Localized Disorders of Skin and Soft Tissue
Haemish Crawford
This chapter focuses on conditions that have orthopaedic manifestations localized to a particular area or region. It is difficult to classify these conditions under any particular systemic diagnosis or define them as a discrete bone or soft-tissue disease. Some of these conditions are complex and involve multiple organ systems; however, this chapter concentrates primarily on the orthopaedic manifestations and just gives a brief overview on the general condition.
CONGENITAL AND DEVELOPMENTAL DISORDERS
Hemangiomas and Vascular Malformations.
Vascular abnormalities are commonly seen in patients and can range in severity from a simple cutaneous hemangioma to a complex arteriovenous malformation in the central nervous system. From an orthopaedic perspective, it is important to recognize which vascular abnormalities give rise to musculoskeletal problems that may require orthopaedic intervention.
The nomenclature for these conditions is historically complex with eponyms such as port wine stains, Sturge-Weber syndrome, Klippel-Trenaunay syndrome, and Proteus syndrome. This has contributed to the confusion in understanding the natural history of these lesions and difficulty in collecting data and developing appropriate treatment strategies. Mulliken and Glowacki (1) simplified our understanding of the underlying pathology and made a distinction between hemangiomas and vascular malformations that forms the basis of their clinical distinction today (1). They based their classification on the clinical presentation and behavior of the lesions and their histology and biochemistry. Hemangiomas exhibit cellular proliferation and have rapid growth in infancy and then subsequent regression. Vascular malformations on the other hand are composed of malformed vessels that do not exhibit endothelial cell proliferation. They are present at birth, and their growth parallels that of the child. They never regress. Vascular lesions can be arterial, venous, capillary, and lymphatic or a combination of any of these.
This classification was modified slightly in 1996 by the International Society for the Study of Vascular Anomalies (ISSVA) to vascular tumors and vascular malformations (2, 3 and 4). This allowed the less common tumors of tufted angioma (5) and kaposiform hemangioendothelioma (6) to be included as vascular tumors.
For simplicity, this chapter uses the classification of Mulliken and Glowacki (1).
Hemangiomas and vascular malformations can present in many different ways in infants and young children. The most common presenting complaint is the disfiguration; however, some patients complain of pain, swelling, leg length discrepancy, and occasionally bleeding. The investigations often need to include detailed imaging including magnetic resonance imaging (MRI) and angiography. The nonoperative management is challenging, and the decision for surgical intervention fraught with technical challenges, complications, and variable outcomes. In this respect, it is useful to have a multidisciplinary approach to these patients including ORL, general, orthopaedic, plastic, and vascular surgeons.
Hemangiomas.
A hemangioma is a congenital malformation of the local blood vessels. They may be cutaneous, subcutaneous, intramuscular, or visceral. There are many different types of vascular tumors, of which infantile hemangiomas are the most common. Others are rare and include tufted angioma, kaposiform hemangioendothelioma, hemangiopericytoma, and angiosarcoma. Infantile hemangiomas are usually single and occur most commonly in the head and neck region (60%) followed by the trunk and extremities. Internal (cavernous) hemangiomas are more common if there are five or more cutaneous hemangiomas present.
Cutaneous hemangiomas are common. They are present in 1.1% to 2.6% of term neonates and up to 12% of children at 1 year of age (7, 8). They can occur in all races but are more common in white infants. The incidence is three times higher in girls than boys (9). These collection of capillary type vessels appear in the neonatal period often as a small cutaneous
mark and will grow disproportionately fast for a few months. The hemangioma is usually a vivid red color with an irregular outline. The lesion does not blanche with direct pressure with the examiner’s finger. These lesions were historically referred to as strawberry naevi or capillary hemangioma. The hemangioma has a natural history that can be divided into three phases: proliferative, involuting, and involuted (10). The proliferative phase is characterized by the rapid dividing of the epithelial cells, whereas the involution phase is slower with far less endothelial activity. There is complete regression of the lesions in 70% of the children by 7 years of age (1). Only 50% of children are left with normal skin; the others may have some residual scaring, telangiectasis, or fibrofatty tissue.
mark and will grow disproportionately fast for a few months. The hemangioma is usually a vivid red color with an irregular outline. The lesion does not blanche with direct pressure with the examiner’s finger. These lesions were historically referred to as strawberry naevi or capillary hemangioma. The hemangioma has a natural history that can be divided into three phases: proliferative, involuting, and involuted (10). The proliferative phase is characterized by the rapid dividing of the epithelial cells, whereas the involution phase is slower with far less endothelial activity. There is complete regression of the lesions in 70% of the children by 7 years of age (1). Only 50% of children are left with normal skin; the others may have some residual scaring, telangiectasis, or fibrofatty tissue.
Deep hemangiomas usually arise in the dermis or muscle and are not always very visible on the skin. Often the only indication of the underlying hemangioma is a slight “bump” in the skin or bluish discoloration. They used to be called cavernous hemangiomas due to their larger size; however, this nomenclature is no longer used. Deep hemangiomas usually involute like their superficial counterparts. They can be confused with a venous malformation (VM); however, on palpation, the hemangioma is fibrofatty rather than soft and compressible, which is characteristic of a VM. Ultrasound scanning or MRI can easily differentiate between the two if any clinical confusion exists.
Although most hemangiomas resolve, up to 20% can cause significant complications. These mainly occur around the head and neck where there may be direct compression on the eyes, significant vessels, or the airway. High-output cardiac failure can occur if the hemangioma is extremely large. When the gastrointestinal tract is involved, internal bleeding can be significant.
TABLE 9-1 Associations of Vascular Malformations in Children | ||||||||||||||||||||||||||||||||||||||||||
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These hemangiomas rarely cause orthopaedic complications; however, knowledge of them is useful as a parent will often ask about these lesions during a consultation. One can usually reassure the family that they will spontaneously resolve; however, if they do not behave in a predictable way, referral to the multidisciplinary vascular clinic is advisable. Occasionally, intralesional or systemic corticosteroids and interferon-a are used for large recalcitrant lesions (8).
Vascular Malformations.
Vascular malformations grow “pari passu” with the child, have normal endothelial mitotic activity in the vessel walls, and never regress (1). They are subclassified further according to their flow characteristics.
Slow flow
Capillary malformations (CMs): port wine stains, telangiectasis
Venous malformations (VM)
Lymphatic malformations (LMs): lymphangiomas and cystic hygromas
High flow
Arterial (AMs) and arterial venous malformations (AVMs)
There are also combined and more complex forms of vascular malformations, for example, Klippel-Trenaunay syndrome, which is a slow-flow lesion that has a combination of CM, VM, and LM. A summary of some more common vascular malformations and their associations is outlined in Table 9-1.
Vascular malformations are more relevant to the orthopaedic surgeon than hemangiomas as they often result in altered limb growth. This can be hypertrophy or atrophy.
Vascular malformations are more relevant to the orthopaedic surgeon than hemangiomas as they often result in altered limb growth. This can be hypertrophy or atrophy.
