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Dermatitis and the Reactive Superficial Unit (note: this S-C-X- page is the first textual parent page along the horizontal axis of tier 2 of this section. Migrations along
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The epidermis is composed of two units, the basal unit and the superficial unit (S2C4VA1-4). In inflammatory reactions, the
response of the units to injury (including changes induced by immune-mediated, traumatic, and infectious processes) impacts greatly on the resulting histologic patterns. The basal unit is concerned with the
replication of cells; it is metabolically active. A mucinous interstitium is a feature of this unit. It is a morphologic correlate of the role the mucinous matrix has in: the movement of nutrients and kinins
into the epidermal interstitium; and the movement of metabolic end-products out of the epidermis and into the dermis. In times of stress, the mucinous matrix often is expanded; the keratinocytes of the basal unit
are more loosely spaced. In areas of spongiosis, inter-cellular bridges among the keratinocytes are taut and accentuated.
In addition to a role in nutrition, the mucinous matrix, especially in an expanded state, is well-suited as an avenue along which inflammatory cells might move about in the interstitium of the epidermis; the spaces
in which the matrix is contained can be a “road,” as well as a conduit. The basal unit of the epidermis is a reservoir of cells awaiting a commitment to the process of terminal differentiation (under normal
conditions, an egress of component keratinocytic cells from the basal to the superficial unit is equally paced with the loss of cell of the superficial unit to the keratin layer); the basal unit is a reserve of
cells. It also is an interface unit, being required to maintain a boundary between dermal connective tissue and the dying epithelium of the superficial unit. In the latter role, the basal unit, particularly the
basal cells, have a major role in establishing, and maintaining, the structure which serves to bind the epithelium to the connective tissue. This structure, the basement membrane, is a physical barrier. It also is
important as an immunologic trap, limiting the movement of antibodies and immune complexes across the barrier into the basal unit. Its structure is so immunologically dedicated that several specific immune disorders
are manifestly damaging to the integrity of the basement membrane.
The components of the basement membrane include: intermediate filaments of basal keratinocytes, a lamina lucida, a lamina densa, anchoring fibrils, and anchoring plaques of the sub-lamina densa region. The importance
of these various structures becomes evident when specific diseases are found to have a substructural relationship to components of the basement membrane. In the basement membrane zone reside the bullous pemphigoid
antigens, integrins (collagens and laminins), and epiligrin. Great significance is attached to the relationship between antibodies and these miniscule components of the basement membrane. It is, as if, disease has
in some way produced antibodies that are specific for these structures. It seems more likely that the relationships between antibodies and basement membrane components are a basic feature of a normal relationship
that is important in preserving health. The antibodies become injurious when an antibody is delivered in excessive amounts. What we speak of as subepidermal vesicular dermatitis is extreme expression of a
“physiologic” response made abnormal by the delivery of an excess load of antibodies. In health, the basement membrane is capable of filtering antibodies to prevent their access to basal keratinocytes. The nature of
the basement membrane is a result of natural selection; it is not so much that the relationships between antibodies and components of basement membrane are an acquired phenomena, but that a normal relationship goes
awry in the presence of excess antibody.
The superficial unit is something other than a collection of spent cells and the basal unit is something other than a simple resevoir for the replenishment of cells lost to the superficial unit (in the basal unit,
physiologic apoptosis allows for the removal of effete cells without a need to deposit the dead cells in the superficial unit. The superficial unit is concerned with a distinctive form of differentiation in which
keratinocytes pack themselves with organelles and with intra-cellular fibrils. The cells, thus engorged, have, in the act, dedicated themselves to a distinctive form of physiologic death. In the process, the cells,
which are most advanced along this pathway of differentiation, become plate-like; they are converted into keratinized plates, closely packed one against the other. In the process of terminal differentiation,
keratinizing cells are “moved” upward to the surface of the skin to compensate for the plates that are regularly lost as they desquamate along the surface (as keratinized cells are denuded at the surface, new
recruits for the process of terminal differentiation are supplied from the basal unit at its interface with the superficial unit, and at a rate that normally compensates for the loss of cells to the surface). In
toto, this process of terminal differentiation is dedicated to the formation of an impervious barrier along the skin surface. With the formation of an impervious barrier at the surface, absorption from the surface
of the skin is limited. In addition, loss of fluids from the dermis and the basal unit of the epidermis to the surroundings is also restricted. The superficial unit is a defensive adaptation whereby a boundary is
defined between organism and environment. In the process of establishing an impervious barrier, the keratinocytes release keratinosomes (Odland bodies) into the interstitial spaces; these bodies are the source of
the materials that contribute a lipid membrane among the keratinizing cells. This membrane also contributes to the imperviousness of the surface of the skin. In addition, the closed inter-cellular spaces of an
intact superficial unit tend to deny migrating inflammatory cells. A hyperplastic superficial unit, as in lesions of lichen planus, is even better adapted to restrict the emigration of inflammatory cells.
