Neutrophilic Collagenosis

Interstitial infiltrates of neutrophils, among collagen bundles of the reticular dermis, qualify as a neutrophilic collagenosis. Such infiltrates are the most distinctive feature of the disorders that generally are characterized as “vasculitides.” Dissembling would be required, if the position, that all examples of leukocytoclastic angiitis are associated with morphologic evidence of fibrinoid necrosis of the walls of blood vessels, is to be promoted. At a histologic level, probably most examples of  “leukocytoclastic vasculitis” are nothing more than “leukocytoclastic neutrophilic collagenosis.” In this approach, the distinctions between vasculitis (leukocytoclastic angiitis) and neutrophilic collagenosis (Sweet’s syndrome) depend on personal prejudices and clinical presentations. The two processes are closely related at the level of microscopic findings. At another extreme, pyoderma gangrenosum is both a neutrophilic collagenosis and a leukocytoclastic vasculitis; at some point in the morphologic spectra of both diseases, distinctions become nebulous.

Sweet’s Syndrome

A diagnosis of Sweet”s syndrome requires clinicopathologic correlations. There is an unpredictable and inconstant, relationship between Sweet’s syndrome and myeloproliferative diseases, particularly chronic granulocytic leukemia.

Histologically, Sweet’s syndrome is characterized by prominent infiltrates of neutrophils in the interstitium of the reticular dermis. The infiltrates generally are most prominent in the upper portion of the reticular dermis (S8C34P20-1-4). Vessels in the areas of involvement are associated with perivascular infiltrates of lymphocytes and histiocytes. Eosinophils are also a feature. Characteristically, vessels in the zone of the collagenosis do not show fibrinoid necrosis. On the other hand, clinical characteristics may be given precedence over histologic findings with the result that occasional cases are accepted, even in the face of a necrotizing angiitis. For such cases, a histologic distinction between pyoderma and Sweet’s syndrome becomes nebulous. Some observers have failed to document vasculitis as a component of the reaction in pyoderma gangrenosum.

The epidemis over a lesion of Sweet’s syndrome may show infiltrates of neutrophils and may even contain collections of neutrophils (pustules). Pustules may form at the dermal-epidermal interface.

The papillary dermis of a lesion of Sweet’s syndrome usually shows marked edema with loose infiltrates of neutrophils and histiocytes ( S8C34P20-1-4). Extravasated erythrocytes may also be a feature of the edematous papillary dermis.

Pyoderma Gangrenosum

Pyoderma gangrenosum is a disease of altered immunity. It is associated with arthritic diseases and inflammatory bowel disease. It often is cited as an example of “pathergy” (an altered response to non-specific insults, such as trauma). It generally is clinically distinct from Sweet’s syndrome. It is a suppurative, necrotizing collagenosis that clinically presents as a boggy ulceration.

Pyoderma gangrenosum is a suppurative collagenosis. Neutrophils form dense, interstitial infiltrates among collagen bundles of the reticular dermis (S8C34aP20a-1-3). The infiltrates may extend to the dermal-epidermal interface but, in some examples, the papillary dermis is edematous. Pustules may be found at the dermal-epidermal interface and in the epidermis (S8C34aP20a-1). The infiltrates characteristically produce suppurative necrosis of the reticular dermis. Histiocytes are a variable feature, but become more prominent in advanced lesions. Granulomas generally are not a feature. Vessels in, and at the margins of, the infiltrates show fibrinoid necrosis (S8C34P20-5, & S8C34aP20a-3), or even thrombosis. In the process of lysis of collagen bundles, the elastica is more resistant. In a healing lesion, the elastic framework persists, but collapses. The resultant pattern has the qualities of a peculiar “hyperelastosis.”

Pseudoepitheliomatous hyperplasia is a variable feature. In some example, the epidermal hyperplasia is prominent; such lesions sometimes are characterized as blastomyosis-like pyoderma.

Powell FC, Su D, Perry HO: Pyoderma gangrenosum: classification and management. J Am Acad Dermatol 1996;34: 395-409.

Calcifying Panniculitis

(calciphylaxsis)

Calcifying panniculitis will be discussed in the section on panniculitides (Section 10). The process, in part, is an expression of the reaction of adipose tissue to vascular injury. Emphasis is often placed on the calcification of the media of muscular vessels, but elastica in the neighboring fibrous tissue also serves as a nidus. The calcifications, in turn, may be related to alterations in calcium and phosphorus levels in the blood. In another turn, the abnormalities in the levels of the ions often are the result of renal failure and renal dialysis. The manifestations often are basically an expression of an infarct involving the skin and subcutaneous tissue; not all of the vascular insults are associated with obvious deposits of calcium.

In well-developed lesions, the changes in the epidermis and the dermis are those of ischemic necrosis (infarction) (S8C35P21-1 & 2); they may even be wedge-shape in the dermis. Vessels of the dermis are dilated and congested; some contain thrombi.

