding.18,19 Kaufman and coworkers conducted a randomized study involving 1553 participants exhibiting predominantly mild to moderate vertex hair loss. The researchers employed standardized photographs of the vertex scalp in order to assess the cosmetic response. After 12 months of oral Finasteride use, they found that 48% of treated males had improved versus only 7% of the placebo group.20

Herbal therapies

Greenberg and Katz compared the efficacy of a herbal preparation containing a 7.5% extract of fennel, polygonum, mentha, chamomile, thuja and hibiscus in an aqueous cream base with that of the aqueous cream base alone. A total of 24 balding males were enrolled in the randomized, double-blind study. The volunteers applied either active or placebo cream to their scalps every 24 hours and also washed daily with a supplied shampoo. Hair status was assessed by harvesting, on a bimonthly basis, a selected area of scalp. After 40 weeks of treatment, the mean total hair count increased by 77% in the actively treated group compared with only 3% in the placebo group (p=0.003). Furthermore, the mean terminal hair count for treated men increased by 169% compared with a mere 33% increase for the placebo treated men. Based on this data, herbal therapy seems to hold great potential as treatment for alopecia and warrants further study.21

For alopecia areata

Minoxidil

It stimulates scalp follicles nonspecifically in the same manner as described for Androgenetic alopecia. The 2% solutions usually ineffective in alopecia areata and topical minoxidil should be applied twice daily at a 5% concentration. An initial positive growth response's generally observed after 3 months of treatment whereas the maximal effect develops after about 1 year. Higher success rates can be expected when the alopecia is milder. Minoxidil is generally ineffective in cases of 100% scalp hair loss.22 After a successful treatment outcome, minoxidil 5% application must be continued in order to sustain the gain in hair growth.

Dithranol

The nature of the dithranol effect in alopecia areata is not well understood but it may be immunemodulatory. The treatment is generally used in children or for patients experiencing severe disease. The application protocol involves rubbing dithranol cream, at a 0.5 or 1% concentration, fora short (20 to 60 minute) time interval to the affected scalp. Upon termination of the contact period, the medication is washed off the scalp with a shampoo. Adverse effects can include pruritus, erythema, scaling and folliculitis. However, such irritation can be minimized by applying smaller amounts of medication and/or by employing shorter contact periods.

Diphencyprone

Research is still being performed to elucidate the exact mechanisms involved. Treatment involves applying Diphencyprone solution to one half of the individual's scalp at weekly intervals. The solution is washed off 48hours after application. Although allergic contact dermatitis is frequently induced, this effect is considered necessary for regrowth to occur. The diphencyprone concentration applied (0.0001 to 2%) is varied according to the intensity of dermatitis provoked by the previous week's application. After successful regrowth develops on one side of the scalp, the other half of the scalp is treated. The main adverse effects of diphencyprone are severe eczema and disseminated contact eczema.

Corticosteroids

Oral prednisolone treatment can be appropriate for rapidly progressing or extensive alopecia areata affecting more than 50% of the scalp. The mode of action seems to be immune-modulatory but prednisolone may also directly stimulate the hair follicles. The initial daily dose varies between 40 to 60 mg, to be reduced by 5 mg per week. For many patients, continuous administration of systemic prednisolone is inappropriate because the dose required to maintain hair growth is usually high and the associated toxicity is unacceptable.15

Ultraviolet light treatment (PUVA)

This involves taking a tablet or applying a cream that makes the skin sensitive to light, and then exposing the bald patches to ultraviolet light, two or three times a week for a number of months. Relapse of the alopecia is common when the treatment is stopped. There is also a possible long-term risk of skin cancers.

Other immunosuppressant

These tablets include sulfasalazine, methotrexate, cyclosporine, and azathioprine. They suppress the immune system, and are occasionally used to treat severe alopecia areata which have not responded to other treatments. The evidence that they can cause hair regrowth in alopecia areata is limited and these tablets can have potentially serious side effects. Tofacitinib and ruloxitinib are potentially new immunosuppressive treatments for alopecia areata. These treatments are not yet available as further studies are needed to confirm their beneficial effects for alopecia areata.10

Herbal therapies

Studies suggest that Korean Red Ginseng The average hair number of group 1 was 44.27/cm2 at baseline. After treatment with corticosteroid ILI and Korean Red Ginseng, it increased to 101.39/cm2 at 12 week. In group 2, the hair density also increased from 40.21/cm2 to 91.17/ cm2. The hair density of group 1 increased relatively more than group 2.29

Telogen effluvium

Iron supplementation

Female patients without systemic inflammation or other underlying disorders, serum ferritin levels below or equal to 30 ng/mL are strongly associated with telogen hair loss. Iron supplementation with oral iron sulphate is recommended until a serum ferritin level of 70 ng/ml is achieved.25.26,3