Slow-Flow Vascular Malformations
Diffuse CM involving an entire limb with congenital hypertrophy of the limb (3). In this condition, the child is born with an enlarged red limb with the adjacent trunk sometimes involved. There is a sharp midline demarcation. The entire limb is enlarged including the soft tissues and bone. There is no progression in the overgrowth after birth. Doppler ultrasound can be used to exclude any AV malformations. No orthopaedic intervention is required.
Diffuse VM of an extremity. The limb is usually blue rather than red (capillary) due to the dermal invasion of the large distorted veins. The venous channels also invade the muscles and the joints, which results in amyotrophy and swelling of the limb. MRI is the best investigation as the T2-weighted images clearly show the soft-tissue and joint involvement (Fig. 9-1). The limb may have slight undergrowth that is usually <2 cm so does not require orthopaedic intervention. Overgrowth is less common and rarely exceeds 2 cm (3). Patients can also get a localized intravascular coagulopathy (LIC) with elevated d-dimer levels and decreased fibrinogen (11). The mainstay of treatment for LIC is low-molecular-weight heparin.
 FIGURE 9-1. A-C: Ten-year-old girl with diffuse venous malformation of the right distal thigh with knee joint involvement. The leg is 1.5 cm shorter than the left. |
The treatment for these slow-flow vascular lesions is usually nonoperative with the use of elastic garments. As well as decreasing the pain and disfiguration, these garments can help prevent LIC. Surgical excision or sclerotherapy can be used; however, both these techniques can convert LIC to a disseminated intravascular coagulation. Laser treatment is useful only for the diffuse CMs (port wine stains) and not the deeper VMs (12).
Fast-Flow Arteriovenous Malformations.
The majority of fast-flow malformations occur in the head and neck region followed by the extremities and then the trunk. They occur equally in males and females. Occasionally, the malformations can be picked up with prenatal ultrasound. The lesions are often difficult to diagnose as there may initially only be subtle discoloration in the skin. Closer examination may reveal increased warmth, a palpable thrill or pulsation, an enlarged extremity, and dilated veins. Enjolras et al. reviewed 200 cases of AVM over a 4-year period and found 40% are present at birth, 35% are detectable during puberty, and 45% are evident in adulthood (13). As the patient grows, changes in the limb can become more pronounced. There is an increase in girth and sometimes length, lymphedema, and skin alteration that includes further discoloration, ulcers, and fibrosis. The bone can also be affected. Bone hypertrophy can occur due to the increased blood supply to the epiphysis. Enjolras also suggests that “hypoxia of the growth cartilage centres” may occur due to the phenomenon known as vascular steal caused by the AVMs (3). Lytic lesions can also occur in the bone and cause pathologic fractures.
Parkes-Weber syndrome is a capillary AVM or a capillary-lymphatic AVM where there is hypertrophy of the limb with increased leg length.
The best investigation for a suspected high-flow malformation is Doppler ultrasound. Arteriography has been used historically; however, this has largely been superseded by MR angiography. Plain radiographs are useful for bone morphology, and serial computed tomography (CT) scanograms are indicated if a leg length discrepancy develops.
The treatment of these malformations is difficult. Initially, elastic stockings are the mainstay as they will help decrease the swelling, minimize vascular steal, and prevent trauma to the skin. Education of foot hygiene and participation in certain sports is also important in preventative care of the limb. Arterial embolization is not a preventative option as there are usually multiple AVMs and it is not possible to embolize them all. It can be used for isolated lesions where there has been a complication, for example, excessive bleeding or a particularly unsightly lesion. There is no role for laser therapy in high-flow AVMs.
The leg length discrepancy is difficult to manage. Not only is the leg length discrepancy hard to predict but the surgery can be fraught with complications. Enjolras et al. reviewed 17 children with lower extremity Parkes-Weber syndrome. Six of the patients were under 8 years of age and had an average leg length discrepancy of 2.75 cm. The other 11 children were over 10 years of age and had an average discrepancy of 3.26 cm. Nine patients underwent epiphysiodesis and seven children had severe worsening of their vascular and skin lesions with complications, one eventually requiring amputation (3).
A cautious approach needs to be taken to treating the leg length discrepancies in these fast-flow vascular malformations. The use of orthotics should be exhausted before considering surgical intervention. If epiphysiodesis is indicated, it may be advisable to perform a percutaneous drilling rather than an open staple or eight-plate surgery to minimize the surgical trauma to the vascular malformations. Consideration should also be given to shortening or lengthening the contralateral “normal” leg to equalize the leg lengths and thereby avoid the potential complications in the hypertrophied limb.
 FIGURE 9-2. A: A 15-year-old boy with Klippel-Trenaunay syndrome of his right lower extremities with typical findings of hypertrophy, varicosities, and superficial complex, combined vascular malformations. B,C: He had aching discomfort from the varicosities, intermittent pain from thrombophlebitis, and drainage from the superficial vascular malformations. |
Complex/Combined Vascular Malformations
Klippel-Trenaunay Syndrome.
In 1900, two French physicians Maurice Klippel and Paul Trenaunay described a syndrome that had three components: (a) cutaneous capillary-venous malformations, (b) varicose veins, and (c) hypertrophy of the bones and soft tissues of the limb (14). Much confusion has arisen subsequently with the nomenclature as different physicians have described similar conditions with variations in this triad. Frederick Parkes-Weber described a clinical syndrome in 1918 very similar to Klippel-Trenaunay except that in addition to the slow-flow vascular malformations there were AVMs as well (15). Naturally, there is an overlap between the two syndromes; however, when the AVMs dominate the clinical picture, the term Parkes-Weber syndrome should be used (Fig. 9-2 and Table 9-2). The AVMs in Klippel-Trenaunay are always trivial and of no clinical importance (10).
The cause of Klippel-Trenaunay is largely unknown. There are often other congenital abnormalities associated with the syndrome that make the diagnosis ambiguous at times. (16)
Lindenauer is the only person to document two siblings as having the syndrome (16). Some authors have suggested the cause of Klippel-Trenaunay syndrome is a mutation in the genes that are involved in angiogenesis and vasculogenesis during embryonic development (17, 18, 19 and 20). Tian et al. (21) identified a mutant angiogenic factor (Glu133Lys in VG5Q) in patients with CMs; however, Boon et al. could not find any of these mutations in bona fide Klippel-Trenaunay patients (10). Translocations (5:11, 8:14) have also been reported as being associated with this syndrome (22). Baskerfield et al. studied 33 patients with Klippel-Trenaunay syndrome and, based on extensive vascular studies, concluded that the syndrome was caused by a mesodermal defect. They felt the persisting vascular malformations were fetal microvascular AV communications (17, 18). Unlike hemihypertrophy, children with Klippel-Trenaunay or Parkes-Weber syndrome do not have an increased incidence of Wilms tumor and therefore do not require abdominal ultrasound screening for this (23, 24).
