Pediatric Neurology 50 (2014) 503e506
Contents lists available at ScienceDirect
Pediatric Neurology journal homepage: www.elsevier.com/locate/pnu
Clinical Observations
Melkersson-Rosenthal Syndrome With Hashimoto Thyroiditis in a 9-Year-Old Girl: An Autoimmune Disorder Yun-Jin Lee MD, PhD a, Chong Kun Cheon MD, PhD a, Gyu Min Yeon MD b, Young Mi Kim MD, PhD c, Sang Ook Nam MD, PhD a, * a
Department of Pediatrics, Pusan National University Children’s Hospital, Pusan National University School of Medicine, Yangsan, Korea b Department of Pediatrics, Kosin University Gospel Hospital, Kosin University, Busan, Korea c Department of Pediatrics, Pusan National University Hospital, Busan, Korea
abstract BACKGROUND: MelkerssoneRosenthal syndrome (MRS) is a rare disorder of unknown cause. The classical triad of MRS is orofacial edema, recurrent facial paralysis, and a fissured tongue. PATIENT: We present a 9-year-old girl with a recurrent peripheral facial paralysis. She experienced the first episode of a peripheral facial paralysis on the same side without orofacial swelling and lingua plicata 1 year ago. She was diagnosed with Hashimoto thyroiditis 9 months earlier, as confirmed by an endocrinologic investigation. RESULTS: While the patient was hospitalized with recurrent facial paralysis, we found that serum levels of free thyroxine (1.3 ng/dL) and thyrotropin (0.4 uIU/ mL) were within normal range, but the level of antithyroperoxidase antibodies (772.0 IU/mL) was very increased. She had been taking an oral prednisolone orally for 2 weeks. At the 1-month follow-up, the patient’s symptoms had completely disappeared. DISCUSSION: The possible correlation between MRS and autoimmune disorders has been documented in only one report, which described an adult with autoimmune thyroiditis (Hashimoto thyroiditis) and MRS. We suggest that the co-occurrence of MRS and Hashimoto thyroiditis is not coincidental but linked to autoimmunity. Keywords: MelkerssoneRosenthal syndrome, Hashimoto disease, child, facial paralysis
Pediatr Neurol 2014; 50: 503-506 Ó 2014 Elsevier Inc. All rights reserved.
Introduction
MelkerssoneRosenthal syndrome (MRS) is a rare disorder of unknown cause.1 Melkersson-Rosenthal syndrome was described in 1928 as a recurrent peripheral facial paralysis (PFP) associated with a swelling of the lips. In 1931, Rosenthal included the presence of a fissured tongue as an additional main feature, completing the classic triad that defines MRS of recurrent facial paralysis, orofacial swelling, and lingua plicata (also defined as “fissured tongue”).2 The
Article History: Received November 7, 2013; Accepted in final form January 1, 2014 * Communications should be addressed to: Dr. Nam; Department of Pediatrics; Pusan National University Children’s Hospital; 20 Geumo-ro, Yangsan-si; Gyeongsangnam-do, 626-770, Korea. E-mail address: [email protected] 0887-8994/$ - see front matter Ó 2014 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.pediatrneurol.2014.01.010
classic triad is not common (18%-70% of cases) in contrast to monosymptomatic forms, which are more prevalent.1,2 The etiology of the disease is incompletely understood. However, genetic factors, chronic infectious diseases, allergic reactions, and alteration of autoimmune mechanisms have been listed as possible causes of the syndrome.3-5 This syndrome is more often found in young adults between the second and the third decades of life.2 Childhood-onset MRS is rare. Until now, there have only been about 30 published reports of MRS in children in the first decade or early teens of life, and no concomitant autoimmune disorder was not noted (Table).1,2,4-13 We present a girl with MRS with recurrent PFP in association with autoimmune (Hashimoto) thyroiditis. A possible correlation between Hashimoto thyroiditis and MRS previously has been suggested in only one adult patient.14,15 Our patient is the first report of childhood-onset MRS with concomitant Hashimoto thyroiditis.
