Churg‐Strauss syndrome with coexistence of eosinophilic vasculitis,granulomatous phlebitis and granulomatous dermatitis in bullous pemphigoid‐like blisters

The main histopathological features in the cutaneous lesions of Churg‐Strauss syndrome (CSS) are dermal leukocytoclastic vasculitis with a variable eosinophilic infiltrate and non‐vasculitic tissue eosinophilia with granuloma formation. This wide histopathological spectrum may account for the various skin manifestations of CSS. However, the unique histopathological combination of dermal eosinophilic vasculitis and subcutaneous granulomatous phlebitis accompanied by bulla formation has not been previously described. We report an unusual CSS case showing dermal necrotizing eosinophilic vasculitis and granulomatous phlebitis in purpuric lesions coupled with subepidermal blistering. The blisters showed dermal granulomatous dermatitis and eosinophilia without evidence of vasculitis. Dermal necrotizing eosinophilic vasculitis was characterized by fibrinoid alteration of the vessel wall, a prominent perivascular eosinophilic infiltrate, a few infiltrating histiocytes along the affected vessel wall, and the absence of neutrophilic infiltration. The underlying subcutaneous granulomatous phlebitis was characterized by an angiocentric histiocytic infiltrate surrounded by marked eosinophilic infiltrate. Deposition of cytotoxic proteins and radicals derived from eosinophils in the vessel walls and papillary dermis followed by a secondary granulomatous response may account for the unique clinical and histopathological features in this case. Ishibashi M, Kudo S, Yamamoto K, Shimai N, Chen K‐R. Churg‐Strauss syndrome with coexistence of eosinophilic vasculitis, granulomatous phlebitis and granulomatous dermatitis in bullous pemphigoid‐like blisters.     

The ulcerative form of skin sarcoidosis

A female patient suffering from the ulcerative form of skin sarcoidosis is described and the literature dealing with this problem is reviewed. Peculiar features of this case are described: ulceration of the nodes, which is an extremely rare phenomenon; no involvement of other organs, lungs included, was detectable, which is not typical of ulcerative sarcoidosis; small-nodular elements are parallelled by nodes (Boeck's small-nodular sarcoid and Darier-Roussy's subcutaneous sarcoids) in this patient, this evidencing an uniform pathologic process in the skin and subcutaneous fat. Ulceration in this patient is explained by the development of allergic vasculitis of the immediate hypersensitivity type (leukocytoclastic vasculitis and manifest increase of the level of circulating immune complexes). Prednisolone therapy has resulted in an excellent clinical effect.     

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.     

Annular vasculitis in association with sarcoidosis.

We report a case of cutaneous vasculitis with annular features in association with sarcoidosis. A 36-year-old woman presented with fever, polyarthralgias, erythema nodosum, bilateral hilar lymphadenopathy, and induration of a long-standing scar on the face. In addition, she developed annular, erythematous, and purpuric patches over her thighs and buttocks that were histologically characterized by a small vessel leukocytoclastic vasculitis. The presence of circulating immune complexes in the early stages of sarcoidosis might be related to the occurrence of the vascular damage.     

Sibutramine (Reductil?)-Induced Cutaneous Leukocytoclastic Vasculitis: A Case Report

A 24-year old woman presented with hemorrhagic vesicles on her legs. She had taken sibutramine (Reductil®, Abbott Labs., Seoul, South Korea) for 3 months and developed skin lesions the week before. A skin biopsy showed leukocytoclastic vasculitis with conspicuous eosinophilic infiltration of the tissue. These lesions showed improvement after discontinuation of sibutramine. However, 3 months later the skin lesions recurred on other sites on the lower extremities when the patient was rechallenged with the same drug for 2 weeks. Herein, we report the first case of necrotizing vasculitis induced by sibutramine.     

