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Vaccinations may induce cutaneous adverse events, due to nonspecific inflammation or immuno-mediated reactions. Several types of vasculitis have been observed. We report on a 71-year-old woman who developed cutaneous small-vessel vasculitis after the second dose of Vaxzevria COVID-19 vaccination, showing leukocytoclastic vasculitis on histopathological examination of a skin biopsy. Cutaneous small-vessel vasculitis is a rare condition which can be idiopathic or secondary to underlying infections, connective tissue disorders, malignancy, and medications. The pathogenesis involves immune complex deposition in small blood vessels, leading to activation of the complement system and recruitment of leukocytes. Exacerbation of small-vessel vasculitis has been reported following the administration of various vaccines, particularly influenza vaccine. It is expected that SARS-CoV-2 vaccine results in the activation of B- and T-cells and antibody formation. We hypothesize that leukocytoclastic vasculitis caused by immune complex deposition within cutaneous small vessels could be a rare side effect of Vaxzevria COVID-19 vaccination., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Case Presentation: A 56-year-old man presented to the pulmonary clinic with dyspnea and hypoxemia on exertion. He was an avid biker and skier who had noticed a significant decrease in high-level physical activity over the past 3 years. He reported dyspnea, desaturations at altitudes higher than 9,000 feet, dry cough, tachycardia, and palpitations with exercise. Review of systems was also notable for gluten-intolerance, Raynaud's phenomenon, recurrent skin lesions and joint swelling, pain, and stiffness in the areas overlying the jaw, wrists, knees, and ankles (after capsaicin exposure). He denied fever, chills, anorexia, weight loss, hair loss, ocular symptoms, jaw claudication, chest pain, or lower extremity swelling. He had a five pack-year smoking history, no history of prematurity, childhood asthma, recurrent infections, or environmental and occupational exposure. Based on pulmonary function tests from an outside provider, he had received a diagnosis of exercise-induced asthma and had been prescribed an albuterol inhaler to use on an as-needed basis, which failed to improve his symptoms. He was later prescribed a mometasone-formoterol inhaler, still with no symptomatic improvement., (Copyright © 2021 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Levamisole-contaminated cocaine toxicity is a serious emerging public health concern, and providers should be aware of its presentation and management. Most cases of levamisole-induced vasculitis/vasculopathy (LIV) are associated with high antineutrophil cytoplasmic antibodies (ANCA). We describe a unique case of a cocaine user who presented with an acute purpuric eruption and negative ANCA laboratory findings. A brief clinical overview of LIV, spanning from patient presentation to treatment, is provided. In addition, we present a summary of all cases of ANCA-negative vasculitis identified via a PubMed literature review., (© 2018 The International Society of Dermatology.)

Scrub typhus is becoming a clinically important cause of acute undifferentiated febrile illness in Taiwan. The incubation period is between 6 and 21 days after exposure. It is transmitted by chiggers (larva of trombiculid mite) in long grasses and in dirt-floor homes, with infection characterized by a flu-like illness of fever, headache, and myalgia lasting approximately 1 week. It has various systemic manifestations, including GI symptoms. In some, the illness progresses to multiorgan dysfunction syndrome and death. We report on a 13-year-old boy who lived in Taipei City and who had initially tentative diagnosis of acute pyrexia of unknown origin with high fever up to 40.3°C for 1 week, but later had thrombocytopenia and diffuse abdominal pain with peritoneal sign suspected acute appendicitis. During the clinical course, septic shock and disseminated intravascular coagulopathy (DIC) were noted. There were skin rash in his trunk and extremities and an eschar with black crust surrounded by a scaling erythematous rim on his right buttock. In addition, we got the information of his travel history in Green Island and Orchid Island for 10 days.With the correct antibiotics, vancomycin, meropenem, and doxycycline, the patient was getting better and corresponding with high level of granulysin and tumor necrosis factor-alpha. The diagnosis of scrub typhus was confirmed by the biopsy of eschar and high quantitative real-time polymerase chain reaction values of Orientia tsutsugamushi (16sRNA and 56 kDa) tested by Centers for Disease Control and Prevention, Taiwan. Histopathological findings of the eschar revealed the leukocytoclastic vasculitis, crust and thrombus formation with many gram-negative microorganisms, O. tsutsugamushi demonstrated by 47 kDa monoclonal antibody immunohistochemical stain and electromicroscopy., Outcomes: After the careful selection of appropriate antibiotics including meropenem, vancomycin, and doxycycline, he recovered and was subsequently discharged 7 days after admission., Lesson Subsections: This case highlights that scrub typhus infection can mimic acute abdomen and septic shock with DIC. This rare presentation of acute abdomen and septic shock with thrombocytopenia and DIC caused by scrub typhus should remind physicians to be alert to the possibility of acute abdomen and febrile illness resulting from scrub typhus.

