A Review of Pediatric Vasculitis with a Focus on Juvenile Polyarteritis Nodosa

Systemic polyarteritis nodosa (PAN) is a vasculitis characterized and defined by necrotizing inflammatory changes in medium and/or small arteries. Children and adults with vasculitis differ in the relative frequency of some clinical manifestations and concomitant diseases. The European League against Rheumatism (EULAR)/Pediatric Rheumatology European Society (PRES) working group has proposed a classification of childhood vasculitis. With support from EULAR, the Pediatric Rheumatology International Trials Organization (PRINTO), and PRES, a formal statistical validation process, which included large-scale, web-based data collection, was undertaken. I now propose a set of criteria for systemic juvenile PAN that combines a modified mix of the EULAR/PRES criteria and the EULAR/PRINTO/PRES criteria. Cutaneous juvenile PAN is characterized by the presence of cutaneous features with no systemic involvement. The common cutaneous manifestations include cutaneous nodules and livedo racemosa. Our research group previously established an algorithm for the differential diagnosis of primary cutaneous vasculitis. We have recently developed a new version of that algorithm to diagnose vasculitis with cutaneous manifestations from a dermatologic point of view. Treatment of systemic juvenile PAN is based on a combination of cortico-steroids and immunosuppressant agents. The clinical course of cutaneous juvenile PAN is generally benign.     

Comparison of cutaneous manifestations in systemic polyarteritis nodosa and microscopic polyangiitis

Background  The cutaneous manifestations of microscopic polyangiitis (MPA) and polyarteritis nodosa (PAN) have not been compared since their distinction.
Objectives  To compare the clinical and pathological cutaneous manifestations in a series of patients with systemic MPA and PAN.
Methods  Patients with MPA ( n  =   162) and PAN ( n  =   248) from the database of the French Vasculitis Study Group were diagnosed according to the American College of Rheumatology and/or the Chapel Hill Consensus criteria. Purpura, livedo, nodules, urticaria, skin necrosis, oral and genital ulcers were recorded when present. Fifty-five skin biopsies were analysed. Clinical and histological skin data were compared in the following groups: MPA, PAN and two PAN subsets: PAN with and PAN without hepatitis B infection. The prevalence of systemic and biological manifestations were analysed in relation to the presence or absence of skin lesions. The χ² test was used for statistical studies.
Results  Cutaneous manifestations were present in 44% of MPA and PAN. Purpura was the most frequent manifestation (26% cases of MPA vs. 19% cases of PAN, P  =   0·026). Urticaria was more frequent during PAN (6% vs. 1·2%, P  =   0·015). Skin lesions were more frequent during PAN in the absence of HBV infection (54% vs. 30%, P  <   0·05). No significant difference was detected from the histological data. Patients with skin lesions (either MPA or PAN) presented arthralgias and ocular manifestations more frequently. Mononeuritis multiplex was associated with skin lesions in the MPA group ( P  <   0·05).
Conclusions  The clinical or histological analysis of cutaneous lesions is not helpful for distinguishing PAN from MPA.     

Kutane Vaskulitiden

Vasculitis is characterized by an inflammatory reaction of vessel walls with damage to the dependent tissues. Forms of vasculitis which frequently have skin changes include leukocytoclastic angiitis (LcV), Henoch-Schönlein purpura (HSP), cutaneous polyarteriitis nodosum (cPAN), erythema elevatum et diutinum (EED) and urticarial vasculitis (UV). In other forms of vasculitis, systemic manifestations predominate but there are a variety of skin changes. Kawasaki disease (MK), cryoglobulinemic vasculitis (kV), Wegener granulomatosis (WG), Churg-Strauss syndrome (CSS) and microscopic polyangitis (MPA) belong to this group. The causes of vasculitis are heterogeneous. Triggers include infections, drugs, collagen vascular diseases, autoimmune diseases and lymphoproliferative disorders. Idiopathic vasculitis, particularly LcV and EED, occur only once and have a self-limited course. The diagnostic work up depends on the clinical picture and includes inflammatory markers, circulating immune complexes, different types of cryoglobulins and anti-neutrophilic cytoplasmic antibodies, collagen vascular disease specific autoantibodies and additional hematological studies. Vasculitis can manifest in many organs and requires a thorough work up specifically in cases where WG, MPA, CSS and PAN are under consideration.     