Nodular vasculitis in systemic lupus erythematosus

A 42-year-old man presented with fever, photosensitivity, headaches, myalgia, hyperhidrosis, muscle weakness, alopecia, nasal crustae, weight loss, painful nails, arthritis, oral ulcers, erythema, discoid cutaneous lesions, and painful subcutaneous nodes. We made a diagnosis of systemic lupus erythematosus (SLE), type II cryoglobulinemia, and nodular vasculitis. In the skin, different types of vasculitis may be observed. Typically, histology shows leukocytoclastic vasculitis of superficial vessels both in SLE and mixed cryoglobulinemia, which clinically results in palpable purpura. In our patient, however, histopathological examination of the subcutaneous nodes not only revealed leukocytoclastic vasculitis of the superficial vasculature but also showed even more extensive involvement of dermal and subdermal small and medium sized vessels, giving rise to a nodular vasculitis.     

Acute hemorrhagic edema of infancy

An 11-month-old boy initially presented to an outside hospital with fever, rhinorrhea, swelling, and papular lesions involving the left foot. He was diagnosed with necrotizing fasciitis and he subsequently underwent debridement of the lower left leg. Tissue cultures were submitted and were negative. Histopathological examination revealed a subcutaneous leukocytoclastic vasculitis. The patient was then transferred to the University of California Davis Medical Center at which time he was noted to have erythematous nontender annular and targetoid patches and plaques with purpuric centers; the lesions were scattered over the legs, right foot, flanks, and pinnae. The clinical and histopathological findings supported a diagnosis of acute hemorrhagic edema of infancy. Supportive care was maintained and the lesions and associated edema resolved. Acute hemorrhagic edema of infancy is a form of leukocytoclastic vasculitis that, despite a rapid and dramatic onset, has a benign prognosis.     

New algorithm (KAWAKAMI algorithm) to diagnose primary cutaneous vasculitis

Palpable purpura tends to indicate involvement of small vessel vasculitis in the upper dermis. Livedo racemosa, nodular lesion and skin ulceration are indicative of involvement of small to medium-sized vessel vasculitis in the lower dermis to subcutaneous fat. We set out to establish a new algorithm (KAWAKAMI algorithm) for primary cutaneous vasculitis based on the Chapel Hill Consensus Conference classification and our research results, and apply to the diagnosis. The first step is to measure serum antineutrophil cytoplasmic antibodies (ANCA) levels. If myeloperoxidase-ANCA is positive, Churg–Strauss syndrome or microscopic polyangiitis can be suspected, and if the patient is positive for proteinase 3-ANCA, Wegener's granulomatosis is most likely. Next, if cryoglobulin is positive, cryoglobulinemic vasculitis should be suspected. Third, if direct immunofluorescence of the skin biopsy specimen reveals immunoglobulin A deposition within the affected vessels, Henoch–Schönlein purpura is indicated. Finally, the presence of anti-phosphatidylserine–prothrombin complex antibodies and/or lupus anticoagulant and histopathological necrotizing vasculitis in the upper to middle dermis (leukocytoclastic vasculitis) indicates cutaneous leukocytoclastic angiitis, whereas if necrotizing vasculitis exists in the lower dermis and/or is associated with the subcutaneous fat, cutaneous polyarteritis nodosa is indicated. The KAWAKAMI algorithm may allow us to refine our earlier diagnostic strategies and allow for efficacious treatment of primary cutaneous vasculitis. In cutaneous polyarteritis nodosa, warfarin or clopidogrel therapies should be administrated, and in cases that have associated active inflammatory lesions, corticosteroids or mizoribine (mycophenolate mofetil) therapy should be added. We further propose prophylactic treatment of renal complications in patients with Henoch–Schönlein purpura.     

A Case of Cutaneous Leukocytoclastic Vasculitis Associated with Granulocyte Colony-Stimulating Factor: An Unusual Presentation

Drug-induced vasculitis is an inflammation of small-sized blood vessel caused by the use of drugs. It accounts for approximately 10% of acute cutaneous vasculitis. Propylthiouracil, hydralazine, and allopurinol have been widely known as causative agents. The most common clinical feature of drug-induced vasculitis is palpable purpura on lower extremities. A 66-year-old Korean female presented with erythematous nodules on upper chest and back. She had been on medication for multiple myeloma. Laboratory results showed neutropenia. After a single injection of filgrastim (recombinant granulocyte colony-stimulating factor), she developed cutaneous lesions with concurrent increase in absolute neutrophil count. A skin biopsy revealed leukocytoclastic vasculitis. After discontinuation of filgrastim injection, her skin lesions disappeared spontaneously.     

