Orofacial granulomatosis presenting as bilateral eyelid swelling
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Ophthalmic Pathology Update Orofacial granulomatosis presenting as bilateral eyelid swelling Curtis W. Archibald, MD a ; Karim G. Punja, MD a ; Allan F. Oryschak, MD a,b,⇑ Abstract Orofacial granulomatosis (OFG) is an uncommon but increasingly recognized disease of unknown etiology. The typical presenta- tion is chronic swelling of the perioral soft tissue, but eyelid edema can be the sole manifestation. Terminology of this disease can be confusing as it may also be referred to as granulomatous cheilitis and a monosymptomatic presentation of Melkersson–Rosenthal syndrome (MRS). Crohn’s disease and sarcoidosis should also be considered in the differential as the histopathology can be similar. Corticosteroids are the mainstay of treatment but can lack efficacy. Atypical presentations and the possibility of systemic disease involvement can further challenge the management. We describe an unusual case in which OFG manifests solely as chronic eyelid swelling. This 69-year old Asian female patient had a delayed diagnosis that responded well to intralesional corticosteroid injection with surgical skin reduction. In addition to describing this unusual presentation of OFG, we review the relevant literature and eval- uate the current terminology used to describe this entity. Keywords: Orofacial granulomatois, Melkersson–Rosenthal syndrome, Granulomatous cheilitis, Eyelid swelling, Histopathology Ó 2012 Saudi Ophthalmological Society, King Saud University. All rights reserved. doi:10.1016/j.sjopt.2012.02.009 Introduction Orofacial granulomatois is a clinicopathological diagnosis that, as the name implies, is characterized by orofacial swell- ing that on histopathologic analysis shows non-caseating granulomata within or in close proximity to the lymphatic vessels. 1 The term orofacial granulomatosis (OFG) was introduced in 1985 by Wiesenfeld et al. to emphasize the importance of systemic investigations, namely for Crohn’s disease as the histopathology is similar. 2 This update in nomenclature was also an attempt to unify, and be an umbrella term for other less descriptive names for this entity, namely Melkersson– Rosenthal syndrome (MRS) and granulomatous cheilitis. MRS was named after the descriptions by Melkersson in 1928 and Rosenthal in 1931. Melkersson described the case of a 35-year old woman with facial edema and palsy and he suggested a relationship between the two findings. 3 Rosenthal later described a similar presentation but noted the additional finding of a fissured tongue and this lead to the triad to be known as Melkersson–Rosenthal syndrome. 4 In 1945, Meischer described a monosymptomatic variant of MRS that was characterized by granulomatous lip swelling and became know as cheilitis granulomatosa. 5 OFG most commonly presents with swelling of the perio- ral area. We describe an unusual case in which eyelid swelling is the sole manifestation of OFG. Case report A 69-year old Asian female presented to our oculoplastics service with a four-year history of bilateral eyelid swelling. She had seen numerous specialists over time but the diagnosis remained elusive. She had seen a dermatologist who had per- formed allergy testing which was negative. Her medical his- tory was significant for diabetes mellitus, hypertension, and Peer review under responsibility of Saudi Ophthalmological Society, King Saud University j Production and hosting by Elsevier Access this article online: www.saudiophthaljournal.com www.sciencedirect.com Received 19 January 2012; received in revised form 14 February 2012; accepted 25 February 2012; available online 3 March 2012. a Department of Surgery, Division of Ophthalmology, University of Calgary, Calgary, Alberta, Canada b Department of Pathology and Laboratory Medicine, University of Calgary, Calgary, Alberta, Canada ⇑ Corresponding author. Address: Rockyview General Hospital, 7007-14th Street SW, Calgary, Alberta, Canada T2V 1P9. Tel.: +1 403 943 3578; fax: +1 403 943 3333. e-mail address: [email protected] (A.F. Oryschak). Saudi Journal of Ophthalmology (2012) 26, 177–179
Transcript of Orofacial granulomatosis presenting as bilateral eyelid swelling
Saudi Journal of Ophthalmology (2012) 26, 177–179
Ophthalmic Pathology Update
Orofacial granulomatosis presenting as bilateral eyelid swelling
Curtis W. Archibald, MD a; Karim G. Punja, MD a; Allan F. Oryschak, MD a,b,⇑
Abstract
Orofacial granulomatosis (OFG) is an uncommon but increasingly recognized disease of unknown etiology. The typical presenta-tion is chronic swelling of the perioral soft tissue, but eyelid edema can be the sole manifestation. Terminology of this disease canbe confusing as it may also be referred to as granulomatous cheilitis and a monosymptomatic presentation of Melkersson–Rosenthalsyndrome (MRS). Crohn’s disease and sarcoidosis should also be considered in the differential as the histopathology can be similar.Corticosteroids are the mainstay of treatment but can lack efficacy. Atypical presentations and the possibility of systemic diseaseinvolvement can further challenge the management. We describe an unusual case in which OFG manifests solely as chronic eyelidswelling. This 69-year old Asian female patient had a delayed diagnosis that responded well to intralesional corticosteroid injectionwith surgical skin reduction. In addition to describing this unusual presentation of OFG, we review the relevant literature and eval-uate the current terminology used to describe this entity.
