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Inflammation
(continued)
A characteristic response of the interstitium of the dermis to injury or inflammation is fibrinoid degeneration. S1C24P14-1 is an example of a dermal injury in which fibrinoid degeneration, in a characteristic distribution, is one of the chief features; this is the characteristic pattern of a lesion of chondrodermatitis nodularis helicis. In this lesion, the process is in part collagenolytic, and in part epidermolytic. A cleft forms at the interface between the epidermis and the dermis; fibrinoid necrosis is a feature of the dermis forming the floor of this defect. Chondrodermatitis nodularis helicis is probably a peculiar reaction to trauma; the dermis is pressed against the underlying cartilage in a manner that promotes the release of inflammatory mediators. Perhaps, damage to the perichondrium has a role in the pathogenesis of the disease.
The character of the dermal interstitium varies with the anatomic unit under consideration. The interstitium of the papillary dermis is normally mucinous; unit collagen fibrils are randomly distributed in the matrix.
The basement membrane zone might be characterized as a specialized connective tissue composed of fibrous components having unique properties. Within the basement membrane zone, several distinctive components are
represented including unique collagens, specialized lamina, anchoring fibrils, and several antigenic proteins. Remarkably, the deposition of antibodies on one of the respective proteins of the basement membrane zone
usually results in a migration of lymphocytes and histiocytes into the zone, presumably having been attracted to the site by the presence of the immune complex. S1C25P15-1 provides a nice demonstration of the localization of a lymphoid infiltrate in the basement membrane region in a lesion of bullous pemphigoid. The infiltrate is associated with vacuolar changes in the affected site; the lesion, in the region at the margin of, but beyond, a subepidermal vesicle is an “interface” dermatitis; most of the lesions in the category of the subepidermal vesiculation are evidence of progression in an interface dermatitis.
Morphea (scleroderma) is a classic example of a disease affecting not only dermal collagen bundles but also its interstitium. It is a process in which inflammation is variable; the variations probably are measures of
the age of any given lesion. In characterizing morphea, emphasis usually is placed on changes in the size and orientation of collagen bundles of the reticular dermis, particularly the lower portion of the reticular
dermis. With increasing depth in the dermis, there is a progressive increase in the size and a decrease in the spacing of collagen bundles. The changes usually are most pronounced at the interface between the
reticular dermis and the subcutaneous fat. In addition, the collagen bundles tend to be altered in their relationships to one another, and to the surface of the skin; the bundles appear to be straight and parallel -
parallel to each other and to the surface of the skin. Little attention has been paid to the process by which the increase in the size of the collagen bundles is accomplished. In early stages, spaces among collagen
bundles are widened. Rarely do the interstitial spaces appear mucinous on an H&E stained section. In the widened spaces, new fibrils are deposited and, on this basis, the process, at least in part, is an
accretive process at the surface of the bundles. It is, however, possible to make a case for an unbundling of collagen bundles (an increase of matrix among collagen fibrils of the bundles), and for a subsequent
deposition of new fibrils in the altered interstitium of individual collagen bundles. A prominent feature at certain stages in the evolution of a lesion of morphea is a spotty, interstitial infiltrate of lymphocytes
and histiocytes (the lymphohistiocytic collagenosis of morphea) (S1C25P15-2-3). This infiltrate is not
peculiar to morphea. Some of the disorders which share this pattern of a collagenosis also tend to be sclerosing processes. Included in the category of diseases with a similar pattern of lymphohistiocytic
collagenosis with sclerosis are lupus profundus and necrobiosis lipoidica (in a qualified manner). These three disorders also are characterized by a variable component of plasma cells in the infiltrates,
particularly in the deeper portion of the dermis, and the subcutaneous fat. These three disorders are also characterized by a process of substitutive collagenosis in which fibrous tissue extends into the fat among
lipocytes; the process progresses into the fat along a rather uniform front; the interface between the fat and the dermis is straightened, and the vertical dimensions of the dermis are increased. In this process, a
layer of newly formed fibrous tissue will eventually extend well below the level of the sweat glands (S1C25P15-4).
With time the sclerosing process will encroach on the adventitia of sweat glands and hair follicles (S1C26P16-2). The
affected skin appendages will undergo atrophy. Not all lesions of morphea progress from the interface between the adipose tissue and the dermis into the upper reaches of the dermis. Some show a superficial component
as well as a deep component, and some evolve in the upper portion of the dermis without a significant deep component. The superficial components share many features with lichen sclerosis et atrophicus (L S & A) (S1C26P16-1). The differences may be too subtle to define. Usually, the superficial lesions of morphea are more densely
sclerotic, and less edematous and hyalinized. Both lesions share the feature of a lymphohistiocytic collagenosis with confinement of the inflammatory infiltrates to an area outside the zone of sclerosis. In
superficial variants of morphea, sclerosis involves the papillary dermis and the adjacent portion of the reticular dermis. Personal prejudices are required to put these overlap lesions in perspective.
