Deoxyribonuclease 1 Like 3 (DNASE1L3) is a member of the deoxyribonuclease I family that is associated with some diseases, including systemic lupus erythematosus and hypocomplementemic urticarial vasculitis. Recently, abnormal DNASE1L3 was preliminarily shown to correlate with tumor pathogenesis. However, its role is still undetermined in nasopharyngeal carcinoma (NPC). Multiple sets of Gene Expression Omnibus (GEO) high-throughput data were utilized to screen the differentially expressed genes. Signal pathway enrichment analysis analyzed the correlation between DNASE1L3 and epithelial-mesenchymal transition (EMT) and cytoskeleton reorganization. An immunohistochemistry assay for analysis of DNASE1L3 expression was used to detect the clinical samples. Woundhealing, migration, invasion assays, and mouse model of lung metastasis were used to assess the role of DNASE1L3 in NPC metastasis. The mechanism of DNASE1L3 inhibition of NPC metastasis by attenuating MYH9/β-catenin/c-Jun/LncRNA-KDM4A-induced E-cadherin ubiquitination degradation was demonstrated by protein stability evaluation, co-immunoprecipitation, immunofluorescence, chromatin immunoprecipitation, dual-luciferase reporter assay, and RNA immunoprecipitation. DNASE1L3 downregulation in patients with NPC was not only negatively related to lymph node metastasis and distant metastasis but was also positively associated with poor prognosis. Overexpression of DNASE1L3 in NPC cells suppresses migration, invasion, and metastasis in vitro and in vivo. Inversely, DNASE1L3 knockdown increased cell migration and invasion abilities. Mechanistically, DNASE1L3 recruited PARK2 to ubiquitinate and degrade MYH9 protein. MYH9 protein activated β-catenin/c-Jun signal and augmented c-Jun-induced LncRNA-KDM4A transcription. In the process of DNASE1L3-induced metastatic suppression, decreased LncRNA-KDM4A attenuated the recruitment of E3 ubiquitin ligase Hakai and thus impeded the degradation of E-cadherin, by which heightened E-cadherin protein stability and finally inactivated the EMT signal. Our data firstly elucidated that DNASE1L3 acts as a metastatic suppressor by attenuating E-cadherin ubiquitination degradation via the MYH9/β-catenin/c-Jun/LncRNA-KDM4A axis in NPC. DNASE1L3 is a potential marker for predicting NPC prognosis.

Biologic therapies have emerged as effective treatments for chronic spontaneous urticaria (CSU), a debilitating skin disease. However, real-world data on their use are limited. This retrospective descriptive study analyzes the time from diagnosis to biologic therapy initiation and the CSU-specific healthcare resource utilization (HCRU) among patients with ≥ 2 urticaria diagnoses or one urticaria and one angioedema diagnosis with no diagnosis of urticarial vasculitis. This study uses data from the Veterans Health Administration from January 2011 through December 2021. We measured time from diagnosis to biologic initiation and CSU-specific HCRU (outpatient visits, inpatient admissions, emergency room visits, and pharmacy claims) in the 12 month pre- and post-index periods. The final cohort included 26 387 Veterans with CSU. In the 12 month post-index period, 23 699 Veterans (89.8%) started treatment, but only 613 Veterans (2.6%) started biologic therapy, with a median initiation time of 337 days. CSU-specific HCRU increased in the post-index period across all categories. 66.8% of Veterans had pharmacy claims pre-index date compared to 89.8% post-index date, and 92.4% of Veterans had outpatient visits pre-index date compared to 96.7% post-index date. The findings suggest that initiation of biologics may be considered sooner in appropriate patients. The increased HCRU observed in the post-index period highlights the burden that CSU places on patients and the healthcare system.