504
Y.-J. Lee et al. / Pediatric Neurology 50 (2014) 503e506
TABLE. Melkersson-Rosenthal syndrome in children of the first decade and early teens of life
Reference Butenschon, 1976
6
Roseman and Mulvihill, 1978
7
Sex, Age, yr
Clinical Features
Management
Four boys, 10-13/11 girls, 5-14 Girl, 7
Monosymptomatic and classic forms of Melkersson-Rosenthal syndrome Recurrent facial swelling, fissured tongue, facial palsy Monosymptomatic form Acquired facial palsy, cheilitis granulomatosa, lingua plicata Swelling of lips, gingival hyperplasia, fissured tongue, sarcoidosis Recurrent cheilitis, sarcoidosis Recurrent upper lip swelling, fissured tongue, right facial palsy Recurrent facial palsy, orofacial edema, fissured tongue Recurrent facial palsy, orofacial edema Upper lip swelling, left facial palsy Granulomatous cheilitis, Crohn’s disease
Triamcinolone acetonide, surgical intervention, corticosteroids, antibiotics Diphenhydramine hydrochloride
Hrdinova et al., 19858 Truy et al., 19929
One child One child
Bourgeois-Droin et al., 19935
Girl, 10
Cohen et al., 199410
Boy, 5 Boy, 10 Girl, 10
Dummer et al., 19994
Boy, 8 Boy, 5 Boy, 3
Stein and Mancini, 199911
Girl, 12 Boy, 10
Ziem et al., 20002
Girl, 9
Caksen et al., 200212
One child
Dodi et al., 20061
Boy, 8
Alp et al., 200913
Boy, 10
Facial and lip swelling, fissured tongue, granulomatous cheilitis Facial and lip swelling, erythematous facial edema Recurrent swelling of upper lip and cheek, facial palsy, recurrent herpes simplex infection, infected adenoids Recurrent facial palsy, lingua plicata, facial edema, Ehlers-Danlos syndrome Swelling of upper lip, gingival hypertrophy, granulomatous cheilitis Recurrent facial palsy, facial edema
Case report A 9-year-old girl was brought to our outpatient clinic because of a recurrent right PFP of 1 years’ duration. One year previously, she had an episode of right PFP without orofacial swelling or lingua plicata. Her previous PFP attack was diagnosed as Bell’s palsy by a different physician and it subsided after several treatments of acupuncture and physical rehabilitation. She is the younger of two children and was born healthy. She had no history of allergies or neurological or gastrointestinal disorders. Her family history was unremarkable. Upon physical examination, nonpainful edema of the left-sided cheek and upper lip and a fissured tongue were noted simultaneously (Figs 1 and 2). No cervical or mandibular lymphadenopathy was present. Her remaining examination was unremarkable. She was diagnosed with Hashimoto thyroiditis 9 months earlier as confirmed by an endocrinologic investigation and laboratory tests. Laboratory tests at that time revealed a low serum level of free triiodothyronine (0.6 ng/mL; normal range, 0.6-1.6 ng/mL), a low serum level of free thyroxine (0.7 ng/dL; normal range, 0.7-1.5 ng/dL), and thyrotropin greater than 22.4 uIU/mL (normal range, 0.3-4.2 uIU/mL). Antithyroglobulin antibodies (108.0 IU/mL) and anti-thyroperoxidase antibodies (anti-TPO, >1000 IU/mL) were highly elevated. On palpation, the thyroid was enlarged and slightly hard in consistency. Ultrasonography of the neck showed increased color flow within its echo pattern, and a thyroid scan showed a diffuse enlarged thyroid. Therefore, a diagnosis of hypothyroidism due to Hashimoto thyroiditis was made. After taking levothyroxine (50 mg/day), her thyroid function normalized. During the hospitalization, her serum levels of free thyroxine (1.3 ng/ dL) and thyrotropin (0.4 uIU/mL) were within normal range, but her antiTPO (772.0 IU/mL) level was very increased. Comprehensive laboratory studies were performed as follows: hemoglobin, erythrocyte sedimentation rate, C-reactive protein, fibrinogen, complement components (C3,
No data available No data available Clofazimine 100 mg daily initially, prednisolone 1 mg/kg daily Prednisolone 2 mg/kg daily Not reported Not reported Not reported Not reported Methylprednisolone 60 mg daily initially, mesalamine 250 mg daily, mesalamine enema 2 g daily Prednisone 30 mg daily over 2 months, 2 100 mg minocycline Prednisone 30 mg daily over 2 months, 2 100 mg minocycline, intralesional triamcinolone Cefaclor 375 mg daily, prednisolone 1 mg/kg daily tapered off over 3 months No data available Intralesional triamcinolone No data available
C4, and C1 inhibitor), TORCH (immune complexes, toxoplasma, rubella, chickenpox virus, herpes virus), Epstein-Barr virus, and rheumatoid factor. We screened with other antibodies, such as antinuclear antibodies, anti-Smith, anti-SSA, anti-SSB, anti Jo1, anti-Scl-70, anticardiolipin, anti-DNA, and antineutrophil cytoplasmic antibodies. All these tests were normal. A chromosomal study revealed a normal 46XX. No abnormality was found on chest X-ray, audiologic and ophthalmologic examinations, electrocardiography, echocardiography, and temporal computed tomography or magnetic resonance imaging. She had been taking prednisolone (1 mg/kg/day administered three times) orally for 2 weeks. At the 1-month follow-up, her symptoms had completely resolved. None of the symptoms have recurred during the last 3 years. We suggest that the elevated serum level of anti-TPO in the reported adult and our pediatric patient may point to a possible correlation between MRS and immunologic variations of autoimmune thyroiditis, such as the Hashimoto thyroditis.
