- Email: [email protected]
Instructive case report
45 Infectious Diseases Newsletter
anterior pituitary cells and to growth hormone and had growth failure while another strain developed antibodies to pancreatic islet cells, functionally resulting in "adult onset" diabetes. Cells of the affected endocrine tissues had normal growth and replicative activity but did not produce normal amounts of the respective hormones (a differentiated function). 9 One possible explanation for these observations and sequelae is that in an approprlate host, antibodies are produced to antigens which are shared by the virus (i.e., reovirus or LCM) and the hormone. Another possibility is that i m m u h e responses to virus altered c e l l s u r f a c e antigens led to th9 inhibition of differentiated function5 ~ That is, hormone production was stemmed despite normalcy of the basic cell structure and other functions. The consequences of virus infections in some patients may be altered function of highly specialized tissues without the overt injury usually expected in these diseases. It is conceivable that human virus infections can cause autoimmune responses such as is seen in some forms of thrombocytopenic purpura that follow specific virus infections. Many of the human endocrinopathies are associated with a plethora of autoimmune antibodies and may prove a fertile field for research in viral etiology. The association of mumps and Coxsackie virus infections with later onset of juvenille diabetes mellitis may be a case in point. Alternatively, more subtle virus influence may be operative resulting in functional incapacity but gross structural integrity. James F. Jones, M.D. Associate Professor Department of Pediatrics Arizona H e a l t h S c i e n c e s Center ..... References i.
2.
Haspel MV, Onodera T, Prabhakar BS, Horita M, Suzuki H, Notkins AL, Virus induced autoimmunity: Monoclonal antibodies that react with endocrine tissues. Science 220:304, 1983. Oldstone MBA, Virus-induced alterations of differentiated functions. Presented at the Fed Soc Experim Biol Meeting, Chicago, IL, April 12, 1983.
INSTRUCTIVE CASE REPORT The patient is a 20-month-old white male who was within normal limits until one week prior to admission when he developed
cough, wheezing, and fever. He was diagnosed as having bronchiolitis and was begun on oral metaproterenol sulfate. Cultures for viruses, mycoplasmae and chlamydia, and acute serum antibody titers were obtained as part of an ongoing viral respiratory investigation. His symptoms improved in two days and all medication was stopped. Three days prior to admission he was noted to have blotchiness of the skin that developed into an erythematou s rash. Two days prior to admission he was febrile to 103OF and his rash spread over the extremities. He became more irritable and his appetite decreased. On the day of admission, he suddenly developed blisters and bullae over his extremities, penis, scrotum, and perianal region. The child has been on sulfasoxasole as prophylaxis for otitis media (500 mg b.i.d, for one month). He had no known allergies and had experienced no rash with sulfa drugs in the past. His immunizations were up to date. On physical examination, he had: (i) a confluent maculopapular erythematous rash on his extremities and to a lesser extent on head and trunk; (2) iris (target) lesions were present; (3) there were scattered bullae; (4) the conjunctivae were hyperemic; (5) the tympanic membranes were distorted by clear fluid and were retracted; (6) there was moderate edema of the nasal mucosa; and (7) his mouth was diffusely erythematous with vesicles on the buccal mucosa and soft palate. A diagnosis of Stevens Johnson Syndrome (SJS) was made. He was given ~ supportive care including intravenous fluids and a course of steroids was instituted. No antibiotics were administered. Analysis, Comment,
and Outcome
Stevens-Johnson syndrome (SJS) has been associated with many infectious and noninfectious processes. The most common noninfectious associations are with drugs, especially with sulfonamides, penicillin, and anticonvulsants. Other noninfectious causes include ulcerative colitis, systemic lupus erythematosis, Kawasaki disease, and certain malignancies. Many specific infectious agents have Oeen associated with SJS; best-known of ~hich is Mycoplasma spp. Herpes simplex ~iruses have been recovered from bullae in patients with SJS and injection of inactivated HSV antigen intradermally has resulted in recurrence of erythema multiforme. Other viruses including varicella-zoster, variola, enteroviruses,
9 1983 by Elsevier Science Publishing Co., Inc.
