Characteristics of patients with orofacial granulomatosis

Oral Diseases (2011) 17 , 696–704 Objectives: Orofacial granulomatosis has mostly been described in reports of very small numbers of cases. Few large case groups have been described. The aim of this study was to describe the demographics, symptoms, clinical features and laboratory findings in a large cohort of cases. Subjects and Methods: Clinical and laboratory data for 119 cases of orofacial granulomatosis who attended oral medicine clinics in Dublin, Ireland, were examined for demographic characteristics at the time of first presentation. The male/female ratio was approximately 1:1, with a median age (and range) of 28 (5–84) years. Results: Symptoms had been present for a median duration of 12 weeks. A food association was suspected by 30% of patients. The predominant complaint was lip swelling (77%) with only 15% reporting facial swelling, while 8% complained of both. Almost all patients had clinical evidence of lip or facial swelling (95%). Other common extra‐oral manifestations were lip fissuring (30%), angular cheilitis (28%) and perioral erythema (28%). Common intra‐oral manifestations were cobblestoning of the buccal mucosa (63%), ulcers (36%), granulomatous gingivitis (33%), mucosal tags (29%) and fissured tongue (17%). Over half of the biopsies (56%) performed were reported as typical of orofacial granulomatosis. Conclusion: This is one of the largest cohorts of orofacial granulomatosis patients to have been described in detail.     

Patch testing for food‐associated allergies in orofacial granulomatosis

J Oral Pathol Med (2011) 40 : 10–13 Background: Food‐associated allergies, especially to benzoates and cinnamon‐related compounds, have been associated with orofacial granulomatosis and both standard and urticarial patch testing have been used to detect such allergies. Elimination diets have also been shown to be effective in some patients. Objectives: To compare the results of standard and urticarial patch testing in a cohort of patients with orofacial granulomatosis. Materials and methods: Records of 120 cases seen in two hospitals were retrieved and examined for patch test details. Results: Standard patch testing was much less likely to detect allergy to benzoates and cinnamon compounds (7%) than urticarial tests (55%). All urticarial tests that were positive had shown a reaction by 60 min. Conclusions: Both standard and urticarial patch tests are required to detect food allergies in orofacial granulomatosis. The difficulties of patient self‐recording of urticarial tests can be eliminated by retaining patients in the testing unit for professional reading of patches at 60 min.     

Antibodies to mycobacterial stress protein in patients with orofacial granulomatosis

Immunoglobulin G antibody liters 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 liters 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 lo be of a diagnostic value for Crohn's disease.     

Mechanisms associated with unusual orofacial pain

This article presents an overview of possible mechanisms associated with pain perception, with a specific focus on understanding unusual manifestations of orofacial pain associated with nerve insult. It includes recent evidence concerning neurobiological changes that occur in the periphery at tissue and nerve sites, or within the central nervous system, and that may involve chemical and inflammatory responses, sensitization, or alterations of cellular function. Moreover, the contribution of the autonomic nervous system, changes in emotional reactivity and vigilance, the roles of high brain centers such as the basal ganglia (nigro-striatal) system, and the influence of aging and gender, are briefly described.     

Psychological factors associated with orofacial pains

This article develops the case for why trigeminal pain is a unique and challenging problem for clinicians and patients alike, and provides the reader with insights for effective trigeminal pain management based on an understanding of the interplay between psychologic and physiologic systems. There is no greater sensory experience for the brain to manage than unremitting pain in trigeminally mediated areas. Such pain overwhelms conscious experience and focuses the suffering individual like few other sensory events. Trigeminal pain often motivates a search for relief that can drain financial and emotional resources. In some instances, the search is rewarded by a treatment that immediately addresses an identifiable source of pain; in other cases, it can stimulate never-ending pilgrimages from one health provider to another.     

Methicillin-resistant Staphylococcus aureus. A continuing infection control challenge

The ability of MRSA and other staphylococci to colonize, persist, and adapt to multiple environmental and tissue conditions has allowed for these bacteria to be virtually ubiquitous in their distribution. The effectiveness of commonly used antibiotics, such as penicillin, has continued to decline against infections caused by MRSA and increasingly resistant strains. The challenge for both dental and medical health professionals is to routinely apply proven, evidence-based infection control precautions. As mentioned earlier in this discussion, when compliance with effective aseptic technique practices improves, the patients and environments. Ensure that reusable equipment is not used for the care of another patient until it has been appropriately cleaned and reprocessed and that single-use items are properly discarded. Clean and disinfect clinical contact surfaces that are not barrier-protected by using an environmental protection agency-registered hospital disinfectant with a low- (ie, HIV and HBV label claims) to intermediate-level (ie, tuberculocidal claim) activity after each patient. When the surface is visibly contaminated with blood, an intermediate-incidence of detectable infections can be reduced. Microorganisms will continue to evolve and adapt in order to survive and thrive, sometimes at the expense of susceptible human hosts. The struggle is to constantly remain aware of impending infectious threats which may challenge current precautions, and maintain and improve the quality of infection control to minimize the potential for disease.     

