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Gorham's disease

(Redirected from Gorham syndrome)

Gorham's disease (pronounced GOR-amz), also known as Gorham vanishing bone disease and phantom bone disease,[1] is a very rare skeletal condition of unknown cause. It is characterized by the uncontrolled proliferation of distended, thin-walled vascular or lymphatic channels within bone, which leads to resorption and replacement of bone with angiomas and/or fibrosis.[2][3]

Gorham's disease
Other namesAcro-osteolysis syndrome, Breschet-Gorham-Stout syndrome,[1] Cystic angiomatosis of bone,[1] Disappearing bone disease, Disseminated lymphangiomatosis, Disseminated osseous bone disease, Essential osteolysis, Gorham-Stout syndrome, Gorham's lymphangiomatosis, Hemangiomata with osteolysis,[1] Idiopathic massive osteolysis, Massive osteolysis,[1] Morbus-Gorham-Stout disease, Osteolysis and angiomatous nevi,[1] Skeletal lymphangiomatosis, Skeletal hemangiomatosis, Thoracic lymphangiomatosis.
Skull x-rays of Gorham's disease
Gorham's disease involving the left parietal bone: X-ray of the skull lateral view (A) showing a osteolytic area in left parietal region. CT scan bony window (B), MRI T1W Axial (C) and T2W Sagittal (D) revealing skull defect with normal brain parenchyma.
SpecialtyRheumatology Edit this on Wikidata

Signs and symptoms

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The symptoms of Gorham's disease vary depending on the bones involved. It may affect any part of the skeleton, but the most common sites of disease are the shoulder, skull, pelvic girdle, jaw, ribs, and spine.[4][5][6][7]

In some cases, no symptoms are seen until a fracture occurs either spontaneously or following minor trauma, such as a fall. An acute onset of localized pain and swelling may occur. More commonly, pain of no apparent cause increases in frequency and intensity over time and may eventually be accompanied by weakness and noticeable deformity of the area. The rate of progression is unpredictable, and the prognosis can be difficult. The disease may stabilize after a number of years, go into spontaneous remission, or in cases involving the chest and upper spine, prove fatal. Recurrence of the disease following remission can also occur. Involvement of the spine and skull base may cause a poor outcome from neurological complications. In many cases, the result of Gorham's disease is severe deformity and functional disability.[4][5][8]

Symptoms such as difficulty breathing and chest pain may be present if the disease is present in the ribs, scapula, or thoracic vertebrae. These may indicate that the disease has spread from the bone into the chest cavity. The breathing problems may be misdiagnosed as asthma, because the damage done to the lungs can cause the same types of changes to lung function testing as seen in asthma.[6] Extension of the lesions into the chest may lead to the development of chylous pleural and pericardial effusions. Chyle is rich in protein and white blood cells that are important in fighting infection. The loss of chyle into the chest can have serious consequences, including infection, malnutrition, and respiratory distress and failure. These complications or their symptoms, such as difficulty breathing, chest pain, poor growth or weight loss, and infection have sometimes been the first indications of the condition.[6][7][8]

Causes

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The specific cause of Gorham's disease remains unknown. Bone mass and strength are obtained and maintained through a lifelong process of bone destruction and replacement that occurs at the cellular level. Cells called osteoclasts secrete enzymes that dissolve old bone, allowing another type of cells called osteoblasts to form new bone. Except in growing bone, the rate of breakdown equals the rate of building, thereby maintaining bone mass. In Gorham's disease, that process is disrupted.[2][3][4][9][10][11]

Gorham and Stout found that vascular anomalies always occupied space that normally would be filled with new bone and speculated that the presence of angiomatosis may lead to chemical changes in the bone.[2][9] Gorham and others speculated that such a change in the bone chemistry might cause an imbalance in the rate of osteoclast to osteoblast activity such that more bone is dissolved than is replaced.[9] Beginning in the 1990s, elevated levels of a protein called interleukin-6 (IL-6) being detected in people with the disease were reported, leading some to suggest that increased levels of IL-6 and vascular endothelial growth factor (VEGF) may contribute to the chemical changes Gorham and others believed were the cause of this type of osteolysis.[4][12]

