Pancreatitis, panniculitis, and polyarthritis syndrome in a dog with hyalinizing pancreatic adenocarcinoma.

A 10-y-old spayed female Cavalier King Charles Spaniel dog was presented to the Veterinary Teaching Hospital because of recurrent chronic abscesses on the distal pelvic limbs, fever, lethargy, lameness of unknown etiology, and chronic pancreatitis. Sterile nodular panniculitis was diagnosed after an extensive workup, and the dog initially responded to immunosuppressive therapy, but relapse and spread of cutaneous lesions and acute lameness occurred after 11 mo, and euthanasia was elected. Postmortem examination confirmed hyalinizing pancreatic adenocarcinoma with pancreatitis, panniculitis, polyarthritis (PPP), and osteomyelitis. Histopathology and bacterial and fungal cultures were supportive of a sterile process, specifically the PPP syndrome, which is a rare, potentially life-threatening, systemic manifestation of pancreatic disease in both people and animals. To our knowledge, a clinicopathologic description of a hyalinizing pancreatic adenocarcinoma associated with this rare syndrome has not been reported previously in a dog.

Gingerol nanoparticles attenuate complete Freund adjuvant-induced arthritis in rats via targeting the RANKL/OPG signaling pathway.

Rheumatoid arthritis (RA) is characterized by inflammatory joint pathology leading to the degradation of articular bone and cartilage, primarily triggered by synovial inflammation, resulting in joint discomfort. The metacarpophalangeal and proximal interphalangeal joints are predominantly affected. Treatment typically involves a combination of biological and synthetic disease-modifying antirheumatic drugs (DAMARDs) alongside steroid therapy. The application of nanomedicine has been instrumental in enhancing treatment efficacy by facilitating controlled release of pharmacologically active compounds, thus augmenting bioavailability and enabling targeted drug delivery. Gingerol, a constituent of ginger, possesses multifaceted properties. including anti-inflammatory, anti-oxidant, antidiabetic, and antipyretic effects. In this study, gingerol-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs), coated with chitosan, were administered orally to rats over a period of 21 days to address RA induced by complete Freund adjuvant (CFA). The rats were segregated into four experimental groups. Upon completion of the treatment regimen, blood samples were collected for the assessment of cyclooxygenase-2 (COX-2), RA factor, interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α). Subsequent gene expression analysis was conducted to evaluate the levels of interleukin-4 (IL-4), interleukin-17a (IL-17a), IL-6, interferon-gamma (INF-γ), TNF-α, interleukin-1 beta (IL-1ß), osteoprotegerin (OPG), and receptor activator of nuclear factor kappa-B ligand (RANKL). Statistical analyses utilizing one-way ANOVA followed by Tukey tests were applied to the data. The gene expression profiling revealed significant disparities in mRNA levels of IL-1ß, IL-6, IL-4, IL-17a, RANKL, INF-γ, and TNF-α between the CFA-induced arthritis group and the control group. Consequently, it was inferred that gingerol-loaded PLGA NPs coated with chitosan exhibited heightened therapeutic efficacy in addressing CFA-induced arthritis in rats.

Polyarthritis in Sjögren's Syndrome: Difficulties in Distinguishing Extraglandular Manifestation and Associated Rheumatoid Arthritis.

