Normocomplementemic urticarial vasculitis (NUV) and hypocomplementemic urticarial vasculitis (HUV) share clinical features, notably wheals, yet clear differential diagnostic criteria are lacking. To describe HUV and NUV features in Chinese inpatients for diagnosis. Retrospective study (March 2017-June 2024, China) of NUV/HUV patients. We analyzed clinical characteristics, laboratory results, and histological features, and compared drug efficacy. Females constituted the majority of patients with urticarial vasculitis(UV). All patients present with wheals persisting for more than 24 hours, and 76.1% of the wheals exhibited partial or complete non-blanching. Angioedema was more common in patients with HUV than in NUV (44.4% vs 25.0%, p<0.05). Systemic involvement was observed in 61.1% of HUV and 41.2% of NUV. HUV was significantly associated with autoimmune diseases (p<0.05), decreased complement levels (C3, C4, C1q, and C1 inhibitor)(p<0.001), and elevated erythrocyte sedimentation rate (ESR) (p<0.01). A negative correlation between ESR and C3 levels was found in HUV, in contrast to a positive correlation in NUV. Direct immunofluorescence (DIF) test showing immunoreactants at the blood vessel were present in 50% of patients with HUV and 18.2% patients with NUV. Regarding treatment, 91.9% of NUV responded effectively to oral corticosteroids, whereas only 66.7% of HUV did; the remaining 33.3% of HUV required combination therapy with biologics. Our study identified key factors associated with the occurrence of UV subtypes. For patients with recurrent wheals, complement levels, ESR, and the distribution pattern of immunofluorescence deposits can serve as basis for classifying UV subtypes and prompt earlier treatment.

Urticarial vasculitis (UV) is an inflammatory condition that affects small vessels, generating urticarial lesions with wheals lasting >24 hours. It can be divided into two main groups: normocomplementemic (NUV) and hypocomplementemic urticarial vasculitis (HUV). The latter is a rare condition, whose association with autoimmune diseases, primarily systemic lupus erythematosus (SLE), makes its diagnosis difficult. We present a 67-year-old female patient with a family history of SLE. She presented with disseminated dermatosis of eight months' duration with wheals lasting >24 hours. Due to a suspected diagnosis of UV, laboratory studies and a skin biopsy were performed, revealing a predominantly neutrophilic perivascular infiltrate, nuclear dust, and mild fibrinoid necrosis, as well as low serum complement levels. Meanwhile, anti-Smith, anti-double-stranded DNA, anti-Ro/SSA, and anti-La/SSB antibodies were all negative. A low-titer ANA (1:100) was detected, although this nonspecific finding is common in healthy individuals and lacks diagnostic significance. Anti-C1q antibodies could not be assessed due to unavailability within the institution. Despite this limitation, the constellation of clinical, laboratory, and histopathological findings supported the diagnosis of HUV, and a favorable therapeutic response was achieved with prednisone at a dose of 0.5 mg/kg per day with a weekly taper of 5 mg until discontinuation, accompanied by close clinical monitoring, including quarterly dermatologic evaluations and semiannual rheumatologic assessments supported by laboratory testing. This case highlights the importance of early identification, the need for a multidisciplinary approach, as well as the exclusion of systemic involvement while ensuring close follow-up, as a high percentage of patients may develop SLE.

BACKGROUND Type II cryoglobulinemic vasculitis is a systemic syndrome that usually develops in the background of chronic HCV infection. Cases of non-hepatitis C (HCV)-related type II cryoglobulinemic vasculitis pose diagnostic and therapeutic challenges in patients with pre-existing hematologic and rheumatic conditions. CASE REPORT We present the case of an 82-year-old woman with a history of skin-limited hypocomplementemic urticarial vasculitis (HUV), monoclonal gammopathy of unknown significance (MGUS), and monoclonal B-cell lymphocytosis (MBL), with new-onset pericarditis, pleuritis, worsening rash, and acute kidney injury. Skin and renal biopsies confirmed a diagnosis of type II (mixed) cryoglobulinemic vasculitis. After an extensive infectious disease workup and an in-depth investigation on our patient's MGUS and MBL, none of the classic causative factors for non-infectious mixed-type cryoglobulinemia were identified. Ultimately, she was started on immunosuppressive treatment, despite which she experienced rapidly progressive disease with pulmonary involvement. Utilizing this case as a basis, we examine the challenges of treating non-HCV-related cryoglobulinemia in patients with complex medical histories. CONCLUSIONS We report a case of mixed cryoglobulinemia in the absence of infection and the presence of 2 premalignant hematologic disorders. Moreover, this case emphasizes the importance of conducting biopsies to differentiate between vasculitis syndromes with overlapping phenotypes, illustrates the diagnostic challenges of recognizing cryoglobulinemia in a timely fashion in patients with pre-existing hematologic and autoimmune comorbidities, and highlights the need for better prognostic and diagnostic methods.

