Impaired neutrophil functions in patients with leukocytoclastic vasculitis

Background Leukocytoclastic vasculitis (LV) is characterized by segmental inflammation of small blood vessels, resulting in ischemic damage to the surrounding tissue. It is considered to be related to a type III hypersensitivity reaction, although the exact etiologic mechanism is not clear. Objective The purpose of this study was to evaluate neutrophil functions in patients with LV in order to understand their role in the pathogenesis of the disease. Methods Neutrophil functions were examined in 25 LV patients. The patients were divided into two groups: Group A consisted of 14 patients with drug-induced LV and Group B consisted of 11 patients where LV was induced by other factors. Results Both groups of patients showed significantly reduced chemotaxis and phagocytosis. Superoxide generation was significantly lower (P < 0.001) only in neutrophils from patients in Group A: 5.8 ± 0.5 nmoles O₂/10⁶ cells/min compared to 9.08 ± 0.8 nmoles O2/106 cells/min in the controls. Preincubation on normal neutrophils with the patients' sera caused an increase in their superoxide generation in accordance with the high IL-8 levels in these sera. Conclusions Neutrophil functions were significantly impaired in patients with LV. It is likely that factors present in LV plasma may chronically activate neutrophils, so that they become refracfory to further stimulation. Our study showed that neutrophil superoxide generation is low only in drug-induced LV; this test may assist in distinguishing such patients from those with LV induced by other causes.     

Prospective study of factors associated with leukocytoclastic vasculitis

The origin of leukocytoclastic vasculitis (LV) being often difficult to determine, we have undertaken since 1980 a prospective study of factors associated with LV. We selected 53 patients whose LV was clinically predominant, and excluded patients in whom LV was an expected phenomenon in a known autoimmune or infectious disease. Twenty-eight of the 53 patients presented with a typical Gougerot-Ruiter disease, 15 with a bullous or necrotic form of the disease and 10 with urticarial lesions. Detail of the prospective laboratory tests performed is given in table I. Correlations between laboratory values and LV-associated factors were significant with the decrease of complement but not with the presence of circulating immune complexes, rheumatoid factor, cryoglobulin or direct immunofluorescence test positivity. Most of the associated factors in our series were infectious agents (streptococci, hepatitis virus), immunological agents (rheumatoid factor, cryoglobulin) or drugs known to be potential LV-inductors; other factors were less common or quite recently described (enterovirus, Yersiniae, cirrhosis, primary liver cancer, Chlamydiae, refractory anemia with an excess of myeloblasts. We do not feel that a large series of laboratory tests should be performed in every case of LV. The clinical context and simple laboratory tests, such as blood cell count, complement assay, plasma electrophoresis and a search for rheumatoid factor should be enough to guide the clinician and help him decide whether further investigations are needed. However, it should be noted that in some cases without clinical pointers only full virological evaluation enabled us to determine that enteroviruses may be involved in the pathogenesis of LV.     

Retrospective analysis of adult patients with cutaneous leukocytoclastic vasculitis

A retrospective analysis was conducted on 93 adult patients with cutaneous leukocytoclastic vasculitis from St. Vincent's Hospital Melbourne to determine the classification, aetiology, severity and prognosis of this population of patients. We developed a new classification system for the purposes of our study based on modifications to the Chapel Hill Consensus Conference definitions for vasculitic syndromes. The results of our study indicate that an obvious cause was not found in 44.1% of patients. Of the patients with secondary vasculitis, the commonest causes were drugs and infections, accounting for a total of 40.9% of patients. Extracutaneous involvement was found in 39.8% of patients. Patients with symptoms resolving in less than 3 months accounted for 59.1% of the population, whereas 24.8% of patients had either symptoms lasting three or more months or evidence of recurrent symptomatology. There were 6 deaths (6.91%) and the rest were lost to follow up. The majority of patients in this retrospective series were classified as having hypersensitivity vasculitis, which is a relatively benign disorder limited mostly to skin with a low incidence of extracutaneous involvement (15.8%). Nevertheless, evidence of systemic involvement or sepsis need to be excluded as this may have important implications for patient treatment and outcome.     

Prevalence of hepatitis C virus antibodies and cryoglobulinemia in patients with leukocytoclastic vasculitis

BACKGROUND: Several dermatologic manifestations of hepatitis C virus (HCV) infection have been described. The association of HCV infection, essential mixed cryoglobulinemia and leukocytoclastic vasculitis (LV) have been published mainly in case reports. OBJECTIVE: The aim of the present study was to determine the prevalence of HCV infection and cryoglobulinemia in patients with LV. METHODS: Twenty-five cases of LV were tested for anti-HCV antibodies by means of a third-generation enzyme-linked immunosorbent assay, and cryoglobulins were detected by the precipitation method. Thirty healthy volunteers served as control group. RESULTS: Anti-HCV antibodies were detected in 2/25 patients with LV (8%) and none of the control group. Cryoglobulinemia was detected in 1 patient with LV and none in the control group. CONCLUSION: Although no significant difference between patients and the control group was detected, the prevalence of anti-HCV antibodies in LV patients is as high as 8%. Considering this, it seems reasonable to investigate the presence of HCV in unexplained cases of LV.     

