Artificial intake of floride has been an obsolete phenomenon. The total intake of floride from various sources already exceeds the MCL of 4 mg per litre and so no further fluoridation is required. Excessive intake of floride leads to dental fluorosis and skeletal fluorosis in human and animals. Intake of florides may be prevented through choice of drinking water with less floride content. More floride intake also leads to several other health hazards
1. WHAT IS FLUORIDE?
Fluoride is any combination of elements containing the fluoride ion. In its elemental form, fluorine is a pale yellow, highly toxic and corrosive gas. In nature, fluorine is found combined with minerals as fluorides. It is the most chemically active nonmetallic element of all the elements and also has the most reactive electro-negative ion. Because of this extreme reactivity, fluorine is never found in nature as an uncombined element.
Fluorine is a member of group VIIa of the periodic table. It readily displaces other halogens - such as chlorine, bromine and iodine - from their mineral salts. With hydrogen it forms hydrogen fluoride gas which, in a water solution, becomes hydrofluoric acid.
There was no US commercial production of fluorine before World War II. A requirement for fluorine in the processing of uranium ores, needed for the atomic bomb, prompted its manufacture.1
Fluorine compounds or fluorides are listed by the US Agency for Toxic Substances and Disease Registry (ATSDR) as among the top 20 of 275 substances that pose the most significant threat to human health.2 In Australia, the National Pollutant Inventory (NPI) recently considered 400 substances for inclusion on the NPI reporting list. A risk ranking was given based on health and environmental hazard identification and human and environmental exposure to the substance. Some substances were grouped together at the same rank to give a total of 208 ranks. Fluoride compounds were ranked 27th out of the 208 ranks.3
Fluorides are cumulative toxins. The fact that fluorides accumulate in the body is the reason that US law requires the Surgeon General to set a Maximum Contaminant Level (MCL) for fluoride content in public water supplies as determined by the EPA. This requirement is specifically aimed at avoiding a condition known as Crippling Skeletal Fluorosis (CSF), a disease thought to progress through three stages. _______________________________________________________________________ *The views expressed in this paper are of the author and not necessarily of the Govt of India or the organization to which he belongs. The MCL, designed to prevent only the third and crippling stage of this disease, is set at 4ppm or 4mg per liter. It is assumed that people will retain half of this amount (2mg), and therefore 4mg per liter is deemed "safe." Yet a daily dose of 2-8mg is known to cause the third crippling stage of CSF.4,5
In 1998 EPA scientists, whose job and legal duty it is to set the Maximum Contaminant Level, declared that this 4ppm level was set fraudulently by outside forces in a decision that omitted 90 percent of the data showing the mutagenic properties of fluoride.6
The Clinical Toxicology of Commercial Products, 5th Edition (1984) gives lead a toxicity rating of 3 to 4 (3 = moderately toxic, 4 = very toxic) and the EPA has set 0.015 ppm as the MCL for lead in drinking water - with a goal of 0.0ppm. The toxicity rating for fluoride is 4, yet the MCL for fluoride is currently set at 4.0ppm, over 250 times the permissible level for lead.
2. Fluorosis
2.1 The disease and how it affects people
Ingestion of excess fluoride, most commonly in drinking-water, can cause fluorosis which affects the teeth and bones. Moderate amounts lead to dental effects, but long-term ingestion of large amounts can lead to potentially severe skeletal problems. Paradoxically, low levels of fluoride intake help to prevent dental caries. The control of drinking-water quality is therefore critical in preventing fluorosis. The condition and its effect on people Fluorosis is caused by excessive intake of fluoride. The dental effects of fluorosis develop much earlier than the skeletal effects in people exposed to large amounts of fluoride. Clinical dental fluorosis is characterized by staining and pitting of the teeth. In more severe cases all the enamel may be damaged. However, fluoride may not be the only cause of dental enamel defects. Enamel opacities similar to dental fluorosis are associated with other conditions, such as malnutrition with deficiency of vitamins D and A or a low protein-energy diet. Ingestion of fluoride after six years of age will not cause dental fluorosis.
Chronic high-level exposure to fluoride can lead to skeletal fluorosis. In skeletal fluorosis, fluoride accumulates in the bone progressively over many years. The early symptoms of skeletal fluorosis, include stiffness and pain in the joints. In severe cases, the bone structure may change and ligaments may calcify, with resulting impairment of muscles and pain.
