CED
Clinical dermatology • Concise report
Clinical and Experimental Dermatology
When nonspecific histology can be a clue to the diagnosis: three cases of trigeminal trophic syndrome J. C. Cardoso,1 K. Cokelaere,2 M. Maertens,3 N. Karim,4 T. J. Jong5 and E. Calonje6 1 Dermatology Department, University Hospital of Coimbra, Coimbra, Portugal; Departments of 2Pathology and 3Dermatology, Regional Ziekenuis Jan Yperman, Ypres, Belgium; 4Pathology and 5Dermatology Departments, Hospital Raja Permaisuri Bainum, Ipoh, Malaysia; and 6Dermatopathology Department, St. John’s Institute of Dermatology, London, UK
doi:10.1111/ced.12332
Summary
Trigeminal trophic syndrome (TTS) is a rare cause of facial ulceration, which is usually associated with damage to the trigeminal nerve pathway, either centrally or peripherally, the most common causes being cerebrovascular accidents and trigeminal nerve ablation procedures. We present three cases of TTS, emphasizing the histopathological features. All three patients presented with facial ulceration. Two patients had a single lesion, and the third had several ulcers. However, in all cases, there was involvement of the nasal ala, and the lesions were strictly unilateral. Histology consistently showed ulceration with signs of severe chronic trauma: scarring, lichenification and/or pseudoepitheliomatous hyperplasia. Diagnosis of TTS can be difficult, and requires close clinicopathological correlation. Histology is important in excluding the majority of possible conditions included in the differential diagnosis, mainly malignancy and infectious processes. Several treatments have been described, but TTS is frequently refractory to treatment.
Trigeminal trophic syndrome (TTS) is a rare cause of facial ulceration. Diagnosis can be difficult, and requires exclusion of all the other main causes of ulcers located on the face.1,2 We present three cases of TTS, emphasizing the histopathological features.
Report Patient 1 was a 54-year-old woman, who presented with a 4-month history of ulceration on the right side of her nose. The lesion had started as a small erosion, which had enlarged rapidly and developed an indurated base. Physical examination disclosed a crescent-shaped ulcer of the right nasal ala, with deformity secondary to significant tissue loss, and surrounding erythema and oedema. The tip and left Correspondence: Dr Jos e Cardoso, Department of Dermatology, University Hospital of Coimbra, Praceta Mota Pinto, 3000-075 Coimbra, Portugal E-mail: [email protected] Conflict of interest: the authors declare that they have no conflicts of interest. Accepted for publication 5 January 2014
596
Clinical and Experimental Dermatology (2014) 39, pp596–599
side of the nose were spared. Initial diagnostic considerations included a basal cell carcinoma (BCC) or other malignancy. The patient’s medical history included several previous cerebrovascular accidents in various locations, including the brainstem, in the context of Sneddon syndrome. Histological examination of a biopsy revealed ulceration with fibrin deposition and scale crust, without significant epidermal regeneration (Fig. 1a). In the dermis, there was prominent fibrosis, vascular proliferation and a sparse mixed inflammatory infiltrate (Fig. 1b). There was no evidence of malignancy, granulomata, vasculitis or features to suggest an infectious process. Patient 2 was a 58-year-old man with a progressive ulceration on the right side of his nose, which had been unresponsive to multiple previous topical treatments. Clinically, the main differential diagnosis included BCC or an infectious process. The patient had a history of chronic obstructive pulmonary disease and two strokes, one of which involved the brainstem. At the time of presentation, three biopsies had been taken, and showed no evidence of malignancy or infection. A further biopsy was sent to one of the
ª 2014 British Association of Dermatologists
Nonspecific histology is a clue to the diagnosis of TTS J. C. Cardoso et al.