Palisaded neutrophilic and granulomatous dermatitis in association with sarcoidosis

Palisaded and neutrophilic granulomatous dermatitis (PNGD) has been associated with many conditions including rheumatoid arthritis, systemic lupus erythematosus, systemic vasculitis, and other diseases with circulating immune complexes. Lymphoproliferative conditions, bacterial endocarditis, and various drugs can also induce this condition. Many patients also have symmetric polyarthritis with various serological abnormalities. We present a case of a 46‐year‐old female who presented with painful erythematous annular plaques and nodules on her legs. The lesions started a week prior to visit and increased in number over the course of the week. The patient had an established history of sarcoidosis with past episodes of uveitis and erythema nodosum. The histopathological findings included a diffuse pandermal infiltrate mostly composed of neutrophils, nuclear debris, and strands of deeply eosinophilic degenerated collagen. Vasculitis was not present. No significant increase in dermal mucin was detected. Based on the clinical and pathological findings, the patient was diagnosed with late‐stage PNGD. To our knowledge, this is the first case of PNGD described in an adult patient of sarcoidosis. Mahmoodi M, Ahmad A, Bansal C, Cusack CA. Palisaded neutrophilic and granulomatous dermatitis in association with sarcoidosis.     

Granulomatous arteritis in cutaneous lesions of Churg-Strauss syndrome

BACKGROUND: Although granulomatous arteritis is usually found in extracutaneous Churg-Strauss syndrome (CSS) lesions, the vasculitis in CSS cutaneous lesions typically shows small vessel vasculitis (leukocytoclastic vasculitis) without demonstrating the feature of granulomatous arteritis confirming the proper classification of CSS in the category of granulomatous vasculitis. METHODS: Four deep excisional biopsies were obtained from three untreated CSS patients who presented with livedo reticularis and subcutaneous nodules. Tissue blocks were recut and submitted for hematoxylin and eosin and elastic tissue staining to evaluate the histological features of the affected vessels. Immunostaining for histiocytes, lymphocytes, and neutrophils were performed on serial sections to confirm the cellular infiltration. RESULTS: In all specimens, subcutaneous granulomatous arteritis was observed. The unique histological feature distinct from other vasculitic disorders is characterized by marked infiltration of histiocytes and multinucleated giant cells in and around the disrupted subcutaneous arterial walls mixed with an eosinophilic infiltrate. In two specimens, granulomatous arteritis was found in the subsequent serial sections, not in the initial sections. The initial section may show extravascular granulomatous inflammation without evidence of vasculitis. CONCLUSIONS: Granulomatous arteritis as identified in the extracutaneous lesions can also be found in subcutaneous CSS lesions presenting with livedo reticularis and/or subcutaneous nodules.     

Circumscribed cicatricial alopecia due to localized sarcoidal granulomas and single‐organ granulomatous arteritis: a case report and systematic review of sarcoidal vasculitis

Vasculitis associated with sarcoid granulomas is an uncommon phenomenon. A 72‐year‐old female presented with an expanding region of circumscribed alopecia and scalp atrophy of 2 months duration. Biopsy showed non‐caseating granulomas, dermal thinning, loss of follicles, fibrosis and muscular vessels disrupted by mixed lymphocyte, macrophage and giant‐cell infiltrates. Affected vessels had loss and fragmentation of the elastic lamina, fibrous replacement of their walls and luminal stenosis (endarteritis obliterans). Dermal and vascular advential intralymphatic granulomas and lymphangiectases were found by D2‐40 expression, suggesting lymphatic obstruction and poor antigen clearance. No evidence of a post‐zoster eruption, systemic sarcoidosis or systemic giant‐cell arteritis was found. Two years later, prednisone had halted – but not reversed – progression of her alopecia. Review of the literature showed two types of vasculitis associated with sarcoid granulomas: (i) acute, self‐limited leukocytoclastic vasculitis and (ii) chronic granulomatous vasculitis (GV). Persistence of non‐degradable material or antigen contributes to the pathogenesis of granulomatous inflammation. In this case, lymphatic obstruction probably impeded clearance of nonimmunologic and/or immunologic stimuli permitting and sustaining the development of sarcoid granulomas and sarcoid GV, ultimately causing scarring alopecia and cutaneous atrophy.     

