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Hematopoyesis Extramedular , Osteoartropatía Hipertrófica Primaria/fisiopatología , Adulto , Médula Ósea/patología , Humanos , Hidroxiurea/uso terapéutico , Masculino , Osteoartropatía Hipertrófica Primaria/sangre , Osteoartropatía Hipertrófica Primaria/tratamiento farmacológico , Osteoartropatía Hipertrófica Primaria/patología , Prednisona/uso terapéuticoRESUMEN
15-Hydroxyprostaglandin dehydrogenase is NAD-dependent catalytic enzyme involved in prostaglandin biosynthesis pathway encoded by HPGD. The pathogenic variations in HPGD cause primary hypertrophic osteoarthropathy (PHO). The objective of the present study is to identify the genetic basis in patients with digital clubbing due to PHO. We performed detailed clinical and radiographic evaluation and exome sequencing in patients from three unrelated Indian families with PHO. Exome sequencing revealed two novel, c.34G>A (p.Gly12Ser) and c.313C>T (p.Gln105*) and a known variant, c.418G>C (p.Ala140Pro) in HPGD. Herein, we add three Indian families to HPGD mutation spectrum and review the literature on variants in this gene.
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Pie Equinovaro/genética , Hidroxiprostaglandina Deshidrogenasas/genética , Osteoartropatía Hipertrófica Primaria/genética , Adulto , Pueblo Asiatico , Niño , Preescolar , Pie Equinovaro/fisiopatología , Familia , Femenino , Humanos , Hidroxiprostaglandina Deshidrogenasas/metabolismo , India , Masculino , Mutación/genética , Mutación Missense/genética , Osteoartropatía Hipertrófica Primaria/fisiopatología , LinajeRESUMEN
Pachydermoperiostosis is a rare condition representing a primary form of hypertrophic osteoarthropathy. It presents in different stages. Patients often overlook early symptoms, because they are benign. The most common manifestations are clubbing of the fingers and toes, skin thickening with characteristic folds on the face and head and widening of joints accompanied by radiological changes. Surgical treatment is not often needed, and, consequently, there are no strict guidelines on surgical management, which is mainly based on case report ana-lysis. This paper presents a case of surgical management of pachydermoperiostosis.
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Pie/fisiopatología , Marcha , Osteoartropatía Hipertrófica Primaria/fisiopatología , Osteoartropatía Hipertrófica Primaria/cirugía , Adulto , Artrodesis , Humanos , Masculino , Articulación Metatarsofalángica/diagnóstico por imagen , Articulación Metatarsofalángica/fisiopatología , Articulación Metatarsofalángica/cirugía , Osteoartropatía Hipertrófica Primaria/diagnóstico por imagen , RadiografíaAsunto(s)
Anamnesis , Osteoartropatía Hipertrófica Primaria/diagnóstico , Espera Vigilante , Adolescente , Predisposición Genética a la Enfermedad , Humanos , Hierro de la Dieta/uso terapéutico , Masculino , Osteoartropatía Hipertrófica Primaria/fisiopatología , Pronóstico , Vitamina D/uso terapéutico , Vitaminas/uso terapéuticoRESUMEN
BACKGROUND: Primary hypertrophic osteoarthropathy also known as pachydermoperiostosis is a rare genetic disorder that has often been confused with acromegaly because of similar clinical features. Vascular endothelial growth factors which have been implicated in the clinical features of pachydermoperiostosis, have also been shown to be present in chronic hepatitis and implicated in the malignant transformation of hepatitis B infection to hepatocellular carcinoma. To the best of our knowledge there is one reported case of pachydermoperiostosis with chronic hepatitis B infection. We do not imply a causal relationship between pachydermoperiostosis and hepatitis B infection because pachydermoperiostosis is a genetic disorder; however, the question is raised whether hypertrophic osteoarthropathy is one of the many extrahepatic manifestations of chronic hepatitis B infection. CASE PRESENTATION: A 21-year-old African (Ghanaian) man with chronic hepatitis B infection was referred to our Endocrine unit as having acromegaly with changing facial features, enlarging hands and feet, and large knee joint effusions which affected activities of daily living. He was finally diagnosed as having pachydermoperiostosis when acromegaly, rheumatological disorders, as well as cardiopulmonary disorders were ruled out. He improved with arthrocentesis, a tapering regime of steroids, non-steroidal anti-inflammatory drugs, and proton pump inhibitors. CONCLUSIONS: The possible role of hepatitis B in hypertrophic osteoarthropathy, that is, secondary hypertrophic osteoarthropathy, needs to be explored; however, with digital clubbing in his father our patient is likely to have pachydermoperiostosis.
