Primary hypertrophic osteoarthropathy: genetics, clinical features and management.

Primary hypertrophic osteoarthropathy (PHO) is a genetic disorder mainly characterized by clubbing fingers, pachydermia and periostosis. Mutations in the HPGD or SLCO2A1 gene lead to impaired prostaglandin E2 (PGE2) degradation, thus elevating PGE2 levels. The identification of the causative genes has provided a better understanding of the underlying mechanisms. PHO can be divided into three subtypes according to its pathogenic gene and inheritance patterns. The onset age, sex ratio and clinical features differ among subtypes. The synthesis and signaling pathways of PGE2 are outlined in this review. Cyclooxygenase-2 (COX-2) is the key enzyme that acts as the rate-limiting step for prostaglandin production, thus COX-2 inhibitors have been used to treat this disease. Although this treatment showed effective results, it has side effects that restrain its use. Here, we reviewed the genetics, clinical features, differential diagnosis and current treatment options of PHO according to our many years of clinical research on the disease. We also discussed probable treatment that may be an option in the future.

Characteristic Facial Appearance Was the Key to Diagnosing Chronic Enteropathy Associated with SLCO2A1-associated Primary Hypertrophic Osteoarthropathy.

Patients with chronic enteropathy associated with SLCO2A1 (CEAS) develop multiple circular, longitudinal, or eccentric ulcers in the ileum. It is sometimes difficult to distinguish CEAS from Crohn's disease. CEAS and primary hypertrophic osteoarthropathy (PHO) are together known to be caused by a mutation of SLCO2A1 gene. The case of a 65-year-old man whose characteristic appearance due to pachydermia of the forehead folds led to the diagnosis of CEAS with PHO is presented.

Pachydermoperiostosis in a patient with chronic hepatitis B virus infection referred as acromegaly: a case report.

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.

Successful treatment of pachydermoperiostosis patients with etoricoxib, aescin, and arthroscopic synovectomy: Two case reports.

RATIONALE: Pachydermoperiostosis (PDP) is a rare hereditary disorder that affects the skin and bones. PDP is characterized by periostosis, digital clubbing, and pachydermia. Previous studies demonstrated that increased prostaglandin E2 (PGE2) levels resulting from defective protein degradation pathways play a crucial role in PDP pathogenesis, and males were more commonly and severely affected than females. Moreover, nearly all PDP patients suffer from refractory arthralgia. Although several different treatment modalities are used for PDP, therapy for this disease remains challenging. PATIENTS CONCERNS: Two cases of PDP showing symptoms consistent with polyarthritis and arthralgia that mainly affected the knees and ankles. DIAGNOSES: The diagnostic criteria for PDP include digital clubbing, periostosis, and pachydermia. The 2 patients were diagnosed as PDP based on the finger clubbing, facial cutis furrowing, knee and ankle arthritis, and radiographic evidence of periosteal proliferation. INTERVENTIONS: Patient 1 had massive joint effusion that was treated by oral administration of etoricoxib and aescin combined with arthroscopic synovectomy, whereas Patient 2 had mild joint swelling and accepted only oral medication. OUTCOMES: Clinical symptoms of the 2 patients greatly improved after the treatment. During the 1-year follow-up, the patient experienced no adverse effects or recurrence. LESSONS: The therapeutic results showed that oral etoricoxib could reduce inflammation and retard progression of pachydermia, or even relieve facial skin furrowing, but had limited efficacy for arthralgia. However, oral aescin had satisfactory efficacy for arthralgia. Thus, etoricoxib combined with aescin is a safe and effective treatment for PDP. Meanwhile, arthroscopic synovectomy can be used to treat joint effusion, but had no therapeutic effect on arthralgia. Therefore, postoperative oral medications would be needed as subsequent therapy for joint problems. In conclusion, this study proposes an effective and safe treatment plan to address symptoms experienced by PDP patients.

[Progress in genetic research on pachydermoperiostosis].

Pachydermoperiostosis is a rare genetic disease characterized by finger clubbing, periostosis, cutis verticis gyrata and pachydermia accompanied by acroosteolysis and hyperhidrosis. Recently, two susceptibility genes, HPGD and SLCO2A1, have been identified, whose protein products are involved in the transportation of prostaglandin and metabolism underlying pachydermoperiostosis. Here the genetic basis of pachydermoperiostosis and its correlation with its clinical phenotype are reviewed, which may provide a reference for basic research and clinic diagnosis for the disease.

Hypertrophic osteoarthropathy: what a rheumatologist should know about this uncommon condition.

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.

Miscellaneous non-inflammatory musculoskeletal conditions. Pachydermoperiostosis.

