PIMS: Symptoms, Cause, Treatment

Brief overview

  • Definition: PIMS (PIMS-TS, also MIS-C) is a severe, acute inflammatory disease affecting multiple organs. PIMS usually manifests two to eight weeks after coronavirus infection in children. In addition, doctors also observe the so-called MIS-A – the “PIMS syndrome in adults” – in very rare cases.
  • Frequency: PIMS is extremely rare; it is estimated that one in 3,000 to 4,000 children affected by Covid-19 may be affected; boys are more frequently affected.
  • Cause: So far unclear; doctors suspect a misdirected, overshooting, immune response throughout the body, caused by a past coronavirus infection.
  • Prevention: Coronavirus vaccinations significantly reduce the risk of contracting PIMS.
  • Treatment: Intensive medical treatment, immune system suppressive therapy, administration of anticoagulant drugs if necessary, antibiotics if necessary in case of concomitant bacterial infection.

What is PIMS?

PIMS is a severe and acute, but rare, inflammatory disease in children and adolescents. It usually occurs a few to several weeks after infection with Sars-CoV-2. Physicians believe that the immune system overreacts to coronavirus infection and causes severe inflammatory processes throughout the body (systemic inflammation).

  • Pediatric Inflammatory Multisystem Syndrome (PIMS)
  • Pediatric Inflammatory Multisystem Syndrome Temporally associated with SARS-CoV-2 (PIMS-TS)
  • Multisystem Inflammatory Syndrome in Children (MIS-C)

Physicians observe that rarely a similar clinical picture occurs in (young) adult patients after a Sars-CoV-2 infection. Doctors then speak of “Multisystem Inflammatory Syndrome in (young) Adults”, MIS-A for short – i.e. the “counterpart of the disease PIMS in adults”.

The main symptom of PIMS is severe fever that persists for at least two to three days. It usually sets in two to eight weeks after a person has had a coronavirus infection.

In addition, the following symptoms may occur with PIMS:

  • Affected individuals experience gastrointestinal symptoms such as vomiting, nausea, diarrhea, and/or abdominal pain.
  • In the eyes, PIMS is manifested by (bilateral) conjunctivitis.
  • Often the lymph nodes are swollen in PIMS.
  • PIMS symptoms of the cardiovascular system are circulatory problems due to a drop in blood pressure, palpitations or heart stuttering, and even circulatory failure. The heart muscle or pericardium may have become inflamed.
  • Problems of the nervous system are manifested by headache, feeling of weakness, sensory disturbances and/or difficulty concentrating.
  • Blood clots form more easily with PIMS. The risk of thrombosis therefore increases.

Important: Not all children develop all of the above symptoms! However, if your child develops symptoms and severe fever and a coronavirus infection is recent, you should consult a doctor immediately!

PIM syndrome in adults (MIS-A) also causes similar symptoms.

Who is affected by PIMS?

However, the exact incidence cannot be reliably quantified due to the limited data available. Experts estimate that one in 3,000 to 4,000 children could be affected. However, the figures vary widely.

In the period from May 27, 2020, to January 23, 2022, a total of 593 PIMS cases were reported in children and adolescents in Germany. More than half of the affected children were four to ten years old at the time of the survey.

If the general infection incidence in the population increased, the registered PIMS cases also increased. It is believed that the risk of PIMS is highly dependent on the viral variant involved.

Nevertheless, unvaccinated children in particular are still at risk from PIMS. But also those who have not yet been infected and therefore have not yet built up immunity. Vaccination or a past infection appears to significantly reduce the risk of PIMS. How long this protection lasts is currently unclear.

What causes PIMS?

Misdirected postviral immune response as a trigger for PIMS.

First, the virus enters the respiratory tract via the throat and multiplies there. This activates the immune system. This in turn stimulates T defense cells, which then produce pro-inflammatory messenger substances (cytokines, chemokines).

Moreover, experts are discussing whether the risk of PIMS in children is increased by a (genetic) predisposition.

PIMS as a vaccination complication?

In very rare cases, coronavirus vaccinations can lead to complications. This is shown by the safety reports published by the Paul Ehrlich Institute (PEI) during the vaccination campaign. Prominent examples of such side effects are severe allergic reactions, inflammation of the heart muscle (myocarditis) or the pericardium (pericarditis).

However, no reliable data or systematic studies are currently available on this very rare complication. In addition, the vaccination benefit is far higher than the risk of suffering vaccination complications, according to experts.

This means that the risk of PIMS after having undergone a coronavirus infection is significantly higher than the risk of PIMS due to vaccination.

When is PIMS present?

Investigations

If physicians suspect PIMS, they will arrange for a number of further investigations. These include:

  • Cardiac ultrasound: Doctors look for abnormal changes, such as an effusion in the pericardial sac (pericardial effusion) or problems with the heart valves. They also check the pumping action.
  • ECG: In PIMS, for example, more extra beats of the heart are seen (extrasystoles).
  • X-ray or CT thorax: In the X-ray images, doctors can detect effusions, pneumonia or pulmonary edema, for example.
  • Ultrasound (sonography) of the abdomen: In the case of complaints of the digestive tract, doctors use ultrasound to rule out other causes such as appendicitis. In addition, they detect abdominal fluid (ascites), an enlarged liver or inflamed intestine, as can occur with PIMS.
  • Determination of blood values: Blood levels of inflammation such as C-reactive protein or interleukin-6 (IL-6) are elevated. Red blood cells or platelets may be reduced by PIMS. In addition, doctors check organ functions and detect clotting disorders.

