The Differential Diagnosis of Pyostomatitis Vegetans and Its Relation to Bowel Disease

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 likely the "abscess" is the tip of a dermal papilla. (Hematoxylin and eosin stain. Original magnification, X375.) tans of Hallopeau). The radiographic examination of the REVIEW OF THE LITERATURE lower gastrointestinal tract was consistent with "ulcerative Our literature search included only those pub colitis," involving the terminal ileum, colon, and rectum. lished cases of Hallopeau's disease, with or without Rectal examination revealed a 4+ friability, a 4+ granu larity, I+ mucus, but no edema or blood. Later within the skin lesions, in which there was a microscopic year a fistula was discovered and treated successfully by description of the oral lesions. Several reports had to surgical means. be excluded because specific histologic findings were 17 19 21 The patient was placed on a regimen of 40 mg. predni not providedY· • • We found that there was a sone daily in decreasing doses. The oraf lesions cleared great deal of confusion surrounding pyostomatitis within weeks, and the patient has been free of oral disease vegetans, stemming from the uncertain and contro for the last I8 months. His bowel disease was treated with versial etiology, the scarcity of patients, and particu intermittent steroids and sulfasalazine. The number of larly the variety of synonyms and similar-sounding stools was reduced to two to three daily, with no blood or diagnoses that have been applied to similar and mucus. A rectal biopsy performed I year after diagnosis possibly overlapping diseases. For this reason, we and initiation of therapy revealed plasma cells, lymphoid think it important at this point to define certain aggregates, and eosinophils, but no granulomas. The diagnostic terms as follows: microscopic diagnosis was follicular hyperplasia. On review of the microscopic, roentgenographic, and 1. Pyostomatitis vegetans. The oral manifesta clinical evidence, the patient was now thought to have tions, with or without skin lesions, of Hallo bowel disease consistent with either Crohn's or "overlap" peau's disorder, pyoderma vegetans (PDVH). disease13 and not ulcerative colitis, the diagnosis made 2. Pemphigus vegetans of Hallopeau (PVH). A years earlier. term recently applied to certain patients with Volume 55 Differential diagnosis of pyostomatitis vegetans 367 Number 4

•

Fig. 4. High-power view of the' stratum spinosum shows an area with dissociation of epithelial cells, but not the acantholysis typical of pemphigus. Arrows point to some of many eosinophils within the intercellular spaces. (Hematoxylin and eosin stain. Original magnification, Xl,SOO.)

the manifestations of Hallopeau's disorder reported cases. Patients' reported ages ranged from 9 exhibiting positive immunofluorescence. The to 70 years. However, some of the stated ages were term is used by those who believe that these pa the age at onset and others were the age at diagnosis, tients have either a benign variant of pemphi and since the disease is chronic and may persist over gus vegetans of Neumann (PV) or an entity dif a number of years, any conclusions should be ferent from pyoderma vegetans of Hallopeau. regarded with caution. Nonetheless, the disease 3. Pemphigus vegetans of Neumann (PV). The seems to affect patients of almost any age. rare variety of pemphigus vulgaris described by Fourteen of the sixteen patients on whom there Neumann in 1876. was information about bowel disease had a history of The controversy over the relationship of PDVH to diarrhea, ulcerative colitis, or Crohn's disease. These PV has been recently rekindled by immunofluores findings support the contention of McCarthy and cent studies, beginning with the work of Ouimet and Shklar18 that the oral lesions are part of a distinctive co-workers22 in 1973. Table I summarizes the clinical syndrome in which bowel disease is characterized by and pathologic features of all these diseases. lesions similar to those in the oral cavity. A review of the reported cases of pyostomatitis Skin lesions were reported in eleven of seventeen vegetans (Table II) indicates that males were af patients. Many therapeutic modalities were insti fected more than females (14:5), a sexual predilec tuted, including various antibiotics, dapsone, x tion that was also found in cases of oral lesions in irradiation, and surgery. Only systemic corticoste patients with Crohn's disease. 24 No firm conclusions roids were effective, sometimes resulting in dramatic can be reached, however, because of the paucity of improvement. 368 Hansen, Silverman, and Daniels Oral Surg. April, 1983

