[Drug-induced vasculitis]. / Vascularites médicamenteuses : à propos d'une série de 13 cas.

INTRODUCTION: Drug-induced vasculitis is reported in almost 10-20 % of vasculitis. Several drugs may be incriminated in their occurrence. Our study aimed to study the epidemiological, clinical, histopathological and evolutionary characteristics of drug-indced vasculitis from a series of cases and to specify the different drugs involved. METHODS: We conducted a retrospective study during the period from January 2006 to December 2015 from the cases notified to the regional pharmacovigilance center of Sousse, Tunisia. The diagnosis was established according to the criteria proposed by the group of the American college of rheumatology (ACR). RESULTS: Our study included thirteen cases of drug-induced vasculitis over a ten-year period, with an mean incidence of 1.3 new cases per year. Mean age of patients was 40.84 years. The mean delay from the treatment onset was 14.46 days with extremes ranging from 5 days to six weeks. Most patients had pure skin involvement. Association with other extracutaneous complaints was present in five cases. Cutaneous biopsy was performed in all patients showing a pathological pattern of leukocytoclastic vasculitis, associated with fibrinoid necrosis, extravasation of red blood cells and allergic capillaritis. The outcome was favorable for all patients. The offending drugs in our series were amoxicillin, pristinamycin, rifampicin, fluconazole, metformin, glimepiride, phenobarbital, gabapentin, fenofibrate, ibuprofen, allopurinol, rituximab and tinzaparin. CONCLUSION: Anamnestic, clinical, biological and histopathological findings allow the early recognition of drug-induced vasculitis. Adequate treatment prevents systemic spreading and a worse prognosis.

Erythema elevatum diutinum: a case report and review of literature.

Erythema elevatum diutinum (EED) is a rare cutaneous leukocytoclastic vasculitis thought to be related to increased levels of circulating antibodies. It has been shown to be associated with HIV infection, tuberculosis, as well as various autoimmune diseases. A retrospective review of all cases of EED indexed in PubMed between 1990 and 2014 was performed. Inclusion criteria for articles was availability of full text in English and a biopsy-confirmed diagnosis of EED. All other articles were excluded. Cases were stratified by age and anatomic location of the lesions. Treatment response was coded as "complete," "partial," and "none." A total of 133 cases of EED with 381 lesions detailed in case reports and case series were included. Twenty-one cases were associated with HIV. Of 47 patients with reported paraproteinemias, IgA paraproteinemia was found in 57.45%, IgG paraproteinemia in 29.8%, IgM paraproteinemia in 10.6%, and IgD paraproteinemia in 2.1% of cases. Of 40 (30.1%) patients with reported comorbid autoimmune disease, rheumatoid arthritis was associated with 10 cases. Cancer was found to be associated with 9.77% of cases. Seventy-five patients were treated with dapsone, with 36 (48%) achieving complete treatment response, 24 (32%) achieving partial response, and seven (9.3%) achieving no response. Keeping the clinical associations of EED in mind, especially malignancy, is critical in management of the disease. More structured studies need to take place in order to fully define the mechanisms and strength of these associations.

Pediatric vasculitis: a single center experience.

BACKGROUND: Existing studies of children with vasculitis are limited. The aim of this study was to assess the epidemiology, clinical manifestations, laboratory findings, course, and outcome of Greek children presenting with vasculitic rash. METHODS: The relevant data included in the study were collected retrospectively using a standardized form from children who were admitted into our department between 2003 and 2013, with the provisional diagnosis of vasculitis of the skin. RESULTS: The study sample consisted of 95 children (58 boys, 37 girls) with a mean age of 5.9 years. In total, 76 out of 95 (80%) of the children were diagnosed with Henoch-Schönlein purpura, 10/95 (10.5%) with hypersensitivity vasculitis, 6/95 (6.3%) with urticarial vasculitis, and 3/95 (3.1%) with acute hemorrhagic edema of infancy. The mean age of the children was 5.7 years for Henoch-Schönlein purpura, 9 years for hypersensitivity vasculitis, 5.1 years for urticarial vasculitis, and 0.5 years for acute hemorrhagic edema of infancy. CONCLUSIONS: (i) The most common vasculitis presenting with skin rash in children is Henoch-Schönlein purpura; (ii) hypersensitivity vasculitis occurs in older children more often when compared to other types of vasculitis; (iii) urticarial vasculitis lesions may be a sign of severe underlying disease; therefore a thorough examination of these patients is warranted; (iv) Despite relapses, the overall prognosis of patients with pediatric skin vasculitides is good, with the exception of those with the urticarial vasculitis type.

