The Safety of Medicinal Plants Used in the Treatment of Vitiligo and Hypermelanosis: A Systematic Review of Use and Reports of Harm

Abstract

Introduction: Vitiligo is disfiguring and devastating condition that can humans feel stigmatic and devalued. Melasma is a general condition of hyperpigmentation particularly involving the face. The pigmentation disorders of vitiligo (hypopigmentation or depigmentation) and melasma (Hypermelanosis) are common among the world's population (around 1% for vitiligo). Objective: The identification of medicinal plants used in the treatment of vitiligo and hypermelanosis. A systematic literature review on harms associated with the medicinal plants used in the treatment of vitiligo and hypermelanosis. To review and summarize information on reported adverse drug reactions (ADRs) associated with these medicinal plants contained in (where access is available) national and global individual case safety report databases. Methods: A systematic review of the literature with special reference to all types of clinical trial and case reports using biomedical databases including Medline, EMBASE, Scopus, International Pharmaceutical Abstracts and so forth to identify medicinal plants alone or as an adjuvant with other treatments and their safety/tolerability in the treatment of vitiligo and Hypermelanosis. Other sources of this search were medicinal plants text books, pharmacopoeias and authentic websites discussing possible treatments for vitiligo/hypermelanosis. It also included databases such as VigiAccess containing data from spontaneous reporting schemes for ADRs. Results: A total of 55 articles (47 clinical trials and 8 case reports) met the inclusion criteria. Some trials did not reported safety information, some did report, but not very well. Reports of blistering, erythema, acute hepatitis and mutagenesis with Psoralea corylifolia. Adverse effects of erythema (mild to severe), phototoxic reactions, mild raise in liver transaminases, gastrointestinal disturbances, burns, itching, scaling, depigmented macules, pruritis, and giddiness with the use of psoralens. Khellin-related erythema, perilesional hyperpigmentation, gastrointestinal disturbances, mild raise in liver transaminases and orthostatic complaints. Infrequent side effects with Ginkgo biloba. Lower grade of erythema and edema reported with the use of Polypodium leucotomos. Conclusion: Primarily the retrieved clinical studies were efficacy oriented and safety parameters were secondary in priority whilst the general protocol of clinical trials requires the screening of drugs/medicinal plants on the basis of safety studies before testing the clinical aspects of efficacy. Thereby it is recommended that efficacy studies may be followed once the safety has been established for a particular medicinal plant in treating vitiligo and hypermelanosis.

Plants as Modulators of Melanogenesis: Role of Extracts, Pure Compounds and Patented Compositions in Therapy of Pigmentation Disorders

“…Both the effects may be achieved through implementation of plant-derived compounds [ 60 ]. Therefore, these molecules may exert a beneficial therapeutic effect on skin of patients with hyperpigmentation or hypopigmentation, including postinflammatory hyperpigmentation, solar lentigines, melasma, café au lait macules, ephelides (freckles) as well as postinflammatory hypopigmentation, vitiligo, pityriasis alba, tinea versicolor [ 61 , 62 , 63 , 64 , 65 ].…”

The Use of Herbal Medicine in the Treatment of Vitiligo: An Updated Review

“…Several adverse reactions have been reported such as photosensitivity, itching, erythema (mild to severe), pruritus, rash, and blistering. Other side effects observed with the use of psoralens were abdominal pain, gastrointestinal disturbances, nausea and vomiting, acute hepatitis, and mutagenesis [23]. The possibility of liver toxicity from a methanol/ water solution extracted from C. corylifolium fruits and its major components (psoralen and isopsoralen), was studied in vitro by Liu and Flynn [74].…”

“…In the case of topical therapy, 2-5 % khellin is applied 30 min before sun exposure or UVA radiation (three sessions a week) [86,87]. Side effects of KUVA therapy such as erythema, perilesional hyperpigmentation, gastrointestinal disorders, increase in liver transaminases, and orthostatic complaints have been described [23,77]. It is important to note that due to the alterations reported in hepatic functional tests during the treatment with A. visnaga, Commission E of the German Ministry of Health advises against the use of Khella fruits in therapy [88].…”

“…Recommended doses of Ginkgo standardized leaf extracts range from 120 – 240 mg daily, taken 2 – 3 times a day, up to a maximum of 12 weeks 20 , 105 . Although minimal and infrequent adverse effects have been described within the daily dose range of ginkgo extracts 23 , 106 , there is a significant risk of interaction with different drugs due to the diversity of mechanisms of action attributed to ginkgo components. Main interactions are related to potential risk of bleeding in patients treated with antiplatelets (e.g., aspirin, NSAIDS, clopidogrel, ticlopidine, dipyridamole) or anticoagulants (e.g., warfarin, heparin) 20 , 107 , 108 .…”

“…Plants, which can be considered multi-compound entities with multi-targeted mechanisms, and plant-derived compounds, have long been used in traditional medicine [20]. The reduced toxicity and side effects of natural products make them a promising therapeutic alternative for vitiligo treatment, especially in countries with a long tradition of using herbal medicine [21][22][23]. Neverthe-less, more scientific evidence is lacking on herbal-based therapy against vitiligo.…”