Polyostotic Melorheostosis: Approach to Clinical Evaluation and Management

Melorheostosis is a rare form of sclerosing bone dysplasia that involves mainly the long bone of the limbs. However, the involvement of more than one long bone, either involving ipsilaterally or contralaterally, is extremely rare. The aetiology still remains unknown despite approximately 400 cases have been reported in the literature up to date. Diagnosis is mainly by conventional radiographic imaging such as plain X-ray, in which the typical melting wax dripping down a candle appearance is seen. The main treatment options are conservative management involving mainly analgesias, physiotherapy, braces, and possible nerve block and symphathectomies if indicated. The aim of this case report is to discuss the approach to a case of melorheostosis involving two long bones of the ipsilateral lower limb (polyostotic) that presented to us in our centre. Appropriate investigations and treatment modalities must be tailored according to the patient’s complaints in order to achieve satisfactory treatment outcomes. With adequate analgesia complimenting with appropriate physiotherapy and rehabilitation, our patient’s symptoms improved dramatically.


Introduction
Melorheostosis (synonyms: candle bone disease, melting wax syndrome, Leri disease) is an atypical, non-hereditary, sclerosing bone dysplasia that affects both cortical bone and adjacent soft tissue structures [1]. It mainly affects the long bone of the limbs, and involvement of more than one long bone is rare. First described in 1922 by Leri and Joanny, it is a benign bone disorder exhibiting patterns of hyperostosis characterised by linear distribution along the major axis of long bones, resembling a "dripping candle wax" appearance [2]. It has equal distribution among men and women [3], which usually presents after early childhood or adolescence [4]. Although benign in nature, it may be debilitating due to limb deformity, contracture, pain and stiffness. Management involves addressing symptoms presented by the patient and is often a multidisciplinary approach involving orthopaedics, physiotherapist, rehabilitation and physical medicine. Here, we described a polyostotic melorheostosis case of a 26-year-old gentleman with chronic pain and deformity of his left knee and leg. The patient agreed to participate in this case report by means of a free and informed consent form.

Case Report
This is a 26-year-old gentleman who presented to our out-patient clinic with a history of left knee deformity for four years associated with gradual pain, swelling and stiffness over left knee and leg progressively worsening for past six months. No recent trauma/fall to suggest a possible traumatic cause. Clinically the left knee has mild valgus deformity and limb length discrepancy of 5 cm longer compared to the contralateral lower limb, with multiple ill-defined nontender hard swelling over the anteromedial aspect of the left knee ( Figure 1). Further examination showed discrepancy of the left femur bone as the causation of the significant limb length difference ( Figure 2). Hyperpigmentation was also noted over the entire length of the left leg. Range of motion of the left knee was slightly limited due to pain. All blood parameters including serum calcium, alkaline phosphatase, C-reactive protein and erythrocyte sedimentation rate were within normal limits.       of chip fracture in knee joint [5].
In view of no evidence of fracture involving the knee joint, surgical intervention was not indicated in this case. As such, conservative management was chosen to address his complaints. The patient was started on Paracetamol 1000 mg QID, Tramadol 50 mg TDS and Celecoxib 200 mg PRN dosing for pain control, and further pain control modalities were not needed as his pain is well controlled with regular 2 monthly follow-ups and review. He was also referred to physiotherapy for the range of motion and stretching exercises of the left knee to alleviate his joint stiffness problem. Occupational therapist was also involved for a shoe lift over the right lower limb to optimize ambulation in view of limb length discrepancy of 5 cm. Subsequent follow-ups showed improvement of symptoms in terms of pain alleviation and improved mobility. Patient is able to return to work as well with no worsening of symptoms.