[Cutaneous leukocytoclastic vasculitis: about 85 cases]. / Vascularites cutanées leucocytoclasiques: à propos de 85 cas.

Clinical manifestation, etiology and outcome of leukocytoclastic vasculitis are little studied. The aim of our study was to examine epidemiological, clinical etiological, and evolutionary characteristics of this entity. We conducted a cross-sectional data collection from medical records of 85 patients with leukocytoclastic vasculitis in the Department of Dermatology at the Farhat Hached University Hospital, Sousse between January 2000 and December 2013. Epidemiological, clinical, paraclinical, etiological data sheets had been completed for each patient. The average age of patients was 47.65 years, ranging between 10 and 78 years. Fifty-three women and 32 men were registered (sex ratio = 0.6). Cutaneous manifestations were dominated by vascular purpura (88.2%). The most common causes of leukocytoclastic vasculitis were systemic diseases (51%), infection (20%) and neutrophilic dermatoses (14.5%). Other causes were drugs (9.1%) and hematologic malignancies (5.4%). The cause of leukocytoclastic vasculitis was not detected in 30 patients (35, 3%). Two predictive factors associated with the acute outcome were retained: the presence of a recent infection (p= 0.014) and drug intake before the rash (p= 0.013). Chronic evolution was positively correlated with antinuclear antibodies (p= 0.009) and cryoglobulinemia (p=0.025). Our study highlights the multitude of causes of leukocytoclastic vasculitis. The search for an underlying disease is an imperative in order to ensure better therapeutic management.

Acute hemorrhagic edema of infancy: the experience of a large tertiary pediatric center in Israel.

BACKGROUND: Acute hemorrhagic edema of infancy (AHEI) is a rare leukocytoclastic vasculitis of the small vessels occurring at a young age and considered as a benign self-limited disease. Due to its low prevalence, there are limited data on the presentation and complications of this disease. METHODS: All computerized files of children who were hospitalized at a tertiary pediatric center due to AHEI over a 10 year period were reviewed. Clinical, laboratory and histopathological data were collected. RESULTS: Twenty-six patients were included in our study, accounting for 0.7 cases per 1000 admissions of children aged 2 years or less. Mean age was 12.9 months. More than two thirds of the children had preceding symptoms compatible with a viral infection. Upon admission, all patients presented with typical findings of a rash and edema. Edema was most profound over the lower extremities (73%). Concomitant viral or bacterial infections were found in six children. Skin biopsy was performed in six patients revealing leukocytoclastic vasculitis. Thirteen children (50%) had systemic involvement including joint involvement (n=9), gastrointestinal hemorrhage (n=4), microscopic hematuria (n=1) and compartment syndrome of the limb (n=1). The latter was diagnosed in a patient with familial Mediterranean fever. CONCLUSIONS: Our largest data series highlighted what is known regarding clinical and histological findings in children with AHEI. However, contrary to what was previously reported, we found a higher rate of systemic involvement. Although AHEI is a rare entity, pediatricians should be familiar with its presentation, management and our reported complications.

Clinical study on single-organ cutaneous small vessels vasculitis (SoCSVV).

Leukocytoclastic vasculitis (LCV) is a heterogenous group of disorders that may manifest as a mild disease isolated to the skin or be a part of life-threatening systemic vasculitis. According to the 2012 Chapel Hill Consensus Conference nomenclature, patients presenting symptoms of LCV confined only to the skin should be defined as suffering from a single-organ cutaneous small vessel vasculitis (SoCSVV). SoCSVV is a benign disease with a good clinical outcome but with a significant risk of relapse and skin ulcer formation.The aim of the current study was to characterize SoCSVV and to identify factors that may be associated with the risk of recurrence and skin ulcers.Medical records of patients with LCV hospitalized at the Department of Dermatology at University Hospital in Cracow in the years 2010 to 2015 were analyzed.A total of 24 patients fulfilled criteria of SoCSVV. Drugs and preceding infections were identified as precipitating factors in 40% and 20% of cases, respectively. Skin lesions other than palpable purpura (i.e., macules, urticarial vasculitis, or ulcers) were identified in almost half of the patients. Interestingly, the presence of macules independently increased the risk of skin ulcer formation (odds ratio = 16; 95% confidence interval: 1.5-176.6; P = 0.0075) in the multivariate logistic regression analysis. One-quarter of patients with SoCSVV experienced relapse during the 6-month follow-up. The greater number of affected skin areas was an independent risk factor of recurrence (odds ratio = 5; 95% confidence interval: 2-45; P = 0.02).SoCSVV was usually associated with drugs and preceding infections. The disease relapses in approximately one-quarter of the patients. The more severe the skin involvement in the course of SoCSVV, the higher is the risk of recurrence.

