A 27-year-old white man, an active-duty soldier who previously had been healthy, presented with a 5-month history of progressively worsening swelling, pain and, eventually, skin hardening in both legs and then arms. Associated symptoms included myalgia, fever, and fatigue. There was no clear toxin exposure or change in diet or medications. The patient, who was very physically active, engaged in strenuous daily activities.

On presentation, the patient was afebrile. The physical examination was notable for mild wrist contractures without synovitis. Taut and woody indurated skin was seen on the bilateral upper and lower extremities but spared the fingers, chest, feet, back, face, and neck. This classic finding is shown in the photograph (left). What term is used to describe it?

Laboratory studies were remarkable for peripheral eosinophilia (eosinophils up to 28%), mild elevation of inflammatory markers, and an elevated IgG level but a normal IgE level. Pertinent findings were negative or normal: serum protein electrophoresis test; HIV test; and antinuclear antibodies, creatine kinase, thyroid-stimulating hormone, and serum glucose levels. A full-thickness biopsy specimen of the patient's forearm (pathology slides, below) revealed panniculitis and underlying fasciitis, with lymphocytes, plasma cells, and eosinophils.

The clinical, laboratory, and pathological findings make this a classic presentation of what disease?

(Click here for the answer and discussion.)

The diagnosis was eosinophilic fasciitis (EF), also known as Shulman disease. 

The photograph of the patient’s elevated left forearm depicts a groove sign, defined as taut, woody skin induration with longitudinal depressions overlying the course of blood vessels.

 This classic finding is frequently seen in patients with EF,

 in which the skin induration affects the extremities but spares the fingers and toes. Peripheral eosinophilia and hypergammaglobulinemia are common laboratory findings. Panniculitis with underlying fasciitis confirms the diagnosis.

EF, or diffuse fasciitis with eosinophilia, was first described by Shulman

 in 1974. EF is a rare connective-tissue disease, with features distinct from those of systemic sclerosis (SSc). Skin induration is not only common in EF, a scleroderma variant, but is also the hallmark of SSc and a reason why the conditions often are confused.

 Distinguishing between EF and SSc is important because the treatment and prognosis differ.

SSc often involves internal organs and is associated with cutaneous telangiectasia or Raynaud phenomenon; EF rarely has those features. The distribution of skin induration is markedly different, often being widespread and symmetrical in SSc.

 Skin induration in patients with EF often has symmetrical limb involvement, sparing the trunk.

Patients with EF typically present with myalgia and arthralgia. Complications may include compartment syndrome, myopathy, carpal tunnel syndrome, inflammatory arthritis, contractures, and peripheral neuropathies. EF has a better prognosis than SSc, which has a lifelong, chronic course. EF has rare associations with myelodysplastic, lymphoproliferative, and hematological disorders.

The diagnosis of EF is based on the patient’s clinical presentation, but a full-thickness skin biopsy and careful histopathological evaluation usually are mandated. As in the case described here, full-thickness biopsy specimens typically reveal panniculitis and underlying fasciitis, with lymphocytes, plasma cells, and eosinophils.

In addition to the typical histopathological findings, the clinical presentation helps differentiate EF from mimickers. Scleroderma variant conditions, unrelated to but often confused with SSc, are a heterogeneous group that includes EF, diffuse morphea, scleromyxedema, scleredema, eosinophilia-myalgia syndrome, and nephrogenic fibrosing syndrome.

Although the causes of scleroderma variant conditions remain unknown, they have been associated with metabolic abnormalities and environmental, drug, and dietary exposures. EF has been linked to l-tryptophan use, toxic oil exposure, an increase in strenuous activity or exercise, and fire ants, as well as other factors.

Treatment of patients with EF is centered on high-dose corticosteroids. An early start of such therapy at the onset of first symptoms provides better results than a delay in treatment.

 For patients with corticosteroid-refractory disease, other therapeutic options have been found to be effective, including cyclosporine, hydroxychloroquine, methotrexate, and tumor necrosis factor Î± inhibitors.

 Our patient’s symptoms improved after a few months of therapy with high-dose corticosteroids.

This case demonstrates a classic presentation of a rare connective-tissue disease. For patients with skin induration, myalgia, arthralgia, and peripheral eosinophilia, the diagnosis of EF must be entertained and full-thickness biopsy is crucial for excluding alternative diagnoses.

Varga J, Paller AS. Localized forms of scleroderma, scleroderma-like syndromes and cutaneous fibroses. 

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 Servy A, ClÃ©rici T, Malines C, et al. Eosinophilic fasciitis: a rare skin sclerosis. 

