Abstract: Steven Johnson Syndrome is an inmune disease charactherized by a detachment of the epidermis from dermis. It could be fatal and the pathophysilogy involves a complex hypersensitivity reaction with the participation of T lymphocytes that induce keratinocyte’s apoptosis. The syndrome can be cause by drigs, infections and malignancies. The diagnosis is difficlut due to the abscense of specific manifestations and laboratory tests. There is a genetic predisposition in individuals with certain HLA types.
The disease Overview: Stevens-Jonhson Syndrome (SJS)is an immune disease. The disorder was described as a delay hypersensitivity reaction with epidermal necrosis and the participation of infections, drugs and genetic factors. The clinical expression varies from a slight form to a serious systemic process that may implicate life-threatening complications and death. In spite of the differences in the severity of the manifestations, the etiology, pathophysiology and genetic influence remain the same (Hazim, 200).
The disorder was reported for the first time by Stevens and Chambers in 1922, after observing a couple of boys with fever, diffuse rash and sores in the mouth and ocular mucosa. It was confused with measles. At the beginning of the 90’s after several investigations, the difference between Erythema Multiforme Major SJS was proposed. Further research revealed there were dissimilarities on the cutaneous lesion’s pattern, whereas EMM referred to target raised edematous papules. SJS was characterized by blisters on top of an erythematous or purpuric base ( Mockenhaupt et al. , 2011). Pathophysiology and Etiology:
The development of a hypersensitivity reaction type 4 has been involved in the pathophysiology of the disease. There are groups of patients with certain conditions that lead to a higher risk of SJS: Slow acetylators, immunocompromised, and patients with cerebral neoplasia undergoing radiotherapy with antiepileptic medications. Slow acetylators cannot detoxify drug residues, resulting in a build-up of drug metabolites that may trigger an immune response at the tissue level. This mechanism has been shown in SJS associated with sulfas. The metabolite can also cause toxic effects per se.
Other mechanisms included the production of Tumor Necrosis Factor that boosts the production of cytotoxic T-lymphocytes (CD8+). The mature CD8+ lymphocytes cause tissular damage inducing epidermic necrosis through the discharge of granzyme and perforin. The perforin kills the keratinocytes by forming complex insoluble arrangements. The activation of the cell surface’s receptor (Fas), and the subsequent induction of the caspase system, lead to DNA instability and cell destruction. In SJS, Fas ligand has been found with high levels, and it promotes Fas expression by epidermal cells.
Finally, the apoptosis of the keratinocytes leads to a detachment of the epidermis from the dermis, and the inflammatory process will turn more intense and the progressive necrolysis of the epidermis will be extended ( Mockenhaupt et al. , 2011). Several causal agents have been related with SJS. These factors have been grouped in four categories: Drug induced, infections, Malignancies and Idiopathic. Medications have been established as the most common cause of SJS overall. Among the different groups, antibiotics predominate followed by analgesics, anticonvulsants and gout treatment drugs respectively.
Sulfas, penicillins, ciprofloxacin, carbamazepine and antiretroviral drugs have been described by researchers as the most important agents related with the onset of the toxic epidermal necrolysis (Hazim et al. , 2008). Viral infections have been reported to be associated with SJS: Herpes virus, AIDS, Mumps, coxsackie, Influenza and Mumps. Other agents linked with the reaction have been: Streptococci, Mycoplasma Pneumoniae, Mycobacterium, Coccidium, Histoplasma and Plasmodium (Finkelstein et al . , 2011). Genetic predisposition constituted an important aspect in the occurrence of the disease.
It has been established the role of the Human Leukocyte Antigen with the possibility of developing a drug-induced SJS. For example, HLA-B 1502 has been associated with carbamazepine reactions, and it has been used as a pre-therapy test. Toxic Epydermal Necrolysis induced by sulfonamides has been linked with HLAB7 and HLA-D7 (Phillips et al. , 2011). Ko Tai-Ming et al. (2011) carried out a research where they could demonstrate the role of the T-cell receptor in the pathophysiology of the SJS induced by Carbamazepine in patients with HLA-B1502.