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Acromegalia/diagnóstico , Actividades Cotidianas/psicología , Depresión/diagnóstico , Cara/anomalías , Hepatitis B Crónica/diagnóstico , Osteoartropatía Hipertrófica Primaria/diagnóstico , Estigma Social , Antiinflamatorios no Esteroideos/uso terapéutico , Diagnóstico Diferencial , Cara/patología , Deformidades Congénitas del Pie , Deformidades Congénitas de la Mano , Humanos , Masculino , Osteoartropatía Hipertrófica Primaria/fisiopatología , Osteoartropatía Hipertrófica Primaria/psicología , Osteoartropatía Hipertrófica Primaria/terapia , Modalidades de Fisioterapia , Inhibidores de la Bomba de Protones/uso terapéutico , Radiografía , Esteroides/uso terapéutico , Resultado del Tratamiento , Adulto JovenAsunto(s)
Etoricoxib/administración & dosificación , Articulaciones del Pie , Articulaciones de la Mano , Transportadores de Anión Orgánico/genética , Osteoartropatía Hipertrófica Primaria , Antiinflamatorios no Esteroideos/administración & dosificación , Diagnóstico Diferencial , Articulaciones del Pie/diagnóstico por imagen , Articulaciones del Pie/patología , Articulaciones de la Mano/diagnóstico por imagen , Articulaciones de la Mano/patología , Humanos , Masculino , Mutación , Osteoartropatía Hipertrófica Primaria/diagnóstico , Osteoartropatía Hipertrófica Primaria/tratamiento farmacológico , Osteoartropatía Hipertrófica Primaria/genética , Osteoartropatía Hipertrófica Primaria/fisiopatología , Tomografía Computarizada de Emisión de Fotón Único/métodos , Resultado del Tratamiento , Adulto JovenRESUMEN
Among proposed mechanisms to explain digital clubbing, the release of cytokines, specifically vascular endothelial growth factor and platelet-derived growth factor, from aggregated platelets and megakaryocytes has emerged as the most likely explanation. This review describes these and other contributory processes.
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Citocinas/metabolismo , Hemiplejía/fisiopatología , Hipoxia/fisiopatología , Péptidos y Proteínas de Señalización Intercelular/metabolismo , Osteoartropatía Hipertrófica Primaria/fisiopatología , Osteoartropatía Hipertrófica Secundaria/fisiopatología , Bradiquinina/metabolismo , Factor de Crecimiento Epidérmico/metabolismo , Ferritinas/metabolismo , Hemiplejía/complicaciones , Hemiplejía/metabolismo , Factor de Crecimiento de Hepatocito/metabolismo , Hormona de Crecimiento Humana/metabolismo , Humanos , Hipoxia/complicaciones , Hipoxia/metabolismo , Interleucina-6/metabolismo , Osteoartropatía Hipertrófica Primaria/metabolismo , Osteoartropatía Hipertrófica Secundaria/etiología , Osteoartropatía Hipertrófica Secundaria/metabolismo , Factor de Crecimiento Derivado de Plaquetas/metabolismo , Prostaglandinas/metabolismo , Serotonina/metabolismo , Factor de Crecimiento Transformador beta1/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismo , Factor de von Willebrand/metabolismoRESUMEN
BACKGROUND: Digital clubbing and hypertrophic osteoarthropathy (HOA) form a diagnostic challenge. Subtle presentations of clubbing are often missed. The underlying pathophysiology remains unclear. Establishing a differential diagnosis based on nonspecific signs can be cumbersome. Finally, the prognostic value of clubbing and HOA remains unclear. OBJECTIVE: This article reviews clinical criteria and pathophysiology of clubbing and HOA. A diagnostic algorithm is proposed, based on etiology and current insights. The prognostic impact on associated diseases is discussed. METHODS: The Internet databases Medline and Embase were searched. Articles were selected based on relevance of abstract, article type and impact of the journal. RESULTS: Diagnostic criteria include Lovibond's profile sign, distal/interphalangeal depth ratio and Schamroth's sign. Three pathophysiological causes of clubbing can be distinguished: hypoxia, chronic inflammation and aberrant vascularization. A prominent role for vascular endothelial growth factor is suggested. Associated symptoms and clinical signs should guide the initial diagnostic evaluation. Finally, clubbing is a negative prognostic factor in certain pulmonary disorders, including cystic fibrosis.
