Refractory polyarticular gouty arthritis as a manifestation of immune reconstitution inflammatory syndrome.

Immune reconstitution inflammatory syndrome (IRIS) describes the initial clinical deterioration some patients manifest upon initiation of effective antiretroviral therapy (ART) for HIV infection. In this report we describe a case of IRIS manifesting as polyarticular gout, a previously unreported rheumatological manifestation of IRIS. A 53-year-old HIV-infected man with a history of intermittent attacks of gout and an initial CD4 count of 112 cells/microL and a viral load of >100,000 copies/mL presented to our institution with severe, refractory, polyarticular gout approximately 4 weeks after initiating ART. At this point, the patient demonstrated significant gains in his CD4 counts (103 cells/microL) and a greater than 3 log decline in his HIV-1- viral load. This episode was prolonged lasting for approximately 10 weeks and required hospitalization for the management of pain and control of inflammation. The temporal associations of this attack with the initiation of ART and the observed immunologic reconstitution make IRIS a clinical possibility.Monosodium urate crystals through their interactions with interleukin 1- beta, and neutrophilic synovitis play a critical role in the pathophysiology of gout. Defects in both neutrophil and macrophage function and imbalances in the cytokine milieu are documented in HIV infected patients. The introduction of ART results in restoration of neutrophil and macrophage function, declines in levels of the anti-inflammatory cytokine IL-10, and increases in levels of proinflammatory cytokines including IL-1 beta, which may provide the necessary milieu for the precipitation of attacks of severe polyarticular gout in the context of ART initiation.

Relation of Blood Pressure in Childhood to Self-Reported Hypertension in Adulthood.

Blood pressure (BP) tracking (maintaining a BP percentile) across life is not well defined but is important in predicting which children will become hypertensive adults. We computed BP tracking in subjects with BP measured in childhood and adulthood and performed logistic regression to determine the ability of childhood BP to predict adult hypertension (N=5035, 46.7 years, 74.2% white, 17.7% black; 39.6% male). Prevalence of hypertension was 29%. Correlations between systolic BP for child and adolescent were r=0.48; for adolescent and young adult were r=0.40, and for child and young adult were r=0.24 (all P<0.0001). Participants self-reporting adult hypertension were less likely to be white (38.7% black, 27.6% white, 20.9% other; P<0.0001) and female (26.4% females, 32.9% male, P<0.0001). Participants with adult hypertension were more likely to have higher BP and adiposity by age 10 years and abnormal lipids and glucose by age 16 years. There was a graded increase in the frequency of self-reported adult hypertension across the BP change groups, even within the persistently normotensive group (X2<0.0001) from 19% in children with a systolic BP% persistently below the median to 80% for individuals with elevated BP in both childhood and adolescence. Although our precision to predict which individual child is at risk of adult BP-related cardiovascular disease is weak, an increase in systolic BP and body mass index percentile from childhood to adolescence should signal a need for lifestyle intervention to prevent future sustained hypertension-related cardiovascular disease.

Usual blood pressure, atrial fibrillation and vascular risk: evidence from 4.3 million adults.

Background: Although elevated blood pressure is associated with an increased risk of atrial fibrillation (AF), it is unclear if this association varies by individual characteristics. Furthermore, the associations between AF and a range of different vascular events are yet to be reliably quantified. Methods: Using linked electronic health records, we examined the time to first diagnosis of AF and time to first diagnosis of nine vascular events in a cohort of 4.3 million adults, aged 30 to 90 years, in the UK. Results: : A 20-mmHg higher usual systolic blood pressure was associated with a higher risk of AF [hazard ratio (HR) 1.21, 95% confidence interval (CI) 1.19, 1.22]. The strength of the association declined with increasing age, from an HR of 1.91 (CI 1.75, 2.09) at age 30-40 to an HR of 1.01 (CI 0.97, 1.04) at age 80-90 years. AF without antithrombotic use at baseline was associated with a greater risk of any vascular event than AF with antithrombotic usage ( P interaction < 0.0001). AF without baseline antithrombotic usage was associated with an increased risk of ischaemic heart disease (HR 2.52, CI 2.23, 2.84), heart failure (HR 3.80, CI 3.50, 4.12), ischaemic stroke (HR 2.72, CI 2.19, 3.38), unspecified stroke (HR 2.59, CI 2.25, 2.99), haemorrhagic stroke, chronic kidney disease, peripheral arterial disease and vascular dementia, but not aortic aneurysm. Conclusions: The association between elevated blood pressure and AF attenuates with increasing age. AF without antithrombotic usage is associated with an increased risk of eight vascular events.