Table II. Summary of data from twenty reported cases of pyostomatitis vegetans, including those cases of Hallopeau's disease with or without skin lesions but not including those cases of pemphigus vegetans (Neumann) or pemphigus vulgaris which have oral manifestations

Case Peripheral Skin No. Author Bowel disease eosinophilia lesions

McCarthy" 1949 26 F Chronic diarrhea 18% None

2 McCarthy14 1949 47 M w Chronic spastic colitis Yes Yes

3 McCarthy'• 1949 33 M None Yes None

4 Hornstein35 1957 56 M Mild colitis 4% None

5 Hays25 1961 61 M w

6 Leydhecker and Lund, 36 1962 9 M Diarrhea 6-25% Yes Hornstein37

7 Zegarelli and Kutscher26 1962 27 F w Chronic ulcerative colitis 14% Yes

8 Zegarelli and Kutscher• 1962 24 M w Chronic ulcerative colitis Normal Yes

9 McCarthy and Shklar18 1963 27 M w Ulcerative colitis Yes

The oral regions involved were the labial and findings of PDVH. Nonetheless, R6ckl8 found that buccal mucosae, gingivae, tongue, upper and lower most of the evidence favored a diagnosis of pyosto vestibules, hard and soft palates, and the tonsillar matitis vegetans (PDVH) rather than a benign form areas. Although the oral lesions varied somewhat of pemphigus vegetans of Neumann (PV). from patient to patient, they were usually described Ten of the eleven patients with reported blood as soft, hyperplastic folds exhibiting miliary counts had a peripheral eosinophilia (up to 25 abscesses, pinpoint to pinhead in size, with superfi percent eosinophils). This seems to be a feature of cial erosions. Sometimes the affected areas were the disease, even though a differential count in the erythematous, but most patients reported little dis remaining patients might have been within normal comfort. Some patients were reported to have multi limits. ple small yellow pustules in addition to fissures. Histologically, the oral lesions were characterized RELATIONSHIP OF PYOSTOMATITIS VEGETANS by miliary intraepithelial andfor subepithelial TO BOWEL DISEASE abscesses containing large numbers of eosinophils. Recent studies on pyostomatitis vegetans and oral 9 24 Although intraepithelial abscesses were reported, at lesions in Crohn's disease • have focused attention least some of the photomicrographs suggested that, on a possible relationship between these two dis rather than being within the epithelium, the eases. abscesses were actually in the tips of tangentially cut Crohn's disease, also known as granulomatous dermal papillae. In a case of particular importance, colitis or regional enteritis, is a chronic inflammatory R6ckl8 found evidence of the supra basilar clefting by disorder that primarily affects segmental areas of the acantholysis seen in PV in addition to the classic distal ileum and right colon. It produces a variety of Volume 55 Differential diagnosis of pyostomatitis vegetans 369 Number 4

Histopathology DIF /IF Treatment Response

Miliary abscesses with Gold+ Na Poor polymorphonuclear neutrophils thiosulphate-penicillin and eosinophils, acanthosis, no sulfa-iron-liver acantholysis Miliary abscesses with Sulfa-vitamins-iron-liver Poor polymorphonuclear neutrophils and eosinophils, acanthosis, no acantholysis Miliary abscesses with Improved polymorphonuclear neutrophils and eosinophils, acanthosis, no acantholysis Miliary intra- and subepithelial Antibiotics and surgery Poor abscess with eosinophils, no acantholysis Miliary intraepithelial abscess Local Poor with eosinophils Marked pseudoepitheliomatous X-ray-antibiotics Dramatic improvement hyperplasia with subepithelial with corticosteroids and intraepithelial eosinophilic abscesses Acanthosis, eosinophils and other Sulfasalazine-triamcinolone Fair inflammatory cells Acanthosis, eosinophils and other Prednisone-triamcinolone Good inflammatory cells Chronic inflammation and Corticosteroids and Good localized acute purulent antispasmodics inflammation consistent with pyostomatitis vegetans, eosinophils in early lesions

