Mycophenolate mofetil as induction and maintenance immunosuppressive therapy in adult primary central nervous system vasculitis: A prospective observational study.

To observe the clinical and angiographic effectiveness of mycophenolate mofetil (MMF) as induction and maintenance immunosuppressive therapy in primary central nervous system vasculitis (PCNSV). In this open-label prospective study done at a tertiary care neurology centre, adult patients with PCNSV, diagnosed by Calabrese's criteria, were recruited from 2017 to 2021 and treated with glucocorticoids, MMF and standard of care. Patients were followed-up and clinical and angiographic changes were recorded. Total 26 patients were recruited with median age 39 years (34-49) with a slight female predilection (61.5%). Angiographic diagnoses were: small vessels disease 11.5%; large vessels disease 42.3% and both in 46.2%. Median duration of follow-up was 24.5 months (14.25-38). Proportion of patients with severe disability (modified Rankin Score (mRS) 4-6) at baseline was 73.08% (19/26) which reduced to 7.69% (2/26) (p < 0.001). At the last follow-up mRS = 0 was achieved in 38.5% (10/26) and mRS of ≤ 1 was achieved in 69.2% (18/26). Median time to achieve a mRS ≤ 1 was 12 months (95% CI: 6.8-17.2). Angiography was repeated in 16 patients after a median duration of 13 months (10.5-19.7), out of which 10 (62.5%) showed improvement and 5 (31.2%) showed non-progression of lesions. MMF may be an effective immunosuppressive therapy in adult PCNSV as both induction and maintenance. Serial DSA of brain may be useful to monitor the effect of treatment. Key Points • Mycophenolate mofetil is effective as induction and maintenance immunosuppressive therapy in PCNSV. • Repeat angiogram may be useful to monitor treatment response in PCNSV.

Immune checkpoint inhibitors associated granulomatous small vessel vasculitis accompanied with tubulointerstitial nephritis: a case report.

BACKGROUND: Immune checkpoint inhibitors (ICIs) have provided significant benefits in cancer treatment, but they could develop immune-related adverse events (irAE). ICI-associated renal adverse effects are rare and tubulointerstitial nephritis (TIN) is the most common in the renal irAE. However, only a few case reports of renal vasculitis associated with ICI have been reported. In addition, the characteristics of infiltrating inflammatory cells of ICI-associated TIN and renal vasculitis have been uncertain. CASE PRESENTATION: A 65-year-old man received immune checkpoint inhibitors (ICIs), anti-CTLA-4 (cytotoxic T-lymphocyte-associated protein 4) and anti-PD-1 (programmed cell death 1) antibodies for aggravated metastatic malignant melanoma. About 1 week after the second administration of nivolumab and ipilimumab, acute kidney injury developed. A renal biopsy was performed that showed TIN and non-necrotizing granulomatous vasculitis in interlobular arteries. Massive CD3+ T cells and CD163+ macrophages infiltrated both tubulointerstitium and interlobular arteries. Many infiltrating cells tested positive for Ki-67 and PD-1 ligand (PD-L1), but negative for PD-1. In CD3+ T cells, CD8+ T cells were predominantly infiltrated, and these cells were positive for Granzyme B (GrB) and cytotoxic granule TIA-1, but negative for CD25, indicating antigen-independent activated CD8+ T cells. Infiltration of CD4+ T cells was noted without obvious CD4+ CD25+ regulatory T (Treg) cells. His renal dysfunction recovered within 2 months of treatment with prednisolone in addition to discontinuation of nivolumab and ipilimumab. CONCLUSIONS: We herein reported a case of ICI-related TIN and renal granulomatous vasculitis with infiltration of massive antigen-independent activated CD8+ T cells and CD163+ macrophages, and none or few CD4+ CD25+ Treg cells. These infiltrating cells might be a characteristic of the development of renal irAE.

Cerebral vasculitis associated with drug abuse.

PURPOSE OF REVIEW: To review understand the epidemiology, background, neuropharmacology, and histopathology of literature verified cases, and likely etiopathogenic mechanisms. RECENT FINDINGS: There are only a handful of histologically confirmed patients in the literature with cerebral vasculitis because of drug abuse. SUMMARY: There is little justification for invasive laboratory investigation given the ready availability of highly accurate vascular neuroimaging techniques to dictate management, which usually rests upon avoidance of further exposure and minimizing the secondary neurotoxic effects of the abused substances and polypharmacy use.

Dapsone-induced DRESS after infliximab-induced vasculitis: a case of cerebral infarction in the context of multiple drug reactions.

Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a life-threatening condition characterised by peripheral eosinophilia, rash and multi-organ failure arising several weeks after exposure to the culprit medication. Although rare, DRESS syndrome triggered by specific agents has been associated with specific genetic polymorphisms more prevalent in different ethnic groups, including an association between dapsone-induced DRESS and Human Leukocyte Antigen (HLA)-B:13*01, a single nucleotide polymorphism more prevalent in those of Asian descent. DRESS and drug-related vasculitis may affect any organ system including the central nervous system (CNS), usually manifesting as encephalitis, meningitis or embolic cerebrovascular accidents related to eosinophilic cardiac disease and thrombosis. CNS vasculitis is a much rarer complication of drug reactions that may manifest as multifocal ischemia on neuroimaging. In circumstances of drug-related vasculitides, treatment with high-dose corticosteroids may lead to rapid improvement and, ultimately, resolution of associated focal neurologic deficits.

Alemtuzumab-related eosinophilic central nervous system vasculitis.

A 36-year-old woman with relapsing remitting multiple sclerosis (MS) presented with right-sided spasms, focal seizures and neuropsychiatric symptoms 10 months after her first course of alemtuzumab. Magnetic resonance imaging (MRI) brain imaging revealed multiple foci of T2 hyperintensity. Subsequent blood and cerebrospinal fluid (CSF) testing for progressive multifocal leukoencephalopathy (PML), vasculitis and infective causes was negative. A brain biopsy was performed, revealing a prominent perivascular inflammatory infiltrate with multiple immune cells including eosinophils, suggesting eosinophilic vasculitis. The patient was treated successfully with cyclophosphamide. The potential sequelae of alemtuzumab treatment are discussed; this treatable complication should be considered when tests for JC virus are negative.

Interstitial granulomatous dermatitis and granulomatous arteritis in the setting of PD-1 inhibitor therapy for metastatic melanoma.

Checkpoint inhibition has become an important target in the management of malignant melanoma. As anti-CTLA4 inhibitors and anti-PD1 antibodies are increasingly utilized, reports of immune-related adverse events (IRAEs) are becoming more frequent. Common noted cutaneous IRAEs are morbilliform, lichenoid, bullous, granulomatous, psoriasiform, and eczematous eruptions. We report a case of interstitial granulomatous dermatitis and granulomatous arteritis in the setting of nivolumab (anti-PD1) monotherapy for metastatic melanoma. There are many different causes for granulomatous vasculitis, such as herpes virus infection, lymphoproliferative disorders, systemic vasculitis, and inflammatory bowel disease. This report adds to the growing literature on granulomatous IRAEs due to checkpoint inhibition.

Ipilimumab-induced renal granulomatous arteritis: a case report.

BACKGROUND: Immune Checkpoint Inhibitors (ICPIs) are promising new drugs in treatment of advanced tumours targeting cytotoxic T-lymphocyte antigen-4 (CTLA-4) and programmed cell death protein-1 (PD1) or its ligand (PDL-1). Ipilimumab is a monoclonal antibody targeting the CTLA-4 receptor used in treatment of metastatic melanoma. By increasing activity of the immune system, ICPIs lead to immune-related adverse events, such as dermatitis, colitis or hepatitis. ICPIs-related kidney adverse events are rare and acute tubulointerstitial nephritis with or without granuloma have mainly been reported. CASE PRESENTATION: We report a case of acute kidney injury in a patient with melanoma treated by ipilimumab. Kidney biopsy revealed acute interlobular and juxtaglomerular granulomatous arteritis, which has not yet been reported in patients treated by ICPIs. Kidney function partially recovered after ipilimumab discontinuation and oral prednisone. Unfortunately, the patient died a few months later from progression of his melanoma. CONCLUSION: This case highlights a new mechanism of acute kidney injury related to ICPIs and supports the interest of kidney biopsy in case of ICPIs related acute renal failure.

Central Nervous System Vasculitis Due to Substance Abuse.

Illicit drug abuse is a common differential diagnosis of acquired central nervous system vasculitis even though there are only a handful of histopathologically confirmed patients in the literature from among the many potential classes of abused drugs traditionally implicated in this disease. This article considers the major classes of illicit drugs in those with and without human immunodeficiency virus type-1 infection and acquired immune deficiency syndrome.

The first case of bacillus Calmette-Guérin-induced small-vessel central nervous system vasculitis.

