Hypertrophic osteoarthropathy

Hypertrophic osteoarthropathy (HOA) is an orphan syndrome characterized by abnormal proliferation of the skin and osseous tissues at the distal parts of the extremities. The main clinical features are: a peculiar bulbous deformity of the tips of the digits conventionally described as “clubbing,” periosteal proliferation of the tubular bones, and synovial effusions.In most instances, HOA develops a reaction to a severe internal illness, such as lung cancer, cyanotic heart disease, or liver cirrhosis. There is a subgroup of patients who do not have underlying pathology. Such cases are classified as having primary HOA.Digital clubbing is easy to recognize. Any patient with newly developed digital clubbing should undergo careful search for an underlying illness with special attention to intra-thoracic pathologies.Painful HOA is treated with non-steroidal anti-inflammatory medications.Vascular endothelial growth factor and prostaglandin E2 have been proposed as key bone proliferating mediators.     

Lower limb hypertrophic osteoarthropathy can reveal aortic graft infection in Behçet syndrome

SIR, Pierre–Marie–Bamberger syndrome [1], or secondaryhypertrophic osteoarthropathy (HOA), is characterized by clubbingof digits, periosteal new bone formation and synovial effusion.Secondary HOA accompanies a variety of disorders, thoracic affectionsin particular, and may precede clinical features of the disease.Forms of HOA localized to one or two limbs occur as the resultof an endothelial injury, such as an infection of arterial aneurysmsor vascular grafts [2]. We report the case of a 44-yr-old womanwith Behçet disease (BD) with predominantly unilaterallower limb HOA revealing an aortic     

Vascular endothelial growth factor and hypertrophic osteoarthropathy

OBJECTIVE: Hypertrophic osteoarthropathy (HOA) is characterized by the coexistence of digital clubbing and periosteal proliferation of the tubular bones. Localized vascular proliferation associated with platelet/endothelial cell activation are recognized features of this syndrome. Current knowledge suggests that HOA develops from the presence in the systemic circulation of one or more growth factors that are normally inactivated in the lungs. The nature of these purported growth factors has not yet been identified. Vascular endothelial growth factor (VEGF) has several features that may fit in with the pathogenesis of HOA. The objective of our study was to measure serum and plasma levels of VEGF in different groups of patients with HOA. METHODS: We studied 24 patients with HOA; of these, in 12 the HOA was secondary to cyanotic congenital heart disease and in 7 to lung cancer, while 5 represented primary cases. As controls we studied 28 individuals without HOA; of these, 12 were apparently healthy individuals, 7 had cyanosis secondary to chronic obstructive pulmonary disease, and 9 had lung cancer. ELISA was used to measure serum and plasma levels of VEGF. RESULTS: Plasma levels of VEGF were significantly higher in the patients with primary HOA (median 46.2; range 19.4-398.8 pg/ml) and in those with lung cancer-HOA (median 75.5; range 24.6-166.7), compared to healthy controls (median 7.4; range: 0-26.1), p < 0.05. Serum VEGF levels were higher in patients with lung cancer and HOA (median 411.4; range 164.2-959.5 pg/ml) compared with lung cancer patients without HOA (median 74.5; range 13.2-205.4), p < 0.001. CONCLUSIONS: Patients with primary HOA and those with HOA and lung cancer have increased circulating levels of VEGF. This cytokine may play a role in the pathogenesis of HOA.     

肥大性骨关节病病例分析并文献复习

目的 提高对肥大性骨关节病(HOA)的认识、诊断和鉴别.方法 报告我院2例原发性HOA(PHOA)及3例继发性HOA(SHOA)确诊病例,并分析既往国内报道16例文献.结果 国内PHOA发病年龄多数在14～24岁,多为男性,最小者1岁起病,最大者为42岁.18例PHOA患者中2例有家族史,2例有近亲结婚史,所有患者均有杵状指(趾)、皮肤增厚粗糙、骨膜增生的临床表现,多汗14例,回状颅皮9例,关节痛和(或)关节积液10例,指(趾)端骨质溶解4例,类风湿因子阳性2例,1例弱阳性.我院报告3例SHOA均继发于肺部肿瘤,中年后起病,病程较短.以关节症状及杵状指(趾)为主要表现,面部及皮肤症状少,全身伴随症状多见.结论 PHOA青少年起病多见.男性多,主要表现为杵状指(趾)、皮肤增厚及骨膜反应.与SHOA需从起病年龄、病程及全身伴随症状等方面鉴别.     