Continued abdominal signs and symptoms, most notably chron histologic features of the two diseases. They conclud ic, intermittent diarrhea and abdominal cramps. It ed that there is a spectrum of radiological and may at times be difficult or impossible to distinguish histologic findings shared by both disease processes, from ulcerative colitis by clinical criteria alone. and in those patients in whom the clinical-radiologic (Although the pathologic changes of ulcerative coli pathologic signs overlap, the diagnosis of the colitis tis were reported in 1889,23 Crohn's disease was not must remain unresolved: "overlap disease." They described until 193227 and was not considered a noted several other studies which also demonstrated 28 29 separate entity until 1960. • ) that histopathologic findings alone could not be The classic histologic findings ascribed to intesti relied upon for the final diagnosis because of overlap nal Crohn's disease include transmural inflammation in the histologic featuresY and numerous well-defined lymphoid follicles, non It is not surprising, then, that there may be caseating granulomas, or both in the submucosa and overlapping clinical and microscopic findings in the serosa. Ulcerative colitis is characterized by a thin, oral mucosa. Indeed, in their review, Bernstein and soft, friable bowel. The serosa is rarely thickened, McDonald24 found a spectrum of oral lesions in and the inflammatory reaction is superficial. Areas Crohn's disease which they grouped as "nonspecific" of ulceration alternate with pseudopolyps of inflam and "specific." The nonspecific lesions are ulcers of matory and hyperplastic origin. the aphthous type and might well be the most Margulis and colleagues, 23 reporting on a series of frequent oral lesions seen in Crohn's disease, just as 150 patients, attempted to differentiate between they are in ulcerative colitis.30 ulcerative colitis and Crohn's disease. They found a The "specific" oral lesions are histologically non substantial overlap in the clinical, radiographic, and caseating epithelioid granulomas which, in and of 370 Hansen, Silverman, and Daniels Oral Surg. April, 1983

Table II. Cont'd

Case Peripheral Skin No. Author Bowel disease eosinophilia lesions

10 McCarthy and Shklar11 1963 15 M Ulcerative colitis None

II McCarthy and Shklar11 1963 25 M Ulcerative colitis Yes

12 R6ckl1 1964 59 M Yes

13 Forman20 1965 45 F Ulcerative colitis 10-20% Yes

14 Forman20 1965 44 F Ulcerative colitis 12% Yes

IS N aisch et al.30 1970 26 M B Ulcerative colitis No

16 Ouimet et al.22 1973 70 F 16% Yes

17 Nelson et al.1 1977 70 M None 15% Yes

18 Nelson34 1978 19 Cataldo et al.9 1981 48 M w Intermittent diarrhea, Crohn's disease 20 Present report 1982 37 M w Chronic ulcerative colitis vs. 4% No Crohn 's disease

themselves, are not diagnostic of Crohn's disease; nor regarded as a separate entity only since 1960, one does their absence militate against the diagnosis. 28 may speculate as to how many of those patients with Granulomas are present in only 60 to 87 percent of "ulcerative colitis" would be diagnosed today as 28 31 cases of intestinal Crohn's disease • and should not having Crohn's disease, on the basis of complete be expected in all biopsy specimens. Even when clinical, radiologic, and histologic findings. present, they may be few in number.24 In summary, our review of twenty cases of pyosto The similarity in the clinical oral findings in some matitis vegetans suggests that patients with the cases of pyostomatitis vegetans and in some cases of classic histologic oral findings of microabscesses Crohn's disease has been noted by Cataldo and his featuring eosinophils are likely to have associated colleagues.9 Fissured or cobblestone lesions of the bowel disease which may eventually be diagnosed as buccal mucosa have been reported to be suggestive of chronic ulcerative colitis, Crohn's disease, or "over 7 9 14 18 25 26 Crohn's disease. • • • • • It is of interest that most lap" disease. reported cases of pyostomatitis vegetans were pub Patients with the classic histologic oral findings of lished in 1970 or earlier and were reported to be noncaseating epithelioid granulomas plus bowel dis associated with "ulcerative colitis." Since 1970 the ease may, after adequate work-up, be diagnosed as only two cases of pyostomatitis reported to have having Crohn's disease. bowel disease were diagnosed as having Crohn's or On the other hand, patients with bowel disease "overlap" disease. As Crohn's disease has been may eventually be diagnosed as having ulcerative Volume 55 Differential diagnosis of pyostomatitis vegetans 371 Number 4

