Hyperinnervation and Mast Cell Activation May Be Used as Histopathologic Diagnostic Criteria for Vulvar Vestibulitis

Abstract

Objective: Vestibulitis is currently diagnosed based only on clinical criteria. To achieve histopathological diagnostic criteria, we carried out a computerized image analysis method. Methods: Vestibular tissues removed from 40 women with severe vestibulitis were immunostained for mast cell count and degranulation by C-kit and mast cell tryptase, respectively. Vestibular nerve cells total area was evaluated after S-100 stain. Controls were 7 women aged 18–48. The images were converted to a digital signal, and analyzed using Image Proplus V4 software. Results: We found a significant increase in inflammatory infiltrate, number of mast cells and degranulated mast cells in vestibulitis compared to normal controls. The inflammatory cells were localized around the superficial minor vestibular glands. The total nerve fiber area was ten times higher in vestibulitis patients than in controls. A significant positive correlation was found between the total nerve fiber area and the number of mast cells in the vestibulitis group of patients. Conclusion: We documented two diagnostic histopathological criteria for vestibulitis: (1) the presence of eight or more mast cells per 10 × 10 microscopic field, and (2) the total calculated area of the nerve fibers is ten times higher than expected. These findings re-establish the inflammatory nature of the vestibulitis. It is speculated that the trigger for the local outburst of nerve fibers could be related to the activation of the mast cells by a topical agent.

Sexual Pain Disorders: Dyspareunia and Vaginismus

“…From the pathophysiologic point of view, vulvar vestibulitis involves the up-regulation of: a) the immunological system, ie of introital mast-cells (with hyperproduction of both inflammatory molecules and nerve growth factors (NGF) [25][26][27]; b) the pain system, with proliferation of local pain fibers induced by the NGF [27][28], which may contribute to the hyperalgesia and allodynia, associated with neuropathic pain, reported by VV patients [2,3,6]; c) hyperactivity of the levator ani, which can be antecedent to vulvar vestibulitis and comorbid with vaginismus of a mild degree [6,16,24], or secondary to the introital pain. In either case, addressing the muscle component is a key part of the treatment [28][29][30].…”

“…They include hormonal/dystrophic, inflammatory, muscular, iatrogenic, neurological and/or post-traumatic, vascular, connective and immunological causes [6,7,[9][10][11][16][17][18][19][20][21][22]27].…”

“…• Multimodal therapy : Vulvar vestibilitis (VV) should be treated with a combined, multimodal treatment aimed at reducing: a) the up-regulation of mastcells, both by reducing the agonist stimuli (such as candida infections, microabrasions of the introital mucosa because of intercourse with a dry vagina and/or a contracted pelvic floor, chemicals, allergens etc) that cause degranulation leading to chronic tissue inflammation, and/or with antagonist modulation of its hyper-reactivity, with amitryptiline or aliamide's gel [6,42,44]; b) the up-regulation of pain system secondary to both the proliferation of introital pain fibers [25][26][27] induced by the Nerve Growth Factor produced by the upregulated mast-cells, and the lowered central pain threshold [45]. A thorough understanding of the pathophysiology of pain, in its nociceptive and neuropathic component, is essential.…”

The experience of pain severity and pain interference in vulvodynia patients: The role of cognitive-behavioural factors, psychological distress and fatigue

“…Whilst the aetiology is still unclear, conceivable factors include abnormal inflammatory response in the vestibule and an increased number and superficialization of pain fibers (4,5) due to genetic polymorphisms associated with functional alterations to IL-1β and TNF-α (6), as well as the presence of recurrent infections due to an altered distribution of mannose-binding lectin (7).…”

Adjuvant therapy of female patients with degenerative processes of the vulva and vulvodynia

“…На ее возникновение могут влиять высокая плот-ность нервов вследствие врожденной гиперплазии, гиперплазия нейронов, вызванная тучными клетка-ми при участии фактора роста нервов, гормональ-ные триггеры стероидных контрацептивов, а также перенесенные аллергические реакции [18][19][20][21][22][23][24].…”