Hypocomplementaemic urticarial vasculitis (HUV) is a rare small-vessel vasculitis characterized by the combination of urticarial vasculitis and hypocomplementaemia. HUV may occur in isolation or be associated with systemic diseases such as systemic lupus erythematosus (SLE). Recently, loss-of-function variants in DNASE1L3 have been reported to cause familial forms of HUV. We aimed to describe the clinical and genetic features of childhood-onset HUV cases in France. We conducted a nationwide retrospective study in France that included 10 patients with childhood-onset HUV. Ten children, all girls, were included. Their median age at onset was 9.5 years (range: 2–14 years), and the median delay between onset and diagnosis was 13 months (range: 6–55 months). Phenotypes were heterogeneous: 3 had systemic HUV syndrome (S-HUVS), all associated with DNASE1L3 deficiency, including 2 siblings; 4 had non-systemic HUVS (NS-HUVS), one of whom had a C2 deficiency; and 3 had SLE-associated HUV. Musculoskeletal features were the most common extracutaneous manifestation (9/10). The most severe manifestations were observed in children with S-HUVS, including pulmonary haemorrhage (2/3) and glomerulonephritis (2/3). Anti-nuclear antibodies were positive in 9/10 patients, anti-C1q antibodies in 6/10, and anti-neutrophil cytoplasmic antibodies in 5/10. Antihistamines were widely used in NS-HUVS, while S-HUVS and SLE-associated HUV required immunosuppressive treatments. Hydroxychloroquine was used in 8/10 patients. These 10 cases highlight the heterogeneity and potential severity of childhood-onset HUV. We report the third familial form of HUVS associated with DNASE1L3 deficiency and an extremely rare case of HUVS associated with C2 deficiency. Childhood-onset HUV is a rare disease with phenotypic and genotypic heterogeneity. Systemic HUVS, associated with DNASE1L3 deficiency but not with positive anti-C1q, is the most severe form. A genetic testing should be systematically performed in childhood-onset HUV.

Urticaria is a mast cell-mediated disorder commonly encountered in women of reproductive age, making its interaction with pregnancy clinically relevant. Gestation induces profound hormonal and immunologic adaptations—including shifts between Th1/Th17 and Th2/Treg responses and sustained exposure to sex steroids and placental hormones—that can modulate mast cell reactivity. As a result, chronic urticaria (CU) shows heterogeneous behavior during pregnancy: approximately half of patients improve, one third worsen, and the remainder remain stable. Pregnancy also presents several urticaria-like dermatoses, notably polymorphic eruption of pregnancy (PEP/PUPPP), atopic eruption of pregnancy (AEP) and pemphigoid gestationis (PG), as well as rare hormone-induced hypersensitivity reactions. Additionally, systemic disorders such as intrahepatic cholestasis of pregnancy (ICP), chronic kidney disease–associated pruritus and urticarial vasculitis may mimic urticaria but differ markedly in prognosis, maternal–fetal risk and management. Given this complexity, accurate diagnosis requires integration of temporal pattern, lesion morphology and duration, distribution, systemic features and targeted investigations, as outlined in the diagnostic algorithm proposed. Most pregnancy-specific eruptions are benign, whereas PG, ICP and urticarial vasculitis warrant prompt recognition due to potential fetal implications. Management of CU in pregnancy generally follows standard guidelines, with second-generation H1-antihistamines as first-line therapy and omalizumab reserved for severe refractory cases.

Objective Biallelic loss‐of‐function variants in DNASE1L3 cause inherited systemic lupus erythematosus and hypocomplementemic urticarial vasculitis. These disorders arise from defective clearance of extracellular chromatin, leading to autoantibody formation, immune complex deposition, and complement consumption. The full clinical and therapeutic spectrum of DNASE1L3 deficiency remains incompletely defined. Methods We evaluated a 24‐year‐old woman with lifelong systemic inflammation characterized by polyarthritis, urticarial vasculitis, episcleritis, recurrent abdominal pain with intestinal angioedema, and persistent hypocomplementemia. Testing included autoantibody profiling, whole‐exome sequencing, DNASE1L3 enzymatic assays in cell lysates and supernatants, and plasma analysis of cell‐free DNA fragmentation. Results The patient lacked antinuclear, anti–double‐stranded DNA, and anti‐Smith antibodies, though antiphospholipid antibodies were intermittently positive. The disease was refractory to multiple immunosuppressive agents but showed partial improvement with JAK inhibition. Genetic analysis revealed compound heterozygous DNASE1L3 variants: a pathogenic frameshift (c.290_291delCA) and a novel missense change (c.179T>G, p.Ile60Ser). Functional testing showed markedly impaired DNA degradation for both variants, with residual activity in the missense mutant. Plasma DNA analysis demonstrated reduced mononucleosomal peaks, altered fragment length distribution, and loss of cytosine–cytosine–rich end motifs, confirming reduced nuclease activity in vivo. Conclusion This case supports the pathogenicity of the DNASE1L3 p.Ile60Ser variant broadening the genetic spectrum. Plasma DNA fragment analysis provides a sensitive biomarker of impaired nuclease function, and JAK inhibition may offer partial therapeutic benefit in DNASE1L3‐related systemic inflammation.