Discussion
MRS is a systemic neuromucocutaneous granulomatous disease, characterized in its classic form by a triad of recurrent PFP, swelling of the lips, and lingua plicata.1 The diagnosis of MRS is often difficult because the complete triad of symptoms are reported in only 8%-18% of MRS patients.1,2 In a patient with persistent or recurrent orofacial edema, the existence of at least one of the clinical signs of idiopathic facial paralysis or lingua plicata is sufficient to make a definitive diagnosis of MRS. The most common feature of MRS is orofacial edema, which is typically acute, diffuse, painless, nonpitting, and mostly confined to the lips.2
Y.-J. Lee et al. / Pediatric Neurology 50 (2014) 503e506
505
FIGURE 1. Photographs depict the facial features during the second episode of rightsided facial paralysis. She was unable to close her right eye completely (A), and she had edema on the left cheek (B). (Color version of figure is available in the online edition.)
The clinical features of childhood-onset MRS do not differ from those of adults. However, the series and frequency of the episodes show distinct differences.2 The initial appearance of unilateral facial palsy is more frequent in children than in adults6 and may precede the edema by months or years. The most common symptom of childhoodonset MRS is painless orofacial swelling involving the lips, chin, cheeks, and periorbital region.1 Lingua plicata occurs in 50%-70% of adult patients with MRS, but the incidence is only about 30% in children.2,6 The published literature has no reports of lingua plicata as an initial symptom of MRS in children. However, lingua plicata may develop during the course of the disease.2 In our patient, the first episode of right PFP was not associated with lingua plicata. She had a second episode of PFP on the same side a year later, with both facial edema and a fissured tongue. The etiology of MRS remains unknown. However, an allergic origin,3 infectious causes,11 and immunologic mechanisms4,5 have all been considered. Concerning the possible link between MRS and immunologic disorders, a relationship with sarcoidosis5 and Crohn’s disease4 has been documented. We report a 9-year-old girl with MRS characterized by recurrent PFP, orofacial edema, a fissured tongue, and highly elevated values of anti-TPO. We believe this is the first report of childhood-onset MRS with concomitant Hashimoto thyroiditis. An elevated serum level of anti-TPO is a serological marker for Hashimoto thyroiditis. The existence of anti-TPO antibodies may suggest a possible correlation between immunological variations and MRS. Because the patient’s recurrent PFP completely disappeared and did not recur following the steroid trial, we speculate that an abnormal autoimmune reaction might be involved in the concomitant occurrence of MRS and Hashimoto thyroiditis. An immunohistochemical study was not performed in our
FIGURE 2. Fissuring of her tongue. (Color version of figure is available in the online edition.)
