[Severe systemic vasculitis induced by ibrutinib]. / Vascularite systémique sévère induite par l'ibrutinib.

INTRODUCTION: The specific cutaneous toxicity of Bruton's tyrosine kinase inhibitors is poorly described. We report a case of severe systemic vasculitis induced by ibrutinib. OBSERVATION: A 73-year-old woman with chronic lymphocytic leukemia was treated with ibrutinib. Eighteen months after treatment onset, ulceronecrotic lesions on toes and tongue occurred. Skin biopsy found vasculitis of small and medium vessels. Biologic tests were negative. This vasculitis was refractory to systemic corticosteroid therapy and azathioprine. Ibrutinib was stopped on the hypothesis of drug-induced vasculitis. Skin lesions improved after discontinuation of ibrutinib. CONCLUSION: The mechanism of action of ibrutinib does not explain the occurrence of vasculitis and an immunoallergic mechanism is suspected.

Small-vessel vasculitis leading to severe acute kidney injury after ipilimumab: a case report.

Immune checkpoint inhibitors are effective monoclonal antibodies used in cancer treatment, particularly in metastatic melanoma. They target proteins responsible for cancer cells evading the immune system. However, their use can lead to immune-related adverse events, with the skin and gastrointestinal tract being commonly affected. Kidney involvement is rarer, with interstitial nephritis being the most common manifestation. In a unique case, kidney biopsy-proven small-vessel vasculitis with arteriolar immune deposition was observed following ipilimumab administration.

[Large-vessel vasculitis developed after use of long-acting granulocyte colony-stimulating factor in a patient with diffuse large B-cell lymphoma].

A 75-year-old man was diagnosed with diffuse large B-cell lymphoma originating from the paranasal sinuses. Curative induction chemotherapy was initiated and pegfilgrastim was administered on day5 of the first cycle as primary prophylaxis. The patient developed headache on day7 and fever on day11. These symptoms persisted despite treatment with antibiotics and antifungal agents. Computed tomography (CT) after admission revealed wall thickening in the aortic arch. Chest contrast-enhanced CT also revealed contrast enhancement in the thickened aortic wall. Results of blood cultures and serological tests for autoantibodies were negative, indicating that the clinical manifestations were not due to infection or a specific collagen disease. The final diagnosis was drag-induced large vessel vasculitis induced by long-acting granulocyte colony-stimulating factor (G-CSF). The patient's symptoms and large-vessel wall thickening immediately resolved after treatment with a glucocorticoid (prednisolone, 0.6 mg/kg/day). Aortitis should be considered as a differential diagnosis when fever is observed in a patient who received long-acting G-CSF during chemotherapy.

[Therapeutic effect of mycophenolate mofetil or cyclophosphamide in children with Henoch-Schönlein purpura nephritis of different age groups]. / ä¸åŒå¹´é¾„æ®µè¿‡æ•æ€§ç´«ç™œæ€§è‚¾ç‚Žæ‚£å„¿æŽ¥å—éœ‰é šé ¸é ¯æˆ–çŽ¯ç£·é °èƒºæ²»ç–—çš„ç–—æ•ˆå·®å¼‚åˆ†æž.

OBJECTIVES: To investigate the difference in the therapeutic effect of mycophenolate mofetil (MMF) or cyclophosphamide (CTX) in children with Henoch-Schönlein purpura nephritis (HSPN) of different age groups. METHODS: A retrospective analysis was conducted on the clinical data of 135 children with HSPN who were treated with MMF or CTX in the Department of Nephrology, Children's Hospital Affiliated to Capital Institute of Pediatrics, from October 2018 to October 2020. According to the immunosuppressant used, they were divided into two groups: MMF group and CTX group, and according to the age, each group was further divided into two subgroups: ≤12 years and >12 years, producing four groups, i.e, the ≤12 years MMF subgroup (n=30), the >12 years MMF subgroup (n=15), the ≤12 years CTX subgroup (n=71), and the >12 years CTX subgroup (n=19). All children were followed up for at least 12 months, and the above groups were compared in terms of clinical outcomes and the incidence rate of adverse reactions. RESULTS: There was no significant difference in the complete response rate between the MMF group and the CTX group after 3, 6, and 12 months of treatment (P>0.05). There were no significant difference in the complete response rate and the incidence rate of adverse reactions between the >12 years MMF subgroup and the ≤12 years MMF subgroup at 3, 6, and 12 months of treatment (P>0.05). The >12 years CTX subgroup had a significantly lower complete response rate than the ≤12 years CTX subgroup at 6 and 12 months of treatment (P<0.05). The >12 years CTX subgroup had a significantly higher incidence rate of adverse reactions than the >12 years MMF subgroup (P<0.05). CONCLUSIONS: The efficacy and adverse reactions of MMF are not associated with age, but the efficacy of CTX is affected by age, with a higher incidence rate of adverse reactions. CTX should be selected with caution for children with HSPN aged >12 years.