Background: Hypocomplementemic urticarial vasculitis syndrome (HUVS) is a rare disease involving urticarial cutaneous vasculitis, hypocomplementaemia and systemic manifestations. Pericardial involvement occurs in very rare cases. We report a case of HUVS associated with specific pericarditis and bullous lesions., Patients and Methods: A 63-year-old woman consulted for chronic urticaria that had appeared ten months earlier. Her skin lesions were associated with weight loss of 10 kg, deterioration of respiratory function and abdominal pain. Leukocytoclastic vasculitis was seen in the skin biopsy sample. Hypocomplementaemia and anti C1q antibodies were present and a diagnosis of HUVS was made. During hospitalisation, extensive compressive pericardial effusion was identified, and histological examination of the biopsy revealed specific pericardial lymphocytic vasculitis. During follow-up, four episodes of infectious pneumonitis were noted. Bullous skin lesions were also observed., Discussion: HUVS is a disease caused by an antibody against C1q complement responsible for urticarial lesions and vasculitis antibodies. To our knowledge, there have been only five reports in the literature of pericardial injury associated with HUVS. In our case, histological examination of the pericardium demonstrated lymphocytic vasculitis., (Copyright © 2014 Elsevier Masson SAS. All rights reserved.)

Cutaneous vasculitis can be limited to skin or a manifestation of primary systemic vasculitis. However, there are no definite markers to predict systemic involvements. Recent studies have shown that a higher red blood cell distribution width (RDW) is associated with disease activity in various disorders. We evaluated whether RDW can be used as an indicator for predicting systemic disease in patients with initial cutaneous involvements. We reviewed clinical and laboratory information of 143 patients with cutaneous vasculitis and 15 pigmented purpuric dermatosis patients seen at single academic hospital in Korea. Various parameters, including RDW, were evaluated in patients with primary cutaneous vasculitis and primary systemic vasculitis with initial cutaneous manifestations. The RDW value between cutaneous and systemic vasculitis patients was compared and RDW level was also investigated whether it can indicate systemic vasculitis in patients with cutaneous involvements. The mean age was 32.0 years, and 102 (64.6 %) patients were female. A total of 132 patients were patients with primary cutaneous vasculitis, and 11 were primary systemic vasculitis. Higher ratio of patients with high RDW was detected in systemic vasculitis group compared with cutaneous vasculitis group (36.4 vs. 7.6 %, P < 0.05). The mean RDW was significantly higher in systemic vasculitis patients (P < 0.05). RDW had the strongest association with systemic vasculitis (P < 0.05, OR 1.834). In conclusion, elevated level of RDW was significantly associated with systemic vasculitis. RDW can be used as one of the marker to predict systemic disease in patients with cutaneous vasculitis.

High-mobility group box-1 (HMGB1) has been implicated as a pro-inflammatory cytokine in the pathogenesis of various inflammatory and autoimmune diseases. However, information about HMGB1 in Henoch-Schönlein purpura (HSP) is still unclear. Herein, we investigated the role of HMGB1 in patients with HSP and the pro-inflammatory effects of HMGB1 on human dermal microvascular endothelial cell line (HMEC-1). Serum HMGB1 levels in patients with HSP together with patients with allergic vasculitis (AV) and urticarial vasculitis (UV) were detected by enzyme-linked immunosorbent assay (ELISA). HMEC-1 cells were treated with HMGB1 at concentrations ranging from 4 ng/ml to 100 ng/ml. Serum HMGB1 levels were significantly increased in patients with HSP, AV and UV, when compared with those in control group. Moreover, abundant cytoplasmic expression of HMGB1 was observed in endothelial cells in lesional skin of HSP patients. Using membrane cytokine antibody array, we indicate that HMGB1 markedly induced TNF-α and IL-6 release in cultured supernatant. Furthermore, by real-time quantitative PCR and ELISA, the effects of HMGB1 on these cytokines production in HMEC-1 cells were established. Finally, Western blot data revealed that HMGB1 can induce phosphorylation of inhibitor of κB-α (IκBα) and the nuclear translocation of nuclear factor-κB (NF-κB) p65 in HMEC-1 cells. In conclusion, this study provides first observations on the association of HMGB1 with HSP. We suggest that HMGB1 may be an important mediator of endothelial inflammation through the induction of TNF-α and IL-6 production and may play a crucial role in the pathogenesis of HSP., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

A middle aged female patient presented with generalised palpable purpura associated with intense pruritus along with subconjunctival haemorrhage and orbital inflammation. There was extensive dermographism. Other systemic examinations were within normal limits. Haematological profile was normal except raised D-dimer. Skin biopsy revealed the presence of leucocytoclastic vasculitis. Antinuclear antibody was positive in a titre of 1 : 160, but antidouble-stranded DNA was negative. Urine examination revealed haematuria and proteinuria. Complement C3, C4 and C1q levels were decreased with the presence of anti-C1q antibody. There was a diagnostic dilemma between systemic lupus erythematosus and hypocomplementaemic urticarial vasculitis syndrome. However, as the patient did not fulfil the American College of Rheumatology criteria for systemic lupus erythematosus, but fulfilled all the criteria for hypocomplementaemic urticarial vasculitis syndrome, the case was finally diagnosed as hypocomplementaemic urticarial vasculitis syndrome and treated accordingly with favourable outcome.