(a)
(a)
(b) (b)
(c) Figure 1 Patient 1. (a) Ulceration with prominent fibrin deposition
and cellular debris on the surface; (b) detail of the dermal vascular proliferation and mild chronic inflammatory infiltrate. Haematoxylin and eosin, original magnification (a) 9 40; (b) 9 100.
authors (EC), and this revealed ulceration with adjacent lichenification, as well as dermal scarring with a mild mixed inflammatory cell infiltrate, without other specific pathological features. Patient 3 was a 50-year-old man with ulceration on his left nasal ala, left side of the scalp, upper eyelid and inner canthus (Fig. 2a). He had type 2 diabetes mellitus, and had experienced a cerebrovascular accident in the previous year, although information regarding the exact location of the attack could not be retrieved. Several biopsies had been taken to exclude squamous cell carcinoma (SCC), and these all showed marked pseudoepitheliomatous hyperplasia (Fig. 2b, c), with no evidence of other pathology, namely malignancy or infection. In all cases, the diagnosis of TTS was based on the clinical findings and consistent previous medical history, supported by the nonspecific histology, which
ª 2014 British Association of Dermatologists
Figure 2 Patient 3. (a) Ulcerations involving the nasal ala, and
the inner and outer canthus on the left side. Note the significant destruction of the ala nasi. (b,c) Surface scale crust overlying pseudoepitheliomatous hyperplasia, Haematoxylin and eosin, original magnification (b) 9 100; (c) 9 200.
allowed exclusion of the main conditions to be considered in the differential diagnosis. Limited follow-up information was available for patients 1 and 3. The first patient was treated with
Clinical and Experimental Dermatology (2014) 39, pp596–599
597
Nonspecific histology is a clue to the diagnosis of TTS J. C. Cardoso et al.
occlusive dressings (hydrocolloid and bandages), resulting in some improvement. The third was started on amitriptyline 50 mg once daily and carbamazepine 400 mg twice daily, with partial improvement of the initial lesions, but subsequent appearance of a new lesion. ‘Trigeminal trophic syndrome’ is the current designation for a condition that has also been referred in the literature as/trigeminal neurotrophic ulceration’, ‘trigeminal neuropathy with trophic ulceration’ or ‘trophic ulceration of the ala nasi’.1,2 It is clinically characterized by a triad of ulceration, anaesthesia and paraesthesia.3 Ulcers may be single or multiple, in some cases quite extensive, but typically unilateral. The nasal ala is the single most common location, although the lip, cheek, forehead, ear, jaw and palate may also be affected.1,2 TTS appears after a variable period of time (weeks to decades) after damage to the trigeminal nerve pathway, centrally or peripherally.1,2 The underlying causes are varied, but the two most common are nerve ablation procedures for the treatment of trigeminal neuralgia (by surgical or nonsurgical methods, such as alcohol injection to the Gasserian ganglion) and stroke involving the posterior encephalic vascular territory. These two causes account for approximately two-thirds of TTS cases.1 In our patients, TTS appeared after cerebrovascular accidents, conforming to the so-called ‘post-apoplectic’ TTS.4 Other more rare causes include tumours, trauma, infections (e.g. herpes, syphilis, leprosy) and syringobulbia.1–3 The direct mechanism leading to ulceration is not fully understood, but it may result from continuous self-manipulation of the area, triggered and perpetuated by the altered sensation.1–3 The differential diagnosis of TTS is broad, and includes all major causes of facial ulceration, including neoplasms (e.g. BCC, SCC, lymphoma), infections (e.g. herpes, syphilis, mycobacteria, dimorphic fungi, leishmaniasis), systemic vasculitis (e.g. Wegener granulomatosis), pyoderma gangrensosum and factitial dermatitis.1,2 Histology is typically referred as nonspecific, although it is important in excluding most of these other causes of facial ulceration.4 However, the histological features have received little attention in the literature. The common denominator in our cases is the presence of features indicating severe chronic trauma: ulceration with marked associated scarring, lichenification and/or pseudoepitheliomatous hyperplasia. We therefore believe that in the right clinical
598
Clinical and Experimental Dermatology (2014) 39, pp596–599
context, these features can be invaluable clues to the diagnosis of TTS. They are also in keeping with the pathophysiological theory that continuous trauma is the main factor associated with the ulcerations in TTS. An important diagnostic pitfall in this context is the potential misinterpretation of pseudoepitheliomatous hyperplasia as SCC, especially given the fact that most cases will be biopsied to exclude malignancy. As ever, careful attention must be paid to the pathological details and the clinical context so that dermatopathologists avoid this important pitfall. It should also be emphasized that repeated biopsies are often needed to adequately exclude malignancy, especially if superficial and/or small fragments of tissue are initially obtained. An adequate sample is necessary before confidently excluding malignancy in the context of a facial ulceration. Treatment is difficult because patients tend to persistently pick, rub or scratch the affected area. Therapeutic approaches reported in the literature include amitryptiline, pharmacological (carbamazepine,3 pimozide, diazepam), transcutaneous electrical nerve stimulation, surgical reconstruction with innervated flaps, sympathectomy, and simple occlusion with dressings or occlusion masks.1,2,4,5 Unfortunately, results are often disappointing. In conclusion, TTS can be a challenging diagnosis requiring close clinicopathological correlation. We cannot overemphasize the importance of a good clinical history, including past medical events and comorbidities, as well as adequate biopsy material, in order to achieve a correct diagnosis.
