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Morphogenesis of inflammatory papillary hyperplasia
Morphogenesis of inflammatory papillary hyperplasia Duane E. Cutright, D.D.S.: Ph.D.* United States Army Institute o[ Dental Research, Walter Reed Array Medical Center, Washington, D. C.
T h e formation of the multiple papillomas f o u n d i n inflammatory papillary hyperplasia (I.P.H.) and epulis fissuratunl associated with the wearing of dentures has been ascribed to many etiologic agents. ~':~ In the most recent survey of 341 cases, the growth or the anatomic changes found in I.P.H. were not discussed. "~This report will attempt to elucidate the factors accounting for the morphogenesis of the multiple papillae and will discuss treatment in relation to this hypothesis. In any discussion of I.P.H., there are certain local environmental and anatomic factors associated with dentures which must be considered as contributing to the formation of the peculiar morphology of I.P.H. Some of these are focal changes such as change in bacterial flora, failure of the salivary flow to cleanse the palate, failure of the food bolus and tongue to cleanse, possible changes in atmospheric pressure, accumulation of toxic substances, allergic response, and trauma by the denture itself. Any or even all of these may act as irritants and bring about an inflammatory response in the submucosa, which this author feels is the initiating factor in the formation of I.P.H. MORPHOGENESIS
Epithelial hyperplasia. The early reaction of the oral epithelium to this inflammation, mild trauma, and constant irritation is a hyperplastic reaction histologically manifested as acanthosis and hyperparakeratosis. This defensive thickening is a primary function of epitheliun~ and demonstrates its ability to grow into the subjacent connective tissue in response to foci of chronic inflammation. This reaction is also found around granulomas, chronic ulcers, fungal infections, and bony sequestra. When it occurs around a sequestrum, it is called "epithelial forceps.":' This epithelial response when mild is histologically manifested as acanthosis but when severe as pseudoepithelionmtous hyperplasia. In the latter situation, epitllelium grows into the conRead before the American Prosthodontic Society in Atlantic City, N. J. *Colonel, DC, USA; Director, United States Army Institute of Dental Research.
380
vol,m~3:* Number 4
Morphogenesis o[ papillary hyperplasia $81
Fig. 1. Gross section of the palate. The elongation of rete pegs extends deep into the connective tissue in the area of dense, chronic inflammation. Clefting of the surface epithelium (arrow) is minimal, and the submucosa shows increased collagen.
Fig. 2. The blood supply: A, supply at the junction of the hard and soft palates showing many areas in the lamina propria with no vascular supply (arrow); B, surface view showing many small, dark areas (arrow) where the rete peg penetrates into the deeper tissue for which there is a decreased vascular supply.
nective tissue and attempts to exteriorize and rid the body of the subjacent chronic inflammatory reaction (Fig. 1). Epithelial splitting. The epithelium itself contains no blood supply and, therefore, must depend upon the diffusion of nutrients. On the palate, when the epithelium under a denture becomes acanthotic and thickens beyond some unknown physiologically accepted limit, clefts appear in tile center of the rete pegs (Fig. 1). This clefting may also be intensified by tile depression of tlle denture during mastication, thus producing increased pressures in the small basal areas of the clefts. Vascular supply. Blood is supplied to the dermal papillae in the oral cavity by small helices which arise from the rete subpapillare and travel upward into each of tile dermal pal)ilia. The rete subpal)illare generally runs parallel to tile mueosal sur-
31t2
Cutright
j. Prosthet. Dent. April~ 1975
Fig. 3. Cross section of the palate. There is a dense collection of collagen fibrils with few vascular channels.
Fig. 4. Cross section of inflammatory papillary hyperplasia on the palate. The inflammation is decreased near the surface but shows a dense infiltrate around the apices of the rete pegs
(arrow). Fig. 5. Cross section of the palate of a denture-wearer with mild inflammatory papillary hyperplasia. The epithelium is acanthotic but otherwise relatively normal.
face. This leaves small areas near the apex of the epithelial rete pegs with a decreased blood supply (Fig. 2, A and B). Collagen deposition. The end result of any inflammatory reaction is healing. In the loose, fibrous, connective tissue of the lamina propria and the deeper, dense, connective tissue, this almost invariably results in the deposition of collagen or in mild scar formation. Scar tissue itself is relatively avascular, resistant to infection, and resistant to trauma (Fig. 3). Chronology. If we now consider the aforementioned pl~enomena and how they bring about tile characteristic appearance of I.P.H., the following sequence of events can be followed. The inflammatory reaction, which is always seen in I.P.H., consists of an acute, subacute, or chronic reaction most often limited to the lamina propria.