A 41-year-old woman with shortness of breath and history of rash and recurrent laryngeal edema.

A 41-year-old Hispanic woman with a 20 pack-year smoking history presented with worsening shortness of breath on exertion that gradually started 2 years ago, then significantly deteriorated over the last 4 months. She was diagnosed with COPD 2 months prior to her presentation and started on treatment with fluticasone propionate and albuterol. Her medical history was relevant for undifferentiated connective tissue disorder diagnosed 5 years prior due to a positive antinuclear antibody test, arthralgia, recurrent urticarial skin rash, peripheral neuropathy, abdominal pain, and diffuse body swelling. She was started on treatment with prednisone and azathioprine at the time and had substantial improvement in the occurrence of her urticaria. She also had a history of recurrent laryngeal edema of unclear etiology. She had no history of IV drug abuse, no exposure to animals, was not sexually active, and had no recent travel outside of Florida. There was no significant family history of lung diseases.

Incidence of leukocytoclastic vasculitis, 1996 to 2010: a population-based study in Olmsted County, Minnesota.

OBJECTIVE: To determine the population-based incidence of leukocytoclastic vasculitis (LCV). PATIENTS AND METHODS: This is a retrospective population-based study of all Olmsted County, Minnesota, residents with a skin biopsy-proven diagnosis of LCV from January 1, 1996, through December 31, 2010. RESULTS: A total of 84 patients (mean age at diagnosis, 48.3 years) with newly diagnosed skin biopsy-proven LCV (43 women and 41 men) were identified. The incidence rate (age and sex adjusted to the 2000 US white population) was 4.5 per 100,000 person-years (95% CI, 3.5-5.4). The incidence of LCV increased significantly with age at diagnosis (P<.001) and did not differ between female and male patients. Subtypes of LCV were cutaneous small-vessel vasculitis (CSVV), 38 patients (45%); IgA vasculitis, 25 (30%); urticarial vasculitis, 10 (12%); cryoglobulinemic vasculitis, 3 (4%); and antineutrophil cytoplasmic antibody-associated vasculitis, 8 (10%). LCV was idiopathic in 29 of 38 patients with CSVV (76%) and 24 of 25 patients with IgA vasculitis (96%). Thirty-nine of 84 patients (46%) had systemic involvement, with the renal system most commonly involved (17 of 39 [44%]). Twenty-four of 80 patients (30%) with follow-up data available had recurrent disease. Compared with the Minnesota white population, observed survival in the incident LCV cohort was significantly poorer than expected (P<.001), including the subset of patients with idiopathic CSVV (P=.03). CONCLUSION: The incidence of LCV was higher than that reported in previously published studies. Idiopathic LCV was more common in our population-based cohort than that described previously. Overall survival was significantly poorer (P<.001) and should be explored further in future studies.

Randomized comparison between polymer-free versus polymer-based paclitaxel-eluting stent: two-year final clinical results.

BACKGROUND: Most drug-eluting stents currently in use are coated with a polymer carrying the drug that is released for several weeks. However, a durable polymer may provoke hypersensitive reaction, delayed artery healing, and eventually stent thrombosis. The aim of this study was to investigate the safety and efficacy of a polymer-free paclitaxel-eluting stent (PF-PES) versus a polymer-based PES (PB-PES). METHODS AND RESULTS: Eligible patients undergoing percutaneous coronary intervention were randomized 1:1 to receive either PF-PES or PB-PES. The primary end point was late loss at 9 months. Intravascular ultrasound analysis at 9 months and final 2-year clinical follow-up were also performed. From October 2007 to April 2009, 164 patients were enrolled and randomized into 2 groups (PF-PES: n = 84; PB-PES: n = 80). Mean in-stent lumen loss was 0.90 ± 0.59 mm for PF-PES and 0.49 ± 0.52 mm for PB-PES (P < 0.001). Mean neointimal area by intravascular ultrasound was higher in PF-PES than in PB-PES (1.42 ± 1.09 versus 0.51 ± 0.61 mm(2); P < 0.001). At 2 years, a composite end point of all-cause death, any myocardial infarction, and target vessel revascularization occurred in 36.9% for PF-PES and 16.3% for PB-PES (P = 0.004), mainly driven by a higher rate of target vessel revascularization (PF-PES: 35.7%; PB-PES: 13.8%; P = 0.001). One late stent thrombosis was observed in PF-PES. CONCLUSIONS: Compared with PB-PES, PF-PES was associated with increased neointimal proliferation and subsequent clinical restenosis. Polymer plays an essential role in the performance of drug-eluting stents. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT01375855.

