Arsenicosis

Synonyms

Arseniasis; Arsenicism; Arsenism; Chronic arsenicosis (“arsenicosis” needs to be differentiated from “acute arsenic poisoning”)

Definition

Arsenicosis is defined by the World Health Organization (WHO) working group as a “chronic health condition arising from prolonged ingestion (not less than 6 months) of arsenic above a safe dose, usually manifested by characteristic skin lesions, with or without involvement of internal organs” (WHO Regional Office for South-East Asia 2003). The maximum permissible limit recommended by WHO in groundwater is 10 μg/L; however, in India, Bangladesh, the accepted level is <50 μg/L in the absence of an alternative source of potable water in the affected area (Smedley and Kinniburgh 2002).

Magnitude of the Problem

Arsenicosis is a global problem with some local predilection. Asian countries are the worst affected with major disease burden reported from countries like Bangladesh, India, and China; however, people are also affected in parts of Mongolia, Hungary, Mexico, Argentina, Chile, Canada, and USA (Table 1) (Ghosh et al. 2008; Smith et al. 2000).

Arsenicosis, Table 1 Country profiles (in decreasing order of population at risk) in relation to arsenic contamination of groundwater

Approximately 40,000-sq. km area in West Bengal (12 out of 19 districts), 118,000-sq. km area in Bangladesh (50 out of 64 districts), and 4,000 sq. km in China (8 provinces and 37 counties) are reported to be affected (Ghosh et al. 2008). Apart from the Asian countries, reports from Hungary (Great Hungarian Plain) reveal that 4,263-sq. km area is having arsenic in groundwater in the range of 25–50 μg/L (Kapaj et al. 2006). With increasing scope of field testing and screening, these figures are on a rising trend, and increasing number of areas affected with arsenic contamination and at-risk population are identified with every new survey conducted. Reports from community-based surveys revealed that one in every five to ten persons in the endemic areas of south eastern Asian countries is actually manifesting the disease (Smith et al. 2000; Ghosh et al. 2008).

Epidemiological Determinants

Arsenicosis is a disease with multifactorial determinants, but the key factor is exposure occurring through naturally contaminated groundwater used for drinking or in food preparation. Sources such as mining and some pesticides and wood preservatives may contribute to human exposure and should be controlled in order to prevent environmental contamination.

Agent Factor

The metalloid arsenic is the obvious agent factor, and the trivalent (arsenite, As ⁺³) and pentavalent (arsenate, As ⁺⁵) states are principally implicated in arsenicosis. Arsenic is perhaps unique among the heavy metalloids and oxyanion-forming elements (e.g., arsenic, selenium, antimony, molybdenum, vanadium, chromium, uranium, rhenium) in its sensitivity to mobilization at the pH values typically found in groundwaters (pH 6.5–8.5) and under both oxidizing and reducing conditions (Smedley and Kinniburgh 2002).

Most oxyanions including arsenate tend to become less strongly sorbed as the pH increases. Under some conditions at least, these anions can persist in solution at relatively high concentrations (tens of μg/L) even at near-neutral pH values. Therefore, the oxyanion-forming elements are some of the most common trace contaminants in groundwaters. However, relative to the other oxyanion-forming elements, arsenic is among the most problematic in the environment because of its relative mobility over a wide range of redox conditions. It can be found at concentrations in the mg/L range when all other oxyanion-forming metals are present in the μg/L range (Smedley and Kinniburgh 2002).

Highest concentration of arsenic in water is found in groundwater, and range of concentration is also pretty wide, hence making it difficult to derive a typical or “usual” value. Moreover, majority of the researches focused on areas endemic for arsenicosis, resulting in extreme values, and these are possibly unrepresentative of global pattern.

Baseline concentration of arsenic in atmospheric precipitation, river water, rainwater, or seawater is found to be quite low. The concentration of arsenic may increase to manifolds in river water or surface water where concentration is usually very low, if it gets contaminated by industrial pollution, by increased geothermal activities, or if water is flowing through bedrocks (with increased alkalinity and pH). Seasonal variation may influence geothermal activity or leaching of arsenic in surface water/river water. In low-flow period during summer months, it gets increased, and this may also be linked to temperature-controlled microbial reduction of As⁺⁵ to As⁺³ with consequent increased mobility of As⁺³ (Smedley and Kinniburgh 2002; Appelo 2006).

