Rheumatologic Disorders Research Articles

Anakinra for the treatment of adult secondary HLH: a retrospective experience.

Anti-cytokine therapies have been gaining attention as a means of improving outcomes in adult secondary HLH (asHLH), which currently has poor outcomes when treated with standard etoposide-based therapies. Anakinra is an interleukin-1 antagonist that is increasingly being used in the management of asHLH. Here is described a multi-hospital series of 16 adult patients with secondary HLH treated with anakinra. Provoking factors of secondary HLH included hematologic malignancy (n = 7, 44%), bacterial infection (n = 7, 44%), viral infection (n = 5, 31%), rheumatologic disorder (n = 4, 25%), and unknown (n = 1, 6%). Five patients remained alive at time of last follow-up (OS = 31%). Median OS was 1.7 months from initiation of anakinra (range 0.2–59). OS among patients with rheumatologic causes of secondary HLH was 75%, whereas only 17% of patients with other provoking factors survived (p = 0.0293). Anakinra was well tolerated, with only 1 patient experiencing associated toxicity (grade 3 liver injury). Anakinra may be useful in the management of asHLH provoked by rheumatologic conditions, although its benefit in asHLH provoked by other factors may be limited.

Cryofibrinogenemia: What Rheumatologists Should Know.

Cryofibrinogenemia refers to the presence of cryofibrinogen in plasma. This protein has the property of precipitating at lower temperatures. Cryofibrinogenemia is a rare disorder, clinically characterized by skin lesions, such as ulcers, necrosis, livedo reticularis, arthralgia, thrombosis, and limb ischemia. These features are most often observed in rheumatological practice and consist of differential diagnoses of antiphospholipid syndrome, primary vasculitis, thrombotic thrombocytopenic purpura, and cryoglobulinemia. Classical histopathological findings include the presence of thrombi within the lumen of blood vessels of the skin without vasculitis. To date, there are no validated classification criteria. Management includes corticosteroids, immunosuppressive therapy, anticoagulants, and fibrinolytic agents. This narrative review aims to make physicians, particularly rheumatologists, aware of the existence of this underdiagnosed condition. There are no epidemiological studies evaluating the prevalence of cryofibrinogenemia in different rheumatological disorders. Studies are also required to investigate if certain features of rheumatological diseases are related to the presence of cryofibrinogenemia.

Twenty Years of Targeted and Biologic Immunomodulatory Drugs: Postmarketing Modifications of Drug Labels Approved by the US Food and Drug Administration

To determine the extent and characteristics of postmarketing safety issues associated with targeted and biologic immunomodulatory drugs. We searched Drugs@FDA to identify immunomodulatory drugs approved between January 1, 1998, and December 31, 2017. Supporting studies characteristics, regulatory pathways, and label modifications from approval to May 2020 were collected from drug labels. The study cohort included 31 drugs, mostly (n=23, 74%) monoclonal antibodies. The most common indications were rheumatologic disorders (n=10, 32%). A total of 372 postmarketing safety-related label modifications were identified, with a median duration of 5 years (interquartile range [IQR], 32 to 105 months) following initial approval. Most drugs were affected by modifications of warnings and precautions (n=25, 81%), 10 drugs (32%) were affected by black box warnings, and 3 drugs (10%) were withdrawn from the market. The most common safety issues were related to infections (n=109, 27%) followed by immunologic phenomena (n=99, 24%). The most common data source was postmarketing reports to pharmacovigilance programs (n=205, 55%). Drugs approved by the FDA through expedited regulatory pathways (n=12, 39%) had more postmarketing safety issues compared with those approved through regular approval (15.5 vs 9.8 per drug, respectively), with longer durations from approval to identification (6 years; IQR, 38 to 111 months, vs 4 years; IQR, 28 to 95 months). Safety issues associated with targeted and biologic immunomodulatory drugs are often identified postmarketing, with substantial time intervals following initial approval. Clinicians should follow updates of the safety profiles of immunomodulatory drugs closely and be vigilant for previously unidentified adverse events.

Pulmonary Embolism in Women: A Systematic Review of the Current Literature.