Two cases of oral infection by methicillin-resistant Staphylococcus aureus

Two cases of oral infection with multi-resistant Staphylococcus aureus (MRSA) are described who were found to carry the same MRSA. Both cases were managed without the use of antibiotics. The practitioner was found not to have worn gloves routinely and this may have been the source of the MRSA.     

Monosodium glutamate-related orofacial granulomatosis. Review and case report

A case is reported in a 15-year-old white girl who had a swollen lower face and lips; a diagnosis of orofacial granulomatosis was made. It was suspected that her condition had an allergic basis because an increase in clinical signs and symptoms was shown to be related to the food additive monosodium glutamate. Treatment with a restricted diet resulted in resolution of the facial swelling.     

Onset and progression of clinical manifestations of orofacial granulomatosis

Background:  There remain few studies describing in detail the early occurrence and long-term progression of clinical manifestations of orofacial granulomatosis (OFG) in a substantial number of patients.
Objectives:  The aim of this study was to determine the early and late clinical manifestations of a large case series of patients with OFG.
Patients/methods:  Clinically relevant data of 49 patients with OFG who attended an Oral Medicine unit in the UK were examined retrospectively. The analyzed parameters included occurrence and typology of initial manifestations at onset and with respect to long-term follow-up.
Results:  Five major patterns of disease onset were observed. Recurrent facial swelling with/without intra-oral manifestations was the single most common presentation at onset followed by intra-oral ulcers, and other intra-oral and neurological manifestations. The majority of patients later developed a spectrum of additional features.
Conclusions:  OFG results in multiple manifestations at different time points. The disease onset is characterized by manifestations other than facial swelling in about half of affected individuals. However, patients can develop cosmetically unacceptable lip/facial swelling at a later stage. Nearly all affected individuals ultimately develop lip/facial swelling while about half of all patients develop oral ulceration.     

The multiform and variable patterns of onset of orofacial granulomatosis

BACKGROUND: The recurrent chronic orofacial swelling caused by orofacial granulomatosis (OFG) can cause significant cosmetic and functional problems but can be prevented if the disease is diagnosed early and promptly treated. Although the enlargement of the lips is described to be the most common presenting complaint, the clinical onset of OFG may be characterized by minor associated mucosal and neurological manifestations, making early diagnosis very difficult or, sometimes, merely presumable. PATIENTS AND METHODS: We retrospectively analyzed the clinical manifestations of 19 patients with OFG, who were examined at our institution between 1998 and 2002, in order to determine their initial manifestations and presenting symptoms. RESULTS: A total of 10 patients showed classical recurrent enlargement of the lips (six lower; four upper) as presenting symptom. In the other nine patients, OFG onset was characterized by transient unilateral facial nerve palsy (two cases), intraoral manifestations (two cases), recurrent swelling of the periorbital area (two cases), of the chin (one case), of the zygomatic area (one case), and of the cheeks (one case). CONCLUSION: Our data underlined that OFG onset could be frequently characterized by widely variable, multiform, and temporary clinical findings. Involvement of atypical sites of the orofacial region and presence of single minor manifestations may occur as presenting symptoms, often preceding the development of traditional clinical findings.     

Biologics in oral medicine: oral Crohn's disease and orofacial granulomatosis

Oral Diseases (2012) 18, 633-638 Antitumour necrosis factor (TNF-α) therapy has a potential to benefit patients with oral lesions of Crohn's disease (CD) and patients with orofacial granulomatosis (OFG). The most appropriate use would appear to be in patients with severe or multisystem features, where other available agents have failed or have been associated with adverse effects. TNF-α antagonists (infliximab in particular) have a role in the management of orofacial CD and OFG, but potential adverse effects of TNF-α antagonists include acute infusion reactions, infection and increased risk of malignancy. Thus, a full risk-benefit analysis is indicated, with patient selection, use and subsequent monitoring coordinated with gastroenterologists with appropriate training and experience in biological therapies.     

Expression of protease-activated receptor-1 and -2 in orofacial granulomatosis

OBJECTIVE: Orofacial granulomatosis (OFG) is a rare condition characterized by non-caseating granulomas in the orofacial region. Protease-Activated Receptors (PARs) play a role in inflammatory diseases in diverse human tissues. The aim of the study was to investigate the expression of PAR-1, PAR-2, MMP-2, MMP-9, COX-1, and COX-2 in tissues taken from OFG patients. METHODS: PAR-1, PAR-2, MMP-2, MMP-9, COX-1, and COX-2 expression was evaluated by immunohistochemistry in biopsies taken from oral Crohn's disease (five cases), Melkersson-Rosenthal syndrome (MRS) (six cases), cheilitis granulomatosa (five cases) and normal oral mucosa (five cases). RESULTS: PAR-1 was observed in mononuclear inflammatory cells in edematous/lichenoid lesions, whereas a strong PAR-2 immunostaining was detected in epithelioid histiocytes and giant cells in granulomatous lesions, irrespective of the clinical features (Crohn vs MRS). MMPs and COX-2 were expressed in the inflammatory component of edematous/lichenoid lesions and markedly overexpressed in granulomatous lesions. COX-1 was weakly and variably expressed in both edematous/lichenoid and granulomatous lesions. CONCLUSION: Thus, PAR-1 and PAR-2 expressions were related to the intensity and type of inflammatory response but not to the type of clinical lesion. Simultaneous overexpression of PARs, MMPs and COXs suggests synergism among these proinflammatory receptors and enzymes.     