Refractory drug-induced systemic small-vessel vasculitis with two varied extracutaneous manifestations: a case report and review of the literature.

BACKGROUND: Clopidogrel and ticagrelor are rarely reported to cause vasculitis via drug hypersensitivity reaction, largely mediated by T cells and immunoglobulin E (IgE). Despite therapeutic advances, the etiology of refractory vasculitides remains incompletely understood. Recently, (non)immunological mechanisms bypassing T cells and IgE have been proposed to explain resistance to standard immunosuppressants. Herein, we report a case of refractory drug-induced systemic small-vessel vasculitis with varied extracutaneous manifestations and incorporate multiple sources of data to provide detailed accounts of complex (non)immunological phenomena involved in this case. Study objectives are to provide an insight about rare presentations of commonly used drugs, upgrade the pathophysiological concepts of drug-induced vasculitis, raise need for further investigation to define causes and risk factors for refractory vasculitis, and discuss most of the current knowledge suggesting novel therapeutic approaches to treat this vasculitis. To our knowledge, this is the first case of the two flares of systemic small-vessel vasculitis in a single patient in response to clopidogrel and ticagrelor exposure, respectively. However, this report is limited by attribution/observer bias. CASE PRESENTATION: We herein report a 24-year-old Caucasian male student with a medical history of mild seasonal allergic rhinoconjunctivitis, tension-type headaches, posttraumatic arterial stenosis, and previous exposure to ibuprofen, acetylsalicylic acid, and mRNA coronavirus disease 2019 (COVID-19) vaccine who suffered largely from acute urticaria and dyspnea after 20 days of acetylsalicylic acid and clopidogrel introduction. A skin punch biopsy confirmed leukocytoclastic vasculitis. Serologic antibody testing, complement analysis, microbiologic testing, and cancer biomarkers revealed no abnormalities. Regarding the patient's medical history, both acetylsalicylic acid and clopidogrel were exchanged for ticagrelor. Furthermore, the addition of naproxen, cyclosporine, bilastine, prednisolone, and montelukast resulted in complete recovery. After 7 days, diarrhea and hematuria occurred. Urinalysis and computed tomography showed reversible proteinuria with gross hematuria and hypodense changes in kidney medulla, respectively, associated with discontinuation of ticagrelor and naproxen. In addition, the patient recovered completely without any immunosuppression up-titration. CONCLUSIONS: This case highlights the role of clopidogrel and ticagrelor as possible triggering agents for systemic small-vessel vasculitis and offers an insight into novel therapeutic strategies for refractory vasculitides. Further research is needed to build on the findings of a current report.

[Vasculitis oft the skin after cocaine use]. / Vaskulitis der Haut nach Kokainkonsum.

HISTORY AND CLINICAL FINDINGS: A 20-years-old patient presented himself to our emergency room with extensive and extremely painful purpura with necrotizing spots and blisters, especially on the lower extremities, but also on the arms, trunk and ears. There was a pre-existing use of cocaine. MEDICAL EXAMINATIONS: Laboratory tests showed increased signs of inflammation as well as an increase in proteinase 3- and myeloperoxidase-ANCA (Anti-neutrophil cytoplasmatic antibody). DIAGNOSIS: In combination with the medical history, the clinical findings, and the laboratory values, vasculitis of the skin after cocaine use was revealed. THERAPY AND COURSE: Under therapy with steroids and cocaine abstinence, there was a regression of the changes. CONCLUSION: Vasculitis is a serious complication of cocaine use.