46 Infectious Diseases Newsletter
mumps, and Epstein-Barr virus have been associated with SJS. Bacterial associations include Salmonella, syphilis, pseudomonas, and mycobacteria. Both coccidioidomycosis and histoplasmosis can cause SJS. This is only a partial list of suspected causes. The Stevens-Johnson syndrome should be considered a severe form of erythema multiforme characterized by bullae formation and systemic symptoms. If one keeps in mind the commonality with the erythema multlforme spectrum, less confusion will result between a diagnosis of SJS and other mucocutaneous conditions. Even in severe SJS, one can usually fifid discrete iris or target lesions even though the centers of some~.Qf these lesions may have become vesiculaf~or bullous. By contrast, Staphylococcal Scalded Skin syndrome tends toward confluency without discrete lesions and Kawasaki disease, although occasionally seen with a typical erythema multiforme rash, does not typically have blisters or bullae. Prodromal symptoms of fever, malaise, cough and multiple other symptoms often precede the onset of eruption in SJS by as long as 1 to 14 days. These symptoms in many cases reflect the prodromal infection which preciptiates SJS. The eruption itself has an explosive course. Consequently, seldom does one observe typical erythema multiforme progress into SJS. Rather, there is a very rapid development of numerous mucocutaneous lesions over a short period of time, some of which retain sufficient characteristics to identify the erythema multiforme spectrum. If the diagnosis is in doubt, a skin biopsy may support clinical suspicion. Mucocutaneous involvement is the most prominent finding but significant pulmonary and airway disease may occur. Diarrhea, polyarthritis and renal failure also occur in some patients. Treatment with corticosteroids remains controversial. 3 There are no controlled studies which demonstrate either efficacy or harm. Some investigators s u g g e s t t h a t steroid treated patients have a less favorable outcome; but those patients selected for steroid therapy in the past may have had more serious disease at the initiation of treatment. Serious bacterial superinfection can be a fatal complication in SJS, hence patients treated with steroids must be closely observed for signs of infection and appropriate therapy instituted promptly. The role of treatment with antibiotics appears clear. Most experts recommend that antibiotics not be used "prophylactically" (i.e., in the absence of obvious signs of bacterial infection). Instead the patient should be closely observed
for early signs and have appropriate specimens taken for culture. Antibiotics should be chosen appropriate to the specific infection present. Most patients with SJS recover without significant long term sequelae. However, death can occur and approximates 5% of a l l reported patients. Ocular sequelae are common and blindness has been frequently reported. 4 The full range of potential complications of SJS was demonstrated in a child treated in our hospital who suffered blindness in one eye resulting in enucleation, hypernatremic dehydration with hypertension, urinary retention requiring suprapubic catheterization, pseudomonas pneumonia with tension pneumothorax, perforation of the tympanic membrane, shedding of all the fingernails and toenails resulting in permanent anonychia and permanent oral mucosal scarring. Fortunately, this degree of morbidity is uncommon. The child herein reported is expected to recover fully without sequelae. Allan D. Friedman, M.D. Adjunct Assistant Professor Department of Pediatrics Arizona Health Sciences Center Ronald C. Hansen, M.D. Assistant Professor Department of Internal Medicine Arizona Health Sciences Center References i.
2. 3.
4.
Goldsmith DD, The erythema syndromes: Erythema multiforme and the Stevens Johnson syndrome, in Practice of Pediatrics, 8(70):1, 1982-83. Ginsburg G , Stevens Johnson syndrome in children. Pediatr Infect Dis 1(3):155, 1982. Rasmussen JE, Erythema multiforme in children - response to treatment with systemic corticosteroids. Br J Dermatol 95:181, 1976. Howard GH, The Stevens-Johnson syndrome: Occular prognosis and treatment. Am J Ophthalmol 55:893, 1963.
INTERNATIONAL NOTES London: More than 400 persons developed hepatitis in 1980-1981 in southeastern England. Of these, 42.6% reported eating cockles compared to 17.5% of controls, in a case-controlled study. O'Mahony et al conclude that the shellfish had been improperly processed (steamed 1 to 2 minutes and boiled for 4 minutes) and were probably the source for some patients. Lancet i:518, 1983.