patient, and we cannot explain detailed pathogenesis based on the molecular mechanisms of this association, which may be a limitation of our report. In the differential diagnosis of MRS, Crohn’s disease, sarcoidosis, granulomatous blepharitis, cheilitis, contact dermatitis, facial trauma, and Bell’s palsy should be considered.4 Particularly, a childhood-onset facial palsy may result from Bell’s palsy, otitis media, sarcoidosis, GuillaineBarre syndrome, leukemia or a solid tumor, Ramsay Hunt syndrome, mycobacterial infections, Hansen disease, and acoustic neuroma. Our consultant ophthalmologist noted no evidence of conjunctivitis and uveitis. Sarcoidosis was not considered in our patient because of the lack of pulmonary symptoms and the presence of normal radiographs. The modality of treatment in MRS is controversial, and treatment does not relieve all symptoms in all age groups. Current therapeutic approaches include topical, intralesional, or systemic steroids, and these have resulted in symptom improvement in 50%-80% and recurrence in 60%75% of cases.1,2 In addition, a combination of corticosteroids and minocycline has been reported as an effective regimen.11 Short courses of systemic corticosteroids, such as prednisolone (1-1.5 mg/kg daily), tapered over 3-6 weeks depending on the severity of the episode, have been found to be effective in MRS. We recommend that in cases with recurrent PFP, including childhood-onset cases, the patient should be questioned about recurrent or persistent orofacial edema
506
Y.-J. Lee et al. / Pediatric Neurology 50 (2014) 503e506
and undergo further examination. MRS should be also considered in patients with recurrent or persistent swelling of the cheek or upper lip. If MRS is diagnosed, we advise consultations with dermatology, immunology, gastroenterology, and ophthalmology to rule out serious underlying causes and to investigate the associated problems. Finally, these patients should be followed up regularly due to the chronic progressive or episodic course of MRS. References 1. Dodi I, Verri R, Brevi B, et al. A monosymptomatic MelkerssonRosenthal syndrome in an 8-year old boy. Acta Biomed. 2006;77:20-23. 2. Ziem PE, Pfrommer C, Goerdt S, Orfanos CE, Blume-Peytavi U. Melkersson-Rosenthal syndrome in childhood: a challenge in differential diagnosis and treatment. Br J Dermatol. 2000;143: 860-863. 3. Chiu CS, Tsai YL. Cheilitis granulomatosa associated with allergic contact dermatitis to betel quid. Contact Dermatitis. 2008;58: 246-247. 4. Dummer W, Lurz C, Jeschke R, Meissner N, Rose C, Brocker EB. Granulomatous cheilitis and Crohn’s disease in a 3-year-old boy. Pediatr Dermatol. 1999;16:39-42. 5. Bourgeois-Droin C, Havard S, Granier F, et al. Granulomatous cheilitis in two children with sarcoidosis. J Am Acad Dermatol. 1993;29: 822-824.
6. Butenschon H. Melkersson-rosenthal syndrome in childhood. Hautarzt. 1976;27:544-547. 7. Roseman B, Mulvihill JJ. Melkersson-Rosenthal syndrome in a 7-year-old girl. Pediatrics. 1978;61:490-491. 8. Hrdinova V, Drizhal I, Steiner I, Frank M, Nozicka A. Oligosymptomatic form of Melkersson-Rosenthal’s syndrome in a child (casehistory). Prakt Zubn Lek. 1985;33:140-145. 9. Truy E, Granade G, Bensoussan J, Kauffman I, Langue J, Morgon A. Acquired peripheral facial palsy in children. Current data illustrated by 66 recent personal cases [in French]. Pediatrie. 1992;47:481-486. 10. Cohen HA, Cohen Z, Ashkenasi A, et al. Melkersson-Rosenthal syndrome. Cutis. 1994;54:327-328. 11. Stein SL, Mancini AJ. Melkersson-Rosenthal syndrome in childhood: successful management with combination steroid and minocycline therapy. J Am Acad Dermatol. 1999;41:746-748. 12. Caksen H, Cesur Y, Tombul T, et al. A case of Melkersson-Rosenthal syndrome associated with Ehlers-Danlos syndrome. Genet Couns. 2002;13:183-186. 13. Alp H, Yavuz H, Alp E. Melkersson-Rosenthal syndrome: a case report on a child. Kulak Burun Bogaz Ihtis Derg. 2009;19:99-102. 14. D’Amore M, Lisi S, Sisto M, Cucci L, Dow CT. Molecular identification of mycobacterium avium subspecies paratuberculosis in an italian patient with Hashimoto’s thyroiditis and Melkersson-Rosenthal syndrome. J Med Microbiol. 2010;59:137-139. 15. Scagliusi P, Sisto M, Lisi S, Lazzari A, D’Amore M. Hashimoto’s thyroiditis in melkersson-rosenthal syndrome patient: casual association or related diseases? Panminerva Med. 2008;50: 255-257.