vo~,,,,,a:~
Numher 4
Morphogenesis o/ papillary hyperplasia ~8~
Fig. 6. Cross section of a palate with mild inflammatory papillary hyperplasia. Epithelial cleft. ing (arrow) has just begun. Islands of chronic inflammation are present in the submucosa. Fig. 7. Cross section of palatal inflammatory papillary hyperplasia. Clefting is moderately deep to the level of the submucosa. Inflammation is chronic. The deeper epithelial cells show a morphology slightly different than that of the more superficial, stratified, squamous epithelium.
Fig. 8. Gross section of inflammatory papillary hyperplasia. Cleft[ng is prominent and extends below the level of the lamina propHa. Inflammation is chronic and intense at the apex of the central rete peg (arrow). This reaction, which is most often chronic, varies according to the intensity of the irritant and is modified by the duration of the reaction. In the early development of inflammatory papillary hyperplasia, the inflammatory reaction may involve the lamina propria completely around the rete peg, from apex of rete peg to apex of dermal papilla (Fig. 1). However, later, the inflammatory reaction lessens at the dermal apex and increases at the rete-peg apex in the area of decreased blood supply (Fig. 4). In addition, by this stage of formation, ttle inflammatory reaction is primarily chronic in nature but may show periods of acute inflammatory cell infiltration. During this time, an increase in the amount of collagen has occurred in the deeper part of the dermal papilla (Fig. 4). T h e intense chronic reaction in the lamina propria stimulates tile epithelium at the apex of the rete peg to continue proliferating into the deeper tissue in an attempt to wall off or exteriorize the chronic inflammatory reaction. This results in lengthening of the epithelial peg. This is a normal defensive reaction of the epithelium. In addition, this inflammatory reaction
384
Cutright
J. e,~,sthet. Dent. April, 1975
Fig. 9, Cross section of inflammatory papillary hyperplasia of the palate. There is multiple clefting when viewed in three dimensions. Inflammation is chronic, and epithelial hyperplasia is prominent. Fig. 10. Cross section of a palate with inflammatory papillary hyperplasia. There is elongation of several papillary projections above the surrounding tiss~m.
is taking place where tile blood supply is less than in other surrounding areas, thus allowing it to continue for long periods of time. With this continued stimulation, the epithelium proliferates and becomes markedly acanthotic. By the time this happens, the upper dermal peg often has lost much of its inflammatory reaction (Fig. 4). Concurrently, due to the marked acanthosis and decreased nutrient supply, the epithelial peg begins to split in these central areas int0 which nutrients fail to diffuse. When this happens, the typical morphology of I.P.H. begins (Figs. 5 to 10). This clef tiny allows the trapping of bacterial toxins, food particles, and cellular debris which propagate a continuing inflammatory reaction within the lamina propria, especially near the apex of the rete peg. With this continued inflammatory reaction and healing, collagen is soon deposited in large amounts in the dermal papillae along the lower margins and apex of the epithelial rete peg. This increase of collagen causes an elongation of the individual papillae similar to that seen in the growth of an irritation fibroma. Indeed, in many patients, the papilla extends above the surrounding connective tissue. This indicates that the length of the papilla is due, in part, to clefting of epithelium and in part, to actual elongation of the papilla with the deposition of collagen. In addition, some of the papillae manifest edema, which is very high in protein. It appears that some of these undergo organization instead of resolution. This also may contribute to the elongation of the papillae. The clefting or splitting of the fete pegs may continue, perhaps influenced by pressure changes under tim denture, until it approaches the depth of the lamina propria. Here, it usually stabilizes unless there is some massive incident which brings about degeneration of the underlying bIood vessels. It is occasionally possible to notice a histologic difference in the epithelium of the lower part of the fete pegs, giving the impression that these proliferating cells are from a different progenitor (See Fig. 7).