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."     

Cutaneous granulomatous vasculitis: its relationship to systemic disease

Microscopic and medical review of twenty-six patients with skin biopsy specimens that showed granulomatous vasculitis demonstrated vascular histiocytic granulomas with fibrinoid destruction of blood vessels in the dermis and panniculus. Cultures of the biopsy specimens were nonspecific. The skin lesions varied from erythema to papulonodular and vesicular eruptions; they were usually on the extremities but also involved the trunk. Eight patients had systemic lymphoproliferative diseases: three, lymphoma; two, angioimmunoblastic lymphadenopathy; two, preleukemia; and one, chronic granulocytic leukemia. Five of these eight patients died within 2 years after the onset of skin lesions. The four patients with systemic vasculitis died within 1 year after the onset of skin lesions. Five patients with arthritis, four with gastrointestinal disease, three with systemic sarcoidosis or sarcoidlike disease, and one with tuberculosis had a more favorable prognosis. The histologic pattern of cutaneous nonlymphomatoid granulomatous vasculitis is associated with significant systemic disease, especially lymphoproliferative disorders. Patients with lymphoproliferative disorders or systemic vasculitis have a much poorer prognosis than those with inflammatory or infectious granulomatous disease.     

Sarcoidosis with subcutaneous lesions

A 30-year-old man presented for evaluation of multiple, hypopigmented macules and erythematous papules on his upper and lower lips and upper extremities. He subsequently developed firm, non-tender, subcutaneous, mobile nodules on the left forearm, left calf, and right thigh. Clinical and histopathologic features were consistent with cutaneous and subcutaneous sarcoidosis. Systemic evaluation showed no evidence of extracutaneous involvement. Subcutaneous sarcoidosis is a rare form of nodular cutaneous sarcoidosis. Typical skin findings are painless, firm, mobile nodules without overlying epidermal involvement and with a predilection for the trunk and extremities. Histopathologic alterations include epilthelioid cell tubercles in the subcutaneous fat. As this is a diagnosis of exclusion, other etiologies of granulomatous inflammation must be ruled out with tests and special stains. The mainstay of treatment is with oral glucocorticoids.     

Granulomatous vasculitis in Crohn's disease: a clinicopathologic correlate of two unusual cases

Cutaneous complications occur not uncommonly in patients with Crohn's disease (CD). Gastrointestinal CD often shows non‐caseating granulomas and a rare cutaneous finding in CD is a sterile granulomatous infiltrate not contiguous with the GI tract, termed extraintestinal CD (ECD). The clinical presentation of ECD is diverse. The most common histopathological presentation is a superficial and deep granulomatous infiltrate that often accompanies a mixed perivascular infiltrate. Here we report two patients with CD and skin lesions characterized on microscopy by granulomatous vasculitis. A 29‐year‐old female presented with papules and ulcerated nodules above the ankle. The biopsy showed dermal and superficial subcutaneous involvement by a vasocentric infiltrate of mononuclear and multinucleated histiocytes as well as mural fibrin deposition. A 35‐year‐old male presented with two tender indurated erythematous plaques with punched‐out centers on the lower leg. Histopathologically, a granulomatous vasculitis of small and medium‐sized vessels in the dermis and subcutis was evident. These two cases represent the rarely described phenomenon of cutaneous granulomatous vasculitis in CD. Previously reported examples of this entity are reviewed. Burns AM, Walsh N, Green PJ. Granulomatous vasculitis in Crohn's disease: a clinicopathologic correlate of two unusual cases.     

