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Intravenous Immunoglobulin Therapy forStevens-Johnson Syndrome ALLAN S. BRETT, MD, DYANNA PHILLIPS, and ANNETTE W. LYNN, MD, Columbia, SC ABSTRACT: Stevens-Johnson syndrome (SJS) is an acute mucocutaneous disorder that can be
associated with considerable morbidity. Several previous reports, all involving either adults
with acquired immunodeficiency syndrome or children , suggest that intravenous
immunoglobulin may be an effective treatment for SJS. We report a case of SJS in an
immunocompetent adult whose condition improved dramatically after therapy with
intravenous immunoglobulin.

STEVENS-JOHNSON SYNDROME (SJS) is an uncom- moderate distress, with drooling and drainage from mon mucocutaneous disorder usually attributed crusted lesions around the mouth and lips. She had to a drug exposure or infection. Treatment is injected conjunctivae with exudates. The tongue wascoated with white plaques, and the gums and buccal primarily supportive; some authors advocate mucosa were ulcerated. There was uvular edema and ton- corticosteroid therapy,1 while others argue sillar enlargement without exudates. An erythematous against it,2 and few data support other therapeu- cutaneous eruption consisting of confluent patches and tic modalities. Administration of intravenous plaques extended from neck to umbilicus, but spared the immunoglobulin for SJS has been reported in extremities. All blood test results were normal, and throatand blood cultures obtained on admission were negative three pediatric cases3,4 and in two adult cases related to AIDS,5 but not for an immunocompe- Methylprednisolone (125 mg intravenously [IV] every 6 tent adult. We report the case of a 27-year-old hours) and diphenhydramine (25 mg intramuscularly immunocompetent woman successfully treated every 6 hours) were started. Because of high fever, systemic with intravenous immunoglobulin for SJS asso- toxicity, and inability to exclude sepsis on admission, the ciated with azithromycin and trimethoprim-sul- patient received a single dose of IV ceftriaxone. Duringher first 48 hours in the hospital, bullous and necrotic le- sions of the skin developed. An ophthalmologist noted dif-fuse corneal ulceration. The oral involvement progressed, CASE REPORT
with increasing odynophagia, hypersalivation, and erosive A 27-year-old woman was admitted with dysphagia, stomatitis. A skin biopsy confirmed the eruption as ery- fever, erosive stomatitis with drooling, and an erythema- tous, pruritic cutaneous eruption. Four days before admis- On the third hospital day, there were additional necrotic sion, sore throat and fever had developed. She went to an plaques and patches with bullae at areas of skin contact. A emergency department at another hospital and was given dermatologist recommended discontinuing all systemic azithromycin; the pharynx was not cultured. Two days medications (including methylprednisolone, of which she later, the patient had generalized pruritus and conjunctivi- had received 6 doses by that time) and giving a dose of IV tis. She returned to the emergency department and immunoglobulin (Polygam) at 1 g/kg (total dose, 60 g).
azithromycin therapy was discontinued. The next day, she On day 5, there was minimal improvement, and a second came to our emergency department with a truncal rash, infusion of 60 g was given. Within 24 hours of the second coated tongue, fever, and progressive dysphagia, and was dose, the skin and mucous membrane lesions improved admitted with a diagnosis of presumed drug reaction to dramatically. The patient was discharged on day 14. One azithromycin. In addition, she had taken trimethoprim-sul- year later, she remained well with no recurrences. famethoxazole twice daily for several days for a urinaryinfection 14 days before admission. She had no known DISCUSSION
The etiology of SJS is frequently unknown, Blood pressure was 102/84 mm Hg, pulse rate 150/min but many cases are associated with recent drug and regular, and temperature 103.4° F. The patient was in exposure or infection with pathogens such asherpes simplex virus or Mycoplasma pneumoniae. From the Divisions of General Internal Medicine and Our patient took azithromycin several days Dermatology, Department of Medicine, University of South before the eruption and trimethoprim-sul- Carolina School of Medicine, Columbia.
famethoxazole about 2 weeks before the erup- Correspondence to Allan S. Brett, MD, University of South tion, without documentation of an infectious Carolina School of Medicine, Department of Medicine, TwoMedical Park, Suite 502, Columbia, SC 29203.
agent at either time. While the close temporal March 2001 • SOUTHERN MEDICAL JOURNAL • Vol. 94, No. 3 relationship suggests that azithromycin may be Clinicians should be aware of several impor- responsible in this case, a role for trimetho- tant caveats about the use of intravenous im- prim-sulfamethoxazole or infection remains munoglobulin. First, it is expensive—currently possible. Sulfonamides are frequently associ- $50/g to $60/g in our hospital pharmacy.