Revisiting clinical differences between hypersensitivity vasculitis and Henoch-Schönlein purpura in adults from a defined population.

OBJECTIVES: Hypersensitivity vasculitis (HV) and Henoch-Schönlein purpura (HSP) are the most common entities included within the category of cutaneous vasculitis (CV). Palpable purpura and histological changes characterised by the presence of leukocytoclastic vasculitis are common in both conditions. Therefore, considerable overlap between them is often seen. It is especially true when the CV occurs in adults. To further establish clinical differences between these two conditions, in the present study we assessed the main clinical differences between HV and HSP in a wide and unselected series of adults with CV from a defined population. METHODS: We reviewed the clinical records of 297 consecutive adults (age >20 years) seen at a single centre between January 1975 and December 2012 that were classified as having HSP or HV according to the criteria proposed by Michel et al. (J Rheumatol 1992; 19: 721-8). RESULTS: Based on the inclusion criteria, 102 adult patients (71 men/31 women) were classified as HSP and 195 (104 men/91 women) as HV. The mean age was similar in both groups (55.8±16.5 years in HSP and 56.8±18.3 years in HV). Precipitating events, usually an upper respiratory tract infection and/or drug intake, were more frequently observed in HV. Both at the beginning of the disease and when the CV was established clinical manifestations were more frequent in patients with HSP than in those with HV. It was the case for gastrointestinal (57.4% vs. 6.8%; p<0.001), joint (51.5% vs. 36.6%; p=0.01) and renal involvement (86.3% vs. 18.3%; p<0.001). Corticosteroid (56.7% vs. 22%; p<0.001) and cytotoxic drug (19.4% vs. 3.2%; p<0.001) use was also more common in patients with HSP. After a median follow-up of 15.5 (interquartile range- IQR; 3-37) months in HSP and 4 (IQR; 2-12) months in HV, the outcome was better in HV than in HSP. In this regard, complete recovery (72.6% vs. 85.4%; p=0.01) was more commonly observed in HV while residual renal involvement (15.3% vs. 4.2%; p<0.001) was more common in HSP. The disease relapsed in 35.3% of patients with HSP and in 24.4% with HV (p=0.07). CONCLUSIONS: Our results confirm the claim that these two diseases presenting with similar cutaneous involvement are certainly two separate entities with greater systemic involvement and less favourable outcome in HSP.

Urticarial vasculitis in northern Spain: clinical study of 21 cases.

Urticarial vasculitis (UV) is a subset of cutaneous vasculitis (CV), characterized clinically by urticarial skin lesions of more than 24 hours' duration and histologically by leukocytoclastic vasculitis. We assessed the frequency, clinical features, treatment, and outcome of a series of patients with UV. We conducted a retrospective study of patients with UV included in a large series of unselected patients with CV from a university hospital. Of 766 patients with CV, UV was diagnosed in 21 (2.7%; 9 male and 12 female patients; median age, 35 yr; range, 1-78 yr; interquartile range, 5-54 yr). Eight of the 21 cases were aged younger than 20 years old. Potential precipitating factors were upper respiratory tract infections and drugs (penicillin) (n = 4; in all cases in patients aged <20 yr), human immunodeficiency virus (HIV) infection (n = 1), and malignancy (n = 1). Besides urticarial lesions, other features such as palpable purpura (n = 7), arthralgia and/or arthritis (n = 13), abdominal pain (n = 2), nephropathy (n = 2), and peripheral neuropathy (n = 1) were observed. Hypocomplementemia (low C4) with low C1q was disclosed in 2 patients. Other abnormal laboratory findings were leukocytosis (n = 7), increased erythrocyte sedimentation rate (n = 6), anemia (n = 4), and antinuclear antibody positivity (n = 2). Treatment included corticosteroids (n = 12), antihistaminic drugs (n = 6), chloroquine (n = 4), nonsteroidal antiinflammatory drugs (n = 3), colchicine (n = 2), and azathioprine (n = 1). After a median follow-up of 10 months (interquartile range, 2-38 mo) recurrences were observed in 4 patients. Apart from 1 patient who died because of an underlying malignancy, the outcome was good with full recovery in the remaining patients. In conclusion, our results indicate that UV is rare but not exceptional. In children UV is often preceded by an upper respiratory tract infection. Urticarial lesions and joint manifestations are the most frequent clinical manifestation. Low complement serum levels are observed in a minority of cases. The prognosis is generally good, but depends on the underlying disease.

