Disorders characterized by excessive mucin deposition, increased collagen production, or fibrocyte hyperplasia are historically categorized as mucinoses, sclerosing disorders, and fibrosing disorders, respectively. The fibroblast is central in each of these conditions. Thus, shifting our focus from the fibroblast product (mucin, collagen, and fibrosis) to the cell of origin, the fibroblast and the mechanisms that stimulate specific fibroblast activities will provide better understanding of the histopathogenesis of these diseases and also lays a foundation for the development of more effective treatments for these incapacitating conditions. In some disorders, a singular fibroblast activity predominates, such as excessive mucin or collagen production [pretibial myxedema (see Chapter 151) and sclerodermoid disorders respectively (see Chapter 157)]. In others, a combination of excessive mucin and collagen production is observed (scleredema) or excessive mucin production and fibroblast hyperplasia occurs [scleromyxedema and nephrogenic systemic fibrosis (see Chapter 150)].
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 (see Chapter 63).
The stimuli that cause fibroblasts to overproduce mucin or collagen or to proliferate or aberrantly immigrate into skin are varied. Infectious triggers, inflammatory states, diabetes mellitus, drugs, genetic mutations, and toxins as well as specific mediators such as eicosanoids, growth factors, cytokines, immunoglobulin-paraproteins, and other circulating factors have been implicated, but the precise mechanisms that result in fibroblast pathology (fibropathy) are poorly characterized. Some of these stimuli may recruit bone-marrow-derived fibroblast precursors to the skin; others may act directly on fibroblasts already residing in the skin.
This chapter will discuss scleredema and scleromyxedema. Other diseases relevant to cutaneous fibroblasts are discussed elsewhere in this textbook and listed in Table 158-1.
Table 158-1 Selected Fibroblast Disorders |Favorite Table|Download (.pdf)
Table 158-1 Selected Fibroblast Disorders
Excessive Collagen Production by Fibroblasts—Sclerosing Disorders
• Sclerodermoid graft-versus-host disease
• Sclerodermoid porphyria cutanea tarda
• Eosinophilic fasciitis
• Sclerodermoid drug reactions (bleomycin, epoxy resin, pentazocine)
• Lipodermatosclerosis (sclerosing panniculitis)
Fibroblast Hyperplasia—Fibrosing Disorders
• Fibromatosis (Dupuytren contracture, Peyronie disease)
Excessive Collagen and Mucin Production by Fibroblasts—Scleromucinoses
Fibroblast Hyperplasia and Excessive Mucin Production by Fibroblasts—Fibromucinoses
• Lichen myxedematosus and scleromyxedema
• Nephrogenic systemic fibrosis/nephrogenic fibrosing dermopathy
• Toxic oil syndrome
• Eosinophilia–Myalgia syndrome
Fibroblast hyperplasia and Excessive Collagen Production by Fibroblasts—Fibrosclerosing Disorders
• Juvenile hyaline fibromatosis
• Gingival fibromatosis
Excessive Mucin Production by Fibroblasts—Mucinoses
• Pretibial myxedema
• Generalized myxedema
• Localized myxedema
• Reticular erythematous mucinosis and ...