 Shulman LE. Diffuse fasciitis with eosinophilia: a new syndrome? 

 Khanna D, Verity A, Grossman JM. Eosinophilic fasciitis with multiple myeloma: a new haematological association. 

 Mallepalli JR, Quinet RJ, Sus R. Eosinophilic fasciitis induced by fire ant bites. 

 Hamilton ME. Eosinophilic fasciitis associated with L-tryptophan ingestion. 

 Chun JH, Lee KH, Sung MS, Park CJ. Two cases of eosinophilic fasciitis. 

 Bischoff L, Derk CT. Eosinophilic fasciitis: demographics, disease pattern and response to treatment: report of 12 cases and review of literature. 

 Khanna D, Agrawal H, Clements PJ. Infliximab may be effective in the treatment of steroid-resistant eosinophilic fasciitis: report of three cases. 

Articles

A 27-year-old white man, an active-duty soldier who previously had been healthy, presented with a 5-month history of progressively worsening swelling, pain and, eventually, skin hardening in both legs and then arms

Woody Skin and Eosinophilia in a Young Man

 Attention to early diagnosis and intervention in patients with osteoarthritis (OA) has increased, but which treatments may have the greatest benefit in slowing or potentially reversing disease progression is unclear. Many interventions have significant positive effects on biomarkers potentially related to disease progression. In many patients, cartilage lesions are likely to be progressive; early intervention aimed at limiting damage to articular cartilage may be critical for decreasing chronic pain and disability. Current therapeutic approaches are considered primarily symptomatic, but there is potential to use available and emerging treatments to ameliorate the progression of OA. Needed are reliable biological markers. In the future, the focus will be not only on reducing pain and improving function but also on early detection and early intervention with chondroprotection.

Osteoarthritis (OA) has been estimated to affect about one-third of persons in the United States aged 65 years or older. Providing effective intervention aimed at avoiding long-term disability stemming from this disease is difficult because there is little capacity to heal articular cartilage damage and damage is likely to be progressive.

Although attention to early diagnosis and intervention in patients with OA has increased, which of the many currently available OA treatments are likely to have the greatest benefit in slowing or potentially reversing disease progression is unclear. There has been no consistent evidence that any treatment can slow the radiological progression of OA, but many interventions have been shown to have significant positive effects on biomarkers potentially related to disease progression.

This is the first article in a 3-part series on managing early knee OA in which we review clinical results for nonpharmacological and pharmacological treatments for patients with OA and summarize data related to their potential for altering disease progression. Although such information is limited, it may help clinicians select treatments for patients who have early OA.

In this first part, we describe the relationships among molecular changes, structural damage, and disease progression, as well as the rationale for early treatment and defining disease modification. The second article will discuss self-help and nonpharmacological interventions. In the third article, we will provide an overview of systemic pharmacotherapy, including acetaminophen, NSAIDs/cyclooxygenase 2 inhibitors, licofelone, diacerein, tramadol and other opioid analgesics, and calcitonin, as well as intra-articular treatments, including corticosteroids and hyaluronates.

Searches of studies for all therapies were carried out using PubMed. Searches for each treatment were focused on citations that included information on “disease modification,” “biomarkers,” “joint space,” “inflammation,” and “cytokines.”

 
Osteoarthritis (OA) is characterized by structural changes, including progressive loss of articular cartilage, increased subchondral plate thickness, the formation of new bone at the joint margins (osteophytes), and the development of subchondral bone cysts. 

OA is characterized by structural changes, including progressive loss of articular cartilage, increased subchondral plate thickness, the formation of new bone at the joint margins (osteophytes), and the development of subchondral bone cysts (

 Many factors that contribute to OA progression have been identified, and much of it may be mediated by aberrant biomechanical forces and pathological responses to them.

Chondrocytes normally respond to mechanical stress by synthesizing extracellular matrix, including the primary components of the articular cartilage matrix, aggrecan, and type II collagen.

 However, abnormal forces in joints affected by OA alter chondrocyte metabolism. The changes result in decreased collagen synthesis and increased production of cartilage-degrading proteases, including matrix metalloproteinases (MMPs) and aggrecanases. Excessive cleavage of type II collagen in OA is thought to result from up-regulation of the synthesis and activity of collagenases, particularly MMP-13.

Chondrocytes in joints affected by OA change phenotype and resemble differentiating chondrocytes in endochondral ossification.

 These cells proliferate; express differentiation-related genes (eg, parathyroid hormone–related peptide); and produce increased levels of type X collagen, annexins, alkaline phosphatase, and osteocalcin.

Cartilage degradation may be preceded by changes in subchondral bone, according to the results of studies of experimental animal models and patients with OA.

