Leukocytoclastic vasculitis in association with linear epidermal basement membrane zone immunoglobulin deposition: Linear vasculitis

Cutaneous leukocytoclastic vasculitis (LCV) has a distinctive clinical and light microscopic presentation; however, the etiologic basis of LCV is varied. Most cases are attributable to immune complex deposition within a vessel wall and represent an Arthus type III immune complex reaction. The prototypic immunoreactant profile is characterized by granular deposits of components of complement activation in concert with immunoglobulin within the cutaneous vasculature. We encountered nine patients with vasculitic and/or vesiculobullous clinical presentations exhibiting an LCV in association with an immunoreactant profile characterized by homogeneous linear deposits of immunoglobulin along the dermal epidermal junction in a fashion resembling an autoimmune vesiculobullous disease.Among the clinical presentations were palpable purpura, urticarial vasculitis, and vesiculobullous eruptions with supervening purpura. Two patients with Crohn disease presented with classic palpable purpura with biopsy-proven LCV, and direct immunofluorescence (DIF) studies demonstrated linear immunoglobulin G (IgG) with floor localization on the salt-split skin assay. Four patients with systemic lupus erythematosus (SLE) showed purpuric vesiculobullous lesions, with evidence of a neutrophilic interface dermatitis and LCV in three of the four. The remaining patient had urticarial nonbullous lesions showing small-vessel vasculitiswith a neutrophilic interface dermatitis. In all of the patients with SLE, DIF studies showed linear immunoglobulin deposits within the basement membrane zone (BMZ). These constellation of findings clinically, light microscopically, and by immunofluorescence were those of a vasculitic presentation of bullous systemic lupus erythematosus. Two patients had linear IgA disease, which was drug induced in one and paraneoplastic in the other, and the dominant morphology on biopsy in both cases was an LCV. One patient microscopically demonstrated drug-associated and eosinophilic enriched LCV with DIF studies showing striking linear deposits of IgG suggestive of bullous pemphigoid, which was consistent with a vasculitic presentation of drug-induced bullous pemphigoid. In all cases, typical granular vascular immunoglobulin and complement deposition compatible with immune complex mediated vasculitis was observed. It is likely that local immune complexes derived from BMZ antigen bound to antibody are pathogenically relevant. We propose the designation of linear vasculitis for this unique scenario of LCV and linear immunoglobulin epidermal BMZ staining, which in some cases represents a vasculitic presentation of conventional autoimmune vesiculobullous disease.     

Leukocytoclastic (small vessel) vasculitis in multiple myeloma

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.     

Leukocytoclastic vasculitis induced by use of glyburide: a case of possible cross-reaction of a sulfonamide and a sulfonylurea

Drug-induced leukocytoclastic vasculitis (LCV) may present as the result of a single offending agent or more uncommonly, from a cross-reaction with a related medication. We describe a patient with sulfonamide allergy who developed LCV after exposure to a sulfonylurea. Sulfur-containing drugs may cross-react to induce LCV in susceptible individuals.     

Cutaneous bullae following acute steroid withdrawal in systemic lupus erythematosus

A patient with systemic lupus erythematosus developed severe widespread bullae following sudden steroid withdrawal. Histologically the lesion was suggestive of leukocytoclastic vasculitis with a regenerating subepidermal bulla, but immunofluorescence on non-lesional skin was typical of lupus erythematosus. Treatment led to resolution of the bullous eruption, and despite exacerbations of the patient's lupus nephropathy, the blisters have not recurred. The differential diagnosis of bullous LE is discussed.     

Urticarial vasculitis: report of a case and review of the literature.

A woman with cutaneous vasculitis had a severe bullous eruption that was suggestive of erythema multiforme. The patient also had a history of recurrent urticaria that continued intermittently for over a year of follow-up examination. Skin biopsy specimens of both urticarial and erythema and multiforme lesions showed leukocytoclastic vasculitis. An illness resembling systemic lupus erythematosus (SLE) is suggested by transient, low-titer, positive antinuclear antibody tests, persistent deposits of immunoglobulin and complement in normal skin, arthralgias, circulating immune complexes, and chronic hypocomplementemia. This case is similar to cases previously reported as "hypocomplementemic vasculitis," an "unusual SLE-related syndrome," and "urticaria with vasculitis."     

Localized bullous eruption after intravenous injection of aciclovir: toxic or immunoallergic mechanism?

OBJECTIVE: To report a case of bullous eruption at and far from the site of aciclovir injection. CASE REPORT: A 50-year-old man was treated with intravenous aciclovir for Herpes simplex meningoencephalitis. Ten days after treatment onset, blisters appeared on his right forearm, at and far from the site of aciclovir injection. DISCUSSION: This adverse effect has not been frequently reported. To date, bullous eruptions were considered to result from extravasation of the aciclovir solution. In this case, an immunoallergic pattern was discussed with the presence of a histological leukocytoclastic vasculitis.     

