Melkersson Rosenthal Syndrome
Early descriptions of this conditon were made by Rossolimo in 1901 and Paul Hübschmann (1878-) in 1894 and Lothar von Frankl-Hochwart (1862-1914) in 1891. It was described by Melkersson in 1928; Rosenthal in 1931 emphasised that lingua plicata is a common related condition.
MELKERSSON SYNDROME Gene map locus 9p11
*Note: Actual cause of MRS is unknown
Treatment is symptomatic and may include surgery to relieve pressure on the facial nerves and to reduce swollen tissue. Drug therapy, including steroids, may also reduce swelling. Massage and electrical stimulation may also be prescribed.
June 7, 2008
Melkersson-Rosenthal SyndromeWhat is Melkersson-Rosenthal Syndrome?
Is there any treatment?
Treatment is symptomatic and may include medication therapies with nonsteroidal anti-inflammatory drugs (NSAIDs) and corticosteroids to reduce swelling, as well as antibiotics and immunosuppressants. Surgery may be recommended to relieve pressure on the facial nerves and to reduce swollen tissue, but its effectiveness has not been established. Massage and electrical stimulation may also be prescribed.
What is the prognosis?
Melkersson-Rosenthal syndrome may recur intermittently after its first appearance. It can become a chronic disorder. Follow-up care should exclude the development of Crohn’s disease or sarcoidosis.
What research is being done?
The NINDS supports research on neurological disorders such as Melkersson-Rosenthal syndrome. Much of this research is aimed at increasing knowledge of these disorders and finding ways to treat, prevent, and ultimately cure them.
Select this link to view a list of all studies currently seeking patients.
National Organization for Rare Disorders (NORD)
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All NINDS-prepared information is in the public domain and may be freely copied. Credit to the NINDS or the NIH is appreciated.
The Melkersson-Rosenthal Syndrome (MRS) is a rare syndrome involving the head and neck. MRS is characterized by a triad of findings:
Chronic orofacial swelling predominately involving the lips
Relapsing peripheral facial nerve paralysis
Furrowed dorsum of the tounge (lingua plicata)
However, there are variants where only 1 or 2 features are present. The most frequent is Granulomatous cheilitis of Miescher (GC). The complete triad is only present in about 25% of cases. The orofacial edema is the dominant finding and may be the presenting sign in 42% of cases
|Gross Appearance and Clinical Variants|
|Histopathological Features and Variants|
|Commonly Used Terms|
DISEASE ASSOCIATIONS CHARACTERIZATION CROHN'S DISEASE
Cheilitis granulomatosa and optic neuropathy as rare extraintestinal manifestations of Crohn's disease.
van de Scheur MR, van der Waal RI, van Bodegraven AA, Volker-Dieben HJ, Starink TM, van der Waal I.
Department of Dermatology, University Hospital Vrije Universiteit/ACTA, P.O. Box 7057, 1007 MB Amsterdam, The Netherlands.
J Clin Gastroenterol 2002 May-Jun;34(5):557-9 Abstract quote
Crohn's disease can be accompanied by extraintestinal manifestations. The authors report on a 39-year-old patient who presented with cheilitis granulomatosa as the first manifestation of Crohn's disease. Four years later, intestinal Crohn's disease was diagnosed.
One year afterward, acute loss of visual acuity from optic neuropathy developed as another rare extraintestinal manifestation of Crohn's disease.
Melkersson-Rosenthal syndrome in a diabetic boy.
Ruza Paz-Curbera E, Fernandez Benitez M.
Department of Pediatrics, University of Clinic of Navarra, Faculty of Medicine, Pamplona, Spain.
Allergol Immunopathol (Madr) 1998 Nov-Dec;26(6):291-3 Abstract quote
The Melkersson-Rosenthal syndrome (MRS) consists of recurrent edema of the lips, intermittent facial palsy and furrowed tongue. This is the classic triad which defines the syndrome, although it is accepted that the presence of two manifestations or one with a granulomatous cheilitis in the biopsy, are sufficient to make the diagnosis.
