Isaacs syndrome (IS) is a rare peripheral nerve hyperexcitability disorder, often associated with an underlying disease. We report a clinical case which appears to be a previously unreported co-occurrence of IS and systemic polyarteritis nodosa, diagnosed in a young woman presenting with subacute back pain, weight loss, fasciculations, diaphoresis, tachycardia, micturition disorder, constipation, cutaneous lesions and mesenteric vasculitis on MRI. The patient achieved clinical remission following treatment with intravenous cyclophosphamide and corticosteroids.

Transfusion-dependent anemia (TDA) in children is often attributed to hemoglobinopathies; however, a spectrum of non-hemoglobinopathy disorders can also lead to transfusion dependence, complicating diagnosis and management. In this article, we share our experience with such non-hemoglobinopathy causes of TDA. A retrospective chart review was conducted over five years (2018-2023) at a tertiary pediatric hematology center. Among 93 children identified with TDA, 80 had hemoglobinopathies, while 13 had alternative diagnoses. These included immune-mediated hematological disorders, marrow failure syndromes, congenital RBC/platelet defects, and systemic illnesses. Descriptive statistics summarized clinical and demographic data. Of the 93 children with TDA, 13 had non-hemoglobinopathy causes: immune-mediated disorders (AIHA, Evans syndrome, PRCA, n = 4), marrow failure syndromes (sideroblastic anemia, dyskeratosis congenita, n = 3), inherited red cell/platelet defects (G6PD deficiency, Glanzmann thrombasthenia, n = 3), and systemic illnesses (vasculitis, Langerhans cell histiocytosis, hypereosinophilic syndrome, n = 3). The mean age was 4 years 5 months, with a male-to-female ratio of 1.16:1. Hepatosplenomegaly was observed in 8/13 cases. Non-hemoglobinopathy causes of TDA are heterogeneous, encompassing systemic, immune, genetic, and marrow failure disorders. Structured diagnostic evaluation is critical to distinguish them from hemoglobinopathies, enabling accurate treatment and improved outcomes.

Lemierre's syndrome is characterized by septic thrombophlebitis of the jugular vein, bacteremia, and septic embolisms, resulting from an oropharyngeal infection frequently caused by Fusobacterium. In recent decades, there have been increasing reports of patients with a variant called Lemierre-like syndrome. In these cases, the pathogen involved is Staphylococcus aureus, particularly methicillin-resistant strains. We report the case of a 64-year-old man with no comorbidities who presented with a chin abscess due to facial folliculitis. He progressed with bacteremia, external jugular vein thrombophlebitis with septic pulmonary embolisms, and mitral endocarditis. Cultures revealed methicillinresistant Staphylococcus aureus. The patient underwent drainage of the abscess, intravenous antibiotic treatment for 6 weeks, and anticoagulation, with favorable clinical outcome. Lemierre-like syndrome should be suspected in patients with sepsis presenting as a result of cervicofacial skin infections. This is an emerging and serious condition, whose early diagnosis and antibiotic treatment are essential for a favorable outcome.

VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome, caused by somatic mutations in UBA1, can mimic adult-onset Still's disease (AOSD) and is often refractory to glucocorticoids. We report a case of VEXAS syndrome in a man in his seventies who had initially been treated as AOSD with interstitial lung disease and large-vessel vasculitis, and who relapsed with high fever, vesiculopustular eruptions, polyarthritis, auricular chondritis, and macrocytic anemia during prednisolone (PSL) tapering. Given the lack of response to PSL escalation and the possibility of VEXAS syndrome, baricitinib, a JAK1/2 inhibitor, was initiated, resulting in rapid clinical and hematologic improvement. Genetic testing identified UBA1 (c.122T>C, p.Met41Thr; variant allele frequency [VAF] 76%), confirming VEXAS syndrome. PSL was tapered to 10 mg/day, and complete remission according to FRENVEX criteria was achieved within 3 months after baricitinib initiation, with no recurrence at 6 months. This case underscores the importance of early UBA1 testing in elderly men with AOSD-like presentations and suggests that baricitinib may serve as a glucocorticoid-sparing therapeutic option in selected cases, although its efficacy should be interpreted cautiously in light of genotype-dependent heterogeneity and the combined effects of JAK1/2 inhibition.

