Camurati–Engelmann disease: case report and review of literature | Revista Colombiana de Reumatología (English Edition)

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Pain in the long bones is the cardinal symptom of CED. There is no curative treatment for the disease, however, a cycle of glucocorticoids in high doses can be given and, occasionally, decompression surgeries of the medullary canal can be performed to help alleviate pain.We present the case of a 54-year-old woman with CED, with tibial commitment and no other bone manifestations. As far as we know, this is the first case of CED reported in Colombia.Clinical caseA 54-year-old woman, who 4 years ago had a blunt trauma in the left tibia, since that time she has persistent pain in both lower limbs. In the review of systems she denied any ocular or auditory disorders, previous fractures, neurological deficit or constitutional symptoms. She received medical treatment with NSAIDs without any improvement, and for this reason it was ordered an X-ray of both legs which showed a sclerosing diaphyseal lesion in the middle third with loss of the medullary canal (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). The MRI in 2008 confirmed these findings (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>). The laboratory data such as CBC, ESR, CRP, BUN, creatinine, LDH, ALP, and urinalysis were normal. It was performed a bone biopsy in which it was observed the presence of a large number of small fragments of dense sclerotic bone tissue without any evidence of tumor or inflammatory lesion. The above findings are compatible with the diagnosis of CED. She was assessed by the Service of Orthopedics, who performed a resection of the sclerotic lesions and recanalization of the left tibia.<elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia>Over the past 2 years she has had pain in the knees associated with exercise, wrists, elbows, shoulders, and lumbar region without inflammatory signs, insomnia and physical fatigue. The initial physical examination showed a patient with normal height and phenotype, pain to the percussion of the long bones of the lower limbs without bone deformity or neurologic deficit with 15/18 tender points. In addition, it was made a diagnosis of fibromyalgia. The laboratory tests at this time showed normal intact PTH, calcium, serum phosphorus, and proteins with differential, with a C-reactive protein of 96mg/l, and therefore treatment was started with prednisolone 50mg QD, calcium + vitamin D QD, sertraline 50mg QD and trazodone 50mg QD.The patient was assessed by endocrinology ruling out hyperparathyroidism. In the subsequent controls the glucocorticoids were gradually reduced until being stopped in 6 months, with cessation of the pain to the percussion of the tibia and the fibula, but the patient continued with clear signs and symptoms of fibromyalgia. The acute phase reactants had become normal. It was requested an evaluation by psychiatry for the management of the associated depression. In the subsequent controls the underlying disease has remained stationary.ReviewThe CED has been known by the names of progressive epiphyseal dysplasia, generalized hyperostosis, congenital multiple hyperostotic disease, sclerosing dysplasia and symmetrical osteosclerosis,<a class="elsevierStyleCrossRef" href="#bib0200">1</a> but the eponym CED is the name most widely known and accepted.The first description was made by Cockayne in 1920,<a class="elsevierStyleCrossRef" href="#bib0205">2</a> 2 years later Camurati suggested its hereditary nature<a class="elsevierStyleCrossRef" href="#bib0210">3</a> and in 1920 Engelmann reported a case characteristic of the disease.<a class="elsevierStyleCrossRef" href="#bib0215">4</a> The CED has an autosomal dominant inheritance with incomplete penetrance and variable expressivity with incomplete penetrance and variable expressivity.<a class="elsevierStyleCrossRef" href="#bib0220">5</a> Recently, the gene responsible for the disease was located in the 19q13.1-13.3 region.<a class="elsevierStyleCrossRef" href="#bib0225">6</a> Mutations in the gene encoding the TGF-β have been found in 90–94% of cases. This gene has 2 exons and the majority of these mutations are in exon 4, followed by exon 1. The 3 most frequent mutant alleles are p Arg210cys, p Arg218His and pCys 225 Arg.<a class="elsevierStyleCrossRef" href="#bib0230">7</a>The transforming growth factor beta (TGF-β) is a bone growth factor, member of the superfamily or the bone morphogenetic proteins;<a class="elsevierStyleCrossRef" href="#bib0235">8</a> it promotes the proliferation, function and survival of the osteoblasts,<a class="elsevierStyleCrossRef" href="#bib0240">9</a> in addition, it has a suppressive action on the differentiation of osteoclasts.<a class="elsevierStyleCrossRef" href="#bib0245">10</a>CED is considered a rare disease with an estimated prevalence of one in a million inhabitants, 200 patients have been identified in the world literature. This pathology has a worldwide distribution based in the report of 24 families from America, Europe, Africa and Oceania. The onset of the disease is in childhood and it usually progresses during the adolescence, but in adulthood its course may be stationary or slowly progressive. The clinical symptoms are present in 74% of patients.<a class="elsevierStyleCrossRef" href="#bib0250">11</a> The limping gait is an early manifestation but it is not the most frequent, occurring in 43%. Progressive muscular atrophy and decreased subcutaneous fat in the limbs also can occur. Easy fatigability is a symptom that has been described in 44%. The cardinal symptom of the disease is bone pain in the extremities in 90% of cases. The patients report that the pain increases with physical activity, stress and cold. Some patients have crises of pain of variable duration (hours-weeks); 58% have pain to bone percussion. Cranial affection occurs in 38% of cases and can be manifested by atrophy of the optic nerve, glaucoma, subluxation of the eyeball, sensorineural or conductive hearing loss in 15%.