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Abstract
Atopic dermatitis (AD) is a chronic, relapsing inflammatory skin disorder affecting 15–20% of children and 1–10% of adults. Staphylococcus aureus (S. aureus) infection is the most frequent complication of AD and is involved in the worsening of the disease. Systemic and topical antibiotics are used in the treatment for AD but there are concerns over increasing resistance. Bleach (sodium hypochlorite, NaOCl) baths are an inexpensive, widely accessible, alternative antibiotic treatment that may not worsen antibiotic resistance. Bleach baths are used as adjunctive treatment in AD patients to treat superinfections, although their mechanism of action is not well understood. Balancing safety concerns with efficacious treatment should be important especially for AD where the majority of patients are in pediatrics age groups. Studies available in PubMed databases were included in this review. Most suggested bleach bath improves clinical symptoms of AD and restores surface microbiome by eradicating bacteria, most notably S. aureus. Some studies have noted that this antimicrobial effect has reduced the need for topical corticosteroids. In addition, bleach seems to have strong anti-inflammatory and antipruritic effects. Overall, bleach baths seem to be safe on human skin, without disrupting the epidermal barrier function. The review concluded, although there are some advantages of use of bleach baths, more studies to investigate long-term efficacy and safety of bleach baths are required before fixing its role in the treatment of AD especially in the context of the Indian scenario.
Keywords: Atopic dermatitis, bleach baths, sodium hypochlorite
Introduction 
Atopic dermatitis (AD) is a chronic, relapsing inflammatory skin disease that affects about 15--20% of children and 1--5% of adults.[1] Although the pathogenesis of AD is not completely elucidated, it is understood that a complex interplay of genetic, environmental, and immunological factors controls the initiation and progress of AD. Multiple trigger factors and pathophysiologic mechanisms have been implicated in the causation of AD, out of which Staphylococcus aureus (S. aureus) infection is one of them.[2] The mainstay treatment for AD is a combination of topical corticosteroids (TCSs), calcineurin inhibitors (TCIs), and emollients. AD patients have deficient skin barriers and are well known to develop superadded skin infection especially by S. aureus. Systemic and topical antibiotics are used in the treatment for infected AD but there are concerns over increasing resistance. Bleach (sodium hypochlorite, NaOCl) baths are an inexpensive, widely accessible, alternative antibiotic treatment that may not worsen antibiotic resistance. Bleach baths are used as adjunctive treatment in AD patients to treat superinfections, although their mechanism of action is not well understood. This article reviewed studies available in PubMed databases, tried to find out the methodology, efficacy, and safety of bleach baths in AD and to delineate its role in the Indian perspective.
Role of Staphylococcus Aureus in the Pathogenesis of AD Staphylococcus aureus colonization/infection is a characteristic feature in the pathophysiology of AD.[3] A meta-analysis concluded that the pooled prevalence of SA colonization was 70% on lesional skin, 39% on nonlesional skin, and 62% for nasal colonization among individuals with AD6 and 3% in nonatopic individuals. In contrast, only 5% of the normal population carry S. aureus, which is largely found in the nares and intertriginous areas.[4]S. aureus infection contributes to disease flare and severity because colonization may deteriorate epidermal barrier function and aggravate inflammation. High S. aureus colonization in AD could be due to multiple factors including decreased innate antibacterial activities, increased bacterial adherence to inflamed skin, and defective epidermal barrier function with associated pH changes toward alkalinity [Table 1].
Table 1: Association of S. aureus in the pathogenesis of atopic dermatitis:Fritz et al. found that a 5-day regimen of intranasal mupirocin twice daily with daily body washes with 4% chlorhexidine solution baths can significantly decrease the incidence of a recurrence of community-acquired S. aureus by 12 months. This regimen is attractive, but S. aureus may develop resistance to these agents.[5]
But there are few studies contradicting this pathogenesis that colonization with S. aureus is not a characteristic feature of atopic skin and can be frequently found in damaged skin and in nonatopic eczema. Moreover, the degree of colonization depends on the severity and duration of the eczematous lesions.[6]
What is a Bleach Bath? A bath with a small amount of bleach or sodium hypochlorite (NaOCl) added to the water often used to lessen the symptoms of atopic eczema in children is known as bleach bath.