Biotin supplementation

Biotin also known as vitamin H or coenzyme R has been shown to improve clinical appearance and combing problems in patients with uncombable hair syndrome. A study performed by Shelley and colleagues showed the effectiveness of the biotin treatment in increasing the root strength, in making the scaling disappear, and in accelerating the growth rate, hence the hair became more pliable and combable. The recommended supplementation is 5 mg daily.3,27

Cysteine supplementation

It is unclear whether cysteine supplements will improve the quality of hair and the growth cycle. Available clinical data do not prove or disprove this theory. The recommended dosage is 500 mg daily.3

Future prospect

In upcoming years, the effectiveness of alopecia treatments might be improved by the use of combination treatments, penetration enhancers, and the application of targeting technology. An additional strategy is the synthesis or discovery of novel hair growth-stimulating molecules.

Targeted delivery to the hair follicle units

Adecadeago-Dervault and coworkers reported that applications of 2-n-nonyl-1,3-dioxolane (dioxolane) resulted in accelerated minoxidil transport through both sections of both hairless rat skin and human skin. It was found that the dioxolane treatments enhanced minoxidil absorption, producing earlier and greater stimulation of scalp hair growth. The authors observed that the effect occurs by either direct penetration enhancement or alternatively by improved minoxidil targeting into the Hair follicle units.15

Nanostructured lipid carrier

It was found that NLC gel showed a biphasic release pattern, and provided a fast release initially for skin saturation followed by a slow and prolonged release profile to maintain the skin concentration. The present study concluded that the NLC-based gel containing minoxidil dissolved in a mixture of solid lipid and liquid lipid in the nano particulate form helped us to attain faster onset.32

Novel combination treatments

In studies performed by Ferry andco-workers, 19 men with Androgenetic alopecia were treated for 20 days with a minoxidil 2% solution either alone or together with daily applications of tretinoin cream or placebo cream. Tretinoin increases systemic minoxidil absorption by 3-fold. These results demonstrated that the cornified layer was permeabilised to minoxidil penetration. Unfortunately, the currently available proprietary forms of minoxidil and tretinoin are mutually incompatible within the same solution. Dual treatment would require twice daily minoxidil application as well as a separate tretinoin application, presenting an impractical protocol for most men.

Gene therapy

Androgenetic alopecia and alopecia areata are both probably polygenic disorders, in the future, more hair growth-regulating genes will be identified for making gene therapy a potential treatment. Treatment for Androgenetic alopecia can be suppression of the synthesis of 5α reductase or the androgen receptor protein. For alopecia areata treatment, gene replacement therapy could eventually allow for permanent correction of defective gene expression.15

Conclusions

Hair loss can be due to genetic factor or by environmental factor. Some time it can be due to mental stress of surrounding. a lot of treatments are there is the market which are showing satisfactory results but further advances are desired as in all fields required, advanced technologies and approaches like targeted delivery to follicle site, novel combinations of drugs to improve drug delivery and effect, various carrier molecule are also introduced to enhance the drug targeting and delivery, more over under development technique like gene therapy is under their development stage that might be boon for alopecia treatment in future.

