The trigeminal trophic syndrome: an unusual cause of nasal ulceration

The trigeminal trophic syndrome: an unusual cause of nasal ulceration

CASE & REVIEW The trigeminal trophic syndrome: An unusual cause of nasal ulceration Seetha U. Monrad, MD,a Jeffrey E. Terrell, MD,c and David M. Aron...

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CASE & REVIEW

The trigeminal trophic syndrome: An unusual cause of nasal ulceration Seetha U. Monrad, MD,a Jeffrey E. Terrell, MD,c and David M. Aronoff, MDb Ann Arbor, Michigan Trigeminal trophic syndrome (TTS) is an unusual complication after peripheral or central damage to the trigeminal nerve, characterized by anesthesia, paresthesias, and ala nasi ulceration. We describe a patient with classic TTS after trigeminal rhizotomy who underwent several extensive evaluations for nasal ulceration and received prolonged immunosuppressive therapy for a presumed autoimmune disorder before the correct diagnosis was made. An understanding of the predisposing factors and clinical presentation of TTS is important to ensure a timely diagnosis of this difficult-to-treat illness. Differentiation of TTS from malignancy, infection, or vasculitis is possible on the basis of clinical history, tissue biopsy, and serologic evaluation. (J Am Acad Dermatol 2004;50:949-52.)

CASE REPORT A 52-year-old woman presented with progressive ulceration of the right ala nasi. Twenty-one years previously she had cryptogenic, ipsilateral Bell’s palsy, complicated by severe trigeminal neuralgia. This was managed successfully with oral carbamazepine, however, adverse effects of the drug required its discontinuation in 1997, leaving the patient with intractable pain. For this reason, the patient underwent radiofrequency trigeminal rhizotomy 4 years before presentation. Postoperatively, she experienced corneal ulceration, anesthesia, and burning paresthesias throughout the trigeminal distribution. Ulceration of the right ala nasi developed 2 years later (Fig 1). Biopsy specimens demonstrated nonspecific inflammatory changes. Her lesions progressed despite repeated courses of topical and systemic antibiotics. The patient’s history included anxiety, fibromyalgia, and borderline systemic lupus erythematosus characterized by fatigue, arthralgias, oral ulcerations, and a positive antinuclear antibody test. She reported childhood tuberculosis exposure. Review From the Department of Internal Medicine, Divisions of Rheumatologya and Infectious Diseasesb, and Department of Otolaryngology,c University of Michigan Health System. Supported by National Institutes of Health grant HL007749. Conflicts of interest: None identified. Reprint requests: David M. Aronoff, MD, 6323 MSRB III, 1150 W Medical Center Dr, Ann Arbor, MI 48109-0642. E-mail: [email protected]. 0190-9622/$30.00 © 2004 by the American Academy of Dermatology, Inc. doi:10.1016/j.jaad.2004.01.038

of systems revealed chronic, diffuse arthralgias and morning stiffness exacerbated by activity. She denied fevers, chills, night sweats, or weight loss. Her medications included gabapentin (400 mg 4 times a day), amitriptyline (150 mg/d), clonazepam (1 mg/ d), and citalopram (40 mg/d). Physical examination demonstrated reduced right-sided lacrimation, xerosis of the right nasal septal mucosa, and a crescentic 1.5- ⫻ 2-cm, sharply demarcated, crusted ulcer of the ala nasi with sparing of the tip of the nose. Neurologic examination confirmed trigeminal anesthesia and diminished corneal reflex. Laboratory evaluation revealed a C-reactive protein of 4.0 mg/dL (normal: 0-0.6 mg/dL). A complete blood cell count and urinalysis were normal. Antinuclear antibody titer was positive (1:160) in a homogenous pattern, with a double-stranded DNA antibody titer of 8.5 IU/mL (normal: 0-7.0 IU/mL). Negative results were obtained for extractable nuclear antigens, antineutrophil cytoplasmic antibodies (antiproteinase-3 and antimyeloperoxidase antibodies), fluorescent treponemal antibodies, and serum rapid plasma reagin. A recent tuberculin skin test was negative. Computed tomography scan revealed opacification and mucosal thickening of numerous sinuses without bony destruction. Repeated biopsy specimens revealed ulceration and nonspecific inflammatory changes without vasculitis, granulomas, or neoplasia. Cultures and special stains were negative for bacteria, fungi, acid-fast bacteria, and viruses. An undifferentiated autoimmune disease was suggested and the patient was treated with oral prednisone (10 mg/d) without improvement. In949

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Table I. Causes of trigeminal nerve damage implicated in cases of trigeminal trophic syndrome

Fig 1. Female patient with crescentic ulceration of ala nasi.

creasing doses of oral azathioprine (up to 150 mg/d) were prescribed but the lesion progressed, spreading toward the right inner canthus. On numerous occasions the patient developed cellulitis, requiring antibiotics. The patient initially denied, but later admitted to, manipulating the wound, at times subconsciously. She routinely “cleaned out” the ulcer to remove blood clots and eschars that obstructed her breathing at night. Trigeminal trophic syndrome (TTS) was diagnosed based on the histopathology and the triad of trigeminal anesthesia, facial paresthesias, and crescentic ala nasi ulceration. The patient was urged to stop manipulating her ulcer and to keep it under a sterile dressing. Unfortunately, she died soon afterwards from an accidental overdose of narcotic analgesics used to control the chronic trigeminal neuralgia. Postmortem examination revealed no systemic disease or alternative diagnosis.

