Galactose-deficient IgA1 in skin and serum from patients with skin-limited and systemic IgA vasculitis.

BACKGROUND: IgA vasculitis (IgAV) encompasses a systemic form involving kidneys, gut, skin, or joints, and a skin-limited form. One characteristic feature of systemic IgAV is deposition of galactose-deficient IgA1 (GD-IgA1) in kidneys (as in IgA nephropathy). The relevance of GD-IgA1 for cutaneous vasculitis is unknown. OBJECTIVE: We investigated whether GD-IgA1 is deposited perivascularly in systemic and also skin-limited IgAV and whether its serum levels differ between both forms. METHODS: In a case-control study, deposition of GD-IgA1 was analyzed immunohistochemically by KM55 antibody in skin biopsy specimens from 12 patients with skin-limited IgAV and 4 with systemic IgAV. GD-IgA1 levels were compared by enzyme-linked immunosorbent assay in sera from 15 patients each with skin-limited and systemic IgAV and from 11 healthy individuals. RESULTS: All biopsy samples from systemic IgAV, and also from skin-limited IgAV, revealed perivascular GD-IgA1 deposition. The average GD-IgA1 concentration in serum was significantly higher in systemic IgAV than in skin-limited IgAV, despite overlap between the groups. LIMITATIONS: Although high GD-IgA1 levels may be predictive of systemic IgAV, patient numbers were too low to determine cutoff values for systemic versus skin-limited IgAV. CONCLUSION: Perivascular GD-IgA1 deposition is a prerequisite for systemic and skin-limited IgAV; however, high GD-IgA1 levels in some patients with systemic IgAV suggest a dose-dependent effect of GD-IgA1 in IgAV.

Are the cutaneous manifestations in patients with primary antiphospholipid syndrome a marker for predicting lung manifestations?

OBJECTIVES: The aim of this study was to investigate association between pulmonary and skin manifestations in a large group of patients with primary antiphospholipid syndrome (PAPS) as well as their connection with antiphospholipid antibodies. METHODS: Our prospective study comprises of 390 patients with primary APS. Antiphospholipid antibody (aPL) analysis included detection of aCL (IgG/IgM), ß2GPI (IgG/IgM) and LA. Distinct pulmonary and skin associations were determined, as well as their associations with aPL. RESULTS: In PAPS patients the presence of LA was more common in PTE (p=0.005) and in pulmonary microthrombosis (p=0.003). We revealed statistical significance considering the presence of aCL IgM and pulmonary microthrombosis (p=0.05). Skin ulcerations correlated with positive titres aCL IgM and ß2 GPI IgM (p=0.03 and 0.04, respectively), while pseudovasculitis correlated with positive titres ß2 GPI IgM (p=0.02). PAPS patients were more more likely to develop pulmonary thromboembolisam if they had livedo reticularis (p=0.005), skin ulcerations (p=0.007), pseudovasculitic lesions (p=0.01), superficial cutaneous necrosis (p=0.005), and digital gangrene (p=0.02). Patients were also more prone to pulmonary microthrombosis if they already had livedo reticularis (p=0.03), skin ulcerations (p=0.007), pseudovasculitic lesions (p=0.05), superficial cutaneous necrosis (p=0.006), and digital gangrene (p=0.02). CONCLUSIONS: There is strong link between some pulmonary and skin manifestations in PAPS patients, suggesting complexity and evolutionary nature of APS. The presence of skin manifestations may be a high risk factor for several types of serious pulmonary manifestations in PAPS. Certain aPL types are associated with distinct pulmonary and skin manifestation, suggesting their predictive role.

Association between peripheral vascular endothelial dysfunction and livedoid vasculopathy.

BACKGROUND: Livedoid vasculopathy (LV) is a disease characterized by multiple painful and recurrent ulcerations on the feet, accompanied by atrophic scars. Many researchers suggest that a hypercoagulable status is the pathogenetic factor for LV. However, the cause of LV remains elusive. OBJECTIVE: We sought to determine if endothelial dysfunction is present in patients with LV. METHODS: This prospective study included 16 patients with LV and active ulcers and 16 matched control subjects. We reviewed detailed clinical parameters, including antinuclear antibody, high-sensitivity C-reactive protein, protein C, protein S, homocysteine, anti-SSA, anti-SSB, anticardiolipin antibody, and serum lipid profiles. Flow-mediated vasodilation of the brachial artery was used as an indicator of vascular endothelial function using high-resolution 2-dimensional ultrasonic imaging. RESULTS: Blood pressure, blood biochemistry, high-sensitivity C-reactive protein, and homocysteine were not significantly different in patients with LV and control subjects. Nitroglycerin-mediated vasodilation was not significantly different in patients with LV and control subjects. However, flow-mediated vasodilation was much less in patients with LV than in the control group (3.58 ± 2.32% vs 7.51 ± 2.40%, P < .001). LIMITATIONS: The study was performed at a single site with a limited sample size. CONCLUSION: Peripheral vascular endothelial dysfunction was demonstrated in patients with LV by reduction of brachial flow-mediated vasodilation.

