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Health Services


Diagnosis and Treatment

Step By Step
You might be surprised when your pediatric rheumatologist tells you that there is no single test for diagnosing any of the rheumatologic illnesses. You might ask why that is true. That is a good question. Let us go over the thinking process.

Rheumatology is a specialty that concerns with inflammation that is caused by body’s own immune system attaching its own tissues, i.e. autoimmune reactions. The heart of the matter is the presence of inflammation, in other words, autoimmune disease by definition requires presence of inflammation significant enough to harm normal cellular structures in the tissues. On the other hand, presence of inflammation does not automatically mean it is autoimmune. There are many reasons why the body generates inflammation. Remember the tissue changes when you injured or burned your skin; it gets swollen, red, warn, and tender. That is the normal body’s reaction until healing takes place.

Inflammation is derived from the Latin word inflammare, meaning to set on fire. This was first described by the founder of the medicine, Hippocrates in 5th century BC. He pointed out that inflammation causes “Rubor” or redness, “calor” or heat, “turgor” or swelling, “dolor” or pain and finally “function laesa” or Loss of function.

Step 1 à To determine if there is inflammation: The conclusions often will be based on nothing more than information derived from the basic history, physical exam and simple laboratories (CBC, ESR, CRP). As parents, it is so important to provide accurate and chronological history in as much detail as possible. For instance, “when did firs signs and symptoms start? Was there any fever, rash? Was there weight loss, or fatigue? Was there any joint pain, morning stiffness? How was the play or school time? Was the sleep restful? Was the child waking up from sleep and crying from pain?

Step 2 à Elimination process to make sure the inflammation is not sue to any other possible cause like injury, infection, or tumor. This step may take time, additional labs, images, and close observation. Your physician may ask you to keep a very close diary on your child’s status, such as you may need to record any fever, rash, headache, or joint pain. This is the period that may require additional testing, imaging, or consultations to other specialties -- a branch of medicine or surgery that a doctor specializes in. This is mostly just to be sure there are no explanations that can cause the signs and symptoms other than an autoimmune disease. Remain in close communication with your physician, follow the directions and have good compliance to follow-ups.

Step 3 à To fit the signs and symptoms to a pattern. Each disease has an unique pattern that your physician can recognize. For instance, the pattern for arthritis is different from the pattern of lupus. The more you know about the illness, the better for your child’s care and future.

Most important message in this section is: THERE IS NO SINGLE TEST FOR ANY OF THE RHEUMATOLOGICAL ILLNESSES. Yet, your rheumatologist may request a long list of blood work during the visit. Naturally, you may ask, “So why are we doing all these labs? What is the point?”

If you are a new patient, then the physician is likely to run labs for establishing the baseline, while searching the leads to reach the correct diagnosis. This includes labs to make sure there is nothing else is going on, such as infection, causing the ongoing concerns.

If you are a follow-up patient with established diagnosis such as arthritis or lupus, then your physician is likely to run the labs periodically to understand the status of disease activity and to make sure the medications given are not harming your body.

Let’s look at each level of laboratories more carefully:

1.The basic laboratories in rheumatology:

a.CBC (Complete blood count): Tells us the count for all three lines of cells that we have in our circulating blood i.e. white cells (WBC), red cells (Hct), and platelets (plt). Remember, that inflammation is caused largely by the WBC in the tissues, so the details of CBC are very important. So, rheumatology labs cannot do without a CBC.
b.ESR (Erythrocyte Sedimentation rate): This is an old fashion test but still works well. It is not very specific test. The higher the number, the more evidence of inflammation in the blood.
c.CRP (C-reactive protein): Another inflammation marker in the blood. Like ESR, CRP is not specific and can be increased in several conditions that are due to illnesses that are not autoimmune diseases or completely different situations such as infection.
d.Urine Test: The urine shows if your kidneys are working well. It is important to monitor kidney health and make sure the medications are not harming the kidneys.

2.Special laboratories in rheumatology:
A big chunk of these tests are antibody based. Before we go any further, let’s make sure we are clear on what the antibody is. Antibodies are protein molecules produced by B cells (a special type of leukocytes) to protect us from infections. For instance, we get flu shot to develop antibodies so we will be protected. In autoimmune diseases, the body develops “AUTOANTIBODY’. Autoantibody means presence of antibodies that are reacting against one’s own body constituents. This is a fundamental finding in many, but not all, of the autoimmune diseases.
a.ANA or anti-nuclear antibodies: This is often misused test and can cause unnecessary fear. It is well documented that about 15% of healthy children do have positive ANA. It is believed viral infections can trigger production of ANA in children without being a true implication for an emerging autoimmune disease. Therefore, it is not a good screening test unless there is clinical relevance at the time of testing, for example, joint swelling or rash. In other words, if your child is healthy, eating, sleeping, playing well, happy and growing and full of energy, the chances are ANA, even it is positive, does not mean anything.
i.ANA can be positive in about 40% of juvenile rheumatoid arthritis (JRA). It really does not prove or disprove there is arthritis. It just tells your physician if your child has increased risk for developing uveitis. So it is a prognostic rather than diagnostic marker for childhood arthritis.
ii.On the other hand, ANA is a good screening test for lupus. Almost all lupus patients do have positive ANA (>97%) and therefore it is used widely as a diagnostic test, but it does not have any value as a prognostic test.
b.RF or Rheumatoid Factor: Presence of RF is not normal. This is in contrast to ANA. If the child truly has positive RF, the reasons for that needs to be explored in full. One big reason for positive RF is the onset of adult type arthritis. RF is positive in 80% of adults with rheumatoid arthritis. With children, they may be starting the disease process in an early age. RF can also be positive in lupus, sjogren’s, sarcoidosis, or overlap syndromes. However, please keep in mind that sometimes a positive RF can be from lab error.
c.ANCA or anti-neutrophil cytoplasmic antibodies: Another lab test that suggests an abnormality. There are two kinds of ANCA. c-ANCA is a marker for severe vasculitis. p-ANCA is also a marker for vasculitis or it can be positive in some illnesses such as inflammatory bowel disease.
d.Autoantibodies specific for lupus: If there is enough evidence warranting detailed work-up for lupus, your physician will be asking for anti-double stranded DNA antibodies and antibodies to extractable nuclear antigens. The results need expert review and conclusions.
e.Anti-phospholipid antibodies: Different subtypes of these antibodies can be checked if there is Raynaud’s, evidence of easy blood clotting or strong family history of heart attacks or strokes.
f.Scl-70: Is the scleroderma antibody that may or may not be positive in children with scleroderma. However if it is positive, then your child needs careful medical follow up and treatment.

