What is Waterhouse-Friderichsen Syndrome?
Waterhouse-Friderichsen syndrome (WFS) is a rare health issue. It was first identified by Rupert Waterhouse and Carl Friderichsen in the early 1900s. They discovered it as a condition that caused both adrenal glands to bleed in children suffering from severe bacterial infections. Through the years, there have been cases where both adrenal glands bled due to various bacterial and viral infections.
Over time, WFS is now understood as a broader term referring to a shortage in adrenal gland function associated with these cases of adrenal gland bleeding. Although this shortage of adrenal gland function is mainly found in patients with bleeding in both adrenal glands, there have been occasional instances of this in cases where only one adrenal gland is bleeding. In these unique situations, the other adrenal gland was worn out to the point where the cortical lipoid (a vital substance in the adrenal gland) was reduced or completely gone.
What Causes Waterhouse-Friderichsen Syndrome?
Waterhouse-Friderichsen syndrome, a serious medical condition, was first identified in people with a specific type of bacterial infection, known as Neisseria meningitidis sepsis. Since then, the syndrome has been linked with a number of different bacteria and viruses, including Streptococcus pneumonia, Hemophilus influenzae, Escherichia coli, Staphylococcus aureus, and others. It has also been associated with conditions such as Rickettsia rickettsii, Bacillus anthracis, and several viral infections like Cytomegalovirus and Epstein-Barr virus.
In a study that looked at 51 children who sadly died from sepsis and a condition where both adrenal glands bleed (bilateral adrenal hemorrhage), the most common bacteria found was Pseudomonas aeruginosa. In another study, however, N. meningitidis was the most common bacteria linked with this type of adrenal bleeding.
The syndrome has some risk factors, too, including the use of blood-thinning medication (anticoagulants), a low platelet count (thrombocytopenia), conditions that increase the tendency of blood clots (hypercoagulable states), and a condition called antiphospholipid syndrome. Injury to the adrenal glands and being in a post-surgery state are other factors.
In a long-term study spanning 25 years at the Mayo Clinic, injury was the cause of adrenal gland bleeding in about 3% of cases. Another study showed trauma causing adrenal bleeding in about 29% of cases.
About 2% of people in the 25-year study had adrenal bleeding related to blood-thinning therapy. Chronic anticoagulation with a specific drug (warfarin) without another type of medication for preventing blood clots (antiplatelet therapy) was less common.
In the same long-term study, bleeding associated with low platelet counts due to heparin (a blood-thinning medication) and antiphospholipid antibody syndrome occurred in 14.2% of patients. Some of these people tested positive for a condition called lupus anticoagulant as well.
In patients with low platelet counts due to heparin, known as heparin-induced thrombocytopenia, about 10% developed adrenal bleeding after surgery, and these patients experienced symptoms of adrenal insufficiency.
Risk Factors and Frequency for Waterhouse-Friderichsen Syndrome
Waterhouse Friderichsen syndrome is a very unusual condition, only found in about 1 percent of regular post-mortem examinations. No extensive studies have been conducted to determine its exact prevalence. However, it’s known to be more common in children than adults.
Signs and Symptoms of Waterhouse-Friderichsen Syndrome
Waterhouse-Friderichsen Syndrome (WFS) is a medical condition that can present suddenly or develop amidst an ongoing infection. It often causes symptoms that suggest adrenal insufficiency. The key sign of WFS is shock. Patients frequently experience generalized symptoms like a sudden headache, fever, weakness, fatigue, abdominal or side pain, loss of appetite, vomiting or nausea, and disorientation or confusion.
In a physical examination of the abdomen, there might be stiffness or a pronounced sensitivity to touch. When WFS occurs with a bacterial infection known as meningococcemia, it often results in a spotty red or purple skin rash (petechial rash), severe and widespread intravascular clotting (DIC), a severe blood disorder that leads to purpura fulminans (a serious condition with patchy areas of skin bleeding), along with neurologic symptoms seen in meningitis, an inflammation of the protective membranes covering the brain and spinal cord. The skin rash usually shows up on the body’s trunk and lower parts, but it can also appear on the mucous membranes. The rash can merge into larger blotchy areas and bruises. The petechiae (small reddish spots) usually relate to the degree of low blood platelet count, a condition known as thrombocytopenia. Therefore, doctors must be watchful about these rashes as they can help predict bleeding complications due to DIC.
Diagnosing WFS can be tough, especially in the context of ongoing sepsis, a life-threatening response to infection, which can mimic the signs of severe infection-induced drop in blood pressure (septic shock). Intriguingly, low blood pressure precedes shock only in around half of the patients.
Testing for Waterhouse-Friderichsen Syndrome
If your doctor thinks you might have a condition called Waterhouse Friderichsen syndrome, they will ask for a complete blood test. If the levels of two components of your blood known as hemoglobin and hematocrit start falling, it may suggest that you are losing blood somewhere in your body – this is often known as hidden or “occult” bleeding. You might also have a high white blood cell count, also known as leukocytosis, due to a bacterial infection.
The hormone mineralocorticoid helps balance the levels of sodium and potassium in your blood. If you have low levels of mineralocorticoid, you could end up with too little sodium (a condition called hyponatremia) and too much potassium (hyperkalemia). You might also have hyponatremia because of a condition called Syndrome of Inappropriate Diuretic Hormone (SIADH) which is caused by a deficiency in the hormone cortisol. Another symptom that may be observed is prerenal azotemia, a condition where the kidneys don’t get enough blood. This might affect electrolyte levels in your blood. However, these potential imbalances in sodium and potassium shouldn’t be the sole basis for a diagnosis.