Cardiovascular disease is the leading cause of death in women. Pulmonary embolism (PE) is the third most-common cause of cardiovascular death, after myocardial infarction (MI) and stroke. We aimed to evaluate the attributes and outcomes of PE specifically in women and explore sex-based differences. We conducted a systematic review of the literature using electronic databases PubMed and Embase up to 1 April 2022 to identify studies investigating PE in women. Of the studies found, 93 studies met the eligibility criteria and were included. The risk of PE in older women (especially >40 years of age) superseded that of age-matched men, although the overall age- and sex-adjusted incidence of PE was found to be lower in women. Risk factors for PE in women included age, rheumatologic disorders, hormone replacement therapy or oral contraceptive pills, pregnancy and postpartum period, recent surgery, immobilization, trauma, increased body mass index, obesity, and heart failure. Regarding pregnancy, a relatively higher incidence of PE has been observed in the immediate postpartum period compared to the antenatal period. Women with PE tended to be older, presented more often with dyspnea, and were found to have higher NT-proBNP levels compared to men. No sex-based differences in in-hospital mortality and 30-day all-cause mortality were found. However, PE-related mortality was higher in women, particularly in hemodynamically stable patients. These differences form the basis of future research and outlets for reducing the incidence, morbidity, and mortality of PE in women.

Prevalence and Determinants of Gastrointestinal Manifestations in Patients with Selected Rheumatologic Diseases.

Many rheumatic diseases may cause gastrointestinal manifestations. The goal of this study was to analyze the prevalence and predictors of gastrointestinal involvement in patients with rheumatic disorders. A retrospective chart review was performed for patients with systemic lupus erythematosus, rheumatoid arthritis, and sys- temic sclerosis who have consulted due to gastrointestinal symptoms. The relationship between clinical symptoms, gastroscopic/colo- noscopic findings, and histopathological results with current drugs and disease duration was evaluated. A total of 364 patients with rheumatic disorders and 740 people as control group were included in the study. Abdominal bloating followed by abdominal pain, regurgitation, and heartburn were reported as the main complaints by more than half of the patients. Most of the patients had gastric mucosal changes expressed as Lanza score, and the presence of major polypharmacy was the most important factor affecting Lanza score (odds ratio: 10, 95% CI: 1.882-54.111, P < .007) followed by disease duration (odds ratio: 1.559, 95% CI: 1.369-1.775, P < .001) and age (odds ratio: 1.069, 95% CI: 1.030-1.109, P < .001). In general, approximately 30% of the patients were posi- tive for Helicobacter pylori infection and 35% showed intestinal metaplasia in histopathological examination. Most of the colonoscopic findings were associated with colonic polyps (n = 81). In multivariate analysis, disease duration was the only factor that affected the pres- ence of colonic lesions (Area Under the Receiver Operating Characteristic (ROC) Curve (AUROC): 0.871, 95% CI: 0.824-0.918, P < .001). Patients with rheumatologic diseases frequently have gastrointestinal manifestations. The most encountered gastrointes- tinal symptom was abdominal bloating, followed by abdominal pain. Being aware of gastrointestinal manifestations and their determi- nants may help physicians manage and follow patients with rheumatologic disorders.

Cohort profile: the Halland osteoarthritis (HALLOA) cohort–from knee pain to osteoarthritis: a longitudinal observational study in Sweden

PurposeThe overall objective in this study is to investigate the early development of radiographic knee osteoarthritis (OA) and its association with hand or/and knee OA, metabolic diseases, biomarkers, chronic pain,...

ID:16534 Prescription Opioids and Steroid Misuse Masking Underlying Infection of Spinal Hardware

The use of opioids for benign rheumatological disorders has been limited by concerns about adverse events and potential misuse. There has been an increase in use of opioids seen over the years for nonmalignant rheumatologic diseases. Opioids are currently approved as complementary therapy in inflammatory joint and rheumatological conditions. Severe adverse events, including abnormal drug-seeking behavior, although relatively rare, have been documented in a number of cases. This specific case report highlights opioid misuse and is an example of a patient becoming obtunded from a constellation of adverse events because of opioid misuse and overdose.

