MANAGEMENT AND THERAPEUTICS OF NICOTINE ADDICTION

Ideally, therapeutics for nicotine addiction should be available for the 80% of the world’s smokers who live in low- and middle-income countries. Within those countries, smokers have the lowest income, are the least educated, and have the poorest access to health care.
Thus, from a world view, cost of therapeutics and access become important considerations. Prevention is obviously an important strategy, but strategies to prevent tobacco addiction must deal with a politically powerful and wealthy multinational industry promoting use of tobacco . The tobacco industry in the United States alone spent 6 billion dollars in 1998 to market cigarettes, about 18 million dollars each day. More is spent promoting tobacco use elsewhere in the world. Although successful prevention strategies exist, well-funded competition encouraging tobacco use will remain .

More intensive therapeutics typically include behavioral interventions combined with NRT delivered over a series of sessions. Individual or group behavioral treatments appear almost equally effective. Intensive treatment programs are effective in assisting even very dependent smokers to stop for a few months. However, as with other addictions, relapse is a major problem. Initial quitting rates of 50% to 60% at 1 month typically decrease to 20% to 30% at 1 year. Various relapse-prevention procedures have been tried. None has proven clearly effective. Most tobacco addicts repeat the quitting process on average every 3.5 years and try three or four times before finally stopping forever (66). In that respect, stopping smoking is similar to overcoming addictions to other psychoactive drugs. Tobacco addiction treatment programs are cost-effective. Average treatment costs per year of life saved are $1,000 to $2,000 per year for brief counseling alone and $2,000 to $4,000 per year of life saved with more intensive counseling and pharmacotherapy to aid in smoking cessation. Smoking cessation treatments are less costly per year of life saved than are enerally accepted therapies for hypertension, hypercholesterolemia, and other chronic disorders.

Therapeutics: Clinical Guidelines

Guidelines for treating tobacco dependence were published in 2000 by the United States Public Health Service. The detailed report resulted from critical review of approximately 6,000 peer-reviewed articles on tobacco addiction therapeutics and 50 metaanalyses based on that literature.

The major general conclusions were as follows:

1. Tobacco dependence is a chronic condition warranting repeated treatment until bstinence is achieved.

2. Effective treatments for tobacco dependence exist. All tobacco users should be offered treatment.

3. Clinicians and health care systems must institutionalize consistent identification, documentation, and treatment

of every tobacco user at every visit.

4. Brief tobacco dependence treatment is effective. Every tobacco user should be offered at least brief treatment.

5. There is a strong relationship between the intensity of tobacco dependence counseling and effectiveness.

6. Three types of counseling are especially effective: practical counseling, social support as a part of treatment, and social support outside of treatment.

7. Five pharmacotherapies for tobacco dependence are effective: nicotine gum, nicotine inhaler, nicotine nasal spray, nicotine patch, and bupropion. At least one of these medications should be prescribed in the absence of contraindications.

8. Tobacco dependence treatments are cost-effective when compared with other medical and disease prevention interventions. Health insurance plans should include as a

benefit the counseling and pharmacotherapies identified as effective in the guideline.

Contemporaneous reviews of tobacco addiction therapeutics and an extensive report on tobacco addiction pharmacology and therapeutics from the Royal College of Physicians offered similar conclusions. A summary review from the Cochrane Tobacco Addiction Review Group identified and summarized evidence of efficacy for tobacco addiction therapeutics. Details of the 20 systematic reviews are available on the Internet in the Cochrane Library. The reviews used a similar strategy and reviewed much the same literature on tobacco addiction therapeutics as did the Public Health Service review. The Cochrane reviews considered the results from randomized controlled trials having at least 6 months of followup. Sustained abstinence or point prevalence quit rates were used in the metaanalysis as necessary. Simple advice from physicians presented during routine care was studied in 31 trials that included 26,000 smokers in a variety of clinical settings. Brief advice increased quit rate more than no advice (odds ratio, 1.69; 95% confidence interval, 1.5 to 1.98). Individual counseling was better than brief advice or usual care. Group therapy was more effective than selfhelp materials alone but not consistently better than interventions with more personal contact. Self-help informational material and printed descriptions of behavioral strategies had a small treatment effect.

Nicotine Replacement Therapeutics

NRT decreases the discomfort of nicotine withdrawal. The relatively stable brain nicotine levels resulting from NRT should facilitate a desensitized state for some nicotinic cholinergic receptors. Because some nicotinic receptor subtypes are more desensitized than others, both nicotine agonistic and desensitization mechanisms could operate together in NRT. In a nicotine-induced desensitized state, norepinephrine release normally stimulated by endogenous acetylcholine would be diminished. Other neurotransmitter release normally stimulated by endogenous acetylcholine could be diminished as well. The resulting NRT modulation of mood states in itself could be rewarding. In addition, some blunting of the reinforcing effects of cigarettes smoked during cessation lapses is likely during NRT. However, the mechanisms of NRT still remain uncertain because the intensity of withdrawal alone is not a good predictor of success for ultimately stopping smoking. Even though withdrawal symptoms can be diminished by NRT, other mechanisms, learning coping skills, and replacing some of the positive effects of nicotine are important as well. Whatever the mechanisms, NRT is clearly effective and safe for helping smokers to quit. The ochrane review of clinical trials with nicotine gum, transdermal nicotine patches, nasal spray, and inhalers concluded that NRT enhanced early cessation and reduced early relapse when compared with placebo. All products enhanced quitting smoking about twofold. Quitting rates, depending on intensity of concurrent behavioral interventions, ranged from 10% to 30% of patients with a 1-year follow-up. Higher nicotine doses were more effective, although the dose–response function is shallow. NRT did not appear to have significant dependence potential or to cause significant harm. Characteristics of long-term NRT users resembled those of treatment failures. It appeared many would be smoking or smoking more if NRT were not available. However, 70% to 90% of addicted smokers fail to stop smoking despite NRT. Why? Most studies included only nicotine-addicted smokers, so the usefulness of NRT for less addicted smokers remains uncertain. Although recommendations have been made for use of combinations of NRT products, for example, patch plus spray, patch plus gum, or higher-dose NRT, too few trials preclude clear evidence of effectiveness. Long-term reduction in smoking by concomitant use of NRT while smoking continues is being investigated. Nicotine inhalers and skin patches have been used safely and with sustained reduction in smoking for up to 30 months.

Particularly for highly dependent smokers, nicotine replacement from patches and gum probably delivers nicotine to the brain too gradually and without the transient but rewarding brief surges in brain nicotine levels from puffing on a cigarette. Nicotine nasal sprays or inhalers more closely approximate smoking in this respect, but only partially so, and clinically they do not offer advantages to patch failures. An inhaled nicotine aerosol would, in principle, be an ideal substitute nicotine delivery system, but despite many attempts, a practical inhaled aerosol system providing the control over dose offered by a tobacco cigarette has not been brought to market.

Non–Nicotine Replacement Pharmacotherapies

The consequences of neuroadaptive changes in brain function associated with chronic nicotine exposure should, in principle, be modified by appropriate neurochemical interventions. Pharmacotherapies mimicking nicotine’s neurochemical effects by increasing or modulating brain levels of dopamine, epinephrine, serotonin, and other neurotransmitters should correct the neurochemical deficiency states associated with nicotine withdrawal. Pharmacotherapies may also mimic some of nicotine’s actions on brain reward systems. Nicotinic receptor antagonism offers an additional strategy. Although treatment with anxiolytics did not improve outcome, antidepressants, bupropion, and nortriptyline increased quit rates. The mechanisms by which antidepressant drugs benefit smoking cessation are yet to be determined. The neurochemical consequences of chronic nicotine exposure have similarities to the effects of some antidepressants.