To present an unrecognized vascular complication of bacillus Calmette-Guérin (BCG) therapy administered for superficial bladder carcinoma. We also review the potential mimickers for primary angiitis of the central nervous system (PACNS) as well as complications of intravesical BCG therapy. An 89-year-old Caucasian man with a history of relapsing high-grade bladder carcinoma treated with intravesical BCG presented with recurring episodes of right upper limb paresthesia with clumsiness and dysarthria. Magnetic resonance imaging of the head revealed multiple predominantly left-sided frontotemporal micronodular peri-vascular lesions. Left frontal lobe biopsy showed non-necrotizing granulomatous vasculitis. Ziehl staining was negative. Initially, he was treated for PACNS but his symptoms relapsed during every attempt to taper the corticosteroids. Six months later, he developed bilateral mycobacterial endophthalmitis, caused by Mycobacterium bovis. Brain biopsy was reviewed and confirmed the presence of perivascular mycobacteria. A retrospective diagnosis of BCG-induced central nervous system vasculitis was made and he was treated with high-dose corticosteroids, moxifloxacin, isoniazid, ethambutol, and rifampicin. BCG is a live attenuated form of Mycobacterium bovis widely used as tuberculosis vaccination and intravesical therapy for superficial forms of bladder cancer. Systemic complications affect roughly 5% of patients and can manifest months or years after the last instillation. Cases of endophthalmitis, meningitis, aortitis, or mycotic aneurysms have been described, but no reports of CNS vasculitis have been found. In disseminated forms of BCG infections, referred to as BCGitis, histopathology usually reveals granulomatous inflammation. Mycobacterial cultures are often negative, making this a diagnostic challenge. This is the first documented case of BCG-induced small-vessel CNS vasculitis. Mycobacterium bovis infection is rare and findings are often nonspecific, making the diagnosis very difficult. Other infectious and non-infectious causes must be ruled out appropriately before considering this entity.

Cerebral vasculitis mimicking intracranial metastatic progression of lung cancer during PD-1 blockade.

BACKGROUND: Stimulation of the immune system by targeting the PD-1/PD-L1 pathway can result in activation of anti-tumor immunity. Besides its clinical benefit immune checkpoint therapy leads to significant immune-related adverse events (irAEs). Some rare irAEs are not well described yet but are critical in patient management. CASE PRESENTATION: Here, we describe a case of autoimmune cerebral vasculitis/encephalitis after PD-1 inhibitor treatment for metastatic adenocarcinoma of the lung. Upon PD-1 blockade, the patient developed cerebral lesions, while having disease stabilization of extracranial metastases. Imaging suggested that the patient had new progressing brain metastases. Despite stereotactic irradiation the lesions progressed further. The largest lesion became symptomatic and had to be surgically resected. On examination, cerebral vasculitis was detected but not evidence of metastatic lung cancer. Analysis of the patient's serum revealed the presence of antinuclear antibodies that were already present before starting PD-1 blockade. In addition, we also found anti-vascular endothelial antibodies in the serum. CONCLUSION: This finding suggests that the patient had preformed autoantibodies and the checkpoint inhibitor induced a clinically relevant autoimmune disease. Taken together, encephalitic lesions in patients under PD-1/PD-L1 blockade can mimic metastatic brain lesions and this rare irAE has to be considered as a differential diagnosis in patients treated with immunotherapy.

Minocycline-induced polyarteritis nodosa-like vasculitis presenting as brainstem stroke.

Minocycline use has been associated with the development of autoimmune disorders, including drug-induced vasculitis. Previously published reports suggest that clinical manifestations are limited to cutaneous, constitutional, or musculoskeletal symptoms. To our knowledge there has been only one reported patient with ischemic stroke in the setting of minocycline-induced vasculitis. We describe a 26-year-old woman, with no vascular risk factors, who had an ischemic pontine stroke in the setting of biopsy-proven minocycline-induced polyarteritis nodosa-like vasculitis. Discontinuation of minocycline resulted in resolution of the vasculitis, and she has not had any recurrent ischemic events. This report shows that ischemic strokes may occur as a result of minocycline-induced vasculitis. While this is likely a rare association, recognition is important given the widespread use of minocycline and the potential for devastating consequences in a young population. Consequently, drug-induced vasculitis should be considered in patients with an ischemic stroke taking minocycline.

Vessel wall MRI to differentiate between reversible cerebral vasoconstriction syndrome and central nervous system vasculitis: preliminary results.

