TRICHOLOGY – O3ZONE LTD

Chemotherapy-induced alopecia Cicatricial Alopecia

ALOPECIA: WHAT IS IT?
Alopecia is a condition characterized by a significant decrease in the quantity of hair or hair follicles, which are the cavities within the dermis from which hair originates. It can manifest as gradual hair loss starting from the crown of the head with the appearance of bald patches, can have a sudden onset, and may also be associated with the loss of hair follicles in other parts of the body.
Alopecia is distinguished into:

Scarring: hair loss is due to the atrophy of hair follicles, which is irreversible;
Non-scarring is caused by processes that reduce or slow down hair growth without irreparably damaging the hair follicle and tends to be temporary.

THE CAUSES
Several factors can cause alopecia:

Genetic factors;
Hormonal factors: involvement of the thyroid or dysfunctions related to the pituitary or testosterone;
Nutritional factors: often generated by nutritional deficiencies, as diet plays a crucial role. For example, anorexia leads to significant hair loss due to insufficient protein and vitamin intake (such as Vitamin D and Iron);
Psychological factors: prolonged periods of stress caused by trauma or depression can lead to hair loss and severe thinning of the scalp;
Chemical-pharmacological factors: strong chemical-pharmacological treatments such as chemotherapy, heart failure treatments, and antidepressants contribute to hair loss.

CHEMOTHERAPY-INDUCED ALOPECIA: DOSAGE

INSTRUCTIONS FOR USE:
03ZONE CAPSULES SIZE OO
3 CAPSULES IN THE MORNING AND
3 CAPSULES IN THE EVENING

In the absence of metastasis
(TOTAL 6 CAPSULES PER DAY)
4 CAPSULES IN THE MORNING AND
4 CAPSULES IN THE EVENING

In the presence of metastasis
(TOTAL 8 CAPSULES PER DAY)
O3ZONE TRICHOLOGY
(SOOTHING LOTION FOR SCALP)
3 ML IN THE MORNING AND 3 ML IN THE EVENING
(TOTAL 6 ML PER DAY)

METHOD OF ADMINISTRATION:
ENTERIC-COATED CAPSULES FOR SYSTEMIC ORAL USE
SOOTHE LOTION FOR TOPICAL USE

TREATMENT DURATION:
3-6 MONTHS

EXCLUSION CRITERIA:
Pregnant women;
Internal and external bleeding;
Surgical interventions (suspend treatment 3 days before and resume 7-10 days after);
Hyperthyroidism;
G6PD deficiency.

TREATMENT OBJECTIVE:
The aim of the integrated treatment is to prevent or reduce chemotherapy-induced alopecia.
Recommended as integrated therapy and prophylaxis for:
Chemotherapy-induced alopecia.

CHEMOTHERAPY-INDUCED ALOPECIA
Breast cancer is currently the most common malignancy for the female gender, with an annual incidence of 43.3/100,000 and mortality rates ranging from 17.7/100,000 to 11.8/100,000 [1-2]. Treatments include cytotoxic chemotherapeutics, target therapy, and radiotherapy, with regimens like FEC (5-fluorouracil, epirubicin, and cyclophosphamide) and EC (cyclophosphamide and epirubicin) being commonly used. Alopecia is a frequent and poorly tolerated side effect of these therapies, with an incidence of approximately 65%, varying based on the drugs used and their combination. Moreover, 20% of patients experience permanent alopecia with incomplete hair regrowth.
Chemotherapeutics cause cytotoxic damage to follicular matrix cells, inducing anagen or telogen effluvium. Stem cells in the bulge region, responsible for promoting the hair follicle cycle, are typically spared, making chemotherapy-induced hair loss reversible in most cases. Hair follicles usually return to their normal cycle within weeks after treatment cessation, with visible regrowth in 3-6 months. Lack of regrowth after 6 months defines permanent alopecia, likely due to irreversible damage to follicle stem cells by certain chemotherapeutics, affecting areas with low hair density, particularly the frontal or occipital hairline [3].
Preventing or treating chemotherapy-induced alopecia remains challenging, impacting patients’ psycho-emotional sphere and quality of life. Scalp cooling, though proposed, yields inconsistent results with often poorly tolerated side effects, inapplicable to platinum derivative users due to cold intolerance induced by these drugs and in patients with conditions like cryoglobulinemia [4-8]. Topical corticosteroids have been suggested, along with emerging studies demonstrating the safety and efficacy of ozone therapy in oncology patients [9]. These studies indicate ozone’s potential to enhance chemotherapeutic efficacy and prevent tumour recurrence, with significantly lower alopecia incidences reported compared to untreated subjects.