Bupropion

As with many pharmacotherapies, recognition that bupropion could be useful for treating tobacco addiction resulted from serendipitous observations. Smokers being treated with bupropion for depression reported less desire to smoke or greater success in stopping smoking. Bupropion is structurally related to phenethylamines resembling an anorectic drug diethylproprion and is believed to assist smoking cessation by blocking neuronal uptake of dopamine and norepinephrine and possibly by decreasing firing of the locus ceruleus. Bupropion and some other antidepressants functionally antagonize some nicotinic cholinergic receptors in muscle and autonomic ganglia and reduce receptor response to nicotine. Whether antidepressant drugs similarly antagonize brain nicotine receptors is undetermined.Bupropion was effective judging from two large trials and two smaller unpublished ones. Bupropion alone or combined with a nicotine patch was more effective than the patch alone. Although the drug caused dry mouth and insomnia, serious side effects were uncommon. Bupropion was as effective in patients with a history of depression as with those without such a history. When given to a group of smokers not trying to quit permanently, bupropion decreased some withdrawal symptoms but had no effect on craving. Bupropion was a more cost-effective therapeutic agent for tobacco addiction than NRT.

Other Therapies With and Without Utility

Clonidine shares some pharmacologic effects of bupropion and tricyclic antidepressants. The Cochrane review of six clinical trials of clonidine found increased smoking quit rates, but side effects of sedation and postural hypotension posed problems for many patients. Sensory stimulants mimic mouth and airway sensory responses to smoking that become associated with the pharmacologic effects of nicotine and thus become reinforcers. Ascorbic acid aerosols and citric acid inhalers evaluated in cessation trials reduce craving and some withdrawal symptoms over the short term. The effects of opiate antagonists on cigarette smoking have been studied to examine how opioid systems modulate smoking behavior and to determine whether opioid antagonists could be useful to aid in smoking cessation. Naloxone precipitates opiate withdrawal-like symptoms and increases desire to smoke. The effects of naloxone or naltrexone on ad libitum smoking over brief periods in a laboratory were inconsistent, but some smokers smoked less.

A clinical trial compared naltrexone, 50 mg daily for 12 weeks, or placebo, with or without transdermal nicotine. Only transdermal nicotine increased abstinence rates.

Naltrexone had no effect on cessation rates. Transdermal nicotine reduced craving and cigarette smoking in smokers who did not quit. Naltrexone had no such effects. Another 4-week trial of naltrexone or placebo found no difference in smoking 6 months later. Thus, the clinical trial data indicate no useful role for opioid antagonists in smoking cessation therapy despite the suggestive laboratory results.

Nicotinic receptor antagonism offers another possible strategy. A nicotine antagonist mecamylamine has been investigated as a cessation aid both alone and in combination with NRT. Mecamylamine started before quitting smoking and continued afterwards appeared useful in two studies. Combined use of mecamylamine and nicotine patch increased quit rate more than nicotine alone, a finding leading to consideration of mecamylamine blockade of nicotine’s rewarding effects.

Circulating antibodies binding nicotine in blood and preventing its reaching the brain would be functionally equivalent to a receptor antagonist’s preventing nicotine receptor access. Antibodies have been induced by immunization of rats with nicotine linked to an immunogen.

Immunized animals had reduced brain nicotine concentrations and reduced behavioral and cardiovascular effects after intravenous nicotine. Whether immunization alters the reinforcing effects of nicotine remains to be determined. Lobeline, a nonpyridine alkaloid and partial nicotine receptor agonist from the Indian tobacco plant (Lobelia inflata),has long been used in proprietary smoking treatments. Although no longer marketed in the United States, lobeline is available elsewhere. No clinical trials had more than a 6-month follow-up. The drug was judged unproven by the Cochrane review.

ACTH has been suggested to aid smoking cessation, based on the notion that nicotine increases ACTH and cortisol release and that during nicotine withdrawal, there may be a state of hypoadrenocorticism. Uncontrolled trials with small numbers of smokers given a few ACTH injections during the first week after quitting reported high quit rates or decreased smoking, but without controlled clinical trials, ACTH must still be considered unproven.

Silver acetate has long been available as an over-the-counter smoking deterrent in the form of chewing gum, lozenges, and spray. A reaction with cigarette smoke produces an unpleasant metallic taste, the basis for this aversive therapy.

Several clinical trials reported short-term efficacy, particularly in less addicted smokers. Whenever the urge to smoke is great, it is easy to stop silver acetate use, so it does not appear an effective therapeutic for severe nicotine addiction.

The effectiveness of other aversion therapies, acupuncture, hypnotherapy, and exercise was at best considered uncertain.

NICOTINE ADDICTION

Nicotine Addiction
Addiction is defined as a situation in which a drug unreasonably controls behavior. The primary criteria for drug dependence are highly controlled or compulsive use of a drug with psychoactive effects and the presence of drug-reinforced behavior. Additional criteria are stereotypic patterns of use, use despite harmful consequences, relapse following abstinence, and recurrent drug cravings.

What are the symptoms of nicotine addiction?
•    irritability
•    impatience
•    hostility
•    anxiety
•    depressed mood
•    difficulty concentrating
•    restlessness
•    decreased heart rate
•    increased appetite or weight gain

Complications of Nicotine addiction?

Nicotine dependence can affect several parts of your body. Common complications of nicotine dependence are:

•    Lung cancer

•    Dry skin

•    Emphysema

•    Chronic bronchitis

•    Increased risk of heart disease.

•    Esophageal cancer

•    Larynx cancer

•    Throat cancer

•    Oral cancer

•    Infertility

•    Pregnancy and newborn complications

•    Dull senses

Dependence-producing drugs often produce “tolerance,” physical dependence, and pleasant effects. Smoking fits these definitions of an addictive behavior.  Approximately 40 percent of smokers attempt to quit annually, yet less than 5 percent do. Most smoking cessation tempts fail within the first two weeks; on average, four or more attempts are necessary before long-term cessation is achieved.

Even in patients with cardiovascular disease, cancer, or chronic obstructive pulmonary disease where stopping smoking is critical to halt further deterioration of their medical condition, fewer than 50 percent quit.

The agent largely responsible for maintaining smoking addiction is nicotine. Animal models demonstrate nicotine’s addictive potential, and several lines of evidence suggest that nicotine is addictive in humans as well. In addition to the difficulty in quitting, research shows that smokers adjust their smoking habits to maintain relatively stable concentrations of nicotine, that the reinforcing effects of nicotine are blocked by pretreatment with the nicotine receptor antagonist mecamylamine, and that quitting smoking is associated with cravings and a characteristic withdrawal syndrome. Nicotine’s neurobiological effects are complex and not entirely understood. Nicotine binds to nicotinic acetylcholine receptors located in the brain, autonomic ganglia, and neuromuscular junctions.

Such binding leads to the release of a number of neurotransmitters and hormones including dopamine, serotonin, norepinephrine, acetylcholine, vasopressin, and beta-endorphin. The release of these substances modulates many of the subjective, cognitive, and behavioral effects associated with smoking, such as increase in pleasure, improved mood, increased attention, enhanced cognition and motor performance, and weight loss.

Chronic use of nicotine results in the development of “tolerance,” which decreases the effect of a given dose of the drug. Tolerance is the result of morphological changes in the brain, such as receptor desensitization and inactivation as well as upregulation of receptor number. As a result of this neuroadaptation, cessation of tobacco use results in a withdrawal syndrome, characterized by depressed mood, insomnia, irritability, frustration or anger, anxiety, difficulty concentrating, restlessness, decreased heart rate, and increased appetite or weight gain. These symptoms generally peak at one week and gradually decrease over time, sometimes eventually reaching lower levels than were experienced while smoking. Thus, nicotine addiction is maintained not only by the subjective positive effects that smokers experience, but also by the desire to avoid the negative symptoms associated with nicotine withdrawal.

The potential for abuse or addiction to a drug is generally determined by the magnitude of the positive reinforcing effects and the speed of drug delivery to the brain. Typically, the relationship between drug dose and the reinforcing effect of the drug is characterized by an inverted U-shaped curve. Administration of an addictive drug will increase until its toxicity reduces the overall desirable effects and therefore decreases its reinforcing effects.

Generally, the more quickly the drug is delivered to the brain, the greater the potential for abuse. Nicotine from a smoked cigarette reaches the brain in ten to twenty seconds, with initial arterial nicotine concentrations far surpassing venous concentration.

