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Scleromyxedema
As an introduction to the category of the collagenoses, scleromyxedema has been selected. It is a disorder in
which a local proliferation of connective tissue cells is accompanied by both an increase in mucinous matrix, and by patterns of dermal sclerosis. In making this selection, the sequential relationship between
mucinous and sclerotic matrices is emphasized. In this approach, connective tissue activation in a mucinous phase might be characterized as a precursor state, often leading to a later expression of connective tissue
activation in a sclerotic phase; one phase facilitates the expression of a later phase.
In scleromyxedema, areas of the reticular dermis show a proliferation of fibroblastic spindle cells. The cells,
in association with a variable number of histiocytes, are individually isolated among altered collagen bundles; in areas they tend to form traceries, producing patterns which are reminiscent of the “incomplete” or
“interstitial” forms of granuloma annulare. It should be emphasized that all variants of granuloma annulare are interstitial; the designation lacks precision. To characterize a pattern in the setting of granuloma
annulare as “interstitial” is an oxymoron.
The altered fibrous tissue in lesions of scleromyxedema, when examined with appropriate special stains, will
characteristically show an increase amount of mucinous matrix among the collagen bundles (S9C8P1-1-6).
Flowers SL, Cooper PH, Landes HB: Acral persistent papular mucinosis J Am Acad Dermatol 1989;21: 293-7.
Pretibial Myxedema
In contrast to the biphasic properties (sequential patterns) of connective tissue in lesions of scleromyxedema,
the mucinoses usually are expressed in pure mucinous (myxoid) patterns; connective tissue activation tends to remain in a mucinous phase with the result that the collagen bundles in the affected areas are not only
thinner, but are also widely spaced. Atrophy of collagen is a parcel of a locally persistent mucinosis.
Pretibial myxedema is characterized histologically by significant alterations in the fibrous matrix of the skin
of the legs; the clinical findings are most evident on the lower extremities, particularly the legs. The disease is a consequence of treated Grave’s disease.
The changes may be manifested primarily in the reticular dermis, but an associated stasis dermatitis may
influence the histologic expressions. In the latter setting in which there is an associated component of angiodermatitis, the mucinosis may be prominently expressed in a widened papillary dermis showing a component
of angiodermatitis, or perhaps a peculiar expression of organizing granulation tissue (elephantiasic pretibial myxedema) (S9C8bP1b-4).
In the reticular dermis in lesions of mucinosis, the collagen bundles are greatly reduced in size, and widely
spaced (S9C8aP1a-1-6); some of the patterns may be expressive of unbundling of collagen bundles with the liberation of collagen
fibrils. Histiocytes probably have a role in the alterations affecting the collagen bundles. Changes in the reactive superficial unit (i.e., the epidermis, and the adventitial dermis) are variable;
for some examples, the changes are hypertrophic; they resemble those of lichen simplex chronicus (S9C8bP1b-1-3).
Dermatomyositis
(mucinosis)
Mucinosis is a common feature of the dermal alterations in the category of collagen-vascular disease. These
qualities have been discussed in SECTION 1. With dermatomyositis as an example, mucinosis is a relatively common feature, often in association with a cell-poor lichenoid reaction. Many of the features in some dermal
lesions of dermatomyositis are similar to those of lupus erythematosus (S9C9P2-1, 5, & 6) but, in dermatomyositis, hyalinization,
and thickening of the basement membrane generally is not a prominent feature.
In dermatomyositis, mucinous changes, if represented, are most prominent in the upper portion of the reticular
dermis (S9C9P2-1-6). In some examples, the mucinous changes may extend to the dermal-epidermal interface. In the affected areas, the
collagen bundles are greatly reduced in size and may be deficient in number (S9C9P2-1-3); some of the changes may be evidence of
unbundling of collagen fibrils from the bundles. With connective tissue stains, there may also be evidence of an elastolytic component in the areas of mucinosis (S9C9P2-4a & b).
Dermatomyositis
(sclerosing patterns)
In some patients, in the clinical setting of dermatomyositis, the dermis is sclerotic, rather than mucinous. The
sclerosis may by prominent in the papillary dermis and the upper reticular dermis; in such examples, the patterns resemble superficial morphea (LS&A-like) (S9C10P3-2 & 3). In some examples, the sclerosis is perifollicular with lichenoid patterns at the interface between follicular
epithelium and the follicular sheath; the basement membrane of the follicle may be thickened and hyalinized (S9C10P3-1).
The sclerosing patterns of dermatomyositis may be a reflection of variations in the activity of the disease.
Mucinous patterns may correlate with active phases of disease; the sclerosing patterns may reflect changes associated with partial remissions. From another perspective, the mucinous phase is followed by a sclerotic
phase in sequential stages in the evolution of connective tissue activation.
Morphea
(sclerosing lymphohistiocytic collagenosis)
Morphea (scleroderma) is, at least in part, an interface disease; it is a disease that characteristically
affects the retinacular tissue of the dermis and subcutis. At the onset, the disease affects interfaces. Changes at the interface between the reticular dermis and the subcutis are most characteristic. In some
lesion, the effects also may be prominent at the interface between the papillary dermis and the reticular dermis. Morphea is manifested in zonal patterns of interstitial inflammation. The zones of inflammation are
sites in which sclerosis occurs. The sclerosis is manifested by coarsening of collagen bundles and by alterations in the orientation of the affected collagen bundles. Changes may be limited to the skin and subcutis
(morphea), or may be associated with variable expressions of visceral involvement (systemic sclerosis). In the viscera, patterns of interstitial sclerosis are associated with sclerosis of muscular arteries.