Bibliography:
[1] Globocan 2012. Estimated Cancer Incidence, Mortality and Prevalence Worldwide in 2012. http://globocan.iarc.fr.
[2] Youlden DR, Cramb SM, Dunn NA, Muller J et al. The descriptive epidemiology of female breast cancer. an international comparison of screening, incidence, survival and mortality. CancerEpidemiol 2012;36:237-248.
[3] Paus R, Haslam IS, Sharov AA, Botchkarev VA. Pathobiology of chemotherapy-induced hair loss. Lancet Oncol 2013; 14: e50.
[4] Hyoseung S, Seong JJ, Do HK, Ohsang K, Seung-K M (2015) Efficacy of interventions for prevention of chemotherapy-induced alopecia: a systematic review and meta-analysis. Int J Cancer 136: E442-E454
[5] Galimont-Collen AF, Vos LE, Lavrijsen AP, Ouwerkerk J, Gelderblom H. Classification and management of skin, hair, nail and mucosal side-effects of epidermal growth factor receptor (EGFR) inhibitors. Eur J Cancer. 2007 Mar;43(5):845-51. Epub 2007 Feb 7
[6] Betticher DC, Delmore G, Breitenstein U, Anchisi S, ZimmerliSchwab B, Müller A, Trueb RR (2013) Efficacy and tolerability of two scalp cooling systems for the prevention of alopecia associated with docetaxel treatment. Supp Care Cancer
21:2565-2573
[7] Shin Hl, Jo SJ, Kim do H, Kwon O, Myung SK.Efficacy of interventions for prevention of chemotherapy-induced alopecia. a systematic review and meta-analysis. Int J Cancer. 2015 Mar 1;136(5):E442-54
[8] Rossi A, Caro G, Fortuna MC, Pigliacelli F, D’Arino A, Carlesimo M. Prevention and Treatment of Chemotherapy-Induced Alopecia. Dermatol Pract Concept. 2020 Jun 29;10(3):e2020074. doi: 10.5826/dpc.1003a74. PMID: 32642317; PMCID: PMC7319796.
[9] Izzotti A, Fracchia E, Rosano C, Comite A, Belgioia L, Sciacca S, Khalid Z, Congiu M, Colarossi C, Blanco G, Santoro A, Chiara M, Pulliero A. Efficacy of High-OzonideOil in Prevention of CancerRelapsesMechanisms and ClinicalEvidence. Cancers (Basel). 2022 Feb 24;14(5):1174. doi: 10.3390/cancers14051174. PMID: 35267482; PMCID: PMC8909345. Breast cancer is currently the most common malignancy for the female gender, with an annual incidence of 43.3/100,000 and mortality rates ranging from 17.7/100,000 to 11.8/100,000 [1-2]. Treatments include cytotoxic chemotherapeutics, target therapy, and radiotherapy, with regimens like FEC (5-fluorouracil, epirubicin, and cyclophosphamide) and EC (cyclophosphamide and epirubicin) being commonly used. Alopecia is a frequent and poorly tolerated side effect of these therapies, with an incidence of approximately 65%, varying based on the drugs used and their combination. Moreover, 20% of patients experience permanent alopecia with incomplete hair regrowth.
Chemotherapeutics cause cytotoxic damage to follicular matrix cells, inducing anagen or telogen effluvium. Stem cells in the bulge region, responsible for promoting the hair follicle cycle, are typically spared, making chemotherapy-induced hair loss reversible in most cases. Hair follicles usually return to their normal cycle within weeks after treatment cessation, with visible regrowth in 3-6 months. Lack of regrowth after 6 months defines permanent alopecia, likely due to irreversible damage to follicle stem cells by certain chemotherapeutics, affecting areas with low hair density, particularly the frontal or occipital hairline [3]. Preventing or treating chemotherapy-induced alopecia remains challenging, impacting patients’ psycho-emotional sphere and quality of life. Scalp cooling, though proposed, yields inconsistent results with often poorly tolerated side effects, inapplicable to platinum derivative users due to cold intolerance induced by these drugs and in patients with conditions like cryoglobulinemia [4-8]. Topical corticosteroids have been suggested, along with emerging studies demonstrating the safety and efficacy of ozone therapy in oncology patients [9]. These studies indicate ozone’s potential to enhance chemotherapeutic efficacy and prevent tumour recurrence, with significantly lower alopecia incidences reported compared to untreated subjects.