The case of a 15 year-old diabetic boy is presented. He had a persistent edema of the upper lip of one-year duration, which started abruptly without any clear etiologic correlation. He was treated with antihistaminics and corticosteroids without improvement but with diabetic imbalance. The complementary examinations were normal and the biopsy was compatible with granulomatous cheilitis.
Despite the low incidence and the fact that there is no specific treatment, MRS has to be considered as a diagnostic possibility in a patient with recurrent edema although not necessarily having the complete triad.
A case of Melkersson-Rosenthal syndrome associated with Ehlers-Danlos syndrome.
Caksen H, Cesur Y, Tombul T, Uner A, Kirimi E, Tuncer O, Odabas D.
Department of Pediatrics, Yuzuncu Yil University, Faculty of Medicine, Van, Turkey.
Genet Couns 2002;13(2):183-6 Abstract quote
Melkersson-Rosenthal syndrome (MRS) is characterized by the triad of recurrent facial palsy, lingua plicata, and facial edema. Herein, we report a case of MRS associated with Ehlers-Danlos syndrome due to rare presentation.
To the best of our knowledge only one case of MRS associated with Ehlers-Danlos syndrome has been reported in the literature until now.
FOOD INTOLERANCE Food or food additive intolerance Clin Allergy 1986;16:331-338
Association of Melkersson-Rosenthal syndrome with rosacea.
Indraprastha Apollo Hospitals, New Delhi, India
Dermatol 1996 Dec;23(12):902-4 Abstract quote
A rare case of Melkersson-Rosenthal syndrome with all the cardinal signs of the triad, including facial swelling, facial nerve palsy and glossitis, is described.
The additional feature of this case was an association with rosacea.
PATHOGENESIS CHARACTERIZATION BORRELIA BURGDORFERI
Granulomatous cheilitis and Borrelia burgdorferi: polymerase chain reaction and serologic studies in a retrospective case series of 12 patients.
Muellegger RR, Weger W, Zoechling N, Kaddu S, Soyer HP, El Shabrawi-Caelen L, Kerl H.
Department of Dermatology, Karl-Franzens University School of Medicine, Auenbruggerplatz 8, A-8036 Graz, Austria.
Arch Dermatol 2000 Dec;136(12):1502-6 Abstract quote
BACKGROUND: Granulomatous cheilitis (GC) is a chronic granulomatous inflammation of the lips of unknown etiology, which may be associated with peripheral facial nerve paralysis and/or lingua plicata (Melkersson-Rosenthal syndrome [MRS]). Borrelia burgdorferi is a spirochete that causes Lyme borreliosis, a multisystemic infectious disease with frequent occurrence of facial nerve paralysis. An etiologic role of B burgdorferi in various granulomatous diseases has been suggested. The present study was performed to examine a possible causative role of B burgdorferi for GC/MRS by B burgdorferi-specific polymerase chain reaction analysis of biopsy specimens from affected lip tissue and determination of B burgdorferi IgG and IgM serum antibodies using enzyme-linked immunosorbent assay and immunoblot tests.
OBSERVATIONS: We examined a retrospective case series of 12 patients with GC/MRS from a Lyme borreliosis endemic area (median duration of disease, 8 months [range, 3-348 months]). Borrelia burgdorferi-specific DNA could not be amplified by polymerase chain reaction in any of the 12 patients. One (13%) of 8 patients tested had a serum B burgdorferi IgG response on enzyme-linked immunosorbent assay, and 2 patients (25%) had an IgM response, but immunoblot testing yielded negative results in all 8 patients.
CONCLUSION: The results of the present study do not indicate that B burgdorferi has an etiologic role in GC/MRS.
Odontogenic infections Oral Surg Oral Med Oral Pathol 1982;54:404-413
Elimination of infections relieved the swelling in 11/16 patients
Melkersson-Rosenthal syndrome and de novo autosomal t(9;21)(p11;p11) translocation.
Smeets E, Fryns JP, Van den Berghe H.
Centre for Human Genetics, University of Leuven, Belgium.
Clin Genet 1994 Jun;45(6):323-4 Abstract quote
In this report we describe a 26-year-old female with the typical clinical symptoms and signs of Melkersson-Rosenthal syndrome, an autosomal dominant with variable expression, and a de novo t(9;21)(p11;p11), and suggest that the "Melkersson-Rosenthal gene" is located at 9p11.