Such rapid delivery contributes to its high abuse potential. Smokeless tobacco and nicotine gum, which take longer to reach the brain, have somewhat less abuse potential, and the nicotine patch, which is very slowly absorbed, has minimal abuse potential

Current and future pharmacological treatments aim to reduce tobacco use by targeting the mechanisms that reinforce tobacco use. Some treatments use agents that mimic the reinforcing effect of nicotine or reduce the negative effects (such as craving or withdrawal symptoms) associated with abstinence. Strategies being considered for future therapies include using agents that block the reinforcing effects of nicotine, prevent nicotine from crossing the blood brain barrier, and alter the metabolism of nicotine.

References

1. http://www.americanheart.org/presenter.jhtml?identifier=4753

2. http://www.mamashealth.com/substance/nicotine.asp

RABIES

DEFINITION: 

An acute infectious disease of warm-blooded animals characterized by involvement of the nervous system resulting in death.

ETIOLOGY

It is caused by the RABIES VIRUS, a rhabdovirus of the genus lyssavirus. RHABDOVIRUS: any group of rod-shaped RNA viruses with 1 important member, rabies virus, pathogenic to man. The virus has a predilection for tissue of mucus-secreting glands and the Central Nervous System. All warm-blooded animals are susceptible to infection with these viruses. LYSSAVIRUS: Greek – frenzy. A genus of the family Rhabdoviridae. There are 2 kinds of rabies. URBAN or CANINE RABIES are transmitted by dogs. SYLVATIC RABIES are transmitted from wild animals and bats which sometimes spread to dogs, cats and livestock.

MODE OF TRANSMISSION: It is commonly communicated to man through the saliva of an infected mammal by an exposure to an open break in the skin such as bites or scratch and inhalation of infectious aerosols such as from bats. In some cases, it is transmitted through organ transplants (corneal transplant), from an infected person.

MEDIA OF TRANSMISSION: Through saliva, tears, urine, serum, liquor and other body fluids.

INCUBATION PERIOD:

The period between the exposure to the virus to the occurrence of the first symptom, is usually 2-8 weeks. It may be as short as 4 days or as long as 2 years depending on depth of laceration and site of wound. The virus moves along nerve axons passively about 3 millimeters per hour. It is not known how the virus remains viable or where it is located during prolonged incubation period.

SUSCEPTIBILITY AND RESISTANCE: All warm-blooded mammals are susceptible. Natural immunity in man is unknown.

DIAGNOSIS:

There is yet no way of immediately segregating those who had acquired rabies infection from those who had been bitten by non-rabid sources. No tests are available to diagnose rabies in humans before the onset of clinical disease. The most reliable test for rabies in patients who have clinical signs of the disease is DIRECT IMMUNOFLUORESCENT STUDY of a full thickness biopsy of the skin taken from the back of the neck above the hair line. The RAPID FLUORESCENT FOCUS INHIBITION TEST is used to measure rabies-neutralizing antibodies in serum. This test has the advantage of providing results within 24 hours. Other tests of antibodies may take as long as 14 days. 

True rabies must be distinguished from RABIES HYSTERIA, a psychological condition in persons who think they have been bitten by a rabid animal. In such cases, a patient ordinarily attempts to emulate convulsive seizures. Patient receiving rabies vaccine treatment may develop paralysis attributable to a sensitization caused by the rabbit brain material in the vaccine. This paralysis may simulate paralytic rabies and may produce symptoms referable to cranial nerves, such as difficulty swallowing, paralysis of the masseter muscles and unilateral or bilateral facial paralysis. Encephalitis without paralysis may be caused by the vaccine treatment and in such cases the disease begins with high fever and headache with may be followed by convulsions and coma.

SIGNS & SYMPTOMS (most common)

a. Sensory change on or near Delirium 

b.the site of entry Insomnia 

c. Fever Convulsions 

d. Laryngeal spasme 

e. Salivation or foaming of the mouth 

f. Sense of apprehension, anxiety, irritabilty 

g. Acute attack: fever, muscle  twitching, hyperventilation and excess salivation 

h. Headache

The usual duration is 2-6 days without medical intervention. Death is often due to convulsion or respiratory paralysis.

MANAGEMENT A. PREVENTION

1.Responsible pet ownership

a) pet immunization, esp. cats, usually starting at 3 months of age and every year thereafter

b) don’t allow pets to roam around the streets

c) take care of your pets, keep them in good health – bathe, feed with clean adequate food and provide clean sleeping quarters

2.Thoroughly clean ALL BITES AND SCRATCHES made by any animal with strong medicinal soap or solution.

3.Responsible awareness. Report immediately rabid or suggestive of rabies domestic or wild animals to proper authorities (local government clinic, veterinarians or community officials).

4. Pre-exposure to high risk individuals. Veterinarians, hunters, people in contact with animals (zoo), butchers, lab-staff in contact with rabies, forest rangers/caretakers.

5.DOH Standard Protocol

a) If dog is apparently healthy, observe the dog for 14 days. If it dies or show signs suggestive or rabies, consult a physician.

b) If the dog shows signs suggestive of rabies, kill the dog immediately and bring head for lab examination. Submit for immunization while waiting for results.

c) If the dog is not available for observation (killed, died or stray), submit for immunization. *see DOH- Revised Guidelines on Management of Animal Bite Patients- 2007 for more complete guide B.

MEDICAL INTERVENTIONS

a. Local wound treatment. Immediately wash wound with soap and water. Treat with antiseptic solutions such as iodine, alcohol and other disinfectants.

b. Antibiotics and anti-tetanus as prescribed by physician.

c. Rabies – Specific Treatment. Post-exposure treatment is given to persons who are exposed to the rabies virus. It consists of active immunization (vaccination) and passive immunization (immune globulin administration).

a. ACTIVE IMMUNIZATION – aims to induce the body to develop antibodies and T-cells against rabies up to 3 years. It induces an active immune response in 7-10 days after vaccination, which may persist for one year or more provided primary immunization is completed MEDICAL AGENT: Human Diploid Cell rabies Vaccine (HDCV)

b.PASSIVE IMMUNIZATION – aims to provide IMMEDIATE PROTECTION against rabies which should be administered within the first 7 days of active immunization. The effect of the immune globulin is only short term. Rabies antibodies are introduced before it is physiologically possible for the patient to begin producing his own antibodies after vaccination. Some of the RIG is infiltrated around the site and the rest is given intramuscularly. MEDICAL AGENT: Rabies Immune Globulin (RIG)

C. NURSING INTERVENTIONS

1. HIGH RISK FOR INFECTION TRANSMISSION

* provide patient isolation

* handwashing. Wash hands before and after each patient contact and following procedures that offer contamination risk while caring for an individual patient. Handwashing technique is important in reducing transient flora on outer epidermal layers of skin.

* Wear gloves when handling fluids and other potential contaminated articles. Dispose of every after patient care. Gloves provide effective barrier protection. Contaminated gloves becomes a potential vehicle for the transfer of organisms.

* Practice isolation techniques. To prevent self-contamination and spread of disease.

 2. KNOWLEDGE DEFICIT

(about the disease, cause of infection and preventive measures)

* assess patient’s and family’s level of knowledge on the disease including concepts, beliefs and known treatment.

* Provide pertinent data about the disease: 

a. organism and route of transmission 

b. treatment goals and process 

c. community resources if necessary

* allow opportunities for questions and discussions

3. ALTERED BODY TEMPERATURE: FEVER RELATED TO THE PRESENCE OF INFECTION. Since fever is continuous, provide other modes to reduce discomfort.

 * If patient is still well oriented, Inform the relation of fever to the disease process. The presence of virus in the body

* Monitor temperature at regular intervals

* Provide a well ventilated environment free from drafts and wind. 

4. DEHYDRATION related to refusal to take in fluids secondary to throat spasms and fear of spasmodic attacks.

•  Assess level of dehydration of patient.

* Maintain other routes of fluid introduction as prescribed by

* the physician e.g. parenteral routes Moisten parched mouth with cotton or gauze dipped in water 

* but not dripping.