Normocomplementemic urticarial vasculitis in a patient with multiple sclerosis on glatiramer acetate.

Glatiramer acetate is one of the oldest and safest disease modifying therapies used to treat relapsing-remitting multiple sclerosis. Urticarial vasculitis is a rare complication of treatment with glatiramer acetate, having been reported by only two others previously. Here, we describe a case of normocomplementemic urticarial vasculitis diagnosed on skin punch biopsy in a patient with multiple sclerosis treated with glatiramer acetate for five years. Upon treatment with steroids and an antihistamine along with discontinuation of glatiramer acetate, the urticaria resolved.

Clinical, radiological and laboratory characteristics of central nervous system histoplasmosis: A systematic review of a severe disease.

BACKGROUND: The knowledge of central nervous system (CNS) histoplasmosis is limited to case reports and series. OBJECTIVES: Our objective was to synthesise clinical, radiological and laboratory characteristics of CNS histoplasmosis to improve our understanding of this rare disease. METHODS: We performed a systematic review using Pubmed/MEDLINE, Embase and LILACS databases accessed on March 2023 without publication date restrictions. Inclusion criteria comprised: (1) histopathological, microbiological, antigen or serological evidence of histoplasmosis; (2) CNS involvement based on cerebrospinal fluid pleocytosis or neuroimaging abnormalities. We classified the certainty of the diagnosis in proven (CNS microbiological and histopathological confirmation), probable (CNS serological and antigen confirmation) or possible (non-CNS evidence of histoplasmosis). Metaproportion was used to provide a summary measure with 95% confidence intervals for the clinical, radiological and laboratory characteristics. Chi-squared test was used to compare mortality between pairs of antifungal drugs. RESULTS: We included 108 studies with 298 patients. The median age was 31 years, predominantly male, and only 23% were immunocompromised (134/276, 95%CI: 3-71), mainly due to HIV infection. The most common CNS symptom was headache (130/236, 55%, 95%CI: 49-61), with a duration predominantly of weeks or months. Radiological presentation included histoplasmoma (79/185, 34%, 95%CI: 14-61), meningitis (29/185, 14%, 95%CI: 7-25), hydrocephalus (41/185, 37%, 95%CI: 7-83) and vasculitis (18/185, 6%, 95%CI: 1-22). There were 124 proven cases, 112 probable cases and 40 possible cases. The majority of patients presented positive results in CNS pathology (90%), serology (CSF: 72%; serum: 70%) or CSF antigen (74%). Mortality was high (28%, 56/198), but lower in patients who used liposomal amphotericin B and itraconazole. Relapse occurred in 13% (23/179), particularly in HIV patients, but less frequently in patients who used itraconazole. CONCLUSION: Central nervous system histoplasmosis usually presents subacute-to-chronic symptoms in young adults. Neuroimaging patterns included not only focal lesions but also hydrocephalus, meningitis and vasculitis. Positive results were commonly found in CSF antigen and serology. Mortality was high, and treatment with liposomal amphotericin B followed by itraconazole may decrease mortality.

Secukinumab-induced IgA vasculitis in a patient with psoriatic arthritis.

OBJECTIVES: Secukinumab (SEC) is an effective and widely used drug in psoriatic disease and axial spondyloarthritis. However, SEC has been found to be associated with inflammatory conditions and vasculitis. These inflammatory adverse effects may complicate the treatment of underlying disease, and clinicians may experience difficulties in recognizing and managing this unusual condition. CASE REPORT: A man aged 56 years with psoriatic disease refractory to conventional disease-modifying antirheumatic drugs was given adalimumab for 6 weeks, then switched to SEC when his psoriatic lesions were exacerbated. After 3 weeks of SEC treatment, he developed systemic features of IgA vasculitis while his skin lesions and arthritis persisted. CONCLUSIONS: Although SEC-related inflammatory adverse events, including vasculitis, are rarely encountered in clinical practice, it is essential to recognize them because they can be mistaken as a component of the underlying inflammatory disease. In addition, the dramatic improvement in many cases after the cessation of SEC underlines the importance of making an accurate diagnosis. Pathogenetically, these adverse events are likely to be paradoxical reactions, except for SEC-induced inflammatory bowel diseases. However, in many aspects, their pathogenesis is controversial and needs clarification.

