Granuloma Annulare in Women: Visualizing the Clinical Implications of Functional Mosaicism and X Chromosome Biology Jeena Sandhu 1, Colleen Reisz 1 UMKC School of Medicine 1 INTRODUCTION RESULTS CONCLUSION CREDITS/DISCLOSURE/REFERENCES 48/56 (88%) of the case group was female. 22/48 (46%) of our female patients noted the onset of disease between ages Within this older group, 15/22 (65%) had a BMI> 25 versus 35% of the control group. P-value =.020 via Fisher’s Exact Test. In 11/48 (23%) of the female GA patients, the onset of disease was temporally associated with the introduction or removal of a drug or supplement. In the 11 that made this association, 9/11 (82%) added or withdrew something that would directly alter steroid pathways. Drug differences between cases and controls were not statistically significant. However, statins, proton pump inhibitors and serotonin reuptake inhibitors were more common amongst the cases, with hormone therapy more common amongst the controls. The sample size was small and type II error is possible. We collected age, gender, Fitzpatrick phototyping, laterality and drug data on 56 patients with granuloma annulare identified by diagnosis codes out of a general dermatology clinic. The largest cohort in this group, females aged 40-70, were compared to an age matched control group without disease. Fitzpatrick phototyping was used as a potential biomarker of genetic variation in aromatase. Laterality was included as a marker of mosaicism. We included drug lists as >20% of patients identified drug introduction or withdrawal as a precipitating event. Keywords: granuloma annulare, folliculogenesis, x chromosome inactivation, mosaicism, spindle assembly checkpoint UMKC IRB METHODS To examine age, gender and medication use in patients with GA along the reproductive continuum. We propose that the key features of granuloma annulare, female predominance, striking annular morphology, presence of laterality and abrupt onset in the later reproductive years may relate to molecular events in germline maturation and repair. Medications may alter meiosis activation and suppression. Information value and detail within the medical record may be improved by including mandatory fields for laterality, specific morphology and exact sequences of medication introduction. This is a small case series and the results may not be generalizable. There was little racial diversity in this group. 56 y/o female with 8 year history of GA. Note the lilac circular plaques with central clearing. Formation of the antral window just prior to the LH surge. The metaphase-anaphase transition is governed by a checkpoint mechanism that ensures spindle assembly. In mice, a prophase I oocyte becomes a metaphase II egg. Prophase is the longest phase; >90% of oogenesis. Metaphase allows for the proper alignment of chromosomes in the center of the cell SUMMARY A 65 y/o white female with new onset GA. Granuloma annulare (GA) can be seen in both genders and all age groups, but is most commonly seen in females between the ages of (1). GA has been associated with diabetes, infection and trauma (1). Over 30 different treatments have been described (1). Diseases that present more commonly in women have been associated with the physiologic changes across the fertility cycle (2, 3, 4,5). Meiosis provides duplication and diversity of genetic material in males and females and includes a checkpoint mechanism for spindle assembly (6). DNA repair mechanisms, which include the ataxia telangiectasia gene and BRCA1, are activated with advancing age and pending reproductive senescence (7,8). We hypothesized that a gendered disease with an abrupt onset and striking annular morphology might relate to a biologic event in the fertility cycle. The formation of the antral window in folliculogenesis corresponds to a surveillance checkpoint that blocks cell cycle progression if the chromosomes are incorrectly attached (6). Cholesterol intermediates control meiosis activation in the testis and ovary. Medications such as verapamil, cimetidine and imidazoles can alter sterol conversion in the gonad (9). 1.Thornsberry LA1, English JC 3rd. Etiology, diagnosis, and therapeutic management of granuloma annulare: an update. Dermatol Aug;14(4): doi: /s Ackerman LS. Sex hormones and the genesis of autoimmunity. Arch Dermatol. 2006;142(3): Rubtsov AV, Rubtsova K, Kappler JW, Marrack P. Genetic and hormonal factors in female-biased autoimmunity. Autoimmun Rev.2010;9(7): Selmi C., Brunetta E, Raimondo MG, et al. The X chromosome and the sex ratio of autoimmunity. Autoimmunity Reviews 11 (2012); A531-A Heikinheimo O, Gibbons WE. The molecular mechanisms of oocyte maturation and early embryonic development are unveiling new insights into reproductive medicine. Mol Hum Reprod Aug;4(8): Lara-Gonzalez P, Westhorpe FG, Taylor S. The spindle assembly checkpoint. Current Biology Vol 22, Issue 22, Nov 20, R Titus S1, Li F, Stobezki RA, et al. Impairment of BRCA1-related DNA double-strand break repair leads to ovarian aging in mice and humans. Sci Transl Med Feb 13;5(172):172ra21. doi: /scitranslmed Ménézo Y, Dale B, Cohen M. DNA damage and repair in human oocytes and embryos: a review. Zygote Nov;18(4): doi: /S Epub 2010 Jul Lindenthal B, Holleran AL, ALdaghlas TA, et al. Progestins block cholesterol synthesis to produce meiosis-activating sterols. FASEB Journal, vol 15, March 2001: OBJECTIVE In this series, GA was found more commonly in females during their later reproductive years. Women with GA were heavier and took more drugs than women without disease. Over half of the cases exhibited laterality; the burden of disease strongly favored one side of the body over the other. Over 20% of patients felt a drug change was temporally related to the onset of GA.