Shah, P.

Background. Solid organ transplant recipients are at risk of severe coccidioidomycosis and are given prophylaxis to mitigate the risk. Patients with seropositive testing typically receive lifelong prophylaxis; currently, this prophylaxis strategy includes patients who are positive only for IgM by enzyme immunoassay (EIA-IgM-only), although this result may be falsely positive. Methods. We conducted a retrospective study at a large-volume transplant center in an endemic coccidioidomycosis region to compare outcomes of non–lung transplant recipients who were seropositive for Coccidioides but discontinued prophylaxis (case patients) to outcomes of patients who continued prophylaxis (controls). Results. No case or control patients developed active coccidioidomycosis during the follow-up period. Before transplant, 62 of 77 case patients (80.5%) had a single positive serologic test, of whom 27 of 62 were EIA-IgM-only positive (43.5%). In contrast, 57 of 77 controls (74.0%) had a single seropositive result (16/57 [28.1%] were EIA-IgM-only). The single EIA-IgM-only result was classified as falsely positive by infectious disease consultants in 20 of 43 patients (46.5%) compared with all other Coccidioides serologic results (13/111 [11.7%], P < 0.001). Lifetime antifungal prophylaxis was felt to be unnecessary for 28 of 43 patients (65.1%) who were EIA-IgM-only versus 31 of 111 patients (27.9%) with other serologic results (P < 0.001). Conclusions. For patients repeatedly positive for EIA-IgM-only and no evidence of seroconversion, compatible clinical illness, or radiographic findings, discontinuing antifungal prophylaxis may be reasonable after the first posttransplant year.

Background: We sought to characterize the outcomes of patients with primary pulmonary coccidioidomycosis whose post-treatment complement fixation (CF) titer increased by more than 2 dilutions (serologic rebound) after discontinuation of antifungal treatment. Methods. We conducted a retrospective chart review of patients with primary pulmonary coccidioidomycosis and identified immunocompetent, non-pregnant adults who received antifungal treatment and then experienced a serologic rebound after treatment discontinuation. We compared these to matched controls similarly treated who did not have serologic rebound. Results. Fifty-eight patients experienced serologic rebound. Thirty (52%) of these were associated with symptoms. Nine were associated with radiographic progression. The median time to serologic rebound was 3.5 months. Antifungal treatment was reinitiated in 37 (63.7%) patients. Four of the 58 (6.9%) with rebounded serology subsequently developed extra-thoracic dissemination. Compared with matched controls, patients with rebounded serology were more likely to have post-treatment symptoms, reinitiation of antifungal therapy, and a longer duration of clinical follow-up. However, they were not more likely to experience extra-thoracic dissemination. Conclusion: Serological rebound, manifested in at least 2-dilution rise of CF titer following antifungal treatment of primary pulmonary coccidioidomycosis, was uncommon, but resulted in longer clinical follow-up. Continued monitoring of such patients is important to identify the patients who develop subsequent symptoms, as well as extra-thoracic dissemination.

Although it is well established that severe chronic hyperglycemia is associated with microvascular disease, it is not known whether transient hyperglycemia similar to that observed with impaired glucose tolerance or early Type 2 diabetes contributes to this pathology by altering microvascular function. To test the hypothesis that acute hyperglycemia decreases microvascular vasodilator responsiveness in human skin, we measured the cutaneous vasodilator response to local warming. This response can be divided into two phases, an initial peak that relies predominantly on local sensory nerves and a second slower phase that is largely dependent on endothelial nitric oxide. We reasoned that a change in one or both phases would indicate a change in the corresponding mechanism(s) with hyperglycemia. Twenty-eight healthy volunteers (14 women, 14 men) were randomly divided into three groups, corresponding to 6 h of euglycemia ( n = 8), 6 h when glucose was clamped at ∼7 mmol/l ( n = 10), or 6 h when glucose was varied to mimic a postprandial pattern (i.e., peak glucose ∼11.1 mmol/l) commonly observed in individuals with impaired glucose tolerance ( n = 10). Insulin concentrations in all instances were maintained at ∼65 pmol/l by means of continuous infusions of somatostatin and insulin. Glucagon and growth hormone were also continuously infused to maintain their basal concentrations. Despite substantial differences in both the level and pattern of glucose concentrations, neither maximum cutaneous vasodilation nor the pattern of the vasodilator response to local warming differed over the 6 h of study. We conclude that acute hyperglycemia similar to levels commonly observed in people with either early Type 2 diabetes or impaired glucose tolerance does not alter the vasodilator response to local warming of the skin in humans.