A Canadian vasculitis patient-driven survey to highlight which prednisone-related side effects matter the most.

OBJECTIVES: Although management of vasculitis has evolved over the last decades, glucocorticoids (GC) have remained the cornerstone of treatment. The side effects (SE) of GC are well known by the clinicians; their importance for patients with vasculitis has not been investigated as extensively as in other rheumatological conditions. METHODS: An online questionnaire surveyed between April 29th. to July 31st, 2022 with Vasculitis Foundation Canada about the patient experience and SE of prednisone. The survey included 5 questions about prednisone dose and duration, 21 about specific SE (with a rating of 1-10, and one question each on worst prednisone, and worst vasculitis, SE), and four other questions about knowledge and perception of possible alternatives to prednisone (namely, avacopan). RESULTS: A total of 97 patients (53 GPA/MPA, 44 other vasculitides) completed the survey. Their mean duration of GC use was 62.7±83.7 months, and 49.5% of patients were still on GC (daily dose, 8.4±6.2mg). All the patients reported ≥1 GC-related SE, and 67.0% reported ≥11/19 pre-specified SE of interest. Among ranked SEs, acne was the lowest score, whereas moon face/torso hump had the highest score, just above weight gain, insomnia and decreased quality of life. Around half of the GPA/MPA patients and one-third of the others had heard about avacopan, and 68% of patients (similarly in both groups) stated they would prefer being the first to take a very new medication, such as avacopan, instead of prednisone. CONCLUSIONS: Ranking given to some GC-related SEs may differ between patients and physicians. GC toxicity/SE indexes should reflect this difference.

De Novo Vasculitis after COVID-19 Vaccination.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic continues to spread around the world. Vaccinations have been administered globally and have been proven to be safe and effective. However, vasculitis has been reported as an adverse event occurring after COVID-19 vaccination. METHODS: In this review, we analyzed the literature to identify original articles that reported on patients who developed vasculitis following COVID-19 vaccination and summarized their clinical manifestations. PubMed and Web of Knowledge were searched to identify relevant studies. RESULTS: A total of 27 patients who developed vasculitis following COVID-19 vaccination were identified from 21 studies. The involved organs included the skin and kidney. The main clinical features of patients whose skin was affected were papules, maculopapular rashes, and plaques. Most of the patients exhibited small vessel vasculitis and single-organ vasculitis; these were resolved within one month. Patients whose kidneys were affected exhibited vasculitis, including anti-neutrophil cytoplasmic antibody glomerulonephritis and IgA nephritis. Most patients were treated with corticosteroid, rituximab, and cyclophosphamide, and one patient needed hemodialysis. The renal function of most patients was improved or recovered, but one patient needed maintenance dialysis. CONCLUSION: Vasculitis was rarely reported after COVID-19 vaccine administration. It often manifested as cutaneous small-vessel vasculitis or glomerulonephritis. Notably, when a patient demonstrates hematuria, proteinuria, and acute kidney injury after COVID-19 vaccination, there is a possibility that the patient could have developed vasculitis. Skin-related problems were quickly resolved, while kidney-related problems may progress to chronic kidney disease.

A case report of possible concurrent vasculitis in vertebral bodies and partial transverse myelitis following COVID-19 vaccination.

INTRODUCTION: Cases with organ-specific and systemic vasculitis associated with corona virus disease 2019 (COVID-19) vaccination have been reported. However, acute partial transverse myelitis (APTM) is rare adverse events following received COVID-19 vaccines. To the best of our knowledge, there is no report on vaccine-associated APTM accompanied by possible concurrent vasculitis. Herein we present a case with possible concurrent spinal vasculitis and APTM following the second dose of inactivated COVID-19 vaccine. CASE SUMMARY: A 33-year-old man presented with weakness of left lower limb and aberrant sensation of his left lower trunk and limb (from T9 level to toes) for 2 days following receipt of an inactivated COVID-19 vaccine. Remarkable demyelinating lesion at T7 spinal cord was showed by 3.0T magnetic resonance imaging (MRI) scan. Moreover, vertebral bodies of T3-T7 also presented high signal in T-2 weighted imaging (T2WI) accompanied by multiple sites of flowing void effect indicating possible vasculitis. Oligoclonal band was positive in cerebrospinal fluid (CSF) while it was negative in sera. Intravenous methylprednisolone (1 g/d) was administrated for 5 days followed by subsequent dose-tapering prednisone. His limb weakness and aberrant sensation both improved and he was able to walk unaided after treatment. The MRI recheck also showed remarkable improvement on the lesions in spinal cord and vertebral bodies. CONCLUSION: this case illustrates the concurrence of possible vasculitis in vertebral bodies and acute transverse myelitis (ATM) following COVID-19 vaccination.

