Hypertrophic Osteoarthropathy Research Articles

A rare helicobacter pylori infection-negative early gastric cancer in a young man with primary hypertrophic osteoarthropathy.

A rare helicobacter pylori infection-negative early gastric cancer in a young man with primary hypertrophic osteoarthropathy.

Epidemiology of Digital Clubbing and Hypertrophic Osteoarthropathy: A Systematic Review and Meta-analysis.

Digital clubbing and hypertrophic osteoarthropathy (HOA) are long-standing clinical entities, but their prevalence have not been synthesized. We aimed to estimate the prevalence of digital clubbing and HOA in people with existing medical conditions.We comprehensively searched PubMed, Embase, and Web of Science to select studies addressing HOA or digital clubbing and published through March 23, 2021. Summary estimates of the prevalence were derived through random-effects meta-analysis and narrative synthesis. The review protocol has been registered with PROSPERO, CRD42021243934.Of 3973 records, we included 142 studies. In adults, the pooled prevalence of digital clubbing was 33.4% (95% confidence interval [CI], 16.6-52.8), 31.3% (95% CI, 22.4-41.1), 27% (95% CI, 9.4-49.5), and 22.8% (95% CI, 10.8-37.6) in subjects with intestinal diseases, interstitial lung diseases, infective endocarditis, and hepatic diseases, respectively. In children and adolescents, the pooled prevalence of digital clubbing was 29.1% (95% CI, 19.4-39.9), 23% (95% CI, 9.0-41.1), 19.5% (95% CI, 4.1-42.4), and 17.1% (95% CI, 9.5-26.5) in subjects with human immunodeficiency virus infection, hemoglobinopathies, cystic fibrosis, and tuberculosis. The pooled prevalence of HOA was 10.1% (95% CI, 2.0-23.1) in adults with cancers, and 5% (95% CI, 2.5-8.2) in children and adolescents with cystic fibrosis.In conclusion, the prevalence of digital clubbing varied across disease groups in both adults and children. Full-spectrum HOA was mostly reported in adults with liver disease and cancers, and in children and adolescents with cystic fibrosis.

Pharmacology update: pamidronate for hypertrophic pulmonary osteoarthropathy in palliative care.

Hypertrophic pulmonary osteoarthropathy (HPOA) is a rare syndrome that causes clubbed fingers, periostitis, and synovial effusions. It can adversely impact a patient's quality of life. It occurs secondary to pulmonary disease - most commonly pulmonary malignancy. The most effective treatment for HPOA is to treat the underlying disease, usually through surgical resection, chemotherapy, or radiation. However, symptomatic treatments rather than definitive treatments (surgical, chemotherapy, or radiation) are more appropriate for the palliative care patient. Pamidronate is a promising medication for the treatment of HPOA for its safety and rapid onset of action. Further research is indicated to determine whether pamidronate is consistently effective.

Intrathoracic Giant Mass: Solitary Fibrous Tumor

Solitary fibrous tumors of the pleura are less than 5% of the pleural tumors. Eighty percent of the cases are caused by visceral pleura and 20% by parietal pleura. They are usually asymptomatic. These tumors, which can reach very large dimensions, can cause coughing and shortness of breath due to compression. Hypoglycemia and hypertrophic pulmonary osteoarthropathy are other symptoms. Definitive diagnosis is usually made after tumor excision. Abundant cellular structure with histologically dense and overlapping nuclei, more than 4 mitotic activities per site, pleomorphism with cytonuclear atypia, presence of large necrotic and hemorrhagic areas support malignancy. In addition, pleural effusion coexistence and atypical localization of the lesion are other findings supporting malignancy. Complete resection of the tumor is the most effective treatment and at the same time the most effective way to prevent recurrence.

