Panniculitis following baricitinib initiation for treatment of rheumatoid arthritis

Alice Fike

Panniculitis following baricitinib initiation for treatment of rheumatoid arthritis

Joint Bone Spine, 2020

Please cite this article in press as: Fike A, et al. Panniculitis following baricitinib initiation for treatment of rheumatoid arthritis. Joint Bone Spine (2020), https://doi.org/10.1016/j.jbspin.2020.04.002 ARTICLE IN PRESS G Model BONSOI-4990; No. of Pages 2 Joint Bone Spine xxx (2020) xxx–xxx Available online at ScienceDirect www.sciencedirect.com Letter to the Editor Panniculitis following baricitinib initiation for treat- ment of rheumatoid arthritis a r t i c l e i n f o Keywords: Drug related side effects and adverse reactions Rheumatoid arthritis JAK inhibitors Panniculitis Baricitinib is a janus kinase (JAK) inhibitor with initial approval for treatment of adults with rheumatoid arthritis (RA) in 2017 [1] that selectively inhibits JAK1 and JAK2 [2] and is under investigation in juvenile dermatomyositis and systemic lupus erythematosus (SLE) [3]. Different JAK inhibitors preferentially target various JAK isoforms, which may result in differences in adverse event proﬁles [4]. We describe what to our knowledge is the ﬁrst reported case of panniculitis developing in a patient receiving baricitinib for treat- ment of RA. A 43-year-old woman with RA presented to clinic on day 23 of baricitinib therapy with a 20-day history of subacute, painful, pruritic lesions on her extremities and buttocks (Fig. 1). On day 17 of therapy, she presented to an Emergency Department (ED) for evaluation. Examinations revealed platelets of 228 K/mcL, D- dimer of < 0.27 mcg/mL, and a doppler ultrasound without evidence of venous thrombus. The patient held baricitinib the days of and after the ED visit (Days 17–18). She resumed baricitinib on Day 19, and experienced acute worsening of symptoms within two days (Fig. 2). After notifying us on day 22, we instructed her to dis- continue baricitinib pending evaluation. The patient’s RA history was complicated by hypersensitivity vasculitis and recalcitrance to numerous biologic treatments. The patient received tofacitinib for six months-years prior without adverse event but stopped due to ineffectiveness. Her autoimmune serologic proﬁle was notable only for anti-cyclic citrullinated peptide antibodies and rheumatoid factor. The patient’s medications included baricitinib 2 mg daily, methotrexate 20 mg weekly, hydroxychloroquine 400 mg daily, and prednisone 7.5 mg daily. On physical examination, the patient’s posterior lower legs demonstrated tender, indurated, coalescing hyperpigmented plaques and subtle plaques on the anterior upper legs, buttocks and forearm. Her musculoskeletal exam was notable for bilateral ankle synovitis. The patient was instructed to discontinue baricitinib per- manently with no other interventions. On Day 58, all evidence of panniculitis was resolved. The differential diagnosis included erythema nodosum, a drug reaction to baricitinib, and vasculitides including erythema indura- tum. The normal d-dimer and negative ultrasound performed on Fig. 1. Skin lesions on Day 17 after starting baricitinib. day 17 made a thrombotic event unlikely. The exam ﬁndings were satisfactory for diagnosis of panniculitis per dermatology. Given the association of the onset of the lesions in relationship to baricitinib initiation, the increase in intensity of inﬂammation documented in photos after a short dechallenge and subsequent rechallenge, this panniculitus was attributed to baricitinib. We submitted a report describing this adverse event to the United States Federal Drug Administration Medwatch program as well as to the manufacturer of baricitinib. Baricitinib has potential applications in dermato- myositis and SLE which can manifest with panniculitis in a similar distribution as our patient, potentially causing confusion in patients treated with baricitinib with previous or new manifestations of panniculitis. We report what we believe to be the ﬁrst case of panniculi- tis occurring with baricitinib. Our review of the literature revealed a case of vasculitis in a patient receiving tofacitinib for RA with histopathology suggestive of vasculitis and acute lobular panniculi- tis [5]. These cases highlight that clinicians must remain vigilant for detecting novel medication-associated adverse reactions occurring https://doi.org/10.1016/j.jbspin.2020.04.002 1297-319X/© 2020 Published by Elsevier Masson SAS on behalf of Soci ´ et ´ e franc¸ aise de rhumatologie.

