Milwaukee Shoulder Research Articles

Basic calcium phosphate crystals induce the expression of extracellular matrix remodelling enzymes in tenocytes.

Basic calcium phosphate (BCP) crystals contribute to several syndromes associated with tendon disease, including acute calcific tendinitis and Milwaukee shoulder syndrome. Interactions between BCP crystals and tenocytes (tendon cells) may contribute to these clinical syndromes. This study aimed to determine the direct effects of BCP crystals on tenocyte function and viability. In vitro assays were used to assess changes in human tenocytes cultured with BCP crystals. Real-time PCR was used to determine changes in the expression of tendon-related genes and extracellular matrix remodelling enzymes (MMPs; a disintegrin and metalloproteases, ADAMTS; and tissue inhibitor of metalloproteinases, TIMPs). ELISA was used to measure protein concentrations in tenocyte supernatants. MTT and alamarBlue™ assays were used to determine changes in cell viability. BCP crystals upregulated tenocyte gene expression of MMP-1, MMP-3, ADAMTS-4 and TIMP-1 after 24 h. Time-course experiments showed expression peaked at 8 h for TIMP-1 and 48 h for MMP-1 and ADAMTS-4. Cyclooxygenase (COX)-1 gene expression was upregulated after 48 h. Tenocytes did not alter expression of scleraxis and tendon collagens, and expression of pro-inflammatory cytokines was not induced with BCP crystals. BCP crystals increased tenocyte release of prostaglandin E2 (PGE2) and MMP-1 protein after 24 h. However, neither COX-1 inhibition nor COX-2 inhibition led to consistent change in BCP crystal-induced tenocyte gene expression of extracellular matrix remodelling enzymes. BCP crystals had no effect on tenocyte viability. BCP crystals induce extracellular matrix remodelling enzymes, but not inflammatory cytokines, in tenocytes.

Hydroxyapatite Crystal Deposition Disease of the Shoulder: A Review of Cases and Literature

AbstractHydroxyapatite crystal deposition diseases (HADDs) are characterized by deposition of insoluble crystals within the joints and periarticular soft tissues, initiating inflammatory destructive reaction. Calcium hydroxyapatite (CHA) is the most common type of calcium in human bone and is also the most common pathologic calcification found in the body. There are three phases of the disease: silent, mechanical, and adhesive phases. The shoulder is the most common site of HADD. CHA crystals are non-birefringent in polarized light. Radiographic characteristics include homogenous, amorphous densities without trabeculations that are variable in size, ovoid, triangular, or linear. The first imaging modalities to identify calcific tendinitis (CT) were X-ray and ultrasound, as calcium deposits are readily identifiable on both. Treatment is chiefly conservative, including nonsteroidal anti-inflammatory drugs (NSAIDs), local heat application, and physiotherapy. Local corticosteroid injections may also be of benefit. When intra-articular, CHA crystals can cause joint destruction such as “ Milwaukee shoulder.” In the acute symptomatic phase of HADD, called acute calcific periarthritis, soft tissue and osseous edema can be present and needs to be differentiated from infection, tumor, and trauma.

Basic calcium phosphate crystal-associated musculoskeletal syndromes: an update.

Basic calcium phosphate (BCP) crystals are associated with two important musculoskeletal syndromes. Deposition of BCP crystals in tendons, bursae, and other soft tissues around joints causes calcific periarthritis, whereas intra-articular BCP crystals contribute to osteoarthritis and cause the highly destructive arthritis known as Milwaukee Shoulder Syndrome. The epidemiology and natural history of these syndromes are poorly understood, and because the pathogenesis remains unclear, few targeted therapies are available. I will review new developments in this field. I will discuss a case collection of calcific periarthritis of the hip, and evidence-based management strategies for shoulder calcific periarthritis that might be applied to calcific periarthritis at other locations. I will summarize several recent articles addressing mechanisms of crystal formation and identifying pathways through which BCP crystals produce tissue damage and explore some newly identified risk factors for pathologic mineralization. We are making slow, but steady progress in understanding the clinical presentation of calcific periarthritis in sites other than the shoulder. A growing appreciation of the mechanisms through which BCP crystals mediate tissue damage should lead to the development of novel management strategies for these common musculoskeletal syndromes.

30. Milwaukee Shoulder Syndrome - an incidental finding but important cause of acute shoulder arthropathy

30. Milwaukee Shoulder Syndrome - an incidental finding but important cause of acute shoulder arthropathy

Bone scintigraphy in apatite-associated destructive arthritis (Milwaukee shoulder syndrome)

We report a case established of Milwaukee shoulder syndrome (apatite-associated destructive arthritis) and describe the bone scintigraphic, radiologic and histologic findings, which are compared with a similar case of rapid noncrystal- deposition arthritis. The cases shall add to the differential diagnosis of shoulder arthropathy on bone scintigraphy.

