Introduction
Melorheostosis was first described by Leri and Joanny in the year 1922 and is also called Leri’s disease, candle wax disease, flowing hyperostosis, etc. Melorheostosis is derived from the Greek word wherein Melos means limb, rheos means flow, and ostosis means bone formation. Melorheostosis is called so because its characteristic appearance on the radiographs (X-rays) resembles the dripping of the hardened wax on the side of a candle. Melorheostosis is a rare disease affecting approximately one in one million people. It can occur in males and females; and usually affects the diaphysis of the long bones of the lower limbs. The onset begins in childhood or adolescence, and no hereditary features are significant.
What Is Melorheostosis?
Melorheostosis is a rare disease of the bone characterized by the deposition of new bone tissues on the outer layers of the bone, leading to an excessively thick or widened bone. It usually affects the bones of the arm or legs on one side, and in some rare cases, it may also affect the pelvis, sternum (breastbone), ribs, etc. Melorheostosis is non-cancerous in nature and does not spread to other parts of the body. Melorheostosis occurs mainly due to somatic gene mutations in bone cells that occur during the lifetime of individuals and is not an inherited disorder and cannot be passed on to future generations.
What Are the Causes of Melorheostosis?
Mitogen-activated protein kinase1 (MAPKK1 or MAP2K1) gene located on chromosome 15 is responsible for providing instructions for the formation of MEK1 protein kinase. It is a part of the RAS-MAPK signaling pathway and is essential for the normal development and formation of bones. This pathway transmits chemical signals from outside to inside (nucleus) of the cell, which helps to control the growth, proliferation (division), differentiation (cell maturation), migration (movement) of the cells, and apoptosis (self-destruction of cells). The mutation in the enzyme MAPK1 gene is known to cause most cases of Melorheostosis. The MEK1 protein kinase is overactive due to mutation, which increases signaling in the bone tissues, resulting in abnormal bone growth.
What Are the Signs and Symptoms of Melorheostosis?
Some of the signs and symptoms of Melorheostosis include:
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Pain, stiffness, and limited motion in the affected joints.
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Limbs appear thick or enlarged with the overlying skin, which is red and shiny.
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Irregular bone growth.
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Unequal length of the limbs.
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Shortening of the tendons and ligaments.
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Ossification of the adjacent soft tissues.
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Abnormal development or absence of muscles.
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Malformation of joints which can be permanent deformity.
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In some rare cases, bone lesions may cause compression of the nerves.
What Are the Associated Conditions of Melorheostosis?
Some of the conditions associated with melorheostosis include:
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Buschke-Ollendorff Syndrome: It is a rare genetic disorder of the connective tissue, characterized by areas of increased bone density and skin growths called connective tissue nevi.
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Osteopoikilosis: It is a benign disorder characterized by multiple areas of increased bone density especially seen bilaterally at the ends of the long bones.
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Hemangioma: Hemangioma is abnormal growth of the small blood vessels, which mainly appears in early infancy.
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Osteopathia Striata: It is a benign disorder of the bone characterized by increased bone density which appears as longitudinal stripes.
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Desmoid Tumor: These tumors mostly develop in the connective tissues that form tendons and ligaments and may spread to the surrounding tissues.
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Linear Scleroderma: It initially appears during early childhood as a band-like thickening of the skin of arms and legs and is characterized by failure in the growth of one limb as rapidly as compared to the other.
How Is Melorheostosis Diagnosed?
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Melorheostosis can be diagnosed clinically by the signs of the condition, and a thorough physical examination reveals skin fibrosis (thickened skin) with indurated and erythematous (red) in nature. A limited range of motion associated with pain is observed.
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Melorheostosis can be radiologically diagnosed by X-rays and bone scans. X-rays reveal sclerotic bone (thickened bone pattern) lesions or dense hyperostosis along the cortex of the bone (thick undulating bone ridges) resembling a dripping candle wax. A bone scan is a diagnostic procedure during which small doses of radioactive material are injected into a vein and scanned to diagnose the abnormalities in the bone.
How Is Melorheostosis Managed?
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The treatment in melorheostosis is often symptomatic and individualized to each patient's need. Mild and moderate cases are managed by symptomatic treatment, whereas severe and complicated cases require surgical management. The priority includes controlling pain using non-steroidal anti-inflammatory drugs (NSAIDs) such as Ibuprofen, Acetaminophen, Naproxen, etc. Calcium channel blockers such as Nifedipine and bisphosphonates may be prescribed. Bisphosphonates get metabolized in the body and act on osteoclasts and macrophages by direct and indirect mechanisms leading to pain relief. Medications may be useful in the initial stages and may be less effective as the disease progresses or in severely affected cases.
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Physiotherapy is also an effective method often used to prevent the development of contractures (deformity and rigidity of joints due to the shortening of muscles or tendons).
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Surgical management to alleviate the effects of mechanical compression caused by melorheostosis is found to be fairly effective. It is more useful in cases where there is asymmetric growth of the bone. Surgery is performed only in cases where pain is due to nerve compression or irritation. It is found to be more effective in adults compared to children.
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The commonly used surgical procedure is osteotomy of the bone, where the affected abnormal growth of the osseous tissue is removed, and an external fixator is applied to promote bone healing. Rotation flaps may also help in improving the outcome of the surgical treatment; however, healing of the tissues is usually unpredictable and varies between individuals.
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The contractures around the involved joint can be relieved by the external fixators, which stretch the area; it is used as an initial option or after the contracture release surgery.
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The involvement of soft tissues makes surgical management less beneficial, as it needs to be treated along with the bone. If the deformity is of recent origin, surgery may be performed to release the surrounding soft tissues; however, the outcome is unpredictable as it may recur, leading to further treatment in the future. The only surgical option in severe and recurrent cases is amputation, which is performed only if appropriate or highly necessary.
Conclusion
Melorheostosis is a rare disorder characterized by the deposition of new bone tissues on the existing outer layers of the bone; it is associated with pain, limited movement, deformity of the joints, and shortening of the tendons and ligaments. The exact cause of this disorder is unknown; however, a somatic gene mutation is believed to be the reason. The initial stages of melorheostosis can be managed by medications and physiotherapy, but some severe cases may require surgical management to overcome the condition.