Lindenauer is the only person to document two siblings as having the syndrome (16). Some authors have suggested the cause of Klippel-Trenaunay syndrome is a mutation in the genes that are involved in angiogenesis and vasculogenesis during embryonic development (17, 18, 19 and 20). Tian et al. (21) identified a mutant angiogenic factor (Glu133Lys in VG5Q) in patients with CMs; however, Boon et al. could not find any of these mutations in bona fide Klippel-Trenaunay patients (10). Translocations (5:11, 8:14) have also been reported as being associated with this syndrome (22). Baskerfield et al. studied 33 patients with Klippel-Trenaunay syndrome and, based on extensive vascular studies, concluded that the syndrome was caused by a mesodermal defect. They felt the persisting vascular malformations were fetal microvascular AV communications (17, 18). Unlike hemihypertrophy, children with Klippel-Trenaunay or Parkes-Weber syndrome do not have an increased incidence of Wilms tumor and therefore do not require abdominal ultrasound screening for this (23, 24).
TABLE 9-2 Differences Between Klippel-Trenaunay and Parkes-Weber Syndrome | ||||||||||||
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Pathophysiology.
The deep venous system is greatly affected and may even be absent. Rarely a fibrous band can also obstruct the veins (25). There is also an anomalous lateral venous system that can extend from the foot up to the right flank area. Baskerfield et al. found this to be present in 64% of the 33 patients they reviewed. The result of these anomalies in the deep venous system is that blood returns to the heart via the tortuous superficial venous system (17, 18). Another series has found this system to be present in 72% of the patients (26). The venous systems are filled with multiple emboli and the venous stasis contributes to the symptoms the patients complain of.
Surgical specimens in 29 patients were examined by Lie, and he reported the most consistent finding was fibromuscular dysplasia in the venous system (20). The layer in the vein wall that was most affected was the media and it was hypertrophied, irregular, or absent. In the most deficient areas, an aneurysm was often present. He also found that when the deep venous system was sometimes present, there were anomalous valves and that AVMs were uncommon. Other tissues were often hypertrophied; however, the lymphatics were hypoplastic.
Clinical Features.
The condition is present from birth; however, the nevus, varicosities, and limb hypertrophy become more evident as the child grows. The lower limb is affected at least 10 times more often than the upper extremities. The affected limb is longer than normal in 90% of the patients (19, 20, 27). The limb girdle and trunk can also be affected and when they are the underlying viscera may also have vascular malformations. The head and neck are rarely involved.
Nevus.
This is almost always present at birth but can be difficult to see. Jacob et al. reviewed 252 patients and found that the malformation was present at birth in 98% (26). It is due to the capillary-venous malformation and results in a pink or port wine discoloration. The nevus usually follows a dermatomal distribution, does not cross the midline, and can be on the affected or contralateral limb (28). The size and color of the nevus can change with growth of the child.
Varicosities.
Varicose veins are inevitably present at birth and increase in size as the child grows. The extent of the varicosities determines the course of the syndrome. A consistent finding is an anomalous lateral varicosity that extends from the ankle to the flank and is not connected to the hypoplastic deep system. Jacob et al. found this embryonic lateral marginal vein to be present in 72% of the patients in their series (26). In the older child, the resulting stasis can lead to secondary skin changes, ulceration, and thrombophlebitis. Thrombi are usually present in both the deep and superficial venous systems; however, pulmonary emboli rarely occur spontaneously.
When the deep varicosities involve the pelvic organs, erosions can occur giving rise to hematuria, rectal, and vaginal bleeding (29, 30). Rarely, the central nervous system can be involved (31, 32). Scoliosis can occur in approximately 5% of adolescents with Klippel-Trenaunay syndrome; however, it is usually mild and does not require surgical correction (33). When the upper limb is involved, carpal tunnel syndrome has been reported (34). In large malformations, the blood shunting can be so large that the child can suffer from high-output cardiac failure. In such cases, especially in neonates, limb amputation may be life saving (35, 36).
Limb Hypertrophy.
Limb overgrowth occurs in both the soft tissues and bone. The increased growth can occur at a distance from the obvious varicosities making the underlying mechanism for this hypertrophy difficult to understand. Sometimes a single digit is involved, part of a limb or half an entire body. Unlike Parkes-Weber syndrome where the degree of AVMs usually determines eventual limb size, the predictability of the hypertrophy in Klippel-Trenaunay is not so straightforward. Not only is there an increase in girth but there is also an increase in length (Fig. 9-2) The girth is very difficult to address surgically; however, surgical correction of the leg length discrepancy is an option especially when a large discrepancy exists. A severe leg length discrepancy is uncommon, and Berry et al. found that only 10% of children will have a discrepancy of >3 cm (19). McCullough and Kenwight even described 2 patients in whom the discrepancy in their leg lengths decreased with growth (37). This shows the importance of following these patients regularly and measuring their leg lengths clinically and radiologically to
“best guess” the timing of surgical intervention for this variable pattern of discrepancy (38). The exact aetiology of the limb length overgrowth is not known but was originally thought to be caused by venous hypertension (39). A more recent theory suggests there may be some genetic cause for both the vascular abnormalities and alterations in limb length and girth.
“best guess” the timing of surgical intervention for this variable pattern of discrepancy (38). The exact aetiology of the limb length overgrowth is not known but was originally thought to be caused by venous hypertension (39). A more recent theory suggests there may be some genetic cause for both the vascular abnormalities and alterations in limb length and girth.
Associated Conditions.
Approximately 25% of patients with Klippel-Trenaunay syndrome have anomalies of the fingers and toes (27). These include syndactyly, polydactyly, and clinodactyly. Jacob et al. found that 10 of the 252 patients they reviewed had developmental dysplasia of the hip (26). Other reports have revealed radial head dislocations, melorheostasis, tuberous sclerosis, metatarsus adductus, congenital clubfoot, scoliosis, and Sturge-Weber syndrome (40).
Diagnosis.
The diagnosis can usually be made at birth by the clinical appearance of the child. Confirmation of this diagnosis then needs to be made with noninvasive imaging. This is best performed when the child has turned 4 years of age to minimize ambiguous results from the ultrasound due to movement artifact and the small size of the vessels. Doppler ultrasound is very useful especially for differentiating between Klippel-Trenaunay and Parkes-Weber syndrome on the basis of AVMs. MRI, MR angiography, and MR venography are additional imaging studies that can help in the diagnosis and define the extent of the vessel malformation (19, 31, 41, 42 and 43). More recently, Bastarrika et al. have prospectively imaged 16 patients with Klippel-Trenaunay syndrome using multidetector computed tomography (MDCT) and fast 3-dimensional magnetic resonance imaging (3D-MRI). They found these techniques alone to be adequate in visualizing the deep and superficial venous systems along with other anatomy in order to plan effective treatment strategies (44). Lymphoscintigraphy is also useful if there is considerable limb oedema (19). Plain radiographs are useful to assess the bony involvement, and serial CT scanograms help determine the growth discrepancy that may occur. Arteriography is best reserved for surgical planning. This is especially useful when a hip disarticulation or hemipelvectomy is planned as the network of vessels can be seen and the approach and deep dissection predetermined (45).