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Osteoartropatía Hipertrófica Primaria , Osteoartropatía Hipertrófica Secundaria , Humanos , Osteoartropatía Hipertrófica Primaria/diagnóstico , Osteoartropatía Hipertrófica Primaria/patología , Osteoartropatía Hipertrófica Primaria/fisiopatología , Osteoartropatía Hipertrófica Secundaria/diagnóstico , Osteoartropatía Hipertrófica Secundaria/patología , Osteoartropatía Hipertrófica Secundaria/fisiopatología , PronósticoAsunto(s)
Predisposición Genética a la Enfermedad , Mano/diagnóstico por imagen , Osteoartropatía Hipertrófica Primaria/genética , Adulto , Mano/patología , Humanos , Masculino , Monitoreo Fisiológico , Osteoartropatía Hipertrófica Primaria/diagnóstico por imagen , Osteoartropatía Hipertrófica Primaria/fisiopatología , Osteoartropatía Hipertrófica Primaria/terapia , Pronóstico , Radiografía , Enfermedades Raras , Medición de Riesgo , Índice de Severidad de la EnfermedadAsunto(s)
Tetralogía de Fallot/fisiopatología , Procedimientos Quirúrgicos Cardíacos , Cianosis/fisiopatología , Ecocardiografía , Electrocardiografía , Femenino , Humanos , Lactante , Recién Nacido , Edad Materna , Osteoartropatía Hipertrófica Primaria/fisiopatología , Embarazo , Complicaciones Infecciosas del Embarazo/epidemiología , Pronóstico , Radiografía Torácica , Factores de Riesgo , Taquipnea/fisiopatología , Tetralogía de Fallot/diagnóstico , Tetralogía de Fallot/epidemiología , Tetralogía de Fallot/cirugía , Virosis/epidemiologíaAsunto(s)
Osteoartropatía Hipertrófica Primaria/diagnóstico , Bronquiectasia/complicaciones , Fibrosis Quística/complicaciones , Dedos/patología , Dedos/fisiopatología , Humanos , Osteoartropatía Hipertrófica Primaria/etiología , Osteoartropatía Hipertrófica Primaria/patología , Osteoartropatía Hipertrófica Primaria/fisiopatología , Fibrosis Pulmonar/complicacionesRESUMEN
This article presents an updated overview of hypertrophic osteoarthropathy and digital clubbing for the practicing rheumatologist. Discussion includes a brief historical perspective, its definition, incidence and prevalence, classification, pathology and pathophysiology, clinical manifestations, demographics, findings on physical examination, imaging techniques for its detection, differential diagnosis, and treatment modalities.