Aim of the study was to investigate the demographic data and disease course characteristics of patients with Sjögren's syndrome (SS) and inflammatory joint pain of various origins and to search for factors that might help with the distinction of polyarthritis as an extraglandular manifestation and rheumatoid arthritis as an associated systemic autoimmune disorder. A total of 355 patients were retrospectively analyzed, 128 of whom served as controls (SS-C), while 159 had polyarthritis as an extraglandular symptom of Sjögren's syndrome (SS-pa) and 68 were diagnosed as having associated rheumatoid arthritis (SS-RA). The patients without any inflammatory joint manifestations were significantly older than the SS-pa patients, while, for the SS-RA group, the difference was not significant. The onset of joint pain appeared significantly earlier in the SS-RA patients. Regarding either extraglandular manifestations or associated autoimmune disorders, there were significant differences between the controls and both SS-pa and SS-RA groups, while no significant difference was found between the SS-pa and SS-RA groups. Thus, laboratory and imaging methods should be used to differentiate between the two conditions, but laboratory biomarkers are even more important for early diagnosis. A ROC curve analysis showed an acceptable diagnostic accuracy in differentiating between SS-pa and SS-RA patients using a binary logistic regression model, where highly positive rheumatoid factor (RF) and anti-cyclic citrullinated peptide (CCP) values, kidney involvement, and anti-Ro/SS-A positivity were shown to significantly raise the odds of having RA, whereas anti-La/SS-B positivity seemed to have a protective role, since it significantly decreased the odds of having it. Further biomarkers are needed to better classify SS patient cohorts with inflammatory joint pain of different origins and, consequently, different management requirements.

Remitting Seronegative Symmetrical Synovitis With Pitting Oedema Associated With Malignancy: A Case Report.

Remitting seronegative symmetrical synovitis with pitting oedema is a rare rheumatological condition, predominating in the elderly male. It is characterised by the abrupt onset of marked pitting oedema, symmetrical distal synovitis, absence of rheumatoid factor and an excellent response to glucocorticoids. RS3PE may be the harbinger of a malignancy so the diagnosis should prompt evaluation and exclusion of such condition; in these cases, the response to glucocorticoids is only partial and treating the neoplasia is essential. The differential diagnosis includes late-onset rheumatoid arthritis, polymyalgia rheumatica and calcium pyrophosphate crystal-related arthritis. We present the case of a patient with remitting seronegative symmetrical synovitis with pitting oedema associated with clear cell renal cell carcinoma.

Idiopathic Granulomatous Mastitis, Erythema Nodosum, and Polyarthritis.

Idiopathic granulomatous mastitis (IGM) is an inflammatory-mediated rare disease that can be linked to rare manifestations. Erythema nodosum (EN) and polyarthritis, seen in a multitude of autoinflammatory and autoimmune diseases, have been rarely linked to IGM. Despite the cause of IGM being unclear, Corynebacterium infections are thought to play a role in the pathophysiology of IGM. Unusually, IGM has a relapsing and remitting course, which also applies to its systemic manifestations. As such, we present a case of IGM in a middle-aged lady who was initially thought to have Corynebacterium-containing unilateral abscesses for which drainage was performed. However, several abscesses devoid of bacterial growth started recurring, and the disease course was complicated by EN and polyarthritis. IGM, EN, and polyarthritis eventually resolved and were managed with symptomatic treatment.

Understanding Palmar Fasciitis and Polyarthritis Syndrome as a Rheumatologic Paraneoplastic Syndrome: A Case Report.

Palmar fasciitis and polyarthritis syndrome (PFPAS) is an exceedingly rare rheumatologic condition characterized by fibrotic changes in the palmar fascia with joint pains. It is known to be associated with gynecological malignancy, especially ovarian adenocarcinoma, gastric cancer, pancreatic, prostate, breast, and lung cancer. We present a unique case of a 75-year-old Caucasian female with PFPAS preceding the diagnosis of ovarian cancer by eight months. Our case highlights the importance of considering PFPAS as a potential paraneoplastic syndrome. It underscores the need for increased awareness and further studies to enhance the early detection of underlying malignancies in patients presenting with similar nonspecific hand symptoms.

An Enigmatic Case of Adult-Onset Still's Disease.

An inflammatory condition known as adult-onset Still's disease (AOSD) is typified by quotidian (daily) fevers, arthritis, and a transient rash. This report details the case of a 21-year-old female patient who presented to our hospital with polyarthritis, a red rash, and a high-grade fever for more than three months. History was suggestive of AOSD, which was further proved by investigation and Yamaguchi criteria for AOSD. Steroids and methotrexate were started, to which the patient responded very well and thereafter.

