Cody Meissner

Clinical and epidemiologic characteristics of patients referred for evaluation of possible Kawasaki disease

Study objectives (1) To determine those diseases that most often mimic Kawasaki disease (KD) in the United States. (2) To examine the physical findings and laboratory studies that influenced experienced clinicians to exclude the diagnosis of KD. (3) To compare epidemiologic features of patients with KD and patients referred for evaluation of possible KD in whom alternative diagnoses were established. Design: Case comparison study. Setting: Seven pediatric tertiary care centers. Patients: Consecutive sample of 280 patients with KD and 42 comparison patients examined within the first 14 days after onset of fever. Measurements and main results: (1) Infectious diseases, particularly measles and group A β-hemolytic streptococcal infection, most closely mimicked KD and accounted for 35 (83%) of 42 patients in the comparison group. (2) The standard diagnostic clinical criteria for KD were fulfilled in 18 (46%) of 39 patients in whom other diagnoses were established. (3) Patients with KD were significantly less likely to have exudative conjunctivitis or pharyngitis, generalized adenopathy, and discrete intraoral lesions, and more likely to have a perineal distribution of their rash. The patients with KD were also more likely to have anemia and elevated erythrocyte sedimentation rate; leukocyte count 3 /mm 3 and platelet count 3 /mm 3 were significantly less prevalent in patients with KD. (4) Residence within 200 yards of a body of water was more common among KD patients. Conclusions: (1) Measles and streptococcal infection should be excluded in patients examined for possible KD. (2) Laboratory studies that may be useful in discriminating patients with KD from those with alternative diagnoses include hemoglobin concentration, erthyrocyte sedimentation rate, and serum alanine aminotransferase activity. (3) Residence near a body of water may be a risk factor for the development of KD.

Administration of oral acyclovir suppressive therapy after neonatal herpes simplex virus disease limited to the skin, eyes and mouth: Results of a phase I/II trial

BACKGROUND Neonatal herpes simplex virus (HSV) infections limited to the skin, eyes and mouth (SEM) can result in neurologic impairment. A direct correlation exists between the development of neurologic deficits and the frequency of cutaneous HSV recurrences. Thus, the National Institutes of Allergy and Infectious Diseases Collaborative Antiviral Study Group conducted a Phase I/II trial of oral acyclovir therapy for the suppression of cutaneous recurrences after SEM disease in 26 neonates. METHODS Infants < or = 1 month of age with virologically confirmed HSV-2 SEM disease were eligible for enrollment. Suppressive oral acyclovir therapy (300 mg/m2/dose given either twice daily or three times per day) was administered for 6 months. RESULTS Twelve (46%) of the 26 infants developed neutropenia (< 1000 cells/mm3) while receiving acyclovir. Thirteen (81%) of the 16 infants who received drug 3 times per day experienced no recurrences of skin lesions while receiving therapy. In comparison, a previous Collaborative Antiviral Study Group study found that only 54% of infants have no cutaneous recurrences in the 6 months after resolution of neonatal HSV disease if oral acyclovir suppressive therapy is not initiated. In one infant, HSV DNA was detected in the cerebrospinal fluid during a cutaneous recurrence, and an acyclovir-resistant HSV mutant was isolated from another patient during the course of the study. CONCLUSIONS Administration of oral acyclovir can prevent cutaneous recurrences of HSV after neonatal SEM disease. The effect of such therapy on neurologic outcome must be assessed in a larger, Phase III study. As such, additional investigation is necessary before routine use of suppressive therapy in this population can be recommended.

The potential role of bacterial superantigens in the pathogenesis of Kawasaki syndrome

Kawasaki syndrome is an acute multisystem vasculitis of infancy and early childhood associated with high fever, mucocutaneous inflammation, and the development of coronary artery abnormalities. Despite the widely held belief that Kawasaki syndrome is an infectious disease, investigations have failed to identify a causal organism. Previous studies have demonstrated that this illness is associated with marked activation of monocyte/macrophages and the selective expansion of Vβ2- and, less so, of Vβ8.1/8.2-expressing T cells in the peripheral blood from Kawasaki syndrome patients during the acute phase of their illness. These immunologic features are characteristic of diseases that are caused by bacterial toxins which act as superantigens. Staphylococcal enterotoxins and streptococcal exotoxins are prototypic superantigens which stimulate large populations of T cells expressing particular T-cell receptorβ-chain variable (Vβ) gene segments. Using the Vβ2+ T-cell expansion as an “immunologic footprint” for a superantigen, we have extended these observations to the identification and isolation of a novel clone of toxic shock syndrome toxin-1-producingStaphylococcus aureus in the majority of patients with Kawasaki syndrome and streptococcal pyrogenic exotoxin B/streptococcal pyrogenic exotoxin C-producing streptococci in a minority of Kawasaki syndrome patients. Toxic shock syndrome toxin-1, streptococcal pyrogenic exotoxin B, and streptococcal pyrogenic exotoxin C are known to stimulate Vβ2+ T cells. These observations support the hypothesis that the activation of Vβ2+ T cells during the acute phase of Kawasaki syndrome is caused by bacterial superantigen(s).