RESUMEN
BACKGROUND: The role of bisphosphonates (BP) in hypertrophic osteoarthropathy (HPOA) is unclear. We presented a case of primary HPOA and performed a systematic review of literature on the effect of BP on treatment response in primary and secondary HPOA. METHODS: The study was prospectively registered in PROSPERO (CRD42022343786). We performed a PubMed literature search that restricted to the English language. We included patients diagnosed with primary or secondary HPOA who received BP. The primary endpoint assessed was the effectiveness of BP on response to pain or arthritis. Secondary outcomes included timing, degree, and duration of response, comparison to other HPOA therapies, impact of BP on radiology, bone scan, bone turnover markers, and adverse effects of BP. RESULTS: Literature search retrieved only case reports. Forty-five patients (21 primary, 24 secondary HPOA) had received BP. Majority(88.3%) experienced improvement in pain or arthritis. Response was gradual for primary HPOA and within a median of 3 to 7 days for secondary HPOA after treatment with BP. Most patients had reduced bone scan uptake after BP. When other HPOA therapies were tried, half responded to BP after not having previously responded to other therapies, while a third received the treatments concurrently, making it difficult to attribute treatment response to a drug. Reporting of other secondary outcomes was very heterogenous and qualitative to draw conclusions. No major adverse effects have been reported for BP in HPOA. CONCLUSION: Bisphosphonates provide an effective and safe treatment option for primary and secondary HPOA. However, there is a lack of randomized controlled trials.
Asunto(s)
Conservadores de la Densidad Ósea , Difosfonatos , Humanos , Difosfonatos/uso terapéutico , Conservadores de la Densidad Ósea/uso terapéutico , Osteoartropatía Hipertrófica Primaria/tratamiento farmacológico , Osteoartropatía Hipertrófica Secundaria/tratamiento farmacológico , Femenino , Resultado del TratamientoAsunto(s)
Anticuerpos Monoclonales Humanizados/uso terapéutico , Enfermedades de la Uña/tratamiento farmacológico , Osteoartropatía Hipertrófica Primaria/tratamiento farmacológico , Periostitis/tratamiento farmacológico , Anciano de 80 o más Años , Femenino , Humanos , Enfermedades de la Uña/etiología , Osteoartropatía Hipertrófica Primaria/etiología , Periostitis/etiología , Psoriasis/complicaciones , Inducción de RemisiónAsunto(s)
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
Pachydermoperiostosis is a rare genetic disorder which commonly presents with clubbing, bone pains and skin changes. The treatment is mostly unsatisfactory. We tried bisphosphonates in our case with encouraging results. We suggest that parenteral bisphosphonates should be tried early in treatment of Pachydermoperiostosis.
Asunto(s)
Difosfonatos/uso terapéutico , Osteoartropatía Hipertrófica Primaria/tratamiento farmacológico , Humanos , PielRESUMEN
BACKGROUND: Pachydermoperiostosis (PDP) is a rare disorder characterized by clubbing of the fingers, thickening of the skin (pachyderma), and excessive sweating (hyperhidrosis). It typically appears during childhood or adolescence, often around the time of puberty, and progresses slowly. Clinical presentations of PDP can be confused with secondary hypertrophic osteoarthropathy, psoriatic arthritis, rheumatoid arthritis, thyroid acropachy, and acromegaly. CASE PRESENTATION: A Mongolian male, aged 19 years, resident of a hilly district of Nepal, with history of consanguinity, presented to our outpatient department with chief complaints of pain and swelling in both hands and feet for 6 years. The pain was insidious in onset, throbbing in nature, and not relieved by over-the-counter medications. The patient also complained of profuse sweating, progressive enlargement of hands and feet, and gradual coarsening of facial features. On examination there were marked skin folds in the forehead, face, and eyelids. Clubbing and swelling of bilateral knee joints and ankle joints was also evident. He was subsequently investigated extensively for acromegaly. Insulin-like growth factor-1 level and oral glucose tolerance test were normal. Radiography of various bones showed periosteal hypertrophy with subperiosteal bone formation. CONCLUSIONS: PDP should be considered as a differential diagnosis when a patient presents with hypertrophic osteoarthropathy and acromegalic features.
