Foreign Body Reactions

Definition

Literally, any material – living or non-living – introduced into the body is a “foreign body” and is treated by our immune system as “non-self” in order to elicit an appropriate response. Such a broad definition also includes infectious agents, but they are covered elsewhere (see Chapter 74, Chapter 75, Chapter 76, Chapter 77, Chapter 78, Chapter 79, Chapter 80, Chapter 81, Chapter 82, Chapter 83, Chapter 84, Chapter 85 ). This chapter will focus on non-living materials that have been introduced into the dermis or subcutis . They represent inorganic compounds or organic material of high molecular weight (or their products) that resist degradation by the body's inflammatory cells. Although granulomatous reaction patterns are most commonly observed, there is a broad range of clinicopathologic presentations. Foreign bodies reported to elicit skin reactions are listed in Table 94.1 .

Routes of Entry

Iatrogenic

Foreign material implanted into the skin for the purpose of tissue augmentation, e.g. injectable soft tissue fillers, can induce reactions in some individuals ( Fig. 94.1 ). Paraffin is still being used illegally for tissue augmentation, and a paraffin foreign body reaction can also occur after the application of paraffin-containing materials such as nasal packs .

Pathogenesis

The initial tissue response to most foreign substances involves an accumulation of neutrophils, which usually fail to properly deal with the foreign body. Its persistence attracts monocytes and local tissue macrophages that engulf the foreign material and become activated. Engulfed material may resist degradation and remain sequestered within the macrophages. Activated macrophages secrete a variety of specific biologically active substances, e.g. cytokines that attract additional macrophages and blood monocytes. The formation of a chronic granuloma represents an attempt by the body to sequester a persistent indigestible material. Individual macrophages may become larger (epithelioid histiocytes) or fuse to form multinucleated foreign body giant cells ( Fig. 94.2 ). The infiltrate also contains T lymphocytes and fibroblasts. The pathogenesis of other patterns of reactions, e.g. lichenoid, pyogenic granuloma-like, pseudolymphomatous, remains speculative.

Clinical Features

The host response and, consequently, the clinical presentations of foreign body implantation are variable ( Tables 94.2 & 94.3 ). An acute inflammatory response occurs shortly after the entry of the foreign material. This may resolve, to be followed weeks, months or even years later by a chronic inflammatory response. Although the latter may have a variety of clinical presentations, red to red–brown papules, nodules and plaques (with or without ulceration) are most commonly observed. Over time, the lesions may become firmer due to fibrosis. The pattern and arrangement of the cutaneous lesions will correspond to the route of inoculation, and observation of this patterning, in association with a relevant patient history, is crucial.

In addition to nodules and plaques, other forms of foreign body reaction include pyogenic granuloma-like lesions , lichenoid lesions , and a chronic draining fistula or wound .

Pathology

Apart from the acute reaction to the trauma that accompanies the introduction of the foreign body, a chronic reaction is the usual response. Although different patterns of chronic local tissue reactions have been described, including lichenoid , eczematous and pseudolymphomatous , the most common is the granulomatous type of reaction (see Table 94.3 ). Granulomas that develop as a reaction to foreign bodies are of two major types:

• allergic (immunologic)

• non-allergic (“foreign body”).

The allergic type is characterized by the presence of collections of individual epithelioid histiocytes associated with variable numbers of lymphocytes and fewer multinucleated Langhans-type giant cells . In the non-immunologic type, the foreign body giant cell is the most conspicuous component of the infiltrate (see Fig. 94.2 ), which also contains histiocytes, lymphocytes and other inflammatory cells .

A histologic decision as to whether a granuloma is of the foreign body type or of the allergic type is not always possible and different patterns may be seen in the same section. It is noteworthy that foreign body reactions in HIV-infected patients are different, with abundant individual macrophages, but no giant cells, suggesting an immunologic dysfunction . The foreign material inciting a reaction may be detected in conventional H&E-stained sections or may require special procedures for its identification (see Table 94.3 ).

