Effects of CXCR3 signaling on development of fatal encephalitis and corneal and periocular skin disease in HSV-infected mice are mouse-strain dependent.

PURPOSE: The host inflammatory response to ocular infection with herpes simplex virus (HSV) can be either protective, with disease-free survival, or it can promote diseases such as HSV corneal disease (or herpes stromal keratitis [HSK] in humans) and encephalitis (HSE), depending on mouse strain. The role of CXCR3 chemokine signaling in HSV-induced central nervous system (CNS) inflammation and corneal disease was evaluated, and responses in genetically susceptible and resistant strains of mice were contrasted. METHODS: Resistant C57BL/6J (B6) and susceptible 129S6 (129) mice were given monoclonal antibodies (mAbs) to neutralize the CXCR3 ligands monokine induced by interferon-gamma (MIG, CXCL9) and interferon inducible protein-10 (IP-10, CXCL10) during HSV infection. In addition, the development of HSV disease was monitored in CXCR3-null mutant mice derived from resistant (B6) and susceptible (BALB/c) strains. Inflammatory cells infiltrating the cornea and brain stem were isolated and stained for flow cytometric analysis. RESULTS: MIG and IP-10 were induced in nervous system tissue after HSV inoculation by the corneal route. HSV-infected 129 mice treated with MIG- or IP-10-neutralizing mAbs showed significantly enhanced survival compared with mice treated with control isotype antibody, whereas survival of the B6 mice was unaltered. Similarly, greater survival was observed for BALB.CXCR3(-/-) mice compared with control BALB/c mice. Reduced CNS inflammation was documented that extended to the cornea, such that HSV corneal disease severity was reduced in susceptible BALB.CXCR3(-/-). In contrast, although survival of B6 and B6.CXCR3(-/-) mice was indistinguishable, B6.CXCR3(-/-) mice developed more severe corneal and periocular skin disease. CONCLUSIONS: The effects of CXCR3 signaling in HSV infection are strongly dependent on mouse strain.

Life-threatening cutaneous viral diseases.

Most viral infections present with a cutaneous eruption that in the greater majority of cases is self-healing. Only in rare instances is the eruption accompanied by constitutional symptoms, and even more rarely, irreversible damage may occur or death may ensue. As with other infectious diseases, prognosis depends on the status of immunologic surveillance. Immunodepressed patients are, therefore, at the greatest risk. It has become more evident, however, that even in immunocompetent patients, eruption that were considered not long ago as benign diseases may in fact result in complications and even death. The introduction of polymerase chain reaction assays has allowed us to attribute conditions to a specific viral infection, which in the past was not possible. Therefore, dermatologists may come across, directly or during consultation, patients presenting with skin lesions that may be related to a viral disease and may lead to possible severe systemic complications. Dermatologists, however, may not be prepared for such developments, and thus the goal of this article is to suggest some of the possibilities. Discussing all the viral diseases that may present with cutaneous manifestations would be cumbersome; thus this article will be limited to the diseases that may endanger the life of a patient who is seeking dermatologic advice and who does not seem to have, at first sight, severe systemic involvement.

Progressive varicella presenting with pain and minimal skin involvement in children with acute lymphoblastic leukemia.

PURPOSE: Here we report the experience at the Children's Hospital of Pittsburgh (CHP) with varicella zoster virus (VZV) in children with acute lymphoblastic leukemia (ALL). This record review was prompted by a patient with ALL who died suddenly of varicella hepatitis within 24 hours of presentation with a single skin lesion. METHODS: We reviewed the medical records of children diagnosed with ALL at the CHP from January 1984 through December 1993, who subsequently developed VZV infection. RESULTS: Of 294 patients aged 0 to 15 years, 41 (14%) were identified as having had 42 episodes of VZV infection. Twenty patients (49%) had received prophylaxis with varicella zoster immunoglobulin (VZIG), and all 39 patients in whom the diagnosis was made premortem were treated with acyclovir. Twenty-nine of the 42 cases (70%) had disease limited to the skin. Thirteen cases (30%) had extracutaneous involvement, and five of these episodes (12% of all cases) ended in death. Risk factors for progressive varicella included age greater than 6 years and intensive immunosuppressive therapy at the time of exposure. Six of eight patients with progressive varicella, including two who died, had received VZIG. The clinical presentation in 10 of 13 patients with progressive disease and in four of five patients who died was dominated by severe abdominal and/or back pain. In seven cases, these symptoms preceded the development of skin lesions by several days, and in six patients were associated with extensive involvement of the spleen by varicella, as demonstrated histopathologically by the presence of Howell-Jolly bodies on peripheral-blood smear or radiographically. No patient with uncomplicated varicella was reported to have had premonitory pain. CONCLUSION: Recognition of these prodromes and suspicion of varicella even in the absence of skin lesions and even in children with a history of prior disease or VZIG administration should prompt early diagnostic and therapeutic measures.