Pachydermoperiostosis (PDP), also known as primary hypertrophic osteoarthropathy, is a rare disease of the skin and bones that has clear genetic predisposition and well-defined clinical features. PDP is characterised by the presence of exuberant skin hypertrophy that, at the most distal parts of the extremities, takes a drumstick configuration. This deformity is conventionally known as digital clubbing. In advanced stages, skin hypertrophy may also be present in the head with furrowing of the facial features and eyelids ptosis. Another characteristic feature of the disease is periosteal proliferation of the long bones. Abnormal vascular endothelial growth factor and/or genetically determined prostaglandins overexpression may play a key role on its pathogenesis. No therapy has been shown to be effective in reversing hypertrophic changes. When bone pain is present, non-steroidal anti-inflammatory drugs are frequently useful. Isolated case reports have described that bisphosphonates may ease recalcitrant bone pain.

Psoriatic onychopachydermoperiostitis (POPP): a perplexing case study.

The following case of a 37-year-old male describes a very rare form of psoriasis known as psoriatic onychopachydermoperiostitis. There have been fewer than 20 cases reported worldwide.

Dor articular na osteoartropatia hipertrófica primária: descrição de caso e revisão de tratamento / Arthralgia in primary hipertrophic osteoarthropathy: case report and review of the treatment

Apresentamos o caso de um paciente com baqueteamento digital e artrite que foi diagnosticado como tendo osteoartropatia hipertrófica primária. Essa é uma doença rara e benigna. Entretanto, artralgia e alterações cutâneas podem reduzir significativamente a qualidade de vida do paciente. Além de um breve resumo da doença, apresentamos o caso e a revisão da literatura, enfatizando o tratamento dessa condição para os clínicos em geral.

We report the case of a patient with clubbing of the digits and arthritis who was diagnosed as having primary hipertrophic osteoarthropathy. This is a rare, benign disease. However, the arthralgia and skin changes can significantly impair the quality of life of the patient. In addition to a brief description of the disease, we present the case and a review of the literature regarding the treatment of this condition to the general practitioner.

[Pachydermoperiostosis (primary hypertrophic osteoarthropathy)]. / Paquidermoperiostosis (osteoartropatia hipertrofica primaria).

Pachydermoperiostosis or primary hypertrophic osteoarthropathy is a rare disease characterized by cutaneous and osteoarthicular involvement. We describe two patients with finger clubbing, watch crystal nails, bones thickenings, arthritis and different grades of skin affection, without other clinical manifestations. Both did not know of having relatives with the same alterations. Radiological studies of the affected areas showed periostosis. Because of normal laboratory results and chest radiography plus the absence of other underlying causes, diagnosis of primary hypertrophic osteoarthropathy was made.

Hypertrophic osteoarthropathy and intrathoracic Hodgkin's disease in children.

BACKGROUND: Hypertrophic osteoarthropathy (HOA) is a syndrome characterized by clubbing of the fingers and toes, periosteal new bone formation of the long bones and polyarthritis. CASE REPORT: In this report, two children with intrathoracic Hodgkin's disease and HOA are presented. CONCLUSIONS: Intrathoracic neoplasms are one of the major causes of HOA in adults; however HOA is rarely associated with intrathoracic malignancies in children. HOA associated with intrathoracic Hodgkin's disease is even more rare, but should be kept in mind.

Paquidermoperiostosis (osteoartropatia hipertrofica primaria) / Pachydermoperiostosis (primary hypertrophic osteoarthropathy)

La paquidermoperiostosis u osteoartropatía hipertrófica primaria es una rara enfermedadcaracterizada por compromiso cutáneo y osteoarticular. Comunicamos dos casos que presentabanhipocratismo digital, uñas en vidrio de reloj, agrandamiento óseo, tumefacción articular y diferentes grados deafectación cutánea, sin otros hallazgos clínicos relevantes. Ambos desconocían antecedentes familiares similares.El estudio radiográfico de las zonas comprometidas mostró periostosis. Con resultados de laboratorio yradiografía de tórax normales, y ausencia de evidencia clínica de otra enfermedad subyacente, se realizó diagnósticode osteoartropatía hipertrófica primaria.

Pachydermoperiostosis orprimary hypertrophic osteoarthropathy is a rare disease characterized by cutaneous and osteoarthicularinvolvement. We describe two patients with finger clubbing, watch crystal nails, bones thickenings,arthritis and different grades of skin affection, without other clinical manifestations. Both did not know of havingrelatives with the same alterations. Radiological studies of the affected areas showed periostosis. Because ofnormal laboratory results and chest radiography plus the absence of other underlying causes, diagnosis of primaryhypertrophic osteoarthropathy was made.