Leukocytoclastic vasculitis induced by low-dose methotrexate: in vitro evidence for an immunologic mechanism

The rare occurrence of methotrexate (MTX)-induced vasculitis has been associated mainly with high or intermediate MTX doses. We report herein a case of cutaneous leukocytoclastic vasculitis (LCV) following treatment with low-dose oral MTX (7.5 mg/week) for rheumatoid arthritis. The histological findings of a cutaneous lesion were consistent with drug-induced vasculitis. The clinical and histological findings, including the temporal relationship between MTX intake and the onset of vasculitis, and the results of withdrawal and rechallenge tests, suggest a causal relationship, and indicate a drug-induced LCV due to MTX. The role of MTX in the induction of the vasculitis was further supported by a positive mast cell degranulation (MCD) test.     

Palisaded neutrophilic granulomatous dermatitis with leukocytoclastic vasculitis in a patient without any underlying systemic disease detected to date

Palisaded neutrophilic granulomatous dermatitis (PNGD) is a rare dermatologic condition which shows various clinical and histopathological features. Although the PNGD lesions have been suggested to begin as leukocytoclastic vasculitis (LCV), there is still insufficient clinicopathological information in the reported cases of PNGD in acute stage with LCV. The relationship between PNGD and interstitial granumatous dermatis (IGD) also remains unclear. This report presents the case of a 60‐year‐old female patient with multiple erythematous nodules on the extremities. She had no underlying systemic disease detected to date, although transient, abnormal liver function tests were seen. The histopathological examination of an erythematous nodule revealed the features of PNGD in the acute stage. The patient presented the characteristic features of LCV including palisaded granulomatous pattern, and the interstitial granulomatous pattern was seen together, suggesting that PNGD with LCV can show an interstitial granulomatous pattern. The present case also suggested that PNGD in the acute stage with LCV tends to clinically manifest as erythematous nodules on the extremities and histopathologically shows a remarkable papillary edema and an extensive fibrin deposition in and around the vessel wall. PNGD may be associated with transient liver dysfunction. Misago N, Shinoda Y, Tago M, Narisawa Y. Palisaded neutrophilic granulomatous dermatitis with leukocytoclastic vasculitis in a patient without any underlying systemic disease detected to date.     

Seltene Vaskulitiden als Hinweis auf Plasmozytom

We report on two female patients who presented with painful recurrent palpable purpura, ulcers and necroses on the extremities. The results of all examinations and laboratory tests considered together suggested a diagnosis of necrotizing leukocytoclastic vasculitis. Leukocytoclastic vasculitis is an inflammatory necrotizing condition of the superficial dermal vessels, presenting with variable clinical symptoms. In most cases it becomes manifest as palpable purpura, but hemorrhagic-necrotizing, bullous, nodular and urticarial presentations also occur. Common etiological factors include bacterial, viral or drug antigens, chronic infections (hepatitis B and C), non-Hodgkin lymphomas (monoclonal gammopathy, multiple myeloma), leukemia (hairy cell leukemia), and tumors (bronchial, breast, and gastric cancer) and also connective tissue disorders. In the course of the work-up, a plasmocytoma was discovered as the cause of the leukocytoclastic vasculitis, presenting in a similar way to livedo reticularis in one case and to pyoderma gangraenosum in the other.     

Tissue Eosinophilia as an Indicator of Drug‐Induced Leukocytoclastic Vasculitis: A Clinicopathologic Investigation

Cutaneous leukocytoclastic vasculitis (LCV) may be idiopathic, drug‐induced, related to infection, or may occur in patients with autoimmune disorders. Our objective was to determine whether tissue eosinophilia is a reliable indicator of a drug‐induced etiology in the setting of LCV. Thorough chart investigation of 63 patients with LCV was performed with division of patients into drug‐induced and non‐drug‐induced groups. Corresponding histopathologic material was reviewed by a dermatopathologist blinded to the etiologic associations. An eosinophil score was tabulated by averaging the number of eosinophils in 10 high‐power fields (400x) and dividing by the density of inflammation. Statistical analysis was performed using the Wilcoxin rank sums test. Mean eosinophil scores in the drug‐induced (n = 16) and non‐drug‐induced (n = 47) groups were 5.20 and 1.05 respectively (p = 0.0126). Vascular fibrin deposition and epidermal changes were present in both groups. Clinical evidence of systemic vasculitis was present in 6%(1/16) of the drug‐induced group vs. 38%(18/47) of the non‐drug‐induced cases. This study establishes tissue eosinophilia as a reliable indicator of drug induction in the setting of LCV. Furthermore, this information may be useful for guiding management decisions, especially in settings of unclear etiology.     