Histopathology DIF /IF Treatment Response

Chronic inflammation and Corticosteroids and Good localized acute purulent antispasmodics inflammation consistent with pyostomatitis vegetans, eosinophils in early lesions Chronic inflammation and Corticosteroids and Good localized acute purulent antispasmodics inflammation consistent with pyostomatitis vegetans, eosinophils in early lesions Eosinophilic abscesses in Corticosteroids Good epithelium and dermis; suprabasilar clefting with acantholysis Dissociation of epithelial cells Intercellular antibodies but no acantholysis; mixed not demonstrated28 inflammation with numerous eosinophils No acantholysis Intercellular antibodies Dapsone Poor not demonstrated28 Acanthosis-mixed inflammatory Prednisone Good infiltrate with eosinophils Inflammation with numerous Intercellular Intercellular lgG, C Corticoids Good eosinophils, microabscesses, lgG,C acantholysis, suprabasilar clefting Painful mouth erosions; no Intercellular lgG Prednisone Good bullae IgG Negative Negative Intraepithelial separation Corticosteroids Good with pustule formation Dissociation of epithelial Intercellular Corticosteroids Good cells, no acantholysis, mixed lgG, lgA inflammation, prominent eosinophilia colitis, Crohn's disease, or "overlap" disease. A very disorder was, in fact, a variant of pemphigus vege small number of these patients may present with oral tans. Others thought that Hallopeau was too quick to 5 33 lesions that exhibit the classic histopathologic find accept his disease, PDVH, as a variant of PV • and ings of pyostomatitis vegetans or the noncaseating believed PDVH to be a separate disease, and the epithelioid granulomas of Crohn's disease. A third, controversy has continued to this day. Certainly, the much larger, group can be expected to present with confusion is exacerbated by the similarity of diagnos nonspecific aphthous-appearing ulcerations of the tic terms. oral mucosa. The clinicopathologic features of both diseases are summarized in Table I. The following features sup DISCUSSION port the concept that PDVH is not PV (or pemphigus Some investigators have proposed that Hallo vulgaris): peau's disorder (PDVH) is a benign form of pemphi 1. PDVH appears to be causally associated with gus vegetans of Neumann (PV). In fact, some bowel disease, whereas in PV no association is authors discuss two types of pemphigus vegetaris: the apparent. Neumann type, which they define as having bullae, 2. PDVH is localized and benign, with a prefer and the Hallopeau type, which has purulent bullae ence for flexural areas of the skin, whereas PV is and pustules.32 Indeed, one of Hallopeau's patients generalized and may be fatal. died of PV and Hallopeau became convinced that his 3. Bullae are rarely seen in PDVH, which tends to 372 Hansen. Silverman, and Daniels Oral Surg. April, 1983 be pustular, whereas PV is characterized by the peau's disorder, with or without skin lesions formation of bullae that extend and coalesce. (PDVH). It must be remembered that most of these 4. Histopathologically, in PDVH the primary cases were diagnosed without the use of immunoflu lesion is in the dermis and the eosinophilic abscess orescent techniques. 15 33 represents epithelial enclosure and elimination, • Three of the most recently reported cases of whereas in PV miliary abscesses contain eosinophils pyostomatitis vegetans, which are clinically and and there is associated suprabasilar clefting and histologically similar, were found to exhibit positive acantholysis. immunofluorescence. The finding of positive immu 5. Direct and indirect immunofluorescent studies nofluorescence in some cases of PDVH is interpreted in cases of PDVH should not yield findings seen in by some to indicate that these cases are variants of PV. 7 PV, 22 whereas others argue that the total clinical, In support of the concept that PDVH is a variant histologic, and immunofluorescent findings are suffi of PV are the following: cient to warrant classification of the cases as a 1. Mucous membrane involvement is seen in both separate entity, pemphigus vegetans of Ha/lopeau diseases. (It must be pointed out that the two (PVH).7 diseases cannot be differentiated on the basis of oral On the other band, in spite of the similar immuno clinical findings alone because of mucosal changes fluorescent findings, none of the three cases of PVH secondary to trauma and infection.) appear to be a benign variant of PV. Our conclusions 2. Histologically, eosinophils are prominent in are based on the benign clinical course and the both PDVH and PV, including eosinophilic, miliary general lack of suprabasilar clefting due to acantho 9 33 34 abscesses, although some think that PDVH may lysis. Most authors agree with this concept. • • If show fewer eosinophils than PV.7 we accept this as fact, the controversy now is whether 3. Histologically, some patients with pyostomati pemphigus vegetans of Hallopeau should be recog tis may demonstrate suprabasilar clefting and some nized as a separate entity from PDVH. As Nelson34 acantholytic cells. Two reported cases of pyostomati points out, the fact that Hallopeau's name is associ 8 22 tis vegetans revealed such a finding. • ated with both entities certainly does not help mat Acantholysis is a nonspecific finding and may be a ters. It is conceivable that if earlier cases had been feature of other dermatoses. Although helpful, it subjected to immunofluorescent studies, some addi cannot be depended upon as a sole differentiating tional cases of PDVH might well have been catego criterion. rized and labeled with the confusing diagnostic term, On the basis of the preponderance of evidence, we pemphigus vegetans of Hallopeau. Because of the see no valid reason to consider PDVH as a benign scarcity of reported cases thus far, clarification will variant of PV (or pemphigus vulgaris). On the basis have to await further studies. of clinical findings, 5 clinical course, and histopatho It is clear that pemphigus vulgaris is related to PV, logic and more recently immunologic criteria, it is but to date no one has suggested any relationship of our opinion that PDVH is probably not related to pemphigus vulgaris to PDVH, except that each may either PV or pemphigus vulgaris. PDVH is benign be at opposite ends of the spectrum interposed by and localized and without bulla formation. PV and PVH and PV 7 (see Table I). pemphigus vulgaris are fulminant and potentially The clinical and microscopic findings of pyosto fatal and are characterized by large vesicles and matitis vegetans as summarized in Table I are fairly bullae. 18 Histologically, the pemphigus diseases specific. Classification depends upon a critical anal exhibit suprabasilar clefting with acantholysis, ysis of the clinical, histologic, and immunofluores whereas in PDVH this feature is usually absent. All cent findings. of the reported cases of pyostomatitis vegetans (Ta The histologic and immunofluorescent findings in ble II) were benign, and all but two lacked the our patient's oral lesions suggested a diagnosis of histologic findings of PV or pemphigus vulgaris, pyostomatitis of the PVH type, associated with a supporting the concept that pyostomatitis vegetans is bowel disorder consistent with Crohn's or "overlap" a manifestation of PDVH. Further support results disease. In the light of our present knowledge, this from the finding that a previous history of bowel case illustrates the difficulties in the differential disease is common in PDVH and is not a feature of diagnosis of the rare pyostomatitis vegetans and its PV or pemphigus vulgaris. relationship to bowel disease.

