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.

Acute Cholecystitis

Definition

Acute cholecystitis is an acute inflammatory process of the gallbladder accompanied with right upper abdominal pain, tenderness, and fever and is usually triggered by obstruction of the cystic duct.  The most common cause of acute cholecystitis is a continuous obstruction of the cystic duct by gall stones causing acute inflammation of the gallbladder.

Epidemiology

The prevalence of cholecystitis is similar to the prevalence of gallstones.  Cholecystitis commonly found in women with 2-3 times greater frequency than in males.  Pregnancy can also increase the risk of cholecystitis, because progesterone in pregnant women can cause gall bladder emptying and common bile litogenesis estrogen increases in pregnancy.  In addition, cholecystitis also influenced by age.  Get older  the greater the risk of gallstones which can cause cholecystitis, because estrogen androgen inhibits enzimatik conversion of cholesterol to bile acids that increase cholesterol saturation of bile.  The groups of different ethnicities, one of them. Indians and Scandinavians have an increased risk of gallstones that can cause cholecystitis.  The risk is lower in sub-Saharan Africa and Asia, in the United States tend to whites than blacks.  Lifestyle factors such as diet, obesity, and medecines separately by hormonal especially in women.

Many patients with cholecystitis to complete recovery for 1-4 days, although it needs to be done surgery or cause complications.  Patients with cholecystitis have a mortality rate of around 10-50%, with 4% of patients suffering from cholecystitis calculous, 15% and 10-15% empysematous cholecystitis caused by perforation.

   

Physiology bile production and flow

Bile produced by the liver as much as 500-600 mL per day which then flowed into the gallbladder and stored there.  Hepatic bile is an isotonic and contain electrolyte which has a composition similar to plasma electrolyte composition.  But the electrolyte composition of bile in the gallbladder that are different from the hepatic bile because many inorganic anions (chloride and bicarbonate) and water reabsorbed through gallbladder epithelium, so that the bile concentration increased from 3-4 g / dL to 10-15 g / dL  in the gallbladder.

The main ingredient contained in the bile are bile acids (80%), phospholipids and non esterified cholesterol (4%).  Lecithin is a major phospholipid found in bile, although it also found lisolesitin and phosphatidil etanolamin in a small percentage.  Phospholipids would be hydrolyzed in the intestine and did not participate in the enterohepatic cycle.

Instead of bile acids into the enterohepatic cycle except litokolat acid.  Some of the major bile acids are cholic acid (cholic acid) and (chenodeoxycholic acid).

These acids conjugated with glycine and taurine, and in the lumen of the colon converted by bacteria into secondary bile acids (amino acids deoxycholate and litokolat).  Acid litokolat almost not found in bile, because this acid is not included in the enterohepatic cycle.  Bile acids are detergent-like molecules, can dissolve substances that are basically insoluble millimolar, bile acid molecules will aggregate to form aggregates called micelles (micelle).  Solubility of cholesterol in bile depends on the concentration of cholesterol itself and comparison between bile acids and lecithin.  Comparison of normal will dissolve cholesterol, whereas the ratio of abnormal causes precipitation of crystals of cholesterol in bile.  This is one of the factors the initial formation of cholesterol stones.  The human body efficiently conserve bile acids through the enterohepatic circulation.

Bile acids, either not conjugated or conjugated, are passively absorbed along the intestinal lumen, but active transport as important role in the conservation of bile acids.  Transport activism is particularly the case in the distal ileum.  Bile acids are absorbed into the portal flow and taken back by the hepatocytes, then reconjugated and secreted.  Under normal circumstances, bile acid enterohepatic circulation experience as much as five to ten times a day.  Bile acid absorption through the intestinal lumen is very efficient, so that bile acids are wasted in faeces only about 0.3 to 0.6 g per day, and the amount will be replaced by de novo synthesis of bile acids in the liver.  Bile acids returning to the liver via enterohepatic circulation will inhibit the de novo synthesis and enterohepatic circulation interruption in return will increase bile acid synthesis.

In the fasting state, Oddi sphincter pressure increased so that impede the flow of bile from the duct into the duodenum choledochus.  This prevents the reflux of duodenal contents into the duct choledochus and also facilitate gallbladder filling.  Cholecystokinin released by the duodenal mucosa in response to amino acid intake of fat and otherwise facilitate the emptying of the gallbladder.

Cholecystokinin cause gall bladder contraction and relaxation of sphincter of Oddi, so that bile can flow from the gallbladder into the duodenum.

  Etiology and Pathogenesis

In nearly 90% of cases accompanied by Cholelitiasis.  Inflammatory response caused by three factors, namely, mechanical, chemical, and bacterial.  Mechanical inflammation due to increased intra-luminal pressure and stretch the lead to depressed blood vessels and ischemia of the mucosal wall infarction and gangrene can occur.  Chemical inflammation caused by the release lisolesitin (due to the action of phospholipase on lecithin in bile), reabsorption of bile salts, prostaglandins and other inflammatory mediators are also involved.  Lisolesitin toxic gallbladder mucosa.  Bacterial inflammation that play a role in 50-85% of cases of acute cholangitis.  Germs are often isolated from the culture fluid gall bladder, among others, E.  Coli, Klebsiella spp, Streptococcus spp and Clostridium spp.