Seropositive,symmetric polyarthritis in a patient with poorly differentiated lung carcinoma: Carcinomatous polyarthritis,hypertrophic osteoarthropathy,or rheumatoid arthritis?

Polyarthritis resembling rheumatoid arthritis (RA) may be the presenting manifestation of occult malignancy. Hypertrophic osteoarthropathy (HOA) may also develop in association with pulmonary neoplasia and consists of clubbing, periostitis, and arthropathy We describe Q patient who presented with a seropositive, symmetric, inflammatory polyarthritis only 4 weeks before a lung tumor became clinically and radiographically apparent. After initiation of chemotherapy she developed features characteristic of HOA. It appears that the patient had both RA and HOA. We discuss the differential diagnosis and review the relationship of RA, HOA, carcinomatous polyarthritis, and malignancy.     

Hypertrophe Osteoarthropathie

Hypertrophic osteoarthropathy (HOA) is the classical neoplastic disease in rheumatology characterized by a combination of digital clubbing, joint and bone pain, and proliferative periostitis. This combination of symptoms should initiate an intensive search for an underlying malignant disease usually of thoracic organs. Here we report the case of a patient with HOA and neuroendocrine carcinoma of the esophagus. Other non-malignant disorders of the lungs, heart and other organs should be considered in the differential diagnosis. In addition, rare cases of a primary hereditary form of HOA exist and the genetic background has recently been discovered. Thus, new insights into the pathophysiology have improved diagnostic and therapeutic options for this disorder.     

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.     

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.     

Hepatic hypertrophic osteoarthropathy and liver transplantation.

OBJECTIVES--To document the variety of liver diseases and the clinical picture of hepatic hypertrophic osteoarthropathy (HOA) complicated by arthritis and to report the effects of successful liver transplantation on this disabling condition. METHODS--Seven patients with severe liver disease (two biliary atresia, two primary sclerosing cholangitis, one Wilson's disease, one primary biliary cirrhosis (PBC) and one alcoholic cirrhosis) complicated by radiologically proven hepatic HOA and suffering from arthritis are described. RESULTS--In four of the six patients who required hepatic transplantation for inadequate liver function successful grafting was achieved with complete clinical remission of the painful arthritis. This occurred three days to 18 months later. CONCLUSIONS--Hepatic HOA with arthritis occurs in a variety of liver diseases. Despite resistance of this arthritis to conventional therapies, successful liver transplantation was associated with complete clinical remission in four of the cases reported.     

Clubbing and hypertrophic osteoarthropathy

Acquired clubbing of the digits and hypertrophic osteoarthropathy are closely related disorders of unknown etiology that derive special significance from their frequent association with serious underlying diseases of the thorax or abdomen. Most importantly, clubbing or HOA may provide the first clinical indication of a chronic infection or an intrathoracic neoplasm. However, clubbing is easily overlooked on physical examination, and hypertrophic osteoarthropathy is often mistaken for some other disorder. The diagnosis of clubbing is based on the finding of an increase in the soft tissue at the base of the finger or toenails. Of the several objective criteria that have been proposed for the diagnosis of digital clubbing, the best documented and most practical is an increase in the ratio of the distal phalangeal depth (DPD) to the interphalangeal depth (IDP) of the index finger to 1.0 or greater. Hypertrophic osteoarthropathy is characterized in advance cases by the combination of digital clubbing, periostitis of the long bones, arthritis-like changes in the knees, elbows, ankles, and wrists, and swelling of the soft tissues in the distal extremities. Bone scintigraphy has emerged as the most sensitive test for HOA; in fact, a bone scan may show evidence of periostitis in patients with no other signs, symptoms, or radiographic abnormalities of the disorder. The symptoms of HOA respond to anti-inflammatory agents, and to ablation or cure of the underlying disorder.     

MRI in psoriatic arthritis: Insights into pathogenesis and treatment response

Psoriatic arthritis (PsA) is a clinically heterogeneous condition, and not surprisingly, its MRI features are diverse. Synovitis and accompanying synovial effusions are clearly depicted, and enthesitis is characterized by extracapsular inflammation at the insertions of ligaments and tendons plus accompanying bone edema at bony attachments. Other forms of MRI bone edema include subchondral and diaphyseal involvement; the latter seeming relatively specific to PsA. The pathology of dactylitis can also be elucidated by MRI, which frequently reveals tenosynovitis and soft tissue edema in conjunction with various degrees of synovitis, bone edema, and erosion. Bone erosions differ from those seen in rheumatoid arthritis in their distribution and associated features such as bone proliferation and sometimes periostitis. Finally, MRI can be used to score and quantify these pathologic features, providing a sensitive tool with which to evaluate disease progression.     