The epidermis and the follicular epithelium are supported by a delicate fibrous matrix, the adventitial dermis. The adventitial dermis is a general term; it designates a functioning unit, consisting of the
papillary dermis and the perifollicular connective sheaths. The adventitial dermis truly is stroma. Stroma is a specialized matrix, ideally suited to support epithelium. In part, the delicate matrix of all true
stroma is a metabolic, as well as a physical adaptation. In the skin, the stroma of the papillary dermis allows for some flexibility in the responses of the epidermis to shearing forces. If the stroma of the
intestinal tract is selected as a model, then the delicate lamina propria of the intestinal tract is the counterpart of the papillary dermis of the skin. The lamina propria is so richly innervated that the fibrous
matrix takes on qualities of a neuromesenchyme. This may also be an appropriate characterization of the papillary dermis. In the normal papillary dermis, the collagenous component is distributed as unit fibrils; the
matrix of the papillary dermis is more richly, and more uniformly, mucinous than is that of the reticular dermis. The papillary dermis is richly vascularized with capillaries that loop into the dermal papillae. The
anatomic relationships facilitate a movement of nutrients from the vessels into the papillary dermis and, then, into the epidermis. In turn, metabolic end-products move from the epidermis into the papillary dermis
and find their way into the circulation. The morphologic combination of the epidermis (with its two units) and the adventitial dermis has a functional counterpart, the reactive superficial unit (S2C4VA1-2).
The reactions involving the reactive superficial unit of the skin are representative of the common dermatitides, including, on one hand, the spongiotic, the psoriasiform (S2C5VA2-1 & 2), and the spongiotic and psoriasiform (S2C4VA1-3) and, on the other, the lichenoid disorders. In these reactions, the main cellular components are T-lymphocytes and
histiocytes. The reactions are not mutually exclusive; in some lichenoid processes, the early stages in the evolution of a lesion may be represented in patterns that have psoriasiform qualities. For a morphologist,
it is tempting to propose that the proliferative changes of an early lichenoid reaction have relevance to the character of the T-cell infiltrate; early on, the infiltrate might be composed of cells with a propensity
for stimulatory effects, rather than the cytopathic effects of coagulation and lysis of target cells. Similarly, in an example in which lysis and coagulation of target cells is a prominent feature, the cellular
lymphoid infiltrates may be mixed in a manner that favors cytopathic effects, rather than stimulatory effects. If this proposition is extended, then the stages in the evolution of some lichenoid reactions may
provide evidence that there are sequential changes in the composition of the cellular infiltrates as the individual lesions evolve.
In this same vein, some lesions tend to manifest both proliferative and cytopathic changes without one coming to replace the other; such lesions show hyperplasia of the basal unit in combination with diffuse, rather
than spotty, infiltrates of lymphoid cells in the basal unit. Lesions showing these combinations are of a histologic type which qualifies as pityriasic (and, fortunately, this histologic characterization often
relates to clinical features which are also pityriasic).