Contents lists available at ScienceDirect
Pediatric Neurology journal homepage: www.elsevier.com/locate/pnu
Clinical Observations
Melkersson-Rosenthal Syndrome With Hashimoto Thyroiditis in a 9-Year-Old Girl: An Autoimmune Disorder Yun-Jin Lee MD, PhD a, Chong Kun Cheon MD, PhD a, Gyu Min Yeon MD b, Young Mi Kim MD, PhD c, Sang Ook Nam MD, PhD a, * a
Department of Pediatrics, Pusan National University Children’s Hospital, Pusan National University School of Medicine, Yangsan, Korea b Department of Pediatrics, Kosin University Gospel Hospital, Kosin University, Busan, Korea c Department of Pediatrics, Pusan National University Hospital, Busan, Korea
abstract BACKGROUND: MelkerssoneRosenthal syndrome (MRS) is a rare disorder of unknown cause. The classical triad of MRS is orofacial edema, recurrent facial paralysis, and a fissured tongue. PATIENT: We present a 9-year-old girl with a recurrent peripheral facial paralysis. She experienced the first episode of a peripheral facial paralysis on the same side without orofacial swelling and lingua plicata 1 year ago. She was diagnosed with Hashimoto thyroiditis 9 months earlier, as confirmed by an endocrinologic investigation. RESULTS: While the patient was hospitalized with recurrent facial paralysis, we found that serum levels of free thyroxine (1.3 ng/dL) and thyrotropin (0.4 uIU/ mL) were within normal range, but the level of antithyroperoxidase antibodies (772.0 IU/mL) was very increased. She had been taking an oral prednisolone orally for 2 weeks. At the 1-month follow-up, the patient’s symptoms had completely disappeared. DISCUSSION: The possible correlation between MRS and autoimmune disorders has been documented in only one report, which described an adult with autoimmune thyroiditis (Hashimoto thyroiditis) and MRS. We suggest that the co-occurrence of MRS and Hashimoto thyroiditis is not coincidental but linked to autoimmunity. Keywords: MelkerssoneRosenthal syndrome, Hashimoto disease, child, facial paralysis
Pediatr Neurol 2014; 50: 503-506 Ó 2014 Elsevier Inc. All rights reserved.
Introduction
MelkerssoneRosenthal syndrome (MRS) is a rare disorder of unknown cause.1 Melkersson-Rosenthal syndrome was described in 1928 as a recurrent peripheral facial paralysis (PFP) associated with a swelling of the lips. In 1931, Rosenthal included the presence of a fissured tongue as an additional main feature, completing the classic triad that defines MRS of recurrent facial paralysis, orofacial swelling, and lingua plicata (also defined as “fissured tongue”).2 The
Article History: Received November 7, 2013; Accepted in final form January 1, 2014 * Communications should be addressed to: Dr. Nam; Department of Pediatrics; Pusan National University Children’s Hospital; 20 Geumo-ro, Yangsan-si; Gyeongsangnam-do, 626-770, Korea. E-mail address: [email protected] 0887-8994/$ - see front matter Ó 2014 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.pediatrneurol.2014.01.010
classic triad is not common (18%-70% of cases) in contrast to monosymptomatic forms, which are more prevalent.1,2 The etiology of the disease is incompletely understood. However, genetic factors, chronic infectious diseases, allergic reactions, and alteration of autoimmune mechanisms have been listed as possible causes of the syndrome.3-5 This syndrome is more often found in young adults between the second and the third decades of life.2 Childhood-onset MRS is rare. Until now, there have only been about 30 published reports of MRS in children in the first decade or early teens of life, and no concomitant autoimmune disorder was not noted (Table).1,2,4-13 We present a girl with MRS with recurrent PFP in association with autoimmune (Hashimoto) thyroiditis. A possible correlation between Hashimoto thyroiditis and MRS previously has been suggested in only one adult patient.14,15 Our patient is the first report of childhood-onset MRS with concomitant Hashimoto thyroiditis.
