Bisphosphonates use in Pachydermoperiostosis.

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.

Pachydermoperiostosis (Touraine-Solente-Gole syndrome): a case report.

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.

A novel homozygous mutation in the SLCO2A1 gene causing pachydermoperiostosis: Efficacy of hydroxychloroquine treatment.

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.

Utility of rituximab treatment for exophthalmos, myxedema, and osteoarthropathy syndrome resistant to corticosteroids due to Graves' disease: a case report.

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.

Effectiveness of non-steroidal anti-inflammatory drugs among patients with primary hypertrophic osteoarthropathy: A systematic review.

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.

Interleukin-6, tumor necrosis factor-alpha and receptor activator of nuclear factor kappa ligand are elevated in hypertrophic gastric mucosa of pachydermoperiostosis.

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.

Clinical, Biochemical, and Genetic Features of 41 Han Chinese Families With Primary Hypertrophic Osteoarthropathy, and Their Therapeutic Response to Etoricoxib: Results From a Six-Month Prospective Clinical Intervention.

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.

Osteoartropatía hipertrófica y enfermedad de Hodgkin / Hypertrophic osteoarthropathy and Hodgkin's disease

No disponible

Touraine-Solente-Gole syndrome in two siblings.

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.

Evaluation of effectiveness of osteoporosis treatment in patient with pachydermoperiostosis according to densitometric findings. Case study.

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.

Primary hypertrophic osteoarthropathy: an update.

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.

Myelofibrosis successfully treated with prednisolone in a patient with pachydermoperiostosis.

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.