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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.


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AGE RANGE-MEDIAN Mean age of onset 33 years and mean age of diagnosis 39 years



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 or food additive intolerance Clin Allergy 1986;16:331-338
Monosodium glutamate
Sunset yellow
Hereditary Melkersson-Rosenthal syndrome and multiple sclerosis.

Cabrera-Gomez JA, Echazabal-Santana N, Real-Gonzalez Y, Romero Garcia K, Junior Sobrinho M, Gil Ocana MA, Gonzalez-Valdes N, Valdes-Montesde Oca ML, Cristofo-Corominas M, Gonzalez de la Nuez J, Garcia Lahera J, Ugarte Suarez C.

International Center of Neurologic Restoration (CIREN), Avenida 25 #15805 entre 158 y 160, Reparto Cubanacan, Playa, Ciudad de La Habana, Cuba.
Mult Scler. 2005 Jun;11(3):364-6. Abstract quote  

The revision of MEDLINE from 1966 to 2003 did not report any association between multiple sclerosis (MS) and Melkersson-Rosenthal syndrome (MRS).

This is a case report of a 51-year-old woman, with history of four recurrent Bell's palsies. In 1999 she developed a right facial paralysis due to a supranuclear pyramidal lesion with right monoparesis. The family history showed five relatives with recurrent Bell's paralysis and plicata tongue. Physical examination: right Bell's paralysis, left supranuclear facial paralysis, furrowed tongue, right hemiparesis with pallor of the optic disks. Brain magnetic resonance imaging (MRI) demonstrated the typical lesions of MS and CSF oligoclonal bands.

This is the first observation of a patient with hereditary MRS and MS. The link between both diseases is discussed.

Association of Melkersson-Rosenthal syndrome with rosacea.

Bose SK.

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.




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.


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.



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.


Painless chronic isolated enlargement of one or both lips due to granulomatous inflammation with a recurrent to gradually persistent course

Young adults
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.


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

Chronic macrocheilia: a clinico-pathological study of 28 patients.

Handa S, Saraswat A, Radotra BD, Kumar B.

Department of Dermatology, Venereology and Leprology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.

Clin Exp Dermatol. 2003 May;28(3):245-50 Abstract quote.  

Chronic macrocheilia has a multifactorial aetiology and is often a diagnostic and therapeutic challenge. Epidemiological information on this condition is scarce, most of the data reported relating only to granulomatous cheilitis.

We have performed a detailed clinico-pathological analysis of all patients with chronic macrocheilia presenting to us during the last 6.5 years. Of the 28 patients identified, 13 (46.4%) had granulomatous cheilitis (GC), six (21.4%) had tuberculosis of the lip, three (10.7%) had leprous macrocheilia, two (7.1%) had multiple endocrine neoplasia type IIb, and one each had Ascher's syndrome and non-Hodgkin's lymphoma. Two patients were diagnosed as 'nonspecific cheilitis'.

Histopathological differentiation between tuberculosis and GC was often not possible; but PCR for Mycobacterium tuberculosis was positive in all patients with tuberculosis and negative in four patients with GC in whom M. tuberculosis was sought. In spite of detailed clinical examination and investigations, a therapeutic trial was required to confirm the diagnosis in five (17.9%) patients.

We have reviewed the available literature on this subject, and to our knowledge this study is the first of its kind. More such studies from other centres will help physicians to make an accurate aetiological diagnosis and treat this uncommon but disfiguring condition with confidence.
Persistent erythema and edema of the midthird and upper aspect of the face (morbus morbihan): evidence of hidden immunologic contact urticaria and impaired lymphatic drainage.

Wohlrab J, Lueftl M, Marsch WC.

Department of Dermatology, Martin Luther University Halle-Wittenberg, Halle/Saale, Germany.
J Am Acad Dermatol. 2005 Apr;52(4):595-602. Abstract quote  

BACKGROUND: A persistent erythema and edema of the midthird and upper aspect of the face, which bears some resemblance to Melkersson-Rosenthal syndrome and rosaceous lymphedema, has been characterized as morbus morbihan (MM) by French dermatologists. The disease of yet unknown cause starts with recurrent facial edema of short duration, which ultimately leads to persistent swelling after a period of weeks or months.

