What is Serum Sickness?
Serum sickness is a reaction caused by your immune system that typically comes with symptoms like fever, rash, and joint pain in multiple places. This condition was first identified in the early 1900s in patients who had been given a type of treatment known as ‘heterologous antisera’, which was formerly used for treating infectious diseases. The symptoms usually start to appear one to two weeks after exposure to the cause and go away within several weeks once the cause is removed. It’s worth noting that serum sickness often resolves on its own and has a very good chance of complete recovery.
What Causes Serum Sickness?
Serum sickness happens when your body’s immune system reacts to foreign (non-human) proteins by trying to fight them. This can happen due to certain medications which contain these foreign substances, such as some vaccinations (like Rabies), drugs used to help regulate your immune system (like rituximab, infliximab), and anti-venom treatments.
It’s important to note that serum sickness is not the same as a serum sickness-like reaction. While the symptoms look very similar, a serum sickness-like reaction does not involve your body forming these immune complexes to fight foreign substances. Some medications that most often cause a serum sickness-like reaction include certain types of antibiotics like penicillins and cephalosporins (especially cefaclor), sulfonamides, bupropion, fluoxetine, and thiouracil. In addition to these medications, there are also some infections, such as from streptococcus and hepatitis B, that can trigger a serum sickness-like reaction.
Risk Factors and Frequency for Serum Sickness
While a relatively uncommon condition, serum sickness tends to affect adults more often than children. According to a study of 72,000 patients, fewer than 0.5 percent of children under ten years old, who were given anti-rabies treatment, developed serum sickness. Some groups of people, including people with a high level of proteins in their blood called hypergammaglobulinemia, and people with a Hepatitis C-related disease known as cryoglobulinemia vasculitis, are more susceptible to getting serum sickness after receiving a specific infusion called rituximab.
Signs and Symptoms of Serum Sickness
Serum sickness is a condition that requires a careful medical history check and physical exam to identify properly. The doctor asks about any potential exposure to elements that might have triggered the condition in the past two weeks, and more immediately if repeat exposure is suspected. The severity of the patient’s symptoms and their overall health condition are assessed to rule out other potential causes of their symptoms.
During the physical exam, the doctor assesses the patient’s current condition and looks for signs of widespread illness. Attention is paid to the patient’s rash. It might be a spectrum of changes including hives, a flat, red rash, or a rash that consists of small spots of bleeding (purpuric eruption). It’s important to note that unlike other skin conditions like Stevens-Johnson syndrome and toxic epidermal necrolysis, the inside of the mouth and other mucous membranes are unaffected in serum sickness.
If the rash is associated with an injection, it usually appears first around the injection spot and can take from a few days to a few weeks to disappear after stopping contact with the trigger. Joint pain (arthralgia) is more frequent than a full-blown inflammation of one or more joints (arthritis but both may occur. The body parts that are most commonly affected include the hands, feet, ankles, knees, and shoulders.
Less common signs during the exam include swelling in the hands, feet and face, enlarged lymph nodes, headaches or blurry vision, enlarged spleen, inflammation of the front layer of the eye, impairment of peripheral nerves, kidney impairment, and vasculitis.
- Rash (could be hives, a flat, red rash, or purpuric eruption)
- Joint pain (most commonly in the hands, feet, ankles, knees, and shoulders)
- Signs of systemic illness
- Less common symptoms such as swelling, enlarged lymph nodes, blurry vision, organ discomfort, or vasculitis
In a specific type of serum sickness called serum sickness-like reaction, the symptoms are usually limited to fever, joint pain, rash/hives, and itching.
Testing for Serum Sickness
If you’re feeling well but your doctor suspects you might have serum sickness, they may do a urinalysis. This simple test checks for potential kidney problems that would require further monitoring. However, if you’re feeling quite unwell or if your symptoms and medical history don’t give a clear picture, other tests may be done as well.
To figure out the cause of your symptoms and to see if other parts of your body are affected, your doctor might order several other lab tests. These include a complete blood count (this checks for the types and numbers of cells in your blood), erythrocyte sedimentation rate and C-reactive protein (these measure inflammation in your body), CH50, C3, C4 (these test the health of your immune system), a basic metabolic panel (this screens for various medical conditions), liver transaminases (these check for liver damage), and antinuclear antibody and rheumatoid factor (these test for autoimmune diseases).
If your medical history suggests it, your doctor may also test for infectious diseases like hepatitis B and Epstein-Barr virus. If they suspect a heart problem, they may do an electrocardiogram, a test that measures the electrical activity of your heart. If you have gastrointestinal symptoms, they may test your stool. If you have neurological symptoms, they might order a CT scan, which takes images of your brain.
