Pyostomatitis Vegetans With Orofacial and Vulvar Granulomatosis in a Pediatric Patient

Differential Diagnosis—The main entity in the clinical differential diagnosis for PSV is PVH, which is considered a variant of pemphigus vulgaris. Pemphigus vegetans of Hallopeau presents with pustules and progresses to hyperpigmented vegetative plaques with peripheral hypertrophic granulation tissue.²² The clinical and histological presentation of PVH can be similar to PSV; in PVH, however, DIF demonstrates intercellular IgG and C3 due to circulating IgG autoantibodies specific for desmoglein 3, a cell adhesion molecule.^22-24 In PSV, DIF typically is negative for IgG, IgA, and C3.⁸ Immunohistochemical findings of PSV may overlap with IgA pemphigus, IgG/IgA pemphigus, and IgG pemphigus, which has sparked debate if PSV is an autoimmune blistering disorder or a secondary finding of epithelial injury.^9,18,24

Pyostomatitis vegetans is most prevalent in patients aged 20 to 59 years²⁵ but can occur at any age.^8,19 Overall, extraintestinal symptoms, including mucocutaneous findings, are common in pediatric patients—in 30% to 71% of children with CD and 21% to 22% of children with ulcerative colitis²⁶—and can predate onset of GI symptoms in 6% of pediatric patients.²⁷

Oral disease is common in CD; manifestations are listed in the Table.^28,29 In a prospective study of 48 children with CD, 42% (20/48) had oral manifestations identified at diagnosis²⁸; in a similar study of 25 children, researchers noted that 48% (12/25) had disease-specific oral lesions.²⁹ None of these children recognized the oral findings prior to the onset of systemic symptoms.²⁸ Pyostomatitis vegetans was the least common oral manifestation, reported in 1 of 73 patients in the 2 studies combined.^28,29

Two recent articles that looked at PSV in pediatric and adolescent populations identified only 9 patients with PSV.^24,30 Only 2 patients (siblings) had documented onset of PSV before 12 years of age,³¹ which suggests an underlying genetic predisposition in young children.

It has been reported that active or subclinical (ie, asymptomatic with positive endoscopic findings) IBD in adults precedes onset of PSV, which may be considered a sign of relapse.^9,30 However, PSV is incredibly rare in children and adolescents and can be an early finding of IBD in children.^16,31,32

Our patient has not developed GI involvement since her initial presentation 5 years prior, though another pediatric patient developed symptomatic CD 9 years after onset of OFG.⁵ A retrospective review of pediatric OFG without CD met criteria for CD at a median of 3.1 years (range, 0.4–6.9 years).³³ Regrettably, the early presence of PSV has been associated with future progression to CD and a complicated disease course.^12,34

Management—Pyoderma stomatitis vegetans is treated with management of underlying IBD,⁸ with scarce literature available regarding pediatric patients. Oral lesions have been treated with antiseptics and topical corticosteroids, though these have limited benefit.⁸ In an adult with IBD, topical tacrolimus initially cleared PSV; however, lesions recurred until mesalamine was initiated.³⁵ Systemic steroids were effective in a 16-year-old patient with CD and PSV,¹² but recurrence is common after corticosteroids are stopped.³⁴

Some patients benefit from steroid-sparing medications, such as dapsone, azathioprine, sulfamethoxypyridazine, methotrexate, mycophenolate mofetil, and tumor necrosis factor α inhibitors such as infliximab and adalimumab.^{8,9,15,23,34,36} A 12-year-old patient with pyodermatitis–PSV without intestinal disease was treated with prednisone, dapsone, and azathioprine with improvement but not complete resolution of oral erosions after 18 weeks of treatment.³² A 15-year-old patient with CD and pyodermatitis–PSV did not show improvement on prednisone, dapsone, and azathioprine but rapidly responded to infliximab.²³ Infliximab led to complete clearance of oral lesions in an adult with severe fistulizing CD who developed PSV.¹¹ However, 2 adolescent patients with CD developed PSV while on adalimumab,^6,34 though 1 did improve after increasing adalimumab from once to twice weekly.⁶

Conclusion

The case described here—PSV in a prepubertal 7-year-old with multiple cutaneous findings suggestive of CD, including OFG, perianal and vulvar edema with biopsy-proven noncaseating granulomas, anal skin tags, and an elevated calprotectin level, noted during a cutaneous flare without clinical or endoscopically identified underlying bowel involvement—is an extremely rare presentation. Literature regarding management of PSV primarily is found in the form of case reports and focuses on treating underlying IBD. In patients with intestinal disease, treatment with biologic therapy appears most effective.^6,23

ADDENDUM

Interestingly, 3 years after the patient’s original presentation to our clinic, chromosomal sequencing analysis to assess for copy number variants and whole exome gene sequencing identified a variant of unknown significance in the heat shock protein family A member 1-like gene, HSPA1L, which has an unknown mode of inheritance, but the literature suggests that both truncating and missense variants could be associated with individuals with ulcerative colitis, CD, and IBD.^37,38 Although we cannot use this information to render a molecular diagnosis, it is highly suspicious that this is the cause of her clinical findings. Additionally, the patient currently is aged 10 years with unchanged cutaneous findings and has not developed gastrointestinal findings of IBD.