Gentian violet: Revisited

Neel Prabha¹ , Ripu Daman Arora² , Satyaki Ganguly¹ , Namrata Chhabra¹

¹ Department of Dermatology, All India Institute of Medical Sciences, Raipur, Chhattisgarh, India
² Department of ENT and HNS, All India Institute of Medical Sciences, Raipur, Chhattisgarh, India

Correspondence Address:
Neel Prabha
Department of Dermatology, All India Institute of Medical Sciences, GE Rd., Tatibandh, Raipur, Chhattisgarh
India

Gentian violet, also known as crystal violet or methyl violet, is a triphenylmethane dye. It is commonly used as a stain in laboratory. Gentian violet was first synthesized in 1861 by French chemist Charles Lauth.^[1] Hans Gram in 1884 noticed its irreversible fixation by Gram positive bacteria.^[2] In 1891, it was introduced as an antiseptic by Stilling. Its antibacterial action against Gram positive bacteria was noticed by Churchman in 1912.^[3] Since then, it was used in a variety of diseases because of its antibacterial, antifungal, anti-helminthic and anti-trypanosomal properties. Following discovery of penicillin and sulfa drugs, its use has declined.

Gentian violet is a symmetric compound with 6 methyl groups. Chemical formula of gentian violet is [4-[bis[4-(dimethylamino) phenyl] methylidene] cyclohexa-2,5-dien-1-ylidene]-dimethylazanium chloride [Figure - 1].^[4]

Figure 1: Chemical structure of gentian violet

For topical use gentian violet is available commercially as 0.5% and 1% aqueous or alcohol solution. Gentian violet and methylene blue antibacterial dressings in polyvinyl alcohol foam and polyurethane foam are also available. Gentian violet as 0.5% aqueous solution is licensed for topical application on unbroken skin but is not recommended for application on mucous membranes or open wounds.^[5] This review discusses the role of gentian violet in dermatology.

Indications of Gentian Violet in Dermatology

Indications of gentian violet in dermatology are given in [Table - 1].

Infections

Gentian violet is effective against Streptococcus, Staphylococcus species, methicillin-resistant Staphylococcus aureus and moderately effective against gram negative bacteria.^[6],[7],[8] Gentian violet also inhibits the growth of Pseudomonas and disrupts Pseudomonas biofilms in vitro.^[6],[9],[10]

Multiple hypotheses for its antibacterial action are given. The bacteriostatic effect is due to the unfavorable oxidation-reduction potential poised by gentian violet and the inhibition of reduced nicotinamide adenine dinucleotides (NADPH) oxidases by it.^[11],[12] It penetrates the bacterial cell wall and forms a covalent adduct with thioredoxin reductase 2 which is essential for cellular activity, ultimately leading to cell death.^[13] It reduces vascular leak by reducing the levels of angiopoietin-2 expression and allows improved antibiotic delivery.^[14]

Gentian violet is also effective against Candida.^{[15],[16],[17]}

Lymphoma

Gentian violet has been tried in lymphoma patients. Regression of primary cutaneous diffuse B cell lymphoma after a single injection of intralesional gentian violet has been reported in a patient who was unfit for conventional therapy.^[18] In another case report, partial clinical response of recalcitrant, localized, stage 1B mycosis fungoides has been reported.^[19] The mechanism for antitumor activity of gentian violet is not fully known. It inhibits reduced NADPH oxidase, an enzyme that converts molecular oxygen to superoxide and hydrogen peroxide. By inhibiting this enzyme, gentian violet decreases local reactive oxygen species, which in turn might inhibit certain tumor suppressor genes like PTEN, Ik-B and p53.^[13] Gentian violet also inhibits NF-kB, possibly through NADPH oxidase inhibition, which has been implicated in proliferation of cutaneous T-cell lymphoma tumor cells.^[19] Wu and Wood found that gentian violet enhances Fas and TRAIL pathway dependent apoptosis of cutaneous T-cell lymphoma cell lines and tumor cells in Sezary syndrome.^[20]

Dermatitis

Gentian violet is also helpful in atopic eczema. In atopic eczema, skin colonization with Staphylococcus aureus and high levels of proinflammatory angiopoietin-2 plays a possible role in the pathophysiology of the disease. Gentian violet by decreasing bacterial colonization and angiopoietin-2 levels reduces the severity of the eczema.^[21]

Gentian violet may be used in treatment of irritant dermatitis. Gloor et al. noted anti-irritative effect of 0.5% gentian violet.^[22] They found that 0.5% gentian violet reduces skin damage in irritative dermatitis. It also provides immediate pain relief in acute painful eczematous lesions.^[23]

Oral hairy leukoplakia

Gentian violet application can be used to treat oral hairy leukoplakia.^[24] The role of gentian violet in oral hairy leukoplakia is based on the evidence that Epstein bar virus oncogenes induce the generation of reactive oxygen species, and gentian violet is a potent inhibitor of reduced NADPH oxidase which generates these reactive oxygen.^[24]

Hair transplantation

Gentian violet can be used for visualizing white hair during the punching procedure and graft preparation in follicular unit extraction for white-haired patients.^[25] The follicular units of white hair are too white or transparent to be distinguished from the surrounding soft tissue. However, after 1% gentian violet dyeing of the scalp skin, the soft tissue is also dyed, allowing for a clear view while trimming and loading into the implanter.

