Skin disorders that are characterized by increased mucin content, excessive collagen deposition, or fibrocyte hyperplasia are designated as mucinoses, sclerosing disorders, or fibrosing disorders, respectively. As the fibrocyte (fibroblast) is the cellular component of their pathogenesis, these conditions are aptly viewed as various forms of “fibropathy.” In some conditions, one fibrocyte product predominates, such as excessive mucin production in pretibial myxedema or collagen deposition in scleroderma. In others conditions there is a combination of excessive mucin and collagen deposition (scleredema) or excessive mucin deposition and fibrocyte hyperplasia (scleromyxedema and nephrogenic systemic fibrosis). Hence, the nosology of some of these conditions does not accurately describe what is observed histopathologically. For example, “fibromyxedema” more accurately depicts the histopathogenesis of scleromyxedema, as scleromyxedema implies a combination of sclerosis and mucinosis, which more accurately describes scleredema.
Fibroblasts are derived from CD34-positive hematopoietic precursors that originate in the bone marrow and populate the skin during development and wound repair. The chief role of the skin fibroblast is to deposit collagen, elastin, and ground substance, the major constituents of the dermis and pannicular septae and the substrate to which the epidermis and skin appendages attach.
Stimuli that cause fibrocytes to overproduce mucin or collagen, or to proliferate are protean and broad ranging. Infectious triggers, inflammatory states, diabetes mellitus, drugs, heavy metals (eg, gadolinium), genetic mutations, and toxins (eg, tainted rapeseed oil and L-tryptophan in eosinophilia myalgia syndrome), as well as specific mediators, such as eicosenoids, growth factors, cytokines, chemokines, immunoglobulins-paraproteins, and other circulating factors, have been implicated, but the precise mechanisms that result in the varied forms of fibrocyte pathology (fibropathy) are poorly characterized. Some of these stimuli may recruit bone-marrow derived fibrocyte precursors to the skin; others may act directly on fibrocytes already residing in the skin.
This chapter focuses on the distinctive conditions of scleredema and scleromyxedema (Table 67-1.). Other diseases relevant to cutaneous fibrocytes are discussed separately in other chapters and are listed in Table 67-2.
Table 67-1Scleredema and Scleromyxedema ||Download (.pdf) Table 67-1 Scleredema and Scleromyxedema
|CONDITION ||EPIDEMIOLOGY ||ASSOCIATED CONDITIONS ||CLINICAL MANIFESTATIONS ||HISTOLOGIC FINDINGS ||COURSE/PROGNOSIS ||TREATMENT OPTIONS |
|Scleredema || |
Childhood or adolescence
Also hyperparathyroidism, connective tissue disease, HIV
|Acute onset, nonpitting neck induration; shoulders, upper back, face, and arms may be affected. Affected skin feels smooth and waxy. ||“Squared” appearance on low-power microscopy; more dermis in affected skin compared to adjacent unaffected skin; decreased number/higher placement of eccrine glands; mucin stains (Alcian blue, colloidal iron) can identify mucin deposits || |
Abates in 1-2 years
Chronic, resistant to therapies
|Treatment of underlying condition (except for postinfectious scleredema); UVA-1 phototherapy may be effective |
|Scleromyxedema (also, lichen myxedematosus) ||Mid to late adulthood, males and females equally affected ||Paraproteinemia || |
Generalized lichenoid eruption has minute papules on extremities and trunk
Confluent, lichenoid plaques
|Superficial to mid-dermal fibroplasia and ...|