Treatment.
The treatment for KTS is tailored to the extent of the disease and how the limb changes with increasing age. In the neonatal period, emergency amputation of a limb occasionally needs to be performed to save a child if there is a lifethreatening shunt and high-output cardiac failure.
Nonoperative management is the mainstay of treatment. Compressive graduated stockings help reduce the size and pressure in the limb and give symptomatic relief. Nocturnal pneumatic calf pumps can help during the night and the daytime compressive stockings should be applied while the child is still recumbent in bed (26, 46). Good foot hygiene is essential to avoid cellulitis. Although pulmonary embolus is lower than one would expect in this syndrome, it still does occur, so avoiding prolonged sitting and occlusive clothing is important. Young women should probably avoid oral contraceptives.
Surgical intervention is useful in a small number of patients. When a significant leg length discrepancy is present and a shoe lift on the unaffected leg is not tolerated, then an equalization procedure is indicated. This is usually an epiphysiodesis of the affected limb and should be carried out with minimal trauma to the soft tissues (47). The use of eight plates (Orthofix, McKinney, TX) may be useful, so the length can be modulated as it is difficult to predict the eventual discrepancy. At the same time, a “one-off” percutaneous drill epiphysiodesis does the least damage to the soft tissues.
The ability to wear footwear is important for these patients both for a protective function and for cosmesis. Excision of the central metatarsals and epiphysiodesis of the others can help reduce the width and length of the foot (35). Similarly, amputation of an associated large digit will make shoe fitting easier. A Symes amputation is useful for severe foot deformities. Complications from this peripheral surgery are uncommon; however, DVT prophylaxis should be administered (47, 48).
Debulking the soft tissue in the leg is usually unsuccessful with recurrence, swelling, and wound healing problems complicating the surgery. Likewise, varicose vein stripping can result in local symptom relief; however, excessive swelling can occur. The swelling in both cases arises from the inability of the severely deficient deep venous system to function. Selective embolization of vessels can occasionally be successful but often results in early recurrence of the problem (49, 50).
One of the difficult decisions to make is whether to amputate a severely disfiguring or dysfunctional limb or part of the limb. When one considers the multiple operations, unpredictability, and wound healing problems associated with some of the other procedures, amputation sometimes appears the “conservative” option. The difficult decision is often what level to perform the amputation at. This is usually determined by the extent of the VMs as the amputation needs to be made proximal to the severely affected area to minimize complications. Even when an amputation is through an area of “normal” looking soft tissues, there may still be microscopic AVMs or VMs that will be traumatized by the prosthesis. Healing of the stump can be a problem after surgery and Letts had five out of seven children who had an amputation have wound complications (47, 51). All the patients in his study functioned much better after their amputation than before. Pulsed dye laser treatments can be used for treating the cutaneous vascular malformations over limited areas (19).
Proteus Syndrome.
Proteus syndrome is a rare condition characterized by skeletal, vascular, and soft-tissue abnormalities that occur in a sporadic fashion. It was originally described in 1979 by Cohen and Hayden; however, it was ascribed the name Proteus syndrome by Wiedermann et al. in 1983 (52). The syndrome was named after the Greek sea god Proteus who was known for his ability to change shape to disguise himself when escaping from his enemies. Proteus syndrome has often been misdiagnosed in the past due to its overlap
with a number of other conditions. It can be confused with Klippel-Trenauany syndrome, epidermal nevus syndrome, neurofibromatosis, idiopathic hypertrophy, Maffucci syndrome, isolated macrodactyly, Ollier disease, and many of the lipomatosis syndromes (53).
with a number of other conditions. It can be confused with Klippel-Trenauany syndrome, epidermal nevus syndrome, neurofibromatosis, idiopathic hypertrophy, Maffucci syndrome, isolated macrodactyly, Ollier disease, and many of the lipomatosis syndromes (53).
Etiology.
The etiology of Proteus syndrome is still not known. It appears to be a sporadic genetic disorder that results in a hamartomatous growth disorder of the tissues in a mosaic pattern. A number of authors have hypothesized about the possible genetic mutations that may occur (54, 55 and 56). Others have investigated germ line loss-of-function mutations in the tumor suppression gene PTEN, which is found on chromosome 10q23.3.This gene encodes for a dual-specific phosphatize that is involved in various cellsurvival pathways. These mutations have been isolated in 20% of patients with Proteus syndrome and 50% of patients with Proteus-like syndromes who also have hamartomatouslike disorders (57, 58). There is only one report of a possible father to son transmission (59).
Clinical Features.
Due to the confusion that existed in the diagnosis of Proteus syndrome, a workshop was held in 1998 at the National Institute of Health in Maryland to define the diagnostic criteria (60). Radiographic diagnostic criteria have also been proposed by Jamis-Dow et al. that help in the evaluation of this syndrome (61).
Proteus syndrome is a highly complex variable disorder that involves overgrowth of the skin and subcutaneous tissues, vascular system, bones, and other soft tissues. The histology reveals “hamartomatous mixed connective tissue lesions, benign neoplasms such as lipomata, and lymphatic rich vascular malformations” (62).
Skin and subcutaneous tissue. Almost all patients with Proteus syndrome have at least one skin lesion and these lesions fall into one of two groups: congenital (type 1) or neonatal onset (type 2) (63). The type 1 lesions include the epidermal nevus and vascular malformations that are present at birth and usually do not progress. The type 2 lesions are the lipomas and cerebriform connective tissue nevi that appear after birth and are unpredictable in their progression. The late onset of these lesions often means a diagnosis of Proteus syndrome is not made until late childhood and the child may have already been labeled as having Klippel-Trenaunay syndrome (60). The cerebriform connective tissue nevi are diagnostic of Proteus syndrome and can cause symptoms of pain and pruritus. They can also become infected, bleed, and have a foul odor. Unfortunately, surgery is largely unsuccessful for these nevi and the mainstay of treatment is good skin care and accommodating footwear to minimize skin breakdown (63, 64).
Vascular system. Vascular malformations are not limited to a single limb like Klippel-Trenaunay syndrome but rather can occur randomly anywhere in the body. The cutaneous malformations include vascular tumors, port wine stains, and venous anomalies. Hoeger et al. found these lesions to be present either individually or together in 100% of the 22 patients with Proteus syndrome they meticulously analyzed (65). They also made the observation that these hemangiomas behave differently in Proteus syndrome. They do not regress spontaneously but rather continue to grow until the child matures around 12 to 14 years of age. The occurrence of thrombosis, thrombocytopenia, and phlebitis is also higher.
Skeletal manifestations. Macrodactyly is probably the most common skeletal manifestation of Proteus syndrome and can occur in the hands or feet and can be independent of the hypertrophied limb (60). The macrodactyly is often not present at birth; however, it can rapidly progress in the first few years of life and then the growth decreases. In the hand, the third and fourth digits are usually affected the most. Macrodactyly can be both disfiguring and functionally limiting. Often partial amputation of a digit is required just to get footwear to fit. A striking finding in the foot is plantar hypertrophy, resulting in cerebriform or gyriform creasing (Fig. 9-3).