Anti-edematous effects of tolvaptan in experimental rodent models.

PURPOSE: The aim of this study was to evaluate the therapeutic efficacy of tolvaptan, a vasopressin V(2) receptor antagonist, on edema in two rat models: 1) histamine-induced vascular hyperpermeability of the dorsal skin and 2) carrageenan-induced paw edema. METHODS: In the skin vascular hyperpermeability model, 3 h after oral administration of tolvaptan or the natriuretic agent furosemide, rats were intravenously injected with Evans Blue (EB), followed by intradermal injection of 10 µg of histamine into the dorsal skin. One hour later, blood was collected to measure serum parameters. EB leakage area into the dorsal skin was also measured. Urine was collected for 4 h to determine urine parameters. In the paw edema model, edema was induced by injecting 1% w/v carrageenan into the right hind paw. Paw volume was measured hourly for 5 h. Tolvaptan or furosemide was orally administered 1 h before carrageenan injection. RESULTS: A single oral dose of tolvaptan (1-10 mg/kg) elicited marked and dose-dependent aquaresis, and improvements in edema. Similar effects were observed with furosemide (30 mg/kg). Tolvaptan tended to elevate the serum sodium level while furosemide caused a significant decrease. CONCLUSION: Tolvaptan had anti-edematous effects in two different rat models. By increasing free water excretion, tolvaptan may be more advantageous for certain patients than loop diuretics because it does not cause electrolyte loss, and may prevent electrolyte abnormities, such as hyponatremia. These results suggest that tolvaptan has potential clinical benefits for the treatment of edema.

Increased serum levels of the chemokine CXCL13 and up-regulation of its gene expression are distinctive features of HCV-related cryoglobulinemia and correlate with active cutaneous vasculitis.

Chemokine CXCL13, also known as BCA-1 (B cell-attracting chemokine-1) or BLC (B-lymphocyte chemoattractant), is a major regulator of B-cell trafficking. Hepatitis C virus (HCV) infection may be associated with B-cell dysfunction and lymphoproliferative disorders, including mixed cryoglobulinemia (MC). This study evaluates circulating levels of CXCL13 protein and specific mRNA expression in chronically HCV-infected patients with and without MC. Compared with healthy controls and HCV-infected patients without MC, CXCL13 serum levels were significantly higher in MC patients. The highest CXCL13 levels strongly correlated with active cutaneous vasculitis. CXCL13 gene expression in portal tracts, isolated from liver biopsy tissues with laser capture microdissection, showed enhanced levels of specific mRNA in MC patients with active cutaneous vasculitis. Specific CXCL13 gene mRNA expression was also up-regulated in skin tissue of these patients. These findings paralleled specific deposits of CXCL13 protein both in the liver and in the skin. Our results indicate that up-regulation of CXCL13 gene expression is a distinctive feature of HCV-infected patients. Higher levels of this chemokine in the liver as well as in the skin of patients with active MC vasculitis suggest a possible interrelation between these biologic compartments.

Cutaneous manifestations of antiphospholipid antibody syndrome.

Many different cutaneous lesions or cutaneous-systemic syndromes can be the presenting sign of antiphospholipid antibody syndrome (APS), or can develop during the course of disease. None of these conditions are specific for APS. Livedo reticularis or racemosa is commonly seen in APS, but it is one of the least specific findings. Other diseases are less commonly seen, in either their idiopathic or APS-associated form, but are more suggestive of APS. APS should be considered in patients who may appear to have idiopathic livedo reticularis with cerebrovascular accidents (Sneddon's syndrome), atrophie blanche, livedoid vasculitis, malignant atrophic papulosis, or anetoderma. Finally, retiform (branching, stellate) purpura or necrosis is perhaps the most characteristic cutaneous lesion of many different cutaneous microvascular occlusion syndromes, including APS.

Uncoupling of protein C and antithrombin III activity in cerebral ischemia patients associated with cutis marmorata.