Retiform purpura (RP) is a morphological pattern of cutaneous ischemia resulting from vascular compromise. Its clinical relevance lies in its orientation toward vasculitis or thrombotic vasculopathy. We report the case of a woman with painful violaceous retiform lesions on the distal lower extremities, Raynaud's phenomenon with a "blue toe" on the hand, and polyarthralgias. Laboratory workup revealed antinuclear antibodies (ANA) 1:2560 (AC-5 pattern), anti-RNP > 240 U/mL, anti-Sm > 320 U/mL, low C4, and negative antineutrophil antibodies (ANCA) and rheumatoid factor. Magnetic resonance imaging showed diffuse muscular edema and bilateral fascial thickening; computed tomography reported reactive adenopathies. Skin biopsy demonstrated ischemic changes consistent with small vessel involvement in a mixed vasculitic/vasculopathic pattern, with epidermal necrosis and intraluminal fibrin. Systemic lupus erythematosus (SLE) with features of small vessel vasculitis was diagnosed. Treatment included methylprednisolone and prednisone pulses, cyclophosphamide, rituximab, and alprostadil for digital ischemia, with clinical improvement. RP may reflect a mixed inflammatory/thrombotic process in the context of overlapping autoimmunity. Deep biopsy, autoimmune profiling, and assessment of prothrombotic state are key axes for decisions regarding immunosuppression and/or antithrombotic strategies. Key Points • Retiform purpura is a high-risk cutaneous pattern that requires early differentiation between vasculitis and thrombotic vasculopathy, as each condition demands divergent therapeutic strategies (immunosuppression versus antithrombotic therapy). • In patients with SLE, cutaneous vasculitis - though uncommon - may present with a dominant ischemic phenotype (retiform purpura, digital ischemia) that initially mimics medium-vessel vasculitis such as polyarteritis nodosa or systemic sclerosis; accurate diagnosis requires integration of clinical, histological, and immunological data. • Management of severe ischemic SLE with a mixed inflammatory/occlusive mechanism may require a parallel approach: intensive immunosuppression to control vascular inflammation, combined with vasoactive and anticoagulant measures to preserve distal perfusion and tissue viability.

The relationship between antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) and solid malignancies is uncommon and poses significant diagnostic challenges, particularly in individuals with underlying immune dysregulation, such as human immunodeficiency virus (HIV) infection. A 61-year-old man with well-controlled HIV infection presented with nephritic syndrome and palpable purpura. Laboratory evaluation revealed active urinary sediment and positive myeloperoxidase (MPO)-ANCA. Alternative causes of vasculitis were reasonably excluded based on clinical, serological, and histopathological evaluation. Skin biopsy demonstrated leukocytoclastic vasculitis, while renal biopsy showed pauci-immune necrotizing glomerulonephritis. During hospitalization, the patient developed hematochezia, for which a colonoscopy was performed, and a mass was identified in the ascending colon. Histopathological analysis confirmed stage IIIA colorectal adenocarcinoma. Treatment included glucocorticoids, plasmapheresis, and azathioprine, followed by right hemicolectomy and adjuvant CAPEOX chemotherapy. Partial improvement in the cutaneous lesions and glomerular filtration rate was observed following vasculitis-directed therapy, the patient achieved complete resolution of both the renal and cutaneous manifestations only after right hemicolectomy and adjuvant CAPEOX chemotherapy. This case is consistent with a possible paraneoplastic link between MPO-AAV and colorectal adenocarcinoma. In patients with HIV infection, distinguishing true vasculitis from incidental autoantibody positivity is challenging. The temporal relationship and improvement with cancer-directed therapy raise the possibility that malignancy may act as a trigger for clinically overt vasculitis. Recognition of this relationship may help guide appropriate management and avoid unnecessary or prolonged immunosuppression.

Hughes-Stovin syndrome (HSS) is a rare and aggressive type of systemic vasculitis which is characterized by peripheral venous thrombosis and pulmonary artery aneurysms (PAAs) at the onset of the disease, as well as the absence of recent or previous attacks of uveitis. The onset of HSS and its dominant clinical disease presentations differ in many aspects from those observed in Behçet's disease (BD). The absence of uveitis is a mandatory exclusion criterion in the preliminary diagnostic criteria proposed by the HSS International Study Group (HSSISG), to avoid misclassification between HSS and BD. The presence of PAAs is an obligatory "entry criterion" for diagnosis, while vascular thrombotic events are a "major criterion" after excluding other causes of coagulopathy-induced thrombosis. The HSSISG regards HSS and BD as one disease, yet exhibiting distinct patterns of disease expression, particularly at disease onset. Differentiating HSS from BD is especially important for early diagnosis and optimal management. While the presence of HLA-B51 is the strongest genetic risk factor for BD, it is not used as a criterion to confirm a diagnosis because it lacks sufficient specificity. The prevalence of HLA-B51 in HSS is relatively low, suggesting that different genetic drivers might exist or that HSS is a unique entity with overlapping features with BD. In HSS, both HLA-B51 positive and negative cases have been described; thus, it cannot be a hallmark of the syndrome, and it does not play a role in the diagnostic criteria.