<a class="elsevierStyleCrossRef" href="#bib0255">12</a> The pathophysiology of this lesions is based on nerve compression or obstruction of the external auditory canal. The sclerosis of the foramen magnum may cause hyperreflexia, weakness, paraparesis and even death.<a class="elsevierStyleCrossRef" href="#bib0260">13</a> The increase in bone mineral density in the diaphyses may increase the risk of fracture with delayed consolidation.<a class="elsevierStyleCrossRef" href="#bib0265">14</a>It has been described a typical disease phenotype characterized by craniomegaly with prominent forehead, exophthalmos, slender limbs with thick and curved bones, marfanoid aspect, flat and valgus feet, lumbar lordosis and scoliosis.Hepatosplenomegaly, Raynaud's phenomenon, hyperhidrosis of the feet and hands, and delayed dentition and puberty have been reported ocassionally.<a class="elsevierStyleCrossRef" href="#bib0270">15</a> Anemia, leukopenia, increased alkaline phosphatase, parathormone, serum calcium, phosphorus, and erythrocyte sedimentation rate can be observed in the laboratory tests, but is not the norm to find these alterations.<a class="elsevierStyleCrossRefs" href="#bib0265">14,16–19</a>The diagnosis of the disease is based on the clinical symptoms and laboratory findings, but is confirmed by the radiological images. The characteristic radiological manifestations are fusiform thickening of the bone cortical. CED has symmetrical affectation and involves both the endosteal and periosteal surfaces. Initially begins in the diaphyses and it extends to the metaphyses, sparing the epiphyses.<a class="elsevierStyleCrossRefs" href="#bib0275">16,20,21</a> As a consequence it can be seen a narrowing of the medullary canal with a shape of an Erlenmeyer-flask. The bones affected in order of frequency are: femur, tibia, fibula, humerus, ulna and radius. It can be seen an involvement of the mandible, scapulae, collarbones, pelvis and the skull base. There is rarely commitment of the carpal bones, tarsal bones and phalanges. The characteristic image of the long bones appears in 94% of patients, 63% in the pelvis and 54% in the skull.<a class="elsevierStyleCrossRef" href="#bib0305">22</a>Glucocorticoids are the cornerstone in the treatment of CED, because they increase the apoptosis of the osteoblasts and osteocytes, and also allow the proliferation and differentiation of the osteoclasts.<a class="elsevierStyleCrossRefs" href="#bib0310">23,24</a> Conversely, it has been demonstrated that glucocorticoids increase the expression of TGF-β, a deleterious situation in these patients.<a class="elsevierStyleCrossRef" href="#bib0320">25</a> Prednisolone 1mg/kg/day followed by a rapid reduction in the dose in order to avoid side effects is used to control bone pain and fatigue. Losartan is an anti-TGF-β drug and it could be used in patients with arterial hypertension who are intolerant to glucocorticoids.<a class="elsevierStyleCrossRef" href="#bib0325">26</a> Other drugs such as bisphosphonates have been used for the management of CED with disappointing results.<a class="elsevierStyleCrossRef" href="#bib0330">27</a> Surgical treatment s reserved as a decompression mechanism for the external auditory canal. Osteotomies and scrapings of the medullary canal have also been reported with recurrence in some cases.<a class="elsevierStyleCrossRef" href="#bib0335">28</a>In <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a> are described the main sclerosing bone diseases. In the malignant infantile form of osteopetrosis the bones are dense and fragile. There may be spontaneous bleeding with anemia and recurrent infections. The neurological complications are blindness and deafness. Patients usually die in the first decade of life. The type II form occurs in adolescence and is manifested by fractures, sometimes recurrent, sandwich vertebrae and the bone-within-bone image in the iliac bone. The compression of cranial nerves due to osteosclerosis is rare.<a class="elsevierStyleCrossRef" href="#bib0340">29</a><elsevierMultimedia ident="tbl0005"></elsevierMultimedia>Pycnodysostosis manifests itself in childhood by short stature and a disproportionately large skull. The hands are square with small fingers and pectus excavatum. The recurrent fractures affect, mainly, the lower limbs.<a class="elsevierStyleCrossRef" href="#bib0345">30</a>Osteopoikilosis means spotted bones, which are confused with bone metastases from prostate and breast cancer.<a class="elsevierStyleCrossRef" href="#bib0350">31</a> It is incidentally found by the presence of circular lesions of osteosclerosis. It affects the ends of the short bones, and the metaphyses and epiphyses of the long bones.<a class="elsevierStyleCrossRef" href="#bib0355">32</a> Sometimes is associated with disseminated lenticular dermatofibrosis. The etiology of the disease is associated with mutations in the LEMD3 gene.<a class="elsevierStyleCrossRef" href="#bib0360">33</a>In Van Buchem disease there is an asymmetric enlargement of the jaw during puberty. There are not fractures but it can be pain to the percussion of long bones. Neurological alterations due to compression of cranial nerves are frequent. The disease progresses with age, and therefore, is more common to see radiological findings in elderly patients. In the form of sclerosteosis (Truswell–Hansen disease) the patients are tall and fat with syndactyly and nail dysplasia. The hyperostosis is classically endosteal. In Worth syndrome occur the same findings but it differs from the other 2 variants by the presence of an enlarged and pointed jaw with a widened forehead.<a class="elsevierStyleCrossRef" href="#bib0365">34</a>The presence of linear striations in the long bones is characteristic of the osteopathia striata; and it can be seen cranial sclerosis with nerve palsy.<a class="elsevierStyleCrossRef" href="#bib0370">35</a>In the melorheostosis is seen an eccentric and irregular hyperostosis of the cortex and the medullary canal, like the wax that trickles down the side of a candle.