Pulmonary arterial hypertension in ANCA-associated vasculitis

BACKGROUND AND AIM OF THE WORK: Pulmonary arterial hypertension (PAH) is a severe condition characterized by chronic obstruction of small pulmonary arteries leading to progressive right heart failure and ultimately death. Inflammatory mechanisms may play an important part in the origin or progression of the disease in a subset of patients. Whereas PAH is well known complication of some connective tissue diseases, it is a rare condition associated with systemic vasculitis. In the present report, we describe 4 cases of anti-neutrophil cytoplasmic antibodies (ANCA)-related systemic vasculitis (3 with Wegener's granulomatosis and 1 with microscopic polyangiitis) associated with PAH. METHODS: We describe the clinical features of both ANCA-associated systemic vasculitis and PAH. RESULTS: PAH was diagnosed after the onset of the systemic vasculitis in 3 cases. In 1 case, the systemic vasculitis was active at the diagnosis of PAH and treatment of the vasculitis led to a significant improvement of PAH. In the 2 other patients, PAH occurred while the vasculitis was inactive. The remaining patient, for whom Wegener's granulomatosis was diagnosed 2 years after PAH was documented, died because of a vasculitis treatment-related side effect. CONCLUSIONS: Systemic vasculitides have to be added to the conditions associated with PAH. The underlying pathophysiological mechanisms of this association have still to be firmly established. It is probable that some PAH are due, at least in part, to direct pulmonary arteries involvement by the vasculitic process.     

Vasculitic condition following instillation of epirubicin hydrochloride in an outpatient chemotherapy

The appearance of vasculitis is often observed following the use of epirubicin hydrochloride in outpatients. As it is important to continue to provide a safe treatment for outpatient with little or no side effects, the aim of this study was to reveal causes underlying the outbreak of vasculitis or the vasculitic state of patients who had undergone instillation of epirubicin hydrochloride as an adjuvant therapy following a breast cancer surgery. The study was conducted based on past investigation records. We extracted relevant factors such as age, previous illness, physical condition and dosage of epirubicin hydrochloride from past records which may all be connected to the outbreak of vasculitis. We administered one dose of epirubicin hydrochloride that was diluted into 50-100 ml of normal saline solution or 5% glucose and instilled over a period of 30 minutes. As a result of this instillation of epirubicin hydrochloride, 35 out of 45 cases displayed vasculitis. We did not observe any relationship among the aged (over 60), previous illness or physical condition (BMI over 25) and the appearance of vasculitis. When a dosage amount of more than 110 mg of epirubicin hydrochloride was administered, 23 out of 29 cases displayed vasculitis. From the past records, it was observed that the cause of vasculitis was dependent on the administrative method itself. As previous studies reported that vasculitis was low when epirubicin hydrochloride was retained in blood vessels for only a short time, our study, however, concentrated on how to administer epirubicin hydrochloride. Our results suggested that an adoption of a single dosage system may suppress the outbreak of vasculitis.     

Vasculitis and Leukemia

Vasculitis may accompany neoplasias and be of paraneoplastic type or associated with drugs used in patient treatment. We evaluated skin biopsies of twenty-eight cases with vasculitis accompanying leukemias reviewed and clinical outcome was evaluated. Eleven of the 28 cases had paraneoplastic vasculitis and 17 had vasculitis associated with various drugs including chemotherapy, cytokines and antibacterial agents. Paraneoplastic vasculitis was seen in 3 cases with chronic myelocytic leukemia in blastic phase, 5 patients with acute myeloblasts leukemia, and 3 with myelodysplastic syndrome. Drugs responsible for the 17 cases of vasculitis included hydroxyurea, vincristine, cytosine-arabinoside, methotrexate, all-trans retinoic acid, granulocyte-colony stimulating factor, interferon and antibiotics.