Keywords: Orofacial granulomatois, Melkersson–Rosenthal syndrome, Granulomatous cheilitis, Eyelid swelling, Histopathology
� 2012 Saudi Ophthalmological Society, King Saud University. All rights reserved.doi:10.1016/j.sjopt.2012.02.009
Introduction
Orofacial granulomatois is a clinicopathological diagnosisthat, as the name implies, is characterized by orofacial swell-ing that on histopathologic analysis shows non-caseatinggranulomata within or in close proximity to the lymphaticvessels.1
The term orofacial granulomatosis (OFG) was introducedin 1985 by Wiesenfeld et al. to emphasize the importanceof systemic investigations, namely for Crohn’s disease asthe histopathology is similar.2 This update in nomenclaturewas also an attempt to unify, and be an umbrella term forother less descriptive names for this entity, namely Melkersson–Rosenthal syndrome (MRS) and granulomatous cheilitis.
MRS was named after the descriptions by Melkersson in1928 and Rosenthal in 1931. Melkersson described the caseof a 35-year old woman with facial edema and palsy and hesuggested a relationship between the two findings.3 Rosenthal
Peer review under responsibilityof Saudi Ophthalmological Society,King Saud University
Received 19 January 2012; received in revised form 14 February 2012; accepte
a Department of Surgery, Division of Ophthalmology, University of Calgary, Cb Department of Pathology and Laboratory Medicine, University of Calgary, C
⇑ Corresponding author. Address: Rockyview General Hospital, 7007-14th St403 943 3333.e-mail address: [email protected] (A.F. Oryschak).
later described a similar presentation but noted the additionalfinding of a fissured tongue and this lead to the triad to beknown as Melkersson–Rosenthal syndrome.4
In 1945, Meischer described a monosymptomatic variantof MRS that was characterized by granulomatous lip swellingand became know as cheilitis granulomatosa.5
OFG most commonly presents with swelling of the perio-ral area. We describe an unusual case in which eyelid swellingis the sole manifestation of OFG.
Case report
A 69-year old Asian female presented to our oculoplasticsservice with a four-year history of bilateral eyelid swelling.She had seen numerous specialists over time but the diagnosisremained elusive. She had seen a dermatologist who had per-formed allergy testing which was negative. Her medical his-tory was significant for diabetes mellitus, hypertension, and
j Production and hosting by ElsevierAccess this article online: www.saudiophthaljournal.comwww.sciencedirect.com
d 25 February 2012; available online 3 March 2012.
algary, Alberta, Canadaalgary, Alberta, Canada
reet SW, Calgary, Alberta, Canada T2V 1P9. Tel.: +1 403 943 3578; fax: +1
Figure 1. (a) Patient at initial presentation. (b) Lateral view of eyelidswelling.
Figure 3. (a) Nine weeks following intralesional triamcinolone injectionand surgical debulking the eyelid swelling has resolved. (b) Lateral view ofresolved eyelid swelling.
178 C.W. Archibald et al.
hypercholesterolemia. She also had recently seen a gastroen-terologist for iron-deficiency anemia. Upper gastrointestinaltract endoscopy revealed helicobacter pylori-associated chronicgastritis. She denied any history of recent trauma, infection, orallergy.
On examination, there was non-tender, non-erythema-tous, firm edema of the upper eyelids (Fig. 1). There was sec-ondary eyelash ptosis. Ocular motility was full. The remainderof the ocular exam was within normal limits. A biopsy was ob-tained via a debulking blepharoplasty and intralesional triam-cinolone was injected.
Histopathological analysis revealed non-caseating granu-lomata in the eyelid dermis in perivascular and perilymphaticdistributions (Fig. 2a). There were granulomata within thelumena of the lymphatic vessels (Fig. 2b). CD68 immunoreac-tivity confirmed the intraluminal cells as histiocytes (Fig. 2c).There was edema of the dermis and the epidermis wasundisturbed. The findings were consistent with orofacialgranulomatosis.
