Melorheostosis or Leri’s disease was first described in 1922 by Leri and Joanny [7]. It was previously hypothesized that melorheostosis was caused by somatic mutations in LEMD3 that is only present in the affected tissues [8]. However, recent discovery in molecular biology had identified the causes of melorheostosis. Kang et al. described somatic mosaicism for MAP2K1-activating mutations and SMAD3 mutations as the causes for the classical “dripping candle wax” appearance in melorheostosis [9, 10].
A wide spectrum of soft tissue involvement in melorheostosis was reported in previous literatures, including subcutaneous fibrosis, erythema, linear scleroderma-like patches, ectopic bone formation, hypertrichosis, fibromas, fibrolipomas, and vascular malformations (e.g., capillary hemangiomas, lymphangiectasia, or arterial aneurysms). Soft tissue fibrosis with ligament and tendon retraction had been reported, manifesting as equinovarus or valgus or varus foot deformities. Early presentation and multiple limb involvement may predict a poorer prognosis in terms of complications [11].
Patients with melorheostosis may remain asymptomatic until late adolescence or early adulthood, though changes usually manifest in childhood. Main presenting symptom is often pain worsened by movements of the affected limb [1]. The onset of symptoms in our case started in early childhood with an atypical presentation of episodic vaginal bleeding. Distribution of bone lesions can be monomelic or hemimelic, with the former being the most common observation. It can also be monostotic or polyostotic, and occasionally bilateral involvement [12]. In polyostotic involvement, bone lesions typically cross joint spaces with a sclerotomal distribution. Whyte reported that limb length discrepancy may develop due to asymmetric early epiphyseal fusion [13]. We did not observe limb length discrepancy in our patient. Our patient experienced intermittent bone pain, predominantly in the right thigh. The skeletal lesions were distributed in a hemimelic-polyostotic fashion.
The soft tissue involvement in our case was vascular malformations and joint contracture of the right knee due to fibrosis. The right internal iliac artery fusiform aneurysm and capillary hemangiomas extending from retroperitoneum to the right lower limb with uterine involvement, explaining the occurrence of episodic vaginal bleeding. The capillary hemangiomas were mistaken for café-au-lait spots, which lead to the initial diagnosis of McCune-Albright syndrome.
Melorheostosis is classically diagnosed using plain radiograph with the pathognomonic appearance of “dripping candle wax or flowing candle wax” appearance due to cortical hyperostosis. CT and MRI may help to identify and delineate the extent of soft tissue involvement. Bone scan may show increased radiotracer uptake in the osseous lesions, albeit plain radiograph is sufficient for the diagnosis of osseous involvement. Serum calcium, serum phosphorus, and alkaline phosphatase are often normal [11, 14]. In our case, the blood results were within normal limit. Histopathologically, findings are nonspecific and often show a mixture of mature and immature bone in a dense formation with increased trabecular bone [3].
Treatment is conservative for pain alleviation and physiotherapy although in severe cases, surgical intervention may be required, including tendon release, osteotomies, and even amputation. A recent study found that melorheostosis can be treated with intravenous zoledronic acid and that treatment can be monitored by using a specific bone resorption marker [15]. Sirolimus can be used to treat vascular malformation with proven safety and efficacy [6].
The differential diagnoses include osteopoikilosis, Buschke-Ollendorff syndrome, osteopathia striata, McCune-Albright syndrome, infantile cortical hyperostosis (Caffey disease), and desmoid tumors [16].