MYCOBACTERIAL STRESS PROTEIN
Antibodies to mycobacterial stress protein in patients with orofacial granulomatosis.
Ivanyi L, Kirby A, Zakrzewska JM.
Department of Oral Immunology, Institute of Dental Surgery, London, England.
J Oral Pathol Med 1993 Aug;22(7):320-2 Abstract quote
Immunoglobulin G antibody titers to the mycobacterial stress protein with molecular weight of 65 kDa (mSP65) were determined by ELISA in sera from 10 patients with orofacial granulomatosis (OFG). Four patients with confirmed Crohn's disease had serum antibodies to mSP65 with titers ranging from 400-950.
Of six remaining patients, three patients had serum antibodies to mSP65, with titers ranging from 180-850, whilst no serum antibody to this antigen could be detected in 3 patients. However, other laboratory investigations failed to show any consistent pattern of disturbance in the 10 tested.
Thus, the presence of serum antibody to mycobacterial 65 kDa stress protein might prove to be of a diagnostic value for Crohn's disease.
GROSS APPEARANCE/CLINICAL VARIANTS CHARACTERIZATION VARIANTS CHILDHOOD
Melkersson-Rosenthal syndrome in childhood: a challenge in differential diagnosis and treatment.
Ziem PE, Pfrommer C, Goerdt S, Orfanos CE, Blume-Peytavi U.
Department of Dermatology, University Medical Center Benjamin Franklin, The Free University of Berlin, H. Fabecstr. 60-62, 14195 Berlin, Germany.
Br J Dermatol 2000 Oct;143(4):860-3 Abstract quote
Facial palsy and orofacial swelling in childhood represent a challenge in differential diagnosis for paediatricians and dermatologists. One possible entity, Melkersson-Rosenthal syndrome (MRS), is a rarity in childhood.
We describe a 9-year-old girl with the diagnosis of MRS who had episodic swelling of the upper lip and complete peripheral facial palsy, associated with herpes and recurrent bacterial infections. Therapeutic options for MRS in childhood are limited. Our patient benefited from a 2-month course of prednisolone 1 mg kg(-1) daily.
We review previously published cases of MRS in childhood, and discuss the differential diagnosis of orofacial swelling and facial palsy as well as treatment options in children.
GRANULOMATOUS CHEILTIS OF MIESCHER
Painless chronic isolated enlargement of one or both lips due to granulomatous inflammation with a recurrent to gradually persistent course
Considered a monosymptomatic form of MRS
Cheilitis granulomatosa: overview of 13 patients with long-term follow-up--results of management.
van der Waal RI, Schulten EA, van der Meij EH, van de Scheur MR, Starink TM, van der Waal I.
Department of Dermatology, University Hospital Vrije Universiteit/ACTA, PO Box 7057, 1007 MB Amsterdam, the Netherlands.
Int J Dermatol 2002 Apr;41(4):225-9 Abstract quote
BACKGROUND: Cheilitis granulomatosa, often regarded as a subtype of orofacial granulomatosis, is characterized by recurrent or persistent swelling of one or both lips. Classically, a non-necrotizing granulomatous inflammation is seen at histologic examination. Although a relationship has been proposed between Melkersson-Rosenthal syndrome (and the monosymptomatic form, cheilitis granulomatosa) and Crohn's disease on the basis of the orofacial swelling and similar histology, several studies of Melkersson-Rosenthal syndrome have not found an association with Crohn's disease.
METHODS: The clinical features, histopathology, association with Crohn's disease, and results of nonsurgical and surgical therapy in 13 patients with cheilitis granulomatosa were investigated in a retrospective case study with a mean follow-up period of 8.2 years.
RESULTS: There was a low chance of developing Crohn's disease. Most patients in this study responded to nonsurgical treatment modalities. Patients with deterioration of lip swelling usually responded to intralesional injections with triamcinolone or to short courses of systemic glucocorticoids. Nonsteroidal systemic modalities, such as clofazimine, hydroxychloroquine, or sulfasalazine, were alternatives to glucocorticoid regimens, thus avoiding the long-term side effects of corticosteroids. Surgical intervention should only be performed in severely disfiguring cases.
