Partho P. Sengupta, MD, DM

• Associate Professor of Medicine
• Director of Noninvasive Cardiology
• Department of Medicine
• University of California Irvine
• Irvine, California

Other possible conditions that pose diagnostic difficulties are chronic exposure to drugs like minocycline erectile dysfunction treatment herbs discount erectafil 20 mg visa, clofazimine impotent rage man discount erectafil 20 mg buy on line, antimalarials erectile dysfunction drugs online cheap erectafil 20 mg free shipping, amiodarone erectile dysfunction pills sold at gnc buy cheap erectafil 20 mg line, and chlorpromazine generic erectile dysfunction drugs online cheap generic erectafil uk. Chronic exposure to heavy metals such as gold, mercury, and lead can also lead to similar skin pigmentation [56]. Various cough syrups, eye drops, nasal sprays [48], and herbal dietary supplements [49] also contained a certain amount of silver. Currently the most common use of silver preparations as a medicinal agent is for burns as silver sulfadiazine cream. Medical devices such as prosthetic implants, splints, catheters, heart valves, stents, bone cement, and dental fillings are other possible sources [48,50]. When the deposit is inconspicuous Certain cosmetics such as eyelash dye [51] and silver earrings [52] can be a potential source of exposure. In case of acute poisoning, gastric lavage with 1% solution of sodium or magnesium sulfate is given initially along with continuous supportive treatment according to the presenting symptoms. Chronic poisoning Chronic poisoning occurs with long-term exposure to various forms of lead in occupational fields and through food, water, cosmetics, hair dye, paints, and toys in the case of children, etc. There is anemia (due to impaired heme synthesis and hemolysis), colicky abdominal pain (lead colic), constipation or diarrhea, neuromuscular symptoms, myalgias, arthralgias, wrist drop (lead palsy), peripheral neuritis, hypertension, and menstrual disturbances in females. Lead and its various salts such as lead acetate, lead carbonate, lead chromate, and lead trioxide (component of vermillion [sindur]) all produce toxicity in humans if exposed to a significant amount. Lead exposure of children from lead paint is an important cause of childhood lead poisoning. With the gaining popularity of ayurvedic medicines, a considerable number of cases with lead toxicity are being reported following their consumption [60­62]. Stippled blue lines over the gums are also seen and are known as lead lines or Burtonian lines, which are often difficult to demonstrate in case of good oral hygiene and should be differentiated from venous congestion of gums, cyanosis, and bismuth and other metallic deposits. Acute poisoning is characterized by abdominal pain, diarrhea, vomiting, hemolytic anemia, hepatitis, and neurologic dysfunction in the form of paraesthesia. Lead prevents the incorporation of iron into the protoporphyrin molecule by interfering with the enzyme ferrochelatase. In case of adults <10 µg/dL is considered to be a normal blood lead level, but in children adverse effects are seen even with levels below 10 µg/dL [66]. Chelation therapy is indicated even in asymptomatic children with blood lead level >45 µg/dL. Cutaneous manifestations Skin contact with mercury can have local side effects such as erythema, formation of indurated plaque, ulceration, etc. Cutaneous mercury granulomas have been reported following accidental injury from mercury [79,80]. Oral lichen planus following dental amalgam filling containing mercury is a well-established entity supported by positive patch test [81]. Allergic contact dermatitis to mercury can occur by both topical as well as systemic exposure [82]. Individuals previously sensitized by small doses of mercury can later develop a form of systemic contact dermatitis known as baboon syndrome [83]. Acrodynia thought to be a hypersensitivity reaction to mercury primarily occurs in infants and children [84], characterized by pinkish discoloration of hands and feet with severe pain and pruritus [85]. Other symptoms such as gingivitis, loosening of teeth, dyspnea, and reduced urine output may also occur [86,87]. Mercury concentrations often exceeding the recommended values have been found in skin lightening creams [74,75]. Exposure to mercury can occur through inhalation, ingestion, injection, or by direct skin contact. Toxicity Toxic manifestation of mercury on humans varies according to the form of this metal, such as metallic, organic, or inorganic. Long-term mercury exposure can be best assessed by its levels in hair and nail, which persist even after exposure has ceased. Treatment Treatment includes avoiding the source of exposure, supportive therapy for acute symptoms, and chelation therapy. After securing provision for ventilatory support and fluid management, all contaminated clothing should be removed and skin should be cleansed thoroughly to prevent further absorption of mercury via skin. Gastric lavage is avoided in inorganic mercury poisoning because of its corrosive action but is preferred in organic poisoning. Plasmapheresis may be tried when conventional hemodialysis is unable to remove protein-bound mercury [91]. Exposure to metallic mercury is mostly occupational by inhalation of mercury vapor. Symptoms range from shortness of breath to bronchiolitis, pneumonitis, and pulmonary edema, ultimately terminating into severe respiratory failure and death. Features of arsenicosis include pigmentary changes, hyperkeratosis and cutaneous malignancies. Argyria has typical blue-gray pigmentation with