Bradykinin-mediated angioedema comprises rare but potentially life-threatening disorders, most notably hereditary angioedema (HAE) due to C1 inhibitor (C1-INH) deficiency or dysfunction. Diagnosis is often difficult, as these conditions can resemble urticaria variants, leading to misdiagnosis and delays in care. Distinguishing features are critical, since bradykinin-mediated forms do not respond to antihistamines or corticosteroids. This review summarizes the differential diagnoses of angioedema, including urticaria variants, cheilitis granulomatosa, and hypocomplementemic urticarial vasculitis, highlighting clinical and diagnostic clues. Particular focus is given to HAE-its subtypes (Type I, Type II, and normal C1-INH), pathophysiology, presentation, and genetic basis. Acquired angioedema and drug-induced forms, such as ACE inhibitor-associated angioedema, are also discussed. The therapeutic landscape is rapidly evolving, spanning acute and prophylactic approaches. Options include C1-INH concentrate, kallikrein inhibitors, bradykinin receptor antagonists, and factor XII inhibitors. While these advances expand treatment opportunities, they also complicate decision-making for patients and physicians. Furthermore, emerging CRISPR-based gene editing therapies represent innovative approaches that pose complex ethical dilemmas, and their long-term safety and efficacy have yet to be established. Although novel therapies reduce attack frequency, their true impact on quality of life is not fully established. Comparative effectiveness data are limited, long-term safety-particularly of gene-based therapies-is unknown, and the real-world utility of new oral on-demand agents for acute therapy is uncertain, especially in severe pharyngeal or laryngeal attacks that may hinder swallowing. Current guidelines remain unclear on the need for short-term prophylaxis in patients already receiving effective long-term prophylactic therapy. In conclusion, despite major therapeutic advances, persistent challenges and unanswered questions underscore the need for pragmatic, patient-centered, long-term studies to optimize care.

Urticarial vasculitis (UV) is a rare entity affecting small blood vessels, characterized by persistent (>24 hours) urticarial lesions with histopathological findings of leukocytoclastic vasculitis. It is classified as normocomplementemic (NUV) and hypocomplementemic (HUV), the latter associated with systemic diseases such as systemic lupus erythematosus (SLE). Its incidence is 0.5 per 100,000 person-years. Clinical presentation: A 66-year-old female with a history of SLE, hypothyroidism, and osteoarthritis developed in 2022. In 2022, she developed a dermatosis disseminated to all four body segments with pruritic wheals lasting up to 72 hours, persisting for more than six weeks, and followed by post-inflammatory hyperpigmentation. No triggering factors were identified. She also presented episodes of palpebral and labial angioedema. Given the clinical features, a skin biopsy and complement measurement were performed. Imaging/laboratory studies: Skin biopsy: Superficial neutrophilic vasculitis (venulitis) with erythrocyte extravasation. Lab results 2023: C3: 79.7 mg/dL. C4: 10.8 mg/dL. This case highlights the importance of considering hypocomplementemic urticarial vasculitis in patients with SLE and persistent urticarial lesions, as well as conducting a targeted history. Given the risk of systemic involvement, close follow-up and a multidisciplinary approach are essential. The diagnosis of UV requires clinical-histopathological correlation, with biopsy recommended for persistent lesions (>24 h), residual bruising, or systemic manifestations. Early identification and appropriate management are essential to prevent systemic complications. Treatment focuses on addressing underlying autoimmune diseases and managing symptoms with antihistamines, corticosteroids, or immunosuppressants, depending on the severity and systemic involvement. La vasculitis urticarial (UV) es una entidad infrecuente que afecta los vasos sanguíneos pequeños, caracterizada por lesiones urticariformes persistentes (>24 horas) con hallazgos histopatológicos de vasculitis leucocitoclástica. Se clasifica en normocomplementémica (NUV) e hipocomplementémica (HUV), esta última asociada a enfermedades sistémicas como el lupus eritematoso sistémico (LES). Su incidencia es de 0.5 por 100 000 personas-año. cuadro clínico: Femenino de 66 años con antecedente de LES, hipotiroidismo y osteoartritis. En 2022 desarrolló una dermatosis diseminada a los cuatro segmentos corporales con ronchas pruriginosas de hasta 72 horas de duración, persistentes por más de seis semanas y seguidas de hiperpigmentación postinflamatoria, no se identificaron factores desencadenantes. Además, presentó episodios de angioedema palpebral y labial. Dadas las características clínicas, se realizó biopsia cutánea y medición de complemento. Estudios de imagen/laboratorio: Biopsia de piel: Vasculitis (Venulitis) neutrofílica superficial con extravasación de eritrocitos. Laboratorios 2023: C3: 79.7 mg/dL. C4: 10.8 mg/dL. El presente caso resalta la importancia de considerar la vasculitis urticarial hipocomplementémica en pacientes con LES y lesiones urticariformes persistentes, así como de realizar un interrogatorio dirigido. Dado el riesgo de afectación sistémica, es fundamental un seguimiento estrecho y un abordaje multidisciplinario. El diagnóstico de UV requiere la correlación clínico-histopatológica, recomendándose biopsia ante lesiones persistentes (>24 h), equimosis residual o manifestaciones sistémicas. La identificación temprana y el manejo adecuado son esenciales para prevenir complicaciones sistémicas. El tratamiento se centra en abordar enfermedades autoinmunes subyacentes y manejar síntomas con antihistamínicos, corticosteroides o inmunosupresores, según la gravedad y afectación sistémica.