Pulmonary pathology in vasculitis.

Pulmonary involvement is frequent in vasculitis, particularly in ANCA-associated small vessel vasculitis. Laboratory and radiological data alone are often sufficient to confirm the clinical hypothesis, but sometimes the pathologist plays a crucial role in the differential diagnosis and the patient's management. In this review, the pathologic features of pulmonary vasculitis and the pathologist's role in this field are illustrated.

Cardiovascular pathology in vasculitis.

Vasculitides are diseases that can affect any vessel. When cardiac or aortic involvement is present, the prognosis can worsen significantly. Pathological assessment often plays a key role in reaching a definite diagnosis of cardiac or aortic vasculitis, particularly when the clinical evidence of a systemic inflammatory disease is missing. The following review will focus on the main histopathological findings of cardiac and aortic vasculitides.

Cutaneous vasculitis: insights into pathogenesis and histopathological features.

The mechanisms underlying the onset and progression of vasculitis remain poorly understood. This condition is characterized by damage to the vascular wall, recruitment of inflammatory cells, and subsequent structural remodeling, which are hallmarks of vasculitis. The histopathological classification of vasculitis relies on the size of the affected vessel and the predominant type of inflammatory cell involved - neutrophils in acute cases, lymphocytes in chronic conditions, and histiocytes in granulomatous forms. Pathological changes progress in every context, and a single vasculitic pattern can be associated with various systemic conditions. Conversely, a single causative agent may lead to multiple distinct clinical and pathological manifestations of vasculitis. Moreover, many cases of vasculitis have no identifiable cause. A foundational understanding of the normal structure of the cutaneous vascular network is crucial. Similarly, identifying the cellular and molecular participants and their roles in forming the "dermal microvascular unit" is propedeutical.This review aims to elucidate the complex mechanisms involved in the initiation and progression of vasculitis, offering a comprehensive overview of its histopathological classification, underlying causes, and the significant role of the cutaneous vascular network and cellular dynamics. By integrating the latest insights from studies on NETosis and the implications of lymphocytic infiltration in autoimmune diseases, we seek to bridge gaps in current knowledge and highlight areas for future research. Our discussion extends to the clinical implications of vasculitis, emphasizing the importance of identifying etiological agents and understanding the diverse histopathological manifestations to improve diagnostic accuracy and treatment outcomes.

A retrospective clinicopathological study of erythema nodosum.

Erythema nodosum (EN) may be idiopathic or secondary, and usually resolves naturally within 1-2 months. In atypical EN cases, the rash extends beyond the lower limbs to the upper limbs and trunk, and histopathological findings may be accompanied by vasculitis in addition to septal panniculitis. Few studies have examined the differences in the clinical characteristics of patients with EN based on rash distribution. We retrospectively examined whether there was a correlation with clinical information, such as the presence or absence of underlying diseases, by classifying the patients into two groups: the lower limbs group (the EN rash was confined to the lower limbs) and the beyond lower limbs group (the EN rash appeared beyond the lower limbs). Among the 86 adult patients diagnosed with EN at the Dermatology Department of Fujita Medical University between 2015 and 2020, there were 65 cases of the lower limbs group and 21 cases of the beyond lower limbs group. The frequency of underlying diseases was significantly higher in the beyond lower limbs group (76.2%, 16 cases) than in the lower limbs group (40.0%, 26 cases; P < 0.005). Vasculitis was more notable in the beyond lower limbs group (P < 0.05). Significantly higher vasculitis was noted in the EN group with underlying diseases (30.2%, 13 cases) than in the idiopathic EN group without underlying diseases (11.6%, 5 cases; P < 0.05). Neutrophil extracellular traps were positive in approximately 40% of cases in both groups. In the beyond lower limbs group, the possibility of severe cases with underlying diseases, vasculitis, and inflammation must be considered for effective treatment.

Acute neutrophilic vasculitis (leukocytoclasia) in 36 COVID-19 autopsy brains.

