Current Rheumatology Reviews - Volume 20, Issue 4, 2024

Panniculitis was first described in the nineteenth century and is characterized by inflammation of the subcutaneous fat. It may be categorized in septal or lobular subtypes, but other histopathological features (e.g., presence of vasculitis, nature of inflammatory infiltrates, characteristics of fat necrosis) are also important for diagnostic purposes. Clinically, panniculitis is characterized by the presence of subcutaneous nodules, and both ulcerative and nonulcerative clinical subtypes have been proposed. In this review, we aimed to describe the occurrence of panniculitis in autoinflammatory disorders (AIDs) and related diseases. Among monogenic AIDs, panniculitis is common in IFN-mediated disorders. Panniculitis is a distinctive feature in proteasome-associated autoinflammatory syndromes (PRAAS), including chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature (CANDLE) syndrome and Nakajo-Nishimura syndrome. On the other hand, erythema nodosum corresponds to the most common clinical form of panniculitis and is common in polygenic AIDs, such as Behçet’s syndrome, inflammatory bowel disease, and sarcoidosis. Cytophagic histiocytic panniculitis, lipoatrophic panniculitis of children, and otulipenia are rare disorders that may also present with inflammation of the subcutaneous fat. Therefore, panniculitis can identify a specific subgroup of patients with AIDs and may potentially be regarded as a cardinal sign of autoinflammation.

As the global population ages, osteoporosis is becoming a more common silent disease. Osteoporosis is characterized by decreased bone quality and strength, which increases the risk of fragility fractures in the elderly. According to estimates, 50% of women eventually suffer from an osteoporotic fracture. Due to increasing disability, more frequent hospital hospitalizations, and most critically, fragility fractures have been linked to a reduced quality of life. Osteoporotic fractures have been linked to an increased mortality risk; and must be considered in awareness as a serious health concern. There are anti-osteoporotic medications available that improve bone quality. Considering the availability of various treatment options, still there are a lot of underserved needs in the treatment of fractures and osteoporosis. For example, the application of natural products and herbal resources for fracture healing, because of the androgen-like and antioxidant characteristics of the plants, they can play a crucial for accelerating the repair of bone fractures. In this article, we’ll discuss the herbal remedies that are essential for treating osteoporosis (bone disease).

Osteoarthritis in the temporomandibular joint (TMJ) is a chronic disease characterized by irreversible damage to articular surfaces, including inflammation, loss of articular cartilage, and subchondral bone alterations, which would be radiographically evident only in later stages. Symptomatic slow-acting so-called nutraceutical drugs have been proposed as a treatment for osteoarthritis in comparison to non-steroidal anti-inflammatory drugs (NSAID) because of their appreciable safety profile even in long-term intake. Glucosamine, being one among them, proved highly efficient in knee osteoarthritis. However, its application in TMJ osteoarthritis dates back only to 2001 and is still inconclusive in its efficiency even with systematic reviews, in restoring the structural and functional aspects of damaged TMJ. Glucosamine, being a natural compound and also a contributor to building the matrix of articular cartilage, can be utilized effectively for TMJ osteoarthritis as an adjunct along with other conventional treatment modalities available till now, which also have moderate prognosis in most of the clinical scenarios. This review summarizes data relating to the mechanism of osteoarthritis and its management using glucosamine formulations. The beneficial effects of glucosamine on the pathophysiology of TMJ osteoarthritis are possibly due to its contribution to hyaluronic acid regulation and in establishing a proper balance between anabolism/catabolism in the articular tissues.

Background: There is conflicting evidence regarding the efficacy of viscosupplementation with intra-articular hyaluronic acid injections in knee osteoarthritis. One possible explanation for the inconsistent findings on its efficacy is that only certain subpopulations of patients benefit from this therapy. Objective: The purpose of this narrative review is to succinctly summarize the existing data on the predictive factors of clinical response to intra-articular hyaluronic acid to identify the patient profile most likely to benefit from this therapy. Methods: For this narrative review, a PubMed search was conducted in January 2023, with no date limits, to identify publications reporting predictive factors of response to viscosupplementation using the following terms: hyaluronic acid OR viscosupplem* AND osteoarthritis AND knee AND predict*. Searches were limited to randomized controlled trials, systematic reviews and meta- analyses, or observational studies written in English. Other relevant references were identified by searching the references of retrieved articles. Results: The disease severity was found to reliably predict response to intra-articular hyaluronic acid injections; patients with less severe disease consistently had a more robust therapeutic response than those with more severe disease. Other clinical variables such as level of baseline pain did not reliably predict response. Body mass index, and possibly age, may also be independent predictors of the response. Conclusion: A review of the existing literature suggests that patients with less severe clinical symptoms and radiological findings, who are younger, and with a lower or normal body mass index are the best candidates for intra-articular hyaluronic acid therapy.