Palisaded neutrophilic granulomatous dermatitis in rheumatoid arthritis

Palisaded neutrophilic granulomatous dermatitis (PNGD) is an entity that has not been clearly defined either clinically or histopathologically. It is seen in patients with rheumatoid arthritis and other connective tissue diseases. In the past, many cases of PNGD have been described under several different names including palisaded neutrophilic and granulomatous dermatitis, linear subcutaneous bands, interstitial granulomatous dermatitis with cutaneous cords and arthritis, rheumatoid papules, and Churg-Strauss granuloma. We report 7 additional cases of PNGD. Clinically, 6 patients presented with erythematous to violaceous plaques, papules, and nodules on multiple body sites; one presented with subcutaneous linear bands on the shoulder. Five had rheumatoid arthritis; one had adult-onset Still's disease; and one showed clinical signs of rheumatoid arthritis, although serologically the rheumatoid factor was negative. On histologic examination, a spectrum of changes was observed ranging from urticaria-like infiltrates to leukocytoclastic vasculitis and granuloma annulare with neutrophils. We report these cases to expand the histologic spectrum of this entity and to further delineate the different forms of clinical presentation.     

Dermatologic perivascular hemophagocytosis: a report of two cases

Hemophagocytic syndrome includes fever, hepatosplenomegaly, cytopenias, coagulopathy, and abnormal liver function tests, with some patients developing lymphadenopathy and cutaneous eruptions. Herein we report two cases of dermal perivascular hemophagocytosis identified in skin biopsies of two patients with no additional symptoms attributable to hemophagocytic syndrome. Biopsies showed capillary ectasia with dermal perivascular infiltrates. The overlying epidermis and adjacent subcutaneous fat was unremarkable. The infiltrate consisted of perivascular neutrophils and benign histiocytes with predominately phagocytized erythrocytes and occasional engulfed karyorrhectic debris. Perivascular nuclear dust (leukocytoclasia) and extravasated erythrocytes were present, but other factors typically found in leukocytoclastic vasculitis were absent, namely fibrin deposition and endothelial hypertrophy and/or necrosis. This appears to be hemophagocytosis, possibly associated with late lesions of leukocytoclastic vasculitis. Both hemophagocytosis and leukocytoclastic vasculitis are associated with activated immunity with increased cytokines and/or immune complexes. It is important to consider this uncommon finding in the evaluation of indeterminate cutaneous eruptions.     

Sarcoidosis with cutaneous granulomatous vasculitis

Ulceration of non‐caseating granulomas is a rare cutaneous presentation of sarcoidosis. Granulomatous vasculitis is classically associated with Wegener's granulomatosis, lymphomatoid granulomatosis or Churg–Strauss syndrome. It is also commonly noted in pulmonary sarcoidosis, but has seldom been reported in cutaneous sarcoidosis, particularly the ulcerative variant. We present a rare case of sarcoidosis with multiple purpuric leg ulcers showing a granulomatous vasculitis histologically.     

Erythema elevatum diutinum in a patient with acquired immunodeficiency syndrome. Another clinical simulator of Kaposi's sarcoma.

Several types of vasculitis have been described in patients with human immunodeficiency virus infection. Erythema elevatum diutinum is a rare variant of cutaneous leukocytoclastic vasculitis which, with the exception of the case reported herein, has been described only once in human immunodeficiency virus-infected patients. Our male patient, a longtime intravenous drug abuser, had cutaneous lesions, closely resembling Kaposi's sarcoma, on the extensor surfaces of the lower extremities. Cutaneous biopsy specimens, however, demonstrated leukocytoclastic vasculitis with fibrinoid necrosis of the vessel walls and areas of basophilic degeneration of collagen bundles in early lesions, whereas late lesions showed dense diffuse fibrosis with proliferation of dermal spindle cells and some foci of residual leukocytoclastic vasculitis. Oral therapy with dapsone resulted in marked clearing of the cutaneous lesions within few days. This case raises the necessity of histologic confirmation for all cases of suspected Kaposi's sarcoma in patients with acquired immunodeficiency syndrome. We discuss the possible pathogenesis of leukocytoclastic vasculitis in human immunodeficiency virus-infected patients.