紫癜型药疹的临床与病理分析

目的 了解紫癜型药疹的临床和病理特点。方法 对23例紫癜型药疹从临床、实验室及组织病理三方面进行分析，并与过敏性紫癜、变应性血管炎、大疱性多形红斑和固定性药疹相鉴别。结果 紫癜型药疹临床以紫癜和血疱为主，18例血浆凝血酶原时间缩短，16例血浆凝血酶时间缩短，组织病理未见血管炎表现。结论 紫癜型药疹可能是血管炎型药疹的前期表现。     

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。     

Cutaneous vasculitis induced by food additives.

A case of leukocytoclastic vasculitis in a 24-year-old woman is described. A severe eruption of vasculitis occurred after placebo-controlled oral challenge with 50 mg ponceau. The patient was asked to adhere to a diet free from food additives, and the vasculitis faded after a period of 2 months.     

Cutaneous vasculitis update: neutrophilic muscular vessel and eosinophilic, granulomatous, and lymphocytic vasculitis syndromes

Most biopsies of cutaneous vasculitis will exhibit a small vessel neutrophilic vasculitis [leukocytoclastic vasculitis (LCV)] that is associated with immune complexes on direct immunofluorescence examination or, less commonly, antineutrophilic cytoplasmic antibodies (ANCA) by indirect immunofluorescence testing. Is in uncommon for skin biopsy to reveal solely a neutrophilic arteritis signifying the presence of cutaneous polyarteritis nodosa or, if accompanied by significant lobular panniculitis, nodular vasculitis/erythema induratum. In other cases, cutaneous vascular damage (fibrinoid necrosis, muscular vessel wall disruption, or endarteritis obliterans) will be mediated by a nonneutrophilic inflammatory infiltrate. Eosinophilic vasculitis can be a primary (idiopathic) process that overlaps with hypereosinophilic syndrome, or it can be a secondary vasculitis associated with connective tissue disease or parasite infestation. Authentic cutaneous granulomatous vasculitis (versus vasculitis with extravascular granulomas) can represent a cutaneous manifestation of giant cell arteritis, an eruption secondary to systemic disease such as Crohn's disease or sarcoidosis, or a localized disorder, often a post-herpes zoster (HZ) phenomenon. Lymphocytic vasculitis is a histologic reaction pattern that correlates with broad clinical differential diagnosis, which includes connective tissue disease - mostly systemic lupus erythematosus (SLE), endothelial infection by Rickettsia and viruses, idiopathic lichenoid dermatoses such as perniosis or ulcerative necrotic Mucha-Habermann disease, and angiocentric cutaneous T-cell lymphomas. Skin biopsy extending into the subcutis, identifying the dominant inflammatory cell and caliber of vessels affected, extravascular histologic clues such as presence of lichenoid dermatitis or panniculitis, and correlation with clinical data allows for accurate diagnosis of these uncommon vasculitic entities.     

Acute generalized exanthematous pustulosis due to clindamycin

Acute generalized exanthematous pustulosis (AGEP) is a rare skin eruption most commonly caused by medications. It is characterized by fever and the acute eruption of non-follicular pustules overlying erythrodermic skin. Histopathology shows subcorneal pustules with a background of dermal edema and spongiosis, leukocytoclastic vasculitis, perivascular eosinophils, and focal necrosis of keratinocytes. Three cases of clindamycin induced AGEP have been reported in the literature. A case of AGEP due to clindamycin is reported in a patient with numerous other drug allergies and without history of psoriasis. Presentation and treatment of AGEP are reviewed.     

Truncal morbilliform eruption due to nifedipine.

A fifty-year-old white woman noted a morbilliform eruption that involved her trunk, arms, and legs but spared her face, following oral administration of nifedipine, a calcium channel blocker. Other dermatologic reactions to nifedipine have included edema with erythema, erythromelalgia, exfoliative erythroderma, leukocytoclastic vasculitis, purpura, and fixed drug reactions.     

