Melkersson-Rosenthal Syndrome: A Case Study

Melkersson-Rosenthal Syndrome: A Case Study Dr. Shruti Bohra Dr Pratik B Kariya Dr Seema Bargale Abstract: Melkersson-Rosenthal syndrome (MRS) classically shows a triad of orofacial swelling, fissured tongue and facial palsy, more commonly the oligosymptomatic form. The orofacial swelling is characterized by fissured, reddish-brown, swollen, nonpruritic lips or firm edema of the face. The facial palsy is indistinguishable from Bells palsy. The least common feature is fissured tongue, although seen in one third to one half of patients but when present it assists in the diagnosis. The histologic finding of MRS includes noncaseating, sarcoidal granulomas, not invariably but their absence does not exclude the diagnosis. All these findings together provoke the careful search for provocative causes for the reactive symptom complex of the Melkersson-Rosenthal syndrome. Key words: Melkersson-Rosenthal syndrome. chelitis granulomatosa, facial palsy, fissured tongue. Introduction: Melkersson-Rosenthal syndrome is considered to be a rare syndrome. Hornstein- estimated the incidence to be 0.08%.1MRS is a non-caseating granulomatous disease showing (complete or incomplete form) a triad of facial paralysis, orofacial oedema and fissured tongue (scrotal tongue, lingua plicata, or furrowed tongue). Orofacial swelling is the most consistent and dominant feature of the Melkersson-Rosenthal syndrome. In a review of 200 patients diagnosed with Melkersson-Rosenthal syndrome, it was the most frequent initial presenting sign.2Most commonly the lips are affected, with the swelling sometimes confined only to the lips. Cheilitis granulomatosa (or granulomatous cheilitis) is achronic inflammatory granulomatous swelling of the lip, which is referred as Miescher cheilitis which is generally regarded as a monosymptomatic form of the Melkersson-Rosenthal syndrome.3 Melkersson-Rosenthal syndrome usually presents in a monosymptomatic or oligosymptomatic form. Around 200 cases are re ported in a review of Zimmer et al2, we hereby report an additional case. Case report: A 16 year old female patient reported to dental OPD with the chief complaint of generalized gingival enlargement as well as swelling in upper and lower lip since 8-9 months. Patient was apparently alright 9 months back when she had an episode of fever which lasted for 8 days and subsided with medication taken from a local clinician. It was followed by episodes of remission exacerbation of gingival enlargement with swelling of upper lip with pus discharge and bleeding to touch since 8-9 months. Then patient was referred to the department of oral pathology for needful. On examination face was bilaterally asymetrical with swelling of face on right side. Both upper and lower lips were swollen (markedly swollen upper lip) (Fig: 1). On palpation the swelling had normal temperature, was not painful, and was nonpitting and rubbery in consistency. Face was flattened on left side. Mandible was deviating on right side on opening of mouth. On intraoral examination generalized gingival enlargement was noticed which was covering cervical 1/3rd of almost all the teeth present in the oral cavity (Fig: 2). Teeth preset were incisors to second molars in all four quadrants. The tongue had deep grooves and fissures. A long prominent central groove was evident on the dorsum of the tongue going in a straight line with numerous small grooves and fissures running laterally from the middle third of the tongue (Fig: 3). An initial diagnosis of angioedema was made. Diphenhydramine hydrochloride, 100 mg, was administered intramuscularly followed by a course of diphenhydramine hydrochloride, 50 mg orally, four times a day. After 24 hours no noticeable reduction in facial swelling was evident. Therefore, re-evaluation of the diagnosis was necessary. As a result of this history, recurrent cheilitis granulomatosa consistent with Melkersson-Rosenthal syndrome (MRS) was added to the differential diagnosis. A biopsy specimen of the affected lip area was sent for histopathologic examination, confirming the final diagnosis of MRS. On histopathological examination the mucosa consisted of parakeratinized, hyperplastic, stratified squamous epithelium overlying collagenous connective tissue. Within the connective tissue there were discrete aggregations of lymphocytes, generally with a perivascular distribution; however, some bad central foci of histiocytes consistent with granulomatous lesions. The histologic findings were consistent with cheilitis granulomatosa. (Fig: 4) Treatment consisted of application of lip gloss to prevent cracking of the exposed mucosa. No further treatment was deemed necessary except continuation of his regular biannual preventive