 References

1. Taber’s Cyclopedic Medical Dictionary 17th Edition. 1994. Singapore: Davis Company. Department of Health.2000.

2. Community Health Nursing Services in the Philippine Department of Health, 9th Edition.Philippines.DOH Smeltzer, Suzanne and Bare, Brenda. 2000.

3. Brunner & Suddarth’s Textbook of Medical-Surgical Nursing, 9th Edition. Philadelphia: Lippincott Williams and Wilkins

Sjogren's Syndrome

Definition
Sjögren's syndrome is an autoimmune disorder in which immune cells attack and destroy the glands that produce tears and saliva. Sjögren's syndrome is also associated with rheumatic disorders such as rheumatoid arthritis. The hallmark symptoms of the disorder are dry mouth and dry eyes. In addition, Sjogren's syndrome may cause skin, nose, and vaginal dryness, and may affect other organs of the body including the kidneys, blood vessels, lungs, liver, pancreas, and brain.
It was found by Henrik Samuel Conrad Sjogren n 1933.

Etiology
Researchers think Sjogren's syndrome is caused by a combination of genetic and environmental factors. Several different genes appear to be involved, but scientists are not certain exactly which ones are linked to the disease since different genes seem to play a role in different people. For example, there is one gene that predisposes Caucasians to the disease. Other genes are linked to Sjogren's in people of Japanese, Chinese, and African American descent. Simply having one of these genes will not cause a person to develop the disease, however. Some sort of trigger must activate the immune system.
Scientists think that the trigger may be a viral or bacterial infection. It might work like this: A person who has a Sjogren's-associated gene gets a viral infection. The virus stimulates the immune system to act, but the gene alters the attack, sending fighter cells (lymphocytes) to the eye and mouth glands. Once there, the lymphocytes attack healthy cells, causing the inflammation that damages the glands and keeps them from working properly. These fighter cells are supposed to die after their attack in a natural process called apoptosis, but in people with Sjogren's syndrome, they continue to attack, causing further damage. Scientists think that resistance to apoptosis may be genetic.
The possibility that the endocrine and nervous systems play a role is also under investigation.

Types of Sjogren's Syndrome
SS comes in two types, primary and secondary.
The main difference between the two is that Primary SS occurs by itself while Secondary SS occurs when it's accompanied by a rheumatic condition such as Lupus, Scleroderma and Arthritis.
The rheumatic diseases cause inflammation and pain in the joints, muscles and skin.
If you have Primary SS you most likely have types of antibodies in your blood called SSA and SSB. Additionally, you may have another group of antibodies called ANA (Anti-Nuclear Antibody) that are a group of antibodies that react against normal components of a cell nucleus, meaning they attack normal and healthy cells. If you have ANA's it doesn't necessarily mean you have Sjogren’s as these antibodies are also present in other autoimmune diseases.
Another indication that you have Sjogren's syndrome is the presence of a high Immunoglobulin (IG) count in your blood; IG's are blood proteins usually elevated in both types of SS.
Although a person can develop Sjogren's syndrome at any age, it is very rare in children and most often occurs in people older than 40. It is estimated that 1 to 4 million Americans have SS and 90% are women. It is estimated that 50% suffer from Primary SS and 50% with Secondary SS.


Signs and Symptoms
•    Dry Eyes - this is a very typical symptom of Sjogren's syndrome, however, not everyone with SS has dry eyes. What do dry eyes feel like? You may feel like you have "sand" in your eyes that causes them to be red and itchy with blurred vision. Fluorescent light could also be an irritant.
•    Dry Mouth - you feel like you need to drink water all day long and may experience difficulty swallowing or chewing.
•    Achy Joints - your hips and knees hurt and are often swollen and stiff. For some people, it gets very painful to kneel down.
•    Sensory Changes – SS can affect your sense of smell and taste.
•    Dry Skin - this is another common symptom that can vary in severity with the extreme being scaly skin.
•    Glands – there can be pain in the parotid glands and with some enlargement.
•    Fatigue – this is a common symptom that is sometimes overlooked by doctors.
•    Low-grade fever, numbness in arms and legs, vaginal dryness, bruising and dry cough.

Symptoms vary and can remain the same, worsen or go into remission. Some people experience mild symptoms while others suffer debilitating ones that can affect their quality of life.
Although Sjogren's syndrome does not represent a life threatening condition there can be serious complications especially for those who suffer from a rheumatic disease as well.


Complications
1.    Peripheral neuropathies in the legs.
2.    Symptoms of numbness, tingling and burning.
3.    Dental cavities.
4.    Dry eyes that can lead to corneal ulcers.
5.    Malabsorption of nutrients due to damage to the mucus of the stomach lining.
Other complications that are less common include: pneumonia, bronchitis, and problems with kidney function, hepatitis or cirrhosis of the liver. Additionally, a small percentage of people with Sjogren's syndrome develop cancer of the lymph nodes (lymphoma).

Diagnosis
The doctor will first take a detailed medical history, which includes asking questions about general health, symptoms, family medical history, alcohol consumption, smoking, or use of drugs or medications. The doctor will also do a complete physical exam to check for other signs of Sjogren's.
You may have some tests, too. First, the doctor will want to check your eyes and mouth to see whether Sjogren's is causing your symptoms and how severe the problem is. Then, the doctor may do other tests to see whether the disease is elsewhere in the body as well.
Common eye and mouth tests are
1.    Schirmer test--This test measures tears to see how the lacrimal gland is working. It can be done in two ways: In Schirmer I, the doctor puts thin paper strips under the lower eyelids and measures the amount of wetness on the paper after 5 minutes. People with Sjogren's usually produce less than 8 millimeters of tears. The Schirmer II test is similar, but the doctor uses a cotton swab to stimulate a tear reflex inside the nose.
2.    Staining with vital dyes (rose bengal or lissamine green)--The tests show how much damage dryness has done to the surface of the eye. The doctor puts a drop of a liquid containing a dye into the lower eye lid. These drops stain on the surface of the eye, highlighting any areas of injury.
3.    Slit lamp examination--This test shows how severe the dryness is and whether the outside of the eye is inflamed. An ophthalmologist (eye specialist) uses equipment that magnifies to carefully examine the eye.
4.    Mouth exam--The doctor will look in the mouth for signs of dryness and to see whether any of the major salivary glands are swollen. Signs of dryness include a dry, sticky mouth; cavities; thick saliva, or none at all; a smooth look to the tongue; redness in the mouth; dry, cracked lips; and sores at the corners of the mouth. The doctor might also try to get a sample of saliva to see how much the glands are producing and to check its quality.
5.    Salivary gland biopsy of the lip--This test is the best way to find out whether dry mouth is caused by Sjogren's syndrome. The doctor removes tiny minor salivary glands from the inside of the lower lip and examines them under the microscope. If the glands contain lymphocytes in a particular pattern, the test is positive for Sjogren's syndrome.
6.    Because there are many causes of dry eyes and dry mouth, the doctor will take other possible causes into account. Generally, you are considered to have definite Sjogren's if you have dry eyes, dry mouth, and a positive lip biopsy. But the doctor may decide to do additional tests to see whether other parts of the body are affected. These tests may include
7.    Routine blood tests--The doctor will take blood samples to check blood count and blood sugar level, and to see how the liver and kidneys are working.
8.    Immunological tests--These blood tests check for antibodies commonly found in the blood of people with Sjogren's syndrome. For example:
a.    Antithyroid antibodies are created when antibodies migrate out of the salivary glands into the thyroid gland. Antithyroid antibodies cause thyroiditis (inflammation of the thyroid), a common problem in people with Sjogren's.
b.    Immunoglobulins and gamma globulins are antibodies that everyone has in their blood, but people with Sjogren's usually have too many of them.
c.    Rheumatoid factors (RFs) are found in the blood of people with rheumatoid arthritis, as well as in people with Sjogren's. Substances known as cryoglobulins may be detected; these indicate risk of lymphoma.
d.    Similarly, the presence of antinuclear antibodies (ANAs) can indicate an autoimmune disorder, including Sjogren's.
e.    Sjogren's antibodies, called SS-A (or SS-Ro) and SS-B (or SS-La), are specific antinuclear antibodies common in people with Sjogren's. However, you can have Sjogren's without having these ANAs.
9.    Chest x ray--Sjogren's can cause inflammation in the lungs, so the doctor may want to take an x ray to check them.
10.    Urinalysis--The doctor will probably test a sample of your urine to see how well the kidneys are working.