Acute high-level exposure to fluoride causes immediate effects of abdominal pain, excessive saliva, nausea and vomiting. Seizures and muscle spasms may also occur.
2.2 The cause
Acute high-level exposure to fluoride is rare and usually due to accidental contamination of drinking-water or due to fires or explosions. Moderate-level chronic exposure (above 1.5 mg/litre of water - the WHO guideline value for fluoride in water) is more common. People affected by fluorosis are often exposed to multiple sources of fluoride, such as in food, water, air (due to gaseous industrial waste), and excessive use of toothpaste. However, drinking water is typically the most significant source. A person's diet, general state of health as well as the body's ability to dispose of fluoride all affect how the exposure to fluoride manifests itself.
2.3 Distribution
Fluoride in water is mostly of geological origin. Waters with high levels of fluoride content are mostly found at the foot of high mountains and in areas where the sea has made geological deposits. Known fluoride belts on land include: one that stretches from Syria through Jordan, Egypt, Libya, Algeria, Sudan and Kenya, and another that stretches from Turkey through Iraq, Iran, Afghanistan, India, northern Thailand and China. There are similar belts in the Americas and Japan. In these areas fluorosis has been reported.
2.4 Scope of the Problem
The prevalence of dental and skeletal fluorosis is not entirely clear. It is believed that fluorosis affects millions of people around the world, but as regards dental fluorosis the very mild or mild forms are the most frequent.
2.5 Interventions
Removal of excessive fluoride from drinking-water is difficult and expensive. The preferred option is to find a supply of safe drinking-water with safe fluoride levels. Where access to safe water is already limited, de-fluoridation may be the only solution. Methods include: use of bone charcoal, contact precipitation, use of Nalgonda or activated alumina (Nalgonda is called after the town in South India, near Hyderabad, where the aluminium sulfate-based defluoridation was first set up at a water works level). Since all methods produce a sludge with very high concentration of fluoride that has to be disposed of, only water for drinking and cooking purposes should be treated, particularly in the developing countries.
Health education regarding appropriate use of fluorides.
Mothers in affected areas should be encouraged to breastfeed since breast milk is usually low in fluoride.
3. DENTAL FLUOROSIS:
3.1 A "Cosmetic" Defect
Dental fluorosis is a condition caused by an excessive intake of fluorides, characterized mainly by mottling of the enamel (which starts as "white spots"), although the bones and virtually every organ might also be affected due to fluoride's known anti-thyroid characteristics. Dental fluorosis can only occur during the stage of enamel formation and is therefore a sign that an overdose of fluoride has occurred in a child during that period.
Dental fluorosis has been described as a subsurface enamel hypomineralization, with porosity of the tooth positively correlated with the degree of fluorosis.7 It is characterized by diffuse opacities and under-mineralized enamel. Although identical enamel defects occur in cases of thyroid dysfunction, the dental profession describes the defect as merely "cosmetic" when it is caused by exposure to fluoride.
Currently up to 80 percent of US children suffer from some degree of dental fluorosis, while in Canada the figure is up to 71 percent. A prevalence of 80.9 percent was reported in children 12-14 years old in Augusta, Georgia, the highest prevalence yet reported in an "optimally" fluoridated community in the United States. Moderate-to-severe fluorosis was found in 14 percent of the children.8
Before the push for fluoridation began, the dental profession recognized that fluorides were not beneficial but detrimental to dental health. In 1944, the Journal of the American Dental Association reported: "With 1.6 to 4 ppm fluoride in the water, 50 percent or more past age 24 have false teeth because of fluoride damage to their own."9
3.2 Total Intake
It is well established that it is TOTAL fluoride intake from ALL sources which must be considered for any adverse health effect evaluation.10,11,12 This includes intake by ingestion, inhalation and absorption through the skin. In 1971, the World Health Organization (WHO) stated:
"In the assessment of the safety of a water supply with respect to the fluoride concentration, the total daily fluoride intake by the individual must be considered."11
Exposure to airborne fluorides from many diverse manu-facturing processes - pesticide applications, phosphate fertilizer production, aluminum smelting, uranium enrichment facilities, coal-burning and nuclear power plants, incinerators, glass etching, petroleum refining and vehicle emissions - can be considerable. In addition, many people consume fluorine-based medications such as Prozac, which greatly adds to fluoride's anti-thyroid effects. ALL fluoride compounds - organic and inorganic - have been shown to exert anti-thyroid effects, often potentiating fluoride effects many fold.13
Household exposures to fluorides can occur with the use of Teflon pans, fluorine-based products, insecticides sprays and even residual airborne fluorides from fluoridated drinking water. Decision-makers at 3M Corporation recently announced a phase-out of Scotchgard products after discovering that the product's primary ingredient - a fluorinated compound called perfluorooctanyl sulfonate (PFOS) - was found in all tested blood bank examinations.14 3M's research showed that the substance had strong tendencies to persist and bioaccumulate in animal and human tissue.
