Trigeminal Trophic Syndrome With Histopathologic Correlation

The etiologies of TTS are wide ranging, and the differential diagnosis should be contemplated when patients present with facial ulcers. Most cases are iatrogenic secondary to trigeminal rhizotomy,⁵ alcohol injections into the gasserian ganglion, or electrocoagulation. Also common are cases caused by ischemic damage to the trigeminal ganglion⁶ or Wallenberg syndrome.⁷ More rare etiologies include trauma,⁷ craniotomy,⁷ astrocytoma, acoustic neuroma, meningioma,⁸ idiopathic causes, basal cell carcinoma, infectious diseases (eg, tertiary syphilis, recurrent herpes simplex virus, leishmaniasis, cutaneous tuberculosis, leprosy, HZ),^9-11 or systemic disease (eg, Wegener granulomatosis, Horton arteritis).

Trigeminal trophic syndrome is rare and there is little agreement on a treatment algorithm. As in our case, a methodical trial-and-error approach is suggested while encouraging the patient not to abandon treatment when efforts are not fruitful. The most important treatment strategy is behavioral modification; patients must become aware of the role of self-manipulation and assiduously avoid it. Using occlusive dressings at the affected site also may be helpful^3,12 Transcutaneous electrical nerve stimulation may lead to improvement, but relapse is common with treatment discontinuation. Therapies directed at reducing paresthesia (eg, carbamazepine, diazepam, amitriptyline, chlorpromazine, pimozide) are sometimes successful, but relapse is common.^1,3 Transplantation of in vitro–cultured epidermal cells is a new experimental treatment that offers hope for future success.¹³ Facial reconstruction of the affected area may help patients who can restrain themselves from self-manipulation.⁴

Skin biopsy findings in our case revealed an interesting aspect of the disease process of TTS. Skin biopsies are helpful in ruling out malignancy and specific stains can be used to further elucidate disease or pathologic processes occurring in the skin. In TTS, no specific changes are seen on hematoxylin and eosin staining, revealing only nonspecific inflammatory changes.^1,5 Strikingly, the pathology of affected skin in patients with postherpetic neuralgia often reveals distal nociceptive axon loss,⁹ as was seen in the skin biopsies from our patient’s left scalp. It has been proven by many researchers in many neuropathic pain conditions that the pathological signature of chronic neuropathic pain is reduction in the density of cutaneous nociceptive innervation.⁹ The most common method for visualizing cutaneous neuritis is using an immunohistochemical labeling method in which antibodies are directed against PGP 9.5. A pan-axonal neurofilament marker, PGP 9.5 allows for visualization of small sensory nerve endings in the skin. As nociceptive axons degenerate in neuropathic pain conditions, it is believed that initiation of proalgesic changes within remaining peripheral nerves and the central nervous system (CNS) occur. Another interesting aspect of our case was the patient’s persistent intractable itching and chronic pain 2 months following the initial HZ outbreak. Although pain and itching can be evoked by similar stimuli and injuries, it has been shown that both have separate neuronal pathways because they produce different conscious and reflex motor actions.¹⁴ For instance, pain causes a withdrawal reflex, while itching causes mechanical stimulation of the affected area. The act of itching is thought to have evolved to protect against threats by the act of dislodging the stimulus rather than withdrawing as seen in pain.¹⁴ It has been hypothesized that postherpetic itching (chronic pruritus following an HZ outbreak) is due to spontaneous firing of denervated CNS itch neurons.⁹

Postherpetic neuralgia–related pain seems to be most closely correlated with degeneration of varicella-zoster virus–infected primary afferent neurons. With deceased afferent neurons sending signals to the CNS and death or dysfunction of inhibitory interneurons in the dorsal horn of the spinal cord due to peripheral nerve injury, there is increased paradoxical electrical activity in specific CNS neurons. This CNS plasticity results in neuropathic pain and other altered sensory abnormalities in patients with TTS.⁹

Conclusion

We present a case of TTS distributed along the V1 branch of the trigeminal nerve on the left frontoparietal scalp following an HZ outbreak in a 49-year-old woman. Skin biopsies were consistent with this diagnosis, which revealed no neuronal innervation of the affected scalp despite intractable itching and chronic pain. Further research of TTS and postherpetic neuralgia is necessary to find appropriate treatment for patients with these conditions.