Clinical History and Diagnosis of Melorheostosis - Case Study Example

Pathology Case Study Introduction Melorheostosis is a disease which affects the bones, cartilaginous tissues and is, in fact, a thickening of the cortical bone. The hyperostosis can affect the limbs, spinal column, thorax, and even skull. In short, any bony structure can be associated with melorheostosis. What causes it is unknown at the present time, however research is ongoing on this disease and several other diseases associated with it including osteopoikilosis, osteopathia striata, scleroderma and Buschke-Ollendorff syndrome (Hellemans 2004). Each of the aforementioned diseases have common traits and differences, however melorheostosis usually exists in consort with them, rather than standing on its own. Melorheostosis is exceedingly rare as a stand alone disease and therefore there can be confounding issues dealing with the other syndromes or co-morbidities in addition to the hyperostosis found in melorheostosis. As we shall see melorheostosis effects depend on the location of the build up of cortical bone tissues and are not limited in scope and effect, ranging from mild to severe. While many times, the effects can be mild and treatment consists of yearly monitoring of advancement of disease and over the counter NSAIDs, many times the disease is completely debilitating and even surgical interventions are useless as the disease reconstructs the hyperostosis in little time in the area which was reduced having been shaved off or excised. Clinical rehabilitation in many severe cases is more palliative than rehabilitative and merely serves to make the patient more comfortable until medical intervention via Bisphosphonates or other approved therapy eases the discomfort or surgery removes the offending hyperostotic buildup and halts painful nerve compression, arterial contraction and obstruction, or decreases the swelling of the area leading to joint and limb immobility. Clinical History and Diagnosis A 63 yr old man presents to his physician with recurrent weakness in both legs. He states that he was able to work as a cook until roughly 2 ½ years ago (MORTON, 1957). The patient had a history of admissions in Canada for pain in the knees, which were diagnosed as septic or rheumatoid arthritis, partly due to the elevated temperature of 102oF (38.9C) on both admissions. All labs came back negative and the patient was usually discharged about one week later, following standard protocols found in the 1950s of course. The patient appeared older than 63 upon physical examination, his blood pressure was elevated (150/100), there was evidence of Rombergism, pulse was normal, but chest and abdomen exam was normal. The extremities examinations revealed multiple anomalies including erythema of the toes on the right and left calf. Further, the upper extremities showed decreased ranges of motion, atrophy of the right forearm, and reflex decreases of the right triceps. The report also stated that there was abnormal deviations in the right hand and wrist, with right elbow extension possible only to 105° (Morton 1957). The patient was diagnosed with Melorheostosis, a painful and often debilitating disease of extra-cortical bone formation resembling candle-wax on x-ray, which is where a definitive diagnosis is usually made and confirmed. The attached document shows the x-ray photographs taken at the time of diagnosis. Anatomical Considerations and Pathology Melorheostosis is one of a group of sclerosing bone disorders. Although it is rare, afflicting less than 1:1,000,000 persons and the cause is unknown, enough has been written to give us a general overview of this fascinating disease process. The pathological mechanism produces thickening of the endosteum and periosteum (Hellemans, 2004). This pathology has a peak age of presentation is 5-20 years, however, minor cases evade detection unless radical presentations are made, (pain is a common presenting symptom), or deformity begins to alter functional aspects of daily living as seen in the case presented. The depositions of extra bone may be monostotic or polyostotic and may involve one entire limb (see graphic 1). Melorheostosis usually does not involve multiple limbs however it is twice as common in lower extremities than elsewhere (Hess 1950). Clinical findings include Pain, Joint stiffness and a deformity that may progress over time often misdiagnosed as a calcium deposit or some unexplained anomaly. Children may present with leg length discrepancies often causing walking or imbalance issues along with joint contractures from compression of the surrounding nerves and soft tissues. According to most