Trigeminal trophic syndrome with extensive ulceration following herpes zoster

ARTICLE

Auteur(s) : Ocko Kautz, Leena Bruckner-Tuderman, Marcel L Müller, Christoph M Schempp

Department of Dermatology, University Medical Center Hauptstraße 7, 79 104 Freiburg, Germany

accepté le 13 Août 2008

A 66-year-old female patient was referred to our department with an extensive ulcer of her right scalp and forehead. In addition there was a small ulcer of the cheek and a crescent ulcer of the ala nasi, both on the right side of the face (figure 1).

Five months before admission the patient was treated intravenously for herpes zoster ophthalmicus with acyclovir in another hospital. The patient had left the hospital after four days of treatment before completion of the acyclovir therapy. The above mentioned ulcers developed only some weeks after the acute inflammatory phase in the zoster-affected areas. Despite the big, disfiguring wounds a physician was not contacted until two weeks before admission to our hospital. The patient had no prior history of dermatological or other diseases.

A malignant process was ruled out by histological examination. Overall, no specific changes were seen in histology, apart from balloon cell degeneration of some keratinocytes, which is not specific for, but is compatible with, viral infection.

Laboratory tests, including a complete blood count, blood chemistry, anti-nuclear antibody, antineutrophil cytoplasmic antibody, HIV-test were all normal or negative, except for an elevation of C-reactive protein (31 mg/L) and a value slightly above normal for alkaline phosphatase and cholesterol.

The chest x-ray was unremarkable. Aside from the known soft tissue defect, a magnetic resonance imaging study of the head showed an inflammatory involvement of the musculus temporalis and a direct connection between the ulcer of the forehead and the sinus frontalis. Several lacunary defects were detectable in the cerebrum, supposedly of vascular origin.

A polymerase chain reaction study from an ulcer smear was positive for varicella-zoster virus but negative for herpes simplex virus type 1 and 2.

The neurological examination was unremarkable; there was no detectable affection of the sensory function of the trigeminal nerve. The patient complained of a persistent feeling of pressure of variable intensity in the affected areas.

The patient was initially treated with acyclovir 8 mg/kg for 14 days and was then referred to the Department of Plastic and Hand Surgery, University Medical Centre Freiburg. The ulcer of the scalp and forehead was covered with a mesh-graft from the thigh. For the ulcer of the cheek a full-thickness graft from the retroauricular area was used. In the post-operative period, both grafts were lost due to automanipulation. A second graft, again, was removed by the patient, so on discharge the ulcers still persisted. Subsequently, the patient was lost to follow-up.

Discussion

In the present case the ulcers occurred after a herpes zoster, with varicella zoster virus DNA still detected in an ulcer smear five months after the acute disease. However, the diagnosis of necrotizing and ulcerating herpes zoster is not convincing. Virus DNA does not prove acute infection or disease activity, at time of admission there was no progression of ulcer size, and no clinical signs of inflammation were seen. In addition, no tendency towards healing was observed after adequate antiviral therapy. Finally, the defect of the ala nasi was not compatible with a necrotizing zoster. The distribution, painlessness, lack of vision impairment and the protracted course argue against a necrotizing vasculitis like arteriitis temporalis, which could otherwise be a cause of ulceration.

Linear scleroderma en coup de sabre (lSc) and progressive facial hemiatrophy (PFH) were also considered. Though one might assume a right-sided atrophy of the patient’s face, this clinical aspect was probably due to scar-traction from the big frontal-parietal ulcer. No induration, sclerosis or subcutaneous atrophy was palpable. The age of our patient, the rapid development of the skin changes and the ulcers themselves make the diagnosis of both lSc and PFH very unlikely [1]. We diagnosed a trigeminal trophic syndrome (TTS).

TTS was first described by Wallenberg in 1901 [2] when he reported an excoriation of one ala nasi in context of a brainstem infarction. In 1933 TTS appeared in independent publications by Loveman [3] and McKenzie [4]. The term “ulceration en arc” was synonymously used for TTS, as a unilateral crescent ulcer or erosion of the ala nasi or cheek is a leading symptom [5-9]. A crescent ulcer of the ala nasi was also seen in our patient, but striking other lesions existed, especially the extensive fronto-parietal ulcer. Involvement of other areas than the nose, including the scalp, forehead, ear, palate, temple, cheek and cornea have been reported [5, 7-9]. Isolated ulcerations and the extent of dermatome involvement are explained by the partial damage or alteration of trigeminal nerve fibres [5].

In most cases TTS is iatrogenic, occurring after surgical treatment of trigeminal neuralgia either via trigeminal rhizotomy, alcohol injection into the Gasserian ganglion or electrocoagulation. Ischemic damage of the trigeminal ganglion or Wallenberg’s syndrome are also common preceding events [5, 7, 9-12]. Further, the lack of neurotrophic factors like substance P and alpha-MSH and an altered vasomotoric tonus are discussed in the pathogenesis of TTS [6, 7, 11]. Among rare causes, such as trauma, craniotomy, astrocytoma, acoustic neuroma, meningioma and idiopathic, herpes zoster is a known trigger factor [5, 7, 10, 12]. Usually the lesions are painless, but patients complain about paraesthesia [5]. This is considered to be at least one cause of auto-manipulation, which is generally regarded as a crucial factor in the development of ulcers or erosions in TTS [5-7, 9-12]. Our patient described a persistent feeling of pressure in the affected areas and painlessness but denied self-manipulating. However, she reported intensive wound-cleansing and the loss of two tissue-grafts due to manipulating highlights the impaired sensitivity combined with unconscious self-mutilation.

The median time until onset of TTS after the triggering event is about 1 year, with a range from weeks to decades. Mainly older patients are affected (mean age 57 years) with a preponderance of women [5, 7, 10-12].

It is a cornerstone of the therapeutic approach that the patient becomes aware of the role of automutilation in TTS [5, 7, 11, 12]. At least in cases of extensive ulceration, plastic reconstructive surgery is the treatment of choice [6, 11]. But without behavioural modification surgery will not lead to therapeutic success. In this patient the grafts were lost due to ongoing self-manipulation; this underlines the role of psychological counselling. Various pharmacological therapies aiming at reducing paraesthesias were only of occasional success, after discontinuation relapses occurred and long term treatment was partially associated with notable side effects [6, 9]. Transcutaneous electric nerve stimulation (TENS) was also reported as a treatment option for TTS, but it is very time-consuming and only effective for the time of implementation [11]. Also, the local application of neurotrophic factors and the transplantation of in vitro cultured epidermal cells have been successful in isolated cases and might be a promising option for the future [5, 7].

In conclusion, one should be aware of TTS as a possible cause of unilateral ulceration of the face. The triad of anaesthesia, paraesthesia and a crescent erosion or ulcer is typical, larger ulcerations are not uncommon. The pathogenesis is not fully understood and the therapy remains difficult. Patient information about self-manipulation is important.
Table 1 Differential diagnosis of facial ulcers

Acknowledgements

References

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