Fellowship Trainee Research Activities of a Faculty of Bangladesh College of Physicians and Surgeons: Analysis of 30 years Dissertation Work and Recommendation for Further Improvements

Physical Medicine and Rehabilitation (PMR) is a diverse specialty with principal focus on disability evaluation and functional restoration of an individual. The PMR Faculty at Bangladesh College of Physicians and Surgeons (BCPS) was established about 30 years ago. As a medical specialist of 21st century, at this point of time, it is important to know and evaluate the spectrum of research activities performed by the trainees of the faculty. Objectives of the study was to make an in-depth analysis of the dissertations completed by the PMR fellow trainees of BCPS since the inception of the Faculty. It was also aimed to discuss the strengths and insights of shortcoming of the research areas and topics with directives for further improvement of the future trainees and faculties ultimately to initiate a dialogue among the stake holders and other specialties. This was an observational mixed method study. Information was gathered from the BCPS webpage, Faculty office and published materials, which was further strengthened with a small group discussion, online literature search and a telephone interview of the PMR fellows to learn their experience that they gained during the dissertation works. A total of 167 (n=167) dissertation topics were available for statistical analysis submitted by the trainee fellows from 1992 to 2021, a period of 30yrs. More than half (50.9%) of the submitted titles were on effectiveness or comparative study of rehabilitation therapy modalities which include therapeutic -electrophysical -agents(TEA), exercises, occupational therapy or orthotics. Musculoskeletal (MSK) and rheumatological disorders constituted (17.4%), neurological disorder 7.1%), risk factor assessment or etiological pattern of MSK conditions (7.2%), disability and functional outcome assessment (5.4%), interventions for regional pain management (4.8%) and other category (7.2%). The initial decade trend was on MSK, which later shifted to TEA and on interventions respectively. Overall, TEA modalities were the predominating titles in all 3 decades. Considering the other category of titles, there were interesting topics which include COVID-19, variation in body mass composition, assessment of drug effects, diagnostics and effectiveness of educational booklet. Of the 09 dissertations approved during the most recent year (2021), 34% were with interventional pain management. In the process of doing a dissertation, a number of opportunities and challenges were identified by the fellows for fellow trainee researchers. There was a clear trend of dissertation titles on MSK pain management and interventions with less attention to rehabilitation procedure and appliances. Identified opportunities include cooperative attitude of the trainers and mentors in the department and there were wide research areas with vast sample population. Time allocation and funding were the biggest barriers for research works during training period. BCPS to support on research methodology, fund placements and to catalyze with other institutes to ensure a reasonable level comfort for research works. J Bangladesh Coll Phys Surg 2022; 40: 51-56

Rash morphology as a predictor of COVID-19 severity: Asystematic review of the cutaneous manifestations ofCOVID-19.

Approximately 6% of those with COVID‐19 will experience cutaneous manifestations. Examining data from this cohort could provide useful information to help with the management of COVID‐19. To that end, we conducted a systematic review primarily to assess rash morphologies associated with COVID‐19 and their relationship with disease severity. Secondary outcomes include demographics, distribution, dermatological symptoms, timeline, diagnostic method and medication history. The literature was searched for all patients with skin manifestations thought to be related to suspected or confirmed COVID‐19. Patients with a history of dermatological, rheumatological or occupational skin disorders were excluded. Of the 2056 patients selected, the most common morphologies were chilblain‐like lesions (54.2%), maculopapular (13.6%) and urticaria (8.3%). Chilblain‐like lesions were more frequent in the younger population (mean age 21.5, standard deviation ± 10.8) and were strongly linked with milder disease, not requiring an admission (odds ratio [OR] 35.36 [95% confidence interval {CI} 23.58, 53.03]). Conversely, acro‐ischaemia and livedo reticularis were associated with worse outcomes, including a need for ICU (OR 34.01 [95% CI 16.62, 69.57] and OR 5.57 [95% CI 3.02, 10.30], respectively) and mortality (OR 25.66 [95% CI 10.83, 60.79] and OR 10.71 [95% CI 4.76, 24.13], respectively). Acral lesions were the most common site (83.5%). 35.1% experienced pruritus, 16.4% had pain and 4.7% reported a burning sensation. 34.1% had asymptomatic lesions. Rash was the only symptom in 20.9% and occurred before or alongside systemic symptoms in 12.4%. 28.3% had a positive polymerase chain reaction nasopharyngeal swab and 5.4% had positive antibodies, while 21.9% tested negative and 45.1% were not tested. In conclusion, COVID‐19 causes a variety of rashes, which may cause symptoms and add to morbidity. Rash type could be helpful in determining COVID‐19 prognosis.