An uncommon feature of lesions of morphea (or at least a feature not documented in the literature to my knowledge) is a pattern that I characterize as collagenous ring-binding. It might be cited as an example of
accretive fibrosis with a pre-existing collagen bundle as the framework; the collagenous ring serves as a marker for a deposit of new fibrous tissue in a circumferential, lamellar pattern (S1C26P16-3).
Both the epidermis and the dermis of normal skin have a mucinous interstitium. In inflammatory diseases affecting an epithelial component (S1C27P17-1), it is easy to dismiss the clusters of inflammatory cells among epithelial cells as evidence that the
inflammatory cells have collected in the domain of the epithelium in defects which are a result of lysis of the native cells. On the other hand, inflammatory cells migrate among epithelial cells; they do so by
availing themselves of the mucinous avenues of the epithelium. They may even promote an increased fluidity, and an increase in the hydrophilic qualities of the mucinous matrices.
The mucinous interstitium of the epidermis is expanded in psoriasiform processes. The spaces among keratinocytes of the basal unit of the epidermis are widened and, with appropriate stains, are myxoid (mucoid) (S1C27P17-2). This expansion of the mucinous interstitium may have a role in facilitating the migration of inflammatory cells
into the epidermis. On the other hand, the superficial unit is characterized by a tendency for the spaces to be closed by the deposition of a lipid-rich membrane; this arrangement may, in turn, make it difficult for
inflammatory cells to find their way into the superficial unit. With these accommodations, a portion of the epidermis may show extensive damage to the basal unit but, if its superficial unit remains intact, an
impervious barrier at the surface of the skin is effectively maintained.
The watery quality of the interstitium of the normal reticular dermis makes it difficult to appreciate the presence of a mucinous component. In certain disorders such as the granulomatous collagenolytic processes,
the region of collagenolysis often has a prominent mucinous quality. This may simply reflect a deposition of new, and altered matrix in the defect. It may, in part, represent a change in the ionic nature of the
glycoaminoglycans and, in addition, may represent an unbundling of collagen bundles with a release of mucinous matrix from the bundle into the defect (S1C27P17-3). In some disorders, mucinoses and sclerosing collagenoses are sequentially related. One seems to be a precursor
of the other, the sclerosing process being a late stage manifestation; chronic lesions of scleredema adultorum often take on a sclerotic (sclerodermoid) quality.
In some disorders, the histiocyte is the preponderant reacting cell. The histiocytic or granulomatous collagenolytic disorders (the palisaded granulomas) are examples. In the category of granulomatous collagenolytic
disorders, the common example, granuloma annulare, is a focal process affecting dense fibrous tissue (S1C28P18-1). It
basically is a disease of the reticular dermis, but similar lesions in the soft tissue are characterized as deep granuloma annulare. Occasionally, a lesion involves the papillary dermis as well as the reticular
dermis, and may press upon the epidermis. In close proximity to the epidermis, the lesion may induce proliferation of keratinocytes; the epithelium may engulf a portion of the adjacent lesion; it may then carry the
inflammatory debris upward, and release it at the surface (perforating granuloma annulare). The histogenesis of granuloma annulare has been clouded by claims that the basic process is a vasculitis. This is
defensible only if common sense is set aside. Clearly, the process is a reaction to a product in the dermal connective tissue; it is an attempt to both confine, and then destroy, what has been deposited in the
interstitium of the dermis. The histiocytes of this type of collagenolysis are activated, but lack the symmetrically rounded configuration of wandering histiocytes; the histiocytes are stellate in outline (S1C28P18-2 & 3). The stellate configuration with delicate cytoplasmic processes is ideally suited to allow the histiocytes
to gain access to the interstitium of collagen bundles. Lesions of granuloma annulare also have a life history. In an early, active phase, the defect produced by the catalytic enzymes of the histiocytes has a
mucinous quality (S1C28P18-3); fibrin may also be represented in the defect. Elastica is variably represented, and is more
resistant to the effects of catalytic enzymes than are the collagen bundles. In resolving lesions, collagen bundles are inlaid in the defect with some restoration of patterns, and a resolution of the granulomatous
reaction. The lesion, however, can be identified as a somewhat hypercellular focus in the dermis in which collagen bundles are coarsened, and more compactly aggregated (S1C28P18-4); the interstitium will contain an increased number of hypertrophied fibroblasts. In occasional lesions, some of
the palisaded histiocytes will be arranged radially around a single collagen bundle (S1C29P19-1); it is as if the histiocytes have
singled out a particular bundle - as if the sequestered bundle is heavily infiltrated with an offending product (antigen or immune complex?). The pattern qualifies as “granulomatous ring-binding” of a collagen
bundle.
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