Waterhouse–Friderichsen Syndrome
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Waterhouse–Friderichsen syndrome (WFS) is defined as
adrenal gland The adrenal glands (also known as suprarenal glands) are endocrine glands that produce a variety of hormones including adrenaline and the steroids aldosterone and cortisol. They are found above the kidneys. Each gland has an outer adrenal corte ...
failure due to hemorrhages in the adrenal glands, commonly caused by
sepsis Sepsis is a potentially life-threatening condition that arises when the body's response to infection causes injury to its own tissues and organs. This initial stage of sepsis is followed by suppression of the immune system. Common signs and s ...
. Typically, the bacteria responsible for triggering the bleeding is '' Neisseria meningitidis''. The bacterial infection leads to massive
bleeding Bleeding, hemorrhage, haemorrhage or blood loss, is blood escaping from the circulatory system from damaged blood vessels. Bleeding can occur internally, or externally either through a natural opening such as the mouth, nose, ear, urethr ...
into one or both adrenal glands. Bilateral adrenal gland hemorrhaging is more common. It is characterized by overwhelming bacterial infection meningococcemia leading to massive blood invasion,
organ failure Organ dysfunction is a condition where an organ does not perform its expected function. Organ failure is organ dysfunction to such a degree that normal homeostasis cannot be maintained without external clinical intervention or life support. It i ...
,
coma A coma is a deep state of prolonged unconsciousness in which a person cannot be awakened, fails to Nociception, respond normally to Pain, painful stimuli, light, or sound, lacks a normal Circadian rhythm, sleep-wake cycle and does not initiate ...
, low blood pressure and shock,
disseminated intravascular coagulation Disseminated intravascular coagulation (DIC) is a condition in which blood clots form throughout the body, blocking Microvessel, small blood vessels. Symptoms may include chest pain, shortness of breath, leg pain, problems speaking, or problems ...
(DIC) with widespread purpura, rapidly developing adrenocortical insufficiency and death.


Signs and symptoms

Waterhouse–Friderichsen syndrome can be caused by a number of different organisms (see below). When caused by ''Neisseria meningitidis'', WFS is considered the most severe form of meningococcal
sepsis Sepsis is a potentially life-threatening condition that arises when the body's response to infection causes injury to its own tissues and organs. This initial stage of sepsis is followed by suppression of the immune system. Common signs and s ...
. The onset of the illness is nonspecific with fever, rigors, vomiting, and headache. Soon a rash appears; first macular, not much different from the rose spots of
typhoid Typhoid fever, also known simply as typhoid, is a disease caused by ''Salmonella enterica'' serotype Typhi bacteria, also called ''Salmonella'' Typhi. Symptoms vary from mild to severe, and usually begin six to 30 days after exposure. Often ther ...
, and rapidly becoming
petechia A petechia (; : petechiae) is a small red or purple spot ( 1 cm in diameter) and purpura (3 to 10 mm in diameter). The term is typically used in the plural (petechiae), since a single petechia is seldom noticed or significant. Causes Physical t ...
l and
purpuric Purpura () is a condition of red or purple discolored spots on the skin that do not Blanch (medical), blanch on applying pressure. The spots are caused by bleeding underneath the skin secondary to platelet disorders, vascular disorders, coagul ...
with a dusky gray color. Low blood pressure (
hypotension Hypotension, also known as low blood pressure, is a cardiovascular condition characterized by abnormally reduced blood pressure. Blood pressure is the force of blood pushing against the walls of the arteries as the heart pumps out blood and is ...
) develops and rapidly leads to septic shock. The
cyanosis Cyanosis is the change of Tissue (biology), tissue color to a bluish-purple hue, as a result of decrease in the amount of oxygen bound to the hemoglobin in the red blood cells of the capillary bed. Cyanosis is apparent usually in the Tissue (bi ...
of extremities can be extreme and the patient is very prostrated or comatose. In this form of meningococcal disease,
meningitis Meningitis is acute or chronic inflammation of the protective membranes covering the brain and spinal cord, collectively called the meninges. The most common symptoms are fever, intense headache, vomiting and neck stiffness and occasion ...
generally does not occur. Low levels of blood glucose and
sodium Sodium is a chemical element; it has Symbol (chemistry), symbol Na (from Neo-Latin ) and atomic number 11. It is a soft, silvery-white, highly reactive metal. Sodium is an alkali metal, being in group 1 element, group 1 of the peri ...
, high levels of potassium in the blood, and the
ACTH stimulation test The ACTH test (also called the cosyntropin, tetracosactide, or Synacthen test) is a medical test usually requested and interpreted by endocrinologists to assess the functioning of the adrenal glands' stress response by measuring the adrenal res ...
demonstrate the acute adrenal failure. Leukocytosis need not be extreme and in fact
leukopenia Leukopenia () is a decrease in the number of white blood cells (leukocytes). It places individuals at increased risk of infection as white blood cells are the body's primary defense against infections. Signs and symptoms Symptoms may include: * s ...
may be seen and it is a very poor prognostic sign. C-reactive protein levels can be elevated or almost normal.
Thrombocytopenia In hematology, thrombocytopenia is a condition characterized by abnormally low levels of platelets (also known as thrombocytes) in the blood. Low levels of platelets in turn may lead to prolonged or excessive bleeding. It is the most common coag ...
is sometimes extreme, with alteration in prothrombin time (PT) and partial thromboplastin time (PTT) suggestive of
disseminated intravascular coagulation Disseminated intravascular coagulation (DIC) is a condition in which blood clots form throughout the body, blocking Microvessel, small blood vessels. Symptoms may include chest pain, shortness of breath, leg pain, problems speaking, or problems ...
(DIC). Acidosis and acute kidney failure can be seen as in any severe sepsis. Meningococci can be readily cultured from blood or
cerebrospinal fluid Cerebrospinal fluid (CSF) is a clear, colorless Extracellular fluid#Transcellular fluid, transcellular body fluid found within the meninges, meningeal tissue that surrounds the vertebrate brain and spinal cord, and in the ventricular system, ven ...
, and can sometimes be seen in smears of cutaneous lesions. Difficulty swallowing, atrophy of the tongue, and cracks at the corners of the mouth are also characteristic features.