statistics about 50% affected develop symptoms by age 20 (Azouze 2005) (Bullough 2009). The most recent research has pin-pointed the cause of melorheostosis as being a loss of function mutation in the LEMD3 gene (Chromosome 12q14) when diagnosed with concurrent Buschke–Ollendorff syndrome and osteopoikilosis (Zhang, 2009). Buschke-Ollendorf Syndrome is a rare connective tissue disease and is now considered a variation of an hamartoma (Zhang, 2009). In isolation, the studies seem to indicate that the LEMD3 gene association is not applicable to melorheostosis alone (Mumm, 2007) (Kim 2003). However, that does not mean the research is concluded and that the science regarding its origination is settled understanding that the germline mutations described in Mumms study (2007) dealing with confirmation of the BOS locus and its association with melorheostosis. The initial studies on the patient with sporadic melorheostosis will show lesions resembling osteoma(s) (King, 2005). It will have a classic candle-wax appearance, will often resemble myositis ossificans or osteopathia striata, with which it is also associated (Munk 2008) . In mixed diseases where BOS might be co-morbid, there are sclerotic lesions of cortical bones, usually in the diaphysis, that also resemble “candle-wax-dripping” along with cortical hyperostosis which has an undulating appearance (Mumm, 2007). This usually affects only one side of a bone (Mumm, 2007). There are associated soft tissue lesions that may show evidence of calcification (Azouze 2005)). If the bones affected area is close to another, the adjacent involved bone will have signs of the original bones pathology. The bony projections may grow to compress nerves and cause pain (McCarthy 1998). Typically, an Xray is sufficient to make an accurate diagnosis (Hellemann, 2004). CT scans and MRI are adjunctive and can lead to further diagnostic information concerning location, depth of lesions, and surgical options, however their main role is determining density of the lesion (Semble, 1986). Differential diagnostic criteria can include the following diseases, all of which have some connection to melorheostosis biochemically or clinically (King, 2005): Scleroderma (contractures are similar to melorheostosis, but osseous changes are lacking) Osteopoikilosis (an Autosomal dominant disease, usually epiphyseal and spotty upon XR examination, no diaphyseal demarcations and findings) Osteopathia striata (typically affects the metaphysis of long bones, thin vertical bands of dense bone) Arthrogryposis multiplex congenita (flexion contractures without bony changes) Albers-Shonberg disease (osteopetrosis) (Marbled bone appearance, autosomal recessive and dominant varieties) Complications of melorheostosis can include associated soft tissue lesions and cutaneous lesions which form near dense bodies of bony deposition (Bullough, 2009). As mentioned above, some patients may present and be misdiagnosed with vascular malformations, but many indeed have them in areas, again, close to the primary deposition zone likely due to the proliferation of growth factors (Zhang, 2009). Extra manifestations of melorheostosis can also include neurofibromatosis due to its manifestations in the soft tissues, tuberous sclerosis, hemangiomas of varying depth and size, muscle contractures from nerve impingements and destruction, and scoliosis in patients with spinal manifestations and complications (King 2005). Treatments and Prognostic Factors Most patients presenting with melorheostosis, after appropriate workup and diagnostics are put on a standard course of analgesics (McCarthy 1998). When presenting in childhood appropriate action should be taken to lower any increase in temperature caused by an increase in cytokine activity mimicking and infection (McCarthy 1998). The majority of cases are treated with bisphosphonates and analgesics (Orthopaedia 2011). Bisphosphonates, especially show promise as a treatment to reduce inflammation and reduce pain of the affected limb (Munk, 2007).AS melorheostosis is progressive and has no known cure or treatment with more than palliative associated mechanisms, ultimately surgically correcting the area, via shaving down the extra growth on the bone, or unfortunately, amputation of the limb or limb-sparing surgery of the external part must be considered (King 2005). In many patients seen on the worldwide Melorheostosis case historys page, many patients describe treatments as far off label as drugs for Parkinsons and no medications at all (Morton 1957). The pain, as patients describe it can be very debilitating and lead to life long disability (Melorheostosis Video 2008). Treatments used can further