In 1991 the US Public Health Service issued a report stating that the range in total daily fluoride intake from water, dental products, beverages and food items exceeded 6.5 milligrams daily.12 Thus, the total intake from those sources alone already greatly exceeds the levels known to cause the third stage of skeletal fluorosis.
Besides fluoridated water and toothpaste, many foods contain high levels of flouride compounds due to pesticide applications. One of the worse offenders is grapes.15 Grape juice was found to contain more than 6.8 ppm fluoride. The EPA estimates total fluoride intake from pesticide residues on food and fluoridated drinking water alone to be 0.095 mg/kg/day, meaning a person weighing 70 kg takes in more than 6.65 mg per day.15b
3.3 Tea
In their drive to fluoridate the public water supplies, dental health officials continue to pretend that no other sources of fluoride exist. This notion becomes absurd when one looks at the fluoride content in tea. Tea is very high in fluoride because tea leaves accumulate more fluoride (from pollution of soil and air) than any other edible plant.16,17,18 It is well established that fluoride in tea gets absorbed by the body in a manner similar to the fluoride in drinking water.16,19
Fluoride content in tea has risen dramatically over the last 20 years due to industry contamination. Recent analyses have revealed a fluoride content of 22.2 mg per teabag or cup in Chinese green tea, and 17.25 mg of soluble fluoride ions per teabag or cup in black tea. Aluminum content was also high - over 8 mg. Normal steeping time is five minutes. The longer a tea bag steeped, the more fluoride and aluminum were released. After ten minutes, the measurable amounts of fluoride and aluminum almost doubled.20
A website by a pro-fluoridation infant medical group states that a cup of black tea contains 7.8 mgs of fluoride21 which is the equivalent amount of fluoride from 7.8 litres of water in an area fluoridated at 1ppm. Some British and African studies from the 1990s showed a daily fluoride intake of between 5.8 mgs and 9 mgs a day from tea alone.22,23,24 Tea has been found to be a primary cause of dental fluorosis.
In Britain, over three-quarters of the population over the age of ten years consumes three cups of tea per day.71 Yet the UK government and the British Dental Association are currently contemplating fluoridation of public water supplies! In Ireland, average tea consumption is four cups per day and the drinking water is heavily fluoridated.
Next to water, tea is the most widely consumed beverage in the world. Tea can be found in almost 80 percent of all US households and on any given day, nearly 127 million people - half of all Americans - drink tea.25
The high content of both aluminum and fluoride in tea is cause for great concern as aluminum greatly potentiates fluoride's effects on G protein activation, the on/off switches involved in cell communication and of absolute necessity in thyroid hormone function and regulation.
4. FLUORIDE AND THE THYROID
The recent re-discovery of hundreds of papers dealing with the use of fluorides in effective anti-thyroid medication poses many questions demanding answers.26,27 The enamel defects observed in hypothyroidism are identical to "dental fluorosis." Endemic fluorosis areas have been shown to be the same as those affected with iodine deficiency, considered to be the world's single most important and preventable cause of mental retardation,28 affecting 740 million people a year. Iodine deficiency causes brain disorders, cretinism, miscarriages and goiter, among many other diseases. Synthroid, the drug most commonly prescribed for hypothyroidism, became the top selling drug in the US in 1999, according to Scott-Levin's Source Prescription Audit, clearly indicating that hypothyroidism is a major health problem. Many more millions are thought to have undiagnosed thyroid problems.
5. Skeletal fluorosis is a crippling bone disease caused by fluoride
5.1 Skeletal Fluorosis in animals and human
Skeletal fluorosis is characterized by hyperostosis, osteopetrosis, and osteoporosis. An extensive review of cattle fluorosis has been given by Obel (1971). Agriculture Canada (1976) found that 25/36 cattle located on several Cornwall Island farms in the Saint Regis Quebec region displayed real or potential symptoms of chronic fluorosis. This diagnosis was based on the presence of lesions in the teeth and skeleton, as well as measurement of inorganic fluoride levels in blood and urine. A subsequent study of livestock in this region reported stiffness and inflamed leg joints, dental fluorosis, osteosclerosis, osteonecrosis and bone deformations (Krook and Maylin, 1979).