In serum sickness, lab results can vary widely. Your complete blood count might show too few or too many white blood cells. Your serum creatinine levels might be high, demonstrating potential kidney issues, but typically return to normal once the triggering factor is eliminated. Inflammatory markers, which indicate inflammation in your body, will be high. Complement levels (part of your immune system) including CH50, C3, and C4, will be low, because your body has been using them up in its immune response.
Remember, though, that if your doctor thinks you have a condition similar to serum sickness but less severe, called a serum sickness-like reaction, you generally won’t have problems in other areas of your body. Similarly, your lab results won’t show low complement levels or kidney problems.
Treatment Options for Serum Sickness
Serum sickness is a condition that typically resolves itself once the cause of it is removed. The cause could be a medication that a person is taking or exposure to a certain substance. Treatment, therefore, is primarily focused on managing symptoms and getting rid of the offending agent, or at least reducing exposure to it if it can’t be completely removed. An example is anti-thymocyte globulin, a medication used to treat a blood disorder called aplastic anemia.
If the symptoms are mild or moderate, relief can be achieved with NSAIDs, which are simple over-the-counter pain relievers, and/or antihistamines, which are medications used to treat things like allergies. Starting these medicines should halt the progression of the rash and itching associated with serum sickness within 48 hours.
When the symptoms are more severe, a 7 to 10-day course of a type of medication called systemic glucocorticoids can be helpful. These are strong anti-inflammatory drugs that can help to reduce inflammation in the body. They’re used at a dose of 0.5 – 2 mg/kg.
Most children with serum sickness can be safely treated at home, but if the symptoms are quite severe, or if there’s evidence of an underlying infection or more serious illness, then they might need to be admitted to the hospital for treatment.
What else can Serum Sickness be?
When doctors are trying to diagnose serum sickness or a similar reaction, they have to look at many possibilities. Essentially, it’s like putting on a detective hat and trying to narrow down a long list of suspects. This list can include:
- Viral illnesses with rashes, such as Chikungunya and Dengue fever
- Acute rheumatic fever – a disease that affects the heart, joints, skin, and brain
- Scarlet fever – an infection that can cause a rash and fever
- Kawasaki disease – which affects the blood vessels in kids
- Meningococcemia – a severe infection of the bloodstream
- Systemic juvenile idiopathic arthritis – a type of arthritis that affects kids
- Lyme disease – an infection caused by ticks
- Hypersensitivity vasculitis – inflammation of the blood vessels, including conditions like IgA vasculitis, Sweet syndrome, and Stevens-Johnson syndrome
- Other drug reactions such as allergic reactions that affect the whole body
To untangle this complicated puzzle, doctors use specific disease characteristics and lab evaluations to lead them towards an accurate diagnosis.
What to expect with Serum Sickness
The outlook for conditions like serum sickness and serum sickness-like reactions is typically very good. Symptoms usually go away within 1-2 weeks after stopping the use of the medication or substance that caused the reaction. However, in cases where the symptoms are severe, the illness reoccurs, or the patient continues to be exposed to the substance that caused the reaction, the recovery period might be longer.
Possible Complications When Diagnosed with Serum Sickness
In most cases, serum sickness clears up by itself and doesn’t cause long-term health problems. So far, there have been no large studies showing long-term effects of serum sickness. However, repeated exposure to whatever caused the illness can, in animal studies, lead to kidney failure and even death in some cases. Thankfully, the outlook is better in humans as studies on patients who got serum sickness after being treated with ‘anti-thymocyte globulin’ for aplastic anemia, showed more positive results.
Information about serum sickness:
- Usually clears up on its own
- No large studies show any long-term effects
- Repeated exposure to the cause can lead to kidney failure and death in animal studies
- Better outcomes in humans are shown in cases where patients are treated with ‘anti-thymocyte globulin’ for aplastic anemia
Preventing Serum Sickness
If a patient has experienced serum sickness or a similar reaction, it’s important that they avoid the substance that caused it from then on. This substance is usually a type of medication, and the patient should familiarize themselves with both the generic and brand names of this medication to make sure they steer clear of it. It’s important to understand that if you’ve had serum sickness once and you’re exposed to the same substance again, you could get even sicker.
Right now, doctors aren’t sure if a patient who has had serum sickness can safely take other medications that are in the same category as the one that caused the reaction. However, some experts suggest that it’s best to avoid medications that are structurally similar to the one that caused serum sickness.
