Pediatric Alopecia Areata
Alopecia areata (AA) is a psychologically devastating autoimmune disorder that affects between 2.11% and 2.47% of the population1, including 4.2 million children worldwide, among which 200’000 patients are in Europe and 125’000 in the
US. AA is characterized by the loss of patches of hair, all scalp hair or all body hair. Although AA is not a life-threatening disease, it is “absolutely life-altering” as described by Beckett2. Beckett also declared “Alopecia areata
can wreak havoc on a person’s esteem at any age”. AA patients often believe that their concerns are dismissed; ‘‘it’s just hair’’ is a commonly referenced phrase. AA imposes immense burden on the emotional well-being of affected children
leading to social isolation, low self-esteem, depression and humiliation3,4.
Bullying, comments and staring have enormous psychological impact on this vulnerable population, where 80% of paediatric patients are further diagnosed with at least one psychiatric disorder5. As a result, in addition to distress about their hair loss, many patients also experience feelings of guilt or self-doubt, as the ‘‘it’s just hair’’ perspective can make them think that their associated emotional suffering is unwarranted or frivolous. Recently, it has been shown that 12.8 % of the subjects with AA were at risk of committing suicide6. In the same trial, 65.9 % of sufferers had signs of depression or anxiety. Another study showed a 39 % lifetime prevalence of major depressive disorder and a 39 % lifetime prevalence of generalized anxiety disorder in patients with AA7.
The caretakers also reported poorer quality of life. Liu et al. showed that parents reported worse impairment in quality of life than did their children with AA8. Interestingly, when compared to the results of this study, the impairment of the quality of life is similar among family members of patients with psoriasis. In comparison with other common skin diseases, such as atopic dermatitis, urticaria or psoriasis, children with AA and their parents both ranked this latter as teasing or bullying the highest9.
Beside the impact on the quality of life, an early-onset AA is known to tend to be more severe and less favorable prognosis10 It has been also demonstrated that an onset of AA in the first two decades is more often associated with severe alopecia11,12,13. Another study with more than 10 years of follow-up on subjects with severe AA showed that 45.4% of the patients with onset earlier than 10 years of age had no hair regrowth, and none achieved complete hair regrowth14. Lyakhovitsky et al., showed that full or signiﬁcant regrowth was observed in 74%, 94% and 100% of childhood-onset, adult-onset and late-onset AA patients, respectively15. There was no regrowth in 13%, 3% and 0% of childhood-onset, adult-onset and late-onset patients, respectively. The relapse rate was 52%, 44% and 30% in the childhood-onset, adult-onset and late-onset groups, respectively.
In addition, several studies suggested that early-onset AA has an increased risk of other concomitant medical disorders, particularly atopic diseases and lupus erythematosus. Notably, one prior epidemiologic study demonstrated that AA cases with an age of onset before 10 years are more frequently associated with atopic diseases and lupus erythematosus, indicating a need for screening for these diseases in this age group16.
Up-to-date, no treatment for AA has ever been approved. In the absence of a dedicated approved treatment, dermatologists recommend the off-label use of topical, oral or intralesional corticosteroids or diphenyl cyclopropenone (DPCP). These treatments need to be administered with regular monitoring to prevent side effects in particular with corticosteroids, such as growth retardation, loss of bone density, adrenocortical suppression, and ocular and cutaneous effects. Therapeutic evaluations and recommendations are based on studies done in adults, and uncommonly in pediatric AA population.
- Lee HH, Gwillim E, Patel KR, Hua T, Rastogi S, Ibler E, et al. Epidemiology of alopecia areata, ophiasis, totalis, and universalis: A systematic review and meta-analysis. J Am Acad Dermatol. mars 2020;82(3):675‑82.
- Beckett ME. The Need for a Treatment: A Patient’s Perspective. J Investig Dermatol Symp Proc. nov 2015;17(2):42‑3.
- Liakopoulou M, Alifieraki T, Katideniou A, et al. Children with alopecia areata: Psychiatric symptomatology and life events. J Am Acad Child Adolesc Psychiatry 1997;36(5):678–84.
- Ghanizadeh A. Comorbidity of psychiatric disorders in children and adolescents with alopecia areata in a child and adolescent psychiatry clinical sample. Int J Dermatol 2008;47(11):1118–20
- Christensen, T., Yang, J. S. & Castelo-Soccio, L. Bullying and Quality of Life in Pediatric Alopecia Areata. Ski. Appendage Disord. 3, 115–118 (2017)
- Vélez-Muñiz, R. del C., Peralta-Pedrero, M. L., Jurado-Santa Cruz, F. & Morales-Sánchez, M. A. Psychological Profile and Quality of Life of Patients with Alopecia Areata. Ski. Appendage Disord. 5, 293–298 (2019).
