Abstract
CANDLE Syndrome (Chronic Atypical Neutrophilic Dermatosis with Lipodystrophy and Elevated Temperature) is an autoinflammatory disease. Clinical characteristics include recurrent fevers, organ inflammation, skin lesions, anemia, lipodystrophy, basal ganglion calcifications, and delayed physical development. Orofacial manifestations include facial lipodystrophy, swollen eyelids, thick lips, macroglossia, generalized microdontia, and jaw osteopenia. We describe a novel finding of multiple inflamed follicular cysts in two patients, diagnosed with CANDLE syndrome, who presented with radiolucent mandibular lesions associated with displaced permanent molars and mandibular bony expansion. To the best of our knowledge, the finding of inflamed follicular cysts in patients with CANDLE syndrome has never been reported in literature. We speculate that the intense inflammation seen in both cases could possibly corelate with the inflammatory dysregulation and generalized organ inflammation seen in this disease process. This new finding of radiolucent mandibular cystic lesions provides further insight into the extent and characterization of the syndrome.
Highlights
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CANDLE Syndrome is an autoinflammatory disease which includes multiple hallmark systemic findings as well as orofacial manifestations.
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We present two cases of children with CANDLE Syndrome who have a novel finding of multiple inflamed follicular cysts of the mandible.
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This new finding of radiolucent mandibular cystic lesions provides further insight into the extent and characterization of CANDLE S Syndrome.
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Currently no definitive therapy for CANDLE syndrome exists.
Introduction
CANDLE Syndrome (Chronic Atypical Neutrophilic Dermatosis with Lipodystrophy and Elevated Temperature) is an autoinflammatory syndrome that is characterized by recurrent febrile episodes, pruritic skin lesions, arthralgia, extremity contractures, delayed physical development, violaceous swollen eyelids, progressive lipodystrophy, anemia, and increased acute phase reactants with onset during the first year of life [ , ]. It is thought to be a part of a continuum of syndromes named the proteasome-associated autoinflammatory syndromes (PRAAS) which are characterized by homozygous or compound heterozygous loss of function mutations in proteasome subunit β 8 (PSMB8) [ ]. These various syndromes appear to be clinical variants of the same genetic disorder with gene mutations coding for immunoproteasome function for protein degradation associated with dysregulation of the patient’s immune function [ , ]. As of 2015, only 30 known cases of CANDLE Syndrome have been reported [ ].
We describe two patients who were diagnosed with CANDLE syndrome with the characteristic features seen with this disease process. A new finding of inflamed follicular cysts, in the mandible, associated with displaced permanent molars and mandibular expansion is presented in this report. This novel finding may be a relevant and previously unknown or under-reported component of this syndromic process.
Presentation of cases
Patient 1
A 9-year-old boy presented to our clinic for evaluation of a left mandibular hypodense lesion that was noted on imaging. The patient was diagnosed with CANDLE syndrome at the National Institutes of Health (NIH) at a young age. The patient, and his parents, reported a non-painful slowly progressing left posterior mandibular swelling. A computed tomography (CT) scan was taken at a recent visit to the National Institutes of Health (NIH), which showed a left mandibular hypodense lesion closely approximated to the first, second and third molars ( Fig. 1 ). The patient denied any altered sensation, change in position of the dentition or change in occlusion. After discussion of the treatment options, we decided to remove the lesion under general anesthesia. A dark brown fluid filled cystic lesion was discovered after unroofing the cavity. The lesion, approximately 2 × 2×0.5cm in size, was enucleated and the surrounding bony cavity was curetted. A 7mm section of the roof of the inferior alveolar canal was found to be eroded by the lesion but no displacement of the inferior alveolar nerve was found. The specimen was sent for histopathological analysis and a follicular cyst with subacute inflammation was diagnosed ( Fig. 2 ). The patient’s immediate postoperative healing was uncomplicated. Close follow-up was conducted.
Approximately two years after the patient’s initial treatment, the patient returned to our clinic with reports that he began to experience intermittent pain in the left mandible that was associated with the posterior dentition. He noted that his dentition had migrated and his occlusion had changed. He denied any change in sensation. A panoramic radiograph was obtained which revealed a recurrence of the left mandibular cyst with displacement of teeth #17 and 18 to the inferior and posterior. After discussion of treatment options with the patient and his parents, it was decided to completely excise the recurrent lesion and remove the associated dentition under general anesthesia. The lesion was unroofed and had an appearance similar to the previous lesion. The cystic cavity measured, approximately, 3 × 2x1cm in size. Teeth # 17 and 18 were found to be enclosed in the lesion and the roots of tooth # 19 were also enveloped, therefore teeth # 17, 18, and 19 were removed, the cyst was enucleated and the surrounding bone was curetted. A 1 cm section of the inferior alveolar nerve was visualized but was not displaced. The lesion and the associated dentition were sent for histopathological analysis. The teeth were not processed and the soft tissue specimen was diagnosed as follicular cyst, subacutely inflamed, very similar to the previous diagnosis. Postoperative healing was within normal limits. No further recurrence has been noted to date upon close clinical and radiographic follow-up. Of note, the patient has undergone exposure and bonding for orthodontic extrusion of multiple impacted permanent dentition, which is typical in CANDLE syndrome [ ].
Patient 2
A 10-year-old boy was referred to the oral and maxillofacial surgery clinic by his pediatric dentist after detection of a right mandibular radiolucency discovered upon routine radiographic examination ( Fig. 3 ). The patient had also been diagnosed with CANDLE Syndrome at the NIH at an early age. He and his parents denied any mandibular expansion, sensory changes, pain, mobility of dentition or changes in occlusion. A cone beam CT was obtained which revealed an approximately 4 × 3x1cm radiolucency of the right mandible associated with an inferiorly displaced tooth # 31. An additional well-circumscribed and radiolucent approximately 1 × 1x1cm lesion of the left mandible was noted associated with the roots of tooth # 19 ( Fig. 3 .). After discussion of these findings with the patient and his parents, we decided to enucleate the left mandibular lesion and marsupialize the right mandibular lesion due to its larger size and proximity to the inferior border of the mandible. Under general anesthesia, the left mandibular lesion was enucleated and the surrounding bone was curetted. The roots of tooth # 19 were discovered to be enveloped in a cystic lining and therefore the tooth was removed. A right mandibular mucosal incision revealed that a portion of the buccal bone was eroded with a cystic lining protruding from the mandible. A portion of the exposed cyst was removed and sent for histopathologic examination. A drain was placed into the cystic cavity and secured. The patient was instructed to irrigate the drain daily. The tissue was submitted for microscopic examination which was diagnosed as a follicular cyst with intense subacute inflammation ( Fig. 4 ). The patient was seen for two subsequent postoperative visits where healing was uneventful. Following this, the patient failed to report for follow up for almost two years. However, the patient eventually returned and an orthopantomogram was obtained which revealed adequate interval bony fill in the cystic cavity of the right mandible ( Fig. 5 ). The patient was therefore taken to the operating room where enucleation and curettage of the remaining right mandibular follicular cyst was performed. Teeth #31 and 32 were enveloped in cystic lining and were removed. Supernumerary tooth #20a was additionally removed. No further recurrence has been noted to date upon close clinical and radiographic follow-up.
