A few weeks ago, a patient was referred to me after she developed a sore throat and a rash. This sounded like a routine strep throat infection, or in medical terms, acute tonsillopharyngitis caused by Streptococcus pyogenes. This is a common illness and is straightforward to treat. A penicillin-type antibiotic like amoxicillin or cephalexin works very well, and there is little resistance to these drugs. We usually treat this with pills as an outpatient. Since she wasn’t feeling very well and wasn’t eating much, we went ahead and admitted her for hydration, and I started ceftriaxone, a third-generation cephalosporin antibiotic, which is very effective against Streptococcus pyogenes.

She did well overnight. The fever went away, and the sore throat got better. However, after two days, the fever and the rash came back. The infection seemed to be improving, so something else was likely going on. We checked laboratory tests that look at the levels of inflammation, and true enough, she had very high levels of CRP (C-reactive protein) and ferritin. At this point, we knew that her body was having a hard time toning down its response to the infection, even if it was already controlled. This unabated inflammation could potentially damage her own tissues and organs. We started corticosteroids (powerful anti-inflammatory medication) and called a rheumatologist.

Most people are familiar with allergies, where a substance can trigger an abnormally exaggerated immune response. Rheumatologic diseases are similar to allergies in that there is an exaggerated immune response that goes beyond the initial inciting event, and it becomes detrimental to the body. In some of the more difficult cases, there is no clear trigger, and the body just starts attacking itself, resulting in serious tissue and organ damage.

Allergies involve mast cells, eosinophils, and immunoglobulin E (IgE, a special type of antibody) and are self-limited. Rheumatologic diseases involve different parts of the immune system, including antibodies, B-cells, T-cells, macrophages, and cytokines. They include both autoimmune diseases, where the body attacks its own cells, and autoinflammatory diseases, which refer to dysregulation of the immune response. The word “rheuma” is derived from the Greek word for “flow” and refers to fluid buildup in joints, which is a common feature of these diseases.

We usually treat allergies with antihistamines and, in severe cases, short courses of corticosteroids. In contrast, rheumatologic diseases can involve different parts of the immune response and may not abate unless strong immunosuppressive medications are started and maintained.

Three of the most common rheumatologic diseases I encounter as an infectious diseases doctor are rheumatic fever, systemic lupus erythematosus (SLE), and adult Still’s disease.

Rheumatic fever usually occurs in childhood, especially among children with repeated strep throat infections. Rheumatic fever can manifest as joint swelling, subcutaneous nodules, rash, swelling of the heart (carditis), and abnormal movements (Sydenham’s chorea). The first instance of rheumatic fever occurs two to four weeks after a strep throat, and subsequent strep throats can cause a flare. The reason for the disease manifestations is that the body makes antibodies against the Streptococcus pyogenes that have autoimmune properties and attack tissues in the heart and in the joints. Damage to the heart valves predisposes the patient to serious heart infection (endocarditis), and we usually have to give prophylactic antibiotics such as penicillin for years to protect the patient from strep throat recurrence that can induce another attack and result in more complications. Our patient was a bit old to have rheumatic fever, and she denied a history of recurrent strep throat, although many features of her disease overlap with rheumatic fever.

Systemic lupus erythematosus, or lupus for short, is one of the most common and deadly autoimmune diseases known to man. Many Filipinos are familiar with SLE since it is one of the rheumatologic diseases (among several) that a celebrity like Kris Aquino is battling against. Lupus is a result of the body producing antibodies against its own cells, particularly against the cell nucleus. No one knows why the body starts producing antibodies against itself, although one of the more plausible theories is that it is triggered by infection with a specific virus known as the Epstein-Barr virus (EBV).

One way to diagnose lupus is with a screening test known as the anti-nuclear antibody (ANA) test. The ANA test checks for many different kinds of antibodies against parts of the nucleus, including double-stranded DNA and ribonucleoproteins. ANA is not specific to lupus, but most lupus patients (around 98 percent) test positive for ANA. Because most of the cells in our body have a nucleus, lupus can affect almost any organ. Common disease manifestations include arthritis, a rash, kidney damage, blood abnormalities, neurologic abnormalities, and oral ulcers. Some patients can have just a few manifestations and present with a mild flare requiring only small amounts of anti-inflammatory medication. On the other hand, some patients have a fulminant course with rapid kidney failure requiring dialysis or a kidney transplant, along with abnormal formation of blood clots, brain swelling, seizures, and pulmonary hemorrhage. Severe lupus requires high-dose corticosteroids and strong immunosuppressants, which increase the risk of severe infection. This is why the treatment of lupus is multidisciplinary, usually led by the rheumatologist but also involving a kidney doctor, an infectious diseases doctor, and other subspecialties as needed. Our patient tested negative for ANA, so it was unlikely she had lupus.

Adult Still’s disease is a rheumatologic disease, but it is not an autoimmune disease. It is also known by the unwieldy term adult-onset juvenile idiopathic arthritis. The exact cause remains a mystery, but it can be triggered by an infection like strep throat. The immune system remains overstimulated and does not calm down even after the infection is resolved. The main symptoms of adult Still’s disease are joint swelling and a rash coupled with a very high ferritin value, which our patient had. Treatment is with anti-inflammatory medications, including corticosteroids. Our patient responded quite well to her treatment. There is, however, no definitive confirmatory test for adult Still’s disease, and so the diagnosis in this case is clinical. In addition, like what Kris is going through, there are many overlapping syndromes, and some connective tissue diseases (another name for rheumatologic diseases) can evolve into other types over time.

The immune system is a double-edged sword. It protects us, but it can also hurt us. Infectious disease doctors and rheumatologists both deal with the immune system, but in different ways. My infectious diseases colleagues and I rely on the immune system to clear infections, and we use antibiotics to assist the body in fighting off bacteria, viruses, and other pathogens. For us, the immune system is a powerful ally. Rheumatologists represent the other end of the spectrum and deal with immune systems that have gone awry and are overreacting. For them, the immune system is something that needs to be reined in and controlled. This situation perfectly encapsulates the complexity of modern medicine and reinforces the idea that it is always best to listen to your doctor in order to stay in the best of health.