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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.

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