Background & Objectives: Cutaneous vasculitis has protean clinical manifestations. It may be idiopathic or associated with a spectrum of conditions such as infections, drugs, etc. Skin is involved in both small vessel vasculitis (SVV) and medium vessel vasculitis (MVV). Overlapping features are seen between SVV and MVV. The histopathological features may not always relate with the clinical lesions. The aim of the present study was to evaluate the aetiological factors and clinicopathological association in patients with cutaneous vasculitis., Methods: In this cross-sectional study, detailed history and clinical examination were done on patients with biopsy proven cutaneous vasculitis. Two skin biopsies were taken from each patient for routine histopathology and direct immunofluorescence., Results: Of the 61 patients studied, hypersensitivity vasculitis (HSV) [23 (37.7%)] and Henoch Schonlein purpura (HSP) [16 (26.2%)] were the two most common forms. Systemic involvement was seen in 32 (52.45%) patients. Drugs were implicated in 12 (19.7%) cases, infections in 7 (11.4%) and connective tissue disorders in 4 (6.5%) cases. Histologically SVV was the most common pattern, seen in all the clinically diagnosed patients with SVV (47), and in 12 of the 14 clinically diagnosed patients with MVV. Direct immunofluorescence showed positivity for at least one immunoreactant in 62 per cent of the patients and the most common deposit was C3 followed by IgG, IgA and IgM., Interpretation & Conclusions: Majority of our patients with cutaneous vasculitis were idiopathic. Histologically, SVV was seen in most of our patients. No association was seen between history of drug intake and tissue eosinophilia and also between histologically severe vasculitis and clinical severity. The presence of immunoreactant IgA was not specific for HSP.

Background: There is a need for a laboratory marker that correlates with the clinical activity of Behçet's disease (BD)., Objective: We aimed to investigate whether serum galectin-3 (Gal-3) levels were affected during the course of the disease with regard to disease activity., Methods: A total of 131 subjects were involved in the study as follows: Group 1: BD active (n = 39); Group 2: BD inactive (n = 31); Group 3: Disease controls with leucocytoclastic vasculitis confirmed with a skin biopsy (n = 22); and Group 4: Healthy control subjects (n = 39). The BD patients were followed regularly and samples were taken in their active and inactive periods of the disease over a 2-year period., Results: Serum Gal-3 levels were significantly higher in active BD patients (mean 2.38) than inactive BD patients (mean 0.63; P < 0.0001) and the healthy control subjects (mean 0.75; P < 0.0001). There was no significant difference between the leucocytoclastic vasculitis and active BD patients (P = 0.093). Serum Gal-3 levels were positively correlated with clinical activity scores of active BD patients (r = 0.66, P < 0.0001). In addition, the Gal-3 levels were significantly higher in the active disease period when compared with the inactive period during the follow-up. There were no significant differences between the two inactive periods of the disease among the same patients. Further analyses revealed that patients with vascular involvement had significantly higher Gal-3 levels than the other active BD patients (mean 7.57; P = 0.007)., Limitations: The limitation of the study is the small number of patients with vascular involvement in the active BD patient group., Conclusion: Gal-3 levels are correlated with the activity of Behçet's disease especially with the vascular involvement., (© 2011 The Authors. Journal of the European Academy of Dermatology and Venereology © 2011 European Academy of Dermatology and Venereology.)

A 58-year-old Japanese woman presented with recurrent abdominal pain, chronic urticaria, and petechiae on her extremities, and hypocomplementemia, findings that were consistent with hypocomplementemic urticarial vasculitis syndrome (HUVS). A laboratory examination revealed that she had markedly elevated IgG levels (4,448 mg/dL; normal range, 870-1,700 mg/dL) with particularly high IgG4 levels (1,050 mg/dL; normal range, 48-105 mg/dL) and a high IgG4/total IgG ratio (0.22; normal range, 0.02-0.05). A skin biopsy demonstrated leukocytoclastic vasculitis with IgG4 deposition in the vascular lumen and vascular walls. A lymph node biopsy revealed reactive lymphoid hyperplasia with numerous IgG4-positive cells in the perifollicular area, but no sclerotic findings. A chromosomal analysis of an enlarged lymph node, without phytohemagglutinin (PHA) stimulation, demonstrated that one in every three analyzed cells had abnormalities, such as 44, XX, -13, add(15)(p11), -17, -17, and mar.

Background: Hypocomplementemic urticarial vasculitis, described by MacDuffie in 1973, is rare. Some doubt surrounds its classification. We report a case of hypocomplementemic urticarial vasculitis (MacDuffie syndrome) treated with dapsone with a favorable outcome., Case Report: Over a number of years, a 43-year-old man presented urticarial vasculitis attacks with palpebral oedema and systemic symptoms such as fever and arthralgia. In 2006, MacDuffie syndrome was diagnosed on the grounds of positive anti-C1q antibodies. Treatment with dapsone was started and resulted in considerable improvement., Discussion: Hypocomplementemic urticarial vasculitis is characterized by urticarial vasculitis lesions, leucocytoclastic vasculitis and systemic symptoms. The latter symptoms are similar to those of systemic lupus erythematosus (SLE), and some authors have suggested that MacDuffie syndrome may in fact belong to SLE. Diagnosis is based on clinical appearance, histology and the presence of anti-C1q antibodies. There is no specific treatment for hypocomplementemic urticarial vasculitis. Immunosuppressant therapy can be used for lesions refractory to systemic corticosteroids., (Copyright 2010 Elsevier Masson SAS. All rights reserved.)