Host Factor

Propensity to develop arsenicosis in a community is variable. In large scale studies, it was noted that manifestation of arsenicosis was present among 11–20% of people living in arsenic contaminated areas of West Bengal, India, and Bangladesh (Ghosh et al. 2008). Understandably the susceptibility of individuals to develop full-blown disease varies in the same community using same water source.

The disease manifestation is strongly associated with malnutrition, especially with deficiency of proximate principle like protein or deficiency of trace element like selenium. People belonging to lower socioeconomic strata are more vulnerable to develop this disease. Age of the individual is also an important parameter which determines the expression of the disease and it usually takes 5–20 year of exposure to develop the disease. Nevertheless, children with <10 year of exposure have developed this disease (Smith et al. 2000).

Genetic factors, viz., decreased capacity of methylation of arsenic and genetic polymorphism of enzymes XPD and XRCC1, having null or variant genotype of at least one of the three (M1/T1/P1) glutathione S-transferases are risk factors for carcinogenesis in arsenicosis patients (Ghosh et al. 2008).

Environmental Factors (Sources of Arsenic)

Arsenicosis is a disease, principally linked to environmental situation. People can get exposed to arsenic due to its presence in water (principal route of entry), soil, air, or less commonly through other miscellaneous agents as detailed below. Arsenic can enter these routes either though natural (geogenic) processes or by man-made (anthropogenic) activities, or both may contribute in certain situations (Ghosh et al. 2008).

Arsenic can gain entry in underground water as result of geochemical processes (vide Table 2), or it may be of anthropogenic origin, e.g., use of pesticide, insecticide, or industrial pollution. Presence of arsenic in soil is thought to be the result of use of phosphate fertilizer which could result increased phosphate concentration in soil and consequently increase in sediment biota leading to increased resorption of arsenic from the sediment (Ghosh et al. 2008).

Arsenicosis, Table 2 Postulated mechanisms of geochemical processes for leaching of arsenic in groundwater

Volcanic eruption contributes to the majority of atmospheric flux of arsenic (as As₂0₃). Natural low-temperature bio-methylation and microbial reduction are the other natural sources of arsenic in air. Of the anthropogenic causes, smelting of nonferrous metal and combustion of fossil fuels are important. The arsenic returns to the earth by wet or dry precipitation and contributes the arsenic load of water and soil (Ghosh et al. 2008).

Organic form of arsenic is primarily found in marine organisms in the form of arsenobetaine in marine animals and dimethyl arsenoyl ribosides in marine algae and can serve as important arsenic source for individuals consuming seafood (Ghosh et al. 2008).

Exposure to arsenic through medications (e.g., Fowler’s solutions or 1% potassium arsenite) containing arsenic is of historical importance, but even in present days, homeopathic medicine containing arsenic is still being used in some countries. Recently, arsenic trioxide (Trisenox) has obtained FDA approval for use in acute promyelocytic leukemia, but its impact in causing arsenicosis is yet to be evaluated.

Gallium arsenide, used as a silicone substitute in computer microchips, poses an emerging threat arising due to the expanding opto-electric and micro-electronic industries (Ghosh et al. 2008).

Bioaccumulation of arsenic is still not an established threat, but case reports and studies of presence of arsenic in crops (particularly rice) irrigated with arsenic contaminated water or milk and meat sample obtained from animal husbandry of arsenic contaminated areas point toward this phenomenon (Ghosh et al. 2008).

Pathogenesis

Arsenic gaining entry in the body undergoes sequential reduction and oxidative methylation and is converted to less toxic methylated metabolite, monomethyl arsenic acid (MMA), and dimethyl arsenic acid (DMA). This bio-methylation is considered as bio-inactivation process, and persons differing in this capability suffer due to accumulation of As⁺³ and As⁺⁵ (Sengupta et al. 2008; Gomez-Caminero et al. 2001a).

As⁺³ has the ability to bind with the sulfhydryl groups present in various essential compounds (e.g., glutathione, cysteine) and can lead to inactivation of many thiol group-containing enzymes (e.g., pyruvate dehydrogenase) and other functional alteration (e.g., prevention of binding of steroid to glucocorticoid receptors). As⁺⁵, on the other hand, mostly mediates its toxicity after conversion to the trivalent state but in certain situation, can render direct toxicity by replacing phosphate during glycolysis (phenomenon known as “arsenolysis”) leading to ineffective adenosine triphosphate (ATP) production (Sengupta et al. 2008; Gomez-Caminero et al. 2001a).