Primary hypertrophic osteoarthropathy – a rare cause of pain and arthritis in children. Description of 5 cases

Primary hypertrophic osteoarthropathy (PHOA) is a very rare disease. The typical triad of symptoms, i.e. digital clubbing, periosteal bone formation with bone and joint deformities and skin hypertrophy, may be accompanied by other specific conditions. In the majority of patients, the picture of the disease is incomplete. The dominant clinical symptom may be osteoarticular complaints. Moreover, the final confirmation of the diagnosis of the primary form of hypertrophic osteoarthropathy requires the analysis of much more frequent secondary causes of the disease. Diagnosing primary osteoarthropathy in children is particularly difficult. Some children report joint pain before the onset of the other symptoms of osteoarthropathy, while the physical and imaging examinations show features of arthritis. This can lead to misdiagnoses including the diagnosis of juvenile idiopathic arthritis (JIA) and the unnecessary use of immunosuppressive treatment. The present description of five patients from the Paediatric Rheumatology Department indicates diagnostic difficulties in children with PHOA. All of them were examined due to pain and features of arthritis. We observed an incomplete clinical picture of the disease. One patient required a revision of the previous diagnosis of JIA and discontinuation of ineffective treatment with disease-modifying antirheumatic drugs (DMARDs). PHOA should always be considered in the differential diagnosis of arthritis in children, due to the slow and often atypical development of symptoms, including the presence of pain and arthritis as the predominant symptom of the disease.

Clinical and biochemical characteristics of 12 Chinese primary hypertrophic osteoarthropathy patients with HPGD mutations.

Primary hypertrophic osteoarthropathy (PHO) is a rare genetic disease mainly affecting the skeletal and skin. Two genes involved in prostaglandin degradation are known to be responsible for PHO: HPGD and SLCO2A1. HPGD gene mutation can cause PHO autosomal recessive 1 (PHOAR1). The purpose of the present study is to analyze the clinical and biochemical characteristics and HPGD gene mutations of 12 Chinese PHOAR1 patients. Twelve PHOAR1 patients from eleven families, including eleven males and one female, were enrolled in this study. Digital clubbing and periostosis came out to be the most common features, which always occur in the early childhood. We performed HPGD gene analysis and identified six novel (c.1A>G, c.34G>T, c.317T>A, c.475G>T, c.548C>T and c.421+1G>T) and one known (c.310_311delCT) HPGD mutations. The recurrent mutation c.310_311delCT were found in all eleven patients, suggesting it is a hotspot mutation. PHOAR1 patients are considered to have an autosomal recessive inheritance pattern. Here, in addition to nine compound heterozygous patients and two homozygous patients, we found one heterozygous patient and reviewed two heterozygous patients reported in other studies. In terms of biochemical characteristics, our PHOAR1 patients have elevated urinary prostaglandin E2 (PGE2) levels (P<0.001) and decreased urinary prostaglandin E metabolite (PGE-M) levels (P=0.04) compared with healthy controls. The patients' PGE2/PGE-M (E/M) ratio came out to be lower than normal subjects (P<0.001). This study provides a comprehensive description of the clinical phenotypes of Chinese PHOAR1 patients and expands the genotypic spectrum of the disease.

Pachydermoperisotosis: A Rare Case Report

Pachydermoperiostosis (PDP) is a rare disorder with variable presentation and it is characterized by clubbing of the fingers (acropachia), skeletal changes (periostosis), thickening of the skin (pachyderma), and excessive sweating (hyperhidrosis). Clinical presentations of PDP can be confused with secondary hypertrophic osteoarthropathy, psoriatic arthritis, rheumatoid arthritis, thyroid acropachy, and acromegaly.We report a patient with complete PDP.