recall appointments. Discussion: Melkersson-Rosenthal syndrome (MRS) classically shows a triad of orofacial swelling, fissured tongue and facial palsy. Oligosymptomatic form of this syndrome is more common one of the example is Miescher cheilitis.3Melkersson-Rosenthal syndrome may often go undiagnosed for some day as in present case. History states that Rossolino in 1901 was the first to describe a particular association of oedema of the face, facial nerve palsy and scrotal tongue, the syndrome was named after Melkersson and Rosenthal.4 In 1928, Ernst Melkersson, a Swedish physician, described a 35-year-old woman with facial edema and paralysis. Shortly after, in 1931, Curt Rosenthal, a German neurologist, described 3 patients who had fissured or plicated tongues in addition to orofacial swelling and facial palsies and proposed a link between the triad of symptoms. Subsequently, the triad of clinical findings came to be known as the Melkersson-Rosenthal syndrome. Although MRS is reported as commonly found during the second to fourth decades of life, there are many published reports of MRS in children and preadolescents, Roseman et al 7 described a case of MRS in a 7-year-old girl, Cohen et al 8 described four cases of MRS in children younger than the age of 11 years, and Yuzuk et al 9 described the case of a 13-year-old girl who presented with the oligosymptomatic form orlabial edema coupled with fissured tongue. Melkersson Rosenthal syndrome does not appear to have an obvious predilection for either sex, although Some claim that it is slightly more common in females. 6,7,8 No particular racial predilection has been noted in MRS. Etiology of this disease remains largely unknown. 10 In granulomatous cheilitis normal lip architecture is altered by presence oflymphoedemaand noncaseating granulomas in the lamina propria.TH1 immunocytes produceinterleukin12 and RANTES/MIP-1alpha and granulomas.Expressionof protease-activatedreceptor1 and 2 occurs in orofacial granulomatosis (OFG).HLA typingmay show HLA-A2 or HLA-A11.11 Pathogenesis of MRS was suggested by Hornstien.1 He suggested that abnormal regulation of the autonomic nervous system leads to excessive permeability of the facial cutaneous vessels. From this abnormal circulation, nonspecific antigens then stimulate the perivascular cells to form granulomas. Obstruction of perivascular vessels by granuloma has been proposed as a causative factor in the swelling. 1 Initially, a patient with MRS usually complains of painless facial swelling that has persisted for a long time. Further investigation may reveal a history of previous episodes of swelling associated with facial paralysis or fissured tongue that the patient has never connected. The most common symptom of MRS is recurring orofacial swelling in which the upper lip is more often affected. Other areas affected by orofacial swelling in MRS in order of frequency, are cheek, nose, eyelid, alveolar process, and chin.2,12 Zimmer et al 2 reported orofacial manifestations in 42 patients with MRS who were examined at their clinic: they also reviewed 220 cases reported in the literature between 1965 and 1990. They found that 82% of patients presented with labial swelling, 40% had swelling in other parts of the face, not including the lip, 24% had Bells palsy, and 59% had fissured tongue. Other areas of intraoral swelling were, in order of frequency, the gingiva ( 11 % ), buccal mucosa ( 16% ) palate (8%). and tongue (7%). The swelling of the face and lip is described as recurrent, nontender, nonpitting, and firm, but not of hard consistency. The orofacial swelling is usually sudden and, in most cases, precedes facial paralysis by weeks, months, and even years. 2, 5, 6. First episodeof edema sometimes accompanied by fever and mild constitutional symptoms (as seen in present case e.g. headache, visual disturbance) usually subsides completely in hours or days. Recurrences can range from days to years, each recurrent episode lasts longer and is more pronounced, and swelling may ultimately become permanent. 2,5,6 The facial paralysis associated with MRS is frequently indistinguishable from Bells palsy. The site affected by paralysis usually corresponds to the site of swelling. As in the present case with facial swelling, the paralysis is on right side. Each recurring episode is more profound and lasts longer. 6,13,14 Other neurologic presentations associated with MRS are altered taste, migraine headaches, and trigeminal neuralgia.2,5,6,13,15 Fissured tongue ( eg. lingual plicata) is usually found at birth and therefore considered an incidental finding of MRS. Nevertheless, fissured tongue is ten times more likely to be found among individuals diagnosed with MRS than in the general population. 