BACKGROUND: Hypercytokinemia, the renin-angiotensin system, hypoxia, immune dysregulation, and vasculopathy with evidence of immune-related damage are implicated in brain morbidity in COVID-19 along with a wide variety of genomic and environmental influences. There is relatively little evidence of direct SARS-CoV-2 brain infection in COVID-19 patients. METHODS: Brain histopathology of 36 consecutive autopsies of patients who were RT-PCR positive for SARS-CoV-2 was studied along with findings from contemporary and pre-pandemic historical control groups. Immunostaining for serum and blood cell proteins and for complement components was employed. Microcirculatory wall complement deposition in the COVID-19 cohort was compared to historical control cases. Comparisons also included other relevant clinicopathological and microcirculatory findings in the COVID-19 cohort and control groups. RESULTS: The COVID-19 cohort and both the contemporary and historical control groups had the same rate of hypertension, diabetes mellitus, and obesity. The COVID-19 cohort had varying amounts of acute neutrophilic vasculitis with leukocytoclasia in the microcirculation of the brain in all cases. Prominent vascular neutrophilic transmural migration was found in several cases and 25 cases had acute perivasculitis. Paravascular microhemorrhages and petechial hemorrhages (small brain parenchymal hemorrhages) had a slight tendency to be more numerous in cohort cases that displayed less acute neutrophilic vasculitis. Tissue burden of acute neutrophilic vasculitis with leukocytoclasia was the same in control cases as a group, while it was significantly higher in COVID-19 cases. Both the tissue burden of acute neutrophilic vasculitis and the activation of complement components, including membrane attack complex, were significantly higher in microcirculatory channels in COVID-19 cohort brains than in historical controls. CONCLUSIONS: Acute neutrophilic vasculitis with leukocytoclasia, acute perivasculitis, and associated paravascular blood extravasation into brain parenchyma constitute the first phase of an immune-related, acute small-vessel inflammatory condition often termed type 3 hypersensitivity vasculitis or leukocytoclastic vasculitis. There is a higher tissue burden of acute neutrophilic vasculitis and an increased level of activated complement components in microcirculatory walls in COVID-19 cases than in pre-pandemic control cases. These findings are consistent with a more extensive small-vessel immune-related vasculitis in COVID-19 cases than in control cases. The pathway(s) and mechanism for these findings are speculative.

Immunohistochemical analysis of myeloperoxidase expression in cutaneous leucocytoclastic vasculitis.

Myeloperoxidase (MPO) is a pro-oxidant enzyme mainly found in the azurophilic granules of neutrophils. It not only displays a key role in the intracellular microbial killing process but also contributes to the extracellular clearance of several pathogens. This study aimed to detect MPO in cutaneous leukocytoclastic vasculitis (LCV) using immunohistochemistry. We retrospectively collected 22 confirmed cases of skin LCV diagnosed in our pathology department over 11 years (2012-2023). Immunohistochemistry was performed using anti-myeloperoxidase antibody (Leica clone 59A5) on the LeicaBond MAX automated system, following manufacturer's instructions. Two pathologists assessed immunohistochemical staining, scoring intensity as weak (+), moderate (++), or strong (+++). Patients' mean age was 56.9 years, with a male-to-female ratio of 1.18. Pathologically, vasculitis involved small blood vessels in all cases. Immunohistochemical analysis showed granular positive MPO staining in 59.1% of cases. Staining intensity was weak in 46.15%, moderate in 46.15%, and strong in 7.69%. Staining was patchy in 84.62% and diffuse in 15.38% of cases. MPO expression, detected in 59.1% of cutaneous LCV tissues, exhibited a patchy and peri-vascular distribution. It holds potential as a diagnostic marker for patients with early or minor histological changes.

Lymphocytic vasculitis in livedoid vasculopathy: A report of 137 cases.

BACKGROUND: Livedoid vasculopathy (LV) is characterized by fibrin deposition and thrombosis in the small vessels of the superficial dermis. It is widely recognized as an occlusive disease, which is primarily treated with anticoagulation therapy. METHODS: We retrospectively analyzed the clinical and histopathological characteristics of patients diagnosed with LV at a tertiary dermatology department to explore the characteristics of lymphocytic vasculitis in LV. The frequency of vasculitis and the types of vessels involved were examined based on the diameters and elastic fiber distribution of the involved vessels. In addition, the immunophenotypes of infiltrating lymphocytes were analyzed. RESULTS: In a large retrospective series including 358 LV cases, we identified 137 (38.3%) cases of lymphocytic vasculitis. Among them, 48 cases involved medium-sized vessels, including arterioles and venules, whereas 89 cases involved only small vessels. In addition, 12 cases displayed a segmental distribution of vasculitis. The infiltrating lymphocytes were mainly T cells, with dominant cells stained positive for CD4. CONCLUSIONS: Lymphocytic vasculitis forms part of the histological spectrum of LV, affecting both medium-sized and small vessels. It is possible that the occlusion of small vessels may represent a phenomenon secondary to lymphocytic vasculitis.

Pseudoxanthoma elasticum veiled as vasculitis: shedding light on an uncommon disorder and an in-depth review of the literature.