BACKGROUND AND PURPOSE: Prospective differentiation between reversible cerebral vasoconstriction syndrome and central nervous system vasculitis can be challenging. We hypothesized that high-resolution vessel wall MRI would demonstrate arterial wall enhancement in central nervous system vasculitis but not in reversible cerebral vasoconstriction syndrome. METHODS: We identified all patients with multifocal segmental narrowing of large intracranial arteries who had high-resolution vessel wall MRI and follow-up angiography at our institute over a 4-year period and performed a detailed chart review. RESULTS: Three patients lacked arterial wall enhancement, and these all had reversal of arterial narrowing within 3 months. Four patients demonstrated arterial wall enhancement, and these had persistent or progressive arterial narrowing at a median follow-up of 17 months (range, 6-36 months) with final diagnoses of central nervous system vasculitis (3) and cocaine vasculopathy (1). CONCLUSIONS: Preliminary results suggest that high-resolution contrast-enhanced vessel wall MRI may enable differentiation between reversible cerebral vasoconstriction syndrome and central nervous system vasculitis.

Adalimumab-induced lupus erythematosus with central nervous system involvement in a patient with Crohn's disease.

The anti-tumor necrosis factor (TNF) agents are drugs that in recent years turned out to be a mainstay of therapy for the treatment of inflammatory bowel disease. Nevertheless, they have several adverse effects such as infectious complications and immunogenicity. One of the most common immunogenic effects is the development of autoantibodies, mainly anti-nuclear antibodies and anti-double-stranded DNA antibodies, only rarely associated with overt clinical manifestations of systemic lupus erythematosus. Adalimumab is a fully humanized monoclonal antibody widely used for the treatment of Crohn's disease and supposed to have less immunogenic activity and a safer profile than other anti-TNF agents. The occurrence of systemic lupus erythematosus with involvement of the central nervous system appears to be a very rare complication of such drugs, and no cases have been reported in the medical literature in patients treated with adalimumab. We report a case of a 53 years-old woman with ileo-colic Crohn's disease where the treatment with adalimumab was complicated by systemic lupus erythematosus with central nervous system vasculitis.

[Cerebral vasculitis associated with gemcitabine]. / Zerebrale Vaskulitis unter Gemcitabin.

Neoadjuvant chemotherapy consisting of cisplatin and gemcitabine was given to a 50-year-old woman suffering from transitional cell carcinoma of the bladder. Whereas the first cycle was administered without major side effects, the patient experienced a generalized tonic-clonic seizure and a prolonged cognitive deficit with the second cycle. Magnetic resonance imaging of the brain was consistent with cerebral vasculitis. The short interval between the application of gemcitabine and the neurological deterioration suggests a causal relationship. Although recent reports have linked this drug with leukoencephalopathy and vasculitis in various localizations, this is the first case of cerebral vasculitis associated with gemcitabine.

[Case of intracerebral hemorrhage due to amphetamine abuse].

We report a case of intracranial hemorrhage due to amphetamine abuse in a young adult. A 34-year-old, confused woman was transferred to our emergency room with right hemiparesis and aphasia. CT at admission demonstrated intracerebral hemorrhage in the left frontal and parietal lobes, associated with subarachnoid hemorrhage. MRA shortly after admission revealed no intracerebral vascular anomaly. Cerebral angiography following admission showed irregularity of the vessel wall in the left anterior and middle cerebral arteries. Later, a toxicology screen test for urine was found to be positive for amphetamines and metamphetamines. These findings suggested that cerebral vasculitis and hypertensive surge induced by amphetamines caused intracranial and subarachnoid hemorrhage. Amphetamine abuse should always be considered as a cause of intracranial hemorrhage in young adults.

BOLD-MRI cerebrovascular reactivity findings in cocaine-induced cerebral vasculitis.

BACKGROUND: An 18-year-old woman presented to a regional stroke center with dysphasia and right hemiparesis 2 days after consuming alcohol and inhaling cannabis and -- for the first time -- cocaine. INVESTIGATIONS: Physical examination, blood tests for inflammatory markers, vasculitis and toxicology screen, echocardiography, electrocardiography, CT scanning, brain MRI, magnetic resonance angiography, magnetic resonance vessel wall imaging, catheter angiography, and correlation of blood oxygen level-dependent (BOLD)-MRI signal intensity with changes in end-tidal partial pressure of carbon dioxide. DIAGNOSIS: Cocaine-induced cerebral vasculitis. MANAGEMENT: No specific therapy was initiated. The patient's vital signs and neurological status were monitored during her admission. Follow-up medical imaging was performed after the patient's discharge from hospital.