Primary synovial sarcoma of the chest: radiographic and clinicopathologic correlation

Primary synovial sarcoma of the thorax is rare. Origin of thoracic synovial sarcoma in the pleura or lung was first described only 7 years ago. Radiologic characteristics of this disease have not yet been studied in a formal series. The authors sought to define the radiologic features of primary thoracic synovial sarcoma and to correlate the findings with clinical and pathologic features. They examined clinical, radiologic, and pathologic features of five patients with primary synovial sarcoma of the chest. Radiologic evaluation included conventional radiographs, computed tomographic scans, and magnetic resonance images of the chest. Patients included three men and two women who ranged in age from 28 to 40 years. Primary tumors involved the chest wall (n = 2), lung (n = 1), or both (n = 2). Chest pain was the most common presenting symptom. Although conventional radiographs often showed the lesions to be ill defined, computed tomographic scans showed well-defined masses in every case. Heterogeneous enhancement and an absence of calcification were also seen. Pathologic evaluation demonstrated synovial sarcoma with equal distribution between the monophasic and biphasic variants. The chromosomal translocation X;18 was demonstrated in four of four cases tested. All patients were treated by resection. Recurrence was demonstrated radiologically in four patients at 2 to 14 months. All patients were alive at 9 to 58 months of follow-up. The authors conclude that primary synovial sarcoma of the chest occurs in young adults, most commonly presenting with chest pain. It is characterized radiologically by a heterogeneously enhancing well-defined mass without calcifications.     

Serological markers of erosive hand osteoarthritis

This review focuses on biomarkers in erosive hand osteoarthritis (EHOA), a subset of hand osteoarthritis (HOA), that primarily affects interphalangeal joints and is characterized by abrupt onset, severe pain and functional impairment, as well as signs of inflammation, in particular stiffness, swelling, erythema, paraesthesiae, and worse outcome. Inflammatory features and radiographic erosions are the main diagnostic hallmarks of this particular disease subset. As in other fields of OA, EHOA biomarkers can be classified as dry and soluble. Soluble biomarkers which are found in serum, synovial fluid and urine can be specific indicators of joint inflammation and degradation. With regard to inflammatory markers, C-reactive protein and myeloperoxidase have been found to be increased in EHOA, with respect to non-erosive HOA. All these markers have, moreover, been found to be correlated with disease activity. Another interesting marker linked to inflammation is hyaluronic acid, considered to be a marker of synovitis, which is frequently found in EHOA. The most useful cartilage markers in both erosive and non-erosive HOA, seems to be collagen (Coll) 2-1, Coll 2-1NO₂ and Col2-3/4C_short. Immunogenetic markers were also determined and an association between EHOA and a single nucleotide polymorphism on the gene encoding interleukin-1β was found in HLA and there was an increased frequency of HLA-B44 and HLA-DRB1*07 in EHOA.     

Juvenile onset spondyloarthropathies: therapeutic aspects

Juvenile onset spondyloarthropathy (SpA) is a term that refers to a group of human leucocyte antigen (HLA)-B27 associated inflammatory disorders affecting children under the age of 16 years, producing a continuum of clinical symptoms through adulthood. This disease is characterised by enthesopathy and arthropathy affecting the joints of the lower extremities and seronegativity for IgM rheumatoid factor and antinuclear antibodies. Children usually present with undifferentiated SpA and progress to differentiated forms over time. Except for the prevalence of some clinical features at onset, the pathogenic and clinical aspects of juvenile onset SpAs resemble those of the adult disease. Thus application of the same or similar therapeutic measures for both juvenile and adult onset SpAs seems logical. Current treatments for juvenile onset SpA provide symptomatic improvement, but do not alter disease progression. The increased expression of tumour necrosis factor alpha (TNFalpha) in synovial tissue of patients with adult and juvenile onset SpA and its correlation with infiltration of inflammatory mediators into the synovia suggest a significant pathogenic role of this cytokine. Clinical trials of anti-TNFalpha antibody (infliximab) therapy in patients with adult onset SpA have demonstrated significant clinical improvement in inflammatory pain, function, disease activity, and quality of life in correlation with histological and immunohistochemical evidence of modulation of synovial inflammatory processes. These promising findings suggest that anti-TNFalpha therapy may confer similar benefits in patients with juvenile onset SpA.     

