Israel Medical Association Journal

Serum sickness is an immune-complex-mediated hypersensitivity reaction that classically presents with fever, rash, polyarthritis, or poly arthralgias. Damage is caused by formation or deposition of antigen-antibody complexes in vessels or tissues. Deposition of immune complexes causes complement activation and/or recruitment of neutrophils by interaction of immune complexes with Fc immunoglobulin G receptors. The condition was first recognized as an entity in the early 1900s in patients who had received heterologous antisera, which was historically used to treat infectious diseases. The symptoms typically occur one to two weeks after exposure to an offending agent and resolve within several weeks of discontinuation [1].

Background: Evaluation of mismatch repair (MMR) deficiency is conducted via immunohistochemistry or by microsatellite instability (MSI) analysis. Heterogeneous immunohistochemistry staining for MMR proteins may show different patterns; however, according to current guidelines, all of those patterns should be interpreted as MMR proficient. This conclusion might lead to false negative results because although most cases of heterogeneity stem from technical factors and biological variability, other types of heterogeneity represent true MMR deficiency.

Objectives: To identify a unique heterogeneity pattern that is associated with true MMR loss.

Methods: We analyzed 145 cases of colorectal carcinoma. Immunohistochemistry staining for MLH1, PMS2, MSH2, and MSH6 were performed. We defined geographic heterogeneity as areas of tumor nuclear staining adjacent to areas of loss of tumor nuclear staining with intact staining in the surrounding stroma. All cases were evaluated for the presence of geographic heterogeneity. In addition, 24 cases were also evaluated by MSI testing.

Results: Of the 145 cases, 24 (16.5%) were MMR deficient. Of the 24 cases for which MSI analysis was also available, 10 cases (41.7%) demonstrated biological heterogeneity, 5 (20.8%) demonstrated technical heterogeneity, and 2 (8.3%) demonstrated geographic heterogeneity. Only the two cases with geographic heterogeneity were MSI-high via MSI analysis. In addition, a germline mutation in MSH-6 was identified in one of these cases.

Conclusions: Geographic heterogeneity may raise a suspicion for a MMR-deficient case, which should be further analyzed using additional methodologies such as MSI analysis.

Background: According to the Israeli immunization schedule 1 year old babies should receive two concomitant vaccinations: MMR (measles-mumps-rubella), and DTap-Hib-IPV (diphtheria tetanus acellular pertussis-Haemophilus influenzae type b-poliomyelitis). However, about one-third of infants in Israel receive these vaccinations separately. Nurses at a primary care prevention clinic in Israel observed that the separate mode of vaccination is associated with a lower rate of side effects.

Objectives: To validate this observation and determine whether it represents an exception or the rule.

Methods: A nested prospective follow-up study was conducted in a primary care clinic in Israel. The survey included 191 mothers and their offspring born during 2004/2005. The mothers were interviewed over the telephone 2 weeks after the day of vaccination.

Results: The rate of adverse effects in children who received the injections separately was significantly lower than among those who were vaccinated simultaneously (40% vs. 57%).

Conclusions: It may be necessary to reconsider the current vaccination policy regarding concomitant injections.