O05 A case of cancer mimicking inflammatory arthritis

Abstract Case report - Introduction Rheumatic disease occurring as a paraneoplastic manifestation such as dermatomyositis is well recognised, whilst the symptoms of cancer may frequently mimic the presentations of common rheumatic disorders. It is essential to recognise these differential diagnoses to avoid delay in the detection of malignancy. We present an unusual case of rheumatoid arthritis where, conversely, the diagnosis of inflammatory arthritis was delayed due to the attribution of musculoskeletal symptoms to existing malignancy undergoing treatment. This case highlights the importance of careful history and examination. Cancer and inflammatory disorders may co-exist and delayed diagnosis of either condition can result in increased morbidity. Case report - Case description A 65-year-old male presented to Ear, Nose and Throat (ENT) clinic with a facial lump in association with swelling in his throat, tongue and neck associated with a decrease in appetite and weight loss. He reported an active lifestyle, including mountain climbing until a month prior. He was a non-smoker with alcohol intake of less than 10units/week. Other medical history included osteoarthritis of his left knee which did not limit function. Imaging of the head and neck confirmed a mass in the oropharynx, tonsils, and tongue muscles. Subsequent biopsy revealed moderate to poorly differentiated squamous cell carcinoma (SCC) of the left tonsil. 11 months prior to this presentation, he had developed pain and swelling involving knees, shoulders, and small joints of hands. His mobility became progressively impaired eventually requiring a wheelchair for any outdoor excursion. The systemic and musculoskeletal symptoms were attributed to a paraneoplastic manifestation of his malignant process. A rheumatology opinion was eventually requested in view of the persistence of joint symptoms despite effective cancer treatment with radical radiotherapy. He described early morning stiffness lasting more than 3 hours. Synovitis was evident at his hands, wrists and knees, whilst shoulder movement was restricted, resulting in a high disease activity score (DAS) of 7.44. Blood workup showed normal rheumatoid factor and cyclic citrullinated peptide (CCP). Acute phase markers were elevated with ESR 99 mm/hr, CRP 79 mg/l and ferritin 1194 ng/ml. Ultrasound (US) hands confirmed widespread active synovitis involving bilateral wrist and metacarpophalangeal joints. X-rays showed only degenerative changes. A diagnosis of seronegative inflammatory arthritis was established, and he was initiated on hydroxychloroquine with reducing regime of prednisolone. Methotrexate (MTX) was briefly deferred pending oncology advice. Following initiation of MTX he improved dramatically, returning to normal mobility, and steroids were successfully tapered off. Case report - Discussion Our patient had symptoms of inflammatory arthritis prior to identification of a SCC with local spread; however, his systemic and musculoskeletal features were initially regarded as paraneoplastic. Paraneoplastic arthritides encompass the musculoskeletal manifestations of malignancy. This includes polyarthritis, inflammatory myopathies, hypertrophic osteoarthropathy and palmar fasciitis. Symptoms may precede or occur concurrently with cancer presentations and often respond to treatment of the underlying cancer. Persistence of musculoskeletal symptoms may be a clue to co-existence of a rheumatic diagnosis. Reassessment of history and examination can guide physicians to a concurrent second diagnosis when clinical progress is not as expected. Our case also highlights the question of safe use of immunosuppressive drugs in rheumatic patients with cancer and whether they may promote or induce malignant disease. Literature is challenging to assess as many systemic inflammatory disorders, including RA, have an established increased risk of certain cancers, including lymphoproliferative disease. He was managed by prednisolone and hydroxychloroquine, followed rapidly by MTX, leading to dramatic symptomatic improvement. Low-dose MTX (25—30mg weekly) is considered first-line treatment in RA. Of the commonly used anti-rheumatic therapies it has the least evidence to suggest a potential increased malignancy risk. Other anti -rheumatic drugs such as Tumour Necrosis Factor (TNF) inhibitors also have a favourable risk profile regarding cancer development. Most observational studies evaluating the use of biologic therapy in RA patients with previous solid tumours do not show an increased risk of recurrence. Coordination of care with the patient and their oncologist is essential in the management of cases of individuals with rheumatic disease and concomitant cancer. Case report - Key learning points

DISPARITIES IN 5-YEAR RELATIVE SURVIVAL FOR EARLY ONSET COLORECTAL CANCER

Prosthetic vascular graft procedures are a common treatment modality for peripheral vascular disease. A relatively common complication is graft infection, occurring at a rate of 0.5–5%. When they occur, graft infections are associated with significant morbidity and mortality. Vascular graft infections also represent a diagnostic and therapeutic challenge for the physicianHere, we report a case where the rare finding of secondary hypertrophic osteoarthropathy was an important indication of underlying aortic graft infection that was initially misdiagnosed. A review of the literature revealed 34 cases of vascular graft infection associated with hypertrophic osteoarthropathy.The mean interval from surgery to time of infection was approximately 5 years. Mortality was 35%. When combined with hypertrophic osteoarthropathy, vascular graft infection was complicated by an aortoenteric fistula in 53% of the cases.The complexity of this case highlights the challenges physicians face in order to diagnose and treat this condition.

