8 Immune-Mediated, Autoimmune, and Granulomatous Conditions
True granulomas are collections of epithelioid histiocytes with variable inflammation and giant cells. Necrotizing granulomas are often seen in infectious processes and diseases of collagen degradation and necrobiosis. Table 8-1 lists the common granulomatous processes affecting the oral cavity; those caused by infections are discussed in Chapter 4.
|Granulomatous Inflammation||Distinguishing Features|
|Foreign body granuloma||Refractile or nonrefractile foreign material present; sometimes foreign material not identified|
|Intrinsic (e.g., ruptured hair follicle, cholesterol, keratin)||History of trauma or introduction of foreign material|
|Extrinsic||Dermal filler, amalgam|
|Bacterial infection (e.g., Bartonella henselae)||Warthin-Starry stain|
|Mycobacterial infection (often necrotizing)||Acid-fast bacillus or Fite stain|
|Spirochetal infection (e.g., tertiary syphilis gumma)||Warthin-Starry, Dieterle, or modified Steiner stain|
|Deep fungal infections||Methenamine silver or PAS stain; may see pseudoepitheliomatous hyperplasia|
|Sarcoidosis||Hilar lymphadenopathy, elevated ACE levels|
|Crohn disease||Gastrointestinal symptoms, positive endoscopic findings|
|Orofacial granulomatosis||Idopathic or related to Crohn disease|
|Wegener granulomatosis||Upper respiratory or renal findings, c-ANCA positive|
|Lichenoid granulomatous inflammation||Coexisting lichenoid stomatitis|
|Palisaded granulomas (e.g., rheumatoid nodule)||History of rheumatoid arthritis or necrobiotic disease|
ACE, Angiotensin converting enzyme; c-ANCA, cytoplasmic antineutrophil cytoplasmic antibodies; PAS, periodic acid–Schiff.
Extrinsic foreign material introduced accidentally (e.g., glass or amalgam filling material) or intentionally (e.g., dermal fillers) excites a histiocytic response. Though generally resorbed, dermal fillers may migrate to sites, distant from the original injection. Foreign body granulomas also form as a reaction to endogenous substances, such as cholesterol from cell membranes, keratin (ruptured epidermal inclusion cysts), and hair (ruptured hair follicle).
• Calcium hydroxylapatite consists of gray-brown microspheres, 25 to 40 microns in diameter, that are nonrefractile; they stimulate endogenous collagen production and are resorbed within a few months, but they may cause a granulomatous response (Fig. 8-5).
• Foreign body granulomas are common in odontogenic cysts (see Chapter 14), around amalgam tattoos (see Chapter 9), and in keratinizing squamous cell carcinomas (see Chapter 11).
FIGURE 8-2 Poly-l-lactic acid granuloma. A, Nodule consists of multinucleated giant cells and fusiform clefts. B, Multinucleated giant cells with bubbly cytoplasm, fusiform clefts, and asteroid bodies. C, Refractile foreign material.
FIGURE 8-4 Silicone granuloma. A, Many vacuolated cells in the lamina propria. B, Macrophages containing vacuoles of varying sizes. C, Macrophages with bubbly vesicular cytoplasm and slight reactive nuclear atypia.
Jham BC, Nikitakis NG, Scheper MA, et al. Granulomatous foreign-body reaction involving oral and perioral tissues after injection of biomaterials: a series of 7 cases and review of the literature. J Oral Maxillofac Surg. 2009;67:280-285.
Sage RJ, Chaffins ML, Kouba DJ. Granulomatous foreign body reaction to hyaluronic acid: report of a case after melolabial fold augmentation and review of management. Dermatol Surg. 2009;35(suppl 2):1698-1700.
Orofacial Granulomatosis and Crohn Disease
• Melkersson-Rosenthal syndrome, in addition to the lip swelling, exhibits fissured tongue and facial palsy; because fissured tongue is very common and facial palsy in this syndrome is very rare, it is unclear if this is a true syndrome.