Paraneoplastic vasculitis is not rare in leukemias and may be a manifestation of the blastic phase of chronic myeloid leukemia. Furthermore paraneoplastic vasculitis can be fatal in myelodysplastic syndromes and may be present clinically before the specific diagnosis is made. Drugs used in routine therapy may be the cause of the vasculitis, thus skin biopsy should be performed in all cutaneous lesions in patients with hemopoietic neoplasias.     

Vasculitis and leukemia.

Vasculitis may accompany neoplasias and be of paraneoplastic type or associated with drugs used in patient treatment. We evaluated skin biopsies of twenty-eight cases with vasculitis accompanying leukemias reviewed and clinical outcome was evaluated. Eleven of the 28 cases had paraneoplastic vasculitis and 17 had vasculitis associated with various drugs including chemotherapy, cytokines and antibacterial agents. Paraneoplastic vasculitis was seen in 3 cases with chronic myelocytic leukemia in blastic phase, 5 patients with acute myeloblastic leukemia, and 3 with myelodysplastic syndrome. Drugs responsible for the 17 cases of vasculitis included hydroxyurea, vincristine, cytosine-arabinoside, methotrexate, all-trans retinoic acid, granulocyte-colony stimulating factor, interferon and antibiotics. Paraneoplastic vasculitis is not rare in leukemias and may be a manifestation of the blastic phase of chronic myeloid leukemia. Furthermore paraneoplastic vasculitis can be fatal in myelodysplastic syndromes and may be present clinically before the specific diagnosis is made. Drugs used in routine therapy may be the cause of the vasculitis, thus skin biopsy should be performed in all cutaneous lesions in patients with hemopoietic neoplasias.     

Renal cell carcinoma and vasculitis: report of two cases

A 63-year-old caucasian male with systemic leukocytoclastic vasculitis involving the skin, lungs, and gastrointestinal tract was found to have a renal cell carcinoma at autopsy. A 77-year-old-woman with a history of hypertension was felt to have temporal arteritis that was confirmed by biopsy. The autopsy revealed a renal cell carcinoma in association with widespread giant cell arteritis. The possible association of renal cell carcinoma with vasculitis and an assessment of the possible clinical usefulness are presented and cases of vasculitis with renal neoplasms are briefly reviewed.     

Stereotactic Radiotherapy in the Treatment of Paraneoplastic Vasculitis in Oligometastatic Renal Cell Carcinoma

Approximately 20% of renal cell carcinoma (RCC) is diagnosed because of paraneoplastic manifestations. RCC has been associated with a large variety of paraneoplastic syndromes (PNS), but it is rarely associated with PNS vasculitis. We present a case of a previously healthy male who presented with systemic vasculitis; bitemporal headaches, diplopia, polyarthritis, palpable purpura, tongue lesion, peri-orbital edema, scleritis, chondritis and constitutional symptoms. He was subsequently found to have oligometastatic RCC. Both his primary lesion and site of oligometastasis were treated with stereotactic radiotherapy (SBRT) and resulted in the resolution of his vasculitis, as well as sustained oncologic response. This is the first case to demonstrate that effective sustained treatment for PNS vasculitis due to oligometastatic RCC is possible with SBRT.     

Capecitabine-induced leukocytoclastic vasculitis under neoadjuvant chemotherapy for locally advanced colorectal cancer

We describe a case of capecitabine-induced leukocytoclastic vasculitis in a patient with locally advanced rectal cancer under curative neoadjuvant concurrent chemoradiation using capecitabine. After 5 days of the initiation of capecitabine the patient developed a pruritic maculopapular rash in her extremities consistent with vasculitis which was confirmed on skin biopsy without any signs of systemic involvement. Capecitabine was held and the rash was treated with topical steroids with complete resolution of both rash and pruritus. Due to a lack of other alternative chemotherapeutic options and the cutaneous-only involvement of vasculitis, the capecitabine was re-introduced. Two days later, the patient developed an identical maculopapular rash with a similar distribution. Prednisone was initiated while the capecitabine was continued with complete resolution of the rash. The patient successfully completed her curative neoadjuvant chemoradiation therapy treatment without the need to permanently discontinue the capecitabine.     

