Approach to the Patient with Rheumatic Disease

Classification of Rheumatic Diseases

More than 100 types of rheumatic diseases have been described. Although the pathogenesis is usually dichotomized as degenerative or inflammatory, these diseases ( Table 236-1 ) are usually subdivided as (1) diseases that are associated with degeneration of connective tissues attributable to trauma, structural/mechanical imbalances, or inherent early demise of cellular components; (2) diseases that are associated with systemic autoimmunity, often linked with measurable autoantibodies that can manifest primarily with synovitis, widespread organ involvement, inflamed blood vessels, or inflammation of muscle; (3) other inflammatory connective tissue diseases involving more dense tissues, not associated with the formation of autoantibodies, and hence termed seronegative rheumatic diseases or spondyloarthropathies ; (4) diseases in which inflammation of the vasculature, particularly small, medium, or large arteries, is the predominant feature; (5) autoinflammatory diseases that can be associated with crystal deposition or genetic mutations involving cytokine pathways; and (6) pain syndromes that often must be considered in the context of these diseases, in which some syndromes appear to be comorbid and closely linked to the underlying rheumatic disease, such as diffuse pain associated with Sjögren syndrome, hypermobility of connective tissue, or regional pain syndromes that are anatomically linked to mechanical disruption. Patients who present with generalized pain syndromes require investigation to exclude a connective tissue disease. Increasingly, genomic phenotypes are being associated with diseases as they have been categorized, and in some cases specific immunologic pathways and mediators have allowed grouping of a set of rheumatic diseases previously considered more distinct.

Mimics of rheumatic diseases exist, and clinicians must be mindful of considering these when evaluating a patient for a rheumatic disease. For instance, arthropathies and syndromes resembling a rheumatic disease can occur in the settings of both infection and malignancy. Autoimmune phenomena are increasingly being recognized in the setting of malignancy or as a consequence of treatment of malignancy with immune checkpoint inhibitors. Red flags for each need to be considered in the assessment of a patient for possible rheumatic disease.

Joint Symptoms as a Common Presenting Feature

Almost all rheumatic diseases can manifest with joint-related symptoms and signs. Typically, pain, stiffness, swelling, and difficulty with joint function are the main symptoms. In some forms of joint inflammation, erythema can be prominent, as in the case of autoinflammatory diseases such as gout or pseudogout ( Chapter 252 ) and in infectious arthritis ( Chapter 251 ).

The pattern of joint involvement, its particular distribution, the number of inflamed joints, the speed of onset, duration, and timing of maximal symptoms all provide clues to diagnosis. Regardless of pathogenetic subclassification, certain patterns can point to inflammatory immune-mediated arthritis, and others to a degenerative process. For instance, joint pain that is worse in the morning, associated with prolonged stiffness, and improves as the day goes on and with activity is a classic presentation of inflammatory joint disease such as rheumatoid arthritis ( Chapter 243 ) or spondyloarthritis ( Chapter 244 ). Conversely, pain that is worse with activity, better with rest, and associated with a short period of stiffness after resting, is typical of osteoarthritis ( Chapter 241 ), which is a predominantly degenerative arthritis.

Location provides a clue to broad classification. Patients describing “pain all over” may have a primary pain syndrome. However, pain with an inflammatory pattern localized to the spine or an enthesis (site of ligament insertion) is more likely to indicate a seronegative spondyloarthropathy.

A patient presenting with an inflammatory pattern of symptoms predominantly involving the small joints of the hands and feet is more likely to have one of the autoimmune rheumatic diseases associated with either a positive antinuclear antibody (ANA), rheumatoid factor (RF) or anti–citrullinated peptide antibody (ACPA). Asymmetric large and small joint pain, swelling, and erythema are more characteristic of psoriatic arthritis. Joint symptoms do not always indicate joint disease. Although a third of people might report having a form of debilitating arthritis, these symptoms can include periarticular and soft tissue syndromes common to many rheumatic diseases. The various locations of articular and nonarticular patterns of pain ( Chapter 26 ; Fig. 236-1 ), including involvement of tendons, ligamentous insertions, and fascia, as well as the organ involvement that is typical of specific rheumatic diseases, highlight the need to assess physical manifestations when making a diagnosis of any rheumatic disease.