SCARRING ALOPECIA: DOSAGE

O3ZONE CAPSULES SIZE 00

1 CAPSULE IN THE MORNING AND 1 CAPSULE IN THE EVENING
(TOTAL 2 CAPSULES PER DAY)

O3ZONE TRICHOLOGY
(SOOTHING LOTION FOR THE SCALP)

3 ML IN THE MORNING AND 3 ML IN THE EVENING
(TOTAL 6 ML PER DAY)

MODE OF ADMINISTRATION:
GASTRO-RESISTANT CAPSULES FOR SYSTEMIC USE VIA ORAL ROUTE
SOOTHING LOTION FOR TOPICAL USE

TREATMENT DURATION:
3-6 MONTHS

EXCLUSION CRITERIA:
Pregnant women;
Internal and external bleeding;
Surgical interventions (suspend treatment 3 days before and resume 7-10 days after);
Hyperthyroidism;
Favism.

TREATMENT OBJECTIVE:
The objective of integrated treatment is to prevent the progression of scarring alopecia forms
Recommended as integrated therapy for:
Scarring alopecia.

SCARRING ALOPECIA
Scarring alopecia refers to alopecia in which the pathogenetic mechanisms leading to the destruction of the hair follicle with subsequent formation of scar tissue; for this reason, they are considered irreversible alopecia once the inflammatory process that characterizes them is concluded. They can be distinguished into lymphocytic and neutrophilic based on the predominant inflammatory infiltrate. Although in the final stages they are irreversible, intervention in the intermediate stages may be able to block inflammation and therefore prevent destruction of the follicular unit. For this purpose, immunosuppressive therapies are used, mainly based on corticosteroids, which often yield disappointing results.
Lichen planopilaris (LPP) is a lymphocytic scarring alopecia of unknown aetiology. Clinically, it is characterized by the formation of keratotic perifollicular papules, erythema, and intense itching. Histologically, a lichenoid infiltrate is observed at the level of the upper segment of the hair follicle[1].
Folliculitis decalvans (FD) is a rare neutrophilic alopecia. It is characterized by the formation of papulopustular lesions that destroy the involved follicles. The etiopathogenesis is not completely known, but microorganisms present at the skin level play an important role [2]. Ozone’s antioxidant activity is well known, and it also has anti-inflammatory and antimicrobial properties [3-4]. Based on this evidence, the use of ozone-based products in the therapy of these alopecias can be hypothesized.

Bibliography:
[1] Lepe K, Nassereddin A, Salazar FJ. Lichen Planopilaris. 2021 Nov 22. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-. PMID: 29262050.
[2] Rossi A, Garelli V, Muscianese M, Pranteda G, Caro G, D’Arino A, Fortuna MC. Clinical and trichoscopic correlation of primary neutrophilic scarring alopecia. folliculitis decalvans and
dissecting cellulitis. G Ital Dermatol Venereol. 2020 Aug;155(4):506-508. doi: 10.23736/S0392-0488.18.06027-3. Epub 2018 Sep 18. PMID: 30229638.
[3] Tartari APS, Moreira FF, Pereira MCDS, Carraro E, Cidral-Filho FJ, Salgado Al, Kerppers II. Anti-inflammatory Effect of Ozone Therapy in an Experimental Model of Rheumatoid Arthritis. Inflammation. 2020 Jun;43(3):985-993. doi: 10.1007/s10753-020-01184-2. PMID: 32382842.
[4] Badhe H, Kalaskar R, Balasubramanian S, Kamki H, Kalaskar A. Antimicrobial Effect of Ozone Therapy in Deep Dentinal Carious Lesion: A Systematic Review. Int J Clin Pediatr Dent. 2022;15(Suppl 2):S252-S260. doi: 10.5005/jp-journals-10005-2168. PMID: 35645523; PMCID: PMC9108844.