An Unusual and Rare Presentation of Diffuse Tophaceous Gout.

Gout is a chronic disease characterized by recurrent attacks on joints from monosodium urate crystal deposition causing inflammation and severe pain. Patients at increased risk of developing gout include those with obesity, high consumption of alcohol or high-purine foods, genetic causes, and medication side effects. Typically, there are three stages of disease progression: acute, inter-critical, and chronic. Monoarticular joint disease is common however polyarticular gouty arthritis can result after years of acute flares. The chronic nature of the disease forms tophi, which are generally painless solid urate crystal collections. We present an unusual case of a 33-year-old male whose initial presentation was severe tophaceous gout affecting multiple joints, including bilateral elbows, knees, as well as hand and foot joints. His presentation was unique in that the tophi were not firm as expected, but were erythematous, tender, and fluctuant resembling an abscess. Laboratory and imaging studies confirmed the diagnosis of tophaceous gout and the patient's symptoms improved after starting systemic steroid therapy and colchicine. A multidisciplinary effort involving the medicine team and infectious disease, podiatry, and rheumatology consultants was essential in reaching the diagnosis. This case highlights the importance of keeping a broad differential diagnosis in a patient with polyarticular lesions and considering gout even with an atypical presentation such as in our patient.

Synthetic viability by BRCA2 and PARP1/ARTD1 deficiencies.

Poly (ADP-ribose) polymerase (PARP) inhibitor (PARPi) olaparib has been approved for treatment of advanced ovarian cancer associated with BRCA1 and BRCA2 mutations. BRCA1- and BRCA2-mutated cells, which are homologous recombination (HR) deficient, are hypersensitive to PARPi through the mechanism of synthetic lethality. Here we examine the effect of PARPi on HR-proficient cells. Olaparib pretreatment, PARP1 knockdown or Parp1 heterozygosity of Brca2(cko/ko) mouse embryonic stem cells (mESCs), carrying a null (ko) and a conditional (cko) allele of Brca2, results in viable Brca2(ko/ko) cells. PARP1 deficiency does not restore HR in Brca2(ko/ko) cells, but protects stalled replication forks from MRE11-mediated degradation through its impaired recruitment. The functional consequence of Parp1 heterozygosity on BRCA2 loss is demonstrated by a significant increase in tumorigenesis in Brca2(cko/cko) mice. Thus, while olaparib efficiently kills BRCA2-deficient cells, we demonstrate that it can also contribute to the synthetic viability if PARP is inhibited before BRCA2 loss.