Systemic Sclerosis (SSc) is a systemic autoimmune disease of unknown etiology with a highly complex pathogenesis that despite extensive investigation is not completely understood. The clinical and pathologic manifestations of the disease result from three distinct processes: 1) Severe and frequently progressive tissue fibrosis causing exaggerated and deleterious accumulation of interstitial collagens and other extracellular matrix molecules in the skin and various internal organs; 2) extensive fibroproliferative vascular lesions affecting small arteries and arterioles causing tissue ischemic alterations; and 3) cellular and humoral immunity abnormalities with the production of numerous autoantibodies, some with very high specificity for SSc. The fibrotic process in SSc is one of the main causes of disability and high mortality of the disease. Owing to its essentially universal presence and the severity of its clinical effects, the mechanisms involved in the development and progression of tissue fibrosis have been extensively investigated, however, despite intensive investigation, the precise molecular mechanisms have not been fully elucidated. Several recent studies have suggested that cellular transdifferentiation resulting in the phenotypic conversion of various cell types into activated myofibroblasts may be one important mechanism. Here, we review the potential role that cellular transdifferentiation may play in the development of severe and often progressive tissue fibrosis in SSc.

Fibromyalgia (FM) is a complex, widespread pain disorder characterized by symptoms such as fatigue, sleep deprivation, mental fog, mood swings, and headaches. Currently, there are only three FDA-approved medications for FM patients: duloxetine, milnacipran, and pregabalin, with outcomes frequently being inadequate. This research team aims to investigate the effects of diet and lifestyle modifications on FM, with emphasis on anti-inflammatory diet, antioxidants, and gluten-free diets, as well as supplementation with Magnesium, CQ10, and Vitamin D, microbiome, sleep, exercise, and cognitive behavioral therapy. We reviewed the pathophysiology of certain foods that can be proinflammatory with the release of cytokines leading to activation of pain, fatigue and aggravation of the majority of Fibromyalgia symptoms. A literature review was performed by identifying FM articles published between 1994 and 2022 via PubMed and EMBASE databases, with particular emphasis on randomized controlled trials, meta-analysis, and evidence-based treatment guidelines. This review article was completed by a comprehensive narrative review process, in which our team systematically examined relevant scientific literature to provide a comprehensive overview of the significant role that diet and other lifestyle modifications play in mediating symptoms of Fibromyalgia. We propose that diet modifications and lifestyle changes, such as sleep, exercise, and weight loss, can be important steps in managing FM.

Background: Rheumatoid arthritis (RA) and osteoarthritis (OA) are the most common forms of skeletal disease worldwide. Objective: The current systematic review investigated the mechanisms of Silybum marianum, silymarin, and silibinin on RA and OA symptoms. Methods: The PRISMA 2020 statement was used for reporting Items in this systematic review. The result was a list of five databases, including Web of Science, Cochrane Library, Embase, PubMed, and Scopus. After determining the inclusion and exclusion criteria, of 437 records identified, 21 studies were eligible. The data were extracted from the studies and imported into an Excel form, and finally, the effects, outcomes, and associated mechanisms were surveyed. Results: Silybum marianum and its main constituents revealed immunomodulatory, anti-inflammatory, antioxidant, and anti-apoptotic properties in humans and laboratory animals. Moreover, they protect the joints against the cartilage matrix's hypocellularity and fibrillation, reduce synovitis, and inhibit degeneration of aggrecan and collagen-II in human chondrocytes. They also, through reducing inflammatory cytokines, show an analgesic effect. Although silymarin and silibinin have low absorption, their bioavailability can be increased with nanoparticles. Conclusion: In experimental studies, Silybum marianum, silymarin, and silibinin revealed promising effects on RA and OA symptoms. However, more clinical studies are needed in this field to obtain reliable results and clinical administration of these compounds.

