Faculty Bibliography

Autoinflammatory diseases are disorders of the innate immune system, which can be either monogenic due to a specific genetic mutation or complex multigenic due to the involvement of multiple genes. The aim of this review is to explore and summarize the recent advances in pathogenesis, diagnosis, and management of genetically complex autoinflammatory diseases, such as Schnitzler's syndrome; adult-onset Still's disease; synovitis, acne, pustulosis, hyperostosis, osteitis syndrome/chronic recurrent multifocal osteomyelitis/chronic non-bacterial osteomyelitis; Adamantiades-Behçet's disease; Yao syndrome; and periodic fever with aphthous stomatitis, pharyngitis, and adenitis syndrome. The PubMed database was screened for relevant articles using free text words and specific search strings. The search was limited to English-language articles, reporting the results of studies in humans, published through March 2021. Evidence from literature suggest that these rare multigenic autoinflammatory diseases can present with different clinical features and the diagnosis of these diseases can be challenging due to a combination of nonspecific manifestations that can be seen in a variety of other conditions. Diagnostic delays and disease complications may occur due to low disease awareness and the lack of pathognomonic markers. The pathogeneses of these diseases are complex and in some cases precise pathogenesis is not clearly understood. Conventional treatments are commonly used for the management of these conditions, but biologics have shown promising results. Biologics targeting proinflammatory cytokines including IL-1, IL-6, TNF-α, IL-17A and IL-18 have been shown to ameliorate signs and symptoms of different multigenic autoinflammatory diseases.

BACKGROUND:Adult Onset Still's disease (AOSD) carries an expansive presentation - typically featuring a triad of fevers, myalgia/arthralgia, and a rash - which can be mistaken for infectious or malignant etiology. As such, the role of reliable biomarkers becomes critical in the diagnosis and management of AOSD. The employment of MBDA panel may be of clinical utility in AOSD management, as we describe two cases where its application drives treatment plan. METHODS:We describe two cases where application of MBDA panel - such as Vectra DA -assisted with disease management. RESULTS:Case 1 features a 68-year-old male who presented with recurrent fevers, malaise, and a rash for three weeks. He was found to have an elevated ferritin level (15,599 ng/mL) with elevated acute phase reactants, consistent with AOSD. Vectra DA score was 77 at time of diagnosis. After treatment (see table), repeat Vectra DA at follow-up was 15. Case 2 features a 25-year-old female with history of juvenile idiopathic arthritis (then inactive) who presented with fevers, malaise, and rash. She was found to have an elevated ferritin level (321 ng/mL) with elevated acute phase reactants, also consistent with AOSD. Her Vectra DA score was 80 at peak of symptoms. She underwent appropriate treatment (see table), and repeat Vectra DA at follow-up was 17. CONCLUSION/CONCLUSIONS:A deeper consideration should be placed on the value of MBDA as a monitoring tool in the management of AOSD, specifically when pertaining to patient's responsiveness to therapies.

Objective. Rheumatoid arthritis (RA) patients are at increased risk of latent tuberculosis infection (LTBI) but there are no clear guidelines for LTBI screening with Tuberculin Skin Test (TST) or Quantiferon TB Gold testing (QFT-G). Methods. A retrospective study was conducted in a high risk, largely foreign-born, inner city, RA population. After screening 280 RA patients, 134 patients who had both TST and QFT-G testing performed during their initial evaluation were included. Results. Out of 132 RA patients included in our analysis, 50 (37.8%) patients were diagnosed with LTBI with either positive TST 42 (31.8%) or QFT-G 23 (17.4%). 15 (11.4%) were positive and 82 (62.1%) were negative for both tests. The agreement between TST and QFT-G was 73.5% (Kappa 0.305, CI = 95% 0.147-0.463, p = 0.081). Conclusions. There was low-moderate agreement (kappa = 0.305) between TST and QFT-G. In the absence of clearly defined gold standard and limitations associated with both tests, we propose early screening with both tests for patients who need prompt treatment with BRMs. Patients who are not immediate candidates for BRM treatment may be safely and cost effectively screened with a two-step process: initial screening with TST and if negative, IGRA testing. Patients positive for either test should be promptly treated.