Learning points TTS is a rare cause of unilateral face ulcera-
tion, which is most common in the nasal ala, and typically accompanied by anaesthesia and paraesthesia. Patients commonly have a history of stroke or procedure to the trigeminal nerve. Histology is not diagnostic, but is important to exclude other causes of facial ulceration. Diagnosis relies on close clinicopathological correlation. Treatment is difficult because patients tend to persistently pick at the area because of the altered sensation secondary to nerve damage.
ª 2014 British Association of Dermatologists
Nonspecific histology is a clue to the diagnosis of TTS J. C. Cardoso et al.
References 1 Sadeghi P, Papay FA, Vidimos AT. Trigeminal trophic syndrome – report of four cases and review of the literature. Dermatol Surg 2004; 30: 807–12. 2 Rashid RM, Khachemoune A. Trigeminal trophic syndrome. J Eur Acad Dermatol Venereol 2007; 21: 725–31. 3 Fr€ uhauf J, Shaider H, Massone C, Kerl H, M€ ullegger RR. Carbamazepine as the only effective treatment for
ª 2014 British Association of Dermatologists
trigeminal trophic syndrome. Mayo Clin Proc 2008; 83: 502–4. 4 Ferrara G, Argenziano G, Cicarelli G, Cusano F, Delfino M. Post-apoplectic trigeminal trophic syndrome. J Eur Acad Dermatol 2001; 15: 153–5. 5 Swan MC, Downie IP, Horlock N. Management of trigeminal trophic syndrome. Plast Reconstr Surg 2009; 123: 1124–6.
Clinical and Experimental Dermatology (2014) 39, pp596–599
599
Clinical dermatology • Concise report
Clinical and Experimental Dermatology
When nonspecific histology can be a clue to the diagnosis: three cases of trigeminal trophic syndrome J. C. Cardoso,1 K. Cokelaere,2 M. Maertens,3 N. Karim,4 T. J. Jong5 and E. Calonje6 1 Dermatology Department, University Hospital of Coimbra, Coimbra, Portugal; Departments of 2Pathology and 3Dermatology, Regional Ziekenuis Jan Yperman, Ypres, Belgium; 4Pathology and 5Dermatology Departments, Hospital Raja Permaisuri Bainum, Ipoh, Malaysia; and 6Dermatopathology Department, St. John’s Institute of Dermatology, London, UK
doi:10.1111/ced.12332
Summary
Trigeminal trophic syndrome (TTS) is a rare cause of facial ulceration, which is usually associated with damage to the trigeminal nerve pathway, either centrally or peripherally, the most common causes being cerebrovascular accidents and trigeminal nerve ablation procedures. We present three cases of TTS, emphasizing the histopathological features. All three patients presented with facial ulceration. Two patients had a single lesion, and the third had several ulcers. However, in all cases, there was involvement of the nasal ala, and the lesions were strictly unilateral. Histology consistently showed ulceration with signs of severe chronic trauma: scarring, lichenification and/or pseudoepitheliomatous hyperplasia. Diagnosis of TTS can be difficult, and requires close clinicopathological correlation. Histology is important in excluding the majority of possible conditions included in the differential diagnosis, mainly malignancy and infectious processes. Several treatments have been described, but TTS is frequently refractory to treatment.
Trigeminal trophic syndrome (TTS) is a rare cause of facial ulceration. Diagnosis can be difficult, and requires exclusion of all the other main causes of ulcers located on the face.1,2 We present three cases of TTS, emphasizing the histopathological features.