Nonspecific Clinical Presentations

When present in the context of fever or cutaneous manifestations, including rashes, vasculitis and systemic lupus erythematosus ( Chapter 245 ) must be considered. Sicca symptoms, though pathognomonic of Sjögren syndrome ( Chapter 247 ), can occur concurrently in patients with systemic lupus erythematosus. Systemic features such as myalgias or fatigue are common to almost all rheumatic diseases regardless of their classification, but true muscle weakness may be the only presenting complaint of an inflammatory myopathy ( Chapter 248 ). Renal involvement is common in seropositive systemic autoimmune diseases and vasculitis.

Cutaneous Manifestations

Although cutaneous manifestations are frequent in patients with seropositive autoimmune diseases, particularly systemic lupus erythematosus ( Chapter 245 ), they are important manifestations of all autoimmune diseases. A nonblanching purpuric rash can indicate a vasculitis, and rashes involving specific extensor regions are common to dermatomyositis ( Chapter 248 ). In cases of systemic lupus erythematosus or dermatomyositis, rashes are triggered or worsened by exposure to ultraviolet light and occur in a light-exposed distribution. Rashes of vasculitic origin can indicate either the presence of an autoimmune disease such as systemic lupus erythematosus or an inflammatory vascular disease such as antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. These rashes tend to be present for days and are often palpable, and a tissue biopsy of the lesions will be very helpful in diagnosis. Rashes can be transient. In adult-onset Still disease (an adult form of systemic inflammatory arthritis classified as an autoinflammatory disease; Chapter 240 ), patients present with daily spiking fevers, peaking late in the day, associated with a salmon-colored evanescent blanching rash lasting only 1 to 2 hours. The specific location of a rash aids in diagnosis. A facial rash that spares the nasolabial folds is classic for lupus. A rash that does not spare the nasolabial folds suggests rosacea. Psoriasis is almost always present in psoriatic arthritis (a spondyloarthropathy variant). Although psoriasis is often widespread, involving extensor surfaces, it can be missed if there are very few lesions or if it is located in areas that are not easily seen (intertriginous regions, such as in the ear, umbilicus, buttock creases, or scalp) or if it involves only the nails. The rash of psoriasis can be seen in any of the variants of the spondyloarthropathies. Occasionally rheumatoid arthritis ( Chapter 243 ) will manifest with nodules over the extensor surfaces; however, nodules over extensor surfaces may also indicate gouty tophi ( Chapter 252 ).

Skin tightness is the hallmark of systemic sclerosis ( Chapter 246 ), often referred to as scleroderma, which most often involves the extremities. Patients typically present initially with swelling of the digits, followed by tightness of the hands and ultimately tightness of the skin. Raynaud phenomenon, though not specific to systemic sclerosis, frequently precedes its onset, often by many years. Skin tightness can progress to involve the face, arms, and, in the case of diffuse systemic sclerosis, trunk, back, and legs. Distal tightening of the skin, presence of telangiectasias, and digital ulcers can be seen.

Systemic Manifestations

Rheumatologic diseases eventually can involve every organ system but particularly can cause glomerulonephritis ( Chapter 113 , especially systemic lupus erythematosus), interstitial lung disease ( Chapter 80 , especially in systemic sclerosis and rheumatoid arthritis), renovascular disease ( Chapter 110 , especially systemic sclerosis), pericardial and pleural disease ( Chapters 62 and 86 , especially systemic lupus erythematosus), and neurologic manifestations (especially systemic lupus erythematosus).

Specific Clinical Scenarios