CONCLUSIONS The authors wish to thank Drs. Joseph Webb and L. It would appear that the published cases of pyosto Roy Eversole for suggesting the diagnosis in the original matitis vegetans are oral manifestations of Hallo- biopsy, lise Sauerwald for translation of the articles in Volume 55 Differential diagnosis of pyostomatitis vegetans 373 Number 4

German, Evangeline Leash for editorial assistance, and 19. McCarthy, P. L., and Shklar, G .: Diseases of the Oral Mucosa, ed. 2, Philadelphia, 1980, Lea & Febiger, p. 547. Teresita Arenas for processing the manuscript. 20. Forman, L.: Two Cases of Pyodermite Vegetante (Hallo peau): An Eosinophilic Pustular and Vegetating Dermatitis REFERENCES With Conjunctival, Oral and Colonic Involvement, Proc. R. Soc. Med. 58: 244-249, 1965. I. Hallopeau, H.: Sur une nouvelle forme de dermatite pus 21. Pindborg, J. J.: Atlas of Diseases of the Oral Mucosa, ed. 2, tuleuse chronique en foyers a progression excentrique, C. R. Copenhagen, 1973, E. Munksgaard, p. 184. Congres International de Dermatologie et de Syphiligraphie 22. Ouimet, G., Menard, A., and Trudeau, J-G.: Immunofluores tennu a Paris en 1889, Paris, 1890, Academic de Medecine, cence dans Ia pyodermite vegetante de Hallopeau, Union pp. 344-362. Med. Can. 103: 1699-1701, 1973. 2. 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