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.     

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.     

New histopathologic findings in drug eruptions.

Several new findings associated with hyperpigmentation have been reported in the past decade, the most notable being amiodarone-induced hyperpigmentation, which was shown to demonstrate both a lymphocytic dermatitis as well as yellowish brown granules that can be found within several cell types. The nature of this material has not been elucidated, although the drug or one of its metabolites composes at least a portion of the granules. The nature of the clofazimine-induced hyperpigmentation was shown to be caused by the accumulation of a ceroid lipofuscin within lipid-laden macrophages. Several chemotherapy-induced clinical and histologic changes have been reported in the past decade because of new chemotherapeutic drugs, better recognition of histologic reaction patterns, and the use of higher dosages by oncologists. A unique dermatitis, cutaneous eruption of lymphocyte recovery--although not directly due to use of chemotherapeutic agents--occurs after the return of immunocompetent lymphocytes in the peripheral circulation and skin, producing a maculopapular eruption that demonstrates a nonspecific superficial perivascular dermatitis on biopsy. Another clinically specific reaction, chemotherapy-induced acral erythema, demonstrates a nonspecific histologic pattern characterized by an interface dermatitis. Specific histologic patterns were reported for reactions following use of etoposide--starburst cells--and of busulfan--large atypical keratinocytes. There have been reports of new reactions due to chemotherapeutic agents involving sweat glands: neutrophilic eccrine hidradenitis, characterized by neutrophils and necrosis; and syringosquamous metaplasia, a histologic reaction of the sweat duct characterized by squamous metaplasia. New inflammatory reaction patterns include drug-induced generalized pustular toxic erythema, which histologically shows subcorneal pustules and occasional eosinophils. Cephalosporins were reported to produce a syndrome that clinically and histologically resembles pemphigus. Naproxen is reported to produce a clinical and histologic reaction similar to porphyria cutanea tarda. Quinine and piroxicam both induce a photosensitive dermatitis that histologically shows a nonspecific spongiotic dermatitis. A histologically unique reaction pattern manifesting as a lichenoid giant cell dermatitis may be produced by use of either methyldopa or chlorothiazide. Both phenytoin and carbamazepine produce a dermatitis that histologically imitates mycosis fungoides. Finally, phytonadione injections may produce a clinical and histologic reaction that resembles morphea.     

Two cases of linear focal elastosis: different histopathologic findings

Case 1 A 16‐year‐old Korean man presented with asymptomatic erythematous striae‐like bands on his back which had been present for 6 months and had migrated to his shoulder ( Fig. 1a ). He had no history of corticosteroid therapy, rapid gain or loss of weight, debilitating infection or illness. Histopathologically, fine, fragmented elastic fibers were shown in the dermis, but there were no clumped elastic fibers ( Fig. 2a ). Electron microscopy showed an irregular, fragmented, electron‐dense granular substance and a fragmented, electron‐lucent substance between the normal collagen fibers, and no microfibrils ( Fig. 3a ). This indicates the degeneration of elastic fibers.

Figure 1 Open in figure viewer PowerPoint Asymptomatic, palpable, erythematous bands extending horizontally across the middle and lower back and propagating to the shoulder. (b) Asymptomatic, palpable, yellowish, striae‐like bands extending horizontally across the middle and lower back     

Sulfone therapy in the treatment of leukocytoclastic vasculitis. Report of three cases

Dapsone therapy for leukocytoclastic (necrotizing) vasculitis has been little used, except for the variant forms of erythema elevatum diutinum and urticarial vasculitis. We report three patients with the common (palpable purpura) form of the disease, limited to the skin, and successfully treated with moderate doses of dapsone (100-150 mg daily). Although the natural course of leukocytoclastic vasculitis is highly unpredictable, the prompt disappearance of new lesion formation after initiation of treatment and the rapid recurrence of lesions after therapy is discontinued (both often within 4 to 8 days after the critical dose level is reached) reflect drug efficacy. We believe that dapsone deserves wider evaluation as a therapeutic agent for chronic or recurrent cases of the common form of leukocytoclastic vasculitis.     