In 1999, Möller and colleagues[4] concluded, "The Gorham-Stout syndrome may be, essentially, a monocentric bone disease with a focally increased bone resorption due to an increased number of paracrine – or autocrine – stimulated hyperactive osteoclasts. The resorbed bone is replaced by a markedly vascularized fibrous tissue. The apparent contradiction concerning the presence or absence or the number of osteoclasts, may be explained by the different phases of the syndrome." They further stated that their histopathological study provided good evidence that osteolytic changes seen in Gorham's disease are the result of hyperactive osteoclastic bone. However, others have concluded that lymphangiomatosis and Gorham's disease should be considered as a spectrum of disease rather than separate diseases.[13]

While a consensus exists that Gorham's is caused by deranged osteoclastic activity,[2][4][9][11] no conclusive evidence has been found as to what causes this behavior to begin.

Diagnosis

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In 1983, Heffez and colleagues[10] published a case report in which they suggested eight criteria for a definitive diagnosis of Gorham's disease:[citation needed]

In the early stages of the disease, X-rays reveal changes resembling patchy osteoporosis. As the disease progresses, bone deformity occurs with further loss of bone mass, and in the tubular bones (the long bones of the arms and legs), a concentric shrinkage is often seen which has been described as having a "sucked candy" appearance. Once the cortex (the outer shell) of the bone has been disrupted, vascular channels may invade adjacent soft tissues and joints. Eventually, complete or near-complete resorption of the bone occurs and may extend to adjacent bones, though spontaneous arrest of bone loss has been reported on occasion. Throughout this process, as the bone is destroyed, it is replaced by angiomatous and/or fibrous tissue.[2][3][4][11][14]

Often, Gorham's disease is not recognized until a fracture occurs, with subsequent improper bone healing. The diagnosis is essentially one of exclusion and must be based on combined clinical, radiological, and histopathological findings.[4] X-rays, CT scans, MRIs, ultrasounds, and nuclear medicine (bone scans) are all important tools in the diagnostic workup and surgical planning, but none has the ability alone to produce a definitive diagnosis. Surgical biopsy with histological identification of the vascular or lymphatic proliferation within a generous section of the affected bone is an essential component in the diagnostic process.[4][5][8]

Recognition of the disease requires a high index of suspicion and an extensive workup. Because of its serious morbidity, Gorham's must always be considered in the differential diagnosis of osteolytic lesions.[3]

Management

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Treatment of Gorham's disease is for the most part palliative and limited to symptom management.[citation needed]

Sometimes, the bone destruction spontaneously ceases and no treatment is required, but when the disease is progressive, aggressive intervention may be necessary. Duffy and colleagues[6] reported that around 17% of people with Gorham's disease in the ribs, shoulder, or upper spine experience extension of the disease into the chest, leading to chylothorax with its serious consequences, and that the mortality rate in this group can reach as high as 64% without surgical intervention.

A search of the medical literature reveals multiple case reports of interventions with varying rates of success as follows:[citation needed]

Cardiothoracic (heart and lung):

Skeletal:

To date, no known interventions are consistently effective for Gorham's, and all reported interventions are considered experimental treatments, though many are routine for other conditions. Some people may require a combination of these approaches. Unfortunately, some people will not respond to any intervention.[citation needed]

Epidemiology

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Gorham's disease is extremely rare and may occur at any age, though it is most often recognized in children and young adults. It strikes males and females of all races and exhibits no inheritance pattern. The medical literature contains case reports from every continent. Because it is so rare, and commonly misdiagnosed, exactly how many people are affected by this disease is not known. The literature frequently cites that fewer than 200 cases have been reported, though a consensus is building that many more cases occur around the world than have been reported.[citation needed]

