Immune deposits in cutaneous lesions of Wegener's granulomatosis: predictor of an active disease

A retrospective analysis was conducted of eight cases of Wegener's granulomatosis (WG), who presented with cutaneous lesions. The clinical, immunopathologic and histopathologic features of the cutaneous lesions were reviewed. Antineutrophil cytoplasmic antibody (ANCA) status of the patients was established. When possible, a comparison of immunofluorescence findings of skin biopsies was made with those of renal biopsies taken at the same time. In all except one, systemic and cutaneous disease developed concurrently. On histopathology, leukocytoclastic vasculitis was noted in five patients and features of lupus erythematosus and pyoderma gangrenosum in one case each. Four patients showed immunoglobulin deposits in subepidermal blood vessel walls, while one patient showed granular immune deposits at dermo-epidermal junction only. Immunoglobulin G was the most common immunoreactant detected. C-ANCA/proteinase 3 (PR3)-ANCA was positive in six patients, P-ANCA/myeloperoxidase (MPO)-ANCA in one patient, while one patient did not show ANCA positivity on indirect immunofluorescence. All four renal biopsies showed pauci-immune glomerulonephritis, irrespective of the presence (n=3) or absence (n=1) of immune deposits in the skin biopsy. Skin manifestations are encountered in nearly half of the patients with WG, thus it is important to be familiar with cutaneous histopathologic as well as immunofluorescence findings in WG patients.     

Cutaneous manifestations of Wegener granulomatosis.

In a series of 19 patients (15 male and 4 female) who had Wegener granulomatosis with specific cutaneous histopathologic findings, the skin was only involved at onset in two. Four distinct histologic subgroups were defined as follows: necrotizing vasculitis (11 patients); necrotizing palisading granuloma (Churg-Strauss lesion) 2 patients); granulomatous vasculitis (2 patients); and lymphomatoid granulomatosis (4 patients). The 11 patients with necrotizing vasculitis had purpuric and hemorrhagic lesions, and the presence of vesicles and ulceration correlated with the severity of onset and extent of disease. The remaining eight patients had papular and nodular lesions. The patients with necrotizing vasculitis and lymphomatoid granulomatosis had a worse prognosis that did those with a predominant granulomatous reaction.     

Crohn's Disease with Cutaneous Polyarteritis Nodosa in a Child: A Case Report

A 10-year-old boy presented with a 1-day history of multiple painful erythematous skin lesions on his upper and lower extremities. He was admitted to the Department of Pediatrics with persistent right lower abdominal pain and diarrhea. Punch biopsy of a skin lesion on his lower leg showed necrotizing granulomatous vasculitis with septal panniculitis consistent with polyarteritis nodosa, and our differential diagnosis included cutaneous manifestations of Croh''s disease. Abdominal ultrasonography revealed distended colonic loops suggestive of inflammatory bowel disease. Upper and lower gastrointestinal endoscopy revealed lesions involving the duodenum, cecum, colon, and rectum. He developed multiple perianal fistulas during hospitalization. Additional laboratory tests revealed positive results for anti-saccharomyces cerevisiae and antinuclear antibodies. Based on his clinical presentation and laboratory findings, he was diagnosed with Crohn''s disease associated with cutaneous polyarteritis nodosa. We report a rare case of a child who presented with cutaneous polyarteritis nodosa as an extraintestinal manifestation of Crohn''s disease.     

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.     

Cutaneous manifestations of Wegener's granulomatosis: a clinicopathologic study of 17 patients and correlation to antineutrophil cytoplasmic antibody status

BACKGROUND: Wegener's granulomatosis (WG), a systemic vasculitis, can be associated with cutaneous signs and symptoms before, during or after the diagnosis of systemic disease. METHODS: We reviewed clinical and histologic features of cutaneous lesions from 17 patients with WG. The temporal relationship between development of cutaneous symptoms and onset of systemic disease was determined, and antineutrophil cytoplasmic antibody (ANCA) status of the patients was also established. RESULTS: In six patients, systemic and cutaneous disease developed concurrently. In eight patients, cutaneous disease developed after patients received the diagnosis of systemic disease. In three patients, cutaneous disease preceded systemic disease. Cytoplasmic ANCA or proteinase-3-ANCA [c-ANCA/proteinase 3 (PR3)-ANCA] serologic test results were negative for one patient when cutaneous disease developed, and one patient had c-ANCA/PR3-ANCA seroconversion a year before systemic disease developed. Histopathologic features of cutaneous WG were not limited to leukocytoclastic vasculitis; they also included acneiform perifollicular and dermal granulomatous inflammation and palisaded neutrophilic and granulomatous inflammation. CONCLUSIONS: Patients with WG can present initially with cutaneous symptoms. Histopathologic patterns vary, but leukocytoclastic vasculitis is most commonly noted. Patients with WG and skin lesions are likely to have positive c-ANCA/PR3-ANCA serologic test results.     