CONCLUSIONS: The management of cheilitis granulomatosa remains a challenge. As this study revealed a low chance of developing Crohn's disease, it does not seem justified to inform patients with cheilitis granulomatosa of the possibility that they might develop Crohn's disease. Patients with a negative history of gastrointestinal complaints should not be exposed to routine investigations of the gastrointestinal tract.
OROFACIAL GRANULOMATOSIS J Am Acad Dermatol 1990;23:444-450
Oral lesions resembling those of in patients with Crohn's disease but with no evidence of intestinal abnormalities
Vulvitis granulomatosa: a cryptogenic chronic inflammatory hypertrophy of vulvar labia related to cheilitis granulomatosa and Crohn's disease.
Guerrieri C, Ohlsson E, Ryden G, Westermark P.
Department of Pathology, University Hospital, Linkoping, Sweden
Int J Gynecol Pathol 1995 Oct;14(4):352-9 Abstract quote
We report the cases of two patients with vulvitis granulomatosa, a chronic inflammatory hypertrophy of the vulvar labia thought to represent the vulvar variant of cheilitis granulomatosa.
One of the women later experienced recurring cheilitis granulomatosa, while the other developed intestinal Crohn's disease 6 years later.
The interrelationships of vulvitis granulomatosa, cheilitis granulomatosa, and Crohn's disease are discussed.
HISTOLOGICAL TYPES CHARACTERIZATION General VARIANTS Granulomatous cheilitis
Small noncaseating epithelioid granulomas, sometimes with multinucleated cells of the Langhans type
Sparsely scattered throughout the edematous connective tissue
Surrounding perivascular and interstitial infiltrates of lymphocytes, plasma cells, and histiocytes
TREATMENT CHARACTERIZATION CLOFAZIMINE
Cheilitis granulomatosa Miescher: treatment with clofazimine and review of the literature.
Ridder GJ, Fradis M, Lohle E.
Department of Otorhinolaryngology-Head and Neck Surgery, University Hospital Freiburg, Germany
Ann Otol Rhinol Laryngol 2001 Oct;110(10):964-7 Abstract quote
Cheilitis granulomatosa Miescher is a rare condition of unknown cause characterized by intermittent lip swelling that gradually persists and causes cosmetic deformity.
We report the case of a young woman with cheilitis granulomatosa as a monosymptomatic manifestation of Melkersson-Rosenthal syndrome successfully treated by the antileprosy agent clofazimine, and propose clofazimine as an alternative treatment in cases refractory to corticosteroids.
The differential diagnosis and current methods of treatment are summarized, and the literature is reviewed and discussed.
Treatment of Miescher's cheilitis granulomatosa in Melkersson-Rosenthal syndrome.
Camacho F, Garcia-Bravo B, Carrizosa A.
Department of Medical-Surgical Dermatology and Venereology, Faculty of Medicine, University Hospital Virgen Macarena, Sevilla, Spain.
J Eur Acad Dermatol Venereol 2001 Nov;15(6):546-9 Abstract quote
Cheilitis granulomatosa is the most frequent dermatological sign in the Melkersson-Rosenthal syndrome.
We reviewed 27 cases of this syndrome diagnosed and treated in the last 20 years. All the patients were surgically treated and received intralesional corticosteroids during surgery and tetracycline hydrochloride (500 mg, twice daily) after the operation to prevent recurrence.
Melkersson-Rosenthal syndrome in childhood: successful management with combination steroid and minocycline therapy.
Stein SL, Mancini AJ.
Department of Dermatology, Northwestern University Medical School, Children's Memorial Hospital, Chicago, Illinois, USA.
J Am Acad Dermatol 1999 Nov;41(5 Pt 1):746-8 Abstract quote
The Melkersson-Rosenthal syndrome consists of a triad of recurrent lip and/or face swelling, fissured tongue, and intermittent facial palsy. Onset of the symptoms may occur during childhood, and treatment of the condition is difficult.