Hemihypertrophy is almost as common and can be partial, complete, or crossed. The resulting limb length inequality is unpredictable and can be severe (66). Angular malalignment also occurs in both the upper and lower limb. Surgical attempts to correct the genu valgum often result in recurrence and bracing is ineffectual (66, 67) (Fig. 9-4). Scoliosis and kyphosis occur in approximately 50% of patients with Proteus syndrome (60, 66, 68, 69). Most of these patients who have progressive deformity do not respond to bracing and require spinal fusion. Other spinal deformities include localized spinal overgrowth and infiltration of the spinal canal by angiolipomatous tissue, which can cause both compression of the spinal cord and potential paraplegia (67, 70, 71, 72 and 73).
Other skeletal manifestations that have been found are hip dysplasia, exostoses that can limit joint movement, hindfoot deformity, and bony protuberances in the skull (61).
 FIGURE 9-3. Adolescent boy with Proteus syndrome with typical gyriform creasing of the sole of his foot. |
 FIGURE 9-4. Adolescent boy with Proteus syndrome with recurrent left genu valgum after a high tibial osteotomy, just prior to repeat osteotomy. |
Extraskeletal manifestations. These are far less common than the skeletal and soft-tissue abnormalities. Splenomegaly and nephromegaly can occur along with various abnormalities in the brain (asymmetric megalencephaly and white matter changes) (53, 74, 75). Unusual tumors like ovarian cystadenomas, parotid adenomas, meningiomas, and others have been described but occur rarely (61, 76, 77). Cystic and emphysematous lung changes have also been observed and can be severe. Thromboembolism is more common than in other syndromes with vascular malformations and can lead to sudden death even in children (78, 79).
Treatment.
Orthopaedic surgery in patients with Proteus syndrome involves correction of leg length inequality and angular deformity and addressing macrodactyly. The leg length inequality is difficult to predict due to the abnormal growth patterns. Serial clinical and radiologic assessments need to be made to optimize the timing of the epiphysiodesis. The use of eight plates (Orthofix, McKinney, TX) may make this a more forgiving procedure and allow more accurate equalization. Likewise with angular deformity, the use of an eight plate (Orthofix, McKinney, TX) on the convex side will allow growth modulation and eventual correction of the deformity. Surgical correction of macrodactyly is discussed in detail later in this chapter.
When assessing the child with Proteus syndrome for surgery, the anesthetic and surgical team must be cognizant of the associated conditions that may affect surgery. The cystic lung disease, tonsillar hyperplasia, and increased risk of pulmonary embolus may affect the child (80).
Gorham Disease.
Gorham disease, sometimes referred to as “disappearing bone disease,” is a rare condition that results in massive osteolysis of bone. The cause of the disease is unknown; however, the histology reveals both lymphangiomatosis and hemangiomatosis tissue, which for the purpose of this chapter is classified as a complex combined lymphatic-venous malformation. The first case of spontaneous absorption of bone was reported back in 1838; however, Gorham and Stout (81) and then Gorham (82) described the clinicopathologic features of the disease in the 1950s.
Clinical Presentation.
Gorham disease usually occurs in the second or third decade of life; however, case reports have occurred from the neonatal period through to 65 years of age (83, 84 and 85). There is no familial inheritance pattern of Gorham disease, and there is no greater incidence in either sex or any particular race.
The most commonly involved bones are the maxilla, shoulder girdle, and pelvis although any bone can be involved including the spine (86, 87, 88 and 89). Gorham disease can present in a number of different ways. It can be recognized on x-rays as an incidental finding following trauma to an area. It can present as a pathologic fracture through an area of osteolysis. Occasionally, there is a history of pain that is not usually severe in the area of underlying osteolysis, and a child can present with some mild deformity of the involved area and some muscle weakness. On rare occasions, the patient may present with symptoms of a chylothorax where the lymphangiomatosis tissue has extended in to the chest from either shoulder girdle or spine involvement. These children usually present with shortness of breath and a chest x-ray will reveal a large pleural effusion (90) (Fig. 9-5). Usually, the disease starts in one bone and can either remain there or spread to adjacent bones with complete disregard for the intervening joint or disc space (91). Other authors have shown that Gorham disease can arise in a multicentric pattern where more than one bone is initially involved but the intervening bone between the lesions is free of disease (92, 93).
Although other causes of osteolytic lesions such as osteomyelitis and metastatic disease can be excluded on the clinical
findings, other causes of primary osteolytic processes must be considered. Torg et al. described a classification system in 1969, which was further expanded by Macpherson et al. in 1973 and remains the most useful one today (94, 95).
findings, other causes of primary osteolytic processes must be considered. Torg et al. described a classification system in 1969, which was further expanded by Macpherson et al. in 1973 and remains the most useful one today (94, 95).
 FIGURE 9-5. A 13-year-old girl with Gorham disease who presented with a large right-sided pleural effusion. |
 FIGURE 9-6. A 13-year-old girl with CT scan (A,B) showing extensive erosion of the scapula. MRI scan (C) shows the extraosseous soft-tissue extension. |
Radiologic Changes.
The plain radiographs will reveal either the monostotic involvement or multiostotic disease outlined above. The initial radiographic features were described by Johnson and McClure in 1958 (96). They show that initially there were multiple intramedullary and subcortical radiolucent foci with associated osteoporosis. They then describe an extraosseous stage when the cortex has been disrupted and there is an extension of the pathologic tissue into the adjacent soft tissues. The ends of the tubular bones then taper off to the area of osteolysis and this is thought to be due to compression by the surrounding soft-tissue involvement. One of the characteristic findings, however, is the lack of sclerosis or osteoblastic reaction in the area (97). CT scanning is the next best investigation to look at the bone destruction and absence of any callus formation. An MRI scan, however, is more useful in looking at the soft-tissue extension in the area of osteolysis and beyond (Fig. 9-6). The MRI signal characteristics will change depending on the stage of the disease. Initially, with the neovascularization, there will be increased uptake on the T1 and T2 imaging; however, as the vascular tissue is replaced with fibrous tissue, the T1 and T2 imaging will become increasingly dark (86, 98, 99). Arteriography, venography, and lymphangiography have all been used to help in establishing a diagnosis and investigating the extent of the disease (83, 84, 97). These investigations, however, are rarely required to make the diagnosis and don’t usually offer any more information than is attained by the plain radiographs, CT, and MRI scan.
 FIGURE 9-7. Histologic slide of a biopsy in Gorham disease showing the thin-walled vessels lined by endothelium cells (arrow) and proteinaceous fluid. |
Histopathology.
