Diagnostic Clinical Parameters

In its general meaning, the term arthritis indicates inflammation in the joint. It is not a specific diagnosis, and there are multiple etiologic agents and diseases that can produce inflammatory responses in joints. These include infections, but also a variety of autoimmune and metabolic disorders. Arthritis is distinguished from arthralgias, which implies aches and pains in the joint. Arthralgias are much more common and do not necessarily mean that the patient suffers from arthritis. Indeed, the most critical component of an examination in clinical practice is the determination of whether inflammation is present in the joint—that is, is it an inflammatory or noninflammatory process? The presence of inflammatory process is much more serious and in some cases, such as infection, creates rheumatology emergency. It should be clarified that the cardinal features of inflammation include the presence of pain (dolor), swelling (tumor), erythema (rubor), and warmth (calor), which are typically detected on physical examination, at least with respect to the peripheral joints. In addition, the elevation of white blood cell (WBC) count in the synovial fluid (>2,000 per mcL), elevated erythrocyte sedimentation rate (ESR), and a high C-reactive protein (CRP) level are also the reliable factors.

In addition to arthritis and arthralgia, there is also a term known as arthropathy, a generic term applied to more than 100 different genetic, autoimmune, metabolic, and other acquired diseases that produce pathologic processes of the joint or joints (Fig. 1.1). Distinguishing these different processes is key to proper imaging and treatment and plays a major role in the critical element of patient’s care.

There are now a large number of standardized objective parameters that are useful to determine whether inflammation is present. The most important is a quality physical examination looking for the four key components of inflammation described in the text above. In addition, there are blood tests available that include the measurements of blood sedimentation rate (ESR) and C-reactive protein (CRP). ESR is a valuable but nonspecific test that measures the rate at which red blood cells sediment in standardized Westergren tube in a period of one hour. The CRP is a protein produced by the liver, induced and generated by cytokine interleukin-6 (IL-6) in response to infection or other cause of inflammation. An elevation of ESR or CRP is a clear indicator of the presence of an inflammatory systemic process and strongly implicates the need for further evaluation of the patient that must incorporate a thorough physical examination as well as synovial fluid analysis, including quantification of cells, the presence or absence of crystals, a Gram stain, and culture for microorganisms. These tests, in conjunction with careful clinical evaluation, provide the cornerstone for the diagnosis and management of patient with joint abnormalities. In this part of the book, we will focus our attention on the clinical aspect of a variety of joint diseases and also on imaging modalities by providing a framework for a logical and systematic approach to both the proper use of imaging techniques as well as their interpretation. In addition, we will place this analysis in the perspective of other diagnostic tests useful for the clinician. Our goal is to provide a structured approach to diagnosis by focusing on some of the common problems seen in several rheumatologic diseases. In doing so, we hope that the clinician will be able to interpret the imaging findings and the pathophysiology involved in the perspective of the patient’s clinical history and physical examination. The cornerstone of rheumatology remains with the bedside examination; generally, the radiologists are at some distant radiologic office preventing the clinician from establishing the relationship between the physical examination and radiologic findings. Nevertheless, the use of imaging techniques is critical to the clinician, because standard radiographs and newly developed techniques, including among others CT, MRI, and PET, have added significantly to the clinician’s armamentarium for evaluating the presence, type, and extent of involvement in various joint abnormalities.

Figure 1.1 ▪ Classification of the arthritides and arthropathies. CPPD, calcium pyrophosphate deposition; MCTD, mixed connective tissue disease.

CLINICAL HISTORY AND PHYSICAL EXAMINATION

Clinical history and physical examination are keys to diagnosis and prognosis in rheumatology. The importance of gaining a clear account and understanding of a clinical problem has long been recognized. Good clinical observation remains central to the management of several rheumatologic disorders. The manner of onset and evolution of symptoms over time is very helpful in establishing the correct diagnosis. A thoughtful and detailed clinical history plays a critical role in determining the nature of the patient’s complaints and provides the focus to the clinical examination. The history should be structured in such a way as to be able to answer the specific questions regarding the symptoms, in particular if they are symmetric or asymmetric in location, and whether they are referred to the one particular region or are generalized. It is important to determine if the symptoms are acute, subacute, or chronic in nature and if they suggest a systemic process. The patient should be questioned regarding muscle weakness, joint pains and stiffness, limitation in joint motion, fever, fatigue, weight loss, anorexia, skin changes, paresthesias and other neurologic symptoms, photosensitivity, mouth and eyes dryness, and similar symptoms among others. It is of utmost importance to find out if there is a family history of similar or related problems.