The degree to which inorganic fluoride can induce skeletal changes varies considerably between the various animal species. Franke (1989) cites data which show that cattle are the most sensitive to skeletal fluorosis, followed by sheep, horses, pigs, rabbits, rats, guinea pigs and poultry. The sensitivity of cattle is attributed to their negative calcium balance, which is particularly noticeable in lactating cattle after calving; another contributing factor is the length of time which the bolus remains in the stomach of ruminants. The calcium found in cow's milk is supplied from both dietary and bone-resorption sources in approximately equal proportions. Inorganic fluoride uptake occurs in bone tissue primarily through the replacement of hydroxyl groups of calcium hydroxyapatite, the major mineral phase in bone, causing the incorporation of the inorganic fluoride as calcium fluorapatite. A histological study of humerus bones from cattle exposed to atmospheric inorganic fluorides from a group of phosphate fertilizer factories in southern Brazil showed very little formation of primary spongiosa with reduced numbers and sizes of osteoblasts (Riet-Correa at al., 1986). Osteons were irregular in shape, size, and distribution in compact mandibular bone. Enlarged Haversian canals, irregular distribution of osteocytes, variation in calcium content, resorption cavities, and increased and irregular interstitial lamellae accompanied symptoms of fluorosis. As a result of excessive exposure to inorganic fluoride, capillaries invade the cartilage unevenly and with difficulty so that the border becomes dented, resulting in isolated islands of cartilage. Bone marrow becomes fibrous and poor in cells, and hyperactivity of the parathyroid may also occur as a result of decreased systemic calcium.
A drop in milk production has been described amongst cattle in the Massena/St. Regis area (Maylin and Krook, 1982). Milk production in a herd located near an aluminum plant was monitored continuously for 20 years. Milk production started to decrease from the fifth year of inorganic fluoride exposure, and although early losses were not statistically significant, by year eight the losses were significant to the 1% level, and by year 10 to the 0.19 level. Maylin and Krook (1982) also described the symptoms in herd of cattle. By 1972 the conception rates were low, retained placentas were very common and the number of abortions increased. The cows were fed from fodder grown on the farm, samples of which averaged 19.5 ug F-/g dry weight), a value considerably lower than the NAS had determined as detrimental. [emphasis added]
Dental fluorosis is generally characterized by the presence of various enamel defects and lesions such as mottling, hypoplasia, hypocalcification and increased wear. Mottled and defective enamel is believed to be solely an indication of inorganic fluoride exposure during the development of the teeth, as effects are not apparent in teeth which have already erupted prior to exposure (Obel, 1971).
Specifically in cattle dental fluorosis results in chalky-white, yellow or brown discolourations, hypoplasia, pitting and loss of enamel and hyperplasia of the cement. This is sometimes accompanied by gingival hyperplasia (Riet-Correa at al., 1986). Ockerse (1941) observed severe tooth lesions in cattle on a farm where the drinking water contained 11.78 mg F-/L, while Neeley and Harbaugh (1954) found dental lesions but no other symptoms in cattle where water contained 4 to 5 mg F-/L (Obel, 1971). Difficulty in eating was observed, however, in a herd of about 200 Brangus cattle whose water supply contained above 3 mg F-/L. Dental examination revealed that the cattle suffered severe dental fluorosis with the teeth having mottled, eroded, and irregular permanent incisors and black molars with irregular surfaces. Serum samples did not support a diagnosis of fluorosis; however bone tissues contained 2400 ug F-/g (rib), 1300 ug F-/g (metacarpal), and 2015 ug F-/g (mandible), while normal bone levels range from 401 to 1221 ug F-/g (Hibbs and Thilsted, 1983). This case indicates that chronic exposure to inorganic fluoride can be missed if only serum levels are used as an indicator of exposure.
Cows which were exposed to inorganic fluoride in drinking water at concentrations of 5, 10 or 12 mg F-/kg produced significantly fewer calves than the controls. This effect preceded the development of clinical symptoms of fluorosis, which therefore suggests that harmful effects on reproduction cannot be considered a secondary effect of fluorosis (Life Systems Inc., 1985).