A CASE REPORT OF HYPERTROPHIC OSTEOARTHROPATHY LEADING TO DIAGNOSIS OF PULMONARY EPITHELIOID HEMANGIOENDOTHELIOMA

TOPIC: Lung Cancer TYPE: Medical Student/Resident Case Reports INTRODUCTION: Hypertrophic Osteoarthropathy (HOA) is a condition characterized by abnormal proliferation of skin and osseous structures of extremities. Periostitis is the imaging hallmark of HOA and most commonly manifests symmetrically along the shaft of tubular bones. Incidence of HOA in patients with intrathoracic malignancy is 5-10%. CASE PRESENTATION: A 49-year-old male presented to his primary care physician for bilateral knee pain with associated swelling. After failing conservative management, bilateral knee x-rays were performed which revealed a thin periosteal reaction in both femoral shafts, prepatellar soft tissue swelling and small bilateral joint effusions.The radiologist recommended a chest x-ray for further evaluation, which showed subtle soft tissue fullness at the right lung base. Chest CT was then performed revealing a 4.2 x 2.2 x 4.7 cm spiculated soft tissue lung mass of the right lower lobe with extension into the mediastinum and right hilar, paratracheal and subcarinal lymph nodes.The patient underwent bronchoscopy with FNA of the right lower lobe mass and station 7 and 11 lymph nodes. Highly atypical cells suspicious for malignancy were noted, but analysis was limited by scant material. IR guided biopsy was subsequently performed revealing patchy proliferation of epithelioid cells with ample eosinophilic cytoplasm, occasional cytoplasmic vacuoles and necrosis. Immunohistochemically, the tumor cells stained positive for ERG, CD31, and CD24. The cytomorphologic and immunohistochemical features support the diagnosis of epithelioid hemangioendothelioma (EHE). DISCUSSION: This case illustrates EHE's heterogeneous presentations. The primary lesion of EHE has been documented in numerous locations throughout the body, but most commonly arises in the liver, lungs, and bones. HOA as the presenting sign in pulmonary EHE is not well documented in the literature and periosteal reaction is considered rare. Digital clubbing was not present in this case and the only known location of periosteal reaction was the femoral shafts. While the mechanism of EHE is not well understood, it is believed that angiogenic stimulators, such as vascular endothelial growth factor (VEGF), may act as promoters of endothelial cell proliferation.The proposed pathogenesis of HOA has been linked to hypersecretion of vasoactive agents such as VEGF, platelet derived growth factor (PDGF), and prostaglandin E2 (PGE2). The proposed pathogenesis of secondary HOA has been linked to hypersecretion of vasoactive agents such as VEGF, PDGF, and PGE2. These agents are released both systemically in response to hypoxemia and by the tumor itself. CONCLUSIONS: Pulmonary Epithelioid Hemangioendothelioma can also present with Hypertrophic Osteoarthropathy.Bone X- ray can lead to the diagnosis of Hypertrophic Osteoarthropathy if careful evaluation is done. Periostitis is frequently a sign of pulmonary and systemic pathology. REFERENCE #1: Chakraborty, Rebanta K. "Secondary Hypertrophic Osteoarthropathy." StatPearls [Internet]., U.S. National Library of Medicine, 1 Mar. 2021, www.ncbi.nlm.nih.gov/books/NBK513342/. REFERENCE #2: Sardaro, Angela, et al. "Epithelioid Hemangioendothelioma: an Overview and Update on a Rare Vascular Tumor." Oncology Reviews, PAGEPress Publications, Pavia, Italy, 13 Oct. 2014, www.ncbi.nlm.nih.gov/pmc/articles/PMC4419652/. REFERENCE #3: Silveira LH;Martínez-Lavín M;Pineda C;Fonseca MC;Navarro C;Nava A; "Vascular Endothelial Growth Factor and Hypertrophic Osteoarthropathy." Clinical and Experimental Rheumatology, U.S. National Library of Medicine, pubmed.ncbi.nlm.nih.gov/10728444/. DISCLOSURES: No relevant relationships by Julia Lawinger, source=Web Response No relevant relationships by Raul Mendoza-Ayala, source=Web Response