Causes

Multiple species of bacteria can be associated with the condition: * Meningococcus is another term for the
bacteria Bacteria (; : bacterium) are ubiquitous, mostly free-living organisms often consisting of one Cell (biology), biological cell. They constitute a large domain (biology), domain of Prokaryote, prokaryotic microorganisms. Typically a few micr ...
l species '' Neisseria meningitidis''; blood infection with said species usually underlies WFS. While many infectious agents can infect the adrenals, an acute, selective infection is usually meningococcus. * ''
Pseudomonas aeruginosa ''Pseudomonas aeruginosa'' is a common Bacterial capsule, encapsulated, Gram-negative bacteria, Gram-negative, Aerobic organism, aerobic–facultative anaerobe, facultatively anaerobic, Bacillus (shape), rod-shaped bacteria, bacterium that can c ...
'' can also cause WFS. * WFS can also be caused by ''
Streptococcus pneumoniae ''Streptococcus pneumoniae'', or pneumococcus, is a Gram-positive, spherical bacteria, hemolysis (microbiology), alpha-hemolytic member of the genus ''Streptococcus''. ''S. pneumoniae'' cells are usually found in pairs (diplococci) and do not f ...
'' infections, a common bacterial pathogen typically associated with meningitis in the adult and elderly population. * ''
Mycobacterium tuberculosis ''Mycobacterium tuberculosis'' (M. tb), also known as Koch's bacillus, is a species of pathogenic bacteria in the family Mycobacteriaceae and the causative agent of tuberculosis. First discovered in 1882 by Robert Koch, ''M. tuberculosis'' ha ...
'' could also cause WFS. Tubercular invasion of the adrenal glands could cause hemorrhagic destruction of the glands and cause
mineralocorticoid Mineralocorticoids are a class of corticosteroids, which in turn are a class of steroid hormones. Mineralocorticoids are produced in the adrenal cortex and influence salt and water balances (electrolyte balance and fluid balance). The primary ...
deficiency. * ''
Staphylococcus aureus ''Staphylococcus aureus'' is a Gram-positive spherically shaped bacterium, a member of the Bacillota, and is a usual member of the microbiota of the body, frequently found in the upper respiratory tract and on the skin. It is often posi ...
'' has recently also been implicated in pediatric WFS. * It can also be associated with ''
Haemophilus influenzae ''Haemophilus influenzae'' (formerly called Pfeiffer's bacillus or ''Bacillus influenzae'') is a Gram-negative, Motility, non-motile, Coccobacillus, coccobacillary, facultative anaerobic organism, facultatively anaerobic, Capnophile, capnophili ...
''. * Adrenal hemorrhage characteristic of the Waterhouse–Friderichsen syndrome has been identified in several autopsies of patients who died of sepsis secondary to '' Capnocytophaga canimorsus'' infection. Viruses may also be implicated in adrenal problems: *
Cytomegalovirus ''Cytomegalovirus'' (CMV) (from ''cyto-'' 'cell' via Greek - 'container' + 'big, megalo-' + -''virus'' via Latin 'poison') is a genus of viruses in the order '' Herpesvirales'', in the family '' Herpesviridae'', in the subfamily '' Betaherp ...
can cause adrenal insufficiency, especially in the immunocompromised. * Ebola virus infection may also cause similar acute adrenal failure.