The fundamentals of physical examination remain the cornerstone of rheumatology, and the examination technique is universally recognized as a sensitive detector of crucial abnormalities. The GALS (gait, arms, legs, spine) locomotor system was devised to rapidly screen the patient for musculoskeletal disorders. The physical examination should be focused among others on the following features: type of gait, joint swelling, deformities and contractures, joint movements (active and passive), skin changes including redness and rashes, and wasting of muscles. Each joint should be individually and systematically examined. Particular attention should be directed to the appearance of the hand, because distinctive patterns of hand involvement and several characteristic abnormalities can point to the specific diagnosis. Swelling of the joints and deformity of the digits resulting from loss of alignment may be consequence of destructive arthritis such as rheumatoid (Fig. 1.2). Swanneck and boutonnière deformities have characteristic clinical appearance suggesting inflammatory arthritis (Fig. 1.3); the presence of Heberden or Bouchard nodes (see Fig. 5.58)
may point to the diagnosis of interphalangeal osteoarthritis; swelling of the proximal and distal interphalangeal joints (Fig. 1.4A) and nail changes such as onycholysis (separation of the nail plate from the nail bed) (Fig. 1.4B), pitting of the nails (Fig. 1.4C), leukonychia (white nails, milk spots) (Fig. 1.4D), splinting hemorrhages (Fig. 1.4E), subungual hyperkeratosis (Fig. 1.4F), and swelling of the entire finger (dactylitis or “sausage digit”) (Fig. 1.4G) are commonly seen in psoriasis; flexible, easy-reducible joint contractures combined with redness and telangiectasia of the nail fold capillaries may be indicative of systemic lupus erythematosus; tapering of the ends of digits and sclerodactyly is characteristic of scleroderma. In the foot, the redness and swelling of the big toe may indicate the presence of gout (Fig. 1.5).

Figure 1.2 ▪ Rheumatoid arthritis. Observe ulnar deviation in the swollen metacarpophalangeal joints of both hands and hyperextension of the thumbs (“hitchhiker’s thumbs”).

Figure 1.3 ▪ Rheumatoid arthritis. A: Flexion in the proximal interphalangeal joints and extension in the distal interphalangeal joints of the index and middle fingers resulted in boutonnière deformity. B: In another patient, note characteristic boutonnière deformity of the index finger. C: Extension in the proximal and flexion in the distal interphalangeal joint is known as a swan-neck deformity.

Figure 1.4 ▪ Psoriatic arthritis. A: Note swelling of the proximal and distal interphalangeal joints and skin changes on the index finger. B: Detachment of the nail from the underlying nail bed is termed onycholysis. C: The surface of the nail develops small pits that look like a surface of a thimble (nail pitting). The number of the pits can vary from a few to dozens. D: White spots on the nail are termed leukonychia. E: Reddish-brown lines and spots, termed splinter hemorrhage, represent tiny blood clots that run vertically under the nail because of damage of small capillaries. F: Typical appearance of hyperkeratosis, a chalky substance that accumulates under the nail. G: Diffusely swollen thumb (sausage digit) represents a dactylitis. Note also typical for psoriasis skin changes.

Figure 1.5 ▪ Gouty arthritis. Observe the big toe swelling and dorsal mass at the site of the first metatarsophalangeal joint representing a tophus. (Reprinted from Klein MJ, Bonar SF, Freemont T, et al., eds. Atlas of Nontumor Pathology. Non-neoplastic Diseases of Bones and Joints. Washington, DC: American Registry of Pathology and Armed Forces Institute of Pathology; 2011, Fig. 8-206, with permission of the author and the Publishers.)