Inorganic arsenic is capable of causing teratogenic effects, and animal studies have demonstrated that it can lead to neural tube defect, inhibition of development of limb-buds, pharyngeal arch defect, anophthalmia, etc. Arsenic can also induce genotoxicity by inhibiting DNA excision repair of thymine dimer, DNA ligase, and tubulin polymerization and altering the activity of tumor suppressor gene p53 by DNA methylation. Arsenic is also thought to build up oxidative stress by the production of oxygen free radical, which in turn can cause chromatid exchange and chromosomal aberration. The genotoxicity in turn is responsible for carcinogenicity. The free radicals generation also leads to increased apoptosis (programmed cell death) seen in arsenicosis (Sengupta et al. 2008; Gomez-Caminero et al. 2001b).

The cutaneous toxicity seen with arsenicosis is influenced by various growth factors and transcription factors. Expression of keratin 16 (marker for hyperproliferation) and keratin 8 and 18 (marker for less-differentiated epithelial cells) is found to be increased by arsenic exposure. Arsenic has shown to reduce transcription factor AP1 and AP2 which in turn reduces keratinocyte differentiation marker, involucrin. Arsenic is shown to trigger production of interleukin (IL)-8 and also stimulate the secretion of IL-1, tumor necrosis factor-alpha (TNFα), transforming growth factor (TGF) beta, and granulocyte monocyte colony-stimulating factor (GM-CSF) by the keratinocytes. The changed cytokine milieu is believed to exert the cutaneous changes (Sengupta et al. 2008; Gomez-Caminero et al. 2001a). The pathogenesis of other systemic manifestations is highlighted in Table 3.

Arsenicosis, Table 3 Proposed mechanism of pathogenesis for systemic manifestations in arsenicosis

Clinical Features

Arsenicosis is a multisystem disorder, but the hallmark clinical manifestations are its cutaneous changes. The cutaneous changes are so pathognomonic that the condition can be clinically confirmed by looking at the skin changes. The skin lesions can take the form of melanosis (pigmentary changes/dyspigmentation), keratosis (thickening of skin), or malignant/premalignant lesions. Respiratory, hepatobiliary, vascular, and nervous systems are among the major systems affected by arsenicosis, apart from constitutional symptoms, including weakness, headache, pedal edema, etc. (Sengupta et al. 2008). Though the systemic features of arsenicosis are nonspecific, but at times they may serve as taletell signs especially in early suspected cases. The cutaneous changes and neurological defects produced by arsenicosis are irreversible, but respiratory, hepatobiliary, gastrointestinal, and vascular effects can be reversed (World Bank technical report vol II). The manifestations of arsenicosis vary according to the cumulative exposure of arsenic, and the description of the exposure dose for different manifestations is detailed in Fig. 1.

Arsenicosis, Fig. 1

Clinical manifestations in arsenicosis (Source: Sengupta et al. (2008) (Permission obtained from editor-in-chief IJDVL))

Cutaneous Manifestations

The cutaneous lesions are typically bilateral and are the earliest and commonest changes seen in arsenicosis patients. It is generally agreed that there is latency of approximately 10 years for development of skin lesion (i.e., exposure of arsenic and development of manifestations), though there are reports of arsenicosis in children less than 10 years (Smith et al. 2000).

Melanosis is found to be the earliest and commonest of all the cutaneous manifestation of arsenicosis and is most pronounced on trunk. The most characteristic arsenical dyspigmentation takes the form of guttate hypopigmented macule on hyperpigmented background, referred to as leucomelanosis (Fig. 2). In some cases, it can also take the form of freckle-like spotty pigmentation, quoted as raindrop pigmentation by some authors (Fig. 3). There can also be appearance of diffuse pigmentation of skin and/or pigmentation of mucosa (e.g., on tongue, buccal mucosa) (Sengupta et al. 2008; GuhaMajumder 2008).