Doctors also rule out other serious conditions that can cause similar symptoms. These may include blood poisoning (sepsis), intestinal infection, or severe heart or lung disease.

Case definition PIMS

  • Children and adolescents up to and including 19 years of age
  • Sars-CoV-2 infection proven or probable due to risk contacts.
  • Fever for at least three days (longer than 48 hours, according to the German Society for Pediatric Infectious Diseases)

And at least two of the following criteria:

  • skin rash (exanthema) or bilateral nonpurulent conjunctivitis or inflammation of the skin or mucous membrane
  • low blood pressure (arterial hypotension) or shock
  • blood coagulation disorder (coagulopathy)
  • acute problems of the digestive tract (diarrhea, vomiting, abdominal pain, suspected appendicitis)

and

  • abnormalities in the blood count
  • elevated inflammation values (CRP, PCT, ESR, etc.)

Currently, there are no uniform diagnostic criteria worldwide. The U.S. Centers for Disease Control (CDC), for example, lists slightly different criteria (e.g. age under 21, fever over 24 hours, at least two affected organ systems such as heart or digestive tract).

PIMS or Kawasaki syndrome?

PIMS is very similar to the so-called Kawasaki syndrome. In both, the immune system overreacts after an infection. Nevertheless, they are different diseases:

In Kawasaki syndrome, small and medium-sized blood vessels become inflamed. It mainly affects young children between the ages of two and five. The disease begins with a high fever that lasts for more than five days. As with PIMS, there are certain criteria that must be met for diagnosis.

PIMS patients, on the other hand, tend to be older than Kawasaki patients and are more likely to have severe courses. Furthermore, children with PIMS are much more likely to have gastrointestinal symptoms. In addition, neurologic abnormalities or respiratory distress may occur, which are rare in Kawasaki.

Because infections can trigger both PIMS and Kawasaki syndrome, diagnosis is not always easy. Moreover, physicians believe that there is overlap.

  • Sars-CoV-2 non-Kawasaki PIMS (non-KS-PIMS): These are pure PIMS cases according to the above criteria. Only one Kawasaki criterion applies at most.
  • (Sars-CoV-2) Kawasaki syndrome (KS): Affected individuals fulfill at least two of the five Kawasaki criteria, but not those for PIMS.
  • Sars-CoV-2 PIMS plus Kawasaki syndrome (KS-PIMS) includes PIMS cases in which children also meet more than two of the five Kawasaki criteria.

PIMS or TSS (Toxic Shock Syndrome)?

The symptoms of PIMS are to some extent also similar to the so-called toxic shock syndrome (TSS).

TSS is also an acute, life-threatening multi-organ illness that sometimes causes severe fever, rapid drop in blood pressure and skin rash. As a rule, TSS progresses rapidly and can be fatal if left untreated.

These toxins are able to activate certain immune cells very strongly, thereby triggering an uncontrolled misdirected immune response. Due to such properties, these bacterial toxins are referred to as “toxins with superantigen property”. TSS also threatens a life-threatening cytokine storm that damages many organ systems.

Read more about toxic shock syndrome and how it is treated here.

How can you protect your child from PIMS?

Treatment of PIMS in children

PIMS can usually be treated very well. Doctors from different specialties – such as infectious diseases, rheumatology or cardiology – work closely together to provide the best possible care for affected children.

Many children and adolescents are admitted to the intensive care unit, where their condition is continuously monitored. In addition, all means are available to react quickly if the condition deteriorates.

  • Administration of anti-inflammatory drugs
  • Administration of anticoagulant drugs
  • Administration of concomitant medications (e.g. to stabilize the circulation)

Medications for PIMS inflammation

But these drugs are not always enough to stop PIMS. Doctors then use other active ingredients:

Anakinra: This is a powerful immunosuppressant (interleukin-1 inhibitor). The drug suppresses the body’s immune response and is usually used for rheumatoid arthritis. To avoid severe side effects after treatment has been given (“rebound effect”), the anakinra dose is gradually reduced and the treatment is thus safely discontinued.

Infliximab: Depending on the case – for example, if the gastrointestinal tract is heavily involved – infliximab (known as a TNF-alpha blocker) can cushion the excessive inflammatory processes. Doctors usually prescribe the active ingredient for ulcerative colitis or Crohn’s disease. It is suitable for children aged six years and older.

Other medications for PIMS

In severe courses, medications are sometimes necessary to stabilize the circulation (catecholamine therapy).

If there is evidence of an additional bacterial infection, antibiotic therapy is given.

Course of disease and prognosis

The inflammatory disease PIMS occurs about two, usually four to eight weeks after a Sars-CoV-2 infection. If left untreated, the inflammatory processes are dangerous and can be fatal in the worst cases.

However, around five percent of affected children develop secondary damage, for example to the cardiovascular system. They presumably result from damage to the heart muscle or blood vessels.

Aftercare

In particular, children whose heart muscle is impaired after PIMS should not engage in (sports) activities for at least three months, even if the acute symptoms improve rapidly. Before they resume sports, a medical stress test is advisable or necessary.

In principle, however, PIMS has very good chances of recovery without serious long-term consequences if treated by a doctor in good time.