2, 6, 15. Miyashita et al 16 described MRS in a 56-year-old woman, who was afflicted with cheilitis granulomatosa caused by lingual candidiasis of a fissured tongue. The edematous lesion, on histopathologic investigation, is a noncaseating epithelial cell granuloma with perivascular mononucleated lymphocytic infiltrate. Fibrosis of the granulomas is typical in long-term and recurrent lesions. 1,2,17 Differential diagnosis includes Crohn’s disease, sarcoidosis, Aschers syndrome, and allergic angioedema, leprosy, tuberculosis.1,5,15,17,18,19 In Lab studies Serum angiotensin-converting enzymetestmay be performed to help exclude sarcoidosis.Reactions to metals, food additives, or other oral antigens are excluded by using Patch tests which may be associated with some cases of granulomatous. 20 If found positive they are advised to avoid the allergen. Imaging studies like gastrointestinaltractendoscopy, radiography, and biopsy may be used to differentiate from Crohn disease. Chest radiography or gallium orpositron emission tomography(PET) scanning may be found helpful in excluding sarcoidosis and tuberculosis. Orthopentamogram (OPG) helps in ruling out presence of a chronic dental abscess. A final diagnosis of MRS is made from the clinical history and histopathologic assessment of the edematous tissue, which usually includes the lip. When biopsy of the edematous tissue is difficult or not warranted, then a history of recurrent idiopathic facial swelling associated with atleast one of the following two entities, idiopathic facial paralysis (ie. Bells palsy) or fissured tongue, is sufficient to make a positive diagnosis of MRS. Treatment of MRS is aimed at the facial swelling and the paralysis. Because the etiology and pathogenesis of MRS are not well understood, treatment continues to be empirical and, in most cases, unsuccessful. Fortunately, both the swelling and the paralysis are selflimiting and usually go into remission on their own. Treatment with oral prednisone or nerve decompression has been shown to be effective.1,5,6 Treatment with oral prednisone or nerve decompression has been shown to be effective.5 Also, interlesional injections with triamcinolone hexacetonide suspension have been shown to provide temporary benefit.12 Plastic surgery may be considered in the case of permanent fibrotic lesions. Nevertheless, thorough documentation by many dentists eventually allowed MRS to be included in the differential diagnosis. This case highlights the importance of good history taking, regular follow-up and thorough documentation for proper patient management. References: HornsteinOP. Melkersson-Rosenthul syndrome: A neuromucocutaneus disease of complex origin. Curr ProbI Dermatoi 1973 ;5:117-156. Zimmer WM, Rogers RS. Reeve CM, Sheridan PJ. Orofacial manifestations of MeIkersson-Rosenthal syndiume: A study uf 41patients and review of 22tn cases from the literature. Oral Surg Oral Med Oral PiU ho I IW:;74:61O-6I9. Rogers RS 3rd: Melkersson-Rosenthal syndrome and orofacial granulomatosis, Dermatol Clin.1996 Apr;14(2):371-9 Magid El Shennawy and Galala El Enany: Melkersson-Rosenthalsyndrome; Review of theliteratureand report of acase, The Journal of Laryngology Otology Volume87 / Issue09 /September 1973, pp 898-902 Green RM. Rogers RS, Melkersson-Rosentlial syndrome: A review of 36 patients. J Am Acad Dermatoi 1989:21:1263-1270. Orlando MR, Atkjns JS Jr. Melkersaon-Rosenthal syndrome. Arch Otolaryngol Mead Neck Surg I99O;116:728-729. Roseman B, Fryns JP, Van den Bergle C Melkersson-Rosenthal syndrome in a 7-year-old girl. Pediatrics 197S;61:490-491. Cohen HA. Cohen Z, Ashkenasi A, Straussberg R. Frydman M, Kauschansky A, Varsano 1. Melkersson-Rosen thai syndrome. Cutis 1994:54:327-32S. Yuzuk S, Trau H, Levy A. Shewaeh-Millet M. Melkersson- Rosenthal syndrome. Int J Dermatoi i9SS:24;456-457. Tilakaratne WM, Freysdottir J, Fortune F. Orofacial granulomatosis: review on aetiology and pathogenesis.J Oral Pathol Med. Apr 2008;37(4):191-5. Ketabchi S, Massi D, Ficarra G, et al. Expression of protease -activated receptor-1 and -2 in orofacial granulomatosis.Oral Dis. Jul 2007;13(4):419-25. Miele FA Jr. Tlie big lip. Diagnostic and treatment considerations. Gen Dent 1994;42O.i8-:59. Graff-Badlord SB. Melkersson-Rosen thai syndrome, A review of the literature and a case report. South Afr Med J 1981:60:71-74, Balatiieh AB. Pillai KG, Maiisour M. Ai-Khail AA. An unusual case of the Melkersson-Rosenthal syndrome. Oral Surg Oral Med Oral Pathol 1995:80:289-292. Winnie R, DeLuke DM. Mel kersson-Rosenthal syndrome: Review of literature and case report. Int J Oral Ma.illofac Surg 199;;; 1:115-117 Miyashita M, Baba S, Suzuki H. Role recurrent oral caniiidiasis associated with lingua plicata in Me I kersson-Rosen thai