The protocol of a clinical effectiveness trial comparing standard step-up care, early combination DMARD therapy and early use of TNF inhibitors for the treatment of moderate to severe psoriatic arthritis: the 3-arm parallel group SPEED randomized controlled trial.

Objectives: The aim of the Severe Psoriatic arthritis - Early intervEntion to control Disease trial is to compare outcomes in psoriatic arthritis (PsA) patients with poor prognostic factors treated with standard step-up conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs), combination csDMARDs or a course of early biologics. Design: This multicentre UK trial was embedded within the MONITOR-PsA cohort, which uses a trial within cohort design. Methods and analysis: Patients with newly diagnosed PsA and at least one poor prognostic factor (polyarthritis, C-reactive protein >5 mg/dL, health assessment questionnaire >1, radiographic erosions) were randomized equally and open-label to either standard care with 'step-up' csDMARD therapy, initial therapy with combination csDMARDs (methotrexate with either sulfasalazine or leflunomide) or to early biologics induction therapy (adalimumab plus methotrexate). The primary outcome is the PsA disease activity score at week 24. Ethics: Ethical approval for the study was granted by the South Central Research Ethics Committee (ref 18/SC/0107). Discussion: Treatment recommendations for PsA suggest more intensive therapy for those with poor prognostic factors but there are no studies that have previously used prognostic factors to guide therapy. Applying initial intensive therapy has shown improved outcomes in other inflammatory arthritides but has never been tried in PsA. Combination csDMARDs have shown some superiority over single therapies but there are limited data and concerns about side effects. Early use of biologics has also been shown to be superior to methotrexate but these drugs are costly and not usually funded first line. However, if a short course of biologics can rapidly suppress inflammation allowing treatment to be withdrawn and response maintained on methotrexate, this may be a cost-effective model for early use. Trial registration: ClinicalTrials.gov (NCT03739853) and EudraCT (2017-004542-24).

Pancreatitis, Panniculitis, and Polyarthritis Syndrome in Two Patients: A Case Series and Literature Review.

Pancreatitis, panniculitis, and polyarthritis (PPP) syndrome presents a unique challenge in diagnosis and management because of its rarity and heterogeneous initial presentation. This manuscript presents a case series of two patients with PPP syndrome, shedding light on the diagnostic process and care for this uncommon condition. PPP syndrome is characterized by the simultaneous occurrence of pancreatitis or pseudocysts alongside polyarthritis and panniculitis. While its exact pathophysiology remains obscure, pancreatic inflammation is assumed to trigger the hematogenous dissemination of pancreatic enzymes, leading to fat necrosis and subsequent panniculitis, as well as chondronecrosis and/or osteonecrosis causing polyarthritis. Despite its recognition in medical literature since the late 1980s, PPP syndrome remains poorly understood, with only a limited number of cases reported globally. Its rarity and varied initial manifestations often result in misdiagnosis, causing delays in appropriate treatment. The presented case series highlights key clinical features and diagnostic clues of PPP syndrome. Both patients exhibited initial symptoms of inflammatory polyarthritis, accompanied by characteristic findings of "ghost cells" on skin biopsy. Additionally, radiographic and laboratory evidence revealed pancreatic changes consistent with this syndrome. This case series underscores the importance of multidisciplinary collaboration in managing PPP syndrome. Early recognition and accurate diagnosis are pivotal in initiating prompt and effective therapeutic interventions, thereby improving patient outcomes and minimizing long-term sequelae.

A rare case of polyarthritis panniculitis and pancreatitis.