Infantile hemangioma

Gentian violet may accelerate healing of ulcerated infantile hemangioma.^[26] Ulceration in infantile hemangiomas is due to an imbalance between angiopoietin-2 and vascular endothelial growth factor. Angiopoietin-2 promotes angiogenesis in the presence of vascular endothelial growth factor. Gentian violet decreases the production of angiopoietin-2 and promotes ulcer healing.^[26]

Erythema multiforme/Stevens-Johnson syndrome/toxic epidermal necrolysis

Topical gentian violet stabilizes and halts the progression of new cutaneous bullae of erythema multiforme.^[27] Angiopoietin-2 induced vascular leak is involved in the pathogenesis of erythema multiforme. Nitric oxide and toxic peroxynitrite are involved in keratinocyte necrosis occuring in this condition. Gentian violet down-regulates the production of angiopoietin-2 and peroxynitrite.^[27] Gupta et al. ²⁸ recommended the use of gentian violet paint in dilution for treating denuded areas in SJS/TEN.

Prurigo nodularis

Gentian violet may be effective in treating prurigo nodularis. Prurigo nodularis is accompanied by STAT6 and STAT3 activation. Gentian violet may be effective in this condition by targeting STAT 6 signal.^[29]

Leg ulcers

Antibacterial foam dressing consisting of polyvinyl alcohol bound to gentian violet and methylene blue (GV/MB PVA) can be a suitable option for chronic leg ulcers, especially diabetic foot ulcers.^[30]

Polyurethane foam bound gentian violet and methylene blue (GV/MB PU) dressings are also available commercially. Gentian violet-methylene blue in polyvinyl alcohol foam requires saline hydration, whereas that in polyurethane foam dressing, do not. Gentian violet-methylene blue in polyurethane foam dressings are best suited for moist wounds that do not require additional hydration.^[30] These dressings absorb and trap bacterial debris away from the wound, aid in autolytic debridement and thus promote re-epithelialization by flattening the wound edges.^[31]

Gram staining

Gentian violet is used as a stain in Gram staining method. This staining method helps in differentiating Gram positive and Gram negative bacteria. Gram staining is also helpful in the diagnosis of Malasezzia folliculitis.^[32]

Other Uses

In vivo gram staining is a bedside diagnostic test for tinea versicolor.^[33] In this test, when gentian violet is applied to the site of tinea versicolor, a dramatic accentuation of the infected areas compared with unaffected skin occurs due of retention of the dye by the fungus. This test differentiates tinea versicolor from other conditions like atopic dermatitis, vitiligo and pityriasis rosea as these conditions do not retain gentian violet.^[33] Ink test can be performed for diagnosing porokeratosis. Circumferential furrow of the lesion can be delineated by applying gentian violet to the lesions of porokeratosis.^[34]

Gentian violet solution is also used in surgery to mark the surgical sites. Chen et al.^[35] described a sterile, effective and economical intraoperative skin marking method by using gentian violet. Four drops of gentian violet was dispensed into microcentrifuge tube, which was then autoclaved after capping. Toothpick was used as the writing instrument. The advantage of this method was that unlike commercially available skin markers, skin moisture did not cause the writing implement to become ineffective.

Side Effects

Common side effect is staining by gentian violet. There are reports of irritant contact dermatitis with gentian violet 3% preparation.^[36],[37] The predisposing factors mentioned in these reports were application on intertriginous area and prolonged contact. Pasricha et al.^[38] and Bajaj et al.^[39] found contact sensitivity to gentian violet. Oral ulceration was reported with its application in oral candidiasis.^[40],[41] A woman developed severe hemorrhagic cystitis due to accidental injection of gentian violet through the urethra.^[42] A patient developed superficial necrosis of the glans penis after topical treatment with 1% gentian violet.^[43] Accidental instillation of gentian violet in eye can lead to keratoconjunctivitis.^[44]

Some consider gentian violet as a potential carcinogen. Rosenkranz et al.^[45] found that gentian violet interacted with the DNA of living cells. They opined that it reacted with the cellular DNA which might induce detrimental changes. Animal studies performed on mice and rats found that increased rate of hepatocellular and thyroid cancer was seen when gentian violet was fed in large doses for long duration.^[46],[47] However, no reports of cancer in human associated with topical gentian violet use have been found in the recent literature.

Conclusion

Gentian violet, in the present era of emerging resistance, is a cheaper and safer alternative to topical antibiotics. As it has anti-angiogenic, anti-tumor and anti-inflammatory properties, it can be used as an adjuvant in other dermatoses. To prevent side effects, it should be applied unoccluded, for a short contact-time and should be kept away from the eyes during application.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

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