SYNOVIAL FLUID

Evaluation of synovial (joint) fluid, in terms of its physical, chemical, and microscopic characteristics, is of prime importance in the differential diagnosis of variety of arthritides. There are four elements to synovial fluid analysis: visual inspection, nucleated cell count, wet preparation, and cytocentrifuge preparation. On visual inspection, synovial fluid is examined for color, clarity, and viscosity. The color of the synovial fluid varies with its content (Fig. 1.6). Knowledge of the formation and composition of normal fluid is a requisite for an evaluation of abnormal findings. Synovial fluid is a dialysate of plasma to which hyaluronate-protein has been added as a result of synthesis by the synovial lining cells. Its lubricating behavior is dependent upon the reaction between the hyaluronans and protein within the fluid, one of the most important being the hyaluronan-binding protein lubricin. Normal synovial fluid is present in small quantities within the diarthrodial joints; it is transparent and almost colorless. It is highly viscous, its viscosity being dependent upon the content of hyaluronic acid, a long-coiled carbohydrate polymer. Normal synovial fluid does not clot, as fibrinogen and other clotting factors are absent; the walls of blood vessels and the normal barrier function of the synovial membrane prevent these and other large molecules from entering the joint cavity. The total protein concentration is ˜1.8 g%, with a relative increase in albumin as compared with globulin. The high molecular weight proteins, such as beta-2-macroglobulin and alpha-2-macroglobulin are usually absent or present in very small amounts. Small molecules such as glucose, uric acid, and bilirubin are found in a concentration in synovial fluid similar to that in plasma. Finally, synovial fluid normally is relatively acellular, with 200 to 300 primarily mononuclear cells per mcL (1 mm³). Most of the cells are synoviocytes, fibrochondrocytes, and lymphocytes. As a guide to differential diagnosis, pathologic fluids can be divided into four general groups: class I—noninflammatory; class II—inflammatory; class III—purulent; and class IV—hemorrhagic (Table 1.1). Noninflammatory fluids, such as accompanied osteoarthritis, osteonecrosis, amyloidosis, or sarcoidosis, have fewer cells (<200 per mcL) and low protein content. Inflammatory fluids present in such conditions as rheumatoid arthritis (Fig. 1.7), seronegative spondyloarthropathies, systemic lupus erythematosus, crystal-induced arthropathies (Figs. 1.8, 1.9, 1.10, 1.11, 1.12), hemochromatosis (Fig. 1.13), dermatomyositis, or mixed connective tissue disease are more cellular with more polymorphs and abnormal cell morphology, protein count is high, and crystals and occasionally bacteria are present. Purulent fluids have white cell count often above 100,000 per mcL and are typically seen in septic arthritis caused by Staphylococcus aureus, streptococci, and gram-negative organisms. Hemorrhagic fluid is commonly posttraumatic, but also present in some neoplastic and tumor-like (such as pigmented villonodular synovitis) conditions.

Figure 1.6 ▪ Synovial fluid. Depending upon the content, the synovial fluids exhibit different colors. From left to right: normal, noninflammatory arthropathy, hemarthrosis, xanthochromic, and ochronotic. (Reprinted from Klein MJ, Bonar SF, Freemont T, et al., eds. Atlas of Nontumor Pathology. Non-neoplastic Diseases of Bones and Joints. Washington, DC: American Registry of Pathology and Armed Forces Institute of Pathology; 2011, Fig. 8-27, with permission of the author and the Publishers.)

The diagnostic and therapeutic indications for arthro-centesis are depicted in Table 1.2. The contraindications for arthrocentesis are shown in Table 1.3. In general, the diagnostic indications include evaluation of any joint with detectable increases in joint fluid where the exact diagnosis of such

effusion is in doubt. In most diagnostic and all therapeutic procedures, an attempt should be made to withdraw all fluid accumulated in the joint space. Nonetheless, although about 5 mL is sufficient for most of the necessary studies, as little as one drop may be diagnostic of gout or pyrophosphate dehydrate crystal deposition disease if the appropriate crystals are present (see Figs. 1.9, 1.10, 1.11, 1.12). Furthermore, most studies can be minimized to scale down the amount of drowned fluid in pediatric patients. If there is doubt regarding the origin of fluid from a tap (i.e., blood vs. bloody tap or subcutaneous fluid vs. synovial fluid), this may be resolved with the mucin test or metachromatic staining for the presence of hyaluronate (Table 1.4).