Extra pancreatic manifestations of pancreatitis are rare, with a prevalence of 2-3%. One such rare manifestation is the triad of joint pain (polyarthritis), tender skin lesions (panniculitis), and pancreatic inflammation (pancreatitis), known as PPP. The pathogenesis of this phenomenon is not fully understood but is believed to involve lipolysis by pancreatic enzymes at lipid-rich skin and joint sites. PPP primarily affects middle-aged males with a history of alcohol use disorder. Diagnosis can be challenging due to the absence of typical abdominal symptoms. Delayed diagnosis may significantly worsen outcomes. Supportive therapy is the mainstay, but resolution requires addressing the underlying pancreatic abnormality. We present a case of a patient with a history of alcohol use disorder and recurrent acute pancreatitis who developed joint pain and skin rash. Extensive work-up ruled out other causes, and imaging and biopsy confirmed the diagnosis of PPP. Symptomatic management and treatment of the underlying pancreatic abnormality led to complete resolution of symptoms. Our case serves to raise awareness of this rare but potentially fatal syndrome.

Leflunomide with prednisone or nonsteroidal anti-inflammatory drug therapy is safe and tolerated for long-term treatment of immune-mediated polyarthritis in 27 dogs.

OBJECTIVE: To retrospectively evaluate safety and tolerance of leflunomide for long-term treatment of canine idiopathic immune-mediated polyarthritis (IMPA). ANIMALS: 27 dogs with clinical signs and synovial fluid cytology supportive of IMPA with ≥ 6 months' follow-up after starting leflunomide. METHODS: Medical records were reviewed to identify dogs prescribed leflunomide for treatment of IMPA from February 2012 to May 2022. Initial leflunomide doses of 2 to 4 mg/kg once daily were prescribed and were titrated to the lowest effective dose with concurrent anti-inflammatory therapy. Complete blood count, serum chemistry, and clinical signs were monitored throughout the course of treatment. RESULTS: Adverse effects potentially attributable to leflunomide noted in 9 of 27 dogs (33%) included vomiting, diarrhea, lethargy, decreased or absent appetite, polyuria and polydipsia, and secondary antibiotic responsive infection and were self-limiting or resolved with outpatient therapy. Alkaline phosphatase (ALP) and alanine aminotransferase (ALT) elevation were documented in all dogs prescribed leflunomide plus prednisone, with persistent liver enzyme elevation in 6 of 9 dogs (67%) and normalization after antibiotic therapy in 3 of 9 dogs (33%). The majority of dogs prescribed leflunomide plus NSAID (11/17 [65%] dogs) did not experience liver enzyme elevation; 2 of 17 (12%) dogs developed transient antibiotic-responsive liver enzyme elevations, and 4 of 17 (23%) dogs had persistent liver enzyme elevation. CLINICAL RELEVANCE: Leflunomide was well tolerated for long-term management of IMPA. A significant difference in liver enzyme elevation was identified between dogs prescribed prednisone versus NSAID in combination with leflunomide. Leflunomide with NSAID therapy resulted in less hepatotoxicity compared with leflunomide with prednisone.

Pancreatitis, Panniculitis, and Polyarthritis Syndrome as the First Symptom of Necrotizing Pancreatitis.

Pancreatitis, panniculitis, and polyarthritis (PPP) syndrome is a very rare cutaneous manifestation found in patients with acute pancreatitis. We report the case of a 44-year-old man presenting with erythematous, painful lesions on the lower extremities and ankle swelling. The rheumatology service was consulted for possible erythema nodosum. Extensive workup revealed elevated lipase and amylase levels, and computed tomography of the abdomen and pelvis revealed acute pancreatitis with necrotizing lesions and peripancreatic thoracic collections. There were also changes of chronic pancreatitis. The original skin manifestations were eventually identified as pancreatic panniculitis by skin biopsy. The patient was treated for pancreatitis and pleural effusions, and his skin and joint symptoms completely resolved. Pancreatic panniculitis with polyarthritis is rare but may be the first presenting symptom of pancreatic disease. Rheumatology may be consulted for these patients especially if there are only skin and joint manifestations and no abdominal pain. Misdiagnosis of pancreatitis can lead to poorer outcomes and delay in care. Therefore, pancreatic disease should be on the differential for any patient with panniculitis and polyarthritis.