Diagnosis

Foreign body reactions should be considered in the differential diagnosis of localized inflammatory nodules and plaques, especially when there is a persistent draining wound or sinus. Occasionally, these reactions present as pyogenic granulomas or localized lichenoid papules. Clinical morphology is usually not distinctive, but there may be a suggestive distribution pattern, and a thorough history is indispensable for arriving at the correct diagnosis.

Histopathologic examination can confirm the granulomatous nature of a lesion and occasionally foreign bodies may show distinctive microscopic features in H&E-stained sections ( Fig. 94.3 ) . However, special procedures are usually required for an accurate diagnosis, particularly microscopic examination with polarized light ( Fig. 94.4 ). In general, imaging techniques such as plain radiography, ultrasonography, CT scanning and MRI are of little practical value in visualizing small cutaneous foreign bodies, even if the foreign body is radio-opaque. However, high frequency ultrasound (20 MHz) may be helpful in detecting inflammatory reactions to tattoos and soft tissue fillers, with ultrasound findings correlating with the histopathology of tattoo reactions .

Identification of the chemical nature of the foreign body requires sophisticated physicochemical procedures (e.g. energy-dispersive X-ray analysis) that necessitate special processing of the tissue sample and are available in only a few research centers.

To summarize, accurate identification of a foreign body reaction depends on a high index of suspicion, thorough history-taking, and histologic examination, including polarized microscopy.

Tattoo

A tattoo may occur accidentally or deliberately for cosmetic and decorative purposes. Accidental tattooing results from unintentional deposition of exogenous pigmented substances such as asphalt, carbon, or graphite (pencils) within injured skin ( Fig. 94.5 ). Automobile, bicycle, and skating accidents as well as puncture wounds are the most common causes of traumatic tattoos. In decorative tattooing, the pigment is introduced into the dermis via needles or a tattoo gun to create various designs, group-identity symbols, or writings. Cosmetic tattoos are also done to define lip contours, replace eyeliner, or hide an abnormality in skin color. An iatrogenic tattoo may remain after the use of ferrous subsulfate (Monsel's solution) for hemostasis. Other hemostatic agents, e.g. aluminum chloride, may cause a foreign body reaction histologically (see below), but do not lead to discoloration of the skin.

Decorative tattoos often contain a number of pigments that are combined to create different hues, but the composition of tattoo inks has not been standardized. The pigments may be inorganic salts of metals, such as mercury in cinnabar (red, becoming historical), cobalt (blue), chromium (green), cadmium (yellow, red), ferric hydrate (sienna) and manganese (purple), or organic preparations, such as sandalwood, brazilwood and carmine. The red color is most commonly associated with several of the reaction patterns ( Fig. 94.6 ).

Pathology

Different patterns of an inflammatory response can be elicited, including sarcoidal, foreign body granulomatous, lichenoid, and pseudolymphomatous . In non-inflamed tattoos, the dermis shows granules of different sizes, shapes and colors, located both within macrophages and extracellularly in the absence of an inflammatory infiltrate. Most tattoo pigments appear black with H&E staining, regardless of the clinical color, but sometimes red or yellow colors are apparent histologically . In the case of ferrous subsulfate (Monsel's solution), coarse granular brown pigment is seen within macrophages and between collagen fibers ( Fig. 94.7 ). In foreign body reactions due to the application of WoundSeal® powder, which contains hydrophilic polymer and potassium ferrate, both large geometric basophilic particles and smaller golden-brown particles are seen .

Paraffin

Paraffin, being a mineral oil, is not hydrolyzed by tissue lipases and is treated by the body as a foreign substance. Augmentation of body contour by local injection of paraffin, although banned in most countries, is still performed in some regions of the world and is mostly done by non-medical personnel. Accidental paraffinoma of the orbit and palpebra has been reported following intraoperative placement of paraffin-impregnated gauze packs within the nasal cavity .