Table 1.1 CATEGORIES OF JOINT FLUID AND DISEASE ASSOCIATIONS

Characteristic	Normal	Noninflammatory Group I	Inflammatory Group II	Purulent Group III	Hemorrhagic
Volume (mL) (knee)	<3.5	Often >3.5	Often >3.5	Often >3.5	Often >3.5
Color	Colorless	Xanthochromic	Xanthochromic to white	Depends on organism	Xanthochromic to frankly bloody
Clarity	Clear	Clear	Translucent to opaque	Opaque	Opaque (clear if centrifuged)
Viscosity	High	High	Low	Varies; may be high	High
Leukocytes (per mm³)	<200	200-2,000	2000 – 100,000 (average 20,000)	20,000 – 200,000 (average 100,000)	Variable (usually)
Polymorphs (%)	<25%	<25%	About 75%	>75%	Variable (usually <75%)
Glucose (mg%; fasting)	Nearly equal to blood	Nearly equal to blood	Often lower than blood	Often >25 mg% lower than blood	Nearly equal to blood
Culture	Negative	Negative	Negative	Positive/Negative	Negative
Spontaneous clot	No	Occasionally	Often	Often	Often
Mucin clot	Firm	Firm	Friable	Friable	Friable

Figure 1.7 ▪ Synovial fluid—rheumatoid arthritis. A: Clotted fibrin viewed between polarizers in a wet preparation of synovial fluid obtained from a patient with active rheumatoid arthritis. B: Ragocytes viewed in diffused light in a wet preparation of synovial fluid from the same patient. Observe characteristic large granules within the ragocytes, representing cytoplasmatic inclusions of ingested aggregated IgG immunoglobulin and fibrin. (Reprinted from Klein MJ, Bonar SF, Freemont T, et al., eds. Atlas of Nontumor Pathology. Non-neoplastic Diseases of Bones and Joints. Washington, DC: American Registry of Pathology and Armed Forces Institute of Pathology; 2011, Fig. 8-190, with permission of the author and the Publishers.)

Figure 1.8 ▪ Synovial fluid—hydroxyapatite crystals. The normally almost invisible crystalloids of hydroxyapatite within a fibrin clot form birefringent red complexes with the alizarin when stained with alizarin red. (Reprinted from Klein MJ, Bonar SF, Freemont T, et al., eds. Atlas of Nontumor Pathology. Non-neoplastic Diseases of Bones and Joints. Washington, DC: American Registry of Pathology and Armed Forces Institute of Pathology; 2011, Fig. 8-34, with permission of the author and the Publishers.)

Figure 1.9 ▪ Synovial fluid—pyrophosphate crystals. Pyrophosphate crystals (blue and red) are identified by polarizing microscopy with interference (compensating) plate in the path of light (H&E, polarized light). (Reprinted from Klein MJ, Bonar SF, Freemont T, et al., eds. Atlas of Nontumor Pathology. Non-neoplastic Diseases of Bones and Joints. Washington, DC: American Registry of Pathology and Armed Forces Institute of Pathology; 2011, Fig. 8-16, with permission of the author and the Publishers.)

Figure 1.10 ▪ Synovial fluid—pyrophosphate crystals. A: Pyrophosphate crystals within the synovial fluid cytocentrifuge stained with Jenner-Giemsa. The unstained spaces contain the crystals. B: Same specimen viewed now in polarized light with a quarter-wave plate shows the crystals more clearly. (Reprinted from Klein MJ, Bonar SF, Freemont T, et al., eds. Atlas of Nontumor Pathology. Non-neoplastic Diseases of Bones and Joints. Washington, DC: American Registry of Pathology and Armed Forces Institute of Pathology; 2011, Fig. 8-222, with permission of the author and the Publishers.)

Figure 1.11 ▪ Synovial fluid—urate crystals. A: The needle-shaped monosodium urate monohydrate crystals in synovial fluid aspirated from a patient with acute gouty arthritis are viewed here in polarized light with a quarter-wave compensating plate. The slow wave vector (the direction of the extraordinary axis of the compensating plate) is indicated by the arrow. B: In the synovial fluid obtained from another patient with acute gouty arthritis and viewed in polarizing light with an interposed quarter-wave plate, the urate crystals are clearly visible. C: Urate crystals within a neutrophil (Jenner-Giemsa stain). (A and C reprinted from Klein MJ, Bonar SF, Freemont T, et al., eds. Atlas of Nontumor Pathology. Non-neoplastic Diseases of Bones and Joints. Washington, DC: American Registry of Pathology and Armed Forces Institute of Pathology; 2011, Figs. 8-31 and 8-213, with permission of the author and the Publishers.)

Only gold members can continue reading. Log In or Register to continue