<a class="elsevierStyleCrossRef" href="#bib0375">36</a>In Kenny-Caffey disease there is intramembranous ossification. The main radiological finding is the internal cortical thickening with lack of differentiation of the tables of the skull. The main clinical findings are: short stature, mucosal paleness and microphthalmia.<a class="elsevierStyleCrossRef" href="#bib0380">37</a>Pyle's disease is characterized by widening of the metaphyses of the long bones called Erlenmeyer flask deformity, with growth of the medial parts of the clavicles, the ischium and the pubis.<a class="elsevierStyleCrossRef" href="#bib0385">38</a>Finally, the low back pain that begins in adolescence is the clinical finding of the osteomesopycnosis, due to sclerosis of the terminal plates. It has been described a cystic lesion in the femoral diaphysis. Other long bones or cranial bones have normal characteristics.<a class="elsevierStyleCrossRef" href="#bib0390">39</a>Ethical disclosuresProtection of human and animal subjectsThe authors declare that no experiments were performed on humans or animals for this study.Confidentiality of dataThe authors declare that no patient data appear in this article.Right to privacy and informed consentThe authors declare that no patient data appear in this article.Conflict of interestThe authors declare that they have no conflict of interest." "textoCompletoSecciones" => array:1 [ "secciones" => array:10 [ 0 => array:3 [ "identificador" => "xres790712" "titulo" => "Abstract" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0005" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec789009" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres790711" "titulo" => "Resumen" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0010" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec789008" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:2 [ "identificador" => "sec0010" "titulo" => "Clinical case" ] 6 => array:2 [ "identificador" => "sec0015" "titulo" => "Review" ] 7 => array:3 [ "identificador" => "sec0020" "titulo" => "Ethical disclosures" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0025" "titulo" => "Protection of human and animal subjects" ] 1 => array:2 [ "identificador" => "sec0030" "titulo" => "Confidentiality of data" ] 2 => array:2 [ "identificador" => "sec0035" "titulo" => "Right to privacy and informed consent" ] ] ] 8 => array:2 [ "identificador" => "sec0040" "titulo" => "Conflict of interest" ] 9 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2015-11-10" "fechaAceptado" => "2016-03-15" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec789009" "palabras" => array:3 [ 0 => "Diaphyseal dysplasia" 1 => "Transforming growth factor beta" 2 => "Hyperostosis" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec789008" "palabras" => array:3 [ 0 => "Displasia diafisiaria" 1 => "Factor de crecimiento transformante beta" 2 => "Hiperostosis" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "Camurati–Engelmann disease is a rare entity due to mutations in the gene encoding the TGF-β. It is characterized by hyperostosis of long bones and skull, accompanied by severe bone pain, and occasionally muscular weakness and a waddling gait. The treatment is based on the use of high doses of glucocorticoids, and in severe cases surgical decompression is indicated. As far as we know, this is the first case reported in Colombia." ] "es" => array:2 [ "titulo" => "Resumen" "resumen" => "La enfermedad de Camurati-Engelmann es una entidad poco común debida a mutaciones en el gen que codifica el TGF-β. Se caracteriza por hiperostosis de huesos largos y cráneo, acompañada de dolor óseo intenso, ocasionalmente debilidad muscular, marcha de pato. El tratamiento se basa en el uso de glucocorticoides en dosis altas y en casos severos la descompresión quirúrgica está indicada. Desde nuestro conocimiento este es el primer caso reportado en Colombia." ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "Please cite this article as: Restrepo JP, Molina MP. Enfermedad de Camurati-Engelmann: reporte de un caso y revisión de la literatura. Rev Colomb Reumatol. 2016;23:218–222." ] ] "multimedia" => array:3 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1779 "Ancho" => 1333 "Tamanyo" => 228931 ] ] "descripcion" => array:1 [ "en" => "AP and lateral X-ray of the tibia and fibula showing a large sclerotic phenomenon in the diaphyses of both bones in a symmetrical manner." ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1431 "Ancho" => 1659 "Tamanyo" => 403389 ] ] "descripcion" => array:1 [ "en" => "MRI of the right leg with coronal section in T2 where it can be seen a hypointense lesion in the diaphyseal region of the tibia that spares the cortical." ] ] 2 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at1" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Osteopetrosis (Albers Schonberg) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Osteomesopycnosis (Maroteaux) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Osteopoikilosis \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Osteopathia striata (Voorhoeve's disease) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Endosteal hyperostosis(Van Vuchem, Worth syndrome, sclerosteosis) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Kenny-Caffey syndrome \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Metaphyseal dysplasia (Pyle's disease) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Progressive diaphyseal dysplasia (Camurati–Engelmann disease) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Melorheostosis \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1321254.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Main causes of sclerosing bone diseases." ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:39 [ 0 => array:3 [ "identificador" => "bib0200" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Observations on the Camurati–Engelmann syndrome" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "B. 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Case report