Myelodysplasia, Vasculitis and Anti-Neutrophil Cytoplasm Antibodies

A cutaneous or systemic vasculitis occurs in myelodysplasia as well as in myeloproliferative and lymphoproliferative disorders. The most common lesion is a leucocytoclastic vasculitis, with neurological or joint involvement occurring less often. The vasculitis may appear contemporaneously with or precede the clinical onset of the blood dyscrasia. Occasionally the lesions respond dramatically to the use of steroids but in general, patients with vasculitis have a worse prognosis than those with uncomplicated myelodysplasia. Vasculitis and myelodysplasia appear together too often for the association to be coincidental and the vasculitis in most cases cannot be attributed to intercurrent infections, therapeutic agents or a pre-existing rheumatological disorder. While autoantibodies are frequently present in myelodysplasia, and ANA and anti-neutrophil cytoplasm antibodies (ANCA) are found in other vasculitides, neither of these antibodies is associated with the vasculitis of myelodysplasia. There has however been one report of ANCA in Sweet's syndrome a non-vasculitic skin condition that also occurs in the myelodysplastic syndromes.     

Acute vasculitis after endovascular brachytherapy

PURPOSE: Angioplasty effectively relieves coronary artery stenosis but is often followed by restenosis. Endovascular radiation (beta or gamma) at the time of angioplasty prevents restenosis in a large proportion of vessels in swine (short term) and humans (short and long term). Little information is available about the effects of this radiation exposure beyond the wall of the coronary arteries. METHODS AND MATERIALS: Samples were obtained from 76 minipigs in the course of several experiments designed to evaluate endovascular brachytherapy: 76 of 114 coronary arteries and 6 of 12 iliac arteries were exposed to endovascular radiation from 32P sources (35 Gy at 0.5 mm from the intima). Two-thirds of the vessels had angioplasty or stenting. The vessels were systematically examined either at 28 days or at 6 months after radiation. RESULTS: We found an unexpected lesion: acute necrotizing vasculitis in arterioles located < or =2.05 mm from the target artery. It was characterized by fibrinoid necrosis of the wall, often associated with lymphocytic exudates or thrombosis. Based on the review of perpendicular sections of tissue samples, the arterioles had received between 6 and 40 Gy. This arteriolar vasculitis occurred at 28 days in samples from 51% of irradiated coronary arteries and 100% of irradiated iliac arteries. By 6 months, the incidence of acute vasculitis decreased to 24% around the coronary arteries. However, at that time, healing vasculitis was evident, often with luminal narrowing, in 46% of samples. Vasculitis was not seen in any of 44 samples from unirradiated vessels (0%) and had no relation to angioplasty, stenting, or their sequelae. This radiation-associated vasculitis in the swine resembles the localized lymphocytic vasculitis that we have reported in tissues of humans exposed to external radiation. On the other hand, it is quite different from the various types of systemic vasculitis that occur in nonirradiated humans. CONCLUSION: Endoarterial brachytherapy using 32P results in vascular effects beyond the adventitia of the target vessel. This necrotizing vasculitis is causally related to radiation, but its mechanism is unclear and a dose effect is not evident. Quite possibly, local upregulation of inflammatory cytokines contributes to this radiation-associated vasculitis, which only involved some of the arterioles in each sample. It is likely that radiation-associated vasculitis also occurs around human coronary arteries and may result in foci of ischemia. To our knowledge, this lesion has not been previously recognized, either in experimental models or in human specimens examined after angioplasty/brachytherapy.     

Cerebral vasculitis associated with hairy cell leukemia

Hairy cell leukemia was diagnosed in a 74-year-old man. He was followed for 5 years when he developed confusion and focal neurological signs. Despite investigation and treatment he died. Postmortem study revealed isolated primary necrotizing vasculitis affecting the cerebral arteries. No leukemic infiltration of the central nervous system was found. There is a recognized association between hairy cell leukemia and generalized necrotizing vasculitis of polyarteritis type, however, this is the first case report of isolated cerebral vasculitis associated with this condition. The importance of excluding infective (mycotic) arteries in this type of case is emphasized.     