PURPOSE: Cutis marmorata is a cutaneous livedoid disorder which can be differentiated from livedo reticularis in both clinical and pathological presentations. Unlike Sneddon syndrome, a detailed immunocoagulation profile has not yet been delineated for cutis marmorata in patients with cerebral ischemia. METHODS: To analyze the immunocoagulation profile in cutis marmorata patients associated with cerebral ischemia (CMCI) in a series of 135 cerebral ischemia patients. RESULTS: A total of 32 patients were found to have cutis marmorata. The blood protein C activity, protein S activity, antithrombin III activity, platelet count, fibrinogen and frequency of abnormal antiphospholipid antibody level were similar among 32 CMCI patients, 103 cerebral ischemia patients without cutis marmorata, and 35 healthy subjects. However, uncoupling of protein C and anti-thrombin III was observed in CMCI patients. Serum antinuclear antibody and Venereal Disease Research Laboratory were not detected in these patients. CONCLUSION: Cutis marmorata is not uncommon in our ischemic stroke patient population, and is characterized by uncoupling of protein C and antithrombin III with altered thrombin hemostasis. Our findings raise the need for a careful cutaneous examination in patients with ischemic stroke. Abnormal immunocoagulating profile should alert physicians to the risk for cerebral ischemia even in the absence of other cardiovascular risk factors.

Cytomegalovirus-associated cutaneous vasculopathy and scleroderma sans inclusion body change.

Viruses have long been held to be of pathogenetic importance in the evolution of autoimmune connective tissue disease. We describe 7 adults who developed cutaneous connective tissue disease stigmata in temporal association with recent cytomegalovirus (CMV) infection but without the classic cytopathic changes of CMV infection. We examined 7 adults with clinical presentations encompassing cutaneous vasculitis in 4 and scleroderma in 3. In all 7 patients, there was either IgM seropositivity for CMV and/or CMV DNA isolation from peripheral blood. Although no CMV inclusions were seen, in situ hybridization studies revealed very focal CMV RNA transcript expression with localization mainly to the endothelium. The patients with vasculitis treated with ganciclovir had improvement or resolution of symptoms, whereas only 1 patient with scleroderma received antiviral therapy, without benefit. Another scleroderma patient responded to infliximab therapy. Abortive/partial CMV reactivation can be associated with a syndrome complex mimicking and/or triggering a primary immune-based cutaneous microvascular injury syndrome. Antiviral therapy appears to be of therapeutic value in those cases associated with active necrotizing vasculitic changes. The role of tumor necrosis factor alpha blockers in scleroderma cases temporally associated with CMV infection requires further evaluation.

Altered hemostasis in migraineurs studied with a dynamic flow system.

INTRODUCTION: Livedo reticularis (LR) refers to the violaceous netlike pattern of skin related to arteriopathy at the dermis-subcutis border. Livedo is associated with migraine, and among migraineurs, LR is more common in those with prior stroke. Other evidence of vascular perturbation in migraine comes from studies showing elevated von Willebrand factor (vWF). The purpose of this study is to evaluate global hemostasis in migraineurs, including the subset with LR, using a dynamic flow system simulating physiological conditions, and measuring vWF activity and antigen levels. MATERIALS AND METHODS: Patients with migraine were enrolled from the headache clinic and presence or absence of LR was noted. Age-matched healthy, non-migraine, LR-free individuals were recruited as controls. To evaluate hemostasis, we used the Clot Signature Analyzer (CSA) measuring platelet hemostasis time (PHT), collagen-induced thrombus formation (CITF), and clot time (CT). vWF activity and vWF antigen levels were also measured. RESULTS: The mean vWF activity level (142.7 vs. 103.4, p<0.01) and antigen level (132.1 vs. 104.5, p<0.05) were higher, and all three hemostasis parameters shorter in the episodic migraineurs than in the controls. The subset of migraineurs with LR had the highest vWF activity (155+/-59, p<0.05) and vWF antigen (141+/-43, p<0.05) levels, and the shortest PHT (3.7+/-1.6, p<0.05). In this subset there was a significant inverse correlation between vWF activity and PHT (r=-0.51, p=0.01). CONCLUSIONS: For migraineurs, the differences from controls in vWF and PHT are most robust in the LR subset, with the inverse correlation suggesting that endothelial perturbation may be causally related to the response of the platelets.

Livedoid vasculopathy: further evidence for procoagulant pathogenesis.