Pitfalls and pearls in diagnosing inflammatory arthritis in older patients.

Given current demographic shifts, the number of older adults continues to grow, with almost half of patients over 65 being diagnosed with some form of arthritis. Rheumatic diseases pose unique diagnostic challenges in older patients due to the convergence of physiologic changes of aging, confounding difficulties to care, and atypical disease manifestations. This review summarizes the current published evidence to guide clinicians in evaluating geriatric patients with rheumatologic concerns, focusing on inflammatory arthritis. Using the background of epidemiologic data on various musculoskeletal diseases, clinical presentations, current diagnostic tests, and known physiologic changes of aging, this review highlights five diagnostic pitfalls in inflammatory polyarthritis among older patients. The pitfalls include: 1) broader differential diagnosis; 2) atypical presentations; 3) communication, cognitive, and social impairments; 4) the role of chronological vs. biological age; and 5) anchoring bias by assuming older adults are simply "older young adults". These pitfalls are discussed in the context of geriatric principles such as the "hallmarks of aging" and the expected pathophysiologic changes of organ systems. Furthermore, the review discusses the strengths and weaknesses of diagnostic tests used in arthritis and introduces some of the geriatric assessment tools that systematically evaluate multimorbidity and geriatric syndromes. With familiarity of the potential diagnostic pitfalls, knowledge of both normal and pathologic aging processes, awareness of the difference between biological and chronological age, and the ability to use geriatric assessment tools to better characterize older patients, clinicians will be better able to diagnose and manage rheumatic conditions in this population.

Immune-mediated polyarthritis and anterior uveitis secondary to zonisamide administration in a dog with refractory epilepsy.

The objective of this article is to describe a case of suspected zonisamide-induced immune-mediated polyarthritis (IMPA) and anterior uveitis in a dog. A 7-year-old male neutered Siberian Husky with a history of refractory idiopathic epilepsy was presented for cluster seizures. Following the addition of zonisamide to the antiepileptic regime, the dog developed new IMPA and anterior uveitis. Within a few weeks of discontinuation of the zonisamide, the dog's IMPA and anterior uveitis resolved. These immune-mediated conditions were thus presumed to be an idiosyncratic reaction to zonisamide. To our knowledge, this is the first report of IMPA and anterior uveitis in dogs associated with zonisamide administration at its recommended dose.

Diagnostic Utility of Thoracic Radiography and Abdominal Ultrasonography in Canine Immune-Mediated Polyarthritis: 77 Cases.

Thoracic radiography and abdominal ultrasonography are part of standard diagnostic investigations in cases of canine immune-mediated polyarthritis (IMPA). However, the clinical importance of thoracic and abdominal imaging towards the management of canine IMPA currently remains unknown. The primary aim of this study was to describe the findings documented on thoracic radiography and abdominal ultrasonography in dogs diagnosed with IMPA, and to evaluate the diagnostic utility of thoracic radiography and abdominal ultrasonography in the initial approach and management of these cases. Seventy-seven dogs diagnosed with IMPA who underwent thoracic radiography and abdominal ultrasonography at a single referral hospital between 2008 and 2022 were included. The diagnostic imaging studies of these 77 dogs were reviewed by one blinded board-certified diagnostic imaging specialist for quality assurance. The medical records, including the diagnostic imaging reports of these dogs, were then reviewed by three blinded board-certified internal medicine specialists. Using a modified version of a previous question and scoring system, the three internal medicine specialists then generated an answer for the overall diagnostic utility and a diagnostic utility score for thoracic radiography and abdominal ultrasonography for each case. The abnormal findings identified in radiography and ultrasonography were described. In the cases where the findings were considered significant enough to immediately affect the case management, the results of the further investigations that were subsequently performed were also described. No abnormalities were detected in thoracic radiography for 30 cases, and none were detected in abdominal ultrasound for 6. The majority of the internists considered thoracic radiography to be not useful in the overall case management at the time of IMPA diagnosis in 70 cases, and considered abdominal ultrasonography to be not useful in the overall case management in 57 cases. The majority of the internists agreed on the utility of thoracic radiography in 95% of the cases, and in 61% of the cases for abdominal ultrasonography. The most common finding in the thoracic radiography was a mild bronchial pulmonary pattern, and the most common in the abdominal ultrasonography was mild lymphadenomegaly. Therefore, although thoracic radiography and abdominal ultrasonography identified numerous abnormal findings in this population of dogs, in the majority of the cases, the findings were deemed not useful towards the overall case management at the time of the initial diagnosis of IMPA. Thus, the use of thoracic radiography and abdominal ultrasonography should be taken into careful consideration when considering initial diagnostic investigations for canine IMPA.