Surgical treatment of livedo vasculitis

Surgical treatment for livedo vasculitis as a primary approach is not mentioned in the literature. A young female patient suffering from livedo vasculitis (atrophie blanche) was admitted with huge ulcerations and pre-ulcerative, infarcted skin areas of both feet and ankles. The lesions were promptly excised and skin grafted with excellent results. The course of treatment, including several surgical procedures, is described.     

Leukocytoclastic vasculitis and acute renal failure after influenza vaccination in an elderly patient with myelodysplastic syndrome

BACKGROUND: Influenza vaccination is recommended for individuals over 65 years of age and for all patients with chronic diseases who are at risk. Side effects which are seen in 1-10% of the vaccinated individuals are usually mild and consist of local reactions and constitutional symptoms. Since 1974, about 30 cases of vasculitis following influenza vaccination have been reported. CASE REPORT: We here describe a 70-year-old male patient with a 5-year history of myelodysplastic syndrome, who had received continuous steroid treatment since 2004 and presented with leukocytoclastic vasculitis and acute renal failure requiring hemodialysis therapy 1 week after influenza vaccination. High-dose steroid treatment was promptly initiated, but hemodialysis was needed for 9 days. Maintained steroid treatment for 2 weeks was associated with complete recovery of renal function and skin lesions. CONCLUSION: As influenza vaccination is increasingly used, physicians should be aware of the potential serious side effect of leukocytoclastic vasculitis, particularly in patients who are immunocompromised either due to an underlying disorder or as a treatment-related side effect.     

Leukocytoclastic vasculitis associated with multifocal sensory neuropathy responsive to intravenous immunoglobulins: a case report

Leukocytoclastic vasculitis (LCV) is a common form of small-vessel vasculitis, which commonly presents as palpable purpura or petechiae, caused by deposition of circulating immune complexes on vessels walls that attracts granulocytes which damage the vascular endothelium and leading to erythrocytes extravasation. The skin is the most commonly involved organ, but also renal, gastrointestinal, pulmonary, cardiovascular and neurological systems may be affected. Skin lesions may be the initial signs of systemic vasculitis. Systemic symptoms may be present, such us fever, myalgia, abdominal pain and arthralgia. The presence of neuropathy/mononeuritis multiplex is expression of severe vasculitic involvement. Herein, we describe the case of a patient with leucocytoclastic vasculitis associated to sensitive neuropathy, responsive to intravenous immunoglobulins (IVIg) therapy, after the failure of classic systemic treatments.     

Cyclic lymphocytic vasculitis associated with chronic lymphocytic leukemia

Lymphocytic cutaneous vasculitis associated with a haematological malignancy has rarely been reported. Here, we describe a 61 year-old woman with chronic lymphocytic leukemia (CLL) who presented with cutaneous lesions on both hands. These lesions improved after all combination chemotherapy courses and recurred before each course. Repetitive skin biopsies revealed lymphocytic vasculitis. After 7 courses of chemotherapy, she had a complete remission. Skin lesions disappeared and did not recur. The cyclic pattern of lymphocytic vasculitis and its relation with CLL disease activity are interesting clinical features in this case.     