syndrome. BrJ Dermatol 199Ã ®:l.l2:.ll 1-312. Minor MW Fo^ RW, Bukant; SC, Lockey RF. Melkersson- Rosenthal sjndrome. J .Miergy Clin Immunol l9a7;S0:64-67. Kano Y, Shiohara T. Yagita A, Nagashima M. Association between cheilitis granulomatosa and Crohns disease. J Am Acad Dermatol 1993:281:801. Lloyd DA, Payton KB, Guenter L, Frydman W. Melliersson-Rosenlhal syndrome and Crohns disease: One disease or two? Report of a case and discussion ofthe literature. J Clin Gastroenterol I994;18:213-2I8. Fitzpatrick L, Healy CM, McCartan BE, Flint SR, McCreary CE, Rogers S. Patch testing for food-associated allergies in orofacial granulomatosis.J Oral Pathol Med. Jan 2011;40(1):10-3. Figure legends: Figure no 1) extraoral photograph showing swollen upper and lower lips. Figure no 2) intraoral photograph showing generalized gingival enlargement Figure no 3) intraoral photograph showing deep grooves on dorsal surface of tongue Figure no 4) photograph showing histological presentation of chilitis glanduralis at low power (10X) and high power (40X) Learning ponts Concomitant presence of orofacial swelling, fissured tongue and facial palsy or any one of them may be a case of Melkersson-Rosenthal syndrome (MRS). A final diagnosis of MRS is made from the clinical history and histopathologic assessment of the edematous tissue. Melkersson–Rosenthal syndrome may recur intermittently and can become a chronic disorder. Gold: History, Properties and Nanoscale Analysis Gold: History, Properties and Nanoscale Analysis Since first extracted in the 5th century, Gold has been regarded as one of the most important matters in the world. When divided into smaller fragment sizes, way below 100nm it becomes even more ‘precious’. The optical, catalytical and electronic properties of Gold nanoparticles differ greatly from those of their bulk counterparts. This is mainly due to the large surface area-to-volume ratio as well as the spatial confinement of the free electrons of Gold nanocyrstals. Gold at Bulk scale Noble metals such as Gold, silver and platinum exhibit plasmonic properties. When the surface of a noble metal is hit with incident light, electrons which are situated on the surface begin to oscillate. This is known as the surface plasmonic resonance (SPR), as illustrated in figured 1. Metals are able to absorb and reflect light with great efficiency to their SPR. It is because of these plasmonic properties that noble metals such as Gold, silver and platinum are widely used in jewellery. Moreover being highly reflective metals makes them very appealing to the eye. Plasmonic properties arise due to noble metals having delocalised electrons on the surface. An atom consists of protons, electrons and neutrons. The nucleus is made up of protons and neutrons and the electrons spin around the nucleus in different orbitals. There are many orbitals in metals which overlap and form metallic bonding between the atoms. In the bulk form, there are many delocalised electrons within the metal that cause metallic bonding. This in turn allows the electrons to flow freely between the nuclei. Good electrical and thermal conductivity is due to the delocalised electrons Gold at Nanoscale Reflection does not occur in particles which are smaller than the wavelength of the incident light; however there is still an interaction between the nanoparticles and the light. The two main interactions are light scattering and light absorption. Electrons tend to oscillate at the same frequency as the light which was absorbed causing a dipole moment around the nanoparticles where all the electrons on the surface of the nanoparticle are oscillating. The oscillating dipole is known as a localised surface plasmon resonance (LSPR). Electromagnetic radiation is released when these electrons are oscillated. This can be seen in figure 2. The secondary electromagnetic radiation released by the nanoparticles is called scattered light. The electromagnetic radiation that is released has the same frequency History The synthesis of colloidal gold, or nanogold as it is now called, has been known to man since the ancient times. Although the process was not fully understood, synthesis of colloidal gold was crucial to the 4th century Lycurgus cup. The Lycurgus cup was known to change colour depending on the direction of light. Later it was used as a method for staining glass. A potion made from gold, which was also known as an Elixir of Life was discussed, and may also have been manufactured, in ancient times. It was not until the 16th century that the alchemist Paracelsus, claimed that he had created a potion called Aurum Potabile. (latin: potable gold). It was in the 17th century that the glass-colouring process was refined byAndreus CassiusandJohann Kunckel, allowing