Thymic epithelial tumours - research trends

The global research trends and potential gaps in global research on thymic epithelial tumours (TETs) were scientometrically identified based on the data retrieved from Web of Science (WoS). The analysis indicates that the global research on TETs is presenting a positive growth trend. The transformative activity index (TAI) value depicts that three Asian countries, China, South Korea, and India, recorded the highest increase in TAI during the last decade, while the maximum decline in TAI was for Norway, Taiwan and Netherlands. The University of Texas has published most papers on TETs, and Heidelberg University had the highest collaboration. There is not enough research ongoing on some paraneoplastic disorders associated with TETs like cerebellar degeneration, erythrocytosis, pancytopenia, rheumatoid arthritis, Sjogren’s syndrome, interstitial pneumonitis, chronic mucosal candidiasis, T-cell deficiency syndromes, ulcerative colitis, and hypertrophic osteoarthropathy. Most of the TET treatment studies were on surgery and chemotherapy. Research on other treatment modalities like immunotherapy and targeted therapy also needs improvement.

Pachydermoperiostosis (PDP): A Case Report

Abstract Pachydermoperiostosis (PDP) is the primary form of hypertrophic osteoarthropathy which accounts for 5% of all cases of the disorder. It is a rare hereditary disorder that is associated with digital clubbing, polyarthritis, cutis verticis gyrata, Seborrhea, eyelid ptosis, and hyperhidrosis. In this case report, we discussed a case of an incomplete form of primary hypertrophic osteoarthropathy characterised by evidence of bone abnormalities without pachydermia. Keywords: Pachydermoperiostosis, hypertrophic osteoarthropathy, periostosis.

Digital Clubbing and Hodgkin Disease in Children: A Case Report and Review of Literature

Introduction: Digital clubbing (hypertrophic osteoarthropathy) as the initial presentation of lymphoma is rarely reported, particularly in children. In this study, we report a patient with intrathoracic Hodgkin Disease (HD) and digital clubbing as the first presentation, and we will review the literature regarding the same condition. Case Presentation: A 10-year-old boy presented with a 2-month history of cough, mild dyspnea, and night sweats, with prominent digital clubbing. A chest x-ray and a computed tomography scan of the chest showed multiple mediastinal masses. A mediastinal lymph node biopsy was done. Pathologic examination was indicative of nodular sclerosis HD. Conclusions: In patients with digital clubbing, intrathoracic malignancies should be considered a differential diagnosis and must be ruled out by precise examination and paraclinical help.