Asunto(s)
Osteoartropatía Hipertrófica Primaria/diagnóstico por imagen , Osteoartropatía Hipertrófica Primaria/patología , Adulto , Antiinflamatorios/uso terapéutico , Huesos/diagnóstico por imagen , Huesos/patología , Inhibidores de la Ciclooxigenasa 2/uso terapéutico , Diagnóstico Diferencial , Humanos , Masculino , Nepal , Osteoartropatía Hipertrófica Primaria/tratamiento farmacológico , Prednisolona/uso terapéutico , Radiografía/métodos , Retinoides/uso terapéutico , Síndrome , Adulto JovenAsunto(s)
Inhibidores de la Ciclooxigenasa 2/uso terapéutico , Etoricoxib/uso terapéutico , Transportadores de Anión Orgánico/genética , Osteoartropatía Hipertrófica Primaria/tratamiento farmacológico , Adulto , Dinoprostona/antagonistas & inhibidores , Dinoprostona/metabolismo , Homocigoto , Humanos , Masculino , Mutación , Osteoartropatía Hipertrófica Primaria/genética , Osteoartropatía Hipertrófica Primaria/patología , Sitios de Empalme de ARN/genética , Resultado del TratamientoRESUMEN
Pachydermoperiostosis (PDP), otherwise known as primary hypertrophic osteoarthropathy, is characterized by digital clubbing, pachydermia and subperiosteal new bone formation. Joint pain, polyarthritis, cutis verticis gyrata, seborrhea, and hyperhidrosis are frequently associated to this condition. We report a 17-year-old boy presented with pain and swelling of knees and ankles, and progressive thickening of skin face with seborrhea from about 4 years. At the admission he also showed digital clubbing of both hands and feet and palmoplantar hyperhidrosis. We hypothesized PDP and molecular analysis confirmed diagnosis showing a novel mutation in a homozygous state in the SLCO2A1 gene coding for prostaglandin transporter. He started therapy with hydroxychloroquine with a great improvement in joint pain and skin conditions. This is the first reported case of PDP who was successfully treated with hydroxychloroquine, with effects not only on arthralgia but also, surprisingly, on skin conditions.
Asunto(s)
Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Homocigoto , Mutación , Transportadores de Anión Orgánico/genética , Osteoartropatía Hipertrófica Primaria/diagnóstico , Osteoartropatía Hipertrófica Primaria/genética , Fenotipo , Adolescente , Alelos , Sustitución de Aminoácidos , Huesos/anomalías , Huesos/diagnóstico por imagen , Exones , Estudios de Asociación Genética/métodos , Humanos , Hidroxicloroquina/uso terapéutico , Masculino , Osteoartropatía Hipertrófica Primaria/tratamiento farmacológico , Radiografía , Piel/patología , Resultado del TratamientoRESUMEN
BACKGROUND: Exophthalmos, myxedema, and osteoarthropathy syndrome is a very rare condition that is associated with Graves' disease. The presence of dermopathy and the involvement of joint/bone tissues indicate that it seems to be related with the severity of the autoimmune process. Owing to its low incidence, there is a lack of information regarding its treatment and clinical follow-up. Some cases improved after use of high doses of steroids; however, some patients do not respond to this treatment. Recently, the effectiveness of rituximab for treatment of Graves' ophthalmopathy resistant to corticosteroids has been demonstrated. However, it has never been used for the treatment of exophthalmos, myxedema, and osteoarthropathy syndrome (particularly for the treatment of osteoarticular manifestations). CASE PRESENTATION: We present the case of a 54-year-old Mexican woman previously treated for Graves' disease who developed post-iodine hypothyroidism and exophthalmos, myxedema, and osteoarthropathy that did not improve after high doses of steroids (intravenous and oral). Her exophthalmos, myxedema, and osteoarthropathy syndrome symptoms improved as early as 6 months after treatment with rituximab. CONCLUSION: Exophthalmos, myxedema, and osteoarthropathy syndrome is a non-classical presentation of Graves' disease, whose clinical manifestations could improve after treatment with rituximab, particularly in those patients with lack of response to high doses of corticosteroids.