9 1983 by Elsevier Science Publishing Co., Inc.
anterior pituitary cells and to growth hormone and had growth failure while another strain developed antibodies to pancreatic islet cells, functionally resulting in "adult onset" diabetes. Cells of the affected endocrine tissues had normal growth and replicative activity but did not produce normal amounts of the respective hormones (a differentiated function). 9 One possible explanation for these observations and sequelae is that in an approprlate host, antibodies are produced to antigens which are shared by the virus (i.e., reovirus or LCM) and the hormone. Another possibility is that i m m u h e responses to virus altered c e l l s u r f a c e antigens led to th9 inhibition of differentiated function5 ~ That is, hormone production was stemmed despite normalcy of the basic cell structure and other functions. The consequences of virus infections in some patients may be altered function of highly specialized tissues without the overt injury usually expected in these diseases. It is conceivable that human virus infections can cause autoimmune responses such as is seen in some forms of thrombocytopenic purpura that follow specific virus infections. Many of the human endocrinopathies are associated with a plethora of autoimmune antibodies and may prove a fertile field for research in viral etiology. The association of mumps and Coxsackie virus infections with later onset of juvenille diabetes mellitis may be a case in point. Alternatively, more subtle virus influence may be operative resulting in functional incapacity but gross structural integrity. James F. Jones, M.D. Associate Professor Department of Pediatrics Arizona H e a l t h S c i e n c e s Center ..... References i.
2.
Haspel MV, Onodera T, Prabhakar BS, Horita M, Suzuki H, Notkins AL, Virus induced autoimmunity: Monoclonal antibodies that react with endocrine tissues. Science 220:304, 1983. Oldstone MBA, Virus-induced alterations of differentiated functions. Presented at the Fed Soc Experim Biol Meeting, Chicago, IL, April 12, 1983.
INSTRUCTIVE CASE REPORT The patient is a 20-month-old white male who was within normal limits until one week prior to admission when he developed
cough, wheezing, and fever. He was diagnosed as having bronchiolitis and was begun on oral metaproterenol sulfate. Cultures for viruses, mycoplasmae and chlamydia, and acute serum antibody titers were obtained as part of an ongoing viral respiratory investigation. His symptoms improved in two days and all medication was stopped. Three days prior to admission he was noted to have blotchiness of the skin that developed into an erythematou s rash. Two days prior to admission he was febrile to 103OF and his rash spread over the extremities. He became more irritable and his appetite decreased. On the day of admission, he suddenly developed blisters and bullae over his extremities, penis, scrotum, and perianal region. The child has been on sulfasoxasole as prophylaxis for otitis media (500 mg b.i.d, for one month). He had no known allergies and had experienced no rash with sulfa drugs in the past. His immunizations were up to date. On physical examination, he had: (i) a confluent maculopapular erythematous rash on his extremities and to a lesser extent on head and trunk; (2) iris (target) lesions were present; (3) there were scattered bullae; (4) the conjunctivae were hyperemic; (5) the tympanic membranes were distorted by clear fluid and were retracted; (6) there was moderate edema of the nasal mucosa; and (7) his mouth was diffusely erythematous with vesicles on the buccal mucosa and soft palate. A diagnosis of Stevens Johnson Syndrome (SJS) was made. He was given ~ supportive care including intravenous fluids and a course of steroids was instituted. No antibiotics were administered. Analysis, Comment,
and Outcome
Stevens-Johnson syndrome (SJS) has been associated with many infectious and noninfectious processes. The most common noninfectious associations are with drugs, especially with sulfonamides, penicillin, and anticonvulsants. Other noninfectious causes include ulcerative colitis, systemic lupus erythematosis, Kawasaki disease, and certain malignancies. Many specific infectious agents have Oeen associated with SJS; best-known of ~hich is Mycoplasma spp. Herpes simplex ~iruses have been recovered from bullae in patients with SJS and injection of inactivated HSV antigen intradermally has resulted in recurrence of erythema multiforme. Other viruses including varicella-zoster, variola, enteroviruses,
9 1983 by Elsevier Science Publishing Co., Inc.