voz,m~ :~3 Number 4
Morphogenesis o[ papillary hyperplasia
385
The continuous presence of local inflammatory changes causes the I.P.H. to form initially, and it is the body's attempt to defend itself against these changes which causes the peculiar papillary appearance. This unremitting cycle of irritation, inflammation, and repair determines the anatomic form and magnitude of the condition. TREATMENT
it is the deposition of large amounts of collagen which dictates whether or not simply removing the denture will allow a rapid return of papillae to normal, because the body cannot rapidly remove dense collagen from the palatal connective tissue. The mature collagen is much more stable and less dynamic than are the other palatal tissues. Therefore, removal of the denture for short periods of time (a week) will allow only the loss of edema and the possible return of normal color due to the decrease of the hyperemia, with little actual regression of the condition. This deposition of collagen and papillary formation dictate that the contemporary method of treatment must include removal of the papilla down to or beyond the bottom of the clefts and then the institution of good oral hygiene to prevent the repetition of events leading to the condition. Recently, tile use of pulsating water-jet devices has been shown to be a possible method of successfully treating and/or preventing I.P.H. ~ These devices, having a nmltiple orifice or shower-head type of tip, when used to lavage the palate twice daily for two minutes, may obviate the traumatic experience of palatal surgery. Thus used, these devices are capable of cleansing even the deepest pockets and clefts under these dentures, thereby eliminating the inflammation and preventing the growth of the I.P.H. SUMMARY
An hypothesis for the peculiar morphology shown in inflammatory papillary hyperplasia has been discussed, and a new method of prevention and treatment has been described. References 1. Izikowitz, L.: A Histological Study of Soft Tissue Reactions Under and Adjoining Fixed Free-End Saddles, Acta Odontol. Scand. 27: 31-46, 1969. 2. Marmelzat, W. L.: Case for Diagnosis: Moniliasis as Possible Etiologic Factor for Pseudoepitheliomatous Hyperplasia? Verruciform Lesions of Mucous Membrane? Arch. Dermatol. 96: 598-601, 1967. 3. Arwill, T., Nilsson, B., and Oberg, G.: Eversion of Columnar Epithelium in Denture-Induced Hyperplasia of the Oral Mucous Membrane of Man, Arch. Oral Biol. 13: 589-591, 1968. 4. Bhaskar, S. N., Beasley, J. D., III, and Cutright, D. E." Inflammatory Papillary Hyperplasia of the Oral Mucosa: Report of 341 Cases, J. Am. Dent. Assoc. 81: 949-952, 1970. 5. Tiecke, R. W.: Oral Pathology, New York, 1965, McGraw-Hill Book Company, Inc. 6. Cutright, D. E." Uupublished data. UNITED STATES A R M Y INSTITUTE OF DENTAL RESEARCH WALTER REED A R M Y MEDICAL CENTER
WASHINCTON, D. G. 20012
T h e formation of the multiple papillomas f o u n d i n inflammatory papillary hyperplasia (I.P.H.) and epulis fissuratunl associated with the wearing of dentures has been ascribed to many etiologic agents. ~':~ In the most recent survey of 341 cases, the growth or the anatomic changes found in I.P.H. were not discussed. "~This report will attempt to elucidate the factors accounting for the morphogenesis of the multiple papillae and will discuss treatment in relation to this hypothesis. In any discussion of I.P.H., there are certain local environmental and anatomic factors associated with dentures which must be considered as contributing to the formation of the peculiar morphology of I.P.H. Some of these are focal changes such as change in bacterial flora, failure of the salivary flow to cleanse the palate, failure of the food bolus and tongue to cleanse, possible changes in atmospheric pressure, accumulation of toxic substances, allergic response, and trauma by the denture itself. Any or even all of these may act as irritants and bring about an inflammatory response in the submucosa, which this author feels is the initiating factor in the formation of I.P.H. MORPHOGENESIS
Epithelial hyperplasia. The early reaction of the oral epithelium to this inflammation, mild trauma, and constant irritation is a hyperplastic reaction histologically manifested as acanthosis and hyperparakeratosis. This defensive thickening is a primary function of epitheliun~ and demonstrates its ability to grow into the subjacent connective tissue in response to foci of chronic inflammation. This reaction is also found around granulomas, chronic ulcers, fungal infections, and bony sequestra. When it occurs around a sequestrum, it is called "epithelial forceps.":' This epithelial response when mild is histologically manifested as acanthosis but when severe as pseudoepithelionmtous hyperplasia. In the latter situation, epitllelium grows into the conRead before the American Prosthodontic Society in Atlantic City, N. J. *Colonel, DC, USA; Director, United States Army Institute of Dental Research.
380
vol,m~3:* Number 4
Morphogenesis o[ papillary hyperplasia $81
Fig. 1. Gross section of the palate. The elongation of rete pegs extends deep into the connective tissue in the area of dense, chronic inflammation. Clefting of the surface epithelium (arrow) is minimal, and the submucosa shows increased collagen.