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.     

Wegener's Granulomatosis: Case Report and Literature Review

Abstract: Wegener's granulomatosis (WG) is a necrotizing granulomatous vasculitis usually affecting the upper and lower respiratory tracts and kidneys. Any organ system can be affected by the pathologic process, which remains an etiologic enigma. Limited forms of the disease are recognized in which few extrapulmonary and no renal lesions occur. Cutaneous manifestations occur in 40% to 50% of patients with WG (1). Early diagnosis is imperative because treatment regimens reduce morbidity and mortality in this potentially fatal disease. We report WG in a 10-year- old boy whose upper respiratory tract symptoms began at age 8 years. The case is illustrative of the difficulties that can be encountered in attempting to make this diagnosis. Skin is an easily accessible organ for biopsy, thus an increasing familiarity with the typical biopsy specimen findings within a consistent clinical setting may aid in earlier diagnosis of WG.     

系统性红斑狼疮性血管炎

系统性红斑狼疮(SLE)中最常累及的是皮肤小血管,也可累及多种内脏器官(如心血管、肺泡、胃肠道、肾小球、中枢神经系统及周围神经)的大、中血管,并引起坏死性损害,导致一系列系统症状的发生。免疫复合物和抗磷脂抗体可能与SLE性血管炎的发生具有密切关系。正确认识SLE性血管炎的发病机理及其所引起的临床表现,有利于疾病的早期诊断和治疗,可有效降低血管炎的发生率和SLE患者的死亡率。     

Cutaneous lymphohistiocytic infiltrates with foamy macrophages: A novel histopathological clue to Stenotrophomonas maltophilia septicemia

The best‐known cutaneous manifestations of septicemia in the skin are the so‐called “septic vasculitis” and “septic vasculopathy,” which represent two sides of the same pathogenetic process. The spectrum of cutaneous presentations of septicemia is, however, more complex, extending beyond septic vasculitis/vasculopathy. We describe the exceptional histopathological findings of skin lesions associated with Stenotrophomonas maltophilia septicemia, featuring a lymphohistiocytic infiltrate characterized by predominance of foamy macrophages containing granular basophilic material negative for PAS, Gram, Fite, and Grocott. Albeit an uncommon occurrence, S. maltophilia septicemia should be included in the broad differential diagnosis of cutaneous lesions occurring in immunocompromised individuals with worsening general conditions. Awareness of these histopathological findings may facilitate the identification of this insidious infectious agent as a source of nosocomial septicemia.     

Kikuchi's disease and the skin: case report and review of the literature

We report scattered indurated erythematous lesions that presented in an 18-year-old Japanese man with Kikuchi's disease (KD; histiocytic necrotizing lymphadenitis). A skin biopsy showed a proliferation of histiocytes and abundant nuclear debris without the presence of neutrophils, which is characteristic of KD. The specific dermatological and pathological details of KD have been yet to be fully described. In order to assess the typical skin features of KD better, we have reviewed all the previously well-documented reports of such lesions. As the clinical and histopathological cutaneous findings in KD are so heterogeneous, it is important that scattered indurated erythematous lesions should be included as one of the possible cutaneous manifestations of this disease.     

The T-lymphocyte and cutaneous Churg-Strauss granuloma

Studies of biopsy specimens from 4 patients with Churg-Strauss granulomas of the skin were performed with monoclonal antibodies to T-lymphocyte subset antigens. The finding of a predominance of a LEU3 antibody-reactive helper T-cell population in the perivascular areas and in the palisading and central granuloma areas was noteworthy. Pronounced reduction of suppressor T-cells in the lesions was observed in 2 patients; the lesions were associated with vasculitis and rheumatoid arthritis in one patient and with vasculitis and lupus erythematosus in the other. The Churg-Strauss granuloma demonstrated features of a cutaneous helper T-cell granuloma.     