Autoimmune pancreatitis (AIP) is an uncommon condition which comprises diffuse or discrete pancreatic enlargement and irregular pancreatic duct strictures of autoimmune origin leading to pain or obstructive jaundice associated with extra-pancreatic manifestations. It is characterized by an elevated IgG, especially IgG4, level. We illustrate the first described case of a patient with AIP in association with leucocytoclastic and renal vasculitis.

Hypocomplementemic urticarial vasculitis is a type of urticarial vasculitis with multisystemic involvement and poor prognosis, sometimes associated with systemic lupus erythematosus. Several therapies have been attempted with no consensus on an effective therapeutic regimen. Intravenous immunoglobulin has been used in severe manifestations of systemic lupus erythematosus and recently in hypocomplementemic urticarial vasculitis. We present a 7-year-old girl with hypocomplementemic urticarial vasculitis associated with systemic lupus erythematosus and pneumonia who responded favorably to intravenous immunoglobulin.

One of the rare causes of secondary vasculitides is malignancy. Hematological malignancies produce secondary vasculitis more frequently than solid malignancies. Here in we report a case of acute myeloid leukemia presenting with anti-neutrophil cytoplasmic antibody-positive vasculitis. This case highlights the importance of looking for underlying malignancies, especially leukemias in patients presenting with features of systemic vasculitides.

Objective: To investigate a possible role of antiphospholipid (aPL) antibodies in adult Henoch-Schönlein purpura (HSP) and cutaneous leukocytoclastic angiitis (CLA)., Methods: We reviewed the records of 30 HSP and 8 CLA adults with an initial cutaneous manifestation of palpable purpura on their lower extremities between 2003 and 2007. Eight microscopic polyangiitis (MPA) patients and 30 healthy persons were recruited as controls. Serum anticardiolipin (aCL), anti-phosphatidylserine-prothrombin complex (anti-PS/PT), and anti-beta(2)-glycoprotein I (anti-beta(2)GPI) antibody levels in HSP, CLA, MPA patients, and healthy controls were measured by enzyme-linked immunosorbent assay., Results: Twenty-two HSP patients (73%) were positive for serum IgA aCL antibodies. Nineteen (63%) had IgA anti-PS/PT antibodies and 4 (13%) had IgA anti-beta(2)GPI antibodies. IgA aCL and anti-PS/PT antibodies showed a significant correlation (P = 0.007). Twenty (67%) HSP patients had IgM anti-PS/PT antibodies and 6 (20%) had IgG anti-PS/PT antibodies. Six (75%) CLA patients had IgM anti-PS/PT antibodies and 2 (25%) had IgG anti-PS/PT antibodies. In contrast, aPL antibodies were not found in any MPA patients or normal controls. Serum IgA aCL antibody levels in HSP patients showed a significant correlation with serum IgA and C-reactive protein (CRP) levels (P = 0.030 and 0.039, respectively). A positive correlation between CRP and serum IgA anti-PS/PT antibody levels was observed in HSP patients (P = 0.023). Serum IgA aCL antibody levels were also significantly associated with proteinuria according to urinalysis (P = 0.024)., Conclusion: Serum levels of IgA aCL and anti-PS/PT antibodies were elevated in adult HSP, suggesting that serum IgA antibodies may play some role in adult HSP. IgA aCL and/or anti-PS/PT antibodies could serve as markers for adult HSP and should be monitored as an indicator of adult HSP activity. Small-vessel vasculitis could be dependently associated with the presence of IgM anti-PS/PT antibodies. These findings suggest that aPL antibodies are closely related to the pathogenic factors that trigger the development of vasculitis.

There might be rheumatic manifestations of malignant diseases, especially those of the hematological type. Until now, antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis in chronic lymphocytic leukemia (CLL) has been reported on only very few occasions. Here, we present our patient with Rai stage II CLL who came to us with constitutional symptoms. She turned out to have hematuria with dysmorphic erythrocytes and developed hemoptysis. She had pulmonary-renal syndrome and was diagnosed with p-ANCA positive microscopic polyangiitis. She is currently using prednisolone and cyclophosphamide and undergoing regular hemodialysis. Constitutional symptoms in patients with hematological malignancies should make the physicians consider systemic vasculitis after exclusion of disease-related complications.

We report two male patients who presented with symmetrical, painful purpura that evolved into bullae and necrotic ulcers, predominantly on the extremities, over two months in spite of conventional therapy including oral steroids. Examination showed livedoid and purpuric patches with necrotic centers in starburst pattern over the extremities and buttocks. The first case also had similar lesions over the ears. The clinical presentation and the histopathological examination suggested a diagnosis of necrotizing leukocytoclastic vasculitis (LCV). Blood testing ruled out connective tissue disease, hepatitis B or C infection or streptococcal infection as underlying cause of vasculitis. Serum antinuclear factor, antineutrophilic cytoplasmic antibody and anticardiolipin anticoagulant were negative in both cases. Cryoglobulins were positive in case 2. An incidental finding was raised serum proteins and globulins in case 2. Further investigations revealed M band on electrophoresis and features of multiple myeloma on bone marrow biopsy in both cases. These cases emphasize the importance of simple investigations like serum proteins in the evaluation of LCV.