Clinical and histopathological spectrum of cutaneous vasculitis in rheumatoid arthritis

BACKGROUND: Cutaneous manifestations are the most frequent, and often the initial feature of extra-articular involvement in patients with rheumatoid vasculitis. OBJECTIVES: The purpose of the study was to evaluate the clinical and histological spectrum of cutaneous vasculitis and the associated systemic involvement in patients with rheumatoid vasculitis. METHODS: Among 525 patients with rheumatoid arthritis, 20 tissue specimens with histologically proven cutaneous necrotizing vasculitis from 11 patients were investigated by studying the types and levels of affected vessels and related clinical features. RESULTS: Small-vessel vasculitis identified as dermal necrotizing venulitis was found in 10 patients, clinically characterized by palpable purpura, maculopapular erythema, erythema elevatum diutinum and haemorrhagic blisters. Arteritis histologically resembling cutaneous polyarteritis nodosa, clinically characterized by subcutaneous nodules, livedo reticularis, atrophie blanche and deep ulcers was identified in four patients all with systemic complications. Coexistence of venulitis and arteritis was identified in three patients. Different cutaneous vasculitic manifestations often coexisted and recurred in the same patient. Three patients with systemic complications of mononeuritis multiplex (two of three), interstitial pulmonary fibrosis (two of three) and abdominal microaneurysms (one of three) died within 1 year of onset of the cutaneous vasculitis. Immunofluorescence demonstrated vessel wall deposition of IgM and/or complement in six of the seven patients examined. CONCLUSIONS: Features of cutaneous rheumatoid vasculitis overlapping both the characteristics of cutaneous necrotizing venulitis and cutaneous polyarteritis nodosa together with coexistence of these different type of vasculitis in the same or different lesional skin account for the associated diverse cutaneous vasculitic manifestations. Although dermal venulitis (leucocytoclastic vasculitis) was the most common presentation, the presence of leucocytoclastic vasculitis in rheumatoid patients did not necessarily indicate a favourable prognosis. Associations with mononeuritis multiplex and bowel involvement had a fatal prognosis, while patients with superficial dermal venulitis without other extra-articular involvement may follow a favourable prognosis.     

Microscopic polyangiitis presenting urticarial erythema and Henoch-Schonlein purpura: two case reports

Microscopic polyangiitis (MPA) is well known as a life-threatening member of a group of systemic vasculitis diseases. We report two cases of MPA. Case 1 was a 79-year-old-man who had been diagnosed with anti-neutrophil-cytoplasmic-antibody associated vasculitis (ANCA associated vasculitis) with alveolar hemorrhage and crescentric glomerulonephritis (CrGN). He presented with urticarial erythema in the abdomen, legs and back. The skin biopsy specimens showed leukocytoclastic vasculitis on the upper dermis. Case 2 was a 74-year-old-man, who presented with purpura on the abdomen, buttocks and legs that were similar to Henoch-Schonlein purpura (HSP). He also suffered from interstinal pneumonia. His renal biopsy specimens showed glomerulosclerosis and the peripheral pattern anti-neutrophil cytoplasmic antibody (P-ANCA) was positive. We reviewed the skin eruptions that had been reported with MPA, including our cases.     

Henoch-Schönlein purpura presenting with anuria in an adult

Henoch-Sch?nlein purpura (HSP) is an immune complex-mediated systemic small vessel vasculitis that is most commonly described in children but may affect patients of any age. Our patient, a 91-year-old man, presented with anuria caused by IgA-mediated nephropathy; he later developed cutaneous leukocytoclastic vasculitis, thereby meeting the criteria for a diagnosis of HSP. This case is unique because of the patient's initial presentation with anuria, the possible underlying malignancy associated with his HSP, and his advanced age.     

Clinical classification of vasculitis

Clinical classification of vasculitis is needed to facilitate diagnosis and management of the disease as well as to assign patients to defined groups for clinical studies. Caliber and size of the vessels predominantly involved strongly influence the clinical features of the different forms of vasculitis and therefore are one major criterion for classification. As such, panarteritis nodosa involves medium-sized vessels and presents on the skin with subcutaneous nodules and livedo racemosa, while it does not cause glomerulonephritis. Leukocytoclastic vasculitis (LcV) involves the small vessels, resulting in palpable purpura, and sometimes also in glomerulonephritis. The classification systems of the American College of Rheumatology (ACR) and of the Chapel Hill Consensus Conference (CHCC) have gained wide acceptance. Yet, they need to be updated, especially with regard to LcV, the most common vasculitis of the skin. Here distinctions must be made for prognostic, diagnostic and therapeutic reasons between IgG/IgM- and IgA-associated LcV (Henoch-Schoenlein purpura, HSP), as well as between HSP of children and HSP of adult age. The latter bears the highest, while IgG/IgM-associated LcV bears the lowest risk for complications. This update on the clinical classification of vaculitis is based on the ACR and CHCC system and focuses on those forms which regularly cause cutaneous symptoms. It provides a survey on the vasculitic syndromes and should help in deciding when i) extensive diagnostic procedures are needed in patients with LcV, ii) therapy should be less or more aggressive, e.g. in cutaneous versus systemic PAN, iii) therapy should be promptly initiated, e.g. when any form of severe, ANCA-associated vasculitis is suspected.     