The gross finding is of bone that is thin, soft, and spongy in texture. Occasionally, small cysts are also seen with the naked eye (84, 85, 100). Fibrous connective tissue replaces the bone. Histologic examination demonstrates benign endothelial proliferation within the bone. There are numerous thin-walled vessels that are lined by endothelial cells, and these capillaries contain red blood cells and/or proteinaceous fluid (101) (Fig. 9-7). There is no evidence of malignancy or inflammation. The role of osteoclast activity in Gorham disease is somewhat controversial. Some authors have reported the presence of osteoclasts in pathologic specimens (102, 103 and 104), whereas others have not found any to be present (87, 91, 97, 105). One of the mysteries of Gorham disease is the actual cause of this massive osteolysis. One thought is that the perivascular cells show some characteristics of osteoclast precursors that may form active osteoclasts (87, 106). Other authors have hypothesized that the osteoclast precursors in the area of osteolysis are more sensitive to humeral factors that promote osteoclast formation and bone reabsorption rather than an actual increase in actual osteoclast numbers (107, 108).
Treatment.
With no obvious known cause and with such a variable natural history, the treatment of Gorham disease is extremely difficult. Although clinical and radiologic features usually confirm the diagnosis, a biopsy is often performed.
The results of treatment have been particularly difficult to evaluate due to the variable natural history of Gorham disease. Occasionally, the multiple treatment modalities have been used over the years with variable results and still no consensus exists on the most effective treatment strategy. An important prognostic factor is the presence of extraosseous involvement. Guitierez and Spjut reviewed 25 patients with extraosseous involvement and found the mortality rate was higher in this group of patients with Gorham disease (105). The extraosseous tissue can invade the pleural cavity giving rise to pulmonary complications due to the persistent chylothorax. This can occur when the shoulder girdle is involved or the thoracic or lumbar spine (90, 91, 109). The management of the chylothorax is extremely difficult and usually not successful. Attempts have been made to tie off the thoracic trunk and use different radiation and pleural adhesion therapies (86).
For more straight forward monostotic disease, the treatment has also been variable and disappointing. Spontaneous regression without treatment can occur; however, in the majority of cases, no new bone is ever made. Local excision of the affected bone and soft tissue and bone grafting with or without internal fixation has also been largely unsuccessful (89, 110, 111). Unfortunately, most of the bone grafts are reabsorbed, and this has encouraged some authors to use vascularized fibula grafts to strut the affected area (112). The use of an endoprosthesis to bridge the gap between the so-called “normal bone” can be successful (85, 89, 112, 113). When limb salvage is not possible due to the extent of both the bone and the soft-tissue disease, then amputation is often indicated. In a limb with extensive bone disease and massive soft-tissue involvement, it may be more functional for the patient to have an amputation or limb disarticulation rather than a salvage procedure. Predicting the level of the amputation is difficult as through joint amputation has not always been shown to control the disease process (93, 98, 114).
One can see that not only the type of surgical procedure is a challenge to decide but the timing of the surgical intervention may also be critical. In rapidly evolving disease, it is difficult to know whether to intervene “early” to try and halt the progress or wait until the disease process has slowed down to assess the extent of the reconstruction or amputation. A pathologic fracture through the area of osteolysis has been shown to increase the rapidity of the osteolytic process and Mendez et al. suggest that surgical intervention earlier in this clinical situation may be indicated (115). The management of vertebral Gorham disease is extremely challenging as resection with adequate margins is usually not possible. Spinal bracing is a temporizing treatment; however, definitive surgical intervention is required when there is neural compromise. Anterior and posterior decompression and fusion has been used successfully in this situation at the cervico-thoracic junction (116). In other examples, bone grafting has been useful but has reabsorbed with time (104, 117).
Hemihypertrophy and Hemihypotrophy.
Hemihypertrophy and hemihypotrophy are two different conditions that have different clinical manifestations and need to be considered separately. For the purposes of this chapter, the two conditions will be discussed in isolation, but at the same time, they share the
same problem of asymmetry between the left and right sides of the body that cannot be attributed to normal variation. In this regard, it is important to explain the nomenclature used in addressing these two conditions.
same problem of asymmetry between the left and right sides of the body that cannot be attributed to normal variation. In this regard, it is important to explain the nomenclature used in addressing these two conditions.
Nomenclature.
Hemihypertrophy is an overgrowth in the size or length of a portion of the body and may involve the extremities, head, trunk, and internal organs. The overgrowth can be limited to an upper or lower limb, head and face, crossed (overgrowth of contralateral limbs) or a full hemihypertrophy where there is overgrowth of the ipsilateral upper and lower limbs.
Hypotrophy is a failure of growth (undergrowth) of a portion of the body and can be classified similarly to hypertrophy above. The term hemiatrophy has been used to describe the same phenomenon; however, it is not used here as this implies a wasting of tissue rather than a failure of growth.
TABLE 9-3 Differential Diagnosis of Hemihypertrophy and Hemihypotrophy | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Classification.
Hemihypertrophy can be classified as congenital or acquired. Acquired asymmetry can occur secondary to infection, trauma, radiation, or inflammation (121, 122).
Congenital hemihypertrophy is further classified according to the extent of the involvement of the child and whether it is part of a recognized clinical syndrome or not. Total forms have involvement of all organ systems, whereas the limited forms have only muscular, vascular, skeletal, or neurologic involvement (121). Limited forms can be further classified according to the area of their involvement: Classic (ipsilateral upper and lower limbs), segmental (within a single limb), facial (head and face), or crossed (contralateral upper and lower limbs) (121, 122 and 123).
Syndromic hemihypertrophy occurs in conditions like neurofibromatosis, Beckwith-Wiedemann syndrome, Bannayan-Zonana syndrome, Klippel-Trenaunay syndrome, and Proteus syndrome (Table 9-3). Nonsyndromic hemihypertrophy
(sometimes referred to as isolated hemihypertrophy) has no other syndromic features; however, along with Beckwith-Wiedemann syndrome is the only type of hemihypertrophy associated with an increased risk of intra-abdominal tumors (52, 124, 125 and 126).
(sometimes referred to as isolated hemihypertrophy) has no other syndromic features; however, along with Beckwith-Wiedemann syndrome is the only type of hemihypertrophy associated with an increased risk of intra-abdominal tumors (52, 124, 125 and 126).
Both hemihypertrophy and hemihypotrophy become entities when the growth or lack of growth varies from “normal.” Although there is no current consensus on what percentage growth difference defines these disorders, the most commonly used reference for normal variation in limb size is a survey from a growth study at Children’s Hospital, Boston, by Pappas and Nehme (127). Another reference group of patients used is a series of a thousand United States army recruits reviewed by Rush and Steiner in 1946 (128).
Pappas and Nehme defined abnormal asymmetry as a 5% or greater difference in the length and/or circumference of the involved limb (127). The magnitude of this discrepancy, however, needs to take the age and size of the child into account, and therefore the Anderson and Green growth charts need to be used in combination with the findings of Pappas and Nehme. These measurements are largely academic and necessary only for the more subtle cases. With hemihypertrophy, the overgrowth may be associated with other abnormalities like vascular and digital malformations or macrodactyly. The patient with hypotrophy may have associated mental retardation, muscular wasting, or neurologic symptoms.