G Model ARTICLE IN PRESS BONSOI-4990; No. of Pages 2 Joint Bone Spine xxx (2020) xxx–xxx Available online at ScienceDirect www.sciencedirect.com Letter to the Editor Panniculitis following baricitinib initiation for treatment of rheumatoid arthritis a r t i c l e i n f o Keywords: Drug related side effects and adverse reactions Rheumatoid arthritis JAK inhibitors Panniculitis Baricitinib is a janus kinase (JAK) inhibitor with initial approval for treatment of adults with rheumatoid arthritis (RA) in 2017 [1] that selectively inhibits JAK1 and JAK2 [2] and is under investigation in juvenile dermatomyositis and systemic lupus erythematosus (SLE) [3]. Different JAK inhibitors preferentially target various JAK isoforms, which may result in differences in adverse event profiles [4]. We describe what to our knowledge is the first reported case of panniculitis developing in a patient receiving baricitinib for treatment of RA. A 43-year-old woman with RA presented to clinic on day 23 of baricitinib therapy with a 20-day history of subacute, painful, pruritic lesions on her extremities and buttocks (Fig. 1). On day 17 of therapy, she presented to an Emergency Department (ED) for evaluation. Examinations revealed platelets of 228 K/mcL, Ddimer of < 0.27 mcg/mL, and a doppler ultrasound without evidence of venous thrombus. The patient held baricitinib the days of and after the ED visit (Days 17–18). She resumed baricitinib on Day 19, and experienced acute worsening of symptoms within two days (Fig. 2). After notifying us on day 22, we instructed her to discontinue baricitinib pending evaluation. The patient’s RA history was complicated by hypersensitivity vasculitis and recalcitrance to numerous biologic treatments. The patient received tofacitinib for six months-years prior without adverse event but stopped due to ineffectiveness. Her autoimmune serologic profile was notable only for anti-cyclic citrullinated peptide antibodies and rheumatoid factor. The patient’s medications included baricitinib 2 mg daily, methotrexate 20 mg weekly, hydroxychloroquine 400 mg daily, and prednisone 7.5 mg daily. On physical examination, the patient’s posterior lower legs demonstrated tender, indurated, coalescing hyperpigmented plaques and subtle plaques on the anterior upper legs, buttocks and forearm. Her musculoskeletal exam was notable for bilateral ankle synovitis. The patient was instructed to discontinue baricitinib permanently with no other interventions. On Day 58, all evidence of panniculitis was resolved. The differential diagnosis included erythema nodosum, a drug reaction to baricitinib, and vasculitides including erythema induratum. The normal d-dimer and negative ultrasound performed on Fig. 1. Skin lesions on Day 17 after starting baricitinib. day 17 made a thrombotic event unlikely. The exam findings were satisfactory for diagnosis of panniculitis per dermatology. Given the association of the onset of the lesions in relationship to baricitinib initiation, the increase in intensity of inflammation documented in photos after a short dechallenge and subsequent rechallenge, this panniculitus was attributed to baricitinib. We submitted a report describing this adverse event to the United States Federal Drug Administration Medwatch program as well as to the manufacturer of baricitinib. Baricitinib has potential applications in dermatomyositis and SLE which can manifest with panniculitis in a similar distribution as our patient, potentially causing confusion in patients treated with baricitinib with previous or new manifestations of panniculitis. We report what we believe to be the first case of panniculitis occurring with baricitinib. Our review of the literature revealed a case of vasculitis in a patient receiving tofacitinib for RA with histopathology suggestive of vasculitis and acute lobular panniculitis [5]. These cases highlight that clinicians must remain vigilant for detecting novel medication-associated adverse reactions occurring https://doi.org/10.1016/j.jbspin.2020.04.002 1297-319X/© 2020 Published by Elsevier Masson SAS on behalf of Société française de rhumatologie. Please cite this article in press as: Fike A, et al. Panniculitis following baricitinib initiation for treatment of rheumatoid arthritis. Joint Bone Spine (2020), https://doi.org/10.1016/j.jbspin.2020.04.002 G Model BONSOI-4990; No. of Pages 2 2 ARTICLE IN PRESS Letter to the Editor / Joint Bone Spine xxx (2020) xxx–xxx Musculoskeletal and Skin Diseases, National Institutes of Health. Dominique Pichard, MD for her contributions in acquiring clinical data. References [1] Olumiant product information, European public assessment report. European Medicines Agency. [Internet. Accessed February 11, 2020]. Available from: https://www.ema.europa.eu/en/medicines/human/EPAR/olumiant #authorisation-details-section. [2] Olumiant product information. Eli Lilly and Company. Indianapolis, IN 46285. Issued May 2018. [Internet. Accessed January 21, 2020]. Available from: https://www.accessdata.fda.gov/drugsatfda docs/label/2018/207924Orig 1s000lbl.pdf. [3] ClinicalTrials.gov. Baricitinib. [Internet. Accessed January 21, 2020]. Available from: https://clinicaltrials.gov/ct2/results?cond=&term=baricitinib&cntry= &state=&city=&dist=. [4] Schwartz D, Kanno Y, Villarino A, et al. JAK inhibition as a therapeutic strategy for immune and inflammatory diseases. Nat Rev Drug Discov 2017;16:843–62. [5] Muraviev Y, Radenska-Lopovok S, Lebedeva V, et al. Nodular polyarteritis as an unforeseeable adverse reaction in RA patient treated with tofacitinib [abstract]. Ann Rheum Dis Suppl 2018;77:1370–1. Fig. 2. Skin lesions on Day 22 after short dechallenge and rechallenge with baricitinib. with newly-approved medications, especially considering potential confusion with disease-related manifestations. Alice Fike a,∗ Rhett Kent b Ann Biehl c Michael M. Ward c a Intramural Research Program, National Institutes of Arthritis, Musculoskeletal and Skin Diseases (NIAMS), 10 Center Drive Rm 10N318 Bethesda, Maryland 20892, United States b Forefront Dermatology, 8505 Arlington Blvd. Suite 210, Fairfax VA 22031, United States c Clinical Trials and Outcomes Branch, Intramural Research Program, National Institutes of Arthritis, Musculoskeletal and Skin Diseases (NIAMS), National Institutes of Health, 10 Center Drive Bethesda, Maryland 20892, United States Disclosure of interest The authors declare that they have no competing interest. Acknowledgments ∗ Corresponding author. E-mail address: alice.fike@nih.gov (A. Fike) Accepted 8 April 2020 Available online xxx This research was financially supported by the Intramural Research Program of the National Institute of Arthritis and Please cite this article in press as: Fike A, et al. Panniculitis following baricitinib initiation for treatment of rheumatoid arthritis. Joint Bone Spine (2020), https://doi.org/10.1016/j.jbspin.2020.04.002