BackgroundNormocomplementemic urticarial vasculitis (NUV) and hypocomplementemic urticarial vasculitis (HUV) share clinical features, notably wheals, yet clear differential diagnostic criteria are lacking.ObjectiveTo describe HUV and NUV features in Chinese inpatients for diagnosis.MethodsRetrospective study (March 2017–June 2024, China) of NUV/HUV patients. We analyzed clinical characteristics, laboratory results, and histological features, and compared drug efficacy.ResultsFemales 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.ConclusionOur 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.

Annular skin lesions are ring-shaped manifestations characterized by an erythematous margin and a preserved or atrophic center. Their pathophysiology involves mechanisms such as peripheral inflammatory mediator expansion or immune tolerance at the center of the lesions. This article reviews some of the most common annular lesions observed in pediatric populations within our setting. We included urticarial vasculitis, childhood cutaneous lupus erythematous, Still's disease, annular granuloma, centriphugal annular erythema, pigmentary dermatoses, erythema migrans, multiform urticaria, acute hemorrhagic edema of the infancy, infectious dermatoses such as dermatophyte infections, and blistering conditions like linear IgA dermatosis, highlighting their clinical presentations, diagnostic approaches, and treatment options, emphasizing the importance of clinical correlation, biopsy findings, and appropriate therapeutic strategies. This review will assist clinicians in diagnosing diseases associated with annular skin lesions.

REPORTreduced air entry and crepitations over the right infrascapular area.Other systems were unremarkable.Investigations (Fig. 2 and Table 1) revealed mild anemia (Hb 10.2 gm/dL), neutrophilia (64%), elevated C-reactive protein (CRP) of 48 mg/ dL, and erythrocyte sedimentation rate (ESR) of 57 mm/hr.Renal function, serum electrolytes, and blood and urine cultures were unremarkable.A chest X-ray on day 1 (Fig. 2A) showed right middle-zone consolidation.The child was started on broadspectrum antibiotics as per institutional protocol (intravenous ceftriaxone) for pneumonia.However, over 48 hours, the condition worsened with persistent high-grade fever, rising inflammatory parameters, worsening pneumonia, and the rash changing in distribution from all over the trunk to predominantly bilateral lower limbs.The antibiotics were therefore escalated to piperacillin-tazobactam. IntroductIonOne of the most frequent causes of community-acquired pneumonia (CAP) in children aged 10-17 is walking pneumonia, which is brought on by Mycoplasma pneumoniae (prevalence: 23%), 1 Lower respiratory tract infections affect 21.3% of children aged 2-4 years, 41.3% of children aged 5-7 years, and nearly 60% of children aged 7 years and beyond. 2 The rate of morbidity rises with age.Attack rates within families are high, with transmission rates of 40 to >80% for adult and child household contacts. 1The incubation period is approximately 14-21 days.Approximately 30% of patients have cutaneous symptoms.The most frequent cutaneous symptoms include exanthematous skin rash (8-33%), urticaria (7%), subacute nodular migratory panniculitis (8%), anaphylactoid purpura, erythema multiforme, Stevens-Johnson syndrome (1-5%), and cutaneous leukocytoclastic vasculitis. 3 case descrIptIonA previously well-immunized-for-age, and developmentally normal 9-year-old boy presented with complaints of highgrade fever with chills for 5 days and cough for 3 days.On day 3 of fever, he was treated at a private clinic with amoxicillin in view of granular pharyngitis.The child developed a widespread urticarial maculopapular rash (Fig. 1) on the 5th day of fever.On assessment, he was febrile (temperature 104F), tachycardic (130/min), and tachypneic (28/min).He had a maculopapular rash that was erythematous and nonpruritic, distributed over the trunk, bilateral upper limbs, and lower limbs.He also had bilateral eye congestion.On systemic examination, bronchial breath sounds were heard in the right inframammary area with

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.

121 Systemic Erythema Elevatum Diutinum Overlapping with Hypocomplementemic Urticarial Vasculitis

Background: Lyme disease is a well-recognized illness commonly associated with skin manifestations such as erythema migrans. However, atypical presentations can complicate diagnosis, particularly when they deviate from classic clinical and histological findings. Methods: We report a potential case of Lyme disease presenting as a dermal hypersensitivity reaction (DHR), with clinical findings resembling urticaria rather than urticarial vasculitis. Skin biopsy findings were reviewed, and Lyme serology testing was performed. Results: The biopsy did not demonstrate the characteristic superficial perivascular lymphocytic infiltrate typically seen with erythema migrans. The patient's history included prior tick exposures, but while Lyme IgM was positive, the Lyme IgG testing was negative, suggesting no prior Lyme exposure. With PCR and repeat IgG scheduled the patient was diagnosed with Lyme disease. Conclusions: This case highlights an atypical presentation of potential Lyme disease and underscores the importance of considering Lyme disease in the differential diagnosis of DHR, especially in patients with a history of tick exposure. In cases of DHR, a thorough clinical history regarding arthropod bites and tick exposure should guide targeted testing for Lyme and other tick-borne illnesses. Keywords: Lyme disease, dermal hypersensitivity reaction, erythema migrans, atypical presentation, tick-borne disease