A design for cancer case-control studies using only incident cases: experience with the GEM study of melanoma.

BACKGROUND: The population-based case-control study is not suited to the evaluation of rare genetic (or environmental) factors. The use of a novel case-control design in which cases have second primaries and controls are cancer survivors has been proposed for this purpose. METHODS: We report results from an international study of melanoma that involved population-based ascertainment of incident cases of second or subsequent primary melanoma as the 'case' group and incident cases of first primary melanoma as the 'control' group. We evaluate the validity of the study design by comparing the results obtained for phenotypic factors that have been shown consistently to be associated with melanoma in previous conventional studies with the results from a conventional case-control study conducted in Connecticut and from literature reviews. RESULTS: All but one of the known risk factors for melanoma were shown to be significantly associated with melanoma in our study, though the individual odds ratios appear to be somewhat attenuated relative to the magnitudes typically observed in the literature. CONCLUSIONS: Patients with a second or subsequent primary cancer of a single type represent a potentially valuable and under-utilized resource for the study of cancer aetiology.

Henoch-Schönlein purpura in an adult Filipino man: a case report and literature review.

Henoch-Schönlein purpura (HSP) is a form of cutaneous small vessel vasculitis that can involve visceral organs and is associated with deposition of immunoglobulin A (IgA)-containing immune complexes. HSP may appear after a remote history of infection (often an upper respiratory tract infection) as a rash with palpable petechiae or purpura. In addition, a patient with HSP usually complains of arthralgia and abdominal pain. Renal involvement also is common. HSP may be confused with other systemic autoimmune diseases because they all can present with similar symptoms. Prognosis is good and recovery usually occurs without treatment. Although HSP predominately affects children, the condition also can be seen in adults. We present a case of adult-onset HSP in an otherwise healthy Filipino man and review the literature.

Interferon-ß and serum 25-hydroxyvitamin D interact to modulate relapse risk in MS.

OBJECTIVE: To determine whether interferon-ß (IFN-ß) medication use is associated with vitamin D levels and whether the two interact in exerting effects on relapse risk. METHODS: In a prospective cohort of 178 persons with clinically definite multiple sclerosis (MS) living in southern Tasmania in 2002-2005, serum 25-hydroxyvitamin D [25(OH)D] was measured biannually, with assessment by questionnaire for relevant factors, including IFN-ß treatment. RESULTS: Subjects reporting IFN-ß use had significantly higher mean 25(OH)D than persons who did not (p < 0.001). This was mediated by an interaction between personal sun exposure and IFN-ß, with treated persons realizing nearly three times 25(OH)D per hour of sun exposure of persons not on therapy. The association between 25(OH)D and 1,25-dihydroxyvitamin D did not differ by IFN-ß therapy (p = 0.82). 25(OH)D was associated with a reduced relapse risk only among persons on IFN-ß (p < 0.001). Importantly, IFN-ß was only protective against relapse among persons with higher 25(OH)D (hazard ratio [HR] 0.58 [95% confidence interval (CI) 0.35-0.98]), while among 25(OH)D-insufficient persons, IFN-ß increased relapse risk (HR 2.01 [95% CI 1.22-3.32]). CONCLUSION: In this study, we found that IFN-ß therapy is associated with greater production of vitamin D from sun exposure, suggesting part of the therapeutic effects of IFN-ß on relapse in MS may be through modulation of vitamin D metabolism. These findings suggest persons being treated with IFN-ß should have vitamin D status monitored and maintained in the sufficiency range. CLASSIFICATION OF EVIDENCE: This study provided Class III evidence that IFN-ß is associated with reduced risk of relapse, and this effect may be modified by a positive effect of IFN-ß on serum 25(OH)D levels.