Undifferentiated Spondyloarthritis

The terms spondyloarthritis or spondyloarthropathies are used to refer to a family of diseases that share a group of similar clinical features. The most distinguishing features are inflammation of axial joints (especially the sacroiliac joints), asymmetric oligoarthritis (especially of the lower extremities), dactylitis (sausage digits), and enthesitis (inflammation at sites of ligament or tendon attachment to bone). Additional features include genital and skin lesions, eye and bowel inflammation, an association with preceding or ongoing infectious disorders, positive family history, elevated acute phase reactants, and a strong association with the human leukocyte antigen (HLA)-B27.

The preferred term for this family of arthritis is “spondyloarthritis” (SpA)

CLASSIFICATION OF SPONDYLOARTHRITIS — The spondyloarthritis (SpA) family consists of the following, sometimes overlapping, disorders:

• Ankylosing spondylitis (AS)
• Non-radiographic axial SpA (nr-axSpA)
• Undifferentiated spondyloarthritis (UspA)
• Reactive arthritis (formerly called Reiter syndrome)
• SpA associated with psoriasis or psoriatic arthritis
• SpA associated with Crohn’s disease and ulcerative colitis
• Juvenile onset spondyloarthritis

The clinical manifestations of spondyloarthritis (SpA) include musculoskeletal findings; eye involvement, skin, genital, mucosal lesions and inflammation of the bowel mucosa. In addition, a family history of SpA can be also present, which is defined as the presence in a first- or second-degree relative of SpA, uveitis, reactive arthritis, psoriasis, or inflammatory bowel disease.
Musculoskeletal features — Musculoskeletal manifestations of SpA include inflammatory back pain, peripheral arthritis, enthesitis, and dactylitis. Other features may also commonly occur.

Inflammatory back pain — Back pain is the most common symptom at disease onset, being present in about 70 percent of patients. Although back pain in general is a common complaint in primary care, back pain due to SpA is comparatively uncommon and can frequently be distinguished from other causes of axial pain. By convention, the back pain of SpA is termed “inflammatory back pain,” while back pain from other causes is termed “mechanical back pain.”

Peripheral arthritis — The peripheral arthritis in SpA usually has an acute onset and predominantly involves the lower extremities, especially the knees and ankles. However, any joint can be involved. Arthritis is typically asymmetrical and often affects only one to three joints. Arthritis of the knees and ankles can be accompanied by considerable swelling.

Enthesitis (enthesopathy) — The enthesis is the site of insertion of ligaments, tendons, joint capsule, or fascia to bone; it is composed of dense collagen, fibrocartilage, adjacent bursae, and synovial folds. Enthesitis (or enthesopathy), which refers to inflammation around the enthesis, is relatively specific to SpA. The most common observable clinical manifestation of enthesitis is swelling at the heels, at the insertion of the Achilles tendon or at the insertion of the plantar fascia ligament into the calcaneus. It is usually associated with severe pain and tenderness.

Dactylitis (sausage digits) — a characteristic feature of SpA, including psoriatic arthritis, is dactylitis, also known sausage toe or sausage finger. Unlike synovitis, in which swelling is confined to the joints, with dactylitis, the entire digit is swollen. Joints do not show the discrete palpable fusiform swelling of synovitis, and there may be surprisingly little pain or tenderness. The diffuse swelling arises from flexor tendon, sheath, and marked adjacent soft tissue involvement. Dactylitis is not specific for SpA and may also be seen when the bones of the digits are involved with tuberculosis, syphilis, sarcoidosis, sickle cell disease, and tophaceous gout.

Anterior chest wall or rib cage pain – some patients with axial SpA complain of anterior chest wall or rib cage pain, but this symptom has poor specificity for SpA.

Buttock pain – pain that can alternate between the left and the right gluteal regions is also commonly reported.