accentuation over sun-exposed sites. Lead poisoning is characterized by stippled blue lines over the gums known as lead lines or Burtonian lines. Treatment includes avoiding the source of exposure, supportive therapy for acute symptoms, and chelation therapy. Arsenic contamination in groundwater: A global perspective with emphasis on the Asian scenario. Genetic variants associated with arsenic susceptibility: Study of purine nucleoside phosphorylase, arsenic (+3) methyltransferase, and glutathione S-transferase omega genes. Arsenic exposure through drinking water leads to senescence and alteration of telomere length in humans: A case-control study in West Bengal, India. Cutaneous manifestations of arsenic poisoning due to certain Chinese herbal medicine. Arsenic-induced toxicity and carcinogenicity: A two-wave cross-sectional study in arsenicosis individuals in West Bengal, India. Arsenic exposure through drinking water increases the risk of liver and cardiovascular diseases in the population of West Bengal, India. Ischemic heart disease mortality reduction in an arseniasis-endemic area in southwestern Taiwan after a switch in the tap-water supply system. An overview on peripheral vascular disease in blackfoot disease-Hyperendemic villages in Taiwan. Doseresponse relation between ischemic heart disease and mortality and long-term arsenic exposure. Neuropathy in arsenic toxicity from groundwater arsenic contamination in West Bengal, India. Comparison of the urinary excretion of arsenic metabolites after a single oral dose of sodium arsenite, monomethylarsonate or dimethylarsenate in man. The emerging role of retinoids and retinoic acid metabolism blocking agents in the treatment of cancer. Randomized placebo-controlled trial of 2,3-dimercaptosuccinic acid in therapy of chronic arsenicosis due to drinking arseniccontaminated subsoil water. Arsenic-safe drinking water and antioxidants for the management of arsenicosis patients. A pharmacological and toxicological profile of silver as an antimicrobial agent in medical devices. Argyria an unrecognized cause of cutaneous pigmentation in Indian patients: A case series and review of the literature. Detection of silver sulfide deposits in the skin of patients with argyria after long-term use of silver-containing drugs. Treatment of argyria using the quality-switched 1,064-nm neodymium-doped yttrium aluminum garnet laser: Efficacy and persistence of results at 1-year follow-up. A case report of adult lead toxicity following use of Ayurvedic herbal medication. Acute lead poisoning with hemolysis and liver toxicity after ingestion of red lead. Acute lead poisoning in nursing home and psychiatric patients from the ingestion of lead-based ceramic glazes. Effect of ascorbic acid and thiamine supplementation at different concentrations on lead toxicity in liver. Garlic oil and vitamin E prevent the adverse effects of lead acetate and ethanol separately as well as in combination in the drinking water of rats. Comparison of therapeutic effects of garlic and d-penicillamine in patients with chronic occupational lead poisoning. Environmental Health Department, Ministry of the Environment, Minimata Disease: the History and Measures, Ministry of the Environment, Government of Japan, Tokyo, Japan, 2002. The Ayurvedic Formulary of India, Part-1, Edn-1, Ministry of Health and Family Planning, Government of India. Ancestry of pink disease (infantile acrodynia) identified as a risk factor for autism spectrum disorders. Detection of mercury and other undetermined materials in skin biopsies of endemic pemphigus foliaceus. Chronic methyl mercury poisoning may trigger endemic pemphigus foliaceus "fogoselvagem. Subclinical neurotoxicity of mercury: A behavioural, molecular mechanisms and therapeutic perspective. The generalized pustular form can manifest as a dermatological emergency and is associated with life-threatening complications. The peak age of incidence is about 40­59 years of age with women outnumbering men in the ratio of 2:1. The proposed mechanism is the bacterial superantigen, which triggers the T-cell-mediated autoimmune reaction resulting in the development of pustular psoriasis. Acute generalized pustular psoriasis (von Zumbusch) There are two main groups of patients. Acute pustulation is associated with pain and is generally accompanied by fever, malaise, and anorexia. Erythema and pustulation can involve flexural areas of the body, the genital region, and web spaces of fingers. There can be involvement of mucous membranes in the form of geographic tongue, redness, scaling of lips, and ulceration of tongue and mouth. Systemic complications like hepatitis, pulmonary and renal dysfunction, and sepsis in addition to arthritis can also occur. Impetigo herpetiformis Described by Hebra in 1872, the disease generally has its onset in the last trimester in pregnancy or the first week of puerperium. The rash is generally flexural in onset, with minute pustules arising symmetrically in acutely inflamed skin. Further progression leads to grouping of pustules extending centrifugally with drying in the center and either healing with reddish-brown pigmentation or progressing into widespread plaques. Hypocalcemia, or recurrence of any of the aforementioned clinical and histologic findings Source: Umezawa Y et al. Potential triggers for the development of pustular psoriasis of pregnancy include increased progesterone in the last trimester of pregnancy, hypocalcemia, and reduced elafin levels. Other associations are hormonal contraception, stress, seasonal variation, bacterial infections, and certain medications. The