Asunto(s)
Osteoartropatía Hipertrófica Primaria , Osteoartropatía Hipertrófica Secundaria , Reumatología/métodos , Diagnóstico Diferencial , Manejo de la Enfermedad , Humanos , Osteoartropatía Hipertrófica Primaria/diagnóstico , Osteoartropatía Hipertrófica Primaria/epidemiología , Osteoartropatía Hipertrófica Primaria/fisiopatología , Osteoartropatía Hipertrófica Primaria/terapia , Osteoartropatía Hipertrófica Secundaria/diagnóstico , Osteoartropatía Hipertrófica Secundaria/epidemiología , Osteoartropatía Hipertrófica Secundaria/fisiopatología , Osteoartropatía Hipertrófica Secundaria/terapiaRESUMEN
CONTEXT: We previously demonstrated that deficiency of the prostaglandin transporter (SLCO2A1) is a cause of primary hypertrophic osteoarthropathy (PHO). However, its clinical and metabolic characteristics have not been well defined. OBJECTIVE: The objective of the study was to expand this mutational spectrum to better delineate the SLCO2A1 deficiency phenotype and investigate the clinical and metabolic characteristics of a cohort of subjects with PHO. DESIGN, SETTING, PATIENTS, AND MAIN OUTCOME MEASURE: Eleven affected individuals and their available healthy family members from 9 unrelated Chinese families with PHO (7 of which were previously undescribed) were clinically studied. The SLCO2A1 gene was screened and analyzed. Urinary levels of prostaglandin E2 (PGE2) and prostaglandin E metabolite (PGE-M) were measured using competitive ELISAs. The serum levels of total T, estradiol, sex hormone-binding protein, LH, FSH, and fasting gastrin were detected. RESULTS: Nine different SLCO2A1 mutations were identified in affected individuals in the 7 previously undescribed families, 7 of which (Glu165X, Ala286GlnfsX35, Gln356AlafsX77, Gly369Asp, Gly379Glu, Glu465Lys, and c.861+2T>C) were novel. The urinary levels of PGE2 and PGE-M were much higher in the SLCO2A1-deficient individuals and decreased with age. There was no relationship between sex hormones and PGE2 or PGE-M. There was no significant difference in the levels of fasting serum gastrin between PHO patients with watery diarrhea and their relatives. CONCLUSIONS: The present findings broaden the allelic spectrum of SLCO2A1 mutations. The urinary levels of PGE2 and PGE-M in the SLCO2A1-deficient individuals decreased with age. The measurement of the excreted PGE2 and PGE-M may have implications in the differential diagnosis, treatment, and follow-up of PHO.
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Mutación , Transportadores de Anión Orgánico/genética , Osteoartropatía Hipertrófica Primaria/genética , Adolescente , Adulto , Factores de Edad , Secuencia de Aminoácidos , China , Estudios de Cohortes , Análisis Mutacional de ADN , Dinoprostona/orina , Salud de la Familia , Femenino , Estudios de Asociación Genética , Humanos , Masculino , Datos de Secuencia Molecular , Transportadores de Anión Orgánico/química , Transportadores de Anión Orgánico/metabolismo , Osteoartropatía Hipertrófica Primaria/metabolismo , Osteoartropatía Hipertrófica Primaria/fisiopatología , Osteoartropatía Hipertrófica Primaria/orina , Linaje , Prostaglandinas/orina , Estructura Secundaria de Proteína , Alineación de Secuencia , Adulto JovenRESUMEN
Digital clubbing, which has been recognized as a sign of systemic disease, is one of the most ancient diseases. However, the pathogenesis of clubbing and hypertrophic osteoarthropathy has hitherto been poorly understood. The study of a clinically indistinguishable idiopathic form (primary hypertrophic osteoarthropathy, PHO) provides an opportunity to understand the pathogenesis of hypertrophic osteoarthropathy. Current advances in the study of PHO are discussed. The impaired metabolism of prostaglandin E2 (PGE2) plays a central role in its pathogenesis.