Severe leukocytoclastic vasculitis of the skin in a patient with essential mixed cryoglobulinemia treated with high-dose gamma-globulin intravenously

We describe a patient with long-standing severe leukocytoclastic vasculitis of the skin and essential mixed cryoglobulinemia type II, who showed a limited reaction to immunosuppressive drugs, plasmapheresis, and colchicine. Therapy with high-dose gamma-globulin intravenously (IV) for five days resulted in disappearance of vasculitis lesions within three weeks. After gamma-globulin IV treatment there was a decrease in cryoglobulin, circulating immune complexes, and IgM, paraprotein, and a rise in complement levels. No serious side effects were noted during or after gamma-globulin IV treatment. The patient has been in remission for 16 months.     

Increased incidence of hypercoagulability in patients with leg ulcers caused by leukocytoclastic vasculitis

Vasculitis is a rare cause of leg ulceration. It is unclear why severe skin infarction develops in some patients with vasculitis, whereas others have only mild symptoms such as purpura, erythema, or urticaria. A coincidence of vasculitis and hypercoagulability may lead to more extensive thrombotic occlusion and hence explain the occurrence of large ulcers in a subset of patients. Our aim was to investigate whether patients with vasculitis ulcers have an increased incidence of hypercoagulability. Thirteen consecutive patients admitted to the hospital with necrotic ulcers caused by histologically confirmed vasculitis were screened for clotting disorders. In 7 of 13 patients (53%), hypercoagulable conditions were found. Five patients had factor V Leiden (38%), and 2 had lupus anticoagulant (15%). The normal frequency of these conditions is 5% to 6% and 3.6%, respectively. These data indicate that there is an increased incidence of hypercoagulable disorders in patients with vasculitis ulcers. We recommend screening these patients routinely for hypercoagulability.     

Azathioprine. An effective, corticosteroid-sparing therapy for patients with recalcitrant cutaneous lupus erythematosus or with recalcitrant cutaneous leukocytoclastic vasculitis

Azathioprine sodium has been reported to be effective therapy for chronic cutaneous lupus erythematosus (LE) but rarely for chronic cutaneous leukocytoclastic vasculitis (LV). We used azathioprine in the treatment of six patients with cutaneous LE, four of whom had subacute cutaneous (nonscarring) LE and two of whom had chronic cutaneous (scarring, discoid) LE, and six patients with chronic cutaneous LV. The conditions of all patients had been resistant to conventional therapy, and they required long-term oral corticosteroid therapy for control of their disease. Two of the patients with LE had prominent palmar and/or plantar involvement. Three patients with LE had an excellent response to azathioprine, with near complete clearing of the skin lesions, allowing a decrease in prednisone dosage. One patient with LE initially demonstrated significant improvement, but azathioprine therapy had to be discontinued because of pancreatitis. The treatment failed in two patients with LE; one had nausea and the other repeatedly developed a drug-induced fever. Five of the six patients with LV had improved conditions, with complete control of the disease occurring in two patients and partial control in three patients. Azathioprine is effective for some patients with cutaneous LE and chronic cutaneous LV, but it should be reserved for patients with severe disease in whom more conventional treatment fails.     

An improved method for in vitro perfusion of human skin

We have developed a procedure for establishing a long-living supravital skin preparation. Our model has made in vitro perfusion of human cutis, fatty tissue and lymph nodes possible. We describe the method of preparation, the technical construction and preliminary results of our experiments.     

Initial cutaneous manifestations associated with histopathological leukocytoclastic vasculitis in two patients with antiphospholipid antibody syndrome