them to produce a deep-ruby coloured form of glass. However modern scientific evaluation was first made by Michael Faraday in the 1850s. Faraday is said to have been inspired by previous work done by Paracelsus. In 1857 Faraday prepared the first pure sample of colloidal gold, which he called activated gold, in 1857. Phosphorus was used to reduce a solution of Gold chloride. For a very long time chemists were unclear about the composition of the Cassius ruby-gold. Several chemists suspected Cassius ruby-gold to be a gold tin compound due to its preparation, However it was Faraday who was the first to recognize that the colour was actually due to the minute size of the gold particles The first colloidal gold in solution was first prepared in 1898 by Richard A. Zsigmondy. Shape and size tuning Fine tuning of shape and size in a controlled environment is one of greatest challenges faced by material scientists. These factors are not only very important in the rational design of nanomaterials, but are also equally as important for their applications. This is because many of their catalytical, optical and electronic properties of nanomaterials depend greatly on their size and shape. In Gold nanorods the longitudinal plasmon wavelength exhibits a nearly linear dependence on their aspect ratio, making it one of the most intriguing properties possessed by Gold nanorods. Moreover, even when looking at Gold nanorods with the same aspect ratio, the plasmon resonance properties are strongly dependent on the shape of their head. Over the past five years, the ability to finely tune the shape and size of Gold nanorods, has made huge progress. Seed mediated growth Gold nanospheres Changing the diameter of the sphere can easily and effectively tune the optical properties of gold nanospheres. This can easily be shown using the Mie Theory, which has been successfully shown to model the light scattering and absorption properties of spherical particles on a nanometer scale. The intense peak in the spectrum for each particle can be seen in figure 9. This peak is caused by the oscillating electrons which in turn produce a single dipole. Increasing the diameter of the gold nanosphere results in shifting the peak to a higher wavelength, this indicates the interaction between the light and particles is changing. In comparison to bulk gold (figure 4), the optical properties of gold nanospheres differ immensely. The local medium can also change the optical properties of the particles. This is due to the LSPR of the particle interacting with the medium. A change in the medium can result in a measurable change in the optical properties of the particles. In addition shape of the gold nanoparticles can significantly alter the optical properties. Gold nanorods Gold nanorods are of great interest due to their biocompatibility and NIR ( near infra-red) optical properties. The shape of the gold nanorod is what determines its NIR properties. The non-spherical shape of the particle causes two different dipoles to form when interacting with light. The transverse dipole (diameter) and the longitudinal dipole (length) account for the oscillating electrons throughout the particle. The dipole interactions affect the optical properties of the particles. GNR LSP illustration Optical properties of GNRs The aspect ratio (A.R) is defined as the length over the diameter of the Gold nanorod (GNR). The shape of the particle causes the absorption and light scattering spectrum to have two peaks: longitudinal and transverse. The interaction between these two dipoles causes the longitudinal peak to be observed in the visible to NIR region. The longitudinal peak is much more intense than the transverse peak and can be tuned by changing the aspect ratio of the gold nanorods. As the A.R of the gold nanorods is increased, the longitudinal peak shifts into the NIR region. The optical properties of GNRs have been successfully modelled using Gans theory and Discrete Dipole Approximation (DDA). Two equations were derived using the two theories to output the longitudinal peak wavelength by inputting a given aspect ratio. GANS THEORY DDA The two equations can predict the A.R of GNRs using absorption data collected from the UV-Vis-NIR spectrophotometer. The equations can give preliminary estimation of the A.R before observing the particles on a TEM. Figure 11 displays the absorption data, estimated A.R from theory, and a visual representation for a set of GNRs with different aspect ratios. The tunable optical properties of the GNRs make them very desirable for a wide range of applications. The visible representation shows a colour shift as the A.R changes. Visual representation of different shapes and sizes of GNRs Normalised absorption of the particles