Generally cholecystitis is associated with colelithiasis.  Cholecystitis

Clinical Overview

Complaints are typical for the attack is acute cholecystitis biliary colic and tenderness as well as an increase in body temperature.  Nearly 60-70% of patients reported ever have previous abdominal colic pain that healed spontaneously.  The pain often occur late at night or dawn, usually on the upper right quadrant of the abdomen or epigastrium and radiating down the right corner of the scapula, the right shoulder.  Pain feels like in the drill or the like is pressed and no comfortable body position.  Pain usually increases to a plateau and can last for 30-60 minutes without abating, his trademark for more than three hours and after that the pain shifted from the epigastrium to the right quadrant of the abdomen, not like a short spasm of biliary colic.

Attacks can be triggered by eating fatty foods or heavy meals at night.  The patient was sweating, lying when moving and curved body position.  Often accompanied by nausea, vomiting and fever.  The spectrum of symptoms in acute cholecystitis wide, in some patients into severe and acute pain in a short time.

On physical examination of patients obtained pain in the right upper quadrant which often extends to the epigastrium.  Classic signs of Murphy showed significant pain and limited inspiration on palpation (that in) below the right costal arch.  In most cases (30-40%) can be touched a gallbladder mass.

Jaundice observed in 20% of cases, mostly mild (bilirubin <4.0 mg / dl).  If the bilirubin concentration is high, should be considered a stone in the bile duct extrahepatic.

Laboratory tests found leukocytosis and counts that showed a shift to the left.  Disruption of liver function tests such as the increase of serum bilirubin, alkaline phosphatase / gamma-GT and serum transaminase suspicious biliary tract obstruction (stone choledochus).  The increase in levels of serum amylase and lipase striking or suspicious of acute pancreatitis.

Ultrasound examination will show gallstones in 90-95% of cases, gallbladder wall thickening (edema), Murphy sign and  pericholestitic cholesyntigraphy (eg HIDA) will confirm the diagnosis when biliary tract showed no visualization of the gallbladder which was evidence of duct obstruction  cystic.

Diagnosis

Diagnosis of acute cholecystitis is established on the basis of disease history typical physical examination.  The existence of the triad of right upper quadrant pain, fever and acute cholecystitis leukocytosis very suspicious.  Abdominal ultrasound examination showed edema and the presence of gallbladder stones in it in most cases.

Complications of Acute cholecystitis

a.  Empyema and gallbladder hydrops

gallbladder empyema usually occurs as a result of progression from acute cholecystitis with persistent cystic duct obstruction, and superinfection with stagnant bile which is accompanied by the formation of pus.

The clinical manifestations  resembling cholangitis with high fever, severe pain in the right upper quadrant and leukocytosis  real.  Empyema at high risk for gram-negative sepsis or perforation.  When the diagnosis suspicious circumstances, immediate surgical intervention with an appropriate antibiotic protection.  Or mucocele from gallbladder hydrops may also arise as a result of prolonged obstruction cystic duct, usually by a large solitary stone.  In these circumstances, a clogged gallbladder lumen widened with progressive by mucus (mucocele) or by a clear transudate (hydrops).  On physical examination found the mass of visible, easily palpable, not pain that sometimes extends from the upper right quadrant to the right iliac fossa in.  Usually asymptomatic although may arise chronic pain in the right upper quadrant.  In these patients needs to be done cholecystectomy.

b.  Gangrene and gallbladder perforation

gangrenous gallbladder caused by ischemia and necrosis of the wall and predispose to the occurrence of perforation.  Gallstones may erode the wall of a necrotic.  Another situation that can be reason including severe distension gallbladder, vasculitis, diabetes mellitus, empyema resulting torque of artery occlusion.  Perforation usually occurs in the fundus, which is part of at least vasculary perforation into the omentum will cause pericholesistic abscess, perforation into adjacent organs will cause internal  fistula biliary into the duodenum, jejunum, hepatic flexure of the colon or the stomach.  More rarely happen again 1-2% free perforation into the peritoneal cavity, the prognosis is poor with mortality rates around 30%.  Handling of adequate antibiotics and surgical measures as soon as possible.

c.  Gallstone ileus

when a large gallstone (> 3.5 cm) into the fistula and into the intestine, gallstone ileus can occur.  Location valvulus ileocaecal obstruction is common.  In these patients there were complaints of symptoms and radiological examination of intestinal obstruction.

Diagnosis is confirmed by radiological examination.  Plain abdomen showed small bowel obstruction in the presence of the bile duct and an ectopic gallstone.  Action choice is laparotomy with stone extraction (or push the stone into the colon)

d.  Abscess pericholesistic

pericholecystic abscess is a form of perforation most often occurs with localized content and tightly restricted by the omentum and adjacent viscera.  This situation need to be suspected when a slow recovery of acute cholecystitis, specially there is  second episode of fever, right upper abdominal pain or mass arising in the upper right abdomen.  By ultrasonography and CT scan of this abscess will appear.  This situation occurs mainly in older patients or patients receiving long-term steroid with a fever and a minimal inflammatory response.

e.  Cholecystitis emphysematus

This term is used to indicate gallbladder infection with gas forming organisms, E coli, Clostridium welchii or Streptocoocus anaerobic.  Patients in a state of severe pain, a palpable mass in the abdomen.  On radiological examination of the gallbladder appears as a shadow of a pear limited gas formed is very clear.  Sometimes it appears air infiltrating the wall and surrounding tissue.  In the upright position the liquid surface appears in the gallbladder.  CT scan can also reveal the gas.  The form of adequate antibiotic therapy and surgery.