Camurati–Engelmann disease: case report and review of literature

Enfermedad de Camurati-Engelmann: reporte de un caso y revisión de la literatura

Juan Pablo Restrepoa,

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jprestrepo@lycos.com

Corresponding author.

, María del Pilar Molinab

a Internista-Reumatólogo, Colombia

b Universidad Médica Laboral, Colombia

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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Camurati&#8211;Engelmann disease &#40;CED&#41;&#44; known as progressive diaphyseal dysplasia&#44; is an uncommon disease due to mutations of the transforming growth factor beta &#40;TGF-&#946;&#41;&#59; which participates in bone proliferation&#46; Pain in the long bones is the cardinal symptom of CED&#46; There is no curative treatment for the disease&#44; however&#44; a cycle of glucocorticoids in high doses can be given and&#44; occasionally&#44; decompression surgeries of the medullary canal can be performed to help alleviate pain&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">We present the case of a 54-year-old woman with CED&#44; with tibial commitment and no other bone manifestations&#46; As far as we know&#44; this is the first case of CED reported in Colombia&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Clinical case</span><p id="par0015" class="elsevierStylePara elsevierViewall">A 54-year-old woman&#44; who 4 years ago had a blunt trauma in the left tibia&#44; since that time she has persistent pain in both lower limbs&#46; In the review of systems she denied any ocular or auditory disorders&#44; previous fractures&#44; neurological deficit or constitutional symptoms&#46; She received medical treatment with NSAIDs without any improvement&#44; and for this reason it was ordered an X-ray of both legs which showed a sclerosing diaphyseal lesion in the middle third with loss of the medullary canal &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46; The MRI in 2008 confirmed these findings &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41;&#46; The laboratory data such as CBC&#44; ESR&#44; CRP&#44; BUN&#44; creatinine&#44; LDH&#44; ALP&#44; and urinalysis were normal&#46; It was performed a bone biopsy in which it was observed the presence of a large number of small fragments of dense sclerotic bone tissue without any evidence of tumor or inflammatory lesion&#46; The above findings are compatible with the diagnosis of CED&#46; She was assessed by the Service of Orthopedics&#44; who performed a resection of the sclerotic lesions and recanalization of the left tibia&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0020" class="elsevierStylePara elsevierViewall">Over the past 2 years she has had pain in the knees associated with exercise&#44; wrists&#44; elbows&#44; shoulders&#44; and lumbar region without inflammatory signs&#44; insomnia and physical fatigue&#46; The initial physical examination showed a patient with normal height and phenotype&#44; pain to the percussion of the long bones of the lower limbs without bone deformity or neurologic deficit with 15&#47;18 tender points&#46; In addition&#44; it was made a diagnosis of fibromyalgia&#46; The laboratory tests at this time showed normal intact PTH&#44; calcium&#44; serum phosphorus&#44; and proteins with differential&#44; with a C-reactive protein of 96<span class="elsevierStyleHsp" style=""></span>mg&#47;l&#44; and therefore treatment was started with prednisolone 50<span class="elsevierStyleHsp" style=""></span>mg QD&#44; calcium &#43; vitamin D QD&#44; sertraline 50<span class="elsevierStyleHsp" style=""></span>mg QD and trazodone 50<span class="elsevierStyleHsp" style=""></span>mg QD&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">The patient was assessed by endocrinology ruling out hyperparathyroidism&#46; In the subsequent controls the glucocorticoids were gradually reduced until being stopped in 6 months&#44; with cessation of the pain to the percussion of the tibia and the fibula&#44; but the patient continued with clear signs and symptoms of fibromyalgia&#46; The acute phase reactants had become normal&#46; It was requested an evaluation by psychiatry for the management of the associated depression&#46; In the subsequent controls the underlying disease has remained stationary&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Review</span><p id="par0030" class="elsevierStylePara elsevierViewall">The CED has been known by the names of progressive epiphyseal dysplasia&#44; generalized hyperostosis&#44; congenital multiple hyperostotic disease&#44; sclerosing dysplasia and symmetrical