504
Y.-J. Lee et al. / Pediatric Neurology 50 (2014) 503e506
TABLE. Melkersson-Rosenthal syndrome in children of the first decade and early teens of life
Reference Butenschon, 1976
6
Roseman and Mulvihill, 1978
7
Sex, Age, yr
Clinical Features
Management
Four boys, 10-13/11 girls, 5-14 Girl, 7
Monosymptomatic and classic forms of Melkersson-Rosenthal syndrome Recurrent facial swelling, fissured tongue, facial palsy Monosymptomatic form Acquired facial palsy, cheilitis granulomatosa, lingua plicata Swelling of lips, gingival hyperplasia, fissured tongue, sarcoidosis Recurrent cheilitis, sarcoidosis Recurrent upper lip swelling, fissured tongue, right facial palsy Recurrent facial palsy, orofacial edema, fissured tongue Recurrent facial palsy, orofacial edema Upper lip swelling, left facial palsy Granulomatous cheilitis, Crohn’s disease
Triamcinolone acetonide, surgical intervention, corticosteroids, antibiotics Diphenhydramine hydrochloride
Hrdinova et al., 19858 Truy et al., 19929
One child One child
Bourgeois-Droin et al., 19935
Girl, 10
Cohen et al., 199410
Boy, 5 Boy, 10 Girl, 10
Dummer et al., 19994
Boy, 8 Boy, 5 Boy, 3
Stein and Mancini, 199911
Girl, 12 Boy, 10
Ziem et al., 20002
Girl, 9
Caksen et al., 200212
One child
Dodi et al., 20061
Boy, 8
Alp et al., 200913
Boy, 10
Facial and lip swelling, fissured tongue, granulomatous cheilitis Facial and lip swelling, erythematous facial edema Recurrent swelling of upper lip and cheek, facial palsy, recurrent herpes simplex infection, infected adenoids Recurrent facial palsy, lingua plicata, facial edema, Ehlers-Danlos syndrome Swelling of upper lip, gingival hypertrophy, granulomatous cheilitis Recurrent facial palsy, facial edema
Case report A 9-year-old girl was brought to our outpatient clinic because of a recurrent right PFP of 1 years’ duration. One year previously, she had an episode of right PFP without orofacial swelling or lingua plicata. Her previous PFP attack was diagnosed as Bell’s palsy by a different physician and it subsided after several treatments of acupuncture and physical rehabilitation. She is the younger of two children and was born healthy. She had no history of allergies or neurological or gastrointestinal disorders. Her family history was unremarkable. Upon physical examination, nonpainful edema of the left-sided cheek and upper lip and a fissured tongue were noted simultaneously (Figs 1 and 2). No cervical or mandibular lymphadenopathy was present. Her remaining examination was unremarkable. She was diagnosed with Hashimoto thyroiditis 9 months earlier as confirmed by an endocrinologic investigation and laboratory tests. Laboratory tests at that time revealed a low serum level of free triiodothyronine (0.6 ng/mL; normal range, 0.6-1.6 ng/mL), a low serum level of free thyroxine (0.7 ng/dL; normal range, 0.7-1.5 ng/dL), and thyrotropin greater than 22.4 uIU/mL (normal range, 0.3-4.2 uIU/mL). Antithyroglobulin antibodies (108.0 IU/mL) and anti-thyroperoxidase antibodies (anti-TPO, >1000 IU/mL) were highly elevated. On palpation, the thyroid was enlarged and slightly hard in consistency. Ultrasonography of the neck showed increased color flow within its echo pattern, and a thyroid scan showed a diffuse enlarged thyroid. Therefore, a diagnosis of hypothyroidism due to Hashimoto thyroiditis was made. After taking levothyroxine (50 mg/day), her thyroid function normalized. During the hospitalization, her serum levels of free thyroxine (1.3 ng/ dL) and thyrotropin (0.4 uIU/mL) were within normal range, but her antiTPO (772.0 IU/mL) level was very increased. Comprehensive laboratory studies were performed as follows: hemoglobin, erythrocyte sedimentation rate, C-reactive protein, fibrinogen, complement components (C3,
No data available No data available Clofazimine 100 mg daily initially, prednisolone 1 mg/kg daily Prednisolone 2 mg/kg daily Not reported Not reported Not reported Not reported Methylprednisolone 60 mg daily initially, mesalamine 250 mg daily, mesalamine enema 2 g daily Prednisone 30 mg daily over 2 months, 2 100 mg minocycline Prednisone 30 mg daily over 2 months, 2 100 mg minocycline, intralesional triamcinolone Cefaclor 375 mg daily, prednisolone 1 mg/kg daily tapered off over 3 months No data available Intralesional triamcinolone No data available
C4, and C1 inhibitor), TORCH (immune complexes, toxoplasma, rubella, chickenpox virus, herpes virus), Epstein-Barr virus, and rheumatoid factor. We screened with other antibodies, such as antinuclear antibodies, anti-Smith, anti-SSA, anti-SSB, anti Jo1, anti-Scl-70, anticardiolipin, anti-DNA, and antineutrophil cytoplasmic antibodies. All these tests were normal. A chromosomal study revealed a normal 46XX. No abnormality was found on chest X-ray, audiologic and ophthalmologic examinations, electrocardiography, echocardiography, and temporal computed tomography or magnetic resonance imaging. She had been taking prednisolone (1 mg/kg/day administered three times) orally for 2 weeks. At the 1-month follow-up, her symptoms had completely resolved. None of the symptoms have recurred during the last 3 years. We suggest that the elevated serum level of anti-TPO in the reported adult and our pediatric patient may point to a possible correlation between MRS and immunologic variations of autoimmune thyroiditis, such as the Hashimoto thyroditis.