disease is characterized by severe systemic symptoms; death may occur due to cardiac or renal failure. The fetus can also be affected due to risk of placental insufficiency leading to stillbirth, premature rupture of membrane, preterm labor, intrauterine growth retardation, and neonatal death or fetal abnormalities. Recurrence has been described in up to nine pregnancies, and on subsequent use of oral contraceptives. Infantile and juvenile generalized pustular psoriasis Pustular psoriasis is rare in this age group, accounting for 1% of severe psoriasis cases. The majority have a past history of seborrheic dermatitis, napkin dermatitis, or sudden-onset napkin psoriasis is obtained. They may manifest as long-standing localized pustular psoriasis of the neck or evolve into more serious forms with constitutional symptoms as in the form of von Zumbusch pattern, but annular and circinate forms are more common in this age group. In such conditions it is always prudent to carry out a biopsy, where the presence of intraepidermal spongiform pustules virtually rules out other possibilities. The treatment is usually governed by the extent of involvement and severity of disease with acitretin, cyclosporine, methotrexate, and infliximab remaining as first lines of therapy. Patients who have systemic symptoms of fever, chills, dyspnea, altered sensorium, and elderly patients with comorbidities such as cardiac, renal, endocrine, and immunodeficient problems will need immediate hospitalization. Systemic glucocorticoid withdrawal is a commonly cited contributor, and maintaining the glucocorticoid dose until disease control is achieved with other therapies and then tapering the systemic glucocorticoid with continuation of alternate therapy are advised. Use of moisturizers, wet wraps, and/or oatmeal baths can be beneficial in patients with this disease. Manage extracutaneous complications Extracutaneous complications such as sepsis or internal organ dysfunction, acute respiratory distress syndrome, hepatic and renal failure, and cholestasis should be actively managed. Patient should be adequately managed with appropriate antibiotics, electrolytes, and hydration. When added with cyclosporine, it enhances the efficacy and rapidity of onset of action. At such high doses, patients may develop serious side effects of pseudotumor cerebri and acute hypertriglyceridemia causing pancreatitis. There are minor, reversible, dose-dependent side effects including hair loss, periungual fibroma, xerosis, cheilitis, dry mucous membranes, hypertriglyceridemia, hair loss, liver function test abnormalities, bone changes, and visual changes which usually resolve when the dose of acitretin is reduced. It takes about Generalized pustular psoriasis 467 2 weeks to produce significant effect and is usually given in the dose of 15 mg/week to a maximum of 25 mg/week.

Diseases

• Antinolo Nieto Borrego syndrome
• Diaphragmatic defect limb deficiency skull defect
• Pulmonary veno-occlusive disease
• Macular degeneration
• Intestinal pseudoobstruction chronic idiopathic
• B-cell lymphomas
• Craniosynostosis Maroteaux Fonfria type
• Congenital mumps
• Landau Kleffner syndrome
• Meckel like syndrome

The World Health Organization expects the number of new cases to rise by 70% over the next two decades erectile dysfunction daily pill 20 mg erectafil buy fast delivery. Tobacco use is the most important causal agent for cancer worldwide and is estimated to cause 22% of all cancer deaths erectile dysfunction from diabetes treatment for buy erectafil 20 mg otc. The global incidence of lung cancer is approximately 13 per 100 natural erectile dysfunction treatment remedies buy erectafil online now,000 females per year and 31 per 100 intracorporeal injections erectile dysfunction discount 20 mg erectafil amex,000 males per year erectile dysfunction keywords buy erectafil 20 mg on-line. The incidence is four to five times higher in developed than in developing countries, with the highest incidence in Hungary, Serbia, Poland, and Korea. As smoking rates increase in developing countries such as India and China, experts expect rates of lung cancer to increase. While most patients will have a history of tobacco use, many will not report symptoms of lung cancer until they have advanced disease. Establish a history of persistent cough, chest pain, dyspnea, weight loss, or hemoptysis. Ask if the patient has experienced a change in normal respiratory patterns or hoarseness. Some patients initially report pneumonia, bronchitis, epigastric pain, symptoms of brain metastasis, arm or shoulder pain, or swelling of the upper body. Ask if the sputum has changed color, especially to a bloody, rusty, or purulent hue. Obtain a smoking history with the type of tobacco use and the quantity and frequency of use. Elicit a history of exposure to risk factors by determining if the patient has been exposed to industrial or air pollutants. The clinical manifestations of lung cancer depend on the type and location of the tumor. Because the early stages of this disease usually produce no symptoms, it is most often diagnosed when the disease is at an advanced stage. In 10% to 20% of patients, lung cancer is diagnosed without any symptoms, usually from an abnormal finding on a routine chest x-ray. Approximately 25% have regional metastasis and 55% have distant metastasis with symptoms that reflect the organ affected (brain, spinal cord, bone, liver). Note rapid, shallow breathing and signs of an airway obstruction, such as extreme shortness of breath, the use of accessory muscles, abnormal retractions, and