• Crohn disease—in addition to the aforementioned features, there may also be papular folds of tissue in the maxillary and mandibular sulci, aphthous-like ulcers, gastrointestinal symptoms, and thickened and erythematous appearance of perivermilion skin (see Fig. 8-7, C); oral findings precede the diagnosis of intestinal disease in 50% of cases; some patients may also present with pyostomatitis vegetans (see later).
FIGURE 8-7 A, Orofacial granulomatosis: young child with lip swelling but without gastrointestinal symptoms. B, Orofacial granulomatosis: lip swelling without gastrointestinal symptoms or signs after 10-year follow-up. C, Crohn disease: typical “orange peel” appearance and thickening of the perivermilion skin and swollen lips.
(A, courtesy of Dr. Bonnie Padwa, Children’s Hospital Boston; C, Courtesy of Dr. Jeffrey Stone, private practice, Lowell, Mass.)
Orofacial granulomatosis may be seen in patients who are sensitive to foodstuffs such as eggs and chocolate, flavorings including cinnamaldehyde, and preservatives such as benzoates and metabisulfites. Crohn disease is thought to be an inflammatory response possibly to intestinal microbes in genetically susceptible hosts (e.g., polymorphisms in the NOD2/CARD15 genes).
• Nonnecrotizing granulomas are noted and may be subtle in early disease (especially in idiopathic orofacial granulomatosis) (Fig. 8-8) or more florid in later disease; granulomas of Crohn disease may occur in salivary glands and may contain eosinophils (Figs. 8-9 and 8-10); multiple levels should be performed, if necessary, through the entire block to locate granulomas; edema and chronic inflammation alone are not sufficient for the diagnosis.
• Granulomas of sarcoidosis are nonnecrotizing and well demarcated or “naked” (Fig. 8-11); patients are often blacks, have hilar lymphadenopathy, and elevated levels of angiotensin-converting enzyme; labial salivary gland biopsies show granulomas in 33% of cases.
• Patch test for the idiopathic type to determine if hypersensitivity to the environment exists; intralesional steroid injections can be done every week for several weeks, but relapse is common; topical, intralesional, and systemic therapy controls disease in 70% of patients; minocycline or thalidomide helps some patients.
• Shallow ulcers and erosions, miliary abscesses and pustules on erythematous mucosa (Fig. 8-12); vegetations may be a feature; sometimes folding and fissuring of the buccal mucosa occurs.
• Most common associations are ulcerative colitis (approximately 70%), Crohn disease (10% to 15%) and liver disease; peripheral blood eosinophilia is present in 90% of cases; some cases are idiopathic.
• Epithelial hyperplasia, spongiosis, and suprabasilar clefting with acantholysis are present; neutrophilic and eosinophilic abscesses are noted within the clefts and in the connective tissue papillae (Fig. 8-13).
Gonzalez-Moles MA, Gil-Montoya JA, Ruiz-Avila I, et al. Pyostomatitis vegetans: dramatic clinical response to clobetasol propionate treatment in aqueous solution. J Eur Acad Dermatol Venereol. 2008;22:252-253.
• Well-demarcated, patchy erythematous depapillation of tongue dorsum; raised, linear or circinate, often with discontinuous white peripheral rim; associated with fissured tongue in 25% of cases (Fig. 8-14, A and B); rare on sites other than the tongue (see Fig. 8-14, C)
There is a strong association with atopy (history of hay fever, eczema, asthma, or food intolerance), and psoriasis (especially pustular forms); some associated with human leukocyte antigen (HLA)-Cw6 (also seen in psoriasis).
• Loss of filiform papillae; psoriasiform epithelial hyperplasia with spongiosis and spongiotic pustules (involving one third to two thirds of the thickness of the epithelium); variable lymphocytic infiltrate (Figs. 8-15 to 8-17)
FIGURE 8-15 Benign migratory glossitis. A, Loss of filiform papillae, psoriasiform epithelial hyperplasia, and chronic inflammation. B, Spongiosis and inflammation involving nearly the full thickness of the epithelium. C, Spongiotic pustules.
• Candidiasis also shows psoriasiform epithelial hyperplasia and spongiotic pustules that are confined to the superficial two to three layers of keratinocytes; candidal hyphae are identified with periodic acid–Schiff stain.
Nonspecific Hypersensitivity Reactions