3.Imaging Studies:
a.Your physician may consider taking an x-ray or MRI or CT to have visual understanding of the tissues concerned. Most of the time the process starts by taking x-rays. For instance, if your child is complaining about knee pain, an x-ray can be taken to make sure there is no bone or soft tissue changes. X-ray is limited on how much details can be captured. If more information is needed for the soft tissues (to assess the swelling, tendons, cartilage) then MRI is a preferred study. Please remember MRI and CT are expensive and need scheduling and specialized radiology equipment and staff; it is not an everyday study. Furthermore, it is good to be conservative for CT as it involves exposure to radiation. MRI on the other hand uses an electromagnetic field and does not cause exposure to radiation.

Drugs Used in Rheumatology

Disease Modifying Anti-Rheumatic Drugs (DMARDS)

Methotrexate (MTX) is widely used for treatment of juvenile idiopathic arthritis among children. It is effective by an array of mechanisms including interfering with DNA metabolism; it is a competitive inhibitor of dihydrofolate reductase (DHFR) enzyme that is essential for de novo production of folic acid, which is needed for purine biosynthesis in the cells.

MTX is provided as a PO or a SQ preparation, the latter is usually regarded more potent for treatment. MTX is reserved for moderate to severe arthritis patients with polyarticular juvenile rheumatoid arthritis, spondyloarthropathy, ankylosing spondylitis or psoriasis with or without arthritis. It can also be used for persistent juvenile rheumatoid arthritis that has partial response to NSAIDs and or intra-articular steroid injections. MTX is also used by the GI or dermatology specialties and psoriasis at similar doses that is usually tolerated well. Whereas, the hem/onc patients are exposed of methotrexate at much higher doses and can be subject to more intense adverse effects.

MTX is metabolized through the liver and excreted from kidneys. The adverse effects include nausea, fatigue, aphthous ulcers, rash, rarely hair thinning, and most importantly bone marrow suppression and liver toxicity. The patient’s on methotrexate should strictly avoid drinking alcohol. Methotrexate is teratogenic and pregnancy precautions should be advised carefully. It is customary to provide patients with supplementary folic acids usually 1 mg a day to minimize adverse effects. It is also customary that the patient should avoid sulfa medications while on methotrexate for escalated bone marrow suppression.

The initial dose is 0.5 mg per kilo giving once weekly. Maximum does usually does not exceed 1 mg per kilo per dose, up to 25 mg per meter square or 37.5 mg once weekly. The pills are 2.5 mg per tablet. The patient should be instructed to take complete dose all together, rather than in divided doses, once a week, on an empty stomach. Subcutaneous injections can be done by the parent or the patient at home. The injections are given over the thighs, back of the upper arms or lower abdominal regions after appropriate alcohol cleaning of skin using a PPD syringe. The liquid preparation comes in a concentration of 25 mg per mL in 2 cc or 10 cc bottles. This is a light sensitive solution and should be kept away from sunlight or in its carton box. For young children, multi-dosing from the same bottle becomes essential. Families are instructed to use vitals carefully to avoid contamination. The bottle top should be cleaned with alcohol before and after each use. The bottle is usually stored in the refrigerator to minimize contamination. The solutions should remain clear. In infants or small children who are not able to take tablets, the liquid preparation can be used by mouth. In those cases, families are instructed to draw the medicine using 1 mL syringe for measurement then mix the medicine in small amount of applesauce or pudding. For example, the usual dose for a 20 kg child is about 10 mg methotrexate per week, which is contained in 0.4 mL of liquid preparation.

Most patients are treated for at least 6 months prior and then assessed for a response to methotrexate. Usually about one third of patients respond to methotrexate beautifully with full recovery from their arthritis. About one third shows partial response to methotrexate and about one third are nonresponders. It is a common practice for a patient to be treated with methotrexate prior to adding another treatment such as a biological response modiferes. This is mostly for cost effectiveness. Patients must have monitoring laboratories every 8 weeks including CBC and liver functions. In the presence of adverse effects (elevated LFTs, depressed WBC, mouth sores, excessive nausea), the patient will need dosage adjustments or discontinuation of methotrexate. The new patients just started on methotrexate should receive laboratories more frequently, every 3-4 weeks, until there is confidence that the patient tolerates methotrexate well.

Slow Acting Anti-Rheumatic Drugs (SAARDs)

 Closing Chart      
 Generic Name   Brand Name   Pill Size   Dose 
 Hydroxychloroquine   Plaquenil  200 mg tabs  6 mg/kg QD
200-400 mg/day
 Sulfasalazine  Azulfidine  500 mg tab  10-20 mg/kg BID
TID Max 2 gm/day
 Colchicine   n/a  0.6 mg tab  1 to 2 tablets a day

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