 Thickening of the subchondral bone plate may contribute to increased chondrocyte stress and damage to the overlying cartilage. Subchondral bone also may release catabolic factors that promote abnormal cartilage metabolism.

Other changes in chondrocyte metabolism associated with OA include increased production of inflammatory mediators, such as interleukin (IL)-1β, IL-8, IL-6, tumor necrosis factor alpha α (TNF-α), prostaglandin E

, and nitric oxide. Proinflammatory cytokines, such as IL-1β and TNF-α, can promote cartilage resorption as well as drive recruitment and activation of other inflammatory cells. Of note, OA has many characteristics of systemic inflammatory disease and involves T-cell–mediated immune responses associated with increased levels of IL-1β and TNF-α.

 Synovial inflammation also is characteristic of OA, and cartilage degradation products are thought to stimulate synovitis in OA.

In addition to declining levels of cartilage during OA, the composition of the joint tissue is altered. Histological evaluation of the knees in patients with OA has demonstrated synovial hypertrophy and hyperplasia, with an increase in the number of lining cells. Calcification of the extracellular matrix, a reduced level of proteoglycans, and an increase in apoptotic cells compared with normal cartilage also are evident by histological analysis.

 Intrusion of calcified cartilage into the articular cartilage may modify the contours of adjacent articulating surfaces within the joint.

OA has been shown to involve vascular pathology and aberrant vascular invasion. Increased vascularization and abnormal innervation of articular cartilage may contribute to the development of tibiofemoral pain in patients with knee OA.

Another possible marker for progression of OA is lubricin (superficial zone protein, proteoglycan 4), a mucinous glycoprotein secreted from synovial fibroblasts and superficial zone articular chondrocytes.

 It has been shown that levels of lubricating protein in cartilage are higher in patients with OA than in normal controls and that the concentration rises with increasing OA severity.

 However, this apparent compensatory response is not sufficient to reduce friction in knees with OA.

The elasticity of collagen is decreased in the cartilage of patients with knee OA.

 The concentration and viscosity of synovial fluid also are decreased.

In a study that involved rabbits with sustained anterior cruciate ligament (ACL) and posterior cruciate ligament damage, the injury decreased lubricin levels and the reduction was associated with damage to the articular cartilage matrix.

 In a study of 30 patients with unilateral ACL insufficiency, lubricin concentrations in synovial fluid were reduced significantly at short intervals after ACL injury compared with those in the intact knee.

 Within 12 months, however, lubricin levels in the damaged knee approached those in the intact knee. In this study, TNF-α levels in injured knees were inversely correlated with lubricin levels.

Several studies have demonstrated close relationships between structural or molecular changes and the progression of symptom severity in patients with knee OA. In the Multicenter Osteoarthritis Study, which assessed 2210 persons at high risk for OA, 14% of them had stable radiographic OA and 27% had worsening radiographic OA between enrollment and the 30-month study end point.

 The risk of incident severe functional limitation in patients with worsening radiographic OA was more than double the risk in those with radiologically stable disease.

In a study of 2483 patients that correlated early changes in biochemical markers of bone (cross linked N-telopeptide of type I collagen), cartilage (C-telopeptide of type II collagen [CTX-II]) degradation, and x-ray film results, a significant relationship was found between higher CTX-II levels and radiological disease progression.

 Also, MRI showed elevated CTX-II levels to be associated with decreases in the mean thickness of medial and lateral tibial cartilage over 1 year of follow-up.

Assessment of concentrations of serum cartilage oligomeric matrix protein (COMP) and cleaved collagen neoepitope compared with cartilage volume in 4 compartments of the tibiofemoral joint showed a significant negative correlation between serum COMP and medial tibial cartilage volume in male patients with knee OA.

 In a small-scale study of 120 patients with knee OA and 45 normal controls, P selectin levels in synovial fluid were significantly correlated with OA severity, as reflected by Kellgren-Lawrence grade.

 Overexpression of bone morphogenetic protein-7 and levels of osteopontin and endoglin in both plasma and synovial fluid also have been shown to be correlated with progression of knee OA, as determined by Kellgren-Lawrence grading.

Damaged articular cartilage has little or no healing capacity because its low metabolic activity and limited blood supply permit only a modest response to injury. In many patients, cartilage lesions are likely to be progressive.

 Therefore, early intervention aimed at limiting damage to articular cartilage may be critical for decreasing the chronic pain and disability associated with OA.

The cost of managing OA increases as the disease progresses. The annual cost of OA in the United States has been estimated at $128 billion

; a major component of the direct costs is the management of later-stage disease (eg, joint replacement).