stridor. Typically, pleural effusion causes dullness on percussion and breath sounds that are decreased below the effusion and increased above it. Monitor the patient for oxygenation problems, such as increased heart rate, decreased blood pressure, or an increased duskiness of the oral mucous membranes. Metastases to the mediastinal lymph nodes may involve the laryngeal nerve and may lead to hoarseness and vocal cord paralysis. The superior vena cava may become occluded with enlarged lymph nodes and cause superior vena cava syndrome; note edema of the face, neck, upper extremities, and thorax. The patient undergoes major lifestyle changes as a result of the physical side effects of cancer and its treatment. The patient is faced with a psychological adjustment to the diagnosis of a chronic illness that frequently results in death. Unless the tumor is small without metastasis or nodes when discovered, it is often not curable. Surgical treatment ranges from segmentectomy or wedge resection (removal of a part of a lobe) to lobectomy (removal of a section of the lung) to pneumonectomy (removal of an entire lung). These procedures all require general anesthesia and a thoracotomy (surgical incision in the chest). Video-assisted thoracoscopic surgery is a minimally invasive procedure used for both diagnosis and treatment. It involves a shorter hospital stay, less pain, and a lower perioperative mortality. Outcome measures along with recurrence rates are currently being followed and compared with those from more invasive procedures. If patients are unable to undergo a thoracotomy because of other serious medical problems or widespread cancer, laser surgery 716 Lung Cancer may be performed to relieve blocked airways and diminish the threat of pneumonia or shortness of breath. Radiation therapy is sometimes the primary treatment for lung cancer, particularly in patients who are unable to undergo surgery. In conjunction with surgery, radiation is sometimes used to kill deposits of cancer that are too small to be seen and thus to be surgically removed. Radiation therapy takes two forms: External beam therapy delivers radiation from outside the body and focuses on the cancer and is most frequently used to treat a primary lung cancer or its metastases to other organs; brachytherapy uses a small pellet of radioactive material that is placed directly into the cancer or into the nearby airway. Teach the patient to use guided imagery, diversional activities, and relaxation techniques. Discuss the expected preoperative and postoperative procedures with patients who are undergoing surgical intervention. Monitor closely the patency of the chest tubes and the amount of chest tube drainage. Notify the physician if the chest tube drainage is greater than 200 mL/hour for more than 2 to 3 hours, which may indicate a postoperative hemorrhage. Help the patient sit up in the bedside chair and assist the patient to ambulate as soon as possible. Secretions may become thick and difficult to expectorate when the patient is having radiation therapy. Percussion, postural drainage, and vibration can be used to aid in clearing secretions. The patient may experience less anxiety if allowed as much control as possible over his or her daily schedule. Explaining procedures and keeping the patient informed about the treatment Lung Cancer 717 plan and condition may also decrease anxiety. Allow for the time needed to adjust while helping the patient and family begin the grieving process. Patients were diagnosed with the following cancers: bladder, brain, breast, colon/rectum, head/neck, liver, kidney, lung, ovary, pancreas, and prostate as well as leukemia and lymphoma. The authors suggest that the answer to the single question can determine the overall burden of a given set of treatments. Provide the patient with the names, addresses, and phone numbers of support groups, such as the American Cancer Society, the National Cancer Institute, the local hospice, the Lung Cancer Alliance, and the Visiting Nurses Association. The course of disease is variable and unpredictable, with episodes of remission and relapse. These complexes are deposited in the basement membranes of the skin and kidneys, disrupting the function of these organs. The most common causes of death are renal failure and infections, followed by neurological and cardiovascular disorders. In the last decades, therapy has reduced mortality from lupus, with 5-year survival rates of more than 90% and 20-year survival rates of 70%. A familial association has been noted that suggests a genetic predisposition, but a genetic link has not been identified. Environmental factors, susceptibility to certain viruses, and an immune system dysfunction with production of autoantibodies are possible causes. Some drugs have been implicated as initiating the onset of lupus-like symptoms and aggravating existing disease; they include hydralazine hydrochloride, procainamide hydrochloride, penicillin, isonicotinic acid hydrazide, chlorpromazine, phenytoin, and quinidine. Possible childhood risk factors include low birth weight, preterm birth, and exposure to farming pesticides. Heritability is estimated at 43%, and there Lupus Erythematosus 719 are now over 80 loci that are associated with lupus erythematosus. Genes encoding proteins of the complement system appear to have the strongest association with lupus erythematosus. It is also more prominent in people with Asian, Latino/Hispanic, and African American ancestry than in other populations. Prevalence is higher in white people living in Western Europe and in people from the Caribbean living in