Treatment for cutaneous arteritis patients with mononeuritis multiplex and elevated C‐reactive protein

Cutaneous arteritis (cutaneous polyarteritis nodosa, CA) is a necrotizing vasculitis of arteries within the skin. CA is a new classification under single‐organ vasculitis, as adopted by the 2012 Chapel Hill consensus conference (CHCC 2012). Some patients originally diagnosed as having CA could develop additional disease manifestations that warrant reclassifying as systemic polyarteritis nodosa (PAN) according to the CHCC 2012. We retrospectively investigated 101 patients with CA seen at our department between 2003 and 2012. There was a significantly higher frequency of inflammatory plaques and leg edema in CA patients with elevated C‐reactive protein (CRP) compared to CA patients with normal CRP. Similarly, there were significant differences in the incidence of arthralgia and mononeuritis multiplex between the two patient groups. We found significantly positive correlations between CRP and creatinine titers in serum in all 101 CA patients. Prednisolone was administrated in a significantly greater percentage of patients with elevated CRP compared to patients with normal CRP. Repeated i.v. cyclophosphamide pulse therapy (IV‐CY) with prednisolone therapy at an early stage resulted in complete resolution without adverse effects or severe complications. We regard inflammatory plaques and leg edema with elevated serum CRP as an indication of a more severe condition, and treated them effectively with prednisolone. Assuming mononeuritis multiplex and/or arthritis exist with elevated CRP, we propose that earlier treatment by IV‐CY with prednisolone should be indicated for CA patients who demonstrate these more severe manifestations to prevent progression to PAN.     

Polyarteritis Nodosa in Childhood: Recognition of Early Dermatologic Signs May Prevent Morbidity

Systemic polyarteritis nodosa (PAN) is a vasculitis that affects small to medium‐size arteries. Onset in childhood is rare and can cause significant morbidity. Often, cutaneous manifestations can provide early clues toward diagnosis. This article describes a case of childhood systemic PAN that presented with fever, a necrotic skin lesion, and oral ulceration. Intestinal perforation complicated this case. Prompt recognition of childhood PAN is important to prevent serious complications.     

The role of mycophenolate in the treatment of antineutrophil cytoplasmic antibody-associated vasculitis

Mycophenolic acid, the active metabolite for mycophenolate mofetil and mycophenolic sodium, is a strong, noncompetitive, reversible inhibitor of inosine monophosphate dehydrogenase, the key enzyme in de novo synthesis of guanosine nucleotides leading to selective inhibition of lymphocyte proliferation. Mycophenolic acid has been evaluated as induction and remission maintenance agent in the treatment of antineutrophil cytoplasmic antibody-associated vasculitis (AAV). Since the course of disease of AAV usually requires long term immunosuppression, mycophenolate has been explored as a less toxic agent compared to cyclophosphamide and azathioprine. Mycophenolate is a potent immunosuppressive agent in the therapy of AAV, non-inferior to other available drugs with comparable side effect profile. Therefore, it could be a valuable alternative in cases of toxicity with life threatening side effects or intolerance to cyclophosphamide or azathioprine, in cases with high cumulative dose of cyclophosphamide, but also in cases with insufficient response. Several studies have shown a higher relapse rate following discontinuation of mycophenolate or in mycophenolate treated subjects that raises concerns about its usefulness in the treatment of AAV. This review describes the efficacy of mycophenolate in AAV as remission induction agent, as remission maintenance agent, and as therapeutic option in relapsing AAV disease, the relapse rate following discontinuation of mycophenolate, and the adverse events related to mycophenolate treatment.     