Behçet's syndrome (BS) is a relapsing, chronic, inflammatory disease characterized by endothelial dysfunction, atherothromboembogenesis, and leukocytoclastic vasculitis with complex immunologic molecular interactions. Generalized derangements of the lymphocyte and neutrophil populations, activated monocytes, and increased PMNLs motility with upregulated cell surface molecules such as ICAM-1, VCAM-1, and E-selectin, which are found on the endothelial cells, leukocytes, and platelets, have all been demonstrated during the course of BS. Our aim is to investigate the association of serum concentrations of soluble P-selectin in patients with BS, and to evaluate whether disease activity has an effect on their blood levels. This multicenter study included 31 patients with BS (15 men and 16 women) and 20 age- and sex-matched healthy control volunteers (11 men and nine women). Neutrophil count, erythrocyte sedimentation rate, and acute-phase reactants as well as soluble P-selectin levels were determined. The mean age and sex distributions were similar (P > .05) between BS patients (35 years) and control volunteers (36 years). Serum levels of soluble P-selectin in patients with BS (399 +/- 72 ng/mL) were significantly (P < .001) higher when compared with control subjects (164 +/- 40 ng/mL). In addition, active BS patients (453 +/- 37 ng/mL) had significantly (P < .001) elevated levels of soluble P-selectin than those in inactive period (341 +/- 52 ng/mL). This study clearly demonstrated that serum soluble P-selectin levels are increased in BS patients when compared with control subjects, suggesting a modulator role for soluble P-selectin during the course of platelet activation and therefore, atherothrombogenesis formation in BS, especially in active disease.

The article presents data on involvement of the nervous system of patients with medicamentous allergy characterized by allergic lesions of body vessels. Cerebral allergic vasculitis is often masked by other vascular conditions such as the following: atherosclerosis, high blood pressure, rheumatism and vegetovascular dystonia. The use of the reaction of a specific injury of basophilic leukocytes exposed to penicillin, streptomycin may be a diagnostic test in the determination of the damage of the nervous system in patients with medicamentous allergy.

Clinical recognition of drug-induced vasculitic and lupus-like syndromes is very important because continued use of the offending drug can lead to irreversible and life-threatening vasculitic organ damage (e.g. end-stage renal disease or pulmonary haemorrhage). Withdrawal of the drug often leads to spontaneous recovery, meaning that immunosuppressive therapy can be avoided. The presence of myeloperoxidase-antineutrophil cytoplasmic antibodies, IgM anticardiolipin antibody, and antihistone antibodies in combination was found to be characteristic of drug-induced vasculitic syndromes caused by the antithyroid drugs propylthiouracil and methimazol. Clinically, skin vasculitis and arthralgias predominated and renal vasculitis was rare.

Unlabelled: Tumor necrosis factor alpha (TNFalpha) plays an important role in the pathogenesis of anti-neutrophil cytoplasmic antibody-associated systemic vasculitis. TNFalpha blockade is a potential therapy for these disorders., Methods: An open-label, multi-center, prospective clinical trial in two subgroups was performed. Study I examined acute disease, either first presentation or relapse (Birmingham Vasculitis Activity Score [BVAS] > or = 10; n = 16); study II examined persistent disease (BVAS > or = 4; n = 16). Patients received infliximab (5 mg/kg) at 0, 2, 6, and 10 wk. Concomitant therapy in study I included prednisolone and cyclophosphamide. Study II patients continued their existing treatment regimens, with prednisolone tapered according to clinical status., Results: Mean age was 52.4 yr, 53% of the patients were female, and follow-up was 16.8 mo. Twenty-eight patients (88%) achieved remission (14 per study group). BVAS decreased from 12.3 (confidence interval [CI] = 10.5 to 14.0) at entry to 0.3 (CI = 0.2 to 0.9) at wk 14 (P < 0.001). C-reactive protein (mg/L) decreased from 29.4 (CI = 16.8 to 42.0) at entry to 7.0 (CI = 3.3 to 10.9) by wk 14 (P = 0.001). Mean prednisolone dose (mg/d) in study II decreased from 23.8 (CI = 15.0 to 32.5) at entry to 8.8 (CI = 5.9 to 11.7) at wk 14 (P = 0.002). There were two deaths and seven serious infections. Relapse occurred in five patients (three in study II) after a mean of 27 wk., Conclusion: TNFalpha blockade with infliximab was effective at inducing remission in 88% of patients with antibody-associated systemic vasculitis and permitted reduction in steroid doses. Severe infections were seen in 21% of patients, and despite continued infliximab, 20% of initial responders experienced disease flares. Infliximab is a promising new therapy for vasculitis both as a component of initial therapy and in the management of refractory disease. These results need confirmation in larger randomized trials.

The hallmark of leukocytoclastic vasculitis (LCV) is palpable purpura. Histologically, there is a neutrophilic, angiocentric, segmental inflammation with endothelial cell injury and fibrinoid necrosis of the blood vessel walls. Leukocytoclastic vasculitis has many associations, including, rarely, multiple myeloma (MM). A total of 2357 patients with a diagnosis of MM were reviewed to retrieve cases that had developed leukocytoclastic vasculitis. Eight patients with MM and LCV showed a predominance of immunoglobulin G (IgG) myeloma paralleling the immunoglobulin secretion seen overall. Overexpression of interleukin 6, which is necessary for myeloma cell growth and survival, may contribute to the pathogenesis of LCV in the setting of MM.