History

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The first known report of the condition came in 1838 in an article titled "A Boneless Arm" in what was then The Boston Medical and Surgical Journal (now The New England Journal of Medicine).[15] It is a brief report chronicling the case of Mr. Brown who had, in 1819 at age 18 years, broken his right upper arm in an accident. The person had two subsequent accidents, which fractured the arm twice more "before the curative process had been completed." At the time of the report in 1838, the person was reported as having remarkable use of the arm, in spite of the humerus bone having apparently disappeared – X-rays did not yet exist. Thirty-four years later, a follow-up report was published in the same journal, following Mr. Brown's death from pneumonia at the age of 70 years.[16] The person had requested the arm "be dissected and preserved for the benefit of medical science" and this report contains a detailed pathological description of the arm and shoulder. Abnormalities of the remaining bones of the arm and shoulder are noted and the authors report that the arteries, veins, and nerves appeared normal. No mention was made of lymphatic vessels. Though several reports of similar cases were published in the interim, more than 80 years passed before another significant report of the condition appeared in the medical literature.[citation needed]

Both born in 1885, Lemuel Whittington Gorham, MD, and Arthur Purdy Stout, MD, had long, distinguished careers in medicine and shared a lifelong interest in pathology.[17][18][19] Dr. Gorham practiced and taught medicine and oncology and from the mid-1950s through the early 1960s conducted and reported the classical clinicopathological investigations of pulmonary embolism. During this time, he also authored several case series on osteolysis of bone. Dr. Stout began his career as a surgeon and became a pioneer in tumor pathology, publishing Human Cancer in 1932. This work became the model for the Atlas of Tumor Pathology project, which Stout oversaw as chairman of the National Research Council in the 1950s. In his later years, Dr. Stout embarked on a systematic study of soft tissue tumors in children and was among the first to link cigarette smoking to lung cancer.[citation needed]

In 1954, Gorham and three others published a two case series, with a brief review of 16 similar cases from the medical literature, that advanced the hypothesis that angiomatosis was responsible for this unusual form of massive osteolysis.[9] That same year, Gorham and Stout presented to the American Association of Physicians their paper (in abstract form), "Massive Osteolysis (Acute Spontaneous Absorption of Bone, Phantom Bone, Disappearing Bone): Its Relation to Hemangiomatosis".[2] The paper was published in its entirety in October 1955 in The Journal of Bone and Joint Surgery, concluding that:

  1. There now exists the basis for a new syndrome which is supported by a remarkable similarity of clinical and [x-ray] findings in twenty-four cases, and by an equally convincing similarity of the histological picture in eight of these, which we have personally studied.
  2. However it is accomplished, the progressive osteolysis is always associated with an angiomatosis of blood and sometimes of lymphatic vessels, which seemingly are responsible for it.

The most typical presentation is that of osteolysis of a single bone or the bones connected by a shared joint, such as the shoulder. Although the disease can attack any bone, the shoulder is one of the most commonly involved areas, along with the skull and pelvic girdle. Spontaneous fractures are common and may be the first sign of the disease.[4] A hallmark of the disease is the lack of bone healing following fracture.[citation needed]