Discussion
MRS is a systemic neuromucocutaneous granulomatous disease, characterized in its classic form by a triad of recurrent PFP, swelling of the lips, and lingua plicata.1 The diagnosis of MRS is often difficult because the complete triad of symptoms are reported in only 8%-18% of MRS patients.1,2 In a patient with persistent or recurrent orofacial edema, the existence of at least one of the clinical signs of idiopathic facial paralysis or lingua plicata is sufficient to make a definitive diagnosis of MRS. The most common feature of MRS is orofacial edema, which is typically acute, diffuse, painless, nonpitting, and mostly confined to the lips.2
Y.-J. Lee et al. / Pediatric Neurology 50 (2014) 503e506
505
FIGURE 1. Photographs depict the facial features during the second episode of rightsided facial paralysis. She was unable to close her right eye completely (A), and she had edema on the left cheek (B). (Color version of figure is available in the online edition.)
The clinical features of childhood-onset MRS do not differ from those of adults. However, the series and frequency of the episodes show distinct differences.2 The initial appearance of unilateral facial palsy is more frequent in children than in adults6 and may precede the edema by months or years. The most common symptom of childhoodonset MRS is painless orofacial swelling involving the lips, chin, cheeks, and periorbital region.1 Lingua plicata occurs in 50%-70% of adult patients with MRS, but the incidence is only about 30% in children.2,6 The published literature has no reports of lingua plicata as an initial symptom of MRS in children. However, lingua plicata may develop during the course of the disease.2 In our patient, the first episode of right PFP was not associated with lingua plicata. She had a second episode of PFP on the same side a year later, with both facial edema and a fissured tongue. The etiology of MRS remains unknown. However, an allergic origin,3 infectious causes,11 and immunologic mechanisms4,5 have all been considered. Concerning the possible link between MRS and immunologic disorders, a relationship with sarcoidosis5 and Crohn’s disease4 has been documented. We report a 9-year-old girl with MRS characterized by recurrent PFP, orofacial edema, a fissured tongue, and highly elevated values of anti-TPO. We believe this is the first report of childhood-onset MRS with concomitant Hashimoto thyroiditis. An elevated serum level of anti-TPO is a serological marker for Hashimoto thyroiditis. The existence of anti-TPO antibodies may suggest a possible correlation between immunological variations and MRS. Because the patient’s recurrent PFP completely disappeared and did not recur following the steroid trial, we speculate that an abnormal autoimmune reaction might be involved in the concomitant occurrence of MRS and Hashimoto thyroiditis. An immunohistochemical study was not performed in our
FIGURE 2. Fissuring of her tongue. (Color version of figure is available in the online edition.)