The spectrum of paraneoplastic cutaneous vasculitis in a defined population: incidence and clinical features.

Cutaneous vasculitis may be associated with malignancies, and may behave as a paraneoplastic syndrome. This association has been reported in a variable proportion of patients depending on population selection. We conducted the current study to assess the frequency, clinical features, treatment, and outcome of paraneoplastic vasculitis in a large unselected series of 766 patients with cutaneous vasculitis diagnosed at a single university hospital. Sixteen patients (10 men and 6 women; mean age ± standard deviation, 67.94 ± 14.20 yr; range, 40-85 yr) presenting with cutaneous vasculitis were ultimately diagnosed as having an underlying malignancy. They constituted 3.80% of the 421 adult patients. There were 9 hematologic and 7 solid underlying malignancies. Skin lesions were the initial clinical presentation in all of them, and the median interval from the onset of cutaneous vasculitis to the diagnosis of the malignancy was 17 days (range, 8-50 d). The most frequent skin lesions were palpable purpura (15 patients). Other clinical manifestations included constitutional syndrome (10 patients) and arthralgia and/or arthritis (4 cases). Hematologic cytopenias (11 cases) as well as immature peripheral blood cells (6 cases) were frequently observed in the full blood cell count, especially in those with vasculitis associated with hematologic malignancies. Specific treatment for vasculitis was prescribed in 10 patients; nonsteroidal antiinflammatory drugs (4 patients), corticosteroids (3 patients), chloroquine (1 patient), antihistamines (1 patient), and cyclophosphamide (1 patient). Ten patients died due to the malignancy and 6 patients recovered following malignancy therapy. Patients with paraneoplastic vasculitis were older, more frequently had constitutional syndrome, and less frequently had organ damage due to the vasculitis than the remaining patients with cutaneous vasculitis. In summary, cutaneous paraneoplastic vasculitis is an entity not uncommonly encountered by clinicians. The most common underlying malignancy is generally hematologic. In these cases the presence of cytopenias and immature cells may be red flags for the diagnosis of cancer. In patients with paraneoplastic cutaneous vasculitis, the prognosis depends on the underlying neoplasia.

Urticarial vasculitis: a retrospective study of 15 cases.

INTRODUCTION: Urticarial vasculitis is a subtype of vasculitis characterized clinically by urticarial lesions and histologically by necrotizing vasculitis. OBJECTIVE: To study the clinical and histologic features of urticarial vasculitis in patients seen in the dermatology department of Hospital Universitario Virgen de Rocío in Seville, Spain, and to examine the association between hypocomplementemia and systemic disease. MATERIAL AND METHODS: We performed a chart review of histologically confirmed cases of urticarial vasculitis in the database of our department covering a period of 10 years. RESULTS: Fifteen patients (9 women and 6 men with a median age of 51 years) were included. In 14 patients (93%), the lesions persisted for more than 24hours, and in 9 cases (60%) the lesions resolved leaving residual purpura or hyperpigmentation. Seven patients (47%) had low complement levels in the blood, 12 (80%) had extracutaneous symptoms, and 8 (53%) had associated systemic disease, the most common of which was systemic lupus erythematosus. CONCLUSIONS: Urticarial vasculitis may be underdiagnosed. Response to treatment is variable, and hypocomplementemia and extracutaneous symptoms may indicate the presence of associated systemic disease.

An 'inflammatory' variant of solar purpura: a simulant of leukocytoclastic vasculitis and neutrophilic dermatoses.

AIMS: To study the clinical and pathological features of cases of apparent solar purpura, with attention to the recently described phenomenon of inflammatory changes within otherwise typical lesions. METHODS: We studied 95 cases diagnosed as solar purpura and identified 10 cases (10.5%) in which significant neutrophilic inflammation was present, potentially simulating a leukocytoclastic vasculitis or neutrophilic dermatosis. An additional three cases were identified in subsequent routine practice. The clinical features, including follow-up for subsequent development of vasculitis and histological features were studied. RESULTS: In all cases the histological features were typical of solar purpura, with the exception of inflammatory changes, typically associated with clefting of elastotic stroma. Clinical follow-up information was available for all patients and none developed subsequent evidence of a cutaneous or systemic vasculitis or neutrophilic dermatosis. CONCLUSIONS: Inflammatory changes appear to be more frequent in solar purpura than is generally recognised. Awareness of this histological variation and correlation with the clinical findings and evolution is important in avoiding misdiagnosis.