Fig. 2. The blood supply: A, supply at the junction of the hard and soft palates showing many areas in the lamina propria with no vascular supply (arrow); B, surface view showing many small, dark areas (arrow) where the rete peg penetrates into the deeper tissue for which there is a decreased vascular supply.
nective tissue and attempts to exteriorize and rid the body of the subjacent chronic inflammatory reaction (Fig. 1). Epithelial splitting. The epithelium itself contains no blood supply and, therefore, must depend upon the diffusion of nutrients. On the palate, when the epithelium under a denture becomes acanthotic and thickens beyond some unknown physiologically accepted limit, clefts appear in tile center of the rete pegs (Fig. 1). This clefting may also be intensified by tile depression of tlle denture during mastication, thus producing increased pressures in the small basal areas of the clefts. Vascular supply. Blood is supplied to the dermal papillae in the oral cavity by small helices which arise from the rete subpapillare and travel upward into each of tile dermal pal)ilia. The rete subpal)illare generally runs parallel to tile mueosal sur-
31t2
Cutright
j. Prosthet. Dent. April~ 1975
Fig. 3. Cross section of the palate. There is a dense collection of collagen fibrils with few vascular channels.
Fig. 4. Cross section of inflammatory papillary hyperplasia on the palate. The inflammation is decreased near the surface but shows a dense infiltrate around the apices of the rete pegs
(arrow). Fig. 5. Cross section of the palate of a denture-wearer with mild inflammatory papillary hyperplasia. The epithelium is acanthotic but otherwise relatively normal.
face. This leaves small areas near the apex of the epithelial rete pegs with a decreased blood supply (Fig. 2, A and B). Collagen deposition. The end result of any inflammatory reaction is healing. In the loose, fibrous, connective tissue of the lamina propria and the deeper, dense, connective tissue, this almost invariably results in the deposition of collagen or in mild scar formation. Scar tissue itself is relatively avascular, resistant to infection, and resistant to trauma (Fig. 3). Chronology. If we now consider the aforementioned pl~enomena and how they bring about tile characteristic appearance of I.P.H., the following sequence of events can be followed. The inflammatory reaction, which is always seen in I.P.H., consists of an acute, subacute, or chronic reaction most often limited to the lamina propria.
vo~,,,,,a:~
Numher 4
Morphogenesis o/ papillary hyperplasia ~8~
Fig. 6. Cross section of a palate with mild inflammatory papillary hyperplasia. Epithelial cleft. ing (arrow) has just begun. Islands of chronic inflammation are present in the submucosa. Fig. 7. Cross section of palatal inflammatory papillary hyperplasia. Clefting is moderately deep to the level of the submucosa. Inflammation is chronic. The deeper epithelial cells show a morphology slightly different than that of the more superficial, stratified, squamous epithelium.
Fig. 8. Gross section of inflammatory papillary hyperplasia. Cleft[ng is prominent and extends below the level of the lamina propHa. Inflammation is chronic and intense at the apex of the central rete peg (arrow). This reaction, which is most often chronic, varies according to the intensity of the irritant and is modified by the duration of the reaction. In the early development of inflammatory papillary hyperplasia, the inflammatory reaction may involve the lamina propria completely around the rete peg, from apex of rete peg to apex of dermal papilla (Fig. 1). However, later, the inflammatory reaction lessens at the dermal apex and increases at the rete-peg apex in the area of decreased blood supply (Fig. 4). In addition, by this stage of formation, ttle inflammatory reaction is primarily chronic in nature but may show periods of acute inflammatory cell infiltration. During this time, an increase in the amount of collagen has occurred in the deeper part of the dermal papilla (Fig. 4). T h e intense chronic reaction in the lamina propria stimulates tile epithelium at the apex of the rete peg to continue proliferating into the deeper tissue in an attempt to wall off or exteriorize the chronic inflammatory reaction. This results in lengthening of the epithelial peg. This is a normal defensive reaction of the epithelium. In addition, this inflammatory reaction
384
Cutright
J. e,~,sthet. Dent. April, 1975
Fig. 9, Cross section of inflammatory papillary hyperplasia of the palate. There is multiple clefting when viewed in three dimensions. Inflammation is chronic, and epithelial hyperplasia is prominent. Fig. 10. Cross section of a palate with inflammatory papillary hyperplasia. There is elongation of several papillary projections above the surrounding tiss~m.