Pseudoxanthoma Elasticum (PXE) is a rare genetic disorder caused by an autosomal recessive mutation in the ABCC6 gene. It manifests with distinctive clinical symptoms impacting the skin, eyes, and cardiovascular system, along with an elevated risk of cardiovascular diseases. We present a case of a 34-year-old male patient who was initially referred to the rheumatology clinic for evaluation due to suspected large vessel vasculitis. The patient's primary complaint was severe hemifacial pain radiating to the neck and upper limb. Radiological imaging studies unveiled substantial vascular narrowing and collateral vessel formation, prompting further investigation to exclude systemic vasculitis. Intriguingly, the patient also exhibited cutaneous manifestations, which were later confirmed via skin biopsy as consistent with PXE. An ophthalmological examination further revealed the presence of the classic PXE findings of angioid streaks. Given the rarity of PXE and its multifaceted clinical presentation, it can be particularly challenging to diagnose and manage. As such, cases like the one presented here may necessitate a referral to a rheumatologist for evaluation of potential systemic involvement. To provide a comprehensive perspective on PXE, we conducted a systematic review of case reports published in the past decade in English, collected from PubMed, Scopus, and the Directory of Open Access databases. The analysis of these cases will be discussed to shed light on the diversity of PXE's clinical features and the diagnostic and management dilemmas it poses and to facilitate ongoing exploration and research into this intricate condition, ultimately leading to improved care for individuals affected by PXE.

Granuloma, vasculitis, and demyelination in sarcoid neuropathy.

BACKGROUND: Despite the suggestion that direct compression by granuloma and ischemia resulting from vasculitis can cause nerve fiber damage, the mechanisms underlying sarcoid neuropathy have not yet been fully clarified. METHODS: We examined the clinicopathological features of sarcoid neuropathy by focusing on electrophysiological and histopathological findings of sural nerve biopsy specimens. We included 18 patients with sarcoid neuropathy who had non-caseating epithelioid cell granuloma in their sural nerve biopsy specimens. RESULTS: Although electrophysiological findings suggestive of axonal neuropathy were observed, particularly in the lower limbs, all but three patients showed ≥1 abnormalities in nerve conduction velocity or distal motor latency. Additionally, a conduction block was observed in 11 of the 16 patients for whom waveforms were assessed; five of them fulfilled motor nerve conduction criteria strongly supportive of demyelination as defined in the European Academy of Neurology/Peripheral Nerve Society (EAN/PNS) guideline for chronic inflammatory demyelinating polyneuropathy (CIDP). In most patients, sural nerve biopsy specimens revealed a mild to moderate degree of myelinated fiber loss. Fibrinoid necrosis was observed in one patient, and electron microscopy analysis revealed demyelinated axons close to granulomas in six patients. CONCLUSIONS: Patients with sarcoid neuropathy may meet the EAN/PNS electrophysiological criteria for CIDP due to the frequent presence of conduction blocks. Based on our results, in addition to the ischemic damage resulting from granulomatous inflammation, demyelination may play an important role in the mechanism underlying sarcoid neuropathy.

Spectrum of renal vascular lesions among patients with lupus nephritis: An experience from a tertiary care center.

Background: Lupus nephritis (LN) is the assemblage of glomerular, tubulointerstitial and vascular changes. Despite the fact that glomerular changes are overemphasized in pathological classification and scoring system, but the existence of vascular damage negatively impact the clinical course. Aims and Objective: This study was conducted to determine the clinicopathological spectrum of renal vascular lesions in lupus nephritis. Materials and Methods: Renal microvascular lesions in biopsy proven lupus nephritis were classified into 5 major categories-thrombotic microangiopathy, true vasculitis; lupus vasculopathy, uncomplicated vascular immune deposits, and arterial. Clinical details, laboratory parameters and histopathological variables were compared among all groups. Summary of chronic changes was also assessed. Results: Biopsies from 56 patients revealed thrombotic microangiopathy (2), lupus vasculopathy (3), uncomplicated vascular immune deposit (6), PAN type vasculitis (1) and arterial sclerosis (13). No renal vascular lesions were found in 35.18% of patients. At the time of biopsy, arterial sclerosis or lupus vasculopathy patients were older Nephritis subtype. Activity indices were higher in lupus vasculopathy group whereas patients with arteriosclerosis showed highest chronicity index. Conclusions: Renal vascular lesions are common in systemic lupus erythematosus patients with nephritis and may be associated with aggressive clinical course.

[Vasculitis as a cause of stroke]. / Vaskulity kak prichina insul'ta.