The single most important thing for the orthopaedic surgeon to recognize is whether the child or adolescent has hemihypotrophy or hemihypertrophy as the latter is associated with the development of embryonal tumors whereas the former is not.
Hemihypertrophy occurs when one side of the body or limb enlarges asymmetrically both in length and width when compared with the contralateral “normal side.” Hemihypertrophy is a rare disease of unknown etiology that affects approximately 1 in 50,000 individuals (121, 123, 127, 129). It is difficult to determine the true prevalence due to the minor asymmetry that can often occur between limbs in normal people (28). Hemihypertrophy is also rarely diagnosed at birth and develops to a variable degree through infancy and early childhood. The asymmetry can also be extremely subtle ranging from an increase in the size of an ear, half the tongue, pupil right up to involvement of abdominal and thoracic organs (122, 124). The skin may be thicker on the involved side and there may be more hair (121). The asymmetrical growth is unpredictable and in some cases can resolve in early childhood or be exaggerated during puberty (130). The total limb inequality rarely exceeds 5 cm by skeletal maturity (124, 127). Approximately twothirds of the patients will require an equalization procedure for the discrepancy (131). This can be achieved by epiphysiodesis of the contralateral knee epiphyses with a drill technique or staples (124, 127). The use of eight plates (Orthofix, McKinney, TX) to achieve this has become increasingly popular, so the equalization can be modulated if the predictable discrepancy was inaccurate. A nonstructural scoliosis can occur secondary to the leg length discrepancy but usually resolves with correction of the inequality.
Nonsyndromic hemihypertrophy can also have other associated anomalies outside the musculoskeletal system. There is an increased incidence of renal disorders including medullary sponge kidney, renal cysts, and horseshoe kidney. Inguinal hernias and cryptorchidism can also occur (121, 129, 132).
There are a number of theories associated with the etiology of nonsyndromic hemihypertrophy; however, none have been proven. Due to the association with embryonal tumors, abnormal cellular growth control mechanisms have been postulated in these children. Other researchers have suggested that possible chromosomal abnormalities, lesions of the nervous system, or endocrine malfunctions may be a cause of the hypertrophy (121, 125, 126, 133). The malignant tumors that occur with nonsyndromic hemihypertrophy in order of frequency are Wilms tumors, adrenal carcinoma, and hepatoblastoma (134, 135, 136 and 137). The problem is defining what is the true incidence of these life-threatening conditions and how best to screen for them. One prospective study suggests the incidence of malignancy is approximately 5.9% (133). Many retrospective studies have been performed that calculate the incidence to be slightly lower, around 3% (134, 138, 139). It is difficult to define strict criteria for screening these children for tumors when the incidence is so low, the development of the tumors unpredictable and no studies that show children who have a tumor found on ultrasound screening has any better outcome than a patient who presents with symptoms of the tumor. In some of the prevalence studies, the tumors were diagnosed in 30% of patients before the hemihypertrophy was even recognized (121, 140, 141). It seems intuitive, however, to have a screening program when one recognizes a patient with asymmetry of one side of the body. Initially, the hemihypertrophy needs to be classified accurately as syndromic or nonsyndromic, often with the help of geneticists and pediatricians. The nonsyndromic children and those with Beckwith-Wiedemann syndrome need to have an abdominal ultrasound. Although controversial, these children should have a regular abdominal ultrasound every 3 months up to 7 years of age and then have a physical abdominal examination every 6 months until skeletal maturity (142). Some clinicians recommend no ultrasound screening at all and others ultrasound until skeletal maturity (121).
Hemihypotrophy.
Idiopathic hemihypotrophy appears to be approximately one-half as frequent as nonsyndromic hemihypertrophy (123). Hemihypotrophy is more likely to be associated with diffuse skeletal abnormalities when compared to hemihypertrophy (123). There is a higher incidence of other dysmorphic features, including cleft palate and facial malformations, congenital scoliosis, and genitourinary malformations (123, 143). Mental retardation is also more common; however, Wilms tumor and other embryonal tumors are not associated with this condition (28). Unlike hemihypertrophy, the leg length discrepancy is rarely more than 2.5 cm and therefore does not require surgical correction (123, 143).
Hemihypotrophy is classified in the same way as congenital hemihypertrophy as total or limited. The limited
forms can therefore be categorized according to the area of involvement: classic, segmental, facial, or crossed (121, 122 and 123). Undergrowth may also occur as a result of secondary nonsyndromic hypotrophy, mosaicism for Turner syndrome, Russell-Silver syndrome, neurologic asymmetry (cerebral palsy, polio), osteochondromatosis, endochondromatosis, or polyostotic fibrous dysplasia (144).
forms can therefore be categorized according to the area of involvement: classic, segmental, facial, or crossed (121, 122 and 123). Undergrowth may also occur as a result of secondary nonsyndromic hypotrophy, mosaicism for Turner syndrome, Russell-Silver syndrome, neurologic asymmetry (cerebral palsy, polio), osteochondromatosis, endochondromatosis, or polyostotic fibrous dysplasia (144).
Russell-Silver syndrome has some features in common with idiopathic hemihypotrophy, but it is characterized by overall short stature, with most patients never exceeding a height of 152 cm. These patients have characteristic small, triangular faces and renal and genital malformations (28). Scoliosis is common and may be congenital or look similar to idiopathic scoliosis. Leg length asymmetry is usually minimal, but as much as 5 cm has been reported (143).
Limb inequalities resulting from neurogenic causes vary in proportion to the asymmetry of the neurologic involvement, rarely exceeding 2.5 cm in the lower extremities in patients with cerebral palsy or 6 cm in patients with polio (145).
It is important for the orthopaedic surgeon to recognize limb overgrowth or undergrowth and therefore classify the deformity accordingly. Although sometimes clinically obvious, growth charts are often required to accurately assess whether the condition is hemihypertrophy or hemihypotrophy. There are different clinical manifestations for each disease as outlined above and different syndromes and clinical features that are associated with the two different conditions. It is not always easy for the orthopaedic surgeon alone to diagnose these conditions and therefore help should often be sought from pediatric and geneticist colleagues.
Macrodactyly.
Macrodactyly (also known as localized gigantism) is a rare condition characterized by large digits of the hand and less commonly of the foot that is usually apparent at birth or in early childhood. Usually, the preaxial side of the hand or foot is involved; however, in rare occasions, all the digits or postaxial enlargement can occur (146). Klein described the first case of macrodactyly in 1824 and up until 1999 only 300 cases of macrodactyly of the hand and 60 cases of macrodactyly of the foot had been reported in the literature (147).