prove ineffective, as many of the case studies listed in the Melorheostosis global web site identify (2011). Many patients can be ramped up to opioid analgesics and feel absolutely no pain relief whatsoever (Bullough, 2009). Typical presentation evaluation may include no further analgesia for pain relief to determining surgical options (Melo, 2011). Many patients will experience no relief whatsoever and will undergo sympathectomy to eliminate the nerve pain generated by the tumor (Hess and Street, 1950). Ultimately, many are forced to opt for complete amputation and removal of the affected sites. Complete surgical options include the following: Capsulotomy Contracture Release Fasciotomy Nerve Decompression Tendon Lengthening Osteotomy Joint Fusion Growth Plate arrest Distraction Limb Lengthening (Ilizarov Technique) It should be noted, that some patients and procedures have as high as a 90% recurrence rate (Melo 2011) with an abnormally high failure rate in certain locations where the joint is also affected (King, 2005) Imaging Modalities in Melorheostosis In bony diseases, typical gamma XR is sufficient to make an accurate diagnostic finding but other modalities are actively used to get a complete finding. Radionuclide Imaging consists of Technitium-99 scintography which will show a marked increase in the focal uptake of the tracer in each area which is abnormal radiographically (Munk, 2007). CT scans will demonstrate cortical and trabecular thickening as hyperostosis has higher attenuation when scanned (Munk, 2007). CT has the advantage of aiding in soft tissue mass findings and enabling narrow space intrusion secondary to endosteal participation (Bullough, 2009). In MRI scans, cortical hyperostosis is evident as a low signal intensity on all sequences, however in the patient of record, no MRI data is available as the patient time period was prior to the development of the MRI technology. MRI is advantageous in that it can demonstrate muscle tissue atrophy and anomalous developments such as fatty infiltration, however these are secondary developments and in no way can give data which can alter the treatment of an already difficult to treat disease (King, 2005). MRI can aid in procedures the patient would opt for which affect the soft tissues such as tendon lengthening, contracture release, and even nerve decompression (Munk, 2007). Further, studies show that the zones of bone affected are usually unilateral, as mentioned before, and have undulating well defined zones where the bone forms and does not form random sharp spicules (Motimayaa, 2006). MRI findings are the best modality to determine the encumbering effects of melorheostosis on the spinal column and canal (McCarthy 1998). We can see the growth of hyperostotic bone on the spine and cord and determine the precise area of impingements to determine future surgical interventions. Additionally, the use of MRI assists in those areas of hyperostotic growth where the hyperlucency is determined but additional study is needed to a more specific level of diagnostic information (Van Hula 2001). While Xray scanning is the definitive initial assessment that should be performed and can yield a diagnostic finding that leads to identification of the disease, it doesnt give detail as to depth and soft tissue involvement that both CT scanning can provide, therefore those studies should not be ignored. In standard XR findings, we can see the areas of increased calcification and deposition as hyperlucent areas, as shown in figure 2 on the left. The bone scans are uniform in the finding of increased signal intensity in various areas, with differences in the location of the density increases. Bone dyscrasias, while poorly studied, are known now to further molecular study due to genetic testing and analytical breakthroughs (Hula, 2001). Scanning with MRI and CT mechanisms will serve to highlight and confirm known statistical patterns of patient outcomes, as surgical intervention is usually the final result in dramatic cases (Bullough 2009). The patient in question would likely have only added a CT scan to his list of diagnostic procedures and the case study itself reveals little about his prognosis and treatment during this early stage of Melorheostosis findings worldwide. Further, the findings would not have likely altered the outcome, even if available (Younge 1979). The patient was already suffering from the disease enough that he was not able to continue in his profession and employment. Of peculiar significance is the finding studies using Technetium-99m pyrophosphate bone images. These images in the CT studies proved helpful when attempting to diagnose superimposed