Stoddard et al. (1963) fed calves from four months of age 10, 28, 55, and 109 ug F-/g in total ration, (dry matter) for 7.5 years. Taking the milk yield as 100% at a level of 10 ug F-/g in the total ration, the treatments 28, 55, and 109 ug F-/g resulted in milk yields of 93%, 82%, and 60% respectively. A linear relationship was established between the milk yield and the inorganic fluoride content of the feed (r = -0 9999). Stoddard at a1.(1963) concluded that the small differences in milk production at treatment levels below 40 ug F-/g were within natural variation, and this level served as the basis for US forage guidelines.
6. Fluorine in Environment
It is well known that trace elements are essential and beneficial to human health in minute concentrations, as they play an important role in many metabolic processes and act as cofactors. However, exceeding their permissible intake is known to be toxic and has adverse effects on general body metabolism. One such trace element, which is ubiquitously distributed in soil, earth and water is fluoride. It is a fact that low amount of fluoride (0.3-1.0 mg/l) in drinking water is helpful in the prevention of dental caries and in treatment of osteoporosis. However, high intake of fluoride (>1.5 mg/l) in drinking water for a prolonged period is known to cause damage to the teeth enamel and eventually leads to skeletal complications that result in fluorosis. With a view to put the problem of high levels of fluoride ingestion in a wider perspective, in the following, we present some basic facts about fluorine chemistry and its distribution in the environment.
On account of its high chemical reactivity, fluorine is one of the most dispersed elements in the environment. Fluorine is very toxic for both plant and animal life.
The importance of fluoride compounds dates back to the time when man first learned to chemically modify the materials for his environment. The fluorine containing compounds are still used to increase the fluidity of melts and slags in the glass and ceramic industries. Fluorspar is used to reduce the viscosity of the slag in the metallurgy of iron. Cryolite is involved in the formation of electrolyte in the metallurgy of iron wherein Aluminium oxide is dissolved in this electrolyte and the metal is reduced electrically from the melt. The fluorocarbon polymers are among the most versatile and valuable compounds. The chemical applications of fluorine and its derivatives are extensive. Industrial plants manufacturing hydrofluoric acid, aluminium, super-phosphate, enamel, bricks and industries consuming high sulphur non-coking coal like thermal power plants are the main sources of fluoride pollution (Griffin et al, 1980; Deshmukh et al, 1995). These days large amount of industrial effluent containing fluoride are generated from high-tech industries such as those manufacturing semiconductors and integrated circuits.
Fluoride dust and fumes pollute the environment. Inhaling dust and fumes is as dangerous as consuming fluoride containing food, water or drugs. Industrial fluorosis is a serious problem in the developed western and other industrialised countries. However, in India, the problem of industrial fluorosis is also reaching an alarming state due to rapid industrialisation.
Except for evaporites, fluorine is the most abundant halogen in the sedimentary rocks (Wedepohl, 1974). Fluorite (48.7 %F), apatite (3.5 %F), mica (0.14-0.22 %F), illite (0.11-0.26 %F) are the chief fluorine bearing minerals in sedimentary rocks (Koritnig; 1963). Therefore, the kind and distribution of fluorine bearing minerals ultimately determine the fluorine content of rocks.
List of industries that use fluoride either as raw materials in the manufacturing process or fluoride arises as a by-product or it may even be end product:
Aluminium
Refrigeration
Steel
Rust removed
Enamel
Oil refinery
Pottery
Plastic
Glass
Pharmaceutical
Bricks
Tooth paste
Phosphate fertiliser
Chemical industries
Welding
Automobile
The fluorine content of hot spring varies from 0.15 to 55.4 mg/l (Matuura and Kokubu, 1955; Sugawara, 1967) and is seen to increase with increasing temperature, but the mole ratio F/Cl remains approximately constant. In India hot springs (35-100o C) are mostly distributed along major lineaments and rifts (Ravi Shankar, 1986). Their fluorine content varies from 10-17 mg/l (Banerjee, 1967; Chowdhury et al, 1964; Chowdhury and Handa, 1973). In rainwater, fluorine may originate from sea and mostly varies from 0-0.089 mg/l, but near cities and industrial areas, values more than 1 mg/l also have been reported (Handa, 1977).