La volonté de poursuivre les échanges amorcés à Marseille lors des premières Rencontres Nord-Sud de Préhistoire récente a été concrétisée par le projet d’une seconde manifestation dont le thème « Habitations et habitats du Néolithique à l’âge du Bronze en France et ses marges » a tout de suite fait consensus. Ces secondes rencontres se sont tenues à Dijon du 19 au 21 novembre 2015 sous le patronage de la Société préhistorique française. Par ailleurs, l’APRAB « l’Association pour la Promotion des Recherches sur l’âge du Bronze », qui couvre l’ensemble du territoire national, s’est jointe à ce nouveau projet, permettant ainsi, avec les RMPR et InterNéo, d’ouvrir à la manifestation tout le champ chronologique et géographique du Néolithique ancien au Bronze final de la France et ses marges. Lors du colloque, quatre thèmes figuraient au programme. Le thème 1 était articulé autour des « architectures comparées » et devait permettre de présenter le renouvellement des connaissances sur l’hétérogénéité de l’habitat en fonction des zones géographiques. Le thème 2, intitulé « Habitats fugaces, traces, fréquentations » proposait d’explorer un type d’habitat dont les plans ne sont pas lisibles à partir de trous de poteaux et les traces d’occupations temporaires. Le thème 3 élargissait le champ en prenant en compte « l’espace habité et ses corolaires ». Enfin, le thème 4 proposait une réflexion autour des notions d’« habitats groupés / habitat dispersés ». Au final, ce sont 55 articles, regroupés par ordre chronologique et diachronique, qui rendent compte de la richesse, de la pérennité, des ruptures, des recompositions, de la continuité des modes de résidence néolithiques et protohistoriques. Il en résulte un bilan général transculturel sur l’habitat néolithique et de l’âge du Bronze en France dans son contexte européen, appuyé par la multiplication des découvertes de plans d’habitations et de structures domestiques, notamment ces dernières années, à l’occasion d’opérations d’archéologie préventive. Cet état de l’art renouvelle fondamentalement notre vision. Un corpus de plans interactif de 177 sites accompagne et complète l’ouvrage. L’ensemble constitue certainement pour un temps encore l’un des ouvrages les plus complets sur l’habitat de ses périodes. We accomplished our goal to continue the discussions that we started in Marseille during the first Rencontres Nord-Sud de Préhistoire récente with a second meeting whose topic “Dwellings and settlements from the Neolithic to the Bronze Age in France and its margins” was immediately agreed upon. This meeting was held in Dijon from November 19 to 21 under the patronage of the Société Préhistorique Française. We were also joined by the APRAB “Association pour la Promotion des Recherches sur l’âge du Bronze”, which covers all of France, thus permitting, with the RMPRs and InterNéo, to open the event to all chronological and geographic fields from the Early Neolithic to the Final Bronze Age in France and its margins. Four topics were addressed during this colloquium. Topic 1 addressed “comparative architectures” and was intended to enable presentations of new information concerning the heterogeneity of settlements in different geographic zones. The aim of Topic 2, entitled “Transient settlements, remains, uses” was to explore a type of settlement whose plans are not readable based on postholes and the remains of temporary occupations. Topic 3 broadened the field of discussion by considering “the living space and its corollaries”. Finally, Topic 4 focused on the notions of “grouped settlements/dispersed settlements”. A total of 55 articles, organized in chronological and diachronic order, thus considered the richness, longevity, breaks, recompositions, and continuity of Neolithic and Protohistoric residence types. They resulted in a general, transcultural synthesis of Neolithic and Bronze Age settlements in the European context, enriched by the multitude of discoveries of settlement and domestic structure plans, especially in recent years, made during preventive archaeology operations. This new synthesis fundamentally renews our knowledge in this domain. A corpus of 177 interactive site plans completes this monography. Together they constitute, probably for years to come, one of the most complete publications on the settlements of this period.