Cutaneous periarteritis nodosa: diagnostic and therapeutic aspects of 9 cases]

BACKGROUND: Cutaneous periarteritis nodosa (PAN) is distinguished from systemic PAN by the lack of visceral involvement. The aim of this study was to describe the clinical presentation, laboratory findings, clinical course, and treatment in cutaneous PAN. PATIENTS AND METHODS: We retrospectively reviewed the files of patients hospitalized for vasculitis in our Dermatology unit where approximately 20 cases of vasculitis are seen each year. Inclusion criteria were skin signs suggestive of PAN and a histological image of leukocytoclastic vasculitis of an arteriole. RESULTS: Nine cases of cutaneous PAN were treated in our unit between 1976 and 1997. Follow-up ranged from 32 months to 22 years. No cases of systemic PAN had been diagnosed during this period. These 9 cases of cutaneous PAN all had the same clinical presentation: nodules on the lower limbs in all cases associated with nodules on the upper limbs in half of the cases. Neuropathy was found in 3 of the 9 cases. No systemic involvement was observed. The most frequently used treatment protocol was general corticosteroid therapy (0.5 mg/kg/d prednisone or prednisolone). Immunosuppressive drugs, colchicine, dapsone, non-steroidal anti-inflammatory drugs and intravenous immunoglobulins were also used with efficacy. DISCUSSION: Cutaneous PAN is a particular form of vasculitis associating skin signs with locoregional neuromuscular involvement. The differential diagnosis with other types of vasculitis is sometimes a difficult task. The clinical course is the fundamental diagnostic clue in cutaneous PAN. A benign course and the absence of visceral involvement allow initiating a symptomatic treatment such as colchicine. The development of neuromuscular signs may warrant the use of general corticosteroid therapy.     

Successful treatment of hemorrhagic bullous Henoch‐Schonlein purpura with intravenous immunoglobulins

Henoch‐Schonlein purpura (HSP) is the most common systemic vasculitis in childhood. There is no consensus about the management for isolated cutaneous manifestations in HSP. We describe a case of HSP presenting with severe skin lesions that did not respond to standard therapy with corticosteroids. The 11‐year‐old child was treated with intravenous immunoglobulins, which induced rapid and persistent resolution of symptomatology.     

Adult Henoch-schönlein purpura in a patient with myelodysplastic syndrome and a history of follicular lymphoma

GOAL: To understand Henoch-Sch?nlein purpura (HSP) to better manage patients with the condition. OBJECTIVES: Upon completion of this activity, dermatologists and general practitioners should be able to: 1. Describe the criteria for diagnosing HSP. 2. Explain the association of malignancy and HSP. 3. Discuss the prevalence of HSP in adults. Henoch-Sch?nlein purpura (HSP) is a systemic leukocytoclastic vasculitis involving arterioles and venules most commonly in the skin, glomeruli, and gastrointestinal tract. In skin, it is associated with IgA deposition around dermal blood vessels. While an exact cause of HSP has not been elucidated, several processes have been implicated in its development, including infections; drugs; and allergic, rheumatologic, and neoplastic diseases. We present a 57-year-old woman with a history of follicular lymphoma who developed HSP likely associated with myelodysplastic syndrome. This case is clinically significant because the patient was thought to be in remission of her hematologic disease until her skin findings prompted further evaluation. Her diagnosis of HSP was based on clinical presentation with palpable purpura and abdominal pain, and was confirmed with biopsy and immunohistochemical analyses of purpuric papules demonstrating leukocytoclastic vasculitis and strong anti-IgA labeling in the dermal endothelial cells consistent with immunocomplex deposition. The occurrence of vasculitis and malignant disease in the same patient often is difficult to interpret, as some patients may exhibit both diseases independently and by chance, while others may have vasculitis as a paraneoplastic syndrome. We review cases of adult HSP associated with malignancy in the literature.     

Relationship among antineutrophil cytoplasmic antibody,blood urea nitrogen and complement in patients with eosinophilic granulomatosis polyangiitis (Churg–Strauss syndrome)