What Type of Doctor Diagnoses and Treats Sjogren's Syndrome?
Because the symptoms of Sjogren's are similar to those of many other diseases, getting a diagnosis can take time--in fact, the average time from first symptom to diagnosis ranges from 2 to 8 years. During those years, depending on the symptoms, a person might see a number of doctors, any of whom may diagnose the disease and be involved in treatment. Usually, a rheumatologist (a doctor who specializes in diseases of the joints, muscles, and bones) will coordinate treatment among a number of specialists. Other doctors who may be involved include
a.    Allergist
b.    Dentist
c.    Dermatologist (skin specialist)
d.    Gastroenterologist (digestive disease specialist)
e.    Gynaecologist (women's reproductive health specialist)
f.    Neurologist (nerve and brain specialist)
g.    Ophthalmologist (eye specialist)
h.    Otolaryngologist (ear, nose, and throat specialist)
i.    Pulmonologist (lung specialist)
j.    Urologist

Medical treatment
There is no known cure for Sjögren's syndrome nor is there a specific treatment to restore gland secretion. Treatment is generally symptomatic and supportive. Moisture replacement therapies may ease the symptoms of dryness. Nonsteroidal anti-inflammatory drugs may be used to treat musculoskeletal symptoms. For individuals with severe complications, corticosteroids or immunosuppressive drugs may be prescribed.

What is the treatment for Sjogren's syndrome?
The treatment of patients with Sjogren's syndrome is directed toward the particular areas of the body that are involved and prevention of complications such as infection. There is no cure for Sjogren's syndrome.
Dryness of the eyes can be helped by artificial tears, using eye-lubricant ointments at night, and minimizing the use of hair dryers. When dryness becomes more significant, the ophthalmologist can plug the tear duct closed so that tears cover the eye longer. Cyclosporine eyedrops (Restasis) are approved medicated eyedrops that can reduce the inflammation of the tear glands, thereby improving their function. Signs of eye infection (conjunctivitis), such as pus or excessive redness or pain, should be evaluated by the doctor. Dietary addition of flaxseed oil may also benefit eye dryness.
The dry mouth can be helped by drinking plenty of fluids, humidifying air, and good dental care to avoid dental decay. The glands can be stimulated to produce saliva by sucking on sugarless lemon drops or glycerin swabs. Additional treatments for the symptom of dry mouth are prescription medications that are saliva stimulants, such as pilocarpine (Salagen) and cevimeline (Evoxac). These medications should be avoided by people with certain heart diseases, asthma, or glaucoma. Artificial saliva preparations can ease many of the problems associated with dry mouth. Many of these types of agents are available as over-the-counter products, including toothpaste, gum, and mouthwash (Biotene). Numoisyn liquid and lozenges are also available for the treatment of dry mouth. Vitamin E oil has been used with some success. Infections of the mouth and teeth should be addressed as early as possible in order to avoid more severe complications. Diligent dental care is very important.
Saltwater (saline) nasal sprays can help dryness in the passages of the nose. Vaginal lubricant should be considered for sexual intercourse if vaginal dryness if a problem.
Hydroxychloroquine (Plaquenil) has been helpful for some manifestations of Sjogren's syndrome. Serious complications, such as vasculitis, can require immune-suppression medications, including cortisone (prednisone and others) and/or azathioprine (Imuran) or cyclophosphamide (Cytoxan).


Prognosis
Sjögren's syndrome can damage vital organs of the body with symptoms that may remain stable, worsen, or go into remission. Some people may experience only the mild symptoms of dry eyes and mouth, while others go through cycles of good health followed by severe disease. Many patients are able to treat problems symptomatically. Others are forced to cope with blurred vision, constant eye discomfort, recurrent mouth infections, swollen parotid glands, hoarseness, and difficulty in swallowing and eating. Debilitating fatigue and joint pain can seriously impair quality of life.

References

1. http://www.ninds.nih.gov/disorders/sjogrens/sjogrens.htm

2. http://www.medicinenet.com/sjogrens_syndrome/article.htm

3. http://www.sjogrens.org/home/about-sjogrens-syndrome/symptoms

4. http://www.medic8.com/skin-disorders/sjogrens-syndrome.htm

Medical Treatment of Steven Johnson Syndrome (SJS)

Management

The management major is to stop the drug suspected as the cause of Steven Johnson Syndrome, morbidity and mortality would increase if the drug is a slow fuse to be avoided.  The study says that low mortality rate in patients caused by medicines in a way immediately avoid the drug when it first appears the originator of the emergence of bull.

General Principles of Treatment SJS

In SJS patients first came to the place of service, the important thing to note on the treatment of SJS is in accordance with emergency care.  First we must note the airway, breathing, balance hemodynamics, wound care and pain control, temperature control environment, maintenance of sterile field and aseptic handling, sterile, avoidance of various adhesive materials, maintenance of peripheral vein away from the affected area (no center line access  if possible), provision of early nutrition with nutrient-filled nasogastric, anticoagulation, prevention of stress ulcer, and administration of medicines for pain and anxiety control is important.

SJS is a systemic damage to the many organs.  So a team approach including dermatologists, specialized burns unit, ICU, nutrition, optalmologist, and pain management team.  With the help of an experienced nurse for more optimal management.

a.  Systemic Management

Pulmonary Care including aerosols, bronchial aspiration and physical therapy.  If the trachea and bronchi are involved, intubation and mechanical ventilation is almost always required.  Early enteral nutrition and continuously reduce the risk of stress ulcer, reduces bacterial translocation and infection enterogenic.  Phosphorus levels should be measured and corrected, if necessary.  Hipophosphoremia important is frequent and can contribute to the occurrence of glisemia and muscular dysfunction.

Most writers do not use prophylactic antibiotics, samples of bacteria from the skin wound made the first day and every 48 hours.  Indications for antibiotic treatment include increasing the number of bacteria cultured from the skin with a selection of single-strain, temperature decreased abruptly, and the declining condition of the patient.  S.  aureus is the main bacteria present on the first days, and gram-negative strains appear later.

Environmental temperature is raised to 30-32 degrees C.  This will reduce the loss of calories through the skin and the resultant shivering and stress.  Heat loss can also be limited by temperature increase antiseptic baths to 35v 'to 38 (C and by using heat shields, infrared lamps, and air fluidized bed.

In SJS patients, especially the severe general condition, skin and mucosa gloving or erosion, it is this which causes patients to lose fluid and electrolyte SJS.  Therefore, fluid management in patients with SJS is very important and management mistakes can be fatal.  To maintain fluid balance should equal the input fluid to replace lost fluids.  Liquids include water and electrolytes.  The aim of fluid therapy is not for perfection fluid balance, but saving souls by lowering mortality rates.

For commonly used resuscitation fluids isotonic crystalloid and colloid.  Isotonic crystalloid has a relatively high Na content (> 100 mEq / L) goals for long-lasting in the extracellular (especially intravascular).  Conversely, the liquid electrolyte maintenance using the appropriate amount of daily needs (moderate Na and K sufficient).  Correction fluid therapy is intended to overcome the severe electrolyte disturbances.

  As for the gift amount equal to resuscitation in burn patients is the initial step of fluid replacement, performed according to Parkland formula: 4 ml / kg x% BSA, where ½ is given in the first 8 hours and the remainder in the next 16 hours.  For maintenance with respect to the production of urine, maintained urine production of 1 ml / kg / hour.  BSA was calculated based on the Rule of Nine.

Selection of fluid in the Steven Johnson syndrome should be based on the patient's hydration status, electrolyte concentrations, and metabolic abnormalities that exist.  Various parenteral solution has been developed according to the physiological needs of various medical conditions.  Intravenous fluids or intravenous therapy is one of the most important aspects that determine the handling and care of patients.