Allergic granulomatosis (Churg-Strauss syndrome)

Allergic granulomatosis is a rare life-threatening systemic disorder of unknown origin, which represents a variant of systemic necrotizing vasculitis affecting medium-sized arteries and venules. Histologically, allergic granulomatosis is characterized by vascular and extravascular necrotizing palisading granulomas with prominent eosinophilia (Churg-Strauss granulomas). The clinical criteria include atopy with severe allergic asthma, pronounced peripheral eosinophilia, and nodular infiltrates of the skin and internal organs (Churg-Strauss granulomas). The internal organs most commonly involved are the lungs, gastrointestinal tract and, less often, the peripheral nerves, heart, and kidneys. Associated symptoms include fever, arthralgias and skin rashes, such as erythema multiforme, necrotizing venolitis, fixed drug eruption, and urticaria. Allergic granulomatosis shares common features with Wegener's granulomatosis and polyarteritis nodosa and may be related to the latter condition; overlap syndromes are a well-known occurrence. Similar to the other manifestations of systemic necrotizing vasculitis, immune complexes have been detected in fresh lesions and are suspected of being the basic pathogenetic findings. The causative antigens are likely to be respiratory antigens. The prognosis of untreated allergic granulomatosis is poor (mortality of approximately 50% within the first year). Systemic corticosteroids and cyclophosphamide are effective; complete remissions following cyclophosphamide treatment have been reported.     

Localized Wegener's granulomatosis

Background Wegener’s granulomatosis (WG) is a rare granulomatous necrotizing vasculitis of small and medium vessels which has predilection for upper airways, lungs and kidney. However, any other organ, including the skin and oral cavity, can be involved. Although mucocutaneous lesions are relatively common, they have only rarely been reported as localized manifestation of the disease. Objectives Our aim was to evaluate the type and sites of skin and mucosal lesions, clinical course and response to treatment, histologic features and laboratory findings in localized WG. Methods The medical records of three patients (two women and one man) with localized WG followed up at our hospitals for a mean time of 10 years were studied. Results All patients presented with facial plaques infiltrating the nasal and palatal mucosae and cartilages and, in one case, perforating the palatal bone. Anti‐neutrophil cytoplasmic antibodies, which are the marker for multisystem WG, were negative. The disease, refractory to various immunosuppressants, responded well, albeit incompletely, to prednisone plus cyclophosphamide. Limitations The limited number of patients is counterbalanced by the rarity of the disease. Conclusions Our cases may represent a rare distinctive subset of WG limited to the facial region and upper airway mucosa but showing a locally aggressive behaviour leading to cartilage and bony destruction.     

Cuadros cutáneo-mucosos asociados al consumo de cocaína

Cocaine and some of its main adulterants, such as levamisole, can cause multiple cutaneous and mucosal manifestations, including ischemic complications, neutrophilic dermatoses, midline destructive lesions, and vasculitis associated with antineutrophil cytoplasmic antibodies (ANCAs). Striking systemic symptoms are generally not seen.In all these conditions, positive test results may be observed for antinuclear antibodies, antiphospholipid antibodies, and various ANCAs, sometimes with characteristic staining patterns. Histology typically shows vascular changes, such as leukocytoclastic vasculitis, necrotizing vasculitis, and thrombi. We review the clinical, serologic, and histologic features of cutaneous and mucosal conditions associated with the use of cocaine and also look at pathophysiologic mechanisms, differential diagnoses, and treatments.     

[Translated article] Cutaneous and Mucosal Conditions Associated With Cocaine Use

Cocaine and some of its main adulterants, such as levamisole, can cause multiple cutaneous and mucosal manifestations, including ischemic complications, neutrophilic dermatoses, midline destructive lesions, and vasculitis associated with antineutrophil cytoplasmic antibodies (ANCAs). Striking systemic symptoms are generally not seen. In all these conditions, positive test results may be observed for antinuclear antibodies, antiphospholipid antibodies, and various ANCAs, sometimes with characteristic staining patterns. Histology typically shows vascular changes, such as leukocytoclastic vasculitis, necrotizing vasculitis, and thrombi. We review the clinical, serologic, and histologic features of cutaneous and mucosal conditions associated with the use of cocaine and also look at pathophysiologic mechanisms, differential diagnoses, and treatments.     