The review considers the clinical picture, key aspects of the diagnosis and treatment of vasculitis that are the causes of strokes (giant cell arteritis, polyarteritis nodosa, varicella zoster virus vasculopathy, cerebrovascular pathology caused by herpes simplex virus types 1 and 2, primary CNS angiitis, adenosine deaminase-2 deficiency).

Treatment Strategies in Neutrophilic Dermatoses: A Comprehensive Review.

Neutrophilic dermatoses (NDs) are a group of noninfectious disorders characterized by the presence of a sterile neutrophilic infiltrate without vasculitis histopathology. Their physiopathology is not fully understood. The association between neutrophilic dermatoses and autoinflammatory diseases has led some authors to propose that both are part of the same spectrum of diseases. The classification of NDs depends on clinical and histopathological features. This review focuses on the recent developments of treatments in these pathologies.

Glomerular Diseases Across Lifespan: Key Differences in Diagnostic and Therapeutic Approaches.

Glomerular diseases are common causes of chronic kidney disease in childhood, adolescence, and adulthood. The epidemiology of glomerular diseases differs between different age groups, with minimal change disease being the leading cause of nephrotic syndrome in childhood, while membranous nephropathy and focal segmental glomerulosclerosis are more common in adulthood. IgA vasculitis is also more common in childhood. Moreover, there is a difference in disease severity with more children presenting with a relapsing form of nephrotic syndrome and a more acute presentation of antineutrophil cytoplasmic antibody-associated vasculitis and concomitant glomerulonephritis, as highlighted by the higher percentage of cellular crescents on kidney biopsy specimens in comparison with older patients. There is also a female preponderance in antineutrophil cytoplasmic antibody-associated vasculitis and more children present with tracheobroncholaryngeal disease. This article aims to summarize differences in the presentation of different glomerular diseases that are encountered commonly by pediatric and adult nephrologists and potential differences in the management.

A Rare Case of Infliximab-Induced Small Vessel Vasculitis With Renal Involvement.

There are few cases in the literature demonstrating vasculitis induced by tumor necrosis factor-α. There exist even fewer cases of systemic inflammation involving the skin, nerves, and kidneys. Here, we present a novel case of a 27-year-old man with Crohn disease refractory to multiple medications, most recently treated with infliximab. He presented with a 3-week history of non-blanching palpable petechial rash involving his bilateral extremities and right upper extremity as well as lesions with black eschar around his ankles. He was found to have refractory cutaneous small vessel vasculitis, nephrotic range proteinuria, and small fiber neuropathy. This case describes the evaluation and treatment of systemic small vessel vasculitis in the setting of infliximab therapy.

Perivascular Cuffing as the Sole Imaging Finding of Pancreatic Cancer.

BACKGROUND: Perivascular cuffing as the sole imaging manifestation of pancreatic ductal adenocarcinoma (PDAC) is an under-recognized entity. OBJECTIVES: To present this rare finding and differentiate it from retroperitoneal fibrosis and vasculitis. METHODS: Patients with abdominal vasculature cuffing were retrospectively collected (January 2011 to September 2017). We evaluated vessels involved, wall thickness, length of involvement and extra-vascular manifestations. RESULTS: Fourteen patients with perivascular cuffing were retrieved: three with celiac and superior mesenteric artery (SMA) perivascular cuffing as the only manifestation of surgically proven PDAC, seven with abdominal vasculitis, and four with retroperitoneal fibrosis. PDAC patients exhibited perivascular cuffing of either or both celiac and SMA (3/3). Vasculitis patients showed aortitis with or without iliac or SMA cuffing (3/7) or cuffing of either or both celiac and SMA (4/7). Retroperitoneal fibrosis involved the aorta (4/4), common iliac (4/4), and renal arteries (2/4). Hydronephrosis was present in 3/4 of retroperitoneal fibrosis patients. PDAC and vasculitis demonstrated reduced wall thickness in comparison to retroperitoneal fibrosis (PDAC: 1.0 ± 0.2 cm, vasculitis: 1.2 ± 0.5 cm, retroperitoneal fibrosis: 2.4 ± 0.4 cm; P = 0.002). There was no significant difference in length of vascular involvement (PDAC: 6.3 ± 2.1 cm, vasculitis: 7.1 ± 2.6 cm, retroperitoneal fibrosis: 8.7 ± 0.5 cm). CONCLUSIONS: Celiac and SMA perivascular cuffing can be the sole finding in PDAC and may be indistinguishable from vasculitis. This entity may differ from retroperitoneal fibrosis as it spares the aorta, iliac, and renal arteries and demonstrates thinner walls and no hydronephrosis.