OBJECTIVE: To further characterize the clinical and pathologic features, disease associations, and laboratory abnormalities of livedoid vasculopathy. DESIGN: Retrospective study of patients identified from our institutional database from January 1, 1990, to December 31, 2000. SETTING: Tertiary care institution. Patients Forty-five patients with biopsy-proved livedoid vasculopathy. MAIN OUTCOME MEASURES: Clinical presentation, histopathologic diagnosis, results of testing for coagulation abnormalities, and assessment of vascular status. RESULTS: Thirty-two patients (71.1%) were female (mean age, 45 years; age range, 10-85 years). Bilateral lower extremity disease occurred in 36 patients (80.0%), ulceration in 31 (68.9%), and atrophie blanche in 32 (71.1%). In patients tested, transcutaneous oximetry measurements were decreased in 20 (74.1%) of 27, and factor V Leiden mutation (heterozygous) was noted in 2 (22.2%) of 9, decreased activity for protein C or protein S in 2 (13.3%) of 15, prothrombin G20210A gene mutation in 1 (8.3%) of 12, and lupus anticoagulant in 5 (17.9%) of 28. Anticardiolipin antibodies were present in 8 (28.6%) of 28 patients, and elevated homocysteine levels in 3 (14.3%) of 21. Intraluminal thrombosis was observed in 44 (97.8%) of 45 skin biopsy specimens. Direct immunofluorescence disclosed multiple vascular conjugates in 31 (86.1%) of 36 biopsy specimens. CONCLUSIONS: Livedoid vasculopathy was predominantly bilateral, affected the lower extremities, and was associated with ulceration and atrophie blanche. Histologic evidence of intraluminal thrombosis was observed in almost all biopsy specimens reviewed. Laboratory testing revealed numerous heterogeneous coagulation abnormalities, providing further evidence of procoagulant mechanisms.

Livedoid vasculopathy associated with plasminogen activator inhibitor-1 promoter homozygosity (4G/4G) treated successfully with tissue plasminogen activator.

BACKGROUND: Livedoid vasculopathy (LV) is an occlusive thrombotic disease that affects primarily the small blood vessels of the lower extremities and often is associated with recurrent painful ulcerations. The pathogenesis of LV is unclear, but the disease is largely attributed to a hypercoagulable state. Factor V Leiden mutation, heterozygous protein C deficiency, homozygous hyperhomocysteinemia, and other inherited thrombophilias have been associated with LV. Plasminogen activator inhibitor-1 (PAI-1) is an important inhibitor of the fibrinolytic system. Elevated levels of PAI-1 are found in some patients with thrombotic diseases. Some of these patients are homozygous for an allele of PAI-1 containing a stretch of 4 guanines at base -675 in the promoter region. This variant is associated with elevated PAI-1 protein levels, impaired fibrinolysis, and increased risk of thrombosis. OBSERVATIONS: A 33-year-old white woman had a 3-month history of painful enlarging ulcers on both ankles. Various therapies, including administration of oral antibiotic agents and prednisone up to 100 mg/d, to treat presumed vasculitis, were unsuccessful. Skin biopsy specimens revealed numerous thick-walled small blood vessels, many of which were filled with fibrin thrombi, in association with minimal perivascular inflammatory infiltrate, extensive epidermal necrosis, and focal ulceration. A diagnosis of thrombotic vasculopathy was made. Clinical workup revealed an elevated plasma level of PAI-1 (31 microM/mL; reference range, <25 microM/mL) and PAI-1 promoter 4G/4G homozygosity detected at DNA sequencing. Treatment with heparin sodium and tissue plasminogen activator dramatically improved the lesions, resulting in complete healing of the ulcerations. Continuation of anticoagulant therapy with warfarin sodium and episodic administration of tissue plasminogen activator was required for symptomatic control. CONCLUSIONS: Patients with LV may have elevated plasma PAI-1 levels. This may be associated with the PAI-1 promoter 4G/4G genotype, which has not previously been linked with LV. Further studies in patients with LV are warranted to determine how frequently this genotype is present because it may identify responsiveness to fibrinolytic therapy.

Livedo vasculopathy vs small vessel cutaneous vasculitis: cytokine and platelet P-selectin studies.