T218 Reticulocyte hemoglobin (CHR) by Mindray BC 6800 plus for the assessment of iron deficient erythropoiesis in rheumatologic disorders

T218 Reticulocyte hemoglobin (CHR) by Mindray BC 6800 plus for the assessment of iron deficient erythropoiesis in rheumatologic disorders

Pattern of rheumatological disorders and its management in rural population of central India

Background: India is home to the world's second largest population. Rheumatology is an emerging specialty in India. We looked at publications in the field of rheumatology from India from over the past six years using Scopus and Medline databases. Despite rheumatologic disorders affecting 6.0%-24.0% of the population, rheumatology in India is still in its infancy. So, we studied the pattern of rheumatological disorders and its management in rural population of central India. Material and Methods: A cross sectional study was done for a period of 18 months on 100 people attending inpatient and outpatient from General Medicine and Orthopaedics departments of Uttar Pradesh University of Medical Sciences, Saifai, India. All patients of age 12 years and above coming to UPUMS with history suggestive of Rheumatological disorders were included in the study. Results: Out of 100 studied patients 85.0%were in age group 31-40 years with female predominance (72.0%). Hypertension was the commonest comorbidity followed by hypothyroidism and diabetes. Rheumatoid arthritis (49.0%) was the most common disease followed by Osteoarthritis (20.0%), Spondyloarthritis (18.0%) and Systemic lupus erythematosus (7.0%). The difference between joint examination in different rheumatic disease was statistically insignificant (p&gt;0.05).

The new onset seropositive rheumatoid arthritis after COVID-19 infection: coincidental or related

Coronavirus disease 2019 (COVID-19) is an infectious disease, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The relationship of COVID-19 with rheumatological disorders has been researched since 2019. Rheumatoid arthritis (RA) is one of the most common rheumatoid diseases. The relationship between RA and COVID-19 is particularly interesting due to common cytokines in etiopathogenesis. SARS-CoV-2 was involved in triggering RF-positive and ACPA-positive arthritis, which might be diagnosed as rheumatoid arthritis, but we cannot rule out the possibility that the onset of this arthritis could have been coincidental. We report the case who has the first flare of RA with a high titer of Rheumatoid Factor (RF) and Anti Citrullinated Protein Antibody (ACPA) after mild SARS-CoV- 2 infection.

Bad to the Bone: The Effects of Therapeutic Glucocorticoids on Osteoblasts and Osteocytes.

Despite the continued development of specialized immunosuppressive therapies in the form of monoclonal antibodies, glucocorticoids remain a mainstay in the treatment of rheumatological and auto-inflammatory disorders. Therapeutic glucocorticoids are unmatched in the breadth of their immunosuppressive properties and deliver their anti-inflammatory effects at unparalleled speed. However, long-term exposure to therapeutic doses of glucocorticoids decreases bone mass and increases the risk of fractures – particularly in the spine – thus limiting their clinical use. Due to the abundant expression of glucocorticoid receptors across all skeletal cell populations and their respective progenitors, therapeutic glucocorticoids affect skeletal quality through a plethora of cellular targets and molecular mechanisms. However, recent evidence from rodent studies, supported by clinical data, highlights the considerable role of cells of the osteoblast lineage in the pathogenesis of glucocorticoid-induced osteoporosis: it is now appreciated that cells of the osteoblast lineage are key targets of therapeutic glucocorticoids and have an outsized role in mediating their undesirable skeletal effects. As part of this article, we review the molecular mechanisms underpinning the detrimental effects of supraphysiological levels of glucocorticoids on cells of the osteoblast lineage including osteocytes and highlight the clinical implications of recent discoveries in the field.

Role of homoeopathy in the management of adhesive capsulitis: A pretest-posttest study