Asunto(s)
Corticoesteroides , Exoftalmia/tratamiento farmacológico , Enfermedad de Graves/complicaciones , Mixedema/tratamiento farmacológico , Osteoartropatía Hipertrófica Primaria/tratamiento farmacológico , Rituximab/uso terapéutico , Antirreumáticos/uso terapéutico , Exoftalmia/etiología , Femenino , Enfermedad de Graves/tratamiento farmacológico , Humanos , Persona de Mediana Edad , Mixedema/etiología , Osteoartropatía Hipertrófica Primaria/etiología , SíndromeRESUMEN
BACKGROUND: Primary hypertrophic osteoarthropathy (PHO), also known as pachydermoperiostosis is a rare genetic disease which predominantly affects skin, bone and soft connective tissue. It is characterized by the triad of pachydermia, digital clubbing and periostosis of long bones. Arthralgia or arthritis is also present in most of the cases. Genetic studies have identified the impaired PGE2 metabolism as a culprit for hypertrophic osteoarthropathy in PHO cases. We conducted a systematic review to examine the effectiveness of Non-Steroidal Anti-Inflammatory Drugs (NSAIDs), a PGE2 synthesis blocker to reduce the symptoms among PHO patients. METHODS: We searched the evidence in five databases; Cochrane Library, CINAHL, EMBASE, MEDLINE, and PubMed. We reported the evidence using narrative synthesis. RESULTS: Out of 238 identified studies, we selected 26 for the synthesis. All were case reports which included a total of 54 patients. Among them, 39 patients were treated with at least one type of NSAIDs. Around 70% of the patients treated with NSAIDs had clinical improvement for their symptoms, mostly arthritis or arthralgia symptoms. CONCLUSION: NSAIDs were effective in improving arthralgia or arthritis symptoms in majority of the PHO patients. Therefore, we recommend the use of NSAIDs in PHO patients to treat arthralgia or arthritis.
Asunto(s)
Inhibidores de la Ciclooxigenasa/uso terapéutico , Dinoprostona/antagonistas & inhibidores , Osteoartropatía Hipertrófica Primaria/tratamiento farmacológico , Enfermedades Raras/tratamiento farmacológico , Dinoprostona/biosíntesis , Humanos , Osteoartropatía Hipertrófica Primaria/genética , Osteoartropatía Hipertrófica Primaria/patología , Enfermedades Raras/genética , Enfermedades Raras/patología , Resultado del TratamientoAsunto(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
Pachydermoperiostosis (PDP) is a rare inherited multisystem disease characterized with digital clubbing, pachydermia and periostosis. Variants in either HPGD or SLCO2A1 that interrupt the prostaglandin E2 (PGE2) pathway have been shown to be involved in PDP. Here, in addition to six confirmed variants in HPGD or SLCO2A1, we identified four novel SLCO2A1 variants in eight PDP patients from seven Chinese Han families. In addition, gastric mucosa hyperplasia was observed in all affected individuals and interleukin-6 (IL-6), tumor necrosis factor-alpha (TNFα) and receptor activator of nuclear factor kappa ligand (RANKL) expression were elevated in hypertrophic gastric mucosa. Two of eight patients who had severe arthralgia were treated with celecoxib. After three months, their arthralgia was partly relieved and IL-6, TNFα and RANKL expression were decreased in accordance with their relieved hypertrophic gastric mucosa. Our study broadens the variation spectrum of SLCO2A1 and suggests that the gastric mucosa hyperplasia might be a common characteristic of PDP. Moreover, celecoxib would be a considerable choice for PDP patients. We also revealed that IL-6, TNFα and RANKL may play important roles in the molecular mechanisms of gastric mucosa hyperplasia in PDP for the first time.