OBJECTIVE: To assess the role of platelets and lymphocyte-related immunological mechanisms in livedo vasculopathy (LV) and cutaneous small vessel vasculitis (CSVV). Livedo vasculopathy is thought to be related to the thrombotic occlusion of small and medium-sized dermal vessels. Cutaneous small vessel vasculitis comprises a heterogeneous group of disorders in which the main pathogenetic events could be modulated by circulating cytokines. DESIGN: Case series study of 2 groups of patients affected respectively with LV and CSVV. SETTING: A large clinical and research institute for the study and treatment of cutaneous diseases. PATIENTS: Consecutive patients with clinically and histologically proved idiopathic LV (n = 8) and CSVV (n = 20) were studied and compared with healthy donors (n = 20). Patients with potentially correlated systemic diseases were excluded. MAIN OUTCOME MEASURES: Surface expression of platelet P-selectin and circulating level of interleukin (IL) 1beta, tumor necrosis factor alpha (TNF-alpha), IL-8, IL-2, and soluble IL-2 receptor. RESULTS: The IL-2 and soluble IL-2 receptor levels were significantly higher in serum samples from patients with both LV (1.24 +/- 0.46 IU/mL [mean +/- SD] vs 0.46 +/- 0.24 IU/mL, P<.001; 899 +/- 368 IU/mL vs 628 +/- 132 IU/mL, P<.02) and CSVV (0.91 +/- 0.57 IU/mL, P<.02; 1087 +/- 451 IU/mL, P<.001) than in those from the healthy controls. The serum levels of IL-1beta, TNF-alpha, and IL-8 were higher in patients with CSVV than in controls (7.53 +/- 6.7 pg/mL vs 4.58 +/- 2.72 pg/mL; 23.7 +/- 12.6 pg/mL vs 10.82 +/- 2.46 pg/mL, P<.001; 37.8 +/- 46 pg/mL vs 8.25 +/- 3.53 pg/mL, P<.02, respectively). No significant difference in the serum levels of IL-1beta (7.2 +/- 4.9 pg/mL), TNF-alpha (12.9 +/- 3.47 pg/mL), and IL-8 (5.9 +/- 4.13 pg/mL) was observed in patients with LV compared with controls. An increased expression of platelet P-selectin was also detected in patients with LV in comparison with controls and patients with CSVV. The mean +/- SD percentage of positive cells for P-selectin was 43% +/- 5% in the patients with LV, 5.1% +/- 2% in the controls (P<.001), and 5.3% +/- 2% in the patients with CSVV (P<.001). CONCLUSIONS: Taken together, these data demonstrate that different pathogenetic mechanisms are operative in LV and CSVV. In fact, platelet and lymphocyte activation is present in LV, whereas the levels of inflammatory mediators are in a normal range. In CSVV, the high serum levels of proinflammatory cytokines suggest that they are actively involved in the pathogenesis of cutaneous vasculitis.

[Abnormal fibrinolysis in Degos disease. A study of 3 cases]. / Anomalies de la fibrinolyse dans la maladie de Degos. Etude de trois cas.

INTRODUCTION: Degos' disease is a rare dermatosis characterized by papular lesions with a porcelain-white central atrophy and histopathological aspect of wedge-shaped infarction necrosis and an endovasculitis in the dermis. Its pathogenesis is unknown but many abnormalities of haemostasis have been reported. PATIENTS AND METHODS: Platelets functions, coagulation and fibrinolysis were estimated in three patients with Degos' disease. For one patient, direct immunoelectron microscopy using an antibody to von Willebrand factor was performed on lesional skin. RESULTS: In all the patients, prolonged euglobulin lysis time, increased plasminogen activator (PA) and plasminogen activator inhibitor (PAI) activities before and after a venous occlusion test were detected and indicated an inhibition of fibrinolysis. Electron microscopy demonstrated in one case an increased number of Weibel-Palade bodies and a raised staining of von Willebrand factor in endothelial cells. Tests for coagulation and circulating anticoagulant were normal. Results of platelets adhesion showed decrease of adhesion in one case and increased adhesion in another. Platelets aggregation studies were normal in two cases and showed hyperactive spontaneous and induced aggregation in one case. CONCLUSION: We showed an inhibition of fibrinolysis in three patients with Degos' disease. These abnormalities could induce a prethrombotic state. The release of PA and PAI from the endothelial cells into the blood stream and the modifications observed with electron microscopy may signify a primary lesion of endothelial cell of still unknown origin.

[Livedo reticularis in patients with systemic lupus erythematosis and its association with anticardiolipin antibodies]. / Livedo reticularis en pacientes con Lupus Eritematoso Sistémico y su asociación con anticuerpos anticardiolipina.