Milwaukee Shoulder Syndrome: A Case Report

Milwaukee shoulder syndrome is a progressively destructive shoulder arthropathy mostly seen in mostly women over 70 years age. It is associated with severe pain and generalized restriction of joint movements, usually associated with rotator cuff tear. A 85 years old female presented to our hospital with chief complain of pain and decreased range of movements in both shoulder joints. Investigations were done including FNAC and Biopsy which could not identify any evident cause. Therefore diagnosis was made on clinico-radiological bases and patient was managed. Surprisingly patient had relief with plain NSAID’s compared to opioids.

Molecular mechanisms of pain in crystal-induced arthritis.

Crystal-induced arthritis (CIA) is characterized by an intense inflammatory reaction triggered by the deposition of monosodium urate, calcium pyrophosphate, and basic calcium phosphate crystals in articular and periarticular tissues. Severe, acute pain constitutes the most important clinical symptom in patients affected by these diseases. Pain along with redness, warmness, swelling, and stiffness in the affected joint arises abruptly in gout and disappears when the acute phase of the attack resolves. While an acute joint attack caused by calcium pyrophosphate crystals can mimic a gout flare, basic calcium phosphate crystal arthritis gives rise to a series of clinical manifestations, the most severe of which are calcific periarthritis, mostly asymptomatic, and a highly destructive arthritis known as Milwaukee shoulder syndrome, which is characterized by painful articular attacks. Pain development in CIA is mediated by several inflammatory substances that are formed after cell injury by crystals. The most important of these molecules, which exert their effects through different receptor subtypes present in both peripheral sensory neurons and the spinal cord, are prostaglandins, bradykinin, cytokines (in particular, interleukin (IL)-1β), and substance P. The pharmacological treatment of pain in CIA is strictly associated with the treatment of acute phases and flares of the disease, during which crystals trigger the inflammatory response. According to international guidelines, colchicines, nonsteroidal anti-inflammatory drugs, and/or corticosteroids are first-line agents for the systemic treatment of acute CIA, while biologics, namely anti-IL-1β agents, should be used only in particularly refractory cases.

Severe bursitis in shoulder arthritis – a manifestation of hydroxyapatite crystal deposition disease

In the present understanding of joint pathology, the exact pathogenic role of hydroxyapatite crystals, both periarticularand intraarticular, is not yet completely clear. An association between rapidly destructive osteoarthritis (OA) andhydroxyapatite or basic calcium crystals was confirmed. This is a case report of a 78-year old female patient presentingwith a five-month history of shoulder pain with swelling of both AC joints. Imaging showed a large bursitis starting in theAC joints of both shoulders. Synovial fluid analysis showed many hydroxyapatite crystals and no calcium pyrophosphateor sodium urate crystals, which confirmed the diagnosis of crystal-induced periarthropathy and AC arthritis. Theseperiarticular radiographic and synovial fluid findings are a frequent and known manifestation of hydroxyapatite crystaldeposition disease, similar to the intra-articular destructive “Milwaukee shoulder syndrome”. Surgical intervention wasthe only therapeutic option to reduce the patient’s shoulder pain.

Milwaukee shoulder syndrome

Milwaukee shoulder syndrome or rapid destructive arthritis of the shoulder is a very rare rheumatological condition characterized by the deposition of hydroxyapatite crystals. The figure 1 shows the shoulder image of a 67-year-old female with a history of bilateral shoulder pain and swelling since 2 years and knee pain since 6 months. Physical examination revealed restriction in shoulder movements. No neurological deficit was reported. X-ray of the right shoulder indicated rotator cuff disruption with marked OA (Fig 2). Normal 0 false false false EN-US X-NONE X-NONE

Milwaukee Shoulder Syndrome

Milwaukee shoulder syndrome (MSS) is a rare destructive, calcium phosphate crystalline arthropathy. It encompasses an effusion that is noninflammatory with numerous aggregates of calcium hydroxyapatite crystals in the synovial fluid, associated with rotator cuff defects. We describe a patient that presented with recurrent shoulder pain and swelling with characteristic radiographic changes and MSS was confirmed on aspiration of the synovial fluid.