The mouth in inflammatory bowel disease and aspects of orofacial granulomatosis

Inflammatory bowel disease has a wide range of possible oral manifestations, many of which overlap with those seen in other conditions, including orofacial granulomatosis. The precise etiology remains unclear, as is the exact relationship between orofacial granulomatosis and Crohn's disease. Overall, there is growing evidence that orofacial granulomatosis and oral Crohn's disease are distinct clinical disorders with optimal management requiring a multidisciplinary approach with input from appropriate specialists in oral medicine, gastroenterology, allergy, dietetics, and clinical psychology. This review details the etiopathogenesis, clinical presentation, epidemiology, extra‐intestinal, and oral manifestations of inflammatory bowel disease and orofacial granulomatosis. It also assesses the current role of investigations in the diagnosis of orofacial granulomatosis and critically reviews the available evidence in relation to medical and surgical interventions for the condition, and its relationship to Crohn's disease.     

Persistent orofacial pain associated with nasopharyngeal extramedullary plasmacytoma

Orofacial pain (OFP) disorders affect the maxillofacial complex and typically involve other locations in the head and neck. Common etiologies of OFP disorders include odontogenic sources, temporomandibular disorders, neuropathic pain, chemosensory disorders, and headaches. Less commonly, benign and malignant neoplasms can be associated with OFP complaints. Patients with OFP symptoms require a thorough evaluation and are often referred to additional healthcare providers for interprofessional management. In those OFP patients whose symptoms do not respond to conventional treatment(s), whose symptoms change over time, or who report positive responses to review of systems questions that suggest more extensive involvement, further investigation is warranted. To the best of our knowledge, this is the first case report of nasopharyngeal extramedullary plasmacytoma, a localized malignant neoplasm, associated with persistent OFP.     

The effect of local antibiotics in treating chronic osseous Staphylococcus aureus infection

The purpose of this study was to determine if antibiotic-supplemented bone allografts (ASBA) would enhance healing and reduce infection in chronic osteomyelitis. Intramedullary injection of Staphylococcus aureus was used to create osteomyelitis in the tibia of New Zealand white rabbits. Twenty-one days postinoculation, the animals were randomly assigned to one of the following six treatment groups: 1. debridement of the infected tibia; 2. debridement + bone graft; 3. debridement + bone graft + gelatin powder; 4. debridement + bone graft + gelatin powder supplemented with antibiotics; 5. debridement + gelatin powder supplemented with antibiotics; and 6. no surgical intervention. The debrided material was cultured for identification of microorganisms. All groups received cephalothin sodium, 100 micrograms/kg subcutaneously every 12 hours for 21-days. At time of death the tibia were assessed to determine the degree of healing. Radiographs, bacterial cultures and specimens for histologic study were obtained. Qualitative grading demonstrated a significant difference between groups (P less than .001). Groups (4 and 5) receiving local antibiotic supplementation demonstrated improved healing compared with the remaining groups. However, there was no difference between groups 4 and 5. Bacteriologic culturing indicated the greatest reduction in colony-forming units of S aureus in the postsacrifice graft sites to be in groups 4 and 5. Histologic findings paralleled qualitative assessment of healing of the gross specimens. The results of this study suggest that local antibiotic supplementation of graft preparations may be useful for treatment of chronic osseous infection.     

Thalidomide for the treatment of recalcitrant oral Crohn's disease and orofacial granulomatosis

It has been suggested that thalidomide may be effective in the management of Crohn's disease, including the associated oral lesions. We detail the clinical response to low-dose thalidomide of 5 patients with clinical features of orofacial granulomatosis or oral Crohn's disease recalcitrant to recognized immunosuppressant therapy. All patients had clinical resolution of their symptoms and signs. Transient somnolence was the only reported adverse effect. Remission was maintained by extending the period between thalidomide doses. Thalidomide should be considered an effective therapy for the short-term treatment of severe orofacial granulomatosis in appropriately counseled patients.     

Orofacial granulomatosis associated with hypersensitivity to dental amalgam

Orofacial granulomatosis is a clinicopathologic entity characterized by chronic swelling of the lip and possible soft tissues in the orofacial region owing to granulomatous inflammation of unknown cause. We present 3 cases of orofacial granulomatosis associated with allergic contact dermatitis to dental materials. Previous treatment with corticosteroids did not have any therapeutic effect. Patch testing revealed a positive reaction to several allergens, including dental amalgam and mercury in 2 cases. A lymphocyte transformation test modified for metals was used to evaluate lymphocyte reactivity. After the removal of the suspected allergens, all patients experienced recovery within 1 month, with the exception of the lip swelling, which gradually subsided over several months.