Juvenile idiopathic arthritis: Clinical sciences

Juvenile idiopathic arthritis, or JIA for short, describes a broad group of autoimmune conditions associated with inflammatory synovitis and arthritis, which can potentially result in bony erosion and joint destruction. It’s important to diagnose and treat JIA early in order to limit joint damage, preserve joint functionality, and avoid chronic pain. Based on the history, physical exam, and lab findings, you can classify subtypes of JIA as oligoarticular, polyarticular, systemic, enthesitis-related, and psoriatic JIA.

When a patient presents with a chief concern suggesting JIA, you should first obtain a focused history and physical exam. Your patient will be younger than 16 years old, with 6 or more weeks of joint swelling. Affected joints might also be warm or painful. Patients will also describe stiffness lasting greater than 30 minutes, either in the morning after waking up, or after periods of inactivity. In either case, the stiffness improves with movement. On exam, you may notice a joint effusion, which can be accompanied by tenderness to palpation or limited range of motion.

With these clinical findings, you can diagnose JIA. Keep in mind that JIA is a clinical diagnosis, meaning it’s typically based on the history and physical exam findings. However, JIA is also a diagnosis of exclusion, meaning you might need labs and imaging to rule out other conditions, such as infections like septic arthritis, or malignancies like leukemia.

Once you diagnose JIA, be sure to order a CBC, CRP, ESR, and serum ferritin; as well as a rheumatoid factor, or RF; anti-cyclic citrullinated peptide or anti-CCP antibodies; and an antinuclear antibody or ANA. Finally, don’t forget to check whether or not your patient is HLA-B27 positive.

Next, assess for a quotidian fever. This is a high fever that spikes and then quickly remits in a daily pattern, such as once in the morning and once in the evening. Assessing for a quotidian fever will help you determine which subtype of JIA your patient has. If this pattern of fever is present, you should suspect systemic JIA.

These patients typically present between the ages of 1 and 5 years with an evanescent, migratory, “salmon-colored” rash, which appears with the fever and disappears when the fever goes away. Arthritis typically involves one or more joints, but it may occur later in the disease process and is frequently overshadowed by other symptoms. On exam, you may find lymphadenopathy, hepatosplenomegaly, or even hear a pericardial friction rub, suggesting pericarditis.

Here’s a clinical pearl! When systemic JIA is diagnosed after 16 years of age, it's called adult-onset Still disease.

Now let’s move on to lab results. The CBC will typically reveal anemia, leukocytosis, and thrombocytosis; while the CRP, ESR, and serum ferritin are elevated. On the flip side, the RF, anti-CCP, and ANA antibodies will be negative. With this combination of findings, you can diagnose systemic JIA.

Now, here’s another clinical pearl! Systemic JIA can be complicated by a life-threatening condition called hemophagocytic lymphohistiocytosis, formerly known as macrophage activation syndrome. Hemophagocytic lymphohistiocytosis can be triggered at any point during the course of a rheumatologic disorder, including on presentation, when therapy is initiated, or if the patient develops an infection. It’s characterized by a high, unremitting fever and excessive immune activation that leads to a shock-like clinical picture. Lab abnormalities include cytopenias, especially thrombocytopenia, a low ESR, and very high ferritin levels. If hemophagocytic lymphohistiocytosis persists, it can cause multi-organ failure, thrombosis, bleeding, and even death. Emergency treatment includes high-dose systemic corticosteroids.

Now let’s discuss the management of systemic JIA. Treatment of any subtype of JIA frequently involves immunosuppression with biologic medications. First, start your patient on either an interleukin-1 inhibitor or an interleukin-6 inhibitor. If these medications fail to control the patient’s symptoms, you can add methotrexate or consider switching to a different biologic medication. Finally, you may even need to consider a course of systemic corticosteroids.

Before we move on, here’s a high-yield fact to keep in mind! Before starting a biologic medication, be sure to screen your patient for tuberculosis and other viral infections like Hepatitis B or C. Similarly, after starting a biologic medication, monitor your patient closely for opportunistic infections, since these individuals are immunocompromised.

Now let’s switch gears and discuss individuals who present without quotidian fever. In this case, your next step is to assess for a rash. If a rash is present, you should suspect psoriatic JIA.

These patients will report a history of arthritis and psoriasis, and they may have a family history of psoriasis in a first-degree relative. On physical exam, the rash will typically consist of a dry patch with a silvery scale. The patient may also present with dactylitis, which is sausage-like swelling of a finger or toe; as well as nail pitting, or onycholysis, where the end of the nail separates from the nail bed. Other important physical exam findings include tenderness of the tendon or ligament insertion point, which is called enthesitis, and limited range of motion in the spine.

As far as labs go, the RF and anti-CCP antibodies are usually negative, while ANA antibodies may or may not be positive. With these findings, you can diagnose psoriatic JIA.