is taking place where tile blood supply is less than in other surrounding areas, thus allowing it to continue for long periods of time. With this continued stimulation, the epithelium proliferates and becomes markedly acanthotic. By the time this happens, the upper dermal peg often has lost much of its inflammatory reaction (Fig. 4). Concurrently, due to the marked acanthosis and decreased nutrient supply, the epithelial peg begins to split in these central areas int0 which nutrients fail to diffuse. When this happens, the typical morphology of I.P.H. begins (Figs. 5 to 10). This clef tiny allows the trapping of bacterial toxins, food particles, and cellular debris which propagate a continuing inflammatory reaction within the lamina propria, especially near the apex of the rete peg. With this continued inflammatory reaction and healing, collagen is soon deposited in large amounts in the dermal papillae along the lower margins and apex of the epithelial rete peg. This increase of collagen causes an elongation of the individual papillae similar to that seen in the growth of an irritation fibroma. Indeed, in many patients, the papilla extends above the surrounding connective tissue. This indicates that the length of the papilla is due, in part, to clefting of epithelium and in part, to actual elongation of the papilla with the deposition of collagen. In addition, some of the papillae manifest edema, which is very high in protein. It appears that some of these undergo organization instead of resolution. This also may contribute to the elongation of the papillae. The clefting or splitting of the fete pegs may continue, perhaps influenced by pressure changes under tim denture, until it approaches the depth of the lamina propria. Here, it usually stabilizes unless there is some massive incident which brings about degeneration of the underlying bIood vessels. It is occasionally possible to notice a histologic difference in the epithelium of the lower part of the fete pegs, giving the impression that these proliferating cells are from a different progenitor (See Fig. 7).
voz,m~ :~3 Number 4
Morphogenesis o[ papillary hyperplasia
385
The continuous presence of local inflammatory changes causes the I.P.H. to form initially, and it is the body's attempt to defend itself against these changes which causes the peculiar papillary appearance. This unremitting cycle of irritation, inflammation, and repair determines the anatomic form and magnitude of the condition. TREATMENT
it is the deposition of large amounts of collagen which dictates whether or not simply removing the denture will allow a rapid return of papillae to normal, because the body cannot rapidly remove dense collagen from the palatal connective tissue. The mature collagen is much more stable and less dynamic than are the other palatal tissues. Therefore, removal of the denture for short periods of time (a week) will allow only the loss of edema and the possible return of normal color due to the decrease of the hyperemia, with little actual regression of the condition. This deposition of collagen and papillary formation dictate that the contemporary method of treatment must include removal of the papilla down to or beyond the bottom of the clefts and then the institution of good oral hygiene to prevent the repetition of events leading to the condition. Recently, tile use of pulsating water-jet devices has been shown to be a possible method of successfully treating and/or preventing I.P.H. ~ These devices, having a nmltiple orifice or shower-head type of tip, when used to lavage the palate twice daily for two minutes, may obviate the traumatic experience of palatal surgery. Thus used, these devices are capable of cleansing even the deepest pockets and clefts under these dentures, thereby eliminating the inflammation and preventing the growth of the I.P.H. SUMMARY
An hypothesis for the peculiar morphology shown in inflammatory papillary hyperplasia has been discussed, and a new method of prevention and treatment has been described. References 1. Izikowitz, L.: A Histological Study of Soft Tissue Reactions Under and Adjoining Fixed Free-End Saddles, Acta Odontol. Scand. 27: 31-46, 1969. 2. Marmelzat, W. L.: Case for Diagnosis: Moniliasis as Possible Etiologic Factor for Pseudoepitheliomatous Hyperplasia? Verruciform Lesions of Mucous Membrane? Arch. Dermatol. 96: 598-601, 1967. 3. Arwill, T., Nilsson, B., and Oberg, G.: Eversion of Columnar Epithelium in Denture-Induced Hyperplasia of the Oral Mucous Membrane of Man, Arch. Oral Biol. 13: 589-591, 1968. 4. Bhaskar, S. N., Beasley, J. D., III, and Cutright, D. E." Inflammatory Papillary Hyperplasia of the Oral Mucosa: Report of 341 Cases, J. Am. Dent. Assoc. 81: 949-952, 1970. 5. Tiecke, R. W.: Oral Pathology, New York, 1965, McGraw-Hill Book Company, Inc. 6. Cutright, D. E." Uupublished data. UNITED STATES A R M Y INSTITUTE OF DENTAL RESEARCH WALTER REED A R M Y MEDICAL CENTER
WASHINCTON, D. G. 20012