Digital clubbing as the predominant manifestation of hypertrophic osteoarthropathy caused by pathogenic variants in HPGD in three Indian families.

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.

Feet Deformity and Gait Disturbance in a Patient with Pachydermoperiostosis (PDP). Case Study.

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.

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.

Digital clubbing: forms, associations and pathophysiology.

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.

Clubbing and hypertrophic osteoarthropathy: insights in diagnosis, pathophysiology, and clinical significance.

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.

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.

Mutations in the SLCO2A1 gene and primary hypertrophic osteoarthropathy: a clinical and biochemical characterization.

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.

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.

Osteoartropatía hipertrófica con acro-osteolisis y neoformación ósea en un paciente con hipertensión pulmonar primaria / Hypertrophic osteoarthropathy with acro-osteolysis in a patient with primary pulmonary hypertension

La osteoartropatía hipertrófica es una entidad caracterizada por la tríada de periostitis de huesos largos, acropaquias y artritis. Radiológicamente se distinguen 2 patrones; uno caracterizado por neoformación ósea que predomina en pacientes con patología pulmonar, y otro por acro-osteolisis que se asocia más frecuentemente con cardiopatías congénitas. Presentamos el caso de un varón de 30 años diagnosticado de hipertensión arterial pulmonar primaria desde los 2 años, que desarrolló una osteoartropatía hipertrófica con un patrón radiológico mixto (AU)

Hypertrophic osteoarthropathy is an entity characterized by a triad of periostitis of long bones, clubbing and arthritis. Radiologically there are two patterns, one characterized by new bone formation which predominates in patients with pulmonary disease, and another by acro-osteolysis that is most frequently associated with congenital heart disease. We report the case of a 30-year-old man diagnosed with primary pulmonary hypertension for two years, developing hypertrophic osteoarthropathy with a mixed radiological pattern (AU)

Tufted hair folliculitis in a patient affected by pachydermoperiostosis: case report and videodermoscopic features.

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.

Osteoartropatía hipertrófica primaria: a propósito de un caso / No disponible

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