Recurrent parvovirus B19 viremia resulting in two episodes of hemophagocytic lymphohistiocytosis

BACKGROUND: Hemophagocytic lymphohistiocytosis (HLH) is a hyperinflammatory condition with uncontrolled activation of lymphocytes and macrophages. Besides a primary (genetic) form, HLH can also be triggered by malignant, autoimmune and infectious diseases. HLH recurrences are rarely described, usually only in primary HLH. Parvovirus B19 (PVB19) Infection is one of the rare and rather benign causes of HLH. Since the infection usually results in long-lasting immunity, recurrent viremia is very uncommon. CASE PRESENTATION: We report an unusual case of a young female with recurrent PVB19 infection that led to repeated episodes of HLH. The first episode occurred at the age of 25 years with a three-week history of high fever and nonspecific accompanying symptoms. The diagnosis of HLH was confirmed by HLH-2004 criteria and HScore, PVB19 viremia was detected as underlying cause. Following guideline-based therapy, the patient was symptom-free for one year, before similar symptoms recurred in a milder form. Again, PVB19 was detected and HLH was diagnosed according to HScore. After successful treatment and a nine-month symptom-free interval, a third phase of hyperinflammation with low PVB19 viremia occurred; this time, treatment with a corticosteroid and intravenous immunoglobulin was initiated before the presence of clear diagnostic criteria for HLH. No further events occurred in the following three years. CONCLUSIONS: In the case of our patient, the recurrent viremia triggered three episodes of hyperinflammation, two of which were clearly diagnosed as HLH. To our knowledge, this is the first published case of recurrent HLH due to PVB19 infection. Therefore, the case gives new insights in triggering mechanisms for HLH

Social Rank Influences the Distribution of Blood Leukocyte Subsets in Female Growing Pigs

The effect of high (DOM) and low (SUB) social rank on blood immune variables was examined in female  growing pigs. Pigs were mixed with unfamiliar pigs at 9 weeks of age and kept in stable groups of 4 pigs for  5 weeks. Social rank was determined using a feeding competition test. SUB pigs showed reduced growth  as compared to DOM pigs confirming their lower social status. Blood was sampled for immunological assessments  immediately before grouping the pigs and again after the 5 weeks of social housing. White Blood  Cell (WBC) counts, percentage of CD4 positive cells (CD4+), percentage of CD8 positive cells (CD8+), percentage  of swine leukocyte antigen II (SLAII) carrying cells, LPS-stimulated Toll-like Receptor 4 (TLR4)  expression, and LPS-stimulated tumor necrosis factor-alpha (TNF-) responsiveness were determined at  both times. IgG and IgM concentrations were measured following the 5 weeks of social housing only.  From the WBC counts it was found that the percentage of neutrophils was higher in SUB pigs and the neutrophil  to lymphocyte ratio was higher in DOM pigs. The percentage of CD4+ cells decreased with time in  both DOM and SUB pigs, but only significantly in SUB pigs. The percentage of CD8+ cells was higher in  SUB pigs than in DOM pigs and decreased with time in both DOM and SUB pigs. In addition, SUB pigs  had a higher ex vivo TNF- responsiveness as compared to DOM pigs. Both the percentage of SLAII carrying  cells and LPS-stimulated TLR4 expression increased with time, but here no significant effect of social  rank was found. In addition, neither IgG nor IgM concentrations showed any relationship with social rank.  The findings indicate that social rank influences the distribution of blood leukocyte subsets in female growing  pigs, suggesting that the pig would be a good model for investigating the effects of long-term immunomodulation  on health.