Dear All

“Rain rain, go to Spain, never come back again” used to be a rhyme we hummed as children. At the moment, this is what the Income Tax Department of Spain seems to be telling Christiano Ronaldo! The incredible mix of destinies this year at the World Cup Soccer events reminds us yet again how unpredictable outcomes can be and that hard work and commitment, as exemplified by Croatia, can make Minnows Masters, in sport, as in science.
This issue brings to the fore two important papers, amongst others, one on the role of the aryl hydrocarbon receptor (AhR) pathway in linking the trigger caused by environmental pollutants to the causation of autoimmune arthritis – the pathway is being incriminated in other diseases too; and the other more clinical one on leflunomide not always leading to pregnancy-related fetal morbidities. More needs to be done and collected before coming to firm conclusions.
Important IRA announcements, details for IRA orations, and award applicants and a glimpse of rheumatology CMEs done in various parts of India are there for you to go through in the Secretary’s newsletter report. Dr. Sanket Shah, JIMPER brings you an intriguing case in the Fellows’ corner. /p>

Dr C Balakrishnan, Consultant Rheumatologist, Hinduja hospital, Mumbai

Leflunomide use during pregnancy and the risk of adverse pregnancy outcomes(Berard et al., Annal of Rheum dis, April 2018)

Objectives:
Leflunomide is known to be embryotoxic and teratogenic in rodents. However, there is less evidence in humans. The risk of major congenital malformation (MCM), prematurity, low birth weight (LBW), and spontaneous abortion associated with leflunomide exposure during pregnancy in humans was evaluated.

Methods:
From a cohort of 289,688 pregnancies in Montreal, Quebec, Canada, from 1998 to 2015, first-trimester leflunomide exposure and other antirheumatic drug exposures were studied for their association with MCM and spontaneous abortions. Also, second- or third-trimester leflunomide exposure was examined for associations with prematurity and LBW. Logistic regression model-based generalized estimating equations were used.

Dr Shefali Sharma, Rheumatology, PGIMER, Chandigarh

Good’s syndrome with Alcaligenes xylosoxidans osteomyelitis and autoimmune neutropenia – A rare disease with rare infection and rare auto immune manifestation

Dr. Chengappa KG, Dr. VS Negi, Clinical Immunology & Rheumatology, JIPMER, Pondicherry

A 43-year-old man with a disease duration of two years presented with recurrent sino-pulmonary infections, recurrent diarrhea, and weight loss. He was found to have a mediastinal mass detected on chest X-ray and confirmed by CT scan (Figure 1), but he had been asymptomatic. Routine investigations suggested hypogammaglobulinemia with a total protein of 3.7 gram/L, albumin 2.7 gram/L, and globulins 1 gram/L. His HIV was negative. An immunoglobulin profile suggested decreased IgA, IgM, and IgE levels. Resection and biopsy from the anterior mediastinal mass were performed, which showed sheets of spindle-shaped cells with minimal lymphoid cells suggestive of type A thymoma (Figure 2). Flow cytometry analysis of the lymphocytes suggested complete absence of CD 19+ B cells and a normal number of T cell and NK cells.

Upadacitinib (ABT-494)

Upadacitinib (ABT-494) is a JAK1 selective inhibitor undergoing phase 2 and 3 clinical trials for rheumatoid arthritis, Crohn's disease, ulcerative colitis, atopic dermatitis, psoriatic arthritis, giant cell arteritis, and axial SpA. It is being developed by abbvie.

Clinical trial in RA

SELECT-COMPARE is a phase 3, multicenter, randomized, double-blind study designed to evaluate the safety and efficacy of upadacitinib compared to placebo and adalimumab in adult patients with moderate-to-severe rheumatoid arthritis who are on a stable background of methotrexate and who have an inadequate response. Patients received background methotrexate and were randomized in a 2:2:1 ratio to receive upadacitinib (15 mg once-daily), placebo, or adalimumab (given as a subcutaneous injection of 40 mg every other week). The primary endpoints of the first phase included the percentage of subjects achieving ACR20 and clinical remission (based on DAS28[CRP]) after 12 weeks of treatment compared to placebo.