One year later, a pre-existing perianal skin tag doubled in size and became exquisitely tender. The calprotectin level—previously within reference range at less than 16 μg/g—was now elevated at 149 μg/g (reference range, 1–120 μg/g) and increased to 336 μg/g 3 weeks later. Testing for C-reactive protein, zinc, and stool occult blood; a comprehensive metabolic panel; and a complete blood cell count were unremarkable.
Repeat upper and lower GI endoscopy did not suggest CD. A biopsy using direct immunofluorescence (DIF) was obtained to evaluate for pyostomatitis vegetans (PSV) and rule out pemphigus vegetans of Hallopeau (PVH). Biopsy of a pustule was attempted but was challenging because of the patient’s age and difficulty cooperating.
The captured biopsy did not demonstrate the intended pustule; instead, it included less-affected mucosa and was obtained during topical treatment when few pustules and erosions persisted. Pathologic analysis revealed noncaseating granulomas without an increase in microabscesses, neutrophils, or eosinophils (Figure 2). Direct immunofluorescence staining for IgG, IgA, and C3 and indirect immunofluorescence staining for desmoglein-1 and desmoglein-3 antibodies were negative. Although the biopsy did not capture the intended pustule, diagnosis of PV was made based on clinical features and the constellation of cutaneous findings associated with IBD.
FIGURE 2. A, Histopathology revealed a wellformed deep granuloma adjacent to a blood vessel, which is characteristic of cutaneous Crohn disease (H&E, original magnification ×200). B, Mild inflammation, predominantly lymphocytic, and irregular acanthosis were noted along with the deep granuloma adjacent to a blood vessel (H&E, original magnification ×40).
Intralesional triamcinolone, which has been of benefit for pediatric patients with orofacial granulomatosis,1,6,7 was instituted and normalized the vulva and perianal mucosa; however, lip swelling improved only minimally.
Comment
Pyostomatitis vegetans is characterized by multiple white or yellow, friable, miliary pustules that rupture, leaving behind ulcerations and erosions that cause a varying degree of oral pain.8 The disorder can involve any area of the oral mucosa—most often the labia-attached gingiva, soft and hard palates, buccal mucosa, vestibule, and tonsillar areas—but often spares the floor of the mouth and tongue.8-11 The term pyostomatitis vegetans was proposed in 1949 by McCarthy12 when he noted in a patient who presented with the characteristic appearance of the oral mucosa, though cases of vaginal, nasal, and periocular involvement have been reported.8,13,14
Histopathology—Pyostomatitis vegetans displays pseudoepithelial hyperplasia with acanthosis, hyperkeratosis, and intraepithelial or subepithelial microabscesses (or both) with neutrophils and eosinophils.8,9,15 There are a few possible explanations for this patient’s lack of tissue eosinophilia. It has been theorized that the presence of granulomas could mask concurrent PSV16 or that tissue in PSV contains fewer eosinophils as the disorder progresses.11 The oral biopsy obtained from our patient did not capture a pustule, and the condition had noticeably improved with topical tacrolimus at the time of biopsy; therefore, neither neutrophils nor eosinophils were identified. Peripheral eosinophilia, which is present in 42% to 90% of cases of PSV,9,17 can be a diagnostic clue.18 However, PE is associated with IBD,24 which usually occurs with PSV, so the absence of peripheral eosinophilia in our patient may be explained by her lack of bowel disease.
Pathogenesis—The pathogenesis of PSV is unknown. A proposed etiology includes cross-reacting antigens in the bowel and skin secondary to IBD as well as an aberrant immune response to an unidentified factor.8 Pyostomatitis vegetans is considered by many to be the mucosal variant of pyodermatitis vegetans,9,15,19 a neutrophilic dermatosis characterized by asymmetric, crusted, erythematous papulopustules that extend peripherally and coalesce to form large vegetating plaques. These lesions commonly manifest in the axillary folds, groin, and scalp and can involve the face, trunk, and distal extremities.9,18 Infection has been suggested as a cause of PSV, though cultures for pathogenic bacteria, viruses, and fungi consistently show only normal flora.20 Zinc deficiency attributed to malabsorption from CD was reported in an adult with PSV.21 The PSV resolved after 6 weeks of zinc supplementation.