We describe two children with Melkersson-Rosenthal syndrome in whom combination treatment with prednisone and minocycline proved effective and well tolerated.
Lip reduction cheiloplasty for Miescher's granulomatous macrocheilitis (Cheilitis granulomatosa) in childhood.
Oliver DW, Scott MJ.
Department of Plastic and Reconstructive Surgery, Stoke Mandeville Hospital, Mandeville Road, Aylesbury, HP21 8AL, UK.
Clin Exp Dermatol 2002 Mar;27(2):129-31 Abstract quote
Miescher's granulomatous macrocheilitis (cheilitis granulomatosa) is a mono- symptomatic presentation of Melkersson-Rosenthal Syndrome which is characterized by granulomatous swelling of the lips, and can affect both children and adults.
We report the successful outcome following lip reduction surgery on an 11-year-old boy. We suggest that surgery may have a role in the management of those patients who have failed to respond to medical treatment.
Long-term results after surgical reduction cheiloplasty in patients with Melkersson-Rosenthal syndrome and cheilitis granulomatosa.
Ellitsgaard N, Andersson AP, Worsaae N, Medgyesi S.
Department of Plastic and Reconstructive Surgery, University Hospital (Rigshospitalet), Copenhagen, Denmark.
Ann Plast Surg 1993 Nov;31(5):413-20 Abstract quote
Cheilitis granulomatosa in patients with Melkersson-Rosenthal syndrome has proven difficult to treat, and various forms of symptomatic treatment of orofacial swellings have been used with varying success.
To evaluate long-term results after surgical reduction cheiloplasty in patients suffering from persistent lip swellings, a follow-up study was performed on 13 patients after 16 years (median). The operations were performed after unsuccessful conservative treatment and regardless of disease activity. Pre- and postoperative medical histories were updated and a clinical examination evaluated the following criteria for a good result: symmetry of the lip, a normalized anterior projection, dimensional harmony between upper and lower lip, no disfiguring cicatrices, and no sensory disturbances. In spite of postoperative disease activity in 6 patients, all 13 patients were satisfied with the long-term result. Clinically, the results in 12 patients were considered good.
We therefore recommend lip resection as described when a stationary swelling becomes associated with permanent aesthetic deformity or functional disturbances and conservative measures are unsuccessful.
Therapeutic response to thalidomide in Melkersson-Rosenthal syndrome: a case report.
Medeiros M Jr, Araujo MI, Guimaraes NS, Freitas LA, Silva TM, Carvalho EM.
Immunology Service, Hospital Universitario Federal University of Bahia, Salvador, Brazil.
Ann Allergy Asthma Immunol 2002 Apr;88(4):421-4 Abstract quote
BACKGROUND: Melkersson-Rosenthal syndrome (MRS) is a rare disorder of unknown etiology characterized by a triad of symptoms: recurrent orofacial swelling, relapsing facial palsy. and a fissured tongue. A differential diagnosis must be made with other granulomatous diseases, such as sarcoidosis and oral Crohn disease; however, the histologic findings of noncaseating, sarcoidal granulomas support the diagnosis of MRS.
RESULTS: Many therapeutic modalities have been described for this disease. In this case report, we present a patient with MRS that was treated with thalidomide because of the identification of tumor necrosis factor a in the lesion by immunohistochemical analysis. This is the first reported detection of tumor necrosis factor a in an MRS lesion, as well the first reported use of thalidomide to treat this clinical condition.
J Am Acad Dermatol 1989;21:1263-1270
Oral Surg Oral Med Oral Pathol 1992;74:610-619.
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Alternative titles; symbolsMROS; MRS
The features are chronic swelling of the face, peripheral facial palsy that tends to relapse and may be bilateral, and in some cases lingua plicata ('scrotal' tongue). The disease often begins in childhood or youth. The swelling is localized especially to the lips. Kunstadter (1965) described a case with onset at 5.5 years of age. The maternal grandmother developed unilateral Bell palsy without facial edema at age 68. A maternal aunt developed unilateral Bell palsy with questionable edema at 10 years of age and recovered completely. Carr (1966) found at least 4 other reported families in which 2 generations were affected and 1 instance of 3 generations affected. In a Greek kindred, Lygidakis et al. (1979) observed 7 cases in 5 sibships of 4 generations, with 1 instance of male-to-male transmission and 1 instance of 'skipped generation.' See amyloidosis V (105120) for a disorder with many similarities.