Discussion
Melorheostosis is a rare connective tissue disease characterized by sclerosing bone dysplasia. The incident is approximately 0.9 cases per million inhabitants [1] [6]. With about 400 cases of melorheostosis being reported in the literature up to date [7], the aetiology of the disease itself remains unknown. Several postulations such as genetic factors, metabolic predisposition or malformation of vessels have been made and proposed, but the exact cause is yet to be proven. Loss of function mutation in LEMD3 gene (12q12-12q14.3) [7] was initially proposed to be the cause of loss of functional protein in the inner nuclear membrane, which is crucial in bone morphogenic protein and tumor growth factor-beta signaling. However, further studies demonstrated that these mutations were not associated with the idiopathic melorheostosis. Hellemans et al. showed that LEMD3 gene mutation was not noted in isolated and sporadic cases of me- hyperpigmentation and restriction of knee movement [3].
Conventional radiographic imaging such as plain X-ray is used to diagnosed melorheostosis, in which the typical melting wax dripping down a candle appearance may be seen, showing extensive, dense, irregular eccentric hyperostosis of both periosteal and endosteal surfaces of cortex resulting in deformity over bones and narrowing of marrow space. Both patients reported by Bruno et al. and Rakesh et al. has similar pathognomonic findings of "dripping candle wax" appearance in plain X-ray suggesting the diagnosis of melorheostosis [3] [6]. Freyschmidt described three additional patterns of radiological patterns: 1) "osteoma-like" hyperostosis involving only the endosteal surface, which orientates in the long axis of involved bone. Lesions may be 5 cm or larger in diameter, may involve more than one bone and eccentrically located. If only one bone involved, circumscribed scleroderma or subcutaneous fibrosis above the lesion may be seen [7].
2) "osteopathia striata-like" hyperostosis, showing unilateral, long and dense hyperostosis striations near the inner surface of the cortex in two or more bones [7].
Computer tomography (CT) can be helpful in showing osseous sclerosis and reduction of medullary space at higher resolution than plain radiology but is often not needed in diagnosing melorheostosis [8].
In our case study, plain imaging shows "osteoma-like" hyperostosis involving the endosteal surface along the long axis of femur and tibia. Calcium deposits can be observed over medial aspect of the femur. Proceeded with CT, which reported as undulating cortical hyperostosis at medial aspect of the femur and proximal tibia plateau with hyperostosis within medulla of proximal tibia and linear hyperdensity is seen between vastus medialis and sartorius with irregular Different modalities of treatment had been used to treat the pain and deformities associated with melorheostosis. Conservative management includes use of oral medications such as bisphosphonates and NSAIDs, physiotherapy, manipulation, braces, serial casting, nerve block and symphathectomies [11]. Good response to treatment was seen in the patient presented by Bruno et al. with physical therapy program and Ibuprofen as analgesia [6]. Bisphosphonate can also be used to reduce inflammatory bone pain as it inhibits osteoclast-mediated bone resorption by direct and indirect actions on osteoblast and macrophages and bone vascularity [12]. In the case reported by Rakesh et al., the patient showed good response with Pamidronate 30 mg daily for 6 days as well as analgesia and physiotherapy [3]. Surgical options are offered after failed conservative therapy, limbs deformity or patient preferences, which includes tendon lengthening, limb lengthening, excision of fibrous tissue, fasciotomies, capsulotomies, osteotomies, excision of hyperostosis, arthrodesis, contralateral epiphysiodesis and amputation [4]. Freyschmidt noted success in relieving bone pain in 2 patient performing cortical fenestration of large hyperostosis, based on the idea that elevated intraosseous pressure leads to pain in melortheostosis patient.
However, it is important to note that surgical therapy often results in recurrence [13]. To sum up, treatment must be tailored according to the patient's presentation and preference in order to achieve good prognosis.

Conclusion
Melorheostosis is a rare benign sclerosing bone dysplasia with an indistinct etiology. It usually remains asymptomatic and undetected until early childhood or adolescence, where cortical hyperostosis and surrounding soft tissues involvement causes pain, joint stiffness, contractures, and limb deformity. Diagnosis is achieved by a combination of clinical assessment and radiological features of extensive, dense, irregular eccentric hyperostosis of the bone cortex which is classically described as "dripping candle wax" appearance. Blood investigations will be within normal limits, and histopathology results are non-specific and only indicated in the exclusion criterion against osteosarcoma. Treatment wise is mainly symptomatic, with care emphasizing on pain and functional limitations management. Thus, a multimodal approach is essential which commonly revolves around orthopedics, physical medicine, rehabilitation, and pain management.