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.

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.

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.

Infliximab treatment in pachydermoperiostosis: a rare disease without an effective therapeutic option.

Hypertrophic osteoarthropathy (HOA) is characterized by periostitis of tubular bones, thickened skin, and digital clubbing. Its pathogenesis is unknown but an inflammatory factor and increased bone remodeling have been implicated. It is a very rare disease, usually diagnosed late with few therapeutic options. Bone and joint pains are secondary to periostitis and are usually difficult to control. Tumor necrosis factor-alpha is a cytokine that induces other inflammatory cytokine production, has an osteoclastogenic effect in different rheumatic diseases and probably also has an important role in periostitis and the systemic inflammatory manifestations in HOA. We describe the case of a patient with the primary form of HOA, who had refractory bone pain and arthritis that responded partially to infliximab treatment.

A case of pachydermoperiostosis treated by oral administration of a bisphosphonate and arthroscopic synovectomy.

Pachydermoperiostosis (PDP) is a rare hereditary disorder characterized by pachydermia, digital clubbing, and periosteal hypertrophy. Here, we report a case of PDP showing symptoms consistent with arthritis, which was treated by oral administration of risedronate sodium and arthroscopic synovectomy.

Primary hypertrophic osteoarthropathy (pachydermoperiostosis): a case report.

Hypertrophic osteoarthropathy is characterized by digital clubbing and periosteal reaction of long bones. Most cases are associated with malignancy or other conditions such as congenital heart disease, liver cirrhosis, pulmonary fibrosis, biliary atresia, and gastrointestinal polyps. We report a 19-year-old man presenting with arthritis, broadening of the fingers and clubbing of the fingers and toes for the previous 3 years. The ankles and knees were swollen. X-rays showed periosteal apposition. The search for a secondary cause remained negative. In cases of arthralgia/arthritis together with clubbed fingers, consideration must be given to hypertrophic osteoarthropathy. The primary or idiopathic form is rare and has a good prognosis.

Paquidermoperiostose: relato de caso / Pachydermoperiostosis: case report

A paquidermoperiostose, forma primária da osteoartropatia hipertrófica, é doença rara de etiologia desconhecida e incidência familiar, caracterizada por periostose de ossos longos e alterações hipertróficas da pele. As manifestações articulares ocorrem em 30% a 40% dos casos e podem ser a principal queixa do paciente. Neste artigo, é relatado o caso de paciente jovem, do sexo masculino, encaminhado ao reumatologista com dor e derrame em joelhos e tornozelos. Foram observadas ainda acne na face, acentuação das pregas cutâneas na região frontal, ptose bipalpebral, alongamento dos dedos das mãos e baqueteamento digital. As radiografias dos ossos longos dos membros superiores e inferiores evidenciaram periostose. Iniciou-se piroxican 20mg/dia, com melhora das manifestações articulares, entretanto essa medicação foi suspensa devido a hemorragia digestiva alta. Prescreveu-se, então, prednisona 10 mg/dia, com boa resposta.

Pachydermoperiostosis or primary hypertrophic osteoarthropathy is a rare disease of unknown etiology with a familial incidence. It is characterized by periostosis of long bones and hypertrophic skin changes. Joint manifestations occur in 30 to 40% of cases and may be the main complaint. A case of a young male patient, referred to a rheumatologist with pain and effusion of the knees and ankles, is described. Coarse facial features, acne, ptosis of the eyelids, and digital clubbing were also observed. Periostosis of the appendicular bones were demonstrated by x-rays. Joint manifestations were successfullv treated with Piroxican, 20 mg, daily, but the occurrence of high digestive hemorrhage required the interruption of this medication. Prednisone, 10 mg, daily, was then administered with positive response.

[Psoriatic onycho-pachydermo- periostitis]. / Psoriatische Onycho-Pachydermo-Periostitis.

BACKGROUND: Psoriatic onycho-pachydermo-periostitis is a rare manifestation of psoriatic arthritis. It is characterized by the trias of psoriatic onychosis, tender soft tissue thickening, and osteoperiostitis of the distal phalanges in the absence of distal interphalangeal arthritis. Recommendations for the treatment of symptomatic POPP are not available. AIM OF THE STUDY: Treatment of a symptomatic 49-year old male. METHODS: Sulfasalazine 1000mg b.i.d., p.o. for 8 months followed by radiotherapy of both hands with 6x0.5 Gy. RESULTS: No clinical response was observed with either of the two treatments. CONCLUSIONS: The course of this single case does not support sulfasalazine treatment or radiotherapy in psoriatic onycho-pachydermo-periostitis.

Hypertrophic osteoarthropathy can indicate recurrence of Whipple's disease.

We report the case of a patient with Whipple's disease (WD) who developed hypertrophic osteoarthropathy (HOA) characterized by digital clubbing, periostosis of the tubular bones, and polysynovitis. The HOA disclosed the recurrence of the patient's WD, since polymerase chain reaction (PCR) analysis clearly demonstrated the presence of Tropheryma whippelii in the synovial fluid from the patient's left knee. Initiation of appropriate antibiotic therapy resulted in complete healing of all clinical rheumatologic manifestations within 2 months and in disappearance of radiographic bone changes at 7-month followup. We suggest that HOA be included within the spectrum of rheumatologic manifestations of WD, and that an evaluation for WD should be considered in patients, especially middle-aged men, presenting with HOA even without gastrointestinal symptoms. PCR analysis may be useful in accurate diagnosis and management of early WD with unusual clinical manifestations, and may contribute to decreased morbidity and mortality.

The medical and surgical treatment of finger clubbing and hypertrophic osteoarthropathy. A blind study with colchicine and a surgical approach to finger clubbing reduction.

In fourteen patients affected with pachydermoperiostosis (PDP), or primary hypertrophic osteoarthropathy, the efficacy of colchicine (0.5 mg day for one month) versus placebo on the main clinical features of the disease (finger clubbing, arthritis and pachydermia) was evaluated. In addition, in one patient the usefulness of surgical reduction of clubbed fingertips was investigated. Colchicine did not demonstrate any appreciable effect on finger clubbing (expressed in degrees) or pachydermia, while an effect on arthralgia (as evaluated by the Ritchie Index and Pain Scale) was observed. The surgical treatment of clubbed fingertips failed to show a satisfactory and stable reduction of the fingertips; two months after surgery the nail matrix apparently produced new tissue, once again enlarging and deforming the finger. These results suggest that low dose colchicine cannot be considered the drug of first choice for the treatment of PDP, while higher dosages, although effective, are not tolerated because of the severe side effects. An effective medical and surgical treatment for PDP will be found only when the pathogenetic mechanisms of the disease are clarified.