SJS patients who start therapy, usually use fluid resuscitation by using 2 liters of Ringer Lactate solution isotonis.  However, Ringer Lactate is not always the best fluid for resuscitation.  Adequate fluid resuscitation to normalize blood pressure in patients combustio 18-24 hours after the burn injury.  Advantages include easy crystalloid fluids available, inexpensive, easy to use, does not cause allergic reactions, and fewer side effects.  Excess fluid in the delivery of crystalloid to continue with edema throughout the body so that the use of excess must be prevented.

Isotonis NaCl solution is also recommended for initial treatment for patients with SJS who experienced hypovolemic shock with hiponatremik, hipokhloremia or metabolic alkalosis.  NaCl 0.45% in Dextrose 5% solution is used as a temporary liquid to replace lost fluids insensibel.

Nutrition is an important part because there was increasing demand hypermetabolic and foods containing protein and energy in proportion to the effect of BSA (translation).

Oral intake is usually difficult because of damage to the upper channel Verna.  Therefore, modification of diet and fluids are very important (translation) mucous membranes are usually exposed to severe erosion during 10-14 days.  However a longer ulceration in the gastrointestinal tract after recovery were also reported.  Although the oropharyngeal cavity was also involved, the erosion may extend as long as gastrointestinal tract produces malnutrition, pain and bleeding.  Severe gastrointestinal complications are bleeding.  Death relate to this complication, however, also required transfusion (briefs).  In SJS patients about including the mucosal injury caused odinofagi, oral food intake and ability to tolerate a little better than liquid food and solid foods increases the risk of aspiration.  Early disease when disfagi and odinofagi occur, given a liquid diet so that the patient more comfortable.

Of particular interest in nutrition is the temperature, acidity (hot, cold, and the acidity of food), texture, and moisture foods like soft food.  Fluid or electrolyte balance settings and nutrition is important because the patient is difficult or can not swallow because of lesions in the mouth and throat, and awareness to decrease .  Ulceration in the gastrointestinal tract will build an all-feeding difficult and painful, perenteral feeding necessary to provide adequate caloric intake.  Nutrition perenteral can be very helpful to provide food, limiting weight loss and support the healing skin.

Supportive therapy is the standard protocols used in patients with SSJ.  Patients generally come with a general state of severe need of fluids and electrolytes, and calorie and protein requirements according parenterally.  Fluid administration depends on the extent of skin and mucosal disorders are involved.  If not possible then it can be used orally, enteral feeding ..  Providing nutrition through a tube nasogastrik done until the oral mucosa returned to normal.  But it is very important to be replaced as soon as possible to avoid the adherence of oral administration of upper GI mucosal lesions in the mouth are given medication and ointments glycerin dessert.

Total perenteral nutrients called hiperalimentation.  Provide your body the nutrients such as protein, sugar, vitamins, minerals and sometimes fat.  TPN is used when there is trouble eating or digesting food.  Usually given to the body through IV are great.  TPN can be used for several days or long-term

Can be given intravenously as 5% glucose solution and Darrow.  If therapy does not provide improvement within 2-3 days, then it can be given a blood transfusion of 300 cc for 2 consecutive days, especially in cases with extensive purpura.  In cases with extensive purpura can also add vitamin C 500 mg or 1000 mg a day intravenously and hemostatic.  To reduce the side effects of corticosteroids are given a poor diet and high salt protein.  Unless it also given anabolic medicines and KCl 3x500 mg daily if there is a decrease C

In SJS patients were children less energy requirements than patients baker injuries in children.  In general the patient's energy needs children (24.6x in kilograms) (% lukax4, 1) 940.  Parenteral feeding early and sustained decrease the risk of stress ulcer, reduce bacterial translocation and infection followed enterogenic and early termination intravenously.  Phosphorus levels should be measured and corrected, if necessary.  The findings are frequent and may hipophosporemia relating to altered regulation of glycemia and muscle dysfunctions.  Blood sugar control, can be a problem as a result of stress and treatment with systemic steroids.  Hyperglycemia risk facto one out-come the bad.  Then the blood glucose control is very important.

In patients with SJS usually occurs colonies of bacteria and associated with sepsis.  Therefore need to be given prophylactic antibiotics

Treatment of skin infections with antibiotics.  Antibiotics are the most high-risk group of betalactam and sulfa should not be used.  For initial therapy can be given broad-spectrum antibiotics, then changed to a narrow spectrum based on culture results and test the resistance of bacteria from skin lesions and blood preparations . To prevent secondary infection such as bronchopneumonia which can cause death, because the immunity of patients to decline due to high dose corticosteroid therapy, can be given antibiotics which rarely causes allergies, broad spectrum, are bactericidal and no or little is nephrotoxic, such as clindamycin 8-16 mg /  kg / day intravenously, was given 2 times / day or 2 x 600 mg, can also use ciprofloksasin 2 x 400 mg iv  Giving antibiotics stopped when dexamethasone reached 5mg per day and no signs of infection exist.

Some researchers do not use antibiotic prophylaxis.  Regular handling to prevent infection include skin care, mucous membranes, the catheter was replaced and cultured regularly.  Sampling of bacteria on the skin lesions on the first day and every 48 hours.  Indication of systemic antibiotics including increasing the amount of bacterial culture from the skin with a single strain selection, patient's temperature suddenly dropped, and the worsening condition of the patient.  S.  Aureus is a major bacterial which seen during the first day and gram-negative strains appear later.

Pain control  is part of the management of SJS or TEN but not much literature is available as a guide except for treatment for burns.  Management of pain is individual, consideration of clinical manifesatations of patients, the risk of respiratory suppression and monitoring facilities.  Non-ICU care in a conscious patient is given an oral therapy for reasons already mentioned.  Transmucous oral, work short term, medium-opioid which is potentially a therapeutic option for painful procedures.  Anxiolitik such as low-dose benzodiazepines may be given and it is more effective for patients with higher anxiety.  In the long-term opioids, mild to moderate given along with paracetamol should be given for pain management.

b.  Topical Management

Because the lesions are usually limited to the epidermis and hair follicles are still intact, it would still allow the growth of the epidermis with a quick return in patients with SJS.  It supports a different approach than in the topical treatment of burns.

SJS same wound care on wound care in patients with SJS because until now there is no standard protocol for wound care patients with SJS.  Various non-stick dressings have been used but contain sulfa should be avoided to prevent systemic sensitization and leukopenia.  Debridement of necrotic epidermis is not required.  Patients with SJS rarely requiring skin graft, doctors usually only enough to compress or dressing to choose which treatment is easiest and usually the material available in each health service, for example by compress 0.9% NaCl was quite helpful.  Replacement compress or dressing depending on the type and condition of the wound dressings and the volume of fluid that comes out, but it should be replaced 1 or 2 times per day or every 2 or 3 days.  Crusting on the lips and the nose should be removed and sprayed with some antiseptic several times a day.

Choice of dressings including xenograft, allograft, and dressings are made from human skin.  Gauze with basitrasin ointment can also be used.  Topical antibiotics can be combined with the dressing.  Topical antiseptic (0.5% silver nitrate or 0.05% chlorhexidine).  Currently there is a change trend from traditional dressings that contain petroleum jelly change to the use of nanocrystalline silver dressings that showed no side effects and wound healing in all patients.

c.  Specific Therapy

Therapeutic options for patients with SJS is still limited and controversial.  Here are described some specific therapies for patients who normally used for SJS.

• Corticosteroids

Use of Corticosteroids is still debated.  This medicine is a mainstay in some units, but other researchers consider systemic corticosteroids to provoke long wound healing, increased risk of infection, masking of early signs of sepsis, severe gastrointestinal bleeding and increased mortality.  A literature review showed only a series of patients and no randomized clinical trials.  Several articles reported corticosteroids useful: Tegelberg used prednisone 400 or 200 mg / day, reduced gradually over a period of 4-6 weeks, and one death were observed among eight patients.  Other series also stated very good results but the diagnosis of SJS-TEN is moot for most cases.  In two retrospective studies, no difference in mortality rates or complications of infection recorded in patients who received steroids before or after landing.