Arsenicosis, Fig. 2

Leucomelanosis affecting the trunk (Source: Sengupta et al. (2008) (Permission obtained from editor-in-chief IJDVL))

Arsenicosis, Fig. 3

Raindrop pigmentation on the trunk, along with arsenical hyperkeratosis affecting the dorsa of hands, fingers, and forearm (Source: Das and Sengupta (2008) (Permission obtained from editor-in-chief IJDVL))

Arsenical keratosis mostly affects the palms and soles, though in long standing cases can affect other areas, including trunk and dorsa of feet or hands (Fig. 3). The keratosis is symmetric and graded according to its severity and extent into mild (grit-like texture or papule less than 2 mm) (Fig. 4), moderate (wart-like excrescence of size 2–5 mm) (Fig. 5), or severe (keratotic elevation of more than 5 mm or diffuse and confluent keratosis) (Fig. 6). Arsenical keratosis is often the forerunner of cutaneous malignancy and sometimes regarded as early clinical marker of carcinogenicity of internal organs (especially carcinoma of lungs and bladder) (Sengupta et al. 2008; GuhaMajumder 2008).

Arsenicosis, Fig. 4

Mild variety of arsenical keratosis producing grit-like texture

Arsenicosis, Fig. 5

Moderate variety of arsenical keratosis

Arsenicosis, Fig. 6

Severe variety of arsenical keratosis (Source: Sengupta et al. (2008) (Permission obtained from editor-in-chief IJDVL))

Carcinogenicity

Arsenic-induced carcinogenicity mostly affects the skin arising usually on keratotic lesions, though it may arise on apparently normal skin too. There is a dose-response relationship between skin cancers and arsenic consumption with a lifetime risk of developing skin cancer ranging from 1 to 2 per 1,000 with the intake of 1-μg/Kg body weight/day (approximately 1 l of water with arsenic concentration of 50 μg/L) (Smith et al. 2000). Bowen’s disease is the most common form of precancerous lesions, and any hyperkeratotic plaque in arsenicosis suspect showing fissures and crusts at places should raise the suspicion for this premalignant form. Multicentric Bowen’s disease affecting both covered and sun-exposed skin is a characteristic feature of arsenicosis (Fig. 7). Untreated Bowen’s disease can transform into squamous cell carcinoma (Fig. 7) and can contribute significantly to the morbidity and mortality associated with the condition. Basal-cell carcinoma (Fig. 8) may also appear as a result of arsenicosis as well as other less-reported malignancies including Merkel cell carcinoma and melanoma (Sengupta et al. 2008; GuhaMajumder 2008).

Arsenicosis, Fig. 7

Squamous cell carcinoma affecting the hands, with Bowen’s disease on the abdomen same patient with arsenical hyperkeratosis affecting the palm and forearm (Source: Sengupta et al. (2008) (Permission obtained from editor-in-chief IJDVL))

Arsenicosis, Fig. 8

Basal-cell carcinoma behind the ear, with arsenical keratosis on the palms (Source: Sengupta et al. (2008) (Permission obtained from editor-in-chief IJDVL))

Cancer risk for arsenicosis patients is not limited to skin malignancies, and there are reports of visceral malignancies including carcinoma of liver, lungs, kidney, and urinary bladder. There are also reports of malignancies arising from prostrate, uterus, and lymphatic tissues in cases of arsenicosis (Sengupta et al. 2008). It has been estimated that lifetime risk of dying from internal malignancy is high (around 13 per 1,000 on consumption of 1 l of water with arsenic concentration of 50 μg/L) than that of skin cancers because the later is detected early and not fatal if treated adequately (Smith, Lingus and Rahman, Smith et al. 2000). Based on the dose-response relationship, it is suggestive that if the patients with skin manifestations continue to drink arsenic contaminated water, the risk of mortality due to internal malignancies would increase when sufficient latency has been reached. Arsenic is regarded as class I human carcinogen by the International Agency for Research on Cancer (International Agency for Research on Cancer 2004).

Respiratory System

Respiratory symptoms include chronic cough and respiratory distress, which may result from restrictive lung disease, obstructive lung disease, combination of both, interstitial lung disease, bronchitis, or bronchiectasis. Crepitation and rhonchi are found on auscultation, and the pulmonary function test shows reduced forced expiratory volume in 1 s (FEV₁) and forced vital capacity (FVC) (Sengupta et al. 2008; GuhaMajumder 2008).