Eosinophilic granulomatosis with polyangiitis (EGPA), also known as Churg–Strauss syndrome, is an antineutrophil cytoplasmic antibody (ANCA)‐associated vasculitis characterized by a history of asthma, hypereosinophilia. The prevalence of ANCA in EGPA is less common than in other ANCA‐associated vasculitis. Increasing evidence of complement activation in the pathogenesis of ANCA‐associated vasculitis has been provided by studies in animal models. We examined EGPA patients with cutaneous manifestations as an initial sign and investigated the correlations among clinical, serological and histopathological findings. We focused on differences among ANCA, blood urea nitrogen and complement levels such as complement 3 (C3), C4 and total complement hemolytic activity (CH50). We retrospectively investigated the records of 22 patients (11 male and 11 female) with EGPA admitted to our hospital from 1997–2012. Ten of the 22 patients (46%) were positive for serum myeloperoxidase (MPO)‐ANCA. In contrast, all the patients were negative for serum proteinase 3 ANCA. There was a significantly positive correlation between serum CH50 and C4 levels in patients with EGPA. Serum blood urea nitrogen (BUN) levels differed significantly between MPO‐ANCA‐positive and ‐negative patients. Serum CH50 levels were higher in MPO‐ANCA‐positive patients compared to negative patients. Serum BUN levels were higher in elevated CH50 patients compared to normal and low CH50‐negative patients. We propose that positive findings for MPO‐ANCA with CH50 high activity may be a risk factor for developing renal insufficiency. Assuming there are correlations between the presence of ANCA and complements, earlier diagnosis based on initial efficacious treatment for EGPA.     

抗Galectin-3抗体在皮肤血管炎中的表达

目的:检测系统性红斑狼疮、荨麻疹性血管炎(UV)、过敏性紫癜(HSP)和变应性皮肤血管炎(LCV)患者血清抗Galectin-3抗体的水平。方法:ELISA法检测15例伴发皮肤血管炎表现的SLE、13例UV、15例HSP和8例LCV患者血清及15例正常人血清(阴性对照)抗Galectin-3抗体水平。结果:SLE和UV患者血清中抗Galectin-3抗体吸光度值分别为:0.89±0.08、0.71±0.05,显著高于对照组的0.46±0.02(P0.05);HSP和LCV患者中分别为0.60±0.05和0.60±0.04,与正常人相比无明显差异。结论:有皮损的荨麻疹性血管炎及系统性红斑狼疮皮肤血管炎可能与血清中抗Galectin-3抗体升高有关。     

The spectrum of cutaneous granulomatous vasculitis: histopathologic report of eight cases with clinical correlation

Cutaneous granulomatous vasculitis is an uncommon histopathologic finding that has been associated with lymphoproliferative disorders, systemic vasculitis, autoimmune inflammatory diseases, and infection. To define further the concept of cutaneous granulomatous vasculitis and to emphasize its clinical importance, we reviewed biopsy material from 8 patients seen from 1985 through 1992. All biopsies showed evidence of blood vessel damage with fibrinoid change or hemorrhage (or both) and granulomatous inflammation in and around vessel walls. Special stains for microorganisms were negative in all cases. Associated medical disorders included neuropathy (2 patients), sarcoid-like disease (2), systemic vasculitis (1), lymphoma and suspected lymphoma (1 each), and associated herpes simplex virus (1). T-cell gene-rearrangement studies were negative in a patient with suspected lymphoma. Granulomatous cutaneous vasculitis is most commonly associated with lymphoma and systemic vasculitis. In selected cases, infection should be considered as an underlying cause.     

A clinical and histologic study of 37 cases of immunoglobulin A-associated vasculitis.

Immunoglobulin (Ig) A-associated vasculitis is commonly equated with the multiorgan systemic vasculitic syndrome Henoch-Schonlein purpura (HSP), which occurs predominantly in the pediatric age group. By natural language search of the databases of two outpatient dermatopathology practices, the authors selected for review 37 cases of IgA-associated vasculitis, 23 of which were associated with antecedent infection, most commonly of the upper respiratory tract. Criteria for a diagnosis of HSP were met in 15 cases, 13 of which were in the setting of prior infection. Lower extremity skin involvement was ubiquitous. A more widespread form of vasculitis was also seen, particularly in the setting of previous infection. Several of the patients with previous infection had underlying medical illnesses including rheumatoid arthritis, atopy, renal failure, lupus erythematosus, insulin dependent diabetes mellitus, autoimmune thyroid disease, and Wegener's granulomatosis. In those patients lacking an apparent microbial trigger, Sjogren's disease with anti-Ro antibodies and hypergammaglobulinemia, lupus erythematosus, inflammatory bowel disease, IgA paraproteinemia, bronchogenic and prostatic carcinoma, cryoglobulinemia, and lymphoma were uncovered. Regardless of whether an infectious stimulus was implicated, certain cofactors with the potential to enhance vascular injury were uncovered; these included anti-Ro antibodies, antineutrophil cytoplasmic antibody, diabetic microangiopathy, and a hyperviscosity state. In the infective group, a pustular vasculitis, defined as a neutrophilic vascular reaction in concert with epithelial pustulation, was seen in 81% of cases versus 33% in the noninfectious group (p = 0.02). The prototypic histomorphology in the noninfective group was one of a mild cell poor leukocytoclastic vasculitis; Vasculitis was of greater severity in patients with antecedent infection (p = 0.026). An infectious trigger, typically of mucosal origin, can frequently be identified in patients with cutaneous IgA-associated vasculitis, especially those with the symptom complex of HSP. The light microscopy appears to distinguish patients who have an infectious trigger from those who do not. IgA-associated vasculitis may be a clue to the presence of certain underlying disorders where there is immune dysregulation or enhanced susceptibility to immune complex entrapment.     