osteosclerosis&#44;<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">1</span></a> but the eponym CED is the name most widely known and accepted&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">The first description was made by Cockayne in 1920&#44;<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">2</span></a> 2 years later Camurati suggested its hereditary nature<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">3</span></a> and in 1920 Engelmann reported a case characteristic of the disease&#46;<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">4</span></a> The CED has an autosomal dominant inheritance with incomplete penetrance and variable expressivity with incomplete penetrance and variable expressivity&#46;<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">5</span></a> Recently&#44; the gene responsible for the disease was located in the 19q13&#46;1-13&#46;3 region&#46;<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">6</span></a> Mutations in the gene encoding the TGF-&#946; have been found in 90&#8211;94&#37; of cases&#46; This gene has 2 exons and the majority of these mutations are in exon 4&#44; followed by exon 1&#46; The 3 most frequent mutant alleles are p Arg210cys&#44; p Arg218His and pCys 225 Arg&#46;<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">7</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">The transforming growth factor beta &#40;TGF-&#946;&#41; is a bone growth factor&#44; member of the superfamily or the bone morphogenetic proteins&#59;<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">8</span></a> it promotes the proliferation&#44; function and survival of the osteoblasts&#44;<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">9</span></a> in addition&#44; it has a suppressive action on the differentiation of osteoclasts&#46;<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">10</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">CED is considered a rare disease with an estimated prevalence of one in a million inhabitants&#44; 200 patients have been identified in the world literature&#46; This pathology has a worldwide distribution based in the report of 24 families from America&#44; Europe&#44; Africa and Oceania&#46; The onset of the disease is in childhood and it usually progresses during the adolescence&#44; but in adulthood its course may be stationary or slowly progressive&#46; The clinical symptoms are present in 74&#37; of patients&#46;<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">11</span></a> The limping gait is an early manifestation but it is not the most frequent&#44; occurring in 43&#37;&#46; Progressive muscular atrophy and decreased subcutaneous fat in the limbs also can occur&#46; Easy fatigability is a symptom that has been described in 44&#37;&#46; The cardinal symptom of the disease is bone pain in the extremities in 90&#37; of cases&#46; The patients report that the pain increases with physical activity&#44; stress and cold&#46; Some patients have crises of pain of variable duration &#40;hours-weeks&#41;&#59; 58&#37; have pain to bone percussion&#46; Cranial affection occurs in 38&#37; of cases and can be manifested by atrophy of the optic nerve&#44; glaucoma&#44; subluxation of the eyeball&#44; sensorineural or conductive hearing loss in 15&#37;&#46;<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">12</span></a> The pathophysiology of this lesions is based on nerve compression or obstruction of the external auditory canal&#46; The sclerosis of the foramen magnum may cause hyperreflexia&#44; weakness&#44; paraparesis and even death&#46;<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">13</span></a> The increase in bone mineral density in the diaphyses may increase the risk of fracture with delayed consolidation&#46;<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">14</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">It has been described a typical disease phenotype characterized by craniomegaly with prominent forehead&#44; exophthalmos&#44; slender limbs with thick and curved bones&#44; marfanoid aspect&#44; flat and valgus feet&#44; lumbar lordosis and scoliosis&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">Hepatosplenomegaly&#44; Raynaud&#39;s phenomenon&#44; hyperhidrosis of the feet and hands&#44; and delayed dentition and puberty have been reported ocassionally&#46;<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">15</span></a> Anemia&#44; leukopenia&#44; increased alkaline phosphatase&#44; parathormone&#44; serum calcium&#44; phosphorus&#44; and erythrocyte sedimentation rate can be observed in the laboratory tests&#44; but is not