The cutaneous symptoms in non-immediate reactions to drugs are not always clinically distinguishable from those induced by viruses, especially during the early phase of the reaction. Moreover, viral infections and drug reactions often coexist and identification of the etiological agent is necessary. Discerning the differences in the immunological response between both may help in the diagnosis. The aim of this study was to determine possible differences in the immunological response in non-immediate cutaneous reactions to drugs versus cutaneous viral-induced diseases in children. Two groups of children were evaluated: one with non-immediate drug-induced cutaneous reactions (DICR) and another with virus-induced cutaneous reactions (VICR). A third group of children taking the same drugs as the DICR group and with no cutaneous disease or viral infections was included as controls. The lymphocyte markers CD3, CD4, CD8, CD16, CD19, CLA, CD25, CD69, CD45RO, CD45RA were determined by flow cytometry. IL-2, IL-4, IL-5, IFN-gamma, TNF-alpha and IL-10 mRNA were measured by RT-PCR. Data were compared by non-parametric and chi(2) statistical analysis. In DICR group (n=8) the diagnosis was established by temporal association, improvement after drug withdrawal, patch testing, and in some cases by controlled administration. All patients in the VICR group (n=10) were diagnosed based on a positive viral serology: the presence of IgM antibodies or seroconversion of IgG antibodies. There were significant differences between the three groups in peripheral lymphocytes expressing the skin homing receptor CLA (P < 0.01), the early activation marker CD69 (P < 0.001), and the memory (CD3+CD45RO+) (P < 0.02) and naive (CD3+CD45RA+) (P < 0.03) T cell subsets. Children with DICR showed a TH1 mRNA cytokine pattern whereas those with VICR showed a TH0 pattern. In lymphocyte subpopulations from children, differences in the immunological response between DICR and VICR can be detected in the expressions of the activation marker CD69 and the cutaneous homing receptor CLA, and in cytokine mRNA profiles.

Systemic vasculitis is a rare complication of therapy with antithyroid medication. Antineutrophilic cytoplasmic antibody (ANCA)-associated vasculitis has been described in patients treated with propylthiouracil (PTU) and methimazole (MMI). The majority of cases have underlying Graves' disease. The authors report 2 children who developed ANCA-associated systemic vasculitis during PTU therapy of Graves' disease. One patient, after PTU treatment for 3 years, developed severe systemic vasculitis. After 3 weeks of arthritis, she abruptly presented with hematuria, proteinuria and edema concomitant with anemia. Her serum creatinine was elevated, to 6 mg/dl. Renal biopsy revealed crescentic glomerulonephritis. After admission, she developed intracerebral hemorrhage and pulmonary hemorrhage. She had positive perinuclear-ANCA (p-ANCA) with a titer of 1:160. Despite intensive therapy with immunosuppressive agents and plasmapheresis, as well as discontinuation of PTU, she died of the complications of severe systemic vasculitis. The other patient developed fever, arthralgia and leukocytoclastic vasculitis of the skin during treatment with PTU for about 2 years. Her symptoms and skin lesions disappeared after discontinuation of PTU. However, she has had a persistently high titer of p-ANCA 1:320 through 17 months follow-up time. Thus, patients who are treated with PTU can develop ANCA-positive vasculitis in a mild or severe form. Therefore, they should be carefully followed and monitored, not only for their thyroid status but also the serious complications of PTU.

Objective: Hypersensitivity vasculitis (HSV) is secondary vasculitis due to an immune response to exogenous substances. Because of the relative rarity of the vasculitides there are no reports on the role cytokines. This report evaluates some of cytokines which might be involved in pathophysiological events of HSV., Material and Methods: Patients with HSV ( n=20) were classified as active ( n=12) ornd inactive ( n=8) according to a vasculitis activity index for systemic necrotizing vasculitis (VAI). All the patients were males. A control group was formed from 20 healthy male employees of our department. We performed tests for serum interleukins 6, IL-10, sIL-2 receptor, tumor necrosis factor (TNF) alpha, C-reactive protein (CRP) levels using enzyme-linked immunosorbent assay and erythrocyte sedimentation rate (ESR)., Results: The mean ESR value, CRP, and fibrinogen levels were significantly different in both active and inactive HSV from those in the healthy group; they were also significantly higher in the active than in the inactive group. There was no significant difference between healthy and inactive groups for serum IL-10, IL-6, sIL-2 receptor, and TNFalpha levels. However, it was also significantly higher for in active HSV patients than in the healthy group. Similar results were obtained comparing active and inactive groups, namely, all cytokine levels were significantly higher for all patients. The most striking finding is the high correlation of ESR (also for CRP, fibrinogen) with serum levels of TNFalpha and IL-10, but not with IL-6 and IL2R., Conclusions: These data show that serum TNFalpha and IL-10 levels can be studied in comparison to traditional markers of inflammation such as sedimentation rate or C-reactive protein. This may lead to new approaches to treating or managing HSV.