Antiphospholipid antibody syndrome (APS) is a multisystem disorder associated with a variety of circulating autoantibodies that target different phospholipid protein complexes. APS is sometimes lethal as a result of severe sequelae, which may be primary or secondary to the underlying disease. We report two women who presented histopathologically with leukocytoclastic vasculitis as the first cutaneous manifestation and were subsequently diagnosed with APS associated with systemic lupus erythematosus (SLE). Patient 1 presented with widespread cutaneous necrosis (WCN) with rapidly spreading pain down the lower extremities. Skin biopsy specimens from her leg purpura and WCN revealed perivascular infiltrates with neutrophils consistent with leukocytoclastic vasculitis and thromboses of small-sized dermal vessels. Patient 2 exhibited livedo reticularis, painful cutaneous nodules with necrosis, ulcer, and erythematous macules on her lower extremities, shoulder, and face. Skin biopsies of her right knee showed intravascular thrombosis of small dermal vessels and infiltration of perivascular tissues with necrotizing granulomatous vasculitis in the dermis. We found that these various cutaneous manifestations with leukocytoclastic vasculitis were present at an early stage of APS. Although progression to leukocytoclastic vasculitis in patients with APS is uncommon, our data suggest that the association between microvascular occlusions and cutaneous vessel vasculitis has a predictive value for the pathogenesis. It is important for dermatologists to recognize these cutaneous signs to permit early and accurate diagnosis and treatment.     

Scurvy masquerading as leukocytoclastic vasculitis: a case report and review of the literature

Scurvy, a disease rarely seen in modern times, results from dietary deficiency of vitamin C and is characterized in adults by hemorrhagic diathesis, hair follicle abnormalities, and osteopenia. We present a 59-year-old man with perifollicular petechiae of the extremities, a painful lower extremity hematoma, and sacral osteopenia, who was repeatedly misdiagnosed with leukocytoclastic vasculitis. The patient's dietary history revealed several months of virtually no vitamin C intake. The patient rapidly improved with vitamin C replacement. We review the biochemical basis and pathophysiology of scurvy, clinical scenarios in which it occurs, clinical signs and radiologic features of the condition, and recommendations for its diagnosis and treatment.     

Erysipelas as a sign of subclinical primary lymphoedema: a prospective quantitative scintigraphic study of 40 patients with unilateral erysipelas of the leg

Background Erysipelas is a common skin infection that is usually caused by β‐haemolytic group A streptococci. After having had erysipelas in an extremity, a significant percentage of patients develops persistent swelling or suffers from recurrent erysipelas. We hypothesize that in cases of erysipelas without a clear precipitating agent, subclinical pre‐existing congenital or acquired disturbances in the function of the lymphatic system are present. The persistent swelling after erysipelas is then most likely caused by lymphoedema. Objectives We designed a study to examine if erysipelas of unknown origin is associated with a pre‐existent insufficiency of the lymphatic system. If our hypothesis is correct, patients with erysipelas of unkown cause without previously evident lymphoedema should have evidence of disturbed lymphatic transport in the unaffected extremity. Methods A prospective study, in which lymphoscintigraphy of both legs was performed in patients 4 months after presenting with an episode of erysipelas only in one leg. No patient had any known risk factor for erysipelas, such as diabetes mellitus, chronic venous insufficiency or clinical signs of lymphoedema. Lymphoscintigraphy was performed in 40 patients by subcutaneous injection of Tc‐99m‐labelled human serum albumin in the first web space of both feet. After 30 and 120 min, quantitative and qualitative scans were performed using a computerized gamma camera. During the lymphoscintigraphy, the patients performed a standardized exercise programme. Lymph drainage was quantified as the percentage uptake of Tc‐99m‐labelled human serum albumin in the groin nodes at 2 h after injection. Groin uptake of < 15% is pathological; uptake between 15–20% is defined as borderline, and uptake of > 20% as normal. Results The mean ± SD percentage uptake in the groin nodes in the affected limbs was 9·6 ± 8·5% vs. 12·1% ± 8·9% in the nonaffected limbs. The mean paired difference in uptake between the nonaffected vs. affected side was 2·5% (95% confidence interval 1·1–3·9%). This indicates that lymphatic drainage in the nonaffected limb was only slightly better than in the affected limb despite the infectious event in the latter. Of 33 patients with objective impairment of lymph drainage in the affected limb, 26 (79%) also had impaired lymph drainage in the nonaffected limb. Agreement in qualitative measurements between affected and nonaffected leg was less pronounced: 21 patients had abnormal qualitative results in the affected leg of whom nine also had impairment of the nonaffected leg (43%). Conclusions Erysipelas is often presumed to be purely infectious in origin, with a high rate of recurrence and a risk of persistent swelling due to secondary lymphoedema. In this study, we show that patients presenting with a first episode of erysipelas often have signs of pre‐existing lymphatic impairment in the other, clinically nonaffected, leg. This means that subclinical lymphatic dysfunction of both legs may be an important predisposing factor. Therefore, we recommend that treatment of erysipelas should focus not only on the infection but also on the lymphological aspects, and long‐standing treatment for lymphoedema is essential in order to prevent recurrence of erysipelas and aggravation of the pre‐existing lymphatic impairment. Our study may change the clinical and therapeutic approach to erysipelas as well as our understanding of its aetiology.