Inflammatory eye disease — Conjunctivitis may be a manifestation of SpA. The involvement is typically transient with symptoms subsiding within a few weeks. A more serious problem is anterior uveitis (iritis). The initial attack is usually acute and unilateral and may be the presenting problem. Patients complain of redness, pain, and photophobia. It is recommend that all patients with symptomatic eye involvement be referred to an ophthalmologist, because an accurate diagnosis of uveitis requires slit lamp examination.
Inflammation of the bowel mucosa — Up to two-thirds of patients with SpA have inflammatory lesions of the bowel mucosa. These are usually clinically silent. There are two types of lesions: an acute lesion, which resembles acute bacterial enterocolitis, and a chronic ileocolitis, which is often indistinguishable from Crohn’s disease.

LABORATORY TESTS — Acute phase reactants, including the erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), are increased in some patients. Testing for bacterial infection that may cause reactive arthritis is useful for the diagnosis of reactive arthritis but not other forms of SpA. In most ethnic groups, more than 90 percent of patients with ankylosing spondylitis and 70 percent of patients with undifferentiated spondyloarthritis (USpA) are positive for human leukocyte antigen (HLA)-B27. HLA-B27 testing is frequently obtained in patients suspected of SpA; however, a positive HLA-B27 by itself is not diagnostic of SpA, because a significant proportion of subjects in the general population are also positive. HLA-B27 is especially useful in supporting the diagnosis of axial SpA in the 30 percent of axial SpA patients who lack sacroiliitis on imaging. HLA-B27 is also useful in that a negative test makes the diagnosis of ankylosing spondylitis less likely. The diagnosis of SpA should be doubted if both HLA-B27 and imaging for sacroiliitis are negative. SpA, predominantly of the peripheral type, can occur in patients infected with the human immunodeficiency virus (HIV), despite the immunodeficiency. The clinical manifestations of peripheral SpA in HIV-infected patients are similar to those seen in HIV-negative individuals. In areas of the world in which HIV infections are highly prevalent, SpA may be common regardless of the presence of HLA-B27.

IMAGING — There are several imaging findings that are fairly specific for spondyloarthritis (SpA) and that can aid in the diagnosis. Plain radiographs are the imaging procedure of choice. Magnetic resonance imaging (MRI) should only be used when plain radiographs are normal but there is still a high index of suspicion for SpA, especially if the designation of SpA in that particular patient will significantly affect choice of therapy. Plain radiographs of peripheral joints are usually unremarkable and do not show the same type of erosions seen in rheumatoid arthritis. Fluffy erosions can be seen in areas of enthesitis such as the heels; while supportive, they are not specifically diagnostic of SpA.
●Active inflammatory lesions of the sacroiliac (SI) joints appear as bone marrow edema (BME) and are clearly present in typical locations (subchondral or periarticular bone marrow edema).
●If there is only one BME lesion for each MRI slice, the lesion should be present on at least two consecutive slices.
The combination of a positive HLA-B27 and severe bone marrow edema of the SI joints on MRI may be predictive for progression to ankylosing spondylitis, but further confirmation of this observation is needed.

TREATMENT — Nonsteroidal antiinflammatory drugs (NSAIDs) are used as the first-line treatment for nonradiographic axial spondyloarthritis (nr-axSpA), formerly termed axial undifferentiated spondyloarthritis (axial USpA), as is done in patients with ankylosing spondylitis. In patients with an inadequate response to NSAIDs, continued pain, and laboratory or imaging evidence of inflammation, we suggest treatment with a TNF inhibitor. These agents are widely available for use in ankylosing spondylitis. Sulfasalazine, Hydroxychloroquine and Methotrexate may also alleviate the synovitis, chronic stiffness and constant pain. Chronic pain management with narcotics or derivatives is not indicated unless for temporary control of unbearable pain. Short courses of oral steroids like prednisone are very efficient in controlling the synovitis, dactilytis, fasciitis and enthesitis. Local injections with long acting steroids are very efficient in controlling both the inflammatory process and the chronic pain.