Further investigation included extensive blood work,including ACE, and showed no significant abnormalities.Abdominal CT scan and chest X-ray were unremarkable.Her previous upper endoscopy included duodenum assess-ment and was normal. Overall, her work-up found no sys-temic involvement or alternative diagnoses.
At nine-week follow-up the eyelid swelling continued tobe in remission (Fig. 3).
Discussion
The etiology of orofacial granulomatosis (OFG) is unknownbut a number of causative agents have been suggested suchas microbes, food substances and additives, dental material,other contact allergens, and immunological processes.6
Figure 2. Histological specimens of eyelid biopsy. All views are of the sameoriginal magnification �200). (b) D2–40 immunoreactivity showing lymphaticimmunoreactivity confirming intralymphatic histiocytes (original magnification
No clear genetic or ethnic predilection has been identifiedfor OFG. Based on the English literature, most case series arefrom Europe and North America and describe Caucasian pa-tients. Our case describes an Asian female which does not fitthe usual profile. The median age of presentation is 28 yearsbut the age range includes children and the elderly.7
In our case, there was a four-year symptomatic period be-fore the diagnosis was made. This long duration is represen-tative of other case reports and highlights the importance ofconsidering OFG in the differential of chronic eyelid swelling.Other important considerations include thyroid-associatedorbitopathy, blepharochalasis, and allergy.
Isolated bilateral eyelid swelling is an unusual presentationof OFG, but appears to be an increasingly recognizedentity.8–14 There have also been reports of unilateral presen-tation.14–16 The eyelid swelling is typically painless, non-pruritic,non-pitting edema, and may fluctuate over time and involveother parts of the face.17
The terminology for this clinicopathologic entity varies inthe literature. It is also referred to as a monosymptomaticvariant of Melkersson–Rosenthal syndrome (MRS) and asgranulomatosis cheilitis when localized to the perioral tissues.Such variations in nomenclature can be confusing and dilutethe catalogue of this disease in the literature. MRS refers tothe triad of findings that include facial swelling, facial palsy,and fissured tongue. Orofacial swelling is the presenting signin 86% of cases but the complete triad is only found in aminority of patients (8–25%).10,18,19 We question the logicof referring to this type of isolated eyelid swelling, or otherisolated facial swelling, as a syndrome when there are noother findings. We feel that orofacial granulomatosis is a betterterm to use in these instances, and the eponym Melkersson–Rosenthal syndrome is best reserved for describing the com-plete triad, or at least two features of the triad (oligosympto-
field. (a) Perivascular and intravascular granulomata (hematoxylin–eosin,vessels that contain granulomata (original magnification �200). (c) CD68�200).
Orofacial granulomatosis presenting as bilateral eyelid swelling 179
matic variant). We can further simplify the nomenclature byreferring to all isolated facial swelling of this nature asOFG, and granulomatosis cheilitis as a subtype classification.
As Wiesenfeld and colleagues intended in their 1985description of OFG, the clinician must investigate for sys-temic involvement. Crohn’s disease may manifest as orofacialswelling and the histopathology findings can be identical toOFG.2 Furthermore, it is important that patients have long-term follow-up as Crohn’s disease may show systemic find-ings at a later time. Sarcoidosis can also have similar clinicaland histopathological findings.6
Biopsy is crucial in diagnosing OFG as it truly is a clinico-pathological correlation. Intralymphatic granulomas are theclassic histopathological findings. Descriptions of OFG with-out histopathology should be critically analyzed. In our case,with an atypical location of facial swelling, the diagnosiscould not have been accurately determined without the nec-essary biopsy. This emphasizes the importance of biopsyingidiopathic eyelid edema.
Treatment of OFG is challenging. Complete remissions arerare and relapses are common. Delayed diagnoses are fre-quent and may further compromise the treatment response.Corticosteroids (topical, intralesional, and systemic) havebeen the mainstay of treatment but results have been mixed.Other medications that have not been overly efficacious haveincluded clofazimine, hydroxychloroquine, dapsone, sulpha-salazine, thalidomide, danazol, and minocycline.15 Eliminationdiets and avoidance of potential allergens have also beenadvocated but with minimal success.6
Our patient’s edematous upper eyelids were treated withintralesional steroid injection and surgical debulking. Her re-sponse was excellent despite a delay in her diagnosis of fouryears. We feel that local treatment such as surgical debulkingand intralesional steroid injection is a logical first step intreating isolated eyelid edema and systemic treatmentshould be reserved for relapsing disease. Further study toelucidate the etiology of OFG will further guide rationaletreatment protocols. Using consistent nomenclature willstreamline future research in order to better understand thiscomplex disease process.
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