ated with SJS, but we are unaware of previously Second, it is occasionally associated with serious reported cases of azithromycin-associated SJS.
toxicity, including renal failure, aseptic menin- Treatment options for SJS are limited and gitis, and anaphylaxis; hematologic and derma- controversial.2 Corticosteroids are commonly tologic adverse effects have also been de- used,1 but our patient had no obvious early scribed.10 Third, as a human plasma product it response to high-dose corticosteroids. Case carries a potential risk for transmission of infec- reports describe the use of cyclosporine A for severe toxic epidermal necrolysis (TEN),6 a In conclusion, to our knowledge this is the disorder considered by some authorities to be first reported case of an apparent response to on a spectrum with SJS.7 A recent report docu- ments that early withdrawal of a drug causing competent adult with SJS. Because we cannot be SJS or TEN—particularly a drug with a short certain that the patient’s response was solely or partially due to intravenous immunoglobulin, We found three reports of therapy with in- more experience is necessary before one can travenous immunoglobulin for SJS. Moudgil et assume with confidence that this therapy favor- al3 described two children with SJS associated ably alters the natural history of SJS.
with cefixime, and Amato et al4 described achild with phenobarbital-associated SJS. Sanwoet al5 reported two cases of SJS in adults with References
AIDS, after exposure to dapsone in one and 1. Patterson R, Miller M, Kaplan M, et al: Effectiveness of early trimethoprim-sulfamethoxazole and sulfadi- therapy with coritcosteroids in Stevens-Johnson syndrome: azine in the other. Among these five patients, experience with 41 cases and a hypothesis regarding patho-genesis. Ann Allergy 1994; 73:27-34 one received a single large dose of intravenous 2. Roujeau JC, Stern RS: Severe adverse cutaneous reactions immunoglobulin (2 g/kg), and the other four to drugs. N Engl J Med 1994; 331:1272-1285 received multiple smaller doses (0.4 to 0.5 3. Moudgil A, Porat S, Brunnel P, et al: Treatment of Stevens- g/kg). In addition, Swiss researchers recently Johnson syndrome with pooled human intravenous im-mune globulin. Clin Pediatr 1995; 34:48-51 described 10 patients with TEN treated with 4. Amato GM, Travia A, Ziino O: The use of intravenous high- intravenous immunoglobulin.9 In each of these dose immunoglobulins (IVIG) in a case of Stevens-Johnson cases, as in our case, clinical improvement ap- syndrome. Pediatr Med Chir 1992; 14:555-556 peared temporally related to immunoglobulin 5. Sanwo M, Nwadiuko R, Beall G: Use of intravenous immuno- globulin in the treatment of severe cutaneous drug reactions therapy. However, it remains possible that our in patients with AIDS. J Allergy Clin Immunol 1996; 98:1112- patient’s improvement was spontaneous or due 6. Arevalo JM, Lorente JA, Gonzalez-Herrada C, et al: Treat- ment of toxic epidermal necrolysis with cyclosporin A. J Although the pathogenesis of SJS is not com- pletely understood, considerable evidence indi- 7. Bastuji-Garin S, Rzany B, Stern RS, et al: Clinical classifica- cates that it is an immune-mediated disorder.2,5 tion of cases of toxic epidermal necrolysis, Stevens-Johnson Intravenous immunoglobulin has a number of syndrome, and erythema multiforme. Arch Dermatol 1993;129:92-96 immunomodulatory effects, including blockade 8. Garcia-Doval I, LeCleach L, Bocquet H, et al: Toxic epider- of reticuloendothelial Fc receptors, inhibition mal necrolysis and Stevens-Johnson syndrome: does early of complement-mediated damage, modulation withdrawal of causative drugs decrease the risk of death?Arch Dermatol 2000; 136:323-327 of cytokines, and neutralization of circulating 9. Viard I, Wehrli P, Bullani R, et al: Inhibition of toxic epider- autoantibodies or antigens.10 Precisely which of mal necrolysis by blockade of CD95 with human intra- these effects are primarily operative during venous immunoglobulin. Science 1998; 282:490-493 intravenous immunoglobulin therapy for SJS is 10. Jolles S, Hughes J, Whittaker S: Dermatological uses of high-dose intravenous immunoglobulin. Arch Dermatol 1998; Brett et al • IV IMMUNOGLOBULIN THERAPY FOR SJS


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