Granulomatous Diseases of the Skin

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What is meant by “granulomatous diseases of the skin”?

Granulomatous disorders of the skin comprise a broad category of diseases that are characterized by the accumulation of activated macrophages with an epithelioid appearance in the dermis or subcutaneous tissue. A granuloma is a distinct aggregate composed of epithelioid macrophages with or without multinucleated giant cells. These aggregates are typically surrounded by a rim of lymphocytes with plasma cells being variably present. Macrophages develop from bone marrow–derived monocytes that leave the circulation and enter the skin.

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What is a “histiocyte”?

A histiocyte is a bone marrow–derived cell that is part of the mononuclear phagocytic system. Examples of histiocytes include tissue macrophages, Langerhans cells, and dermal dendritic cells. Histiocytes play an important role in the immune system, particularly with phagocytosis and antigen presentation.

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What is the difference between an immune granuloma and a foreign body granuloma?

Immune granuloma formation is a local tissue response to a poorly soluble substance that can induce a cell-mediated immune response (e.g., cutaneous tuberculosis). The persistent presence of a poorly soluble substance in the skin causes the activation of T cells, which secrete various cytokines that activate additional T cells, which transform macrophages into epithelioid macrophages and multinucleated giant cells. In contrast, foreign body granulomas typically are the result of larger aggregates of inert foreign material that cannot be phagocytized by a single macrophage (e.g., wood splinter). In general, granulomas are produced by infectious agents, foreign bodies, or alterations in the host immune system.

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List some common granulomatous diseases that affect the skin

See Table 13.1 .

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Can granulomas be recognized clinically?

Sometimes. Granulomas usually present as dermal and/or subcutaneous nodules, although epidermal changes can be present. Foreign body granulomas may demonstrate a central erosion or ulceration secondary to an attempt by the body to extrude the foreign material. Granulomas often present as nonspecific erythematous nodules; however, they also may present as dermal nodules with an “apple-jelly hue” that is highly suggestive of an underlying granulomatous process. This apple-jelly hue can frequently be appreciated by using diascopy (applying pressure to the lesion with a glass slide).

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How do endogenous “foreign” bodies cause granulomas?

Endogenous substances produce a granulomatous reaction when they come in contact with the dermis or subcutaneous fat. For example, one of the most common foreign body reactions occurs when an epidermal inclusion cyst wall ruptures and its keratin contents come in contact with the dermis. Normally, the keratin within the cyst is protected from the dermis by the cyst's epithelial lining. However, when a cyst ruptures, the keratin is exposed to the dermis, and being a poorly soluble substance, it produces a granulomatous response.

A second mechanism occurs when endogenous substances that are normally soluble crystallize into large aggregates, which then provoke a granulomatous foreign body reaction (e.g., uric acid crystals in gouty tophi and calcium in calcinosis cutis).

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What are the sources of the exogenous foreign body agents?

See Table 13.2 and Fig. 13.1 .

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Do cosmetic fillers ever produce foreign body granulomas?

Yes. Numerous cosmetic fillers, including products made from collagen ( Fig. 13.2 ), silicone, hyaluronic acid, poly- l -lactic acid, calcium hydroxylapatite, and polymethylmethacrylate, have been reported to produce foreign body granulomas. Granulomas due to biodegradable cosmetic fillers may disappear spontaneously, while granulomas due to nonbiodegradable fillers may be permanent. As the use of cosmetic fillers for wrinkle reduction and soft tissue augmentation becomes more common, the number of reported cases of filler-induced foreign body granulomas is increasing.

Parada MB, Michalany NS, Hassun KM, et al. A histologic study of adverse effects of different cosmetic skin fillers. Skinmed . 2015;4:345–346. Requena L, Requena C, Christensen L, et al. Adverse reactions to injectable soft tissue fillers, J Am Acad Dermatol . 2011;64:1–34.

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Can the cause of a foreign body reaction be diagnosed histologically?

Sometimes. A tattoo granuloma may retain some color or pigment that can help with the diagnosis. Silicone, paraffin, and other oils are often accompanied by fibrosis and a characteristic “Swiss cheese” appearance. The Swiss cheese–like holes are cavities formerly filled with the oily material that is lost during tissue processing. Also, some foreign bodies are birefringent under polarized light (e.g., talc, starch, silica, and some types of sutures).

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What is sarcoidosis?

Sarcoidosis is a systemic granulomatous disease characterized by the formation of noncaseating granulomas. The most commonly involved organs are the lungs, lymph nodes, and skin. The cause of sarcoidosis is unknown, but certain individuals may have a genetic predisposition. Sarcoidosis is more common in African Americans and women. The course is unpredictable, as the granulomas in sarcoidosis may resolve or progress to fibrosis.

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