Pemphigus foliaceus (PF) is a rare autoimmune blistering disease, occasionally associated with lymphoproliferative disorders. Urticarial vasculitis (UV) is classified as normocomplementemic or hypocomplementemic (HUV), the latter linked to systemic involvement and increased risk of malignancy. We present a rare case of atypical HUV syndrome in a 55-year-old female with a 24-year history of PF. She presented with recurrent heat, redness, and discoloration of the right hand. Examination revealed an erythematous-violaceous, edematous lesion with irregular but well-defined borders over the thenar region, without urticarial lesions. Laboratory evaluation showed marked hypocomplementemia (C3 0.73 g/L, C4 0.01 g/L), thrombocytopenia (32×10³/µL), leukocytosis, and positive ANA. Hepatomegaly was noted on systemic examination. Hematology consultation revealed a CD5-negative, CD19-positive B-cell lymphoproliferative disorder. Genetic testing excluded hereditary cancer mutations. This case underscores the clinical importance of recognizing atypical HUV presentations without urticaria and highlights the association of hypocomplementemia and thrombocytopenia with underlying hematologic malignancy. In patients with autoimmune background and cutaneous vasculitic lesions, hematologic malignancies should be considered, and thorough evaluation is essential to exclude paraneoplastic processes.

Eosinophilic Granulomatosis with Polyangiitis (EGPA) is a rare systemic vasculitis with eosinophilic inflammation and variable clinical presentations. Although skin manifestations are frequent, current classification criteria do not include them, which may underestimate their diagnostic value. This prospective observational study aimed to assess systemic and skin involvement as well as eosinophilia, anti-neutrophil cytoplasmic antibody (ANCA), and Anti-nuclear antibodies (ANA) serum levels in 20 EGPA patients followed for one year at the University Hospital of Messina, Italy, before starting Mepolizumab, 300 mg. Eosinophilia, ANCA status, systemic and skin involvement were also evaluated at 6 and 12 months; a literature review on these data supplements our findings. Skin involvement was present in 55% of patients, including purpura, urticarial vasculitis, angioedema, maculopapular rash, and nodules, mostly in ANCA-negative patients, though purpura was more frequent in ANCA-positive cases but without any statistically significant correlation. ANAs were present in 50% of patients, together with ANCA in two subjects and without in eight. Mepolizumab significantly reduced eosinophil levels, BVASs, and corticosteroid dependence, with notable improvement in skin symptoms. In conclusion, skin manifestations are common in EGPA and may represent useful indicators of disease activity. Their integration with ANCA status, eosinophil counts, and positivity to other autoantibodies could enhance diagnostic and monitoring strategies identifying different clusters of EGPA patients even if the small sample size limits the generalizability of the findings.

Current therapeutic options for adult patients with urticarial vasculitis: A scoping review.

