Dyspareunia is associated with chronic pain in premenopausal women with sickle cell disease

<p><b>Objectives:</b> Pain is common in women with sickle cell disease (SCD), but the prevalence of dyspareunia in this unique patient population is unknown. In this study, we sought to determine whether chronic pain is associated with an increased prevalence of dyspareunia in premenopausal women with SCD.</p> <p><b>Methods:</b> A cross-sectional study of premenopausal women with SCD was systematically assessed for symptoms of dyspareunia and chronic pain using a standard questionnaire. These results were correlated with each subject's clinical pain phenotype determined by a review of the patient's electronic medical record.</p> <p><b>Results:</b> Ninety-one premenopausal women with SCD were examined. Thirty-two percent of the women reported dyspareunia. Women with dyspareunia were more likely to have a history of chronic pain (90% versus 61%, <i>p</i> = .006), report more pain days per week (median (interquartile range): 6 (4–7) vs. 3 (0–7), <i>p</i> = .005)), and had a higher oral morphine equivalent dose (145 (45–226) mg vs. 60 (9–160) mg, <i>p</i> = .030). Using a multivariable classification tree analysis, number of days of pain experienced per week was an important predictor of dyspareunia (<i>p</i> = .001).</p> <p><b>Conclusion:</b> Dyspareunia is common in women with SCD, and more common in women with SCD and chronic pain. Providers should assess women with SCD for dyspareunia, especially those with a chronic pain syndrome.</p

Correlation analysis of peak biomarker versus time to treatment with N-acetylcysteine (NAC)^*.

<p>*Log transformation of peak measurement of parameter.</p><p>Correlation analysis of peak biomarker versus time to treatment with N-acetylcysteine (NAC)^{<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0131010#t003fn001" target="_blank">*</a>}.</p

Comparison of Sensitized and Non-Sensitized Children for Dendritic Cell Expression of IgE and FcεRI.

†<p>: Mann-Whitney test.</p><p>IQR: interquartile range, cDC: conventional dendritic cells, pDC: plasmacytoid dendritic cells.</p

Comparison of time to reach peak bile acid, presented as a function of peak APAP protein adduct < or ≥ 1.0 nmol/mL APAP protein adduct.

<p>*denotes > 2.0 times the 25–75^th percentile; ^Odenotes > 1.5 times the 25–75^th percentile. GCA, Glycocholic acid; GDCA, Glycodeoxycholic acid; TDCA, Taurodeoxycholic acid.</p

Sensitization status regression models with significant Pearson correlations.

<p>Ln indicates the natural log transformation.</p

Correlation of cDC expression of FcεRI with IgE.

<p>Expression of FcεRI and IgE on the surface of cDC was determined by flow cytometry. (A) Data are presented as fold MFI FcεRI versus fold MFI IgE expression, with non-sensitized subjects (n = 15) in red circles and sensitized subjects (n = 12) in black x's. Note the difference in the slope of the fitted lines (non-sensitized subjects in red dotted line; sensitized subjects in black solid line) above and below a fold MFI IgE of 12, suggesting that there is differential regulation of FcεRI on cDC around this level of cell bound IgE. For all subjects the data was fit with the following cubic equation (blue line): Ln(cDC FcεRI) = 2.26+0.72*ln(cDC IgE)-0.43*ln(cDC IgE)²+0.082*ln(cDC IgE)³); r = 0.86; p = 0.045. For equations based on sensitization status, see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0032556#pone-0032556-t003" target="_blank">Table 3</a>. (B) Expression of cell bound IgE on cDC compared with serum (free) IgE levels. Data are presented as in (A) with fold MFI IgE expression versus serum IgE (kU/L). Note that a cell bound IgE fold MFI of 12 correlates with a serum IgE of around 38 (based on statistical fitting of the curve, this value could range between 34 and 42 kU/L).</p

Expression of FcεRI on pDC does not correlate with serum IgE or age of subject.

<p>Expression of FcεRI on peripheral blood pDC was determined by flow cytometry and compared to subject's age (panel A) and serum IgE level (panel B). Data are presented as in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0032556#pone-0032556-g001" target="_blank">Figure 1</a>.</p

Expression of FcεRI on cDC correlates with serum IgE but not with subject's age.

<p>(A) Gating strategy used to identify expression of FcεRI and IgE on cDC and pDC. Cells were gated on scatter (R1) and lack of expression of CD19 (R2, PerCP negative). Those events that satisfied both of these criteria were examined for expression of ILT7 (R3, PE positive) versus CD1c (R4, APC positive). Cells that were CD19⁻ILT7⁺CD1c⁻ were considered pDC and CD19⁻ILT7⁻CD1c⁺ were considered cDC. The expression of FcεRI (left histograms, FITC positive) or IgE (right histograms, FITC positive) on these cells was then determined and compared to an appropriate isotype control. (B) Expression of FcεRI on peripheral blood cDC was determined by flow cytometry and compared to subject's age or (C) serum IgE level. Data are presented as fold MFI FcεRI versus age in months (B) or serum IgE in kU/L (C), with non-sensitized subjects (n = 15) in circles and sensitized subjects (n = 12) in x's. Sensitization was defined as having at least one positive allergen specific IgE by ImmunoCAP.</p

Summary data for peak alanine aminotransferase values (ALT), acetaminophen (APAP) protein adducts, and bile acids by group.

<p>Data presented as median (range).</p><p>*p value for three way comparison.</p><p>**p value for pairwise comparison.</p><p>Bold p values indicate significance p<0.01; bold, italicized p values represent p = 0.01–0.05.</p><p>Summary data for peak alanine aminotransferase values (ALT), acetaminophen (APAP) protein adducts, and bile acids by group.</p

Subject Characteristics.

<p>*Atopy history: defined as self reported or MD diagnosed allergic rhinitis/hayfever/environmental allergies, asthma/wheeze, atopic dermatitis, food allergy. Family history of atopy was based on self-reporting only.</p>†<p>Sensitized: defined as any elevated food or inhalant serum specific IgE.</p>§<p>Only 4 of these subjects had a clinical history suggestive of an allergy for the foods to which they had IgE against.</p