the norm to find these alterations&#46;<a class="elsevierStyleCrossRefs" href="#bib0265"><span class="elsevierStyleSup">14&#44;16&#8211;19</span></a></p><p id="par0060" class="elsevierStylePara elsevierViewall">The diagnosis of the disease is based on the clinical symptoms and laboratory findings&#44; but is confirmed by the radiological images&#46; The characteristic radiological manifestations are fusiform thickening of the bone cortical&#46; CED has symmetrical affectation and involves both the endosteal and periosteal surfaces&#46; Initially begins in the diaphyses and it extends to the metaphyses&#44; sparing the epiphyses&#46;<a class="elsevierStyleCrossRefs" href="#bib0275"><span class="elsevierStyleSup">16&#44;20&#44;21</span></a> As a consequence it can be seen a narrowing of the medullary canal with a shape of an Erlenmeyer-flask&#46; The bones affected in order of frequency are&#58; femur&#44; tibia&#44; fibula&#44; humerus&#44; ulna and radius&#46; It can be seen an involvement of the mandible&#44; scapulae&#44; collarbones&#44; pelvis and the skull base&#46; There is rarely commitment of the carpal bones&#44; tarsal bones and phalanges&#46; The characteristic image of the long bones appears in 94&#37; of patients&#44; 63&#37; in the pelvis and 54&#37; in the skull&#46;<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">22</span></a></p><p id="par0065" class="elsevierStylePara elsevierViewall">Glucocorticoids are the cornerstone in the treatment of CED&#44; because they increase the apoptosis of the osteoblasts and osteocytes&#44; and also allow the proliferation and differentiation of the osteoclasts&#46;<a class="elsevierStyleCrossRefs" href="#bib0310"><span class="elsevierStyleSup">23&#44;24</span></a> Conversely&#44; it has been demonstrated that glucocorticoids increase the expression of TGF-&#946;&#44; a deleterious situation in these patients&#46;<a class="elsevierStyleCrossRef" href="#bib0320"><span class="elsevierStyleSup">25</span></a> Prednisolone 1<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#47;day followed by a rapid reduction in the dose in order to avoid side effects is used to control bone pain and fatigue&#46; Losartan is an anti-TGF-&#946; drug and it could be used in patients with arterial hypertension who are intolerant to glucocorticoids&#46;<a class="elsevierStyleCrossRef" href="#bib0325"><span class="elsevierStyleSup">26</span></a> Other drugs such as bisphosphonates have been used for the management of CED with disappointing results&#46;<a class="elsevierStyleCrossRef" href="#bib0330"><span class="elsevierStyleSup">27</span></a> Surgical treatment s reserved as a decompression mechanism for the external auditory canal&#46; Osteotomies and scrapings of the medullary canal have also been reported with recurrence in some cases&#46;<a class="elsevierStyleCrossRef" href="#bib0335"><span class="elsevierStyleSup">28</span></a></p><p id="par0070" class="elsevierStylePara elsevierViewall">In <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a> are described the main sclerosing bone diseases&#46; In the malignant infantile form of osteopetrosis the bones are dense and fragile&#46; There may be spontaneous bleeding with anemia and recurrent infections&#46; The neurological complications are blindness and deafness&#46; Patients usually die in the first decade of life&#46; The type II form occurs in adolescence and is manifested by fractures&#44; sometimes recurrent&#44; sandwich vertebrae and the bone-within-bone image in the iliac bone&#46; The compression of cranial nerves due to osteosclerosis is rare&#46;<a class="elsevierStyleCrossRef" href="#bib0340"><span class="elsevierStyleSup">29</span></a></p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0075" class="elsevierStylePara elsevierViewall">Pycnodysostosis manifests itself in childhood by short stature and a disproportionately large skull&#46; The hands are square with small fingers and pectus excavatum&#46; The recurrent fractures affect&#44; mainly&#44; the lower limbs&#46;<a class="elsevierStyleCrossRef" href="#bib0345"><span class="elsevierStyleSup">30</span></a></p><p id="par0080" class="elsevierStylePara elsevierViewall">Osteopoikilosis means spotted bones&#44; which are confused with bone metastases from prostate and breast cancer&#46;<a class="elsevierStyleCrossRef" href="#bib0350"><span class="elsevierStyleSup">31</span></a> It is incidentally found by the presence of circular lesions of osteosclerosis&#46; It affects the ends of the short bones&#44; and the metaphyses and epiphyses of the long bones&#46;<a class="elsevierStyleCrossRef" href="#bib0355"><span