بنام خداوند جان و خرد مرکز تحصیلات تکمیلی درس‌نامه آموزش نرم‌افزار لیزرل جلسه چهارم: انجام معادلات ساختاری (تحلیل مسیر به همراه تحلیل عامل) با کنترل جنسیت افراد به روش تفکیکی دکتر یحیی علی بابایی استاد گروه جامعه‌شناسی دانشکده علوم اجتماعی دانشگاه تهران تهیه و تنظیم: میثم ماهیدشتی دانشجوی دوره دکتری جامعه‌شناسی نیمسال اول 96-1395 مقدمه: در جلسه سوم به این نتیجه رسیدیم که ریشه «رضایت شغلی» در میزان «مهارت شغلی» است. به عبارتی اگر ما در یک محیط کاری بتوانیم میزان «مهارت شغلی» افراد را افزایش بدهیم میزان «رضایت شغلی» آنان را افزوده‌ایم. به‌این‌ترتیب که با افزایش اقسام مهارت به فراخور نوع کار، روزمرگی کاهش‌یافته و با کاهش «روزمرگی شغلی»، «استقلال شغلی» و درنهایت رضایت از شغل افزایش می‌یابد. نکته: آماره RMSEA اگر مساوی و کمتر از 0.05 باشد ایده آل است، اگر بین 0.05 تا 0.08 باشد قابل‌قبول است. بین 0.08 تا 0.1 ضعیف و از 0.1 به بالا غیرقابل‌قبول است. در مدل جلسه گذشته مقدار آماره RMSEA مدل ما را قابل‌قبول اعلام می‌کند، اما مقدار P-Value مربوط به آماره کا-اسکوئر نزدیک مرز اما کمی زیر 0.05 است و مدل ما را تقریباً تأیید می‌نماید. شاخص بعدی یا سوم ما «نسبت آماره کا-اسکوئر بر درجه آزادی آن» کمتر از عدد دو (2) یعنی مرز ایده آل است: Chi-Square/DF=1.31 حال سؤالی که در این جلسه به دنبال پاسخ به آن هستیم به این مسئله برمی‌گردد که: 1) آیا مدل تأییدشده نهایی ما «فرا جنسیتی» است؟ یعنی مهم نیست که پرسش‌شونده زن باشد یا مرد؟ 2) یا اینکه مدل نهایی ما تک جنسیتی است یعنی مردانه یا زنانه است؟ 3) و درنهایت اینکه: با کنترل متغیر جنسیت مدل نهایی ما در هردو جنسیت بی‌معنا می‌شود. نکته: در صورت بی‌معنا شدن مدل نهایی در هر دو جنسیت اعلام می‌کنیم که مدل نهایی ما کاذب بوده است چون با کنترل متغیر جنسیت، مدل نهایی ما در هر دو جنسیت بی‌معنا از کار درآمدهاست. کاری که در این جلسه (معادله ساختاری با کنترل متغیر جنسیت) انجام می‌شود به روش تفکیکی یا سنتی در نرم‌افزار لیزرل است؛ یعنی شبیه کاری که قبلاً در رگرسیون انجام می‌گرفت. در شیوه سنتی ابتدا یک رگرسیون (با داده‌های زنان و مردان) گرفته می‌شد سپس به‌طور جداگانه یک رگرسیون برای زنان و یک رگرسیون برای مردان گرفته می‌شد و در پایان نتایج هر سه رگرسیون با هم مقایسه می‌شد.