Report Patient 1 was a 54-year-old woman, who presented with a 4-month history of ulceration on the right side of her nose. The lesion had started as a small erosion, which had enlarged rapidly and developed an indurated base. Physical examination disclosed a crescent-shaped ulcer of the right nasal ala, with deformity secondary to significant tissue loss, and surrounding erythema and oedema. The tip and left Correspondence: Dr Jos e Cardoso, Department of Dermatology, University Hospital of Coimbra, Praceta Mota Pinto, 3000-075 Coimbra, Portugal E-mail: [email protected] Conflict of interest: the authors declare that they have no conflicts of interest. Accepted for publication 5 January 2014
596
Clinical and Experimental Dermatology (2014) 39, pp596–599
side of the nose were spared. Initial diagnostic considerations included a basal cell carcinoma (BCC) or other malignancy. The patient’s medical history included several previous cerebrovascular accidents in various locations, including the brainstem, in the context of Sneddon syndrome. Histological examination of a biopsy revealed ulceration with fibrin deposition and scale crust, without significant epidermal regeneration (Fig. 1a). In the dermis, there was prominent fibrosis, vascular proliferation and a sparse mixed inflammatory infiltrate (Fig. 1b). There was no evidence of malignancy, granulomata, vasculitis or features to suggest an infectious process. Patient 2 was a 58-year-old man with a progressive ulceration on the right side of his nose, which had been unresponsive to multiple previous topical treatments. Clinically, the main differential diagnosis included BCC or an infectious process. The patient had a history of chronic obstructive pulmonary disease and two strokes, one of which involved the brainstem. At the time of presentation, three biopsies had been taken, and showed no evidence of malignancy or infection. A further biopsy was sent to one of the
ª 2014 British Association of Dermatologists
Nonspecific histology is a clue to the diagnosis of TTS J. C. Cardoso et al.
(a)
(a)
(b) (b)
(c) Figure 1 Patient 1. (a) Ulceration with prominent fibrin deposition
and cellular debris on the surface; (b) detail of the dermal vascular proliferation and mild chronic inflammatory infiltrate. Haematoxylin and eosin, original magnification (a) 9 40; (b) 9 100.
authors (EC), and this revealed ulceration with adjacent lichenification, as well as dermal scarring with a mild mixed inflammatory cell infiltrate, without other specific pathological features. Patient 3 was a 50-year-old man with ulceration on his left nasal ala, left side of the scalp, upper eyelid and inner canthus (Fig. 2a). He had type 2 diabetes mellitus, and had experienced a cerebrovascular accident in the previous year, although information regarding the exact location of the attack could not be retrieved. Several biopsies had been taken to exclude squamous cell carcinoma (SCC), and these all showed marked pseudoepitheliomatous hyperplasia (Fig. 2b, c), with no evidence of other pathology, namely malignancy or infection. In all cases, the diagnosis of TTS was based on the clinical findings and consistent previous medical history, supported by the nonspecific histology, which
ª 2014 British Association of Dermatologists
Figure 2 Patient 3. (a) Ulcerations involving the nasal ala, and
the inner and outer canthus on the left side. Note the significant destruction of the ala nasi. (b,c) Surface scale crust overlying pseudoepitheliomatous hyperplasia, Haematoxylin and eosin, original magnification (b) 9 100; (c) 9 200.
allowed exclusion of the main conditions to be considered in the differential diagnosis. Limited follow-up information was available for patients 1 and 3. The first patient was treated with
Clinical and Experimental Dermatology (2014) 39, pp596–599
597
Nonspecific histology is a clue to the diagnosis of TTS J. C. Cardoso et al.
