Understanding diagnosis and management of specific autoimmune diseases is based on existing classifications or diagnostic criteria. However, patients frequently present with broad, multisystem features that mimic multiple autoimmune diseases. Recognizing clinical mimicry is crucial because overclassifying these features as distinct coexisting diseases often presents a diagnostic challenge. We report the case of a 36-year-old man who presented with progressive weakness. The patient initially complained of facial rash and skin lesions, which then developed into tetraparesis, arthralgia, and difficulty swallowing. Physical examination revealed various skin and musculoskeletal manifestations, including erythematous plaques on the face without involving the nasolabial folds, discoid rash, heliotrope rash, Gottron's sign, and multiple ulcers. Neurological examination showed decreased muscle strength and motor lesions. Laboratory results showed an increase in inflammatory markers, positive antinuclear antibodies (ANAs) as well as positive myositis-specific antibodies for melanoma differentiation-associated protein (MDA)-5. Electromyography (EMG) examination showed findings consistent with myogenic lesions. Chest CT scan showed interstitial lung disease (ILD), and hand radiography showed juxta-articular wrist osteopenia consistent with early signs of inflammatory arthritis. Based on these findings, the patient was diagnosed with MDA-5 dermatomyositis (DM) with lupus-like features and inflammatory arthritis, representing a high-risk DM phenotype that clinically mimics a triple overlap syndrome, rather than three distinct confirmed diseases. Initial treatment involved the administration of high-dose methylprednisolone followed by a gradual dose reduction, hydroxychloroquine, and mycophenolate sodium after the secondary skin infection resolved. The patient received multidisciplinary care involving various specialties. After treatment, the patient's motor weakness improved. Distinguishing severe phenotypes of connective tissue diseases (CTDs) from true overlapping syndromes is a diagnostic challenge due to overlapping symptoms and laboratory findings. Accurate diagnosis requires a comprehensive clinical and serological evaluation, as well as a deep understanding of the classification criteria for each disease to avoid overclassification. Early diagnosis and aggressive treatment targeting the primary driving pathology can improve the prognosis and quality of life of patients.

Mucocutaneous leishmaniasis (MCL) is a parasitic infection transmitted through sand fly bites. This disease affects people who are living in or traveling to endemic regions around the world. Cases of MCL remain underreported due to its clinical presentation and potential misdiagnosis, with cases in older adults rarely described in the literature. We present a case of an elderly Salvadoran farmer who developed MCL involving the nasal septum following travel abroad and a subsequent ulcerative lesion in the right lower limb. We discuss his diagnosis, treatment, histopathology, and outcome.

Sphingosine-1-phosphate (S1P) signaling is a bona fide drug target as evidenced by the S1P receptor modulator drug class for treating multiple sclerosis and ulcerative colitis. Despite this clinical success, on-target adverse events have been reported. To circumvent these, we hypothesized that interdicting the S1P transport cascade will have the same physiological benefits without undesired events. This led to the first reported S1P release inhibitor (SRI), SLF1081851, that supported this concept. Subsequent structural improvements led to new generations of SRIs. Herein, we report a structure-activity relationship study of novel indazole compounds inspired by modifications on a previously reported scaffold. Studies revealed compounds 6c (IC50 = 651 ± 3 nM) and 6k (IC50 = 719 ± 50 nM) to be viable SRIs with molecular modeling suggesting that conformational effects are observed and potency can be influenced by these effects. Thus, both 6c and 6k provide valuable insight into the chemical space within Spns2 and help influence the next generation of SRIs.

Donovanosis is a chronic granulomatous sexually transmitted infection that may clinically mimic malignancy. We report a 64-year-old man with well-controlled HIV infection presenting with a chronic infiltrated vegetative scrotal ulcer showing progressive enlargement, exophytic growth, and hemorrhagic ulceration. Despite prolonged antimicrobial therapy with azithromycin and doxycycline, followed by adjunctive acyclovir because of suspected chronic herpes simplex coinfection, the lesion continued to progress, raising concern for squamous cell carcinoma. Initial histopathological and microbiological investigations, including cytology for Donovan bodies, were inconclusive. Repeat biopsy demonstrated pseudoepitheliomatous hyperplasia with a dense plasma cell-rich inflammatory infiltrate without cytological atypia, while periodic acid-Schiff staining identified intracellular Donovan bodies, confirming donovanosis. Doxycycline was reintroduced and maintained until complete healing after four months. This case highlights the diagnostic challenges of pseudotumoral donovanosis in patients living with HIV.

This prospective paired-sample study evaluated fecal calprotectin changes after polyethylene glycol-based bowel preparation in ulcerative colitis patients in remission. Calprotectin increased modestly, particularly in patients with Mayo 1 endoscopic subscore, but clinical worsening was uncommon and healthy individuals showed no significant change.

