What Is Waterhouse Friderichsen Syndrome?
Waterhouse Friderichsen syndrome is a rare clinical entity. This was first described among children during the early years of the 20th century by Rupert Waterhouse and Carl Friderichsen and was characterized by bilateral adrenal hemorrhage with a bacterial sepsis precursor. Multiple etiologies have been associated with Waterhouse Friderichsen syndrome ranging from bacterial to viral infectious causes. The terminology is used to describe a broader spectrum of symptoms following adrenal insufficiency secondary to bilateral bleeding into the adrenal gland.
Who Is Susceptible to Waterhouse Friderichsen Syndrome?
Although no definitive studies have been conducted till now, the rarity of the condition is established by the recognition of features in not more than one percent of routine autopsies. However, one thing may be established: the condition is more common in children than in adults.
What Causes Waterhouse Friderichsen Syndrome?
In the initial days of discovery, Neisseria meningitidis-associated sepsis was recognized as the sole etiology of Waterhouse Friderichsen syndrome. Over the years, several other bacterial and viral etiologies have been identified and studied. But researchers expect a much greater number of causative organisms are yet to be discovered. Some of the recognized sepsis-associated causative organisms include Streptococcus pneumonia, Haemophilus influenzae, Escherichia coli, Staphylococcus aureus, Group A beta-hemolytic Streptococcus, Capnocytophaga canimorsus, Enterobacter cloacae, Pasteurella multocida, Plesiomonas shigelloides, Neisseria gonorrhoeae, and Moraxella duplex.
Additionally, bilateral adrenal hemorrhage has been reported in infections caused by Rickettsia rickettsii, Bacillus anthracis, Treponema pallidum, Legionella pneumophila bacteria, and Cytomegalovirus, Parvovirus B19, Epstein-Barr, and Varicella zoster viruses. Pseudomonas aeruginosa is the most commonly identified pathogen in children's autopsies who died of sepsis and bilateral adrenal hemorrhage.
What Is the Pathophysiology of Waterhouse Friderichsen Syndrome?
Owing to the anatomical status (around 50 to 60 small adrenal arterial branches and only a few venules), any changes in the adrenal venous pressure make the organ susceptible to intergranular hemorrhage. The release of the primary stress hormone, cortisol, and increased ACTH (adrenocorticotropic hormone increases adrenal blood flow) and adrenaline-induced platelet aggregation within the adrenal veins further grave the condition. This is one of the hypotheses for the pathophysiological cascade of Waterhouse Friderichsen syndrome.
Another hypothesis suggests that toxin-mediated vasculitis and coagulopathy in collaboration with DIC (disseminated intravascular coagulation) is the causative pathophysiology. This states that endotoxin induces the production of corticosteroids by increasing gland activity. This induces intragranular hemorrhage. It is also theorized that DIC may lead to venous thrombosis within the gland with consequent intragranular hemorrhage.
What Are the Clinical Features of Waterhouse Friderichsen Syndrome?
Patients often complain of infectious symptoms and signs of adrenal insufficiency. Shock is one of the most common manifestations of this syndrome. Other non-specific symptoms include:
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Rapid onset headache.
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Fever.
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Weakness.
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Fatigue.
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Abdominal or flank pain.
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Anorexia.
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Nausea.
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Vomiting.
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Confusion.
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Disorientation.
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Abdominal rigidity or rebound tenderness.
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Petechial rash (developing on the truck, lower body parts, and mucous membranes).
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DIC (disseminated intravascular coagulation-overactive coagulation proteins).
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Purpura fulminans.
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Hypotension (in about half of the patients and precedes shock).
How to Diagnose Waterhouse Friderichsen Syndrome?
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Blood Panel: In suspected cases of Waterhouse Friderichsen syndrome, first, a complete blood panel is done. Any decrease in hemoglobin and hematocrit levels may be suggestive of occult bleeding. Owing to the infectious etiology, leukocytosis (high white blood cells count) may be seen. Adrenal insufficiency deteriorates mineralocorticoid levels, which translates to hyponatremia (low blood sodium) and hyperkalemia (high blood potassium). Cortisol deficiency may also cause the syndrome of inappropriate diuretic hormone (SIADH), which may also precipitate hyponatremia. Azotemia or abnormal concentrations of urea and blood nitrogen products is also a characteristic blood panel finding. Moderate hypoglycemia may be present and is correctable. Blood gas analysis may reveal metabolic acidosis.
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Hormone Panel: ACTH (adrenocorticotropic hormone), cortisol, aldosterone, and renin activity panels should be ordered to assess adrenal function accurately. The panel usually reveals high levels of ACTH and renin with a corresponding fall in aldosterone and cortisol levels. This type of imbalance is in line with adrenal insufficiency.
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Imaging: CT (computed tomography) scans may be ordered to assess adrenal hemorrhage in stable patients, whereas unstable patients may suffice with bedside ultrasound. Hyperkalemia induces cardiac changes that may be evaluated with electrocardiography.
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Histopathology: Upon gross examination, hemorrhage is evident in the glad. Samples of the gland are stained with hematoxylin-eosin which reveals hemorrhage in all layers of the gland with areas of necrosis and microvascular thrombi (clots in very small vessels).
How to Treat Waterhouse Friderichsen Syndrome?
The patients often present with sepsis, which warrants immediate management with supportive therapy with volume resuscitation, appropriate antibiotic coverage, vasopressor to ensure end-organ perfusion, and other supportive care. Hypoglycemia, hyponatremia, and hyperkalemia, if present, should be corrected with intravenous administration. Electrolyte and water balance maintenance should be a prime goal. Once all this settles, attention should be shifted to restoring glucocorticoid and mineralocorticoid balance.
Conservative management for adrenal hemorrhage should be done only in the absence of active bleeding and must include supportive care, hematocrit monitoring, and blood transfusion. This management should be followed with imaging to assess the hematoma. If surgery is required, angioembolization of one of the feeding vessels is necessary to control the bleeding.
What Is the Prognosis of Waterhouse Friderichsen Syndrome?
The fatality of the condition with significant acute bilateral adrenal bleeding is as high as 15 percent. Delayed diagnosis and lack of appropriate management raise the fatality rate to about 50 percent. However, proper management can lead to recovery, and such patients need to follow up treatment with mineralocorticoid and glucocorticoid. Despite definitive data, one can say that the patient may recover some degree of adrenal function. Even with surgically managed patients, the rate of adrenalectomy was 3.1 percent.
What Is the Differential Diagnosis of Waterhouse Friderichsen Syndrome?
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Septic shock (very low blood pressure due to infection).
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Hypovolemic shock (very low blood pressure due to loss of about 15 percent blood volume).
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Congenital adrenal hyperplasia (birth defect causing impaired cortisol synthesis).
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Obstructive uropathy (lack of urination due to blockage of the urinary tract).
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Pyelonephritis (inflammatory bacterial infection of the kidney).
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Tubulointerstitial nephritis (immune-mediated infiltration of the kidney interstitium).
Conclusion
Waterhouse Friderichsen syndrome is a rare condition and requires immediate diagnosis and supportive management. A lack of which is the reason for fatalities reaching 50 percent. An interprofessional team of doctors coordinating and syncing the therapies, even after the emergency has been passed over, is the key to obtaining a good long-term prognosis. Antibiotic therapies are necessary to manage sepsis and several other therapeutic management, with or without surgical intervention.