patient, and we cannot explain detailed pathogenesis based on the molecular mechanisms of this association, which may be a limitation of our report. In the differential diagnosis of MRS, Crohn’s disease, sarcoidosis, granulomatous blepharitis, cheilitis, contact dermatitis, facial trauma, and Bell’s palsy should be considered.4 Particularly, a childhood-onset facial palsy may result from Bell’s palsy, otitis media, sarcoidosis, GuillaineBarre syndrome, leukemia or a solid tumor, Ramsay Hunt syndrome, mycobacterial infections, Hansen disease, and acoustic neuroma. Our consultant ophthalmologist noted no evidence of conjunctivitis and uveitis. Sarcoidosis was not considered in our patient because of the lack of pulmonary symptoms and the presence of normal radiographs. The modality of treatment in MRS is controversial, and treatment does not relieve all symptoms in all age groups. Current therapeutic approaches include topical, intralesional, or systemic steroids, and these have resulted in symptom improvement in 50%-80% and recurrence in 60%75% of cases.1,2 In addition, a combination of corticosteroids and minocycline has been reported as an effective regimen.11 Short courses of systemic corticosteroids, such as prednisolone (1-1.5 mg/kg daily), tapered over 3-6 weeks depending on the severity of the episode, have been found to be effective in MRS. We recommend that in cases with recurrent PFP, including childhood-onset cases, the patient should be questioned about recurrent or persistent orofacial edema
506
Y.-J. Lee et al. / Pediatric Neurology 50 (2014) 503e506
and undergo further examination. MRS should be also considered in patients with recurrent or persistent swelling of the cheek or upper lip. If MRS is diagnosed, we advise consultations with dermatology, immunology, gastroenterology, and ophthalmology to rule out serious underlying causes and to investigate the associated problems. Finally, these patients should be followed up regularly due to the chronic progressive or episodic course of MRS. References 1. Dodi I, Verri R, Brevi B, et al. A monosymptomatic MelkerssonRosenthal syndrome in an 8-year old boy. Acta Biomed. 2006;77:20-23. 2. Ziem PE, Pfrommer C, Goerdt S, Orfanos CE, Blume-Peytavi U. Melkersson-Rosenthal syndrome in childhood: a challenge in differential diagnosis and treatment. Br J Dermatol. 2000;143: 860-863. 3. Chiu CS, Tsai YL. Cheilitis granulomatosa associated with allergic contact dermatitis to betel quid. Contact Dermatitis. 2008;58: 246-247. 4. Dummer W, Lurz C, Jeschke R, Meissner N, Rose C, Brocker EB. Granulomatous cheilitis and Crohn’s disease in a 3-year-old boy. Pediatr Dermatol. 1999;16:39-42. 5. Bourgeois-Droin C, Havard S, Granier F, et al. Granulomatous cheilitis in two children with sarcoidosis. J Am Acad Dermatol. 1993;29: 822-824.
6. Butenschon H. Melkersson-rosenthal syndrome in childhood. Hautarzt. 1976;27:544-547. 7. Roseman B, Mulvihill JJ. Melkersson-Rosenthal syndrome in a 7-year-old girl. Pediatrics. 1978;61:490-491. 8. Hrdinova V, Drizhal I, Steiner I, Frank M, Nozicka A. Oligosymptomatic form of Melkersson-Rosenthal’s syndrome in a child (casehistory). Prakt Zubn Lek. 1985;33:140-145. 9. Truy E, Granade G, Bensoussan J, Kauffman I, Langue J, Morgon A. Acquired peripheral facial palsy in children. Current data illustrated by 66 recent personal cases [in French]. Pediatrie. 1992;47:481-486. 10. Cohen HA, Cohen Z, Ashkenasi A, et al. Melkersson-Rosenthal syndrome. Cutis. 1994;54:327-328. 11. Stein SL, Mancini AJ. Melkersson-Rosenthal syndrome in childhood: successful management with combination steroid and minocycline therapy. J Am Acad Dermatol. 1999;41:746-748. 12. Caksen H, Cesur Y, Tombul T, et al. A case of Melkersson-Rosenthal syndrome associated with Ehlers-Danlos syndrome. Genet Couns. 2002;13:183-186. 13. Alp H, Yavuz H, Alp E. Melkersson-Rosenthal syndrome: a case report on a child. Kulak Burun Bogaz Ihtis Derg. 2009;19:99-102. 14. D’Amore M, Lisi S, Sisto M, Cucci L, Dow CT. Molecular identification of mycobacterium avium subspecies paratuberculosis in an italian patient with Hashimoto’s thyroiditis and Melkersson-Rosenthal syndrome. J Med Microbiol. 2010;59:137-139. 15. Scagliusi P, Sisto M, Lisi S, Lazzari A, D’Amore M. Hashimoto’s thyroiditis in melkersson-rosenthal syndrome patient: casual association or related diseases? Panminerva Med. 2008;50: 255-257.