People with this syndrome may have low blood sugar levels, also known as hypoglycemia. This usually isn’t severe and can be easily corrected. A test called arterial blood gas analysis can show if there’s too much acid in the blood, a condition known as metabolic acidosis.
To check how well your adrenal glands are working, your doctor may test the levels of cortisol, aldosterone and ACTH (hormones produced by the adrenal glands), as well as renin (an enzyme that helps control blood pressure). People with Waterhouse Friderichsen syndrome usually have low cortisol and aldosterone levels and high levels of ACTH and renin. If there’s still doubt about your diagnosis, your doctor might give you a synthetic version of ACTH, called cosyntropin, to see how your adrenal glands respond.
If medically stable, they may use a CT scan to look for bleeding in the adrenal glands. However, if these tests aren’t possible, an ultrasound can be done at your bedside. Lastly, an electrocardiogram, a test that records your heart’s electrical activity, will be required to check for any abnormal heart rhythms that can be caused by high potassium levels in your blood.
Treatment Options for Waterhouse-Friderichsen Syndrome
If someone develops Waterhouse Friderichsen syndrome, they may experience a severe body-wide infection called sepsis. To treat this, doctors will carry out a blood test and begin treatment while waiting for the results, rather than waiting to confirm the diagnosis. This is done because complications can arise rapidly in sepsis, so it’s crucial to start treatment as soon as possible.
Treatment includes supportive therapies for sepsis, which helps the body fight infection. Other treatments are fluids to replenish volume lost to dehydration, antibiotics, and drugs that regulate your blood pressure and ensure your organs are getting enough blood. In some cases, there might be a chance of low blood sugar, known as hypoglycemia, so doctors will provide a glucose solution to correct this.
If a patient is still in shock—the body’s response to low blood flow—more fluids are given. For patients with extremely low blood sugar, they receive a glucose solution. If necessary, a type of medication called hydrocortisone (a steroid) is given, with the amount depending on the patient’s age. This helps control symptoms and improve their condition. This steroid is usually divided into four equal doses over a 24-hour period.
Mineral replacement isn’t typically necessary during the emergency stage of the illness, because the effects take a long time to occur. However, once the patient’s condition has stabilized, steroid and mineral replacement will be administered regularly.
Patients’ bodily fluids and electrolyte levels (like potassium and sodium) are monitored throughout treatment. In many cases, fluids and the administration of hydrocortisone help correct any sodium or potassium imbalances. Severe cases may require treatment with insulin and glucose.
For individuals who experience bleeding in the adrenal gland due to injury, a conservative approach is usually recommended—this means avoiding surgery when possible. Instead, these patients receive supportive care, monitoring of red blood cell levels, and possible blood transfusions. Regular imaging exams are also important to monitor the bleeding and distinguish between harmless adrenal bleeding and more serious conditions that might require surgery.
However, sometimes surgery is necessary to stop the bleeding. In a small percentage of cases, a procedure called angioembolization may be performed to stop blood flow to specific parts of the adrenal gland. In even rarer cases, the adrenal gland may need to be removed.
What else can Waterhouse-Friderichsen Syndrome be?
Diagnosing Waterhouse Friderichsen syndrome can be quite tricky, especially during an ongoing bacterial infection, as it can easily be mistaken for septic shock. Important signs that could lead a doctor towards considering Waterhouse Friderichsen syndrome as a potential diagnosis include a situation where the patient’s shock is not getting better despite the use of intravenous fluids or medications to raise blood pressure. When patients have unusually low blood pressure, low body fluids, low sodium levels and signs of kidney dysfunction, they could also be suffering from hypovolemic shock. So, Waterhouse Friderichsen syndrome could be mistaken for this condition, especially if the patient doesn’t show signs of bacterial infection and mainly experiences stomach sickness as a distinct symptom.
Certain other conditions that present symptoms of an adrenal crisis should also be factored in while making the diagnosis. For instance, babies in their first few days to weeks of life could experience such a crisis due to a condition called congenital adrenal hyperplasia resulting from a deficiency of the enzyme 21-hydroxylase. Infants suffering from obstructive uropathy, kidney inflammation or tubulointerstitial nephritis could also present similar symptoms such as stomach sickness, low sodium levels and high potassium levels, often termed as a salt-losing crisis.
What to expect with Waterhouse-Friderichsen Syndrome
The outlook for patients with Waterhouse-Friderichsen syndrome will depend on how severe the disease is. It’s estimated that around 15% of patients who experience major bleeding in their adrenal glands will unfortunately die from the condition. In situations where diagnosis or treatment is delayed, the fatality rate can increase to nearly 50%.
Despite these high mortality rates, it’s important to know that patients can recover with proper and timely management. Once recovered, ongoing treatment is needed with drugs called mineralocorticoid and glucocorticoid, which will depend on their level of electrolytes and their response to treatment. Although it’s hard to predict the recovery, studies have shown that some people can regain some function of their adrenal glands after the acute phase of the disease.
Because there are no exact guidelines on how long the treatment should last, regular check-ups and reevaluation are crucial. Some long-term follow-up studies have suggested that recovery could be complete in some cases to a point where they no longer require hormone replacement.