Asunto(s)
Mucosa Gástrica/metabolismo , Mucosa Gástrica/patología , Interleucina-6/metabolismo , Osteoartropatía Hipertrófica Primaria/metabolismo , Osteoartropatía Hipertrófica Primaria/patología , Ligando RANK/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Biomarcadores , Biopsia , Celecoxib/uso terapéutico , Análisis Mutacional de ADN , Humanos , Hipertrofia , Inmunohistoquímica , Interleucina-6/genética , Oxidorreductasas Intramoleculares/genética , Oxidorreductasas Intramoleculares/metabolismo , Masculino , Mutación , Transportadores de Anión Orgánico/genética , Transportadores de Anión Orgánico/metabolismo , Osteoartropatía Hipertrófica Primaria/tratamiento farmacológico , Osteoartropatía Hipertrófica Primaria/genética , Linaje , Fenotipo , Ligando RANK/genética , Factor de Necrosis Tumoral alfa/genéticaRESUMEN
Primary hypertrophic osteoarthropathy (PHO) is a rare inherited disease caused by genetic defects in the prostaglandin metabolism pathway; disturbed prostaglandin E2 (PGE2 ) catabolism resulting in increased PGE2 level is suggested in the pathogenesis. Forty-three Han Chinese patients with PHO were studied and 41 of them were treated. Mutations in the HPGD gene, causing hypertrophic osteoarthropathy, primary, autosomal recessive 1 (PHOAR1; OMIM 259100), were identified in seven patients, and mutations in the SLCO2A1 gene, causing hypertrophic osteoarthropathy, primary, autosomal recessive 2 (PHOAR2; OMIM 614441), were identified in 36 patients. Clinical phenotypes of PHO varied, ranging from mild isolated finger clubbing to severe pachydermia and disabling joint swelling, even within families. Circulating PGE2 metabolism features of PHOAR2 were different from those of PHOAR1. Different frequency and severity of pachydermia between the subgroups were also indicated. A percentage of PHOAR2 patients suffered from gastrointestinal hemorrhage, but this symptom was not observed in the PHOAR1 subgroup. Clinical evidence highlighted the essential role of sex hormones in prostaglandin transporter regulation with respect to PHOAR2 onset, although no significant associations of urinary PGE2 or PGE-M with sex hormones were identified. Treatment with etoricoxib, a selective cyclooxygenase-2 inhibitor, was proved to be beneficial and safe. We detected its notable efficacy in decreasing urinary PGE2 levels in the majority of the enrolled patients during 6 months of intervention; clinical phenotypes assessed, including pachydermia, finger clubbing, and joint swelling, were improved. We found no visible evidence of a positive effect of etoricoxib on periostosis; however, significant links between urinary PGE2 and serum bone turnover markers indicated a potential role of decreased PGE2 in periostosis management. This is the largest reported cohort of subjects genetically diagnosed with PHO. For the first time, we systematically investigated the biochemical and clinical differences between PHOAR1 and PHOAR2, and prospectively showed the positive efficacy and safety of etoricoxib for PHO patients. © 2017 American Society for Bone and Mineral Research.