Europe, and it is lower in Africa and China. The patient may report musculoskeletal and cutaneous symptoms, including joint and muscle pain, puffiness of hands and feet, joint swelling and tenderness, hand deformities, and skin lesions such as the characteristic "butterfly rash" (fixed reddish and flat rash that extends over both cheeks and the bridge of the nose). Other symptoms may include maculopapular rash (small, colored area with raised red pimples), sensitivity to the sun, photophobia, vascular skin lesions, leg ulcers, oral ulcers, and hair loss. Other symptoms originate in the genitourinary tract (menstrual abnormalities, amenorrhea, spontaneous abortion) or central nervous system (visual problems, memory loss, mild confusion, headache, seizures, psychoses, loss of balance, depression). Establish a history of symptoms related to the hematologic system (venous or arterial clotting, bleeding tendencies), cardiopulmonary system (chest pain, shortness of breath, lung congestion), or gastrointestinal system (nausea, vomiting, difficulty swallowing, diarrhea, and bloody stools). Ask if the patient has a history of hormonal abnormality or ultraviolet radiation. Ask the patient if he or she is taking or has taken any of the medications implicated as initiating lupus-like symptoms. Inspect the integumentary system thoroughly, including the mucous membranes, to determine the site of skin rashes and lesions. Check for lesions and necrosis on the fingertips, toes, and elbows; these may be caused by inflammation of terminal arterioles. Determine the extent of range of motion and movement of extremities and level of joint discomfort. Auscultate the lungs and heart to determine the presence of a pleural or pericardial friction rub. Palpate the spleen and liver to determine the presence of tenderness, splenomegaly, or hepatomegaly. Assess for fever, pallor, and signs of bleeding, including petechiae and bruising. The patient may have problems maintaining professional and family roles and may experience loss over a deteriorating health status. Lupus is associated with an increased incidence of spontaneous abortion, fetal death, and prematurity. To make the diagnosis of lupus, the American College of Rheumatology developed the following list. General supportive therapy includes adequate sleep and avoidance of fatigue because mild disease exacerbations may subside after several days of bedrest. A physical therapy program is important to maintain mobility and range of motion without allowing the patient to get overtired. Encourage the patient to maintain activity when the symptoms are mild or in remission. Encourage the patient to use a hair stylist or barber who specializes in caring for people with scalp disorders and to protect all body surfaces from direct sunlight. The patient should use sunscreen with a protective factor of at least 20 and wear a hat and long sleeves while in the sun. Note that certain drugs (tetracycline) and foods (figs, parsley, celery) augment the effects of ultraviolet light and therefore should be avoided. Explore the meaning of the chronic illness and coping strategies with the patient. A total of 2,527 surveys were returned; 94% of the surveys were returned by females. The most common self-reported symptoms that interfered with daily life were fatigue/weakness (91%) and joint/pain swelling (77. Seventythree per cent acknowledged having problems from their symptoms as they carried out their usual daily activities. Thirty-two per cent of the respondents were using non-traditional therapies such as acupuncture and massage to manage their symptoms. Explain to the patient the disease process, the purpose of treatment regimens, and the importance of compliance. Teach the patient to wear a Medic Alert bracelet noting the disease and medications so appropriate action can be taken in an emergency. Encourage the patient to keep all vaccinations current such as the meningococcal vaccine, pneumococcal vaccine, and routine flu vaccines. Teach the female patient the importance of planning pregnancies with medical supervision because pregnancy is likely to cause an exacerbation of the disease. Discuss all precipitating factors that need to be avoided, including fatigue, vaccination, infections, stress, surgery, certain drugs, and exposure to ultraviolet light. Encourage the patient to contact the Arthritis Foundation, the Lupus Foundation, and other appropriate support groups that are available in the area. This disease is named for the town in Connecticut where it was first recognized in the 1970s. Although the number of cases vary from L Lyme Disease 723 year to year, approximately 30,000 cases are reported annually in the United States, making it the leading tick-borne disease in the country. Lyme disease typically begins in summer or early fall and develops in three stages with varying, progressive symptoms over weeks and months if untreated. The most frequent carrier of the disease is the deer tick, a small insect the size of a poppy seed. The deer tick is predominantly found in the New England and mid-Atlantic states, Wisconsin, Minnesota, and northern California, although cases of Lyme disease have been documented in 48 states. Incubation lasts 7 to 10 days, but diagnosis generally must wait for 4 to 6 weeks after the patient is bitten by a tick in order to make laboratory tests reliable. Complications include pericarditis and myocarditis, cardiac dysrhythmias, encephalitis, peripheral neuropathies, and arthritis. This organism can be transmitted through the saliva of the tick while it is ingesting blood from a host.