In the subcutaneous fat, the septa and the lobules are affected. The septa show edema and fibrinoid degeneration. Some of the septal vessels contain fibrin thrombi. Portions, or entire, lobules of adipose show coagulation necrosis. The fat cells are preserved in outline but are anuclear; they are dead. Fibrin deposits are found among the dead lipocytes. Small vessels, among the lipocytes, contain fibrin thrombi (S8C35P21-4). In older lesions, newly formed fibrous tissue, as an expression of organization, extends from septa into the lobules. Dead cells are phagocytyzed and lipogranulomas become a feature. Vacuoles, which are outlined by pale, convoluted membranes (membranous lipodystrophy), may be a  feature in the fat, or the neighboring fibrous tissue.

Some of the muscular vessels of the subcutaneous tissue show calcification of the media; a crystalline plate obliterates the mucularis of the involved vessels (S8C35P21-3). In the process of preparing and sectioning such tissue, the plates often are fractured. Some of the calcified vessels contain thrombi.

Kawasaki’s Disease

Kawasaki’s disease is a necrotizing arteritis, affecting elastic and muscular arteries.The affected vessels include aorta and its major branches; coronary vessels may be affected. The affected vessels show infiltrates of neutrophils, lymphocytes, and histiocytes. Walls of the affected vessels show smudgy, basophilic necrosis. Some of the affected vessels contain thrombi (S8C35P21-5-7). The involved vessels may be aneurysmal.

Wegener’s Granulomatosis

Wegener’s granulomatosis is a form of vasculitis associated with interstitial granulomas and anti-neutrophilic cytoplasmic antibodies (ANCA). The cutaneous manifestations of Wegener’s granulomatosis often are dismissed as a form of leukocytoclastic vasculitis. As such, biopsies of the skin may be diagnostic of vasculitis, but otherwise non-specific. On the other hand, patterns, that at first glance might be accepted as those of a common leukocytoclastic angiitis (S8C36P22-1), may take on a degree of specificity when the patterns are more closely examined (S8C36P22-2-4).

In the viscera, palisaded granulomas, in an inflamed, fibrous matrix, are prominent, extravascular features. Focally, in old lesions, as in early lesions, areas of neutrophilic collagenosis and necrosis are features. In older lesions, the zones of necrosis are focal; they are defined at their margins by palisades of histiocytes and giant cells (S8C36P22-5-8). Even the zone of necrosis may organize and take on a fibrous quality; the fibrous tissue is relatively acellular and laminated. Zones of fibrinoid necrosis may be found in the fibrotic, palisaded granulomas.

Palisaded Granulomas

(Collagen-Vascular Diseases)

Palisaded granulomas (granulomatous collagenoses) are encountered in a variety of settings, with granuloma annulare the most common variant. The category of granuloma annulare, as a generic category embracing a group of palisaded granulomas that are apparently independent of other disease processes and of unknown origin, is a hodge-podge of disorders. Granuloma annulare-like lesions may be encountered in the setting of the collagen-vascular diseases. The allergic granuloma of allergic granulomatosis is an example; it is somewhat distinguished by local infiltrates of eosinophils and by the intense eosinophilia of the zone of necrosis (Churg-Strauss granuloma). The rheumatoid nodule is an example of a palisaded granuloma with a central zone of basophilic necrosis. Somewhat similar, but small, palisaded granulomas may be encountered in the skin in association with collagen-vascular diseases (granulomatous interstitial dermatitis of immune complex disease, or palisaded neutrophilic and granulomatous dermatitis); in these examples, zones of necrosis are characterized by stringy deposits of basophilic material [necrotic material rich in the nucleic acids of disintegrating inflammatory cells (S8C36aP22a-1-3)].

Temporal (Giant Cell) Arteritis

Temporal arteritis is a localized process in which a limited anatomic distribution is given recognition. This apparently localized process may be a manifestation of a disease affecting branches of the carotid arteries, namely giant cell arteritis.

In giant cell arteritis, muscular arteries of the carotids are affected. The inflammatory infiltrates tend to concentrate in the vicinity of the internal elastic lamina and extermal elastic lamina. The internal elastic lamina undergoes fragmentation; histiocytes and giant cells are attracted to the sites of inflammation. The lamina undergoes lysis and phagocytosis (S8C37P23-1-4). The process may be associated with focal areas of necrosis in the media (S8C38P24-1-3). Giant cells may rim, and even engulf, portions of the elastic lamina. The intima undergoes hyperplasia; the lumen of the vessel is narrowed. Thrombosis is a complication. The involvement, along the vessel, is focal with skip areas.

Buerger’s Disease

Buerger’s disease is a occlusive disease of muscular arteries; the effects of the disease primarily are manifested as peripheral, vascular insufficiency.

In the fully developed lesion, significant muscular arteries show fibrous occlusion of the lumen with an intact internal elastic lamina. The initial insult is a thrombotic occlusion of the affected artery. The corresponding vein may also contain a thrombus. A superficial thrombophlebitis with neutrophilic infiltrates and multi-nucleated histiocytic giant cells may be a feature of the disease (S8C37P23-5-7). In the viscera, the vascular changes of Degos disease share features with those of Buerger’s Disease.