 The indirect costs of OA also are elevated in patients with later-stage disease; in a 2010 study, annual costs resulting from lost productivity were $6096, $13,251, and $17,214 per patient for self-reported mild, moderate, and severe OA, respectively.

 Quality of life for patients with OA also declines with progression of the disease.

Successful treatment for patients with early OA would greatly benefit them as well as the health care system because it could reduce long-term morbidity and the consequent high level of use of health service resources.

 Early diagnosis and management of OA (perhaps even before it becomes symptomatic) to prevent subsequent pain and disability associated with this disease is supported by the National Public Health Agenda for Osteoarthritis, published by the CDC and the Arthritis Foundation.

A disease-modifying agent for OA has been defined as one that can slow, halt, or reverse the rate of disease progression. Of note, there is no current clear consensus on what end point in a clinical trial would provide evidence of disease-modifying capacity for an OA therapy.

 Although the current therapeutic approaches for OA are considered to be primarily symptomatic, there is potential to use available and emerging treatments to ameliorate the progression of OA.

Detecting decreases in joint-space width on plain x-ray films is the currently recognized technique for evaluation of cartilage damage and OA structural progression.

 However, the use of plain x-ray films for assessment of disease progression in patients with knee OA has significant limitations. Most important, radiographic evidence of OA is seen only after significant cartilage degradation has already taken place.

 In addition, there are substantial differences in the apparent rate of joint-space width decline among knee OA patient cohorts that may be the result, at least in part, of inconsistent positioning of the knee when serial x-ray films are obtained and other technical factors.

Needed are reliable biological markers that have the capacity to predict cartilage loss and that can be used for assessment of the disease-modifying effects of OA treatments. There is no generally accepted preradiographic biomarker that can be used to assess the potential disease-modifying effects. However, several candidate markers may be useful for assessing the potentially disease-modifying effects of therapy in the later disease stages.

 These include serum hyaluronic acid; serum COMP; urinary CTX-II; and serum and urinary Coll2-1 and its nitrated form, Coll2-1NO

The OA Biomarker Global Initiative, aimed at developing biomarkers for assessment of patients with OA, is a partnership with the National Institute on Musculoskeletal Diseases, the Osteoarthritis Research Society International, the American Orthopedic Society for Sports Medicine, and the Orthopaedic Research Society.

 The efforts of this group may lead to identification and validation of biomarkers that can be used in assessment of the disease-modifying capacities of established and emerging OA treatments.

Future therapies for knee OA will continue to be focused on reducing patients' pain and improving their function. However, they also will be aimed at early detection and early intervention with chondroprotection.

Goldring SR, Goldring MB. Clinical aspects, pathology and pathophysiology of osteoarthritis. 

 Sellam J, Berenbaum F. The role of synovitis in pathophysiology and clinical symptoms of osteoarthritis. 

 Samuels J, Krasnokutsky S, Abramson SB. Osteoarthritis: a tale of three tissues. 

 Block JA, Shakoor N. The biomechanics of osteoarthritis: implications for therapy. 

 Tchetina EV. Developmental mechanisms in articular cartilage degradation in osteoarthritis. 

 Attur M, Samuels J, Krasnokutsky S, Abramson SB. Targeting the synovial tissue for treating osteoarthritis (OA): where is the evidence? 

 Martel-Pelletier J, Pelletier JP. Is osteoarthritis a disease involving only cartilage or other articular tissues? 

 Walsh DA, McWilliams DF, Turley MJ, et al. Angiogenesis and nerve growth factor at the osteochondral junction in rheumatoid arthritis and osteoarthritis. 

 Martel-Pelletier J, Kwan Tat S, Pelletier JP. Effects of chondroitin sulfate in the pathophysiology of the osteoarthritic joint: a narrative review. 

 Musumeci G, Loreto C, Carnazza ML, Martinez G. Characterization of apoptosis in articular cartilage derived from the knee joints of patients with osteoarthritis. 

Attention to early diagnosis and intervention in osteoarthritis (OA) has increased, but which treatments may have the greatest benefit is unclear. However, available and emerging treatments can ameliorate progression.

Managing Knee Osteoarthritis: Rationale for Early Treatment

 Patients with anterior cruciate ligament injuries typically need operative reconstruction to restore normal knee biomechanics and prevent the early development of osteoarthritis. Conventional nonanatomical reconstructive techniques have been ineffective. True anatomical reconstruction may be achieved only by customizing each procedure on the basis of an individual patient’s native anatomy. A comprehensive history and physical examination, including an assessment of the rupture pattern, help preoperative planning. The physical examination should assess knee function, range of motion, swelling, laxity, and pain and include tests to rule out concomitant injuries and neurovascular involvement. Imaging with conventional radiography, MRI, and other modalities plays a definitive role in diagnosis. The main priorities of rehabilitation are regaining range of motion and quadriceps strength.