In contrast, another study states that the use of corticosteroids was hurt.  Thirty patients with SJS or TEN were included in a prospective study without control.  The first 15 patients received corticosteroids and the mortality rate was 66%.  Therefore, 15 further patients were treated without corticosteroids and the mortality rate was 33%.  The two groups were the same described in other aspects.  However, 11 of 15 patients "without corticosteroids" had received corticosteroids prior to referral.  So no conclusions can be drawn about the early administration of corticosteroids exclusive.  In a retrospective study multivariate analysis of prognostic factors showed that corticosteroid therapy is an independent factor for increased mortality.  Other series describe the same conclusion.

• human intravenous immunoglobulin (IVIG)

Use of human intravenous immunoglobulin (IVIG) has been reported in several cell-mediated autoimmune disorders of skin, including severe drug reactions in the skin.  IVIG seems to be a useful and safe therapy for children with severe drug reactions.  Still further research is needed to determine the optimal dosage guidelines and compare the effectiveness and safety of IVIG with a potentially effective modality lainnya.Mengingat importance of immune mechanisms in inflammatory drug reactions, IVIG has emerged as a potential immunomodulator therapy for SJS / TEN.  Although well-controlled trials has not been designed, the results of a small number of patients treated so far seems favorable.

Medicines can trigger the production of a ligand to activate keratinocyte apoptosis, known as CD95 (fas) ligand.  Binding of this ligand to CD95 (fas) receptors located on the surface of apoptotic ceratinocyte cells cause programmed cell death.  IVIG showed the capacity to block apoptosis of ligand binding to this receptor, thus preventing keratinocyte apoptosis and epidermal detachment of the next.

In one study, an open uncontrolled, IVIG given to 10 adult patients with drug-induced.  Dose regimen used, 0.4 to 0.75 g / kg / day for 4 consecutive days, based on the recommendation of IVIG treatment for immune thrombocytopenic purpura.  Although the details of this research is limited, the authors noted a disruption of the skin and signs of wound healing, which occurred in all patients within 24 to 48 hours after administration of IVIG.

IVIG obtained from plasma collected from thousands of healthy blood donors and thus contain a variety of protective immune antibodies against human pathogens and foreign antigens.  Half-life of IVIG on average in immunocompetent immunity who is 3 weeks.  Immunomodulatory effect of IVIG is complex, involving modulation of expression and function of the reticuloendothelial Fc receptors, interference with complement activation and cytokine network, provision of antibodies anti-companion, and its effects on activation, differentiation, and function of effector T and B cells.  Therefore, in addition to its ability to block keratinocyte-mediated apoptosis, IVIG may have additional effects that contribute to the overall therapeutic benefit in patients with drug reactions in the skin tough.  A number of factors, including the presence of other diseases that occur simultaneously and immune status, especially in populations of older adults, can play a role in this difference.

Combination therapy with corticosteroids and IVIG showed a tendency to reduce the death rate compared with corticosteroids alone.  Decrease in mortality rate, however, not statistically significant.  Combination therapy also reduced hospitalization time, which means that the total dose of corticosteroids can be reduced.  Side effects of IVIG occurred in <5% of cases and generally mild and self-limited.  The main factor limiting widespread use of IVIG for SJS are the availability and cost.

Cyclosporine

if given early in the disease, at 3-5 mg / kg per day, either intravenously or orally, more than 2 weeks, it shows the progression of the disease without an increased risk of sepsis.  But there are other sources that mention the short-term use to avoid the side effects that usually occurs in long-term use, the use of this agent seemed promising but needs further research.

• Plasmapheresis and hemodialysis.

It has been suggested by some authors to remove drug metabolites and cytokines from the circulation, but both are of questionable benefit.

Complication

Stevens-Johnson Syndrome, often causes complications in the form simblefaron eye and corneal ulcers.  It also can arise swollen, fever or hypothermia, and the hardest part is sepsis.  Another complication that usually occurs as follows:

- Ophthalmologic

Corneal ulcers, anterior uveitis, panophthalmitis, blindness

- Gastroenterologic

Esophageal stricture

- Genitourinary

Renal tubular necrosis, kidney failure, penile scarring, vaginal stenosis

- Pulmonary

Bronchopneumonia

- Cutaneous

Scar and cosmetic disturbance, disturbance of healing if infection occurs

Prognosis

In cases that are not severe, the prognosis good, and healing occurs within 2-3 weeks.  Mortality ranges from 5-15% in severe cases with complications or delayed and inadequate treatment.  Prognosis is more severe if there is a wider purpura.  Death is usually caused by fluid and electrolyte balance disorders, bronchopneumonia, and sepsis.

STEVEN JOHNSON Syndrome (SJS)

Definition

Stevens-Johnson syndrome (SJS) is a collection of symptoms characterized by a triad of clinical disorders of the skin, eyes and mucous orifice and can be accompanied by a severe general symptoms.  First introduced in 1922, SJS is a process of immune complex-mediated hypersensitivity that is a combination of symptoms of erythema multiforme is severe abnormalities of the skin form of erythema, vesicles / bull, can be accompanied by purpura.  SJS is a rare disease vesikobulous and has the characteristics of an acute cutaneous eruption, involving the skin and mucous membranes.

Etiology

Almost all patients with SJS is caused by the toxic reactions of medicines especially antibiotics  (eg group of sulfonamides and penicillin), anti-convulsive, anti-pain, and medications obtained without ressep from a doctor.

SJS etiology determined exactly difficult because the cause involves a variety of factors, although in general are often associated with immune response to the drug.  Several factors cause of SJS include: infection (viral, bacterial, fungal, parasitic), medicines (salicylates, sulfa, penicillin, Ethambutol, Tegretol, tetracyclines, digitalis, and contraceptive), food (chocolate), physical (cold air, sunlight  and X-rays), and others (collagen disease, malignancy and pregnancy).

Epidemiology

SJS occurs approximately 1-3 cases per one million residents each year SJS also reportedly common in Caucasians.  SJS can hit all ages.  But from some reports, SJS occurs more often in adults with a comparison of male and female 1:2.  For children while the ratio between boys and girls is 1:1.

Pathophysiology

Pathogenesis of SJS has not been clear, although often associated with hypersensitivity reaction type III and IV.

• Hypersensitivity Reaction Type III

This occurs when the complex antigens of circulating antibodies in the blood buildup in blood vessels, the antibodies are trapped in the capillary network.  In some cases, foreign antigens can be attached to the network causes the formation of antigen-antibody complex place.  Then type III hypersensitivity reaction occurs that activates complement and mast cell degranulation leading to tissue damage or capillary in place of the reaction.

Neutrophil are attracted to the area and will begin to accumulate and phagocytes damaged cells resulting in release of cellular enzymes and residual accumulation of cells.  This causes inflammation cycle continues.

• Hypersensitivity Reaction Type IV

This reaction is mediated by T cells, where there is activation of lymphokine-producing T cells or cytotoxic by an antigen that resulted in the destruction of the cells concerned.  Reactions mediated by these cells is slow (delayed) may take 14 hours to 27 hours for the formation.

Hypersensitivity process will cause damage to the skin are:

1.  Skin malfunction causing loss of fluid,

2.  Hormonal stress followed by increased insulin resistance, hyperglycemia and glucosuria,

3.  Failure of thermoregulation,

4.  Failure of immune function, and

5.  Infection.

Another theory associated with Stevens-Johnson Syndrome include:

• Theory Apoptosis of keratinocytes

Apoptosis of keratinocytes is a very rare occurrence in normal epidermis, but in this incident will increase SJS.  NK-cell and cytotoxic T-lymphocytes release porphyrin will then make a hole in the target cells so that the polymer changes shape and 3-dimensional tubular structure keratosit which makes it easy to experience apoptosis.

Many medicines, whether swallowed or used as eye drops, can trigger apoptosis of epidermal keratinocytes is widespread in individuals with SJS, causing the skin to blister and peel.  Several theories have been proposed for this condition.  

(A) Medicines may induce upregulation of FasL by keratinocytes constitutively express Fas, which leads to the point of death receptor-mediated apoptosis.  