Smeets et al. (1994) described a 26-year-old female with typical clinical features of Melkersson-Rosenthal syndrome and a de novo t(9;21)(p11;p11) translocation, and suggested that the gene is located at 9p11. The patient's mother had normal chromosomes. The patient developed episodes of recurrent and transient swelling of the upper lip in late adolescence. The swelling gradually became persistent and more manifest, also involving the lower lip. Her tongue had been of the scrotal type since childhood. There had been no facial palsy, although she complained of loss of taste in the anterior part of the tongue. On physical examination, discrete swelling of her chin and eyelids was also noted.
Cockerham et al. (2000) reviewed the clinicopathologic features of eyelid involvement in Melkersson-Rosenthal syndrome. The 3 men and 1 woman studied ranged in age from 33 to 74 years. Each had insidious, painless, nonpitting eyelid edema: 3 had unilateral edema; 1 had bilateral, asymmetric involvement. Ipsilateral lip edema was present in 1 case. Computed tomography aided in the diagnosis. Histopathology of each eyelid biopsy in this study revealed granulomatous lymphangitis unique to Melkersson-Rosenthal syndrome. The authors recommended biopsy of all cases of unexplained nonpitting eyelid edema.
Caksen et al. (2002) described Melkersson-Rosenthal syndrome in association with Ehlers-Danlos syndrome and found 1 previously reported instance of the association.
McKusick - updated : 8/23/2002
Jane Kelly - updated : 5/23/2000
Victor A. McKusick : 6/2/1986
mgross : 3/17/2004http://omim.org/entry/155900
Department of Ophthalmology and Visual Sciences, QEII Health Sciences Centre, Dalhousie University, Halifax, Nova Scotia, Canada.
PurposeTo report the clinicopathologic features of a series of patients with Melkersson-Rosenthal syndrome(MRS).MethodsPatients in this clinicopathological case series were identified through retrospective review. Five Caucasian patients (2 women and 3 men; age range, 46 to 73 years) with isolated eyelid swelling presented over an 11-month period to two Canadian tertiary Oculoplastic referral centres. All underwent clinical examination and had tissue biopsies.ResultsThe patients presented with non-pitting, non-pruritic, painless and recurrent eyelid swelling. None had evidence of cranial nerve palsy or fissured tongue. The duration of symptoms before referral was between 1-5 years. Histopathological examination showed granulomatous inflammation in four patients. Granulomatous folliculitis was a novel finding in three patients.ConclusionsMonosymptomatic patients with MRS require a high index of suspicion. Histopathological confirmation is vital for the diagnosis.Eye advance online publication, 4 November 2011; doi:10.1038/eye.2011.285.
Departments of Pathology, Ramón y Cajal Hospital, University of Alcalá, Madrid, Spain.
Orofacial granulomatosis, an uncommon immunologically mediated disorder, includes cheilitis granulomatosa andMelkersson-Rosenthal syndrome. It is clinically characterized by recurrent or persistent swelling of the orofacial tissues with a spectrum of other orofacial features and sometimes with neurological symptoms. The pathological findings are varied but are often characterized by the presence of noncaseating granuloma. We present a new case of orofacial granulomatosis with unusual histopathological findings, namely, intralymphatic granulomas. These may be the cause of the tissue edema. We demonstrated, by immunohistochemical studies, the lymphatic nature of the vessels affected by the granulomatous process.
Wrong Diagnosis (1)
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Melkersson-Rosenthal syndrome with isolated immunoglobulin E hypogammaglobulinaemia. - Nov/Dec 2007
Melkersson-Rosenthal syndrome: a form of pseudoangioedema - Aug 2007
Cheilitis granulomatosa and Melkersson-Rosenthal syndrome: evaluation of gastrointestinal involvement and therapeutic regimens in a series of 14 patients. - Sept 2007
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