Objectives: To examine the clinical spectrum of hypersensitivity vasculitis (HV) in an unselected population of adults and establish differences between patients with HV limited to the skin and those with systemic involvement., Methods: Retrospective study of adult patients (> 20 years) with biopsy-proven cutaneous leukocytoclastic vasculitis diagnosed as having HV, who were seen at the single hospital serving a well defined population between 1984 and 1998. Patients were classified as having HV according to the criteria of Michel et al. (9). To examine outcome and relapses of the disease only those patients with a follow-up of at least 1 year were included in this study., Results: 64 patients with a mean follow-up of 4.9 +/- 3.5 (range: 1.1-13.6) years were studied. Ten (15.6%) had visceral involvement (3 gastrointestinal and 7 renal manifestations) during the course of the disease. The remaining patients had a leukocytoclastic vasculitis limited to the skin. When the study was concluded persistent hematuria and proteinuria was only observed in 1 patient and none developed renal insufficiency. Patients with a history of drug treatment and elevated ESR had more systemic complications but the difference was not statistically significant. The outcome was excellent in both patients with HV limited to the skin and in those with systemic complications during the course of the disease., Conclusions: In unselected adults HV is generally a benign disease confined exclusively to the skin. In those patients with systemic manifestations, visceral involvement is generally mild and transient.

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.

A 75-year-old man presented with a progressive eruption of 6 weeks' duration. Purpura and focal areas of cutaneous infarction were present on the legs. There were scabies burrows on the wrists and hands, and a mite was extracted. Histology of a skin biopsy showed a necrotizing leucocytoclastic vasculitis. Circulating lupus anticoagulant was detected. Treatment consisted of topical 5% permethrin cream and systemic steroids.

Hypocomplementaemic urticarial vasculitis syndrome is a leukocytoclastic vasculitis characterized by urticarial lesions, associated with fever, arthralgias, arthritis and abdominal pain. Other systemic manifestations include glomerulonephritis, uveitis, episcleritis, chronic obstructive pulmonary disease and neurological abnormalities. Some case associated with systemic lupus erythematosus have been described and SLE diagnosis was made by previous or concomitant diagnostic criteria before onset of urticarial vasculitis. Urticarial vasculitis prior to SLE diagnosis is rare. The development of anti-Ro/SS-A antibody for the diagnosis of SLE is emphasized. The authors alert to the importance of periodically searching for this marker in patients with urticarial 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 O2/10(6) cells/min compared to 9.08 +/- 0.8 nmoles O2/10(6) 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 refractory 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.

A 24-patient lot with hypersensitivity vasculitis was investigated for serological determinations of ICAM and ELAM adhesion molecules. Determinations were made in attack and in remission. Over two thirds of the cases presented elevated serological levels of ICAM and ELAM in attack, with twofold higher values than normal. In remission, in the absence of clinical signs, ICAM and ELAM values were normal in 19 cases (ICAM) and 22 cases (ELAM). Serological level of ICAM and ELAM was concordant with serological level of IL-2, IL-6, circulating immune complexes and clinical status. The increased values of ICAM and ELAM are due to the expression of these molecules both on the surface of endothelial cells and on immune cells. The adherence of leukocytes on the endothelial cells, by adhesion molecules involvement, followed by their extravasation represents an important event in the vascular lesion pathogeny of the hypersensitivity vasculitis.

Background: Autoantibodies may be detected in the serum of some patients with cutaneous leukocytoclastic vasculitis. We have previously reported the presence of IgA anticardiolipin antibodies (ACAs) in one patient with leukocytoclastic vasculitis associated with IgA nephropathy., Objective: Our purpose was to determine the prevalence of IgA ACAs in unselected groups of patients with cutaneous vasculitis, IgA nephropathy, and Henoch-Schönlein purpura., Methods: Thirty patients (10 each with cutaneous vasculitis, IgA nephropathy, and Henoch-Schönlein purpura) and 31 healthy control subjects were studied. ACA titers were measured by a standardized enzyme-linked immunosorbent assay., Results: ACAs restricted to the IgA isotype were present in 6 of 10 patients with cutaneous leukocytoclastic vasculitis. IgA ACA levels were significantly higher in these patients than in the control subjects. The presence of IgA ACAs did not correlate with disease severity or involvement of other organs and persisted after resolution of the vasculitis in most patients. In five of the six patients with IgA ACAs, drugs were implicated in the pathogenesis of the vasculitis. By contrast, ACAs were present in only a minority of children with Henoch-Schönlein purpura and adults with IgA nephropathy and were not restricted to the IgA isotype., Conclusion: We have demonstrated a clear association between IgA ACAs and cutaneous leukocytoclastic vasculitis. The absence of IgA ACAs in Henoch-Schönlein purpura argues against their being an epiphenomenon in vasculitis.