References

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  1. ^ a b c d e f "Gorham vanishing bone disease information". Disease Database. Retrieved 19 April 2012.
  2. ^ a b c d e f Gorham LW, Stout AP (October 1955). "Massive osteolysis (acute spontaneous absorption of bone, phantom bone, disappearing bone); its relation to hemangiomatosis". J Bone Joint Surg Am. 37-A (5): 985–1004. doi:10.2106/00004623-195537050-00008. PMID 13263344.
  3. ^ a b c d Ross JL, Schinella R, Shenkman L (August 1978). "Massive osteolysis. An unusual cause of bone destruction". Am J Med. 65 (2): 367–72. doi:10.1016/0002-9343(78)90834-3. PMID 686022.
  4. ^ a b c d e f g h i j Möller G, Priemel M, Amling M, Werner M, Kuhlmey AS, Delling G (May 1999). "The Gorham-Stout syndrome (Gorham's massive osteolysis). A report of six cases with histopathological findings". J Bone Joint Surg Br. 81 (3): 501–6. doi:10.1302/0301-620x.81b3.9468. PMID 10872375.
  5. ^ a b c Yalniz E, Alicioglu B, Benlier E, Yilmaz B, Altaner S (2008). "Gorham-Stout disease of the humerus". JBR-BTR. 91 (1): 14–7. PMID 18447124.
  6. ^ a b c d Duffy BM, Manon R, Patel RR, Welsh JS (May 2005). "A case of Gorham's disease with chylothorax treated curatively with radiation therapy". Clin Med Res. 3 (2): 83–6. doi:10.3121/cmr.3.2.83. PMC 1183437. PMID 16012125.
  7. ^ a b Lee WS, Kim SH, Kim I, Kim HK, Lee KS, Lee SY, Heo DS, Jang BS, Bang YJ, Kim NK (December 2002). "Chylothorax in Gorham's disease". J Korean Med Sci. 17 (6): 826–9. doi:10.3346/jkms.2002.17.6.826. PMC 3054959. PMID 12483010.
  8. ^ a b c Chattopadhyay P, Bandyopadhyay A, Das S, Kundu AJ (July 2009). "Gorham's disease with spontaneous recovery". Singapore Med J. 50 (7): e259–63. PMID 19644614.
  9. ^ a b c d e Gorham LW, Wright AW, Shultz HH, Maxon FC (November 1954). "Disappearing bones: a rare form of massive osteolysis; report of two cases, one with autopsy findings". Am J Med. 17 (5): 674–82. doi:10.1016/0002-9343(54)90027-3. PMID 13207148.
  10. ^ a b Heffez L, Doku HC, Carter BL, Feeney JE (April 1983). "Perspectives on massive osteolysis. Report of a case and review of the literature". Oral Surg Oral Med Oral Pathol. 55 (4): 331–43. doi:10.1016/0030-4220(83)90185-8. PMID 6574409.
  11. ^ a b c Johnson PM, McClure JG (July 1958). "Observations on massive osteolysis; a review of the literature and report of a case". Radiology. 71 (1): 28–42. doi:10.1148/71.1.28. PMID 13568048.
  12. ^ Dupond JL, Bermont L, Runge M, de Billy M (March 2010). "Plasma VEGF determination in disseminated lymphangiomatosis-Gorham-Stout syndrome: a marker of activity? A case report with a 5-year follow-up". Bone. 46 (3): 873–6. doi:10.1016/j.bone.2009.11.015. PMID 19931435.
  13. ^ Aviv RI, McHugh K, Hunt J (March 2001). "Angiomatosis of bone and soft tissue: a spectrum of disease from diffuse lymphangiomatosis to vanishing bone disease in young patients". Clin Radiol. 56 (3): 184–90. doi:10.1053/crad.2000.0606. PMID 11247693.
  14. ^ Torg JS, Steel HH (December 1969). "Sequential roentgenographic changes occurring in massive osteolysis". J Bone Joint Surg Am. 51 (8): 1649–55. doi:10.2106/00004623-196951080-00017. PMID 5357185.
  15. ^ Jackson, JBS (1838). "A boneless arm". Boston Med Surg J. 18: 368–9. doi:10.1056/NEJM1838071101823 (inactive 1 November 2024).{{cite journal}}: CS1 maint: DOI inactive as of November 2024 (link)
  16. ^ Jackson, JBS (1872). "Absorption of the humerus after fracture". Boston Med Surg J. 10: 245–7.
  17. ^ "Arthur Purdy Stout Society". Archived from the original on 28 May 2012. Retrieved 2 September 2011.
  18. ^ Azar HA (August 1998). "Arthur Purdy Stout (1885-1967), a pioneer of surgical pathology: a survey of his Notes on the Education of an "Oncological" Surgical Pathologist". Ann Diagn Pathol. 2 (4): 271–9. doi:10.1016/s1092-9134(98)80017-8. PMID 9845748.
  19. ^ Wright IS (1969). "Memorial. L. Whittington Gorham, M.D". Trans Am Clin Climatol Assoc. 80: xlvii–xlviii. PMC 2440984. PMID 4896317.

Further reading

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