METHODS: We recruited 6 patients with MM and acquired their history, routine blood tests, and individual UV light tolerability. To check for contact allergies the allergen patch test and the open epicutaneous patch test were performed. To objectify the skin conditions laser Doppler flowmetry and 20-MHz ultrasound were used. Five patients with similar symptoms, but with definitely transient facial erythema and edema caused by proven contact urticaria on cosmetics served as a comparison group.

RESULTS: In all patients, routine blood tests and UVA/UVB light tests showed no pathologic results. Observations of 6 patients with MM revealed the common feature of a clinically relevant immunologic contact urticaria caused by various cosmetic ingredients, which could be diagnosed in all of them. Delayed resorption of the acute edema and prolonged inflammation were shown by laser Doppler flowmetry and 20-MHz ultrasound in the affected skin areas in patients with MM after induction of immunologic contact urticaria by a cosmetic ingredient. Strict avoidance of cosmetics yielded a remarkable clinical benefit in the follow-up examinations.

CONCLUSIONS: We conclude that recurrent and possibly subclinical inflammation caused by immunologic contact urticaria in conjunction with a locally pre-existing lowered lymphatic drainage plays a crucial role in the evolution of MM.
Localized cutaneous polyvinylpyrrolidone storage disease mimicking cheilitis granulomatosa.

Chi CC, Wang SH, Kuo TT.

Department of Dermatology, Chang Gung Memorial Hospital-Chiayi, Chiayi, Taiwan.

J Cutan Pathol. 2006 Jun;33(6):454-7. Abstract quote  

Polyvinylpyrrolidone (PVP), a polymer of the monomer N-vinylpyrrolidone with various molecular weights, was originally developed as a plasma expander.

Currently, it is widely used in hair sprays, skin care products, fruit juices, and as a retarding agent in drugs such as procaine and hormones. PVP polymers with a molecular weight greater than 20,000 cannot be excreted by the kidneys and therefore are phagocytosed and permanently stored in the reticular endothelial system, leading to the so-called PVP storage disease.

We report a case of localized cutaneous PVP storage disease presenting with persistent upper lip swelling and mimicking cheilitis granulomatosa, which has never been reported before.



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.

Surgical Treatment of Persistent Macrocheilia in Patients With Melkersson-Rosenthal Syndrome and Cheilitis Granulomatosa

Birgit Kruse-Lösler, MD, DMD; Dagmar Presser, MD; Dieter Metze, MD; Ulrich Joos, MD, DMD

Arch Dermatol. 2005;141:1085-1091. Abstract quote

Background  Various conservative methods for treatment of labial swelling in patients with cheilitis granulomatosa have been attempted, often with only moderate success and sometimes with persistent disfiguring lip swelling. Severe macrocheilia can produce an unaesthetic facial deformity associated with functional disturbances. In patients with persistent macrocheilia, reduction cheiloplasty with excision of excess tissue may be indicated when conservative treatment has proven ineffective in reducing swelling but may have been successful in stabilizing disease.

Objective  To evaluate long-term results after reduction cheiloplasty in patients with macrocheilia caused by Melkersson-Rosenthal syndrome or cheilitis granulomatosa.

Design  Follow-up study in 7 patients with severe persisting macrocheilia, including 3 patients with Melkersson-Rosenthal syndrome and 4 patients with cheilitis granulomatosa in a stable state of disease, treated by reduction cheiloplasty at our hospital between January 1, 1987, and December 31, 2002. Preoperative and postoperative medical histories were obtained, and criteria for the success of surgical treatment were evaluated by clinical examination. Different techniques of reduction cheiloplasty are described and demonstrated in representative cases of severe macrocheilia.

Results  Surgical treatment in all 7 patients showed satisfying aesthetic and functional outcomes that persisted throughout follow-up (median follow-up, 6.5 years).

Conclusions  Reduction cheiloplasty is an effective method to correct persistent macrocheilia and improve lip aesthetics in patients with Melkersson-Rosenthal syndrome or granulomatous cheilitis in the persistent state of disease. With careful planning, proper sequencing of treatment, and proficiency in the various surgical techniques, optimal results can be achieved.

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.

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