A Spotlight on Drug-Induced Vasculitis.

PURPOSE OF REVIEW: Drug-induced vasculitis (DIV) is a rare form of vasculitis related to the use of various drugs. DIV primarily affects small to medium size vessels, but it can potentially involve vessels of any size. Differentiating between primary systemic vasculitis and DIV can be challenging; however, it is crucial, so that the offending agent can be discontinued promptly. RECENT FINDINGS: The clinical phenotype of DIV is protean and depends on the size of the affected vessels. It ranges from arthralgias, to an isolated cutaneous rash, to severe single or multi-organ involvement. While withdrawal of the offending drug is the most important step in management, a significant number of patients require immunosuppressive therapy for varying periods of time. DIV can affect any vascular bed size, leading to protean vasculitic syndromes. Increased awareness among general practitioners, specialty, and subspecialty physicians is crucial for early recognition, and withdrawal of drug for better outcomes.

Immune-mediated diseases after coronavirus disease 2019 vaccination: rare but important complication.

Since the beginning of mass vaccination against coronavirus disease 2019 (COVID-19), vaccine-linked immune-mediated diseases have been increasingly reported. The development of these diseases after COVID-19 vaccination may be attributed to the mechanisms of molecular mimicry and cross-reactivity between the viral spike protein and self-antigens. The most frequent vaccine-linked glomerular disease is immunoglobulin A nephropathy (IgAN). Cutaneous vasculitis has also been reported after COVID-19 vaccination. In both diseases, deposition of immune complexes activates the inflammatory response with end-organ damage. We report on a case of de novo IgAN in a young man and a case of severe cutaneous vasculitis in a 68-year-old woman, both after the second dose of Pfizer-BioNTech COVID-19 vaccine. Neither of the patients had a history of autoimmunity or adverse reactions to vaccines. The temporal association between vaccination and disease development in the absence of other possible intercurrent inciting events suggests a causal mechanism, although coincidental co-occurrence cannot be excluded. In both cases, immunosuppressive treatment was warranted to stop disease progression and to partially or completely resolve the disease. A timely reaction is needed if new-onset signs of an immune-mediated disease appear after vaccination.

Sivelestat's effect on Candida albicans water-soluble fraction-induced vasculitis.

BACKGROUND: We investigated the efficacy of sivelestat sodium hydrate (SSH) as a treatment for Kawasaki disease, and its pharmacological action sites, in mice with Candida albicans water-soluble fraction-induced vasculitis. METHODS: Sivelestat sodium hydrate was administered intraperitoneally to Candida albicans water-soluble fraction-induced vasculitis model mice to assess its efficacy in preventing the development of coronary artery lesions based on the degree of inflammatory cell infiltration in the aortic root and coronary arteries (vasculitis score). The pharmacological sites of action were investigated based on changes in neutrophil elastase (NE) and intercellular adhesion molecule 1 (ICAM-1) positive areas, ICAM-1 and tumor necrosis factor-α mRNA expression levels in the upper heart, and the proportion of monocytes in the peripheral blood. RESULTS: The vasculitis score decreased below the lower limit of the 95% confidence interval of untreated mice in 69% of the SSH-treated mice. The NE- and ICAM-1-positive regions, and the mRNA expression of ICAM-1 and tumor necrosis factor-α were lower in the SSH-treated mice than in the untreated mice. The proportion of monocytes in the peripheral blood was higher in the SSH-treated mice than in the untreated mice, whereas monocyte migration to inflammation areas was suppressed in the SSH-treated mice. CONCLUSIONS: Our results showed that SSH might prevent the development of coronary artery lesions and ameliorate disease activity. In addition to its NE-inhibitory effect, SSH sites of action may also include monocytes.