Segregation or Integratıon: Gated Communities in Modern Urban Life Turgut Cansever’in mimarlık disiplinini varlığın tüm alanlarını kapsayan bir bilim olarak gören bakış açısı, mimarlığın içinde yaşadığımız 21.yüzyılın sadece şehirleri oluşturmasında değil; insan hayatının sosyolojik, psikolojik ve kültürel alanlarını da etkilediği bilim insanlarınca tespit edilmiştir. 20. yüzyılın en önemli mimarlarından Chicago ekolünün de temsilcilerinden F.L. Wright, “Mimarlık, biçim haline gelmiş yaşamın ta kendisidir” sözüyle zaten doğa ile yapının kendiliğinden bir uyum içinde olması gerektiğini ifade ederek mimarlığın insan hayatının tüm evrelerini kapsadığını savunmuştur. Eserlerine de bu bakış açısını yerleştiren Wright, meşhur şelale evi projesini açıklarken yapının toprağı kucaklayabilmesi gerektiğini; orada yaşayacak insanların doğaya sadece bakmalarını değil, doğayla birlikte bütünleşerek yaşamalarını istediğini belirtmiştir. Peki, Cansever’in mimarlığı varlığın aşkın bir tanımı olarak gören bakış açısı bize ne söylemektedir? Cansever, insanın çevreyi idrak etmesini ve içinde yaşadığımız güzel dünyayı sonsuz bir saygı ile koruyup güzelleştirmesini ahlaki bir sorumluluk vazifesi olarak görmesi gerektiğini belirtir ve ardından sorar: 21.yüzyılın modern ve modern olma yolunda ilerleyen kentleri insanı mutlu edebilir mi, edebiliyor mu? Mimarlık özelinde ilerleyecek olursak, insan nasıl bir çevrede ve nasıl bir yaşamalıdır ki mutlu olabilsin? Bu sorulara elbette cevap vermek zor olsa da, en azından mimarlık disiplininin modern şehir hayatında insanı mutlu edebilecek koşullara hizmet edip edemediğini tartışabiliriz herhalde, değil mi? Köksal Alver’in “Siteril Hayatlar: Kentte Mekânsal Ayrışma ve Güvenlikli Siteler” başlığıyla yayımladığı kitabı , ilk baskı tarihi 2007’den itibaren, önemi her geçen zaman içinde artan, yukarıdaki sorularımıza da cevap arayan, analiz ettiği cevaplarıyla günümüz modern toplum hayatına ışık tutan önemli eserlerden biri. Alver’in modern kent hayatını incelediği ve son yıllarda dünyanın hemen her yerinde artan “güvenlikli site” yaşamını konu edindiği kitabı, bir yandan “güvenlikli site” yaşamının tercih edilmesinin sebeplerini araştırırken, diğer yandan ise “güvenlikli site” yaşamının toplum hayatına getirdiği olumlu olumsuz yanlarını inceliyor. Biz bu yazımızda Alver’in modern kent hayatına dair ileri sunduğu tezleri tartışırken, kitabın ilk yayımlandığı 2007 yılından itibaren sorduğu soruların ve analizlerin ne derece değişip değişmediğini tartışacağız.

Log In

Panniculitis following baricitinib initiation for treatment of rheumatoid arthritis