Anterior cruciate ligament (ACL) injuries occur frequently in young and active persons. Patients typically have a need for operative reconstruction of the ligament to restore normal knee biomechanics and, subsequently, prevent the early development of osteoarthritis (OA) of the injured knee. However, conventional nonanatomical reconstructive techniques have been ineffective in restoring rotational stability and in preventing early degenerative changes of the articular cartilage.

To restore knee biomechanics and function adequately, returning the anatomy to its native situation as closely as possible is of paramount importance. Objectifying anatomy by taking measurements helps determine surgical technique. Surgery should be individualized to each patient, and nonanatomical techniques should be eliminated because they are a risk factor for the development of early OA. In this article, we provide a concise rationale for our evaluation and treatment of patients who have a torn ACL.

The ACL is one of the main knee stabilizers; specifically, it controls anteroposterior (AP) and rotational stability. As such, this ligament is prone to tearing in sports that involve cutting and pivoting, and ACL injury has become one of the most common sports injuries in an increasingly young and active population. The incidence rate for ACL rupture is 35 of 100,000 persons; the risk of injury is 2 to 3 times higher for females.

 Because the ACL does not have the potential to heal adequately when torn, reconstructive surgery generally is the treatment of choice.

 
A 3-dimensional CT scan shows a nonanatomical single-bundle (SB) anterior cruciate ligament reconstruction and demonstrates a posterolateral (PL) tibial tunnel and a “high” anteromedial (AM) femoral tunnel. 

Although the ACL has been acknowledged as consisting of 2 distinct functional bundles-anteromedial (AM) and posterolateral (PL)-the ligament has long been reconstructed nonanatomically with a single graft (

 The conventional nonanatomical single-bundle (SB) technique has shown good results in the short term, with improvement in subjective knee stability.

 At long-term follow-up, however, nonanatomical SB ACL reconstruction (ACL-R) does not restore native knee biomechanics and the early onset of OA seems to occur at the same rate as in knees that have not undergone surgery.

In addition, subjective knee instability may persist, leaving patients unable to return to their previous activity level. In a study conducted by Ardern and asso­ciates,

 only 45% of patients had returned to their previous level of activity at 2 to 7 years after SB ACL-R.

Anatomical double-bundle (DB) ACL-R, an alternative to SB ACL-R, is suggested to more closely reproduce the native anatomy of the ACL by restoring both the AM and the PL bundles individually.

9 In cadaver studies, anatomical DB ACL-R demonstrated better restoration of biomechanical properties of the knee, especially rotational stability, than did nonanatomical SB ACL-R.

 conducted a study (level of evidence, I) that demonstrated the clinical superiority of anatomical ACL-R. At 3- to 5-year follow-up with an 85% follow-up rate, both AP and rotational knee stability were better restored with an anatomical DB or SB ACL-R than with a nonanatomical SB ACL-R.

True anatomical ACL-R may be achieved only by customizing each procedure on the basis of an individual patient’s native anatomy. Only then can the ACL be functionally restored to its native dimensions, collagen orientation, and insertion sites.

Patients who have a torn ACL typically present with an unstable, swollen, and painful knee. They may complain of difficulty in bearing weight and diminished range of motion. Swelling typically decreases and, consequently, range of motion improves within the first weeks after the injury. Patients with chronic ACL deficiency may have less evident complaints and experience only a nonspecific pain and recurrent instability of the knee. For the greatest potential for a successful outcome, surgery should be performed when swelling has diminished and range of motion is near normal.

A comprehensive history and physical examination, including an assessment of the rupture pattern and the presence of concomitant injuries, help preoperative planning. The physical examination should assess knee function, range of motion, swelling, laxity, and pain. The examination also should include tests to rule out any concomitant injuries and neurovascular involvement. Specific assessments include the anterior and posterior drawer, Lachman, pivot shift, varus/valgus stress, McMurray, and dial tests. AP instability may be quantified by KT-1000 arthrometer testing.