Historical Use of Sodium Hypochlorite in Medicine Bleach or sodium hypochlorite (NaOCl) has been used as a disinfectant and antiseptic since the 18th century.[7] Depending on the pH, bleach may exist as hypochlorous acid (HOCl), as hypochlorite ion, or in its molecular form (chlorine, Cl2). Hypochlorous acid is naturally produced by neutrophils and acts as a major oxidant and microbicidal agent. Because HOCl is not shelf-stable, it was not used in commercial formulation until recently.[8]
NaOCl was used for the treatment of gangrene in 1732 and Paris surgeons used it for the treatment of burns, operative wounds, and ulcers. The antiseptic properties of NaOCl were also reported by Koch in 1880. Later, Dakin developed a buffered solution of 0.45–0.5% NaOCl that was not irritating while preserving its antiseptic properties.[9]In vitro studies have shown that NaOCl concentrations as low as 0.005% are effective specifically against S. aureus in wounds and skin ulcers.[10]
Because HOCl is not shelf-stable, it was not used in commercial formulations until recently. In 2007, Wang et al.[11] described a method for preparing and stabilizing a pure form of HOCl (NVC-101) by minimizing Cl2 formation. Stabilized HOCl is more potent and, at concentrations of 0.1--2.8 Kg/mL, has improved and broader antimicrobial activity in vitro compared with NaOCl.
More recent antiseptic uses of NaOCl include the treatment of burns, wounds, pressure sores, and deep ulcers at concentrations ranging from 0.02518 to 0.5%. Further there have been many studies with varying concentrations of NaOCl proved to be effective against S. aureus infected wounds and ulcers.[12]
Mechanism of Action of Bleach in AD NaOCl has been used and discussed quite a lot for the treatment of AD as it is known to decrease staphylococcal colonization and decrease AD severity as it is readily accessible, inexpensive, and well-tolerated.[8] NaOCl has been shown to have both in vitro and in vivo antimicrobial activity against S. aureus, including methicillin-resistant resistant S. aureus.
When mixed with water, NaOCl dissociates to form HOCl and sodium hydroxide (NaOH). Hypochlorous acid non-selectively eradicates S. aureus, commensal bacteria, fungi, and viruses. In addition to microbial eradication, bleach seems to affect AD through several other important mechanisms; reduces T-cell activation by antigen-presenting cells and subsequent cutaneous inflammatory response; reduces IL-12 response and thus prevents TH2-to-TH1 shifts and chronicity of AD; decreases IgE production by B cells; decreases mast cell activation and histamine release; downregulates MAPK and NF-KB pathways, leading to decreased production of proinflammatory cytokines (IL-1A, IL-6, tumor necrosis factor >, IL-4, IL-13, and thymus- and activation-regulated chemokine) and pruritogenic cytokines (TSLP); and decreases neurosensory transmission of pruritogenic stimuli by decreasing intracellular calcium concentration in the dorsal root ganglia [Figure 1].[13]
Properties of Household Bleach NaOCl is the active compound found in commercial household bleaches. Household bleach is a clear, yellowish, alkaline (pH 11–13) aqueous solution with a characteristic odor and strong oxidizing properties, Dakin solution is an effective agent against a broad spectrum of aerobic and anaerobic bacteria as well as viruses, fungi, and spores.
The relative amounts of the various active chlorine species depend mainly on the pH and to a lesser extent on the concentration of chloride ions. Chlorine gas is generated significantly below pH 2; HOCl is the predominant species between pH 2 and 7.5, whereas ClO+ is predominant in the alkaline region.[12]
Bleach has a broad spectrum of action, being effective against bacteria (both Gram-positive and Gram-negative), spores, fungi, and viruses.