Background: Adhesive capsulitis (AC) is an insidious and painful stiffening of the glenohumeral (shoulder) joint, resulting in compromised functional ability and quality of life (QoL). Objectives: Primary objective was to evaluate change in shoulder pain after individualised homoeopathy treatment for over 2 months. Secondary objective was to assess the change in the QoL and outcome related to impact on daily living (ORIDL). Methods: A single-arm, pretest-posttest, clinical study on AC was conducted on 40 participants recruited from the outpatient clinic of rheumatological disorders at Clinical Research Unit (Homoeopathy), Siliguri, West Bengal, India. Medicines were prescribed on the basis of the totality of symptoms. Changes in shoulder pain over 2 months were evaluated using the shoulder pain and disability index (SPADI). QoL was evaluated using SF-12v2 and ORIDL (participants and physician assessed), respectively. Results: Thirty-six participants completed the study and four participants dropped out. A protocol compliant sample of n = 36 was analysed. There was a statistically significant reduction of SPADI score (91.92 ± 10.22 vs. 34.14 ± 24.43; mean reduction 57.78, 95% CI 49.41–66.14, P < 0.001) and statistically significant increase in SF-12 v2 score (44.39 ± 9.70 vs. 72.27 ± 10.97; mean increase 27.87, 95% CI 23.89–31.85, P < 0.001). The Spearman’s correlation between the changes in physician assessment ORIDL scores and participants assessment ORIDL scores over 2 months suggested a statistically significant correlation (rs = 0.998, P < 0.01). Conclusion: The findings showed symptom alleviation, and improvement in the QoL after homoeopathic treatment. Randomised controlled trials are further warranted.

Post-chikungunya arthritis: a longitudinal study in a tertiary care hospital in Bangladesh

Background and objectiveTo identify the clinical patterns and consequences of post-chikungunya arthritis was the study's objective.MethodsThis longitudinal study was carried out among 143 Chikungunya virus (CHIKV) infected adult patients at the rheumatology department, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh, during the outbreak of CHIKV infection in 2017. The disease was categorized into three phases: acute or febrile (lasting up to 10 days), subacute (11–90 days), and chronic (> 90 days). Patients who progressed towards the chronic phase were followed up to 1-year. Post-CHIKV de novo chronic inflammatory rheumatisms (CIRs) were characterized by persistent mono or oligoarthritis, undifferentiated polyarthritis, or meet the criteria rheumatoid arthritis (RA) or Spondyloarthritis (SpA). In addition, functional status was assessed by the validated Bangla version of the Health Assessment Questionnaire (HAQ).ResultsMean age was 43.3 ± 11.5 years, and 51.0% were male. Within 1-year follow-up, 60 (41.9%) patients were suffering from arthralgia/ arthritis. Of them 52 patients did not have any pre-existing arthralgia/arthritis. 35 (65.3%) had undifferentiated arthritis, 10 (19.2%) had SpA, and 7 (13.5%) had RA. Patients with pre-existing rheumatological disorders, 6(4.2%) had SpA, 1(0.7%) had RA and 1(0.7%) had osteoarthritis. Polyarthralgia (n = 33, 55.0%) and polyarthritis (n = 20, 33.3%) were the main presentations. Female gender (OR: 0.45; CI: 0.21–0.96), positive IgG (OR: 0.30; CI: 0.12–0.76), and moderate to severe functional disability (OR: 3.46; CI: 1.62–7.40) were independent predictors of developing chronic post-CHIKV rheumatism.ConclusionsAt 1-year follow-up, more than one-third of the patients remained symptomatic. Female gender, positive IgG, and moderate to severe functional disability contributed to the development of chronicity.

Pyoderma Gangrenosum with Splenic Abscess- A Rare Association

Pyoderma gangrenosum is a rare, chronic neutrophilic dermatosis of unknown etiology. The classical clinical feature of pyoderma gangrenosum is a pustule or plaque that rapidly progresses to a painful, necrotic ulcer with undermined violaceous margins. Pyoderma gangrenosum may be associated with underlying inflammatory bowel diseases, hematological malignancies, or rheumatologic disorders in 50–70% of the cases. The visceral involvement by pyoderma gangrenosum is rare. Sterile neutrophilic infiltrates in organs other than the skin are uncommon systemic manifestations of neutrophilic dermatoses, but have occasionally been reported. We report a case of a 38-year-old female with pyoderma gangrenosum and visceral involvement manifesting as splenic abscess.