Scleroderma Associated With Organising Pneumonia and Polyarthritis: A Report of a Rare Case.

Cryptogenic organising pneumonia (COP) is a form of idiopathic diffuse interstitial lung disease (ILD) that develops in response to a variety of unknown irritants. An essential component of the development of organising pneumonia (OP) is damage to type II pneumocytes and the alveolar basement membrane. An autoimmune illness called systemic sclerosis (SSc) has a significant death rate from cardiopulmonary involvement such as pulmonary hypertension and ILD. Arthritis is an autoimmune disorder, in which the patients experience extra-articular symptoms such as ILD during the course of their disease, and COP frequently coexists with these conditions. It is exceedingly uncommon for OP to occur as the initial sign of arthritis, and its clinical characteristics are still unclear. Scleroderma and inflammatory polyarthritis related to COP are presented in this report.

Retinal Vasculitis in a Patient with Rhupus.

This case report describes a case of retinal vasculitis in a patient with Rhupus, which has not been reported earlier in the literature. A 39-year-old female patient with a history of Rhupus presented with sudden vision loss in her left eye. The patient was treated earlier, for her polyarthritis, with oral corticosteroids, hydroxychloroquine, and oral methotrexate, which were discontinued after 1 year of treatment. At presentation, fundus examination of the left eye revealed mild vitritis, perivenous sheathing, and hemorrhagic periphlebitis. The patient was administered three doses of pulse corticosteroid, resulting in a reduction in retinal vasculitis and macular edema. The patient was continued on oral corticosteroids and started on oral methotrexate and hydroxychloroquine. At 6-week follow-up, the patient's vision had improved to 6/9, and fundus examination revealed resolving phlebitis and retinal hemorrhages. This case also highlights the importance of prompt diagnosis and treatment of retinal vasculitis in patients with Rhupus.

Synovial extramedullary hematopoiesis in a dog.

OBJECTIVE: Synovial extramedullary hematopoiesis is a rarely reported condition in humans and, to date, has never been reported in canines. This case report describes the clinical presentation, diagnostic work-up, treatment, and outcome of a canine case confirmed to have hematopoietic tissue within multiple joints. ANIMAL: A client-owned canine. CLINICAL PRESENTATION, PROGRESSION, AND PROCEDURES: The clinical presentation was most consistent with immune-mediated polyarthritis, and arthrocentesis was performed in multiple joints for cytological evaluation and culture. Cytology revealed evidence of extramedullary hematopoiesis, and shortly thereafter the dog was diagnosed with immune-mediated hemolytic anemia and thrombocytopenia. TREATMENT AND OUTCOME: Pregabalin, prednisolone, clopidogrel, and cyclosporine were started, and after several recheck appointments and dose adjustments, the dog's clinical signs resolved for all conditions. CLINICAL RELEVANCE: Unusual sites of extramedullary hematopoietic tissue may result in a clinical presentation for which more traditional etiologies and differentials are not applicable.