- Colón, E. A., Popkin, M. K., Callies, A. L., Dessert, N. J. & Hordinsky, M. K. Lifetime prevalence of psychiatric disorders in patients with alopecia areata. Compr. Psychiatry 32, 245–51
- Liu LY et al. Alopecia areata is associated with impaired health-related quality of life: A survey of affected adults and children and their families. J Am Acad Dermatol. 2018 Sep;79(3):556-558.e1
- Beattie PE, Lewis-Jones MS, QoL impairment in children with skin disease vs. other diseases. British Journal of Dermatology 2006; 155(1): 145-151
- De Waard-van der Spek FB, Oranje AP, De Raeymaecker DM, Peereboom-Wynia JD. Juvenile versus maturity-onset alopecia areata--a comparative retrospective clinical study. Clin Exp Dermatol 1989;14:429-433
- Sharma VK, Dawn G, Kumar B. Profile of alopecia areata in Northern India. Int J Dermatol. janv 1996;35(1):22‑7.
- Tan E, Tay YK, Goh CL, Chin Giam Y. The pattern and profile of alopecia areata in Singapore – a study of 219 Asians. Int J Dermatol. 2002;41(11):748–753
- Yang S, Yang J, Liu JB, et al. The genetic epidemiology of alopecia areata in China. Br J Dermatol. 2004;151(1):16–23.
- Jang YH et al. Long-Term Prognosis of Alopecia Totalis and Alopecia Universalis: A Longitudinal Study with More than 10 Years of Follow-Up: Better than Reported. Dermatology. 2017;233(2-3):250-256
- Lyakhovitsky A et al. Alopecia areata: a long-term follow-up study of 104 patients. J Eur Acad Dermatol Venereol. 2019 Aug;33(8):1602-1609
- 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;62:177-188, quiz 189-190.
Chemotherapy Induced Alopecia
Alopecia is one of the most common adverse events caused by numerous chemotherapy drugs. It affects approximately 65% of patients treated with chemotherapy1. Although alopecia in cancer patients is not a life-threatening event,
it has a significantly negative psychological and social impact. Chemotherapy-induced alopecia (CIA) is considered by the patients as one of the most distressing side effects of cancer therapies, even before nausea2 To avoid
alopecia, 8 to 10% of women suffering from breast cancer are even ready to refuse the treatment with chemotherapy3,4. It has been demonstrated in different studies that CIA is associated with multiple adverse outcomes, including
depression, impaired social and role function, problems with sexuality, and poor quality of life5,6>.
The hair loss can be partial or total and occurs usually after 6 to 8 weeks of treatment. Although hair growth usually resumes 3 to 5 months after the completion of chemotherapy, it has been shown that approximately 30% of adult breast cancer survivors will experience a persistence of the alopecia which might be permanent (Permanent-CIA)7.
While effective management strategies are available for other side effects of chemotherapy, such as nausea, constipation, or pain, CIA remains a major challenge in clinical oncology8. Up-to-date, there is no approved pharmacologic treatment available for CIA or Permanent-CIA. Scalp cooling is the only modality approved by the FDA. It is used to prevent alopecia in some patients, but its efficacy is variable, the likelihood of a patient that uses scalp cooling during chemotherapy maintaining enough hair to not require a wig is approximately 50%9. In addition, cooling caps are not always well tolerated and do not help hair re-growth in case the prevention of hair loss fails especially in Permanent-CIA.
- Trüeb RM. Chemotherapy-Induced Alopecia. Semin Cutan Med Surg. mars 2009;28(1):11‑4.
- Mulders M, Vingerhoets A, Breed W. The impact of cancer and chemotherapy: perceptual similarities and differences between cancer patients, nurses and physicians. Eur J Oncol Nurs Off J Eur Oncol Nurs Soc. avr 2008;12(2):97‑102.
- Roe H. Chemotherapy-induced alopecia: advice and support for hair loss. Br J Nurs. 26 mai 2011;20(Sup5):S4‑11.
- Ross M, Fischer-Cartlidge E. Scalp Cooling: A Literature Review of Efficacy, Safety, and Tolerability for Chemotherapy-Induced Alopecia. Clin J Oncol Nurs. 1 avr 2017;21(2):226‑33.
- Choi EK, Kim I-R, Chang O, Kang D, Nam S-J, Lee JE, et al. Impact of chemotherapy-induced alopecia distress on body image, psychosocial well-being, and depression in breast cancer patients. Psychooncology. oct 2014;23(10):1103‑10
- Hunt N, McHale S. The psychological impact of alopecia. BMJ. 22 oct 2005;331(7522):951‑3.
- Freites-Martinez A, Shapiro J, van den Hurk C, Goldfarb S, Jimenez J, Rossi AM, et al. CME Part 2: Hair disorders in cancer survivors Persistent chemotherapy-induced alopecia, persistent radiotherapy-induced alopecia, and hair growth disorders related to endocrine therapy or cancer surgery. J Am Acad Dermatol. 13 avr 2018;
- Montemurro F, Mittica G, Cagnazzo C, Longo V, Berchialla P, Solinas G, et al. Self-evaluation of Adjuvant Chemotherapy-Related Adverse Effects by Patients With Breast Cancer. JAMA Oncol. 1 avr 2016;2(4):445.
- Dunnill CJ, Al-Tameemi W, Collett A, Haslam IS, Georgopoulos NT. A Clinical and Biological Guide for Understanding Chemotherapy-Induced Alopecia and Its Prevention. The Oncologist. 2018;23(1):84‑96.