The changes are generally most developed at the interface between the reticular dermis
and the subcutis. In a fully developed lesion, a band of sclerosis at the lower margin of the dermis shows coarsening of collagen bundles. The collagen bundles are individually enlarged in cross-sectional diameter. In addition, the collagen bundles assume a streaked pattern; the coarsened bundles appear rigid. They do not interlace in a normal pattern. They are straight and are arranged with their long axes parallel to the surface of the skin (pattern of streaked collagen bundles) (S9C11P4-1 & S9C15P7-2 & 4-7). In well-developed lesions, the spaces between bundles are narrowed. In old lesions, the sclerotic band at the lower
margin of the dermis may appear more brightly acidophilic with an eosin stain; it may also show PAS positivity. The patterns may become homogeneous; the band becomes hyalinized (S9C11P4-7 & S9C15P7-3). The fibrosing
process extends upward to progressively higher levels in the reticular dermis.
It is uncommon for the altered dermis in a lesion of morphea to show significant mucinosis (S9C13P6-1, 3 & 4)
Elastica generally is neither increased nor reduced in amount, but the distribution of the elastic fibers
is altered in compliance with the direction of the collagen bundles (S9C13P6-5 & S9C15P7-2).
A sclerosis of different, more delicate nature is apparent in young lesions at the interface between the dermis
and the fat. The fibrosing process extends into the adipose among individual lipocytes. The entrapped lipocytes undergo atrophy. This type of early fibroplasia also replaces the delicate fibrous tissue, or adipose
tissue that forms the adventitia of the sweat glands (S9C16P8-3 & 4). This fibrous replacement of adipose tissue
qualifies as substitutive fibrosis. In another special form of fibrosis, follicles lose their right of domain in the areas of sclerosis; since this fibrous restriction affects the general domain of the hair bulb,
the follicles tend to undergo atrophy (S9C16P8-2).
In the fibrosing process, which proceeds from dermis into the adipose tissue, the newly formed fibrous tissue
initially is delicate. It is loosely and spottedly inflamed (S9C11P4-2); the infiltrates are lymphohistiocytic in type; plasma cells
are a common feature of the deep infiltrates. The fibrous tissue extends into the adipose tissue among lipocytes (S9C11P4-3);
entrapped lipocytes undergo atrophy as the sclerosis advances. In the process of fibrosis, portions of the subcutis are incorporated in the advancing, abnormal fibrous mat of the dermis (substitutive fibrosis) (S9C14VA1-1). The sclerosing process alters the contours of the interface between the dermis and the subcutis; the
normal convolutions are eliminated and the interface becomes straight. On a punch biopsy specimen, the interface between the dermis and the fat is straight across from one margin to the other; the surgical
margins along the dermal component in combination with the horizontal margin at the lower margin of the dermis, if diagrammed as lines, produce a geometric pattern that can be characterized as “squared-off.”
In active lesions, inflammation often is a prominent feature of the reticular dermis. Infiltrates are variable
in distribution; they may be both perivascular and interstitial in distribution. Perivascular components often contain plasma cells (S9C16P8-6). The interstitial infiltrates are lymphohistiocytic in character. They may be most prominent in the lower
portion of the dermis (S9C12P5-1), or they may be extensive throughout the reticular dermis (S9C11P4-4). In early lesions, inflammation may be prominent at the interface between the dermis and the fat (S9C12P5-3). Areas of interstitial inflammation are associated with edema and widening of the spaces among collagen bundles (S9C11P4-6). In the areas of inflammation, bundles may appear fibrillated (loosely bundled) with increased prominence of spaces among
collagen fibrils (S9C11P4-5, S9C12P5-2 & 6, & S9C13P6-2).
In morphea, the same process, as described above for the interface between the dermis and the fat, may affect
the interface between the papillary dermis
and the reticular dermis. It is characterized by fibrosis affecting the papillary dermis and extending progressively downward into the reticular dermis. In the process, the domain of the altered fibrous tissue (including an altered papillary dermis) is widened; the connective tissue, of the affected area, becomes abnormally more fibrotic. The fibrosing process extends downward into the upper portion of the reticular dermis.The elastic fibers of the reticular dermis become entrapped in the sclerotic zone; they provide a marker for the depth to which the fibrosing process has extended into the reticular dermis. A lymphohistiocytic collagenosis is present at the interface between the abnormal fibrous tissue and the more normal reticular dermis (S9C12P5-5). The resulting patterns overlap with those of LS&A. This pattern of sclerosis, in a lesion which also shows more
characterisitc patterns of sclerosis at the interface between the reticular dermis and the fat, is easily accepted as a combination of superficial morphea and deep dermal morphea in a single lesion. If, however,
this superficial pattern is found in isolation, the lesion, clinically and histologically, is likely to assigned to the category of LS&A. Perhaps, the distinctions are unimportant and the two disorders are
simply variations of a single process. On the other hand, in the lesions showing both superficial and deep patterns,
the superficial component usually is more densely sclerotic and less edematous than in classic LS&A.
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