Fluorine content of plants, mostly cultivated plants, is generally low, except for tea, which contains upto 440 mg/l fluorine (Deshmukh et al, 1995). Sea food contains significantly higher amounts of fluorine compared to freshwater food. In animals, including man, the fluorine ingestion is primarily from drinking water but considerable amount of fluorides are also ingested through food and polluted atmosphere (Srikantia, 1977; Batra et al, 1995). It is observed that fluorine content of food items grown in fluorosis endemic areas is anomalously high and, therefore, fluoride ingestion of affected population through food is also significantly large (Jyothi Kumari et al, 1995). It is observed that fluorine intake in jowar (Sorghum julgare), wheat (Triticum aestivam), rice (Oryza sativa), red gram Dal (Cajanus cajan) and red chillies (Capsicum annuum) is in proportion to the fluorine distribution in their rooting media (Batra et al, 1995; Jyothi Kumari, 1995).
6.1 Effects of fluoride/ fluorosis on soft tissues/ organs/ systems
The conventional belief that fluoride affects only bone and teeth has been negated in recent years, as the evidence on the involvement of the soft tissues/ organs/ systems of the body are convincing. Although radiographs taken on the fluorosed individuals do reveal that ligaments do calcify, very little attention was paid in past to understand the extent of soft tissue involvement in fluorosis.
Convincing evidence now demonstrate the damage or involvement of: 1) Skeletal muscle 2) Erythrocytes 3) Gastro-intestinal systems as well as 4) Ligaments in human fluorosed patients. There are evidences of involvement of other organs and systems of the animal models, viz., kidney, liver, adrenal gland and reproductive organs.
Studies have shown that skeletal muscle is directly involved in fluorosis. Muscle involvement was earlier considered as 'secondary' effect due to neuronal involvement. The electron microscopic observations and biochemical data suggests that there is primary muscle destruction in fluorosis. It is evident from patient of fluorosis that they suffer from muscle weakness, loss of muscle energy and cannot carry out normal routine work.
6.2 Fluoride toxicity, fluorosis and its effects on red blood cells
As red blood cell membrane is an important structural entity which lodges the chemical factors responsible for blood group substances, considerable work on membrane structure and function has been carried out. It is now known that when fluoride is ingested, it will also accumulate on erythrocyte membrane, besides other cells, tissues and organs. The erythrocyte membrane in turn loses calcium content. The membrane which is now deficient in calcium content, becomes pliable and is thrown into folds. The RBCs attain the shape of an amoeba with pseudopodia like folds projecting in different directions. Such RBCs are termed as Echinocytes. The Echinocytes will be found in large numbers, depending upon the extent of fluoride poisoning and duration of exposure to fluoride. The RBCs, in human beings, have life span of 120-130 days, the Echinocytes undergo phagocytosis (eaten-up-by macrophages) and are eliminated from the circulation. This would mean that RBCs in individuals exposed to fluoride poisoning shall not live their entire life span of 120-130 days, but are likely to be eliminated as Echinocytes. This would lead to low haemoglobin levels in patients chronically ill due to fluoride toxicity.
6.3 Effects of fluoride poisoning on the gastro-intestinal mucosa
Acute abdominal pain, diarrhoea, constipation, blood in stool, bloated feeling (gas), tenderness in stomach, feeling of nausea (flu-like symptoms) and mouth sores, loss of appetite are common complaints due to fluoride toxicity.
Fluoride is known to combine with HCl of the stomach and is converted to hydrofluoric acid. Hydrofluoric acid is highly corrosive. The stomach and intestinal lining (Mucosa) is destroyed with loss of microvilli (the structure which is responsible for absorbing the nutrients from food), drying up and cracking of the cell surface and mucus (the slimy substance required for comfortable bowl movements) production is hampered.
6.4 Neurological manifestations
Nervousness, depression, tingling sensation in fingers and toes, excessive thirst (Polydypsia) and tendency to urinate frequently (Polyurea) are controlled by certain regions of brain that appears to be adversely affected.
6.5 Allergic manifestations
Very painful skin rashes which are perivascular inflammations, pinkish red or bluish red round or oval shaped spots on the skin prevalent in women and children that fade and clear up in 7-10 days can also occur.
6.6 Urinary tract manifestations
Urine may be much less in volume yellow-red in colour and itching in the genitals may occur.
6.7 Ligaments and blood vessels calcification
A unique feature of the disease is that soft tissues like ligaments, blood vessels tends to harden and calcify and blood vessels get blocked. Calcified ligaments and blood vessels can be seen in radiographs.