class="elsevierStyleSup">32</span></a> Sometimes is associated with disseminated lenticular dermatofibrosis&#46; The etiology of the disease is associated with mutations in the LEMD3 gene&#46;<a class="elsevierStyleCrossRef" href="#bib0360"><span class="elsevierStyleSup">33</span></a></p><p id="par0085" class="elsevierStylePara elsevierViewall">In Van Buchem disease there is an asymmetric enlargement of the jaw during puberty&#46; There are not fractures but it can be pain to the percussion of long bones&#46; Neurological alterations due to compression of cranial nerves are frequent&#46; The disease progresses with age&#44; and therefore&#44; is more common to see radiological findings in elderly patients&#46; In the form of sclerosteosis &#40;Truswell&#8211;Hansen disease&#41; the patients are tall and fat with syndactyly and nail dysplasia&#46; The hyperostosis is classically endosteal&#46; In Worth syndrome occur the same findings but it differs from the other 2 variants by the presence of an enlarged and pointed jaw with a widened forehead&#46;<a class="elsevierStyleCrossRef" href="#bib0365"><span class="elsevierStyleSup">34</span></a></p><p id="par0090" class="elsevierStylePara elsevierViewall">The presence of linear striations in the long bones is characteristic of the osteopathia striata&#59; and it can be seen cranial sclerosis with nerve palsy&#46;<a class="elsevierStyleCrossRef" href="#bib0370"><span class="elsevierStyleSup">35</span></a></p><p id="par0095" class="elsevierStylePara elsevierViewall">In the melorheostosis is seen an eccentric and irregular hyperostosis of the cortex and the medullary canal&#44; like the wax that trickles down the side of a candle&#46;<a class="elsevierStyleCrossRef" href="#bib0375"><span class="elsevierStyleSup">36</span></a></p><p id="par0100" class="elsevierStylePara elsevierViewall">In Kenny-Caffey disease there is intramembranous ossification&#46; The main radiological finding is the internal cortical thickening with lack of differentiation of the tables of the skull&#46; The main clinical findings are&#58; short stature&#44; mucosal paleness and microphthalmia&#46;<a class="elsevierStyleCrossRef" href="#bib0380"><span class="elsevierStyleSup">37</span></a></p><p id="par0105" class="elsevierStylePara elsevierViewall">Pyle&#39;s disease is characterized by widening of the metaphyses of the long bones called Erlenmeyer flask deformity&#44; with growth of the medial parts of the clavicles&#44; the ischium and the pubis&#46;<a class="elsevierStyleCrossRef" href="#bib0385"><span class="elsevierStyleSup">38</span></a></p><p id="par0110" class="elsevierStylePara elsevierViewall">Finally&#44; the low back pain that begins in adolescence is the clinical finding of the osteomesopycnosis&#44; due to sclerosis of the terminal plates&#46; It has been described a cystic lesion in the femoral diaphysis&#46; Other long bones or cranial bones have normal characteristics&#46;<a class="elsevierStyleCrossRef" href="#bib0390"><span class="elsevierStyleSup">39</span></a></p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Ethical disclosures</span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Protection of human and animal subjects</span><p id="par0115" class="elsevierStylePara elsevierViewall">The authors declare that no experiments were performed on humans or animals for this study&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Confidentiality of data</span><p id="par0120" class="elsevierStylePara elsevierViewall">The authors declare that no patient data appear in this article&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Right to privacy and informed consent</span><p id="par0125" class="elsevierStylePara elsevierViewall">The authors declare that no patient data appear in this article&#46;</p></span></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Conflict of interest</span><p id="par0130" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflict of interest&#46;</p></span></span>"
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        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Camurati&#8211;Engelmann disease is a rare entity due to mutations in the gene encoding the TGF-&#946;&#46; It is characterized by hyperostosis of long bones and skull&#44; accompanied by severe bone pain&#44; and occasionally muscular weakness and a waddling gait&#46; The treatment is based on the use of high doses of glucocorticoids&#44; and in severe cases surgical decompression is indicated&#46; As far as we know&#44; this is the first case reported in Colombia&#46;</p></span>"
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Article information