 
Shown are special anterior cruciate ligament (ACL) sequences on MRI in which the slices are parallel to the plane of the ACL 

 
Preoperative measurements for anterior cruciate ligament (ACL) surgery made on standard sagittal MRI include tibial insertion site length (A) 

Imaging with conventional radiography, MRI, and other modalities plays a definitive role in diagnosis and helps preoperative planning of individualized surgery. Special oblique MRI planes obtained in alignment with the ACL allow for a more complete evaluation of the two bundles (

 Preoperative measurements include tibial insertion site length, ACL length, ACL inclination angle, and quadriceps and patellar tendon thickness on standard sagittal MRI. These measurements are critical to the individualization process, and they help determine reconstruction technique and graft choice (

 
For anterior cruciate ligament surgery, the patient lies in the supine position with the operative leg in the leg holder and the nonoperative leg in the lithotomy position (A). The operative knee should allow for 120° of flexion (B) and full extension (C). 

Once anesthesia is induced, the physical examination is repeated to evaluate ligamentous knee function more specifically. The patient is placed in the supine position. A tourniquet is placed high on the operative extremity, which is fixed in a leg holder allowing for at least 120° of knee flexion. The contralateral leg is positioned in the lithotomy position outside of the surgical field (

A high anterolateral portal (ALP) is created above the fat pad to allow for an unobstructed view of the notch and the tibial ACL insertion site. At this point,  diagnostic arthroscopy of the knee is performed.

 
Approximation of portals is shown here. The anterolateral portal (ALP) is placed high, above the fat pad. 

Next, with a spinal needle under arthroscopic visualization, the central medial portal (CMP) and accessory medial portal (AMP) are placed as described by Araujo and associates (

 The CMP provides an overview of the intercondylar notch and the femoral ACL insertion site, which is critical for evaluating the rupture pattern and appreciating the native anatomy. The AMP is used mainly as a working portal.

Intraoperative measurements of the insertion sites and notch size are obtained with an arthroscopic ruler 

). On the basis of both the preoperative and intra-operative measurements, the surgeon makes a final decision on surgical technique and graft choice.

A tibial insertion site length of less than 14 mm or a narrow notch (less than 12 mm wide) technically precludes DB ACL-R. As such, an SB technique would be preferred. Insertion site lengths between 14 and 18 mm permit the SB and the DB techniques. When the tibial insertion site is longer than 18 mm, a DB procedure is preferred.

 
At the tibial insertion site, the site length (A), midwidth (B), and individual bundle widths are measured with an arthroscopic ruler. 

The notch and ACL remnants are visualized through the CMP and carefully dissected with a thermal device to identify the AM and PL insertion sites and their bony margins. The scope is then switched to the AMP to visualize and measure the femoral insertion site (

 
The notch width is measured at 3 levels: the base (A), the middle (B), and the apex (C). Subsequently, the notch height is measured on the lateral and medial wall of the notch (D). 

A DB procedure may be performed with soft tissue grafts or a split quadriceps graft with a bone block (

). For soft tissue grafts, 2 femoral tunnels should be placed in the center of the AM or PL insertion site. However, if a quadriceps graft is used, a single femoral tunnel positioned midway between the AM and PL insertion sites is preferred to accommodate the bone block.

 
With an arthroscopic ruler, the femoral insertion site length (A), midwidth (B), and individual bundle widths are measured. 

A pointed awl is used to create the initial hole in the PL bundle insertion site center for the first tunnel, and a guidewire is advanced. The femoral PL tunnel is then drilled over this guidewire through the AMP. The knee is flexed to 120° to avoid iatrogenic damage and to obtain maximum tunnel length. The drill diameter should be 1 mm smaller than the desired tunnel size. The tunnel is drilled to a depth of at least 20 mm. A suspensory device drill is used to breach the far lateral cortex. The total length of the tunnel is measured, and the tunnel is then drilled by hand to an adequate depth for suspensory device fixation. The desired diameter is achieved with the use of a hand dilator.

Attention is then turned to the tibial side. A 3- to 4-mm vertical incision is made in the proximal AM aspect of the leg between the anterior tibial tubercle and the medial tibial crest. This incision is used for tibial AM and PL tunnel drilling. With the scope through the ALP, the tibial insertion site is dissected carefully with a thermal device and the PL and AM insertion sites are marked. A tip-to-tip tibial aiming guide set to 45° is then placed in the marked PL insertion site.

 
For split quadriceps autograft with bone block, the purple arm is placed in the posterolateral position and the other arm in the anteromedial position. The suspensory device is already mounted on the bone block. 

A guidewire is drilled through the aiming device (

), which is then reset to 55° for AM tunnel placement through the CMP following the same steps. To ensure adequate bone bridge between the tunnels, the entrances should be 1 cm apart on the leg and intra-articular pin spread should be measured. The PL tunnel is drilled first and advanced over the guidewire. Desired tunnel diameter (1 mm larger than the drill size) is achieved subsequently with a hand dilator. The same steps apply to AM tunnel drilling.