Milwaukee shoulder syndrome affecting the elbow

Milwaukee shoulder syndrome affecting the elbow

Milwaukee shoulder syndrome (apatite associated destructive arthritis): therapeutic aspects

Milwaukee shoulder is a well defined clinical entity that can be observed in particular in older women. It is a destructive arthropathy associated with the deposition of calcium pyrophosphate dihydrate crystals, characterized by the presence of large amount of synovial fluid and a complete tear of the rotator cuff. Clinical features include pain, swelling and progressive functional impairment. The first-line treatment include the use of analgesic drugs and repeated arthrocentesis followed by intra-articular steroid administration; closed-needle tidal irrigation has been reported to be useful. In late phase we can observe narrowing of the acromion-humeral and of the gleno-humeral joint and progressive degenerative changes at the humeral head, leading to almost complete functional impairment. In these cases a surgical approach with total shoulder arthroplasty may be considered.

Positive Alizarin Red Clumps in Milwaukee Shoulder Syndrome

To the Editor: Milwaukee shoulder syndrome is a destructive, basic calcium phosphate crystalline arthropathy characterized by pain, large-joint effusion, and loss of function in the affected joint1. It classically affects those over 70 years of age, 90% of whom are female. The syndrome is often associated with rotator cuff defects, and the effusion is noninflammatory with numerous aggregates of calcium hydroxyapatite crystals in the synovial fluid. Identifying individual calcium hydroxyapatite crystals in synovial fluid can be elusive, since these crystals are not identified under plain and polarized microscopy, unlike monosodium urate (MSU) and calcium pyrophosphate dihydrate (CPPD) crystals. However, globular clumps of hydroxyapatite crystals may appear using plain light microscopy, but they are not birefringent. Such clumps have been described as “shiny coins,” although often they either are … Address correspondence to Dr. C.J. Forster; E-mail: christopher.forster{at}us.army.mil

Shoulder Pain in the Elderly

Shoulder disorders are a common and sometimes underestimated cause of pain and disability in elderly people. Prevalence of shoulder disorders in the elderly community is 21% and this represents important implications in the provision of community health services. Shoulder disorders are more common in women (25%) than in men (17%). Although many of these patients do not seek medical advice, shoulder pain is a frequent cause of disability, poor subjective perception of health and depression. Soft tissue lesions are the most common cause of shoulder pain in the elderly, including rotator cuff tendinitis or rupture, subacromial impingement, frozen shoulder and acromioclavicular joint osteoarthritis. These conditions are amenable to treatment that in turn will improve patient quality of life. Minimally invasive techniques, especially shoulder arthroscopy, have demonstrated to be extremely useful for this purpose. Glenohumeral osteoarthritis, rheumatoid disease and Milwaukee shoulder are also frequent origins of shoulder ache. In these entities associated with joint destruction, shoulder replacement achieves excellent clinical results and survival rates comparable with knee or hip arthroplasty. Another common cause of shoulder problems in the elderly is fractures of the proximal humerus. These fractures should be regarded as typical osteoporotic fractures, and their incidence is increasing dramatically. They constitute the third most frequent osteoporotic fracture after vertebral and distal radius fractures and usually occur in active people. Half of these fractures are displaced and require surgical treatment. Since proximal humeral fractures usually occur at a younger age than hip fractures, they represent an important warning, forecasting more severe osteoporotic fractures.

Calcium pyrophosphate dihydrate and basic calcium phosphate crystal-induced arthropathies: update on pathogenesis, clinical features, and therapy.

Calcium-containing crystals are the most common class for the osteoarthritic joint. They are responsible for acute periarthritis and destructive arthropathies, and for tissue deposits mimicking tumor-like masses. These crystals encompassed mainly calcium pyrophosphate dihydrate and basic calcium phosphate crystals, with the latter being related to hydroxyapatite, carbonate-substituted apatite, and octacalcium phosphate. Calcification deposit mechanisms will be reviewed with respect to extracellular inorganic pyrophosphate dysregulation mainly caused by modulation of specific membrane channel disorders. Genetic defects have been extensively studied and identified mutation of specific genes such as ANKH and COL. Pathogenesis of crystal-induced inflammation is related to synovial tissue and direct cartilage activation. Besides classical knee or wrist pseudogout attacks or Milwaukee shoulder arthropathies, clinicians should be aware of other specific common presentations, such as erosive calcifications, spinal cord compression by intraspinal masses, ligamentum flavum calcification, or atypical calcified tophus. Promising clinical results for preventing calcium crystal deposits and cartilage degradation are lacking. Practical imaging tools are needed to monitor reduction of calcification of fibrocartilage and articular cartilage as markers of drug efficacy.

Hydroxyapatite deposition disease of the joint.