The results of the investigation showed an 84 percent of the patients that developed carbamazepine induced SJS were HLA-B1502 positive in the antigen presenting cells that will activate the TCR of CD8 lymphocytes. Diagnosis and treatment: The disease is often misdiagnosed. The onset of symptoms like fever, sorethorat, and malaise may be interpreted as an infection and treated with antibiotic, which can aggravate the course. The laboratory tests are not specific and do not confirm the disorder. The skin biopsy shows the epidermal detachment and the presence of bullas.
The high mobility group one protein (HMGB1) has turned recently in an important instrument for the diagnosis (Nakajima et al. , 2011). The management is focused to treat the skin lesions as burns with the correspondent supportive treatment, infection precautions and fluid’s therapy. Antibiotics and immunosuppressive agents should be considered as well as cyclophosphamide, cyclosporine and immunotherapy (Hazim et al. , 2008). Conclusions: Steven Jonhson Syndrome is a life-threatening condition characterized by a detachment of the epidermis from the dermis.
The pathophysiology involves a complex immunologic mechanism consistent in a hypersensitivity reaction with the proliferation of cytotoxic lymphocytes and the subsequent stimulation of the apoptosis mechanism. Medications and infection constitute the most common factors associated with the etiology of the disease and there is a predisposition in certain HLA genotypes. REFERENCES Finkelstein, Y. Y. , Soon, G. S. G. S. , Acuna, P. P. , George, M. M. , Pope, E. E. , Ito, S. S. , . . . Garcia-Bournissen, F. (2011). Recurrence and outcomes of stevens-johnson syndrome and toxic epidermal necrolysis in children. Pediatrics, 128(4), 723-728.
Retrieved from http://ezproxy. fiu. edu/login? url=http://search. proquest. com/docview/896205631? accountid=10901 Hazim, R. , Ibrahim, O. , & Hazim, M. (2008). Stevens-Johnson syndrome: pathogenesis, diagnosis, and management. Annals of Medicine, 40(2), 129-138. Retrieved June 7, 2012 from http://www. ncbi. nlm. nih. gov/pubmed/18293143 Ko, T. , Chung, W. , Wei, C. , Shih, H. , Chen, J. et al. (2011, December). Shared and restricted T- cell receptor use is crucial for carbamazepine-induced Stevens-Johnson syndrome. The Journal of allergy and clinical immunology 128. 6, 128(6), 1266-1276. Retrieved July 3, 2012 from http://www.
ncbi. nlm. nih. gov/pubmed/21924464? dopt=AbstractPlus Mockenhaupt, M. M. (2011). The current understanding of stevens-johnson syndrome and toxic epidermal necrolysis. Expert Review of Clinical Immunology, 7(6), 803-13; quiz 814-5. Retrieved June 2 from http://ezproxy. fiu. edu/login? url=http://search. proquest. com/docview/900631464? accountid=10901 Nakajima, S. S. , Watanabe, H. H. , Tohyama, M. M. , Sugita, K. K. , Iijima, M. M. , Hashimoto, K. K. , . . . Kabashima, K. K. (2011). High-mobility group box 1 protein (HMGB1) as a novel diagnostic tool for toxic epidermal necrolysis and stevens-johnson syndrome.
United States: Retrieved from http://ezproxy. fiu. edu/login? url=http://search. proquest. com/docview/893270838? accountid=10901 Paiz, J. M. , Angeli, E. , Wagner, J. , Lawrick, E. , Moore, K. , Anderson, M. , & Soderlund, L. (2012, May 30). General Format. InThe Purdue Online Writing Lab. Retrieved July 12, 2012, from http://owl. english. purdue. edu/owl/resource/560/01/. Phillips, E. J. E. J. , & Mallal, S. A. S. A. (2011). HLA-B*1502 screening and toxic effects of carbamazepine. United States: Retrieved from http://ezproxy. fiu. edu/login? url=http://search. proquest. com/docview/884423149? accountid=10901