复发性皮肤坏死性嗜酸性血管炎1例

患者男,74岁。双小腿胫前红肿、水疱、大疱2个月,伴痒。皮肤科情况:双小腿胫前大片浮肿性紫红色斑片,其上可见大小不等的糜烂。皮损组织病理示:真皮全层弥漫性嗜酸性粒细胞为主的浸润,部分小血管壁纤维素样变性。诊断:复发性皮肤坏死性嗜酸性血管炎。治疗:口服米诺环素及小剂量糖皮质激素有效。     

Cutaneous necrotizing vasculitis as a manifestation of familial Mediterranean fever

Familial Mediterranean Fever (FMF) is a hereditary autoinflammatory disease, which is characterized by recurrent and paroxysmal fever, peritonitis, arthritis, myalgia, and skin rashes. Although various skin lesions such as “erysipelas‐like erythema”, urticaria, nonspecific purpura, and subcutaneous nodules have been described, cutaneous vasculitis is rare. We report a Japanese case of sporadic FMF accompanied by cutaneous arteritis at the time of febrile attacks of FMF. Gene analysis revealed M694I mutation in a single allele of the MEFV gene, and oral colchicine successfully controlled both periodic fever and subcutaneous nodules of arteritis. Cutaneous necrotizing vasculitis repeatedly emerging with febrile attacks should be included among the skin manifestations of FMF.     

Skin lesions in human yersiniosis

Various types of skin manifestations of human yersiniosis were examined with routine histological and immunohistological methods. The biopsy material consisted of sixteen cases of erythema nodosum, eight cases of erythema multiforme, and one case of erythema figuratum. The principal histopathological changes in erythema nodosum were septal or diffuse, mild panniculitis and in seven cases also necrotizing vasculitis in small, medium-sized or large arteries. Perivascular lymphocytic infiltration without vasculitis was the most prominent feature in erythema figuratum. By using a polyvalent conjugate, immunoglobulins in vessel walls in the dermis were found in two cases of EM. The rapid course of the skin eruptions and the frequency of necrotizing vasculitis in arteries fit the changes seen in an experimental Arthus reaction, in which necrotizing vasculitis is followed by lymphocytic inflammation consistent with a delayed type of reaction.     

A case of cutaneous extravascular necrotizing granuloma without systemic manifestations

Cutaneous extravascular necrotizing granuloma, an unusual palisading dermal granuloma, was first described by Churg and Strauss in 1951 in association with the syndrome of allergic granulomatosis (Churg-Strauss syndrome), for which it was though to be pathognomonic. It has subsequently been described in association with a number of autoimmune and immunoreactive diseases, and is regarded as a cutaneous marker of systemic pathology. To our knowledge, only one patient has been reported with clinical features confined to the skin. We report a 46-year-old woman with recurrent cutaneous lesions over a 10-year period and the classic histopathological pattern, but no underlying systemic disease.     

An atypical cutaneous presentation of vasculitis with features of Churg–Strauss syndrome,associated with anti‐neutrophil cytoplasmic antibodies and anti‐glomerular basement membrane antibodies

We report the case of a 59‐year‐old woman who presented with a persistent papular and nodular cutaneous eruption and new‐onset asthma, with normal renal function but persistent haematuria and proteinuria. Investigations revealed eosinophilia, both antineutrophil cytoplasmic antibodies and antiglomerular basement membrane antibodies on serological testing (double‐positive vasculitis), and a focal necrotizing glomerulonephritis on renal biopsy. Histological examination of a skin biopsy showed a dense neutrophilic infiltrate with focal fibrinoid necrosis and few eosinophils. The clinical and pathological features suggested a double‐positive vasculitis/Churg–Strauss overlap syndrome presenting with a predominantly neutrophilic dermatosis. Specific cutaneous features in patients with double‐positive vasculitis have not been documented previously. The patient has responded extremely well to immunosuppressive treatment and her disease is currently in remission.