Preparation of Bleach Bath The optimal bleach concentration required to kill community-associated methicillin-resistant S. aureus has been shown to be 2.5 micro L/mL or 0.005% NaOCl, which is suggested to be equivalent to (half a cup of 6% common household bleach in a standard 150-L bathtub full of water).[13]
The American Academy of Dermatology recommends a ''soak-and-smear'' regimen for patients with AD, with limited use of non-soap cleansers that are neutral to low pH, hypoallergenic, and fragrance-free. However, when visible signs of infection are present, dilute bleach baths for 5--10 min. 2 to 3 times weekly are the preferred regimen.[14]
There have been various protocols used to develop and use a bleach bath in AD patients. One of them has been shown in the table demonstrated by Krakowski et al. [Table 2].[15]
Table 2: Protocol to make a bleach bath (reproduced from Krakowski and colleagues) Safety Concerns of Bleach ToxicityIngesting diluted sodium hypochlorite generally causes only mild stomach irritation; however, swallowing large amounts can cause more serious symptoms, including chest pain, delirium, hypotension, burns to the gastrointestinal tract, shock, bradycardia, nausea, and vomiting.[15]
HCl is formed when chlorine gas contacts moist tissues like the eyes or lungs. HCl is a digestive juice that damages tissue; it can damage the airways, cause asphyxiation, and result in death.
It is important to note that activated charcoal does not effectively treat (adsorb) sodium hypochlorite. Treatment will depend on the severity of the toxicity with medical management for mild-moderate cases of toxicity, to surgery if there are perforations noted along the gastrointestinal tract.[12]
NaOCl has been used in medicine as a topical antiseptic in many applications such as for the treatment of burns, wounds, and ulcers, or for cleaning the root canal system in endodontics. When used in this fashion, its toxicity is extremely low, a fact that has been proven with animal models as well as in human studies.[12]
Carcinogenicity and genotoxicityNaOCl has been shown to have some mutagenic activity in both bacterial and mammalian cells in vitro. However, there is no data in humans on the carcinogenicity of hypochlorite salts. The International Agency for Research on Cancer has assigned hypochlorite salts to group 3; compounds that are not classifiable as to their carcinogenicity in humans.[16]
Asthma and irritation of SkinExposure to chlorine in swimming pools has been shown in some studies to increase the risk of developing asthma in children and adults as well as causing dermatitis and irritating the skin.[12] Similar safety concerns can be there for bleach bath also, given that bleach baths have been likened to swimming in chlorinated pool water. There were some reports of asthma exacerbations due to inhalation of fumes from bleach baths.
Efficacy of Bleach Baths in Atopic Dermatitis: A Review of Literature A meta-analysis searched the following databases for articles on bleach baths in AD: Cochrane Library, PubMed, MEDLINE, EMBASE, and Scopus. There were more than 100 articles, of which they could five studies targeted at the efficacy of bleach baths in reducing the severity of atopic dermatitis. Among the 5 studies, 3 were RCT, one was a randomized crossover trial, and one was a single-arm pilot study. Two studies were double-blinded, two were single-blinded, and one was unblinded. Four studies were prospective and one was partially prospective and retrospective. Four trials included only children and one included both children and adult patients.[17]
Efficacy of bleach bathAmong 4 studies comparing bleach to water baths, only 2 found significantly greater reductions in AD severity with bleach baths, 1 with water baths, and 1 found no significant differences.
At 4 weeks, one study found a significant reduction in AD severity compared to controls (EASI, BSA, IGA), two found no significant differences (EASI [n = 2], IGA [n = 1], local-EASI [n = 1], BSA [n = 1], VAS-itch [n = 1], and patient self-assessment [n = 1]), and one showed mixed results. In one study at 8 weeks, bleach baths caused significant reductions in EASI and BSA assessments, but not VAS-itch or the patient's self-assessment. In one study at 12 weeks, bleach baths caused significant reductions in EASI and BSA, but not IGA.[17]
Bacteriologic assessmentsAt least three studies showed reductions in S. aureus density after both bleach and normal baths, but there were no significant differences between the groups. Studies also found no significant differences in antibiotic resistance between groups.[17] In a study by Kaplan et al., bleach baths twice weekly for 15 min. for 3 months plus hygienic measures did result in a reduction of MA-SSTI recurrences (17%) compared with hygienic measures alone (21%) within a year of enrollment, although this difference was not statistically significant.[18]
Interestingly, in a study conducted to study on in vitro antibacterial effect of NaOCl on S. aureus, Sawada et al.[19] found that when S. aureus was incubated with 0% and 0.01% NaOCl with water there was no bacteriocidal activity seen. A bactericidal effect of dilute bleach against these strains of S. aureus was only evident at concentrations of greater than 0.03%, a concentration of bleach that is cytotoxic to human cells and much greater than should be used clinically.