The role of heat shock protein 60, vascular endothelial growth factor and antiphospholipid antibodies in Behçet disease

Background Behçet disease is a systemic inflammatory disease of unknown aetiology. T cells in this disease proliferate vigorously in response to a specific peptide of heat shock protein (HSP) 60 in an antigen‐specific fashion. Vascular endothelial cell growth factor (VEGF) is a cytokine participating in the inflammatory process. One of the prominent features of Behçet disease is vasculitis as a result of endothelial dysfunction. Antiphospholipid antibodies (APA) may play a role in the development of thrombosis by inhibiting production of prostacyclin by endothelial cells. Objectives To investigate the role of HSP60, VEGF and APA in Behçet disease and their relation to clinical manifestations and disease activity. Methods Thirty patients with Behçet disease were included; 17 were in the active stage and 13 were in the inactive. Fifteen age‐ and sex‐matched healthy subjects served as controls. Complete clinical examination and Doppler examination were done. Serum levels of HSP60, VEGF and APA were performed. Results Serum levels of HSP60, VEGF and APA were significantly higher in patients than in controls; however, their level did not correlate with disease activity. The serum level of VEGF correlated significantly with the presence of vascular manifestations and ocular involvement. The serum level of APA was greater in patients with thrombosis. HSP60 has an important role in aetiopathogenesis of Behçet disease, which sheds new light on its autoimmune nature. Conclusions An elevated serum level of VEGF may be a risk factor for the development of ocular disease contributing to poor visual outcome.     

Reticulohistiocytoma cutis—review of 15 cases and an association with systemic vasculitis in two cases

We reviewed 15 cases of reticulohistiocytoma cutis (RHC). Three cases were of solitary lesions. Four cases were associated with a destructive arthritis but no other systemic features. One additional patient had a destructive arthritis and lesions of reticulohistiocytoma in synovium, larynx, and mucosa. Three patients had associated xanthelasma. Two cases were associated with internal malignancy (metastatic malignant melanoma, adenocarcinoma of the bowel). Two cases were sequentially associated with systemic vasculitis (Wegener's granulomatosis, periarteritis nodosa). This occurrence of systemic vasculitis in RHC patients is unique. RHC may have variable cutaneous and systemic manifestations and associations with malignancy and immunoinflammatory diseases, including vasculitis.     

Cutaneous polyarteritis nodosa

The term polyarteritis nodosa (PAN) presently includes classic systemic PAN, cutaneous PAN, and microscopic PAN (microscopic polyangeiitis). Cutaneous PAN involves the deep dermis and the panniculus, with anatomopathological findings diagnostic for arteritis. The most frequent clinical manifestation of cutaneous PAN is the presence of nodules on the lower legs, which frequently are found at different stages of development. At times, they may not leave residual changes, but generally a violaceous livedoid color or pigmentation with retiform appearance persists for months and even years. Ulceration also is a frequent complication of cutaneous PAN. Pain, arthralgias, malaise, and moderate fever are frequently associated symptoms. Histopathologically, cutaneous PAN shows a single artery involved with diagnostic inflammatory changes. The involved artery is always located in the deep dermis or in the panniculus. Inflammatory active skin nodules show a necrotizing arteritis with variable amounts of fibrinoid necrosis and leukocytoclasia, edema and inflammatory cells. The presence of focal panniculitis surrounding the involved artery is characteristic, in contrast with the more diffuse panniculitis usually found in other nodular diseases. Cutaneous PAN has a variable course, with repeated exacerbations. Salicilates relieve the pain in most instances and may be the only treatment required to improve the symptoms in patients with moderate flare-ups. A short course of corticosteroids therapy at a moderate dose is the most effective treatment to relieve the symptoms and to reduce the inflammation. Patients with an increased ASO titer should always be treated with penicillin.