Corynebacterium minutissimum (C. minutissimum) is usually considered a skin commensal and is best known as the causative organism of erythrasma. Although invasive infections caused by this organism are rare, its clinical significance can be difficult to determine when it is isolated from wound specimens. Here, we present the case of a 14-year-old boy with progressive ulceration, swelling, malodor, and soft tissue destruction of the left lower leg. Intraoperative exploration revealed areas of nonviable fascia and adjacent soft tissue with purulent exudation, and a diagnosis of necrotizing soft tissue infection (NSTI) was made based on intraoperative findings. Surgical debridement was performed to remove visibly nonviable tissue, followed by temporary wound management using antibiotic-loaded bone cement. A deep purulent specimen obtained during surgery grew C. minutissimum, whereas anaerobic and fungal cultures showed no growth. After local infection control was achieved, the patient underwent repeat debridement and pedicled fascial flap reconstruction, with satisfactory wound healing and no evidence of recurrent infection during follow-up. Although the isolation of C. minutissimum was considered clinically relevant in this case, its role as the sole causative organism could not be confirmed because only one positive culture was available and additional microbiological evidence was lacking. This case illustrates the challenges in interpreting uncommon skin-associated organisms isolated from complex wounds and emphasizes that microbiological results should be assessed together with specimen characteristics, operative findings, clinical course, and treatment response. Early surgical debridement and staged reconstruction remain essential for achieving infection control and functional recovery in patients with NSTI.

Based on the previously reported neuroprotective, neurochemical, and behavioral effects of syringic acid, the present study was designed to investigate its antinociceptive and anti-inflammatory potential and to elucidate its possible mechanisms of action using in vitro and in silico methods. The antinociceptive effects of syringic acid were evaluated using the tail-clip, tail-immersion, hot-plate, formalin, and acetic acid-induced writhing tests in Balb/c mice, whereas its anti-inflammatory activity was assessed using the carrageenan-induced paw edema model in Sprague-Dawley rats. Motor performance was examined using the activity meter and Rota-rod tests. The potential ulcerogenic effect was also evaluated. Syringic acid (50 and 100 mg/kg, p.o.) did not significantly alter motor performance. It also did not alter nociceptive response parameters in the tail-clip, tail-immersion, or hot-plate tests. However, it significantly decreased writhing behavior in the writhing test and reduced paw-licking time during the second phase of the formalin test. Moreover, syringic acid attenuated carrageenan-induced paw edema. These findings indicate that syringic acid exerts peripheral antinociceptive and anti-inflammatory activities. In addition, acute administration of syringic acid did not induce gastric ulceration in mice. Enzyme inhibition studies showed that syringic acid inhibited cyclooxygenase-2 and 5-lipoxygenase at μM concentrations. In silico studies further revealed stable interactions between syringic acid and both enzymes.

Although immune checkpoint inhibitors (ICIs) have improved oncological outcomes, they can cause a myriad of inflammatory conditions known as immune-related adverse events (irAEs). Raynaud's phenomenon (RP) is a rare rheumatologic irAE that may arise de novo or present as an exacerbation of preexisting disease. This case series aims to describe ICI-induced RP in patients without a rheumatological diagnosis seen at a large, specialized cancer center. Our case series describes five patients with ICI-induced RP who were evaluated by rheumatology at a cancer center during the past 3 years where their cancers, type of ICIs, diagnostic tests, and treatments are discussed in detail. Among our five patients, one patient had preexisting psoriatic arthritis, and one had preexisting RP. The outcome of our patients' ICI-induced RP varied widely. Although three patients had significant digital ischemia resulting in ulceration requiring epoprostenol infusions, the remaining two patients had mild digital ischemia that were controlled conservatively. However, none of our patients had clinical features to suggest systemic sclerosis (SSc), where RP is often the first symptom. Interestingly, interferon-γ and interleukin-6 were the most frequently elevated cytokines when checked in these patients. This is the first case series, to the authors' knowledge, to describe ICI-induced RP, which may occur without other clinical features of an autoimmune rheumatological disease. The severity of the disease may vary, but it warrants increased awareness and prompt initiation of appropriate treatment.

Complex aortic atheroma is a recognized potential source of cerebral embolism, particularly when plaques are thick, protruding, irregular, ulcerated, or mobile. However, establishing a direct causal relationship between aortic atheroma and cerebral infarction remains challenging when competing arterial mechanisms coexist. We describe a 65-year-old man with hypertension, dyslipidemia, and active tobacco use who presented with headache and an acute confusional state. Neurological examination revealed left-sided dysmetria and gait instability. Brain imaging demonstrated multiple ischemic lesions confined to the posterior circulation, involving the left cerebellum, left thalamus, and bilateral occipital regions. Computed tomography angiography revealed subocclusive stenosis of the left V4 vertebral artery, a right vertebral artery terminating as the posterior inferior cerebellar artery, and an irregular atheromatous plaque involving the distal aortic arch and isthmus. Transesophageal echocardiography demonstrated diffuse aortic atheromatosis, including a protruding distal aortic arch plaque measuring 26.03 × 12.79 mm and a descending aortic plaque with a maximum thickness of 12.35 mm. Transthoracic echocardiography, telemetry, and 72-hour Holter monitoring identified no cardiac embolic source or arrhythmia. Given the exclusively posterior infarct distribution and vertebral anatomy, symptomatic left V4 atherosclerotic stenosis, through artery-to-artery embolism, distal hypoperfusion, or both, was considered the more likely mechanism. The patient received dual antiplatelet therapy followed by long-term aspirin, high-intensity statin therapy, and intensive vascular risk-factor management, with favorable neurological improvement. The aortic atheroma may have been contributory, incidental, or a marker of systemic atherosclerosis rather than the direct embolic source. As definitive causal attribution was not possible, the stroke was classified as being of undetermined etiology under the TOAST framework.