 
A tip-to-tip tibial aiming guide is placed in the center of the marked posterolateral (PL) and anteromedial (AM) insertion sites. 

The AM femoral tunnel can be drilled through the AM tunnel (100% of cases) or through the PL tibial tunnel (about 60% of cases). If the transtibial approach allows for an anatomical placement of the AM tunnel, this method should be used. However, it necessitates a half moon drill bit, because the tibial PL tunnel has a smaller diameter than the would-be femoral AM tunnel.

If an anatomical position is not feasible with the transtibial approach, AMP drilling is required. The femoral AM tunnel drilling follows the same steps as described for the femoral PL tunnel drilling.

Next, the grafts are passed. The PL graft is passed first and fixed on the femur with a suspensory device, followed by passing of the AM graft, which is fixed in similar fashion. The knee is then cycled several times with tension applied to the tibial ends of the grafts. On the tibial side, the PL bundle is fixed at 0° and the AM bundle at 45° of knee flexion, both with bioabsorbable interference screws.

This reconstruction follows the same protocol as the DB procedure. However, it has the following differences: 1 femoral tunnel and 1 tibial tunnel positioned midway between the AM and PL insertion sites and graft fixation at 15° of knee flexion.

Anatomical SB and DB procedures have the same general complications, including wound infection, hemarthrosis, arthrofibrosis, effusion, neurovascular injury, tunnel widening, tibial or femoral fractures, and deep venous thrombosis. The DB technique is more complex technically and therefore more prone to complications in inexperienced hands. Therefore, the DB concept should be first solidified in an SB approach before a DB reconstruction is attempted.

Protocols are the same for anatomical SB and DB ACL-R. The main priorities of rehabilitation are regaining range of motion and quadriceps strength.

For the first postoperative week, patients are kept in a hinged knee brace locked in full extension. Ambulation is permitted with crutches. At the end of week 1, continuous passive motion is initiated and progresses to full extension.

Patients typically are weaned from braces and crutches at about 6 weeks, depending on quadriceps muscle strength. At this point, straight-line walking can begin, with gradual progression to straight-line jogging and stationary biking at about 3 months. Pivoting and cutting generally are permitted at about 6 months, with a gradual return to sports activity at about 9 to 12 months (for both autografts and allografts).

Anterior cruciate ligament injuries occur frequently in young and active persons.

Anatomical Anterior Cruciate Ligament Reconstruction: A Rationale

The woman presented with ongoing renal insufficiency and anemia. She had received a diagnosis of bilateral scleritis 8 years earlier. More recently, she experienced elbow pain, swelling, and decreased range of motion. A review of symptoms was negative for eye pain and visual complaints, photophobia, rash, oral ulcers, and Raynaud phenomenon. Physical examination findings were mostly normal. Laboratory findings were significant for a positive rheumatoid factor. Elbow MRI scans showed generalized synovitis and marked synovial proliferation. A renal biopsy specimen revealed a pauci-immune glomerulonephritis with crescents. The diagnosis of bilateral scleritis could be attributed to a subsequent diagnosis of rheumatoid arthritis or to a new diagnosis of antineutrophil cytoplasmic autoantibody vasculitis. The case demonstrates how a common rheumatologic condition may present in an uncommon way.

A 54-year-old Asian woman presented with ongoing renal insufficiency and anemia that were thought to be the result of analgesic nephropathy caused by NSAIDs. Her medical history also was significant for hypertension that was well controlled. In this article, we describe her case to demonstrate how a common rheumatologic condition may present in an uncommon way.

Eight years earlier, the patient received a diagnosis of bilateral scleritis and also had mild joint discomfort. She was treated with methotrexate and corticosteroids; there was good resolution of her symptoms.

Over the past year, the patient experienced right elbow pain and swelling, followed by decreased range of motion. A review of symptoms was negative for eye pain and visual complaints, photophobia, rash, oral ulcers, and Raynaud phenomenon. She had no other joint complaints and no morning stiffness. There was no history of blood clots, epistaxis, or hemoptysis.

Findings from the patient's physical examination were normal except for a blood pressure of 199/70 mm Hg (normal, 120/80 mm Hg) and a painful, swollen right elbow with decreased extension. Her hand, wrist, shoulder, knee, ankle, and foot joints did not show synovitis and were not tender. Her sclera were not injected, and the results of an eye examination were otherwise unremarkable.