Background: Balance weaknesses related to mobility and fall risk in patients with rheumatic diseases are well-known. Vestibular dysfunction could negatively contribute to the balance ability of this patient population. This study aims to investigate the effects of Rheumatoid Arthritis (RA) and Ankylosing Spondylitis (AS), among the most common rheumatic diseases, on postural balance related to vestibular function. Methods: Seventy-eight participants were grouped as RA (n=34, 43%), AS (n=24, 30.7%), and the control group consisted of healthy individuals (n=20, 25.6%). Cervical Vestibular Evoked Myogenic Potentials (cVEMP) test, which assesses the vestibular function objectively, Dizziness Handicap Inventory (DHI), which evaluates vertigo subjectively, and Berg Balance Scale (BBS) were performed. Results: Different degrees of VEMP latency prolongations were found in the AS and RA groups. Right, and left ear N1 latencies were significantly longer in the AS group than in RA and control. Right ear P1 latency prolongation was statistically significant in the RA group. Amplitude asymmetry ratio (AAR) was found to be considerably higher in the RA and AS groups than in the control group (p < 0.05). The mean BBS score in the AS group was below the fall risk score of 45. A negative statistically significant effect was observed between latency prolongation and BBS in AS groups. Conclusion: The abnormal VEMP findings in individuals with RA and AS shows inner ear vestibular system dysfunction. This vestibular impairment strictly contributes to their postural imbalance and requires a focused vestibular rehabilitation program for balance treatment.

Introduction: Tumor necrosis factor alpha (TNF alpha) blockers such as infliximab (IFX) and adalimumab (ADA) had significantly changed the course of inflammatory diseases such as rheumatoid arthritis (RA), spondyloarthritis (SpA) and Crohn's disease (CD). However, about 30% of patients do not respond to these treatments. This lack of response may be due to the formation of antibodies against these drugs (anti-drug antibodies: ADAbs). The aim of this study was to determine the prevalence of ADAbs against IFX and ADA, and the trough serum concentration of IFX and ADA in RA, SpA or CD patients and to assess their impact on the therapeutic response. Methods: A cross sectional, multi-centric study was conducted, including patients with RA, SpA or CD treated with IFX or ADA as a first biotherapy for at least 6 months. ADAbs and trough levels were measured by an Enzyme Linked Immunosorbent assay (ELISA). Results: 197 patients were included (57 RA, 73 SpA and 67 CD). ADAbs were positive in 40% of cases for IFX and 25% for ADA. They were positive in 40% of SpA, 35% of RA, and 21% of CD. The presence of ADAbs was inversely correlated to the trough levels of IFX and ADA during RA (p = 0.01 and p < 0.0001), SpA (p < 0.01 and p < 0.0001) and CD (p = 0.001 and p = 0.04). For all pathologies, the presence of ADAbs was not correlated with disease activity. Concomitant methotrexate significantly reduced immunogenicity. Conclusion: In our study, the presence of ADAb and low trough levels seem to not affect the therapeutic response in patients on TNF alpha antagonists. Other tracks more than immunogenicity should be investigated to explain the loss of response to these biotherapies.

Introduction: Generally, patients with chronic rheumatic diseases use complementary and alternative medicine (CAM) in addition to their conventional treatments to manage their health. Discussing these treatments with their physician is still rare, which might be directly related to patients’ trust toward them. Aim: The primary objective of this study was to assess the association between patients’ trust in their physician and the use of complementary and alternative medicine among patients with chronic inflammatory rheumatic diseases. As secondary objectives, to estimate the prevalence of CAM use, and to identify the associated factors with their use and with trust in physicians. Methods: This is a cross-sectional study, which included patients with established chronic inflammatory rheumatic diseases, at the University Hospital Center in Tangier. The questionnaire included demographic and clinical information, use of conventional therapy, complementary and alternative therapy, as well as interpersonal trust in patient-physician relationships using the Trust in Physician Scale (TPS). A regression analysis was conducted to identify factors associated with CAM use and with trust in physicians. Results: The study included 189 patients. 57.14% of patients reported using complementary medicine at least once, most patients were women (77.78%), mean age was 46.67 ± 13.25 years with an average course of the disease of 11.11 ± 9.23 years. The most frequently used CAM treatments were cupping therapy, massage and the ingestion of a mixture of plants. Mean ± SD Trust in Physician Scale was 47.64 ± 7.2. There was no significant difference between CAM users vs. non-users (48.08 ± 6.9 vs 47.04 ± 7.4; p = 0.35). In uni and multivariate analysis, a low level of education was significantly associated with the use of CAM. However, no statistically significant difference was found with trust in physicians (OR = 1.020, 95% CI (0.978-1.063), p = 0.354). Conclusion: CAM therapy is common in patients with chronic inflammatory rheumatic diseases. No statistically significant association was found with trust in physicians, it was rather observed with level of education.