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Treatment Avoiding stress impotence and age 20 mg erectafil visa, both psychological and physical erectile dysfunction protocol scam or not 20 mg erectafil order with visa, as well as substances such as alcohol erectile dysfunction kit buy 20 mg erectafil with visa, spicy foods erectile dysfunction caused by obesity buy discount erectafil 20 mg online, and medications that precipitate a flushing reaction might be sufficient in early cases erectile dysfunction after age 40 erectafil 20 mg buy lowest price. Medical treatment with somatostatin analogues (octreotide and lanreotide) has proven extremely efficacious for symptomatic relief. Because most tumors in patients with the carcinoid syndrome are malignant at the time of clinical presentation, surgical cure is seldom obtained. Resection of local disease or regional nodular metastatic disease can cure some patients. However, even if radical surgery cannot be performed, debulking procedures and bypass should always be considered [23]. Awareness of these cutaneous signs may result in early diagnosis and prompt management that, at times, can even be lifesaving. Neuroendocrine gastrointestinal and lung tumors (carcinoid tumors), the carcinoid syndrome and related disorders. Numerous chemicals have the potential to cause harm to human beings, such as natural gases (as in the gas leak in China in 2003 that killed many) and toxic gases (release of carbon monoxide, hydrogen sulfide, and methylisocyanate in Bhopal in 1984 that caused many deaths), and methanol. However, only a few important chemicals are discussed in this chapter with particular attention to the dermatological effects of such poisoning. Source Arsenic exposure in humans may be through inhalation, ingestion, or absorption via skin. The discovery that arsenic exposure can occur through food and crops grown in fields with high arsenic content in the groundwater is really worrisome. Other possible sources are pesticides, paints, smelting, semiconductors, and transistors. Arsenic toxicity has been repeatedly reported following use of traditional ayurvedic and homeopathic medicines. Moreover, the concentration of arsenic in these products is much above the level found in groundwater. In the present era, it has proved to be the prime cause of one of the deadliest disasters mankind has ever witnessed, killing millions of people through drinking the (ground) water and possibly many other foods grown in the fields with contaminated water. Arsenic is a heavy metal that is widely spread in nature in its various environmental sources, such as soil and water. Arsenic is a colorless, odorless, tasteless agent that makes it a suitable choice for a poison that is easily incorporated with food or drink [1­3]. A significant population of the world, especially the Asian countries such as Bangladesh, India, and China [4], are battling the deleterious effects of arsenic from groundwater contamination, in the form of various respiratory, hepatobiliary, neurological, and vascular system abnormalities along with characteristic cutaneous features that are possibly mediated via the damage caused to epidermal stem cells [5]. Pathogenesis Arsenic has the ability to bind various molecular side chains of different enzymes required for normal physiological function. The trivalent form of arsenic (As3+) binds to the sulfhydryl group of keratin present in skin, hair, nail, and mucosae, and thus it gets deposited in these sites. Arsenic induces premalignant and malignant dermatological lesions, nondermatological health effects, and cancers in humans through various known and unknown complex mechanisms [6­9]. The lethal doses of acute ingested inorganic arsenic compounds 451 452 Skin manifestations of poisoning range from 120 to 200 mg, but toxicity can appear with a dose range of 5­50 mg [10]. Gastrointestinal, cardiovascular, neurological, and renal systems are principally affected in acute poisoning. Death from arsenic is generally caused by circulatory collapse associated with intense gastroenteritis. Other manifestations are hemoglobinuria, disseminated intravascular coagulation, pulmonary edema, cardiomyopathy, encephalopathy, and renal failure. Arsenic also causes peripheral neuropathy that may present as ascending weakness like that of Guillain-Barré syndrome. Diagnosis Complete blood count done in such cases may show microcytic hypochromic anemia and at times, acute hemolytic anemia. A 24-hour urine collection for total arsenic excretion can be diagnostic, and a level >50 mcg is suggestive of high arsenic exposure. Consumption of seafood within the last 3 days and high presence of organic arsenic from nutritional sources can give false positivity. Chelation therapy should be started as early as possible to get the desired effects. Follow-up may be required for months after acute poisoning, as peripheral neuropathy can occur as a long-term sequelae. These may range from pigmentary changes