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Antiinflamatorios no Esteroideos/uso terapéutico , Dinoprostona/metabolismo , Osteoartropatía Hipertrófica Primaria , Osteoartropatía Hipertrófica Secundaria , Diagnóstico Diferencial , Glucocorticoides/uso terapéutico , Humanos , Osteoartropatía Hipertrófica Primaria/complicaciones , Osteoartropatía Hipertrófica Primaria/diagnóstico , Osteoartropatía Hipertrófica Primaria/tratamiento farmacológico , Osteoartropatía Hipertrófica Primaria/metabolismo , Osteoartropatía Hipertrófica Primaria/fisiopatología , Osteoartropatía Hipertrófica Secundaria/diagnóstico , Osteoartropatía Hipertrófica Secundaria/etiología , Osteoartropatía Hipertrófica Secundaria/metabolismo , Osteoartropatía Hipertrófica Secundaria/fisiopatología , Osteogénesis , Resultado del TratamientoRESUMEN
A 25-year-old man presented with Touraine-Solente-Golé syndrome (primary pachydermoperiostosis), with an area of inflammatory dermatosis (12-month evolution) of the scalp at the cranial vertex. The patient presented with arthropathy, clubbing of the digits, diffuse periostosis, pachydermia of the hands and feet, and periosteal hyperostosis of the knee. Facial seborrhea and sebaceous gland hyperplasia were evident (Figure 1A and 1B and Figure 2A and 2B). Examination of the scalp revealed an erythematous pruritic plaque with erosions, crusts, and pustules, on which multiple tufts of 10 to 20 normal-looking hairs emerged from single follicular openings (Figure 3A). Slight pressure on the perifollicular areas resulted in the discharge of purulent material through the dilated follicular openings. Cervical and occipital lymph nodes were not enlarged, and the patient was in generally good health. Routine laboratory findings were normal. Immunologic studies, including a screening for antinuclear antibody, complement, and immunoglobulins, were normal. Both potassium hydroxide staining and fungal culture were negative. Bacteriologic culture of purulent material taken from the affected area was positive for Staphylococcus aureus. Videodermoscopy of the lesion showed rarefied interfollicular twisted red loops centered around actively affected follicles and white dots with absence of normal vascular pattern (Figure 3B). These dermoscopy patterns are markers for folliculitis decalvans, of which tufted hair folliculitis (THF) is a clinical variant. Histologic examination showed hair plugging, a dense perifollicular infiltrate of plasma cells, lymphocytes, neutrophils, and large areas of scarring and fibrosis, which would confirm suspected THE THF was diagnosed on the grounds of clinical, microbiologic, histologic, and videodermoscopy data. The patient was treated with amoxicillin 875 mg plus clavulanic acid 125 mg twice daily and topical nadifloxacin 1% twice daily for 20 days, achieving substantial clinical improvement. One month after antimicrobial therapy, a single area of cicatricial alopecia with a few hair tufts emerging from single orifices was observed, and no new lesions or symptoms had appeared.
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Foliculitis/diagnóstico , Osteoartropatía Hipertrófica Primaria/complicaciones , Infecciones Estafilocócicas/diagnóstico , Adulto , Combinación Amoxicilina-Clavulanato de Potasio/uso terapéutico , Antibacterianos/uso terapéutico , Dermoscopía/métodos , Fluoroquinolonas/uso terapéutico , Foliculitis/tratamiento farmacológico , Foliculitis/microbiología , Humanos , Masculino , Microscopía por Video/métodos , Osteoartropatía Hipertrófica Primaria/fisiopatología , Quinolizinas/uso terapéutico , Infecciones Estafilocócicas/tratamiento farmacológico , Infecciones Estafilocócicas/microbiología , Staphylococcus aureus/aislamiento & purificación , Resultado del TratamientoAsunto(s)
Extremidad Inferior/patología , Osteoartropatía Hipertrófica Primaria/diagnóstico , Prótesis Vascular/efectos adversos , Prótesis Vascular/microbiología , Humanos , Extremidad Inferior/fisiopatología , Masculino , Persona de Mediana Edad , Osteoartropatía Hipertrófica Primaria/etiología , Osteoartropatía Hipertrófica Primaria/patología , Osteoartropatía Hipertrófica Primaria/fisiopatología , Falla de Prótesis/efectos adversos , Infecciones Relacionadas con Prótesis/complicaciones , Infecciones Relacionadas con Prótesis/microbiología , Choque Séptico/complicaciones , Choque Séptico/etiologíaRESUMEN
OBJECTIVE: Homozygous recessive germline mutations of the 15-hydroxyprostaglandin dehydrogenase (HPGD) gene, encoding 15-hydroxyprostaglandin dehydrogenase, result in persistent elevation of circulating PGE(2) levels, causing the syndrome of primary hypertrophic osteoarthropathy (PHO). Homozygous HPGD mutations have so far been reported in 10 families, all but one displaying parental consanguinity. Only two of these families were of European origin. We wished to determine the role of HPGD in causing PHO in non-consanguineous European families. METHODS: Five previously unreported families of Caucasian European origin, with one or more individuals affected with typical PHO, were characterized clinically and by complete sequencing of the HPGD coding exons. RESULTS: Biallelic HPGD mutations were identified in affected individuals in all the five families, confirming a very specific association of this phenotype with HPGD mutations. The previously described c.175_176delCT frameshift mutation was observed in association with two different alleles of an adjacent single nucleotide polymorphism. CONCLUSIONS: Biallelic HPGD mutations are found in the majority of patients with typical PHO, and sequencing of the HPGD gene is a highly specific first-line investigation for patients presenting in this way, particularly during childhood. The c.175_176delCT frameshift mutation appears to be recurrent and to be the commonest HPGD mutation in Caucasian families.