DISCUSSION TTS is an unusual condition after damage to the sensory root of the trigeminal nerve, with subsequent progressive ulceration in the affected dermatome. Initially described by Wallenberg,1,2 TTS first appeared in the English-language literature 32 years later in independent publications by Loveman3 and McKenzie.4 More than 100 cases have subsequently been described.2,5 The most common presentation of TTS follows trigeminal ablation by rhizotomy or alcohol injection into the gasserian ganglion.2,5,6 Other causes of trigeminal sensory nerve damage implicated in TTS are listed in Table I. The period of latency between trigeminal injury and ulceration ranges from weeks to decades and the syndrome is more common in women and the elderly.2 The ala nasi is the most usual location of ulceration, although lesions may occur on the scalp, forehead, ear, palate, and jaw.5 The tip of the nose is

Trigeminal rhizotomy Alcohol or glycerol injection of gasserian ganglion Cortical and brainstem infarctions Vertebrobasilar insufficiency Acoustic neuroma Astrocytoma Intracranial meningioma Spinal cord degeneration Mycobacterium leprae neuritis Herpes zoster opthalmicus Syringobulbia Postencephalitic parkinsonism Trauma Idiopathic Data compiled from references2,4-7,9.

spared, as a result of innervation by the medial branch of the anterior ethmoidal nerve.7,8 Alar ulceration occurs in noncartilagenous areas, adopting a crescentic shape that helps differentiate it from ulcers secondary to neoplastic or other inflammatory processes. Destruction of the adjacent lip and cheek may result in a characteristic sneer.5 Histologically, chronic ulceration is identified with minimal inflammatory infiltrate (in the absence of a secondary superinfection) and no giant cells, granulomas, or vasculitic lesions.9,10 The mechanism of ulceration is primarily traumatic, usually self-induced. Often patients have paresthesias in the affected area, prompting touching, rubbing, or picking to relieve the perceived irritation.5,9 In some cases, anesthesia creates a sensation of nasal congestion and impaired airflow, precipitating repetitive nasal manipulation.5 The self-mutilating behavior may become compulsive; patients are sometimes unaware of their actions and deny wound manipulation. Although self-induced trauma is the primary cause of ulceration, there may be specific neurologic injuries responsible for the intractable paresthesias and poor wound healing of TTS. It is notable that herpes zoster, an important noniatrogenic trigger of TTS, can result in similar self-induced ulcers when recalcitrant pruritus follows the initial rash.11 Investigations into the neurologic abnormalities underlying postherpetic itch11 may result in a better understanding of the cause of TTS lesions. The differential diagnosis of TTS is broad and a definitive diagnosis relies on excluding other causes of nasal/facial ulceration (Table II). Treatment of TTS is difficult and involves prevention of the compulsive behaviors in response to facial paresthesias.6

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Table II. Diseases mimicking trigeminal trophic syndrome Disease

Infectious Herpes simplex and zoster viruses Invasive molds (mucormycosis, aspergillosis, sporotrichosis) Other fungi (blastomycosis, paracoccidiodomycosis) Cutaneous anthrax (Bacillus anthracis) Syphilis (Treponema pallidum subsp. pallidum) Yaws (T pallidum subsp. pertenue) Mycobacterium tuberculosis Leprous trigeminal neuritis (M leprae) Cutaneous leishmaniasis Neoplastic Basal cell, squamous cell carcinoma, sinonasal (angiocentric) T/NK cell lymphoma Autoimmune Wegener granulomatosis Pyoderma gangrenosum Psychiatric Factitious trauma

Educating the patient about the self-induced nature of the ulceration is important.2 Protective devices or prostheses to cover the affected area, meticulous fingernail care, and cotton glove use may help.2 Topical therapy with saline nasal sprays and moisturizers is of unproven benefit and promotes wound manipulation. Systemic and topical antibiotics should be applied to treat secondary infections. Numerous pharmacologic therapies aimed at diminishing paresthesias and compulsive behaviors have been applied with anecdotal success, including pimozide12,13; carbamazepine14; chlorpromazine15; amitriptyline and diazepam16; vitamin B supplements17; and clonazepam.9 Notably, our patient developed TTS while receiving gabapentin, citalopram, amitriptyline, and clonazepem. Immunosuppressive agents provide no benefit.18 Other interventions include transcutaneous electrical stimulation19; iontopheresis and nerve blockade20; ionizing radiation3; ipsilateral cervical sympathectomy4,21; and stellate ganglionectomy.4,22 Surgical reconstruction with innervated skin flaps has been successfully performed.9,10,23 In conclusion, TTS is an uncommon disorder complicating peripheral or central damage to the