osseous disease with the 3 dyscrasia variants of osteopoikilosis, osteopathia striata, or melorheostosis (Whyte 1978). Conclusion Melorheostosis is a debilitating disease similar to osteopoikilosis and osteopathia striata that affects children and adults and has a peak incidence of 20 years of age regardless of sex. The patient in the case was typical of many current melorheostosis patients, even if we do not fully know the outcome of his individual case. It has gained more press of late, even an article by Janet Kornblum in USA Today (October 14, 2008) highlighted a case of a famous actors child who has been stricken with the disease since its discovery at age 6. Current research focuses on genetic causes and the use of Bisphosphonates along with current modalities of NSAIDs and surgical correction, reduction of area dyscrasia overgrowth, and amputation in seriously debilitating cases. The imaging modalities remain constant in the last 20 yrs with XR scans being the first finding modality leading to diagnosis, but with MRI and CT uses assisting in determining more precise location and tissue involvement in cases where patient disease progression is debilitating. Resources Azouz, M.E. Orphanet, "Orphanet Melorheostosis." Last modified February 1, 2005. Accessed September 22, 2011. http://www.orpha.net/consor/cgi-bin/OC_Exp.php?Lng=GB&Expert=2485. Bullough, Peter G. MB ChB, 2009 Atlas of Orthopaedic Pathology, 1st Ed. University Park Press Denhard, Andy. "Matt’s melorheostosis lie upsets advocates, CBS okay airing things “we do not condone”." Reality Blurred, July 23, 2010. http://www.realityblurred.com/realitytv/archives/big_brother_12/2010_Jul_23_matt_melorheostosis_lie (accessed September 22, 2011). Hellemans J, Preobrazhenska O, Willaert A, Debeer P, Verdonk PC, Costa T, et al. 2004. Loss-of-function mutations in LEMD3 result in osteopoikilosis, Buschke-Ollendorff syndrome and melorheostosis. Nat Genet. Nov;36(11):1213-8 Hess, WALLACE E. . 1950 "MELORHEOSTOSIS RELIEF OF PAIN BY SYMPATHECTOMY."Journal Bone Joint Surg Am. 32. no. 2 (Nov): 422-427. Kim JE, Kim EH, Han EH, Park RW, Park IH, Jun SH, Kim JC, Young MF, Kim IS, 2000. "A TGF-beta-inducible cell adhesion molecule, betaig-h3, is downregulated in melorheostosis and involved in osteogenesis.” J Cell Biochem 77 (2): 169-78 King, Jeffrey. Michigan State University, "Overview of Orthopedic Aspects of Melorheostosis." PDF (Accessed September 22, 2011). http://www.melorheostosis.com/king%202005.pdf. King, Jeffrey. Melorheostosis, "Surgical Management of Melorheostosis: General Information and Considerations." Last modified unknown. (Accessed September 22, 2011). http://www.melorheostosis.com/default_files/Page1654.htm. Kornblum, Janet. USA Today, "Melorheostosis: A rare and painful bone disease." Last modified October 14, 2008. (Accessed September 22, 2011). http://www.usatoday.com/news/health/2008-10-14-melorheostosis_N.htm McCarthy, Edward & Frassica, Frank. Pathology of Bone and Joint Disorders. Philadelphia: W.B. Saunders company, 1998. Morton, K.S. "MELORHEOSTOSIS: A CASE REPORT* .”Canadian Med Assoc J.. 77. no. 6 (1957): 590-592. Motimayaa, A.M. 2006 "Melorheostosis Involving the Cervical and Upper Thoracic Spine: Radiographic, CT, and MR Imaging Findings." American Journal of Neuroradiology. 27. : 1198-1200. Mumm S, Wenkert D, Zhang X,McAlister WH,Mier RJ,Whyte MP. 2007 Deactivating germline mutations in LEMD3 cause osteopoikilosis and Buschke-Ollendorff syndrome, but not sporadic melorheostosis. J Bone Miner Res. Feb;22(2):243-50. Munk, Peter. 2008 Teaching Atlas of Musculoskeletal Imaging. New York: Thieme Medical. No Author "Melorheostosis,"Promotional Video, George Harper, 2008, Web, http://www.melorheostosis.com/melorheostosis_medium.mov. Semble EL, Poehling GG, Prough DS, White RE, Pisko EJ. 1986. Successful symptomatic treatment of melorheostosis with nifedipine. Clin Exp Rheumatol. Jul-Sep;4(3):277-80. Van Hula, Wim. 2001:”Molecular and radiological diagnosis of sclerosing bone dysplasias ."European Journal of Radiology. Vol 40. no. 3 : 198-207. Whyte, Michael P. 1978. “99mTc-Pyrophosphate Bone Imaging in Osteopoikilosis, Osteopathia Striata, and Melorheostosis." Radiology . 127. 439-443. YOUNGE, Derek, DRUMMOND, Denis, HERRING, John, CRUESS, Richard .1979. Melorheostosis in children: clinical features and natural history, Journal of Bone and Joint Syn., VOL. 61-B, No. 4. (Accessed September 22, 2011) http://web.jbjs.org.uk/cgi/reprint/61-B/4/415.pdf Zhang, YL. 2009. "Novel and recurrent germline LEMD3 mutations causing Buschke–Ollendorff syndrome and osteopoikilosis but not isolated melorheostosis."Clinical Genetics. 75. no. 6 (556–561). Read More