Macrodactyly usually occurs as an isolated condition but may also occur in patients with neurofibromatosis, vascular malformations (hemangiomatosis, lymphangiomatosis, or mixed disease), Proteus syndrome, and Klippel-Trenaunay syndrome (148, 149, 150 and 151). Children with multiple enchondromatosis, Maffucci syndrome, and tuberosclerosis also have enlarged digits. In recognizing macrodactyly, it is therefore important to look for other physical abnormalities that may be present in order to diagnose another underlying disorder. In infancy, cutaneous manifestations of neurofibromatosis or the vascular malformations may not be present making a definitive diagnosis often difficult. Traditionally, it was thought that two types exist: the more common static type, in which the proportion of enlargement remains the same, and the progressive type, in which this proportion or ratio increases with time (152). These common forms fall under Upton classification of “type 1” and are by far the most common and occur with the most common frequency; however, it is important to consider the other three types so that other disorders are not overlooked.
Type 1: Macrodactyly with nerve-oriented lipofibromatosis
a. Static subtype
b. Progressive subtype
Type 2: Macrodactyly with neurofibromatosis
Type 3: Macrodactyly with hyperostosis
Type 4: Macrodactyly with hemihypertrophy
When the cause of type 1 macrodactyly is unknown, it is thought that it may be due to a “neuroinduction” type disorder. This is supported by the clinical findings that the most common distribution of the macrodactyly is along either the median nerve distribution or digital nerve distribution of the digits (151).
Clinical Features.
Macrodactyly occurs more commonly in the hand than it does in the foot and is unilateral in 95% of cases (152). The condition occurs slightly more often in men than woman (153). The macrodactyly is commonly seen soon after birth; however, in some cases, it will become more evident as the child grows especially in the type 1b progressive subtype. The second ray is the most commonly enlarged, followed in descending frequency by the third, first, fourth, and fifth rays (Fig. 9-8). Syndactyly may coexist. Usually, the palmar or plantar surfaces are more hypertrophied than the dorsal surface, resulting in hyperextension of the metatarsals or metacarpal phalangeal joints (149, 154) (Fig. 9-9). If two adjacent digits are affected, they usually grow apart from each other. In static macrodactyly, the digits involved are approximately 1.5 times the normal length and width. In the progressive subtype, however, the enlargement can progress well beyond this and can involve tissue more proximal than the digits. As well as the digits, the hand and foot may be involved and even more
proximally the whole limb may be slightly increased in length and width (149, 155, 156). When one sees a macrodactyly of a digit, a very careful clinical examination and sometimes radiologic investigation of the whole limb is paramount to assess the extent of the enlargement. This clinical examination will also help in trying to ascertain whether the macrodactyly is associated with any of the other conditions mentioned earlier. The only radiologic investigation required is usually an x-ray. This is also useful in planning the surgical procedures that may be necessary. The bone age may be advanced in the phalanges involved in the macrodactyly (149, 155).
proximally the whole limb may be slightly increased in length and width (149, 155, 156). When one sees a macrodactyly of a digit, a very careful clinical examination and sometimes radiologic investigation of the whole limb is paramount to assess the extent of the enlargement. This clinical examination will also help in trying to ascertain whether the macrodactyly is associated with any of the other conditions mentioned earlier. The only radiologic investigation required is usually an x-ray. This is also useful in planning the surgical procedures that may be necessary. The bone age may be advanced in the phalanges involved in the macrodactyly (149, 155).
 FIGURE 9-8. Macrodactyly of the second toe in a 12-year-old boy. He was asymptomatic and has not required treatment. |
 FIGURE 9-9. A 2.5-year-old girl with progressive macrodactyly of both feet, with macrodystrophica-lipomatosa. A: There is significant plantar hypertrophy, resulting in hyperextension of the digits, and there is marked asymmetry in the digital enlargement. B,C: The plain radiographs demonstrate soft-tissue enlargement, as well as underlying bony enlargement. D: The magnetic resonance imaging demonstrates overgrowth of essentially all the elements of the digit, particularly the fibroadipose tissue typically seen in macrodystrophica-lipomatosa. |
Pathology.
The most consistent finding in macrodactyly is the overgrowth of the fibrofatty tissue but in fact all tissues are enlarged in the involved digit (149, 152, 155). This fibrofatty issue in fact resembles adult subcutaneous tissue rather than
children’s fat (152). Usually, there is greater involvement of the tissues distally rather than proximally. There is an increase in the amount of fat and fibrous tissue that surrounds the nerves. The perineurium is thickened and there is proliferation of the fibrous tissue in the endoneurium (149, 151, 152, 157). The muscle is infiltrated in a similar way. The bone is increased in both width and length. Ben-Bassat et al. found that there was a proliferation of fibroblasts or osteoblasts between the periosteum and the cortical bone that may account for the phalangeal overgrowth (149, 155). There does not appear to be any pathologic features in the blood vessels.
children’s fat (152). Usually, there is greater involvement of the tissues distally rather than proximally. There is an increase in the amount of fat and fibrous tissue that surrounds the nerves. The perineurium is thickened and there is proliferation of the fibrous tissue in the endoneurium (149, 151, 152, 157). The muscle is infiltrated in a similar way. The bone is increased in both width and length. Ben-Bassat et al. found that there was a proliferation of fibroblasts or osteoblasts between the periosteum and the cortical bone that may account for the phalangeal overgrowth (149, 155). There does not appear to be any pathologic features in the blood vessels.
Treatment.
The treatment of macrodactyly is challenging due to the unpredictable progression of the disease that may occur. The patient and family need to be counseled carefully about this before embarking on surgical treatment as sometimes multiple procedures will be necessary. The most important goal of surgery is to improve the function of the involved hand or foot and in most cases to improve the cosmesis. Careful surgical planning is therefore required to maximize the ultimate long-term outcome and especially to improve the function of the limb. A number of factors therefore need to be considered in the treatment of macrodactyly and these include the classification, the age of the patient, the extent of the overgrowth, and which digit/s are involved. The treatment options include debulking of the soft tissue, shortening procedures of the digit, growth modulation of the physeal plate, or amputation. In the static subtype, debulking and shortening procedures including epiphysiodesis or phalangeal resection are usually successful. In the progressive subtype, however, more proximal procedures like ray dissection or even amputations are necessary due to the progressive nature of the disease and the multiple procedures that are often required. Multiple debulking procedures often compromise the blood supply to the area, which can result in wound healing problems. In mild to moderate macrodactyly, the gigantism can be addressed with soft-tissue debulking and epiphysiodesis (152). The epiphysiodesis needs to be performed before the child is 8 years of age and it must be done on all the involved segments of bone (149, 152, 158, 159). In older children, it is better to perform a phalangeal resection combined with a staged debulking (157, 160, 161). These procedures do not address the increased width that may also be present in the hand or the foot. Increased width is not usually a functional problem in the hand but in the foot it can cause significant problems with shoe wearing. In order to address this increased width in the foot, a ray dissection including one or more metatarsals and a wedge from the tarsal bones is required (151, 153, 162, 163). The minimal numbers of rays to maintain a functional foot is 3. The first ray should never be amputated in isolation because of its importance in weight bearing and balance (164). A metatarsal excision may also be useful in the hand when excessive width is present. Ray resection also prevents “gap formation,” which can lead to digit deviation and soft-tissue enlargement.
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