Diagnosis

Diagnostic criteria are based on clinical features of adrenal insufficiency as well as identifying the causal agent. If the causal agent is suspected to be meningitis a lumbar puncture is performed. If the causal agent is suspected to be bacterial a blood culture and complete blood count is performed. An adrenocorticotropic hormone stimulation test can be performed to assess adrenal function.


Prevention

Routine vaccination against meningococcus is recommended by the
Centers for Disease Control and Prevention The Centers for Disease Control and Prevention (CDC) is the National public health institutes, national public health agency of the United States. It is a Federal agencies of the United States, United States federal agency under the United S ...
for all 11- to 18-year-olds and people who have poor splenic function (who, for example, have had their spleen removed or who have
sickle-cell disease Sickle cell disease (SCD), also simply called sickle cell, is a group of inherited haemoglobin-related blood disorders. The most common type is known as sickle cell anemia. Sickle cell anemia results in an abnormality in the oxygen-carrying ...
which damages the spleen), or who have certain immune disorders, such as a complement deficiency.


Treatment

Fulminant infection from meningococcal bacteria in the bloodstream is a medical emergency and requires emergent treatment with vasopressors, fluid resuscitation, and appropriate antibiotics. Benzylpenicillin was once the drug of choice with
chloramphenicol Chloramphenicol is an antibiotic useful for the treatment of a number of bacterial infections. This includes use as an eye ointment to treat conjunctivitis. By mouth or by intravenous, injection into a vein, it is used to treat meningitis, pl ...
as a good alternative in allergic patients. Ceftriaxone is an antibiotic commonly employed today.
Hydrocortisone Hydrocortisone is the name for the hormone cortisol when supplied as a medication. It is a corticosteroid and works as an anti-inflammatory and by immune suppression. Uses include conditions such as adrenocortical insufficiency, adrenogenit ...
can sometimes reverse the adrenal insufficiency. Amputations, reconstructive surgery, and tissue grafting are sometimes needed as a result of tissue necrosis (typically of the extremities) caused by the infection.


Prognosis

The prognosis of Waterhouse–Friderichsen syndrome varies by severity of the illness. Around 15% of patients with significant acute bilateral adrenal bleeding experience a fatal outcome. In cases where diagnosis and appropriate treatment are delayed, the case fatality rate approaches 50%. Recovery is possible with appropriate, timely management of the illness. Mineralocorticoid and glucocorticoid treatments may be necessary depending on the recovering patient's electrolyte status and response to treatment. Research shows that people with adrenal hemorrhage can regain adrenal function to some degree.


History

Waterhouse–Friderichsen syndrome is named after Rupert Waterhouse (1873–1958), an English
physician A physician, medical practitioner (British English), medical doctor, or simply doctor is a health professional who practices medicine, which is concerned with promoting, maintaining or restoring health through the Medical education, study, Med ...
, and Carl Friderichsen (1886–1979), a Danish pediatrician, who wrote papers on the syndrome, which had been previously described.


References

{{DEFAULTSORT:Waterhouse-Friderichsen syndrome Bacterial diseases Syndromes affecting the endocrine system Adrenal gland disorders