Diagnostic aids

Lesions typically painful; Tzanck smear; culture Immunosuppressed patient; bone/sinus destruction present; culture/biopsy Biopsy/culture; serology Occupational exposure; painless black eschar; culture/biopsy Serology; dark-field microscopy; direct fluorescent antibody test Travel to endemic area; serology; dark-field microscopy; direct fluorescent antibody test Exposure history; caseating granulomas, organisms on biopsy Exposure history; trigeminal nerve biopsy Exposure history; identification of amastigotes by histology or direct microscopy; growth of promastigotes in culture; polymerase chain reaction Tissue invasion; may cross midline; biopsy diagnostic Sinopulmonary, renal disease; erosion through skin unusual; granulomas, vasculitis on biopsy; antineutrophilic cytoplasmic antibodies Lesions painful; undermined, violaceous borders; biopsy may be useful Lesions usually tender; may be bilateral; absence of neurologic signs

trigeminal nerve, characterized by crescentic ala nasi ulceration in the setting of anesthesia and paresthesias. Treatment of TTS is aimed at suppressing paresthesias, preventing manipulation, and covering defects with innervated skin flaps. It is important to differentiate this syndrome from autoimmune disorders, infectious diseases, and neoplastic processes that may mimic TTS. REFERENCES 1. Wallenberg A. Klinische Beitrage zur Diagnostik akuter Herderkrankungen des Verlangerten Marks und der Bruke. Dt Z Nervenheilk 1901;19:227-31. 2. Litschel R, Winkler H, Dazert S, Sudhoff H. Herpes zoster-associated trigeminal trophic syndrome: a case report and review. Eur Arch Otorhinolaryngol 2003;260:86-90. 3. Loveman AB. An unusual dermatosis following section of the fifth cranial nerve. Arch Dermatol Syph 1933;28:369-75. 4. McKenzie KG. Observations on the results of the operative treatment of trigeminal neuralgia. Can Med Assoc J 1933;29:492-6. 5. Weintraub E, Soltani K, Hekmatpanah J, Lorincz AL. Trigeminal trophic syndrome: a case and review. J Am Acad Dermatol 1982; 6:52-7. 6. Dicken CH. Trigeminal trophic syndrome. Mayo Clin Proc 1997; 72:543-5. 7. Bauer F. Trophic ulceration of the ala nasi following trigeminal denervation. J Laryngol Otol 1966;80:422-5.

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8. Cliff IS, Demis DJ. Giant ulcer of the face following surgery for trigeminal neuralgia. Arch Intern Med 1967;119:218-22. 9. Goodnight JW, Calcaterra T. Trigeminal trophic syndrome: a report of two cases and review. Am J Otolaryngol 1994;15:219-22. 10. Munnoch DA, Morris AM. Trigeminal neuralgia, trophic ulceration and the plastic surgeon. J R Coll Surg Edinb 1998;43:185-8. 11. Oaklander AL, Cohen SP, Raju SV. Intractable postherpetic itch and cutaneous deafferentation after facial shingles. Pain 2002; 96:9-12. 12. Duke EE. Clinical experience with pimozide: emphasis on its use in postherpetic neuralgia. J Am Acad Dermatol 1983;8:845-50. 13. Mayer RD, Smith NP. Improvement of trigeminal neurotrophic ulceration with pimozide in a cognitively impaired elderly woman–a case report. Clin Exp Dermatol 1993;18:171-3. 14. Bhushan M, Parry EJ, Telfer NR. Trigeminal trophic syndrome: successful treatment with carbamazepine. Br J Dermatol 1999; 141:758-9. 15. Kavanagh GM, Tidman MJ, McLaren KM, Goldberg A, Benton EC. The trigeminal trophic syndrome: an under-recognized complication. Clin Exp Dermatol 1996;21:299-301. 16. Finlay AY. Trigeminal trophic syndrome. Arch Dermatol 1979; 115:1118.

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17. Philpott OS. Trophic ulcer complicating operative procedures for the relief of trigeminal neuralgia. Rocky Mt Med J 1941;38: 626-9. 18. Datta RV, Zeitouni NC, Zollo JD, Loree TR, Hicks WL Jr. Trigeminal trophic syndrome mimicking Wegener’s granulomatosis: a case report with a review of the literature. Ann Otol Rhinol Laryngol 2000;109:331-3. 19. Westerhof W, Bos JD. Trigeminal trophic syndrome: a successful treatment with transcutaneous electrical stimulation. Br J Dermatol 1983;108:601-4. 20. Tada J, Ueda M, Abe Y, Fujiwara H, Arakawa K, Arata J. Trigeminal trophic syndrome—a report of three patients. J Dermatol 1991; 18:613-5. 21. Walton S, Keczkes K. Trigeminal neurotrophic ulceration–a report of four patients. Clin Exp Dermatol 1985;10:485-90. 22. Harris W. An analysis of 1,433 cases of paroxysmal trigeminal neuralgia (trigeminal-tic) and the end-results of Gasserian alcohol injection. Brain 1940;63:209-44. 23. Abyholm FE, Eskeland G. Defect of the ala nasi following trigeminal denervation: case report. Scand J Plast Reconstr Surg 1977; 11:87-90.