Abstract Cutaneous vasculitides (CVs) are autoimmune and autoinflammatory conditions affecting small blood vessels in the skin. This can cause urticaria, petechiae or purpuric papules. Few studies on the epidemiology and clinical presentation of CVs exist. This 2011–20 retrospective regional cohort study identified patients with biopsy-proven CV from pathology reports in a single secondary centre covering a total patient exposure of 6 631 136. Age-standardized incidence rates and age-specific rates were calculated using the European 2013 standard population and are reported per 100 000 person-years (PY) alongside 95% confidence intervals. The Office for National Statistics census 2011 postcode data, 2021 census regional population data and annual estimates were used to estimate representative postcode population counts. Electronic patient records (EPRs) were used to summarize potential triggers and investigation results. The difference in incidence were compared using χ2-tests. Histologically confirmed cases of CV were diagnosed in 257 patients over the age of 18 years (56.0% female) in this regional cohort between 2011 and 2020. Diagnoses were leucocytoclastic vasculitis (58.4%), IgA vasculitis (15.2%), urticarial vasculitis (10.1%), eosinophilic granulomatosis with polyangiitis (1.9%), polyarteritis nodosa (0.8%) and vasculitis ‘not otherwise specified’ (13.6%). The median age at diagnosis was 61 years (range 19–91). The 2011–20 age-standardized incidence rate was 3.8 (95% confidence interval 0.28–0.35) per 100 000 PY for the whole population. The CV age-specific rates rose steadily with age, with a large increase in people aged &amp;gt; 60 years. The age-specific rates also showed a bimodal female-to-male distribution. For those aged &amp;lt; 50 and &amp;gt; 75 years, female patients had higher rates than male patients. However, this difference was not statistically significant (P &amp;gt; 0.05). The EPRs of 107 patients included documentation about new medications. New medications within 6 months of symptom onset were reported for 63 of 107 (58.9%) patients, 34 of 63 (54%) of whom had been started on antibiotics. Of 129 EPRs including documentation on recent illness, 88 patients (68.2%) had an infection or intercurrent sepsis. The biochemistry results were available for 220 patients. Of these, urea and creatine were raised for 34 (15.5%) and 35 (15.9%) patients, respectively. C-reactive protein and erythrocyte sedimentation rate were elevated in 126 of 192 (65.6%) and 62 of 165 (37.6%) patients, respectively. Antineutrophil cytoplasmic antibody was tested in 192 patients and positive in 19 (9.9%). CV is uncommon and there is a lack of epidemiological studies in the literature, perhaps because cases are not easily identified through routinely collected healthcare data. Blood tests were generally unremarkable except for raised C-reactive protein, and commonly found triggers included infection and medications, as expected. Our data are essential to support future evidence-based research into this condition.

Chronic urticarial lesions, a common condition of mostly unknown cause, can occur in immune dysregulation disorders such as hypocomplementaemic urticarial vasculitis syndrome (HUVS), neutrophilic urticarial dermatosis (NUD) and systemic autoinflammatory diseases (SAIDs), including Schnitzler syndrome. To identify the molecular basis of nonpruritic chronic urticarial eruptions in four unrelated patients initially diagnosed with neonatal NUD, Schnitzler syndrome, HUVS or giant-cell arteritis. Conventional next-generation sequencing (NGS) of leucocyte DNA was supplemented with high-depth NGS (> 1500×) to improve the detection of low-level mosaicism in SAID-related genes. Functional assays were performed on recombinant NLRP3 proteins to assess the impact of the identified variations on the nuclear factor-κB (NF-κB) pathway. One patient presented with persistent isolated urticarial lesions since birth, while the other three experienced late-onset skin lesions. In contrast to the initially suspected diagnoses, conventional NGS revealed NLRP3 mosaicism in two patients, with variant allele fractions (VAFs) of 5% and 11%, respectively. In the other two patients, high-depth NGS uncovered NLRP3 mosaicism with VAFs as low as 2-3%. All identified variations activated the NF-κB pathway, demonstrating a gain-of-function effect. Subsequent anti-interleukin-1 therapy led to symptom improvement for all patients. This study highlights the importance of considering NLRP3 mosaicism as an underlying pathological mechanism in chronic urticarial lesions, whether of early or late onset, and whether isolated or mimicking other conditions. As blood contains key target cells for NLRP3 inflammasome activation, even extremely low-level leucocyte mosaicism can be pathogenic. High-depth NGS-based diagnosis of NLRP3-related disorders enables timely initiation of anti-IL-1 therapy, which is crucial to preventing complications such as systemic amyloidosis.

