Reprinted from ORAL SURGERY, ORAL MEDJCJNE,ORAL PATHOLOGY St. Louis Vol. 55, No.4, pp. 363-373, April, 1983, (Printed in the U.S.A.) (Copyright © 1983, by The C.V. Mosby Company) Editor: JAMES J. SCIUBBA, D.M.D., Ph.D. American Academy of Oral Pathology Department of Dentistry Long Island Jewish-Hillside Medical Center New Hyde Park, New York I 1042 The differential diagnosis of pyostomatitis vegetans and its relation to bowel disease Louis S. Hansen, D.D.S., M.S., M.B.A.,* S. Silverman, Jr., M.A., D.D.S.,** and Troy E. Daniels, D.D.S., M.S.,*** San Francisco, Calif. SCHOOL OF DENTISTRY, UNIVERSITY OF CALIFORNIA Pyostomatitis vegetans is a rare oral disorder that is usually associated with bowel and/or skin disease. The clinical appearance is of soft hyperplastic folds of mucosa characterized by small miliary abscesses with superficial erosions. Upon analysis of the clinical, histologic, and immunofluorescent findings, cases of pyostomatitis vegetans may be classified as the oral manifestation of either pyoderma vegetans of Hallopeau, pemphigus vegetans of Hallopeau, or pemphigus vegetans of Neumann, although the exact definitions and even the existence of these diseases as separate entities are still a matter of controversy. By 1898 Hallopeau had collected five cases of an both produce bullae and both may be fulminant and eosinophilic pustular and vegetating skin condition in fatal. It differs clinically in that small epithelial adults which he called pyodermite vegetante. t-l Some proliferations, or "vegetations," may arise from the of his patients had oral mucosal involvement. The base of the ruptured bullae. Histologically, both condition is rare, as there have been few case reports pemphigus vulgaris and pemphigus vegetans are since that time. It soon became known as dermatitis characterized by suprabasilar clefting and acantho­ vegetans and later as pyoderma vegetans or pyoder­ lysis, but eosinophils and microabscesses are promi­ ma vegetans of Hallopeau. Controversy has sur­ nent in pemphigus vegetans and absent in pemphigus rounded the etiology of this disease for almost a vulgaris. Pemphigus vegetans may occur as infre­ century,""6 since some authors consider Hallopeau's quently as one case for every fifty cases of pemphigus disorder nothing more than a benign variant of vulgaris, 12 a rare disease in itself. Both pemphigus pemphigus vegetans of Neumann, while others vegetans and pemphigus vulgaris commonly exhibit 7 10 believe it to have an infectious origin. - The possi­ oral manifestations, but in this article we are con­ bility that we are dealing with two or more separate cerned primarily with the oral findings of Hallo­ diseases must also be considered.6 peau's disorder. Pemphigus vulgaris has been known since ancient The association of Hallopeau's disorder (pyosto­ times, but it was not until 1876 that Neumann11 matitis vegetans) with gastrointestinal disturbances described a rare variant of pemphigus vulgaris which is very well established. There have been several he called pemphigus vegetans. Pemphigus vegetans reported cases in which there was a history of bowel 6 13 14 15 of Neumann is similar to pemphigus vulgaris in that disease,"" • • and in 1966 Forman discussed twelve cases of Hallopeau's disorder, of which nine had presented with evidence of colitis. In 1949 Brunsting *Professor and Chai rman, Division of Oral Pathology, Depart­ and Underwood 16 reported five cases of pyoderma ment of Oral Medicine and Hospital Dentistry. **Professor and Chairman, Department of Oral Medicine and vegetans associated with ulcerative colitis and found Hospital Dentistry. some correlation between control of the colitis and ***Professor of Oral Medicine and Oral Pathology. control of the skin lesions. 363 364 Hansen, Silverman, and Daniels Oral Surg. April, 1983 Fig. 1. Clinical appearance of the oral mucosa in pyostomatitis vegetans. The mucosa is arranged in folds, with minute areas covered with a pseudomembrane. There is a tendency to bleed easily, but no unusual discomfort. Table 1. Differential diagnosis of pyostomatitis vegetans lmmuno- Eo- lntraepi- A can- Oral Papillomatous fluor- sino- thelia/ History of tho- Disease findings proliferations Prognosis escence phi/s abscesses "colitis" lysis Pyoderma vegetans Yes Yes Localized and DIF- Yes ++ Often; good Rare (PDVH) (Hallopeau benign; no bullae IIF- correlation 1889-1898) Pemphigus vegetans of Yes Yes Benign; no bullae DlF+ Yes +++ Incomplete Rare Hallopeau (PVH) IIF + data (Nelson et al. 1977) Pemphigus vegetans Often Usually Fulminant and DlF+ Yes +++ No Yes (PV)* (Neumann vesicles potentially fatal; IIF + +++ 1876) bullae Pemphigus vulgaris* Often No Fulminant and DIF+ No No No Yes potentially fatal; IIF + ++++ bullae *The oral manifestations of