Laboratory findings were significant for a positive rheumatoid factor (RF) at 40.2 IU/mL (normal, lower than 13 IU/mL) and an anti–cyclic citrullinated peptide (anti-CCP) antibody level of 24 U/mL (normal, lower than 7 U/mL), perinuclear antineutrophil cytoplasmic antibodies (pANCA) titer of 1:320 (normal, lower than 1:20), and myeloperoxidase (MPO) antibody level of 40.2 IU/mL (normal, lower than 9 IU/mL). Her antinuclear antibody test result was negative, and C3 and C4 levels were normal. Her erythrocyte sedimentation rate was 68 mm/h (normal, 0 to 20 mm/h), and her creatinine and hemoglobin levels were 1.46 mg/dL (normal, 0.7 to 1.2 mg/dL) and 7.1 g/dL (normal, 13.5 to 18 g/dL), respectively; urinalysis did not show an active sediment.


A coronal view of the patient's right elbow shows erosions and synovial thickening.

MRI scans of the patient's right elbow obtained without contrast showed generalized synovitis and marked synovial proliferation along with a joint effusion (

). There also was extensive erosive arthropathy. A renal biopsy specimen revealed a pauci-immune glomerulonephritis with crescents (

Given the biopsy results, the patient received 500 mg of methylprednisolone intravenously for 3 days and then therapy was transitioned to prednisone, 60 mg/d. Therapy with cyclophosphamide, 100 mg PO daily, also was started. In addition, the patient received atovaquone for 

 pneumonia prophylaxis because she had a sulfa allergy. Calcium plus vitamin D and nasal calcitonin were given concomitantly with her prednisone for bone health protection.


A sagittal view of the patient's elbow shows chondromalacia and synovial thickening.

The diagnosis of bilateral scleritis that the patient received 8 years earlier could be attributed to a subsequent diagnosis of rheumatoid arthritis (RA) or to a new diagnosis of antineutrophil cytoplasmic autoantibody (ANCA) vasculitis. The physical examination and MRI findings for her elbow, in addition to her positive anti-CCP antibody test result, strongly suggest that she has RA, but the renal biopsy specimen indicates a renal vasculitis. Because having these two diseases at the same time is very unusual, the question becomes, Is the patient's condition an overlap syndrome of two diseases that do not occur together frequently or a subset of rheumatoid vasculitis?


The patient's renal biopsy specimen revealed a pauci-immune glomerulonephritis with crescents.

Rheumatoid vasculitis usually occurs in patients who are RF-positive and have long-standing disease that has gone untreated. The most common findings are nail bed infarctions (not present in our patient) and mononeuritis multiplex (which our patient also did not have) found by history or examination.

Patients with RA have been reported to have positive pANCA titers, but having a concurrent ANCA vasculitis is quite rare. There have been reports of RA overlapping with granulomatosis with polyangiitis (formerly Wegener granulomatosis), microscopic polyangiitis, and Churg-Strauss syndrome.

Our patient probably has RA–microscopic polyangiitis overlap syndrome. Treatment should be chosen to manage both conditions. The agents most frequently used are corticosteroids and other disease-modifying antirheumatic drugs, such as methotrexate and azathioprine. Rituximab often is used for severe RA and recently was approved for treatment of patients with ANCA vasculitides.

 One case series, currently in abstract form, recently suggested that the use of rituximab was beneficial in 3 cases of these overlap syndromes.

Our patient initially will receive oral cyclophosphamide for 6 to 9 months, with a likely change to azathioprine or methotrexate for maintenance therapy. If she relapses or if therapy with cylcophosphamide is not successful, rituximab will be a likely option; it could have been the initial choice for therapy.

The patient's prednisone regimen currently is reduced to 15 mg/d. At her last visit, she received an intra-articular corticosteroid injection into the right elbow. With regard to her renal function, her overlap syndrome is responding nicely to treatment-her most recent creatinine level was 1.08 mg/dL. Repeated MPO and pANCA testing are pending.

 Szilasi M, MÃ¡tyus J, File I, et al. Association of ANCA-associated vasculitis-rheumatoid arthritis overlap syndrome in four patients: rituximab may be the right choice? 

 Stone JH, Merkel PA, Spiera R, et al; RAVE-ITN Research Group. Rituximab versus cyclophosphamide for ANCA-associated vasculitis. 

A 54-year-old Asian woman presented with ongoing renal insufficiency and anemia that were thought to be the result of analgesic nephropathy caused by NSAIDs.

The Journal of Musculoskeletal Medicine Vol 29 No 6

Woody Skin and Eosinophilia in a Young Man

Managing Knee Osteoarthritis: Rationale for Early Treatment

Anatomical Anterior Cruciate Ligament Reconstruction: A Rationale

RA and Microscopic Polyangiitis: Overlap Syndrome or Vasculitis Subset?