The lymphohistiocytic infiltrates (i.e., those which are characteristic of inflammatory reactions in the superficial reactive unit of the skin), in selecting the reactive superficial unit of the skin, are the
morphologic expression of a close relationhip beween lymphoid cells and antigen-presenting cells that reside in the superficial reactive unit. They do so, in large part, because dendritic histiocytes reside in the
skin in this anatomic compartment. The category of histiocytes includes those that are immunoreactive for KP-1 (CD-68), those that react for S-100 protein, and those that react for factor XIIIa. Immunopathologists
tend to consider each subcategory as a specific cell line but, on occasion, the immunoreactivities seem not to be exclusive; a histiocyte, in certain settings, may react to more than one of these antibodies. In
analyzing the cell types in infiltrates involving the superficial reactive unit, migratory histiocytes are often a prominent feature; they might be characterized as reserve cells with a potential to express one, or
more, of the optional phenotypes. Some of the migratory histiocytes find their way into the epidermis and, under normal conditions, reside there as S-100+ dendritic cells (so-called Langerhans cells). Similar cells
may be found in the dermis, particularly the papillary dermis; they may also be found in the stroma of certain neoplasms. The S-100+ dendritic histiocyte functions as a receptacle for the fixation, and presentation,
of antigens along its surface. In response to antigens, these cells may also elaborate kinins that favor the movement of lymphoid cells out of vessels and into the immediate vicinity of the antigenically burdened
histiocytes. In the ensuing encounters between the histiocytes and lymphocytes, the lymphocytes are activated; they are either of a helper type, or a “suppressor” type. Their role is to assist in the removal, or
alteration of the offending antigens. The S-100+ histiocytes has a major role in determing the distribution of inflammatory infiltrates and in defining the role of the superficial reactive unit.
In the spongiotic (S2C4VA1-6) and psoriasiform disorders (S2C4VA1-1), the interplay between inflammatory cells, antigens, antibodies, and native cells of the skin, including epidermis and
adventitial dermis, has a stimulatory effect on the epidermis. In this process, the basal unit undergoes hyperplasia and the interstitial spaces are widened; they tend to become watery (S2C4VA1-5). The widened spaces allow for freer movement of inflammatory cells among keratinocytes of the basal unit. The changes in
the epidermis are most pronounced over the tips of the dermal papillae. Epidermal histiocytes tend to concentrate in the same areas; in turn the capillaries most closely approach the epidermis near the tips of the
dermal papillae. Inflammatory cells escape from vessels near the region of the capillary loop of the dermal papillae; they then have access to the epidermis in a site that is most suited for the migration of
lymphoid cells and/or neutrophils into the basal unit of the epidermis among keratinocytes (S2C5VA2-3). In both spongiotic and
psoriasiform processes, the alterations in the basal unit may contribute keratinocytes to the superficial unit at a rate that exceeds the ability of the upwardly moving cells to properly keratinize; the end-result
is a faulty keratin layer, a zone of parakeratosis. This alteration, having compromised the integrity of the impervious barrier at the surface,
evokes a migration of neutrophils into the epidermis; they collect in the zones of parakeratosis (Munro microabscess). All of these factors produce a pattern in which degrees of epidermal hyperplasia are variable, but zones of intra-epidermal edema and of epidermal infiltrates of lymphocytes and histiocytes tend to be focal in distribution. The infiltrates tend to concentrate in a limited epidermal domain over the tips of dermal papillae. As an example of psoriasiform processes, a review of the life-history of a lesion of psoriasis is informative (S2C5VA2-4).
In the category of the lichenoid reactions, the infiltrates of lymphocytes and histiocytes at the dermal-epidermal interface tend to be more diffuse, if comparisons are made with the focal patterns in the
spongiotic-psoriasiform category. Instead of being most prominent at the tips of dermal papillae, the infiltrates in the lichenoid categories tend to involve not only the interface at the tips of papillae, but also
the entire perimeters of the neighboring rete ridges; in addition, there is less evidence of skip areas, so that several contiguous rete ridges and their dermal papillae are involved.
In the lichen planus-like category, lytic defects often are along the perimeters of rete ridges; they tend to be equally erosive on both sides of an affected rete ridge. If attention is paid to the extent of the
para-epithelial dermal domain that contains reduplicated basement membrane (a marker for the effects of the lichenoid process and for the expanse of the zone of accretive fibrosis), then the likely conclusion would
be that, at an earlier stage, the relatively unaffected rete ridge was elongated with an increased circumference. It would appear that in the initial stage in even the lichen planus-like reactions, the epidermal
patterns would be psoriasiform. At a certain stage, the distinctions between psoriasiform and lichenoid reactions becoms relative (S2C4VA1-7).
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