Pyostomatitis vegetans

Pyostomatitis vegetans is a very rare benign oral disorder of unknown etiology characterized by pustules and vegetative lesions on an erythematous base that affect oral mucosa ¹. Multiple white or yellow pustules on erythematous base may rupture lead to widespread ulceration and form folded, fissured appearance resembling a ‘snail trail’ appearance ². The labial gingiva, soft and hard palate, buccal and labial mucosa are most commonly affected ³. Histopathology of gingival and tongue lesions showed a diffuse dermal and epidermal infiltrate with neutrophils and eosinophils, forming microabscesses. Tongue and floor of the mouth is rarely involved ⁴. Skin and other mucous membrane involvement may also be seen.

Pyostomatitis vegetans is a rare oral lesion which may affect any age group but it is commonest in young and middle aged adults between 20 and 59 years, with an average of 34 years and has a predilection for males with male to female ratio of 2:1 to 3:1 ³. Pyostomatitis vegetans has strong association with inflammatory bowel disease (ulcerative colitis or Crohn’s disease) especially Crohn’s disease ⁵ and may be the first sign of it ¹. Thus, a presumptive diagnosis of pyostomatitis vegetans should suggest a complete gastrointestinal investigation ³. The management of pyostomatitis vegetans is usually based on the management of underlying bowel disease.

The term pyostomatitis vegetans has long been a matter of great confusion. Several authors considered this disease as a mucosal variant of pyodermatitis vegetans and therefore both diseases would represent a single identity ³. This claim is corroborated by the finding of identical histological features and association with IBD (inflammatory bowel disease) for both conditions ⁶. Other authors identify the pyodermatitis vegetans as a variant of pemphigus vulgaris or pemphigus vegetans of Hallopeau. In support of this thesis there is the finding of clear suprabasal acantholysis, positivity both of direct immunofluorescence that reveals deposits of IgG and C3 in the intercellular spaces of the epider-mis and of indirect immunofluorescence that reveals circulating antiepithelial IgG antibodies ⁶. Thus, pyostomatitis and pyodermitis would be distinct conditions. Femiano et al ³ prefer distinguish between two different entities with identical clinical manifestations but with different pathogenesis: pyodermatitis vegetans as cutaneous variant of pyostomatitis vegetans and pyodermite vegetans or pemphigus vegetans of Hallopeau ⁷. The main difference between pyostomatitis vegetans and pemphigus vulgaris and pemphigus vegetans is the blistering nature of pemphigus. On the other hand, the association of pyostomatitis vegetans with inflammatory bowel disease (IBD) is another important differentiating feature. Considering histopathology of the lesions, the characteristic feature of pyostomatitis vegetans is intraepithelial abscesses filled with numerous eosinophils ⁸. Histopathologic findings in pemphigus vulgaris is suprabasal clefting, row of tombstone, acantholysis, and presence of Tzank cells ⁸. Pemphigus vegetans (Neumann type) showed intra-epidermal vesicles with suprabasal acantholysis without eosinophilic microabscesses. Hallopeau type pemphigus vegetans, showed eosinophilic spongiosis and microabscesses ³. Direct and indirect immunofluorescence in pemphigus is positive ⁹. Some authors believe that immunofluorescence is the only way to distinguish between pyostomatitis vegetans and pemphigus ³. But the others suggest that there is heterogeneity in the findings and the possibility of both false positive and false negative results must be considered ¹⁰.

One of the characteristic feature of pemphigus vegetans is tongue involvement with typical sulci and gyri pattern over the dorsum of the tongue called cerebriform tongue ¹¹ and accepted as “Premalatha sign” ¹². Conversely, in pyostomatitis vegetans tongue involvement is rare ⁴.

Nico et al. ⁹, reported a case of pyostomatitis vegetans with oral lesions and prolonged course of disease (several years) that never exacerbated into cutaneous lesions. This is unlike what usually occurs in non treated pemphigus. They suggested this finding as one of the issues while differentiating Pyostomatitis vegetans from pemphigus vegetans ⁹.

Consistently today’s the literature is inclined to believe that pyodermatitis-pyostomatitis vegetans is an identical entity belonging to the spectrum of chronic pustular dermatoses and that it must be differentiated from pemphigus vegetans of Hallopeau (first described as “pyodermite vegetans” ) even if the cutaneous lesions of both disease do not show significant clinical differences ¹³.

In fact, the association of pyodermite vegetans and ulcerative colitis has rarely been reported in literature ⁶, unlike pyodermatitis-pyostomatitis vegetans, which is strongly associated with inflammatory bowel diseases ¹⁴.

Figure 1. Pyostomatitis vegetans

Footnote: Multiple exophytic pustules on the erythematous base that covered the gingiva and oral mucosa resembling “snail tracks”.

Pyostomatitis vegetans causes

Pyostomatitis vegetans exact cause is unknown, although immunological and microbial factors have been suggested as possible etiological factors ¹⁵. Deposits of proteins in skin vessels in pyoderma gangrenosum lesions are suggestive of an Arthus-like reaction ¹⁶. Although some authors have considered microbial pathogenesis for this disease, no bacteria, fungi or viruses have been found in research ¹⁷.