Pachydermoperiostosis: A Rare Masquerader of Acromegaly and Thyroid Acropachy

Background: Pachydermoperiostoasis is a rare disease of prostaglandin metabolism that presents with extensive clubbing, skin thickening, and enlargement of hands and feet, often misdiagnosed as acromegaly or thyroid acropachy. Clinical Case: A 29-year-old male presented with progressive enlargement of hands and feet for the past three years, with increased sweating, seborrhea, acne, arthralgia, and photophobia. On examination, facial furrowing and severe clubbing in all fingers and toes was noticed, with palmoplantar hyperhidrosis, tenderness and widening around distal forearms, and increased heel pad thickness. He had nodulocystic acne, injected right eye with ptosis, normal pupil, and visual field. Slit-lamp examination showed extensive pannus formation, with yellow nodules, suggestive of phlyctenular conjunctivitis, secondary to a systemic inflammatory process. No prominent supraorbital ridge, prognathism, proptosis, goiter, or pretibial myxedema. No family history of a similar condition. Labs showed normal cell counts and metabolic panel. Normal IGF-1 (112 ng/mL, n 84-250 ng/ml), TSH (3.82 mIU/L, n 0.27-4.2 mIU/L), fT4 (1.19 ng/dL, n 0.93-1.7 ng/dL), Testosterone (354 ng/dL, n 249-836 ng/dL) and Prolactin (15.2 ng/mL, n 2.1-17.7 ng/mL). Inflammatory markers were elevated with ESR of 54 mm/hr (n 0-15 mm/hr) and CRP of 12.45 mg/L (n 1-4 mg/L). ANA, RF, anti-CCP, and HLA-B27 were negative. C3 and C4 levels were normal as well. Interferon-gamma release assay was negative. Imaging showed a normal chest X-ray. Brain MRI showed normal pituitary gland and increased scalp skin thickness with cutis verticis gyrata “undulating skin sign.” X-ray of hands and feet showed diffuse periosteal reaction. A diagnosis of pachydermoperiostosis (PDP) was made based on clinical criteria (thickened skin, periosteal reaction, and finger clubbing). PDP is a genetic disorder of prostaglandin metabolism with variable expression and incomplete penetrance. It manifests after puberty and affects males more than females with a 7:1 ratio. PDP has been recently shown to go through an inflammatory phase, in which patients may benefit from immunosuppressants or NSAIDs. PDP should be distinguished from hypertrophic pulmonary osteoarthropathy, thyroid acropachy, and acromegaly. Our patient had a normal chest radiograph and normal hormone levels (TSH, T4, and IGF-1). The patient received topical steroids and antibiotics with artificial tears for his eyes, which resulted in a good response, and was referred to a rheumatology clinic for further management. Clinical Lesson: PDP can be mistaken for acromegaly or thyroid acropachy and should be considered in any patient with acromegaloid features with normal IGF-1 and no evident pituitary pathology. Awareness of this condition can help in reaching the diagnosis promptly.

A Case of Paraneoplastic Arthralgias

Hypertrophic Osteoarthropathy (HOA) is a rare condition that presents with arthralgias, digital clubbing, and abnormal periosteal bone deposition seen on x rays. The secondary form of HOA may be associated with an underlying malignancy, thus highlighting the importance of early clinical recognition. We present the case of a 44-year-old woman who presented with several weeks of lower extremity swelling, arthralgias, and digital clubbing who was later found to have non-small cell lung cancer. Diagnosis can be challenging due to variable presentations that can often mimic other forms of inflammatory arthritis. Treatment is focused on addressing the underlying cause. Nonsteroidal anti-inflammatory drugs (NSAIDS) are commonly used for pain relief while intravenous bisphosphonates have been trialed with some success in case reports.

Establishment of a novel human iPSC line (SDQLCHi032-A) derived from a patient with primary hypertrophic osteoarthropathy caused by HPGD homozygous mutation.

Primary hypertrophic osteoarthropathy, autosomal recessive type 1 (PHOAR1, MIM259100) is caused by mutations in the 15-hydroxyprostaglandin dehydrogenase gene (HPGD, MIM601688) on chromosome 4q34. An induced pluripotent stem cells (iPSCs) line was generated in our lab from peripheral blood mononuclear cells (PBMCs) of a 2-year-7-month-old girl with PHOAR1 carrying a homozygous mutation of c.310_311del in HPGD. The expression of pluripotency markers, absence of episomal vectors, preservation of normal karyotype, the potential of trilineage differentiation in vitro, were confirmed in the obtained iPSCs line.

SLCO2A1 gene is the causal gene for both primary hypertrophic osteoarthropathy and hereditary chronic enteropathy.

SLCO2A1 gene is the causal gene for both primary hypertrophic osteoarthropathy and hereditary chronic enteropathy.