Funding: No funding sources

Conflict of interest: None declared

References

  1. Ito T. Recent advances in the pathogenesis of autoimmune hair loss Disease alopecia areata. Hindawi publishing corporation clinical and developmental immunology. 2013;348546:1-6.
  2. Amin SS, Sachdeva S. Alopecia areata: A review. J Saudi Society Dermatol Dermatologic Surg. 2013;17:37-45.
  3. França K, Rodrigues TS, Ledon J, Savas J, Chacon A. Comprehensive Overview and Treatment Update on Hair Loss. J Cosmetics, Dermatological Sci Applications. 2013;3:1-8.
  4. Alkhalifah A, Alsantali A, Wang E, McElwee KJ, Shapiro J. Alopecia areata update. Part I. Clinical picture, histopathology, and pathogenesis. J Am Acad Dermatol. 2010;62(2):177–88.
  5. Kligman AM. The Human Hair Cycle. J Investigative Dermatol. 1959;33:307-16.
  6. Harrison S, Sinclair R. Telogen Effluvium. Clin Experimental Dermatol. 2002;27(5):389-95.
  7. Kligman A. Pathological Dynamics of Reversible Hair Loss in Humans. Arch Dermatol. 1961;83:175-98.
  8. Cash TF, Price VH, Savin RC. Psychological effects of androgenetic alopecia on women: comparisons with balding men and with female control subjects. J Am Acad Dermatol. 1993;29:568–75.
  9. Ohyama M. Management of hair loss diseases. Dermatologica sinica. 2010;28(4):139–45.
  10. British association of dermatologists patient information leaflet produced may 2007 updated may 2010, august 2013, October 2016 review date October 2019.
  11. Cafardi J. The manual of dermatology. Springer. 2012;8:573.
  12. Kurata S, Uno H, Allen-Hoffmann BL. Effects of hypertrichoticagents on follicular and nonfollicular cells in vitro. Skin Pharmacol 1996;9:3-8.
  13. Michelet JF, Commo S, Billoni N, Mahé YF, Bernard BA. Activation of cytoprotectiveprostaglandin synthesase-1 by minoxidil as a possibleexplanation for its hair growth-stimulating effect. J Invest Dermatol 1997;108(2):205-9.
  14. Shapiro J, Price VH. Hair regrowth: therapeutic agents. Dermatol Clin. 1998;16(2):341-56.
  15. Meidan VM, Touitou E. Treatments for androgenetic alopecia and alopecia areataCurrent options and future prospects. Drugs. 2001;61:53-69.
  16. Philpott M, Sanders D, Kealy T. Whole follicular culture. Dermatol Clin 1996;14:595-607.
  17. Olsen E. Androgenetic alopecia. Disordersof hair growth. New York: McGraw-Hill Inc; 1994: 257.
  18. Dallob A, Sadick N, UngerW. The effect of finasteride, a5αreductase inhibitor, on scalp skin testosterone and dihydrotestosterone concentrations in patients with male patternbaldness. J Clin Endocrinol Metab. 1994;79:703-6.
  19. Kaufman K. Clinical studies on the effects of oral finasteride, atype II 5α-reductase inhibitor, on scalp hair in men with malepattern baldness. In: Van Nesteb D, Randall V, editors. Hairresearch for the next millenium. Amsterdam: Elsevier Science; 1996: 363.
  20. Kaufman KD, Olsen EA, Whiting D, Savin R, DeVillez R, Bergfeld W, et al. Finasteride in thetreatment of men with androgenetic alopecia: FinasterideMale Pattern Hair Loss Study Group. J Am Acad Dermatol. 1998;39:578-89.
  21. Greenberg JH, Katz M. Treatment of androgeneticalopeciawitha 7.5% herbal preparation. J Dermatol Treat. 1996;7:159-62.
  22. Price VH. Rogaine (topical minoxidil) in the management ofmale-pattern baldness and alopecia areata: summary. J Am Acad Dermatol 1987;16:749-50.
  23. Pericin H, Trueb RM. Topical immunotherapy of severe alopeciaareata with diphenylcyclopropenone: evaluation of 68cases. Dermatol. 1998;196:418-21.
  24. Shapiro J. Alopecia areata. Dermatol Clin. 1993;11:35-40.
  25. Rushton DH. Nutritional Factors and Hair Loss. Clin Experimental Dermatol. 2002;27(5):396-404.
  26. Boccaletti V, Zendri E, Giordano G, Gnetti L, De Panfilis G. Familial Uncombable Hair Syndrome: Ul- trastructural Hair Study and Response to Biotin. Pediatr Dermatol. 2007;24(3):E14-6.
  27. Shelley WB, Shelley D. Uncombable Hair Syndrome: Observations on Response to Biotin and Occurrence in Siblings with Ectodermal Dysplasia. J Am Acad Dermatol. 1985;13(1):97-102.
  28. Mccoy A, Ziering C. Botanical extracts for the treatment of androgeneticAlopecia. Int J Life Sci Pharma Res. 2012;2:31-8.
  29. Oh GN, Son SW. Efficacy of Korean Red Ginseng in the Treatment of Alopecia Areata. J Ginseng Res. 2012;36:391-5.
  30. Khidhir1 KG, Mahmood KI. The effects of traditional kurdistan plant extracts on rat hair growth in vivo. Int J Scientific Res Publicat. 2016;6:450-4.
  31. Jaybhaye D, Varma S, Gagne N, Bonde V, Gite A, Bhosle D. Effect of tectonagrandislinn. Seeds on hair growth activity of albino mice. Int J Ayurveda Res. 2010;4:211-5.
  32. Uprit S, Sahu RK, Roy A, Pare A. Preparation and characterization of minoxidil Loaded nanostructured lipid carrier gel for effective Treatment of alopecia. Saudi Pharm J. 2013;21:379-85.
  33. Kashyap R, Shukla K, Mahajan SC, Sharma A. Formulation and evaluation of hair oil for hair loss disorders. 2016;4(3):13-7.
  34. Meena AK, Singh U, Yadav AK, Singh B, Rao MM. Pharmacological and phytochemical evidences for the extracts from plants of the genus vitex – a review. Int J Pharma Clin Res. 2010;2(1):1-9.

Refbacks

  • There are currently no refbacks.




Copyright (c) 2017 Pharmaceutical and Biological Evaluations

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.



Creative Commons License

 

© Copyright 2017 - Pharmaceutical and Biological Evaluations