Pediatric and Young Adult Vulvovaginal Graft-versus-Host Disease

Abstract

Vulvovaginal graft-versus-host disease (GVHD) is an underdiagnosed and poorly recognized complication of hematopoietic stem cell transplantation (HSCT). Previous studies have reported findings restricted to predominantly adult populations. We report a case series of pediatric and young adult vulvovaginal GVHD, which was identified in 19 patients (median age, 11.8 years; range, 2.4 to 21.9 years) out of a total 302 female patients who underwent transplantation over an 8-year period at a pediatric HSCT center. The majority of patients had concomitant nongenital GVHD; only 1 patient had isolated vulvovaginal GVHD. The median time from bone marrow transplantation to diagnosis of vulvovaginal GVHD was 30 months (range, 2.3 to 97.5 months). A high percentage of the patients in our series were without vulvar or vaginal symptoms (n = 8; 42%), even though 17 patients (89%) presented with grade 3 disease based on current adult grading scales. Vulvar examination findings most frequently included interlabial and clitoral hood adhesions (89%), loss of architecture of the labia minora or clitoral hood (42%), and skin erosions or fissures (37%). Only 5 patients underwent a speculum exam, none of whom had vaginal GVHD. Examination findings of primary ovarian insufficiency (POI) can overlap with those of GVHD, and 6 patients (32%) in our cohort were diagnosed with POI. Only 1 patient was on systemic hormone replacement therapy at the time of vulvovaginal GVHD diagnosis. The majority of patients (n = 16) were treated with topical steroid therapy, with a median time to response of 43 days. Five patients (26%) had a complete response to therapy, and 10 patients (53%) had a partial response. This case series provides valuable insight into pediatric and young adult vulvovaginal GVHD and highlights the need for increased screening for vulvar disease in this population.

Early Detection of Vulvovaginal Graft-Versus-Host Disease: An Integrative Review

“… Cizek and colleagues (2019) completed a retrospective analysis over a 10-year period of 302 pediatric and young adult female patients who underwent HSCT to determine risk factors for presenting symptoms of GvHD. In this study, 5.9% of patients developed VVGvHD.…”

“…The presence of chronic GvHD in another organ was a common risk factor. In the Cizek and colleagues (2019) study, most patients had a matched unrelated donor and underwent transplant for a nonmalignant condition. Authors reported that primary ovarian insufficiency may overlap with the presentation of VVGvHD.…”

“…All articles included in this review discussed patient signs and symptoms of VVGvHD. Cizek and colleagues (2019) reported that 42% of their patients were asymptomatic at time of diagnosis of VVGvHD, but the remainder of patients experienced a plethora symptoms, such as interlabial and clitoral hood adhesions (89%), loss of architecture of the labia minora and clitoral hood (42%), and skin erosions/fissures (37%). In Smith Knutsson and colleagues' (2014) study, patients frequently described dryness, pain, smarting pain ( p < .5), and dyspareunia ( p = .001).…”

“…It is a main contributor to morbidity and mortality in patients who have undergone alloHSCT. For example, generalized GvHD has a 30% to 88% prevalence in transplant patients ( Cizek et al, 2019 ; Jacobson et al, 2019 ; Machado et al, 2019 ; Stratton et al, 2007 ).…”

“…Delayed diagnosis may be attributed to various factors such as the coexistence of hypoestrogenism, misunderstanding of the disease, patient or provider embarrassment, or synchronous GvHD symptoms that compete for priority or urgency ( Jacobson et al, 2019 ). Failure to identify and treat VVGvHD may lead to sclerotic changes of the external genital organs and result in complete vaginal obstruction ( Cizek et al, 2019 ; Jacobson et al, 2019 ). Patients with VVGvHD are at a higher risk of opportunistic genital infections such as human papillomavirus ( Da Silva Lara et al, 2010 ).…”