Anti-inflammatory effectsSodium hypochlorite solution has been shown to reduce irradiation dermatitis in a mouse model through inhibition of nuclear factor JB (NF-JB), a key transcription factor that regulates the inflammatory response.[20] In animal studies, Fukuyama et al.[21] showed HOCl hydrogel application results in a decrease in serum IgE and skin histamine concentration and also in a reduction in proinflammatory cytokines like interleukin 1A [IL-1A], IL-6, tumor necrosis factor-alpha, IL-4, IL-13, and thymus- and activation-regulated chemokine and propruritogenic cytokines LIKE thymic stromal lymphopoietin [TSLP] and IL-31.
Antipruritic effectsA study showed bleach and water baths both led to a reduction in itch, measured by visual analog score. At 2 months, the patients of atopic dermatitis treated with bleach bath showed a significant reduction in itch (P = 0.02). However, the study could show no significant difference when compared with those patients who were given a water bath (P = 0.53)[22]
Safety, tolerabilityFour studies documented the adverse effects of bleach baths. Adverse effects included stinging/burning (11%), itch (0.5%), xerosis (10.5%), erythema (6.9%), urticaria (5%), oozing (1/20; 5%). There were no differences in adverse effects between bleach and water baths.[17]
Alternatives to Bleach Topical antiseptics are used as alternative treatments to antibiotics for patients with AD. The advantage of the use of antiseptics is in their low chance of resistance against S. aureus strains, in spite of repeated use. Easily available antiseptic for use during bathing include benzalkonium chloride and triclosan.
Benzalkonium chloride, a quaternary ammonium compound commonly used as antiseptic, and preservative, is safe for use at a concentration of 0.1%. Triclosan is a synthetic, nonionic, broad-spectrum, chlorinated bisphenol antiseptic, is commonly added in cleanser and emollients used in AD.[12]
A randomized, double-blind parallel-group study found that the daily use of antiseptic bath oil containing benzalkonium chloride and triclosan over a 4 week period can reduce the level of S. aureus on eczematous skin and leads to a significant improvement in clinical symptoms.[23]
Other antiseptics with future potential for use in baths at home include chlorhexidine gluconate and potassium permanganate.[24]
Conclusion: Use of Bleach Bath in Indian Perspective Bleach bath is a widely known and accepted therapy for the treatment of infection in AD. But its exact mechanism is still not fully understood. The anti-microbial, anti-inflammatory, and antipruritic effects are known to cause improvement in AD.
There is a paucity of literature in the efficacy and safety of the bleach bath, and the limited amount of data available fails to show the superiority of the bleach bath over the water bath. It may be that water baths alone can reduce the risk of bacterial infection in AD patients and future studies are needed to elucidate this point.
The advantages of using NaOCl in the form of bleach baths as an adjunctive treatment for patients with infected atopic eczema are that it has a broad spectrum of action, being effective against bacteria spores, fungi, and viruses; no microbial resistance phenomena have been reported with NaOCl, unlike most antibiotics; it is widely available and is inexpensive.[12]
However, bleach baths can cause irritation, stinging, and contact dermatitis to the treated skin. It can have some ocular discomfort.
In the Indian scenario, where we have extremes of temperature with humidity in major parts almost through out the years, it is still not a well-accepted treatment in Indian patients. However, it is economically suitable for our resource-poor setup. It also has a distinct advantage of having relatively low resistance against S. aureus; given that we have a very high hospital- and community-acquired resistance in our country.[25]
Overall, bleach bath needs to be evaluated more for its efficacy and safety, and good quality study needed to be conducted on Indian patients, before fixing its role in the treatment of infected atopic eczema especially in the context of the Indian scenario.
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Conflicts of interest
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