Hepatobiliary System

Arsenicosis produces hepatocellular toxicity mostly the form of non-cirrhotic portal fibrosis associated with portal hypertension, though cirrhosis of liver is rarely reported too. The portal fibrosis is characterized by expansion of portal zones with streak fibrosis containing leash of blood vessels. Prevalence of hepatomegaly is found to be significantly higher in patients with arsenicosis, and degree of liver enlargement shows a dose-response relationship (Sengupta et al. 2008; GuhaMajumder 2008).

Cardiovascular System

Vascular effects are mostly seen in southwest coast of Taiwan, where Blackfoot disease is endemic. This is characterized by dry gangrene and spontaneous amputation resulting from severe systemic arteriosclerosis. Signs of ischemia, including intermittent claudication, rest pain, and ischemic neuropathy, along with diminished or absent arterial pulsation, pallor on elevation, and rubor on dependency, are diagnostic of blackfoot disease. Histology shows either arteriosclerosis obliterans or thromboangiitis obliterans in this unique peripheral vascular disease.

Apart from peripheral vasculature, chronic arsenic poisoning can also affect cardio- and cerebrovascular systems, leading to hypertension, ischemic heart disease, cerebrovascular disease, and carotid atherosclerosis (Sengupta et al. 2008; GuhaMajumder 2008).

Neurological System

Peripheral sensory neuropathy is characteristic of arsenicosis and is manifested by paraesthesia (e.g., burning and tingling sensation), numbness, pain, etc. Motor involvement is rare and if occurs, can result in distal limb weakness and atrophy and diminished or absent tendon reflexes. The neuropathy is due to distal axonopathy with axonal degeneration, especially the large myelinated fibers. Decreased nerve conduction amplitude is found in arsenic-induced sensory neuropathy with little/no change in nerve conduction velocity and visual/auditory evoked potential (Sengupta et al. 2008; GuhaMajumder 2008).

Other Systems

Arsenicosis can give rise to gastrointestinal symptoms in the form of dyspepsia, anorexia, nausea, vomiting, diarrhea, and abdominal pain. Anuria and dysuria are also reported in arsenicosis, arising due to renal tubular necrosis. Potential of arsenic to cross the placental barrier is thought to be the reason behind bad obstetrical outcome with increased incidence of spontaneous abortion, still birth, preterm birth, and infant mortality that are reported with arsenicosis. Anemia, leucopenia, and thrombocytopenia are usual accompaniment of arsenicosis and are the result of decreased erythropoiesis. There are also reports of diabetes mellitus, conjunctival congestion, and non-pitting edema of feet in arsenicosis, apart from constitutional symptoms including headache and weakness (Sengupta et al. 2008; GuhaMajumder 2008).

Diagnosis

Diagnosis of arsenicosis relies both on clinical manifestations (as detailed above) and laboratory estimation of arsenic content in drinking water and biological samples (Table 4). In countries where the laboratory backup cannot be made available in field situation, the cases can be clinically confirmed by virtue of its characteristic clinical features. WHO has proposed an algorithmic approach for diagnosing arsenicosis (Fig. 9) with the locally available resources. This approach has shown to have both the sensitivity and specificity of more than 80% (WHO Regional Office for South-East Asia 2003; Das and Sengupta 2008).

Arsenicosis, Fig. 9

Algorithmic approach toward diagnosis of arsenicosis (Adopted with modification from World Health Organization, regional office of Southeast Asia, A Field Guide for Detection, Management and Surveillance of Arsenicosis Cases; Editor, Deoraj Caussy) (Source: Das and Sengupta (2008) (Permission obtained from editor-in-chief IJDVL))

Arsenicosis, Table 4 Characteristic clinical and laboratory criteria for diagnosis of arsenicosis

High index of suspicion for arsenicosis is important while assessing persons hailing from areas documented to have high-arsenic content in drinking water, especially if history of similar skin lesions in persons (family members or neighbors) drinking water from the same source. At the same time, it is also important to thoroughly examine the suspected/probable cases to rule out clinical mimickers of arsenicosis (Table 5) (Das and Sengupta 2008).