Recurrent Pancreatic Arteritis and Vasculogenic Relapsing Pancreatitis in Rheumatoid Arthritis – A Retrospective Clinicopathologic and Immunohistochemical Study of 161 Autopsy Patients

The aim of this study was to determine: the prevalence, and histological characteristics of vasculitis in the pancreas, and to follow the formal pathogenesis of multifocal pancreatitis due to arteritis and/or arteriolitis (multifocal vasculogenic pancreatitis). A randomized autopsy population of 161 in-patients with rheumatoid arthritis (RA) was studied. Systemic vasculitis (SV) complicated RA in 36 (22.36%) of 161 cases; tissue samples of pancreas were available for histologic evaluation in 28 patients. Pancreatitis and vasculitis were characterized histologically and immunohistochemically. Vasculogenic, multifocal pancreatitis was not recognized clinically. Vasculitis of the pancreatic arterioles and small arteries (branches of splenic artery, upper and lower gastroduodenal arteries) can lead to local ischaemia and to regressive changes in the pancreas. This vasculogenic process is more or less widespread and multifocal, depending on the number of involved vessels and is followed by reactive inflammation, depending on the stages of the pathological process. Because of the recurrent nature of vasculitis with time these regressive changes accumulate within the pancreas and may contribute to an unexpected circulatory failure and sudden death of the patient. Vasculogenic microinfarcts in the pancreas may be clinically characterized by unexplained recurrent abdominal symptoms and spontaneous remissions which insidiously may lead to metabolic failure resistant to therapy.     

Localized isolated angiitis of the central nervous system associated with primary intracerebral lymphoma

Isolated angiitis of the central nervous system (IACNS) is a form of granulomatous vasculitis that is confined to the nervous system. A patient with localized IACNS affecting the left internal carotid and posterior cerebral artery adjacent to a primary intracerebral lymphoma of the midbrain along with associated granulomatous inflammation of the dura, leptomeninges, and ependyma of the aqueduct of Sylvius is described. His course was complicated by many neurologic complications before his death. Prednisone and cyclophosphamide were unable to control his disease. More aggressive therapy may be indicated for patients with lymphoproliferative lesions and associated central nervous system (CNS) vasculitis who fail to respond to conventional therapy.     

Vasculitis due to gemcitabine

We report the first occurrence of gemcitabine-induced vasculitis. It concerns a 45-year-old man diagnosed with non-small lung cancer since 2 months. After the first cycle of chemotherapy, consisting of gemcitabine and cisplatin, he developed myalgia and swelling of arms and legs with impairment of movement. This re-occurred during the second cycle of chemotherapy. Further anemia, elevated ESR and increased creatininephosphokinase. A surgical biopsy showed leucocytoclastic vasculitis and necrosis of muscle tissue. The chemotherapy was stopped and the complaints disappeared and did not return.     

Amphotericin B-induced cutaneous leucocytoclastic vasculitis: case report

A 37-year-old female patient was diagnosed with ulcerative colitis 8 months ago and medical treatment with oral azathioprine, low-dose corticosteroids and 5-ASA was started. Following 3 months without any symptoms, the patient had total colectomy and ileostomy. After this period, liposomal amphotericin B (3 mg kg(-1) day(-1)) was given with the diagnosis of probable fungal infection. Palpable purpuric skin lesions on the anterior surface of both legs appeared on the 55th day of amphotericin B treatment. Histological examination of a skin biopsy was consistent with leucocytoclastic vasculitis. We present a case of cutaneous leucocytoclastic vasculitis in which amphotericin B might presumably be the aetiological factor.     

Paraneoplastic vasculitis of central nervous system presenting as recurrent cryptogenic stroke

We report the case of paraneoplastic vasculitis of the central nervous system associated with breast cancer. A 54-year old woman had a complete workup because of recidivant seizures. Magnetic resonance imaging (MRI) showed cerebral and medullary cryptogenic lesions, and a diagnosis of encephalomyelitis of unknown origin was made. She was treated with corticosteroids, but because of cognitive impairment and recurrence of epileptic seizures, she was finally transferred to our Neurology Department. The previous diagnosis was then changed, because a poorly differentiated invasive lobular breast cancer was discovered. Thoracic and abdominal computed tomography (CT) scans diagnosed pulmonary, pericardial, adrenal, and renal metastases. Because MRI findings did not fit with the diagnosis of brain metastases, a CT-guided cerebral biopsy was performed, and she was eventually diagnosed with paraneoplastic vasculitis of the central nervous system.