Laminar periostitis and multiple osteonecrosis in systemic lupus erythematosus

Summary Bone affectation in systemic lupus erythematosus (SLE) is caused both by the disease itself and by the treatment used. We report the case of a woman diagnosed of SLE, who, in the course of her illness, develops multiple aseptic osteonecrosis (AON) and laminar periostitis, radiologically compatible with the diagnosis of hypertrophic osteoarthropathy (HOA), with no evidence of acropaquia. In this case, the patient shows all the risk factors involved in the pathogenesis of the development of ischemia in bone microcirculation.     

原发性肥大性骨关节病(附一例报告)

目的 提高对原发性肥大性骨关节病的认识。方法 报告１例原发性肥大性骨关节病的临床表现、实验室检查、Ｘ线改变及皮肤透射电镜改变,并复习文献。结果 总结原发性肥大性骨关节病的病理生理改变、临床特点、诊断标准、治疗手段及预后。结论原发性肥大性骨关节病为一种自限性疾病,其临床表现呈多样性,与诊断及分型相关的临床表现为骨膜成骨亢进、杵状指（趾）、面部肥厚及脑回样头皮,诊断成立尚需排除继发性因素。血流变学改变     

Primary meningococcal polyarthritis

We report a case of primary meningococcal polyarthritis simulating bacteraemic gonococcal infection. The clinical similarity between extragenital gonococcal and meningococcal infections is well illustrated. If the clinical features of meningococcal and gonococcal infections are usually different, they may sometimes be indistinguishable. Both gonococcal pharyngitis and meningococcal urethritis have been recorded. The onset of acute polyarthritis, fever and skin lesions is typical of gonococcal infection but these clinical features may also indicate infection due to Neisseria meningitidis. In the case we report, the correct diagnosis of meningococcal arthritis was established only after N. meningitidis group C had been identified in synovial fluid from the knee.     

A case of renal synovial sarcoma treated with adjuvant ifosfamide and doxorubicin

Primary renal synovial sarcomas (SS) are rare tumors of the kidney. Faria et al first described primary renal synovial sarcoma in 1999 (Mod Pathol 12:94A). In this paper we present a primary renal synovial sarcoma case and review the 41 primary renal synovial sarcoma cases reported to date. Primary renal synovial sarcomas can exist in either a monophasic or a biphasic pattern. The monophasic variant of primary renal synovial sarcoma is more common and tends to have a better prognosis than the biphasic variant. We present in this paper, a 68-year-old woman with primary renal synovial sarcoma. She presented with right flank pain and abdominal distention. Postoperative pathology of the 20 cm mass on magnetic resonance imaging showed histologic and immunochemical features of synovial sarcoma with coexisting spindle and epithelial cells. She underwent adjuvant ifosfamide and doxorubicin chemotherapy and was free of disease at 1 year after diagnosis. As a conclusion, physicians should be aware of the possibility of malignancy in cystic renal masses and that synovial sarcoma is one of the possibilities.     

Neoplastic and paraneoplastic synovitis

Arthritis is a common finding in patients who have cancer. In this population, it is crucial to rule out septic arthritis and metastatic synovitis. Culture, crystallography, (table see text) and cytology of synovial fluid are useful initial diagnostics tools. If all are negative, histopathology of synovial tissue should be considered. Crystal synovitis is another frequent cause of arthritis in patients who have cancer, but it can also coexist with other conditions such as septic arthritis. Independent rheumatic disorders, drug-induced arthritis, and paraneoplastic syndromes should be considered after the exclusion of sepsis and metastatic disease. The diagnosis of a paraneoplastic syndrome is easier when the malignancy is evident or typical findings such as HOA or palmar fasciitis are present. However, these paraneoplastic phenomena can occur before the cancer diagnosis, and it is important to be aware of the association of these conditions with an underlying tumor. Rheumatic disorders with atypical clinical presentation in older patients, poor response to usual treatment, systemic features such as weight loss, and clinical findings compatible with well recognized paraneoplastic syndromes should alert clinicians to the possible coexistence of an occult malignancy.     

Hypertrophic osteoarthropathy and primary intestinal lymphoma

Hypertrophic osteoarthropathy (HOA) in association with primary bowel disease is rare, but is usually seen in patients with chronic diarrheal states, such as Crohn's disease and ulcerative colitis. We record the first case of HOA associated with primary intestinal lymphoma in a patient who presented with chronic diarrhea.