Asunto(s)
Dinoprostona/orina , Transportadores de Anión Orgánico/genética , Osteoartropatía Hipertrófica Primaria , Piridinas/administración & dosificación , Sulfonas/administración & dosificación , Adulto , Pueblo Asiatico , China , Etoricoxib , Familia , Femenino , Humanos , Masculino , Persona de Mediana Edad , Osteoartropatía Hipertrófica Primaria/tratamiento farmacológico , Osteoartropatía Hipertrófica Primaria/genética , Osteoartropatía Hipertrófica Primaria/patología , Osteoartropatía Hipertrófica Primaria/orina , Estudios ProspectivosAsunto(s)
Osteoartropatía Hipertrófica Primaria/diagnóstico , Adulto , Analgésicos/uso terapéutico , Antiinflamatorios no Esteroideos/uso terapéutico , Diagnóstico Diferencial , Humanos , Masculino , Osteoartropatía Hipertrófica Primaria/diagnóstico por imagen , Osteoartropatía Hipertrófica Primaria/tratamiento farmacológico , RadiografíaAsunto(s)
Antiinflamatorios no Esteroideos/uso terapéutico , Progresión de la Enfermedad , Osteoartropatía Hipertrófica Primaria/diagnóstico , Osteoartropatía Hipertrófica Primaria/tratamiento farmacológico , Adolescente , Factores de Edad , Preescolar , Femenino , Humanos , Masculino , Pronóstico , Medición de Riesgo , Muestreo , Índice de Severidad de la Enfermedad , Factores Sexuales , Resultado del Tratamiento , Adulto JovenRESUMEN
Hypertrophic Osteoarthropathy secondary to various causes is not a common entity but primary hypertrophic osteoarthropathy (also called Touraine-Solente-Gole Syndrome) is an extremely rare genetic disorder. It was first described in 1868 by Friedrich and has premier features of clubbing, periostosis and pachydermia. Based on clinical manifestations Touraine Solente and Gole distinguished it into three forms as complete, incomplete and fruste form. Most of the cases described up till now had onset in late adolescence. This report describes two siblings having symptoms consistent with Touraine-Solente-Gole Syndrome which had onset in early childhood.
Asunto(s)
Dedos/patología , Osteoartropatía Hipertrófica Primaria/diagnóstico , Hermanos , Antiinflamatorios no Esteroideos , Niño , Femenino , Humanos , Masculino , Osteoartropatía Hipertrófica Primaria/tratamiento farmacológico , Osteoartropatía Hipertrófica Primaria/genéticaRESUMEN
This study presents the outcome of osteoporosis treatment in a 29-year-old male patient with full-blown Touraine-Solente-Gole syndrome. His first DXA densitometry of the proximal femur demonstrated severe osteoporosis (BMD 0.628 g/cm(2); T-score -3.84 SD, Z-score -3.37 SD). Bisphosphonate treatment (alendronate 70 mg once weekly) produced considerable clinical improvement during a 36-month follow-up. A follow-up densitometry showed a reduction of the osteoporotic indices (BMD 0.665 g/cm(2); T-score -3.54 SD, Z-score -2.93 SD). These findings indicate that it is necessary to treat osteoporosis in pachydermoperiostosis and prevent pathologic bone fractures in these patients.
Asunto(s)
Conservadores de la Densidad Ósea/uso terapéutico , Difosfonatos/uso terapéutico , Osteoartropatía Hipertrófica Primaria/diagnóstico , Osteoartropatía Hipertrófica Primaria/tratamiento farmacológico , Absorciometría de Fotón/métodos , Adulto , Densidad Ósea/efectos de los fármacos , Estudios de Seguimiento , Fracturas Óseas/prevención & control , Humanos , MasculinoRESUMEN
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.
Asunto(s)
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 TratamientoAsunto(s)
Gastritis Hipertrófica/complicaciones , Hernia Hiatal/complicaciones , Osteoartropatía Hipertrófica Primaria/complicaciones , Osteoartropatía Hipertrófica Primaria/diagnóstico , Adulto , Antiinflamatorios no Esteroideos/uso terapéutico , Humanos , Masculino , Osteoartropatía Hipertrófica Primaria/tratamiento farmacológico , Osteoartropatía Hipertrófica Primaria/patologíaRESUMEN
Pachydermoperiostosis (PDP) is a rare disorder of bone and connective tissue growth. A 21-year-old man was referred to our hospital with anemia. He showed characteristics of PDP. Bone marrow biopsy showed myelofibrosis. Chromosomal abnormalities or JAK2 mutation were not found. Anemia gradually progressed, and he became transfusion-dependent. Oral prednisolone was initiated; it gradually improved his anemia and rendered the patient free of transfusion. However, other clinical symptoms such as clubbed fingers and skin hypertrophy remained unimproved. In this case, the serum concentration of vascular endothelial growth factor and transforming growth factor-ß levels were increased. Further investigation will be necessary to establish appropriate treatment strategies for this disease.