of various types and hyperkeratosis to cutaneous malignancy [5,13­17]. Hyperkeratosis may be graded as mild where there are minute wart-like papules (<2 mm), moderate form with raised wart-like thickening (2­5 mm), and severe with large (>5 mm) discrete or confluent elevations and even fissuring. Arsenical keratosis is more marked in areas subjected Chronic arsenicosis 453 to trauma and friction. Apart from the classical keratotic papules, diffuse palmoplantar thickening and fissuring may sometimes be seen. Histopathological examination of the liver mostly shows noncirrhotic portal fibrosis [26]. Clinically it presents as coldness of extremities (usually in the feet), decreased peripheral pulses, pain, and intermittent claudication, progressing to gangrene and spontaneous amputation [28]. Underlying histopathology often shows arteriosclerosis obliterans and thromboangiitis obliterans, particularly affecting small vessels [29]. Other than peripheral vascular disease hypertension [30], ischemic heart disease can also occur [31]. Peripheral neuropathy (sensory > motor) manifesting as paresthesias, pain, weakness, and atrophy of the affected limb further impairs the quality of life of patients with chronic arsenic toxicity [5,32]. Arsenic exposure during pregnancy is associated with adverse pregnancy outcomes such as spontaneous abortions, stillbirths, and preterm births [5]. Measurement of 24-hour urinary arsenic level can be a good indicator of recent arsenic exposure as it is principally excreted via the kidneys [34,35]. Arsenic has a very short half-life in blood, so blood arsenic level is not of much help in chronic poisoning. In some cases there may be basal cell pigmentation, dysplasia, and malignant changes [37]. Cutaneous lesions Hyperkeratosis of the palm and sole can be treated by local application of 5%­10% salicylic acid and 10%­20% urea-based ointment and emollients. Retinoids are suitable choices for severe arsenical keratosis which has malignant potential [39,40]. More serious problems such as portal hypertension may require sclerotherapy or banding. Distressing peripheral neuropathy is often difficult to manage, but a tricyclic antidepressant can be helpful in some. Peripheral vascular disease eventually ends up in gangrene requiring amputation, but pentoxifylline and calcium channel blockers can be tried with some benefit in the initial stage. The method for removing arsenic content from water and making it operational at mass level are yet to be developed, so finding an arsenic-free water source would be of primary concern. Severe toxicity may progress to decreased blood pressure, depressed respiration, convulsions, and shock [47], although these corrosive effects are likely to be due to the nitrate in the compound rather than to the silver itself [47]. Organic silver compounds, such as colloidal silver, are less toxic but may have effects like pleural edema, hemolysis, and coma if consumed in large doses [49]. This prompts the use of agents such as vitamin C, vitamin E [44], polyphenols, and extracts of green and black tea [45] as antioxidants in ameliorating the symptoms of arsenic toxicity. Chronic toxicity Long-term exposure to silver and its compounds results in a distinctive condition known as argyria. Generalized argyria is a manifestation of long-term systemic absorption of silver affecting the skin, eyes, mucosa, nails, and internal organs such as the spleen and liver. There is a typical blue-gray pigmentation with a bit of a shiny tinge with accentuation over the sun-exposed site. The pigmentation appears gradually over years and is often mistaken by the patient as tanning in the beginning. After absorption, silver binds to tissue proteins and is converted to metallic silver in the presence of light, which then further oxidizes to form silver sulfide and silver selenide, which are responsible for the blackish discoloration. Source Exposure to silver can occur through ingestion or inhalation or by direct impregnation into the skin. Exposure may be localized through direct skin contact, or it may be generalized by inhalation of fumes containing silver particles. The main limiting factor is the possibility of acute catastrophic side effects of pancytopenia, fulminant hepatitis, and pneumonitis [5]. Due to this drawback, a test dose of methotrexate for 1 week delays adequate treatment favoring cyclosporine, acitretin, and infliximab as first-line treatment. It is mandatory to use the drug in its maximum dermatological dose of 5 mg/kg/day in two to three divided doses. The onset of action is fairly rapid, as early as 2 weeks, with subsequent tapering of 0. It is mandatory not to discontinue or decrease the dose of cyclosporine prematurely as intense inflammation has momentum. Few studies have suggested that if the patient is not controlled with 5 mg/kg/day, the dosage can be increased, which carries the advantage of suppressing the ongoing inflammation and reducing sepsis. Whenever cyclosporine