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Hidroxiprostaglandina Deshidrogenasas/genética , Mutación , Osteoartropatía Hipertrófica Primaria/genética , Población Blanca/genética , Adolescente , Adulto , Niño , Preescolar , Consanguinidad , Femenino , Predisposición Genética a la Enfermedad/genética , Humanos , Lactante , Recién Nacido , Masculino , Osteoartropatía Hipertrófica Primaria/fisiopatología , Linaje , Fenotipo , Adulto JovenRESUMEN
Primary hypertrophic osteoarthropathy, or pachydermoperiostosis (PDP), is an infrequent genetic condition characterized by digital clubbing, periostosis, and pachydermia and is distinct from a more common form, secondary hypertrophic osteoarthropathy, which always associates with an underlying cause (frequently pulmonary or cardiac disease). The diagnosis of this disorder as well as its clinical evaluation can be difficult. We report a 15-year-old boy presenting with intermittent arthralgias and clubbing of fingers and toes for the previous 2 years. The ankles and knees were enlarged, and X-rays showed periosteal apposition. The search for a secondary cause was negative. The skin appearance was normal, but a skin biopsy was indicative of pachydermia, further confirming the diagnosis of PDP. Bone turnover markers were increased at diagnosis and progressively decreased during follow-up; prostaglandin E(2), a recently implicated mediator of this disorder, was markedly elevated. In the present case, carrying out a skin biopsy helped us to diagnose this condition. In addition, bone turnover markers were useful for monitoring the disease activity; whereas, increased prostaglandin E(2) levels seems to confirm the role of this mediator in the etiopathogenesis of this disorder.
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Huesos/metabolismo , Dinoprostona/sangre , Osteoartropatía Hipertrófica Primaria/diagnóstico , Osteoartropatía Hipertrófica Primaria/metabolismo , Adolescente , Fosfatasa Alcalina/sangre , Biomarcadores/sangre , Biopsia , Resorción Ósea/fisiopatología , Colágeno Tipo I/sangre , Humanos , Masculino , Osteoartropatía Hipertrófica Primaria/fisiopatología , Osteocalcina/sangre , Osteogénesis/fisiología , Fragmentos de Péptidos/sangre , Péptidos/sangre , Procolágeno/sangre , Piel/patologíaRESUMEN
PURPOSE OF REVIEW: The review seeks to update advances on the pathogenesis of hypertrophic osteoarthropathy, describe a previously unrecognized palindrome that occurs in hypertrophic osteoarthropathy and that may have pathogenic implications, and review the role of bisphosphonates in the treatment of this condition. RECENT FINDINGS: Some patients with primary hypertrophic osteoarthropathy display an interesting palindrome. Many years after the onset of the osteoarthropathy, they develop diseases that in other circumstances are known to generate secondary hypertrophic osteoarthropathy. This palindrome has been reported in cases of patent ductus arteriosus, Crohn's disease and myelofibrosis. Additionally, primary hypertrophic osteoarthropathy and POEMS syndrome share important clinical features. The many diseases associated with hypertrophic osteoarthropathy have in common abnormal production of vascular endothelial growth factor. This cytokine has been proposed to play a major role in the pathogenesis of Crohn's disease, myelofibrosis and POEMS syndrome. A controlled study showed that vascular endothelial growth factor is abnormally expressed in cases of hypertrophic osteoarthropathy. The biologic effects of vascular endothelial growth factor may explain hypertrophic osteoarthropathy histological features. Several isolated reports suggest that pamidronate is effective in relieving painful osteoarthropathy. SUMMARY: Hypertrophic osteoarthropathy is a palindromic syndrome. Anomalous vascular endothelial growth factor expression may explain this phenomenon. Bisphosphonates may have a role in the symptomatic treatment of hypertrophic osteoarthropathy.