Diagnosing Down Syndrome-Related Arthritis

Pediatric patients with arthropathy of Down syndrome (A-DS) may present with signs of joint damage, at least in part due to communication challenges that may make it difficult for these patients to verbally express pain or disability. The delay in diagnosis in this population is also due to a dearth of research, the lack of a biomarker, and a general lack of awareness of the increased incidence and prevalence of A-DS compared with non-Down syndrome-related arthropathy, says Andrew Zeft, MD, MPH, Director of Cleveland Clinic Children’s Center for Pediatric Rheumatology and Immunology.

Dr. Zeft sat down with Consult QD to discuss A-DS in the context of a case series presented at the 2019 Annual Meeting of the American College of Rheumatology and the Association of Rheumatology Professionals. The abstract suggests that the prevalence of A-DS is 2-3 times greater than reported previously and points to multifactorial reasons for significant delays in diagnosis.

Challenges to assessment

“Children with Down syndrome (DS) may not clearly communicate their pain, which can make it challenging for parents to know when to seek medical advice,” Dr. Zeft says. “Because of these communication issues, physicians may also miss out on important aspects of medical history, such as the presence of morning stiffness, that contribute to a diagnosis of arthritis.”

Additionally, the physical exam in patients with DS can be difficult at times, according to Dr. Zeft. “It can be difficult to distinguish between lymphedema and joint swelling in these patients, and their joint hypermobility adds a layer of complexity,” says Dr. Zeft. “It’s a unique patient population, and if you don’t have arthritis on your radar, it might take a while to reach that conclusion.”

The impact of a delayed diagnosis

Delayed diagnosis can lead to joint damage from persistent inflammation, such as joint space narrowing, cartilage thinning, bone erosions and resultant loss of motion. “This is difficult for patients, as these patients are in pain and don’t know what to do,” Dr. Zeft notes.

The assessment

“When assessing patients with DS for arthritis, it’s helpful to remember that they may have a different baseline, and take extra care to objectively assess each joint for swelling and/or loss of mobility. Listening to the patient’s — and the parents’ — interpretation of what’s going on is also very important,” Dr. Zeft continues. “Unfortunately, there’s no definitive lab test to diagnose juvenile arthritis. It’s more about getting a good history, conducting a thorough exam, and having a heightened awareness.”

Available treatments

There are very effective treatments for inflammatory arthritis, depending on the patient, and the type and severity of the arthritis. “While there are no cures for A-DS, we can take measures to quiet the inflammatory burden on patients and lessen the related stiffness and discomfort. In general, our goal is to deactivate a patient’s arthritis as safely as possible,” states Dr. Zeft. “The challenge with patients with A-DS is that their hematologic baseline may be a lower than normal total white blood cell count, making treatment options with immune modulators or biologic treatments available to patients with juvenile idiopathic arthritis (JIA) less clear. The popular disease-modifying antirheumatic drug (DMARD), methotrexate, may not be appropriate. Physicians should be watchful when a child is taking a DMARD, and especially so with patients with DS.”

Proposed name change

“In pediatric rheumatology, we’ve suspected for a while that arthritis is more prevalent in those with DS syndrome than the general population. However, we couldn’t quantify it. The case series presented at the ACR meeting suggests that the prevalence is at least 2-3 times greater than previously reported,” says Dr. Zeft.

Authors of the ACR abstract also recommend a name change from A-DS to DS-associated arthritis to better reflect the erosive nature of the condition. Dr. Zeft says that this name change “wouldn’t be unreasonable because it would increase awareness.”

Dr. Zeft suggests that the name of DS-related arthritis might help to raise awareness while also better reflecting the inflammatory process associated with the arthritis condition, as “arthropathy is a more general term describing joint pathology, which could refer to many different qualities of the joint issues, such as hypermobility associated joint pain and pain-related to abnormal joint mechanics and stresses.”