Background: Tumor necrosis factor alpha (TNFα) is a pivotal cytokine involved in the pathogenesis of certain inflammatory diseases, such as rheumatoid arthritis (RA), spondyloarthropathies, and inflammatory bowel diseases. In the last two decades, TNFα inhibitors (TNFi) have revolutionized the treatment and outcome of the above disorders. However, the use of TNFi has been associated with the development of many autoimmune phenomena and paradoxical skin manifestations that may present as the same type of clinical indications for which the TNFi effectively used. Thus, they may display as arthritis, uveitis, colitis, psoriasis, and several other cutaneous clinical manifestations, among them the development of morphea, a localized scleroderma skin lesion. Case Presentation: We describe a 58-year-old woman with seronegative RA, refractory to methotrexate, who was treated with ABP-501 (Hefiya), an adalimumab (ADA) biosimilar and developed an oval-shaped, deep skin lesion of approximately 3.5cm in size, affecting the left part of her back compatible with morphea 3 months after the initiation of therapy. ADA biosimilar was discontinued and two months later, she had substantial skin improvement. Conclusion: This is the first report of morphea manifestation during TNFi biosimilar since the patient had no other trigger factors for morphea development like trauma and infections. Physicians dealing with patients treated with TNFi biosimilars should be aware of paradoxical skin reactions, among them morphea; thus, close monitoring, a minute and careful clinical examination, and a follow- up check are required.

Background: Primary hyperoxaluria consists of a group of inherited disorders with enzymatic defects in the glyoxylate pathway, leading to decreased oxalate metabolism. The resulting oxalic deposition is specifically responsible for kidney disease and joint disease. Neonatal oxalosis is the most severe form of primary hyperoxia type 1, with the onset of end-stage renal disease in childhood. Case Presentation: A 55-year-old hemodialysis man was referred to Nephrology because of inflammatory polyarthralgia and periarticular swelling evolving for six months. He had been on hemodialysis for six years for end-stage chronic renal failure, diagnosed at the same time as primary hyperoxaluria. Radiological investigation showed a rugby jersey appearance on the lumbar spine, budding calcium tone opacities next to large joints and clavicles, vascular calcifications and tumoral calcinosis. The synovial fluid contained a few cells with polymorphic intracellular crystals. We ruled out hyperparathyroidism, hypoparathyroidism, and related phosphocalcic disorders, and we retained arthropathy and tumoral calcinosis secondary to primary hyperoxaliuria. The patient also had congestive heart failure. Despite intensification of hemodialysis, he did not improve and died at the age of 56 in the context of cachexia. Conclusion: This rare case documents the possible occurrence of late clinical presentation and long survival in primary oxalosis with extra renal complications.

Background and Aim: A tenosynovial giant cell tumor (TGCT) is a proliferative lesion of the synovial membrane of the joints, tendon sheaths and/or bursae. There are two described subtypes, including the localized and diffuse forms. A TGCT can also be intraarticular or extraarticular. An intraarticular localized tenosynovial giant cell tumor (L-TGCT) of the knee is characterized by nodular hyperplasic synovial tissue that can remain asymptomatic for a long time, but as the mass grows, it may cause mechanical symptoms that may require surgical treatment. The aim of our study is to present a rare case of an L-TGCT of the knee joint treated with an arthroscopic excision. Case Report: We describe the case of a 17-year-old female with pain, swelling and knee locking in the absence of trauma. The magnetic resonance imaging (MRI) displayed a well-circumscribed small mass in the anterior medial compartment, adherent to the infrapatellar fat pad. The lesion presented the typical MRI characteristics of an intraarticular localized TGCT. The patient was treated with an arthroscopic mass removal and partial synovectomy. The gross pathology showed an ovoid nodule that was covered by a fibrous capsule; a histopathology examination confirmed the diagnosis. The patient was able to return to normal daily activities one month after surgery; at the three-year follow-up, she was free of symptoms with no evidence of disease on the MRI. Conclusion: In patients with a small-dimension L-TGCT in the anterior compartment of the knee that presents an MRI pattern and causes mechanical symptoms, an arthroscopic en-bloc excision can be performed that results in good outcomes and a rapid return to preinjury levels.

Background: Avascular necrosis (AVN) is a potentially serious multifactorial disease. In COVID-19 patients, AVN of many bones has been reported. Usually, the condition is linked to steroid therapy. In this case report, we describe our experience with bilateral AVN of femoral heads in an elderly patient months after being cured of COVID-19 infection without the use of steroids. Case Presentation: A 68-year-old male was referred to the outpatient clinic of the rheumatology and rehabilitation department for progressive bilateral hip pain starting on the left side 5 months ago. An extensive review of the patient’s medical history identified documented COVID-19 infection that required hospitalization 9 months before presentation. Multiplanar MRI with fat suppression of both hips showed ill-defined areas of abnormal signal intensity affecting the left femoral head, neck and intertrochanteric regions with associated subchondral fissuring and mild joint effusion. A similar smaller area was also seen affecting the postero-superior aspect of the right femoral head. Conclusion: AVN in COVID-19 patients can be encountered even in the absence of steroid therapy.