Clinical and genetic characteristics of patients with chronic enteropathy associated with SLCO2A1 gene

Objective: To determine the clinical features and genetic characters of patients with chronic enteropathy associated SLCO2A1 gene (CEAS). Methods: Five CEAS patients diagnosed at Peking Union Medical College Hospital from January 2012 to December 2019 were enrolled in this study. The clinical manifestations, laboratory test, radiological and endoscopic findings, gene detections, treatments and prognosis of these patients were reviewed and analyzed. Results: Five male patients presented gastrointestinal symptoms after puberty, including abdominal pain, diarrhea, intermittent melena or hematochezia, incomplete bowel obstruction, anemia, hypoalbuminemia and hypokalemia. The whole gastrointestinal tract except esophagus could be involved, especially the stomach and ileum. Intestinal lesions were characterized by multiple shallow ulcers with stenosis in the layers of mucosa and submucosa. Five patients were all accompanied with primary hypertrophic osteoarthropathy (PHO), and 1 with myelofibrosis and thoracic duct dysplasia. All patients were homozygous or compound heterozygous mutations of SLCO2A1 gene. Conventional treatment of inflammatory bowel disease and COX-2 inhibitors were ineffective. Conclusions: CEAS is an autosomal recessive genetic disease which widely involves the gastrointestinal tract, and can be associated with skin and bone involvement. There is no effective treatment for CEAS at present. CEAS is a different entity from other inflammatory gastrointestinal diseases.

Secondary Hypertrophic Osteoarthropathy or Pierre-Marie Syndrome Bamberger: Clinical Case and Literature Review

Secondary hypertrophic osteoarthropathy, or Pierre-Marie Bamberger syndrome, is characterized by the association of digital clubbing, polyarthritis and periostitis affecting the long bones. Most commonly it is a paraneoplastic syndrome associated with lung cancer in 80% of cases. We report the case of a 49-year-old female patient who is actively smoking, one pack per day for 20 years. Seen in consultation for pain and swelling of the hands, elbows, knees, ankles, and feet evolving for about 5 months, associated with a poorly differentiated pulmonary adenocarcinoma. On history, she told us about a weight loss of about 8 kg, no fever, no cough, no family history of inflammatory rheumatism or cancer. Bilateral digital clubbing was noted. The diagnosis was based on imaging and histology. Treatment with nonsteroidal anti-inflammatory drugs (NSAIDs) and chemo-radiotherapy was started.

Characterization of Mineral and Bone Metabolism Biomarkers in a Chinese Consanguineous Twin Family with Primary Hypertrophic Osteoarthropathy.

Purpose Primary hypertrophic osteoarthropathy (PHO) is a rare, autosomal, recessive genetic disease characterized by digital clubbing, periostosis, and pachydermia. The underlying cause for the pathogenesis of this disease is a defect in prostaglandin E2 (PGE2) degradation, caused by mutations in HPGD or SLCO2A1. In this study, we describe the clinical characteristics, SLCO2A1 mutations, and bone metabolic markers of a PHO pedigree from a Chinese consanguineous twin family. Methods Whole blood and urine samples were collected from all the family members. All the exons and exon-intron boundaries of the HPGD and SLCO2A1 genes were amplified using polymerase chain reaction (PCR) and sequenced. The biomarkers of mineral and bone metabolism, including calcium, phosphorus, parathyroid hormone (PTH), 25-hydroxyvitamin D (25(OH)D), bone Gla-protein (BGP), C-terminal telopeptide of type I collagen (β-CTX), and urinary calcium/creatinine ratio (Uca/Ucr) were detected. Results A homozygous (nonsense) mutation in the SLCO2A1 gene (c.1807C >T/p.R603∗) was detected in the proband. Five heterozygous carriers were also identified among his relatives, including his twin brother. The serum BGP (225.5 ng/ml), β-CTX (4112 pg/ml), and Uca/Ucr (0.63) levels were significantly elevated, while the 25(OH)D (37.1 nmol/L) level was reduced in the proband. The proband's twin brother displayed increased levels of β-CTX (901 pg/ml) and insufficiency of 25(OH)D (67.29 nmol/L), while the other heterozygous carriers only displayed 25(OH)D insufficiency. Conclusion The patients with PHO displayed an active state of bone reconstruction. There may be a lack of vitamin D, accompanied by an increase in BGP and β-CTX levels. Heterozygous mutations of SLCO2A1 might lead to mild PHO.