(B) the medicines can also cause the production of peripheral mononuclear blood cells of sFasL, which moves receptor Fas on keratinocytes.  

(C) In another scenario, the drug can interact with MHC class I-expressing cells.  As a result, drug-specific cytotoxic CD8 + T cells to accumulate in the epidermal blisters and release perforin and granzyme B which kills keratinocytes.  

(D) provides evidence that these medicines can also trigger the activation of CD8 T cells, NK cells and NKT cells to secrete granulysin.  Consequently, keratinocytes die in a way that does not require cell contacts.

• The theory of metabolism associated with genetic defects.

Patients have metabolic functions that are not perfect the first level as a result of a genetic defect so that the work be imperfect biotransformation metabolism making it possible to produce a toxic metabolite.

Clinical manifestations

Prodromal symptoms ranges from 1-14 days of fever, lethargy, cough, runny nose, painful swallowing, chest pain, vomiting, muscle aches and atralgia which vary in degrees of weight and combination of symptoms.  After that will arise lesions in several areas namely:

a.  Skin

The lesions arise suddenly, beginning with the macula which develop into papules, vesicles, bull, urticaria or erythematous plaques accompanied by a comprehensive and systemic symptoms from internal organs.  These lesions can attack less than 10% body surface.  Specific lesions of atypical target lesions that are similar to the target lesion tipical on erythema multiforme.

   Skin Lesions In Stevens-Johnson Syndrome

b.  Mucosa (mouth, throat and genital)

Form of vesicles, bull, erosion, excoriation, bleeding and crusting red.  Bula to hemorrhagic and to the mucous membranes.  Oral mucosa and lips most often affected (100%), eyes (91%), genital (57%) and rectum (5%).  The initial symptoms are perceived is swelling, redness, and burning of the lips and oral mucosa, followed by the emergence of bull and shallow ulcers.

Bula easily broken, so leave erosion.  Covered with grayish white pseudomembranehypersalivation.  On a more serious condition of lesions can be on the gums, tongue, pharynx, nasal mucosa, larynx, esophagus or bronchus so that people with breathing difficulty.

In the genital area, the lesions cause pain and redness that can develop into vesicles, shallow ulcers and erosion.  Vulvovaginitis can occur in women who are very painful, whereas in men can occur at the external urethral meatus erosion of pain accompanied by the formation of purulent secretions.  Bleeding from the urethra or vagina can occur because of damage to the urethra.

  Mucosal Lesions In Stevens-Johnson Syndrome

c.  Eye

Catarrhalis form of conjunctivitis, blepharoconcjutivitis, iritis, iridocyclitis, eyelid edema and hard to open, in severe cases erosion and perforation of the cornea.  Lesions can occur on the conjunctiva that is characterized by symptoms of redness, swelling, and the bull or erosion causing a very painful feeling, photophobia and bilateral hyperlacrimation.

  Eye Lessions of Stevens-Johnson Syndrome

Diagnosis

Diagnosis of Stevens-Johnson Syndrome, 90% based on the clinical picture.  If caused by medication, there is a correlation between drug administration with the onset of symptoms.  Diagnosis directed against manifestations of the disorder according to the triad of skin, mucosa, eye, and its relationship with clinical factors that have shaped the target lesion, or eye sliced beef, abnormalities in the mucosa and fever.

Also supported by laboratory tests including peripheral blood examination, immunological examination, bacterial culture and resistance testing of blood and the lesion, and histopathological examination of skin biopsy.  Anemia can be found in severe cases with bleeding, leukocytes are usually normal or slightly elevated, there is an increase of eosinophils.  Levels of IgG and IgM can be high, C3 and C4 were normal or slightly decreased and can be detected circulating immune complexes.

Skin biopsy was planned if there is no classic lesions.  Histopathological and immunohistochemical examination to support the enforcement of the diagnosis.

Differential Diagnosis 

Differential diagnosis in the case of Stevens-Johnson Syndrome include:

1.  Toxic Epidermal Necrolisis.

Stevens-Johnson Syndrome is very close to TEN.  SJS with more than 30% bull called TEN.

2.  Staphylococcal Scalded Skin Syndrome (Ritter's disease).

In this disease is characterized by crusting skin lesions on the skin peeling.  Mucosa usually not affected.

Medical Treatment of Acute Cholecystitis

Treatment and Therapy

a.  Common actions

Bed rest, intravenous fluid administration, pain relief with petidin (demerol) and buscopa low-fat diet.  There are several factors that cause the occurrence of gallbladder disease, including obesity, high fat consumption, particularly the increasing trigleserida dyslipidemia associated with high intake of fat and sugar, weight loss quick reply.

Nutritional intervention needs to be done to prevent gallbladder disease: weight control, limiting fat intake to <30? Ri total calorie and fat intake no more than 30 grams / day, limiting the consumption of pure sugar (white sugar and other sweet food), avoid  weight reduction program drastically.  The principles of diet on gallbladder disease:

1.  Food for breakfast do not contain much fat, preferably in the form of cereals and fruits

2.  Using low-fat milk (fat level 1%) or skim milk to reduce fat consumption.  Vegetable milk such as soy milk is the best option.

3.  Using sugar substitutes such as aspartame as a sweetener in coffee, tea or cereal.

4.  Buying a low-fat snack foods such as fruit, low fat crackers

5.  Eating lots of vegetables that do not cause gas such as carrots, spinach, eggplant (cabbage, jackfruit, durian gas producer)

6.  Relaxing exercise such as walking or cycling.

7.  diet

- In a state of acute patients are usually fasted and get through the infusion of fluids and electrolytes.  After about 12-24 hours, clear liquid diet and then continued to offer low-fat diet.

- Low-fat diet, the consumption of fat 20-40 grams / day in patients with gallbladder

- Should be good and balanced diet to avoid deficiencies of calories, protein and micronutrient

- Diet may not contain foods that stimulate and contain gas

- Consumption of supplements of vitamins a, d, e, k

- Low-fat diet is recommended 4-6 weeks before the acute phase and surgery.

b.  Antibiotic

Given to treat peritonitis and septicemia and prevent empyema.  Microorganisms are often found was Escherichia coli, Streptococcus faecalis, Klebsiella, often in combination.  Anaerob germs can also be found as Bacteroides and Clostridia.

c.  Surgery

In acute cholecystitis should be performed immediately Cholycystectomy laparoscopic in one to two days of treatment.  Some surgeons prefer to wait and treat patients with hope for the better during treatment, and reserves the surgery when the patient's condition is almost completely recovered, with the rationale that the technical aspects of cholecystectomy would be easier if inflammation process has begun to heal.  The problem that approximately 25% of these patients fail to experience improvement or even deteriorate and require urgent surgery.  At this moment the tendency is to perform surgery immediately after diagnosis is certain and the patient's general condition is stable overall.

Compared with conventional cholecystectomy, the patient is out of the hospital within one to two days post-surgery and minimal scarring can re-move more quickly.  Approximately 10% of laparoscopic cholecystectomy should be changed to open surgery (conventional Cholecystectomy) in room of surgery because of extensive inflammation, adhesions or the presence of adhesion complications such as bile duct injury that requires repair.  In patients who require immediate treatment, but in a state of serious illness or very high risk for cholecystectomy, should be treated with the administration of medical fluids, antibiotics and analgesics, if this therapy fails to consider a percutaneous cholecystectomy.  Here the contents of the gall bladder removed and the lumen in the drainage with a catheter that was left.  In patients who experienced cholecystectomy and have recovered from an acute situation, cholecystectomy should be performed six to eight weeks later when conditions are good enough.

Prognosis

About 75% of patients treated with medical will experience a remission from acute symptoms within two to seven days of hospital care.  In 25% of cases, complications arise such as empyema and hydrops, gangrene and perforation, fistula formation, gallstone ileus.  In this case required surgery.

Than 75% of patients with symptoms of acute cholecystitis subsides, nearly a quarter will relapse within one year, and 60% at least will get a one-time relapse attack within six years.  Therefore it is best to early surgery.