Basic calcium phosphate (BCP) crystals include partially carbonate-substituted hydroxyapatite, octacalcium phosphate, and tricalcium phosphate. They may form deposits, which are frequently asymptomatic but may give rise to a number of clinical syndromes including calcific periarthritis, Milwaukee shoulder syndrome, and osteoarthritis, in and around joints. Recent data suggest that magnesium whitlockite, another form of BCP, may play a pathologic role in arthritis. Data from the past year have provided further understanding of the mechanisms by which BCP crystals induce inflammation and degeneration. There remains no specific treatment to modify the effects of BCP crystals. Although potential drugs are being identified as the complex pathophysiology of BCP crystals is unraveled, much work remains to be done in order to translate research advances to date into tangible clinical benefits.

Crystal deposition disease of the shoulder (including calcific tendonitis and milwaukee shoulder syndrome).

Calcific tendinitis of the shoulder is a dynamic process. Osteopontin is present in cells surrounding tendon calcifications. Resorption is probably mediated by cathepsin K-containing multinucleated giant cells. Rotator cuff tears are associated with an inflammatory response based on the presence of interleukin-1 and a proliferative synovitis. Metalloproteinases are found in the synovial fluids of patients with rotator cuff tears. Some patients with large rotator cuff tears progress to a severe destructive arthropathy characterized by large joint effusions, which are noninflammatory but contain basic calcium phosphate crystals. These crystals stimulate metalloproteinase production in vitro and also suppress metalloproteinase inhibitor production. Mutations in the ank gene result in decreased extracellular inorganic pyrophosphate in murine progressive ankylosis, and increased extracellular inorganic pyrophosphate in some cases of familial chondrocalcinosis.

Hydroxyapatite crystal deposition disease.

Hydroxyapatite (HA) crystal deposition disease (HADD) is a well-recognized systemic disease of unknown etiology that is caused by para-articular and/or intra-articular deposition of HA crystals. The disease is clinically manifested by localized pain, swelling, and tenderness about the affected joint along with variable limitation of joint motion, although not all patients are symptomatic. Plain radiographs may show calcifications of varying size and shape in the para-articular tendons, bursae, and capsule. The disease may be mono- or polyarticular in distribution. The shoulder is most commonly involved with calcification in the supraspinatus tendon. When intra-articular, HA crystals can cause joint destruction. Any joint can be involved; the shoulder is most commonly affected, resulting in "Milwaukee shoulder." Treatment of HADD usually requires use of analgesics, local heat, needling with or without aspiration of the calcific deposits, steroid injections, and, at times, even surgery for relief of pain.

Nonseptic monoarthritis: imaging features with clinical and histopathologic correlation.

Diagnosis of septic arthritis requires aspiration and analysis of joint fluid. However, nonseptic articular disorders are fairly common and represent a significant diagnostic and therapeutic challenge. Such disorders include gout, Milwaukee shoulder, rapidly destructive articular disease, amyloid arthropathy, hemophilic arthropathy, primary synovial osteochondromatosis, pigmented villonodular synovitis, neuropathic arthropathy, and foreign-body synovitis. The clinical signs of articular disease, which include pain, swelling, and limitation of motion, are often nonspecific and can overlap with those of osseous or extraarticular disorders. Many articular processes have characteristic radiologic appearances that allow definitive diagnosis. Radiography is an important part of the evaluation of patients with articular disease. However, magnetic resonance (MR) imaging is the method of choice for characterizing the various disorders and assessing the full extent of osseous, chondral, and soft-tissue involvement. MR imaging can exquisitely demonstrate joint effusions, synovial proliferation, articular cartilage abnormalities, subchondral bone, ligaments, muscles, and juxtaarticular soft tissues. Although a wide spectrum of noninfectious processes may involve the joints, careful analysis of the imaging findings and correlation of these findings with the patient's clinical history can suggest a more specific diagnosis in most cases. Awareness and understanding of the underlying histopathologic findings aids in interpretation of MR images.

Rapid destructive arthritis of the shoulder.

Rapid destructive arthritis of the shoulder, although uncommon, has received much attention in the recent medical literature. It has been described by several authors under varied names: hemorrhagic shoulder of the elderly, Milwaukee shoulder syndrome, rapid destructive arthritis of the shoulder, apatite-associated destructive arthritis and idiopathic destructive arthritis of the shoulder. This particular form of arthritis affects mainly elderly patients, predominantly women, with limited pain, rotator cuff tear, joint instability, voluminous mildly inflammatory, blood-stained effusion, basic calcium phosphate crystals, and marked joint and bone destruction.