pemphigus vegetans and pemphigus vulgaris are not considered to be pyostomatitis, but these diseases are included here for comparison purposes and to suggest a possible overlapping relationship among all four diseases. Similarly, many cases of pyoderma vegetans have of pyostomatitis vegetans, review the literature on presented with, or developed, oral lesions. Forman this disease, and suggest a differential diagnosis states that the mouth and tongue were severely based on an analysis of the clinical and pathologic affected in all of Hallopeau's five casesY Oral findings. lesions comparable to skin lesions were described in CASE REPORT several reports,4-6 including that of Forman,I 5 which described stomatitis in ten of twelve cases. A 37-year-old white man was referred with a complaint However, it remained for McCarthy14 to focus of "fissures" in his mouth for the past 4 months. He also complained of a "swollen feeling" and said that his mouth attention on the oral manifestations of Hallopeau's was sensitive to citrus fruits. He gave a 15-year history of disorder, which he called pyostomatitis vegetans. persistent diarrhea, consisting of six or more stools daily. A Although oral lesions were mentioned in many of the letter from his physician stated that a diagnosis of "ulcer­ thirty-five cases already published, McCarthy was ative colitis" had been made 12 years earlier, based on the first to describe the histopathology of the oral clinical observation, anoscopy, and sigmoidoscopy. findings. Oral examination revealed more or less generalized, The purpose of this article is to report a new case fissured, "pebbly" changes on the right and left buccal and Volume 55 Differential diagnosis of pyostomatitis vegetans 365 Number 4 Fig. 2. Low-power view of microscopic section of oral mucosa seen in Fig. 1. There is a uniform downgrowth of blunt-tipped rete ridges with dermal papillae reaching almost to the surface. Inflammatory cells with prominent eosinophils have infiltrated both the epithelium and the connective tissues. Arrows point to dense collections of eosinophils. (Hematoxylin and eosin stain. Original magnification, XlOO.) labial mucosae. The mucosa, arranged in folds, tended to to the epithelium, there was a dense infiltrate of plasma bleed easily, and some minute areas appeared ulcerated cells, lymphocytes, and eosinophils (Fig. 2). Deeper in the and covered with a pseudomembrane (Fig. 1). The patient submucosa was a mild perivascular infiltrate composed of had no skin lesions, and there was no lymphadenopathy. similar cells. There was no evidence of noncaseating Routine microscopic examination of the oral mucosa epithelioid granulomas. revealed moderately vascular, dense, fibrous connective Tissue was also removed for direct immunofluorescence. tissue covered by stratified squamous epithelium with a Reaction with antihuman IgG showed finely granular wavy surface of thin parakeratin. There was a relatively fluorescence in the intercellular spaces of most of the uniform downgrowth of blunt-tipped rete ridges with a epithelium covering one end of the specimen. It was most corresponding increase in the height of the dermal papillae intense in the superficial layers and also faintly present (Fig. 2). The surface epithelium was infiltrated with a few throughout most of the epithelium. Reaction with antihu­ lymphocytes and polymorphonuclear neutrophils, but par­ man IgA showed a similar pattern and distribution of ticularly noticeable was a moderate number of eosinophils fluorescence, but with less intensity than that seen with (Fig. 3). Mitoses were prominent but appeared to be IgG. Reaction with antihuman fibrinogen showed faint, normal. There was no evidence of dysplasia. Microab­ linear, intermittent fluorescence in the basement zone. scesses containing large numbers of eosinophils appeared Reactions with antihuman IgM and C'3 were negative. to be within the tips of the dermal papillae cut tangentially. The pattern and distribution of fluorescence with IgG was In a few focal areas of the stratum spinosum, dissociation not suggestive of the overall fluorescent pattern seen with of squamous epithelial cells was seen, but it was not the pemphigus vulgaris and pemphigus vegetans. acantholysis seen in pemphigus. Eosinophils were promi­ The patient was referred back to his physician for nent in these areas (Fig. 4.) Within the lamina propria, further examination and treatment with a diagnosis of especially in the connective tissues immediately subjacent pyostomatitis vegetans (consistent with pemphigus vege- 366 Hansen, Silverman, and Daniels Oral Surg . • April, 1983 Fig. 3. High-power view of the microabscess shown in Fig. 2 reveals that it is packed with eosinophils. It appears to be within the epithelium, but more