Arsenicosis, Table 5 Clinical mimickers of arsenicosis

Arsenicosis, Table 6 Details of the methods for obtaining arsenic-free safe water

Determination of Arsenic Content in Water and Biological Samples (Hair, Nail, and Urine)

Atomic absorption spectrometry is considered as the standard reference methods (“gold standard”) for determination of arsenic content due to its high sensitivity and specificity. Other methods of arsenic estimation including colorimetric, inductive-coupled plasma, radiochemical methods, voltammetry, x-ray spectroscopy, hyphenated techniques, etc. are also described, but they suffer the inadequacy of being semiquantitative methods with low sensitivity. The development for test kits for arsenic detection is a much felt need for use in field situations, but unfortunately, none of the presently available test kit has proven reliable (Das and Sengupta 2008).

Maximum permissible limit for arsenic content in drinking water was reduced to 10 from 50 μg/L in 1993 by WHO. It has to be kept in mind that this limit is set depending on the analytical capability of available infrastructure to detect arsenic, and this limit would have been much lower if standard basis of risk assessment for industrial chemical is followed for arsenic. Though many countries, like United States and Japan, have adopted the new standard, developing nations which are worst affected by arsenicosis, like India and Bangladesh, are still operating under the national water quality standard of 50 μg/L due to inadequate testing facility (Smedley and Kinniburgh, 2002). This is making the residents more vulnerable to develop the disease by making them drink unsafe water under the false impression of safe water.

Newer Biomarkers of Arsenic Exposure

Biomarkers that reflect the exposure to arsenic in preclinical stage are being explored to take remedial measures before full-blown expression of disease has occurred. In this respect, raised urinary uroporphyrin-III and coproporphyrin-III have shown promise to detect arsenic exposure. Lowered metallothionein (metal-binding protein that protects against metal intoxication) in blood and tissue has also shown association in arsenic-exposed group and can be utilized in future (Das and Sengupta 2008).

Histology as Diagnostic Clues

Histology is invaluable in diagnosing the malignant changes and for early detection of premalignant lesions. Dysplastic keratinocytes, with presence of anisocytosis and mitotic figures, and dyskeratosis are important histological features of malignant changes (Fig. 10). Loss of cellular architecture and polarity with wind-blown appearance and intact basement membrane suggests Bowen’s disease. Hyperkeratosis, parakeratosis, acanthosis, and papillomatosis are features of keratotic lesions but are not specific for arsenical keratosis. It is important to evaluate the histology of keratotic lesions because of their malignant potential. Histology of pigmented lesions has fallen out of grace because of their nonmalignant potential (Sengupta et al. 2008).

Arsenicosis, Fig. 10

Parakeratotic hyperkeratosis with focal hypergranulosis, increased basal layer pigmentation, and early dysplastic changes (H&E stain, × 400) (Source: Sengupta et al. (2008) (Permission obtained from editor-in-chief IJDVL))

Strategies for Control of Arsenicosis

Basic principle for arsenic mitigation program should include the following (WHO Regional consultation meeting 1997):

• Identification of the affected people

• Provision of symptomatic management including nutritional supplement

• Medical management of seriously ill patients in health centers

• Improved and rapid diagnostic facility in the regional centers

• Provision of safe drinking water

• Capacity building of health care providers

• Awareness generation in susceptible community

• Implement comprehensive and integrated studies for better alternatives

In addition to these, comprehensive program implementation plan, evaluation of existing technologies, research and development for newer approaches, networking with stakeholders, and better convergence should be part of long-term policy.

Provision of Safe Drinking Water

Of all sources of arsenic exposure to human beings, drinking water remains the most crucial one. Safe drinking water sources either can be identified (rainwater harvesting/surface water/safe aquifers, etc.) or engineered (arsenic treatment units/arsenic removal plants) (Table 6) (Ghosh et al. 2008; Yamamura et al. 2000).

It is technically feasible to achieve arsenic concentrations of 5 μg/L or lower using any of several possible treatment methods. However, this requires careful process optimization and control, and a more reasonable expectation is that 10 μg/L should be achievable by conventional treatment (e.g., coagulation) (Ghosh et al. 2008; Yamamura et al. 2000).