Pyostomatitis vegetans differential diagnosis

The differential diagnosis of pyostomatitis vegetans includes blistering disease affecting the oral cavity such as pemphigus vegetans, pemphigus vulgaris and especially its rare variation pemphigus vegetans ³, bullous pemphigoid, erythema multiforme, herpes simplex and bullous drug eruption. However, clinically the presence of pustules with characteristic “snail track” ulcers and histopathological features of intraepithelial eosinophilic abscesses suggests pyostomatitis vegetans rather than other blistering diseases ³. The differential diagnosis should be established with Neumann type pemphigus vegetans since in both cases lesions are clinically similar and histology reveals an important eosinophil response, acanthosis and the formation of intraepithelial miliary microabscesses ¹⁸.

Pyostomatitis vegetans symptoms

Clinical presentation and distribution of the disease may vary among patients. Pyostomatitis vegetans is characterized by erythematous, thickened oral mucosa with multiple pustules and superficial erosions. A peripheral eosinophilia has been observed in most cases reported.

Oral mucosa is usually thickened and vegetating lesions on erythematous mucosa are seen. Multiple white to yellow pustules that often easily rupture and convert to erosive-ulcerative chronic lesions are usually observed. Granular appearance of oral mucosa, degeneration of vegetative pustules and erosive lesions always lead to a folded, fissured appearance named “snail tracks” ¹⁹.

All parts of the oral mucosa may be involved, but labial mucosa, attached gingiva, soft and hard palate and buccal mucosa are more commonly affected ²⁰.

Cutaneous lesions are usually seen in the armpits, groin and scalp areas in an asymmetrical pattern. They present as crusted, erythematous papulo-pustules that extend peripherally and coalesce to form large vegetating plaques ²¹.

Oral lesions of pyostomatitis vegetans can be seen without skin lesions but it is rare for them to be present in the absence of gastrointestinal disturbances ²².

Pyostomatitis vegetans is associated with inflammatory bowel disease in 75% of cases ²³. Inflammatory bowel disease (IBD) often appears months or years before oral and skin findings, sometimes the symptoms may be minimal and not sufficient to make an early diagnosis ⁵. In these cases the identification of pyostomatitis vegetans could represent a reason to encourage diagnostic investigations intended to reveal subclinical intestinal diseases ⁵.

Nigen in 2003 ²⁰ reported two patients with pyodermatitis-pyostomatitis vegetans. Both patients had lesions on the skin and mouth ²⁰.

Leibovitch ²⁴ also reported the first case of pyodermatitis-pyostomatitis vegetans in 2005 that involved the eyelid in addition to the skin and mouth.

If pyostomatitis vegetans is associated with pyodermatitis vegetans, cutaneous lesions are included of vesicopustular, vegetating plaques that are observed in 58% of patients ¹⁹.

Nigen ²⁰ reported pseudoepitheliomatous hyperplasia in two cases with pyodermatitis-pyostomatitis vegetans. Deleporte ²³ suggested that pyodermatitis-pyostomatitis vegetans belongs to the spectrum of neutrophilic dermatoses.

Pyostomatitis vegetans diagnosis

The diagnosis of pyostomatitis vegetans is based on clinical features (snail tracks appearance), presence of inflammatory bowel disease (ulcerative colitis or Crohn’s disease), peripheral eosinophilia, negative culture of pus from lesions and characteristic histological features (intraepithelial abscesses with large amount of eosinophils) ¹. Direct and indirect immunofluorescence in pyostomatitis vegetans lesions is usually negative or may be weakly positive in direct immunofluorescence and the results are inconclusive ²⁵.

Histopathological findings are similar in the skin and oral lesions. Epidermal hyperplasia is a constant feature in skin specimens. Focal acanthosis and hyperkeratosis may be seen in oral lesions. Intraepithelial and subepithelial microabscesses with abundant eosinophils and neutrophils are another finding in biopsy specimens ³. The inflammatory infiltrate shows a predominance of cytotoxic (CD3+/CD8+) lymphocytes ²⁶. As the lesion matures there are fewer eosinophils ²⁵. Viral, bacterial and fungal cultures of oral lesions of pyostomatitis vegetans are usually negative. Both direct and indirect immunofluorescence studies are usually negative ³.

Pyostomatitis vegetans treatment

Management of pyostomatitis vegetans is often based on treating the underlying gastrointestinal disease (ulcerative colitis or Crohn’s disease). The oral lesions can be managed with local therapies utilizing antiseptic mouthwashes such as chlorhexidine, and topical corticosteroids such as triamcinolone acetonide paste or betamethasone mouthwash. However, topical steroid therapy has limited success. Strategic treatment initially consists of systemic steroid therapy aimed at resolving and controlling the lesions ²⁷. This therapy can be associated with azathioprine and sulfamethoxypyridazine that can be used for their steroid sparing effect. Dapsone has been effectively employed as a second line agent to control a relapse when steroid therapy has been halted or tapered down. Unfortunately, dapsone’s utility is limited by its side effects, which include hemolytic anemia, hepatitis, agranulocytosis, and the possibility of a drug mediated allergic reaction ²⁸. A recent study declare that three injections of infliximab and successive maintenance therapy with methotrexate can cause a rapid and complete regression of both the pyostomatitis vegetans and the Crohn’s disease ²⁹. Surgical treatment in severe IBD cases involves total colectomy and has resulted in permanent remission of symptoms ³⁰.

References

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