BACKGROUND: ASIA is an autoimmune/inflammatory syndrome induced by adjuvants. Symptoms can be diverse, and the recurrent angioedema is one of the dominant manifestations. Genetic screening is discussed as a preventive option. The following alleles of genes: HLA type II (DRB1*0301 or in combination with HLA-B*08, DRB1*01, and DRB4), as well as Arg620Trp polymorphism in the PTPN22 gene are discussed as a cause of autoimmune diseases, including ASIA syndrome. AIM: To identify the presence of causative genetic factors in patients with ASIA syndrome by genetic screening, to identify adjuvants acting as a trigger, and to evaluate the efficacy of current therapy. MATERIALS AND METHODS: A single center observational study of 16 patients with ASIA syndrome and 10 controls was performed. Genetic screening was performed in 14 patients from the ASIA group and 10 patients from the control group. Further inclusion of patients in the study is planned. RESULTS: All patients with ASIA were women, potential triggers included hyaluronic acid fillers 10/16 (62.5 %), including in combination with breast silicone implants 1/16 (6.25 %), arthroplasty with shoulder joint replacement 1/16 (6.25 %), face hyaluronic acid injections 5/16 (31.25 %), and calcium hydroxyapatite 1/16 (6.25 %). The main site of angioedema was the face 15/16 (93.75 %), also larynx (1/16 (6.25 %)), upper (2/16) and lower extremities (1/16 (6,25 %)). Other symptoms included arthralgia, myalgia, muscle weakness — 1/16 (6.25%), hypocomplementemic urticarial vasculitis, lymphocytic colitis — 1/16 (6.25 %), arthralgia combined with lymphadenopathy — 1/16 (6.25 %), chronic spontaneous and solar urticaria — 1/16 (6.25 %), fixed erythema of the shoulder skin with fever, antiphospholipid syndrome — 1/16 (6.25 %), normocomplementemic urticarial vasculitis — 1/16 (6.25 %), Still’s disease — 1/16 (6.25 %). Autoimmune response was represented by autoantibodies in 10 (62.5 %) of 16 patients. Ten (62.5 %) patients received non-sedative antihistamines at standard and escalated doses (5 as monotherapy, 1 in combination with filler removal, 1 with hydroxychloroquine, 3 with hydroxychloroquine and omalizumab), 1 (6.25 %) received tranexamic acid, 1 (6.25 %) with danazol, 1 (6.25 %) with hydroxychloroquine, and 3 (18.75 %) patients received no therapy. A combination of two genetic factors was detected in 3 (21.4 %) patients: DRB1*0301, B1*08 (in 2 patients additionally Arg620Trp polymorphism). Isolated Arg620Trp polymorphism was detected in 6 (42.8 %) patients. CONCLUSION: Genetic factors increasing the risk of autoimmune conditions were found in 9 out of 16 patients. No genetic abnormalities were found in the control group. More than half of the patients with ASIA syndrome had genetic factors associated with autoimmunity. Further studies are needed to create reliable diagnostic and treatment algorithms.

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Urticarial vasculitis induced by paroxetine: wood grain morphology.

Abstract Chronic obstructive pulmonary disease (COPD) is commonly seen in older populations with over 20 years of smoking history. However, around 15% of COPD cases are unrelated to tobacco exposure. Among these, Alpha-1antitrypsin (A1AT) deficiency is a significant but relatively rare contributor accounting for approximately 1% of cases. This report discusses other less common causes. A 42-year-old African American male with 7-year history of emphysema and 18-years of tobacco use with normal serum A1AT, presented to the ED with sudden onset shortness of breath and respiratory distress. Imaging revealed extensive bullous disease of bilateral lungs with a right-sided pneumothorax. A pigtail catheter was placed bedside and repeat imaging showed resolution and successfully transitioned to nasal cannula (CT imaging below). Lab work was unremarkable, HIV negative. Subsequent days he was unable to tolerate the chest tube de-escalation on multiple attempts, leading to talc pleurodesis while awaiting accepting transplant center. Eventually transferred, the patient successfully underwent bilateral orthotopic lung transplantation (BOLT). He was placed on immunosuppression medication and had post-operative complications with multiple bacterial pathogens, resolved with intravenous antibiotics. Two weeks post op he had left airway dehiscence via bronchoscopy and a metallic stent was placed, Serial bronchoscopies requiring dilation with stenosis were noted. The stent was removed once the airways healed appropriately. Five months post-op, he is asymptomatic and on immunosuppression. COPD is diagnosed by symptoms and evidence of air flow limitation. The pathogenesis of COPD is well-studied and believed to be multifaceted. The pathogenesis of COPD is complex, with the most accepted theory involving an exaggerated protective response to inhaled toxins, leading to tissue damage and impaired lung defenses. Other factors include imbalances in proteases vs. antiproteases and oxidative stress. Genetic factors may also play a role, as not all smokers develop COPD, and other less common causes should be considered including A1AT deficiency, HIV, Hypocomplementemia urticarial vasculitis syndrome, Birt Hogg Dube syndrome, Swyer James Macleod syndrome. Early COPD is managed with inhaled bronchodilators, LABAs, anticholinergic agents and steroids. More aggressive treatments include lung volume reduction surgery (LVRS) and endobronchial valve placement. LVRS has been shown to provide symptom relief and survival advantages more apical disease and low baseline exercise capacity according to National Emphysema Treatment Trial (NETT). The definitive therapy is lung transplant. This case highlights the need for further research into the risk factors of this common condition and improved diagnostic approaches that aid in early detection and management.