Cancer Related Fatigue
Cancer-Related Fatigue (CRF) is one of the most debilitating symptoms of cancer due to cancer itself and cancer treatment, such as surgery, chemotherapy, hormonal, endocrine and radiotherapies. The fatigue symptom is characterized by a feeling of extreme
physical tiredness, emotional, and mental exhaustion, can’t be resolved by normal resting and sleeping. It causes disruption in all aspects of quality of life and may lead to discontinuation or poor compliance with treatment regimens.
CRF may be a risk factor for reduced survival as it persists through all stages of the disease trajectory, even in cancer survivors.1-4, 7
The etiology underlying CRF is still not well-understood. Some factors (e.g. inflammation and immune system) have been identified to be involved in CRF.7, 11
The prevalence of CRF ranges from 70% -100% during active treatment and around 30% in post-treatment.5,6
Cancer-related fatigue cannot be measured objectively since there exist no standard “test markers”. However, CRF can be described through a numerical rating scale (NRS) from 0 to 10, where 0 is not tired at all and 10 is severely tired. Internationally, it has been considered that a score below 4 indicates mild fatigue, between 4 and 7 moderate fatigue, and above 7 severe fatigue. 10
While there is not yet approved pharmacological gold-standard treatment, agents like stimulants, antidepressants and erythropoietin, etc., have been used to manage CFR in selected patients with modest effects. 7 Non-pharmacologic interventions (e.g. exercise/physical activity) are more widely accepted thanks to the reported effect in reducing CRF during the active- and posttreatment phases. 7 Results from studies using nutritional and dietary supplements (e.g. ginseng, guarana and L-carnitine or appetite stimulants) are still limited or even inconsistent. 7-9
The multidimensional nature of CRF should be considered when setting up therapeutic strategies. Naturally occurring multiple components in botanical drugs allow simultaneously addressing different targets, therefore represent an insightful approach to manage cancer related fatigue.
- National Coalition for Cancer Survivorship. Cancer survivorship survey: findings from an online survey of adult cancer patients. 2019.https://www.canceradvocacy.org/wp-content/uploads/2019/09/NCCS-Survivorship-Survey-Final-Report.pdf. Accessed on 22 October 2020.
- Morrow GR., Cancer-Related Fatigue: Causes, Consequences, and Management. The Oncologist 2007; 12(suppl 1):1–3 www.The Oncologist.com
- FS3 Cancer-Related Fatigue Facts, Leukemia & Lymphoma Society, Information Specialist: 800.955.4572,www.LLS.org. October 2016"
- Andrea Barsevick, R.N., Director, Nursing Research and Education, Fox Chase Cancer Center. What Is the Difference Between Cancer-Related Fatigue and Normal Everyday Fatigue? ABC News 8 May 2008. https://abcnews.go.com/Health/OnCallPlusTreatment/difference-cancer-related-fatigue-normal-everyday-fatigue/story?id=4815775
- Ripamonti CI et al., Fatigue, a major still underestimated issue. Current Opinion in Oncology: July 2018 - Volume 30 - Issue 4 - p 219-225.
- Bower JE et al., Screening, Assessment, and Management of Fatigue in Adult Survivors of Cancer: An American Society of Clinical Oncology Clinical Practice Guideline Adaptation. JOURNAL OF CLINICAL ONCOLOGY, ASCO SPECIAL ARTICLE, VOLUME 32 NUMBER 17 JUNE 10 2014 2014;32(17).
- Melissa SY et al., Cancer-Related Fatigue: Causes and Current Treatment Options. Curr. Treat. Options in Oncol. (2020) 21:17
- Paschoin M. et al., Cancer-related fatigue: a review. Rev Assoc Med Bras 2011; 57(2):206-214
- Hiroki M et al., L-Carnitine supplementation reduces the general fatigue of cancer patients during chemotherapy. MOLECULAR AND CLINICAL ONCOLOGY 8: 413-416, 2018.
- Fabi A. et al., Cancer-related fatigue: ESMO Clinical Practice Guidelines for diagnosis and treatment. Annals of Oncology, Volume 31 - Issue 6 – 2020
- Bower JE. Et al., Cancer-related fatigue: Links with inflammation in cancer patients and survivors. Brain, Behavior, and Immunity 21 (2007) 863–871.
Botanical Drug Pathway
Both US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) have released guidelines enabling the development of drugs from full botanical extracts in 2004. These are called Botanical Drugs (or Herbal Medicines,
Botanical drugs are equivalent to any other drugs, whether synthetic or biologic. To be approved, the sponsor of a Botanical drug needs to demonstrate the efficacy and safety of his drug candidate in Ph III clinical trials.
Botanical drugs have two major benefits
When made from plants known to be safe for human use, they are in general extremely safe, and a better fit for the treatment of chronic conditions requiring long-term exposures to the drug substance.
Also, the molecules naturally present in botanical extracts can address multiple targets simultaneously, enabling better treatment of multifactorial chronic and age-related diseases.
For further information, we recommend to check
The US FDA guidelines on Botanical Drugs
The EMA guidelines on Herbal Medicines (Stand-alone or mixed application)