is used in higher doses it is mandatory for the patient to be well hydrated to prevent renal hypoperfusion. Potential adverse effects of cyclosporine include hypertension, renal toxicity, and increased risk for infections and malignancy. Laboratory tests as well as blood pressure should be monitored closely during therapy. The fast onset of infliximab has been evident in the time required to achieve clearance of pustules; pustules cleared in a median of 2 days (range 1­8 days). Alternatively, the patient can be put on other first-line therapies once the acute disease is controlled. Potential adverse effects of infliximab include infusion reactions and increased risk for infection, malignancy, heart failure, and demyelinating disease. In addition, there is concern for the serious side effects from long-term glucocorticoid therapy. In addition, the onset or worsening of pustular psoriasis following ustekinumab treatment has been reported. Evidence suggests application of topical triamcinolone ointment with application of wet wraps, other topical steroids, topical calcipotriene, and tacrolimus, and some benefit does occur [7]. In children, it might be combined with prednisolone to have faster control during the acute phase. Cyclosporin is relatively safe in children as compared to other modalities in the dose of 1­3 mg/ kg/day, and they may show improvement after 2­4 weeks. Given the contraindication for pregnancy during acitretin treatment and for 3 years after drug discontinuation, its use in girls must be considered carefully. In addition, topical compresses, wet wraps, or oatmeal baths may be helpful for soothing the skin lesions. Topical therapy for annular pustular psoriasis is less practical when a large proportion of the body surface is affected. Patients who cannot be managed only with topical therapy can be treated with systemic agents. Therefore, the recommendations for childhood psoriasis are almost similar to those for adults. First-line therapy in pregnancy consists of cyclosporine, infliximab, and oral corticosteroids [10]. Despite cyclosporine being a category C drug, no birth defects have been documented, and it can be safely used in pregnancy [11]. Biological agents are category B drugs and are therefore safer to use in pregnancy. Infliximab should be preferentially considered, being a safer and faster-acting alternative. Oral prednisolone in a dose of 30­40 mg per day has shown efficacy, especially when combined with cyclosporine. In pregnancy and hepatic dysfunction, generally acitretin and methotrexate are contraindicated, while in patients with renal dysfunction and hypertension, cyclosporin is generally contraindicated. In some series, the resolution of fever and pustulation occured within 24­72 hours [13]. Concomitant use of methotrexate is advocated to decrease the formation of anti-infliximab antibodies. Various case reports and series suggest the successful use of etanercept, ustekinumab, adalimumab, and anakinra in psoriasis. The newer biologicals including inhibitors of the Th17 pathway show a promising role in pustular psoriasis and include drugs like secukinumab and ixekizumab. Secukinumab (150 mg once weekly at baseline; weeks 1, 2, 3, and 4; and then every 4 weeks, with the option to increase the dose to 300 mg in patients who showed minimal or no improvement) has shown good response rates at week 16. Tofacitinib is a newer Janus kinase inhibitor given in the dosage of 5 mg twice a day or 10 mg once a day; it has been shown to be effective in chronic plaque psoriasis and is currently under trial for pustular psoriasis. Secukinumab: 150 mg once weekly at baseline; weeks 1, 2, 3, and 4; and then every 4 weeks 5. Ixekizumab: 160 mg at week 0, 80 mg at weeks 2, 4, 6, 8, 10, 12 followed by 80 mg every 4 weeks 6. Generalized pustular psoriasis of von Zumbusch is characterized by sudden onset of generalized pustules which can expand and coalesce to form lakes of pus. Cyclosporine and infliximab are drugs of choice in severe cute cases while methotrexate and acitretin are good drugs for the less severe subacute cases. Clinical profile, morbidity, and outcome of adult onset generalized pustular psoriasis: Analysis of 35 cases seen in a tertiary hospital in Johor, Malaysia. Treatment of pustular psoriasis: From the Medical Board of the National Psoriasis Foundation. National Transplant Pregnancy Registry- Outcome of 154 pregnancies in cyclosporine treated female kidney transplant recipients. Long term management of generalized pustular psoriasis with infliximab: Case series.

Mockeel Root (Water Hemlock). Erectafil.

• How does Water Hemlock work?
• What is Water Hemlock?
• Migraine headaches, painful menstrual periods, skin inflammation, and worm infestations.
• Dosing considerations for Water Hemlock.
• Are there safety concerns?
• Are there any interactions with medications?

Source: http://www.rxlist.com/script/main/art.asp?articlekey=96911

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