46 Infectious Diseases Newsletter
mumps, and Epstein-Barr virus have been associated with SJS. Bacterial associations include Salmonella, syphilis, pseudomonas, and mycobacteria. Both coccidioidomycosis and histoplasmosis can cause SJS. This is only a partial list of suspected causes. The Stevens-Johnson syndrome should be considered a severe form of erythema multiforme characterized by bullae formation and systemic symptoms. If one keeps in mind the commonality with the erythema multlforme spectrum, less confusion will result between a diagnosis of SJS and other mucocutaneous conditions. Even in severe SJS, one can usually fifid discrete iris or target lesions even though the centers of some~.Qf these lesions may have become vesiculaf~or bullous. By contrast, Staphylococcal Scalded Skin syndrome tends toward confluency without discrete lesions and Kawasaki disease, although occasionally seen with a typical erythema multiforme rash, does not typically have blisters or bullae. Prodromal symptoms of fever, malaise, cough and multiple other symptoms often precede the onset of eruption in SJS by as long as 1 to 14 days. These symptoms in many cases reflect the prodromal infection which preciptiates SJS. The eruption itself has an explosive course. Consequently, seldom does one observe typical erythema multiforme progress into SJS. Rather, there is a very rapid development of numerous mucocutaneous lesions over a short period of time, some of which retain sufficient characteristics to identify the erythema multiforme spectrum. If the diagnosis is in doubt, a skin biopsy may support clinical suspicion. Mucocutaneous involvement is the most prominent finding but significant pulmonary and airway disease may occur. Diarrhea, polyarthritis and renal failure also occur in some patients. Treatment with corticosteroids remains controversial. 3 There are no controlled studies which demonstrate either efficacy or harm. Some investigators s u g g e s t t h a t steroid treated patients have a less favorable outcome; but those patients selected for steroid therapy in the past may have had more serious disease at the initiation of treatment. Serious bacterial superinfection can be a fatal complication in SJS, hence patients treated with steroids must be closely observed for signs of infection and appropriate therapy instituted promptly. The role of treatment with antibiotics appears clear. Most experts recommend that antibiotics not be used "prophylactically" (i.e., in the absence of obvious signs of bacterial infection). Instead the patient should be closely observed
for early signs and have appropriate specimens taken for culture. Antibiotics should be chosen appropriate to the specific infection present. Most patients with SJS recover without significant long term sequelae. However, death can occur and approximates 5% of a l l reported patients. Ocular sequelae are common and blindness has been frequently reported. 4 The full range of potential complications of SJS was demonstrated in a child treated in our hospital who suffered blindness in one eye resulting in enucleation, hypernatremic dehydration with hypertension, urinary retention requiring suprapubic catheterization, pseudomonas pneumonia with tension pneumothorax, perforation of the tympanic membrane, shedding of all the fingernails and toenails resulting in permanent anonychia and permanent oral mucosal scarring. Fortunately, this degree of morbidity is uncommon. The child herein reported is expected to recover fully without sequelae. Allan D. Friedman, M.D. Adjunct Assistant Professor Department of Pediatrics Arizona Health Sciences Center Ronald C. Hansen, M.D. Assistant Professor Department of Internal Medicine Arizona Health Sciences Center References i.
2. 3.
4.
Goldsmith DD, The erythema syndromes: Erythema multiforme and the Stevens Johnson syndrome, in Practice of Pediatrics, 8(70):1, 1982-83. Ginsburg G , Stevens Johnson syndrome in children. Pediatr Infect Dis 1(3):155, 1982. Rasmussen JE, Erythema multiforme in children - response to treatment with systemic corticosteroids. Br J Dermatol 95:181, 1976. Howard GH, The Stevens-Johnson syndrome: Occular prognosis and treatment. Am J Ophthalmol 55:893, 1963.
INTERNATIONAL NOTES London: More than 400 persons developed hepatitis in 1980-1981 in southeastern England. Of these, 42.6% reported eating cockles compared to 17.5% of controls, in a case-controlled study. O'Mahony et al conclude that the shellfish had been improperly processed (steamed 1 to 2 minutes and boiled for 4 minutes) and were probably the source for some patients. Lancet i:518, 1983.
9 1983 by Elsevier Science Publishing Co., Inc.