The ideal solution is to use alternative sources of water that are low in arsenic. However, it is important that this does not result in risk substitution. Especially tropical countries most affected by arsenicosis area also bear the major burden of gastrointestinal disease. A large group of population is exposed to water source contaminated with enteric pathogen. Water safety frameworks should be used during planning, installation, and management of all new water points, especially ones based on surface water and very shallow groundwater, to minimize risks from fecal and other non-arsenic contamination. Screening for arsenic and other possible chemical contaminants of concern that can cause problems with health or acceptability, including fluoride, nitrate, iron, and manganese, is also important to ensure that new sources are acceptable. Periodic screening may also be required after a source is established to ensure that it remains safe (Ghosh et al. 2008; Yamamura et al. 2000; Johnston et al. 2001).

Many of the major problems lie in rural areas, where there are many small supplies, sometimes to the household level. At this level, water availability and financial and technical resources are all limited. There are several available approaches, but a basic requirement for education can never be overemphasized. In particular, there is a need to understand the risks of high-arsenic exposure and the sources of arsenic exposure.

To achieve safe arsenic concentration in water for human consumption, a number of approaches have been successfully used in rural areas, including source substitution and the use of both high- and low-arsenic sources blended together. Pond water supply, piped water supply of surface water, rainwater harvesting, deep tube well from safe aquifers, and community-/household-based arsenic removal plants are there as alternatives. Best suited one or combination of these methods has been tried in different parts of the world with variable success. These sources may be used to provide drinking water and cooking water or to provide water for irrigation. High-arsenic water can still be used for bathing and clothes washing or other requirements that do not result in contamination of food, in situation where no better alternative is available (Ghosh et al. 2008; Ahmed et al. n.d.).

Arsenic removal process can be of four basic types: Oxidation sedimentation, coagulation filtration, sorption techniques, and membrane techniques. Decision for selecting the most suitable alternative depends upon effectiveness of the process in removing arsenic, installation and running cost, water output, etc. A report revealed that most cost effective method for long-term solution is piped water supply, whereas for medium-term solution at community level, oxidation and filtration or coagulation filtration are better alternatives. For household purpose, iron-filings/iron-coated sand filters are preferable choices for getting arsenic-free water (Ghosh et al. 2008; Ahmed et al. n.d.).

Health Communication

General community should be made aware of relevant health effects of arsenic poisoning, available alternatives for health protection, safe water options, testing facilities for detection of arsenic contamination, dispelling myths, and misconception about the disease. Communication should be a continuous process, and ultimate aim is to involve the community in planning, implementing, and evaluating arsenicosis control program at the local level to make it a sustainable one. Translational research should be carried out to bring the fruits of scientific research and development to the doorsteps of those who need it most (Galway n.d.).

Treatment of Arsenicosis

The treatment of arsenicosis is essentially symptomatic since no effective remedial measures are known till date. The symptomatic relief that can be offered is also very limited because most of the changes are irreversible and for some clinical manifestations even supportive therapy are not available.

Hyperkeratosis can be treated to some extent by using different keratolytic agents. Five to ten percent salicylic acid or 10–20% urea is recommended by WHO for treatment of arsenical keratosis. Retinoids are also tried in arsenicosis, but their use is limited by their cost and side effect profile. The malignant and premalignant lesions are to be treated by surgical excision at the earliest (Das and Sengupta 2008).

Dyspeptic symptoms are treated by H₂ blockers or proton pump inhibitors along with prokinetic agents. For manifestations of portal hypertension, like esophageal varices, sclerotherapy or banding may be done. Peripheral vascular diseases can be managed by vasodilator drugs (e.g., pentoxifylline or calcium channel blocker) with limited success. Tricyclic antidepressant (e.g., amitriptyline) is sometimes used for relieving the painful dysesthesia of arsenical peripheral neuropathy. Bronchodilators are used for controlling symptoms of obstructive lung diseases; also, it is important to avoid smoking and dusty environment (Das and Sengupta 2008).

Role of chelation therapy using dimercaptosuccinic acid (DMSA), dimercaptopropane succinate (DMPS), or d-penicillamine has not shown any favorable reports in recent studies. Presently, they are not considered for the treatment in spite of early success stories.

In arsenicosis, it is important to be vigilant to detect malignancies (either cutaneous or internal) at the earliest so as to offer the benefit of early intervention. Hence, constant follow-up and surveillance is needed for all who reside in arsenic contaminated zone.

Cross-References

Arsenic in Nature

Arsenic in Therapy

Arsenic Methyltransferases

Arsenic, Free Radical and Oxidative Stress

Arsenic-Induced Diabetes Mellitus