P44A case of contact dermatitis caused by a NSAID''s soluble agent

Infliximab is a chimeric antitumor necrosis factor‐alpha monoclonal antibody used to treat Crohn's disease and rheumatoid arthritis. Acute infusion reactions, headache, fever, chills, urticaria and chest pain were seen in 17% of patients with infliximab compared with 7% of those receiving placebo. Other adverse cutaneous reactions are fungal dermatitis, eczema, seborrhoea, hordeolum, bullous eruption, furunculosis, periorbital oedema, hyperkeratosis, rosacea, verruca, skin pigmentation, alopecia, leukocytoclastic vasculitis, lichenoid drug eruption, erythema multiforme, perniosis‐like eruption, granuloma annulare and acute folliculitis. Any pathogenic mechanism has been suggested. Patch test with infliximab can induce flare‐up of lesions, nausea and malaise and suggest a percutaneous absortion. A sixty years‐old man with atopy background and rheumatoid arthritis treated with Remicare®, infliximab who developed a severe acute urticaria with angioedema is presented. The lesions appearance after previous endovenous administrations and the worsening spreading wheals days after the injection clinically suggested an hypersensitivity mechanism. The protocolized study drug hypersensitivity performed showed only the Prick Test positivity with infliximab at 30/60 minutes. Patch test with infliximab was negative and any adverse event was reported. Actually the patient is treated with etanercept and this drug is well tolerated. This result suggested a type I hypersensitivity mediated reaction. Urticaria could be induced as immunologic reaction of the host against the murine part of infliximab, just as it hapens with other antichimeric antibodies.     

Cutaneous histopathology of Rocky Mountain spotted fever

The dermatologic diagnosis of Rocky Mountain spotted fever (RMSF) is often presumptive; the clinical presentation includes skin rash and febrile illness with or without a clear history of tick bite. The characteristic cutaneous manifestations include a generalized skin eruption with purpuric, blanching or non-blanching macules and papules usually involving the extremities. Although skin biopsies are often performed to confirm the diagnosis, the spectrum of cutaneous histopathology in RMSF has not been well described. We studied a series of 26 cases of RMSF, of which 10 were surgical specimens and 16 were autopsies. The microscopic changes were correlated with the duration of illness. The main histopathologic feature was lymphohistiocytic capillaritis and venulitis with extravasation of erythrocytes, edema, predominantly perivascular and some interstitial infiltrate. Leukocytoclastic vasculitis (LCV) with neutrophilic infiltrate and nuclear dust was seen in 11 of 15 (73%) specimens from involved skin. These lesions with LCV also showed notable epidermal change including basal layer vacuolar degeneration with mild dermoepidermal interface lymphocytic exocytosis. Six lesions with LCV displayed focal fibrin thrombi and capillary wall necrosis. Apoptotic keratinocytes were noted in 3 lesions with LCV. Subepidermal blister was observed in the skin lesion of an autopsied patient with LCV changes. Another lesion of a fetal case with LCV also contained features of acute neutrophilic eccrine hidradenitis. Focal small nerve twig inflammation was noted in a third autopsy case with LCV. Plasma cells were seen in 6 of 34 specimens (18%); and eosinophils were observed in 3 (9%). The subcutaneous fat contained a mild perivascular inflammation and one case revealed focal lobular neutrophilic inflammation. Immunohistologic (IH) staining using polyclonal rabbit anti-Rickettsia rickettsii demonstrated positive staining of the organisms in the affected endothelial cells in all 12 cases tested. The cutaneous histopathology of RMSF is caused by endothelial damage by the rickettsial organisms which elicit an initial lymphohistiocytic small vessel vasculitis with progression to LCV. The vasculitis in RMSF is, therefore, considered to be a form of septic vasculitis.     

Adverse skin reactions to anti-TNF-alpha monoclonal antibody therapy

Various adverse cutaneous reactions to anti-TNF-alpha monoclonal antibody have been reported. In clinical studies with infliximab (Remicade) adverse drug reactions were most frequently reported in the respiratory system and in the skin and appendages. We describe here 6 patients receiving anti- TNF-alpha therapy (infliximab) for Crohn's disease or rheumatoid arthritis who consulted our out-patient department for adverse cutaneous reactions between November 1999 and February 2002. The following diagnoses were made: leukocytoclastic vasculitis, lichenoid drug reaction, perniosis-like eruption (2 patients), superficial granuloma annulare and acute folliculitis.     

Widespread Bullous Fixed Drug Eruption Mimicking Toxic Epidermal Necrolysis

This paper is written to heighten awareness of the presence of the most severe form of fixed drug eruption. Two patients with a widespread bullous form of fixed drug eruption (FDE) were initially given the diagnosis of toxic epidermal necrolysis (TEN). Both gave a history of a previous widespread eruption from the responsible drug, each had biopsies consistent with fixed drug eruption, and most importantly, both had an uncomplicated course, with complete cutaneous reepithelialization within 10 days. These observations suggest that widespread bullous fixed drug eruption may portend a more favorable prognosis than TEN, thus stressing the potential importance of distinguishing the two diseases. A review of fixed drug eruption and possible means of differentiating the widespread bullous form from TEN are discussed.