With the purpose of determining whether a relationship exists between Livedo Reticularis (LR) and anticardiolipine antibodies (ACA) in patients with Systemic Lupus Erithemathosus (SLE), a clinical prospective and descriptive study was carried out on 17 female lupus patients with LR, aged 15-46, from the Immunology and Dermatology outpatient clinic of the Enrique Tejera Hospital Compound in Valencia, Venezuela, during 1998. A complete clinical evaluation of each patient was done, from which a diagnosis of LR was made. This was categorized as mild, moderate or severe (Weinstein and col. criteria), depending on the severity of the lesions. Immunoenzymatic techniques were used to determine ACA Ig or IgM. The study followed the Guidelines of Good Practices in Clinical Research, and a signed informed consent was obtained from each patient. The average age of the studied patients was 28.5 +/- 10.9 years; 52.9% of them presented serum levels of ACA IgG above normal. In all cases, levels of ACA IgM were within normal limits (4.41 +/- 2.63 U/mL. Range: 0.51-9.53). All patients with mild LR had normal levels of ACA IgG, and 83.3% and 80% of those in the Moderate and Severe categories, respectively, had high levels of ACA IgG (> or = 10 U/mL), and there was a statistically significant association between each of the three categories and their respective ACA levels (p < 0.05). 82.4% of the patients had severe manifestations of the disease which included: CNS involvement, lower limb vasculitis, renal insult, pericarditis, thrombocytopenia, and recurrent miscarriages. No statistically significant association was found between each of these manifestations and the severity of LR (p > 0.05), probably due to the small number of patients studied in each group; nor between the medium serum levels of ACA IgG and each of the manifestations, except for lower limb vasculitis (ACA IgG'values-presence or absence: Fisher p: < 0.05) However, a statistically significant association (p < 0.05) was observed when the number of severe manifestations of the disease of each patient was related to the levels of ACA IgG, and the severity of LR.

[Sneddon's syndrome and Willebrand's factor antigen]. / Sindrom Sneddona i antigen faktora Villebranda.

An enzyme immunoassay examination of Willebrand factor antigen (WFA) was conducted in 36 patients with Sneddon's syndrome. The syndrome in 25 females and 11 males (mean age 40 years) was mainly characterized by ischemic cerebrovascular disorders in combination with advanced skin livedo. All the patients were not in an acute stroke phase. Increased WFA (above 2 IU/ml) occurred in 12 (33%) patients. Clinical manifestations, the condition severity, incidence of phospholipid antibodies, CIC levels in them were similar to those in patients with normal WFA values. The thrombotic trend in Sneddon's syndrome may result in some cases from structural endothelial damage responsible for WFA levels elevation, while under normal WFA content endothelial cell function may be affected.

Cutaneous vasculopathy and neutropenia associated with levamisole-adulterated cocaine.

BACKGROUND: Levamisole has recently been implicated as a cause of cutaneous vasculopathy in cocaine abusers. The objective of this study was to describe this relatively new entity by reviewing published cases identified through a literature search. METHODS: Published reports identified through a search of PubMed database (from 1964 to November 2011) were reviewed to record clinical, serological and pathologic findings. RESULTS: A cohort of 32 patients had a mean age of 44 ± 9 years with a female predominance (75%). Rash predominately affected lower extremities (87.5%), followed by face (78%) and ears (69%) and typically presented as purpuric plaques, which were seen in a retiform pattern in 16 (50%) and had central necrosis in 11 patients (34%). Leukopenia and neutropenia were found in 20 patients (63%). Antinuclear cytoplasmic antibody (ANCA) was positive in 30 patients (94%); p-ANCA in 28 patients (87.5%), c-ANCA in 19 (59%) and both in 17 patients (53%). Skin biopsy results were available for 29 patients: 14 (48%) had pure thrombotic vasculopathy, 4 (14%) had pure small vessel vasculitis and 11 (38%) had evidence of both. Treatment information was available for 30 patients. Only supportive care was given to 11 patients (37%), steroids to 16 (53%) and surgical treatment for 5 (17%). Clinical course of lesions was available for 24 patients. Rash resolved in 11 patients (46%) and improved in 13 (54%). During median follow-up of 21 days (range, 7-270 days), 10 of 22 patients had recurrences related to cocaine use. CONCLUSION: Levamisole-induced cutaneous vasculopathy in cocaine users is characterized by a female predominance, a retiform purpuric rash with a predilection for lower extremities, autoantibody production, leukopenia and/or neutropenia and recurrences with future cocaine use.