Salivary Gland Disorders in Pediatric Patients: A 20 Years’ Experience

Salivary gland disorders are uncommon in children; they show a lower prevalence when compared to adults. The literature has a relative lack of information about the management and the different treatment protocols regarding these diseases. The aim of this research is to investigate the prevalence of both benign and malignant salivary gland disorders, focusing on diagnostic and therapy. An audit of patients diagnosed with salivary gland disorders was conducted from 2000 to 2020. 99 patients’ records were selected and analyzed: 51 males’ and 48 females’, age 10 ± 4 SD. Obstructive pathologies were the most frequently diagnosed (49 patients) followed by oncologic (21 patients), inflammatory (20 patients), rheumatologic (4 patients), malformative (3 patients) and infective disorders (2 patients). The parotid was the most affected major gland in 47 cases with a prevalence of diagnosis of juvenile recurrent parotitis (JRP) (40.4%), followed by the sublingual gland in 14 cases of ranula (100%) and the submandibular gland in 11 patients suffering from sialolithiasis (84.6%). Swelling was the most common symptom (75.7% of patients). Seven different neoplasms were documented. A greater prevalence of low-grade mucoepidermoid carcinoma among the malignant group (38.1% of oncologic cases) was noted. In regards to benign tumors, pleomorphic adenoma was the most common diagnosis (47.6% of cases). The symptoms and outcomes showed statistical significance concerning gender. Although salivary gland diseases in children and adolescents are rare, it is essential to observe and monitor all of the symptoms to intervene if necessary, as painless swelling is a symptom common from both benign and malignant diseases.

Sympathetic Blocks for Raynaud's Phenomena in Pediatric Rheumatological Disorders.

Sympathetic blocks are invaluable to prevent morbidity from Raynaud's phenomenon (RP). RP may occur in children with rheumatological disorders and causes severe pain, discoloration of digits, gangrene, and auto-amputation. We describe the planning and execution of sympathectomy blocks in children with rheumatological disorders presenting with RP. With upper-limb involvement, ultrasound-guided stellate ganglion block (USGB) was given with ropivacaine and clonidine. When all four limbs were involved, intrathecal block with bupivacaine and clonidine was also given. A total of 68 sympathectomy blocks were performed: 28 bilateral USGBs, two unilateral USGBs, and 10 intrathecal injections. Multiple interventions in a single day were frequently required. For safety, all USGBs were performed with an ultrasound with strict adherence to local anaesthetic volume was maintained, with periprocedure monitoring of 2-3 hours. All blocks were performed by an experienced specialist. All children reported immediate pain relief with prevention of major amputation. With meticulous planning, monitoring, and precautions, sympathectomy of limbs in pediatric rheumatological disorders with RP can be safely undertaken. Bilateral stellate ganglion block with ultrasound is safe in children, and clonidine is a useful adjunct for vasodilation and prolongation of the effect of sympathectomies in children.

Nutritivne preporuke tokom dugotrajne primene glukokortikoida

Glucocorticoids are highly effective medications used for the treatment of inflammatory and autoimmune disorders in rheumatology, pulmonology and neurology. However, using these medications for a long period of time, or in excessive doses, carries the risk of unwanted effects. Most typical sideeffects can be successfully prevented or reduced with adequate nutritional strategies. Increased appetite and weight gain can be reduced with regular meals with a selection of fresh, unprocessed foods in accordance with the principles of proper nutrition. Hypertension requires a reduced salt intake by &lt; 3.75 g (1/2 teaspoon), along with the use of other herbs spices. Insulin resistance and elevated blood sugar levels can be reduced, by avoiding foods rich in simple carbohydrates, sugar and by preferring complex carbohydrates (whole grains, starchy foods, fruits, vegetables). Due to the high risk of osteoporosis, it is recommended to consume three servings of dairy products and fish per day in order to obtain an adequate intake of vitamin D. However, patients may find these recommendations unclear or overly strict, and they may require assistance, motivation, and repetition of information for practical application of these advice in everyday life.

International definition of iMCD-TAFRO: future perspectives.

Since thrombocytopenia, anasarca, fever, reticulin fibrosis, renal insufficiency, and organomegaly (TAFRO) syndrome was first proposed in 2010, there has been considerable progress in this area, particularly regarding its association with idiopathic multicentric Castleman disease (iMCD). TAFRO syndrome is a heterogeneous category with a constellation of symptoms that can develop in the setting of infection, rheumatologic disorder, malignancy, and iMCD. Now, iMCD with TAFRO symptoms is subtyped as iMCD-TAFRO. However, confusion between TAFRO syndrome and iMCD-TAFRO remains. In this article, we discuss the current understanding and future research agenda of TAFRO syndrome and iMCD-TAFRO from the perspective of its new validated international definition.