ISSN: 24444405
Original language: English

DOI:10.1016/j.rcreue.2016.06.004

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Year/Month	Html	Pdf	Total

2024 November	8	0	8
2024 October	50	9	59
2024 September	69	11	80
2024 August	45	12	57
2024 July	69	10	79
2024 June	66	10	76
2024 May	55	6	61
2024 April	80	8	88
2024 March	59	5	64
2024 February	65	12	77
2024 January	99	13	112
2023 December	68	10	78
2023 November	116	12	128
2023 October	111	13	124
2023 September	46	3	49
2023 August	43	6	49
2023 July	60	5	65
2023 June	66	6	72
2023 May	126	2	128
2023 April	110	2	112
2023 March	112	3	115
2023 February	93	8	101
2023 January	104	8	112
2022 December	99	7	106
2022 November	64	15	79
2022 October	47	13	60
2022 September	58	12	70
2022 August	59	16	75
2022 July	52	10	62
2022 June	62	10	72
2022 May	71	10	81
2022 April	90	15	105
2022 March	89	11	100
2022 February	97	10	107
2022 January	131	13	144
2021 December	74	9	83
2021 November	109	16	125
2021 October	114	19	133
2021 September	114	19	133
2021 August	79	14	93
2021 July	69	10	79
2021 June	73	8	81
2021 May	72	22	94
2021 April	140	29	169
2021 March	85	15	100
2021 February	99	16	115
2021 January	91	8	99
2020 December	88	16	104
2020 November	110	19	129
2020 October	57	11	68
2020 September	86	9	95
2020 August	104	13	117
2020 July	80	47	127
2020 June	49	14	63
2020 May	53	12	65
2020 April	53	6	59
2020 March	67	1	68
2020 February	77	8	85
2020 January	69	7	76
2019 December	72	8	80
2019 November	70	6	76
2019 October	65	4	69
2019 September	44	8	52
2019 August	39	1	40
2019 July	38	15	53
2019 June	120	20	140
2019 May	263	26	289
2019 April	87	39	126
2019 March	20	4	24
2019 February	37	14	51
2019 January	23	5	28
2018 December	11	2	13
2018 November	32	5	37
2018 October	34	6	40
2018 September	45	25	70
2018 August	32	7	39
2018 July	21	5	26
2018 June	38	12	50
2018 May	24	9	33
2018 April	16	3	19
2018 March	33	1	34
2018 February	11	1	12
2018 January	34	4	38
2017 December	15	0	15
2017 November	13	4	17
2017 October	18	4	22
2017 September	20	3	23
2017 August	19	5	24
2017 July	14	3	17
2017 June	34	12	46
2017 May	42	4	46
2017 April	43	3	46
2017 March	32	18	50
2017 February	18	10	28
2017 January	4	5	9
2016 December	4	5	9
2016 November	5	8	13
2016 October	10	7	17

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