occlusive dressings (hydrocolloid and bandages), resulting in some improvement. The third was started on amitriptyline 50 mg once daily and carbamazepine 400 mg twice daily, with partial improvement of the initial lesions, but subsequent appearance of a new lesion. ‘Trigeminal trophic syndrome’ is the current designation for a condition that has also been referred in the literature as/trigeminal neurotrophic ulceration’, ‘trigeminal neuropathy with trophic ulceration’ or ‘trophic ulceration of the ala nasi’.1,2 It is clinically characterized by a triad of ulceration, anaesthesia and paraesthesia.3 Ulcers may be single or multiple, in some cases quite extensive, but typically unilateral. The nasal ala is the single most common location, although the lip, cheek, forehead, ear, jaw and palate may also be affected.1,2 TTS appears after a variable period of time (weeks to decades) after damage to the trigeminal nerve pathway, centrally or peripherally.1,2 The underlying causes are varied, but the two most common are nerve ablation procedures for the treatment of trigeminal neuralgia (by surgical or nonsurgical methods, such as alcohol injection to the Gasserian ganglion) and stroke involving the posterior encephalic vascular territory. These two causes account for approximately two-thirds of TTS cases.1 In our patients, TTS appeared after cerebrovascular accidents, conforming to the so-called ‘post-apoplectic’ TTS.4 Other more rare causes include tumours, trauma, infections (e.g. herpes, syphilis, leprosy) and syringobulbia.1–3 The direct mechanism leading to ulceration is not fully understood, but it may result from continuous self-manipulation of the area, triggered and perpetuated by the altered sensation.1–3 The differential diagnosis of TTS is broad, and includes all major causes of facial ulceration, including neoplasms (e.g. BCC, SCC, lymphoma), infections (e.g. herpes, syphilis, mycobacteria, dimorphic fungi, leishmaniasis), systemic vasculitis (e.g. Wegener granulomatosis), pyoderma gangrensosum and factitial dermatitis.1,2 Histology is typically referred as nonspecific, although it is important in excluding most of these other causes of facial ulceration.4 However, the histological features have received little attention in the literature. The common denominator in our cases is the presence of features indicating severe chronic trauma: ulceration with marked associated scarring, lichenification and/or pseudoepitheliomatous hyperplasia. We therefore believe that in the right clinical
598
Clinical and Experimental Dermatology (2014) 39, pp596–599
context, these features can be invaluable clues to the diagnosis of TTS. They are also in keeping with the pathophysiological theory that continuous trauma is the main factor associated with the ulcerations in TTS. An important diagnostic pitfall in this context is the potential misinterpretation of pseudoepitheliomatous hyperplasia as SCC, especially given the fact that most cases will be biopsied to exclude malignancy. As ever, careful attention must be paid to the pathological details and the clinical context so that dermatopathologists avoid this important pitfall. It should also be emphasized that repeated biopsies are often needed to adequately exclude malignancy, especially if superficial and/or small fragments of tissue are initially obtained. An adequate sample is necessary before confidently excluding malignancy in the context of a facial ulceration. Treatment is difficult because patients tend to persistently pick, rub or scratch the affected area. Therapeutic approaches reported in the literature include amitryptiline, pharmacological (carbamazepine,3 pimozide, diazepam), transcutaneous electrical nerve stimulation, surgical reconstruction with innervated flaps, sympathectomy, and simple occlusion with dressings or occlusion masks.1,2,4,5 Unfortunately, results are often disappointing. In conclusion, TTS can be a challenging diagnosis requiring close clinicopathological correlation. We cannot overemphasize the importance of a good clinical history, including past medical events and comorbidities, as well as adequate biopsy material, in order to achieve a correct diagnosis.
Learning points TTS is a rare cause of unilateral face ulcera-
tion, which is most common in the nasal ala, and typically accompanied by anaesthesia and paraesthesia. Patients commonly have a history of stroke or procedure to the trigeminal nerve. Histology is not diagnostic, but is important to exclude other causes of facial ulceration. Diagnosis relies on close clinicopathological correlation. Treatment is difficult because patients tend to persistently pick at the area because of the altered sensation secondary to nerve damage.
ª 2014 British Association of Dermatologists
Nonspecific histology is a clue to the diagnosis of TTS J. C. Cardoso et al.
References 1 Sadeghi P, Papay FA, Vidimos AT. Trigeminal trophic syndrome – report of four cases and review of the literature. Dermatol Surg 2004; 30: 807–12. 2 Rashid RM, Khachemoune A. Trigeminal trophic syndrome. J Eur Acad Dermatol Venereol 2007; 21: 725–31. 3 Fr€ uhauf J, Shaider H, Massone C, Kerl H, M€ ullegger RR. Carbamazepine as the only effective treatment for
ª 2014 British Association of Dermatologists
trigeminal trophic syndrome. Mayo Clin Proc 2008; 83: 502–4. 4 Ferrara G, Argenziano G, Cicarelli G, Cusano F, Delfino M. Post-apoplectic trigeminal trophic syndrome. J Eur Acad Dermatol 2001; 15: 153–5. 5 Swan MC, Downie IP, Horlock N. Management of trigeminal trophic syndrome. Plast Reconstr Surg 2009; 123: 1124–6.
Clinical and Experimental Dermatology (2014) 39, pp596–599
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