Takayasu arteritis and cutaneous necrotizing vasculitis

Takayasu arteritis (TA) is an inflammatory arteriopathy involving predominantly the aorta and its main branches. The disease evolves in two phases: a first, nonspecific inflammatory stage and a late 'pulseless' stage, in which complications related to arterial stenosis and aneurysm formation predominate. In both phases, skin manifestations, such as inflammatory nodules, erythema-nodosum- and pyoderma-gangrenosum-like ulcers, have been described. We report 2 patients with TA, who had cutaneous necrotizing vasculitis as presenting manifestation of the disease. A review of the literature revealed 8 similar cases. TA does not only involve large arteries, but also small blood vessels. The observation that in TA the inflammatory process of the large arteries affects regions of the walls supplied by the vasa vasorum, the anatomy of which bears resemblance to the cutaneous vessel system, suggests that primary involvement of small vessels contributes to the development of the clinicopathological features of TA. Knowledge of the skin manifestations associated with TA remains important for its diagnosis and prompt instauration of life-saving treatment.     

毛霉病七例临床与病理分析

目的 探讨毛霉病的临床表现、预后和病理表现之间可能存在的关系。方法 回顾性分析1989-2006年我院诊治的7例经真菌培养证实为毛霉病患者的临床资料和病理切片。结果 7例中鼻脑毛霉病1例、皮肤毛霉病6例，其中2例为毛霉性坏死性筋膜炎。鼻脑毛霉病和毛霉性坏死性筋膜炎患者病情进展快，均以死亡告终；其皮损组织病理表现呈混合性炎症细胞浸润，坏死明显，可见大量菌丝和侵血管现象。4例以浸润性红斑为主要表现的皮肤毛霉病患者病情进展慢，有2例已治愈；其皮损组织病理呈肉芽肿性炎症，菌丝较少，未见明显的侵血管现象。7例均未见明确的菌丝侵神经现象。结论 毛霉病皮损组织病理表现呈混合性炎症细胞浸润，菌丝多，出现明显侵血管现象者预后较差。     

Circulating immune complexes and necrotizing vasculitis]

55 patients with necrotizing and with various forms of lymphocytic vasculitis were investigated for the presence of vascular deposits of immunoglobulins (Ig) and C3 by immunofluorescence testing of skin biopsies and with a 125I-Clq-binding assay for the presence of circulating immune complexes. Vascular deposits of Ig and C3 were found frequently both in patients with necrotizing and with lymphocytic vasculitis. In contrast, C1q binding activity was found almost exclusively in sera of patients with systemic necrotizing vasculitis. With one exception, all sera with C1q binding activity were from patients with vascular deposits of Ig and C3. The implications of these findings for our understanding of the development of system involvement in necrotizing vasculitis are discussed.     

An immunohistopathologic study in cutaneous necrotizing vasculitis

In order to investigate the importance of timing in the immunophenotypical characteristics of the inflammatory infiltrate and in the adhesion molecules expression in cutaneous necrotizing vasculitis (CNV) we carried on an immunohistopathologic study. An avidin-biotin-streptavidin peroxidase technique was performed on 21 lesional skin biopsy specimens obtained sequentially at 0 to 24, 72 and 120 hours from seven patients with a CNV presenting as palpable purpura. A panel of monoclonal antibodies specific for inflammatory cells (T lymphocytes, polymorphonuclear leukocytes, macrophages, dendritic cells) and different adhesion molecules (E-selectin, ICAM-1, VCAM-1, LFA-1, VLA-4) was used. Moreover, HECA-450 monoclonal antibody was used to identify cutaneous lymphocyte antigen (CLA) in the inflammatory infiltrate. In all cases, polymorphonuclear leukocytes predominated in the early phase of CNV and their number decreased significantly with time (p = 0.0001). The T lymphocytes were present from the beginning and their number remained stable or increased slightly in time (p = 0.1), thus becoming predominant in the perivascular infiltrate in older lesions. Macrophages were scattered on interstitium since the early phase and they showed a time-dependent increase (p = 0.0003). E-selectin (ELAM-1) expression was detected at the first biopsy and it decreased depending on the age of the evolving vasculitis (p = 0.0033). The expression of CLA decreased also with time in 5 of the 7 cases (p = 0.0001). Our study supports the existence of an unique histopathologic pattern in CNV, in which the inflammatory infiltrate varies with time at the expense of the number of polymorphonuclear cells and macrophages.     

Metastatic hypopharyngeal carcinoma mimicking necrotizing vasculitis of the skin.

Clinical features of cutaneous necrotizing vasculitis were the presenting signs of a hypopharyngeal carcinoma in a forty-three-year-old man. A definite diagnosis was established by examination of fine-needle aspiration biopsy and scalpel biopsy specimens. Among the dermatoses simulated by metastatic pharyngeal carcinoma, necrotizing vasculitis has not, to our knowledge, been reported previously.