Background and Design: Hepatitis C virus (HCV) infection is associated with mixed cryoglobulinemia, which can cause a vasculitis affecting various organs. To determine the prevalence of cutaneous vasculitis in patients infected with HCV, information concerning a series of 408 HCV antibody-positive outpatients was analyzed. Patients with a skin eruption were evaluated by a dermatologist for objective evidence of cutaneous vasculitis, and the sensitivity of cryoglobulins was compared with that of rheumatoid factor activity as a serologic marker of mixed cryoglobulinemia in these patients., Results: Cutaneous vasculitis was identified in 10 of 408 HCV-infected patients (prevalence of at least 2%). The vasculitis was manifested as palpable purpura in eight patients, livedo reticularis in one patient, and urticaria in one patient. The skin eruption was a major presenting feature in each of the 10 patients and even led to the discovery of occult HCV infection in two patients. Histologic examination revealed leukocytoclastic vasculitis in six patients and necrotizing arteritis consistent with polyarteritis nodosa in two patients. All 10 patients had chronic active hepatitis and exhibited rheumatoid factor activity. Variable features attributable to mixed cryoglobulinemia included arthropathy, central nervous system abnormalities, and glomerular disease. Serum cryoglobulins were detected in only four patients., Conclusions: Practitioners should be alert to the possibility of HCV infection in patients presenting with palpable purpura, livedo reticularis, or urticaria, in which the underlying histologic features are those of leukocytoclastic vasculitis or necrotizing panarteritis. Positive serologic test results for HCV antibody and rheumatoid factor in such patients virtually confirm the diagnosis of HCV-induced mixed cryoglobulinemia.

Background: Several patients were observed with a peculiar cutaneous eruption limited to the dorsa of the hands and fingers. Clinically the lesions had some resemblance to those seen in Sweet's syndrome, but biopsy specimens showed severe leukocytoclastic vasculitis., Objective: Our purpose was to characterize this eruption clinically and histologically and compare it with previously described diseases., Methods: Six patients observed since 1977 are described. Skin biopsy specimens were obtained., Results: In six women (age, 41 to 79 years) a symmetric eruption of papules and plaques limited to the dorsa of the radial sides of the hands and first three digits developed. The lesions resembled those of Sweet's syndrome and were associated with fever, sterile culture, blood neutrophil leukocytosis, nonresponse to antibiotic therapy, and rapid response to prednisone. Biopsy specimens showed a severe leukocytoclastic vasculitis., Conclusion: These patients appear to have a distinct entity that we have termed pustular vasculitis of the hands.

The american college of rheumatology (ACR) proposed in 1990 revised clinical criteria for systemic vasculitis classification to define homogeneous group of patients for clinical trials. However, microscopic polyarteritis (MPA) was not clearly identified from polyarteritis nodosa (PAN). Since anti-neutrophil cytoplasm antibodies (ANCA) are markers of disease activity of small vessel vasculitides including MPA, we tested the clinical significance of ANCA in 24 patients with PAN according to the ACR 1990 criteria. Two of 24 patients had ANCA, as defined by indirect immunofluorescence on normal human neutrophils, antigen-specific ELISA and Western blot analysis. However, they exhibited histologically proven small vessel but not medium vessel vasculitis. Furthermore, they had neither artery microaneurysms nor large organ injury consequent upon large vessel occlusion. Although they satisfied ACR criteria for PAN, they probably were misclassified and should be considered as MPA. We conclude that: (i) ANCA are not found in patients with classical PAN in the absence of MPA features; (ii) caution should be exercised when defining PAN according to the ACR 1990 criteria; (iii) ANCA may help systemic vasculitis classification.

Hypocomplementemic urticarial vasculitis syndrome (HUVS) is a syndrome of recurrent urticarial vasculitis, arthralgia/arthritis, and hypocomplementemia. Angioedema, ocular inflammation, glomerulonephritis, and obstructive lung disease are other clinical findings. Although the etiology of HUVS is unknown, its resemblance to systemic lupus erythematosus (SLE) suggests a similar pathogenesis. SLE is known to occur in identical twins. This is the first report of a pair of identical twins with HUVS. Concordance for HUVS in identical twins suggests that the pathogenesis of the disease involves abnormal genetic immunoregulation.

We describe 3 cases of hypocomplementemic urticarial vasculitis syndrome (HUVS) with Jaccoud's hands deformity and cardiac valve disease (aortic regurgitation, mitral regurgitation, mitral disease). In one case, the valve lesions required valve replacement and later a heart transplant. Valve disease and articular deformities developed 2 and 4 years, respectively, after the onset of HUVS. This as yet undescribed combination of diseases suggests a new syndrome. Pathogenesis of periarticular and cardiac lesions is unknown. The role of Clq and anti-Clq antibody is discussed.

We have evaluated the effects of an elimination diet in 5 patients with hypersensitivity vasculitis and a personal or family history of allergy. The presence of autoimmune disorders, infections and neoplastic diseases was excluded on the basis of physical examination, clinical history and laboratory data. Three patients had elevated serum immune complexes and evidence of complement consumption before the oligoantigenic diet. In one patient food allergy was diagnosed on the basis of a positive and concordant challenge test, skin prick test and RAST. The study consisted of a 3 week elimination diet, followed by open and double blind challenge tests with specific foods and additives. Four patients achieved a complete remission and one patient experienced great improvement on the elimination diet. In three cases the vasculitis relapsed following the introduction of food additives; in one case with the addition of potatoes and green vegetables (i.e., beans and green peas) and in the last case with the addition of eggs to the diet. The offending foods and additives were subsequently eliminated from the usual diet and no relapses were observed in 2 years of follow-up. These results show that in selected patients with a history of allergy, hypersensitivity vasculitis can be triggered and sustained by food antigens or additives.

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.